FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Citterio, E Van Den Boom, V Schnitzler, G Kanaar, R Bonte, E Kingston, RE Hoeijmakers, JHJ Vermeulen, W AF Citterio, E Van Den Boom, V Schnitzler, G Kanaar, R Bonte, E Kingston, RE Hoeijmakers, JHJ Vermeulen, W TI ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; YEAST SWI/SNF COMPLEX; NUCLEOTIDE EXCISION-REPAIR; SWI-SNF COMPLEX; HISTONE OCTAMER; NUCLEOSOMAL TEMPLATES; FACTOR CSB/ERCC6; DHFR GENE; WILD-TYPE; PROTEIN AB The Cockayne syndrome B protein (CSB) is required for coupling DNA excision repair to transcription in a process known as transcription-coupled repair (TCR). Cockayne syndrome patients show UV sensitivity and severe neurodevelopmental abnormalities. CSB is a DNA-dependent ATPase of the SW12/SNF2 family. SW12/SNF2-like proteins are implicated in chromatin remodeling during transcription. Since chromatin structure also affects DNA repair efficiency, chromatin remodeling activities within repair are expected. Here we used purified recombinant CSB protein to investigate whether it can remodel chromatin in vitro. We show that binding of CSB to DNA results in an alteration of the DNA double-helix conformation. In addition, we find that CSB is able to remodel chromatin structure at the expense of ATP hydrolysis. Specifically, CSB can alter DNase I accessibility to reconstituted mononucleosome cores and disarrange an array of nucleosomes regularly spaced on plasmid DNA. In addition, we show that CSB interacts not only with double-stranded DNA but also directly with core histones. Finally, intact histone tails play an important role in CSB remodeling. CSB is the first repair protein found to play a direct role in modulating nucleosome structure. The relevance of this finding to the interplay between transcription and repair is discussed. C1 Erasmus Univ, Ctr Biomed Genet, Dept Cell Biol & Genet, Ctr Med Genet, NL-3000 DR Rotterdam, Netherlands. Dr Daniel den Hoed Canc Ctr, Dept Radiat Oncol, Rotterdam, Netherlands. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Hoeijmakers, JHJ (reprint author), Erasmus Univ, Ctr Biomed Genet, Dept Cell Biol & Genet, Ctr Med Genet, POB 1738, NL-3000 DR Rotterdam, Netherlands. NR 68 TC 233 Z9 238 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 20 BP 7643 EP 7653 DI 10.1128/MCB.20.20.7643-7653.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 357MB UT WOS:000089504500022 PM 11003660 ER PT J AU Nishikawa, K Sawasdikosol, S Fruman, DA Lai, J Songyang, Z Burakoff, SJ Yaffe, MB Cantley, LC AF Nishikawa, K Sawasdikosol, S Fruman, DA Lai, J Songyang, Z Burakoff, SJ Yaffe, MB Cantley, LC TI A peptide library approach identifies a specific inhibitor for the ZAP-70 protein tyrosine kinase SO MOLECULAR CELL LA English DT Article ID RECEPTOR SIGNAL-TRANSDUCTION; DESIGN; SYSTEM AB We utilized a novel peptide library approach to identify specific inhibitors of ZAP-70, a protein Tyr kinase involved in T cell activation. By screening more than 6 billion peptides oriented by a common Tyr residue for their ability to bind to ZAP-70, we determined a consensus optimal peptide. A Phe-for-Tyr substituted version of the peptide inhibited ZAP-70 protein Tyr kinase activity by competing with protein substrates (K-I of 2 muM). The related protein Tyr kinases, Lck and Syk, were not significantly inhibited by the peptide. When introduced into intact T cells, the peptide blocked signaling downstream of ZAP-70, including ZAP-70-dependent gene induction, without affecting upstream Tyr phosphorylation. Thus, screening Tyr-oriented peptide libraries can identify selective peptide inhibitors of protein Tyr kinases. C1 Beth Israel Deaconess Med Ctr, Div Signal Tranduct, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Int Med Ctr Japan, Dept Clin Pharmacol, Res Inst, Tokyo, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Tranduct, Boston, MA 02115 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIAID NIH HHS [AI7258]; NIGMS NIH HHS [GM56203, R01 GM056203] NR 13 TC 20 Z9 21 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD OCT PY 2000 VL 6 IS 4 BP 969 EP 974 DI 10.1016/S1097-2765(00)00095-2 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368UW UT WOS:000090136700021 PM 11090635 ER PT J AU Huang, LL Pardee, AB AF Huang, LL Pardee, AB TI Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment SO MOLECULAR MEDICINE LA English DT Article ID LEUKEMIA-DERIVED FACTOR; TRANSFORMED-CELL DIFFERENTIATION; MAMMALIAN HISTONE DEACETYLASE; HUMAN THIOREDOXIN HOMOLOG; WAF1/CIP1 GENE PROMOTER; HUMAN BLADDER-CANCER; GELSOLIN EXPRESSION; RETINOBLASTOMA PROTEIN; POLY(ADP-RIBOSE) POLYMERASE; TRANSCRIPTIONAL REPRESSION AB Background: Suberoylanilide hydroxamic acid (sAHA) is a prototype of the newly developed, second-generation, hybrid polar compounds. It is a novel histone deacetylase inhibitor with high potency for inducing cell differentiation of cultured murine erythroleukemia cells. Studies with SAHA have primarily been performed with hematopoietic tumor cells. Here we extent these studies with SAHA to human breast cancer cell lines in an attempt to find better therapeutic agents for breast cancer treatment. Materials and Methods: Human breast cancer cell lines, MCF7, MDA-MB-231, and MDA-MB-435, as well as normal cells, including the normal breast epithelial cell line MCF-10A, and fibroblasts, were treated with sAHA. Cells assayed for cell survival by using trypan blue exclusion assay, colony formation assay, and cell cycle and apoptosis analysis. The effects of sAHA on cell cycle and apoptosis regulatory proteins were examined by Western blots analysis. The identification of additional target genes was carried out by differential display (DD) and reverse transcription-polymerase chain reaction (RT-PCR). Results: SAHA inhibited clonogenic growth of MCF7, MDA-MB-231, and MDA-MB-435 breast cancer cells. These cells were more sensitive to SAHA-mediated cytotoxic effects than normal breast epithelial cells and fibroblasts. The cytotoxic effects of sAHA on breast cancer cells were manifested by G1 and G2/M cell cycle arrest and eventual apoptosis. The pan-caspase inhibitor, Z-VAD.fmk, blocked SAHA-induced cell death, DNA laddering, and cleavage of poly(ADP-ribose) polymerase, indicating the involvement of caspases in SAHA-mediated apoptosis. In addition, SAHA modulated cell cycle and apoptosis regulatory proteins. For example, cyclin-dependent kinase (CDK) inhibitors p21WAF1/Cip1 and p27Kip1 were induced, and retinoblastoma protein pRb was hypophosphorylated. Moreover, SAHA induced several genes associated with differentiation and/ or growth inhibition. These genes encode gelsolin, isopentenyl-diphosphate delta isomerase (IDI1), and 1,25-dihydroxyvitamin D-3 up-regulated protein 1 (VDUP1), the last two of which were identified by DD. Induction of these genes may contribute to SAHA-mediated pro-differentiating and antiproliferative effects. Conclusions: SAHA induced growth inhibition, cell cycle arrest, and eventual apoptosis in human breast cancer cells, possibly by modulating cell cycle and apoptosis regulatory proteins, such as CDK inhibitors p21 and p27, pRb, and other differentiation and/or growth inhibition-associated genes, including gelsolin, IDI1 and VDUP1. This, together with the low toxicity in normal cells, suggests that SAHA might have therapeutic potential for the treatment of human breast cancers. C1 Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [R01CA61253] NR 89 TC 122 Z9 125 U1 0 U2 7 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 OCT PY 2000 VL 6 IS 10 BP 849 EP 866 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 368AF UT WOS:000090094600004 PM 11126200 ER PT J AU Tietze, MK Chin, L AF Tietze, MK Chin, L TI Murine models of malignant melanoma SO MOLECULAR MEDICINE TODAY LA English DT Article ID SUSCEPTIBILITY; MICE; RAS C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Tietze, MK (reprint author), Harvard Univ, Sch Med, Dept Dermatol, 44 Binney St, Boston, MA 02115 USA. NR 6 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD OCT PY 2000 VL 6 IS 10 BP 408 EP 410 DI 10.1016/S1357-4310(00)01781-0 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 362FM UT WOS:000089768000010 PM 11006531 ER PT J AU Altshuler, D Daly, M Kruglyak, L AF Altshuler, D Daly, M Kruglyak, L TI Guilt by association SO NATURE GENETICS LA English DT Editorial Material ID COMPLEX TRAITS; SUSCEPTIBILITY; CHROMOSOME-2; DISEASE; GENES AB Positional cloning of common disease genes is a central but elusive goal of human geneticists. Progress is now reported by Bell and colleagues in their study of NIDDM1, a locus implicated in type 2 diabetes. The complex nature of the reported association illustrates the challenge of implicating a specific gene and mutation in the causation of polygenic disease. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA USA. Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Genet Program, Seattle, WA 98104 USA. RP Altshuler, D (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 16 TC 88 Z9 94 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 OCT PY 2000 VL 26 IS 2 BP 135 EP 137 DI 10.1038/79839 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 359YC UT WOS:000089638800005 PM 11017062 ER PT J AU Morita, Y Perez, GI Paris, F Miranda, SR Ehleiter, D Haimovitz-Friedman, A Fuks, Z Xie, ZH Reed, JC Schuchman, EH Kolesnick, RN Tilly, JL AF Morita, Y Perez, GI Paris, F Miranda, SR Ehleiter, D Haimovitz-Friedman, A Fuks, Z Xie, ZH Reed, JC Schuchman, EH Kolesnick, RN Tilly, JL TI Oocyte apoptosis is suppressed by disruption of the acid sphingomyelinase gene or by sphingosine-1-phosphate therapy SO NATURE MEDICINE LA English DT Article ID PROGRAMMED CELL-DEATH; SPHINGOSINE 1-PHOSPHATE; CHEMOTHERAPY; SURVIVAL; BAX; EXPRESSION; GROWTH; MOUSE; INVOLVEMENT; REQUIREMENT AB The time at which ovarian failure (menopause) occurs in females is determined by the size of the oocyte reserve provided at birth, as well as by the rate at which this endowment is depleted throughout post-natal life. Here we show that disruption of the gene for acid sphingomyelinase in female mice suppressed the normal apoptotic deletion of fetal oocytes, leading to neonatal ovarian hyperplasia. Ex vivo, oocytes lacking the gene for acid sphingomyelinase or wild-type oocytes treated with sphingosine-1-phosphate resisted developmental apoptosis and apoptosis induced by anti-cancer therapy, confirming cell autonomy of the death defect. Moreover, radiation-induced oocyte loss in adult wild-type female mice, the event that drives premature ovarian failure and infertility in female cancer patients, was completely prevented by in vivo therapy with sphingosine-1-phosphate. Thus, the sphingomyelin pathway regulates developmental death of oocytes, and sphingosine-1-phosphate provides a new approach to preserve ovarian function in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. Burnham Inst, Program Apoptosis & Cell Death Res, La Jolla, CA 92037 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RI Paris, francois/L-4915-2015 OI Paris, francois/0000-0002-0176-7348 FU NIA NIH HHS [R01-AG12279]; NICHD NIH HHS [R01-HD34226]; NIEHS NIH HHS [R01-ES08430] NR 46 TC 381 Z9 396 U1 2 U2 18 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 OCT PY 2000 VL 6 IS 10 BP 1109 EP 1114 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 360NT UT WOS:000089674700034 PM 11017141 ER PT J AU Folkman, J Hahnfeldt, P Hlatky, L AF Folkman, J Hahnfeldt, P Hlatky, L TI Cancer: looking outside the genome SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; TUMOR ANGIOGENESIS; GROWTH; CELLS; RESISTANCE; PATTERNS AB The 'gene-centric' approach has produced a wealth of information about the origins and progression of cancer, and investigators seek a full compilation of altered gene expressions for tumour characterization and treatment. However, the cancer genome appears to be far more unstable than previously thought. It may therefore be prudent to augment gene-level approaches with supra-genomic strategies that circumvent the genomic variability of cancer cells. C1 Childrens Hosp, Dept Surg, Surg Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Folkman, J (reprint author), Childrens Hosp, Dept Surg, Surg Res Lab, Boston, MA 02115 USA. NR 30 TC 138 Z9 149 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD OCT PY 2000 VL 1 IS 1 BP 76 EP 79 DI 10.1038/35036100 PG 4 WC Cell Biology SC Cell Biology GA 381LV UT WOS:000165765100020 PM 11413493 ER PT J AU Woolf, CJ AF Woolf, CJ TI Pain SO NEUROBIOLOGY OF DISEASE LA English DT Article; Proceedings Paper CT Symposium on Neuroscience 2000: a New Era of Discovery CY APR 11-13, 1999 CL WASHINGTON, D.C. SP Soc Neurosci C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02139 USA. Harvard Univ, Sch Med, Charlestown, MA 02139 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,4309, Charlestown, MA 02139 USA. NR 0 TC 25 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD OCT PY 2000 VL 7 IS 5 BP 504 EP 510 DI 10.1006/nbdi.2000.0342 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 367XE UT WOS:000090086300005 PM 11042064 ER PT J AU Di Cunto, F Imarisio, S Hirsch, E Broccoli, V Bulfone, A Migheli, A Atzori, C Turco, E Triolo, R Dotto, GP Silengo, L Altruda, F AF Di Cunto, F Imarisio, S Hirsch, E Broccoli, V Bulfone, A Migheli, A Atzori, C Turco, E Triolo, R Dotto, GP Silengo, L Altruda, F TI Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis SO NEURON LA English DT Article ID RHO-ASSOCIATED KINASE; SMALL GTPASE RHO; ACTIN CYTOSKELETON; CEREBRAL-CORTEX; CLEAVAGE FURROW; PROTEIN-RHO; MUTANT MICE; CELL-DEATH; RAC GTPASE; PHOSPHORYLATION AB Citron-kinase (Citron-K) has been proposed by in vitro studies as a crucial effector of Rho in regulation of cytokinesis. To further investigate in vivo its biologic functions, we have inactivated Citron-K gene in mice by homologous recombination. Cifron-K-/- mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with depletion of specific neuronal populations. These abnormalities arise during development of the central nervous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in specific neuronal precursors. Moreover, they suggest a novel molecular mechanism for a subset of human malformative syndromes of the CNS. C1 Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy. Telethon Inst Genet & Med, Milan, Italy. Univ Turin, Dept Neurosci, Neuropathol Lab, I-10126 Turin, Italy. Univ Turin, Dipartimento Sci Biomed & Oncol Umana, Turin, Italy. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Di Cunto, F (reprint author), Univ Turin, Dept Genet Biol & Biochem, Via Santena 5 Bis, I-10126 Turin, Italy. RI Hirsch, Emilio/F-4848-2013; OI Hirsch, Emilio/0000-0002-9073-6024; di cunto, ferdinando/0000-0001-9367-6357 FU NCI NIH HHS [CA73796, CA16038]; NIAMS NIH HHS [AR39190]; Telethon [405/BI, F.2, TGM00P13, TGM06S01] NR 54 TC 153 Z9 156 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 2000 VL 28 IS 1 BP 115 EP 127 DI 10.1016/S0896-6273(00)00090-8 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 370VN UT WOS:000165143500015 PM 11086988 ER PT J AU Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P AF Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P TI Increased CSF volumes are associated with diminished subjective responses to cocaine infusion SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cocaine; euphoria; subjective; CSF; ventricles; cortex; frontal ID MAGNETIC-RESONANCE; GRAY-MATTER; BRAIN; ABUSERS; LOBE; HIPPOCAMPUS; DEPENDENCE; PERFUSION; DOPAMINE; USERS AB We evaluated the hypothesis that ventricular and cortical CSF volume increases are associated with reductions in the magnitude of euphoric effects produced by intravenous IV cocaine infusion in cocaine dependent (CD) individuals. Eleven CD patients participating in a cocaine-infusion study and eleven control subjects underwent magnetic resonance imaging (MRI). Two CSF regions of interest (lateral ventricles and frontal cortex CSF) and two comparison regions (third ventricle and posterior cortex CSF) were measured. Self-reported ratings of the intensify of euphoric response ("high") were obtained from the CD subjects at 3, 20, and 30 minutes after IV administration of cocaine. A significant negative correlation was observed between the volume of the lateral ventricles and subjective ratings of the "high" experienced at 3 minutes, but riot at 20 and 30 minutes after cocaine infusion. In contrast, a significant negative correlation between frontal cortex CSF volume and the intensity of euphoric response was observed at 30 minutes after IV cocaine. No significant associations were observed between the volumes of the two comparison regions and ally subjective ratings of "high." No significant volume differences were observed between the CD and control groups in any region. The results suggest larger lateral ventricular volumes are associated with a decrease in immediate euphoria while larger frontal cortex CSF volumes are associated with a decrease in the duration? of the euphoria induced by cocaine infusion. The age-related brain volume reductions underlying the volume increase in these two CSF spaces may be the neurobiological basis of the age-related reduction in the rates of addiction. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Greater Los Angeles VA Healthcare Syst, W Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90074 USA. NIDA, Medicat Dev Div, Rockville, MD 20857 USA. RP Bartzokis, G (reprint author), Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, 2200 Ft Roots Dr,Bldg 170,116A-NLR, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [1YO1 DA 50038] NR 27 TC 6 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 2000 VL 23 IS 4 BP 468 EP 473 DI 10.1016/S0893-133X(00)00122-6 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 355KV UT WOS:000089385600013 PM 10989274 ER PT J AU Chung, RY Carter, BS Norbash, A Budzik, R Putnam, C Ogilvy, CS AF Chung, RY Carter, BS Norbash, A Budzik, R Putnam, C Ogilvy, CS TI Management outcomes for ruptured and unruptured aneurysms in the elderly SO NEUROSURGERY LA English DT Article DE elderly; outcome; subarachnoid hemorrhage; unruptured aneurysm ID INCIDENTAL INTRACRANIAL ANEURYSMS; SUBARACHNOID HEMORRHAGE; SURGICAL-MANAGEMENT; CEREBRAL ANEURYSMS; SACCULAR ANEURYSMS; GRADING SYSTEM; MORTALITY; COMMUNITY; AUTOPSY; INDEX AB OBJECTIVE: In a patient older than 70 years, the decision to treat an intracranial aneurysm remains difficult whether it is ruptured or unruptured. We sought to review our institutional risks of treatment of such lesions in the context of the risks of rupture and its associated morbidity and mortality in this age group. METHODS: One hundred twenty-nine consecutive patients aged 70 years or older, who were treated at a single institution for an intracranial aneurysm, were retrospectively reviewed. forty patients were treated for unruptured aneurysms, and 89 patients presented after subarachnoid hemorrhage. Seven additional patients in this age group who had solely intracavernous lesions, as well as one patient with a dolichoectatic fusiform basilar lesion, were excluded. Management outcomes were assessed using a modification of the Glasgow Outcome Scale, and additional physical and functional disability was assessed using the Barthel index and the Reintegration to Normal Living index. RESULTS: Six-month outcomes for the unruptured group were: excellent, 70%; good, 15%; fair, 5%; poor, 7.5%; and death (2.5%). Outcomes for all patients with ruptured lesions (including those not offered aggressive therapy) were: excellent, 34%; good, 9%; fair, 5.6%; poor, 3.4%; and death, 45%. Long-term follow-up was performed by questionnaire to assess physical and functional disability. Although physical disability (Barthel index) was similar among survivors, the Reintegration to Normal Living index, a global assessment of function, was significantly higher in patients with unruptured aneurysms (84.8 versus 70.1; P = 0.05), which highlights the disabling effects of hemorrhage. CONCLUSION: On the basis of an individual treatment center's management risks, annual aneurysmal rupture rates can be estimated that justify treatment in this difficult patient population. Despite recent controversy regarding aneurysmal hemorrhage rates, we think that symptomatic unruptured aneurysms should be treated and good results can be achieved, even in older patients. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Intervent Neuroradiol Serv, Dept Radiol, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Vincent Burnham 710,Fruit St, Boston, MA 02114 USA. FU PHS HHS [KO8] NR 33 TC 51 Z9 51 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 OCT PY 2000 VL 47 IS 4 BP 827 EP 832 DI 10.1097/00006123-200010000-00006 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 356HM UT WOS:000089437900015 PM 11014421 ER PT J AU Proctor, SP Letz, R White, RF AF Proctor, SP Letz, R White, RF TI Validity of a computer-assisted neurobehavioral test battery in toxicant encephalopathy SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 7th International Symposium on Neurobehavioral Methods and Effects in Occupational and Environmental Health CY JUN 20-23, 1999 CL STOCKHOLM, SWEDEN DE toxicant encephalopathy; validation; computer assessment ID BEHAVIORAL EVALUATION SYSTEM; NITROUS-OXIDE EXPOSURE; OCCUPATIONAL EXPOSURE; ORGANIC-SOLVENTS; ENVIRONMENTAL EPIDEMIOLOGY; CONSTRUCTION PAINTERS; TEST-PERFORMANCE; WORKERS; TERM; NEUROTOXICITY AB The computer-assisted Neurobehavioral Evaluation System 2 (NES2) test battery provides an efficient method of measuring neurobehavioral effects in epidemiological studies, and a newer computer-assisted battery, NES3, has been developed to assist in neuropsychological assessment. This study assesses the validity of some NES2 and NES3 tests in patients diagnosed with toxicant encephalopathy (TE) following exposure to lead or to mixed solvents. This information can be used to improve the interpretation of NES test results in research studies and clinical evaluations examining central nervous system function. Performance on a battery of computer-assisted tests, consisting of several NES2 and NES3 tasks, by persons diagnosed with TE was compared to that of control subjects to determine ii performance differences reflected a priori hypothesized brain-behavior relationships. Performance on the NES2 and NES3 tests was also correlated with performance on analogous standard neuropsychological tests. Significant performance differences between the patient cases and controls were observed in most of the predicted domains on the NES tests. Overall, moderate correlations were obtained between standard neuropsychological tests and NES2 and NES3 tests from the same functional domains. The results suggest that a rest battery composed of NES2 and NES3 tests can identify clinically significant performance deficits in solvent-exposed patients who have been diagnosed with TE using traditional clinical neuropsychological test methods. The results with lead-exposed TE patients are less robust. Possible explanations for these differences are discussed. (C) 2000 Inter Press, Inc. C1 Boston Environm Hazards Ctr 116B 4, VA Boston Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Publ Hlth Environm Hlth, Boston, MA USA. Boston Univ, Sch Med Neurol, Boston, MA USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Univ So Denmark, Odense, Denmark. RP Proctor, SP (reprint author), Boston Environm Hazards Ctr 116B 4, VA Boston Healthcare Syst, 150 So Hungtington Ave, Boston, MA 02130 USA. FU NIOSH CDC HHS [KO1-OH00136] NR 58 TC 13 Z9 15 U1 0 U2 1 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD OCT PY 2000 VL 21 IS 5 BP 703 EP 714 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 378ZZ UT WOS:000165617600008 PM 11130274 ER PT J AU Cheatham, B AF Cheatham, B TI Adipose as an endocrine organ: Regulation of leptin secretion SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA I70 BP 11S EP 11S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100045 ER PT J AU Wisse, BE Frayo, RS Cummings, DE AF Wisse, BE Frayo, RS Cummings, DE TI A central melanocortin antagonist reverses cancer anorexia in rats SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Univ Washington, Div Metab Endocrinol & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O159 BP 53S EP 53S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100210 ER PT J AU Hoppin, AG Regan, S Wiklund, RA Kaplan, LM AF Hoppin, AG Regan, S Wiklund, RA Kaplan, LM TI Impact of obesity on medical outcomes in an unselected population of hospitalized patients: An interim report SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA O196 BP 62S EP 62S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100248 ER PT J AU Huffman, EK Gulick, T Chabris, C Ariely, D Aharon, I Breiter, HC Kaplan, LM AF Huffman, EK Gulick, T Chabris, C Ariely, D Aharon, I Breiter, HC Kaplan, LM TI Reward value of visual representations of food depends on a satiety deficit state. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Motivat & Emot Neurosci Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PB56 BP 81S EP 81S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100322 ER PT J AU Wee, CC Rigotti, NA Davis, RB Phillips, RS AF Wee, CC Rigotti, NA Davis, RB Phillips, RS TI The relationship between weight control efforts and smoking among US adults. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PD15 BP 100S EP 100S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100395 ER PT J AU Hopkin, AG Premdas, JS Davis, PJ Kaplan, LM AF Hopkin, AG Premdas, JS Davis, PJ Kaplan, LM TI Identification of genetically determined events underlying non-alcoholic fatty liver disease. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD OCT PY 2000 VL 8 SU 1 MA PF36 BP 124S EP 124S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 364DE UT WOS:000089876100489 ER PT J AU Chen, D Cho, SI Chen, CZ Wang, XO Damokosh, AI Ryan, L Smith, TJ Christiani, DC Xu, XP AF Chen, D Cho, SI Chen, CZ Wang, XO Damokosh, AI Ryan, L Smith, TJ Christiani, DC Xu, XP TI Exposure to benzene, occupational stress, and reduced birth weight SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE birth weight; benzene; work stress ID SPONTANEOUS-ABORTION; MATERNAL STRESS; ASSOCIATION; PREGNANCY; COMMUNITY; COHORT; METABOLITES; SOLVENTS; SMOKING; LENGTH AB Objectives-The association between birth weight and exposure to benzene, work stress, and other occupational and environmental hazards was investigated. Methods-in a large petrochemical industry, 792 pregnant workers were enrolled and followed up through delivery between May 1996 and December 1998. Exposure to benzene and other solvents was assessed by an industrial hygienist based on each woman's job title and workplace information. Other occupational and environmental exposures and personal information, including perceived work stress, exposure to noise, physical exertion at work, and passive smoking, were obtained by an interview questionnaire. Univariate and multivariate regression models were used to examine the individual and combined associations of occupational and environmental exposures with birth weight, with adjustment for major confounders including gestational age. Results-In the univariate model, birth weight was negatively associated with exposure to benzene (-58 g (95% confidence interval (95% CI), -115 to -2)) and with work stress (-84 g (95% CI, -158 to -10)). In the multivariate model, there was a significant interaction between exposure to benzene and work stress relative to reduced birth weight, after adjustment for other environmental and occupational exposures and personal variables. Adjusted mean birth weight was 3445 g (95% CI 3401 to 3489) among those with neither exposure, 3430 g for those with exposure to benzene only, 3426 g for those with work stress only, and 3262 g (95% CI 3156 to 3369) for those with both exposures. In other words, there was 183 g (95% CI 65 to 301) reduction in birth weight among those with both exposure to benzene and work stress compared with those with neither exposure. Other work or environmental factors could not explain these findings. Conclusions-Low level exposure to benzene and work stress interact to reduce birth weight in this population. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Beijing Med Univ, Ctr Ecogenet, Beijing 100083, Peoples R China. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Cambridge, MA 02138 USA. RP Xu, XP (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,FXB-101, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NICHD NIH HHS [1RO1 HD32505-01]; NIEHS NIH HHS [1RO1 ES08337-01]; NIOSH CDC HHS [1RO1 OH03027] NR 38 TC 28 Z9 30 U1 1 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD OCT PY 2000 VL 57 IS 10 BP 661 EP 667 DI 10.1136/oem.57.10.661 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 357EN UT WOS:000089485700003 PM 10984337 ER PT J AU Stone, TW Siddiqui, N Arroyo, JG McCuen, BR Postel, EA AF Stone, TW Siddiqui, N Arroyo, JG McCuen, BR Postel, EA TI Primary scleral buckling in open-globe injury involving the posterior segment SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 10-15, 1998 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID PENETRATING OCULAR TRAUMA; VITRECTOMY AB Purposes To determine whether scleral buckle placement at the time of primary repair of open-globe injury of the posterior segment is beneficial. Design: Retrospective; comparative, nonrandomized interventional study. Participants: One hundred twenty-five open-globe injuries treated at the Duke University Medical Center from June 1980 to May 1997. Methods: Open-globe injuries were classified with the Open-globe Injury Classification. Eyes that had zone 2 and 3 injuries that had a primary buckle placed were compared with those that did not. Main Outcome Measures: Subsequent retinal detachment, visual outcome, and need for subsequent scleral buckling. Results: The rate of retinal detachment and the visual outcome were similar in the two groups. More than half of those who did not have a primary buckle placed had subsequent scleral buckling surgery. Conclusions: Many open-globe injuries of the posterior segment require eventual scleral buckle. There may be a role for placement of a scleral buckle at the time of primary repair. Ophthalmology 2000;107:1923-1926 (C) 2000 by the American Academy of Ophthalmology. C1 Duke Univ, Ctr Eye, Durham, NC 27710 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Postel, EA (reprint author), Duke Univ, Ctr Eye, Box 3802,Erwin Rd, Durham, NC 27710 USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD OCT PY 2000 VL 107 IS 10 BP 1923 EP 1926 DI 10.1016/S0161-6420(00)00212-8 PG 4 WC Ophthalmology SC Ophthalmology GA 359FP UT WOS:000089601100043 PM 11013200 ER PT J AU Zeitels, SM AF Zeitels, SM TI Phonomicrosurgery I: Principles and equipment SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID VOCAL FOLD; CLINICAL EXPERIENCE; LASER SURGERY; MICROFLAP; CO2-LASER; EXPOSURE; CANCER AB Phonomicrosurgery arose from 19th century endolaryngeal surgery, which was done through a natural passage and was one of the earliest forms of minimally invasive procedural interventions. The evolution and growth of laryngology as a specialty is inextricably connected to the development of endoscopic laryngeal surgery. Phonomicrosurgical techniques have evolved in the last decade of the 20th century as a group of procedures that are guided by physiologic principles of vocal fold oscillation so as to improve vocal outcome. The anatomic premise of these techniques is to maximally preserve the vocal fold's layered microstructure, epithelium, and lamina propria. Phonomicrosurgery has acquired increasing importance because a dependable voice has become a necessity in our communication-based society. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 68 TC 11 Z9 12 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD OCT PY 2000 VL 33 IS 5 BP 1047 EP + DI 10.1016/S0030-6665(05)70263-2 PG 17 WC Otorhinolaryngology SC Otorhinolaryngology GA 357XV UT WOS:000089528100009 PM 10984768 ER PT J AU Colden, DG Busaba, NY AF Colden, DG Busaba, NY TI Sarcoidosis presenting as recurrent nasal polyps SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 29-31, 1999 CL PROVIDENCE, RHODE ISLAND SP Amer Laryngol Rhinol & Otol Soc Inc, Eastern Sect C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Boston VA Healthcare Syst, Div Otolaryngol, Boston, MA USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 2000 VL 123 IS 4 BP 519 EP 521 DI 10.1067/mhn.2000.106193 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 363JT UT WOS:000089833100035 PM 11020201 ER PT J AU Orf, J Thomas, SH Ahmed, W Wiebe, L Chamberlin, P Wedel, SK Houck, C AF Orf, J Thomas, SH Ahmed, W Wiebe, L Chamberlin, P Wedel, SK Houck, C TI Appropriateness of endotracheal tube size and insertion depth in children undergoing air medical transport SO PEDIATRIC EMERGENCY CARE LA English DT Article DE endotracheal tube size; endotracheal tube insertion depth; pediatric airway management ID HELICOPTER; SOUNDS AB Objectives: Guidelines for pediatric endotracheal tube (ETT) size and insertion depth are important in the helicopter EMS (HES) setting, where intubated patients are frequently transported by a non-physician flight crew providing protocol-based care in an environment noted for Limitations in clinical airway assessment. The objectives of this study were to characterize, in a HEMS pediatric population, the frequency of compliance with guideline-recommended ETT size and insertion depth, and to test for association between guideline noncompliance and subsequent receiving hospital adjustment of ETT size or insertion depth. Design: This retrospective review analyzed 216 consecutive pediatric (age <14) scene and interfacility HEMS transports, of patients intubated before or during HEMS transport, by an urban two-helicopter HEMS service providing protocol-based care with a nurse/paramedic crew configuration. Patients were transported to one of three receiving academic pediatric referral centers. Pediatric Advanced Life Support(PALS) criteria for ETT size and insertion depth were used to assess guideline-appropriateness of pediatric ETTs. Receiving hospital records were reviewed to determine if post-transport ETT size or lipline adjustment were associated with guideline-appropriateness of size and lipline during HEMS transport. Univariate (chi-square and Fisher's exact) and multivariate (logistic regression) statistics were used to assess and control for the following covariates: intubator group (physician, flight crew, ground EMS), transport year, sex, age, transport type (scene versus interfacility), and receiving hospital. For all analyses, statistical significance was set at the 0.05 level. Results: The initial ETT size was within 0.5 mm of guideline-recommended sizes in 178 (83.6%) of the 213 patients for whom this data were available. Inappropriate sized ETTs were nearly always (32 of 35, 91.4%) too small. Compared to initial ETTs placed by ground EMS personnel, initial ETTs placed by flight crew or physicians mere more likely to be appropriate as defined by guidelines (P = .008 and .032, respectively). Receiving hospitals changed the ETT size in 18 (8.3% of 216) cases. Receiving hospital ETT size change was more likely with later transport year (P = .018) and less likely in patients over 2 years of age (P = .03); there was no significant association between receiving hospital ETT size change and intubator group (P > .22) or guideline-appropriateness of ETT size (P = 0.94). The initial ETT insertion depth was within 1 cm of the guideline-recommended lipline in 86 (43.2%) of the 199 patients for whom this data were available. Inappropriate liplines were almost always (109 of 113, 96.5%) too deep. Compared to initial ETT liplines determined by ground EMS personnel, initial liplines determined by Right crew (P = .007), but not physician (P = .47) were more likely to be appropriate as defined by guidelines. Receiving hospitals changed the ETT insertion depth in 72 (33.3% of 216) cases. Receiving hospital lipline change was more likely (P = .03) in patients older than 2 years of age, but was not associated with intubator group (P = .75) or lipline guideline-appropriateness (P = .35). Conclusions: As judged by frequently used guidelines, pediatric ETTs are often too small and commonly inserted too deep. However, this retrospective study, limited by lack of clinical correlation for ETT size and insertion depth, failed to find an association between lack of ETT size or lipline guideline compliance and subsequent ETT adjustment at receiving pediatric centers. This study's findings, which should be confirmed with prospective investigation, cast doubt upon the utility of pediatric ETT size/lipline guidelines as strict clinical or quality assurance tools for use in pediatric airway management. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Thomas, SH (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 115,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 13 Z9 13 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-5161 J9 PEDIATR EMERG CARE JI Pediatr. Emerg. Care PD OCT PY 2000 VL 16 IS 5 BP 321 EP 327 DI 10.1097/00006565-200010000-00004 PG 7 WC Emergency Medicine; Pediatrics SC Emergency Medicine; Pediatrics GA 364XX UT WOS:000089920300004 PM 11063359 ER PT J AU Rivkees, SA Crawford, JD AF Rivkees, SA Crawford, JD TI Dexamethasone treatment of virilizing congenital adrenal hyperplasia: The ability to achieve normal growth SO PEDIATRICS LA English DT Article DE congenital adrenal hyperplasia; dexamethasone; growth ID VELOCITY; HEIGHT AB Objective. To assess whether treatment of virilizing congenital adrenal hyperplasia (CAH) with long-acting glucocorticoids is associated with favorable growth outcomes. Method. We examined the long-term growth of 17 boys and 9 girls with CAH treated with dexamethasone (.27 +/- .01 mg/m(2)/day). Results. For individuals with comparable bone age (BA) and chronological age (CA) at the onset of dexamethasone therapy, males were 2.8 +/- .8 years (mean +/- standard error of the mean; n = 13) and females were 2.4 +/- 1.0 years (n = 6). Males were treated for 7.3 +/- 1.1 years (Delta CA) over which time the change in BA (Delta BA) was 7.0 +/- 1.3 years, and the change in height age (Delta HA) was 6.9 +/- 1.1 years. Females were treated for 6.8 +/- 1.3 years, over which time the Delta BA was 6.5 +/- 1.0 years, and the Delta HA was 6.3 +/- .8 years. During treatment 17 ketosteroid excretion rates were normal for age and 17-hydroxyprogesterone values were 69.6 +/- 18 ng/ dL. Testicular enlargement was first detected at 10.7 +/- .8 years and breast tissue at 9.9 +/- 1.2 years. Three boys and 1 girl had final heights of 171.8 +/- 6 cm and 161 cm, respectively, compared with midparental heights of 176.1 +/- 4.1 cm and 160 cm. Predicted adult heights for 6 other boys and 5 girls were 176.8 +/- 2.0 cm and 161.4 +/- 2.8 cm, respectively, compared with midparental heights of 174.6 +/- 1.4 cm and 158.2 +/- 2.0 cm. Statural outcomes were less favorable for 7 children started on dexamethasone when BAs were considerably advanced, although height predictions increased during therapy. Conclusions. These observations show that children treated with dexamethasone for CAH can achieve normal growth with the convenience of once-a-day dosing in most cases. C1 Yale Univ, Sch Med, Dept Pediat, Sect Pediat Endocrinol, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Endocrine Unit, Boston, MA USA. RP Rivkees, SA (reprint author), Yale Pediat, Box 208081,464 Congress St, New Haven, CT 06520 USA. NR 26 TC 57 Z9 61 U1 1 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 OCT PY 2000 VL 106 IS 4 BP 767 EP 773 DI 10.1542/peds.106.4.767 PG 7 WC Pediatrics SC Pediatrics GA 359QG UT WOS:000089623100037 PM 11015521 ER PT J AU Biederman, J Faraone, SV Monuteaux, MC Feighner, JA AF Biederman, J Faraone, SV Monuteaux, MC Feighner, JA TI Patterns of alcohol and drug use in adolescents can be predicted by parental substance use disorders SO PEDIATRICS LA English DT Article DE substance use; adolescent; exposure; critical period ID ATTENTION-DEFICIT HYPERACTIVITY; RISK-FACTORS; PSYCHIATRIC-DISORDERS; YOUNG ADULTHOOD; MALE TWINS; ABUSE; CHILDREN; FAMILY; PSYCHOPATHOLOGY; COMORBIDITY AB Objective. To examine the specificity of risk for alcohol or drug abuse or dependence (substance use disorders [SUDs]) in offspring exposed to particular subtypes of parental SUDs. Methods. The original sample was derived from 2 groups of index children: 140 attention-deficit/hyperactivity disorder (ADHD) probands and 120 non-ADHD comparison probands. These groups had 174 and 129 biological siblings and 279 and 240 parents, respectively. Results. Independent of familial risk, exposure to parental SUDs predicted SUDs in the offspring. Controlling for duration of exposure, we found that adolescence was a critical developmental period for exposure to parental SUDs. Because all our analyses controlled for social class, ADHD status, and parental lifetime history of SUDs, these results show that exposure to parental SUDs predicts offspring SUDs independently of these risk factors. Conclusions. These results support the critical importance of familial environmental risk factors for the development of SUDs in youth in general and particularly in those at high risk for these disorders. These results highlight adolescence as a critical period for the deleterious effects of exposure to parental SUDs, supporting the need to develop preventive and early intervention strategies targeted at adolescents at high risk for SUDs. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC-725,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-50657-04, R01 MH41314-07, R01 MH57934] NR 39 TC 95 Z9 96 U1 2 U2 9 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 OCT PY 2000 VL 106 IS 4 BP 792 EP 797 DI 10.1542/peds.106.4.792 PG 6 WC Pediatrics SC Pediatrics GA 359QG UT WOS:000089623100040 PM 11015524 ER PT J AU Kohane, DS Lipp, M Kinney, RC Lotan, N Langer, R AF Kohane, DS Lipp, M Kinney, RC Lotan, N Langer, R TI Sciatic nerve blockade with lipid-protein-sugar particles containing bupivacaine SO PHARMACEUTICAL RESEARCH LA English DT Article DE local anesthetics; sciatic nerve; controlled release ID DURATION LOCAL-ANESTHESIA; POLYLACTIC ACID MICROSPHERES; PULMONARY DRUG-DELIVERY; CONTROLLED-RELEASE; EVALUATION INVITRO; LIDOCAINE; RAT AB Purpose. To assess the efficacy of lipid-protein-sugar particles (LPSPs) in providing prolonged duration local anesthesia by percutaneous injection. Methods. Bupivacaine-containing LPSPs were characterized and optimized in vitro. Male Sprague-Dawley rats were given sciatic nerve blocks with bupivacaine-containing LPSPs. Sensory and motor nerve blockade were measured in the hindpaw, as were contralateral functional deficits (a measure of systemic drug distribution). Poly(lacticco-glycolic) acid (PLGA) microspheres were used as a reference. Results. 10% (w/w) bupivacaine LPSPs (60% dipalmitoylphosphatidylcholine) were 4.4 +/- 0.39 mum in diameter, with a tap density of 0.11 +/- 0.04 g/ml. These LPSPs and 50% (w/w) PLGA microspheres had comparable durations of sensory blockade (468 +/- 210 min vs. 706 +/- 344 min, p = 0.08), although the LPSPs produced a much lesser duration of motor blockade (508 +/- 258 min vs. 1062 +/- 456 min, p = 0.005). Systemic toxicity was minimal in both groups. Conclusions. LPSPs provide sensory blockade durations comparable to those from PLGA microspheres, with a smaller amount of drug loading. Motor blockade is shorter with LPSPs than with PLGA microspheres. LPSPs appear to be suitable for extended nerve blockade. Given their size and low density, they may be useful for topical anesthesia of the airway. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Technion Israel Inst Technol, Dept Biomed Engn, Haifa, Israel. RP Langer, R (reprint author), MIT, Dept Chem Engn, Bldg E-25,Rm 342,77 Main St, Cambridge, MA 02139 USA. FU NIGMS NIH HHS [GM00684-01, GM26698] NR 23 TC 40 Z9 44 U1 0 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD OCT PY 2000 VL 17 IS 10 BP 1243 EP 1249 DI 10.1023/A:1026470831256 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 383JQ UT WOS:000165879700012 PM 11145230 ER PT J AU Malone, DC Carter, BL Billups, SJ Valuck, RJ Barnette, DJ Sintek, CD Okano, GJ Ellis, S Covey, D Mason, B Jue, S Carmichael, J Guthrie, K Sloboda, L Dombrowski, R Geraets, DR Amato, MG AF Malone, DC Carter, BL Billups, SJ Valuck, RJ Barnette, DJ Sintek, CD Okano, GJ Ellis, S Covey, D Mason, B Jue, S Carmichael, J Guthrie, K Sloboda, L Dombrowski, R Geraets, DR Amato, MG TI An economic analysis of a randomized, controlled, multicenter study of clinical pharmacist interventions for high-risk veterans: The IMPROVE study SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Spring Meeting of the American-College-of-Clinical-Pharmacy CY APR 11-14, 1999 CL ORLANDO, FLORIDA SP Amer Coll Clin Pharm ID PHARMACEUTICAL CARE; AFFAIRS; EVENTS AB Study Objective. To determine if clinical pharmacists could affect economic resource use and humanistic outcomes in an ambulatory high-risk population. Design. Prospective, randomized, controlled study. Setting. Nine Veterans Affairs medical centers. Patients. Patients who were at high risk for medication-related problems. Intervention. Patients were randomized to usual medical care with input from a clinical pharmacist (intervention group) or just usual medical care (control group). Measurements and Main Results. Of 1054 patients enrolled, 523 were randomized to the intervention group and 531 to the control group. The number of clinic visits increased in the intervention group (p=0.003), but there was no difference in clinic costs. Mean increases in total health care costs were $1020 for the intervention group and $1313 for the control group (p=0.06). Conclusion. including the cost of pharmacist interventions, overall health care expenditures were similar for patients randomized to see a clinical pharmacist versus usual medical care. C1 Univ Colorado, Hlth Sci Ctr, Sch Pharm, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO USA. James A Haley Vet Hosp, Tampa, FL 33612 USA. Boise VA Med Ctr, Boise, ID USA. Reno VA Med Ctr, Reno, NV USA. John L McClellan Mem Vet Hosp, Little Rock, AR USA. VA Chicago Hlth Care Syst, Lakeside Div, Chicago, IL USA. Baltimore VA Med Ctr, Baltimore, MD USA. Iowa City VA Med Ctr, Iowa City, IA USA. STVHCS, Audie Murphy Div, San Antonio, TX USA. RP Malone, DC (reprint author), Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, POB 210207, Tucson, AZ 85721 USA. NR 29 TC 47 Z9 47 U1 1 U2 8 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD OCT PY 2000 VL 20 IS 10 BP 1149 EP 1158 DI 10.1592/phco.20.15.1149.34590 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 360RM UT WOS:000089681100001 PM 11034037 ER PT J AU Hamblin, MR Miller, JL Ortel, B AF Hamblin, MR Miller, JL Ortel, B TI Scavenger-receptor targeted photodynamic therapy SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID TUMOR-ASSOCIATED MACROPHAGES; HOST-CELL POPULATIONS; BREAST-CARCINOMA; OVARIAN-CANCER; GROWTH-FACTOR; PHOTOFRIN ACCUMULATION; MEDIATED RECOGNITION; DRUG-DELIVERY; IN-VIVO; ALBUMIN AB Covalent conjugation of a photosensitizer to a ligand that specifically recognized and internalized by a cell-surface receptor may be a way of improving the selectivity of photodynamic therapy (PDT). The class A Type-I scavenger receptor of macrophages, which among other ligands recognizes maleylated serum albumin and has a high capacity is a good candidate for testing this approach, Chlorin(e6) was covalently attached to bovine serum albumin to give conjugates with molar substitution ratios of 1:1 and 3:1 (dye to protein), and these conjugates could then be further modified by maleylation, A novel way of purifying the conjugates by acetone precipitation was developed in order to remove traces of unbound dye that could not be accomplished by size-exclusion chromatography, Conjugates were characterized by polyacrylamide gel electrophoresis and thin-layer chromatography, Photosensitizer uptake was measured by target J774 murine macrophage-like cells and nontarget OVCAR-5 human ovarian cancer cells, and phototoxicity was examined after illumination by a 660 nm diode laser by a tetrazolium assay, All of the purified conjugates were taken up by and after illumination killed J774 cells while there was only small uptake and no phototoxicity toward OVCAR-5 cells. The higher dye:protein ratio and maleylation of the conjugates both produced higher uptakes and lower survival ratios in J774 cells. The uptake and phototoxicity by J774 cells were decreased after incubation at 4 degreesC demonstrating internalization, and confocal microscopy with organelle-specific green fluorescent probes showed largely lysosomal localization. Uptake and phototoxicity by J774 cells could both be competed by addition of the scavenger receptor ligand maleylated albumin. These data show that scavenger receptor-targeted PDT gives a high degree of specificity toward macrophages and may have applications in the treatment of tumors and atherosclerosis. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, 55 Fruit St, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 54 TC 69 Z9 74 U1 0 U2 8 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 2000 VL 72 IS 4 BP 533 EP 540 DI 10.1562/0031-8655(2000)072<0533:SRTPT>2.0.CO;2 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 366VU UT WOS:000090027600017 PM 11045726 ER PT J AU Kochevar, IE Lynch, MC Zhuang, SG Lambert, CR AF Kochevar, IE Lynch, MC Zhuang, SG Lambert, CR TI Singlet oxygen, but not oxidizing radicals, induces apoptosis in HL-60 cells SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PROTEIN-KINASE-C; PHOTODYNAMIC THERAPY; HYDROGEN-PEROXIDE; CASPASE-3 ACTIVATION; PLASMA-MEMBRANE; DEATH; BCL-2; OVEREXPRESSION; INVOLVEMENT; FIBROBLASTS AB Oxidizing species (OS), produced by photosensitization or derived from cytotoxic agents, activate apoptotic pathways. We investigated whether two different OS, formed at the same subcellular sites, have equivalent ability to initiate apoptosis in HL-60 cells. Our previous work showed that absorption of visible light by rose bengal (RE) produces singlet oxygen exclusively, whereas absorption of ultraviolet A produces RE-derived radicals in addition to singlet oxygen. Singlet oxygen, but not the RE-derived radicals, induced nuclear condensation and DNA fragmentation into nucleosome-size fragments in a dose dependent manner. In contrast, the RE-derived radicals caused greater lipid oxidation than singlet oxygen. These results indicate that different OS, produced at the same subcellular sites, do not have the same ability to induce apoptosis and that the ability of an OS to initiate lipid oxidation does not necessarily correlate with its ability to induce apoptosis. C1 Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Sch Med,Massachusetts Gen Hosp, WEL-224, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM30755] NR 41 TC 64 Z9 71 U1 0 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 2000 VL 72 IS 4 BP 548 EP 553 DI 10.1562/0031-8655(2000)072<0548:SOBNOR>2.0.CO;2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 366VU UT WOS:000090027600019 PM 11045728 ER PT J AU Richardson, RD Boswell, T Woods, SC Wingfield, JC AF Richardson, RD Boswell, T Woods, SC Wingfield, JC TI Intracerebroventricular corticotropin-releasing factor decreases food intake in white-crowned sparrows SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE birds; body weight; intraventricular; regulation ID MELOSPIZA-MELODIA; PASSERINE BIRDS; CRF; STRESS; CORTICOSTERONE; PEPTIDE; COMMUNICATION; LOCALIZATION; INVOLVEMENT; METABOLISM AB Neuropeptides such as corticotropin-releasing factor (CRF) may play a role in regulating the pronounced seasonal changes in food intake shown by white-crowned sparrows (Zonotrichia leucophrys gambelii). White-crowned sparrows held on short day length received injections into the third ventricle (icv) of saline or 5.0, 15.0, and 30 mug/kg. Meal size over the subsequent 180 min was significantly depressed in a dose-dependent fashion. Other non-specific behaviors such as preening, hopping, and immobile behaviors appeared to not be affected by a dose that suppressed food intake. This experiment suggests that white-crowned sparrows, when weight-stable, respond to CRF in a manner comparable with several mammalian species. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, MHC 116, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Roslin Inst, Roslin EH25 9PS, Midlothian, Scotland. Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Washington, Dept Zool, Seattle, WA 98195 USA. RP Richardson, RD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, MHC 116, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-17844] NR 36 TC 15 Z9 15 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD OCT 1 PY 2000 VL 71 IS 1-2 BP 213 EP 216 DI 10.1016/S0031-9384(00)00326-7 PG 4 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 385GC UT WOS:000165994400027 PM 11134705 ER PT J AU Stone, JM Heard, JE Asai, T Ausubel, FM AF Stone, JM Heard, JE Asai, T Ausubel, FM TI Simulation of fungal-mediated cell death by fumonisin B1 and selection of fumonisin B1-resistant (fbr) Arabidopsis mutants SO PLANT CELL LA English DT Article ID DISEASE RESISTANCE RESPONSE; INDUCED HYPERSENSITIVE RESPONSE; PHYTOALEXIN-DEFICIENT MUTANTS; PATHOGENESIS-RELATED PROTEINS; SYSTEMIC ACQUIRED-RESISTANCE; SYRINGAE PV-SYRINGAE; FREE SPHINGOID BASES; SALICYLIC-ACID; GENE-EXPRESSION; PLANT-DISEASE AB Fumonisin B1 (FB1), a programmed cell death-eliciting toxin produced by the necrotrophic fungal plant pathogen Fusarium moniliforme, was used to simulate pathogen infection in Arabidopsis. Plants infiltrated with 10 muM FB1 and seedlings transferred to agar media containing 1 muM FB1 develop lesions reminiscent of the hypersensitive response, including generation of reactive oxygen intermediates, deposition of phenolic compounds and callose, accumulation of phytoalexin, and expression of pathogenesis-related (PR) genes. Arabidopsis FB1-resistant (fbr) mutants were selected directly by sowing seeds on agar containing 1 muM FB1, on which wild-type seedlings fail to develop. Two mutants chosen for further analyses, fbr1 and fbr2, had altered PR gene expression in response to FB1. fbr1 and fbr2 do not exhibit differential resistance to the avirulent bacterial pathogen Pseudomonas syringae pv maculicola (ES4326) expressing the avirulence gene avrRpt2 but do display enhanced resistance to a virulent isogenic strain that lacks the avirulence gene. Our results demonstrate the utility of FB1 for high-throughput isolation of Arabidopsis defense-related mutants and suggest that pathogen-elicited programmed cell death of host cells may be an important feature of compatible plant-pathogen interactions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM048707, R01-GM48707] NR 96 TC 134 Z9 147 U1 1 U2 11 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD OCT PY 2000 VL 12 IS 10 BP 1811 EP 1822 DI 10.1105/tpc.12.10.1811 PG 12 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 371AJ UT WOS:000165155200002 PM 11041878 ER PT J AU Asai, T Stone, JM Heard, JE Kovtun, Y Yorgey, P Sheen, J Ausubel, FM AF Asai, T Stone, JM Heard, JE Kovtun, Y Yorgey, P Sheen, J Ausubel, FM TI Fumonisin B1-induced cell death in Arabidopsis protoplasts requires jasmonate-, ethylene-, and salicylate-dependent signaling pathways SO PLANT CELL LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; PHENYLALANINE AMMONIA-LYASE; LYCOPERSICON-ESCULENTUM MILL; PLANT-DISEASE RESISTANCE; INDUCED PHYSIOLOGICAL-CHANGES; HYPERSENSITIVE RESPONSE; DEFENSE RESPONSES; PERONOSPORA-PARASITICA; METHYL JASMONATE; LEAF SENESCENCE AB We have established an Arabidopsis protoplast model system to study plant cell death signaling. The fungal toxin fumonisin B1 (FB1) induces apoptosis-like programmed cell death (PCD) in wild-type protoplasts. FB1, however, only marginally affects the viability of protoplasts isolated from transgenic NahG plants, in which salicylic acid (SA) is metabolically degraded; from pad4-1 mutant plants, in which an SA amplification mechanism is thought to be impaired; or from jar1-1 or etr1-1 mutant plants, which are insensitive to jasmonate (JA) or ethylene (ET), respectively. FB1 susceptibility of wild-type protoplasts decreases in the dark, as does the cellular content of phenylalanine ammonia-lyase, a light-inducible enzyme involved in SA biosynthesis. Interestingly, however, FB1-induced PCD does not require the SA signal transmitter NPR1, given that npr1-1 protoplasts display wild-type FB1 susceptibility. Arabidopsis cpr1-1, cpr6-1, and acd2-2 protoplasts, in which the SA signaling pathway is constitutively activated, exhibit increased susceptibility to FB1, The cpr6-1 and acd2-2 mutants also constitutively express the JA and ET signaling pathways, but only the acd2-2 protoplasts undergo PCD in the absence of FB1. These results demonstrate that FB1 killing of Arabidopsis is light dependent and requires SA-, JA-, and ET-mediated signaling pathways as well as one or more unidentified factors activated by FB1 and the acd2-2 mutation. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM048707, R01-GM48707] NR 94 TC 221 Z9 236 U1 2 U2 16 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD OCT PY 2000 VL 12 IS 10 BP 1823 EP 1835 DI 10.1105/tpc.12.10.1823 PG 13 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 371AJ UT WOS:000165155200003 PM 11041879 ER PT J AU Dewdney, J Reuber, TL Wildermuth, MC Devoto, A Cui, JP Stutius, LM Drummond, EP Ausubel, FM AF Dewdney, J Reuber, TL Wildermuth, MC Devoto, A Cui, JP Stutius, LM Drummond, EP Ausubel, FM TI Three unique mutants of Arabidopsis identify eds loci required for limiting growth of a biotrophic fungal pathogen SO PLANT JOURNAL LA English DT Article DE defense response; plant-pathogen interactions; disease susceptibility; Arabidopsis; Erysiphe orontii; mutant ID ENHANCED DISEASE SUSCEPTIBILITY; SYSTEMIC ACQUIRED-RESISTANCE; SIGNAL-TRANSDUCTION PATHWAY; SALICYLIC-ACID; POWDERY MILDEW; PSEUDOMONAS-SYRINGAE; DEFENSE RESPONSES; GENE-EXPRESSION; BACTERIAL PATHOGENS; NONHOST RESISTANCE AB To identify components of the defense response that limit growth of a biotrophic fungal pathogen, we isolated Arabidopsis mutants with enhanced disease susceptibility to Erysiphe orontii. Our initial characterization focused on three mutants, eds14, eds15, and eds16. None of these is considerably more susceptible to a virulent strain of the bacterial pathogen Pseudomonas syringae pv. maculicola (Psm). All three mutants develop a hypersensitive response when infiltrated with Psm expressing the avirulence gene avrRpt2, which activates resistance via the LZ-NBS/LRR resistance protein encoded by RPS2. The growth of Psm(avrRpt2), while somewhat greater in the mutants than in the wild type, is less than growth of the isogenic virulent strain. These results indicate that resistance mediated via LZ-NBS/LRR R genes is functional. Analysis of the growth of avirulent Peronospora parasitica strains showed that the resistance pathway utilized by TIR-NBS/LRR R genes is also operative in all three mutants. Surprisingly, only eds14 and eds16 were more susceptible to Erysiphe cichoracearum. Analysis of the expression profiles of PR-1, BGL2, PR-5 and PDF1.2 in eds14, eds15, and eds16 revealed differences from the wild type for all the lines. In contrast, these mutants were not significantly different from wild type in the deposition of callose at sites of E. orontii penetration. All three mutants have reduced levels of salicylic acid after infection. eds16 was mapped to the lower arm of chromosome I and found by complementation tests to be allelic to the salicylic acid-deficient mutant sid2. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Sainsbury Lab, Norwich NR4 7UH, Norfolk, England. Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. Harvard Coll, Cambridge, MA USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. OI Reuber, Lynne/0000-0001-7806-2437 FU NIGMS NIH HHS [GM48707] NR 73 TC 125 Z9 130 U1 2 U2 29 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0960-7412 J9 PLANT J JI Plant J. PD OCT PY 2000 VL 24 IS 2 BP 205 EP 218 DI 10.1046/j.1365-313x.2000.00870.x PG 14 WC Plant Sciences SC Plant Sciences GA 365ER UT WOS:000089935900007 PM 11069695 ER PT J AU Bencardino, JT Rosenberg, ZS Brown, RR Hassankhani, A Lustrin, ES Beltran, J AF Bencardino, JT Rosenberg, ZS Brown, RR Hassankhani, A Lustrin, ES Beltran, J TI Traumatic musculotendinous injuries of the knee: Diagnosis with MR imaging SO RADIOGRAPHICS LA English DT Article DE knee, anatomy; knee, injuries; muscles, injuries; tendons, injuries ID EXTENSOR MECHANISM; POPLITEUS TENDON; MUSCLE INJURY; AVULSION; FRACTURE; ANATOMY; RUPTURE AB Magnetic resonance (MR) imaging is the imaging modality of choice for evaluation of acute traumatic musculotendinous injuries of the knee. Three discrete categories of acute injuries to the musculotendinous unit can be defined: muscle contusion, myotendinous strain, and tendon avulsion. Among the quadriceps muscles, the rectus femoris is the most susceptible to injury at the myotendinous junction due to its superficial location, predominance of type II fibers, eccentric muscle action, and extension across two joints. Among the muscles of the pes anserinus, the sartorius is the most susceptible to strain injury due to its superficial location and biarticular course. The classic fusiform configuration of the semimembranosus along with a propensity for eccentric actions also make it prone to strain injury. MR imaging findings associated with rupture of the iliotibial tract include discontinuity and edema, which are best noted on coronal images. The same mechanism of injury that tears the arcuate ligament from its fibular insertion can The gastrocnemius also result in avulsion injury of the biceps femoris. muscle is prone to strain injury due to its action across two joints and its superficial location. Injuries of the muscle belly and myotendinous junction of the popliteus are far more common than tendinous injuries. C1 Long Isl Jewish Med Ctr, Dept Radiol, New Hyde Pk, NY 11042 USA. Hosp Joint Dis & Med Ctr, Dept Radiol, Orthopaed Inst, New York, NY USA. Maimonides Hosp, Dept Radiol, Brooklyn, NY 11219 USA. RP Bencardino, JT (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. NR 33 TC 43 Z9 45 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2000 VL 20 SI SI BP S103 EP S120 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 481GW UT WOS:000171512400009 PM 11046166 ER PT J AU Rosenberg, ZS Beltran, J Bencardino, JT AF Rosenberg, ZS Beltran, J Bencardino, JT TI From the RSNA refresher courses - MR imaging of the ankle and foot SO RADIOGRAPHICS LA English DT Article; Proceedings Paper CT 85th Annual Meeting and Scientific-Assembly of the Radiological-Society-of-North-America (RSNA) CY NOV 28-DEC 03, 1999 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE ankle, anatomy; ankle, fractures; ankle, injuries; ankle, MR; foot, anatomy; foot, fractures; foot, injuries; foot, MR ID POSTERIOR TIBIAL TENDON; PIGMENTED VILLONODULAR SYNOVITIS; OSTEOCHONDRITIS-DISSECANS; ANTEROLATERAL IMPINGEMENT; PLANTAR FASCIITIS; ABNORMAL FINDINGS; PERONEUS LONGUS; MORTON NEUROMA; DIABETIC FOOT; BREVIS TENDON AB Magnetic resonance (Mlr,) imaging has opened new horizons in the diagnosis and treatment of many musculoskeletal. diseases of the ankle and foot. It demonstrates abnormalities in I the bones and soft tissues before they become evident at other imaging modalities. The exquisite soft-tissue contrast resolution, noninvasive nature, and multiplanar capabilities of MR imaging make it especially valuable for the detection and assessment of a variety of soft-tissue disorders of the ligaments (eg, sprain), tendons (tendinosis, peritendinosis, tenosynovitis, entrapment, rupture, dislocation), and other soft-tissue structures (eg, anterolateral impingement syndrome, sinus tarsi syndrome, compressive neuropathies [eg, tarsal tunnel syndrome, Morton neuroma], synovial disorders). MR imaging has also been shown to be highly sensitive in the detection and staging of a number of musculoskeletal infections including cellulitis, oft-tissue abscesses, and osteomyelitis. In addition, MR imaging is excellent for the early detection and assessment of a number of osseous abnormalities such as bone contusions, stress and insufficiency fractures, osteochondral fractures, osteonecrosis, and transient bone marrow edema. MR imaging is increasingly being recognized as the modality of choice for assessment of pathologic conditions of the ankle and foot. C1 NYU Med Ctr, Hosp Joint Dis, Dept Radiol, New York, NY 10003 USA. Maimonides Hosp, Dept Radiol, Brooklyn, NY 11219 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. RP Rosenberg, ZS (reprint author), NYU Med Ctr, Hosp Joint Dis, Dept Radiol, 305 E 17th St, New York, NY 10003 USA. OI Rosenberg MD, Zehava/0000-0003-1902-6350 NR 75 TC 84 Z9 90 U1 1 U2 8 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD OCT PY 2000 VL 20 SI SI BP S153 EP S179 PG 27 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 481GW UT WOS:000171512400012 PM 11046169 ER PT J AU McMahon, PM Araki, SS Neumann, PJ Harris, GJ Gazelle, GS AF McMahon, PM Araki, SS Neumann, PJ Harris, GJ Gazelle, GS TI Cost-effectiveness of functional imaging tests in the diagnosis of Alzheimer disease SO RADIOLOGY LA English DT Article DE Alzheimer disease; cost-effectiveness; magnetic resonance, (MR), utilization ID CEREBRAL BLOOD-VOLUME; CONTROLLED TRIAL; DONEPEZIL; DEMENTIA; MILD AB PURPOSE: To evaluate the cost-effectiveness of functional neuroimaging in the work-up of patients at specialized Alzheimer disease clinics. MATERIALS AND METHODS: A decision model was used to calculate costs and benefits (in quality-adjusted life-years [QALYs]) that accrued to hypothetical cohorts of patients at presentation to an Alzheimer disease center. Sensitivity analysis was performed to examine the effects of diagnostic test characteristics, therapeutic efficacy, disease severity, and costs on cost-effectiveness. RESULTS: The incremental cost-effectiveness ratio of dynamic susceptibility contrast material-enhanced magnetic resonance (MR) imaging was $479,500 per QALY (compared with the usual diagnostic work-up), while visual or quantitative single photon emission computed tomography (SPECT) ws dominated (higher cost, lower effectiveness) by the usual diagnostic work-up. These results depend critically on the sensitivity and specificity of the standard diagnostic work-up, the effectiveness of drug treatment, and the disease severity. Varying these parameters resulted in estimates of incremental cost-effectiveness for dynamic susceptibility contrast-enhanced MR imaging of $24,680 to $8.6 million per QALY. SPECT either was dominated by the usual diagnostic work-up or had cost-effectiveness ratios of $180,200 to $6 million per QALY. CONCLUSION: The addition of functional neuroimaging to the usual diagnostic regimen at Alzheimer disease clinics is not cost-effective given the effectiveness of currently available therapies. C1 Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Comp Assisted Diagnost Lab, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Program Econ Evaluat Med Technol, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Zero Emerson Pl,Ste 2H, Boston, MA 02114 USA. NR 33 TC 51 Z9 53 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2000 VL 217 IS 1 BP 58 EP 68 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 356PW UT WOS:000089452500012 PM 11012424 ER PT J AU Reimer, P Jahnke, N Fiebich, M Schima, W Deckers, F Marx, C Holzknecht, N Saini, S AF Reimer, P Jahnke, N Fiebich, M Schima, W Deckers, F Marx, C Holzknecht, N Saini, S TI Hepatic lesion detection and characterization: Value of nonenhanced MR imaging, superparamagnetic iron oxide-enhanced MR imaging, and spiral CT-ROC analysis SO RADIOLOGY LA English DT Article DE contrast media; iron; liver neoplasms; liver neoplasms, MR; magnetic resonance (MR), contrast media ID FOCAL LIVER-LESIONS; ARTERIAL PORTOGRAPHY; CLINICAL-APPLICATION; SPIN-ECHO; METASTASES; EFFICACY; METHODOLOGY; FERUMOXIDES; EXPERIENCE; SEQUENCES AB PURPOSE: To determine the accuracy for detection and characterization of focal hepatic lesions of nonenhanced, superparamagnetic iron oxide (SPIO)-enhanced, or a combination of nonenhanced and SPIO-enhanced MR imaging and contrast-enhanced spiral computed tomography (CT). MATERIALS AND METHODS: Spiral CT and T2-weighted SPIO-enhanced (ferucarbotran-enhanced) MR imaging were performed in 35 patients within 2 weeks before surgery for malignant hepatic lesions. Only malignant lesions with histopathologic proof were considered. A total of 875 images with and 800 images without focal lesions were presented to five readers, who were asked to assess the presence and characterization of lesions by using a five-point confidence scale. Receiver operating characteristic analysis was performed. RESULTS: Nonenhanced and SPIO-enhanced images together and SPIO-enhanced images alone yielded the best performance for lesion detection. No differences were found among all imaging techniques with regard to lesion characterization (benign vs malignant). The combined approach resulted in larger area under the ROC curve (A(z) = 0.9062) and accuracy (85.3%) (P < 0.02), as compared with SPIO-enhanced MR imaging (A(z) = 0.8667; accuracy, 73.1%). CONCLUSION: SPIO-enhanced T2-weighted MR imaging was more accurate than nonenhanced T1-weighted and T2-weighted MR imaging and contrast-enhanced spiral CT for the detection of focal hepatic lesions. The combined analysis of nonenhanced and SPIO-enhanced images was more accurate in the characterization of focal hepatic lesions than was review of SPIO-enhanced images alone. C1 Stadt Klinikum Karlsruhe, Dept Radiol, D-76133 Karlsruhe, Germany. Univ Munster, Dept Clin Radiol, D-4400 Munster, Germany. Univ Vienna, Dept Radiol, A-1010 Vienna, Austria. Univ Ziekenhuis Antwerpen, Dept Radiol, Edegem, Belgium. Ruhr Univ Bochum, Knappschafts Krankenhaus, Langendreer Klin, Dept Radiol, Bochum, Germany. Univ Munich, Klinikum Grosshadern, Dept Diagnost Radiol, D-8000 Munich, Germany. Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. RP Reimer, P (reprint author), Stadt Klinikum Karlsruhe, Dept Radiol, Moltkestr 90, D-76133 Karlsruhe, Germany. NR 35 TC 131 Z9 134 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 2000 VL 217 IS 1 BP 152 EP 158 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 356PW UT WOS:000089452500024 PM 11012438 ER PT J AU Krause, WL Leiter, JC Tenney, SM Daubenspeck, JA AF Krause, WL Leiter, JC Tenney, SM Daubenspeck, JA TI Acute hypoxia activates human 8-12 Hz physiological tremor SO RESPIRATION PHYSIOLOGY LA English DT Article DE hypocapnia, tremor; hypoxia, arousal, tremor; mammals, humans; peripheral chemoreceptors, hypoxia, hypocapnia; somatomotor system, hypoxia, tremor ID MUSCLE SYMPATHETIC ACTIVITY; MOTOR-UNIT-ACTIVITY; HYPOXEMIC HUMANS; RESPONSES; REST AB Hypoxia causes arousal. Therefore, we hypothesized that hypoxia activates the human somatomotor system and should augment tremor. We determined the effects of hypoxia, PETO2 = 45 +/- 2.2 mm Hg, hypocapnia, and the hypocapnic-hypoxic interaction on finger tremor during elastic loading. A total of 12 healthy male volunteers were studied during five conditions: eupnea, hypocapnic hypoxia, eucapnic hypoxia, hypocapnic normoxia, and eucapnic normoxia. Acceleration power spectra were computed to quantify 8-12 Hz tremor. Hypoxia significantly augmented 8-12 Hz physiological tremor (P = 0.002). Furthermore, six subjects (50%) exhibited significantly more tremor during hypocapnic hypoxia (hH) than during eucapnic hypoxia (eH). We conclude that acute hypoxia augments 8-12 Hz physiological tremor, and hypocapnia further augments this tremor in some subjects. As such, hypoxic tremor is activated physiological tremor, and entrainment of spinal alpha-motoneuron activity may be the final common pathway. (C) 3000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA. RP Krause, WL (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Med Serv, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL07449] NR 40 TC 5 Z9 5 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 OCT PY 2000 VL 123 IS 1-2 BP 131 EP 141 DI 10.1016/S0034-5687(00)00146-8 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 357DA UT WOS:000089482200012 PM 10996194 ER PT J AU Ferrando, AA Look, AT AF Ferrando, AA Look, AT TI Clinical implications of recurring chromosomal and associated molecular abnormalities in acute lymphoblastic leukemia SO SEMINARS IN HEMATOLOGY LA English DT Review ID PEDIATRIC-ONCOLOGY-GROUP; CHILDRENS CANCER GROUP; ACUTE LYMPHOCYTIC-LEUKEMIA; CELL ACUTE-LEUKEMIA; GERMAN MULTICENTER TRIALS; T-CELL; POOR-PROGNOSIS; HEMATOLOGICAL MALIGNANCIES; TEL/AML1 FUSION; CYTOGENETIC ABNORMALITIES C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Mayer-630,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 59571] NR 130 TC 101 Z9 102 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD OCT PY 2000 VL 37 IS 4 BP 381 EP 395 DI 10.1016/S0037-1963(00)90018-0 PG 15 WC Hematology SC Hematology GA 365TX UT WOS:000089967500007 PM 11071360 ER PT J AU Treon, SP Raje, N Anderson, KC AF Treon, SP Raje, N Anderson, KC TI Immunotherapeutic strategies for the treatment of plasma cell malignancies SO SEMINARS IN ONCOLOGY LA English DT Review ID COLONY-STIMULATING-FACTOR; CYTOTOXIC T-LYMPHOCYTES; INTERCELLULAR-ADHESION MOLECULE-1; ANTI-CD20 MONOCLONAL-ANTIBODY; HEPARAN-SULFATE PROTEOGLYCAN; TRANSCRIPTION FACTOR PU.1; MAMMARY EPITHELIAL-CELLS; MULTIPLE-MYELOMA CELLS; FAS APO-1/CD95 LIGAND; NECROSIS-FACTOR-ALPHA C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01CA78378] NR 153 TC 47 Z9 50 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD OCT PY 2000 VL 27 IS 5 BP 598 EP 613 PG 16 WC Oncology SC Oncology GA 362YB UT WOS:000089804900011 PM 11049026 ER PT J AU McMahon, PM Gazelle, GS AF McMahon, PM Gazelle, GS TI The case for colorectal cancer screening SO SEMINARS IN ROENTGENOLOGY LA English DT Review ID FECAL-OCCULT-BLOOD; DOUBLE-CONTRAST BARIUM; COLONOGRAPHY VIRTUAL COLONOSCOPY; RANDOMIZED CONTROLLED TRIAL; COST-EFFECTIVENESS; COLON-CANCER; ADENOMATOUS POLYPS; RISK-FACTORS; ENEMA; ENDOSCOPY C1 Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Decis Anal & Technol Assessment Grp, Zero Emergency Pl,Suite 2H, Boston, MA 02114 USA. NR 113 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 0037-198X J9 SEMIN ROENTGENOL JI Semin. Roentgenology PD OCT PY 2000 VL 35 IS 4 BP 325 EP 332 DI 10.1053/sroe.2000.17753 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 365TN UT WOS:000089966700003 PM 11060919 ER PT J AU Carey, K AF Carey, K TI Hospital cost containment and length of stay: An econometric analysis SO SOUTHERN ECONOMIC JOURNAL LA English DT Article ID EXCESS BED CAPACITY; PROSPECTIVE PAYMENT; PANEL-DATA; IMPACTS; DEMAND; CARE AB In recent years, concern in the United States over rising health care costs has led to precipitous reductions in the lengths of hospitalizations. While perceptions of compromised medical care quality following this practice and others have prompted policy makers to consider stricter regulation of health insurance organizations, little attention has been given to the extent to which length of stay reductions are responsible for decreasing hospital costs. This paper provides empirical evidence on that point. The method utilizes a hospital total operating cost function estimated on 2792 U.S. hospitals for the period 1987-1992. Three different panel data estimating techniques are applied, including a random effects model that is distinctive in allowing for correlation between hospital effects and observable regressors, circumventing inconsistency problems following from standard generalized least-squares estimations. The cost elasticity of length of stay is calculated from the regression results. This measure is low, falling in the range 0.09-0.12. It suggests that common perceptions regarding the extent of cost savings resulting from length of stay reductions have been overestimated. C1 US Dept Vet Affairs, Managemetn Sci Grp, Bedford, MA 01730 USA. RP Carey, K (reprint author), US Dept Vet Affairs, Managemetn Sci Grp, 200 Springs Rd, Bedford, MA 01730 USA. NR 33 TC 12 Z9 12 U1 2 U2 7 PU UNIV NORTH CAROLINA PI CHAPEL HILL PA SOUTHERN ECONOMIC JOURNAL, CHAPEL HILL, NC 27514 USA SN 0038-4038 J9 SOUTHERN ECON J JI South. Econ. J. PD OCT PY 2000 VL 67 IS 2 BP 363 EP 380 DI 10.2307/1061475 PG 18 WC Economics SC Business & Economics GA 367CA UT WOS:000090043000007 ER PT J AU Laufs, U Gertz, K Huang, P Nickenig, G Bohm, M Dirnagl, U Endres, M AF Laufs, U Gertz, K Huang, P Nickenig, G Bohm, M Dirnagl, U Endres, M TI Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice SO STROKE LA English DT Article DE blood platelets; cerebral ischemia; HMG-CoA reductase inhibitors; nitric oxide; thrombosis ID 3-HYDROXY-3-METHYLGLUTARYL-COA REDUCTASE INHIBITORS; ACUTE CORONARY SYNDROMES; CHOLESTEROL REDUCTION; ENDOTHELIAL-CELLS; STROKE RISK; RHO-GTPASE; STATINS; HYPERCHOLESTEROLEMIA; SIMVASTATIN; EXPRESSION AB Background and Purpose-Thrombosis superimposed on atherosclerosis causes approximately two thirds of all brain infarctions. We previously demonstrated that statins protect from cerebral ischemia by upregulation of endothelial type ill nitric oxide synthase (eNOS), but the downstream mechanisms have not been determined. Therefore, we investigated whether antithrombotic effects contribute to stroke protection by statins. Methods-129/SV wild-type and eNOS knockout mice were treated with atorvastatin for 14 days (0.5, 1, and 10 mg/kg). eNOS mRNA from aortas and platelets was measured by reverse-transcriptase polymerase chain reaction. Platelet factor 4 (PF 4) and beta-thromboglobulin (beta-TG) in the plasma were quantified by ELISA, Transient cerebral ischemia was induced by filamentous occlusion of the middle cerebral artery followed by reperfusion. Results-Stroke volume after 1-hour middle cerebral artery occlusion/23-hour reperfusion was significantly reduced by 38% in atorvastatin-treated animals (10 mg/kg) compared with controls. Serum cholesterol levels were not affected by the treatment. eNOS mRNA was significantly upregulated in a dose-dependent manner in aortas and in thrombocytes of statin-treated mice compared with controls. Moreover, indices of platelet activation in vivo, ie, plasma levers of PF 4 and beta-TG, were dose-dependently downregulated in the treatment group. Surprisingly, atorvastatin-treatment did not influence PF 4 and beta-TG levels in eNOS knockout mice. Conclusions-The synthetic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin upregulates eNOS in thrombocytes, decreases platelet activation in vivo, and protects from cerebral ischemia in normocholesterolemic mice. Antithrombotic and stroke-protective effects of statins an mediated in part by eNOS upregulation. Our results suggest that statins may provide a novel prophylactic treatment strategy independent of serum cholesterol levels. C1 Humboldt Univ, Charite, Neurol Klin & Poliklin, Inst Expt Neurol, D-10098 Berlin, Germany. Univ Cologne, Innere Med Klin 3, D-5000 Cologne 41, Germany. Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Endres, M (reprint author), Humboldt Univ, Charite, Neurol Klin & Poliklin, Inst Expt Neurol, Schumannstr 20-21, D-10098 Berlin, Germany. RI Gertz, Karen/J-1603-2015; OI Dirnagl, Ulrich/0000-0003-0755-6119 NR 51 TC 234 Z9 265 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD OCT PY 2000 VL 31 IS 10 BP 2442 EP 2448 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 360FN UT WOS:000089655900027 PM 11022078 ER PT J AU Behnia, K Bhatia, S Jastromb, N Balis, U Sullivan, S Yarmush, M Toner, M AF Behnia, K Bhatia, S Jastromb, N Balis, U Sullivan, S Yarmush, M Toner, M TI Xenobiotic metabolism by cultured primary porcine hepatocytes SO TISSUE ENGINEERING LA English DT Article ID ARTIFICIAL LIVER SUPPORT; ADULT-RAT HEPATOCYTES; CYTOCHROME-P-450; BIOTRANSFORMATION; INDUCTION; MAINTENANCE; COCULTURES; FAILURE; INVITRO; ABSENCE AB Considering the large yield of viable cells comparable to human liver, primary porcine hepatocytes offer a valuable resource for constructing a bioartificial liver device. In this study, the ability of cultured primary porcine hepatocytes to detoxify xenobiotics has been examined using various known substrates of cytochrome P450 isoenzymes and UDP-glucuronosyltransferases. Present investigation demonstrated the stability of the isoenzymes responsible for the metabolism of diazepam in native state and stabilization of other isoenzymes, as judged by ethoxycoumarin o-dealkylase (ECOD), ethoxyresorufin o-dealkylase (EROD), benzyloxyresorufin o-dealkylase (BROD), and pentoxyresorufin o-dealkylase (PROD) activities following induction in culture environment, for a period of 8 days. Resorufin O-dealkylase activities were found to be the most unstable and deteriorated within first 5 days in culture. These activities were restored following induction with 3-methylcholanthrene (3-MC) or sodium phenobarbital (PB) to 20-fold of 1 activity for EROD, and 60 and 174% of day 1 activity for PROD and BROD on day 8, respectively. Metabolism of methoxyresorufin was most strikingly increased following induction with 3-MC to approximately 60-fold of day 1 activity, on day 8. UDP-glucuronosyltransferase-dependent glucuronidation of phenol red, however, stayed intact during the course of our study without induction. Our study indicated that porcine hepatocytes in vitro maintain many important liver-specific functions including detoxification (steady state and inducibility). C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA USA. Organogenesis Inc, Canton, MA USA. RP Toner, M (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. NR 37 TC 58 Z9 59 U1 0 U2 3 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 OCT PY 2000 VL 6 IS 5 BP 467 EP 479 DI 10.1089/107632700750022125 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 369VD UT WOS:000165087100001 PM 11074934 ER PT J AU Washizu, J Chan, C Berthiaume, F Tompkins, RG Toner, M Yarmush, ML AF Washizu, J Chan, C Berthiaume, F Tompkins, RG Toner, M Yarmush, ML TI Amino acid supplementation improves cell-specific functions of the rat hepatocytes exposed to human plasma SO TISSUE ENGINEERING LA English DT Article ID BIOARTIFICIAL LIVER; SANDWICH CONFIGURATION; CULTURED-HEPATOCYTES; SUPPORT; INJURY; GLYCINE; FAILURE AB Maintaining hepatocyte function during plasma exposure is critical for the successful development of hepatocyte-based bioartificial liver assist systems. Past attempts to culture hepatocytes in plasma yielded discouraging results. Using a stable culture model based on sandwiching hepatocytes between two layers of collagen gel, we investigated the effect of hormone and amino acid supplementation during exposure of rat hepatocytes to heparin-treated human plasma for 1 week. Morphology and hepatocyte-specific functions were evaluated for hepatocytes cultured in Dulbecco's Modified Eagle medium (DMEM), nonsupplemented plasma, plasma supplemented with hormones, or with hormones plus amino acids. Amino acids were supplemented at four-fold concentration of Basal Medium Eagle with 4 mM glutamine, whereas hormones included 7.5 mug/mL of hydrocortisone and 50 muU/mL of insulin. Cuboidal structure and bile canaliculi formation were observed throughout the 1-week exposure period for control hepatocytes in DMEM and for hepatocytes cultured in hormone supplemented plasma. Albumin and urea synthesis rates of hepatocytes in hormone plus amino acid supplemented plasma during the last day of plasma exposure were 60.4 +/- 13.7 and 75.6 +/- 6.5 (mug/day per 1 x 10(6) cells, mean +/- SD), respectively, comparable to cultures in standard culture medium. On the other hand, hepatocytes exposed to nonsupplemented plasma suffered significant morphological and functional damage. The results of this study indicate that hormone plus amino acid supplementation help to restore function in hepatocytes exposed to plasma. 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 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, GRB 1401,55 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM07035]; PHS HHS [D41709] NR 24 TC 24 Z9 24 U1 0 U2 1 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 OCT PY 2000 VL 6 IS 5 BP 497 EP 504 DI 10.1089/107632700750022143 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 369VD UT WOS:000165087100003 PM 11074936 ER PT J AU Peretti, GM Randolph, MA Villa, MT Buragas, MS Yaremchuk, MJ AF Peretti, GM Randolph, MA Villa, MT Buragas, MS Yaremchuk, MJ TI Cell-based tissue-engineered allogeneic implant for cartilage repair SO TISSUE ENGINEERING LA English DT Article ID RABBIT ARTICULAR-CARTILAGE; CHONDROCYTE TRANSPLANTATION; OSTEOCHONDRAL DEFECTS; POLYMER; MATRIX; MODEL; SCAFFOLDS; SURFACES; ALGINATE; KNEE AB The potential for using of allogeneic cartilage chips, transplanted in a biologic polymer with articular chondrocytes, as a tool for articular cartilage repair was studied. Small lyophilized articular cartilage chips were mixed with a cell/fibrinogen solution and thrombin to obtain implantable constructs made of fibrin glue, chondrocytes, and cartilage chips. Specimens were implanted in the subcutaneous tissue on the backs of nude mice (experimental group A). Three groups of controls (groups B, C, and D) were also prepared. Group B consisted of fibrin glue and cartilage chips without chondrocytes. Group C consisted of fibrin glue and chondrocytes without cartilage chips, and group D was composed solely of fibrin glue. All samples were carefully weighed before implantation in the mice. The constructs were harvested from the aninals at 6, 9, and 12 weeks, examined grossly, and weighed. The samples were then processed and stained with hematoxylin and eosin for histological examination. Gross evaluation and weight analysis of the constructs at the time of retrieval showed retention of the original mass in the samples made of fibrin glue, chondrocytes, and cartilage chips (group A) and demonstrated a cartilaginous consistency upon probing. Specimens from constructs of fibrin glue and cartilage chips without chondrocytes (control group B) retained most of their volume, but were statistically lighter than specimens from group A and were much softer and more pliable than those in group A. Samples of specimens from constructs of fibrin glue and chondrocytes (groups C) and fibrin glue alone (group D) both showed a substantial reduction of their original masses over the experimental time periods when compared to the samples in groups A and B, although specimens from group C demonstrated new cartilage matrix formation. Histological analysis of specimens in experimental group A demonstrated the presence of cartilage chips surrounded by newly formed cartilaginous matrix, while specimens of control group B showed only fibrotic tissue surrounding the devitalized cartilage pieces. Cartilaginous matrix was also observed in control group C, in which cartilage chips were absent, whereas only fibrin glue debris was observed in control group D. This study demonstrated that a composite of fibrin glue and devitalized cartilage can serve as a scaffold for chondrocyte transplantation, preserve the original phenotype of the chondrocytes, and maintain the original mass of the implant. This may represent a valid option for addressing the problem of articular cartilage repair. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Hosp San Raffaele, Dept Orthopaed, I-20132 Milan, Italy. RP Randolph, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Plast Surg, WACC 453, Boston, MA 02114 USA. RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 FU NIAMS NIH HHS [R03 AR45059] NR 36 TC 47 Z9 53 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD OCT PY 2000 VL 6 IS 5 BP 567 EP 576 DI 10.1089/107632700750022206 PG 10 WC Cell & Tissue Engineering SC Cell Biology GA 369VD UT WOS:000165087100009 PM 11074942 ER PT J AU Kruskall, MS Uhl, L Yu, N Hussein, S Yunis, EJ Knoll, J AF Kruskall, MS Uhl, L Yu, N Hussein, S Yunis, EJ Knoll, J TI Misinterpretation of HLA typing in a woman with congenital chimerism due to postzygotic fusion of two embryos SO TRANSFUSION LA English DT Meeting Abstract C1 Childrens Mercy Hosp, Kansas City, MO 64108 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Amer Red Cross, Blood Serv, Dedham, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 2000 VL 40 IS 10 SU S BP 12S EP 12S PG 1 WC Hematology SC Hematology GA 364CN UT WOS:000089874600046 ER PT J AU Castle, SC AF Castle, SC TI Impact of age-related immune dysfunction on risk of infections SO ZEITSCHRIFT FUR GERONTOLOGIE UND GERIATRIE LA English DT Article DE aging; immunology; immunosenescence; host defenses; SENIEUR protocol ID BLOOD MONONUCLEAR-CELLS; INFLUENZA VACCINATION; VITAMIN-E; ANTIBODY-RESPONSE; HUMAN-LYMPHOCYTES; ELDERLY SUBJECTS; UP-REGULATION; SYSTEM; ZINC; SUPPLEMENTATION AB The elderly have clearly been found to have both increased risk and severity of infections. Immunosenescence, the state of dysregulated immune function with aging, is felt to be a significant contributor to this increased risk. Extensive studies on inbred laboratory animals and in very healthy elderly humans have identified changes in immunity and have identified primarily phenotypic and functional changes in the T cell component of adaptive immunity. However, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population. This perspective will at tempt to shed light on this dilemma. First, it will review clinically relevant infections in the elderly, focusing on influenza and influenza vaccination and how chronic illness contributes to increased risk and severity of infection/failed vaccine response. Next, key changes in immunity will be reviewed, keeping perspective of the impact of confounding variables such as nutrition. If the goal is to prevent serious infections in the elderly, it appears that the field of geriatric immunology/infectious disease is faced with the tremendous challenge of studying a very diverse population of chronically ill individuals in addition to the study of the very healthy elderly. Grouping individuals by dis ease severity or by level of impairment of specific components of immunity may assist in advancing our ability to improve host defense in an at risk population. C1 VA Greater Los Angeles Healthcare Syst, GRECC 11G, Los Angeles, CA 90073 USA. RP Castle, SC (reprint author), VA Greater Los Angeles Healthcare Syst, GRECC 11G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 53 TC 31 Z9 33 U1 0 U2 3 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0044-281X J9 Z GERONTOL GERIATR JI Z. Gerontol. Geriatr. PD OCT PY 2000 VL 33 IS 5 BP 341 EP 349 DI 10.1007/s003910070030 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 375JK UT WOS:000165395600002 PM 11130187 ER PT J AU Sarkar, S Aziz, Q Woolf, CJ Hobson, AR Thompson, DG AF Sarkar, S Aziz, Q Woolf, CJ Hobson, AR Thompson, DG TI Contribution of central sensitisation to the development of non-cardiac chest pain SO LANCET LA English DT Article ID SECONDARY HYPERALGESIA; VISCERAL PAIN; HUMANS; RAT; INFLAMMATION; CAPSAICIN; FIELDS; STATES AB Background Non-cardiac chest pain mimics angina pectoris but generally originates from the oesophagus, Visceral hypersensitivity may contribute, but its neurophysiological basis, is unclear. We investigated whether central sensitisation, an activity-dependent amplification of sensory transfer in the central nervous system, underlies visceral pain hypersensitivity and non-cardiac chest pain. Methods We studied 19 healthy volunteers and seven patients with non-cardiac chest pain. Acid was infused into the lower oesophagus. Sensory responses to electrical stimulation were monitored within the acid-exposed lower oesophagus, the non-exposed upper oesophagus, and the cutaneous area of pain referral, before and after the infusion. Findings In healthy volunteers, acid infusion into the lower oesophagus lowered the pain threshold in the upper oesophagus (mean decrease 18.2% [95% CI 10.4 to 26.0]; p=0.01) and on the chest wall (24.5% [10.2 to 38.7]; p=0.01). Patients with non-cardiac chest pain had a lower resting oesophageal pain threshold than healthy controls (45 [30 to 58] vs 64 [49 to 81] mA; p=0.04). In response to acid infusion, their pain threshold in the upper oesophagus fell further and for longer (mean fall in area under threshold/time curve 26.7 [11.0 to 42.3] vs 5.8 [2.8 to 8.8] units; p=0.04). Interpretation The finding of secondary viscerovisceral and viscerosomatic pain hypersensitivity suggests that central sensitisation may contribute to visceral pain disorders. The prolonged visceral pain hypersensitivity in patients with noncardiac chest pain suggests a central enhancement of sensory transfer. New therapeutic opportunities are therefore possible. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Manchester, Hope Hosp, Gastroenterol Sect, Salford M6 8HD, Lancs, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. NR 23 TC 239 Z9 245 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 30 PY 2000 VL 356 IS 9236 BP 1154 EP 1159 DI 10.1016/S0140-6736(00)02758-6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 359CQ UT WOS:000089594300013 PM 11030295 ER PT J AU Martinez-Picado, J Savara, AV Shi, L Sutton, L D'Aquila, RT AF Martinez-Picado, J Savara, AV Shi, L Sutton, L D'Aquila, RT TI Fitness of human immunodeficiency virus type 1 protease inhibitor-selected single mutants SO VIROLOGY LA English DT Article DE HIV-1 drug resistance; protease inhibitors; viral replicative fitness; indinavir ID REVERSE-TRANSCRIPTASE; INCREASED RESISTANCE; CROSS-RESISTANCE; HIV-1 PROTEASE; KINETIC CHARACTERIZATION; DRUG-RESISTANCE; VARIANTS; TRANSMISSION; INFECTION; MUTATIONS AB Human immunodeficiency virus type 1 (HIV-1) evolution under chemotherapeutic selection pressure in vivo involves a complex interplay between an increasing magnitude of drug resistance and changes in viral replicative capacity To examine the replicative fitness of HIV-I mutants with single, drug-selected substitutions in protease (PR), we constructed virus that contained the most common mutations in indinavir-selected clinical isolates, PR M461 and V82T, and the most common polymorphic change in drug-naive patients, PR L63P These mutants were competed in vitro in the absence of drug against the otherwise isogenic WT virus (NL4-3). Phenotypic drug susceptibility was determined with a recombinant virus assay using a single cycle of virus growth. PR M461 and L63P were as fit as WT However, PR V82T was out-competed by WT. None of these mutants had appreciable phenotypic resistance to any of the protease inhibitors, including indinavir. The PRV82T mutant was hypersusceptible to saquinavir. Thus, the impaired fitness of the V82T single mutant is consistent with its low frequency in protease inhibitor-naive patients The similar fitness of WT (NL4-3), L63P, and M461 is consistent with the common occurrence of L63P in the absence of protease inhibitor-selection pressure, but not with the rare detection of M461 in drug-naive patients. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Fdn Irsi Caixa, Barcelona, Spain. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 149 13th St, Charlestown, MA 02129 USA. RI Martinez-Picado, Javier/G-5507-2012 OI Martinez-Picado, Javier/0000-0002-4916-2129 FU NIAID NIH HHS [AI27659, AI29193] NR 33 TC 61 Z9 61 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2000 VL 275 IS 2 BP 318 EP 322 DI 10.1006/viro.2000.0527 PG 5 WC Virology SC Virology GA 360ZU UT WOS:000089697900013 PM 10998332 ER PT J AU Lee, JT AF Lee, JT TI Disruption of imprinted X inactivation by parent-of-origin effects at Tsix SO CELL LA English DT Article ID BECKWITH-WIEDEMANN-SYNDROME; METHYLATED CPG ISLAND; CHROMOSOME INACTIVATION; DNA METHYLATION; MOUSE EMBRYOS; EXPRESSED TRANSCRIPT; DOSAGE COMPENSATION; XIST EXPRESSION; CONTROL REGION; SNRPN GENE AB In marsupials and in extraembryonic tissues of placental mammals, X inactivation is imprinted to occur on the paternal chromosome. Here, we find that imprinting is controlled by the antisense Xist gene, Tsix. Tsix is maternally expressed and mice carrying a Tsix deletion show normal paternal but impaired maternal transmission. Maternal inheritance occurs infrequently, with surviving progeny showing intrauterine growth retardation and reduced fertility. Transmission ratio distortion results from disrupted imprinting and postimplantation loss of mutant embryos. In contrast to effects in embryonic stem cells, deleting Tsix causes ectopic X inactivation in early male embryos and inactivation of both X chromosomes in female embryos, indicating that X chromosome counting cannot override Tsix imprinting. These results highlight differences between imprinted and random X inactivation but show that Tsix regulates both. We propose that an imprinting center lies within Tsix. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01-GM58839] NR 56 TC 195 Z9 202 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 29 PY 2000 VL 103 IS 1 BP 17 EP 27 DI 10.1016/S0092-8674(00)00101-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 359XB UT WOS:000089636400005 PM 11051544 ER PT J AU Kim, KS Sun, ZYJ Wagner, G Reinherz, EL AF Kim, KS Sun, ZYJ Wagner, G Reinherz, EL TI Heterodimeric CD3 epsilon gamma extracellular domain fragments: Production, purification and structural analysis SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CD3; T cell receptors; signal transduction; NMR; Ig-like domains ID T-CELL RECEPTOR; BIOSPECIFIC INTERACTION ANALYSIS; SURFACE-PLASMON RESONANCE; CD3 GAMMA-CHAIN; ANTIGEN RECEPTOR; TCR/CD3 COMPLEX; ALPHA-BETA; CRYSTAL-STRUCTURE; ZETA-CHAIN; MONOCLONAL-ANTIBODY AB The CD3 polypeptides (epsilon, gamma, and delta) are non-covalently associated signaling subunits of the T cell receptor which form non-disulfide linked epsilon gamma and epsilon delta heterodimers. With the goal of investigating their structure, Escherichia coli expression was utilized to produce CD3 ectodomain fragments including the murine CD3 epsilon subunit N-terminal Ig-like extracellullar domain alone or as a single chain construct with that of CD3 gamma. The latter links the CD3 gamma segment to the C terminus of the CD3 epsilon segment via a 26 amino acid peptide (scCD3 epsilon gamma 26). Although CD3 epsilon could be produced at high yield when directed to inclusion bodies, the refolded monomeric CD3 epsilon was not native as judged by monoclonal antibody binding using surface plasmon resonance and was largely unstructured by N-15-H-1 two-dimensional NMR analysis. In contrast, scCD3 epsilon gamma 26 could be refolded readily into a native state as shown by CD, NMR and mAb reactivity. The linker length between CD3 epsilon and CD3 gamma is critical since scCD3 epsilon gamma 16 containing a 16 residue connector failed to generate a stable heterodimer. Collectively, the results demonstrate that: (i) soluble heterodimeric fragments of CD3 can be produced; (ii) cotranslation of CD3 chains insures proper folding even in the absence of the conserved ectodomain stalk region (CxxCxE); and (iii) CD3 epsilon has a more stable tertiary protein fold than CD3 gamma. (C) 2000 Academic Press. C1 Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. FU NIAID NIH HHS [AI37581, AI19807] NR 67 TC 16 Z9 16 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 29 PY 2000 VL 302 IS 4 BP 899 EP 916 DI 10.1006/jmbi.2000.4098 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361GW UT WOS:000089716200011 PM 10993731 ER PT J AU Ahveninen, J Kahkonen, S Tiitinen, H Pekkonen, E Huttunen, J Kaakkola, S Ilmoniemi, RJ Jaaskelainen, IP AF Ahveninen, J Kahkonen, S Tiitinen, H Pekkonen, E Huttunen, J Kaakkola, S Ilmoniemi, RJ Jaaskelainen, IP TI Suppression of transient 40-Hz auditory response by haloperidol suggests modulation of human selective attention by dopamine D-2 receptors SO NEUROSCIENCE LETTERS LA English DT Article DE 40-Hz response; auditory; D-2 receptors; dopamine; event-related potentials; magnetoencephalography; electroencephalography; haloperidol ID CORTEX AB Cognitive processes including selective attention may depend on synchronous activity of neurons at the gamma-band (around 40 Hz). To determine the effect of neuroleptic challenge on transient auditory evoked 40-Hz response, simultaneous measurement of 122-channel magnetoencephalogram (MEG) and 64-channel electroencephalogram (EEG) was used. Either 2 mg of dopamine D-2-receptor antagonist haloperidol or a placebo was administered orally to 11 healthy subjects in a double-blind randomized crossover design in two separate sessions. The subjects attended to tones presented to one ear and ignored those presented to the other ear. Haloperidol significantly suppressed the transient 40-Hz electric response to the attended stimuli, while no significant effect was observed in the electric responses to the unattended tones or in the magnetic responses. The present result suggests that dopamine Dp receptors modulate selective attention. (C) 2000 Published by Elsevier Science Ireland ltd. C1 Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Neurol, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Med Engn Ctr, BioMag Lab,Hosp Dist Helsinki & Uusimaa, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Psychiat, Hosp Dist Helsinki & Uusimaa, Helsinki, Finland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA USA. RP Ahveninen, J (reprint author), Univ Helsinki, Dept Psychol, Cognit Brain Res Unit, POB 13, FIN-00014 Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; Ilmoniemi, Risto/E-9704-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Ilmoniemi, Risto/0000-0002-3340-2618 NR 20 TC 43 Z9 46 U1 0 U2 0 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 SEP 29 PY 2000 VL 292 IS 1 BP 29 EP 32 DI 10.1016/S0304-3940(00)01429-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 357YC UT WOS:000089528900008 PM 10996442 ER PT J AU Altshuler, D Pollara, VJ Cowles, CR Van Etten, WJ Baldwin, J Linton, L Lander, ES AF Altshuler, D Pollara, VJ Cowles, CR Van Etten, WJ Baldwin, J Linton, L Lander, ES TI An SNP map of the human genome generated by reduced representation shotgun sequencing SO NATURE LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CANDIDATE GENES; IDENTIFICATION; DIVERSITY; DISCOVERY AB Most genomic variation is attributable to single nucleotide polymorphisms (SNPs), which therefore offer the highest resolution for tracking disease genes and population history(1-3). It has been proposed that a dense map of 30,000-500,000 SNPs can be used to scan the human genome for haplotypes associated with common diseases(4-6). Here we describe a simple but powerful method, called reduced representation shotgun (RRS) sequencing, for creating SNP maps. RRS re-samples specific subsets of the genome from several individuals, and compares the resulting sequences using a highly accurate SNP detection algorithm. The method can be extended by alignment to available genome sequence, increasing the yield of SNPs and providing map positions. These methods are being used by The SNP Consortium, an international collaboration of academic centres, pharmaceutical companies and a private foundation, to discover and release at least 300,000 human SNPs. We have discovered 47,172 human SNPs by RRS, and in total the Consortium has identified 148,459 SNPs. More broadly, RRS facilitates the rapid, inexpensive construction of SNP maps in biomedically and agriculturally important species. SNPs discovered by RRS also offer unique advantages for large-scale genotyping. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Diabet Unit, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 22 TC 413 Z9 444 U1 9 U2 60 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 28 PY 2000 VL 407 IS 6803 BP 513 EP 516 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 361MT UT WOS:000089727400050 PM 11029002 ER PT J AU Rosenberg, ES Altfeld, M Poon, SH Phillips, MN Wilkes, BM Eldridge, RL Robbins, GK D'Aquila, RT Goulder, PJR Walker, BD AF Rosenberg, ES Altfeld, M Poon, SH Phillips, MN Wilkes, BM Eldridge, RL Robbins, GK D'Aquila, RT Goulder, PJR Walker, BD TI Immune control of HIV-1 after early treatment of acute infection SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTE; ACTIVE ANTIRETROVIRAL THERAPY; CELL RESPONSES; DISCONTINUATION; RESISTANCE; EFFECTOR; VIREMIA; MICE AB Virus-specific T-helper cells are considered critical for the control of chronic viral infections(1,2). Successful treatment of acute HIV-1 infection leads to augmentation of these responses(3-5), but whether this enhances immune control has not been determined. We administered one or two supervised treatment interruptions to eight subjects with treated acute infection, with the plan to restart therapy if viral load exceeded 5,000 copies of HIV-1 RNA per millilitre of plasma (the level at which therapy has been typically recommended) for three consecutive weeks, or 50,000 RNA copies per ml at one time. Here we show that, despite rebound in viraemia, all subjects were able to achieve at least a transient steady state off therapy with viral load below 5,000 RNA copies per ml. At present, five out of eight subjects remain off therapy with viral loads of less than 500 RNA copies per ml plasma after a median 6.5 months (range 5-8.7 months). We observed increased virus-specific cytotoxic T lymphocytes and maintained T-helper-cell responses in all. Our data indicate that functional immune responses can be augmented in a chronic viral infection, and provide rationale for immunotherapy in HIV-1 infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RI Robbins, Gregory/F-7988-2011 NR 29 TC 737 Z9 751 U1 1 U2 16 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 28 PY 2000 VL 407 IS 6803 BP 523 EP 526 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 361MT UT WOS:000089727400053 PM 11029005 ER PT J AU Simoncini, T Hafezl-Moghadam, A Brazil, DP Ley, K Chin, WW Liao, JK AF Simoncini, T Hafezl-Moghadam, A Brazil, DP Ley, K Chin, WW Liao, JK TI Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase SO NATURE LA English DT Article ID NITRIC-OXIDE SYNTHASE; ENDOTHELIAL GROWTH-FACTOR; HUMAN ESTROGEN-RECEPTOR; PHOSPHOINOSITIDE 3-KINASE; PROTEIN; ACTIVATION; CELLS; AKT; INSULIN; PHOSPHORYLATION AB Oestrogen produces diverse biological effects through binding to the oestrogen receptor (ER)(1). The ER is a steroid hormone nuclear receptor, which, when bound to oestrogen, modulates the transcriptional activity of target genes(2). Controversy exists, however, concerning whether ER has a role outside the nucleus(3), particularly in mediating the cardiovascular protective effects of oestrogen(4). Here we show that the ER isoform, ER alpha, binds in a ligand-dependent manner to the p85 alpha regulatory subunit of phosphatidylinositol-3-OH kinase (PI(3)K). Stimulation with oestrogen increases ER alpha-associated PI(3)K activity, leading to the activation of protein kinase B/Akt and endothelial nitric oxide synthase (eNOS). Recruitment and activation of PI(3)K by ligand-bound ERa are independent of gene transcription, do not involve phosphotyrosine adapter molecules or src-homology domains of p85 alpha, and extend to other steroid hormone receptors. Mice treated with oestrogen show increased eNOS activity and decreased vascular leukocyte accumulation after ischaemia and reperfusion injury. This vascular protective effect of oestrogen was abolished in the presence of PI(3)K or eNOS inhibitors. Our findings define a physiologically important non-nuclear oestrogen-signalling pathway involving the direct interaction of ERa with PI(3)K. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Virginia, Hlth Sci Ctr, Dept Biomed Engn, Charlottesville, VA 22908 USA. Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. RP Liao, JK (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 221 Longwood Ave, Boston, MA 02115 USA. OI Simoncini, Tommaso/0000-0002-2971-0079 FU NHLBI NIH HHS [P01 HL048743, P01 HL048743-080008, P01 HL048743-090008, R01 HL052233, R01 HL052233-05, R01 HL052233-06, R01 HL052233-07, R01 HL052233-08, R01 HL070274, R01 HL070274-01, R01 HL070274-02, R01 HL070274-03, R01 HL070274-04, R01 HL070274-05]; NIDDK NIH HHS [R01 DK062729, R01 DK062729-01A1, R01 DK062729-02, R01 DK062729-03, R01 DK062729-04, R01 DK062729-05] NR 30 TC 984 Z9 1010 U1 1 U2 17 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 28 PY 2000 VL 407 IS 6803 BP 538 EP 541 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 361MT UT WOS:000089727400057 PM 11029009 ER PT J AU Mayer, RJ AF Mayer, RJ TI Moving beyond fluorouracil for colorectal cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED TRIAL; IRINOTECAN; FAILURE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 TC 21 Z9 21 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 SEP 28 PY 2000 VL 343 IS 13 BP 963 EP 964 DI 10.1056/NEJM200009283431309 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 357KT UT WOS:000089501400009 PM 11006373 ER PT J AU Gwinn-Hardy, K Chen, JY Liu, HC Liu, TY Boss, M Seltzer, W Adam, A Singleton, A Koroshetz, W Waters, C Hardy, J Farrer, M AF Gwinn-Hardy, K Chen, JY Liu, HC Liu, TY Boss, M Seltzer, W Adam, A Singleton, A Koroshetz, W Waters, C Hardy, J Farrer, M TI Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese SO NEUROLOGY LA English DT Article ID PROGRESSIVE SUPRANUCLEAR PALSY; RICHARDSON-OLSZEWSKI-SYNDROME; MOLECULAR ANALYSIS; ALPHA-SYNUCLEIN; RISK-FACTORS; DISEASE; GENE; FAMILIES; CRITERIA; POPULATION AB Objective: To describe the clinical and molecular genetic analysis of a large family of northern Chinese descent with a mutation at the SCA2 locus causing carbidopa-levodopa-responsive parkinsonism. Background: Most causes of parkinsonism remain unknown. However, molecular genetic analysis of families with parkinsonism has recently identified five distinct loci and pathogenic mutations in four of those. Additionally, some of the spinocerebellar ataxia syndromes (SCA), particularly Machado-Joseph syndrome (SCA3), are known to cause parkinsonism. Spinocerebellar ataxia type 2 (SCA2) has not previously been described as causing a typical dopamine-responsive asymmetric PD phenotype. Methods: A large family was evaluated clinically and molecularly for apparent autosomal dominant parkinsonism. Results: The phenotype includes presentation consistent with typical dopamine-responsive parkinsonism. Other presentations in this family include a parkinsonism/ataxia phenotype, which is classic for SCA2 and parkinsonism, resembling progressive supranuclear palsy. Conclusions: Patients presenting with a family history of parkinsonism, including familial progressive supranuclear palsy and PD, should be tested for the spinocerebellar ataxia type 2 expansion. C1 Mayo Clin Jacksonville, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin Jacksonville, Dept Pharmacol, Jacksonville, FL 32224 USA. Meharry Med Coll, Nashville, TN 37208 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Athena Corp, Worcester, MA USA. Univ So Calif, Los Angeles, CA USA. Vet Gen Hosp, Taipei, Taiwan. RP Gwinn-Hardy, K (reprint author), Mayo Clin Jacksonville, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009 NR 33 TC 110 Z9 115 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP 26 PY 2000 VL 55 IS 6 BP 800 EP 805 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 357ED UT WOS:000089484800011 PM 10993999 ER PT J AU Classon, M Salama, S Gorka, C Mulloy, R Braun, P Harlow, E AF Classon, M Salama, S Gorka, C Mulloy, R Braun, P Harlow, E TI Combinatorial roles for pRB, p107, and p130 in E2F-mediated cell cycle control SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; ADENOVIRUS E1A PROTEINS; HISTONE DEACETYLASE; REPRESS TRANSCRIPTION; TUMOR SUPPRESSION; MICE LACKING; INK4A LOCUS; S-PHASE; RB; EXPRESSION AB Numerous studies have implicated the pRB family of nuclear proteins in the control of cell cycle progression. Although overexpression experiments have revealed that each of these proteins, pRB, p107, and p130, can induce a G(1) cell cycle arrest, mouse knockouts demonstrated distinct developmental requirements for these proteins, as well as partial functional redundancy between family members. To study the mechanism by which the closely related pRB family proteins contribute to cell cycle progression, we generated 3T3 fibroblasts derived from embryos that lack one or more of these proteins (pRB(-/-), p107(-/-), p130(-/-), pRB(-/-)/p107(-/-), pRB(-/-)/p130(-/-). and p107(-/-)/p130(-/-)), By comparing the growth and cell cycle characteristics of these cells, we have observed clear differences in the manner in which they transit through the G(1) and S phases as well as exit from the cell cycle. Deletion of Rb, or more than one of the family members. results in a shortening of G(1) and a lengthening of S phase, as well as a reduction in growth factor requirements. In addition, the individual cell lines showed differential regulation of a subset of E2F-dependent gene promoters, as well as differences in cell cycle-dependent kinase activity. Taken together, these observations suggest that the closely related pRB family proteins affect cell cycle progression through distinct biochemical mechanisms and that their coordinated action may contribute to their diverse functions in various physiological settings. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Classon, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Braun, Pascal/B-9669-2013 OI Braun, Pascal/0000-0003-2012-6746 NR 35 TC 79 Z9 83 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 26 PY 2000 VL 97 IS 20 BP 10820 EP 10825 DI 10.1073/pnas.190343497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 358PH UT WOS:000089566100030 PM 10995475 ER PT J AU Classon, M Kennedy, BK Mulloy, R Harlow, E AF Classon, M Kennedy, BK Mulloy, R Harlow, E TI Opposing roles of pRB and p107 in adipocyte differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; ADENOVIRUS E1A PROTEINS; SKELETAL-MUSCLE CELLS; HISTONE DEACETYLASE; REPRESS TRANSCRIPTION; BINDING; CYCLE; INHIBITION; EXPRESSION; TRANSFORMATION AB The retinoblastoma (RB) family of proteins, pRB, p107. and p130, have been postulated to be partially redundant in their ability to regulate progression through the G(1) phase of the cell cycle. However, pRB appears to be unique in its capacity as a classical tumor suppressor, possibly because of a specialized role in maintaining the balance between proliferation and differentiation. A variety of studies have in fact revealed an apparent role for pRB in cellular differentiation and development. However, roles for p107 and p130 in differentiation have not yet been established, and knockout mouse studies have indicated that they may be functionally redundant during development, and possibly perform a role in differentiation distinct from that of pRB. Using adipogenesis as a model, we have indeed found distinct roles for the pRB family proteins in regulating differentiation. 3T3 fibroblasts deficient in p107 and p130 differentiate with high efficiency, whereas pRB(-/-) 3T3 cells exhibit defects in their differentiation potential. Moreover. over-expression of pRB in wild-type cells promotes differentiation, whereas over-expression of p107 antagonizes differentiation. The seemingly opposing roles of pRB family members in adipocyte differentiation can be explained, at least in part, by a requirement for pRB in maintaining cell cycle exit as well as potentiating the activity of the differentiation-associated transcription factor. C/EBP alpha. p107 does not affect C/EBP alpha-driven transcription and is not required for cell cycle exit, but instead, loss of p107 lowers the requirement for the differentiation factor PPAR gamma. These findings suggest contrasting biological roles for individual members of the pRB family of proteins that may explain why pRB, but not p107, is commonly mutated during human tumor development. C1 Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Charlestown, MA 02129 USA. RP Classon, M (reprint author), Massachusetts Gen Hosp, Ctr Canc, Mol Oncol Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 34 TC 107 Z9 110 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 26 PY 2000 VL 97 IS 20 BP 10826 EP 10831 DI 10.1073/pnas.190343597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 358PH UT WOS:000089566100031 PM 10995476 ER PT J AU Martinez-Picado, J DePasquale, MP Kartsonis, N Hanna, GJ Wong, J Finzi, D Rosenberg, E Gunthard, HF Sutton, L Savara, A Petropoulos, CJ Hellmann, N Walker, BD Richman, DD Siliciano, R D'Aquila, RT AF Martinez-Picado, J DePasquale, MP Kartsonis, N Hanna, GJ Wong, J Finzi, D Rosenberg, E Gunthard, HF Sutton, L Savara, A Petropoulos, CJ Hellmann, N Walker, BD Richman, DD Siliciano, R D'Aquila, RT TI Antiretroviral resistance during successful therapy of HIV type 1 infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG-RESISTANCE; IN-VIVO; REVERSE-TRANSCRIPTASE; PROTEASE INHIBITORS; LYMPH-NODES; SEQUENCES; MUTATIONS; BLOOD; PERSISTENCE AB HIV type 1 (HIV-1) drug resistance mutations were selected during antiretroviral therapy successfully suppressing plasma HIV-1 RNA to <50 copies/ml. New resistant mutant subpopulations were identified by clonal sequencing analyses of viruses cultured from blood cells. Drug susceptibility tests showed that biological clones of virus with the mutations acquired during successful therapy had increased resistance. Each of the five subjects with new resistant mutants had evidence of some residual virus replication during highly active antiretroviral therapy (HAART). based on transient episodes of plasma HIV-1 RNA > 50 copies/ml and virus env gene sequence changes. Each had received a suboptimal regimen before starting HAART. Antiretroviral-resistant HIV-1 can be selected from residual virus replication during HAART in the absence of sustained rebound of plasma HIV-1 RNA. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Hosp Univ Germans Trias & Pujol, Fundacio irsiCaixa, Badalona 08916, Spain. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. San Diego Vet Affairs Healthcare Syst, La Jolla, CA 92093 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. ViroLog Inc, S San Francisco, CA 94080 USA. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 149 13th St, Charlestown, MA 02129 USA. RI gunthard, huldrych/F-1724-2011; Martinez-Picado, Javier/G-5507-2012 OI gunthard, huldrych/0000-0002-1142-6723; Martinez-Picado, Javier/0000-0002-4916-2129 FU NIAID NIH HHS [U01 AI027670, AI07387, AI29193, AI43222, P30 AI036214, R01 AI029193, R01 AI043222, T32 AI007387, U01 AI038858] NR 36 TC 167 Z9 169 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 SEP 26 PY 2000 VL 97 IS 20 BP 10948 EP 10953 DI 10.1073/pnas.97.20.10948 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 358PH UT WOS:000089566100052 PM 11005867 ER PT J AU Mueller, E Smith, M Sarraf, P Kroll, T Aiyer, A Kaufman, DS Oh, W Demetri, G Figg, WD Zhou, XP Eng, C Spiegelman, BM Kantoff, PW AF Mueller, E Smith, M Sarraf, P Kroll, T Aiyer, A Kaufman, DS Oh, W Demetri, G Figg, WD Zhou, XP Eng, C Spiegelman, BM Kantoff, PW TI Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN BREAST-CANCER; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; TERMINAL DIFFERENTIATION; RETINOIC ACID; COLON-CANCER; IN-VITRO; TROGLITAZONE; CELLS; THIAZOLIDINEDIONE AB Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that plays a key role in the differentiation of adipocytes. Activation of this receptor in liposarcomas and breast and colon cancer cells also induces cell growth inhibition and differentiation. In the present study, we show that PPAR gamma is expressed in human prostate adenocarcinomas and cell lines derived from these tumors. Activation of this receptor with specific ligands exerts an inhibitory effect on the growth of prostate cancer cell lines. Further, we show that prostate cancer and cell lines do not have intragenic mutations in the PPAR gamma gene, although 40% of the informative tumors have hemizygous deletions of this gene. Based on our preclinical data, we conducted a phase II clinical study in patients with advanced prostate cancer using troglitazone, a PPAR gamma ligand used for the treatment of type 2 diabetes. Forty-one men with histologically confirmed prostate cancer and no symptomatic metastatic disease were treated orally with troglitazone. An unexpectedly high incidence of prolonged stabilization of prostate-specific antigen was seen in patients treated with troglitazone. In addition, one patient had a dramatic decrease in serum prostate-specific antigen to nearly undetectable levels. These data suggest that PPAR gamma may serve as a biological modifier in human prostate cancer and its therapeutic potential in this disease should be further investigated. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. RP Kantoff, PW (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012; Figg Sr, William/M-2411-2016 OI Oh, William/0000-0001-5113-8147; FU NCI NIH HHS [P30CA16058, P30 CA016058] NR 25 TC 329 Z9 337 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 26 PY 2000 VL 97 IS 20 BP 10990 EP 10995 DI 10.1073/pnas.180329197 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 358PH UT WOS:000089566100059 PM 10984506 ER PT J AU Fischl, B Dale, AM AF Fischl, B Dale, AM TI Measuring the thickness of the human cerebral cortex from magnetic resonance images SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atrophy; morphometry; Huntington's; Alzheimer's; schizophrenia ID SURFACE-BASED ANALYSIS; CORTICAL SURFACE; ALZHEIMERS-DISEASE; DEFORMABLE TEMPLATES; COORDINATE SYSTEM; BRAIN ATROPHY; GRAY-MATTER; SCHIZOPHRENIA; RECONSTRUCTION; LOBE AB Accurate and automated methods for measuring the thickness of human cerebral cortex could provide powerful tools for diagnosing and studying a variety of neurodegenerative and psychiatric disorders. Manual methods for estimating cortical thickness from neuroimaging data are labor intensive, requiring several days of effort by a trained anatomist. Furthermore, the highly folded nature of the cortex is problematic for manual techniques, frequently resulting in measurement errors in regions in which the cortical surface is not perpendicular to any of the cardinal axes. As a consequence, it has been impractical to obtain accurate thickness estimates for the entire cortex in individual subjects, or group statistics for patient or control populations. Here. we present an automated method for accurately measuring the thickness of the cerebral cortex across the entire brain and for generating cross-subject statistics in a coordinate system based on cortical anatomy. The intersubject standard deviation of the thickness measures is shown to be less than 0.5 mm, implying the ability to detect focal atrophy in small populations or even individual subjects. The reliability and accuracy of this new method are assessed by within-subject test-retest studies, as well as by comparison of cross-subject regional thickness measures with published values. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP Dale, AM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [R01-RR13609, P41-RR14075, P41 RR014075]; NINDS NIH HHS [R01-NS39581] NR 40 TC 1941 Z9 1960 U1 17 U2 73 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 SEP 26 PY 2000 VL 97 IS 20 BP 11050 EP 11055 DI 10.1073/pnas.200033797 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 358PH UT WOS:000089566100069 PM 10984517 ER PT J AU Turner, BJ Cunningham, WE Duan, N Andersen, RM Shapiro, MF Bozzette, SA Nakazono, T Morton, S Crystal, S St Clair, P Stein, M Zierler, S AF Turner, BJ Cunningham, WE Duan, N Andersen, RM Shapiro, MF Bozzette, SA Nakazono, T Morton, S Crystal, S St Clair, P Stein, M Zierler, S TI Delayed medical care after diagnosis in a US national probability sample of persons infected with human immunodeficiency virus SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02, 1998 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID LOW-PREVALENCE DISEASES; HEALTH-CARE; SERVICES UTILIZATION; HIV DISEASE; ACCESS; AIDS; INSURANCE; PHYSICIAN; WOMEN; ZIDOVUDINE AB Objective: To identify health care and patient factors associated with delayed initial medical care for human immunodeficiency virus (HIV) infection. Design: Survey of a national probability sample of persons with HIV in care. Settings Medical practices in the contiguous United States. Patients: Cohort A (N=1540) was diagnosed by February 1993 and was in care within 3 years; cohort B (N=1960) was diagnosed by February 1995 and was in care within 1 year of diagnosis. Main Outcome Measure: More than 3- or 6-month delay. Results: Delay of more than 3 months occurred for 29% of cohort A (median, 1 year) and 17% of cohort B. Having a usual source of care at diagnosis reduced delay, with adjusted odds ratios (ORs) of 0.61 (95% confidence interval [CI], 0.48-0.77) in cohort A and 0.70 (95% CI, 0.50-0.99) in cohort B. Medicaid coverage at diagnosis showed lower adjusted ORs of delay compared with private insurance (cohort A: adjusted OR, 0.52; 95% CI, 0.30-0.92; cohort B: adjusted OR, 0.48; 95%, CI, 0.27-0.85). Compared with whites, Latinos had 53%, and 95% higher adjusted ORs of delay (P<.05) in cohorts A and B, respectively, and African Americans had a higher adjusted OR in cohort A (1.56; 95%, CI, 1.19-2.04). The health care factors showed similar effects on delay of greater than 6 months. Conclusions: Medicaid insurance and a usual source of care were protective against delay after HIV diagnosis. After full adjustment, delay was still greater for Latinos and, to a lesser extent, African Americans compared with whites. C1 Univ Penn, Philadelphia, PA 19104 USA. US Dept Vet Affairs, Washington, DC 20420 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Rutgers State Univ, Inst Hlth, New Brunswick, NJ 08903 USA. Crit Path AIDS Project, Philadelphia, PA USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Rhode Isl Hosp, Providence, RI USA. Brown Univ, Providence, RI 02912 USA. RP Turner, BJ (reprint author), Univ Penn, 1119 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU AHRQ HHS [HS08578] NR 34 TC 126 Z9 129 U1 2 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 SEP 25 PY 2000 VL 160 IS 17 BP 2614 EP 2622 DI 10.1001/archinte.160.17.2614 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 357GX UT WOS:000089491100007 PM 10999975 ER PT J AU Koh, TJ Chen, D AF Koh, TJ Chen, D TI Gastrin as a growth factor in the gastrointestinal tract SO REGULATORY PEPTIDES LA English DT Article DE amidated gastrin; glycine-extended gastrin; trophic targets ID GLYCINE-EXTENDED GASTRIN; ENTEROCHROMAFFIN-LIKE CELLS; HUMAN-COLON-CANCER; CHOLECYSTOKININ-B/GASTRIN RECEPTOR; RAT STOMACH; ENDOGENOUS HYPERGASTRINEMIA; GENE-EXPRESSION; PANCREATIC GROWTH; SELF-REPLICATION; TRANSGENIC MICE AB The peptide hormone gastrin, released from antral G cells, is known to stimulate the synthesis and release of histamine from ECL cells in the oxyntic mocosa via CCK-2 receptors. The mobilized histamine induces acid secretion by binding to the H-2 receptors located on parietal cells. Recent studies suggest that gastrin, in both its fully amidated and less processed forms (progastrin and glycine-extended gastrin), is also a growth factor for the gastrointestinal tract. In this article, we review the recent evidence (including those from the transgenic and knockout mice) for the trophic targets of both the amidated and less processed forms of gastrin in the gastrointestinal tract, pancreas and liver. It has been established that the major trophic effect of amidated gastrin is for the oxyntic mucosa of stomach, where it causes increased proliferation of gastric stem cells and ECL cells, resulting in increased parietal and ECL cell mass. There is insufficient evidence to support that amidated gastrin is a trophic factor for the rest of gastrointestinal tract, exocrine pancreas and liver. On the other hand, the major trophic target of the less processed gastrin (e.g. glycine-extended gastrin) appears to be the colonic mucosa. There is no evidence to suggest that it is trophic for the stomach. It remains to be examined whether the rest of gastrointestinal tract, pancreas and liver are the trophic targets by glycine-extended gastrin and progastrin. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Norwegian Univ Sci & Technol, Univ Trondheim Hosp, Dept Surg, Inst Intraabdominal Dis, N-7006 Trondheim, Norway. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chen, D (reprint author), Norwegian Univ Sci & Technol, Univ Trondheim Hosp, Dept Surg, Inst Intraabdominal Dis, N-7006 Trondheim, Norway. NR 82 TC 78 Z9 79 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD SEP 25 PY 2000 VL 93 IS 1-3 SI SI BP 37 EP 44 DI 10.1016/S0167-0115(00)00176-2 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 368CJ UT WOS:000090099800006 PM 11033051 ER PT J AU Slice, LW Bui, L Mak, C Walsh, JH AF Slice, LW Bui, L Mak, C Walsh, JH TI Differential regulation of COX-2 transcription by Ras- and Rho-family of GTPases SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Rho; GTP-binding proteins; cyclooxygenase-2; gene expression ID SYNTHASE-2 GENE-EXPRESSION; ALPHA-DEPENDENT INDUCTION; GROWTH-FACTOR; BINDING PROTEINS; KAPPA-B; CYCLOOXYGENASE-2; ACTIVATION; CELLS; INHIBITION; CARCINOMA AB Cyclooxygenase-2 (Cox-2) gene expression which is rapidly induced by cytokines, growth factors and tumor promoters, is important for inflammation, angiogenesis, and is markedly enhanced in various cancer cells. Many of these factors initiate signaling through Ras- and Rho-family small GTPases. Here, we investigated the ability of Has, Rac, Rho, and Cdc42Hs to differentially regulate transcription from the murine COX-2 promoter in NIH 3T3 cells. Over-expression of constitutively active mutants of Ras, Rac, Rho, but not Cdc42Hs induced transcription from the COX-2 promoter. Transactivation by Rac and Rho required cis-acting elements located between -80 and -40 of the COX-2 promoter whereas deletion of this region enhanced transactivation by Ras. A CRE/ATF element located at -56 was critical for Ras- and Rac-induced transactivation of the COX-2 promoter, but was not required for transactivation by Rho. This demonstrates Rho-dependent transactivation of the COX-2 promoter through novel trans-acting elements and suggests that, in NM 3T3 cells, signaling by small GTPases that result in COX-2 expression is not through a sequential pathway from Cdc42 to Rac to Rho, but rather through independent, parallel signaling pathways. (C) 2000 Academic Press. C1 Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Digest Dis Res Ctr,CURE, Dept Med,Div Digest Dis, Los Angeles, CA 90095 USA. RP Slice, LW (reprint author), Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Digest Dis Res Ctr,CURE, Dept Med,Div Digest Dis, 900 Vet Ave, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [DK17294, DK35740] NR 31 TC 35 Z9 37 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 SEP 24 PY 2000 VL 276 IS 2 BP 406 EP 410 DI 10.1006/bbrc.2000.3487 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 358LB UT WOS:000089558600003 PM 11027488 ER PT J AU Fishman, JA AF Fishman, JA TI Infection in xenotransplantation - Studies with cell free virus are needed to define infection - there is no proof yet of safety or danger SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID ENDOGENOUS RETROVIRUS C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Novartis, Biotransplant, Genzyme, Fujisawa, Kanagawa, Japan. Gilead Sci Inc, Foster City, CA 94404 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD SEP 23 PY 2000 VL 321 IS 7263 BP 717 EP 718 DI 10.1136/bmj.321.7263.717 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 358FE UT WOS:000089546600003 PM 10999885 ER PT J AU Million, M Wang, LX Martinez, V Tache, Y AF Million, M Wang, LX Martinez, V Tache, Y TI Differential Fos expression in the paraventricular nucleus of the hypothalamus, sacral parasympathetic nucleus and colonic motor response to water avoidance stress in Fischer and Lewis rats SO BRAIN RESEARCH LA English DT Article DE Fos-immunoreactivity; corticotropin-releasing hormone (CRF); CRF antagonist; sacral parasympathetic nucleus ID CORTICOTROPIN-RELEASING FACTOR; C-FOS; STRAIN DIFFERENCES; HORMONE; CRF; SYSTEM; NEUROENDOCRINE; BRAIN; SUSCEPTIBILITY; PROJECTIONS AB The responsiveness of hypothalamic CRF to various stressors is reduced in the young female Lewis relative to the histocompatible Fischer rat. Whether such a difference impacts the brain-gut response to water avoidance stress was investigated by monitoring Fos immunoreactivity in the brain and sacral spinal cord and fecal pellet output. Exposure for 60 min to water avoidance stress increased the number of Fos positive cells in the paraventricular nucleus of the hypothalamus (PVN), nucleus tractus solitarius (NTS), and the parasympathetic nucleus of the lumbo-sacral spinal cord (L6-S1) in both Lewis and Fischer rats compared with non stress groups. The Fos response was lower by 32.0% in the PVN, and 63% in sacral parasympathetic nucleus in Lewis compared with Fischer rats while similar Fos expression was observed in the NTS. Stress-induced defecation was reduced by 52% in Lewis compared with Fischer rats while colonic motor response to CRF injected intracisternally resulted in a similar pattern and magnitude of defecation in both strains. The CRF receptor antagonist [D-Phe12,Nle(21,38)C(a)MeLeu(37)]-CRF12-41 injected intracisternally antagonized partly the defecation response in Lewis and Fischer rats. These data indicate that a lower activation of PVN and sacral parasympathetic nuclei in Lewis compared with Fisher rats may contribute to the differential colonic motor response and that the blunted CRF hypothalamic response to stress, unlike responsiveness to central CRF plays a role. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. RP Million, M (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-33061, DK-41301] NR 42 TC 50 Z9 51 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 SEP 22 PY 2000 VL 877 IS 2 BP 345 EP 353 DI 10.1016/S0006-8993(00)02719-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 355MB UT WOS:000089388500026 PM 10986349 ER PT J AU Pratt, MB Husain, SS Miller, KW Cohen, JB AF Pratt, MB Husain, SS Miller, KW Cohen, JB TI Identification of sites of incorporation in the nicotinic acetylcholine receptor of a photoactivatible general anesthetic SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING-SITE; NONCOMPETITIVE ANTAGONIST; AMINO-ACID; GLYCINE RECEPTORS; ION-CHANNEL; M2 SEGMENT; GABA(A); ALCOHOL; MUTATIONS; ETOMIDATE AB Most general anesthetics including long chain aliphatic alcohols act as noncompetitive antagonists of the nicotinic acetylcholine receptor (nAChR), To locate the sites of interaction of a long chain alcohol with the Torpedo nAChR, we have used the photoactivatible alcohol 3-[H-3]azioctanol, which inhibits the nAChR and photoincorporates into nAChR subunits. At 1 and 275 mu M, 3-[H-3]azioctanol photoincorporated into nAChR subunits with increased incorporation in the rw-subunit in the desensitized state. The incorporation into the cu-subunit was mapped to two large proteolytic fragments. One fragment of similar to 20 kDa (alpha V8-20), containing the M1, M2, and M3 transmembrane segments, showed enhanced incorporation in the presence of agonist whereas the other of similar to 10 kDa (alpha V8-10), containing the M4 transmembrane segment, did not show agonist-induced incorporation of label. Within alpha V8-20, the primary site of incorporation was alpha Glu-262 at the C-terminal end of alpha M2, labeled preferentially in the desensitized state. The incorporation at alpha Glu-262 approached saturation between 1 mu M, with similar to 6% labeled, and 215 mu M, With similar to 30% labeled. Low level incorporation was seen in residues at the agonist binding site and the protein-lipid interface at similar to 1% of the levels in alpha Glu-262. Therefore, the primary binding site of 3-azioctanol is within the ion channel with additional lower affinity interactions within the agonist binding site and at the protein-lipid interface. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Cohen, JB (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM 58448] NR 35 TC 61 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 22 PY 2000 VL 275 IS 38 BP 29441 EP 29451 DI 10.1074/jbc.M004710200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 356JH UT WOS:000089439800037 PM 10859324 ER PT J AU Tzivion, G Luo, ZJ Avruch, J AF Tzivion, G Luo, ZJ Avruch, J TI Calyculin A-induced vimentin phosphorylation sequesters 14-3-3 and displaces other 14-3-3 partners in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTERMEDIATE FILAMENT REORGANIZATION; KINASE-ACTIVITY; DNA-DAMAGE; 14-3-3-PROTEINS; BINDING; RAF; CHECKPOINT; CELLS; ASSOCIATION; INHIBITION AB 14-3-3 proteins bind their targets through a specific serine/threonine-phosphorylated motif present on the target protein. This binding is a crucial step in the phosphorylation-dependent regulation of various key proteins involved in signal transduction and cell cycle control, We report that treatment of COS-7 cells with the phosphatase inhibitor calyculin A induces association of 14-3-3 with a 55-kDa protein, identified as the intermediate filament protein vimentin, Association of vimentin with 14-3-3 depends on vimentin phosphorylation and requires the phosphopeptide-binding domain of 14-3-3, The region necessary for binding to 14-3-3 is confined to the vimentin amino-terminal head domain (amino acids 1-96). Monomeric forms of 14-3-3 do not bind vimentin in vivo or in vitro, indicating that a stable complex requires the binding of a 14-3-3 dimer to two sites on a single vimentin polypeptide. The calyculin A-induced association of vimentin with 14-3-3 in vivo results in the displacement of most other 14-3-3 partners, including the protooncogene Raf, which nevertheless remain capable of binding 14-3-3 in vitro, Concomitant with 14-3-3 displacement, calyculin A treatment blocks Raf activation by EGF; however, this inhibition is completely overcome by 14-3-3 overexpression in vivo or by the addition of prokaryotic recombinant 14-3-3 in vitro, Thus, phosphovimentin, by sequestering 14-3-3 and limiting its availability to other target proteins can affect intracellular signaling processes that require 14-3-3. C1 Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Boston Univ, Med Ctr, Diabet & Metab Unit, Boston, MA 02118 USA. RP Tzivion, G (reprint author), Texas A&M Univ Syst, Hlth Sci Ctr, Coll Med, Div Mol Cardiol,Cardiovasc Res Inst, 1901 S 1st St,Bldg 162, Temple, TX 76504 USA. RI Tzivion, Guri/D-8954-2011 NR 32 TC 95 Z9 100 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 SEP 22 PY 2000 VL 275 IS 38 BP 29772 EP 29778 DI 10.1074/jbc.M001207200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 356JH UT WOS:000089439800081 PM 10887173 ER PT J AU Bruning, JC Gautam, D Burks, DJ Gillette, J Schubert, M Orban, PC Klein, R Krone, W Muller-Wieland, D Kahn, CR AF Bruning, JC Gautam, D Burks, DJ Gillette, J Schubert, M Orban, PC Klein, R Krone, W Muller-Wieland, D Kahn, CR TI Role of brain insulin receptor in control of body weight and reproduction SO SCIENCE LA English DT Article ID GROWTH-FACTOR-I; CENTRAL-NERVOUS-SYSTEM; FOOD-INTAKE; GENE; RAT; RESISTANCE; KNOCKOUT; NEURONS; NIDDM AB Insulin receptors (IRs) and insulin signaling proteins are widely distributed throughout the central nervous system (CNS). To study the physiological role of insulin signaling in the brain, we created mice with a neuron-specific disruption of the IR gene (NIRKO mice), Inactivation of the IR had no impact on brain development or neuronal survival. However, female NIRKO mice showed increased food intake, and both male and female mice developed diet-sensitive obesity with increases in body fat and plasma leptin levels, mild insulin resistance, elevated plasma insulin Levels, and hypertriglyceridemia. NIRKO mice also exhibited impaired spermatogenesis and ovarian follicle maturation because of hypothalamic dysregulation of luteinizing hormone. Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction. C1 Univ Cologne, Klin & Poliklin Innere Med 2, D-50931 Cologne, Germany. Univ Cologne, Ctr Mol Med, D-50931 Cologne, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. European Mol Biol Lab, D-69117 Heidelberg, Germany. RP Bruning, JC (reprint author), Univ Cologne, Klin & Poliklin Innere Med 2, Stelzmann Str 9, D-50931 Cologne, Germany. RI Klein, Ruediger/C-6147-2008; Schubert, Markus/F-5150-2010 OI Klein, Ruediger/0000-0002-3109-0163; FU NIDDK NIH HHS [DK31036, DK55326-01A2] NR 28 TC 1151 Z9 1195 U1 7 U2 72 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 SEP 22 PY 2000 VL 289 IS 5487 BP 2122 EP 2125 DI 10.1126/science.289.5487.2122 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 356EG UT WOS:000089430900044 PM 11000114 ER PT J AU Walker, BD Goulder, PJR AF Walker, BD Goulder, PJR TI AIDS - Escape from the immune system SO NATURE LA English DT Editorial Material ID T-LYMPHOCYTE RESPONSE; PRIMARY INFECTION; SELECTION; IMMUNODOMINANT; PROGRESSION; PRESSURE; VACCINE; VIRUS C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 10 TC 35 Z9 35 U1 0 U2 1 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 2000 VL 407 IS 6802 BP 313 EP 314 DI 10.1038/35030283 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 355NA UT WOS:000089390700028 PM 11014174 ER PT J AU Burks, DJ de Mora, JF Schubert, M Withers, DJ Myers, MG Towery, HH Altamuro, SL Flint, CL White, MF AF Burks, DJ de Mora, JF Schubert, M Withers, DJ Myers, MG Towery, HH Altamuro, SL Flint, CL White, MF TI IRS-2 pathways integrate female reproduction and energy homeostasis SO NATURE LA English DT Article ID RECEPTOR SUBSTRATE FAMILY; PHOSPHOTYROSINE PROTEIN; CAENORHABDITIS-ELEGANS; INSULIN-RECEPTORS; LEPTIN RECEPTOR; FOOD-INTAKE; DB/DB MICE; SYSTEM; CELL; HYPOTHALAMUS AB Severe dietary restriction, catabolic states and even short-term caloric deprivation impair fertility in mammals. Likewise, obesity is associated with infertile conditions such as polycystic ovary syndrome(1,2). The reproductive status of lower organisms such as Caenorhabditis elegans is also modulated by availability of nutrients(3,4). Thus, fertility requires the integration of reproductive and metabolic signals. Here we show that deletion of insulin receptor substrate-2 (IRS-2), a component of the insulin/insulin-like growth factor-1 signalling cascade, causes female infertility. Mice lacking IRS-2 have small, anovulatory ovaries with reduced numbers of follicles. Plasma concentrations of luteinizing hormone, prolactin and sex steroids are low in these animals. Pituitaries are decreased in size and contain reduced numbers of gonadotrophs. Females lacking IRS-2 have increased food intake and obesity, despite elevated levels of leptin. Our findings indicate that insulin, together with leptin and other neuropeptides, may modulate hypothalamic control of appetite and reproductive endocrinology. Coupled with findings on the role of insulin-signalling pathways in the regulation of fertility, metabolism and longevity in C. elegans and Drosophila(3-5), we have identified an evolutionarily conserved mechanism in mammals that regulates both reproduction and energy homeostasis. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Univ Salamanca, Fac Med, Ctr Invest Canc, Salamanca 37007, Spain. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. RI Schubert, Markus/F-5150-2010; Withers, Dominic/D-7671-2014; Font de Mora, Jaime/H-6304-2015 OI Withers, Dominic/0000-0002-8009-7521; Font de Mora, Jaime/0000-0002-6816-2095 NR 30 TC 303 Z9 312 U1 6 U2 25 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 21 PY 2000 VL 407 IS 6802 BP 377 EP 382 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 355NA UT WOS:000089390700047 PM 11014193 ER PT J AU Jackson, JG Kreisberg, JI Koterba, AP Yee, D Brattain, M AF Jackson, JG Kreisberg, JI Koterba, AP Yee, D Brattain, M TI Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells SO ONCOGENE LA English DT Article DE forkhead; FKHR; EGF; breast cancer ID PROTEIN-KINASE-B; CAENORHABDITIS-ELEGANS; DEPENDENT ACTIVATION; SIGNAL-TRANSDUCTION; FACTOR RECEPTORS; BINDING-SITE; INSULIN; AKT; TRANSLOCATION; LONGEVITY AB Akt, when activated by IGF/insulin, can phosphorylate forkhead transcription factors. We undertook this study to determine whether epidermal growth factor (EGF) treatment could produce a signaling cascade resulting in phosphorylation of the forkhead transcription factor FKHR in a breast cancer cell line, MDA-MB-231, After establishing ErbB1, cbl, PI3 kinase and Akt were activated in EGF treated MDA-MB-231, we determined by immunoblot with FKHR antiserum that the electrophoretic mobility of FKHR was retarded after EGF treatment. This mobility retardation was reversible by treatment with alkaline phosphatase, and immunoblot with phospho-Ser(256) FKHR antibody further confirmed phosphorylation on an Akt consensus site after EGF treatment. EGF stimulated FKHR phosphorylation was blocked by the PI3 kinase inhibitor LY294002, and the ErbB1 inhibitor AG1478, FKHR immunoblotting after purification of nuclear and cytoplasmic proteins showed that EGF induced a simultaneous increase of FKHR in the cytoplasm and decrease in the nucleus. This finding was confirmed by immunofluorescence staining. Treatment of cells with pharmacological inhibitors of PI3 kinase or ErbB1 blocked this effect. Thus, these results demonstrate the phosphorylation and nuclear exclusion of FKHR after EGF treatment by a PI3 kinase dependent mechanism, and represent the first report of growth factor regulation of endogenous FKHR localization. C1 Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, Div Res & Dev, San Antonio, TX 78229 USA. Univ Minnesota, Ctr Canc, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. RP Brattain, M (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [CA54807, CA74285, CA34432] NR 39 TC 63 Z9 63 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 21 PY 2000 VL 19 IS 40 BP 4574 EP 4581 DI 10.1038/sj.onc.1203825 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 356HQ UT WOS:000089438200003 PM 11030146 ER PT J AU Sonntag, KC Haller, GW Giauffret, D Germana, S Reeves, SA Levy, J Sachs, DH LeGuern, C AF Sonntag, KC Haller, GW Giauffret, D Germana, S Reeves, SA Levy, J Sachs, DH LeGuern, C TI Regulated expression of an MHC class II gene from a promoter-inducible retrovirus SO HUMAN GENE THERAPY LA English DT Article ID SV40 LATE PROMOTER; TRANSGENIC MICE; BONE-MARROW; MONOCLONAL-ANTIBODIES; MAMMALIAN-CELLS; DRB GENES; IN-VIVO; TETRACYCLINE; DELIVERY; ANTIGEN AB Specific immune tolerance to fully allogeneic kidney grafts can be achieved in a miniature swine transplantation model by retrovirus-mediated transfer of allogeneic MHC class II genes into bone marrow cells (BMCs) of recipient animals. Graft survival correlated with transient expression of the somatic transgene (Tg) in the induction phase of tolerance, With the aim of investigating the effects of timing and threshold levels of Tg expression on induction of hyporesponsiveness to the grafted tissues, two recombinant retrovirus constructs containing the tetracycline binary regulatory system were used to achieve conditional expression of either the green fluorescent protein (tetGFP) as a control, or the porcine MHC class II DR beta chain (tetDRB), Effective downregulation of GFP gene transcription was demonstrated in transduced murine fibroblasts after doxycycline treatment, leading to a >90% reduction of GFP fluorescence, Similar diminution of the DRB gene transcription was achieved in transduced pig endothelial cells (ECs). Drug-dependent downregulation of DRBc gene expression in SLA(d) pig ECs coincided with complete inhibition of allogeneic activation of anti-class IIc-primed SLA(d) T cells, These in vitro results suggest that the binary tetracycline retrovirus system may also be adequate to regulate MHC class II Tg expression in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Blaise Pascal, UFR Sci Exactes & Nat, F-63177 Clermont Ferrand, France. Cent Iowa Hlth Syst, Human Gene Therapy Res Inst, Des Moines, IA 50321 USA. RP LeGuern, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [5RO1 HL46532]; NIAID NIH HHS [2RO1 AI31046] NR 32 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP 20 PY 2000 VL 11 IS 14 BP 1961 EP 1969 DI 10.1089/10430340050143390 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 359BU UT WOS:000089592300001 PM 11020796 ER PT J AU Peel, DJ Ziogas, A Fox, EA Gildea, M Laham, B Clements, E Kolodner, RD Anton-Culver, H AF Peel, DJ Ziogas, A Fox, EA Gildea, M Laham, B Clements, E Kolodner, RD Anton-Culver, H TI Characterization of hereditary nonpolyposis colorectal cancer families from a population-based series of cases SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REPAIR-GENE-MUTATIONS; MUIR-TORRE SYNDROME; COLON-CANCER; MISMATCH-REPAIR; MICROSATELLITE INSTABILITY; ADENOMATOUS POLYPOSIS; 3-YEAR EXPERIENCE; MLH1 MUTATIONS; LYNCH SYNDROME; BREAST-CANCER AB Background: The incidence of hereditary nonpolyposis colon cancer (HNPCC) in the general population is not well defined because of the lack of large population-based studies. We characterized the incidence of HNPCC in a large, population-based cohort of colorectal cancer probands and analyzed the location of colorectal tumors. Methods: Of the participating 1134 probands from three counties in Southern California, 907 had a negative family history of colorectal cancer and 227 had a positive family history of colorectal cancer. In addition, 11 referral case subjects with HNPCC were used to study mutation frequencies in two mismatch repair genes (MSH2 and MLH1) and microsatellite instability. All statistical tests were two-sided. Results: Among the probands diagnosed in Orange County during 1994 (population-based sample, all ages), five were consistent with the Amsterdam criteria for HNPCC (0.9%; 95% confidence interval [CI] = 0.3%-2.1%). Among probands diagnosed at less than 65 years of age-from the wider three-county area and a longer time span-16 (2.1%; 95% CI = 1.2%-3.4%) had a clinical history consistent with the Amsterdam criteria for HNPCC, Five (approximately 45%) of 11 of the referral HNPCC case subjects had a mutation in MSH2 or MLH1 and also showed microsatellite instability. The family members of case subjects with mutations tended to show an earlier age at diagnosis of HNPCC and more multiple primary cancers than those of case subjects without detectable mutations. Many of the known characteristics of HNPCC, including the presence of ureteral and endometrial cancers, were seen in both sets of families. The previously reported proximal location of colorectal tumors in HNPCC kindreds was not seen in the population-based dataset but was similar to the location reported in the referral cases. Conclusions: On the basis of our data, we believe that the prevalence of HNPCC in the general population is likely to be closer to 1% than to 5%. Furthermore, our study suggests that some previously reported characteristics of HNPCC, such as the proximal location of tumors in the syndrome, may not always hold true in a population-based sample. C1 Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92697 USA. Univ Calif San Diego, Sch Med, Ludwig Inst Canc Res, San Diego, CA 92103 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anton-Culver, H (reprint author), Univ Calif Irvine, Dept Med, Div Epidemiol, 224 Irvine Hall, Irvine, CA 92697 USA. FU NCI NIH HHS [5R01CA63706, 5R01CA67151]; PHS HHS [50N-8707-S1527] NR 51 TC 69 Z9 73 U1 0 U2 0 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 SEP 20 PY 2000 VL 92 IS 18 BP 1517 EP 1522 DI 10.1093/jnci/92.18.1517 PG 6 WC Oncology SC Oncology GA 353XH UT WOS:000089300400010 PM 10995807 ER PT J AU Ullrich, R Scherrer-Crosbie, M Bloch, KD Ichinose, F Nakajima, H Picard, MH Zapol, WM Quezado, ZMN AF Ullrich, R Scherrer-Crosbie, M Bloch, KD Ichinose, F Nakajima, H Picard, MH Zapol, WM Quezado, ZMN TI Congenital deficiency of nitric oxide synthase 2 protects against endotoxin-induced myocardial dysfunction in mice SO CIRCULATION LA English DT Article DE echocardiography; heart failure; inflammation; inhibitors; sepsis ID NECROSIS-FACTOR-ALPHA; CARDIAC MYOCYTES; CONTRACTILE FUNCTION; SEPTIC SHOCK; IN-VITRO; PEROXYNITRITE; DEPRESSION; HEART; EXPRESSION; DOGS AB Background-Sepsis can be complicated by severe myocardial dysfunction and is associated with increased nitric oxide (NO) production by inducible NO synthase (NOS2). To investigate the role of NOS2 in endotoxin-induced myocardial dysfunction in vivo, we studied wild-type and NOS2-deficient mice. Methods and Results-Serial echocardiographic parameters of myocardial function were measured before and at 4, 7, 16, and 24 hours after an endotoxin challenge. Seven hours after challenge with either endotoxin or saline, systemic and left ventricular pressures were measured, and the first derivative of left ventricular developed pressure (dP/dt), slope of the end-systolic pressure-dimension relationship (Slope(LVESPD)), and time constant of isovolumic relaxation (tau) were calculated. Endotoxin challenge in wild-type mice decreased left ventricular fractional shortening, velocity of circumferential shortening, dP/dt(max), Slope(LVESPD) and dP/dt(min) and increased time constant tau. Endotoxin-induced myocardial dysfunction was associated with increased ventricular NOS2 gene expression and cGMP concentrations. Seven hours after endotoxin challenge, NOS2-deficient mice had greater fractional shortening, dP/dt(max), and Slope(LVESPD) than did endotoxin-challenged wild-type mice. Measures of diastolic function, dP/dt(min) and time constant tau, were preserved in endotoxin-challenged NOS2-deficient mice. After endotoxin challenge in wild-type mice, early (3-hour) inhibition of NOS2 with L-N-6-(1-iminoethyl)lysine hydrochloride prevented, whereas later (7-hour) inhibition could not reverse, endotoxin-induced myocardial dysfunction. Conclusions-These results suggest that NOS2 is required for the development of systolic and diastolic dysfunction in murine sepsis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Ullrich, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. RI Quezado, Zenaide/O-4860-2016; OI Quezado, Zenaide/0000-0001-9793-4368; Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-42397, HL-55377] NR 27 TC 92 Z9 96 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 SEP 19 PY 2000 VL 102 IS 12 BP 1440 EP 1446 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 354NE UT WOS:000089335900018 PM 10993865 ER PT J AU Ilag, LL Yadav, RC Huang, N Ronald, PC Ausubel, FM AF Ilag, LL Yadav, RC Huang, N Ronald, PC Ausubel, FM TI Isolation and characterization of disease resistance gene homologues from rice cultivar IR64 SO GENE LA English DT Article DE NBS-LRR; NRH; Xa4; Xanthomonas ID NUCLEOTIDE-BINDING; REPEAT CLASS; SEQUENCE-ANALYSIS; RFLP MARKERS; TOMATO; PROTEIN; THALIANA; BELONGS; CLONES; RPS2 AB We initiated a search for disease resistance (R) gene homologues in rice cultivar IR64, one of the most agronomically important rice varieties in the world, with the assumption that some of these homologues would correspond to previously identified disease resistance loci. A family of rice R gene homologues was identified using the Arabidopsis NBS-LRR disease resistance gene RPS2 as a hybridization probe. Because member genes of this rice R gene family exhibit features characteristic of the NBS-LRR class of resistance genes, the family was given the name NRH (for NBS-LRR resistance gene homologues), Three members of the NRH family, NRH1 NRH2, and NRH3, were cloned and studied in detail. In IR64, NRH1 and NRH2 appear to encode full-length polypeptides, whereas NRH3 is prematurely truncated with a stop codon generated by a frameshift. NRH1 maps on chromosome 5, and NRH2 and NRH3 are less than 48 kb apart on chromosome 11. Although NRH1, NRH2, and NRH3 map to regions of the rice genome where disease resistance loci to Xanthomonas oryzae pv. oryzae (Xoo) have been identified, susceptible rice varieties transformed with either NRH1 or NRH2 failed to exhibit increased resistance to a set of well-characterized Xoo strains. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Int Rice Res Inst, Dept Plant Breeding Genet & Biochem, Genome Mapping Lab, Manila 1099, Philippines. Univ Calif Davis, Dept Plant Pathol, Davis, CA 95616 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM48707, 1F32GM16527] NR 30 TC 18 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 19 PY 2000 VL 255 IS 2 BP 245 EP 255 DI 10.1016/S0378-1119(00)00333-4 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 362KR UT WOS:000089777600011 PM 11024284 ER PT J AU Li, XG Multon, MC Henin, Y Schweighoffer, F Venot, C LaVecchio, J Josef, J Stuckert, P Mhashilkar, A Tocque, B Marasco, WA AF Li, XG Multon, MC Henin, Y Schweighoffer, F Venot, C LaVecchio, J Josef, J Stuckert, P Mhashilkar, A Tocque, B Marasco, WA TI Upregulation of the apoptosis-associated protein Grb3-3 in HIV-1-infected human CD4(+) lymphocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE apoptosis; CD4(+) T cell; Grb3-3; HIV-1 ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROGRAMMED CELL-DEATH; DNA FRAGMENTATION; BINDING-PROTEIN; ISOFORM GRB3-3; GRB2 ISOFORM; T-CELLS; INFECTION; PATHWAY; AIDS AB The mechanism(s) by which HIV-1 infection contributes to depletion of CD4(+) T cell is not well understood. In this report, we investigated whether a recently identified isoform of growth factor receptor bound protein (Grb2), named Grb3-3, a signaling molecule that is associated with the MAP kinase pathway and with apoptosis could be involved. We find that Grb3-3 is markedly up-regulated following HIV-1infection of CD4(+) peripheral blood mononuclear cells undergoing apoptosis. Although IL-2 deprived CD4(+) cells also undergo apoptosis to a similar extent, Grb3-3 upregulation is not detected under these experimental conditions. Transient overexpression of Grb3-3 in Jurkat T-cells also causes apoptosis. Upon staurosporine stimulation, Grb3-3 predisposes Sup-T1 cell to apoptosis. Finally, analysis of the HIV-1genes responsible for Grb3-3 expression demonstrates that Tat and Nef can independently induces its expression, suggesting these two earliest viral gene products of HIV-1 may share some common pathway(s) in up-regulating Grb3-3 expression. (C) 2000 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Aventis Pharma, F-94403 Vitry Sur Seine, France. Exonhit Therapeut, F-75013 Paris, France. RP Li, XG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI41954, AI28785] NR 38 TC 8 Z9 8 U1 0 U2 6 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 SEP 16 PY 2000 VL 276 IS 1 BP 362 EP 370 DI 10.1006/bbrc.2000.3415 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 355LX UT WOS:000089388100059 PM 11006130 ER PT J AU Fugit, RV Resch, ND AF Fugit, RV Resch, ND TI Conversion of patients from simvastatin to lovastatin in an outpatient pharmacy clinic SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article; Proceedings Paper CT Western States Conference for Pharmacy Residents, Fellows, and Preceptors CY MAY 05, 1999 CL PACIFIC GROVE, CALIFORNIA ID HYPERCHOLESTEROLEMIA; MANAGEMENT; CARE; PRAVASTATIN; EFFICACY AB The Notes section welcomes the following types of contributions: (1) practical innovations or solutions to everyday practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) shore research reports, including practice surveys, of modest scope or interest. Notes should be submitted with AJHP's manuscript checklist. The text should be concise, and the number of references, tables, and figures should be limited. C1 Denver Vet Affairs Med Ctr, Dept Pharm 119, Denver, CO 80220 USA. Vet Affairs Med Ctr, Albuquerque, NM USA. RP Fugit, RV (reprint author), Denver Vet Affairs Med Ctr, Dept Pharm 119, 1055 Clemont St, Denver, CO 80220 USA. NR 16 TC 14 Z9 14 U1 1 U2 1 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 SEP 15 PY 2000 VL 57 IS 18 BP 1703 EP 1708 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 358JY UT WOS:000089556000013 PM 11006798 ER PT J AU Biederman, J Mick, E Faraone, SV Spencer, T Wilens, TE Wozniak, J AF Biederman, J Mick, E Faraone, SV Spencer, T Wilens, TE Wozniak, J TI Pediatric mania: A developmental subtype of bipolar disorder? SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Biopolar Disorder - From Clinical to Clinical, Facing the New Millennium CY JAN 19-21, 2000 CL SCOTTSDALE, ARIZONA SP Soc Biol Psychiat DE bipolar disorder; child; age of onset ID DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; CATCHMENT-AREA SURVEY; CONDUCT DISORDER; PREPUBERTAL CHILDREN; PANIC DISORDER; JUVENILE MANIA; AGGRESSIVE-CHILDREN; COMORBID DISORDERS; DEPRESSIVE ILLNESS AB Despite ongoing controversy, the view that pediatric mania is rare or nonexistent has been increasingly challenged not only by case reports, but also by systematic research. This research strongly suggests that pediatric mania may not be rare but that it may be difficult to diagnose. Since children with mania are likely to become adults with bipolar disorder, the recognition and characterization of childhood-onset mania may help identify a meaningful developmental subtype of bipolar disorder worthy of further investigation. The major difficulties that complicate the diagnosis of pediatric mania include: 1) its pattern of comorbidity may be unique by adult standards, especially its overlap with attention-deficit/hyperactivity disorder, aggression, and conduct disorder; 2) its overlap with substance use disorders; 3) its association with trauma and adversity; and 4) its response to treatment is atypical by adult standards. (C) 2000 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 75 TC 159 Z9 159 U1 7 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2000 VL 48 IS 6 BP 458 EP 466 DI 10.1016/S0006-3223(00)00911-2 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 356PY UT WOS:000089452700008 PM 11018219 ER PT J AU Thase, ME Sachs, GS AF Thase, ME Sachs, GS TI Bipolar depression: Pharmacotherapy and related therapeutic strategies SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Bipolar Disorder - From Pre-Clinical to Clinical, Facing the New Millennium CY JAN 19-21, 2000 CL SCOTTSDALE, AZ SP Soc Biol Psychiat DE bipolar affective disorder; depression; antidepressants; mood stabilizers ID RESISTANT RECURRENT DEPRESSION; MONOAMINE-OXIDASE INHIBITORS; LONG-TERM TREATMENT; TRICYCLIC ANTIDEPRESSANTS; MAJOR DEPRESSION; MOOD DISORDERS; ELECTROCONVULSIVE-THERAPY; PROPHYLACTIC EFFICACY; REUPTAKE INHIBITORS; AFFECTIVE-ILLNESS AB The depressed phase of bipolar affective disorder is a significant cause of suffering, disability, and mortality and represents a major challenge to treating clinicians. This article first briefly reviews the phenomenology and clinical correlates of bipolar depression and then focuses on the major pharmacological treatment options. We strongly recommend use of mood stabilizers as the first-line treatment for the type I form of bipolar depression, largely because longer-term preventative therapy with these agents almost certainly will be indicated. Depressive episodes that do not respond to lithium, divalproex, or another mood stabilizer, or episodes that "breakthrough" despite preventive treatment, often warrant treatment with an antidepressant or electroconvulsive therapy. The necessity of mood stabilizers in the type II form of bipolar depression is less certain, aside from the rapid cycling presentation. Both experts and practicing clinicians recommend bupropion and the selective serotonin reuptake inhibitors as coequal initial choices, with venlafaxine and monoamine oxidase inhibitors, such as tranylcypromine, preferred for more resistant cases. The risk of antidepressant-induced hypomania or mania with concomitant mood stabilizer therapy is low, on the order of 5% to 10% during acute phase therapy. Additional therapeutic options and optimal durations of therapy also are discussed. (C) 2000 Society of Biological Psychiatry. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Thase, ME (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH-30915, 1N01 MH-80001-01] NR 129 TC 113 Z9 116 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2000 VL 48 IS 6 BP 558 EP 572 DI 10.1016/S0006-3223(00)00980-X PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 356PY UT WOS:000089452700016 PM 11018227 ER PT J AU Sachs, GS Thase, ME AF Sachs, GS Thase, ME TI Bipolar disorder therapeutics: Maintenance treatment SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Biopolar Disorder - From Clinical to Clinical, Facing the New Millennium CY JAN 19-21, 2000 CL SCOTTSDALE, ARIZONA SP Soc Biol Psychiat DE bipolar disorder; maintenance; relapse prevention; prophylaxis; continuation; combination treatment ID DOUBLE-BLIND; FOLLOW-UP; LITHIUM PROPHYLAXIS; AFFECTIVE-ILLNESS; ACUTE MANIA; I DISORDER; DEPRESSIVE ILLNESS; DRUG-THERAPY; CARBAMAZEPINE; LONG AB Although most of the care received by bipolar patients occurs during the maintenance phase, relatively little empirical data is available to guide long-term treatment decisions. We review literature pertaining to key questions related to use of pharmacotherapy in the maintenance phase of bipolar disorder. The few double-blind trials with a reasonable sample size are restricted to bipolar I patients and address a modest range of questions mostly related to use of lithium. One rigorous multicenter trial found valproate to have prophylactic benefit. Other studies with valproate alone and in combination suggest efficacy equivalent to lithium and perhaps greater than carbamazepine. Data available for combination treatment are sparse but moderately encouraging. Maintenance treatment with standard antidepressant medications appears destabilizing for some bipolar patients, particularly following a mixed episode. Although some bipolar patients may benefit from combined treatment with a mood stabilizer and a standard antidepressant medication, current knowledge does not allow confident selection of the bipolar patients who might benefit Clozapine and perhaps other atypical antipsychotics are promising options for maintenance treatment but have not been evaluated in double-blind trials. The numerous other agents used in maintenance treatment are primarily adjuncts to lithium, valproate, or carbamazepine, and information about them is largely anecdotal and uncontrolled. Study design for maintenance trials remains an imperfect art. Conclusions must be drawn cautiously, given the limited generalizability of study designs that accession samples enriched with presumed treatment responders, randomize patients after brief periods of partial remission, abruptly taper prior treatment, make no attempt to distinguish relapse from recurrence, use no formal outcome assessments, or report hospitalization as the only outcome criterion. (C) 2000 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Partners Bipolar Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Partners Bipolar Treatment Ctr, WACC 815,15 Parkman St, Boston, MA 02114 USA. FU DS NIH HHS [DS-1998-0001] NR 63 TC 57 Z9 62 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2000 VL 48 IS 6 BP 573 EP 581 DI 10.1016/S0006-3223(00)00991-4 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 356PY UT WOS:000089452700017 PM 11018228 ER PT J AU Rush, AJ Post, RM Nolen, WA Keck, PE Suppes, T Altshuler, L McElroy, SL AF Rush, AJ Post, RM Nolen, WA Keck, PE Suppes, T Altshuler, L McElroy, SL TI Methodological issues in developing new acute treatments for patients with bipolar illness SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Biopolar Disorder - From Clinical to Clinical, Facing the New Millennium CY JAN 19-21, 2000 CL SCOTTSDALE, ARIZONA SP Soc Biol Psychiat DE acute phase treatment; bipolar illness; methodological issues ID DEPRESSIVE SYMPTOMATOLOGY IDS; PARTIAL-ONSET SEIZURES; ANTIEPILEPTIC DRUGS; LITHIUM TREATMENT; CONTROLLED TRIAL; WORKSHOP REPORT; DOUBLE-BLIND; DISORDER; MANIA; THERAPY AB One important aim of the recent reorganization of the National Institute of Mental Health (NIMH) is to streamline the development of new treatments for patients with severe mental illnesses, such as bipolar disorder, Researching new treatments for patients with bipolar disorder presents specific problems not readily addressed by traditional efficacy trial methodologies that aim to maximize internal validity. This article reexamines several assumptions that have guided the design of these efficacy trials but that also create obstacles for studies of bipolar disorder and suggests potential solutions. This article draws on literature from neurology and psychiatry and discussions at a MacArthur Foundation-sponsored Conference on Longitudinal Methodology in 1992 (David J. Kupfer, MD., Chair), which brought together investigators to consider alternative designs for patients with severe and persistent mental illness, In addition, we benefited from discussions at two NIMH-sponsored conferences, one held in 1989 (Prien and Potter 1990) and the other in 1994 (Prien and Rush 1996), at which investigators and methodologists discussed issues surrounding the development and conduct of informative efficacy trials for patients with bipolar disorder. Based on these discussions and recent literature reviews, we 1) outline common problems in the development and evaluation of effective acute treatments for bipolar disorder and 2) suggest possible solutions to these impediments. We also discuss alternative designs by which to build a sequence of acute treatment studies from which efficacy, safety, and the comparative value of different treatments can be established (C) 2000 Society of Biological Psychiatry. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Utrecht, Med Ctr, HC Rumke Grp, Utrecht, Netherlands. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH USA. Stanley Fdn Bipolar Network, Bethesda, MD USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd 9086, Dallas, TX 75390 USA. RI Nolen, Willem/E-9006-2014; OI Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [MH-53899] NR 68 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 2000 VL 48 IS 6 BP 615 EP 624 DI 10.1016/S0006-3223(00)00898-2 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 356PY UT WOS:000089452700021 PM 11018232 ER PT J AU Nash, RA Antin, JH Karanes, C Fay, JW Avalos, BR Yeager, AM Przepiorka, D Davies, S Petersen, FB Bartels, P Buell, D Fitzsimmons, W Anasetti, C Storb, R Ratanatharathorn, V AF Nash, RA Antin, JH Karanes, C Fay, JW Avalos, BR Yeager, AM Przepiorka, D Davies, S Petersen, FB Bartels, P Buell, D Fitzsimmons, W Anasetti, C Storb, R Ratanatharathorn, V TI Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; SEVERE APLASTIC-ANEMIA; T-CELL DEPLETION; TERM FOLLOW-UP; BONE-MARROW; CONTROLLED TRIAL; ACUTE GVHD; PREVENTION AB After the transplantation of unmodified marrow from human leukocyte antigen-, matched unrelated donors receiving cyclosporine (CSP) and methotrexate (MTX), the incidence of acute graft-versus-host disease (GVHD) is greater than 75%, Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was effective in combination with MTX for the prevention of acute GVHD, Between March 1995 and September 1996, 180 patients were randomized in a phase 3, open-label, multicenter study to determine whether tacrolimus combined with a short course of MTX (n = 90), more than CSP and a short course of MTX (n = 90), would reduce the incidence of acute GVHD after marrow transplantation from unrelated donors, There was a significant trend toward decreased severity of acute GVHD across all grades (P =.005), Based on the Kaplan-Meier estimate, the probability of grade II-IV acute GVHD in the tacrolimus group (56%) was significantly lower than in the CSP group (74%; P =.0002). Use of glucocorticoids for the management of GVHD was significantly lower with tacrolimus than with CSP (65% vs 81%, respectively; P =.019). The number of patients requiring dialysis in the first 100 days was similar (tacrolimus, 9; CSP, 8), Overall and relapse-free survival rates for the tacrolimus and CSP arms at 2 years was 54% versus 50% (P =.46) and 47% versus 42% (P =.58), respectively. The combination of tacrolimus and MTX after unrelated donor marrow transplantation significantly decreased the risk for acute GVHD than did the combination of CSP and MTX, with no significant increase in toxicity, infections, or leukemia relapse.(Blood. 2000;96:2062-2068) (C) 2000 by The American Society of Hematology. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Wayne State Univ, Detroit, MI USA. Baylor Univ, Sammons Canc Ctr, Dallas, TX USA. Ohio State Univ Hosp, Columbus, OH 43210 USA. Emory Clin, Atlanta, GA 30322 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Fairview Univ Hosp, Minneapolis, MN USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Fujisawa Healthcare, Deerfield, IL USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Nash, RA (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [CA18029] NR 57 TC 339 Z9 349 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2000 VL 96 IS 6 BP 2062 EP 2068 PG 7 WC Hematology SC Hematology GA 358VN UT WOS:000089578000008 PM 10979948 ER PT J AU Gesbert, F Griffin, JD AF Gesbert, F Griffin, JD TI Bcr/Abl activates transcription of the Bcl-X gene through STAT5 SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; CELL-LINE; SIGNAL TRANSDUCERS; JAK-STAT5 PATHWAY; TYROSINE KINASE; ABL ONCOGENES; DNA-BINDING; TRANSFORMATION; APOPTOSIS AB Several tyrosine kinase oncogenes have been associated with myeloproliferative diseases, including Bcr/Abl, Tel/Abl, Tel/Jak2, and Tel/PDGFR. One target molecule shared by these oncogenes is known to be STAT5. We generated sublines of Ba/F3 cells in which either wild-type STAT5 or a constitutively active mutant of STAT5 (STAT5-1*6) were expressed under the control of a tetracycline-inducible promoter. These cell lines were compared with a Ba/F3 cell line in which the expression of p210(Bcr/Abl) was made inducible by a similar promoter. Before induction, all cells were dependent on interleukin 3 (IL-3) for growth and survival. Both STAT5-1*6 and Bcr/Abl enhanced viability and induced proliferation in the absence of IL-3. We found that the proviability protein Bcl-X-L, but not Bcl-2, was induced by both p210(Bcr/Abl) and STAT5-1*6. Using a Bcl-X gene promoter construct fused to a luciferase complementary DNA (cDNA), both p210(Bcr/Abl) and STAT5-1*6 were shown to induce transcription of Bcl-X. The increase in transcription of the Bcl-X promoter and the increase in Bcl-X protein, due to p210(Bcl/Abl), were blocked by expression of a dominant negative STAT5 mutant, Interestingly, however, STAT5-1*6 required the continued presence of IL-3 to cause a significant increase in Bcl-X-L protein, whereas p210(Bcr/Abl) did not need IL-3. Studies with enzyme inhibitors suggest that the extra signal supplied by IL-3 may be supplied by the PI3K pathway. Overall, these data suggest that constitutively activated STAT5 can increase viability and proliferation of Ba/F3 cells. This may contribute to, but is not likely sufficient for, the enhanced viability associated with Bcr/Abl transformation. (Blood, 2000;96:2269-2276) (C) 2000 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA66996] NR 36 TC 208 Z9 218 U1 1 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2000 VL 96 IS 6 BP 2269 EP 2276 PG 8 WC Hematology SC Hematology GA 358VN UT WOS:000089578000036 PM 10979976 ER PT J AU Ablashi, DV Chatlynne, L Thomas, D Bourboulia, D Rettig, MB Vescio, RA Viza, D Gill, P Kyle, RA Berenson, JR Whitman, JE AF Ablashi, DV Chatlynne, L Thomas, D Bourboulia, D Rettig, MB Vescio, RA Viza, D Gill, P Kyle, RA Berenson, JR Whitman, JE TI Lack of serologic association of human herpesvirus-8 (KSHV) in patients with monoclonal gammopathy of undetermined significance with and without progression to multiple myeloma SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; BONE-MARROW; DENDRITIC CELLS; PERIPHERAL-BLOOD; DNA-SEQUENCES; INFECTION; HUMAN-HERPESVIRUS-8; HHV-8; IDENTIFICATION AB Because human herpesvirus-8 (HHV-8) DNA has been found in multiple myeloma (MM) patients by polymerase chain reaction, it was suggested that HHV-8 may play a role in the transformation of monoclonal gammopathy of undetermined significance (MGUS) to MM. Therefore, 362 MGUS sera with and without progression to MM were tested for IgG antibody to HHV-8. Only 7.8% of the MGUS sera contained HHV-8 antibody to lytic proteins, and IgG antibody to HHV-8 latent antigen was even lower than lytic antibody (2.9%). No differences were observed in the distribution of antibody to HHV-8 in sera from MGUS patients who progressed to MM, The seroprevalences of HHV-8 in MGUS (7.8%), MM (5.4%), and healthy donors (5.9%) were similar, thus arguing for the lack of epidemiologic evidence of HHV-8 participation in the pathogenesis of MM, MGUS patients were immune competent in response to Epstein-Barr virus (EBV) infection be cause 97% contained antibody to EBV virus capsid antigen. (Blood, 2000;96:2304-2306) (C) 2000 by The American Society of Hematology. C1 Adv Biotechnol Inc, Columbia, MD 21046 USA. Georgetown Univ, Sch Med, Washington, DC USA. UCL, Dept Oncol, London WC1E 6BT, England. UCL, Dept Mol Pathol, Windeyer Inst Med Sci, London WC1E 6BT, England. Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Div Hematol & Oncol, Los Angeles, CA 90073 USA. Saints Peres, Fac Med, Immunol Lab, Paris, France. Univ So Calif, Dept Med, Div Hematol, Los Angeles, CA USA. Mayo Clin, Div Hematol, Rochester, MN USA. RP Ablashi, DV (reprint author), Adv Biotechnol Inc, 9108 Guilford Rd, Columbia, MD 21046 USA. EM dablashi@abionline.com FU NCI NIH HHS [CA62242] NR 26 TC 14 Z9 14 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2000 VL 96 IS 6 BP 2304 EP 2306 PG 3 WC Hematology SC Hematology GA 358VN UT WOS:000089578000041 PM 10979981 ER PT J AU Kilic, T Alberta, JA Zdunek, PR Acar, M Iannarelli, P O'Reilly, T Buchdunger, E Black, PM Stiles, CD AF Kilic, T Alberta, JA Zdunek, PR Acar, M Iannarelli, P O'Reilly, T Buchdunger, E Black, PM Stiles, CD TI Intracranial inhibition of platelet-derived growth factor-mediated glioblastoma cell growth by an orally active kinase inhibitor of the 2-phenylaminopyrimidine class SO CANCER RESEARCH LA English DT Article ID TYROSINE KINASE; C-ABL; TRANSFORMED PHENOTYPE; APOPTOTIC RESPONSE; MALIGNANT GLIOMAS; FACTOR RECEPTORS; DNA-DAMAGE; EXPRESSION; AUTOCRINE; PDGF AB Glioblastoma multiforme is the most common primary human brain tumor, and it is, for all practical purposes, incurable in adult patients, The high mortality rates reflect the fact that glioblastomas are resistant to adjuvant therapies (radiation and chemicals), the mode of action of which is cytotoxic, We show here that an p.o.-active small molecule kinase inhibitor of the 2-phenylaminopyrimidine class may have therapeutic potential for glioblastomas. STI571 inhibits the growth of U343 and U87 human glioblastoma cells that have been injected into the brains of nude mice, but it does not inhibit intracranial growth of ras-transformed cells, Studies on a broad panel of genetically validated human and animal cell lines show that STI571 acts by disruption of the ligand:receptor autocrine loops for platelet-derived growth factor that are a pervasive feature of malignant astrocytoma. The cellular response of glioblastoma cells to STI571 does not appear to involve an apoptotic mechanism. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Novartis Pharma AG, Oncol Res, CH-4002 Basel, Switzerland. RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [HD24926] NR 27 TC 246 Z9 255 U1 0 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 SEP 15 PY 2000 VL 60 IS 18 BP 5143 EP 5150 PG 8 WC Oncology SC Oncology GA 358GQ UT WOS:000089550600026 PM 11016641 ER PT J AU Eid, JE Kung, AL Scully, R Livingston, DM AF Eid, JE Kung, AL Scully, R Livingston, DM TI P300 interacts with the nuclear proto-oncoprotein SYT as part of the active control of cell adhesion SO CELL LA English DT Article ID SYNOVIAL SARCOMA TRANSLOCATION; TRANSCRIPTION FACTORS; PROTEINS; INTEGRINS; DIFFERENTIATION; FAMILY; SSX; CBP; TRANSFORMATION; IDENTIFICATION AB Complexes containing p300, but not CBP, and the nuclear proto-oncoprotein SYT were detected in confluent cultures of G1-arrested cells but not in sparse cells or during S or G2. SYT sequences constitute the N-terminal segment of a fusion oncogene product, SYT-SSX, routinely detected in synovial sarcoma, an aggressive human tumor. SYT/p300 complex formation promotes cell adhesion to a fibronectin matrix, as reflected by compromise of this process in cells expressing SYT dl mutants that retain p300 binding activity and in the primary fibroblasts of p300 but not CBP heterozygous null mice. The mechanism linking the action of SYT/p300 complexes to adhesion function is, at least in part, transcription activation-independent and results in proper activation of beta 1 integrin, a major adhesion receptor. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013; OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [K01 CA079576] NR 36 TC 70 Z9 71 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 15 PY 2000 VL 102 IS 6 BP 839 EP 848 DI 10.1016/S0092-8674(00)00072-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 355PZ UT WOS:000089395200015 PM 11030627 ER PT J AU Sado, T Fenner, MH Tan, SS Tam, P Shioda, T Li, E AF Sado, T Fenner, MH Tan, SS Tam, P Shioda, T Li, E TI X inactivation in the mouse embryo deficient for Dnmt1: Distinct effect of hypomethylation on imprinted and random X inactivation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE X inactivation; imprinting; DNA methylation; Dnmt1; mouse embryo ID CHROMOSOME INACTIVATION; XIST EXPRESSION; GENE-EXPRESSION; DNA; METHYLATION; LOCALIZATION; MECHANISMS; CELLS; METHYLTRANSFERASES; MAINTENANCE AB It has been suggested that DNA methylation plays a crucial role in genomic imprinting and X inactivation. Using DNA methyltransferase 1 (Dnmt1)-deficient mouse embryos carrying X-linked lacZ transgenes, we studied the effects of genomic demethylation on X inactivation. Based on the expression pattern of lacZ, the imprinted X inactivation in the visceral endoderm, a derivative of the extraembryonic lineage, was unaffected in Dnmt1 mutant embryos at the time other imprinted genes showed aberrant expression. Random X inactivation in the embryonic lineage of Dnmt1 mutant embryos, however, was unstable as a result of hypomethylation, causing reactivation of, at least, one lacZ transgene that had initially been repressed. Our results suggest that maintenance of imprinted X inactivation in the extraembryonic lineage can tolerate extensive demethylation while normal levels of methylation are required for stable maintenance of X inactivation in the embryonic lineage. (C) 2000 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp East, Sch Med, Dept Med, Charlestown, MA 02129 USA. Univ Melbourne, Howard Florey Inst, Parkville, Vic 3052, Australia. Childrens Med Res Inst, Embryol Unit, Wentworthville, NSW, Australia. RP Sado, T (reprint author), Natl Inst Genet, Div Human Genet, 1111 Yata, Mishima, Shizuoka 4118540, Japan. RI Fenner, Martin/A-7225-2008 OI Fenner, Martin/0000-0003-1419-2405 FU NCI NIH HHS [CA82389, CA82230]; NIGMS NIH HHS [GM52106] NR 41 TC 177 Z9 185 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 SEP 15 PY 2000 VL 225 IS 2 BP 294 EP 303 DI 10.1006/dbio.2000.9823 PG 10 WC Developmental Biology SC Developmental Biology GA 355NY UT WOS:000089392800003 PM 10985851 ER PT J AU Champliaud, MF Virtanen, I Tiger, CF Korhonen, M Burgeson, R Gullberg, D AF Champliaud, MF Virtanen, I Tiger, CF Korhonen, M Burgeson, R Gullberg, D TI Posttranslational modifications and beta/gamma chain associations of human laminin alpha 1 and laminin alpha 5 chains: purification of laminin-3 from placenta SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE laminin-3; laminin isoforms; placenta; choriocarcinoma ID CHORIOCARCINOMA CELLS; CARCINOMA-CELLS; B-CHAINS; A-CHAIN; EXPRESSION; DIFFERENTIATION; ANTIBODIES; CONTAINS; VARIANTS; JUNCTION AB Laminins assemble into trimers composed of alpha, beta, and gamma chains which posttranslationally are glycosylated and sometimes proteolytically cleaved. In the current paper we set out to characterize posttranslational modifications and the laminin isoforms formed by laminin alpha 1 and alpha 5 chains. Comparative pulse-chase experiments and deglycosylation studies in JAR cells established that the M-r 360,000 laminin al chain is glycosylated into a mature M-r 400,000 band while the M-r 370,000 laminin alpha 5 chain is glycosylated into a M-r 390,000 form that upon secretion is further processed into a M-r 380,000 form. Hence, despite the shorter peptide length of alpha 1 chain in comparison with the alpha 5 chain, secreted alpha 1 assumes a larger size in SDS-PAGE due to a higher degree of N-linked glycosylation and due to the lack of proteolytic processing. Immunoprecipitations and Western blotting of JAR laminins identified laminin alpha 1 and laminin alpha 5 chains in laminin-1 and laminin-10. In placenta laminin alpha 1 chain (M-r 400,000) and laminin alpha 5 chain (M-r 380,000/370,000 doublet) were found in laminin-1/-3 and laminin-10/-11. Immunohistochemically we could establish that the laminin alpha 1 chain in placenta is deposited in the developing villous and trophoblast basement membrane, also found to contain laminin beta 2 chains. Surprisingly, a fraction of the laminin alpha 1 chain from JAR cells and placenta could not be precipitated by antibodies to laminin beta 1-beta 3 chains, possibly pointing to an unexpected complexity in the chain composition of alpha 1-containing laminin isoforms. (C) 2000 Academic Press. C1 Uppsala Univ, Dept Cell & Mol Biol, BMC, S-75124 Uppsala, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Helsinki, Inst Biomed, Dept Anat, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland. RP Gullberg, D (reprint author), Uppsala Univ, Dept Cell & Mol Biol, BMC, Box 596, S-75124 Uppsala, Sweden. RI Gullberg, Donald/H-2495-2016 OI Gullberg, Donald/0000-0002-7245-4437 NR 35 TC 27 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 15 PY 2000 VL 259 IS 2 BP 326 EP 335 DI 10.1006/excr.2000.4980 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 353EM UT WOS:000089261900002 PM 10964500 ER PT J AU Lin, CP Lynch, MC Kochevar, IE AF Lin, CP Lynch, MC Kochevar, IE TI Reactive oxidizing species produced near the plasma membrane induce apoptosis in bovine aorta endothelial cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE apoptosis; singlet oxygen; rose bengal; photosensitization; plasma membrane; evanescent wave; endothelial cells ID REFLECTION FLUORESCENCE MICROSCOPY; PHOTODYNAMIC THERAPY; SINGLET OXYGEN; HYDROGEN-PEROXIDE; PROTEIN-KINASE; HL-60 CELLS; DNA-DAMAGE; CASPASE-3 ACTIVATION; P53; LIGAND AB Many cytotoxic agents initiate apoptosis by generating reactive oxidizing species (ROS). The goal of this study was to determine whether apoptosis could be induced by initial reactions of ROS near the plasma membrane. Bovine aorta endothelial cells (BAEC) were illuminated with evanescent wave visible radiation, which has limited penetration into the basal surface of cells, or by trans-radiation. Imaging of fluorescent dyes localizing in the plasma membrane, mitochondria, or nucleus confirmed that evanescent wave radiation excited only dyes in and near the plasma membrane. Singlet oxygen, an ROS generated by photosensitization, has a very short lifetime, ensuring that it oxidizes molecules residing in or very close to the plasma membrane when evanescent wave radiation is used. Cells with condensed nuclei were considered apoptotic and were quantified after treatment with varying doses of light. Annexin V staining without propidium iodide staining confirmed that these cells were apoptotic. The doses required to induce apoptosis using evanescent wave radiation were 10-fold greater than those needed for trans-irradiation. Quantitative analysis of the evanescent wave penetration into cells supports a mechanism in which the singlet oxygen created near the plasma membrane, rather than at intracellular sites, was responsible for initiation of apoptosis. (C) 2000 Academic Press. C1 Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Wellman Labs Photomed, Dept Dermatol, Massachusetts Gen Hosp,Sch Med, WEL-224,37 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM30755] NR 47 TC 33 Z9 35 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 15 PY 2000 VL 259 IS 2 BP 351 EP 359 DI 10.1006/excr.2000.4979 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 353EM UT WOS:000089261900004 PM 10964502 ER PT J AU Warren, MC Bump, EA Medeiros, D Braunhut, SJ AF Warren, MC Bump, EA Medeiros, D Braunhut, SJ TI Oxidative stress-induced apoptosis of endothelial cells SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE endothelial cells; matrix metalloproteinases; apoptosis; oxidative stress; Free radicals ID FREE-RADICALS; EXTRACELLULAR-MATRIX; HUMAN-DISEASE; METALLOPROTEINASES; INFLAMMATION; EXPRESSION; DEATH; MODULATION; INHIBITORS; RADIATION AB Endothelial cells (ECs) are subjected to oxidative stress during many pathological processes, including ischemia/reperfusion and general inflammation. In the present study, we examined the effects of oxidative stress on rates of apoptosis in EC cultures. We treated large and microvessel ECs with menadione for 1 h in vitro to simulate the most common physiological form of oxidative stress, exposure to O-2(.-). Capillary ECs were resistant to menadione-induced apoptosis when compared with large-vessel ECs. Treatment with 35 mu M menadione resulted in an apoptotic rate of similar to 5% in capillary EC cultures compared with similar to 45% in large-vessel EC cultures. At higher concentrations of menadione (35-75 mu M), both types of ECs exhibited a concentration-related increase in apoptosis. Necrotic cell death only became evident at menadione concentrations ranging from 75-100 mu M for both cell types. The timing of the apoptotic response to a 1 h menadione exposure was very specific. For both EC types, peaks of apoptosis occurred in two distinct waves, at 6-8 and 18-22 h after treatment. Analysis of the events leading up to the first peak of apoptosis indicated that specific matrix metalloproteinases (MMPs) were activated, suggesting that MMPs may be involved in initiating the apoptotic process. (C) 2000 Elsevier Science Inc. C1 Univ Massachusetts, Dept Biol Sci, Lowell, MA 01854 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Braunhut, SJ (reprint author), Univ Massachusetts, Dept Biol Sci, Olsen Hall 609, Lowell, MA 01854 USA. FU NIGMS NIH HHS [GM58583-02] NR 45 TC 54 Z9 60 U1 1 U2 4 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 SEP 15 PY 2000 VL 29 IS 6 BP 537 EP 547 DI 10.1016/S0891-5849(00)00353-1 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 362KP UT WOS:000089777400006 PM 11025197 ER PT J AU Ewen, ME AF Ewen, ME TI Where the cell cycle and histones meet SO GENES & DEVELOPMENT LA English DT Editorial Material ID DNA-REPLICATION; DEPENDENT KINASES; S-PHASE; CENTROSOME DUPLICATION; MAMMALIAN FIBROBLASTS; PROTEIN-KINASE; COILED BODIES; BINDING-SITE; E GENE; PHOSPHORYLATION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ewen, ME (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 52 TC 72 Z9 74 U1 0 U2 3 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 SEP 15 PY 2000 VL 14 IS 18 BP 2265 EP 2270 DI 10.1101/gad.842100 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 358AG UT WOS:000089534600002 PM 10995383 ER PT J AU Zhao, JY Kennedy, BK Lawrence, BD Barbie, DA Matera, AG Fletcher, JA Harlow, E AF Zhao, JY Kennedy, BK Lawrence, BD Barbie, DA Matera, AG Fletcher, JA Harlow, E TI NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription SO GENES & DEVELOPMENT LA English DT Article DE NPAT; cyclin E-Cdk2; histone gene transcription; nuclear foci ID PRE-MESSENGER-RNA; CELL-CYCLE; PHASE-TRANSITION; H2B GENE; INVITRO TRANSCRIPTION; BINDING-PROTEIN; MAMMALIAN-CELLS; FACTORS H4TF-1; COILED BODIES; DNA-SEQUENCES AB In eukaryotic cells, histone gene expression is one of the major events that mark entry into S phase. While this process is tightly linked to cell cycle position, how it is regulated by the cell cycle machinery is not known. Here we show that NPAT, a substrate of the cyclin E-Cdk2 complex, is associated with human replication-dependent histone gene clusters on both chromosomes 1 and 6 in S phase. We demonstrate that NPAT activates histone gene transcription and that this activation is dependent on the promoter elements (SSCSs) previously proposed to mediate cell cycle-dependent transcription. Cyclin E is also associated with the histone gene loci, and cyclin E-Cdk2 stimulates the NPAT-mediated activation of histone gene transcription. Thus, our results both show that NPAT is involved in a key S phase event and provide a link between the cell cycle machinery and activation of histone gene transcription. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. RP Zhao, JY (reprint author), Univ Rochester, Med Ctr, Ctr Canc Biol, Rochester, NY 14642 USA. FU NIGMS NIH HHS [R01 GM053034] NR 78 TC 220 Z9 227 U1 0 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 SEP 15 PY 2000 VL 14 IS 18 BP 2283 EP 2297 DI 10.1101/gad.827700 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 358AG UT WOS:000089534600005 PM 10995386 ER PT J AU Faccio, L Fusco, C Viel, A Zervos, AS AF Faccio, L Fusco, C Viel, A Zervos, AS TI Tissue-specific splicing of Omi stress-regulated endoprotease leads to an inactive protease with a modified PDZ motif SO GENOMICS LA English DT Article ID CHROMOSOME 2P13; DNA-BINDING; TRANSLOCATION; GENE; RECOGNITION; GENERATION; ACTIVATION; LEUKEMIA; HOMOLOG; CLONING AB Omi is a human serine protease whose catalytic domain is homologous to a bacterial heat shock endoprotease (HtrA), a protein indispensable to the survival of bacteria at elevated temperatures. Omi is expressed ubiquitously, and its protein product is predominantly localized in the endoplasmic reticulum of mammalian cells. Here we present the genomic structure of Omi, consisting of eight exons located on human chromosome 2p12-p13. Furthermore, we describe an alternatively splice form of Omi (D-Omi) that is expressed predominantly in the kidney, colon, and thyroid. D-Omi lacks peptide sequence encoded by two exons (exons III and VII). The absence of exon VII leads to a protein with a modified PDZ domain unable to interact with a known partner, the Mxi2 protein. The absence of exon III affects the catalytic domain and leads to a protein with no detectable protease activity. Our studies suggest that D-Omi may have a unique role in the normal function of kidney, colon, and thyroid. (C) 2000 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. RP Zervos, AS (reprint author), Univ Cent Florida, Ctr Discovery Drugs & Diagnost, CD3, Orlando, FL 32816 USA. FU NIDDK NIH HHS [R01 DK55734-01] NR 25 TC 26 Z9 27 U1 0 U2 0 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 SEP 15 PY 2000 VL 68 IS 3 BP 343 EP 347 DI 10.1006/geno.2000.6263 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 358GH UT WOS:000089549900014 PM 10995577 ER PT J AU Bergeron, B AF Bergeron, B TI The loyalty effect SO HOSPITAL PRACTICE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD SEP 15 PY 2000 VL 35 IS 9 BP A44 EP A44 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 355NF UT WOS:000089391200010 ER PT J AU Segev, DL Ha, TU Tran, TT Kenneally, M Harkin, P Jung, M MacLaughlin, DT Donahoe, PK Maheswaran, S AF Segev, DL Ha, TU Tran, TT Kenneally, M Harkin, P Jung, M MacLaughlin, DT Donahoe, PK Maheswaran, S TI Mullerian inhibiting substance inhibits breast cancer cell growth through an NF kappa B-mediated pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMARY EPITHELIAL-CELLS; HUMAN OVARIAN-CANCER; FETAL-RAT LUNG; FACTOR-BETA; TRANSCRIPTIONAL ACTIVATION; SEXUAL DEVELOPMENT; B/REL EXPRESSION; RESPONSE GENE; TUMOR-GROWTH; II RECEPTOR AB Mullerian inhibiting substance (MIS), a member of the transforming growth factor-beta superfamily, induces regression of the Mullerian duct in male embryos. In this report, we demonstrate MMS type II receptor expression in normal breast tissue and in human breast cancer cell lines, breast fibroadenoma, and ductal adenocarcinomas. MIS inhibited the growth of both estrogen receptor (ER)-positive T47D and ER-negative MDA-MB-231 breast cancer cell lines, suggesting a broader range of target tissues for MIS action. Inhibition of growth was manifested by an increase in the fraction of cells in the G(1) phase of the cell cycle and induction of apoptosis, Treatment of breast cancer cells with MIS activated the NF kappa B pathway and selectively up-regulated the immediate early gene IEX-1S, which, when overexpressed, inhibited breast cancer cell growth. Dominant negative I kappa B alpha expression ablated both MIS-mediated induction of IEX-1S and inhibition of growth, indicating that activation of the NF kappa B signaling pathway was required for these processes. These results identify the NF kappa B-mediated signaling pathway and a target gene for MIS action and suggest a putative role for the MIS ligand and its downstream interactors in the treatment of ER-positive as well as negative breast cancers. C1 Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Queens Univ, Dept Oncol, Belfast BT9 7AB, Antrim, North Ireland. Georgetown Univ, Med Ctr, Dept Radiat Med, Washington, DC 20057 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Lab, WRN1024,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA17393]; NICHD NIH HHS [HD32112] NR 65 TC 94 Z9 99 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 SEP 15 PY 2000 VL 275 IS 37 BP 28371 EP 28379 DI 10.1074/jbc.M004554200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 354KY UT WOS:000089330700007 PM 10874041 ER PT J AU Hanada, T Lin, LH Tibaldi, EV Reinherz, EL Chishti, AH AF Hanada, T Lin, LH Tibaldi, EV Reinherz, EL Chishti, AH TI GAKIN, a novel kinesin-like protein associates with the human homologue of the Drosophila discs large tumor suppressor in T lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYNEIN SUPERFAMILY PROTEINS; SYNAPTIC BOUTON STRUCTURE; KINASE-LIKE DOMAIN; POSTSYNAPTIC DENSITY; GUANYLATE KINASES; PDZ DOMAINS; GENE DLG; CHROMOSOME SEGREGATION; ORGANELLE TRANSPORT; BINDING INTERFACE AB Reorganization of the cortical cytoskeleton is a hallmark of T lymphocyte activation, Upon binding to antigen presenting cells, the T cells rapidly undergo cytoskeletal re-organization thus forming a cap at the cell-cell contact site leading to receptor clustering, protein segregation, and cellular polarization. Previously, we reported cloning of the human lymphocyte homologue of the Drosophila Discs Large tumor suppressor protein (hDlg), Here we show that a novel protein termed GAKIN binds to the guanylate kinase-like domain of hDlg, Affinity protein purification, peptide sequencing, and cloning of GAKIN cDNA from Jurkat J77 lymphocytes identified GAKIN as a novel member of the kinesin superfamily of motor proteins. GAKIN mRNA is ubiquitously expressed, and the predicted amino acid sequence shares significant sequence similarity with the Drosophila kinesin-73 motor protein. GAKIN sequence contains a motor domain at the NH, terminus, a central stalk domain, and a putative microtubule-interacting sequence called the CAP-Gly domain at the COOH terminus, Among the MAGUK superfamily of proteins examined, GAKIN binds to the guanylate kinase-like domain of PSD-95 but not of p55. The hDlg and GAKIN are localized mainly in the cytoplasm of resting T lymphocytes, however, upon CD2 receptor cross-linking the hDlg can translocate to the lymphocyte cap. We propose that the GAKIN-hDlg interaction lays the foundation for a general paradigm of coupling MAGUKs to the microtubule-based cytoskeleton, and that this interaction may be functionally important for the intracellular trafficking of MAGUKs and associated protein complexes in vivo. C1 Tufts Univ, Sch Med, St Elizabeths Med Ctr, Sect Hematol Oncol Res,Dept Med, Boston, MA 02135 USA. Tufts Univ, Sch Med, St Elizabeths Med Ctr, Sect Hematol Oncol Res,Dept Anat, Boston, MA 02135 USA. Tufts Univ, Sch Med, St Elizabeths Med Ctr, Sect Hematol Oncol Res,Dept Cellular Biol, Boston, MA 02135 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RP Chishti, AH (reprint author), Tufts Univ, Sch Med, St Elizabeths Med Ctr, Sect Hematol Oncol Res,Dept Med, CBR 404,736 Cambridge St, Boston, MA 02135 USA. FU NIAID NIH HHS [AI21226] NR 90 TC 100 Z9 105 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 15 PY 2000 VL 275 IS 37 BP 28774 EP 28784 DI 10.1074/jbc.M000715200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 354KY UT WOS:000089330700059 PM 10859302 ER PT J AU D'Amico, AV Whittington, R Malkowicz, SB Wu, YH Chen, MH Hurwitz, M Kantoff, PW Tomaszewski, JE Renshaw, AA Wein, A Richie, JP AF D'Amico, AV Whittington, R Malkowicz, SB Wu, YH Chen, MH Hurwitz, M Kantoff, PW Tomaszewski, JE Renshaw, AA Wein, A Richie, JP TI Utilizing predictions of early prostate-specific antigen failure to optimize patient selection for adjuvant systemic therapy trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; CANCER; PROGRESSION; RECURRENCE; CARCINOMA; SURVIVAL AB Purpose: Prostate-specific antigen (PSA)failure within 2 years after radical prostatectomy (RP) has been shown to be a clinically significant predictor of distant failure. This study was performed to estimate 2-year PSA failure rates on the basis of readily available clinical and pathologic factors to identify patients for whom effective adjuvant systemic therapy is needed. Patients and Methods: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies, PSA level, and the pathologic findings at RP in 1,728 men provided clinically relevant information about PSA outcome after RP, A bootstrapping technique with 2,000 replications was used to provide 95% confidence intervals for the predicted 2-year PSA failure rates, which were determined on the basis of the independent clinical and pathologic predictors of PSA outcome. Results: The independent predictors of time to PSA failure included a percentage of positive prostate biopsies of greater than 34% (P less than or equal to .009), PSA level greater than 10 ng/mL (P less than or equal to .01), seminal vesicle invasion (P = .02), prostatectomy Gleason score of 8 to 10 (P = .04), and positive surgical margins (P = .0001). Predictions of 2-year PSA failure rates and bootstrap estimates of the 95% confidence intervals ware arranged in a tabular format, stratified by independent clinical and pathologic predictors of PSA outcome. Conclusion: Patients who are most likely to benefit from effective adjuvant systemic therapy after RP can be identified using readily available clinical and pathologic data. (C) 2000 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Therapy, 75 Francis St,L-2 Level, Boston, MA 02115 USA. NR 22 TC 38 Z9 39 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 SEP 15 PY 2000 VL 18 IS 18 BP 3240 EP 3246 PG 7 WC Oncology SC Oncology GA 356FQ UT WOS:000089433700006 PM 10986056 ER PT J AU Earle, CC Chapman, RH Baker, CS Bell, CM Stone, PW Sandberg, EA Neumann, PJ AF Earle, CC Chapman, RH Baker, CS Bell, CM Stone, PW Sandberg, EA Neumann, PJ TI Systematic overview of cost-utility assessments in oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID METASTATIC BREAST-CANCER; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; EFFECTIVENESS LEAGUE TABLES; DECISION-ANALYSIS MODEL; CELL LUNG-CANCER; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; ECONOMIC-ANALYSES; EFFICACY AB Purpose: Cost-utility analyses (CUAs) present the value of an intervention as the ratio of its incremental cost divided by its incremental survival benefit, with survival weighted by utilities to produce quality-adjusted life years (QALYs). We critically reviewed the CUA literature and its role in informing clinical oncology practice, research priorities, and policy. Methods: The English-language literature was searched between 1975 and 1997 for CUAs, Two readers abstracted from each article descriptions of the clinical situation and patients, the methods used, study perspective, the measures of effectiveness, costs included, discounting, and whether sensitivity analyses were performed. The readers then made subjective quality assessments, We also extracted utility values from the reviewed papers, along with information on how and from whom utilities were measured. Results: Our search yielded 40 studies, which described 263 health states and presented 89 cost-utility ratios. Both the number and quality of studies increased over time. However, many studies are at variance with current standards, Only 20% of studies took ct societal perspective, more than a third failed to discount both the costs and QALYs, and utilities were often simply estimates from the investigators or other physicians. Conclusion: The cost-utility literature in oncology is not large but is rapidly expanding. There remains much room for improvement in the methodological rigor with which utilities are measured. Considering quality-of-life effects by incorporating utilities into economic studies is particularly important in oncology, where many therapies obtain modest improvements in response or survival at the expense of nontrivial toxicity. (C) 2000 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Harvard Ctr Risk Anal, Program Econ Evaluat Med Technol, Boston, MA USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Adult Oncol, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. RI Bell, Chaim/C-4611-2015 OI Bell, Chaim/0000-0002-3778-9469 NR 73 TC 209 Z9 209 U1 1 U2 17 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 SEP 15 PY 2000 VL 18 IS 18 BP 3302 EP 3317 PG 16 WC Oncology SC Oncology GA 356FQ UT WOS:000089433700014 PM 10986064 ER PT J AU Rosenzweig, M Connole, M Forand-Barabasz, A Tremblay, MP Johnson, RP Lackner, AA AF Rosenzweig, M Connole, M Forand-Barabasz, A Tremblay, MP Johnson, RP Lackner, AA TI Mechanisms associated with thymocyte apoptosis induced by simian immunodeficiency virus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFECTED RHESUS-MONKEYS; SCID-HU MOUSE; CELLS; INDUCTION; THYMUS; NEF; EXPRESSION; DEPLETION; AIDS; DIFFERENTIATION AB Despite considerable research, the mechanisms by which HIV disrupts thymic function remain controversial. We have described the phenotypic changes that occur in the thymus of SIV-infected macaques during acute SIV infection, In this study, we analyzed the effects of SIV infection on apoptotic pathways in thymic tissue from newborn macaques infected with SIV, Thymocyte apoptosis was accompanied by a modest increase in surface Fas expression, a profound decrease in the frequency of bcl-2-positive cells, as well as the amount of bcl-2 per cell. With control of viral replication, levels of bcl-2 and Fas returned to baseline together with a return to basal levels of apoptosis, In the thymus, SIV infection resulted in depletion of CD4(+)CD8(+) thymocytes, an increase in apoptosis of thymocytes, and a down-regulation of MHC class I molecules, These changes peaked 14-21 days after infection at or just after peak viremia, This data further suggests disruption of the antiapoptotic pathway regulated by bcl-2 plays a critical role in SIV-induced apoptosis of thymocytes. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Pathol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Rosenzweig, M (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR-00168]; NIAID NIH HHS [AI-139423]; NINDS NIH HHS [NS-30763] NR 31 TC 32 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 2000 VL 165 IS 6 BP 3461 EP 3468 PG 8 WC Immunology SC Immunology GA 384JB UT WOS:000165938100071 PM 10975867 ER PT J AU Matsushita, K Wu, YQ Qiu, JH Lang-Lazdunski, L Hirt, L Waeber, C Hyman, BT Yuan, JY Moskowitz, MA AF Matsushita, K Wu, YQ Qiu, JH Lang-Lazdunski, L Hirt, L Waeber, C Hyman, BT Yuan, JY Moskowitz, MA TI Fas receptor and neuronal cell death after spinal cord ischemia SO JOURNAL OF NEUROSCIENCE LA English DT Article DE caspase-8; caspase-3; spinal cord ischemia; Fas; DISC; cell death ID SIGNALING COMPLEX DISC; CYTOCHROME-C; CEREBRAL-ISCHEMIA; DNA FRAGMENTATION; INDUCED APOPTOSIS; ACTIVATION; CASPASE-8; PROTEASE; INDUCTION; NECROSIS AB Cell death from spinal cord injury is mediated in part by apoptotic mechanisms involving downstream caspases (e.g., caspase-3). Upstream mechanisms may involve other caspases such as procaspase-8, a 55 kDa apical caspase, which we found constitutively expressed within spinal cord neurons along with Fas. As early as 1.5 hr after transient ischemia, activated caspase-8 (p18) and caspase-8 mRNA appeared within neurons in intermediate gray matter and in medial ventral horn. We also detected evidence for an increase in death receptor complex by co-immunoprecipitation using Fas and anti-procaspase-8 after ischemia. At early time points, Fas and p18 were co-expressed within individual neurons, as were activated caspase-8 and caspase-3. Moreover, we detected p18 in cells before procaspase-3 cleavage product (p20), suggesting sequential activation. The appearance of cytosolic cytochrome c and gelsolin cleavage after ischemia was consistent with mitochondrial release and caspase-3 activation, respectively. Numerous terminal deoxynucleotidyl transferase-mediated DNA nick end-labeling-positive neurons contained p18 or p20 (65 and 80%, respectively), thereby supporting the idea that cells undergoing cell death contain both processed caspases. Our data are consistent with the idea that transient spinal cord ischemia induces the formation of a death-inducing signaling complex, which may participate in caspase-8 activation and sequential caspase-3 cleavage. Death receptors as well as downstream caspases may be useful therapeutic targets for limiting the death of cells in spinal cord. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02129 USA. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009; Hirt, Lorenz/G-3553-2010 OI Waeber, Christian/0000-0001-6078-0027; Hirt, Lorenz/0000-0002-2921-5000 FU NINDS NIH HHS [1 R01 NS374141, 5 P01 NS10828] NR 53 TC 94 Z9 106 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 2000 VL 20 IS 18 BP 6879 EP 6887 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 355GY UT WOS:000089379000018 PM 10995832 ER PT J AU Wang, XY Jung, JC Asahi, M Chwang, W Russo, L Moskowitz, MA Dixon, CE Fini, ME Lo, EH AF Wang, XY Jung, JC Asahi, M Chwang, W Russo, L Moskowitz, MA Dixon, CE Fini, ME Lo, EH TI Effects of matrix metalloproteinase-9 gene knock-out on morphological and motor outcomes after traumatic brain injury SO JOURNAL OF NEUROSCIENCE LA English DT Article DE brain trauma; controlled cortical impact; extracellular matrix; proteolysis; neurodegeneration; mouse ID CONTROLLED CORTICAL IMPACT; SPINAL-CORD INJURY; CENTRAL-NERVOUS-SYSTEM; KAPPA-B ACTIVATION; NEURONAL APOPTOSIS; CEREBRAL-ISCHEMIA; RAT-BRAIN; EXPRESSION; MOUSE; DEFICITS AB Matrix metalloproteinases (MMPs) belong to a class of extracellular proteinases responsible for maintaining and remodeling the extracellular matrix. In addition to multiple functions in normal physiology, abnormal MMP expression and activity may also participate in the pathophysiology of cerebral disease. Here, we show that MMP-9 (gelatinase B; EC. 3.4.24.35) contributes to the pathophysiology of traumatic brain injury. After controlled cortical impact in mice, MMP-9 was increased in traumatized brain. Total MMP-9 levels at 24 hr were significantly increased as measured by a substrate cleavage assay. Zymograms showed that MMP-9 was elevated as early as 3 hr after traumatic brain injury, reaching a maximum at aproximate 24 hr. Increased MMP-9 levels persisted for up to 1 week. Western blot analysis indicated increased profiles of MMP-9 expression that corresponded with the zymographic data. Knock-out mice deficient in MMP-9 gene expression were compared with wild-type littermates in terms of morphological and motor outcomes after trauma. Motor outcomes were measured at 1, 2, and 7 d after traumatic brain injury by the use of a rotarod device. MMP-9 knock-out mice had less motor deficits than wild-type mice. At 7 d, traumatic brain lesion volumes on Nissl-stained histological sections were significantly smaller in MMP-9 knock-out mice. These data demonstrate that MMP-9 contributes to the pathophysiology of traumatic brain injury and suggest that interruption of the MMP proteolytic cascade may be a possible therapeutic approach for preventing the secondary progression of damage after brain trauma. C1 Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA 02129 USA. Tufts Univ, Sch Med, New England Eye Ctr, Vis Res Labs, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. Univ Pittsburgh, Dept Neurol Surg, Brain Trauma Res Ctr, Pittsburgh, PA 15260 USA. RP Lo, EH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E 149 2322, Dept Neurol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [R01-NS37074, R01-NS38731, R01-NS40529] NR 54 TC 251 Z9 269 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 2000 VL 20 IS 18 BP 7037 EP 7042 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 355GY UT WOS:000089379000035 PM 10995849 ER PT J AU Wei, ML Memmott, J Screaton, C Andreadis, A AF Wei, ML Memmott, J Screaton, C Andreadis, A TI The splicing determinants of a regulated exon in the axonal MAP tau reside within the exon and in its upstream intron SO MOLECULAR BRAIN RESEARCH LA English DT Article DE MAP tau; cryptic splice sites; branch point competition; Cis determinants and trans factors in regulation of alternative splicing ID PRE-MESSENGER-RNA; TRACT-BINDING-PROTEIN; PERIPHERAL NERVOUS-SYSTEM; ALTERNATIVE 3'-SPLICE-SITE SELECTION; INHERITED DEMENTIA FTDP-17; EMBRYONAL CARCINOMA-CELLS; BRANCH POINT SELECTION; MICROTUBULE-BINDING; SR PROTEINS; SECONDARY STRUCTURE AB Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system. Exon 6 of the gene is an alternatively spliced cassette whose expression profile is distinct from that of the other tau regulated exons, implying the utilization of distinct regulatory factors, previous work had established the use of cryptic splice sites within exon 6 and the influence of flanking exons on the ratio of exon 6 variants, The present work shows that, in addition to the previously identified participants, the ratio of exon 6 isoforms is affected by: (I) suppression of the cryptic sites, (2) deletions of the upstream intron, and (3) the splicing regulators PTB and U2AF, both of which act on the branch point/polypyrimidine tract region. These results strongly suggest that factors binding immediately upstream of exon 6 are involved in regulation of this exon. They also lead to the conclusion that splicing of exon 6 is primarily governed by multiple branch points. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Eunice Kennedy Shriver Ctr Mental Retardat Inc, Dept Biomed Sci, Waltham, MA 02452 USA. John Radcliffe Hosp, Inst Mol Med, Human Immunol Grp, Oxford OX3 9DU, England. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02116 USA. Massachusetts Gen Hosp, Boston, MA 02116 USA. RP Andreadis, A (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. NR 98 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD SEP 15 PY 2000 VL 80 IS 2 BP 207 EP 218 DI 10.1016/S0169-328X(00)00137-6 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 355JG UT WOS:000089382100010 ER PT J AU Bergeron, B AF Bergeron, B TI The loyalty effect SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 SEP 15 PY 2000 VL 108 IS 4 BP A44 EP A44 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 355YK UT WOS:000089416000012 ER PT J AU Carmeliet, P Jain, RK AF Carmeliet, P Jain, RK TI Angiogenesis in cancer and other diseases SO NATURE LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; HUMAN COLON ADENOCARCINOMA; TUMOR ANGIOGENESIS; DRUG-DELIVERY; SOLID TUMORS; MICE; VESSELS; CELLS; MICROENVIRONMENT; PLASMINOGEN AB Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases. Concentrated efforts in this area of research are leading to the discovery of a growing number of pro- and anti- angiogenic molecules, some of which are already in clinical trials. The complex interactions among these molecules and how they affect vascular structure and function in different environments are now beginning to be elucidated. This integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases. But owing to several unanswered questions, caution is needed. C1 Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Carmeliet, P (reprint author), Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. EM peter.carmeliet@med.kuleuven.ac.be; jain@steele.mgh.harvard.edu RI Yin, ming/F-3737-2012 NR 75 TC 4961 Z9 5253 U1 100 U2 816 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 14 PY 2000 VL 407 IS 6801 BP 249 EP 257 DI 10.1038/35025220 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 352VX UT WOS:000089241000061 PM 11001068 ER PT J AU D'Amico, AV Schultz, D Loffredo, M Dugal, R Hurwitz, M Kaplan, I Beard, CJ Renshaw, AA Kantoff, PW AF D'Amico, AV Schultz, D Loffredo, M Dugal, R Hurwitz, M Kaplan, I Beard, CJ Renshaw, AA Kantoff, PW TI Biochemical outcome following external beam radiation therapy with or without androgen suppression therapy for clinically localized prostate cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RADICAL PROSTATECTOMY AB Context Combined treatment using radiation therapy (RT) and androgen suppression therapy (AST) is used to treat men with clinically localized adenocarcinoma of the prostate, but outcome using this combined therapy compared with RT alone is not known. Objective To determine the relative efficacy of RT plus AST vs RT alone among men with clinically localized prostate cancer. Design, Setting, and Patients Retrospective cohort study of 1586 men with prostate cancer who were treated between January 1989 and August 1999 using 3-dimensional conformal RT with (n = 276) or without (n = 1310) 6 months of AST. Main Outcome Measure Relative risk (RR) of prostate-specific antigen (PSA) failure (defined according to the American Society for Therapeutic Radiology and Oncology consensus statement), by treatment and high-, intermediate-, or low-risk group based on serum PSA level, biopsy Gleason score, and 1992 American Joint Commission on Cancer clinical tumor category. Results Estimates of 5-year PSA outcome after RT with or without AST were not statistically different among low-risk patients (P = .09), whereas intermediate- and high risk patients treated with RT plus AST had significantly better outcomes than those treated with RT alone (P < .001 and = .009, respectively). The RR of PSA failure in low-risk patients treated with RT plus AST was 0.5 (95% confidence interval [CI], 0.3-1.1) compared with patients treated with RT alone. The RRs of PSA failure in intermediate-risk and high-risk patients treated with RT plus AST compared with RT alone were 0.2 (95% CI, 0.1-0.3) and 0.4 (95% CI, 0.2-0.8), respectively. Conclusions Our data suggest a significant benefit in 5-year PSA outcomes for men with clinically localized prostate cancer in intermediate- and high-risk groups treated with RT plus AST vs those treated with RT alone. Results from prospective randomized trials currently under way are needed to validate these findings. C1 Brigham & Womens Hosp, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Millersville Univ, Dept Math, Millersville, PA 17551 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Joint Ctr Radiat Therapy, 75 Francis St,L-2 Level, Boston, MA 02115 USA. NR 12 TC 116 Z9 116 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 SEP 13 PY 2000 VL 284 IS 10 BP 1280 EP 1283 DI 10.1001/jama.284.10.1280 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 350WL UT WOS:000089124600035 PM 10979115 ER PT J AU Simons, M Bonow, RO Chronos, NA Cohen, DJ Giordano, FJ Hammond, HK Laham, RJ Li, W Pike, M Sellke, FW Stegmann, TJ Udelson, JE Rosengart, TK AF Simons, M Bonow, RO Chronos, NA Cohen, DJ Giordano, FJ Hammond, HK Laham, RJ Li, W Pike, M Sellke, FW Stegmann, TJ Udelson, JE Rosengart, TK TI Clinical trials in coronary angiogenesis: Issues, problems, consensus - An expert panel summary SO CIRCULATION LA English DT Article DE angiogenesis; coronary disease; growth substances; revascularization; clinical trials ID FIBROBLAST-GROWTH-FACTOR; COLLATERAL-DEPENDENT MYOCARDIUM; QUALITY-OF-LIFE; ENDOTHELIAL PROGENITOR CELLS; POSITRON-EMISSION-TOMOGRAPHY; TUMOR-INDUCED ANGIOGENESIS; ISCHEMIC-HEART-DISEASE; ARTERY DISEASE; GENE-TRANSFER; IN-VIVO AB The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease. C1 Harvard Univ, Sch Med, BIDMC, Angiogenesis Res Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, BIDMC, Div Cardiothorac Surg, Boston, MA 02215 USA. Northwestern Univ, Sch Med, Div Cardiol, Chicago, IL USA. Atlanta Cardiol, Atlanta, GA USA. Yale Univ, Sch Med, Div Cardiol, New Haven, CT USA. Chiron Corp, Sunnyvale, CA USA. VA Med Ctr, San Diego, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Angiogenesis Fdn, Cambridge, MA USA. Fulda Hosp, Dept Thorac & Cardiovasc Surg, Fulda, Germany. New England Med Ctr, Div Cardiol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Northwestern Univ, Evanston Hosp, Div Cardiothorac Surg, Chicago, IL 60611 USA. RP Simons, M (reprint author), Harvard Univ, Sch Med, BIDMC, Angiogenesis Res Ctr, SL-423,330 Brookline Ave, Boston, MA 02215 USA. RI Simons, Michael/G-8553-2014 OI Simons, Michael/0000-0003-0348-7734 NR 95 TC 238 Z9 249 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 12 PY 2000 VL 102 IS 11 BP E73 EP E86 PG 14 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 352PG UT WOS:000089226600001 PM 10982554 ER PT J AU Nasrin, N Ogg, S Cahill, CM Biggs, W Nui, S Dore, J Calvo, D Shi, Y Ruvkun, G Alexander-Bridges, MC AF Nasrin, N Ogg, S Cahill, CM Biggs, W Nui, S Dore, J Calvo, D Shi, Y Ruvkun, G Alexander-Bridges, MC TI DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; CARBOXYKINASE GENE-TRANSCRIPTION; HORMONE-RECEPTOR COACTIVATOR; HEPATIC NUCLEAR FACTOR-3; PHOSPHOENOLPYRUVATE CARBOXYKINASE; CAENORHABDITIS-ELEGANS; RESPONSE ELEMENT; THYROID-HORMONE; KINASE-B; ACTIVATION DOMAIN AB Insulin negatively regulates expression of the insulin-like growth factor binding protein 1 (IGFBP-1) gene by means of an insulin-responsive element (IRE) that also contributes to glucocorticoid stimulation of this gene. We find that the Caenorhabditis elegans protein DAF-16 binds the IGFBP-1 IRE with specificity similar to that of the forkhead (FKH) factor(s) that act both to enhance glucocorticoid responsiveness and to mediate the negative effect of insulin at this site. In HepG2 cells, DAF-16 and its mammalian homologs, FKHR, FKHRL1. and AFX, activate transcription through the IGFBP-1.IRE; this effect is inhibited by the viral oncoprotein E1A, but not by mutants of E1A that fail to interact with the coactivator p300/CREB-binding protein (CBP), We show that DAF-16 and FKHR can interact with both the KIX and E1A/SRC interaction domains of p300/CBP, as well as the steroid receptor coactivator (SRC). A C-terminal deletion mutant of DAF-16 that is nonfunctional in C. elegans fails to bind the KIX domain of CBP, fails to activate transcription through the IGFBP-1-IRE, and inhibits activation of the IGFBP-1 promoter by glucocorticoids. Thus, the interaction of DAF-16 homologs with the KIX domain of CBP is essential to basal and glucocorticoid-stimulated transactivation, Although AFX interacts with the KIX domain of CBP, it does not interact with SRC and does not respond to glucocorticoids or insulin. Thus, we conclude that DAF-16 and FKHR act as accessory factors to the glucocorticoid response, by recruiting the p300/CBP/SRC coactivator complex to an FKH factor site in the IGFBP-1 promoter, which allows the cell to integrate the effects of glucocorticoids and insulin on genes that carry this site. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Calif San Diego, Ludwig Inst Canc Res, San Diego, CA 92093 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Alexander-Bridges, MC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Diabet Res Unit, Wellman 306,50 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA73818-1, R01 CA073818]; NIA NIH HHS [R37 AG014161, AG05790, F32 AG005790, R01 AG014161]; NIDDK NIH HHS [T32 DK007028, T32 DK07028-24]; NIGMS NIH HHS [R01 GM058012] NR 45 TC 125 Z9 125 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 12 PY 2000 VL 97 IS 19 BP 10412 EP 10417 DI 10.1073/pnas.190326997 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 354QP UT WOS:000089341400024 PM 10973497 ER PT J AU Wilkin, DJ Liberfarb, R Davis, J Levy, HP Cole, WG Francomano, CA Cohn, DH AF Wilkin, DJ Liberfarb, R Davis, J Levy, HP Cole, WG Francomano, CA Cohn, DH TI Rapid determination of COL2A1 mutations in individuals with Stickler syndrome: Analysis of potential premature termination codons SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Stickler syndrome; COL2A1; mutation; premature termination codon ID II PROCOLLAGEN GENE; HEREDITARY ARTHRO-OPHTHALMOPATHY; SYNDROME ARTHROOPHTHALMOPATHY; LINKAGE; FAMILY; PHENOTYPES; EXCLUSION; COLLAGEN; 2A1 AB Stickler syndrome is one of the milder phenotypes resulting from mutations in the gene that encodes type-II collagen, COL2A1, All COL2A1 mutations known to cause Stickler syndrome result in the formation of a premature termination codon within the type-II collagen gene. COL2A1 has 10 inframe CGA codons, which can mutate to TGA STOP codons via a methylationdeamination mechanism. We have analyzed these sites in genomic DNA from a panel of 40 Stickler syndrome patients to test the hypothesis that mutations that cause Stickler syndrome preferentially occur at these bases. Polymerase chain reaction (PCR) amplification of genomic DNA containing each of the in-frame CGA codons was done by one of two methods: either using primers that amplify DNA that includes the CGA codon, or using allele-specific primers that either amplify normal sequence containing a CGA codon or amplify a mutant sequence containing a TGA codon, Analysis of PCR products by restriction endonuclease digestion or sequencing demonstrated the presence of a normal or mutated codon, TGA mutations were identified in eight patients, at five of the 10 in-frame CGA codons, The identification of these mutations in eight of 40 patients demonstrates that these sites are common sites for mutations in individuals with Stickler syndrome and, we propose, should be analyzed as a first step in the search for mutations that result in this disorder. Published 2000 Wiley-Liss, Inc.(dagger). C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Hosp Sick Children, Div Orthopaed, Toronto, ON M5G 1X8, Canada. Univ Calif Los Angeles, Sch Med, Dept Pediat,Cedars Sinai Res Inst, Steven Spielberg Pediat Res Ctr, Los Angeles, CA 90024 USA. RP Wilkin, DJ (reprint author), Fed Bur Invest Acad, Forens Sci Res Unit, Bldg 12,FSRU, Quantico, VA 22135 USA. NR 31 TC 13 Z9 15 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 11 PY 2000 VL 94 IS 2 BP 141 EP 148 DI 10.1002/1096-8628(20000911)94:2<141::AID-AJMG6>3.0.CO;2-A PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 345TN UT WOS:000088831400006 PM 10982970 ER PT J AU Sanders, RD Keshavan, MS Forman, SD Pieri, JN McLaughlin, N Allen, DN van Kammen, DP Goldstein, G AF Sanders, RD Keshavan, MS Forman, SD Pieri, JN McLaughlin, N Allen, DN van Kammen, DP Goldstein, G TI Factor structure of neurologic examination abnormalities in unmedicated schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 01-05, 1996 CL NEW YORK, NEW YORK SP Soc Biol Psychiat DE schizophrenia; neurological examination; factor analysis ID SOFT SIGNS AB The heterogeneity and uncertain significance of neurologic exam abnormalities in schizophrenia prompted us to evaluate their factor structure. We administered a modified version of the Neurological Evaluation Scale (NES) to 103 unmedicated patients with schizophrenia. Data were distilled by combining right- and left-side scores, and by eliminating superfluous, rarely abnormal and unreliable items from the analysis. Exploratory principal components analysis yielded four factors: repetitive motor tasks (fist-ring, fist-edge-palm, alternating fist-palm, dysdiadochokinesis); cognitive-perceptual tasks (memory, audiovisual integration, right-left orientation, face-hand test, rhythm tapping reproduction); balancing tasks (Romberg, tandem gait); and the palmomental reflex. Evaluation of the relationship between these factors and clinical and demographic variables revealed a robust correlation between the cognitive-perceptual factor and full-scale IQ score. This analysis is a step toward developing empirical subscales of a modified NES, which may provide insights into the nature of neurologic impairment in schizophrenia and may prove clinically useful. (C) 2000 Published by Elsevier Science Ireland Ltd. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div 7180, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Nevada, Las Vegas, NV 89154 USA. Robert Wood Johnson Pharmaceut Res Inst, Raritan, NJ USA. RP Goldstein, G (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div 7180, 151 R,7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 25 TC 34 Z9 34 U1 0 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 SEP 11 PY 2000 VL 95 IS 3 BP 237 EP 243 DI 10.1016/S0165-1781(00)00176-1 PG 7 WC Psychiatry SC Psychiatry GA 356VL UT WOS:000089463500006 PM 10974362 ER PT J AU Chauhan, D Pandey, P Hideshima, T Treon, S Raje, N Davies, FE Shima, Y Tai, YT Rosen, S Avraham, S Kharbanda, S Andersons, KC AF Chauhan, D Pandey, P Hideshima, T Treon, S Raje, N Davies, FE Shima, Y Tai, YT Rosen, S Avraham, S Kharbanda, S Andersons, KC TI SHP2 mediates the protective effect of interleukin-6 against dexamethasone-induced apoptosis in multiple myeloma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE PHOSPHATASES; PHOSPHOTYROSINE PHOSPHATASE; SIGNAL-TRANSDUCTION; KINASE ACTIVATION; ADHESION KINASE; PYK2; PATHWAY; IDENTIFICATION; EXPRESSION; MECHANISM AB Our previous studies have shown that activation of a related adhesion focal tyrosine kinase (RAFTK) (also known as Pyk2) is required for dexamethasone (Dex)-induced apoptosis in multiple myeloma (MM) cells and that human interleukin-6 (IL-6), a known growth and survival factor for MM cells, blocks both RAFTK activation and apoptosis induced by Dex. However, the mechanism whereby IL-6 inhibits Dex-induced apoptosis is undefined. In this study, we demonstrate that protein-tyrosine phosphatase SHP2 mediates this protective effect. me show that IL-6 triggers selective activation of SHP2 and its association with RAFTK in Dex-treated MM cells. SHP2 interacts with RAFTK through a region other than its Src homology 2 domains. We demonstrate that RAFTK is a direct substrate of SHP2 both in vitro and in vivo, and that Tyr(906) in the C-terminal domain of RAFTK mediates its interaction with SHP2. Moreover, overexpression of dominant negative SHP2 blocked the protective effect of IL-6 against Dex-induced apoptosis. These findings demonstrate that SHP2 mediates the anti-apoptotic effect of IL-6 and suggest SHP2 as a novel therapeutic target in MM. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Harvard Inst Med, Div Expt Med & Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Chicago, IL 60611 USA. RP Andersons, KC (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 50947, CA 75216] NR 36 TC 137 Z9 139 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2000 VL 275 IS 36 BP 27845 EP 27850 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 352CN UT WOS:000089197100045 PM 10880513 ER PT J AU Sawamura, N Morishima-Kawashima, M Waki, H Kobayashi, K Kuramochi, T Frosch, MP Ding, K Ito, M Kim, TW Tanzi, RE Oyama, F Tabira, T Ando, S Ihara, Y AF Sawamura, N Morishima-Kawashima, M Waki, H Kobayashi, K Kuramochi, T Frosch, MP Ding, K Ito, M Kim, TW Tanzi, RE Oyama, F Tabira, T Ando, S Ihara, Y TI Mutant presenilin 2 transgenic mice - A large increase in the levels of A beta 42 id presumably associated with the low density membrane domain that contains decreased levels of glycerophospholipids and sphingomyelin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID-BETA-PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; A-BETA; IN-VIVO; MISSENSE MUTATIONS; ANCHORED PROTEINS; TRANSFECTED CELLS; PRECURSOR PROTEIN; SENILE PLAQUES; BRAIN AB The N141I mutation in presenilin (PS) 2 is tightly linked with a form of autosomal dominant familial Alzheimer's disease in the Volga German families. We previously reported that mouse brains harboring mutant PS2 contained increased levels of amyloid beta protein (A beta) 42 in the Tris-saline-soluble fraction (Oyama, F., Sawamura, N., Kobayashi, K., Morishima-Kawashima, M., Kuramochi, T., Ito, M., Tomita, T., Maruyama, K., Saido, T. C., Iwatsubo, T., Capell, A., Waiter, J., Grunberg, J., Ueyama, Y., Haass, C. and Ihara, Y. (1998) J. Neurochem. 71, 313-322). Here, using a new extraction protocol, we quantitated the A beta 40 and A beta 42 levels in the Tris-saline-insoluble fraction. The insoluble A beta levels were found to be higher than the soluble A beta levels, and the insoluble A beta 42 levels were markedly increased in mutant PS2 transgenic mice. To investigate the origin of the insoluble A beta 42, we prepared the detergent-insoluble, low density membrane fraction. This fraction from two independent lines of mutant PS2 transgenic mice contained remarkably increased levels of A beta 42 and significantly low levels of glycerophospholipids and sphingomyelin. This unexpected finding suggests that a large increase in the levels of A beta 42 in mutant PS2 mice is presumably induced through alterations of the lipid composition in the low density membrane domain in the brain. C1 Univ Tokyo, Fac Med, Dept Neuropathol, Bunkyo Ku, Tokyo 1130033, Japan. Tokyo Metropolitan Inst Gerontol, Dept Membrane Biochem, Itabashi Ku, Tokyo 1730015, Japan. Cent Inst Expt Anim, Miyamae Ku, Kawasaki, Kanagawa 2160001, Japan. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Div Neuropathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Natl Inst Neurosci, Natl Ctr Neurol & Psychiat, Dept Demyelinating Dis & Aging, Tokyo 1878502, Japan. Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Kawaguchi 3320012, Japan. RP Ihara, Y (reprint author), Univ Tokyo, Fac Med, Dept Neuropathol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. NR 62 TC 69 Z9 72 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 8 PY 2000 VL 275 IS 36 BP 27901 EP 27908 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 352CN UT WOS:000089197100052 PM 10846187 ER PT J AU von Boehmer, H AF von Boehmer, H TI T-cell lineage fate: Instructed by receptor signals? SO CURRENT BIOLOGY LA English DT Article ID CD4; EXPRESSION; SELECTION; ANTIGEN; HELPER AB Mechanisms of lineage choice represent a challenging problem in developmental biology. Recent studies have shown that different T-cell receptor signals can affect CD4 or CD8 lineage choice. Thus, all the ingredients for instructive mechanisms of lineage fate are in place but other mechanisms cannot be completely ruled out. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 16 TC 8 Z9 8 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD SEP 7 PY 2000 VL 10 IS 17 BP R642 EP R645 DI 10.1016/S0960-9822(00)00665-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353YW UT WOS:000089303900011 PM 10996091 ER PT J AU Tian, M Alt, FW AF Tian, M Alt, FW TI Immunology - RNA editing meets DNA shuffling SO NATURE LA English DT Editorial Material ID CYTIDINE DEAMINASE C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02119 USA. Ctr Blood Res, Boston, MA 02119 USA. RP Tian, M (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02119 USA. NR 8 TC 3 Z9 3 U1 1 U2 1 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD SEP 7 PY 2000 VL 407 IS 6800 BP 31 EP 33 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 350WE UT WOS:000089124000026 PM 10993058 ER PT J AU Shifren, JL Braunstein, GD Simon, JA Casson, PR Buster, JE Redmond, GP Burki, RE Ginsburg, ES Rosen, RC Leiblum, SR Caramelli, KE Mazer, NA Jones, KP Daugherty, CA AF Shifren, JL Braunstein, GD Simon, JA Casson, PR Buster, JE Redmond, GP Burki, RE Ginsburg, ES Rosen, RC Leiblum, SR Caramelli, KE Mazer, NA Jones, KP Daugherty, CA TI Transdermal testosterone treatment in women with impaired sexual function after oophorectomy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; MENOPAUSAL WOMEN; ANDROGEN; LIFE AB Background The ovaries provide approximately half the circulating testosterone in premenopausal women. After bilateral oophorectomy, many women report impaired sexual functioning despite estrogen replacement. We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause. Methods Seventy-five women, 31 to 56 years old, who had undergone oophorectomy and hysterectomy received conjugated equine estrogens (at least 0.625 mg per day orally) and, in random order, placebo, 150 mu g of testosterone, and 300 mu g of testosterone per day transdermally for 12 weeks each. Outcome measures included scores on the Brief Index of Sexual Functioning for Women, the Psychological General Well-Being Index, and a sexual-function diary completed over the telephone. Results The mean (+/- SD) serum free testosterone concentration increased from 1.2 +/- 0.8 pg per milliliter (4.2 +/- 2.8 pmol per liter) during placebo treatment to 3.9 +/- 2.4 pg per milliliter (13.5 +/- 8.3 pmol per liter) and 5.9 +/- 4.8 pg per milliliter (20.5 +/- 16.6 pmol per liter) during treatment with 150 and 300 mu g of testosterone per day respectively (normal range, 1.3 to 6.8 pg per milliliter [4.5 to 23.6 pmol per liter]). Despite an appreciable placebo response, the higher testosterone dose resulted in further increases in scores for frequency of sexual activity and pleasure orgasm in the Brief Index of Sexual Functioning for Women (P = 0.03 for both comparisons with placebo). At the higher dose, the percentages of women who had sexual fantasies masturbated, or engaged in sexual intercourse at least once a week increased two to three times from base line. The positive-well-being, depressed-mood, and composite scores of the Psychological General Well-Being Index also improved at the higher dose (P = 0.04, P = 0.03, and P = 0.04, respectively, for the comparison with placebo), but the scores on the telephone-based diary did not increase significantly. Conclusions In women who have undergone oophorectomy and hysterectomy transdermal testosterone improves sexual function and psychological well-being. (N Engl J Med 2000; 343: 682-8.) (C) 2000, Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Dept Obstet & Gynecol, Boston, MA 02114 USA. Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA. Womens Hlth Res Ctr, Laurel, MD USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Fdn Dev Endocrinol, Cleveland, OH USA. Brigham & Womens Hosp, Ctr Reprod Med, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, Piscataway, NJ 08854 USA. Watson Labs, Dept Clin Res, Salt Lake City, UT USA. Univ Utah, Med Ctr, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. Abesta Corp, Salt Lake City, UT USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Dept Obstet & Gynecol, VBK-113, Boston, MA 02114 USA. NR 25 TC 520 Z9 532 U1 2 U2 12 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 SEP 7 PY 2000 VL 343 IS 10 BP 682 EP 688 DI 10.1056/NEJM200009073431002 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 350KU UT WOS:000089100500002 PM 10974131 ER PT J AU Grinspoon, S Corcoran, C Parlman, K Costello, M Rosenthal, D Anderson, E Stanley, T Schoenfeld, D Burrows, B Hayden, D Basgoz, N Klibanski, A AF Grinspoon, S Corcoran, C Parlman, K Costello, M Rosenthal, D Anderson, E Stanley, T Schoenfeld, D Burrows, B Hayden, D Basgoz, N Klibanski, A TI Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting - A randomized, controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NANDROLONE DECANOATE; WEIGHT; BODY AB Background: Substantial loss of muscle mass occurs among men with AIDS wasting. Objective: To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting. Design: Randomized, controlled trial. Setting: University hospital. Patients: 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%). Intervention: In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks. Measurements: Cross-sectional muscle area and other indices of muscle mass. Results: Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm(2) vs. 206 +/- 264 mm(2) [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm(2) vs. 523 +/- 872 mm(2) [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm(2) vs. 194 +/- 215 mm(2) [P < 0.001]; change in leg muscle mass, 1236 +/- 881 mm(2) vs. 399 +/- 729 mm(2) [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P = 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052). Conclusions: In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Vet Adm Med Ctr, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [P32-DK07028, R01-DK49302] NR 20 TC 121 Z9 123 U1 0 U2 1 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 SEP 5 PY 2000 VL 133 IS 5 BP 348 EP 355 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 350QD UT WOS:000089111900004 PM 10979879 ER PT J AU Anzueto, A Angel, L AF Anzueto, A Angel, L TI Update in pulmonary disease SO ANNALS OF INTERNAL MEDICINE LA English DT Review C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Affairs Hlth Care Syst, San Antonio, TX USA. RP Anzueto, A (reprint author), Vet Affairs Med Ctr, 111E,7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 5 PY 2000 VL 133 IS 5 BP 360 EP 366 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 350QD UT WOS:000089111900006 PM 10979881 ER PT J AU Collins, MM MacDonald, R Wilt, TJ AF Collins, MM MacDonald, R Wilt, TJ TI Diagnosis and treatment of chronic abacterial prostatitis: A systematic review SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CHRONIC IDIOPATHIC PROSTATITIS; NON-BACTERIAL PROSTATITIS; PELVIC PAIN SYNDROME; NONBACTERIAL PROSTATITIS; DOUBLE-BLIND; ULTRASONOGRAPHIC FINDINGS; PHYSICIAN VISITS; NATIONAL SURVEY; SYMPTOM INDEX; YOUNGER MEN AB Purpose: The optimal management of chronic abacterial prostatitis is not known. A systematic review of the literature was done to answer the following questions: Are there accurate, reliable tests to diagnose chronic abacterial prostatitis? Are there effective therapies for it? Data Sources: Studies were identified by searching MEDLINE (1966 to 1999), the Cochrane Library, and bibliographies of identified articles and reviews and by contacting an expert. Study Selection: Diagnostic test articles were included if they reported on controlled studies; treatment articles were included if they reported on randomized or controlled trials. No language restrictions were applied. Data Extraction: For each selected article, two investigators independently extracted key data on study design, patient characteristics, diagnostic test or treatment characteristics, and outcomes. Data Synthesis: 19 diagnostic test articles and 14 treatment trials met the inclusion criteria. The disparity among studies in design, interventions, and other factors precluded quantitative analysis or pooling of the findings. Diagnostic test articles included 1384 men (mean age, 33 to 67 years) and evaluated infection; inflammation, immunology, and biochemistry; psychological factors; and ultrasonography. Treatment trials included 570 men (mean age, 38 to 45 years) and evaluated medications used to treat benign prostatic hyperplasia, anti-inflammatory drugs, antibiotics, thermotherapy, and miscellaneous medications. No trial was done in the United States. Conclusions: There is no gold-standard diagnostic test for chronic abacterial prostatitis, and the methodologic quality of available studies of diagnostic tests is low. The few treatment trials are methodologically weak and involved small samples. The routine use of antibiotics acid alpha-blockers to treat chronic abacterial prostatitis is not supported by the existing evidence. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res 1110, Vet Affairs Coordinating Ctr Cochrane Review Grp, Minneapolis, MN 55417 USA. Minneapolis Vet Affairs Ctr Chron Dis Outcomes Re, Minneapolis, MN USA. RP Wilt, TJ (reprint author), Vet Affairs Med Ctr, Ctr Chron Dis Outcomes Res 1110, Vet Affairs Coordinating Ctr Cochrane Review Grp, 1 Vet Dr, Minneapolis, MN 55417 USA. FU AHRQ HHS [HS 08397]; NIDDK NIH HHS [DK53736] NR 89 TC 66 Z9 70 U1 0 U2 1 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 SEP 5 PY 2000 VL 133 IS 5 BP 367 EP 381 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 350QD UT WOS:000089111900007 PM 10979882 ER PT J AU Robinson, BR Houng, AK Reed, GL AF Robinson, BR Houng, AK Reed, GL TI Catalytic life of activated factor XIII in thrombi - Implications for fibrinolytic resistance and thrombus aging SO CIRCULATION LA English DT Article DE embolism; fibrinolysis; thrombus ID EXPERIMENTAL PULMONARY-EMBOLISM; COAGULATION-FACTOR-XIII; CROSS-LINKING; ALPHA-2-PLASMIN INHIBITOR; INCREASES; PEPTIDE AB Background-Because the increased fibrinolytic resistance of older thrombi may be caused by the continuous cross-linking action of fibrin-bound activated factor XIII (FXIIIa), we examined the persistence of FXIIIa catalytic activity in clots of various ages. Methods and Results-The time-related changes in FXIIIa activity in clots was measured with (1) alpha(2) -antiplasmin (alpha(2)AP), a physiological glutamine substrate; (2) alpha(2)AP(13-24) a peptide; and (3) pentylamine, a nonspecific lysine substrate. The cross-linking of a(2)AP, alpha(2)AP(13-24,) and pentylamine into fibrin by clot-bound FXIIIa declined rapidly with half-lives of 19, 21, and 26 minutes, respectively. Mutational studies showed that glutamine 14 (but not glutamine 3 or 16) and valine 17 of alpha(2)AP(13-24) were required for efficient cross-linking to fibrin. The loss of activity was not due primarily to FXIIIa proteolysis and was partially restored by reducing agents, suggesting that oxidation contributes to the loss of the enzyme's activity in clots. In vivo, the ability of thrombus-bound FXIIIa to cross-link an infused alpha(2)AP(13-24) peptide into existing pulmonary emboli also declined significantly over time. Conclusions-FXIIIa cross-links alpha(2)AP and an alpha(2),AP peptide, in a sequence-specific manner, into formed clots with a catalytic half-life of approximate to 20 minutes. This indicates that FXIIIa activity is a hallmark of new thrombi and that the antifibrinolytic cross-linking effects of FXIIIa are achieved more rapidly in thrombi than previously believed. C1 Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reed, GL (reprint author), Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, 677 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-57314, HL-58496] NR 25 TC 34 Z9 35 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 5 PY 2000 VL 102 IS 10 BP 1151 EP 1157 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 351KY UT WOS:000089157400015 PM 10973845 ER PT J AU Jones, GB Mitchell, MO Weinberg, JS D'Amico, AV Bubley, GJ AF Jones, GB Mitchell, MO Weinberg, JS D'Amico, AV Bubley, GJ TI Towards enzyme activated antiprostatic agents SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; CANCER; PRODRUGS; DESIGN AB A prodrug conjugate designed to undergo activation by enzymatic prostate specific antigen has been synthesized, The prodrug system undergoes activation with PSA or alpha-chymotrypsin, and shows selective cytotoxicity in a PSA secreting cell line. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Northeastern Univ, Dept Chem, Bioorgan & Med Chem Labs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Jones, GB (reprint author), Northeastern Univ, Dept Chem, Bioorgan & Med Chem Labs, Boston, MA 02115 USA. NR 15 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD SEP 4 PY 2000 VL 10 IS 17 BP 1987 EP 1989 DI 10.1016/S0960-894X(00)00386-3 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 349GH UT WOS:000089037000022 PM 10987433 ER PT J AU Billings, JA AF Billings, JA TI Recent advances - Palliative care SO BRITISH MEDICAL JOURNAL LA English DT Review ID ILL HOSPITALIZED-PATIENTS; TERMINALLY ILL; DEATH; LIFE; END; MANAGEMENT; ONCOLOGY; OUTCOMES; SUPPORT; TRIAL C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Founders 600,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [R25 CA066818, R25 CA 66818-04] NR 40 TC 27 Z9 28 U1 2 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD SEP 2 PY 2000 VL 321 IS 7260 BP 555 EP 558 DI 10.1136/bmj.321.7260.555 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 351TK UT WOS:000089174100024 PM 10968822 ER PT J AU Rhodes, KV Gordon, JA Lowe, RA AF Rhodes, KV Gordon, JA Lowe, RA CA Soc Acad Emergency Med Public Hlth TI Preventive care in the emergency department, part I: Clinical preventive services - Are they relevant to emergency medicine? SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE preventive services; emergency medicine; evidence-based medicine; practice guidelines; prevention research ID DOMESTIC VIOLENCE; INTERVENTION; SURVEILLANCE; IMMUNIZATION; POPULATION; QUESTIONS; INFLUENZA; ACCESS; WOMEN; COSTS AB In 1998 the Society for Academic Emergency Medicine's (SAEM's) Board of Directors asked the SAEM Public Health and Education Task Force to develop recommendations for prevention, screening, and counseling activities to be conducted in emergency departments (EDs). The Task Force's work was divided into two phases: 1) a discussion of the rationale for preventive services in the ED, along with generation of a preliminary list of prevention activities that could be studied for ED implementation; and 2) a formal evidence-based review of topics chosen from the preliminary list, along with recommendations for ED implementation and further study. This paper represents Phase I of the project. Phase II, the formal evidence-based review and recommendations, is published separately in this issue. C1 Univ Chicago, Med Ctr, Robert Wood Johnson Clin Scholars Program, Chicago, IL 60637 USA. Univ Chicago, Med Ctr, Sect Emergency Med, Chicago, IL 60637 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Emergency Med, Dept Emergency Med, Boston, MA USA. Univ Penn, Sch Med,Leonard Davis Inst Hlth Econ, Ctr Clin Epidemiol & Biostat, Dept Emergency Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med,Leonard Davis Inst Hlth Econ, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Rhodes, KV (reprint author), Univ Chicago, Med Ctr, Robert Wood Johnson Clin Scholars Program, 5841 S Maryland,MC 2007,B-234, Chicago, IL 60637 USA. NR 35 TC 108 Z9 109 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD SEP PY 2000 VL 7 IS 9 BP 1036 EP 1041 PG 6 WC Emergency Medicine SC Emergency Medicine GA 355BG UT WOS:000089365300012 PM 11044001 ER PT J AU Riess, H Fishel, AK AF Riess, H Fishel, AK TI The necessity of continuing education for psychotherapy supervisors SO ACADEMIC PSYCHIATRY LA English DT Article ID PSYCHIATRY; FUTURE AB Over the past decade, the practice of neurobiology has come to dominate hospital-based psychotherapy, and the teaching of psychotherapy has become marginalized in psychiatry residency programs across the country. As a result, psychotherapy supervisors must play an increasingly important role in maintaining the viability of this discipline. Moreover, because the supervisory relationship is the main way that trainees develop their identity ns psychotherapists, supervisors' development of knowledge and skill is critical to their role as mentor The authors describe a symposium? and lecture series for trainee supervisors that enabled them to come together and offer a forum for a lively exchange of ideas and information. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Riess, H (reprint author), Wang Ambulatory Care Ctr, Suite 708,15 Parkman St, Boston, MA 02114 USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FAL PY 2000 VL 24 IS 3 BP 147 EP 155 DI 10.1176/appi.ap.24.3.147 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 349JK UT WOS:000089041800006 ER PT J AU Mischoulon, D Rosenbaum, JF Messner, E AF Mischoulon, D Rosenbaum, JF Messner, E TI Transfer to a new psychopharmacologist - Its effect on patients SO ACADEMIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 151st Annual Meeting of the American-Psychiatric-Association CY MAY 30-JUN 05, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID FORCED TERMINATIONS AB The authors surveyed 38 psychiatry residents to determine the effect of end-of-residency transfer of care all psychopharmacology patients. Senior residents reported that 19% of patients worsened after notification about the upcoming transfer, 32% required medication changes, and up to 9% became noncompliant. Junior residents reported that, after transfer, 10% of patients worsened, 7% required medication changes, and up to 12% became noncompliant. Approximately 29% of patients considered the change of residents a major treatment disruption. The authors propose a system for minimizing deleterious effects and improving outcome in the transfer of psychopharmacology patients. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, WAC-812,15 Parkman St, Boston, MA 02114 USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FAL PY 2000 VL 24 IS 3 BP 156 EP 163 DI 10.1176/appi.ap.24.3.156 PG 8 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 349JK UT WOS:000089041800007 ER PT J AU Bremer, J Beresin, EV AF Bremer, J Beresin, EV TI Computers in psychiatry today SO ACADEMIC PSYCHIATRY LA English DT Article ID SKILLS; GAMES C1 Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Bremer, J (reprint author), Univ Chicago, Dept Psychiat, 5841 S Maryland Ave,MC 3077, Chicago, IL 60637 USA. NR 19 TC 8 Z9 8 U1 1 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD FAL PY 2000 VL 24 IS 3 BP 168 EP 172 DI 10.1176/appi.ap.24.3.168 PG 5 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 349JK UT WOS:000089041800009 ER PT J AU Biederman, J Mick, E Faraone, SV Spencer, T Wilens, T Wozniak, J AF Biederman, J Mick, E Faraone, SV Spencer, T Wilens, T Wozniak, J TI Pediatric mania: a developmental subtype of bipolar disorder? SO ACTA NEUROPSYCHIATRICA LA English DT Article C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MISSET UITGEVERIJI BV PI MAARSSEN PA POSTBUS 1110, 3600 BC MAARSSEN, NETHERLANDS SN 0924-2708 J9 ACTA NEUROPSYCHIATR JI Acta Neuropsychiatr. PD SEP PY 2000 VL 12 IS 3 BP 131 EP 131 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 357QC UT WOS:000089511500018 PM 26975271 ER PT J AU Hausler, R Levine, RA AF Hausler, R Levine, RA TI Auditory dysfunction in stroke SO ACTA OTO-LARYNGOLOGICA LA English DT Review DE auditory system; hearing evaluation; stroke; central hearing loss; tinnitus; sound localization; auditory hallucination; cortical deafness ID BRAIN-STEM LESIONS; MULTIPLE-SCLEROSIS; EVOKED-POTENTIALS; CLINICAL SYNDROMES; CEREBELLAR ARTERY; DISCRIMINATION; HEARING; LATERALIZATION; INFARCTION; HALLUCINATIONS AB The auditory and vestibular systems share the same end organ and cranial nerve, yet vestibular signs and symptoms are common with stroke, whereas hearing disturbances are much less frequent. Several reasons would appear to account For this striking dissimilarity. One is that the auditory pathway is less ubiquitous than the vestibular pathways. The likelihood that a stroke involves the auditory pathway is, therefore, less on this basis alone. A second difference, to our knowledge not previously reported, is that the auditory pathway is often spared by the most common strokes. This is because major parts of the auditory pathway, such as the cochlear nucleus, inferior colliculus and medial geniculate body, have multiple sources of blood supply. A third well-recognized factor is the redundancy of the central auditory system and its strong bilateral representation above the level of the cochlear nuclei. Consequently, rostral to the cochlear nuclei gross deficits in hearing, such as those measured by standard pure-tone audiometry and speech discrimination, only occur if lesions are bilateral. Furthermore, widespread bilateral lesions of the auditory system typically render the patient unable to respond or are incompatible with life. In contrast, language disorders are more frequent because language is usually unilaterally represented in the cortex. Certainly, cerebral stroke often includes the auditory system, resulting in various types of auditory disorders, but most hemispherical lesions produce subtle hearing dysfunctions that can only be detected with sophisticated psychoacoustic acid electrophysiological testing. The purpose of this review is to provide an overview of the auditory system and its blood supply and to review how auditory processing can be affected by stroke. Psychoacoustic and electrophysiological test procedures for identifying lesions in the central auditory system are described. The literature of hearing disorders due to stroke is reviewed and illustrative cases are presented. C1 Univ Bern, Inselspital, Dept ENT Head & Neck Surg, CH-3010 Bern, Switzerland. Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Massachusetts Gen Hosp,Auditory Neurol Unit, Boston, MA USA. RP Hausler, R (reprint author), Univ Bern, Inselspital, Dept Otorhinolaryngol Head & Neck & Craniomaxillo, CH-3010 Bern, Switzerland. NR 100 TC 49 Z9 53 U1 0 U2 6 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD SEP PY 2000 VL 120 IS 6 BP 689 EP 703 PG 15 WC Otorhinolaryngology SC Otorhinolaryngology GA 366WK UT WOS:000090029100002 PM 11099144 ER PT J AU Mataix-Cols, D Baer, L Rauch, SL Jenike, MA AF Mataix-Cols, D Baer, L Rauch, SL Jenike, MA TI Relation of factor-analyzed symptom dimensions of obsessive-compulsive disorder to personality disorders SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE comorbidity; factor analysis; obsessive-compulsive disorder; personality disorders; symptom dimensions AB Objective: To assess the relation between symptom dimensions of obsessive-compulsive disorder (OCD) and comorbid personality disorders (PDs). Method: The scores of 75 OCD outpatients on five previously identified symptom dimensions were entered into multiple regression models as predictors of: 1) the presence of any type of PD; 2) the number of PDs; 3) the presence of any cluster A, B or C PD; and 4) the presence of each individual PD. Results: Twenty-eight patients (37.3%) met criteria for one or more PDs. High scores on the 'Hoarding' dimension were strongly related to the presence of any Axis II diagnosis, and to the number of PDs. Cluster C PDs (especially obsessive-compulsive and avoidant) had the highest partial correlations with 'Hoarding'. These results were independent of OCD symptom severity. Conclusion: Previous conflicting findings about the prevalence of certain PDs in OCD might be due in part to differences in the constitution of the particular patient groups studied. C1 Univ Barcelona, Dept Psiquiatria & Psicobiol Clin, E-08035 Barcelona, Spain. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. RP Mataix-Cols, D (reprint author), Univ Barcelona, Dept Psiquiatria & Psicobiol Clin, Passeig de la Vall dHebron 171, E-08035 Barcelona, Spain. RI Mataix-Cols, David/G-3843-2010 OI Mataix-Cols, David/0000-0002-4545-0924 NR 19 TC 77 Z9 78 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. PD SEP PY 2000 VL 102 IS 3 BP 199 EP 202 DI 10.1034/j.1600-0447.2000.102003199.x PG 4 WC Psychiatry SC Psychiatry GA 349RD UT WOS:000089058600007 PM 11008855 ER PT J AU Oliva, E Clement, PB Young, RH AF Oliva, E Clement, PB Young, RH TI Endometrial stromal tumors: An update on a group of tumors with a protean phenotype SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE endometrial stromal nodule; endometrial stromal sarcoma; high-grade endometrial sarcoma; uterine tumor resembling ovarian sex-cord tumor; highly cellular leiomyoma; immunohistochemistry ID FLOW CYTOMETRIC ANALYSIS; SMOOTH-MUSCLE TUMORS; CORD-LIKE DIFFERENTIATION; IN-SITU HYBRIDIZATION; GRANULOSA-CELL TUMORS; LOW-GRADE; MESENCHYMAL TUMORS; UTERINE-TUMORS; INTRAVENOUS LEIOMYOMATOSIS; CLINICOPATHOLOGIC ANALYSIS AB Endometrial stromal tumors are reviewed with emphasis on their wide morphologic spectrum and problems in differential diagnosis, highlighting issues that have received particular attention in the recent literature. These neoplasms are divided into two major categories-endometrial stromal nodules and endometrial stromal sarcomas-a distinction made on the basis of the lack of significant infiltration at the periphery of the former. The division of endometrial stromal sarcomas into low-grade and high-grade categories has fallen out of favor and the designation endometrial stromal sarcoma is now considered best restricted to neoplasms that were formally referred to as "low-grade" stromal sarcoma. Endometrial sarcomas without recognizable evidence of a definite endometrial stromal phenotype, designated poorly differentiated "endometrial sarcomas," are almost invariably high grade and often resemble the mesenchymal component of a malignant mullerian mixed tumor. Two features of endometrial stromal tumors that may cause confusion are smooth muscle differentiation and epithelial patterns. Cases in the former category often have a characteristic "starburst" pattern of collagen formation. The most common epithelial patterns resemble those seen in ovarian sex-cord stromal tumors. Much less common is endometrioid gland differentiation. Some endometrial stromal tumors have a prominent fibrous or myxoid appearance and the myxoid tumors should be distinguished from myxoid leiomyosarcoma. Other unusual features of endometrial stromal tumors are also discussed. Lesions in the differential diagnosis of uterine endometrial stromal neoplasms include highly cellular leiomyoma, cellular intravenous leiomyomatosis, adenomyosis with sparse glands, metastatic carcinoma, and lymphoma. Endometrial stromal sarcomas at extrauterine sites may be primary or metastatic from a uterine tumor, the latter sometimes being occult and difficult to definitively establish, particularly if there is a history of a remote hysterectomy for "leiomyomas." Endometrial stromal sarcomas of the ovary, whether primary or metastatic, may be difficult to distinguish from ovarian sex-cord stromal tumors. Extragenital endometrial stromal sarcomas may be confused with diverse lesions such as gastrointestinal stromal tumors, hemangiopericytoma, lymphangiomyomatosis, or mesenchymal cystic hamartoma of the lung. Immunohistochemistry may play a role in evaluating these tumors and in some instances establishing the diagnosis although conventional light microscopic analysis suffices in the majority of cases. The unusual tumor, the "uterine tumor resembling an ovarian sex-cord tumor," is also considered in this review as it is almost certainly of endometrial stromal derivation in many cases. These neoplasms may have a striking resemblance to granulosa cell tumors or Sertoli cell tumors, including those with a retiform pattern, and have recently been shown to be frequently inhibin positive. C1 Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol,Sch Med, Boston, MA 02114 USA. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Oliva, E (reprint author), Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol,Sch Med, 32 Fruit St, Boston, MA 02114 USA. NR 101 TC 111 Z9 113 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD SEP PY 2000 VL 7 IS 5 BP 257 EP 281 DI 10.1097/00125480-200007050-00001 PG 25 WC Pathology SC Pathology GA 348FN UT WOS:000088975000001 PM 10976906 ER PT J AU Hofmann-Lehmann, R Swenerton, RK Liska, V Leutenegger, CM Lutz, H McClure, HM Ruprecht, RM AF Hofmann-Lehmann, R Swenerton, RK Liska, V Leutenegger, CM Lutz, H McClure, HM Ruprecht, RM TI Sensitive and robust one-tube real-time reverse transcriptase-polymerase chain reaction to quantify SIV RNA load: Comparison of one- versus two-enzyme systems SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; RTTH DNA-POLYMERASE; RHESUS-MONKEYS; MESSENGER-RNA; MOLECULAR BEACONS; TYPE-1 RNA; PCR; AMPLIFICATION; MACAQUES; PRODUCT AB Plasma viral RNA load is a key parameter in disease progression of lentiviral infections. To measure simian immunodeficiency virus (SIV) RNA loads, we have established a quantitative one-tube assay based on Taq-Man chemistry. This real-time reverse transcriptase-polymerase chain reaction (RT-PCR) has advantages compared with previous methods, such as higher sensitivity, shorter time consumption, and low risk of cross-contamination. The sensitivity of the assay was optimized by comparing different enzyme systems. The one-enzyme protocol using rTth DNA polymerase was superior to two assays employing two enzymes. It detects 100% of the samples containing four copies of RNA transcript and allows quantification of viral RNA loads over an 8-log unit dynamic range. As few as 50 copies per milliliter of plasma can be detected within RNA extracted from 140 mu l of plasma. This is especially relevant in studies employing neonatal macaques, from which only small volumes of blood can be sampled, and in studies in which low viral RNA loads are expected. Because of the use of rTth DNA polymerase, DNA contamination can be avoided by carryover prevention with uracil N-glycosylase (UNG). We demonstrate that for optimization of real-time PCR sensitivity, not only concentrations of different reagents but also different enzyme systems must be evaluated. Our assay facilitates and enhances the quantification of plasma RNA loads, a critical parameter for many studies, including evaluations of vaccine candidates or antiviral regimens. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Zurich, Fac Med Vet, Dept Vet Internal Med, Clin Lab, CH-8057 Zurich, Switzerland. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St,JFB809, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 FU NIAID NIH HHS [R21-AI46177-1] NR 49 TC 128 Z9 131 U1 1 U2 2 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 SEP PY 2000 VL 16 IS 13 BP 1247 EP 1257 DI 10.1089/08892220050117014 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 347HC UT WOS:000088921400006 PM 10957722 ER PT J AU Gilbert, PB Hanna, GJ De Gruttola, V Martinez-Picado, J Kuritzkes, DR Johnson, VA Richman, DD D'Aquila, RT AF Gilbert, PB Hanna, GJ De Gruttola, V Martinez-Picado, J Kuritzkes, DR Johnson, VA Richman, DD D'Aquila, RT TI Comparative analysis of HIV type 1 genotypic resistance across antiretroviral trial treatment regimens SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIGH-LEVEL RESISTANCE; REVERSE-TRANSCRIPTASE CONTRIBUTES; POL GENE-MUTATIONS; NONNUCLEOSIDE INHIBITORS; ZIDOVUDINE RESISTANCE; PROTEASE INHIBITOR; DRUG-RESISTANCE; DOUBLE-BLIND; THERAPY AB From data on HIV-1 genotypes collected from antiretroviral trial participants who fail virologically, we describe methods for comparing distributions of acquired HIV-1 mutations across different treatment regimens. Given a definition of a "mutational distance" that summarizes the genetic change of a subject's virus in a way that captures the resistance cost of exposure to an antiretroviral regimen, these comparative analyses inform about the relative treatability of emergent virus by next-line therapy directed to the same viral target. The utility of the methods is illustrated by application to data from AIDS Clinical Trials Group (ACTG) Study 241. We find that patients failing zidovudine/didanosine/nevirapine accumulated a 2.41-fold greater nonnucleoside reverse transcriptase inhibitor (RTI) mutational distance than patients failing zidovudine/didanosine [95% confidence interval (1.55, 5.26), p< 0.000001], quantitating expectations that adding a nonnucleoside RTI to a double nucleoside regimen may attenuate future effectiveness of nonnucleoside RTI therapy for nucleoside-experienced patients if viremia is not suppressed. We also find that persons with extensive prior experience with suboptimal nucleoside therapy who were virologically failing zidovudine/ didanosine/nevirapine or zidovudine/ didanosine accumulated a similar nucleoside RTI mutational distance, implying that the addition of the nonnucleoside RTI did not preserve future nucleoside options. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Univ Germans Trias I Pujol, Fdn IrsiCaixa, Badalona, Spain. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Univ Alabama, Sch Med, Birmingham, AL 35294 USA. Vet Affairs Med Ctr, Birmingham, AL 35294 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. RP Gilbert, PB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. RI Martinez-Picado, Javier/G-5507-2012 OI Martinez-Picado, Javier/0000-0002-4916-2129 FU NIAID NIH HHS [5-RO1-AI29193, 5-U01-AI28076, 5-U01-AI38855] NR 53 TC 6 Z9 6 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 SEP PY 2000 VL 16 IS 14 BP 1325 EP 1336 DI 10.1089/08892220050140874 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 359CC UT WOS:000089593100001 PM 11018852 ER PT J AU Forman, SA Zhou, Q AF Forman, SA Zhou, Q TI Nicotinic receptor pore mutations create a sensitive inhibitory site for ethanol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE acetylcholine; alcohol; ion channel; gamma-aminobutyric acid; serotonin ID ACETYLCHOLINE-RECEPTOR; GLYCINE RECEPTORS; ANESTHETIC ACTION; CORTICAL-NEURONS; CHANNEL; MODULATION; VOLUME; ALCOHOLS; SUBUNIT; GABA(A) AB Background: Ethanol (EtOH) inhibition and enhancement of ligand-gated ion channel functions may be due to direct interactions with sites on these membrane proteins. Peripheral nicotinic receptors have pore sites that long-chain alcohols inhibit but EtOH does not, either because of weak binding (low affinity) or inability to impair ion translocation (low efficacy). We tested whether nicotinic pore mutations that increase hydrophobicity and/or size can create a site where EtOH inhibits at physiological concentrations. Methods: We studied recombinant expressed mouse muscle receptors with patch-clamp electrophysiology to measure EtOH effects both on single-channel conductance and on multichannel currents elicited with rapid agonist superfusion. We studied pairs of mutants with similar residue sizes but different hydrophobicities at position alpha 252 to determine if size or hydrophobicity determines EtOH sensitivity. Results: Inhibition of wild-type currents is seen at EtOH concentrations >300 mM. Receptors that contain the alpha S252I (serine to isoleucine) mutation are significantly inhibited by 100 mM EtOH. Adding a second homologous mutation on the beta subunit (beta T263I) further enhances sensitivity and creates receptors that are inhibited significantly by 50 mM EtOH. The open-state conductance of single nicotinic channels is reduced in the presence of EtOH, which closely parallels EtOH inhibition of multichannel currents. In two isosteric mutant pairs at position alpha 252, only hydrophobic side-chains significantly increase receptor sensitivity to EtOH. Conclusions: Wild-type nicotinic receptors have a very low affinity for EtOH, but only one or two mutations in the pore site create receptors inhibited by physiological EtOH concentrations. Ethanol inhibition is due primarily to channel interactions in the open state. At amino acid alpha 252, side-chain hydrophobicity, not size, determines receptor sensitivity to EtOH inhibition. We propose that similar sites may exist within the pores of other EtOH-sensitive ion channels, such as NMDA receptors and neuronal nicotinic receptors. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN-3, Boston, MA 02114 USA. FU NIAAA NIH HHS [K21-AA00206] NR 29 TC 12 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 2000 VL 24 IS 9 BP 1363 EP 1368 DI 10.1111/j.1530-0277.2000.tb02104.x PG 6 WC Substance Abuse SC Substance Abuse GA 355BB UT WOS:000089364800006 PM 11003201 ER PT J AU Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA AF Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA TI Increased risk of congestive heart failure among infarctions with nighttime onset SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; Q-WAVE INFARCTION; SLEEP; PATTERNS; EPISODES; SIZE AB Background The onset of acute myocordial infarction varies by time of day, with a peak in the morning and a trough at night. Whether infarct-related complications differ by the timing of the infarction is unknown. Methods and Results In the Determinants of Myocardial Infarction Onset study, we performed chart reviews and Face-to-face interviews with 3625 patients with acute myocardial infarction. We assessed the time of onset of symptoms, the presence of ventricular tachycardia or congestive heart failure, and peak creatine kinase levels (in 1043 patients). We Found significant circadian variation in the risk of congestive heart failure (P = .001). The risk dropped from 17% for infarctions that began between 6 PM and midnight to 10% for infarctions that began between 6 AM and noon. Adjustment for differences in the time from symptom onset to presentation for care and use of thrombolytic agents did not change the results, We found no circadian variation in the risk of ventricular tachycardia or in peak creatine kinase levels. Conclusions The risk of congestive heart failure is highest among infarctions that begin at night. Further research may clarify whether this reflects differences in the pathophysiologic characteristics of infarction or the quality of medical care provided for daytime and nighttime infarctions. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Gen Med & Primary Care, 330 Brookline Ave,LY-303, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL41016]; NIAAA NIH HHS [K23AA00299] NR 17 TC 34 Z9 34 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD SEP PY 2000 VL 140 IS 3 BP 438 EP 442 DI 10.1067/mhj.2000.108830 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 351EK UT WOS:000089144700017 PM 10966545 ER PT J AU Sadr, IM Tan, PE Kieran, MW Jenkins, KJ AF Sadr, IM Tan, PE Kieran, MW Jenkins, KJ TI Mechanism of pulmonary vein stenosis in infants with normally connected veins SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID FIBROBLASTS IN-VITRO; DIFFERENTIATION AB We used microscopy. immunohistochemistry, and cell culture to identify the mechanism of restenosis in 4 infants with isolated pulmonary vein stenosis, Recurrent obstruction appears to be due to myofibroblastic proliferation in this fatal disease. C1 Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Sadr, IM (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. OI Kieran, Mark/0000-0003-2184-7692 FU NHLBI NIH HHS [K08HL02936-01] NR 13 TC 42 Z9 42 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 1 PY 2000 VL 86 IS 5 BP 577 EP + DI 10.1016/S0002-9149(00)01022-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 347JX UT WOS:000088926800025 PM 11009286 ER PT J AU Berkey, CS Gardner, JD Frazier, AL Colditz, GA AF Berkey, CS Gardner, JD Frazier, AL Colditz, GA TI Relation of childhood diet and body size to menarche and adolescent growth in girls SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adolescence; body mass index; child nutrition; diet; growth; menarche ID BONE-MINERAL DENSITY; BREAST-CANCER; RISK-FACTORS; HEIGHT VELOCITY; NURSES HEALTH; HIP FRACTURE; AGE; WOMEN; DETERMINANTS; STANDARDS AB Adolescent growth and development may be affected by factors such as dietary intake and body size from much earlier in childhood. In a longitudinal study of 67 Caucasian girls in Boston, Massachusetts, data were collected prospectively from birth during the 1930s and 1940s. Heights and weights were measured semiannually, and dietary history interviews were conducted with mothers. Stepwise linear regression methods were used to seek factors which best predicted age at menarche, adolescent peak height growth velocity, and the age at which peak growth velocity occurred. Girls who consumed more (energy-adjusted) animal protein and less vegetable protein at ages 3-5 years had earlier menarche, and girls aged 1-2 years with higher dietary fat intakes and girls aged 6-8 years with higher animal protein intakes became adolescents with earlier peak growth. Controlling for body size, girls who consumed more calories and animal protein 2 years before peak growth had higher peak growth velocity. These findings may have implications regarding adult diseases whose risks are associated with adolescent growth and development factors. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkey, CS (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356]; NIDDK NIH HHS [DK 46200] NR 36 TC 86 Z9 89 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 2000 VL 152 IS 5 BP 446 EP 452 DI 10.1093/aje/152.5.446 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 349BM UT WOS:000089024000009 PM 10981459 ER PT J AU Small, GW AF Small, GW TI Investigations into geriatric psychiatry challenges - AAGP Senior Investigator Award 2000 SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID ONSET ALZHEIMER-DISEASE; CEREBRAL GLUCOSE-METABOLISM; MEMORY SELF-APPRAISAL; E TYPE-4 ALLELE; APOLIPOPROTEIN-E; HLA-A2 ALLELE; MASS HYSTERIA; OLDER ADULTS; ASSOCIATION; AGE AB The author summarizes the American Association for Geriatric Psychiatry Senior Investigator Award presentation delivered at the 13th Annual Meeting March 12-15, 2000, in Miami Bench, Florida, and reviews his research studies that define a trajectory leading to investigations of early detection and prevention of Alzheimer's disease (AD). Themes and critical transitions that fostered the research are emphasized and effective collaboration mentoring, and timing are discussed These studies have combined neuroimaging and genetic methods to identify subjects before they develop AD, so that interventions might delay dementia onset. The eventual goal is to translate the clinical research discoveries into modern clinical practice. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Alzheimers Dis Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Aging, Los Angeles, CA 90024 USA. VA Greater Los Angles Healthcare Syst, Los Angeles, CA USA. RP Small, GW (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Room 88-201,760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIA NIH HHS [AG13308, AG10123]; NIMH NIH HHS [MH52453] NR 33 TC 1 Z9 1 U1 4 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 2000 VL 8 IS 4 BP 276 EP 283 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 364RG UT WOS:000089906200002 PM 11069266 ER PT J AU Oxman, TE Barrett, JE Sengupta, A Williams, JW AF Oxman, TE Barrett, JE Sengupta, A Williams, JW TI The relationship of aging and dysthymia in primary case SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the American-Association-Geriatric-Psychiatry CY MAR 08-11, 1998 CL SAN DIEGO, CALIFORNIA SP Amer Assoc Geriatr Psychiat ID PRIMARY CARE PRACTICE; MENTAL-DISORDERS; DEPRESSION; HEALTH; OUTCOMES; ILLNESS AB The authors compared symptomatic and functional characteristics between older (age greater than or equal to 60; n =9 1) and younger (age 18-59 n = 125)primary care patients with dysthymia. Three of six significantly different depression symptoms were of moderate-to-large effect size with the older group having a lower proportion reporting the symptom. The older group had a worse physical health function score brit a better mental health function score. There appears to be a core of symptoms and functional impatient that generalizes across the age span. There are also significant age differences. Growing older appears to have an impact on the nature of what it means to have dysthymia. C1 Dartmouth Med Sch, Dept Psychiat, Lebanon, NH 03756 USA. Western Psychiat Inst, Pittsburgh, PA USA. Univ Texas, S Texas Vet Hlth Care Syst, Audie Murphy Div, Gen Internal Med Sect, San Antonio, TX 78285 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Oxman, TE (reprint author), Dartmouth Med Sch, DHMC, 1 Med Ctr Dr, Lebanon, NH 03756 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 32 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 2000 VL 8 IS 4 BP 318 EP 326 DI 10.1176/appi.ajgp.8.4.318 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 364RG UT WOS:000089906200008 PM 11069272 ER PT J AU Joenje, H Levitus, M Waisfisz, Q D'Andrea, A Garcia-Higuera, I Pearson, T van Berkel, CGM Rooimans, MA Morgan, N Mathew, CG Arwert, F AF Joenje, H Levitus, M Waisfisz, Q D'Andrea, A Garcia-Higuera, I Pearson, T van Berkel, CGM Rooimans, MA Morgan, N Mathew, CG Arwert, F TI Complementation analysis in Fanconi anemia: Assignment of the reference FA-H patient to group A SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LYMPHOBLASTOID CELL-LINES; GENE; FANCG/XRCC9; MOSAICISM; COMPLEX; PATHWAY; MAPS AB Fanconi anemia (FA) is an autosomal recessive disorder with diverse clinical symptoms and extensive genetic heterogeneity. Of eight FA genes that have been implicated on the basis of complementation studies, four have been identified and two have been mapped to different loci; the status of the genes supposed to be defective in groups B and H is uncertain. Here we present evidence indicating that the patient who has been the sole representative of the eighth complementation group (FA-H) in fact belongs to group FA-A. Previous exclusion from group A was apparently based on phenotypic reversion to wild-type rather than on genuine complementation in fusion hybrids. To avoid the pitfall of reversion, future assignment of patients with FA to new complementation groups should conform with more-stringent criteria. A new group should be based on at least two patients with FA whose cell lines are excluded from all known groups and that fail to complement each other in fusion hybrids, or, if only one such cell line were available, on a new complementing gene that carries pathogenic mutations in this cell line. On the basis of these criteria, the current number of complementation groups in FA is seven. C1 Free Univ Amsterdam, Dept Clin Genet & Human Genet, Med Ctr, NL-1081 BT Amsterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Univ Orange Free State, Dept Neurol, Div Human Genet, Bloemfontein, South Africa. Guys Hosp, GKT Sch Med, Div Med & Mol Genet, London SE1 9RT, England. RP Joenje, H (reprint author), Free Univ Amsterdam, Dept Clin Genet & Human Genet, Med Ctr, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. RI Morgan, Neil/A-5475-2009; Garcia-Higuera, Irene/L-5004-2014; Mathew, Christopher/G-3434-2015 OI Morgan, Neil/0000-0001-6433-5692; Mathew, Christopher/0000-0003-4178-1838 NR 20 TC 87 Z9 87 U1 0 U2 1 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 SEP PY 2000 VL 67 IS 3 BP 759 EP 762 DI 10.1086/303067 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 348TJ UT WOS:000089002300023 PM 10936108 ER PT J AU Gordon, HS Aron, DC Fuehrer, SM Rosenthal, GE AF Gordon, HS Aron, DC Fuehrer, SM Rosenthal, GE TI Using severity-adjusted mortality to compare performance in a veterans affairs hospital and in private-sector hospitals SO AMERICAN JOURNAL OF MEDICAL QUALITY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the Department-of-Veterans-Affairs-Health-Services-Research-and-Development- Service CY FEB 29, 1996 CL WASHINGTON, D.C. SP Dept Vet Affairs Htlh Serv Res & Dev Serv DE hospital mortality; outcome assessment; regression analysis; veterans hospitals ID HEALTH-CARE SYSTEM; POSTOPERATIVE MORTALITY; QUALITY; VA; DEATH; MEDISGROUPS; ADMISSION; SURGERY; STAY; RISK AB The objective of this study was to compare hospital mortality in Veterans Affairs (VA) and private-sector patients. The study included 5016 patients admitted to 1 VA hospital. Admission severity of illness was measured using a commercial methodology that was developed in a nationwide database of 850,000 patients from 111 private-sector hospitals. The method uses data abstracted from patients' medical records to predict the risk of death in individual patients, based on the normative database. Analyses compared actual and predicted mortality rates in VA patients. VA patients had higher (P < .05) severity of illness than private-sector patients. The observed mortality rate in VA patients was 4.0% and was similar (P = .09) to the predicted risk of death (4.4%; 95% confidence interval 4.0-4.9%). In subgroup analyses, actual and predicted mortality rates were similar in medical and surgical patients and in groups stratified according to severity of illness, except in the highest severity stratum, in which actual mortality was lower than predicted mortality (57% vs 73%; P < .001), We found that in-hospital mortality in 1 VA hospital and a nationwide sample of private-sector hospitals were similar, after adjusting for severity of illness. Although not directly generalizable to other VA hospitals, our findings nonetheless suggest that the quality of VA and private-sector care may be similar with respect to one important and widely used measure. C1 Houston VAMC, Dept Internal Med, Sect Gen Med, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Case Western Reserve Univ, Sch Med, Div Clin & Mol Endocrinol, Cleveland, OH USA. Case Western Reserve Univ, Sch Med, Inst Hlth Care Res, Cleveland, OH USA. Cleveland Vet Affairs Med Ctr, Cleveland, OH USA. Univ Iowa, Div Gen Internal Med, Iowa City, IA USA. Iowa City VA Med Ctr, Iowa City, IA USA. RP Gordon, HS (reprint author), Houston VAMC, Dept Internal Med, Sect Gen Med, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 28 TC 18 Z9 18 U1 1 U2 2 PU AMER COLLEGE MEDICAL QUALITY PI BETHESDA PA 4334 MONTGOMERY AVE, 2ND FL, BETHESDA, MD 20814-4402 USA SN 1062-8606 J9 AM J MED QUAL JI Am. J. Med. Qual. PD SEP-OCT PY 2000 VL 15 IS 5 BP 207 EP 211 DI 10.1177/106286060001500505 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 360MF UT WOS:000089671100005 PM 11022367 ER PT J AU Chesnut, CH Silverman, S Andriano, K Genant, H Gimona, A Harris, S Kiel, D LeBoff, M Maricic, M Miller, P Moniz, C Peacock, M Richardson, P Watts, N Baylink, D AF Chesnut, CH Silverman, S Andriano, K Genant, H Gimona, A Harris, S Kiel, D LeBoff, M Maricic, M Miller, P Moniz, C Peacock, M Richardson, P Watts, N Baylink, D CA PROOF Study Grp TI A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the prevent recurrence of osteoporotic fractures study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID 2-SITE IMMUNORADIOMETRIC ASSAY; INCIDENT VERTEBRAL FRACTURES; LONG-TERM TREATMENT; BONE MASS; NEUTRALIZING ANTIBODIES; INTRANASAL CALCITONIN; PARATHYROID-HORMONE; BIOCHEMICAL MARKERS; PAGETS-DISEASE; DOSE-RESPONSE AB PURPOSE: We conducted a 5-year, double-blind, randomized, placebo-controlled study to determine whether salmon calcitonin nasal spray reduced the risk of new vertebral fractures in postmenopausal women with osteoporosis. SUBJECTS AND METHODS: A total of 1,255 postmenopausal women with established osteoporosis were randomly assigned to receive salmon calcitonin nasal spray (100, 200, or 400 IU) or placebo daily. All participants received elemental calcium (1,000 mg) and vitamin D (400 IU) daily. Vertebral fractures were assessed with lateral radiographs of the spine. The primary efficacy endpoint was the risk of new vertebral fractures in the salmon calcitonin nasal spray 200-IU group compared with the placebo group. RESULTS: During 5 years, 1,108 participants had at least one follow-up radiograph. A total of 783 women completed 3 years of treatment, and 511 completed 5 years. The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03]. In the 817 women with one to five prevalent vertebral fractures at enrollment, the risk was reduced by 36% (RR = 0.64, 95% CI: 0.43- to 0.96, P = 0.03). The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo. Lumbar spine bone mineral density increased significantly from baseline (1% to 1.5%, P <0.01) in all active treatment groups. Bone turnover was inhibited, as shown by suppression of serum type-I collagen cross-linked telopeptide (C-telopeptide) by 12% in the 200-IU group (P <0.01) and by 14% in the 400-IU group (P <0.01) as compared with placebo. CONCLUSION: Salmon calcitonin nasal spray at a dose of 200 IU daily significantly reduces the risk of new vertebral fractures in postmenopausal women with osteoporosis. Am J Med. 2000;109:267-276. (C) 2000 by Excerpta Medica, Inc. C1 Univ Washington, Med Ctr, Seattle, WA 98105 USA. Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Beverly Hills, CA USA. Novartis Pharmaceut, E Hanover, NJ USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Novartis Pharma AG, Basel, Switzerland. Rhode Isl Hosp, Providence, RI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Arizona, Arizona Hlth Sci Ctr, Tucson, AZ USA. Colorado Ctr Bone Res, Lakewood, CO USA. Kings Coll Hosp London, London, England. Indiana Univ, Med Ctr, Indianapolis, IN USA. Emory Clin, Atlanta, GA 30322 USA. Loma Linda Univ, Jerry L Pettis Mem Vet Hosp, Loma Linda, CA 92357 USA. RP Chesnut, CH (reprint author), Univ Washington, Med Ctr, 1107 NE 45th St,Suite 440, Seattle, WA 98105 USA. OI Kiel, Douglas/0000-0001-8474-0310 NR 53 TC 592 Z9 633 U1 5 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD SEP PY 2000 VL 109 IS 4 BP 267 EP 276 DI 10.1016/S0002-9343(00)00490-3 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 354XM UT WOS:000089356600001 PM 10996576 ER PT J AU Lev, MH Grant, PE AF Lev, MH Grant, PE TI MEG versus BOLD MR imaging: Functional imaging, the next generation? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2000 VL 21 IS 8 BP 1369 EP 1370 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 355HY UT WOS:000089381300001 PM 11003263 ER PT J AU Thiers, FA Sakai, O Poe, DS Curtin, HD AF Thiers, FA Sakai, O Poe, DS Curtin, HD TI Persistent stapedial artery: CT findings SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article AB CT of a patient with conductive hearing loss showed a small vascular structure leaving the carotid canal and passing through the stapes to join the facial nerve canal. The small bony channel paralleled the anterior tympanic segment of the facial nerve, continuing beyond the geniculate ganglion into the middle cranial fossa. Otoendoscopic photography documented the presence of a persistent stapedial artery. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. RP Curtin, HD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 12 Z9 13 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD SEP PY 2000 VL 21 IS 8 BP 1551 EP 1554 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 355HY UT WOS:000089381300033 PM 11003295 ER PT J AU Poe, DS Pyykko, I Valtonen, H Silvola, J AF Poe, DS Pyykko, I Valtonen, H Silvola, J TI Analysis of eustachian tube function by video endoscopy SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE eustachian tube; video endoscopy ID OTITIS-MEDIA; EFFUSION AB Objective: Human eustachian tubes (ET) were inspected in vivo endoscopically, and video recordings were made for careful slow-motion analysis of normal physiologic function. Setting: Ambulatory office in a tertiary referral center. Subjects: Thirty-four adults, 17 with no history of ET dysfunction (2 of whom had tympanic membrane perforations), 17 with known ET dysfunction. Interventions: Transnasal endoscopic examination of the nasopharyngeal opening of the eustachian tube during rest, swallowing, and yawning. Main Outcome Measures: Video analysis of ET opening movements. Results: Normal ETs had four consistent sequential movements: (1) palatal elevation causing passive, then active, rotation of the medial cartilaginous lamina; (2) lateral excursion of the lateral pharyngeal wall; (3) dilation of the lumen, caused primarily by tensor veli palatini muscle movement beginning distally and inferiorly, then opening proximally and superiorly; and (3) opening of the tubal valve at the isthmus caused by dilator tubae muscle contraction. Dysfunctional ETs had intraluminal edema, polyps, or minimal muscle movement. Conclusions: Slow-motion endoscopic video analysis may be a useful new technique for the study of eustachian tube physiology. Consistent muscle movement patterns were demonstrated in normal subjects but were absent in abnormal subjects. More studies of normal and abnormal patterns are needed to establish useful clinical correlates. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Karolinska Inst, Sekt Oron Nas & Halssjukdomar, Stockholm, Sweden. Jyvaskyla Cent Hosp, Dept Otolaryngol, Jyvaskyla, Finland. Dept Otolaryngol Rito, Tromso, Norway. RP Poe, DS (reprint author), Zero Emerson Pl,Suite 2C, Boston, MA 02114 USA. NR 14 TC 38 Z9 44 U1 0 U2 3 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 SEP PY 2000 VL 21 IS 5 BP 602 EP 607 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 350PZ UT WOS:000089111500002 PM 10993444 ER PT J AU LaMuraglia, GM Schiereck, J Heckenkamp, J Nigri, G Waterman, P Leszczynski, D Kossodo, S AF LaMuraglia, GM Schiereck, J Heckenkamp, J Nigri, G Waterman, P Leszczynski, D Kossodo, S TI Photodynamic therapy induces apoptosis in intimal hyperplastic arteries SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; GROWTH-FACTOR; GENE-THERAPY; RESTENOSIS; INJURY; NECROSIS; PHTHALOCYANINE; IRRADIATION; ANGIOPLASTY; MECHANISMS AB Photodynamic therapy (PDT) generates free radicals through the absorption of light by photosensitizers. PDT shows promise in the treatment of intimal hyperplasia, which contributes to restenosis, by completely eradicating cells in the vessel wall. This study investigates the mechanisms of PDT-induced cell death. PDT, using the photosensitizer chloroaluminum-sulfonated phthalocyanine (1 mg/kg) and laser light (lambda = 675 nm) 100 J/cm(2) was administered to rat carotid arteries after balloon injury-induced intimal hyperplasia. Apoptosis was determined by cell morphology with light microscopy and transmission electron microscopy, DNA cleavage by terminal dUTP nick-end labeling staining, and nucleosomal fragmentation (ladder pattern) by DNA agarose gel electrophoresis. Four hours after PDT, apoptosis was observed in vascular cells, as evidenced by terminal dUTP nick-end labeling staining and transmission electron microscopy. Within 24 hours no cells were present in the neointima and media. Immunofluorescence using an cu-smooth muscle cell actin antibody confirmed the disappearance of all neointimal and medial cells within 24 hours. No inflammatory cell infiltrate was observed during this time frame. Apoptosis was sharply confined to the PDT treatment held. These data demonstrate that vascular PDT induces apoptosis as a mechanism of rapid, complete, and precise cell eradication in the artery wall. These findings and the lack of inflammatory reaction provide the basis for understanding and developing PDT for a successful clinical application in the treatment of hyperplastic conditions such as restenosis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, ACC 464, Boston, MA 02114 USA. NR 31 TC 35 Z9 37 U1 0 U2 0 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 SEP PY 2000 VL 157 IS 3 BP 867 EP 875 DI 10.1016/S0002-9440(10)64600-7 PG 9 WC Pathology SC Pathology GA 352GP UT WOS:000089207200020 PM 10980126 ER PT J AU Brown, EN Choe, Y Luithardt, H Czeisler, CA AF Brown, EN Choe, Y Luithardt, H Czeisler, CA TI A statistical model of the human core-temperature circadian rhythm SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE biological clock; dynamical system; harmonic regression; perturbation expansion; thermoregulation; van der Pol equation ID BRIGHT LIGHT; PACEMAKER; LESIONS; PHASE; CYCLE AB We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator (similar to 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Stat Res Lab, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med,Neuroendocrine & Sleep Disorders Sect, Brigham & Womens Hosp,Div Endocrinol, Boston, MA 02115 USA. RP Brown, EN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Stat Res Lab, 55 Fruit St,Clin 3, Boston, MA 02114 USA. FU NIA NIH HHS [1-P01-AG-09975, 1-R01-AG-06072]; NIGMS NIH HHS [1-R01-GM-53559] NR 49 TC 28 Z9 29 U1 0 U2 2 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 SEP PY 2000 VL 279 IS 3 BP E669 EP E683 PG 15 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 345TB UT WOS:000088830300025 PM 10950837 ER PT J AU Deavall, DG Raychowdhury, R Dockray, GJ Dimaline, R AF Deavall, DG Raychowdhury, R Dockray, GJ Dimaline, R TI Control of CCK gene transcription by PACAP in STC-1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cholecystokinin; pituitary adenylate cyclase-activating; polypeptide; calcium/cyclic AMP response element; calcium/3,5 '-monophosphate response element binding protein; adenosine 3 ' 5 '-cyclic monophosphate ID CYCLASE-ACTIVATING POLYPEPTIDE; STIMULATE CHOLECYSTOKININ SECRETION; VASOACTIVE INTESTINAL POLYPEPTIDE; ELEMENT-BINDING PROTEIN; BETA-HYDROXYLASE GENE; GASTROINTESTINAL-TRACT; CHROMAFFIN CELLS; CAMP-RESPONSE; LINE STC-1; C-FOS AB The mechanisms by which neuroendocrine stimulants regulate CCK gene transcription are unclear. We examined promoter activation by pituitary adenylate cyclase-activating polypeptide (PACAP), a known CCK secretagogue, in the enteroendocrine cell line STC-1. The promoter region from -70 to -87 bp, relative to the transcriptional start site, contains a composite calcium/cyclic AMP response element (CRE)/activator protein 1 (AP1) site that may bind CRE binding protein (CREB) and AP1. PACAP (with IBMX) stimulated expression of an 87-bp construct 3.35 +/- 0.36-fold but had no effect on a 270 construct. The effect was blocked by the protein kinase A inhibitor H-89 and by a dominant-negative CREB plasmid. Mutation of the CRE/AP1 site to a canonical CRE site did not affect the response to PACAP, but mutation to a canonical AP1 site prevented it. CREB phosphorylation was increased after PACAP treatment. Electrophoretic mobility shift assay and supershift analysis revealed that CREB and not AP1 bound to the CRE/AP1 site and that PACAP increased the proportion of phosphorylated CREB that was bound. We conclude that PACAP increases CCK gene expression via a cAMP-mediated pathway involving CREB phosphorylation by protein kinase A and activation of a composite CRE/AP1 site. C1 Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dimaline, R (reprint author), Univ Liverpool, Physiol Lab, Crown St, Liverpool L69 3BX, Merseyside, England. NR 36 TC 14 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2000 VL 279 IS 3 BP G605 EP G612 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 347UB UT WOS:000088946600018 PM 10960361 ER PT J AU Yang, H Kawakubo, K Wong, H Ohning, G Walsh, J Tache, Y AF Yang, H Kawakubo, K Wong, H Ohning, G Walsh, J Tache, Y TI Peripheral PYY inhibits intracisternal TRH-induced gastric acid secretion by acting in the brain SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE immunoneutralization; vagus; dorsal vagal complex ID THYROTROPIN-RELEASING-HORMONE; DORSAL MOTOR NUCLEUS; INTRACEREBROVENTRICULAR PASSIVE-IMMUNIZATION; FOS-LIKE IMMUNOREACTIVITY; MEDULLARY RAPHE NUCLEI; PEPTIDE-YY; RAT-BRAIN; VAGAL COMPLEX; BINDING-SITES; RECEPTOR AB The site of action of peripheral peptide YY (PYY)-induced inhibition of vagally stimulated gastric acid secretion was studied using immunoneutralization with PYY antibody in urethan-anesthetized rats. Gastric acid secretion (59 +/- 7 mmol/90 min) stimulated by intracisternal injection of the stable thyrotropin-releasing hormone (TRH) analog RX-77368 (14 pmol/rat) was dose-dependently inhibited by 52%, 69%, and 83% by intravenous infusion of 0.25, 0.5, and 1.0 nmol.kg(-1).h(-1) PYY, respectively. PYY or PYY3-36 (2.4 pmol/rat) injected intracisternally also inhibited the acid response to intracisternal RX-77368 by 73% and 80%, respectively. Intravenous pretreatment with PYY antibody (4.5 mg/rat), which shows a 35% cross-reaction with PYY3-36 by RIA, completely prevented the inhibitory effect of intravenously infused PYY (1 nmol.kg(-1).h(-1)). When injected intracisternally, the PYY antibody (280 mu g/rat) reversed intracisternal PYY (2.4 pmol)- and intravenous PYY (1 nmol.kg(-1).h(-1))-induced inhibition of acid response to intracisternal RX-77368 by 64% and 93.5%, respectively. These results provide supporting evidence that peripheral PYY inhibits central vagal stimulation of gastric acid secretion through an action in the brain. C1 Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Div Digest Dis, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-50255, DK-30110] NR 43 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD SEP PY 2000 VL 279 IS 3 BP G575 EP G581 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 347UB UT WOS:000088946600014 PM 10960357 ER PT J AU Cornford, EM Nguyen, EV Landaw, EM AF Cornford, EM Nguyen, EV Landaw, EM TI Acute upregulation of blood-brain barrier glucose transporter activity in seizures SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE blood-brain barrier glucose transporter; maximal velocity; half-saturation constant; pentylene tetrazole seizures; unsaturated permeability-surface area products; transporter recruitment; intrinsic activity ID ELECTRON-MICROSCOPIC IMMUNOGOLD; RAT-BRAIN; DOWN-REGULATION; FLOW; METABOLISM; REGIONS; KINETICS; GERBIL; INFLUX; PLASMA AB Brain extraction of F-18-labeled 2-fluoro-2-deoxy-D-glucose (FDG) was significantly higher in pentylene tetrazole (PTZ)-treated rats (32 +/- 4%) than controls (25 +/- 4%). The FDG permeability-surface area product (PS) was also significantly higher with PTZ treatment (0.36 +/- 0.05 ml.min(-1).g(-1)) than in controls (0.20 +/- 0.06 ml.min(-1).g(-1)). Cerebral blood flow rates were also elevated by 50% in seizures. The internal carotid artery perfusion technique indicated mean [C-14]glucose clearance (and extraction) was increased with PTZ treatment, and seizures increased the PS by 37 +/- 16% (P < 0.05) in cortical regions. Because kinetic analyses suggested the glucose transporter half-saturation constant (K-m) was unchanged by PTZ, we derived estimates of 1) treated and 2) control maximal transporter velocities (V-max) and 3) a single K-m. In cortex, the glucose transporter V-max was 42 +/- 11% higher (P < 0.05) in PTZ-treated animals (2.46 +/- 0.34 mu mol.min(-1).g(-1)) than in control animals (1.74 +/- 0.26 mu mol.min(-1).g(-1)), and the K-m = 9.5 +/- 1.6 mM. Blood-brain barrier (BBB) V-max was 31 +/- 10% greater (P < 0.05) in PTZ-treated (2.36 +/- 0.30 mu mol.min(-1).g(-1)) than control subcortex (1.80 +/- 0.25 mu mol.min(-1).g(-1)). We conclude acute upregulation of BBB glucose transport occurs within 3 min of an initial seizure. Transporter V-max and BBB glucose permeability increase by 30-40%. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Vet Adm W Los Angeles Med Ctr, Neurol Serv W127, SW Reg Vet Adm Epilepsy Ctr, Los Angeles, CA 90073 USA. RP Cornford, EM (reprint author), VA Greater Los Angeles Healthcare Syst, Vet Adm W Los Angeles Med Ctr, Neurol Serv W127, SW Reg Vet Adm Epilepsy Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [NS-25554, NS-37360] NR 28 TC 33 Z9 33 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 2000 VL 279 IS 3 BP H1346 EP H1354 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 355HC UT WOS:000089379400058 PM 10993802 ER PT J AU Chen, R Mukhin, YV Garnovskaya, MN Thielen, TE Iijima, Y Huang, C Raymond Jr Ullian, ME Paul, RV AF Chen, R Mukhin, YV Garnovskaya, MN Thielen, TE Iijima, Y Huang, C Raymond, JR Ullian, ME Paul, RV TI A functional angiotensin II receptor-GFP fusion protein: evidence for agonist-dependent nuclear translocation SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE green fluorescent protein; losartan; confocal microscopy; internalization ID GREEN FLUORESCENT PROTEIN; VASCULAR SMOOTH-MUSCLE; LIGAND-INDUCED TRAFFICKING; BETA(2)-ADRENERGIC RECEPTOR; SIGNAL-TRANSDUCTION; BINDING SITES; INTERNALIZATION; CELLS; VISUALIZATION; ENDOCYTOSIS AB We constructed an expression vector for a fusion protein [ANG II type 1a receptor-green fluorescent protein (AT(1a)R-GFP)] consisting of enhanced GFP attached to the COOH terminus of the rat AT(1a)R. Chinese hamster ovary (CHO) cells transfected with AT(1a)R-GFP demonstrated specific, high-affinity (125)I-labeled ANG II binding (IC(50) 21 nM). ANG II exposure stimulated sodium-proton exchange and cytoplasmic calcium release to a similar extent in cells transfected with AT(1a)R or AT(1a)R-GFP; these responses were desensitized by prior exposure to ANG II and were sensitive to the AT(1)R blocker losartan. ANG II-driven internalization of AT(1a)R-GFP in transfected CHO cells was demonstrated both by radioligand binding and by laser scanning confocal microscopy. Colocalization of GFP fluorescence with that of the nuclear stain TOTO-3 in confocal images was increased more than twofold after 1 h of ANG II exposure. We conclude that AT(1a)R-GFP exhibits similar pharmacological behavior to that of the native AT(1a)R. Our observations also support previous evidence for the presence of AT(1a)R in the nucleus and suggest that the density of AT(1a)R in the nucleus may be regulated by exposure to its ligand. C1 Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Med Specialty Serv, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. RP Paul, RV (reprint author), Med Univ S Carolina, Div Nephrol, 829 CSB, Charleston, SC 29425 USA. EM paulr@musc.edu FU NCRR NIH HHS [S10-RR-13005]; NIDDK NIH HHS [R01-DK-52448] NR 31 TC 71 Z9 71 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 SEP PY 2000 VL 279 IS 3 BP F440 EP F448 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 349FX UT WOS:000089033900005 PM 10966923 ER PT J AU Nierenberg, AA Farabaugh, AH Alpert, JE Gordon, J Worthington, JJ Rosenbaum, JF Fava, M AF Nierenberg, AA Farabaugh, AH Alpert, JE Gordon, J Worthington, JJ Rosenbaum, JF Fava, M TI Timing of onset of antidepressant response with fluoxetine treatment SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; TRUE DRUG RESPONSE; PATTERN-ANALYSIS; TRIALS; AMITRIPTYLINE; OUTPATIENTS; EFFICACY; PLACEBO; DESIPRAMINE; IMPROVEMENT AB Objective: The purpose of this study was to assess the time until onset of antidepressant response with fluoxetine treatment. Method: The authors evaluated 182 outpatients with major depression who had a sustained acute response to fluoxetine treatment. The Outpatients received 8 weeks of treatment with 20 mg/day of fluoxetine and were assessed biweekly with the 17-item Hamilton Depression Rating Scale. The onset of response was defined as a 30% decrease in score on the Hamilton depression scale that persisted and led to a 50% decrease by week 8. The Kaplan-Meier product limit and Cox regression analysis were used to model the relationship between relevant variables and time until onset of response. Results: The authors found that at weeks 2, 4, and 6, the probabilities of having an onset of response (for responders) were 55.5%, 24.7%, and 9.3%, respectively. The cumulative probabilities of onset of response at each time point were 55.5%, 80.2%, and 89.5%,Neither demographics nor clinical characteristics of depression predicted time until initial response. Conclusions: These data suggest that more than half of eventual responders to fluoxetine treatment at 8 weeks start to respond by week 2; over 75% start to respond by week 4. Conversely, the lack of onset of response at 4-6 weeks was associated with about a 73%-88% chance that patients would not have an onset of response by 8 weeks. C1 Massachusetts Gen Hosp, Depress & Clin Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Depress & Clin Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [MH-48483] NR 34 TC 141 Z9 144 U1 2 U2 3 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 SEP PY 2000 VL 157 IS 9 BP 1423 EP 1428 DI 10.1176/appi.ajp.157.9.1423 PG 6 WC Psychiatry SC Psychiatry GA 349QH UT WOS:000089056800011 PM 10964858 ER PT J AU Viguera, AC Tondo, L Baldessarini, RJ AF Viguera, AC Tondo, L Baldessarini, RJ TI Sex differences in response to lithium treatment SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RECURRENT AFFECTIVE DISORDERS; PROPHYLACTIC LITHIUM; GENDER DIFFERENCES; MANIA; PREDICTORS; WOMEN AB Objective: Although sex differences occur with some psychotropic drug treatments, they are not well defined for mood-stabilizing agents, including lithium. The authors' goal was to investigate whether there are differences between the sexes in response to lithium. Method: Studies identified in a literature search were analyzed for reports of sex differences in clinical response to lithium in major affective syndromes. Results: Data from 17 studies published in 1967-1998, involving 1,548 adults treated with lithium for a mean of 38.6 months (SD=30.5), yielded similar weighted response rates to lithium in 1,043 women (65.6% [N=684]) and 505 men (61.0% [N=308]). Conclusions: The results indicate little difference between the sexes in clinical response to lithium treatment of bipolar and related affective disorders. C1 Massachusetts Gen Hosp, Dept Psychiat, Perinatal Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr,Dept Psychiat, Belmont, MA 02178 USA. Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr,Neurosci Program, Belmont, MA 02178 USA. Univ Cagliari, Dept Psychol, I-09124 Cagliari, Italy. Lucio Bini Stanley Fdn Mood Disorders Res Ctr, Cagliari, Italy. RP Viguera, AC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Perinatal Psychopharmacol Unit, Fruit St, Boston, MA 02114 USA. FU NIMH NIH HHS [MH-01609, MH-47370] NR 26 TC 32 Z9 33 U1 0 U2 0 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 SEP PY 2000 VL 157 IS 9 BP 1509 EP 1511 DI 10.1176/appi.ajp.157.9.1509 PG 3 WC Psychiatry SC Psychiatry GA 349QH UT WOS:000089056800025 PM 10964872 ER PT J AU Bencardino, J Rosenberg, ZS Beltran, J Liu, X Marty-Delfaut, E AF Bencardino, J Rosenberg, ZS Beltran, J Liu, X Marty-Delfaut, E TI Morton's neuroma: Is it always symptomatic? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID MR AB OBJECTIVE. We determined the prevalence of clinically silent Morton's neuroma and searched fur distinguishing MR imaging features of Morton's neuroma in patients with clinical complaints related to this entity and in patients with clinically silent lesions. MATERIALS AND METHODS. One radiologist who was unaware of clinical findings retrospectively reviewed 85 consecutive foot MR examinations. MR imaging criteria fur Morton's neuroma included a low- to intermediate-signal-intensity soft-tissue mass in the intermetatarsal space. The size, location, and signal intensity of each neuroma and the presence of intermetatarsal bursae were recorded. The patients were subdivided into symptomatic or asymptomatic groups on the basis of the patients' answers on a questionnaire documenting the locations and characteristics of symptoms and discussions with each referring physician about clinical findings. Surgical confirmation was available in eight of 25 symptomatic patients. RESULTS. The prevalence of Morton's neuroma in patients with no clinical evidence of this condition was 33% (19/57). Twenty-five patients had symptomatic Morton's neuroma, 19 had Morton's neuroma based on MR imaging findings with no clinical manifestations, and 41 did not have Morton's neuroma. Slightly larger lesions were observed in the symptomatic group, although significant overlap was noted between the two groups. The mean transverse diameter of symptomatic neuromas was 5.3 mm (standard deviation, 2.14) compared with 4.1 mm (standard deviation, 1.75) for asymptomatic neuromas; this difference was marginally significant (p = 0.05). CONCLUSION. The MR imaging diagnosis of Morton's neuroma does not imply symptomatology. Careful correlation between clinical and MR imaging findings is mandatory before Morton's neuroma is considered clinically relevant. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Hosp Joint Dis, Dept Radiol, New York, NY 10003 USA. Maimonides Med Ctr, Dept Radiol, Brooklyn, NY 11219 USA. Long Isl Jewish Med Ctr, Dept Radiol, New Hyde Park, NY 11040 USA. RP Bencardino, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,Ste 515, Boston, MA 02114 USA. NR 16 TC 50 Z9 52 U1 1 U2 2 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 SEP PY 2000 VL 175 IS 3 BP 649 EP 653 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 347CR UT WOS:000088910300013 PM 10954445 ER PT J AU Nucci, MR Ferry, JA Young, RH AF Nucci, MR Ferry, JA Young, RH TI Ectopic prostatic tissue in the uterine cervix - A report of four cases and review of ectopic prostatic tissue SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Review DE uterine cervix; prostatic tissue; ectopia; glandular hyperplasia ID PAPILLARY ADENOMA; URETHRA; ADENOCARCINOMA; GLANDS; HYPERPLASIA; HEMATURIA; TERATOMAS; CARCINOMA; ANTIGEN; LESION AB We report four examples of prostatic tissue occurring in the uterine cervix of patients aged 22, 25, 31, and 77 years. Three were incidental findings in loop excisions (two patients) and cone biopsy (one patient) of the cervix for high-grade squamous dysplasia. One presented as a cervical mass, clinically suspected to represent a fibroid. The prostatic tissue consisted of duets and acini, some of which had papillary or cribriform patterns. Squamous metaplasia was prominent in all cases. No Wolffian duct tissue was present. The glandular epithelium in all cases was positive for prostatic acid phosphatase and prostate-specific antigen. High molecular weight keratin, performed in two cases, highlighted basal cells in a manner similar to the normal prostate. These unusual cases, only one of which is documented previously, further complicate the often-challenging area of interpretation of benign glandular lesions of the cervix. The unusual phenomenon of ectopic prostate tissue in general is reviewed. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nucci, MR (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. NR 58 TC 37 Z9 41 U1 0 U2 3 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 SEP PY 2000 VL 24 IS 9 BP 1224 EP 1230 DI 10.1097/00000478-200009000-00005 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 350PU UT WOS:000089111000005 PM 10976696 ER PT J AU Misdraji, J Ino, Y Louis, DN Rosenberg, AE Chiocca, EA Harris, NL AF Misdraji, J Ino, Y Louis, DN Rosenberg, AE Chiocca, EA Harris, NL TI Primary lymphoma of peripheral nerve - Report of four cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE malignant lymphoma; diffuse large B-cell lymphoma; peripheral nervous system; neurolymphomatosis; CDKN2A/p16; p16 ID NON-HODGKINS-LYMPHOMA; T-CELL LYMPHOMA; PRIMARY MALIGNANT-LYMPHOMA; SCIATIC-NERVE; CLINICAL CORRELATIONS; GENE DELETIONS; RB ALTERATIONS; 5'-CPG ISLAND; NEUROLYMPHOMATOSIS; FREQUENT AB Lymphoma presenting as a solitary tumor of peripheral nerve is exceedingly rare, with only six previously reported cases. The authors describe an additional four cases of primary lymphoma of peripheral nerve involving the sciatic nerve (two cases), the radial nerve, and the sympathetic chain and spinal nerve. The patients were two men and two women with an average age of 55.5 years. All tumors were high-grade B-cell lymphomas. Two patients experienced relapse of disease with involvement of other nervous system sites and died of lymphoma. One patient is alive with stable local disease at 57 months. The fourth patient is alive with no evidence of disease at 54 months. Expression of neural cell adhesion molecule (CD56) has been reported to correlate with an increased incidence of central nervous system involvement in peripheral T-cell lymphoma; all their cases were CD56 negative. Recent reports indicate a high proportion of primary brain lymphomas show loss of CDKN2A/p16 gene expression. Therefore, CDKN2A/p16 was evaluated in their patients both by polymerase chain reaction and by immunohistochemistry for the p16 protein. The authors found homozygous deletion of the CDKN2A/p16 gene in one of three patients studied, confirmed immunohistochemically by absent staining for p16. The fourth patient showed absent staining for p16, suggesting inactivation of the gene in this case as well. The two patients with p16 loss both died of lymphoma, whereas the two patients with normal p16 expression are alive. Primary lymphoma of peripheral nerve is a rare neoplasm, usually of large B-cell type, has a variable prognosis, and appears to have less consistent loss of p16 expression than primary central nervous system lymphoma. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, 55 Fruit St, Boston, MA 02114 USA. NR 60 TC 46 Z9 47 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 2000 VL 24 IS 9 BP 1257 EP 1265 DI 10.1097/00000478-200009000-00009 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 350PU UT WOS:000089111000009 PM 10976700 ER PT J AU Ciraulo, DA Nace, EP AF Ciraulo, DA Nace, EP TI Benzodiazepine treatment of anxiety or insomnia in substance abuse patients SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ALCOHOL-WITHDRAWAL; CONTROLLED TRIAL; DEPENDENCE; DISORDERS; ALPRAZOLAM; LIABILITY; RECEPTORS; BUSPIRONE; DIAZEPAM; MEN C1 Boston Med Ctr, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Texas, Dept Psychiat & Behav Sci, SW Med Sch, Dallas, TX 75230 USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. RP Ciraulo, DA (reprint author), Boston Univ, Sch Med, Div Psychiat, 720 Harrison Ave,Suite 914, Boston, MA 02118 USA. NR 28 TC 19 Z9 19 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD FAL PY 2000 VL 9 IS 4 BP 276 EP 282 PG 7 WC Substance Abuse SC Substance Abuse GA 383VV UT WOS:000165905700002 PM 11155783 ER PT J AU Taylor, E AF Taylor, E TI Psychotherapeutics and the problematic origins of clinical psychology in America SO AMERICAN PSYCHOLOGIST LA English DT Article AB The problematic place of psychotherapy within the larger history of scientific psychology is reviewed, especially in the absence of any definitive history of clinical psychology yet written. Although standard histories of psychology imply that psychotherapy was somehow derived from the tradition of German laboratory science, modem historiography reveals a dramatically different story. Personality, abnormal, social, and clinical psychology have their roots in an international psychotherapeutic alliance related more to French neurophysiology, and this alliance flourished for several decades before psychoanalysis. Reconstruction of the American contribution to this alliance, the so-called Boston school of abnormal psychology, suggests an era of medical psychology in advance of today. Note is also made of the possible misattribution of Lightner Witmer as the father of clinical psychology. C1 Massachusetts Gen Hosp, Psychol Testing Ctr, Boston, MA 02114 USA. Harvard Univ, Saybrook Inst, Cambridge, MA 02138 USA. RP Taylor, E (reprint author), Massachusetts Gen Hosp, Psychol Testing Ctr, 5 Emerson Pl, Boston, MA 02114 USA. NR 29 TC 6 Z9 6 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD SEP PY 2000 VL 55 IS 9 BP 1029 EP 1033 DI 10.1037//0003-066X.55.9.1029 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 360DB UT WOS:000089650200009 PM 11036704 ER PT J AU Hirakura, Y Yiu, WW Yamamoto, A Kagan, BL AF Hirakura, Y Yiu, WW Yamamoto, A Kagan, BL TI Amyloid peptide channels: blockade by zinc and inhibition by Congo red (amyloid channel block) SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Article DE amyloid; membranes; pores; electrophysiology; amylin; prion ID PRION PROTEIN-FRAGMENT; DIABETES-MELLITUS; TRANSGENIC MICE; NEUROTOXICITY; DISEASE; BIOLOGY AB Amyloid peptides are the major constituents of amyloid deposits in various amyloid diseases including Alzheimer's disease, type II diabetes mellitus, prion diseases and others. The hallmark of amyloid is the binding of the dye, Congo red, which creates characteristic staining doe to the dye's ability to bind the beta sheet aggregates referred to as amyloid. Previous reports have demonstrated that several cytotoxic, amyloidogenic peptides can form ion channels in planar phospholipid bilayer membranes and have suggested that these channels may represent the pathogenic mechanism of cell and tissue destruction in amyloid disease. Furthermore, zinc and Congo red can ameliorate or prevent the pathogenic effect of certain amyloid peptides. We report here that zinc at micromolar concentrations caused a reversible blockade of islet amyloid polypeptide (IAPP, amylin) and PrP 106-126 channels whereas calcium and magnesium did not. Congo red completely inhibited channel formation if preincubated with amyloid peptides, but had no effect on IAPP or PrP 106-126 channels once formed These results suggest a requirement for aggregation for the formation of amyloid peptide channels and are consistent with the "channel hypothesis" of amyloid disease. They also suggest potential avenues for ameliorative therapy of these illnesses. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Dept Psychiat,Neuropsychiat Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. RP Kagan, BL (reprint author), 760 Westwood Plaza, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MHO1174] NR 25 TC 59 Z9 59 U1 1 U2 7 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD SEP PY 2000 VL 7 IS 3 BP 194 EP 199 DI 10.3109/13506120009146834 PG 6 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 359FH UT WOS:000089600500005 PM 11019860 ER PT J AU Maslow, AD Haering, JM Heindel, S Mashikian, J Levine, R Douglas, P AF Maslow, AD Haering, JM Heindel, S Mashikian, J Levine, R Douglas, P TI An evaluation of prosthetic aortic valves using transesophageal echocardiography: The double-envelope technique SO ANESTHESIA AND ANALGESIA LA English DT Article ID DOPPLER-ECHOCARDIOGRAPHY; CONTINUITY EQUATION; ORIFICE AREA; HEMODYNAMIC PERFORMANCE; PRESSURE RECOVERY; STENOSIS; POSITION; BIOPROSTHESIS; VALIDATION; INVITRO AB The conventional continuity equation uses nonsimultaneous measurements of blood flow velocities through the left ventricular outflow tract and across the aortic valve to calculate aortic valve area (AVA). We have noted that both velocities can be simultaneously obtained from continuous wave (CW) Doppler analysis (double-envelope [DE]). We hypothesize that prosthetic AVA can be calculated by using the DE technique, during transesophageal echocardiography (TEE). Prosthetic AVA was calculated in 41 of 45 patients immediately after aortic valve replacement by using the DE/AVA technique. Left ventricular outflow tract diameter was obtained from an esophageal view, while subvalvular (V-1) and valvular (V-2) peak velocities were simultaneously obtained from transgastric views by using CW Doppler. Prosthetic AVA and V-1/V-2 ratio (Doppler velocity index) were calculated. V-1 was also measured by using pulse wave Doppler, as is conventionally done. Twenty-three Carbomedic (CM) and 18 Carpentier-Edwards (CE) AVA were evaluated. DE/AVAs for CM and CE valves correlated and agreed with that reported by the manufacturer (CM r(2) = 0.91, mean bias -0.25 cm(2) [SD 0.18]; CE r(2) = 0.73, mean bias -0.02 cm(2) [SD 0.27]). Calculated Doppler velocity index values agree with available data (mean bias 0.03 [SD 0.05]). The V-1 obtained by using the DE method was nearly identical to the V-1 obtained by using pulse wave (r(2) = 0.95, mean bias 0.02 m/s [SD 0.04 m/s]). TEE assessment of prosthetic AVA using the DE technique agrees with data reported by the manufacturer. Obtaining subvalvular and valvular velocities from the same CW Doppler trace may simplify the continuity equation and help avoid errors caused by beat-to-beat changes in blood flow. Quantitative prosthetic aortic valve assessment can be performed, on-line, with TEE by using the DE technique. C1 Beth Israel Deaconess Med Ctr, Dept Anesthesia, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Maslow, AD (reprint author), Rhode Isl Hosp, Dept Anesthesia, 593 Eddy St,Davol 129, Providence, RI 02903 USA. NR 31 TC 3 Z9 3 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 SEP PY 2000 VL 91 IS 3 BP 509 EP 516 PG 8 WC Anesthesiology SC Anesthesiology GA 348EZ UT WOS:000088973700002 PM 10960367 ER PT J AU Mao, JR Chen, LL AF Mao, JR Chen, LL TI Gabapentin in pain management SO ANESTHESIA AND ANALGESIA LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; MULTIPLE-SCLEROSIS PATIENTS; NEUROPATHIC PAIN; POSTHERPETIC NEURALGIA; FORMALIN TEST; INTRATHECAL GABAPENTIN; NOCICEPTIVE BEHAVIORS; TRIGEMINAL NEURALGIA; ANTICONVULSANT DRUG; ADJUNCTIVE THERAPY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr, 15 Parkman St,Suite WACC 324, Boston, MA 02114 USA. FU NIDA NIH HHS [DA08835] NR 68 TC 90 Z9 94 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 SEP PY 2000 VL 91 IS 3 BP 680 EP 687 PG 8 WC Anesthesiology SC Anesthesiology GA 348EZ UT WOS:000088973700034 PM 10960399 ER PT J AU Dershwitz, M Walsh, JL Morishige, RJ Conners, PM Rubsamen, RM Shafer, SL Rosow, CE AF Dershwitz, M Walsh, JL Morishige, RJ Conners, PM Rubsamen, RM Shafer, SL Rosow, CE TI Pharmacokinetics and pharmacodynamics of inhaled versus intravenous morphine in healthy volunteers SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 17-21, 1998 CL ORLANDO, FL SP Amer Soc Anesthesiologists DE drug aerosol; pulmonary drug absorption; pulmonary drug delivery ID AEROSOL DELIVERY SYSTEM; MORPHINE-6-GLUCURONIDE; REMIFENTANIL; FENTANYL; ALFENTANIL; DISEASE; PAIN AB Background: A new pulmonary drug delivery system produces aerosols from disposable packets of medication. This study compared the pharmacokinetics and pharmacodynamics of morphine delivered by an AERx prototype with intravenous morphine. Methods: Fifteen healthy volunteers were enrolled. Two subjects were administered four inhalations of 2.2 mg morphine each at 1-min intervals or 4.4 mg over 3 min by intravenous infusion. Thirteen subjects were given twice the above doses, i.e., eight inhalations or 8.8 mg intravenously over 7 min. Arterial blood sampling was performed every minute during administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, and 240 min after administration. The effect of morphine was assessed by measuring pupil diameter and ventilatory response to a hypercapnic challenge; Pharmacokinetic and pharmacodynamic analyses were performed simultaneously using mixed-effect models, Results: The pharmacokinetic data after intravenous administration were described by a three-exponent decay model preceded by a lag time. The pharmacokinetic model for administration by inhalation consisted of the three-exponent intravenous pharmacokinetic model preceded by a two-exponent absorption model. The authors found that, with administration by inhalation, the total bioavailability was 59%, of which 43% was absorbed almost instantaneously and 57% was absorbed with a half-life of 18 min. The median times to the half-maximal miotic effects of morphine were 10 and 5.5 min after inhalation and intravenous administration, respectively (P < 0.01). The pharmacodynamic parameter k(e0) was approximately 0.003 min(-1). Conclusions: The onset and duration of the effects of morphine are similar after intravenous administration or inhalation via this new pulmonary drug delivery system. Morphine bioavailability after such administration is 59% of the dose loaded into the dosage form. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dershwitz, M (reprint author), UMass Mem, Dept Anesthesia, 55 Lake Ave N, Worcester, MA 01655 USA. EM mark.dershwitz@umassmed.edu NR 20 TC 76 Z9 84 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 EI 1528-1175 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3 BP 619 EP 628 DI 10.1097/00000542-200009000-00009 PG 10 WC Anesthesiology SC Anesthesiology GA 351AD UT WOS:000089133100005 PM 10969293 ER PT J AU Addona, GH Tseng, A Miller, KW AF Addona, GH Tseng, A Miller, KW TI Investigation of the general anesthetic binding sites on firefly luciferase using a photoreactive general anesthetic SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A116 BP U131 EP U131 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800114 ER PT J AU Addona, GH Sandberg, WS Miller, KW AF Addona, GH Sandberg, WS Miller, KW TI Location of a general anesthetic binding site in protein kinase C cys-2 region identified by photoaffinity labeling and mass spectrometry SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A115 BP U131 EP U131 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800113 ER PT J AU Carter, C Mayfield, JB AF Carter, C Mayfield, JB TI Evaluation of a new supraclavicular brachial plexus catheter technique for shoulder surgery anesthesia and analgesia SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A849 BP U197 EP U197 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800799 ER PT J AU Chao, W Matsui, T Li, L Rosenzweig, A AF Chao, W Matsui, T Li, L Rosenzweig, A TI IGF-I gene transfer prevents hypoxia-induced cardiomyocyte (CM) apoptosis SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Anesthesia & Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A627 BP U170 EP U170 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800593 ER PT J AU Dogra, S Jaynes, T Morning, A Washington, C King-Zeller, S AF Dogra, S Jaynes, T Morning, A Washington, C King-Zeller, S TI Post-operative pain control in patients after lung transplant surgery SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A850 BP U197 EP U197 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800800 ER PT J AU Head, INCA Montero-Huerta, P Tang, JX Addona, GH Bridges, KR AF Head, INCA Montero-Huerta, P Tang, JX Addona, GH Bridges, KR TI Nitric oxide gas (NO) attenuates sickle hemoglobin polymerization SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A658 BP U172 EP U172 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800623 ER PT J AU Meiler, SE Gerszten, RE Hung, R Matsui, T Rosenzweig, A AF Meiler, SE Gerszten, RE Hung, R Matsui, T Rosenzweig, A TI Adenoviral overexpression of a dominant-negative IKK beta specifically blocks NF-kappa B activation in TNF-alpha challenged vascular endothelium and prevents endothelial adhesion of neutrophils under laminar flow conditions SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A609 BP U169 EP U169 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800575 ER PT J AU Melo, MFV Call, DM Harris, RS Layfield, JDH Venegas, JG AF Melo, MFV Call, DM Harris, RS Layfield, JDH Venegas, JG TI Mapping of regional pulmonary PaO2, PaCO2, and pH through mathematical modeling of positron emission tomography (PET) data SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A1339 BP U233 EP U233 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136801270 ER PT J AU Standl, TG Chang, YC de Bronkart, S Willsey, DB D'Ambra, MN AF Standl, TG Chang, YC de Bronkart, S Willsey, DB D'Ambra, MN TI Reducing the incidence of heparin resistance: An evidence-based guideline for heparin dosing for cardiopulmonary bypass SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A206 BP U138 EP U138 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800198 ER PT J AU Sugita, H Kaneki, M Yasuhara, S Sugita, M Martyn, J AF Sugita, H Kaneki, M Yasuhara, S Sugita, M Martyn, J TI iNOS inhibitors prevent LPS-induced hyperglycemia and insulin resistance in rats SO ANESTHESIOLOGY 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 2000 VL 93 IS 3A SU S MA A467 BP U157 EP U157 PG 1 WC Anesthesiology SC Anesthesiology GA 351BU UT WOS:000089136800447 ER PT J AU Emmons, KM Goldstein, MG Roberts, M Cargill, B Sherman, CB Millman, R Brown, R Abrams, DB AF Emmons, KM Goldstein, MG Roberts, M Cargill, B Sherman, CB Millman, R Brown, R Abrams, DB TI The use of nicotine replacement therapy during hospitalization SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID SMOKING-CESSATION; TRANSDERMAL NICOTINE; TOLERANCE QUESTIONNAIRE; COST-EFFECTIVENESS; RANDOMIZED TRIAL; CHEWING-GUM; PATCH; METAANALYSIS; EFFICACY AB Recent findings suggest that smokers who are hospitalized experience significant craving for cigarettes. Thus, nicotine replacement therapy (NRT) may be a particularly important tool for use during hospitalization. The goal of this study is to evaluate the utilization of the transdermal nicotine patch and/or nicotine gum by hospitalized smokers. The data represented in this article are from 580 smokers who participated in a study of a motivational intervention for smoking cessation that was delivered during hospitalization. The primary outcome for this analysis was use of NRT during hospitalization. The results revealed that, among the entire sample, only 7.1% of the overall sample used NRT during hospitalization; 6% of the hospitalized smokers used the transdermal nicotine patch, and 1.1% used nicotine gum. Use of NRT was significantly greater among patients who reported that they were doing anything to help themselves quit smoking at the time of admission (OR = 4.1), those who were seriously planning to quit smoking within the next 30 days(OR = 2.36), those who were nicotine dependent(OR = 2.81), and those for whom a physician had ever offered to prescribe NRT (OR = 1.9). The finding that there is a very low rate of NRT use during hospitalization provides important information to hospital-based care providers and smoking cessation intervention planners. Barriers to NRT use among hospitalized patients should be identified, and strategies designed to maximize use when appropriate. The AHCPR Guideline on Smoking Cessation recommends routine use of NRT in health cave settings. Further research is needed to determine why NRT use was so low. In addition, these data suggest that efforts to increase NRT use during hospitalization are needed. C1 Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [1RO1CA38309]; NHLBI NIH HHS [1RO1HL50017, 1RO1HL48180] NR 21 TC 17 Z9 18 U1 1 U2 2 PU SOC BEHAVIORAL MEDICINE PI MIDDLETON PA 7600 TERRACE AVE, STE 203, MIDDLETON, WI 53562-3174 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD FAL PY 2000 VL 22 IS 4 BP 325 EP 329 DI 10.1007/BF02895669 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 404AY UT WOS:000167076300008 PM 11253444 ER PT J AU Rowe, BH Bretzlaff, JA Bourdon, C Bota, GW Camargo, CA AF Rowe, BH Bretzlaff, JA Bourdon, C Bota, GW Camargo, CA TI Intravenous magnesium sulfate treatment for acute asthma in the emergency department: A systematic review of the literature SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID RANDOMIZED CLINICAL-TRIALS; NEBULIZED IPRATROPIUM; PEDIATRIC ASTHMA; ACUTE CHILDHOOD; META-ANALYSIS; MANAGEMENT; CHILDREN; METAANALYSIS; EFFICACY; HOSPITALIZATION AB Study objectives: There is some evidence that magnesium, when infused into asthmatic patients, can produce bronchodilation in addition to that obtained from standard treatments. This systematic review examined the effect of intravenous magnesium sulfate used for patients with acute asthma managed in the emergency department. Methods: Only randomized controlled trials were eligible for inclusion. Studies were included if patients presented with acute asthma and were treated with intravenous magnesium sulfate versus placebo. Trials were identified from the Cochrane Airways Review Group register, which consists of a combined search of EMBASE, MEDLINE, and CINAHL databases and hand-searching of 20 key respiratory journals. Bibliographies from included studies and known reviews were searched. Primary authors and content experts were contacted. Data were extracted and methodologic quality was assessed independently by 2 reviewers. Missing data were obtained from authors. Results: Seven trials (5 adult, 2 pediatric) involving a total of 668 patients were included. Overall, admission to hospital was not statistically reduced using magnesium sulfate (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.09 to 1.02). In the severe subgroup, admissions were reduced in those receiving magnesium sulfate (OR 0.10, 95% CI 0.04 to 0.27). Overall, patients receiving magnesium sulfate demonstrated nonsignificant improvements in peak expiratory flow rates (PEFR) when all studies were pooled (weighted mean difference [WMD] 29 L/min, 95% CI -3 to 62). In studies of patients with severe acute asthma, PEFR WMD improved by 52 L/min (95% CI 27 to 78) favoring magnesium sulfate treatment. The absolute FEV, also improved by 10% predicted (95% CI 4 to 16) in patients with severe acute asthma. No clinically important changes in vital signs or side effects were reported. Conclusion: Current evidence does not clearly support routine use of intravenous magnesium sulfate in all patients with acute asthma presenting to the ED. However, magnesium sulfate appears to be safe and beneficial for patients who present with severe acute asthma. Practice guidelines need to be changed to reflect these results. C1 Univ Alberta, Fac Med & Dent, Div Emergency Med, Edmonton, AB T6G 2B7, Canada. Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB T6G 2B7, Canada. Sudbury Reg Hosp Corp, Dept Emergency Med, Sudbury, ON, Canada. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. RP Rowe, BH (reprint author), Univ Alberta, Fac Med & Dent, Div Emergency Med, 1 G1-63 Walter Mackenzie Ctr,8440-112 St, Edmonton, AB T6G 2B7, Canada. FU NHLBI NIH HHS [HL-07427, HL-03533] NR 59 TC 75 Z9 80 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2000 VL 36 IS 3 BP 181 EP 190 DI 10.1067/mem.2000.105659 PG 10 WC Emergency Medicine SC Emergency Medicine GA 351EJ UT WOS:000089144600001 PM 10969218 ER PT J AU Emond, SD Reed, CR Graff, LG Clark, S Camargo, CA AF Emond, SD Reed, CR Graff, LG Clark, S Camargo, CA TI Asthma education in the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID SELF-MANAGEMENT EDUCATION; PEAK EXPIRATORY FLOW; PATIENT EDUCATION; TRADITIONAL TREATMENT; COST-EFFECTIVENESS; HEALTH-EDUCATION; CARE; PROGRAM; ADULTS; HOSPITALIZATION AB Study objective: We surveyed emergency department-based asthma researchers to study the presence of formal asthma education programs (AEPs), and examined data from prospective cohort studies to compare sites with and without AEPs. Methods: We contacted site investigators in the Multicenter Airway Research Collaboration (MARC) in July 1998 by mail, fax, or telephone. Main outcomes were the percentage of sites using AEPs and the percentage of AEPs using each of 7 "key" teaching items in national guidelines. MARC data provided site and patient characteristics. Results: All 77 site investigators (100%) responded to the survey. Using a scale from 1 to 5 (mean+/-SD), respondents identified instruction in proper inhaler technique (4.8+/-0.5), "spacer use (4.3+/-0.7), recognition of asthma triggers (4.3+/-0.8), and rationale for medications (4.6+/-0.6) as priorities for teaching. Twelve sites (16%; 95% confidence interval [CI] 8% to 26%) had AEPs; most (8) were at pediatric sites. Patients presenting to sites with AEPs were younger (22+/-16 years versus 25+/-15 years, P<.001), more likely to be uninsured (26% versus 23%, P<.001), and less likely to be taking inhaled corticosteroids (30% versus 37%, P<.001). AEP sites uniformly stressed "key" items, except for "written action plan" (50% of sites) and "peak flow diary" (33% of sites). Conclusion: Although asthma researchers agree that patient education is very important, few EDs involved in asthma research use AEPs. Sites with AEPs appear to serve patients at higher risk of poor asthma outcomes. Further study is needed to address the effectiveness of AEPs in the ED. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Cornell Univ, New York Presbyterian Hosp, Dept Emergency Med, New York, NY USA. Cornell Univ, Weill Med Coll, New York, NY USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. New Britain Gen Hosp, Dept Emergency Med, New Britain, CT USA. Univ Connecticut, Sch Med, Farmington, CT USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin Bldg 116, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-63253, HL-03533] NR 44 TC 22 Z9 22 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD SEP PY 2000 VL 36 IS 3 BP 204 EP 211 DI 10.1067/mem.2000.109168 PG 8 WC Emergency Medicine SC Emergency Medicine GA 351EJ UT WOS:000089144600004 PM 10969221 ER PT J AU Gibson, GE Haroutunian, V Zhang, H Park, LCH Shi, Q Lesser, M Mohs, RC Sheu, RKF Blass, JP AF Gibson, GE Haroutunian, V Zhang, H Park, LCH Shi, Q Lesser, M Mohs, RC Sheu, RKF Blass, JP TI Mitochondrial damage in Alzheimer's disease varies with apolipoprotein E genotype SO ANNALS OF NEUROLOGY LA English DT Article ID ALPHA-KETOGLUTARATE DEHYDROGENASE; CEREBRAL GLUCOSE-METABOLISM; E EPSILON-4 ALLELE; COMPLEX ACTIVITY; PYRUVATE-DEHYDROGENASE; RELATIVE IMPORTANCE; ENZYME-ACTIVITIES; OXIDATIVE STRESS; POSTMORTEM BRAIN; DLST GENOTYPE AB Brain metabolism and the activity of the alpha -ketoglutarate dehydrogenase complex (KGDHC), a mitochondrial enzyme, are diminished in brains from patients with Alzheimer's disease (AD). In 109 subjects, the Clinical Dementia Rating (CDR) score was highly correlated with brain KGDHC activity. In AD patients who carried the epsilon 4 allele of the apolipoprotein E gene (ApoE4), the CDR score correlated better with KGDHC activity than with the densities of neuritic plaques or neuritic tangles. In contrast, in patients without ApoE4, the CDR score correlated significantly better with tangles and plaques than with KGDHC activity. The results suggest that mitochondrial/oxidative damage may be more important for the cognitive dysfunction in AD patients who early ApoE4 than in those who do not. C1 Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurol, White Plains, NY 10605 USA. Cornell Univ, Weill Med Coll, Dept Neurosci, White Plains, NY 10605 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. Northshore Hosp, Manhasset, NY USA. RP Gibson, GE (reprint author), Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurol, 785 Mamaroneck Ave, White Plains, NY 10605 USA. FU NIA NIH HHS [AG11921, AG14600, AG14930] NR 50 TC 118 Z9 120 U1 2 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 SEP PY 2000 VL 48 IS 3 BP 297 EP 303 DI 10.1002/1531-8249(200009)48:3<297::AID-ANA3>3.0.CO;2-Z PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 349BU UT WOS:000089024600003 PM 10976635 ER PT J AU Arroyo, JG Brinton, DA Zarbin, MA AF Arroyo, JG Brinton, DA Zarbin, MA TI Endogenous endophthalmitis initially misdiagnosed as anterior uveitis SO ANNALS OF OPHTHALMOLOGY LA English DT Article ID BACTERIAL ENDOPHTHALMITIS AB A diabetic man was found to have endogenous endophthalmitis associated with a bilobar prostatic abscess. Initially, anterior uveitis had been diagnosed which delayed definitive diagnosis and therapy. After the correct diagnosis, the patient was successfully treated with vitrectomy as well as intravitreal, topical, and systemic antibiotics. Endogenous endophthalmitis should always be considered early in the differential diagnosis of anterior uveitis. C1 Univ Calif San Francisco, Dept Ophthalmol, Sch Med, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Med & Dent New Jersey, Sch Med, Dept Ophthalmol, Newark, NJ 07103 USA. RP Arroyo, JG (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 12th Floor, Boston, MA 02114 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CONTEMPORARY OPHTHALMOLOGY PI CHICAGO PA 820 N ORLEANS, STE 208, CHICAGO, IL 60610 USA SN 1079-4794 J9 ANN OPHTHALMOL JI Ann. Ophthalmol. PD FAL PY 2000 VL 32 IS 3 BP 199 EP 200 DI 10.1007/s12009-000-0053-y PG 2 WC Ophthalmology SC Ophthalmology GA 362TE UT WOS:000089793700008 ER PT J AU MaWhinney, S Brown, ER Malcolm, J VillaNueva, C Groves, BM Quaife, RA Lindenfeld, J Warner, BA Hammermeister, KE Grover, FL Shroyer, ALW AF MaWhinney, S Brown, ER Malcolm, J VillaNueva, C Groves, BM Quaife, RA Lindenfeld, J Warner, BA Hammermeister, KE Grover, FL Shroyer, ALW TI Identification of risk factors for increased cost, charges, and length of stay for cardiac patients SO ANNALS OF THORACIC SURGERY LA English DT Article ID SEVERITY; QUALITY; SURGERY; ILLNESS; HEALTH; MODEL AB Background. In this study we explored different risk model options to provide clinicians with predictions for resource utilization. The hypotheses were that predictors of mortality are not predictive of resource consumption, and that there is a correlation between cost estimates derived using a cost-to-charge ratio or a product-line costing approach. Methods. From March 1992 to June 1995, 2,481 University of Colorado Hospital patients admitted for ischemic heart disease were classified by diagnosis-related group code as having undergone or experienced coronary bypass procedures (CBP), percutaneous cardiovascular procedures (PCVP), acute myocardial infarction (AMI), and other cardiac-related discharges (Other). For each diagnosis-related group, Cox proportional hazards models were developed to determine predictors of cost, charges, and length of stay. Results. The diagnosis groups differed in the clinical factors that predicted resource use. As the two costing methods were highly correlated either approach may be used to assess relative resource consumption provided costs are reconciled to audited financial statements. Conclusions. To develop valid prediction models for costs of care, the clinical risk factors that are traditionally used to predict risk-adjusted mortality may need to be expanded. (Ann Thorac Surg 2000;70:702-10) (C) 2000 by The Society of Thoracic Surgeons. C1 Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. USAF Acad, Dept Math, Colorado Springs, CO 80840 USA. Dept Vet Affairs Med Ctr, Denver, CO USA. RP Shroyer, ALW (reprint author), Denver VA Med Ctr, Div Cardiac Res, 1035 Clermont St 151R, Denver, CO 80220 USA. RI Brown, Elizabeth/A-8984-2008; Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 20 TC 17 Z9 18 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 2000 VL 70 IS 3 BP 702 EP 710 DI 10.1016/S0003-4975(00)01510-1 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 356MQ UT WOS:000089447400003 PM 11016297 ER PT J AU Hengstler, JG Bauer, A Wolf, HK Bulitta, CJ Tanner, B Oesch, F Gebhard, S Boettger, T AF Hengstler, JG Bauer, A Wolf, HK Bulitta, CJ Tanner, B Oesch, F Gebhard, S Boettger, T TI Mutation analysis of the cationic trypsinogen gene in patients with pancreatic cancer SO ANTICANCER RESEARCH LA English DT Article DE pancreatic cancer; mutation analysis; cationic trypsinogen gene; hereditary pancreatitis ID HEREDITARY PANCREATITIS; OVARIAN-CANCER; HETEROGENEITY; FAMILIES AB Recently, an Alg to His mutation at residue 117 of the cationic trypsinogen gene (Arg117His) has been shown to be associated with hereditary pancreatitis (hp). A serious complication of hp is development of pancreatic cancer: Patients suffering from om hp have been reported to have a 53-fold increased risk to die fi om pancreatic cancel: However, the quantitative contribution of mutations in the cationic trypsinogen gene to all pancreatic cancel cases is unknown. A relevant contribution of the Arg117His-mutation to pathogenesis of pancreatic cancer might be possible, since also asymptomatic individuals have been reported to carry this mutation and individuals with only mild symptoms may be undiagnosed as: hp. In the present study we analyzed genomic DNA obtained fi om pancreatic cancer tissue fi om 34 patients and corresponding normal tissue fi om 28 of these individuals. The third exon of the cationic trypsinogen gene was amplified by nested PCR and digested with AflIII, since the Arg117His mutation creates an AflIII-restriction site. None of the examined samples carried the Arg117His mutation, whereas the amplification product obtained from a patient with known hp was clearly positive. Sequencing of the complete third exon of the cationic trypsinogen gene in 10 of the pancreatic cancer patients resulted exclusively in the wild-type sequence. In addition DNA obtained from venous blood of 116 further patients with pancreatic cancel did not carry the Arg117His mutation. Our results show that the Arg117His mutation does not contribute to pathogenesis of a substantial fraction of all pancreatic adenocarcinomas. In contrast to most oncogenes or tumor suppressor genes the cationic trypsinogen gene (3rd exon) does not contain mutational hot spots. C1 Univ Mainz, Inst Toxicol, D-55131 Mainz, Germany. Univ Mainz, Inst Pathol, D-55131 Mainz, Germany. Univ Mainz, Dept Gynecol, D-55131 Mainz, Germany. Univ Mainz, Dept Surg, D-55131 Mainz, Germany. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Hengstler, JG (reprint author), Hengstler Inst Toxicol, Obere Zahlbacher Str 67, D-55131 Mainz, Germany. RI Hengstler, Jan/O-1415-2013 NR 16 TC 13 Z9 14 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 2000 VL 20 IS 5A BP 2967 EP 2974 PG 8 WC Oncology SC Oncology GA 367BQ UT WOS:000090042100024 PM 11062709 ER PT J AU Rasheed, JK Anderson, GJ Yigit, H Queenan, AM Domenech-Sanchez, A Swenson, JM Biddle, JW Ferraro, MJ Jacoby, GA Tenover, FC AF Rasheed, JK Anderson, GJ Yigit, H Queenan, AM Domenech-Sanchez, A Swenson, JM Biddle, JW Ferraro, MJ Jacoby, GA Tenover, FC TI Characterization of the extended-spectrum beta-lactamase reference strain, Klebsiella pneumoniae K6 (ATCC 700603), which produces the novel enzyme SHV-18 SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; MOLECULAR CHARACTERIZATION; FAMILY ENTEROBACTERIACEAE; CEFOTAXIME RESISTANCE; PLASMID; GENE; IDENTIFICATION; CEPHALOSPORINS; MEMBERS AB Klebsiella pneumoniae K6 (ATCC 700603), a clinical isolate, is resistant to ceftazidime and other oxyimino-beta-lactams. A consistent reduction in the MICs of oxyimino-beta-lactams by at least 3 twofold dilutions in the presence of clavulanic acid confirmed the utility of Ii. pneumoniae K6 as a quality control strain for extended-spectrum beta-lactamase (ESBL) detection. Isoelectric-focusing analysis of crude lysates of K6 demonstrated a single beta-lactamase with a pi of 7.8 and a substrate profile showing preferential hydrolysis of cefotaxime compared to ceftazidime. PCR analysis of total bacterial DNA from K6 identified the presence of a bla(SHV) gene. K6 contained two large plasmids with molecular sizes of approximately 160 and 80 kb, Hybridization of plasmid DNA with a bla(SHV)-specific probe indicated that a bla(SHV) gene was encoded on the 80-kb plasmid, which was shown to transfer resistance to ceftazidime in conjugal mating experiments With Escherichia coli HB101. DNA sequencing of this bLa(SHV)-related gene revealed that it differs from bla(SHV-1) at nine nucleotides, five of which resulted in amino acid substitutions: Ile to Phe at position 8, Arg to Ser at position 43, Gly to Na at position 238, and Glu to Lys at position 240. In addition to the production of this novel ESBL, designated SHV-18, analysis of the outer membrane proteins of K6 revealed the loss of the OmpK35 and OmpK37 porins. C1 Ctr Dis Control & Prevent, Nosocomial Pathogens Lab Branch G08, Natl Ctr Infect Dis, Hosp Infect Program, Atlanta, GA 30333 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. Univ Las Islas Baleares, Dept Biol, Area Microbiol, Palma de Mallorca, Spain. Massachusetts Gen Hosp, Microbiol Lab, Boston, MA 02114 USA. Edith Nourse Rogers Mem Vet Adm Hosp, Bedford, MA 01730 USA. Lahey Clin Fdn, Med Ctr, Burlington, MA 01805 USA. RP Rasheed, JK (reprint author), Ctr Dis Control & Prevent, Nosocomial Pathogens Lab Branch G08, Natl Ctr Infect Dis, Hosp Infect Program, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. NR 55 TC 70 Z9 74 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 2000 VL 44 IS 9 BP 2382 EP 2388 DI 10.1128/AAC.44.9.2382-2388.2000 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 345TH UT WOS:000088830900023 PM 10952583 ER PT J AU Rusconi, S Merill, DP Catamancio, SL Citterio, P Bulgheroni, E Croce, F Chou, TC Yang, OO Herrmann, SH Galli, M Hirsch, MS AF Rusconi, S Merill, DP Catamancio, SL Citterio, P Bulgheroni, E Croce, F Chou, TC Yang, OO Herrmann, SH Galli, M Hirsch, MS TI In vitro inhibition of HIV-1 by Met-SDF-1 beta alone or in combination with antiretroviral drugs SO ANTIVIRAL THERAPY LA English DT Article; Proceedings Paper CT 6th Conference on Retroviruses and Opportunistic Infections CY JAN 31-FEB 04, 1999 CL CHICAGO, ILLINOIS ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CXCR4; RECOMBINANT SOLUBLE CD4; SMALL-MOLECULE INHIBITOR; DOWN-MODULATION; TROPIC HIV-1; ENTRY; INFECTION; CORECEPTOR; MACROPHAGES AB Compounds that can block the CXCR4 chemokine receptor are a promising new class of antiretroviral agents. In these experiments we studied the effect of a modified form of the native stromal cell-derived factor-1 (SDF-1), Met-SDF-1 beta. The in vitro susceptibility of two different CXCR4-tropic HIV-1 strains was determined. Antiviral effect was assessed by the reduction of p24 antigen production in PHA-stimulated peripheral blood mononuclear cells with exposure to the modified SDF-1 molecule. The 50% inhibitory concentrations (IC50) were derived from six separate experiments. The IC50 against the two HIV-1 isolates was in 1.0-2.8 mug/ml range for Met-SDF-1 beta. Met-SDF-1 beta showed synergy to additivity with either zidovudine or nelfinavir at IC75, IC90 and IC95. Additivity was seen when Met-SDF-1 beta was combined with efavirenz. No cellular toxicity was observed at the highest concentrations when these agents were used either singly or in combination. This compound is a promising new candidate in a receptor-based approach to HIV-1 infection in conjunction with currently available combination antiretroviral drug therapies. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Milan, Osped Luigi Sacco, Ist Malattie Infett & Trop, Milan, Italy. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Genet Inst, Cambridge, MA 02140 USA. RP Rusconi, S (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RI Chou, Ting-Chao/B-4111-2009; Rusconi, Stefano/H-9263-2012 OI Chou, Ting-Chao/0000-0002-3340-1594; FU NCI NIH HHS [CA 12464] NR 43 TC 10 Z9 10 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD SEP PY 2000 VL 5 IS 3 BP 199 EP 204 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 369ZL UT WOS:000165097600004 PM 11075940 ER PT J AU Datta, MW Shahsafaei, A Nadler, LM Freeman, GJ Dorfman, DM AF Datta, MW Shahsafaei, A Nadler, LM Freeman, GJ Dorfman, DM TI Expression of MHC class II-associated invariant chain (Ii;CD74) in thymic epithelial neoplasms SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 08, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE thymus; thymoma; thymic carcinoma; immunohistochemistry ID SURFACE EXPRESSION; TUMORS; CARCINOMAS; CD74; MOLECULES; THYMOMA; MCL-1; BCL-2 AB Thymic epithelial cells express major histocompatibility complex (MHC) class II and are involved in T-cell ontogeny. In these cells, MHC class II-associated invariant chain (CD74) is involved in antigen presentation during T-cell selection. We studied a range of thymic epithelial neoplasms for CD74 expression by neoplastic epithelial cells to determine whether such expression correlates with MHC class IT expression and tumor type. Sixty-four thymic epithelial neoplasms (27 cases of benign thymoma, 20 cases of invasive thymoma, and 17 cases of true thymic carcinoma) were studied for neoplastic epithelial cell expression of CD74 and MHC class II molecules by immunohistochemical staining of paraffin-embedded tissue. Neoplastic epithelial cells in 88% of thymic carcinomas (15/17), 70% of invasive thymomas (14/20), but only 33% of benign thymomas (9/27) were immunoreactive for CD74. A subset of CD74-positive neoplasms was positive for MHC class II as well, with higher relative rates of dual positivity in more aggressive neoplasms. In addition, specific histologic subtypes of thymic epithelial neoplasms displayed differing patterns of CD74 positivity. Based on these findings, CD74 and MHC class II are useful markers for the classification of thymic epithelial neoplasms. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Dorfman, DM (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02115 USA. NR 24 TC 29 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD SEP PY 2000 VL 8 IS 3 BP 210 EP 215 DI 10.1097/00022744-200009000-00007 PG 6 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 349JC UT WOS:000089041100007 PM 10981873 ER PT J AU Tsao, H Zhang, X Kwitkiwski, K Finkelstein, DM Sober, AJ Haluska, FG AF Tsao, H Zhang, X Kwitkiwski, K Finkelstein, DM Sober, AJ Haluska, FG TI Low prevalence of germline CDKN2A and CDK4 mutations in patients with early-onset melanoma SO ARCHIVES OF DERMATOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-for-Human Genetics CY OCT 27-31, 1998 CL DENVER, COLORADO SP Amer Soc Human Genet ID MALIGNANT-MELANOMA; FAMILIAL MELANOMA; P16; CANCER; GENE; POPULATION; BREAST; NEVI AB Background: In patients with cutaneous melanoma, early age at disease onset is characteristic in familial cases and in individuals with multiple primary melanomas. Both subsets of patients with melanoma are at risk for harboring germline CDKN2A or CDK4 mutations. Objective: We set out to prospectively determine the prevalence of CDKN2A and CDK4 mutations in a group of young patients with melanoma. Design: We prospectively screened 913 patients over a 6-month period and identified 519 patients with invasive melanomas. We invited 172 patients with melanoma who were younger than 40 years to participate in the study, and 49 patients consented and donated peripheral blood samples. Forty-nine percent (n=24) of our patients developed cutaneous melanoma before the age of 30 years. Setting: A melanoma clinic in the Boston, Mass, area. Main Outcome Measurer We used a combination of single-strand conformation analysis and direct sequencing of samples of peripheral blood leukocyte DNA to search for mutations in exons 1 alpha, 1 beta, 2, and 3 of CDKN2A and in exon 2 of CDK4. Results: The mean and median ages at diagnosis in our group were 30 and 32 years, respectively. Among a group of 49 patients, we detected 1 (2%; 95% confidence interval, 0.07%-10.8%) Met 53 Ile CDKN2A mutation, which was found in a patient xith a strong family history of melanoma. This alteration has been previously shown to impair p16 function. One patient had an Ala 148 Thr change in CDKN2A, which has also been shown to be a polymorphism. We also detected a sequence polymorphism tin the 3' untranslated region [3'UTR] of CDKN2A) in 27% of our patients. A similar incidence of this 3'UTR polymorphism was observed in a control population. We found no CDK4 mutations. Conclusions: Germline CDKN2A and CDK4 mutations are not common in patients who develop melanoma at an early age. This finding contrasts with ether cancer-predisposition syndromes, in which there is an increased incidence of germline mutations among young patients. Selection of patients with melanoma for genetic testing based solely on age at onset may not be warranted at the current time. C1 Massachusetts Gen Hosp, Dana Farber Partners Canc Care, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dana Farber Partners Canc Care, Dept Med, Div Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dana Farber Partners Canc Care, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dana Farber Partners Canc Care, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. China Med Univ, Dept Cell Biol & Med Genet, Shenyang, Peoples R China. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dana Farber Partners Canc Care, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. NR 35 TC 54 Z9 54 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD SEP PY 2000 VL 136 IS 9 BP 1118 EP 1122 DI 10.1001/archderm.136.9.1118 PG 5 WC Dermatology SC Dermatology GA 353NW UT WOS:000089283200006 PM 10987867 ER PT J AU Johnson, DA Yeh, CK Dodds, MWJ AF Johnson, DA Yeh, CK Dodds, MWJ TI Effect of donor age on the concentrations of histatins in human parotid and submandibular/sublingual saliva SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE histatins; parotid saliva; submandibular/sublingual saliva; ageing ID HISTIDINE-RICH POLYPEPTIDES; CANDIDA-ALBICANS; FLOW-RATE; ANTIMICROBIAL PROTEINS; ANTIFUNGAL ACTIVITY; FUNGICIDAL ACTIVITY; HIV-1 INFECTION; HEALTHY-ADULTS; SECRETORY IGA; WHOLE SALIVA AB Histatins are small proteins of human glandular saliva that have antifungal properties. Recent studies show that oral candidal infections increase with age, suggesting an age-associated compromise in oral host defence. Here, the effect of age and of physiological gland stimulation on the concentration and secretion of salivary histatins was investigated. Parotid and submandibular/sublingual salivas were collected from six young adults under unstimulated, mechanical (chewing) and gustatory (0.025 M and 0.1 M citric acid) stimulation, and the concentration and secretion of histatins was measured by cationic polyacrylamide gel electrophoresis with subsequent densitometric scanning of the stained gels. With gland stimulation, parotid saliva showed no significant increase in histatin concentration (mu g/ml); however, histatin secretion (mu g/min) increased up to 26-fold (p < 0.005; ANOVA). Stimulation of submandibular/sublingual saliva resulted in significant increases in both histatin concentration (p < 0.005) and secretion (p < 0.0005). Ageing effects on salivary histatins were determined in citric acid (0.1 M)-stimulated parotid and submandibular/sublingual saliva samples collected from 80 individuals (divided into four age groups having approximately equal numbers of males and females: 35-44 years; 45-54 years; 55-64 years and 65-76 years). None of the patients was taking medications or wore dentures. ANOVA showed no sex differences in histatins. Regression analysis showed significant age-associated decreases for parotid saliva histatin concentration (p < 0.002) and secretion (p < 0.002) as well as for submandibular/sublingual saliva histatin concentration (p < 0.0001) and secretion (p < 0.0001). Both saliva types showed significant (p < 0.0001) decreases in the histatin concentration per mg of total protein, suggesting a preferential decrease in salivary histatins compared to total salivary protein. These results suggest that the salivary histatin component of the oral host defence system is compromised with increasing age. (C) 2000 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Community Dent 7917, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Dent Diagnost Sci 7919, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA. RP Johnson, DA (reprint author), Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Community Dent 7917, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIDCR NIH HHS [DE10756] NR 47 TC 37 Z9 40 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD SEP PY 2000 VL 45 IS 9 BP 731 EP 740 DI 10.1016/S0003-9969(00)00047-9 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 346AP UT WOS:000088848200003 PM 10869486 ER PT J AU Burnfield, JM Josephson, KR Powers, CM Rubenstein, LZ AF Burnfield, JM Josephson, KR Powers, CM Rubenstein, LZ TI The influence of lower extremity joint torque on gait characteristics in elderly men SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 51st Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 20-24, 1998 CL PHILADELPHIA, PENNSYLVANIA SP Gerontol Soc Amer DE gait; muscles; strength; geriatrics, elderly; rehabilitation ID RECURRENT FALLS; STRENGTH; EXERCISE; PREDICTORS; VELOCITY; PEOPLE; MUSCLE; WOMEN; HOME; AGE AB Objective: To examine the relation between certain lower extremity isokinetic muscle torque capabilities and selected stride characteristics for a group of elderly, sedentary men. Study Design: Descriptive analysis of convenience sample. Setting: Veterans Administration (VA) ambulatory care center. Subjects: Eighty-one elderly men, capable of independent ambulation, were recruited from outpatient clinics and the local community (mean age, 74.7yr). Main Outcome Measures: Maximal isokinetic torque in the sagittal plane of hip, knee, and ankle muscles; stride characteristics of speed, stride length, and cadence recorded during walking at a self-selected velocity. Results: Stepwise regression analysis revealed that hip extension torque was the only significant independent predictor for free walking speed, stride length, and cadence, and accounted for 37% (r = .611), 35% (r = .590), and 12% (r = .341) of the total variance, respectively. Other joint torques correlated with gait parameters but did not add significantly to the multivariate model. Conclusions: Hip extension torque was the only significant independent predictor for free walking velocity, stride length, and cadence in this group. These results support the idea that strengthening the hip extensors may improve stride characteristics in elderly individuals. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Geriatr Res Educ & Clin Ctr 11E, Sepulveda, CA 91343 USA. Univ So Calif, Dept Biokinesiol & Phys Therapy, Los Angeles, CA USA. RP Rubenstein, LZ (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Geriatr Res Educ & Clin Ctr 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. RI Powers, Christopher/J-2662-2014 NR 24 TC 33 Z9 33 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD SEP PY 2000 VL 81 IS 9 BP 1153 EP 1157 DI 10.1053/apmr.2000.7174 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 350PM UT WOS:000089110400004 PM 10987153 ER PT J AU Ohmura, K Ji, H Benoist, C Mathis, D AF Ohmura, K Ji, H Benoist, C Mathis, D TI Genetics of end-stage disease process in a mouse model of inflammatory arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Immunol & Immunogenet, 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 2000 VL 43 IS 9 SU S MA 35 BP S56 EP S56 PG 1 WC Rheumatology SC Rheumatology GA 357JU UT WOS:000089495800036 ER PT J AU Kanamori, A Woo, SLY Ma, CB Zeminski, J Rudy, TW Li, GA Livesay, GA AF Kanamori, A Woo, SLY Ma, CB Zeminski, J Rudy, TW Li, GA Livesay, GA TI The forces in the anterior cruciate ligament and knee kinematics during a simulated pivot shift test: A human cadaveric study using robotic technology SO ARTHROSCOPY LA English DT Article DE knee; anterior cruciate ligament; knee kinematics; in situ force; pivot shift test ID IN-SITU FORCES; METHODOLOGY; ROTATION; INJURIES; INVITRO; SENSOR; MOTION; LAXITY; JOINT AB Purpose: Although it is well known that the anterior cruciate ligament (ACL) is a primary restraint of the knee under anterior tibial load, the role of the ACL in resisting internal tibial torque and the pivot shift test is controversial. The objective of this study was to determine the effect of these 2 external loading conditions on the kinematics of the intact and ACL-deficient knee and the in situ force in the ACL. Type of Study: This study was a biomechanical study that used cadaveric knees with the intact knee of the specimen serving as a control, Materials and Methods: Twelve human cadaveric knees were tested using a robotic/universal force-moment sensor testing system. This system applied (1) a 10-Newton meter (Nm) internal tibial torque and (2) a combined IO-Nm valgus and 10-Nm internal tibial torque (simulated pivot shift test) to the intact and the ACL-deficient knee. Results: In the ACL-deficient knee,the isolated internal tibial torque significantly increased coupled anterior tibial translation over that of the intact knee by 94%, 48%, and 19% at full extension, 15 degrees, and 30 degrees of flexion, respectively (P < .05). In the case of the simulated pivot shift test, there were similar increases in anterior tibial translation, i.e., 103%, 61%, and 32%, respectively (P < .05), Furthermore, the anterior tibial translation under the simulated pivot shift test was significantly greater than under an isolated internal tibial torque (P < .05). Under the simulated pivot shift test, the in situ forces in the ACL were 83 +/- 16 N at full extension and 93 +/- 23 N at 15 degrees of knee flexion. These forces were also significantly higher when compared with those for an isolated internal tibial torque (P < .05). Conclusion: Our data indicate that the ACL plays an important role in restraining coupled anterior tibial translation in response to the simulated pivot shift test as well as under an isolated internal tibial torque, especially when the knee is near extension. These findings are also consistent with the clinical observation of anterior tibial subluxation during the pivot shift test with the knee near extension. C1 Univ Pittsburgh, Med Ctr, Musculoskeletal Res Ctr, Dept Orthopaed Surg, Pittsburgh, PA 15213 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Biomech Lab, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA USA. Tulane Univ, Dept Engn, New Orleans, LA 70118 USA. RP Woo, SLY (reprint author), Univ Pittsburgh, Med Ctr, Musculoskeletal Res Ctr, Dept Orthopaed Surg, 210 Lothrop St,E1641-BST,Box 71199, Pittsburgh, PA 15213 USA. RI Woo, Savio/A-8543-2009 FU NIAMS NIH HHS [AR39683] NR 38 TC 165 Z9 167 U1 0 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD SEP PY 2000 VL 16 IS 6 BP 633 EP 639 DI 10.1053/jars.2000.7682 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 351QZ UT WOS:000089170800011 PM 10976125 ER PT J AU Navder, KP Baraona, E Lieber, CS AF Navder, KP Baraona, E Lieber, CS TI Dilinoleoylphosphatidylcholine protects human low density lipoproteins against oxidation SO ATHEROSCLEROSIS LA English DT Article DE phospholipids; anti-oxidants; low-density lipoproteins; atherosclerosis ID VITAMIN-E CONSUMPTION; LIPID-PEROXIDATION; FATTY-ACIDS; POLYENYLPHOSPHATIDYLCHOLINE; ATHEROSCLEROSIS; RISK; SUSCEPTIBILITY; FIBROSIS; BABOONS; ALCOHOL AB LDL oxidation may promote atherosclerosis. We found that polyenyphosphatidylcholine (PPC), a mixture of polyunsaturated phospholipids extracted from soybeans, has antioxidant effects in in vivo models of oxidative stress. To assess whether components of PPC affect the in vitro oxidizability of LDL, plasma from 15 healthy volunteers was incubated with 10 mu M of either dilinoleoyl-, palmitoyl-linoleoyl-, linoleoyl-palmitoyl- or distearoyl-phosphatidylcholine as well as 10 mu M and 1 mM alpha-tocopherol. LDL oxidation was initiated with 5 mu M Cu2+ sulfate and monitored by conjugated diene production, or with 2,2'-azobis (2-amidinopropane) dihydrochloride. a free radical generator, and monitored by O-2 consumption. After addition of Cu2+, the lag phase (indicative of resistance of LDL to oxidation) was longer (140% of controls; P < 0.001) for LDL incubated with dilinoleoyl-. but not with the other phosphatidylcholine species. This effect was similar to that of 1 mM alpha-tocopherol (135%,). After addition of 2,2'-azobis (2-amidinopropane) dihydrochloride, the inhibition time (also reflecting the antioxidant content of LDL) was prolonged (P<0.001) for alpha-tocopherol (206%) and dilinoleoyl-( 188%), but not for distearoyl-phosphatidyl-choline. Thus, dilinoleoyl-phosphatidylcholine (the main component of PPC) protects against LDL oxidation, a possible mechanism for its reported anti-atherosclerosis effects. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Bronx Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment, Bronx, NY 10468 USA. Mt Sinai Sch Med, Bronx, NY 10468 USA. CUNY Hunter Coll, Nutr & Food Sci Urban Publ Hlth Program, New York, NY 10010 USA. RP Lieber, CS (reprint author), Vet Affairs Med Ctr, Alcohol Res Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NIAAA NIH HHS [AA11115] NR 32 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD SEP PY 2000 VL 152 IS 1 BP 89 EP 95 DI 10.1016/S0021-9150(99)00454-2 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 356MU UT WOS:000089447700011 PM 10996343 ER PT J AU Lopes-Virella, MF Koskinen, S Mironova, M Horne, D Klein, R Chassereau, C Enockson, C Virella, G AF Lopes-Virella, MF Koskinen, S Mironova, M Horne, D Klein, R Chassereau, C Enockson, C Virella, G TI The preparation of copper-oxidized LDL for the measurement of oxidized LDL antibodies by EIA SO ATHEROSCLEROSIS LA English DT Article DE arteriosclerosis; autoimmunity; autoantibodies; oxidized low-density lipoprotein antibodies; oxidized low-density lipoprotein antibody enzyme immunoassay; oxidized low-density lipoprotein ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVELY-MODIFIED LDL; CAROTID ATHEROSCLEROSIS; VASCULAR-DISEASE; AUTOANTIBODIES; INVIVO AB In the present study we try to define the optimal conditions for preparation of copper-oxidized low-density lipoprotein (oxLDL) to be used for the assay of oxLDL antibodies by enzyme immunoassay (EIA). Oxidation of LDL was monitored by measuring the formation of conjugated dienes at 234 nm and the generation of fluorescent products with emission at 430 nm when excitation is performed at 360 nm. The generation of immunogenic epitopes was evaluated by testing the reactivity of aliquots collected at different times during the oxidation process with human sera with high oxLDL antibody levels and with a purified human oxLDL antibody. The values of fluorescence emission at 430 nm correlated best with reactivity with oxLDL antibodies; strong reactivity was usually associated with values greater than 1.1 U. The time needed for fluorescence emission to reach maximum levels varied between 6 and 14 h for most LDL, but it was considerably longer in a few LDL preparations. The maximal reactivity of oxLDL with oxLDL antibodies was observed when the LDL oxidation reaction was stopped 4 or more hours after the fluorescence readings reached their peak. At this stage of the oxidation reaction, apolipoprotein B fragmentation and aggregation were observed as shown by Western blot analysis. The CV for 13 EIA runs of two reference oxLDL antibodies reacting with four different pools of standardized oxLDL prepared according to the stated guidelines was 14.5 and 3.9%, confirming the reproducibility of our oxidation conditions. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Ralph H Johnson VAMC, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Lopes-Virella, MF (reprint author), Ralph H Johnson VAMC, Dept Med, Div Endocrinol Diabet & Med Genet, Strom Thurmond Bldg,Room 530,114 Doughty St,POB 2, Charleston, SC 29403 USA. FU NHLBI NIH HHS [HL-55782] NR 24 TC 20 Z9 21 U1 0 U2 1 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 SEP PY 2000 VL 152 IS 1 BP 107 EP 115 DI 10.1016/S0021-9150(99)00456-6 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 356MU UT WOS:000089447700013 PM 10996345 ER PT J AU Lovy, MR Starkebaum, G AF Lovy, MR Starkebaum, G TI Rheumatic disorders associated with hepatitis C SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE hepatitis C; rheumatic disorders; Sjogren's syndrome; mixed cryoglobulinaemia; arthritis; liver disease; skin disorder; glomerulonephritis; neurological manifestations; dermatological manifestations; non-Hodgkin's lymphoma; serological abnormalities; diagnostic tests ID PRIMARY SJOGRENS-SYNDROME; PORPHYRIA-CUTANEA-TARDA; NON-HODGKINS-LYMPHOMA; HCV-INFECTED PATIENTS; CHRONIC LIVER-DISEASE; ORAL LICHEN-PLANUS; VIRUS CORE PROTEIN; B-CELL EXPANSIONS; MIXED CRYOGLOBULINEMIA; POLYARTERITIS-NODOSA AB The hepatitis C virus (HCV) is a common virus of world-wide distribution affecting up to 3% of the world's population. Its genetic diversity, with multiple subtypes, and existence in the form of quasispecies in individual hose, is, in part, responsible for high rates of chronic infection. Individuals with HCV infection will undoubtedly present to rheumatologists and other health care professionals with rheumatic and other immunological disorders related to what was usually a remote and asymptomatic acute infection. The goals of this review are: (I) to summarize clinical observations regarding rheumatological and immunological diseases linked with HCV infection; (2) to provide relevant information on the molecular biology of HCV; (3) to discuss the state of the art regarding the use of diagnostic studies; (4) to consider the differential diagnosis of liver disease and rheumatic disorders; and (5) to provide a practical guide to the history, physical examination, laboratory work-up, disease monitoring, and therapy of HCV patients with rheumatic disorders. C1 Univ Washington, Tacoma, WA 98405 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA 98108 USA. RP Lovy, MR (reprint author), Univ Washington, 1310 S Union,Suite A, Tacoma, WA 98405 USA. NR 99 TC 4 Z9 4 U1 1 U2 2 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD SEP PY 2000 VL 14 IS 3 BP 535 EP 557 DI 10.1053/berh.2000.0092 PG 23 WC Rheumatology SC Rheumatology GA 359DA UT WOS:000089595200008 PM 10985985 ER PT J AU Holz, GG Leech, CA Habener, JF AF Holz, GG Leech, CA Habener, JF TI Insulinotropic toxins as molecular probes for analysis of glucagon-like peptide-1 receptor-mediated signal transduction in pancreatic beta-cells SO BIOCHIMIE LA English DT Article DE cholera toxin; pertussis toxin; mastoparan; maitotoxin; alpha-latrotoxin; insulin; GLP-1 ID ALPHA-LATROTOXIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; ISLET-ACTIVATING PROTEIN; TERMINAL EXTRACELLULAR DOMAIN; NUCLEOTIDE-BINDING-PROTEINS; INTRACELLULAR CA2+ STORES; ADRENAL CHROMAFFIN CELLS; CYCLIC-AMP ACCUMULATION; PERTUSSIS-TOXIN; ADP-RIBOSYLATION AB Cholera toxin, pertussis toxin, mastoparan, maitotoxin, and alpha -latrotoxin are complex protein or polyether-based toxins of bacterial, insect, or phytoplankton origin that act with high potency at the endocrine pancreas to stimulate secretion of insulin from beta -cells located in the islets of Langerhans. The remarkable insulinotropic properties of these toxins have attracted considerable attention by virtue of their use as selective molecular probes for analyses of beta -cell stimulus-secretion coupling. Targets of the toxins include heptahelical cell surface receptors, GTP-binding proteins, ion channels, Ca2+ stores, and the exocytotic secretory apparatus. Here we review the value of insulinotropic toxins from the perspective of their established. use in the study of signal transduction pathways activated by the blood glucose-lowering hormone glucagon-like peptide-1 (GLP-1). Our analysis of one insulinotropic toxin (alpha -latrotoxin) leads us to conclude that there exists a process of molecular mimicry whereby the 'lock and key' analogy inherent to hormone-receptor interactions is reproduced by a toxin related in structure to GLP-1. (C) 2000 Societe francaise de biochimie et biologie moleculaire / Editions scientifiques et medicales Elsevier SAS. C1 NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA USA. RP Holz, GG (reprint author), NYU, Sch Med, Dept Physiol & Neurosci, Med Sci Bldg,Room 442,550 1st Ave, New York, NY 10016 USA. RI Holz, George/A-3386-2012 FU NIDDK NIH HHS [R01DK52166, R01 DK045817, R01 DK045817-06A2, R01DK45817] NR 86 TC 8 Z9 9 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD SEP-OCT PY 2000 VL 82 IS 9-10 BP 915 EP 926 DI 10.1016/S0300-9084(00)01171-8 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 381XT UT WOS:000165789900013 PM 11086221 ER PT J AU Tung, CH Stein, S AF Tung, CH Stein, S TI Preparation and applications of peptide-oligonucleotide conjugates SO BIOCONJUGATE CHEMISTRY LA English DT Review ID SOLID-PHASE SYNTHESIS; TRIPLE-HELIX FORMATION; NUCLEAR-LOCALIZATION PROPERTIES; HUMAN-IMMUNODEFICIENCY-VIRUS; SEQUENCE-SPECIFIC CLEAVAGE; SITE-SPECIFIC CLEAVAGE; ANTISENSE OLIGONUCLEOTIDES; MESSENGER-RNA; IN-VIVO; HYBRIDIZATION PROPERTIES C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. RP Tung, CH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NIDDK NIH HHS [R21DK55713] NR 112 TC 139 Z9 140 U1 2 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 2000 VL 11 IS 5 BP 605 EP 618 DI 10.1021/bc0000334 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 358KY UT WOS:000089558300001 PM 10995203 ER PT J AU Tsuang, MT Stone, WS Faraone, SV AF Tsuang, MT Stone, WS Faraone, SV TI Towards the prevention of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Review DE schizotaxia; genetics; negative symptoms; neuropsychology; risperidone ID FIRST-LINE TREATMENT; NONPSYCHOTIC RELATIVES; WORKING-MEMORY; INTERVENTION; RISK; RISPERIDONE; RATIONALE; PSYCHOSIS; HETEROGENEITY; INDICATORS AB There is a growing emphasis on attempts to identify the early signs and symptoms of schizophrenia, largely because early detection and treatment of psychosis (i.e., secondary prevention) are associated with relatively favorable clinical outcomes. This raises the issue of whether prevention of psychosis itself is possible. The achievement of this goal will require the identification of a premorbid state that could serve as the foundation for treatment strategies aimed ultimately at the prevention of schizophrenia. Fortunately evidence for such a state is emerging, in part because schizophrenia may result from a neurodevelopmental disorder that is associated with a variety of clinical, neurobiological, and neuropsychologic features occurring well before the onset of psychosis. These features may serve as both indicators of risk for subsequent deterioration and the foundation of treatment efforts. We reformulated Meehl's term schizotaxia to describe this liability and discuss here how its study could form the basis for future strategies of prevention. We also include a description of our initial attempts to devise treatment protocols for schizotaxia. II is concluded that schizotaxia is a feasible concept on which to base prevention efforts, anal that treatment of adult schizotaxia may be among the next steps in the process. (C) 2000 Society of Biological Psychiatry. C1 Harvard Univ, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsuang, MT (reprint author), Harvard Univ, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 R01MH4187901, 1R37MH4351801, 5 UO1 MH4631802] NR 55 TC 39 Z9 39 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 1 PY 2000 VL 48 IS 5 BP 349 EP 356 DI 10.1016/S0006-3223(00)00934-3 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 352RY UT WOS:000089232700002 PM 10978718 ER PT J AU Chen, MH Ibrahim, JG AF Chen, MH Ibrahim, JG TI Bayesian predictive inference for time series count data SO BIOMETRICS LA English DT Article DE calibration; correlated counts; Gibbs sampling; historical data; Poisson regression; posterior distribution; prediction; predictive distribution ID MODEL; SELECTION AB Correlated count data arise often in practice, especially in repeated measures situations or instances in which observations are collected over time. In this paper, we consider a parametric model for a time series of counts by constructing a likelihood-based version of a model similar to that; of Zeger (1988, Biometrika 75, 621-629). The model has the advantage of incorporating both overdispersion and autocorrelation. We consider a Bayesian approach and propose a class of informative prior distributions for the model parameters that are useful for prediction. The prior specification is motivated from the notion of the existence of data from similar previous studies, called historical data, which is then quantified into a prior distribution for the current study. We derive the Bayesian predictive distribution and use a Bayesian criterion, called the predictive L measure, for assessing the predictions for a given time series model. The distribution of the predictive L measure is also derived, which will enable us to compare the predictive ability for each model under consideration. Our methodology is motivated by a real data set involving yearly pollen counts, which is examined in some detail. C1 Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, MH (reprint author), Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. FU NCI NIH HHS [CA 74015, CA 70101]; NIEHS NIH HHS [ES0002] NR 13 TC 7 Z9 7 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2000 VL 56 IS 3 BP 678 EP 685 DI 10.1111/j.0006-341X.2000.00678.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 349WX UT WOS:000089069500004 PM 10985202 ER PT J AU Goggins, WB Finkelstein, DM AF Goggins, WB Finkelstein, DM TI A proportional hazards model for multivariate interval-censored failure time data SO BIOMETRICS LA English DT Article DE correlated survival; Cox model; HIV; missing data ID GROUPED SURVIVAL-DATA; REGRESSION-ANALYSIS AB This paper focuses on the methodology developed for analyzing a multivariate interval-censored data set from an AIDS observational study. A purpose of the study was to determine the natural history of the opportunistic infection cytomeglovirus (CMV) in an HIV-infected individual. For this observational study, laboratory tests were performed at scheduled clinic visits to test for the presence of the Ch IV virus in the blood and in the urine (called CMV shedding in the blood and urine). The study investigators were interested in determining whether the stage of HIV disease at study entry was predictive of an increased risk for CMV shedding in either the blood or the urine. If all patients had made each clinic visit, the data would be multivariate grouped failure time data and published methods could be used. However, many patients missed several visits, and when they returned, their lab tests indicated a change in their blood and/or urine CMV shedding status, resulting in interval-censored failure time data. This paper outlines a method for applying the proportional hazards model to the analysis of multivariate interval-censored failure time data from a study of CMV in HIV-infected patients. C1 Hong Kong Baptist Univ, Kowloon, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. RP Goggins, WB (reprint author), Hong Kong Baptist Univ, Kowloon, Hong Kong, Peoples R China. FU NCI NIH HHS [CA 74302]; NIAID NIH HHS [N0-AI 38855] NR 12 TC 46 Z9 46 U1 0 U2 5 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2000 VL 56 IS 3 BP 940 EP 943 DI 10.1111/j.0006-341X.2000.00940.x PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 349WX UT WOS:000089069500042 PM 10985240 ER PT J AU Tilles, AW Classen, JM Toner, M Van de Water, L AF Tilles, AW Classen, JM Toner, M Van de Water, L TI Simple devices to facilitate the analysis of collagen contraction by cells SO BIOTECHNIQUES LA English DT Article ID REORGANIZATION; FIBROBLASTS; MATRIX C1 Shriners Hosp Children, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Van de Water, L (reprint author), Shriners Burns Hosp, Room 222,51 Blossom St, Boston, MA 02114 USA. NR 7 TC 2 Z9 2 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 SEP PY 2000 VL 29 IS 3 BP 412 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 352DR UT WOS:000089199700002 PM 10997250 ER PT J AU Ahn, SC Baek, BS Oh, T Song, CS Chatterjee, B AF Ahn, SC Baek, BS Oh, T Song, CS Chatterjee, B TI Rapid mini-scale plasmid isolation for DNA sequencing and restriction mapping SO BIOTECHNIQUES LA English DT Article C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 5 TC 15 Z9 16 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 2000 VL 29 IS 3 BP 466 EP 468 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 352DR UT WOS:000089199700011 PM 10997259 ER PT J AU Ohyama, H Zhang, X Kohno, Y Alevizos, I Posner, M Wong, DT Todd, R AF Ohyama, H Zhang, X Kohno, Y Alevizos, I Posner, M Wong, DT Todd, R TI Laser capture microdissection-generated target sample for high-density oligonucleotide array hybridization SO BIOTECHNIQUES LA English DT Article AB Current advances in biomolecular technology allow precise genetic fingerprinting of specific cells responsible for the pathogenesis of human diseases. This study demonstrates the feasibility of generating target samples from laser capture microdissection (LCM) tissues suitable for hybridization of high-density oligonucleotide arrays for gene expression profiling. RNA was successfully isolated by LCM from three paired specimens of oval cancer and linearly amplified using T7 RNA polymerase. Evaluation of the cDNA revealed that five of five cellular maintenance transcripts are detected Biotinylated cRNA was generated and hybridized to the human Test I GeneChip(R) probe arrays, which demonstrated that the RNA is of sufficient quality and integrity to warrant further analysis Subsequent hybridization of the samples to the HuGenFL GeneChip probe arrays revealed that 26.5%-33.0% of the approximately 7000 represented genes are expressed in each of the six samples. These results demonstrate that LCM-generated tissues can generate sufficient quality cRNA for high-density oligonucleotide microarray analysis, an important step in determining comprehensive gene expression profiling using this high-throughput technology. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. China Med Univ, Shenyang, Peoples R China. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Ohyama, H (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,1 Fruit St, Boston, MA 02114 USA. FU NIDCR NIH HHS [P01 DE12467, P30 DE11814, R29 DE11983] NR 9 TC 112 Z9 120 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 SEP PY 2000 VL 29 IS 3 BP 530 EP + PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 352DR UT WOS:000089199700020 PM 10997267 ER PT J AU Ghaemi, SN Cherry, EL Katzow, JA Goodwin, FK AF Ghaemi, SN Cherry, EL Katzow, JA Goodwin, FK TI Does olanzapine have antidepressant properties? A retrospective preliminary study SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; depression; drug therapy; mood disorders; mood stabilizers; olanzapine ID PSYCHOTIC MOOD DISORDERS; SCHIZOAFFECTIVE DISORDER; CLINICAL PREDICTORS; RISPERIDONE; SCHIZOPHRENIA; HALOPERIDOL; MANIA AB Objective: Mood-stabilizing agents are ideally conceptualized as possessing antimanic and antidepressant properties. While research on olanzapine's antimanic effects is growing, data on its possible antidepressant properties are limited. We sought to determine if olanzapine is effective in the add-on treatment of major affective disorders, particularly depressive symptoms, in a naturalistic setting. Methods: All charts of patients meeting DSM-IV criteria for bipolar disorder or unipolar major depressive disorder treated with olanzapine in a private psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impression Scale for Improvement (CGI-I). Results: Olanzapine was moderately effective in 6/10 (60%) patients. Side-effects were present in 8/10 (80%), most commonly weight gain. Conclusions: Olanzapine appears to be moderately effective in open add-on treatment in patients with mainly depressive symptoms. Accumulating evidence suggests that olanzapine, and atypical antipsychotics in general, possess mild to moderate adjunctive antidepressant properties. C1 Harvard Univ, Bipolar Res Program, Massachusetts Gen Hosp, Consolidated Dept Psychiat, Boston, MA 02114 USA. George Washington Univ, Dept Psychiat, Washington, DC USA. George Washington Univ, Ctr Neurosci Med Progress & Soc, Dept Psychiat, Washington, DC USA. RP Ghaemi, SN (reprint author), Harvard Univ, Bipolar Res Program, Massachusetts Gen Hosp, Consolidated Dept Psychiat, 50 Stniford St,5th Floor, Boston, MA 02114 USA. NR 16 TC 26 Z9 27 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2000 VL 2 IS 3 BP 196 EP 199 PN 1 PG 4 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 428PN UT WOS:000168470200007 PM 11256687 ER PT J AU Sachs, GS Koslow, CL Ghaemi, SN AF Sachs, GS Koslow, CL Ghaemi, SN TI The treatment of bipolar depression SO BIPOLAR DISORDERS LA English DT Review DE affective switch; bipolar depression; lithium; mood stabilizer ID LITHIUM-CARBONATE; AFFECTIVE-ILLNESS; DOUBLE-BLIND; IMIPRAMINE; UNIPOLAR; EFFICACY; CARBAMAZEPINE; BUPROPION; DISORDERS; MANIA AB Objectives: The treatment of the depressed phase of bipolar disorder is understudied and remains a common clinical dilemma for clinicians. Compared to the manic phases, episodes of bipolar depression are more frequent and of longer duration, yet the literature on this problem is minimal. The few methodologically sound studies find that treatment effective for unipolar depression are also efficacious for bipolar depression. However, standard antidepressant agents may cause acute mania or a long-ten worsening of bipolar illness. This paper reviews the available literature on the treatment of bipolar depression and offers recommendations for clinical management. Methods: A literature search was conducted using keywords 'bipolar disorder', 'depression', 'drug therapy', 'antidepressants', 'lithium', and 'anticonvulsants'. Results: If effectively treated by lithium, patients are spared the risk of antidepressant-induced mania. If lithium is not sufficient treatment for acute depression, the combination of lithium and a standard antidepressant appears to reduce the risk of affective switch, as well as the induction of a long-term rapid-cycling course. Additionally tapering antidepressant medication after periods of sustained remission can be beneficial in limiting the risk of affective switch and acceleration of the cycle rate. Conclusions: Doctors must be cautious in prescribing antidepressants for bipolar depression. Use of antidepressants alone should be avoided. C1 Harvard Univ, Massachusetts Gen Hosp, Bipolar Res Program, Sch Med,Consolidated Dept Psychiat, Boston, MA 02114 USA. RP Sachs, GS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bipolar Res Program, Sch Med,Consolidated Dept Psychiat, 50 Staniford St,5th Floor, Boston, MA 02114 USA. NR 33 TC 42 Z9 45 U1 1 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD SEP PY 2000 VL 2 IS 3 BP 256 EP 260 DI 10.1034/j.1399-5618.2000.20306.x PN 2 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 428PP UT WOS:000168470300006 PM 11249803 ER PT J AU Kuang, Y Garcia-Higuera, I Moran, A Mondoux, M Digweed, M D'Andrea, AD AF Kuang, Y Garcia-Higuera, I Moran, A Mondoux, M Digweed, M D'Andrea, AD TI Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity SO BLOOD LA English DT Article ID NUCLEAR-LOCALIZATION; C-GENE; INTERACT; COMPLEX; CELLS; FORM; FAA; COMPLEMENTATION; ACCUMULATION; INSTABILITY AB Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with eight complementation groups. Four of the FA genes have been cloned, and at least three of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a nuclear complex, required for the maintenance of normal chromosome stability. In the current study, mutant forms of the FANCA and FANCG proteins have been generated and analyzed with respect to protein complex formation, nuclear translocation, and functional activity. The results demonstrate that the amino terminal two-thirds of FANCG (FANCG amino acids 1-428) binds to the amino terminal nuclear localization signal (NLS) of the FANCA protein. On the basis of 2-hybrid analysis, the FANCA/FANCG binding is a direct protein-protein interaction. Interestingly, a truncated mutant form of the FANCG protein, lacking the carboxy terminus, binds in a complex with FANCA and translocates to the nucleus; however, this mutant protein fails to bind to FANCC and fails to correct the mitomycin C sensitivity of an FA-G cell line. Taken together, these results demonstrate that binding of FANCG to the amino terminal FANCA NLS sequence is necessary but not sufficient for the functional activity of FANCG, Additional amino acid sequences at the carboxy terminus of FANCG are required for the binding of FANCC in the complex. (C) 2000 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Div Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Humboldt Univ, Charite, Inst Humangenet, Berlin, Germany. RP D'Andrea, AD (reprint author), Harvard Univ, Sch Med, Div Pediat Oncol, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Garcia-Higuera, Irene/L-5004-2014 FU NHLBI NIH HHS [P01HL54785-04, R01HL52725-04] NR 45 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2000 VL 96 IS 5 BP 1625 EP 1632 PG 8 WC Hematology SC Hematology GA 358VR UT WOS:000089578300001 PM 10961856 ER PT J AU Anagnostopoulos, I Hansmann, ML Franssila, K Harris, M Harris, NL Jaffe, ES Han, J van Krieken, JM Poppema, S Marafioti, T Franklin, J Sextro, M Diehl, V Stein, H AF Anagnostopoulos, I Hansmann, ML Franssila, K Harris, M Harris, NL Jaffe, ES Han, J van Krieken, JM Poppema, S Marafioti, T Franklin, J Sextro, M Diehl, V Stein, H CA European Task Force Lymphoma TI European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; B-CELL LYMPHOMA; REED-STERNBERG CELLS; TRANSFORMED GERMINAL-CENTERS; LATENT MEMBRANE-PROTEIN; MONOCLONAL-ANTIBODIES; INSITU HYBRIDIZATION; PARAFFIN SECTIONS; H VARIANTS; T-CELLS AB Paraffin blocks and clinical data from 521 patients with lymphocyte predominance Hodgkin disease (LPHD) diagnosed between 1970 and 1994 were collected from 16 European and United States oncological centers to establish the pathologic and clinical characteristics of a large patient cohort, to determine how frequent T-cell-rich large B-cell lymphoma (TCRLBCL) is among LPHD, and to find differential diagnostic criteria distinguishing between the 2 lymphoma categories. For this purpose, conventionally and immunohistologically stained sections were reviewed by a panel of hematopathologists, The diagnosis of LPHD was confirmed in only 219 of the 388 assessable cases (56.5%), This low confirmation rate was due mainly to the presence of a new variant of classical Hodgkin disease (CHD), which resembled, in terms of nodular growth and lymphocyte-richness, nodular LPHD and, in terms of the immunophenotype of the tumor cells, CHD and was designated nodular lymphocyte-rich CHD (NLRCHD). The nodules of LRCHD consisted - as in nodular LPHD - predominantly of B cells but differed from those present in LPHD in that they represented expanded mantle zones with atrophic germinal centers. Clinically, patients with LPHD and NLRCHD showed similar disease characteristics at presentation but differed in the frequency of multiple relapses and prognosis after relapse. Patients with LPHD and NLRCHD clearly differed from patients with CHD with nodular sclerosis or mixed cellularity, as they presented with an earlier disease stage and infrequent mediastinal involvement. As 97% of the LPHD cases showed a complete or partial nodular growth pattern, their differentiation from TCRLBCL was a rare problem in the present series, (C) 2000 by The American Society of Hematology. C1 Free Univ Berlin, Klinikum Benjamin Franklin, Inst Pathol, D-12200 Berlin, Germany. Univ Frankfurt, Senkenberg Ctr Pathol, D-6000 Frankfurt, Germany. Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland. Christie Hosp, Dept Pathol, Manchester, Lancs, England. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. Univ Nijmegen, Ctr Med, Dept Pathol, Nijmegen, Netherlands. Univ Groningen, Fac Med Sci, Dept Pathol, Groningen, Netherlands. Univ Cologne, Clin Internal Med 1, Cologne, Germany. RP Stein, H (reprint author), Free Univ Berlin, Klinikum Benjamin Franklin, Inst Pathol, Hindenburgdamm 30, D-12200 Berlin, Germany. RI Marafioti, Teresa/B-4493-2009; Poppema, Sibrand/D-1204-2012; van Krieken, Joannes/D-4138-2009 OI van Krieken, Joannes/0000-0001-6544-1040 NR 55 TC 134 Z9 140 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2000 VL 96 IS 5 BP 1889 EP 1899 PG 11 WC Hematology SC Hematology GA 358VR UT WOS:000089578300040 PM 10961891 ER PT J AU Tajima, F Sato, T Lever, JH Ogawa, M AF Tajima, F Sato, T Lever, JH Ogawa, M TI CD34 expression by murine hematopoietic stem cells mobilized by granulocyte colony-stimulating factor SO BLOOD LA English DT Article ID BONE-MARROW CELLS; PERIPHERAL-BLOOD; AUTOLOGOUS TRANSPLANTATION; IN-VIVO; ANTIGEN; PROGENITOR AB Controversy has existed about CD34 expression by hematopoietic stem cells, We recently reported that CD34 expression reflects the activation state of stem cells by using a murine transplantation model. It has been generally held that mobilized blood stem cells express CD34. However, it has also been reported that mobilized stem cells and progenitors are in G0/G1 phases of the cell cycle. To address the state of CD34 expression by the mobilized stem cells, we again used the mouse transplantation model. We prepared CD34(-) and CD34(+) populations of nucleated blood cells from granulocyte colony-stimulating factor-treated Ly-5.1 mice and assayed each population for long-term engrafting cells in lethally irradiated Ly-5.2 mice, The majority of the stem cells were in the CD34(+) population. The CD34 expression by mobilized stem cells was reversible because re-transplantation of Ly-5.1 CD34(-) marrow cells harvested from the Ly-5.2 recipients of CD34(+)-mobilized stem cells 8 months posttransplantation revealed long-term engraftment These results may support the use of total CD34(+) cells in mobilized blood as a predictor for engraftment and CD34 selection for enrichment of human stem cells. (C) 2000 by The American Society of Hematology. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 22 TC 42 Z9 45 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 1 PY 2000 VL 96 IS 5 BP 1989 EP 1993 PG 5 WC Hematology SC Hematology GA 358VR UT WOS:000089578300054 PM 10961905 ER PT J AU Louis, D AF Louis, D TI Molecular diagnostic approaches to neuro-oncology SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2000 VL 10 IS 4 BP 602 EP 602 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 334YB UT WOS:000088213000240 ER PT J AU Hedley-Whyte, ET Difiglia, M Myers, RM Hobbs, W Richardson, EP Vonsattel, JPG AF Hedley-Whyte, ET Difiglia, M Myers, RM Hobbs, W Richardson, EP Vonsattel, JPG TI Coincidence of Alzheimer changes and Alzheimer disease in Huntington disease brains. SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2000 VL 10 IS 4 BP 629 EP 630 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 334YB UT WOS:000088213000289 ER PT J AU Piccardo, P Vidal, R Calero, M Farlow, MR Unverzagt, FW Gomez-Tortosa, E Ghiso, J Hyman, B Frangione, B Ghetti, B AF Piccardo, P Vidal, R Calero, M Farlow, MR Unverzagt, FW Gomez-Tortosa, E Ghiso, J Hyman, B Frangione, B Ghetti, B TI Dementia associated with amyloid beta angiopathy, tau perivascular pathology and APOE epsilon 4 genotype SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 Indiana Univ Penn, Sch Med, Indiana, PA USA. NYU, Sch Med, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Calero, Miguel/H-5691-2015 OI Calero, Miguel/0000-0001-5366-3324 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2000 VL 10 IS 4 BP 714 EP 714 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 334YB UT WOS:000088213000469 ER PT J AU Shibata, N Hedley-Whyte, T Kato, S Hirano, A Sasaki, S Kobayashi, M AF Shibata, N Hedley-Whyte, T Kato, S Hirano, A Sasaki, S Kobayashi, M TI Role for protein-bound carbonyls in familial and sporadic amyotrophic lateral sclerosis SO BRAIN PATHOLOGY LA English DT Meeting Abstract C1 Tokyo Womens Med Univ, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tottori Univ, Tottori 680, Japan. Montefiore Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD SEP PY 2000 VL 10 IS 4 BP 775 EP 775 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 334YB UT WOS:000088213000585 ER PT J AU Guzman-Marin, R Alam, MN Szymusiak, R Drucker-Colin, R Gong, H McGinty, D AF Guzman-Marin, R Alam, MN Szymusiak, R Drucker-Colin, R Gong, H McGinty, D TI Discharge modulation of rat dorsal raphe neurons during sleep and waking: effects of preoptic/basal forebrain warming SO BRAIN RESEARCH LA English DT Article DE preoptic area; basal forebrain; preoptic warming; serotonergic neurons; REM-off neuron; single unit recording; rat ID EYE-MOVEMENT SLEEP; SINGLE-UNIT RESPONSES; FREELY MOVING CATS; THERMOSENSITIVE NEURONS; 5-HT1A AUTORECEPTORS; HYPOTHALAMIC NEURONS; NUCLEUS; SEROTONIN; CYCLE; WAKEFULNESS AB In cats, putative serotonergic neurons (PSNs) recorded from the dorsal raphe nucleus (DRN) across the sleep-wake cycle exhibit the so-called rapid eye movement sleep-off (REM-off) discharge pattern. Since, the sleep-wake discharge patterns of DRN neurons in behaving rats is poorly known, the present study examined this neuronal populations. The PSNs recorded in this study exhibited: (1) progressive decrease in discharge rate from waking to NREM to REM sleep; (2) long action potential duration, and (3) reduction of discharge rate after systemic administration of a selective 5-HT1A agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT). Evidence supports the hypothesis that NREM sleep is modulated by thermoregulatory mechanisms localized in the preoptic area and adjacent basal forebrain (POA/BF). We previously reported that POA/BF warming suppresses the discharge of wake-promoting neurons in the posterior hypothalamus and the basal forebrain. Since the DRN is one component of the brainstem arousal system and receives projections from POA/BF, we examined the effects of local POA/BF warming by 1.5-2.0 degrees C during waking on the discharge of DRN neurons. POA/BF warming reduced the discharge in 14 of 19 PSNs and in 12 of 17 other wake-related neurons in the DRN. DRN neuronal discharge reduction occurred without accompanying EEG frequency or behavioral changes. These results suggest that PSNs recorded in DRN in unrestrained and unanesthetized rats exhibit a "wake-active REM-off" discharge pattern and further support the hypothesis that the POA/BF warm-sensitive hypnogenic system induces sleep by a coordinated inhibition of multiple arousal systems including that modulated by the DRN. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Vet Affairs Greater Los Angeles Healthcare Syst, N Hills, CA 91343 USA. Univ Nacl Autonoma Mexico, Fac Med, Dept Fisiol, Mexico City 04510, DF, Mexico. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Neurociencias, Mexico City 04510, DF, Mexico. RP McGinty, D (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, 16111 Plummer St, N Hills, CA 91343 USA. FU NHLBI NIH HHS [HL 60296]; NIMH NIH HHS [MH 47480] NR 54 TC 43 Z9 49 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 1 PY 2000 VL 875 IS 1-2 BP 23 EP 34 DI 10.1016/S0006-8993(00)02561-0 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 352DM UT WOS:000089199300003 PM 10967295 ER PT J AU Pootanakit, K Brunken, WJ AF Pootanakit, K Brunken, WJ TI 5-HT1A and 5-HT7 receptor expression in the mammalian retina SO BRAIN RESEARCH LA English DT Article DE 5-HT1A; 5-HT7; rabbit retina; rat retina; rod pathway; scotopic pathway ID RABBIT RETINA; ADENYLATE-CYCLASE; CAMP FORMATION; RAT RETINA; SYSTEM; LOCALIZATION; CLONING AB Serotonin or 5-hydroxytryptamine (5-HT) is a common neurotransmitter found widely in the nervous system. Here, using RT-PCR, we have identified both the 5-HT1A and 5-HT7 receptor transcripts in the rabbit retina. Furthermore, we found the same two receptors in the rat retina which was previously believed not to have a serotoninergic system. These results confirm previous reports of 5-HT7 gene expression in retina and together with other biochemical, physiological and anatomical studies, they support the presence of multiple 5-HT receptors in the mammalian retina and suggest that the action of serotonin in the retina may he more complicated than previously believed. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Brunken, WJ (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. NR 18 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 1 PY 2000 VL 875 IS 1-2 BP 152 EP 156 DI 10.1016/S0006-8993(00)02553-1 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 352DM UT WOS:000089199300017 PM 10967309 ER PT J AU Wood, SJ Ramsdell, CD Mullen, TJ Oman, CM Harm, DL Paloski, WH AF Wood, SJ Ramsdell, CD Mullen, TJ Oman, CM Harm, DL Paloski, WH TI Transient cardio-respiratory responses to visually induced tilt illusions SO BRAIN RESEARCH BULLETIN LA English DT Article; Proceedings Paper CT Conference on Autonomic Control During Action CY SEP, 1999 CL OPIO, FRANCE DE visual; illusions; vestibular; autonomic; cardiovascular; orthostatic ID MOTION SICKNESS; VESTIBULAR STIMULATION; AUTONOMIC REGULATION; LINEAR ACCELERATION; HUMANS; PRESSURE; SYNCOPE; SYSTEM; MICROGRAVITY; POSTURE AB Although the orthostatic cardio-respiratory response is primarily mediated by the baroreflex, studies have shown that vestibular cues also contribute in both humans and animals. We have demonstrated a visually mediated response to illusory tilt in some human subjects. Blood pressure, heart and respiration rate, and lung volume were monitored in 16 supine human subjects during two types of Visual stimulation, and compared with responses to real passive whole body tilt from supine to head 80 degrees upright. Visual tilt stimuli consisted of either a static scene from an overhead mirror or constant velocity scene motion along different body axes generated by an ultra-wide dome projection system. Visual vertical cues were initially aligned with the longitudinal body axis. Subjective tilt and self-motion were reported verbally, Although significant changes in cardio-respiratory parameters to illusory tilts could not be demonstrated for the entire group, several subjects showed significant transient decreases in mean blood pressure resembling their initial response to passive head-up tilt. Changes in pulse pressure and a slight elevation in heart rate were noted. These transient responses are consistent with the hypothesis that visual-vestibular input contributes to the initial cardiovascular adjustment to a change in posture in humans. On average the static scene elicited perceived tilt without rotation. Dome scene pitch and yaw elicited perceived tilt and rotation, and dome roll motion elicited perceived rotation without tilt. A significant correlation between the magnitude of physiological and subjective reports could not be demonstrated. (C) 2000 Elsevier Science Inc. C1 NASA, Lyndon B Johnson Space Ctr, Natl Space Biomed Res Inst, Houston, TX 77058 USA. Baylor Coll Med, Bobby R Alford Dept Otorhinolaryngol & Commun Sci, Houston, TX USA. Harvard Univ, Sch Med, Dept Anesthesia & Crit Care Clin, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Man Vehicle Lab, Cambridge, MA USA. NASA, Lyndon B Johnson Space Ctr, Life Sci Res Labs, Houston, TX 77058 USA. RP Wood, SJ (reprint author), NASA, Lyndon B Johnson Space Ctr, Natl Space Biomed Res Inst, Mail Code SD3, Houston, TX 77058 USA. NR 39 TC 13 Z9 13 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD SEP 1 PY 2000 VL 53 IS 1 BP 25 EP 31 DI 10.1016/S0361-9230(00)00305-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 363XC UT WOS:000089862100005 PM 11033205 ER PT J AU Berry, JE Murphy, CM Smith, GA Ranasinghe, E Finberg, R Walton, J Brown, J Navarrete, C Metcalfe, P Ouwehand, WH AF Berry, JE Murphy, CM Smith, GA Ranasinghe, E Finberg, R Walton, J Brown, J Navarrete, C Metcalfe, P Ouwehand, WH TI Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA-5 alloantigens SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE platelets; monoclonal antibody-specific immobilization; of platelet antigens (MAIPA); Gov system; immunogenicity ID NEONATAL ALLOIMMUNE THROMBOCYTOPENIA; HUMAN PLATELET ALLOANTIGENS; GLYCOPROTEIN IIIA; RECEPTOR-III; ANTIGEN; IDENTIFICATION; EXPRESSION; ACTIVATION; P1(A1) AB The glycosylphosphatidylinositol-linked platelet protein CD109 carries the biallelic alloantigen system Gov. There is limited information on the incidence of Gov alloantibodies in neonatal alloimmune thrombocytopenia (NAITP), post-transfusion purpura (PTP) and platelet refractoriness. We adapted the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay to the detection of Gov antibodies and determined their incidence in 605 archived samples (112 with HPA antibodies) referred for the aforementioned conditions. Here, we show that CD109 expression was reduced upon platelet storage in saline or by cryopreservation, but was stable when stored as whole blood or therapeutic platelet concentrate. Fourteen of the 605 samples contained Gov alloantibodies (anti-Gov(a), n = 10; anti-Gov(b), n = 4), with the majority in platelet refractoriness (n = 9) and, of the remaining five, four in NAITP and one in PTP In seven cases, no other HPA antibodies were detected, three being NAITP cases. The incidence of Gov antibodies was significantly lower than HPA-1 system antibodies (n = 87), but equalled the number of HPA-5 system antibodies (n = 14) and outnumbered HPA-2 and -3 system antibodies (10 altogether). C1 Univ Cambridge, Dept Haematol, Div Transfus Med, Natl Blood Serv E Anglia, Cambridge CB2 2PT, England. Univ Cambridge, Dept Haematol, Cambridge, England. Natl Blood Serv, London, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Inst Biol Stand & Controls, Div Haematol, Potters Bar EN6 3QG, Herts, England. RP Ouwehand, WH (reprint author), Univ Cambridge, Dept Haematol, Div Transfus Med, Natl Blood Serv E Anglia, Long Rd, Cambridge CB2 2PT, England. RI Metcalfe, Paul/D-2864-2013; Finberg, Robert/E-3323-2010 NR 24 TC 65 Z9 72 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 SEP PY 2000 VL 110 IS 3 BP 735 EP 742 DI 10.1046/j.1365-2141.2000.02170.x PG 8 WC Hematology SC Hematology GA 362AF UT WOS:000089755900032 PM 10997989 ER PT J AU Lee, KR Flynn, CE AF Lee, KR Flynn, CE TI Early invasive adenocarcinoma of the cervix - A histopathologic analysis of 40 cases with observations concerning histogenesis SO CANCER LA English DT Article; Proceedings Paper CT Meeting of the US-Canadian-Academy-of-Patholo gy CY MAR 28, 2000 CL NEW ORLEANS, LOUISIANA SP US Canadian Acad Pathol DE uterus; cervix; adenocarcinoma; adenocarcinoma in situ; microinvasive carcinoma; adenosquamous carcinoma; microglandular hyperplasia; histogenesis; oral contraceptives; cervical cancer screening ID UTERINE CERVIX; IN-SITU; MICROINVASIVE ADENOCARCINOMA; YOUNG-WOMEN; INSITU; CARCINOMA; LESIONS; MARGINS; MANAGEMENT; DIAGNOSIS AB BACKGROUND. Adenocarcinoma of the cenix is increasing in frequency. There is a dearth of specific detail concerning the histomorphology, histogenesis, and associated findings in early invasive cervical adenocarcinoma. METHODS, Forty cases of cervical adenocarcinoma invasive to 5 mm or less were examined in detail. RESULTS. Mean patient age was 40.9 years. In 78% of die cases, the midpoint of the invasive focus was in the region of the squamocolumnar junction or transformation zone; more than 1 invasive focus was present in 4 cases. Eighty-five percent of cases also had adenocarcinoma in situ (AIS). In 9 of 10 minimally invasive cases, small invasive glands were present in the stroma adjacent to AIS. In some of these, the AIS had preinvasive buds that were still attached. Endometrioid adenocarcinomas were associated with AIS but were located higher in the canal than the more common endocervical type. AU three adenosquamous carcinomas were associated with both squamous intraepithelial neoplasia and AIS. Vascular space invasion was observed in two cases, microglandular hyperplasia In four. CONCLUSIONS. Adenocarcinoma in situ is the precursor to most adenocarcinomas of the cervix with an average interval between clinically detected AIS and early invasion of approximately 5 years, supporting the potential far Papanicolaou test screening to prevent this disease. However, the existence of small carcinomas in the absence of AIS suggests the possibility of rapid progression in some cases. Invasion occurs by budding from or expansion of AIS glands, usually in the region of the squamocolumnar junction Multifocal invasion is uncommon, as is vascular invasion in early lesions. The endometrioid variant has the same histogenesis as the endocervical type but may arise higher in the canal, The precursor of adenosquamous carcinoma has a similar bimorphic differentiation potential. Microglandular hyperplasia is not related to early invasive adenocarcinoma. (C) 2000 American Cancer Society. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Lee, KR (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. NR 36 TC 48 Z9 48 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD SEP 1 PY 2000 VL 89 IS 5 BP 1048 EP 1055 DI 10.1002/1097-0142(20000901)89:5<1048::AID-CNCR14>3.0.CO;2-S PG 8 WC Oncology SC Oncology GA 347QX UT WOS:000088941600014 PM 10964335 ER PT J AU Yang, QH Olshan, AF Bondy, ML Shah, NR Pollock, BH Seeger, RC Look, AT Cohn, SL AF Yang, QH Olshan, AF Bondy, ML Shah, NR Pollock, BH Seeger, RC Look, AT Cohn, SL TI Parental smoking and alcohol consumption and risk of neuroblastoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DNA ADDUCTS; PREGNANCY; TRENDS; CANCER; US AB Previous studies and animal evidence have suggested a relationship between parental tobacco or alcohol use and the risk of some childhood canters, including neuroblastoma. A case-control study was conducted to investigate the relationship between parental tobacco smoking, alcohol consumption, and risk of neuroblastoma. Cases were children diagnosed with neuroblastoma over the period 1992-1994 at Children's Cancer Group and Pediatric Oncology Group institutions throughout the United States and Canada. One matched control was selected using random-digit dialing. Information on parental smoking and drinking history was obtained from 504 case and 504 control parents by telephone interview. Overall, there was no consistent pattern of association with parental smoking and alcohol consumption, For example, both maternal smoking and drinking during the period from 1 month before pregnancy through breastfeeding had adjusted odds ratios (ORs) of 1.1 [95% confidence interval (CI), 0.8-1.4], There was no association with paternal smoking (OR, 1.2; 95% CI, 0.8-1.6) or paternal drinking 1 month before conception (OR, 1.0; 95% CI, 0.7-1.4), There was no consistent increase in risk by the amount of smoking or drinking during any time period relative to pregnancy. There was no suggestion of an increased risk when only one parent smoked. Smoking or drinking among both parents did not jointly increase the risk of neuroblastoma in their offspring. The child's age at diagnosis, stage, or MYCN oncogene amplification status did not materially alter the OR estimates. it is concluded that the results from this study do not indicate any evidence for a relationship between neuroblastoma and parental tobacco or alcohol use. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Geisinger Med Ctr, Dept Pediat Hematol, Danville, PA 17822 USA. Univ Florida, Pediat Oncol Grp, Stat Off, Gainesville, FL 32610 USA. Dept Hlth Policy & Epidemiol, Gainesville, FL 32610 USA. Childrens Hosp Los Angeles, Childrens Canc Grp, Neuroblastoma Resource Lab, Los Angeles, CA 90027 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. Northwestern Univ, Dept Pediat, Chicago, IL 60614 USA. RP Olshan, AF (reprint author), Childrens Canc Grp, POB 60012, Areadia, CA 91066 USA. OI Cohn, Susan/0000-0001-5749-7650 FU NCI NIH HHS [CA57004] NR 23 TC 20 Z9 20 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 2000 VL 9 IS 9 BP 967 EP 972 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 355NW UT WOS:000089392600016 PM 11008916 ER PT J AU Hanna, NN Seetharam, S Mauceri, HJ Beckett, MA Jaskowiak, NT Salloum, RM Hari, D Dhanabal, M Ramchandran, R Kalluri, R Sukhatme, VP Kufe, DW Weichselbaum, RR AF Hanna, NN Seetharam, S Mauceri, HJ Beckett, MA Jaskowiak, NT Salloum, RM Hari, D Dhanabal, M Ramchandran, R Kalluri, R Sukhatme, VP Kufe, DW Weichselbaum, RR TI Autitumor interaction of short-course endostatin and ionizing radiation SO CANCER JOURNAL LA English DT Article DE antiangiogenic therapy; ionizing radiation; targeting; vasculature ID TUMOR ANGIOGENESIS; THERAPY; CANCER; RESISTANCE; METASTASIS; CARCINOMA; STRATEGY AB PURPOSE The purpose of this study was to evaluate whether endostatin, an antiangiogenic cleavage fragment of collagen XVIII, enhances the antitumor effects of ionizing radiation (IR). Endostatin was injected to coincide with fractionated radiotherapy. METHODS Xenografts of radioresistant SQ-20B tumor cells were established in athymic nude mice. Lewis lung carcinoma cells were injected into C57B1/6 mice, Mice bearing SQ-20B xenografts were injected intraperitoneally with 2.5 mg/kg/day of murine recombinant endostatin 5 limes per week for 2 weeks 3 hours before IR treatment (50 Gy total dose). Mice bearing Lewis lung carcinoma tumors were injected intraperitoneally with endostatin (2.5 mg/ kg/day) four times; the first injection was given 24 hours before the first IR dose (15 Gy) and then 3 hours before IR (15 Gy/day) for 3 consecutive days. Microvascular density was assessed on tumor tissue sections by use of CD31 immunohistochemistry and light microscopy. Endothelial cell survival analyses were employed to evaluate endostatin effects on human aortic endothelial cells and human umbilical vein endothelial cells. Endothelial cell apoptosis was examined by use of FAGS analysis and DAPI microscopy. RESULTS In SQ-20B xenografts, combined treatment with endostatin and IR produced tumor growth inhibition that was most pronounced at the nadir of regression (day 21), By day 35, tumors receiving combined treatment with endostatin and IR were 47% smaller than tumors treated with endostatin alone. Interactive cytotoxic treatment effects between endostatin and IR were also demonstrated in mice bearing Lewis lung carcinoma tumors. Significant tumor growth inhibition was observed in the endostatin/IR group at days 11 and 13 compared with IR alone. Histologic analyses demonstrated a reduction in microvascular density after combined treatment with endostatin and IR compared with endostatin treatment alone. Survival analyses confirmed interactive cytotoxicity between endostatin and IR in both human aortic endothelial cells and human umbilical vein endothelial cells but not in SQ-20B tumor cells. Combined treatment with endostatin and IR produced an increase in cow pulmonary artery endotheljal apoptosis compared with either treatment alone. DISCUSSION The tumor regression observed after combined treatment with endostatin and IR suggests additive antitumor effects in both human and murine tumors. importantly, the concentrations of endostatin employed produced little tumor regression when endostatin was employed as a single agent. The results from the clonogenic and apoptosis assays support the hypothesis that the endothelial compartment is the target for the endostatin/IR interaction. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Beth Israel Deaconess Med Ctr, Div Renal, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weichselbaum, RR (reprint author), Univ Chicago, Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. FU NCI NIH HHS [CA81151]; NIDCR NIH HHS [P50DE/CA11921]; NIDDK NIH HHS [DK51711] NR 20 TC 58 Z9 74 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD SEP-OCT PY 2000 VL 6 IS 5 BP 287 EP 293 PG 7 WC Oncology SC Oncology GA 372HT UT WOS:000165228800005 PM 11079167 ER PT J AU McGowen, R Biliran, H Sager, R Sheng, S AF McGowen, R Biliran, H Sager, R Sheng, S TI The surface of prostate carcinoma DU145 cells mediates the inhibition of urokinase-type plasminogen activator by maspin SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSING SERPIN; TISSUE-TYPE; BREAST-CANCER; PROTEINASE-INHIBITOR; RECEPTOR; BINDING; VITRONECTIN; EXPRESSION; MAMMARY; PROTEOLYSIS AB Maspin is a novel serine protease inhibitor (serpin) with tumor suppressive potential in breast and prostate cancer, acting at the level of tumor invasion and metastasis, It was subsequently demonstrated that maspin inhibits tumor invasion, at least in part, by inhibiting cell motility, Interestingly, in cell-free solutions, maspin does not inhibit several serine proteases including tissue-type plasminogen activator and urokinase-type plasminogen activator (uPA), Despite the recent biochemical evidence that maspin specifically inhibits tissue-type plasminogen activator that is associated with fibrinogen or poly-L-Lysine, the molecular mechanism underlying the tumor-suppressive effect of maspin remains elusive. The goal of this study was to investigate the effect of maspin on cell surface-associated uPA. In our experimental system, we chose prostate carcinoma DU145 cells because these cells mediate plasminogen activation primarily by uPA, as shown by two different colorimetric enzyme activity assays. Purified recombinant maspin produced in baculovirus-infected Spodoptera frugiperda Sf9 insect cells [rMaspin(i)] binds specifically to the surface of DU145 cells, inhibits the DU145 cell surface-bound uPA, and forms a stable complex with the uPA in DU145 cell lysate, The inhibitory effect of rMaspin(i) on fell surface-bound uPA was similar to that of an uPA-neutralizing antibody and was reversed by a polyclonal antibody against the reactive site loop sequence of maspin. The K-i value for rMaspin(i) in cell surface-mediated plasminogen activation was 20 nM, which was comparable to the K-i values for plasminogen activator inhibitor 1 and plasminogen activator inhibitor 2, respectively. Furthermore, the proteolytic inhibitory effect of rMaspin(i) was quantitatively consistent with its inhibitory effect on the motility of DU145 cells in vitro. Our data demonstrate an important role for the prostate carcinoma cell surface in mediating the inhibitory interaction between rMaspin(i) and uPA, Thus, future maspin-based therapeutic strategies may prove useful in blocking the invasion and metastasis of uPA-positive prostate carcinoma. C1 Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Dana Farber Canc Inst, Div Canc Genet, Boston, MA 02115 USA. RP Sheng, S (reprint author), Wayne State Univ, Sch Med, Dept Pathol, 540 E Canfield Ave, Detroit, MI 48201 USA. FU NCI NIH HHS [CA69845, CA61253] NR 48 TC 77 Z9 80 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 SEP 1 PY 2000 VL 60 IS 17 BP 4771 EP 4778 PG 8 WC Oncology SC Oncology GA 352FM UT WOS:000089203900022 PM 10987285 ER PT J AU Hibbard, MK Kozakewich, HP Dal Cin, P Sciot, R Tan, XL Xiao, S Fletcher, JA AF Hibbard, MK Kozakewich, HP Dal Cin, P Sciot, R Tan, XL Xiao, S Fletcher, JA TI PLAG1 fusion oncogenes in lipoblastoma SO CANCER RESEARCH LA English DT Article ID MOUSE HYALURONAN SYNTHASE; TISSUE TUMORS; SOLID TUMORS; IDENTIFICATION; GENE; ABNORMALITIES; ACTIVATION; PROMOTER; ADENOMAS; REGION AB Lipoblastomas are pediatric neoplasms resulting from transformation of adipocytes. These benign tumors are typically composed of adipose cells in different stages of maturation within a variably myxoid matrix, and they contain clonal rearrangements of chromosome band 8q12, Because lipoblastomas resemble embryonic adipose tissue, characterization of their transforming mechanisms might reveal biological pathways in physiological adipogenesis, Herein, we demonstrate that lipoblastoma chromosome 8q12 rearrangements bring about promoter-swapping events in the PLAG1 oncogene, We show that the hyaluronic acid synthase 2 (HAS2) or collagen 1 alpha 2 (COL1A2) gene promoter regions are fused to the entire PLAG1 coding sequence in each of four lipoblastomas. PLAG1 is a developmentally regulated zinc finger gene whose tumorigenic function has been shown previously only in epithelial salivary gland cells. Our findings reveal that PLAG1 activation, presumably resulting from transcriptional up-regulation, Is a central oncogenic event in lipoblastoma. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Hosp, Dept Pathol, B-3000 Louvain, Belgium. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NIGMS NIH HHS [T32-GM07748-19] NR 29 TC 119 Z9 125 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 SEP 1 PY 2000 VL 60 IS 17 BP 4869 EP 4872 PG 4 WC Oncology SC Oncology GA 352FM UT WOS:000089203900037 PM 10987300 ER PT J AU Joki, T Heese, O Nikas, DC Bello, L Zhang, JP Kraeft, SK Seyfried, NT Abe, T Chen, LB Carroll, RS Black, PM AF Joki, T Heese, O Nikas, DC Bello, L Zhang, JP Kraeft, SK Seyfried, NT Abe, T Chen, LB Carroll, RS Black, PM TI Expression of cyclooxygenase 2 (COX-2) in human glioma and in Vitro inhibition by a specific COX-2 inhibitor, NS-398 SO CANCER RESEARCH LA English DT Article ID HUMAN GLIOBLASTOMA-MULTIFORME; COLON-CANCER CELLS; HUMAN BRAIN-TUMORS; GENE-EXPRESSION; RAT-BRAIN; CARCINOMA; GROWTH; P53; ADENOCARCINOMAS; HETEROZYGOSITY AB The up-regulation of cyclooxygenase 2 (COX-2) expression is a frequent occurrence in a variety of different tumors. In this study, COX-2 protein expression was investigated in 50 glioma and 3 normal brain specimens by immunohistochemistry. Expression of COX-2 protein was observed in all normal brain and glioma specimens by immunohistochemistry, regardless of histological grade. The immunoreactive score was significantly higher in high-grade glioma than low-grade glioma and normal brain specimens. For a subset of these tumors (nine gliomas and three normal brain), Western blot analysis was also performed. COX-2 protein was detected in all specimens by Western blot analysis. The effect of the specific COX-2 inhibitor NS-398 on monolayer cell cultures and three-dimensional glioma spheroids was investigated using U-87MG and U-251MG human glioblastoma cell lines. The proliferation rate was assessed in monolayer cultures. In addition, a growth assay, a migration assay, an apoptosis assay, and a tumor invasion assay were performed in a three-dimensional spheroid culture system. NS-398 was able to reduce the proliferation of monolayer cell cultures, as well as the growth of spheroids and tumor fell migration, in a dose-dependent manner. There was also a moderate increase in the number of apoptotic cells in the treated spheroids. NS-398 did not have an inhibitory effect on tumor invasion in the coculture spheroid system. Our study provides evidence that COX-2 is up-regulated in the majority of high-grade gliomas and that a potential role of COX-2 inhibitors as an adjuvant therapy for brain tumors may exist. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Brain Tumor Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Jikei Univ, Sch Med, Dept Neurosurg, Tokyo, Japan. Univ Milan, Osped Maggiore Policlin, IRCCS, Inst Neurosurg, Milan, Italy. RP Carroll, RS (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Brain Tumor Res Ctr, LMRC Room 121,221 Longwood Ave, Boston, MA 02115 USA. NR 43 TC 207 Z9 226 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 SEP 1 PY 2000 VL 60 IS 17 BP 4926 EP 4931 PG 6 WC Oncology SC Oncology GA 352FM UT WOS:000089203900045 PM 10987308 ER PT J AU Tung, CH Mahmood, U Bredow, S Weissleder, R AF Tung, CH Mahmood, U Bredow, S Weissleder, R TI In vivo imaging of proteolytic enzyme activity using a novel molecular reporter SO CANCER RESEARCH LA English DT Article ID TRANSFECTED CATHEPSIN-D; MATRIX METALLOPROTEINASES; PROTEASE INHIBITORS; TURBID MEDIA; GROWTH; BLOOD; MODEL; QUANTITATION; SPECTROSCOPY; SCATTERING AB The single biggest challenge facing in vivo imaging techniques is to develop biocompatible molecular beacons that are capable of specifically and accurately measuring in vivo targets at the protein, RNA, or DNA level. Our efforts have focused on developing activatable imaging probes to measure specific enzyme activities in vivo. Using cathepsin D as a model target protease, we synthesized a long-circulating, synthetic graft copolymer bearing near-infrared (NIR) fluorochromes positioned on cleavable substrate sequences. In its native state, the reporter probe was essentially nonfluorescent at 700 nm due to energy resonance transfer among the bound fluorochromes (quenching) but became brightly fluorescent when the latter were released by cathepsin D. NIR fluorescence signal activation was linear over at least 4 orders of magnitude and specific when compared with scrambled nonsense substrates, Using matched rodent tumor models implanted into nude mice expressing or lacking the targeted protease, it could be shown that the former generated sufficient NIR signal to be directly detectable and that the signal was significantly different compared with negative control tumors. The developed probes should find widespread applications for real-time in vivo imaging of a variety of clinically relevant proteases, for example, to detect endogenous protease activity in disease, to monitor the efficacy of protease inhibitors, or to image transgene expression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,Room 5403, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NIDDK NIH HHS [R21-DK55713-01] NR 40 TC 264 Z9 269 U1 2 U2 55 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2000 VL 60 IS 17 BP 4953 EP 4958 PG 6 WC Oncology SC Oncology GA 352FM UT WOS:000089203900049 PM 10987312 ER PT J AU Haque, NSK Isacson, O AF Haque, NSK Isacson, O TI Neurotrophic factors NGF and FGF-2 alter levels of huntingtin (IT15) in striatal neuronal cell cultures SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 6th Annual Meeting of the American-Society-for-Neural-Transplantation-and-Repair (ASNTR) CY APR, 1999 CL CLEARWATER, FLORIDA SP Amer Soc Neural Transplantat & Repair DE Huntington's disease; Western blotting; striatum; cell cultures; basic fibroblast growth factor (FGF-2); brain-derived neurotrophic factor (BDNF); nerve growth factor (NGF) ID FIBROBLAST GROWTH-FACTOR; INTERLEUKIN-1-BETA CONVERTING-ENZYME; EXPANDED CAG REPEAT; CORTICAL-NEURONS; GABAERGIC NEURONS; TRANSGENIC MICE; IN-VITRO; DISEASE; EXPRESSION; MODEL AB A mutation of the human IT15 gene is responsible for Huntington's disease (HD) and the causative factor in the major neuronal loss observed in the striatum. The growth factors basic fibroblast growth factor (FGF-2), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) improve survival and promote differentiation of striatal neurons, as well as exert a neuroprotective effect when such neurons are challenged with metabolic toxins or excitatory amino acids. Using Western blotting and striatal cell cultures, we found that FGF-2 increased the level of huntingtin in a dose-dependent fashion, whereas NGF decreased huntingtin expression. The neurotrophic factor-specific, dose-dependent effect on striatal levels of huntingtin may be relevant to understanding the normal role of IT15 and developing new therapies against the disease provoking mutated IT15. C1 Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Program Neurosci, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Dept Neurol, Belmont, MA 02178 USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Labs, MRC 119,115 Mill St, Belmont, MA 02178 USA. FU NINDS NIH HHS [NS30064] NR 26 TC 13 Z9 13 U1 2 U2 3 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD SEP-OCT PY 2000 VL 9 IS 5 BP 623 EP 627 PG 5 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 380LE UT WOS:000165702700007 PM 11144959 ER PT J AU Adams, SG Anzueto, A AF Adams, SG Anzueto, A TI Treating acute exacerbations of chronic bronchitis in the face of antibiotic resistance SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Review ID OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY-TRACT INFECTIONS; HAEMOPHILUS-INFLUENZAE; ANTIMICROBIAL RESISTANCE; STREPTOCOCCUS-PNEUMONIAE; UNITED-STATES; LUNG-DISEASE; CATARRHALIS; EFFICACY; THERAPY AB Antibiotics can be effective against acute exacerbations of chronic bronchitis and chronic obstructive pulmonary disease, but with bacterial resistance to multiple antibiotics increasing worldwide, appropriate antibiotic selection is critical. Categorizing patients with acute exacerbations according to age, number of exacerbations per year, disease severity, degree of pulmonary impairment, and presence of comorbid conditions helps to direct therapy. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Med & Crit Care Med, San Antonio, TX 78284 USA. RP Anzueto, A (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, Pulm Dis Sect 111E, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 31 TC 4 Z9 4 U1 0 U2 1 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD SEP PY 2000 VL 67 IS 9 BP 625 EP + PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 353EP UT WOS:000089262100005 PM 10992620 ER PT J AU Carroll, RS Brown, M Zhang, JP DiRenzo, J De Mora, JF Black, PM AF Carroll, RS Brown, M Zhang, JP DiRenzo, J De Mora, JF Black, PM TI Expression of a subset of steroid receptor cofactors is associated with progesterone receptor expression in meningiomas SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER; COACTIVATOR; ESTROGEN; GENE; HORMONES; PROTEINS; AIB1 AB The predominance of meningiomas in females, their accelerated growth during the luteal phase of the menstrual cycle and during pregnancy, and the association between meningiomas and breast cancer have led to a number of studies examining the potential role of steroids on the growth of meningiomas. There are numerous discrepancies in the literature about the mitogenic effects of steroids on meningiomas in both in vitro and in vivo models. The aim of this study was to examine the expression of three steroid receptor coactivators, along with progesterone receptor and estrogen receptor in meningiomas. This additional regulatory layer may explain the heterogeneity of hormone responses observed in these tumors. Using Western blot analysis and immunohistochemistry, we demonstrate the expression of the steroid coactivators steroid receptor cofactor (SRC-1), amplified in breast cancer protein (AIB1), and transcriptional intermediary factor 2 (TIF2) in 81, 76, and 76% of meningiomas, respectively. The expression of SRC-1 and TIF2 is significantly related to progesterone but not to estrogen receptor expression. In contrast, seven normal brain specimens were positive for TIF2 and SRC-I but negative for AIB1, One leptomeningeal specimen was positive for AIB1, SRC-1, and progesterone receptor, The differential expression of steroid receptor coactivators may explain the differential response of these tumors to hormonal therapy. C1 Brigham & Womens Hosp, Neurosurg Labs, Boston, MA 02115 USA. Brigham & Womens Hosp, Brain Tumor Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Carroll, RS (reprint author), Brigham & Womens Hosp, Neurosurg Labs, 221 Longwood Ave,Room 121, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; Font de Mora, Jaime/H-6304-2015; OI Font de Mora, Jaime/0000-0002-6816-2095; Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57374, CA80111] NR 24 TC 41 Z9 41 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 2000 VL 6 IS 9 BP 3570 EP 3575 PG 6 WC Oncology SC Oncology GA 352NK UT WOS:000089224600029 PM 10999746 ER PT J AU Palmer-Toy, DE Sarracino, DA Sgroi, D LeVangie, R Leopold, PE AF Palmer-Toy, DE Sarracino, DA Sgroi, D LeVangie, R Leopold, PE TI Direct acquisition of matrix-assisted laser desorption/ionization time-of-flight mass spectra from laser capture microdissected tissues SO CLINICAL CHEMISTRY LA English DT Meeting Abstract ID CELLS C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. ProteiGene Inc, Billerica, MA 01821 USA. NR 7 TC 59 Z9 61 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD SEP PY 2000 VL 46 IS 9 BP 1513 EP 1516 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 351WQ UT WOS:000089182500053 ER PT J AU Huttin, C Moeller, JF Stafford, RS AF Huttin, C Moeller, JF Stafford, RS TI Patterns and costs for hypertension treatment in the United States - Clinical, lifestyle and socioeconomic predictors from the 1987 National Medical Expenditures Survey SO CLINICAL DRUG INVESTIGATION LA English DT Article ID CHRONIC ILLNESS; HEALTH-STATUS; CARE; PREVENTION; ADJUSTMENT; INSURANCE; ALCOHOL; DISEASE; ACCESS AB Objective: To estimate the impact of clinical and non-clinical predictors of patterns of medication use and expenditures for the treatment of hypertension in the USA. Data Sources: The 1987 National Medical Expenditures Survey was used to identify 6398 individuals with hypertension over the age of 18 years. Pharmacological treatment was identified through patient self-reports of antihypertensive medications. Study Design: This retrospective, cross-sectional study used a multivariate two-stage decision model to estimate the demand for antihypertensive medications conditional on receipt of at least one antihypertensive prescription drug. Results: Women and the elderly were more likely to obtain medications and had greater expenditures on antihypertensive medications. Privately insured patients were 59% (if non-elderly) or 163% (if elderly with Medicare) more likely to receive drug therapy than uninsured patients. Patients with only Medicaid coverage were 126% more likely to receive drug therapy than uninsured patients. Compared with patients characterised as lower risk-takers, very high and high risk-takers were 38% and 24% less likely to be on drug therapy, respectively. Black, non-Hispanics were 30% more likely to be on drug therapy than White, non-Hispanics, but had lower annual expenditures on antihypertensive drugs. Severely overweight individuals [bodymass index (BMI) >30] were 62% more likely than patients with a BMI <27 to be on drug therapy and also had higher drug expenditures. Conclusions: Insurance had a more striking effect on access to antihypertensive drug therapy than on patterns of drug use or expenditures. Race/ethnicity and patient attitudes towards, risk were important determinants of access to antihypertensive drug therapies, as well as patterns of drug use and expenditures. C1 Univ Paris 10, Business Dept, Fac Econ, Paris, France. Agcy Healthcare Res & Qual, Ctr Cost & Financing Studies, Rockville, MD USA. Partners Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA USA. RP Huttin, C (reprint author), Univ Paris 10, BP 14, F-92420 Vaucresson, France. NR 32 TC 13 Z9 13 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-2563 J9 CLIN DRUG INVEST JI Clin. Drug Invest. PD SEP PY 2000 VL 20 IS 3 BP 181 EP 195 DI 10.2165/00044011-200020030-00006 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 358FY UT WOS:000089549000006 ER PT J AU Miller, KK Grinspoon, S Klibanski, A AF Miller, KK Grinspoon, S Klibanski, A TI Cardiovascular risk markers in hypothalamic amenorrhoea SO CLINICAL ENDOCRINOLOGY LA English DT Article ID MODERATE ALCOHOL INTAKE; CORONARY HEART-DISEASE; RAISES HDL CHOLESTEROL; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; ESTROGEN USE; LIPOPROTEIN(A); MENOPAUSE; EXERCISE; INTERVENTION AB OBJECTIVE To determine whether women with oestrogen deficiency due to hypothalamic amenorrhoea (HA) would demonstrate a lipid and lipoprotein pattern similar to that seen in menopause with higher total cholesterol (TC), LDL, triglyceride and Lp(a) and lower HDL levels than women with regular menstrual cycles. DESIGN Cross-sectional. PATIENTS Fifty subjects: 21 women with HA and 30 eumenorrhoeic controls (NL) matched for age, BMI and fat-free mass. MEASUREMENTS Lipid and lipoprotein levels. RESULTS There was a significant difference in Lp(a) levels in the HA group between women with >19% fat intake and those <19% fat intake (352 +/- 231 vs. 116 +/- 62 mg/l, P = 0.006). Percent fat intake was the most significant determinant of Lp(a) levels in HA, accounting for 51% of the variation in Lp(a) levels. Mean HDL levels were higher in the women with HA compared with the controls (1.3 +/- 0.3 vs. 1.1 +/- 0.2 mmol/l, P = 0.002). There was no significant difference between the groups in TC [4.4 +/- 0.9 (HA) vs. 4.1 +/- 0.8 mmol/l (NL), P> 0.05], LDL [2.8 +/- 0.6 (HA) vs. 2.7 +/- 0.7 mmol/l (NL), P> 0.05], triglycerides [1.8 +/- 0.5 (HA) vs. 1.7 +/- 0.5 mmol/l (NL), P>0.05] or Lp(a) [234 +/- 199 (HA) vs. 247 +/- 222 (NL) mg/l, P>0.05] levels. CONCLUSION Reduced Lp(a) levels were associated with low dietary fat in women with HA. Moreover, in contrast to menopausal oestrogen deficiency, young women with HA and oestrogen deficiency have increased levels of HDL and no increases in TC, LDL and triglycerides. These data suggest that the negative effects of oestrogen deficiency on cardiovascular risk factors may be modified in women with hypothalamic amenorrhoea. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Dept Med, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R01-DK-52625] NR 47 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD SEP PY 2000 VL 53 IS 3 BP 359 EP 366 DI 10.1046/j.1365-2265.2000.01100.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 359BF UT WOS:000089591100013 PM 10971454 ER PT J AU Mannion, RJ Woolf, CJ AF Mannion, RJ Woolf, CJ TI Pain mechanisms and management: A central perspective SO CLINICAL JOURNAL OF PAIN LA English DT Article; Proceedings Paper CT Symposium on Mechanisms of Chronic Pain held at the 1999 International-Association-for-the-Study-of-Pain Meeting CY AUG 23, 1999 CL VIENNA, AUSTRIA DE central sensitization; nociceptive pain; pain mechanisms; pathologic pain; spinal plasticity ID RAT SPINAL-CORD; SUBSTANTIA-GELATINOSA NEURONS; PERIPHERAL-NERVE INJURY; PRIMARY SENSORY NEURONS; DORSAL HORN; INFLAMMATORY PAIN; NEUROPATHIC PAIN; POSTHERPETIC NEURALGIA; CENTRAL SENSITIZATION; CELLULAR MECHANISMS AB Although pain is always intense and unpleasant, the capacity to experience this sensation is, under normal circumstances, fundamental to the preservation of bodily integrity. Clinically, however, after injury to peripheral tissue or directly to the nervous system, spontaneous and evoked pain manifest that serve no physiologic function, cue crippling to patients, and are difficult to treat. Here, we review the specific role of the dorsal horn of the spinal cord in the mechanisms of nociceptive protective pain and the spinal plasticity that occurs after nerve and tissue injury. This spinal neuronal plasticity is shown to be a key contributor to pathologic pain hypersensitivity. The potential for the molecular mechanisms responsible for the spinal plasticity in revealing new targets for future treatment is also discussed. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4310, Charlestown, MA 02129 USA. NR 53 TC 66 Z9 77 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD SEP PY 2000 VL 16 IS 3 SU S BP S144 EP S156 PG 13 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 356AJ UT WOS:000089420500006 PM 11014459 ER PT J AU Woolf, CJ AF Woolf, CJ TI Mechanisms of chronic pain - Proceedings of a symposium Vienna, Austria, August 23, 1999 - Introduction SO CLINICAL JOURNAL OF PAIN LA English DT Editorial Material C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD SEP PY 2000 VL 16 IS 3 SU S BP S113 EP S113 PG 1 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 356AJ UT WOS:000089420500001 ER PT J AU Shouse, MN Farber, PR Staba, RJ AF Shouse, MN Farber, PR Staba, RJ TI Physiological basis: how NREM sleep components can promote and REM sleep components can suppress seizure discharge propagation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE sleep; epilepsy; animal models; cats ID AMYGDALA-KINDLED KITTENS; CYCLIC ALTERNATING PATTERN; GENERALIZED EPILEPSY; CELLULAR MECHANISMS; FOCAL EPILEPSY; OSCILLATIONS; MODULATION; EEG AB Objectives: To describe how the neural generators of different sleep components can provoke seizure discharge propagation during NREM sleep and can suppress it during REM sleep. Methods: Experimental manipulations of discrete physiological components were conducted in feline epilepsy models (n = 64), mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy. Procedures included seizure induction as well as quantifying norepinephrine concentrations (microdialysis) and the sleep-waking state distribution of seizures before and after lesions, systemic and localized drug administration and/or photic stimulation. Results: (1) Neural generators of synchronous EEG oscillations, including tonic background slow waves and phasic 'arousal' events (sleep EEG transients such as sleep spindles, k-complexes), can combine to promote electrographic seizure propagation during NREM and drowsiness; anti-gravity muscle tone permits seizure-related movement. (2) Neural generators of asynchronous neuronal discharge patterns can reduce electrographic seizures during alert waking and REM sleep; skeletal motor paralysis blocks seizure-related movement during REM. (3) Etiology of the seizure disorder can interact with sleep and arousal mechanisms to determine sleep-waking state distribution of interictal and ictal events. Conclusions: Differential effects of NREM versus REM sleep components on seizure discharge propagation are to some extent non-specific and in other ways specific to seizure etiology. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 VA Greater Los Angeles Hlth Care Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90024 USA. RP Shouse, MN (reprint author), 2242 S Bentley Ave 4, Los Angeles, CA 90064 USA. NR 43 TC 51 Z9 53 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD SEP PY 2000 VL 111 SU 2 BP S9 EP S18 DI 10.1016/S1388-2457(00)00397-7 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 363QZ UT WOS:000089847200003 PM 10996550 ER PT J AU Janicek, MJ Shaffer, K AF Janicek, MJ Shaffer, K TI Manifestations of toxic lung effects on Ga-67 scans in aggressive non-Hodgkin's lymphoma with high-dose CHOP chemotherapy SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE Ga-67; toxic effects on the lung; non-Hodgkin's lymphoma ID TRANSPLANTATION C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Med Sch,Dept Radiol, Boston, MA 02115 USA. RP Janicek, MJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Med Sch,Dept Radiol, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 2000 VL 25 IS 9 BP 734 EP 735 DI 10.1097/00003072-200009000-00022 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 349HW UT WOS:000089040500022 PM 10983770 ER PT J AU Chen, XM Jacobson, AF AF Chen, XM Jacobson, AF TI Nonosseous uptake on bone scan in adenocarcinoma of unknown primary origin SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE adenocarcinoma; bone scan; soft tissue C1 VA Puget Sound Hlth Care Syst, Nucl Med Sect S113 NUC, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. RP Jacobson, AF (reprint author), VA Puget Sound Hlth Care Syst, Nucl Med Sect S113 NUC, 1660 S COlumbian Way, Seattle, WA 98108 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD SEP PY 2000 VL 25 IS 9 BP 751 EP 752 DI 10.1097/00003072-200009000-00030 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 349HW UT WOS:000089040500030 PM 10983778 ER PT J AU Gilron, I Max, MB Lee, G Booher, SL Sang, CN Chappell, AS Dionne, RA AF Gilron, I Max, MB Lee, G Booher, SL Sang, CN Chappell, AS Dionne, RA TI Effects of the 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid/kainate antagonist LY293558 on spontaneous and evoked postoperative pain SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID IONOTROPIC GLUTAMATE RECEPTORS; SPINAL-CORD; CENTRAL SENSITIZATION; NOCICEPTIVE RESPONSE; KAINATE; HYPERALGESIA; AMPA; NMDA; RAT; FORMALIN AB Background: Previous studies suggest that 2-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA)/kainate antagonists reduce experimentally induced pain. There have been no studies of AMPA/kainate antagonists in clinical pain. Methods: Analgesic efficacy of intravenous LY293558 (0.4 or 1.2 mg/kg) was compared with that of intravenous ketorolac tromethamine (INN, ketorolac; 30 mg) and placebo in a randomized, double-blind, parallel-group study after oral surgery (n = 70). Study drugs were administered at the onset of moderate pain; pain intensity and relief were measured for 240 minutes. Results: High-dose LY293558 and ketorolac tromethamine were superior to placebo (P < .05) for pain evoked by mouth opening and one of several measures of spontaneous pain: SPID240 +/- SEM for pain evoked by mouth opening was highest for ketorolac tromethamine (151 +/- 58), intermediate for high-dose LY293558 (-45 +/- 35), and least for low-dose LY293558 (-151 +/- 39) and placebo (-162 +/- 50). High-dose LY293558 was superior to placebo at individual time points (45 to 240 minutes) for pain evoked by mouth opening but not for spontaneous pain. The spontaneous summed pain intensity difference over 240 minutes (SPID240 +/- SEM) was highest for ketorolac tromethamine (303 +/- 84), intermediate for high-dose LY293558 (-51 +/- 40) and low-dose LY293558 (-96 +/- 45), and least for placebo (-180 +/- 24), LY293558 was well tolerated, with dose-dependent and reversible side effects including hazy vision in 20% of patients and sedation in 15%. Conclusions: This is the first evidence that an AMPA/kainate antagonist reduces clinical pain. Tests of evoked pain may be more sensitive to certain analgesics than those of spontaneous pain. The evaluation of evoked pain as an outcome measure in analgesic trials may identify potentially useful compounds otherwise missed if only spontaneous pain is evaluated. C1 Natl Inst Dental & Cranofacial Res, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Gilron, I (reprint author), Natl Inst Dental & Cranofacial Res, Pain & Neurosensory Mech Branch, NIH, Rm 3C-434, Bethesda, MD 20892 USA. NR 30 TC 49 Z9 50 U1 1 U2 3 PU MOSBY, 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 SEP PY 2000 VL 68 IS 3 BP 320 EP 327 DI 10.1067/mcp.2000.108677 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 358LR UT WOS:000089560000012 PM 11014414 ER PT J AU Lader, AS Prat, AG Jackson, GR Chervinsky, KL Lapey, A Kinane, TB Cantiello, HF AF Lader, AS Prat, AG Jackson, GR Chervinsky, KL Lapey, A Kinane, TB Cantiello, HF TI Increased circulating levels of plasma ATP in cystic fibrosis patients SO CLINICAL PHYSIOLOGY LA English DT Article DE adenosine triphosphate; cystic fibrosis; hereditary diseases ID TRANSMEMBRANE CONDUCTANCE REGULATOR; MULTIDRUG-RESISTANCE; BRONCHIAL REACTIVITY; AIRWAY INFLAMMATION; CANCER; EXPRESSION; CHANNEL; GENES; RISK AB Recent studies have shown that the cystic fibrosis transmembrane conductance regulator (CFTR), an ATP-binding cassette (ABC) transporter whose mutations are responsible for cystic fibrosis (CF), permeates ATP. However, little information is available concerning extracellular ATP concentrations in CF patients. Thus, the goal of this preliminary study was to determine the circulating levels of plasma ATP in CF patients. Circulating levels of plasma ATP were determined by the luciferin-luciferase assay in both CF patients and healthy volunteer control subjects. The two groups were compared using an analysis of variance. CF genotype and age, which ranged from 7 to 56 years, were also used to compare data by single-blind analysis. With comparable sample numbers, CF patients had statistically higher levels of circulating ATP (34%, P < 0.01) when compared by analysis of covariance with the age of the subjects as the cofactor. The CF patients bearing the Delta F508 genotype had a 54% (n = 33, P < 0.01) higher plasma ATP concentration compared to controls, while patients bearing other CF genotypes were similar to controls (n = 10, P < 0.4). We conclude that CF patients have higher circulating levels of ATP when compared to controls. Increased levels of plasma ATP, which is an important autocrine/paracrine hormone in many cell types, may be associated with chronic manifestations of the disease. C1 Massachusetts Gen Hosp E, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pediat, Ctr Cyst Fibrosis Care & Res, Boston, MA USA. Harvard Med Sch, Dept Med, Boston, MA USA. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. NR 27 TC 19 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0144-5979 J9 CLIN PHYSIOL JI Clin. Physiol. PD SEP PY 2000 VL 20 IS 5 BP 348 EP 353 DI 10.1046/j.1365-2281.2000.00272.x PG 6 WC Physiology SC Physiology GA 346RZ UT WOS:000088886000004 PM 10971545 ER PT J AU Saini, S Sharma, R Baron, RL Turner, DA Ros, PR Hahn, PF Small, WC Delange, EE Stillman, AE Edelman, RR Runge, VM Outwater, EK AF Saini, S Sharma, R Baron, RL Turner, DA Ros, PR Hahn, PF Small, WC Delange, EE Stillman, AE Edelman, RR Runge, VM Outwater, EK TI Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging SO CLINICAL RADIOLOGY LA English DT Article DE MR imaging; contrast media; liver ID SUPERPARAMAGNETIC IRON-OXIDE; FOCAL HEPATIC-LESIONS; CONTRAST AGENTS; HEPATOCELLULAR-CARCINOMA; CLINICAL-TRIAL; FERUMOXIDES; ENHANCEMENT; SAFETY AB AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences, Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast, On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials. (C) 2000 The Royal College of Radiologists. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Grady Mem Hosp, Atlanta, GA 30335 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Virginia, Charlottesville, VA USA. Univ Minnesota, Minneapolis, MN USA. Beth Israel Hosp, Boston, MA USA. Univ Kentucky, Lexington, KY USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 13 TC 25 Z9 27 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD SEP PY 2000 VL 55 IS 9 BP 690 EP 695 DI 10.1053/crad.2000.0504 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 352ZH UT WOS:000089248900006 PM 10988047 ER PT J AU Duckett, S Kradin, R Galle, P AF Duckett, S Kradin, R Galle, P TI The pathogenesis of beryllium-induced pulmonary granulomatosis. A scanning secondary ion analytical microscopy study SO COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES LA English DT Article DE pulmonary berylliosis; pathogenesis; ion microprobe ID LUNG-DISEASE; CARCINOGENICITY; LOCALIZATION AB Chronic granulomatous pneumonitis was induced in rats with beryllium to study the pathogenesis of that disease, by identifying and localizing the beryllium in histological sections of the pulmonary tissues. This was done with scanning secondary ion mass spectrometry (SIMS). Thus, our observations suggest that the route of the Be from the site of injection into the lung, passes first by the blood, th rough the vascular wall and into the surrounding pulmonary tissues where Be was phagocytized by macrophages. There resulted in acute vasculitis throughout the lung. It was noted that the granuloma were focal inflammatory sites, solely observed within the vascular wall, distributed along the course of the affected vessel. These findings raise the question as to whether pulmonary granulomatous lesions of other origins are also localized within the vascular wall. (C) 2000 Academie des sciences/Editions scientifiques et medicales Elsevier SAS. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Hop La Pitie Salpetriere, Lab Neuropathol R Escourolle, F-75651 Paris 13, France. Ecole Natl Vet, Chim Phys Lab, F-94704 Maisons Alfort, France. RP Duckett, S (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0764-4469 J9 CR ACAD SCI III-VIE JI Comptes Rendus Acad. Sci. Ser. III-Sci. Vie-Life Sci. PD SEP PY 2000 VL 323 IS 9 BP 769 EP 774 DI 10.1016/S0764-4469(00)01218-X PG 6 WC Biology; Multidisciplinary Sciences SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics GA 367XC UT WOS:000090086100003 PM 11072622 ER PT J AU Cariani, P AF Cariani, P TI Anesthesia, neural information processing, and conscious awareness SO CONSCIOUSNESS AND COGNITION LA English DT Editorial Material ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL METABOLISM; HUMANS; HALOTHANE; THRESHOLD AB Possible systemic effects of general anesthetic agents on neural information processing are discussed in the context of the thalamocortical suppression hypothesis presented by Drs. Alkire, Haier, and Fallen (this issue) in their PET study of the anesthetized state. Accounts of the neural requisites of consciousness fail into two broad categories. Neuronal-specificity theories postulate that activity in particular neural populations is sufficient for conscious awareness, while process-coherence theories postulate that particular organizations of neural activity are sufficient. Accounts of anesthetic narcosis, on the other hand, explain losses of consciousness in terms of neural signal-suppressions, transmission blocks, and the disruptions of signal interpretation. While signal-suppression may account for the actions of some anesthetic agents, the existence of anesthetics, such as choralose, that cause both loss of consciousness and elevated discharge rates, is problematic for a general theory of narcosis that is based purely on signal suppression and transmission-block. However, anesthetic agents also alter relative firing rates and temporal discharge patterns that may disrupt the coherence of neural signals and the functioning of the neural networks that interpret them. It is difficult at present, solely on the basis of regional brain metabolic rates, to test process-coherence hypotheses regarding organizational requisites for conscious awareness. While these pioneering PET studies have great merit as panoramic windows of mind-brain con-elates, wider ranges of theory and empirical evidence need to be brought into the formulation of truly comprehensive theories of consciousness and anesthesia. (C) 2000 Academic Press. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Cariani, P (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. NR 41 TC 26 Z9 27 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 J9 CONSCIOUS COGN JI Conscious. Cogn. PD SEP PY 2000 VL 9 IS 3 BP 387 EP 395 DI 10.1006/ccog.1999.0420 PG 9 WC Psychology, Experimental SC Psychology GA 361RU UT WOS:000089737900005 PM 10993666 ER PT J AU Dana, MR Qian, Y Hamrah, P AF Dana, MR Qian, Y Hamrah, P TI Twenty-five-year panorama of corneal immunology - Emerging concepts in the immunopathogenesis of microbial keratitis, peripheral ulcerative keratitis, and corneal transplant rejection SO CORNEA LA English DT Review DE Acanthamoeba; antigen presentation; cornea; corneal transplantation; chemokines; cytokines; herpes virus; keratitis; immune modulation; Langerhans cell; Mooren's ulcer; Pseudomonas ID HERPES-SIMPLEX VIRUS; SYSTEMIC LUPUS-ERYTHEMATOSUS; CD4(+) T-CELLS; EXPERIMENTAL PSEUDOMONAS KERATITIS; MAJOR HISTOCOMPATIBILITY COMPLEX; CHEMOKINE GENE-EXPRESSION; LATENTLY INFECTED-RABBITS; INDUCED STROMAL KERATITIS; NECROSIS-FACTOR-ALPHA; SCID MOUSE MODEL AB To describe the most recent advances in our understanding of the cellular and molecular mechanisms involved ed in the immunopathogenesis of corneal immunoinflammatory disorders including microbial keratitis, peripheral ulcerative keratitis, and allograft I injection. Methods. Review of the published peer-reviewed literature that has contributed significantly to our modern understanding of corneal immunology. In addition, the authors have summarized the information in conceptual diagrams that highlight the critical cellular and molecular pathways that lead to corneal immune responses in the two most thoroughly studied corneal immune disorders, hel pes simplex keratitis (ILSK) and transplant rejection. Results. In spite of the wide array of molecular and cellular factors that mediate corneal immunity, critical mechanistic facets are shared by the various corneal immunoinflammatory disorders. These include activation and migration of local antigen-presenting cells (APCs), including Langerhans cells (LCs), upregulation in pleiotropic proinflammatory cytokines such as interleukin-1 (IL-1)and tumor necrosis factor-alfa (TNF-alpha) that can mediate a wide allay of immune functions in addition to upregulating protease expression, and chemokines that play a critical role on the one hand in attracting nonantigen-specific inflammatory cells such as neutrophils and on the other in attracting CD4(+) T helper type 1 (Th 1) cells that mediate most of the destruction in the cornea. Conclusions. In the last 25 years, we have seen our field develop from a descriptive stage into a new phase where: the fundamental processes that mediate and effect corneal immunity are being accurately deciphered. It is anticipated that this new knowledge will allow development of specific molecular and genetic therapeutic strategies that could target critical steps in the immunopathogenesis of disease without the untoward side-effects of nonspecific generalized immune suppression that still remains the standard of care today. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst,Lab Immunol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Cornea Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Dana, MR (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Schepens Eye Res Inst,Lab Immunol, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu NR 337 TC 87 Z9 91 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD SEP PY 2000 VL 19 IS 5 BP 625 EP 643 DI 10.1097/00003226-200009000-00008 PG 19 WC Ophthalmology SC Ophthalmology GA 352ZJ UT WOS:000089249000006 PM 11009315 ER PT J AU Silverman, PR AF Silverman, PR TI Research, clinical practice, and the human experience: Putting the pieces together SO DEATH STUDIES LA English DT Article ID PARENT AB Ther work of the clinician and that of the researcher are presented as representing 2 cultures that cannot exist without each other. A third culture is described to reflect the common human experience of death and grief that invariably info,ms the work of both clinicians and researchers. At different times in our lives we ran be both the subjects and the objects of the work in which we are involved. the author's experience as co-principal investigator with lire Massachusetts General Hospital/Haroard Child Bereavement Study and the application of qualitative research is used to exemplify these ideas and demonstrate how the cultures can be integrated. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Silverman, PR (reprint author), 18 Ingleside Rd, Lexington, MA 02420 USA. NR 31 TC 18 Z9 18 U1 0 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0748-1187 J9 DEATH STUD JI Death Stud. PD SEP PY 2000 VL 24 IS 6 BP 469 EP 478 DI 10.1080/07481180050121453 PG 10 WC Psychology, Multidisciplinary; Social Issues; Social Sciences, Biomedical SC Psychology; Social Issues; Biomedical Social Sciences GA 351PG UT WOS:000089166900002 PM 11503664 ER PT J AU Smith, DM Nielsen, C Tabin, CJ Roberts, DJ AF Smith, DM Nielsen, C Tabin, CJ Roberts, DJ TI Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut boundary SO DEVELOPMENT LA English DT Article DE BMP4; BMP receptor; Nkx2.5; gut; gizzard; pyloric sphincter; chick ID SONIC-HEDGEHOG; HOX GENES; GUT DEVELOPMENT; DEVELOPING LIMB; EXPRESSION; DIFFERENTIATION; MORPHOGENESIS; INDUCTION; REGIONALIZATION; MISEXPRESSION AB Patterning of the gut into morphologically distinct regions results from the appropriate factors being expressed in strict spatial and temporal patterns to assign cells their fates in development. Often, the boundaries of gene expression early in development correspond to delineations between different regions of the adult gut. For example, Bmp4 is expressed throughout the hindgut and midgut, but is not expressed in the early gizzard, Ectopic BMP4 in the gizzard caused a thinning of the muscularis. To understand this phenotype we examined the expression of the receptors transducing BMP signaling during gut development. We find that the BMP receptors are differentially expressed in distinct regions of the chicken embryonic gut. By using constitutively activated versions of the BMP type I receptors, we find that the BMP receptors act similarly to BMP4 in the gizzard when ectopically expressed. We show that the mesodermal thinning seen upon ectopic BMP signaling is due to an increase in apoptosis and a decrease in proliferation within the gizzard mesoderm, The mesodermal thinning is characterized by a disorganization and lack of differentiation of smooth muscle in the gizzard mesoderm. Further, ectopic BMP receptors cause an upregulation of Nkx2.5, the pyloric sphincter marker, similar to that seen with ectopic BMP4. This upregulation of Nkx2.5 is a cell-autonomous event within the mesoderm of the gizzard, We also find that Nkx2.5 is necessary and sufficient for establishing aspects of pyloric sphincter differentiation. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tabin, CJ (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD34448] NR 37 TC 73 Z9 75 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 SEP PY 2000 VL 127 IS 17 BP 3671 EP 3681 PG 11 WC Developmental Biology SC Developmental Biology GA 356EE UT WOS:000089430700003 PM 10934012 ER PT J AU White, FA Behar, O AF White, FA Behar, O TI The development and subsequent elimination of aberrant peripheral axon projections in Semaphorin3A null mutant mice SO DEVELOPMENTAL BIOLOGY LA English DT Article DE DRG; axon guidance; Semaphorin3A ID MOUSE SPINAL-CORD; SENSORY AXONS; GROWTH; GUIDANCE; EXPRESSION; SYSTEM; DEATH; CNS AB Semaphorin3A (previously known as Semaphorin III, Semaphorin D, or collapsin-1) is a member of the semaphorin gene family, many of which have been shown to guide axons during nervous system development. Semaphorin3A has been demonstrated to be a diffusible chemorepulsive molecule for axons of selected neuronal populations in vitro. Analysis of embryogenesis in two independent lines of Semaphorin3A knockout mice support the hypothesis that this molecule is an important guidance signal for neurons of the peripheral nervous system (M. Taniguchi et al., 1997, Neuron 19, 519-530; E. Ulupinar et al., 1999, Mel. Cell. Neurosci. 13, 281-292). Surprisingly, newborn Semaphorin3A null mutant mice exhibit no significant abnormalities (O. Behar et al., 1996, Nature 383, 525-528). In this study we have tested the hypothesis that guidance abnormalities that occurred during early stages of Semaphorin3A null mice development are corrected later in development. We have found that the extensive abnormalities formed during early developmental stages in the peripheral nervous system are largely eliminated by embryonic day 15.5. We demonstrate further that at least in one distinct anatomical location these abnormalities are mainly the result of aberrant projections. In conclusion, these findings suggest the existence of correction mechanisms that eliminate most sensory axon pathfinding errors early in development. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA. Yale Univ, Sch Med, PVA EPVA Neurosci Res Ctr, New Haven, CT 06510 USA. RP Behar, O (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. RI White, Fletcher/F-2895-2012 NR 24 TC 41 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 1 PY 2000 VL 225 IS 1 BP 79 EP 86 DI 10.1006/dbio.2000.9822 PG 8 WC Developmental Biology SC Developmental Biology GA 354FR UT WOS:000089319600006 PM 10964465 ER PT J AU Kavka, AI Green, JBA AF Kavka, AI Green, JBA TI Evidence for dual mechanisms of mesoderm establishment in Xenopus embryos SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Xenopus embryo; mesoderm; VegT; determinants; morphogen ID BOX TRANSCRIPTION FACTOR; POSTERIOR DEVELOPMENT; GENE; EXPRESSION; ENDODERM; INDUCTION; RECEPTOR; VEGT; FGF; PREPATTERN AB In Xenopus embryos, the maternally encoded transcription factor VegT (also known as Xombi, Antipodean, Brat, and Xtbx6) is essential for normal endoderm and mesoderm formation. This finding and the localization of VegT mRNA in the vegetal hemisphere of the oocyte are consistent with several models of germ layer patterning. Specific models have been proposed in which (1) combinations of cytoplasmic determinants, (2) inductive signals, or (3) intracellular concentration (morphogen effects) predominate. We test predictions of these models, We show that contrary to previous proposals, FGF does not suppress endoderm formation and so cannot be an anti-endoderm mesodermal determinant. We further show that, at the right dose, VegT can induce mesodermal marker expression cell autonomously and that it induces mesoderm at concentrations below those that induce endoderm, These results are consistent with a dual mechanism of mesoderm establishment in which both VegT-initiated inductive signals and an intracellular VegT morphogen gradient play a part. (C) 2000 Wiley-Liss, Inc. 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 FU NICHD NIH HHS [R01HD36345] NR 33 TC 10 Z9 11 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 2000 VL 219 IS 1 BP 77 EP 83 DI 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1025>3.0.CO;2-E PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 349TX UT WOS:000089062600009 PM 10974673 ER PT J AU Kekelidze, T Khait, I Togliatti, A Holtzman, D AF Kekelidze, T Khait, I Togliatti, A Holtzman, D TI Brain creatine kinase and creatine transporter proteins in normal and creatine-treated rabbit pups SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT 4th International Conference on Brain Energy Metabolism CY AUG 14-18, 1999 CL OXFORD, ENGLAND DE mitochondrial creatine kinase; cytosolic creatine kinase; brain; creatine; P-31 NMR spectroscopy ID IN-VIVO; CEREBRAL GRAY; WHITE-MATTER; MAGNETIC-RESONANCE; RAT-BRAIN; PHOSPHOCREATINE; EXPRESSION; MATURATION; SEIZURES; DISEASE AB Systemic creatine (Cr) supplementation increases brain phosphocreatine (PCr) and prevents hypoxic seizures in 15-day-old rabbits, Between 5 and 30 days of age during normal development, rabbit gray matter mitochondrial creatine kinase (MI-CK) increases 400% while cytosolic CK (BB-CK) increases 60%. In white matter, both isoenzymes show smaller, similar increases (40%) during this period, The Cr transporter protein decreases 60% between 5 and 15 days in both regions. In vivo CK rate constants measured by P-31 nuclear magnetic resonance increase 30% between 10 and 20 days, and then fall 50% between 20 and 30 days in predominantly gray matter slices. Similar maturational changes are seen in predominantly white matter slices. Injecting Cr at 15 days does not significantly change BB-CK or MI-CK isoenzymes or the in vivo CK reaction rate constants, Thus, the largest change in the CK system associated with suppression of hypoxic seizures in Cr-treated rabbits is increased PCr in gray and white matter, Copyright (C) 2000 S. Karger AG, Basel. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Kekelidze, T (reprint author), Brigham & Womens Hosp, Dept Radiol, 221 Longwood Ave,LMRC Bldg, Boston, MA 02115 USA. FU NINDS NIH HHS [NS 26371, NS 10176] NR 36 TC 10 Z9 10 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD SEP-DEC PY 2000 VL 22 IS 5-6 BP 437 EP 443 DI 10.1159/000017473 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 383BX UT WOS:000165864200012 PM 11111160 ER PT J AU Kaiyala, KJ Prigeon, RL Kahn, SE Woods, SC Schwartz, MW AF Kaiyala, KJ Prigeon, RL Kahn, SE Woods, SC Schwartz, MW TI Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs SO DIABETES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; INDUCED HYPERTENSION; GLUCOSE-TOLERANCE; ZUCKER RATS; BODY-FAT; IN-VIVO; RESISTANCE; PLASMA; SENSITIVITY AB Insulin transported from plasma into the central nervous system (CNS) is hypothesized to contribute to the negative feedback regulation of body adiposity, Because CNS insulin uptake is likely mediated by insulin receptors, physiological interventions that impair insulin action in the periphery might also reduce the efficiency of CNS insulin uptake and predispose to weight gain, We hypothesized that high-fat feeding, which both reduces insulin sensitivity in peripheral tissues and favors weight gain, reduces the efficiency of insulin uptake from plasma into the CNS, To test this hypothesis, we estimated parameters for cerebrospinal fluid (CSF) insulin uptake and clearance during an intravenous insulin infusion using compartmental modeling in 10 dogs before and after 7 weeks of high-fat feeding, These parameters, together with 24-h. plasma insulin levels measured during ad libitum feeding, also permitted estimates of relative CNS insulin concentrations. The percent changes of adiposity, body weight, and food intake after high-fat feeding were each inversely associated with the percent changes of the parameter k(1)k(2), which reflects the efficiency of CNS insulin uptake from plasma (r = -0.74, -0.69, -0.63; P = 0.015, 0.03, and 0.05, respectively). These findings were supported by a non-model-based calculation of CNS insulin uptake: the CSF-to-plasma insulin ratio during the insulin infusion. This ratio changed in association with changes of k(1)k(2) (r = 0.84, P = 0.002), body weight (r = -0.66, P = 0.04), and relative adiposity (r = -0.72, P = 0.02), By comparison, changes in insulin sensitivity according to minimal model analysis, were not associated with changes in k(1)k(2), suggesting that these parameters are not regulated in parallel, During high-fat feeding, there was a 60% reduction of the estimated CNS insulin level (P = 0.04), and this estimate was inversely associated with percent: changes in body weight (r = -0.71, P = 0.03), These results demonstrate that increased food intake and weight gain during high-fat feeding are associated with and may be causally related to reduced insulin delivery into the CNS. C1 Univ Washington, Sch Dent, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. RP Schwartz, MW (reprint author), Harborview Med Ctr, Box 359757,325 9th Ave, Seattle, WA USA. RI Schwartz, Michael/H-9950-2012; OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [DK-35816, DK-12829, DK-17047] NR 40 TC 181 Z9 186 U1 2 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2000 VL 49 IS 9 BP 1525 EP 1533 DI 10.2337/diabetes.49.9.1525 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 349TZ UT WOS:000089062800017 PM 10969837 ER PT J AU Hebinck, J Hardt, C Schols, L Vorgerd, M Briedigkeit, L Kahn, CR Ristow, M AF Hebinck, J Hardt, C Schols, L Vorgerd, M Briedigkeit, L Kahn, CR Ristow, M TI Heterozygous expansion of the GAA tract of the X25/frataxin gene is associated with insulin resistance in humans SO DIABETES LA English DT Article ID TRINUCLEOTIDE REPEAT POLYMORPHISM; FRIEDREICHS ATAXIA GENE; GLUCOSE-INTOLERANCE; IRON ACCUMULATION; SUPPRESSION TEST; FRATAXIN GENE; IN-VIVO; HOMOLOG; SENSITIVITY; OCTREOTIDE AB Friedreich's ataxia (FA) is an autosomal recessive disease that has been attributed to a GAA triplet repeat expansion in the first intron of the X25/frataxin gene. Impaired glucose tolerance is present in up to 39% of FA patients, and clinically apparent diabetes is seen in similar to 18% of the affected individuals. Subjects carrying the X25/frataxin GAA repeat in a heterozygous state do not develop FA and, therefore, represent an ideal model to study the underlying metabolic defects that contribute to the diabetes associated with this disorder. In the present study, we have compared 11 first-degree relatives of FA patients (i.e., parents or heterozygous siblings of FA patients) with matched normal control subjects to study the parameters of glucose metabolism. An oral glucose tolerance test revealed diabetes in one of the heterozygous subjects who was excluded from further analyses. Using an octreotide-based quautification of insulin sensitivity, similar to 18% of the remaining 10 study subjects showed pronounced insulin resistance, reflecting a significant difference from the control group (P = 0.001), In conclusion, a heterozygous expansion of the X25/frataxin GAA repeat in healthy individuals is associated with insulin resistance and might be considered a genetic co-factor in the pathogenesis of mitochondrial subtypes of diabetes. C1 Univ Cologne, Klin 2, Cologne, Germany. Univ Cologne, Poliklin Innere Med, Cologne, Germany. Med Klin Bergmannstrost, Halle, Germany. Univ Essen Gesamthsch, Inst Humangenet, Essen, Germany. Ruhr Univ Bochum, Inst Labs Med & Klin Chem, D-4630 Bochum, Germany. Harvard Univ, Sch Med, Div Res, Sect Cellular & Mol Physiol, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Ristow, M (reprint author), Uniklin, BHE5 039, D-50931 Cologne, Germany. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 FU NIDDK NIH HHS [DK-45935] NR 33 TC 16 Z9 16 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 2000 VL 49 IS 9 BP 1604 EP 1607 DI 10.2337/diabetes.49.9.1604 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 349TZ UT WOS:000089062800028 PM 10969848 ER PT J AU Boyko, EJ de Courten, M Zimmet, PZ Chitson, P Tuomilehto, J Alberti, KGMM AF Boyko, EJ de Courten, M Zimmet, PZ Chitson, P Tuomilehto, J Alberti, KGMM TI Features of the metabolic syndrome predict higher risk of diabetes and impaired glucose tolerance - A prospective study in mauritius SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE; CARDIOVASCULAR RISK; CHINESE MAURITIANS; PLASMA LEPTIN; FOLLOW-UP; AFRICAN-AMERICANS; BASE-LINE; MELLITUS; MEN; POPULATION AB OBJECTIVE - To assess the independent and joint effects of the components of the metabolic syndrome, including leptin, which is a recently proposed addition to this syndrome, in predicting the cumulative incidence of impaired glucose tolerance (IGT) and diabetes among individuals with normal glucose tolerance. RESEARCH DESIGN AND METHODS - This prospective study involved 2,605 residents of Mauritius with normal glucose tolerance who were followed for 5 years for IGT or diabetes onset in relation to total and regional adiposity (BMI, waist-to-hip ratio [WHR]), fasting and 2-h 75-g oral glucose load glucose and insulin, total and HDL cholesterol, blood pressure, serum uric acid, triglyceride, and leptin levels. RESULTS - A multivariate logistic regression model adjusted for age, sex, ethnicity and diabetes family history showed a significantly higher linear increase in risk of IGT and diabetes in association with the following variables only: lasting glucose (odds ratio 1.89 [95% CI 1.51-2.34]), 2-h glucose (1.68 [1.50-1.88]), WHR (1.30 [1.10-1.52]), BMI (1.04 [1.00-1.08]), and serum uric acid (1.37 [1.20-1.57]). However, a nonlinear increase was seen with serum triglyceride and plasma leptin concentrations. No risk factors resulted in joint effects that were greater than expected from combining individual effects. CONCLUSIONS - Metabolic syndrome features independently predict a higher risk of diabetes or IGT in normoglycemic subjects bur in combination confer no higher-than-expected risk of these outcomes. At higher concentrations of triglycerides and leptin, risk plateaus and even declines slightly. C1 Int Diabet Inst, Melbourne, Vic, Australia. Vet Affairs Puget Sound, Epidemiol Res & Informat Ctr, Seattle, WA USA. Minist Hlth, Port Louis, Mauritius. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Univ Newcastle Upon Tyne, Human Diabet & Metab Res Ctr, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. RP Boyko, EJ (reprint author), Vet Affairs Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-25446] NR 35 TC 62 Z9 69 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2000 VL 23 IS 9 BP 1242 EP 1248 DI 10.2337/diacare.23.9.1242 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 348UT UT WOS:000089005400007 PM 10977013 ER PT J AU Boyko, EJ AF Boyko, EJ TI Proportion of type 2 diabetes cases resulting from impaired fetal growth SO DIABETES CARE LA English DT Article ID THRIFTY PHENOTYPE HYPOTHESIS; BIRTH-WEIGHT; GLUCOSE-TOLERANCE; ATTRIBUTABLE RISK; MEN; MELLITUS; EXPOSURE; DISEASE; POPULATION; ADULTS AB OBJECTIVE - During the past decade, several researchers have demonstrated a higher risk of type 2 diabetes in relation to lower birth weight. This theory, referred to as the "thrifty phenotype'' hypothesis, postulates that impaired fetal growth predisposes individuals to the development of diabetes and other metabolic abnormalities. This article examines the importance of fetal growth in the etiology of diabetes by estimating the proportion of diabetes cases associated with this exposure. RESEARCH DESIGN AND METHODS - The importance of an exposure or its correlate as a potential cause of a disease can be assessed by estimating the proportion of cases that could he prevented if the exposure was eliminated from a defined population. This proportion is referred to as the population-attributable fraction (PAF). Published studies of the association between diabetes and birth weight were reviewed and selected for further analysis if data were presented that enabled PAP calculation. In addition, PAFs were calculated for higher birth weight cutoffs because researchers have postulated that the lowest birth weight category may not capture all cases of fetal growth retardation. Studies have shown that exposure classified in this broader manner can produce unbiased PAP estimates, even if many subjects are falsely classified as exposed. RESULTS - PAFs for the lowest birth weight category ranged from 0.01 to 0.25. In this analysis, PAFs for diabetes did not exceed 0.35. In contrast, >50% of diabetes cases in the First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study were attributable to excess adiposity as reflected by a BMI of greater than or equal to 26 kg/m(2) (PAF >0.50). CONCLUSIONS - Impaired fetal growth or its correlates account for a minority (<0.50) of type 2 diabetes cases. C1 Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Epidemiol Res & Informat Ctr, Seattle, WA USA. RP Boyko, EJ (reprint author), Vet Affairs Med Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK-31170, DK-43134, DK-48152] NR 26 TC 30 Z9 30 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 SEP PY 2000 VL 23 IS 9 BP 1260 EP 1264 DI 10.2337/diacare.23.9.1260 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 348UT UT WOS:000089005400010 PM 10977016 ER PT J AU Snoek, FJ Pouwer, F Welch, GW Polonsky, WH AF Snoek, FJ Pouwer, F Welch, GW Polonsky, WH TI Diabetes-related emotional distress in Dutch and US diabetic patients - Cross-cultural validity of the problem areas in diabetes scale SO DIABETES CARE LA English DT Article ID QUESTIONNAIRE; PREVALENCE; MELLITUS; STRESS; PEOPLE AB OBJECTIVE - To examine the cross-cultural validity of the Problem Areas in Diabetes Scale (PAID) in Dutch and U.S. diabetic patients. RESEARCH DESIGN AND METHODS - A total of 1,472 Dutch people with diabetes completed the PAID along with other self-report measures of affect. Statistics covered Cronbach's or, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA), Pearson's product-moment correlation, and t tests. Psychometric properties of PAID were compared for Dutch and U.S. diabetic patients. RESULTS - Internal consistency of the Dutch PAID was high and stable across sex and type of diabetes. Test-retest reliability was high. Principal component analyses confirmed 1 general 20-item factor, whereas EFA identified 4 new subdimensions: negative emotions, treatment problems, food-related problems, and lack of social support. These dimensions were confirmed with CFA and were replicated in the U.S. sample. The PAID and its subscales demonstrated moderate to high associations in the expected direction with other measures of affect. Dutch and U.S. subjects reported having the same problem areas, with U.S. patients reporting higher emotional distress levels both in type 1 and type 2 diabetes. CONCLUSIONS - The Dutch and U.S. 20-item PAID appeared to be psychometrically equivalent, which allowed for cross-cultural comparisons. C1 Free Univ Amsterdam, Med Ctr, Dept Med Psychol, NL-1081 BT Amsterdam, Netherlands. Joslin Diabet Ctr, Behav Res Sect, Boston, MA 02215 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. RP Snoek, FJ (reprint author), Free Univ Amsterdam, Med Ctr, Dept Med Psychol, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. NR 30 TC 182 Z9 186 U1 3 U2 18 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 2000 VL 23 IS 9 BP 1305 EP 1309 DI 10.2337/diacare.23.9.1305 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 348UT UT WOS:000089005400018 PM 10977023 ER PT J AU Lipsky, BA Berendt, AR AF Lipsky, BA Berendt, AR TI Principles and practice of antibiotic therapy of diabetic foot infections SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Article; Proceedings Paper CT 3rd International Symposium on the Diabetic Foot CY MAY 05-08, 1999 CL NOORDWIJKERHOUT, NETHERLANDS DE foot infections; osteomyelitis; antibiotic therapy; diabetic foot ID CONTROLLED TRIAL; OSTEOMYELITIS; ULCERS; MANAGEMENT; AMPUTATION AB Foot infections are a common and serious problem in diabetic patients. They usually occur as a consequence of a skin ulceration, which initially is colonized with normal flora, and later infected with pathogens. Infection is defined clinically by evidence of inflammation, and appropriate cultures can determine the microbial etiology. Aerobic gram-positive cocci are the most important pathogens; in chronic, complex or previously treated wounds, gram-negative bacilli and anaerobes may join in a polymicrobial infection. In all diabetic foot infections a primary consideration is whether or not surgical intervention is required, e.g. for undrained pus, wound debridement or revascularization. Antibiotic regimens are usually selected empirically initially, then modified if needed based on results of culture and sensitivity tests and the patient's clinical response. Initial therapy especially in serious infections, may need to be broad-spectrum, but definitive therapy can often be more targeted. Severe infections usually require intravenous therapy initially, but milder cases can be treated with oral agents. Treatment duration ranges from 1-2 weeks (for mild soft tissue infection) to more than 6 weeks (for osteomyelitis). The choice of a specific agent should be based on the usual microbiology of these infections, data from published clinical trials, the severity of the patient's infection, and the culture results. Extension of infection into underlying bone can be difficult to diagnose and may require imaging tests, e.g. magnetic resonance scans. Cure of osteomyelitis usually requires resection of infected bone, but can be accomplished with prolonged antibiotic therapy. Various non-antimicrobial adjunct therapies may sometimes be helpful. Published in 2000 by John Wiley & Sons, Ltd. C1 Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Gen Internal Med Clin, Seattle, WA 98108 USA. Univ Oxford, Oxford, England. RP Lipsky, BA (reprint author), Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Gen Internal Med Clin, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 23 TC 51 Z9 51 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1520-7552 J9 DIABETES METAB RES JI Diabetes-Metab. Res. Rev. PD SEP-OCT PY 2000 VL 16 SU 1 BP S42 EP S46 DI 10.1002/1520-7560(200009/10)16:1+<::AID-DMRR109>3.3.CO;2-2 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 369NB UT WOS:000165071300010 PM 11054887 ER PT J AU Guarita, DR Deng, X Huh, YB Wood, PG Reeve, JR Whitcomb, DC AF Guarita, DR Deng, X Huh, YB Wood, PG Reeve, JR Whitcomb, DC TI PYY regulates pancreatic exocrine secretion through multiple receptors in the awake rat SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE gut-brain axis; brain stem; dorsal vagal complex; Y receptor ID DORSAL VAGAL COMPLEX; PEPTIDE YY PYY; NEUROPEPTIDE-Y; RELEASE; DOG; RADIOIMMUNOASSAY; CHOLECYSTOKININ; LOCALIZATION; STIMULATION; INHIBITION AB Peptide YY (PYY) is one of several regulatory peptides reported to modulate pancreatic secretion. PYY circulates in two forms, PYY1-36 and PYY3-36 and binds to multiple receptor subtypes. We sought to determine if PYY1-36 or PYY3-36 regulates neurally mediated pancreatic secretion through the Y1, Y2, and/or Y5 receptor subtypes. Experiments were conducted in awake, surgically recovered rats. In order to determine the effects of the PYYs on basal pancreatic secretion, either PYY1-36, [pro(34)] PYY1-36 (a Y1/Y5 agonist), or PYY3-36 (a Y2/Y5 agonist) were infused for 40 min at doses of 0, 12.5, 25, or 50 pmol/kg/hr while measuring pancreatic juice volume and protein. PYY1-36 increased pancreatic protein secretion at 25 and 50 pmol/kg/hr (P < 0.05) in a dose-dependent manner (P < 0.001, R-2 = 0.990). The Y2/Y5 receptor agonist PYY3-36 significantly inhibited pancreatic juice volume and protein at 12.5 and 25 pmol/kg/hr, but stimulated protein secretion at higher doses (P < 0.001, R-2 = 0.995). The Y1/Y5 agonist,[Pro(34)] PYY1-36, had no significant effect on basal pancreatic exocrine secretion. Therefore, PYY1-36 PYY3-36 and [Pro(34)] PYY1-36 produced different, dose-dependent changes on basal pancreatic exocrine secretion. Inhibition of pancreatic secretion by circulating PYY1-36 and PYY3-36 are primarily mediated by the Y2 receptor. Since [Pro(34)] PYY1-36 did not change pancreatic secretion, it can be concluded that circulating PYY1-36 or PYY3-36 does not modulate pancreatic secretion through the Y1 or Y5 receptors. Since the stimulatory effects of PYY1-36 on pancreatic secretion could not be explained by the actions of PYY3-36 or [Pro(34)] PYY1-36 on Y1 or Y2 receptors, and since PYY1-36 fails to bind to Y3 or Y4 receptors, we also conclude that PYY1-36 may stimulate pancreatic secretion in a dose-dependent mechanism through a PYY receptor subtype different from Y1, Y2, Y3, Y4 or Y5. C1 Univ Pittsburgh, Dept Med, Div Gastroenterol & Hepatol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Pittsburgh Vet Affairs Med Ctr, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Dept Med, Div Gastroenterol & Hepatol, 571 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. FU NIDDK NIH HHS [DK 41301, R01 DK50236, R29 DK45781] NR 33 TC 13 Z9 13 U1 0 U2 2 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 SEP PY 2000 VL 45 IS 9 BP 1696 EP 1702 DI 10.1023/A:1005550732146 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 365TH UT WOS:000089966200002 PM 11052307 ER PT J AU Raitt, DC Posas, F Saito, H AF Raitt, DC Posas, F Saito, H TI Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway SO EMBO JOURNAL LA English DT Article DE Cdc42; MAP kinase; signal transduction; Ste20; stress response ID SACCHAROMYCES-CEREVISIAE GENE; PROTEIN-KINASE; CELL POLARITY; FILAMENTOUS GROWTH; FUNCTIONAL-CHARACTERIZATION; RESPONSE PATHWAY; STE11P MAPKKK; BINDING; HOMOLOG; CASCADE AB The adaptive response to hyperosmotic stress in yeast, termed the high osmolarity glycerol (HOG) response, is mediated by two independent upstream pathways that converge on the Pbs2 MAP kinase kinase (MAPKK), leading to the activation of the Hog1 MAP kinase. One branch is dependent on the Sho1 transmembrane protein,whose primary role was found to be the binding and translocation of the Pbs2 MAPKK to the plasma membrane, and specifically to sites of polarized growth. The yeast PAK homolog Ste20 is essential for the Sho1-dependent activation of the Hog1 MAP kinase in response to severe osmotic stress. This function of Ste20 in the HOG pathway requires binding of the small GTPase Cdc42. Overexpression of Cdc42 partially complements the osmosensitivity of ste20 Delta mutants, perhaps by activating another PAK-like kinase, while a dominant-negative Cdc42 mutant inhibited signaling through the SHO1 branch of the HOG pathway. Since activated Cdc42 translocates Ste20 to sites of polarized growth, the upstream and downstream elements of the HOG pathway are brought together through the membrane targeting function of Sho1 and Cdc42. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Saito, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 FU NIGMS NIH HHS [GM50909, GM56699] NR 46 TC 163 Z9 174 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 2000 VL 19 IS 17 BP 4623 EP 4631 DI 10.1093/emboj/19.17.4623 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353LL UT WOS:000089275600020 PM 10970855 ER PT J AU Powell, CMH Rudge, TL Zhu, Q Johnson, LF Hansen, U AF Powell, CMH Rudge, TL Zhu, Q Johnson, LF Hansen, U TI Inhibition of the mammalian transcription factor LSF induces S-phase-dependent apoptosis by downregulating thymidylate synthase expression SO EMBO JOURNAL LA English DT Article DE apoptosis; cell cycle progression; G(1)-S transition; LSF; thymidylate synthase ID GROWTH-STIMULATED CELLS; COLON-CARCINOMA CELLS; HUMAN CYCLIN-E; THYMINELESS DEATH; DNA-BINDING; FACTOR CP2; GENE-EXPRESSION; 5'-FLANKING REGION; INITIATION SITES; CANCER CELLS AB The thymidylate synthase (TS) gene, which is induced at the G(1)-S transition in growth-stimulated cells, encodes an enzyme that is essential for DNA replication and cell survival. Here we demonstrate that LSF (LBP-1c, CP2) binds to sites within the TS promoter and intronic regions that are required for this induction. Mutation of the LSF binding sites inhibits G(1)-S induction of mRNA derived from a TS minigene, Furthermore, expression of dominant-negative LSF (LSFdn) prevents the increase in TS enzyme levels during G(1)-S, and induces apoptosis in growth-stimulated mouse and human cell lines. Such apoptosis can be prevented either by circumventing the TS requirement through addition of low concentrations of thymidine, or by coexpression of the TS gene driven by a heterologous promoter. Induction of apoptosis by LSFdn parallels the process known as thymineless death, which is induced by the TS inhibitor and chemotherapeutic drug 5-fluorodeoxyuridine. Thus, LSF is a novel regulatory factor that supports progression through S-phase by targeting a single gene that is critical for cell survival. C1 Harvard Univ, Sch Med, Comm Virol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Mol Genet, Boston, MA 02115 USA. Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. RP Hansen, U (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA. FU NCI NIH HHS [P30 CA016058, R01 CA081157, R01 CA081157-05, T32 CA009361, CA81157, CA38038, CA16058] NR 65 TC 48 Z9 50 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 2000 VL 19 IS 17 BP 4665 EP 4675 DI 10.1093/emboj/19.17.4665 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353LL UT WOS:000089275600024 PM 10970859 ER PT J AU Macian, F Garcia-Rodriguez, C Rao, AJN AF Macian, F Garcia-Rodriguez, C Rao, AJN TI Gene expression elicited by NFAT in the presence or absence of cooperative recruitment of Fos and Jun SO EMBO JOURNAL LA English DT Article DE activation-induced cell death; AP-1; cytokine expression; nuclear factor of activated T cells; transcriptional regulation ID ACTIVATED T-CELLS; FACTOR-ALPHA GENE; FAS-LIGAND EXPRESSION; TRANSCRIPTION FACTOR; NUCLEAR-FACTOR; CYCLOSPORINE-A; KAPPA-B; AP-1; DNA; CALCINEURIN AB Cooperation between nuclear factor of activated T cells (NFAT) and AP-1 (Fos-Jun) proteins on composite NFAT-AP-1 DNA elements constitutes a powerful mechanism for signal integration of the calcium and protein kinase C/Ras pathways in the regulation of gene expression. sere we report that NFAT can induce expression of certain genes in T cells without the need for cooperative recruitment of Fos and Jun. Using NFAT1 mutant proteins that are unable to interact with Fos-Jun dimers but are unaffected in DNA binding or transcriptional activity, we show that expression of interleukin (IL)-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, IL-4, MIP1 alpha and Fas ligand mRNAs is absolutely dependent on cooperation between NFAT and Fos-Jun; in contrast, NFAT induces tumor necrosis factor alpha (TNF alpha) mRNA and IL-13 promoter activity without any necessity to recruit Fos and Jun. Furthermore, we show that NFAT-Fos-Jun cooperation is also essential to elicit the NFAT-dependent program of activation-induced cell death. Our results support the hypothesis that even in a single cell type, NFAT activation can evoke two distinct biological programs of gene expression, dependent or independent of NFAT-AP-1 cooperation. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Rao, AJN (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471, R01 CA042471, R37 CA042471] NR 56 TC 195 Z9 198 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 1 PY 2000 VL 19 IS 17 BP 4783 EP 4795 DI 10.1093/emboj/19.17.4783 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 353LL UT WOS:000089275600034 PM 10970869 ER PT J AU Hoare, SRJ Rubin, DA Juppner, H Usdin, TB AF Hoare, SRJ Rubin, DA Juppner, H Usdin, TB TI Evaluating the ligand specificity of zebrafish parathyroid hormone (PTH) receptors: Comparison of PTH, PTH-related protein, and tuberoinfundibular peptide of 39 residues SO ENDOCRINOLOGY LA English DT Article ID SUPRAOPTIC NUCLEUS; FISH; EXPRESSION; IDENTIFICATION; AGONIST; TISSUES; RAT AB Homologs of mammalian PTH1 and PTH2 receptors, and a novel PTH3 receptor have been identified in zebrafish (zPTH1, zPTH2, and zPTH3). zPTH1 receptor ligand specificity is similar to that of mammalian PTH1 receptors. The zPTH2 receptor is selective for PTH over PTH-related protein (PTHrP); however, PTH produces only modest cAMP accumulation. A PTH2 receptor-selective peptide, tuberoinfundibular peptide of 39 residues (TIP39), has recently been purified from bovine hypothalamus. The effect of TIP39 has not previously been examined on zebrafish receptors. The zPTH3 receptor was initially described as PTHrP selective based on comparison with the effects of human PTH. We have now examined the Ligand specificity of the zebrafish PTH-recognizing receptors expressed in COS-7 cells using a wide range of ligands. TIP39 is a potent agonist for stimulation of cAMP accumulation at two putative splice variants of the zPTH2 receptor (EC50, 2.6 and 5.2 nM); in comparison, PTH is a partial agonist [maximal effect (E-max) of PTH peptides ranges from 28-49% of the TIP39 E-max]. As TIP39 is much more efficacious than any known PTH-like peptide, a homolog of TIP39 may be the zPTH2 receptor's endogenous ligand. At the zPTH3 receptor, rat PTH-(1-34) and rat PTH-(1-84) (EC50, 0.22 and 0.45 nM) are more potent than PTHrP (EC50, 1.5 nM), and rPTH-(1-34) binds with high affinity (3.2 nM). PTH has not been isolated from fish. PTHrP-like peptides, which have been identified in fish, may be the natural ligands for zPTH1 and zPTH3 receptors. C1 NIMH, Cell Biol Unit, Genet Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Usdin, TB (reprint author), NIMH, Cell Biol Unit, Genet Lab, NIH, Bldg 36,Room 3D06,36 Convent Dr,MSC4094, Bethesda, MD 20892 USA. EM usdin@codon.nih.gov NR 22 TC 36 Z9 36 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2000 VL 141 IS 9 BP 3080 EP 3086 DI 10.1210/en.141.9.3080 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346LE UT WOS:000088872200007 PM 10965877 ER PT J AU Wang, QF Keutmann, HT Schneyer, AL Sluss, PM AF Wang, QF Keutmann, HT Schneyer, AL Sluss, PM TI Analysis of human follistatin structure: Identification of two discontinuous N-terminal sequences coding for activin A binding and structural consequences of activin binding to native proteins SO ENDOCRINOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX GLYCOPROTEIN; EPIDERMAL-GROWTH-FACTOR; HEPARAN-SULFATE; DISULFIDE-ISOMERASE; PORCINE FOLLISTATIN; SYNTHETIC PEPTIDES; EF-HAND; CELLS; SITE; INHIBITION AB A primary physiological function of follistatin is the binding and neutralization of activin, a transforming growth factor-beta family growth factor, and loss of function mutations are lethal. Despite the critical biological importance of follistatin's neutralization of activin, the structural basis of activin's binding to follistatin is poorly understood. The purposes of these studies were 1) to identify the primary sequence(s) within the N-terminal domain of the follistatin coding for activin binding, and 2) to determine whether activin binding to the native protein causes changes in other structural domains of follistatin. Synthetic peptide mimotopes identified within a 63-residue N-terminal domain two discontinuous sequences capable of binding labeled activin A. The first is located in a region (amino acids 3-26) of follistatin, a site previously identified by directed mutagenesis as important for activin binding. The second epitope, predicted to be located between amino acids 46 and 59, is newly identified. Although the sequences 3-26 and 46-59 code for activin binding, native follistatin only binds activin if disulfide bonding is intact. Furthermore, pyridylethylation of Cys residues followed by N-terminal sequencing and amino acid analysis revealed that all of the Cys residues in follistatin are involved in disulfide bonds and lack reactive free sulfhydryl groups. Specific ligands were used to probe the structural effects of activin binding on the other domains of the full-length molecule, comprised largely of the three 10-Cys follistatin module domains. No effects on ligand binding to follistatin-libe module I or II were observed after the binding of activin A to native protein. In contrast, activin binding diminished recognition of domain III and enhanced that of the C domain by their respective monoclonal antibody probes, indicating an alteration of the antigenic structures of these regions. Thus, subsequent to activin binding, interactions are Likely to occur between regions of follistatin located in different domains and separated by considerable lengths of linear sequence. Such interactions could have important functional significance with respect to the structural heterogeneity of naturally occurring follistatins. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Cooperat Program Infertil Res, Boston, MA 02114 USA. RP Sluss, PM (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Assay Lab, Edwards 003, Boston, MA 02114 USA. EM sluss.patrick@mgh.harvard.edu FU NICHD NIH HHS [HD-29164, P30-HD-28138]; NIDDK NIH HHS [DK-53828] NR 45 TC 31 Z9 33 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2000 VL 141 IS 9 BP 3183 EP 3193 DI 10.1210/en.141.9.3183 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346LE UT WOS:000088872200019 PM 10965889 ER PT J AU Li, QL Jansen, E Brent, GA Naqvi, S Wilber, JF Friedman, TC AF Li, QL Jansen, E Brent, GA Naqvi, S Wilber, JF Friedman, TC TI Interactions between the prohormone convertase 2 promoter and the thyroid hormone receptor SO ENDOCRINOLOGY LA English DT Article ID RETINOID-X-RECEPTOR; VASOACTIVE INTESTINAL PEPTIDE; MESSENGER-RNA EXPRESSION; CAMP RESPONSE ELEMENTS; ANTERIOR-PITUITARY; PROPROTEIN CONVERTASE; NEGATIVE REGULATION; GENE-EXPRESSION; CHROMOSOMAL LOCALIZATION; NEUROENDOCRINE TISSUES AB The majority of prohormones are cleaved at paired basic residues to generate bioactive hormones by prohormone convertases (PCs). As PC1 and PC2, two neuroendocrine-specific PCs, appear to be the key enzymes capable of processing a variety of prohormones, alterations of PC2 and/or PC1 levels will probably have a profound effect on hormonal homeostasis. We investigated the regulation of PC2 messenger RNA (mRNA) by thyroid hormone using GH(3) cells to demonstrate that T-3 negatively regulated PC2 mRNA levels in a dose- and time-dependent fashion. Functional analysis of progressive 5'-deletions of the human (h) PC2 promoter luciferase constructs in GH, cells demonstrated that the regulation probably occurs at the transcriptional level, and that putative negative thyroid hormone response elements were located within the region from -44 to +137 bp relative to the transcriptional start site. Transient transfections in JEG-3 cells and COS-1 cells showed that the suppressive effect of T-3 was equally mediated by the thyroid hormone receptor (TR) isoforms TR alpha 1 and TR beta 1. Electrophoretic mobility shift assays using purified TR alpha 1 and retinoid X receptor-beta protein as well as GH(3) nuclear extracts showed that regions from +51 to +71 bp and from +118 to +137 bp of the hPC2 promoter bind to TR alpha 1 as both a monomer and a homodimer and with TR alpha 1/retinoid X receptor-beta as a heterodimer. Finally, the in vivo regulation of pituitary PC2 mRNA by thyroid status was demonstrated in rats. These results demonstrate that T-3 negatively regulates PC2 expression at the transcriptional level and that functional negative thyroid hormone response elements exist in the hPC2 promoter. We postulate that the alterations of PC2 activity may mediate some of the pathophysiological consequences of hypo- or hyperthyroidism. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Sch Med, Dept Med,Div Endocrinol, Los Angeles, CA 90048 USA. Catholic Univ Louvain, Ctr Human Genet, Mol Oncol Lab, B-3000 Louvain, Belgium. Flanders Interuniv Inst Biotechnol, B-3000 Louvain, Belgium. W Los Angeles Vet Affairs Med Ctr, Dept Med, Div Endocrinol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. Univ Maryland, Dept Med, Div Endocrinol & Metab, Baltimore, MD 21201 USA. RP Univ Calif Los Angeles, Charles R Drew Univ Med & Sci, Div Endocrinol, 1721 E 120th St, Los Angeles, CA 90059 USA. EM friedman@hotmail.com FU NIDA NIH HHS [DA-00276]; NIDDK NIH HHS [DK-287235, DK-43714] NR 87 TC 16 Z9 16 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2000 VL 141 IS 9 BP 3256 EP 3266 DI 10.1210/en.141.9.3256 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346LE UT WOS:000088872200026 PM 10965896 ER PT J AU Uysal, KT Scheja, L Wiesbrock, SM Bonner-Weir, S Hotamisligil, GS AF Uysal, KT Scheja, L Wiesbrock, SM Bonner-Weir, S Hotamisligil, GS TI Improved glucose and lipid metabolism in genetically obese mice lacking aP2 SO ENDOCRINOLOGY LA English DT Article ID FREE FATTY-ACIDS; TYPE-2 DIABETES-MELLITUS; INSULIN-SECRETION; BINDING PROTEIN; PLASMA-GLUCOSE; UNITED-STATES; RESISTANCE; TISSUE; NIDDM; GENE AB Adipocyte fatty acid-binding protein, aP2, is a member of the intracellular fatty acid binding protein family. Previously, studies have shown increased insulin sensitivity in aP2-deficient mice with dietary obesity. Here, we asked whether aP2-related alterations in lipolytic response and insulin production are features of obesity-induced insulin resistance and investigated the effects of aP2-deficiency on glucose homeostasis and lipid metabolism in ob/ob mice, a model of extreme obesity. ob/ob mice homozygous for the aP2 null allele (ob/ ob-aP2(-/-)) became more obese than ob/ob mice as indicated by significantly increased body weight and fat pad size but unaltered body length. However, despite their extreme adiposity, ob/ob-aP2(-/-) animals were more insulin-sensitive compared with ob/ob controls, as demonstrated by significantly lower plasma glucose and insulin levels and better performance in both insulin and glucose tolerance tests. These animals also showed improvements in dyslipidemia and had lower plasma triglyceride and cholesterol levels. Lipolytic response to beta-adrenergic stimulation and lipolysis-associated insulin secretion was significantly reduced in ob/ob-aP2(-/-) mice. Interestingly, glucose-stimulated insulin secretion, while virtually abolished in ob/ob controls, was significantly improved in ob/ob-aP2(-/-) animals. There were no apparent morphological differences in the structure or size of the pancreatic islets between genotypes. Taken together, the data indicate that in obesity, aP2-deficiency not only improves peripheral insulin resistance but also preserves pancreatic beta cell function and has beneficial effects on Lipid metabolism. C1 Harvard Univ, Sch Publ Hlth, Div Biol Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Hotamisligil, GS (reprint author), Harvard Univ, Sch Publ Hlth, Div Biol Sci, 665 Huntington Ave, Boston, MA 02115 USA. EM ghotamis@hosp.harvard.edu NR 41 TC 182 Z9 208 U1 1 U2 9 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 2000 VL 141 IS 9 BP 3388 EP 3396 DI 10.1210/en.141.9.3388 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346LE UT WOS:000088872200041 PM 10965911 ER PT J AU Bastepe, M Juppner, H AF Bastepe, M Juppner, H TI Pseudohypoparathyroidism - New insights into an old disease SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID ALBRIGHT-HEREDITARY-OSTEODYSTROPHY; NUCLEOTIDE-BINDING PROTEIN; DISTAL IMPRINTING REGION; HORMONE-RELATED PEPTIDE; STIMULATORY G-PROTEIN; PARATHYROID-HORMONE; ALPHA-SUBUNIT; BLOMSTRAND-CHONDRODYSPLASIA; ADENYLATE-CYCLASE; RECEPTOR GENE AB The complex GNAS1 gene (chromosome 20q13.3) encodes the stimulatory G protein (Gs-alpha) and at least three additional, alternatively spliced transcripts, XLas, NESP55, and AS, which are derived either from the paternal or the maternal allele, or from both. Pseudohypoparathyroidism type Ia (PHP-Ia) and pseudopseudohypoparathyroidism (pPHP) are caused by heterozygous mutations in the coding exons of GNAS1, but the endocrine abnormalities occur only if the genetic defect is inherited from an obligate female carrier. Recent linkage studies have shown that the genetic defect responsible for pseudohypoparathyroidism type Ib (PHP-Ib) maps also to the GNAS1 locus and that this disorder is paternally imprinted just as PHP-Ia/pPHP. It therefore appears likely that mutations in distinct regions of the GNAS1 gene are the cause of at least three different forms of PHP. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Mass Gen Hosp Children, Boston, MA USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Wellman 5, Boston, MA 02114 USA. NR 88 TC 34 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2000 VL 29 IS 3 BP 569 EP + DI 10.1016/S0889-8529(05)70151-1 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358QT UT WOS:000089553900008 PM 11033761 ER PT J AU Thomas, MK Demay, MB AF Thomas, MK Demay, MB TI Vitamin D deficiency and disorders of vitamin D metabolism SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID D-DEPENDENT RICKETS; END-ORGAN RESISTANCE; D-BINDING-PROTEIN; MINERAL ION HOMEOSTASIS; RECEPTOR-ABLATED MICE; HEREDITARY RESISTANCE; POSTMENOPAUSAL WOMEN; PROSTATE-CANCER; 1-ALPHA-HYDROXYLASE GENE; CALCIUM INFUSIONS AB The disorders of vitamin D metabolism are inherited metabolic abnormalities involving mutations of the vitamin D receptor or enzymes involved in the metabolism of vitamin D to its biologically active form 1,25-dihydroxyvitamin D. Although these mutations are rare, studies in affected patients and animal models have helped to identify critical actions of vitamin D and the mechanism by which it exerts its effects. Vitamin D deficiency, however, is an increasingly recognized problem among the elderly and in the general population. Screening for vitamin D deficiency only in those patients with known risk factors will result in a large proportion of unrecognized affected patients. C1 Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Mol Endocrinol Lab, Boston, MA USA. Harvard Univ, Sch Med, Endocrine Unit, Boston, MA USA. RP Demay, MB (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Dept Med, Wellman 501,50 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 46974, DK02476] NR 101 TC 54 Z9 55 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD SEP PY 2000 VL 29 IS 3 BP 611 EP + DI 10.1016/S0889-8529(05)70153-5 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 358QT UT WOS:000089553900010 PM 11033763 ER PT J AU DeGiorgio, CM Schachter, SC Handforth, A Salinsky, M Thompson, J Uthman, B Reed, R Collins, S Tecoma, E Morris, GL Vaughn, B Naritoku, DK Henry, T Labar, D Gilmartin, R Labiner, D Osorio, I Ristanovic, R Jones, J Murphy, J Ney, G Wheless, J Lewis, P Heck, C AF DeGiorgio, CM Schachter, SC Handforth, A Salinsky, M Thompson, J Uthman, B Reed, R Collins, S Tecoma, E Morris, GL Vaughn, B Naritoku, DK Henry, T Labar, D Gilmartin, R Labiner, D Osorio, I Ristanovic, R Jones, J Murphy, J Ney, G Wheless, J Lewis, P Heck, C TI Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures SO EPILEPSIA LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the American-Academy-of-Neurology CY APR 17-24, 1999 CL TORONTO, CANADA SP Amer Acad Neurol DE vagus nerve stimulation; intractable epilepsy ID VAGAL-STIMULATION; EPILEPSY; TRIAL AB Purpose: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. Methods: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. Results: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. Conclusions: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures. C1 Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. USC, Dept Neurol, Houston, TX USA. Synergos Consultants Biomed Res, Houston, TX USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ N Carolina, Chapel Hill, NC USA. DVA, Gainesville, FL USA. Univ Florida, Gainesville, FL USA. So Illinois Univ, Springfield, IL USA. UC San Diego, La Jolla, CA USA. Emory Univ, Atlanta, GA 30322 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Res Inst Kansas, Wichita, KS USA. Cornell Univ, New York, NY USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Kansas, Kansas City, KS USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Arizona, Tucson, AZ USA. Univ Wisconsin, Madison, WI USA. Childrens Mercy Hosp, Kansas City, KS USA. Long Isl Jewish Hosp, New Hyde Park, NY USA. Univ Texas, Houston, TX USA. W Los Angeles VA, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP DeGiorgio, CM (reprint author), Olive View UCLA Med Ctr, 14445 Olive View Dr, Sylmar, CA 91342 USA. OI Henry, Thomas/0000-0002-5708-903X NR 17 TC 243 Z9 248 U1 3 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD SEP PY 2000 VL 41 IS 9 BP 1195 EP 1200 DI 10.1111/j.1528-1157.2000.tb00325.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 350YA UT WOS:000089128200014 PM 10999559 ER PT J AU Rohde, LA Biederman, J Zimmermann, H Schmitz, M Martins, S Tramontina, S AF Rohde, LA Biederman, J Zimmermann, H Schmitz, M Martins, S Tramontina, S TI Exploring ADHD age-of-onset criterion in Brazilian adolescents SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY LA English DT Article DE attention deficit hyperactivity disorder; hyperkinetic disorders, inattention; hyperactivity ID DEFICIT HYPERACTIVITY DISORDER; CHILD-BEHAVIOR CHECKLIST; GLOBAL ASSESSMENT SCALE; IV FIELD TRIALS; EMPIRICAL-EVALUATION; ATTENTION; DEFINITION; SAMPLE AB Objective: To explore age-of-onset criterion for the diagnosis of attention-deficit hyperactivity disorder (ADHD) in a school sample of young Brazilian adolescents. Methods: 191 students aged 12 to 14 years were evaluated using DSM-IV ADHD criteria, measures of ADHD symptoms and global impairment. Results: Both adolescents with ADHD (n = 30) and adolescents who fulfilled all DSM-IV ADHD criteria, except age of onset of impairment criterion (ADHD w/o age-of-onset, n = 27) had significantly higher scores on Attention Problems, Delinquent and Aggressive Behavior scales of the Child Behavior Checklist (CBCL) and lower scores on the Child Global Assessment scale (CGAS) than non-ADHD adolescents (n = 134). Adolescents with ADHD and youths with ADHD w/o age-of-onset did not differ significantly in any measure assessed. Conclusion: These results concur with recent literature proposing revision of the age-of-onset criterion for the diagnosis of ADHD. C1 Hosp Clin Porto Alegre, Serv Psiquiat Infancia & Adolescencia, BR-90035003 Porto Alegre, RS, Brazil. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Rohde, LA (reprint author), Hosp Clin Porto Alegre, Serv Psiquiat Infancia & Adolescencia, Rua Ramiro Barcellos 2350, BR-90035003 Porto Alegre, RS, Brazil. RI Rohde, Luis Augusto/A-6426-2008 OI Rohde, Luis Augusto/0000-0002-4552-4188 NR 31 TC 35 Z9 40 U1 3 U2 7 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 1018-8827 J9 EUR CHILD ADOLES PSY JI Eur. Child Adolesc. Psych. PD SEP PY 2000 VL 9 IS 3 BP 212 EP 218 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 366NP UT WOS:000090011700008 PM 11095044 ER PT J AU Shomali, ME Hussain, MA AF Shomali, ME Hussain, MA TI Cushing's syndrome: from patients to proteins SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID IN-VIVO; MICE; 7B2; MATURATION; ACTIVATION; PITUITARY; RECEPTORS; MECHANISM; DISEASE; PROPC2 C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Shomali, ME (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [R01 DK081472, DK10001-01] NR 17 TC 3 Z9 3 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA 16 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD SEP PY 2000 VL 143 IS 3 BP 313 EP 315 DI 10.1530/eje.0.1430313 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 356HK UT WOS:000089437700002 PM 11022170 ER PT J AU Yu, B Gauthier, L Hausmann, DHF Wucherpfennig, KW AF Yu, B Gauthier, L Hausmann, DHF Wucherpfennig, KW TI Binding of conserved islet peptides by human and murine MHC class II molecules associated with susceptibility to type I diabetes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE autoimmunity; diabetes; MHC; autoantigen; antigen presentation ID GLUTAMIC-ACID DECARBOXYLASE; T-CELL EPITOPE; HIGH-AFFINITY; NOD MICE; INSULIN; MELLITUS; PROTEIN; COMPLEXES; IDENTIFICATION; TOLERANCE AB The major histocompatibility complex (MHC) is the most important susceptibility locus for type I diabetes in humans and NOD mice. NOD mice express a single MHC class II molecule (I-A(g7)) which carries a unique beta chain sequence. In humans, DQ alleles that encode DQ8 and DQ2 confer the highest risk for the disease. Soluble DQ8 and I-A(g7) were used to directly compare the binding specificity of these MHC molecules. Peptides from three islet antigens - insulin, GAD 65 and HSP 60 - bound to both CQ8 and I-A(g7). These peptides included epitopes that are immunodominant in NOD mice, namely insulin (9-23), GAD (206-220) and HSP 60 (441-460). All of these peptide sequences are highly conserved between the human and murine antigens. The binding specificity of DQ8 and I-A(g7) was similar, but not identical, since two peptides eluted from splenocytes of NOD mice did not bind to DQ8. DQ8 formed long-lived complexes with the majority of these peptides, indicating that DQ8 is not a poor peptide binder. These results demonstrate functional similarities between human and murine MHC class II molecules that confer susceptibility to type I diabetes. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI 39619] NR 30 TC 49 Z9 50 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2000 VL 30 IS 9 BP 2497 EP 2506 DI 10.1002/1521-4141(200009)30:9<2497::AID-IMMU2497>3.0.CO;2-J PG 10 WC Immunology SC Immunology GA 352NB UT WOS:000089223800008 PM 11009082 ER PT J AU Weiss, T Miltner, WHR Huonker, R Friedel, R Schmidt, I Taub, E AF Weiss, T Miltner, WHR Huonker, R Friedel, R Schmidt, I Taub, E TI Rapid functional plasticity of the somatosensory cortex after finger amputation SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE phantom limb; cortical reorganization; magnetoencephalography; somatosensory evoked magnetic fields (SEF) ID PHANTOM-LIMB PAIN; CORTICAL REORGANIZATION; DIGIT DENERVATION; MACAQUE MONKEYS; IMMEDIATE; INJURY; HUMANS; NERVE; MAPS; REPRESENTATION AB Recent research indicates that areas of the primary somatosensory (SI) and primary motor cortex show massive cortical reorganization after amputation of the upper arm, forearm or fingers. Most of these studies were carried out months or several years after amputation. In the present study, we describe cortical reorganization of areas in the SI of a patient who underwent amputation of the traumatized middle and ring fingers of his right hand 10 days before cortical magnetic source imaging data were obtained. Somatosensory-evoked;ed magnetic fields (SEF) to mechanical stimuli to the finger tips were recorded and single moving dipoles were calculated using a realistic volume conductor model. Results reveal that the dipoles representing the second and fifth fingers of the affected hand were closer together than the comparable dipoles of the unaffected hand. Our findings demonstrate that neural cell assemblies in SI which formerly represented the right middle and ring fingers of this amputee became reorganized and invaded by neighbouring cell assemblies of the index and little finger of the same hand. These results indicate that functional plasticity occurs within a period of 10 days after amputation. C1 Univ Jena, Dept Biol & Clin Psychol, D-07743 Jena, Germany. Univ Jena, Ctr Biomat, D-077401 Jena, Germany. Univ Jena, Dept Surg, D-07740 Jena, Germany. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Phys Med & Rehabil Serv, Birmingham, AL 35233 USA. RP Miltner, WHR (reprint author), Univ Jena, Dept Biol & Clin Psychol, Steiger 3,Haus 1, D-07743 Jena, Germany. EM miltner@biopsy.uni-jena.de NR 38 TC 60 Z9 64 U1 7 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD SEP PY 2000 VL 134 IS 2 BP 199 EP 203 DI 10.1007/s002210000456 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 354PV UT WOS:000089339600007 PM 11037286 ER PT J AU Zainal, TA Oberley, TD Allison, DB Szweda, LI Weindruch, R AF Zainal, TA Oberley, TD Allison, DB Szweda, LI Weindruch, R TI Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle SO FASEB JOURNAL LA English DT Article DE aging; free radicals; immunogold; lipid peroxidation; reactive oxygen species; sarcopenia ID PROTEIN-TURNOVER; DIETARY RESTRICTION; SARCOPLASMIC-RETICULUM; TYROSINE NITRATION; SERCA2A ISOFORM; NITRIC-OXIDE; CA-ATPASE; RAT; GROWTH; ANTIOXIDANT AB In laboratory rodents, caloric restriction (CR) retards several age-dependent physiological and biochemical changes in skeletal muscle, including increased steady-state levels of oxidative damage to lipids, DNA, and proteins. We used immunogold electron microscopic (EM) techniques with antibodies raised against 4-hydroxy-2-nonenal (HNE) -modified proteins, dinitrophenol, and nitrotyrosine to quantify and localize the age-dependent accrual of oxidative damage in rhesus monkey vastus lateralis skeletal muscle, Using immunogold EM analysis of muscle from rhesus monkeys ranging in age from 2 to 34 years old, a fourfold maximal increase in levels of HNE-modified proteins was observed. Likewise, carbonyl levels increased twofold with aging, Comparing 17- to 23-year-old normally fed to age-matched monkeys subjected to CR for 10 years, levels of HNE-modified proteins, carbonyls, and nitrotyrosine in skeletal muscle from the CR group were significantly less than control group values. Oxidative damage largely localized to myofibrils, with lesser labeling in other subcellular compartments. Accumulation of lipid peroxidation-derived aldehydes, such as malondialdehyde and 4-hydroxy-2-alkenals, and protein carbonyls were measured biochemically and confirmed the morphological data. Our study is the first to quantify morphologically and localize the age-dependent accrual of oxidative damage in mammalian skeletal muscle and to demonstrate that oxidative damage in primates is lowered by CR. C1 William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, Madison, WI 53705 USA. William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53705 USA. Univ Wisconsin, Dept Lab Med & Pathol, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53705 USA. Columbia Univ Coll Phys & Surg, St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10032 USA. Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA. RP Oberley, TD (reprint author), William S Middleton Mem Vet Hosp, Pathol & Lab Med Serv, 2500 Overlook Terrace,Room A35, Madison, WI 53705 USA. OI Allison, David/0000-0003-3566-9399 NR 56 TC 131 Z9 141 U1 2 U2 8 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 SEP PY 2000 VL 14 IS 12 BP 1825 EP 1836 DI 10.1096/fj.99-0881com PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 352JU UT WOS:000089212400022 PM 10973932 ER PT J AU Pfutzer, RH Barmada, MM Brunskill, APJ Finch, R Hart, PS Neoptolemos, J Furey, WF Whitcomb, DC AF Pfutzer, RH Barmada, MM Brunskill, APJ Finch, R Hart, PS Neoptolemos, J Furey, WF Whitcomb, DC TI SPINK1/PSTI polymorphisms act as disease modifiers in familial and idiopathic chronic pancreatitis SO GASTROENTEROLOGY LA English DT Article ID SECRETORY TRYPSIN-INHIBITOR; CYSTIC-FIBROSIS GENE; HEREDITARY PANCREATITIS; 3-DIMENSIONAL STRUCTURE; LINKAGE ANALYSIS; KAZAL-TYPE; MUTATIONS AB Background & Aims: Gain-of-function trypsin mutations cause acute pancreatitis and chronic pancreatitis. Loss of trypsin inhibitor function may have similar effects. We investigated the prevalence of SPINK1 (PSTI) mutations in familial pancreatitis, idiopathic chronic pancreatitis, and controls. Methods: Genetic-linkage studies were performed in 5 familiar pancreatitis families. The entire SPINK1 gene was sequenced in 112 affected individuals and 95 control DNA samples, and exon 3 was sequenced in 95 additional controls. X-ray crystallography- based model building and statistical studies were performed. Results: Significant linkage between pancreatitis and 5q31.1-2 was excluded. Novel SPINK1 mutations, one D50E mutation, one IVS3+125 C>A, and five IVS3+184 T>A intronic polymorphisms were identified. The N34S and P55S mutations were observed in 29 of 112 patients (25%) as N34S/N34S (n = 7), N34S/wt (n = 19), N34S/P55S (n = 2), and N34S/D50E (n = 1). Three hundred eighty control alleles revealed 3 N34S (0.77%), 2 P55S (0.53%), and no D50E mutations. Age of disease onset and severity were similar between homozygous and heterozygous patients. Structural modeling revealed several possible pathophysiologic mechanisms for the N34S mutation. Conclusions: SPINK1 mutations are common in the population (similar to 2%), but are clearly associated with pancreatitis. The mutation-associated risk is low. Modeling and familial clustering suggest that SPINK1 mutations are disease modifying, possibly by lowering the threshold for pancreatitis from other genetic or environmental factors, but by themselves do not cause disease. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Ctr Genom Sci, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Biocrystallog Lab, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Div Gastroenterol, Pittsburgh, PA USA. Univ Liverpool, Dept Surg, Liverpool L69 3BX, Merseyside, England. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Dept Med, 930 Scaife Hall, Pittsburgh, PA 15260 USA. RI Neoptolemos, John/G-4488-2010; OI Barmada, M Michael/0000-0002-3604-6460 FU NIDDK NIH HHS [DK54709] NR 42 TC 307 Z9 312 U1 1 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2000 VL 119 IS 3 BP 615 EP 623 DI 10.1053/gast.2000.18017 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000007 PM 10982753 ER PT J AU Gralnek, IM Hays, RD Kilbourne, A Naliboff, B Mayer, EA AF Gralnek, IM Hays, RD Kilbourne, A Naliboff, B Mayer, EA TI The impact of irritable bowel syndrome on health-related quality of life SO GASTROENTEROLOGY LA English DT Article ID OF-LIFE; CLINICAL-TRIALS; UNITED-STATES; PATIENT OUTCOMES; MEDICAL OUTCOMES; SURVEY SF-36; DISEASE; INSTRUMENT; DISORDERS; SYMPTOMS AB Background & Aims: Few data are available to evaluate health-related quality of life (HRQOL) of people with irritable bower syndrome (IBS), We evaluated and compared the impact of IBS on HRQOL using previously reported HRQOL data for the U.S. general population and for people with selected chronic diseases. Methods: Using the SF-36 Health Survey, we compared the HRQOL of IBS patients (n = 877) with previously reported SF-36 data for the general U.S. population and for patients with gastroesophageal reflux disease (GERD), diabetes mellitus, depression, and dialysis-dependent end-stage renal disease (ESRD). Results: On all 8 SF-36 scales, IBS patients had significantly worse HRQOL than the U.S. general population (P < 0.001). Compared with GERD patients, IBS patients scored significantly lower on all SF-36 scales (P < 0.001) except physical functioning. Similarly, IBS patients had significantly worse HRQOL on selected SF-36 scales than patients with diabetes mellitus and ESRD. IBS patients had significantly better mental health SF-36 scale scores than patients with depression (P < 0.001), Conclusions: IBS patients experience significant impairment in HRQOL. Decrements in HRQOL are most pronounced in energy/fatigue, role limitations caused by physical health problems, bodily pain, and general health perceptions. These data offer further insight into the impact of IBS on patient functional status and well-being. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Gen Internal Med Hlth Serv Res, Los Angeles, CA 90024 USA. CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Study Digest Hlth Care Qual & Outcomes, Los Angeles, CA USA. RAND, Santa Monica, CA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Calif Los Angeles, Neuroenter Dis Program, Los Angeles, CA USA. RP Gralnek, IM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,CURE Bldg 115,Room 318, Los Angeles, CA 90073 USA. RI Hays, Ronald/D-5629-2013 NR 44 TC 330 Z9 345 U1 5 U2 18 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2000 VL 119 IS 3 BP 654 EP 660 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000012 PM 10982758 ER PT J AU Beck, PL Xavier, R Lu, NF Nanda, NN Dinauer, M Podolsky, DK Seed, B AF Beck, PL Xavier, R Lu, NF Nanda, NN Dinauer, M Podolsky, DK Seed, B TI Mechanisms of NSAID-induced gastrointestinal injury defined using mutant mice SO GASTROENTEROLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; NEUTROPHIL-DEPENDENT PROCESS; GASTRIC-MUCOSAL INJURY; LEUKOCYTE ADHESION; T-CELLS; ASPIRIN; RATS; EXPRESSION; ULCERATION; DISEASE AB Background & Aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used agents that have a high incidence of gastrointestinal side effects resulting in significant morbidity and mortality. Leukocytes have been implicated in NSAID-induced injury, but the mechanisms are unclear. We established a murine model of NSAID-induced gastrointestinal damage to assess the roles of candidate gene products in the pathogenesis of this injury. Methods: Indomethacin-induced gastrointestinal injury was assessed in wild-type and several mutant murine lines, Leukocyte involvement was assessed by neutrophil depletion, impairment of recruitment (resulting from targeted disruption of fucosyltransferase VII [FTVII]), and the absence of mature T and B cells with the use of Rag 2(-/-) mice. Activation and oxygen free radicals were assessed using gp91(phox-/-) mice that exhibit normal leukocyte recruitment but are deficient in myeloid cell activation and oxygen free radical generation, Results: impairment of leukocyte recruitment (FTVII/(-)) and neutrophil depletion resulted in more than a 50% reduction in NSAID-induced injury. However, mice deficient in mature T and B cells had NSAID-induced damage comparable to control mice. Leukocyte activation was required for NSAID-induced damage because the gp91(phox-/-) mice were less susceptible to NSAID injury than wild-type mice. Conclusions: In this murine model system, FTVII-dependent leukocyte recruitment, leukocyte activation via gp91(phox), and neutrophils are required for NSAID-induced gastrointestinal injury, whereas T and B cells are not essential. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Indiana Univ, James Whitcomb Riley Hosp Children, Med Ctr, Herman B Well Ctr Pediat Res,Dept Pediat, Indianapolis, IN 46223 USA. Indiana Univ, James Whitcomb Riley Hosp Children, Med Ctr, Dept Med & Mol Genet, Indianapolis, IN 46223 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NIAID NIH HHS [AI27849]; NIDDK NIH HHS [DK-43351, DK-46906] NR 37 TC 57 Z9 60 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2000 VL 119 IS 3 BP 699 EP 705 DI 10.1053/gast.2000.16497 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000018 PM 10982764 ER PT J AU De Jong, YP Comiskey, M Kalled, SL Mizoguchi, E Flavell, RA Bhan, AK Terhorst, C AF De Jong, YP Comiskey, M Kalled, SL Mizoguchi, E Flavell, RA Bhan, AK Terhorst, C TI Chronic murine colitis is dependent on the CD154/CD40 pathway and can be attenuated by anti-CD154 administration SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD40 LIGAND; IN-VIVO; IMMUNODEFICIENT MICE; SCID MICE; INDUCTION; ACTIVATION AB Background & Aims: Experimental colitis in most animal models is caused by dysregulation of T lymphocytes that display a T helper 1 (Th1) phenotype, CD154 (CD40L/gp39), a member of the tumor necrosis factor (TNF) family, is up-regulated on T cells on activation and has been shown to play a key role in the induction of a Th1 response. We investigated whether chronic experimental colitis is dependent on the CD154/CD40 pathway and whether disease can be prevented by anti-CD154 antibody treatment, Methods: Two models of chronic colitis were used: CD45Rb(hi) cell transfer into recombination activation gene-deficient (Rag(-/-)) mice and bone marrow transplant of tg epsilon 26 animals, In both models, mice were reconstituted with cells from CD154-deficient animals. In another series of experiments, wildtype CD45Rb(hi) T cell-reconstituted recipients were treated with anti-CD154, either from the start of the experiment or after onset of disease, Results: T cells deficient in CD154 induced a milder clinical disease, less weight loss, and fewer histologic signs of colitis than wild-type cells. The level of interleukin 12 in the serum of CD154-deficient T-cell recipients was 5-fold less than that of wild-type cell recipients. Nevertheless, no signs of deviation from a Th1 phenotype were observed, Treatment with anti-CD154 antibodies substantially impaired disease development, even when started after the onset of colitis, Conclusions: The CD154/CD40 pathway plays a critical role in Th1-induced chronic experimental colitis, Blocking CD154, even after the onset of disease, ameliorates colitis but does not induce a T helper 2 (Th2) phenotype. C1 Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Biogen Inc, Dept Inflammat, Cambridge, MA USA. Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06510 USA. RP Terhorst, C (reprint author), Beth Israel Deaconess Med Ctr, Div Immunol, 330 Brookline Ave,RE-204, Boston, MA 02215 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NIDDK NIH HHS [DK43351, DK47677, DK52510] NR 46 TC 73 Z9 73 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2000 VL 119 IS 3 BP 715 EP 723 DI 10.1053/gast.2000.16485 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000020 PM 10982766 ER PT J AU Chen, D Zhao, CM Dockray, GJ Varro, A Van Hoek, A Sinclair, NF Wang, TC Koh, TJ AF Chen, D Zhao, CM Dockray, GJ Varro, A Van Hoek, A Sinclair, NF Wang, TC Koh, TJ TI Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin-deficient mice SO GASTROENTEROLOGY LA English DT Article ID ENTEROCHROMAFFIN-LIKE CELLS; RAT STOMACH; ALPHA-FLUOROMETHYLHISTIDINE; COLONIC PROLIFERATION; BIOLOGICAL-ACTIVITY; TRANSGENIC MICE; PROGASTRIN; HISTAMINE; DEPLETION; RECEPTOR AB Background & Aims: Studies in gastrin-deficient mice have demonstrated critical roles for gastrin peptides in the regulation of gastric acid secretion, but the relative contributions of amidated (G-17) and glycine-extended (G17-Gly) gastrin remain unclear, We examined the effects of these 2 forms of gastrin on acid secretion in gastrin-deficient mice. Methods: Sixty gastrin-deficient mice received infusions of saline, or 1, 6, or 14 days of amidated gastrin 17 (G-17), G17-Gly, or both G-17 and G17-Gly at 10 nmol.kg(-1).h(-1). Twenty-four gastrin-deficient mice were then infused for 14 days with 1, 2, or 5 nmol.kg(-1).h(-1) of G-17 or G-17 and G17-Gly. Add secretion was determined 4 hours after pyloric ligation, and gastric tissue was processed for histology, immunohistochemistry, and electron microscopy. Results: Infusion of G-17 increased acid secretion in a dose-dependent manner with a peak at 5 nmol.kg(-1).h(-1) and a subsequent decrease in acid secretion at higher doses. Infusion of G17-Gly alone had no effect on acid secretion, but coinfusion with G-17 resulted in significantly higher levels of acid secretion at all doses examined than infusion with G-17 alone. The potentiating effect of G17-Gly on G-17-induced acid secretion was associated with increased parietal cell activation but was independent of changes in parietal and enterochromaffin-like cell number, fundic proliferation rates, and H+,K+-adenine triphosphatase expression. G17-Gly also prevented the formation of vacuolar canaliculi and lipofuscin bodies in the parietal cells induced by G-17. Conclusions: G17-Gly appears to synergize with G-17 to up-regulate acid secretion and prevent parietal cell degradation. These results suggest that G17-Gly plays an important role in parietal cell function. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Univ Liverpool, Physiol Lab, Liverpool, Merseyside, England. Univ Trondheim Hosp, Dept Surg & Lab Med, Trondheim, Norway. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Jackson 724, Boston, MA 02114 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NIDDK NIH HHS [K08 DK02545-01, R01 DK 52778, R01 DK55864] NR 40 TC 52 Z9 52 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 SEP PY 2000 VL 119 IS 3 BP 756 EP 765 DI 10.1053/gast.2000.16480 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000024 PM 10982770 ER PT J AU Mashimo, H Kjellin, A Goyal, RK AF Mashimo, H Kjellin, A Goyal, RK TI Gastric stasis in neuronal nitric oxide synthase-deficient knockout mice SO GASTROENTEROLOGY LA English DT Article ID ENTERIC INHIBITORY NEUROTRANSMISSION; INTERSTITIAL-CELLS; SMALL-INTESTINE; LIQUID MEAL; RATS; MOTILITY; HUMANS; CAJAL; CONTRACTILITY; MEDIATORS AB Background & Aims: Nitric oxide (NO) is a major inhibitory neurotransmitter in the gut. This study aimed to identify the effect of chronic deprivation of NO derived from neuronal (nNOS) or endothelial (eNOS) nitric oxide synthase on gastric emptying. Methods: nNOS-deficient (knockout) mice were compared with wild-type mice for gastric size, fluoroscopic appearance after gavage of contrast, and histology of the pyloric sphincter. Wild-type mice treated with the NOS inhibitor N-omega-nitro L-arginine (L-NA) and eNOS-deficient mice were also compared with wild-type and nNOS-deficient mice for liquid and solid gastric emptying, Results: nNOS-deficient mice showed gastric dilation. Fluoroscopy showed delayed gastric emptying of radiologic contrast. There was no marked localized hypertrophy or luminal narrowing at the pyloric sphincter by histology of relaxed wild-type, nNOS-deficient, and eNOS-deficient tissues. Gastric emptying of both solids (28% +/- 27%) and liquids (22% +/- 18%) was significantly delayed in nNOS-deficient mice compared with control wild-type mice (82% +/- 22% for solids; 48% +/- 17% for liquids). eNOS-deficient mice showed no significant difference from wild-type mice (74% +/- 28% for solids; 47% +/- 23% for liquids). Wildtype mice treated acutely with L-NA showed delay in emptying of solids (43% +/- 31%) but not liquids (39% +/- 15%). Conclusions: Chronic depletion of NO from nNOS, but not eNOS, results in delayed gastric emptying of solids and liquids. C1 W Roxbury Vet Affairs Med Ctr, Res & Dev Serv 151, W Roxbury, MA 02132 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Karolinska Inst, Stockholm, Sweden. RP Mashimo, H (reprint author), W Roxbury Vet Affairs Med Ctr, Res & Dev Serv 151, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NIDDK NIH HHS [DK 31092, K08-DK02462] NR 42 TC 98 Z9 100 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2000 VL 119 IS 3 BP 766 EP 773 DI 10.1053/gast.2000.16509 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000025 PM 10982771 ER PT J AU Chung, DC AF Chung, DC TI The genetic basis of colorectal cancer: Insights into critical pathways of tumorigenesis SO GASTROENTEROLOGY LA English DT Review ID GROWTH-FACTOR-BETA; FAMILIAL ADENOMATOUS POLYPOSIS; TUMOR-SUPPRESSOR PROTEIN; II RECEPTOR GENE; MICROSATELLITE MUTATOR PHENOTYPE; HUMAN COLON-CANCER; MISMATCH-REPAIR; APC GENE; PPAR-GAMMA; FRAMESHIFT MUTATIONS C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. NR 125 TC 260 Z9 269 U1 2 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD SEP PY 2000 VL 119 IS 3 BP 854 EP 865 DI 10.1053/gast.2000.16507 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000034 PM 10982779 ER PT J AU Leder, BZ Kronenberg, HM AF Leder, BZ Kronenberg, HM TI Gastroenterologists and choosing the right bisphosphonate SO GASTROENTEROLOGY LA English DT Editorial Material ID INFLAMMATORY BOWEL-DISEASE; BONE-MINERAL DENSITY; IN-VITRO; POSTMENOPAUSAL OSTEOPOROSIS; HORMONE REPLACEMENT; ALENDRONATE; FRACTURES; WOMEN; SUPPLEMENTATION; PREVENTION C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, 32 Fruit St, Boston, MA 02114 USA. NR 28 TC 32 Z9 32 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 SEP PY 2000 VL 119 IS 3 BP 866 EP 869 DI 10.1053/gast.2000.17841 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 350ED UT WOS:000089087000035 PM 10982780 ER PT J AU Smith, JS Tachibana, I Lee, HK Qian, JQ Pohl, U Mohrenweiser, HW Borell, TJ Hosek, SM Soderberg, CL von Deimling, A Perry, A Scheithauer, BW Louis, DN Jenkins, RB AF Smith, JS Tachibana, I Lee, HK Qian, JQ Pohl, U Mohrenweiser, HW Borell, TJ Hosek, SM Soderberg, CL von Deimling, A Perry, A Scheithauer, BW Louis, DN Jenkins, RB TI Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using fluorescence in situ hybridization and novel microsatellite markers SO GENES CHROMOSOMES & CANCER LA English DT Article ID BRAIN-TUMORS; OLIGODENDROGLIAL TUMORS; SV40-TRANSFORMED CELLS; CYTOGENETIC ANALYSIS; HUMAN ASTROCYTOMAS; GENOMIC STRUCTURE; CANDIDATE REGION; PHOSPHATASE GENE; PROSTATE-CANCER; ALLELIC LOSS AB Allelic loss of chromosome arm 19q is a frequent event in human diffuse glioma, suggesting the presence of a tumor suppressor gene. Previous loss of heterozygosity (LOH) analyses have mapped this gene to a 1.4-megabase interval, between the genetic markers D19S412 and STD. Further narrowing of this interval has been limited by the resolution of mapped polymorphic markers. In the present study, we have used genomic clones mapped to 19q as fluorescence in situ hybridization (FISH) probes to map the breakpoints of 13 gliomas with 19q13.3 deletion boundaries. In addition, we have developed three new polymorphic microsatellite markers (D19S1180, D19S1181, and D19S1182) that map between D19S412 and STD and have used these new markers to identify two gliomas with small deletions between the D19S412 and STD markers. Collectively, these data suggest that the region of common deletion may be as narrow as 150 kb and should facilitate future efforts to identify the glioma 19q tumor suppressor gene. Genes Chromosomes Cancer 29:16-25, 2000. (C) 2000 Wiley-Liss, Inc. C1 Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Div Lab Genet, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Div Anat Pathol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Pathol Neuropathol, Mol Neurooncol Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. Lawrence Livermore Natl Lab, Ctr Human Genome, Livermore, CA USA. Univ Hosp, Dept Neuropathol, Bonn, Germany. Washington Univ, Sch Med, Div Neuropathol, St Louis, MO USA. RP Jenkins, RB (reprint author), Mayo Clin, Dept Cytogenet, 200 1st St SW, Rochester, MN 55905 USA. EM rjenkins@mayo.edu RI imoto, Issei/D-8065-2012; von Deimling, Andreas/F-7774-2013; OI von Deimling, Andreas/0000-0002-5863-540X; Perry, Arie/0000-0002-8300-7261 FU NCI NIH HHS [CA50905, CA57683, CA69285] NR 55 TC 64 Z9 65 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 2000 VL 29 IS 1 BP 16 EP 25 DI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1007>3.3.CO;2-9 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 342KQ UT WOS:000088644100003 PM 10918389 ER PT J AU O'Hagan, RC Ohh, M David, G de Alboran, IM Alt, FW Kaelin, WG DePinho, RA AF O'Hagan, RC Ohh, M David, G de Alboran, IM Alt, FW Kaelin, WG DePinho, RA TI Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression SO GENES & DEVELOPMENT LA English DT Article DE Myc; Cul1; ubiquitin-dependent proteolysis; cell cycle; p27(kip1) ID C-MYC; INHIBITOR P27(KIP1); PROTEIN-SYNTHESIS; BREAST-CANCER; P27; DEGRADATION; GENE; ACCUMULATION; ARREST; TRANSFORMATION AB The c-Myc oncoprotein plays an important role in the growth and proliferation of normal and neoplastic cells. To execute these actions, c-Myc is thought to regulate functionally diverse sets of genes that directly govern cellular mass and progression through critical cell cycle transitions. Here, we provide several lines of evidence that c-Myc promotes ubiquitin-dependent proteolysis by directly activating expression of the Cull gene, encoding a critical component of the ubiquitin ligase SCFSKP2. The cell cycle inhibitor p27(kip1) is a known target of the SCFSKP2 complex, and Myc-induced Cull expression matched well with the kinetics of declining p27(kip1) protein. Enforced Cull expression or antisense neutralization of p27(kip1) was capable of overcoming the slow-growth phenotype of c-Myc null primary mouse embryonic fibroblasts (MEFs). In reconstitution assays, the addition of in vitro translated Cull protein alone was able to restore p27(kip1) ubiquitination and degradation in lysates derived from c-myc(-/-) MEFs or density-arrested human fibroblasts. These functional and biochemical data provide a direct link between c-Myc transcriptional regulation and ubiquitin-mediated proteolysis and together support the view that c-Myc promotes G(1) exit in part via Cul1-dependent ubiquitination and degradation of the CDK inhibitor, p27(kip1). C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA068490, R01CA68490]; NIAID NIH HHS [AI35714, P01 AI035714]; NICHD NIH HHS [R01HD28317] NR 44 TC 149 Z9 152 U1 0 U2 3 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 SEP 1 PY 2000 VL 14 IS 17 BP 2185 EP 2191 DI 10.1101/gad.827200 PG 7 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 351AL UT WOS:000089133800007 PM 10970882 ER PT J AU Martin-Vasallo, P Wetzel, RK Garcia-Segura, LM Molina-Holgado, E Arystarkhova, E Sweadner, KJ AF Martin-Vasallo, P Wetzel, RK Garcia-Segura, LM Molina-Holgado, E Arystarkhova, E Sweadner, KJ TI Oligodendrocytes in brain and optic nerve express the beta 3 subunit isoform of Na,K-ATPase SO GLIA LA English DT Article DE Na,K-ATPase; glia; oligodendrocytes; optic nerve; cerebellum; myelinated axons; immunofluorescence; isoenzymes ID NA+-K+-ATPASE; ADHESION MOLECULE; SKELETAL-MUSCLE; GENE-EXPRESSION; ALPHA-SUBUNITS; MICE DEFICIENT; CELL-CULTURES; MOUSE RETINA; GLIAL-CELLS; RAT AB The Na,K-ATPase, which catalyzes the active transport of Na+ and K+, has two principal subunits (alpha and beta) that have several genetically distinct isoforms. Most of these isoforms are expressed in the nervous system, but certain ones are preferentially expressed in glia and others in neurons. Of the beta isoforms, beta 1 predominates in neurons and beta 2 in astrocytes, although there are some exceptions. Here we demonstrate that beta 3 is expressed in rat and mouse white matter oligodendrocytes. Immunofluorescence microscopy identified beta 3 in oligodendrocytes of rat brain white matter in typical linear arrays of cell bodies between fascicles of axons. The intensity of stain peaked at 20 postnatal days. beta 3 was identified in cortical oligodendrocytes grown in culture, where it was expressed in processes and colocalized with antibody to galactocerebroside, In the mouse and rat optic nerve, beta 3 stain was seen in oligodendrocytes, where it colocalized with carbonic anhydrase II. For comparison, optic nerve was stained for the beta 1 and beta 2 subunits, showing distinct patterns of labelling of axons (beta 1) and astrocytes (beta 2). The C6 glioma cell line was also found to express the beta 3 isoform preferentially. Since beta 3 was not found at detectable levels in astrocytes, this suggests that 06 is closer to oligodendrocytes than astrocytes in the glial cell lineage. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. Univ La Laguna, Dept Bioquim & Biol Mol, Lab Biol Desarrollo, Tenerife, Spain. CSIC, Inst Cajal, E-28002 Madrid, Spain. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149 13th St, Charlestown, MA 02129 USA. RI Molina-Holgado, Eduardo/C-2714-2008 OI Molina-Holgado, Eduardo/0000-0001-6693-1682 FU NINDS NIH HHS [5RO1NS27653] NR 55 TC 22 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0894-1491 J9 GLIA JI Glia PD SEP PY 2000 VL 31 IS 3 BP 206 EP 218 DI 10.1002/1098-1136(200009)31:3<206::AID-GLIA20>3.0.CO;2-1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 349VG UT WOS:000089065800002 PM 10941147 ER PT J AU Saintfort, R Stern, TA AF Saintfort, R Stern, TA TI Cross-cultural and neuropsychiatric aspects of a postpartum delusional state SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID NON-MEDICAL TREATMENTS; OUTCOMES C1 Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. RP Saintfort, R (reprint author), Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD SEP PY 2000 VL 8 IS 3 BP 141 EP 147 PG 7 WC Psychiatry SC Psychiatry GA 347KX UT WOS:000088929400004 PM 10973938 ER PT J AU Jones, SE Buchbinder, BR Aharon, I AF Jones, SE Buchbinder, BR Aharon, I TI Three-dimensional mapping of cortical thickness using Laplace's equation SO HUMAN BRAIN MAPPING LA English DT Article DE cortex; MRI; thickness; brain ID SURFACE-BASED ANALYSIS; HUMAN-BRAIN; SEGMENTATION; MRI; RECONSTRUCTION; DISEASE AB We present a novel, computerized method of examining cerebral cortical thickness. The normal cortex varies in thickness from 2 to 4 mm, reflecting the morphology of neuronal sublayers. Cortical pathologies often manifest abnormal variations in thickness, with examples of Alzheimer's disease and cortical dysplasia as thin and thick cortex, respectively. Radiologically, images are 2-D slices through a highly convoluted 3-D object. Depending on the relative orientation of the slices with respect to the object, it is impossible to deduce abnormal cortical thickness without additional information from neighboring slices. We approach the problem by applying Laplace's Equation (del(2)psi = 0) from mathematical physics. The volume of the cortex is represented as the domain for the solution of the differential equation, with separate boundary conditions at the gray-white junction and the gray-CSF junction. Normalized gradients of psi form a vector field, representing tangent vectors along field lines connecting both boundaries. We define the cortical thickness at any point in the cortex to be the pathlength along such lines. Key advantages of this method are that it is fully three-dimensional, and the thickness is uniquely defined for any point in the cortex. We present graphical results that may cortical thickness everywhere in a normal brain. Results show global variations in cortical thickness consistent with known neuroanatomy. The application of this technique to visualization of cortical thickness in brains with known pathology has broad clinical implications. Hum. Brain Mapping 11:12-32, 2000. (C) 2000 Wiley-Liss, Inc. C1 Tufts Univ, Sch Med, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP Jones, SE (reprint author), 97 Hoitt Rd, Belmont, MA 02478 USA. NR 26 TC 265 Z9 266 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD SEP PY 2000 VL 11 IS 1 BP 12 EP 32 DI 10.1002/1097-0193(200009)11:1<12::AID-HBM20>3.0.CO;2-K PG 21 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 350UK UT WOS:000089119400002 PM 10997850 ER PT J AU Passani, LA Bedford, MT Faber, PW McGinnis, KM Sharp, AH Gusella, JF Vonsattel, JP MacDonald, ME AF Passani, LA Bedford, MT Faber, PW McGinnis, KM Sharp, AH Gusella, JF Vonsattel, JP MacDonald, ME TI Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis SO HUMAN MOLECULAR GENETICS LA English DT Article ID PALLIDOLUYSIAN ATROPHY; MUTANT HUNTINGTIN; PROTEINS; INTERACTS; INCLUSIONS; EXPRESSION; PATHOLOGY; MOTIF AB An elongated glutamine tract in mutant huntingtin initiates Huntington's disease (HD) pathogenesis via a novel structural property that displays neuronal selectivity, glutamine progressivity and dominance over the normal protein based on genetic criteria, As this mechanism is likely to involve a deleterious protein interaction, we have assessed the major class of huntingtin interactors comprising three WW domain proteins. These are revealed to be related spliceosome proteins (HYPA/FBP-11 and HYPC) and a transcription factor (HYPB) that implicate huntingtin in mRNA biogenesis, In HD post-mortem brain, specific antibody reagents detect each partner in HD target neurons, in association with disease-related N-terminal morphologic deposits but not with filter trapped insoluble-aggregate. Glutathione S-transferase partner 'pull-down' assays reveal soluble, aberrantly migrating, forms of full-length mutant huntingtin specific to HD target tissue, Importantly, these novel mutant species exhibit exaggerated WW domain binding that abrogates partner association with other huntingtin isoforms, Thus, each WW domain partner's association with huntingtin fulfills HD genetic criteria, supporting a direct role in pathogenesis. Our findings indicate that modification of mutant huntingtin in target neurons may promote an abnormal interaction with one, or all, of huntingtin's WW domain partners, perhaps altering ribonucleoprotein function with toxic consequences. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21287 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Bedford, Mark/E-7856-2011 FU NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [NS32765, NS16367] NR 27 TC 62 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP 1 PY 2000 VL 9 IS 14 BP 2175 EP 2182 DI 10.1093/hmg/9.14.2175 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 351WF UT WOS:000089181300013 PM 10958656 ER PT J AU Vern, TZ Alles, AJ Kowal-Vern, A Longtine, J Roberts, DJ AF Vern, TZ Alles, AJ Kowal-Vern, A Longtine, J Roberts, DJ TI Frequency of factor V-Leiden and prothrombin G20210A in placentas and their relationship with placental lesions SO HUMAN PATHOLOGY LA English DT Article DE factor V-Leiden; prothrombin; placenta; fetal; thromboemboli ID ACTIVATED PROTEIN-C; FETAL THROMBOTIC VASCULOPATHY; HEMORRHAGIC ENDOVASCULITIS; VENOUS THROMBOSIS; CEREBRAL-PALSY; RISK-FACTORS; CLINICAL-SIGNIFICANCE; RESISTANCE; MUTATION; PREGNANCY AB The most common hereditary hypercoaguable states are factor V-Leiden (FVL) and prothrombin mutations (PRO). FVL and PRO present with an incidence of approximately 5% in a heterogeneous population, and 45% to 63% of the thrombophilic population. The frequency of these mutations in the fetal population and their clinical importance is unknown. Fetal side thromboembolic events (FST) include congenital stroke and renal vein thromboses. In some cases, FST can be diagnosed by placental histopathology when avascular (infarcted) villi are present in a patent maternal vascular space. FST can present as placenta-fetal-vascular or fetal-visceral-vascular lesions. Causes include vascular damage from cord compression or inflammation, but most remain unclear. Potential causes of FST include FVL and PRO. We describe the incidence of FVL and PRO from a prospective group of 169 consecutive placentas and in a retrospective group of archived placentas diagnosed with placental FST. One each of FVL and PRO heterozygosity was found in the prospective set (<1% incidence for each). Five prospective placentas were diagnosed with placental FST, for an incidence of 3%; all were wild-type for FLV and PRO. Twenty-seven of 65 archived FST cases had analyzable DNA to find 5 FVL heterozygotes (18.5%); all were wild-type for PRO. Twenty-one of 65 retrospective archived controls analyzable found 1 case of FVL heterozygosity (<5%). We find that the frequency of FVL and PRO may be decreased in the pregnant population but increased in cases of placental FST. Because factor V Leiden heterozygosity carries an increased risk for thrombotic complications, we suggest placental diagnosis of fetal side thromboemboli warrants clinical evaluation for FVL in infant and potentially the parents. Copyright (C) 2000 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Northwestern Univ, Evanston, IL USA. Cooks Childrens Hosp, Ft Worth, TX USA. Loyola Univ, Med Ctr, Burn Shock Trauma Inst, Maywood, IL 60153 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 32 Fruit St,WRN 225, Boston, MA 02114 USA. NR 52 TC 46 Z9 47 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2000 VL 31 IS 9 BP 1036 EP 1043 DI 10.1053/hupa.2000.16281 PG 8 WC Pathology SC Pathology GA 355ZK UT WOS:000089418300006 PM 11014568 ER PT J AU Kronz, JD Silberman, MA Allsbrook, WC Bastacky, SI Burks, RT Cina, SJ Mills, SE Ross, JS Sakr, WA Tomaszewski, JE True, LD Ulbright, TM Weinstein, MW Yantiss, RK Young, RH Epstein, JI AF Kronz, JD Silberman, MA Allsbrook, WC Bastacky, SI Burks, RT Cina, SJ Mills, SE Ross, JS Sakr, WA Tomaszewski, JE True, LD Ulbright, TM Weinstein, MW Yantiss, RK Young, RH Epstein, JI TI Pathology residents' use of a Web-based tutorial to improve Gleason grading of prostate carcinoma on needle biopsies SO HUMAN PATHOLOGY LA English DT Article DE Gleason grading; prostate cancer; needle biopsy; Internet; education AB Little is known about pathology residents' ability to Gleason grade or their ability to learn surgical pathology using Internet-based technology. A free Web-based program (available at www.pathology. jhu.edu/prostate) was developed that consisted of 20 pretutorial images for grading, 24 tutorial images, and the same 20 posttutorial images for Gleason grading. The grading images were selected from cases that had a consensus Gleason grade from 10 uropathology experts. In 2.5 months, 255 residents visited the website, and 151 (59%) completed it. Of those who completed the website, their year in training was known in 85 (56%): 1st year, 25.8%; 2nd year, 20%; 3rd year, 22.3%; 4th year, 14.1%; 5th year, 15.3%; and 6th year, 2.4%. Eighty percent learned Gleason grading in residency versus being self-taught, and 66% were male. In a multivariate analysis, higher pretutorial scores were associated with both their year in training (P = .001) and their hospital size (P = .003). Improvements in grading posttutorial rc ere not related to the residents' year in training. Overall, the website significantly improved grading in 11 of 20 images and had no effect in 9 of 20 images. Improvements were noted in 1 of one Gleason score 4; 2 of 7 Gleason score 5 to 6; 2 of 6 Gleason score 7; and 6 of 6 Gleason score above 7 tumors. In summary, a Web-based tutorial improved Gleason grading accuracy by pathology residents to an equal extent regardless of their year hi training. It is more difficult to teach residents to grade Gleason scores 5 to 7 tumors, and additional training should be concentrated in this area. Cop)right (C) 2000 by W.B. Saunders Company. C1 Johns Hopkins Hosp, Dept Pathol, Baltimore, MD 21287 USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Med Coll Virginia, Charlottesville, VA USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. Virginia Commonwealth Univ, Hlth Sci Ctr, Richmond, VA USA. Albany Med Ctr, Albany, NY USA. Wayne State Univ, Detroit, MI USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Univ Washington, Hlth Sci Ctr, Seattle, WA 98195 USA. Indiana Univ Hosp, Indianapolis, IN 46202 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Epstein, JI (reprint author), Johns Hopkins Hosp, Dept Pathol, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 12 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2000 VL 31 IS 9 BP 1044 EP 1050 DI 10.1053/hupa.2000.16278 PG 7 WC Pathology SC Pathology GA 355ZK UT WOS:000089418300007 PM 11014569 ER PT J AU Kommoss, F Oliva, E Bittinger, F Kirkpatrick, CJ Amin, MB Bhan, AK Young, RH Scully, RE AF Kommoss, F Oliva, E Bittinger, F Kirkpatrick, CJ Amin, MB Bhan, AK Young, RH Scully, RE TI Inhibin-alpha, CD99, HEA125, PLAP and chromogranin immunoreactivity in testicular neoplasms and the androgen insensitivity syndrome SO HUMAN PATHOLOGY LA English DT Article DE testicular tumors; sex cord-stromal tumors; inhibin; CD99; HEA125; PLAP; chromogranin; immunohistochemistry ID CORD-STROMAL TUMORS; GRANULOSA-CELL TUMORS; MONOCLONAL-ANTIBODY; TESTIS; CARCINOMAS; EXPRESSION; DIAGNOSIS; ACTIVINS; MARKER; OVARY AB We investigated 115 testicular and 3 epididymal tumors and 6 cases of the complete androgen insensitivity syndrome (AIS) for the expression of inhibin-alpha, CD99, HEA125, PLAP, and chromogranin, using monoclonal antibodies and standard immunhistochemical techniques. Inhibin-alpha was detected in the neoplastic cells in 27 of 27 primary Leydig cell tumors (LCTs), 1 of 1 metastatic LCT, 6 of 20 Sertoli eel tumors (SCTs), 4 of 5 juvenile granulosa cell tumors (JGCTs), and 2 of 5 unclassified sex cord-stromal tumors (USCSTs). Except for 2 choriocarcinomas, the choriocarcinomatous component of 1 mixed germ cell tumor, and a small focus of inhibin-positive syncytiotrophoblast in 1 embryonal carcinoma, inhibin-alpha immunoreactivity was not present in the neoplastic cells of the 38 remaining testicular germ cell tumors; 11 B-cell and 1 T-cell lymphomas; 1 granulocytic sarcoma; and 1 rhabdomyosarcoma of the testis; 1 adenoma of the rete testis, and 3 adenomatoid tumors of the epididymis. Inhibin-alpha immunoreactivity was present in the Sertoli cells and Leydig cells in 5 testicular hamartomas and in 1 Sertoli cell adenoma in 6 cases of AIS; both Sertoli and Leydig cells were also positive in the extranodular testicular parenchyma present in 2 of these cases. CD99 was detected in 10 of 15 primary LCTs, 1 of 7 SCTs, 3 of 5 JGCTs, and in 1 of 5 USCSTs but was not found in any tumor outside the sex cord-stromal category. HEA125 immunostaining was not detected in sex cord-stromal tumors; however, 3 of 12 seminomas, 3 of 12 embryonal carcinomas, 6 of 8 yolk sac tumors, and 1 of 2 teratomas were HEA125 positive. PLAP was not detected in sex cord-stromal tumors except for 4 of 15 primary LCTs but was present in most germ cell tumors. Chromogranin immunostaining was present in the sex cord-like element in 1 of 5 USCSTs, 1 of 8 YSTs, 1 of 2 teratomas, and in 1 of 1 rete adenoma, and in normal adjacent rete testis. In conclusion, although inhibin-alpha and PLAP, and, to a somewhat lesser extent, CD99 and HEA125 immunostaining are helpful in the differential diagnosis of certain testicular neoplasms that are difficult to distinguish on morphologic grounds, chromogranin is far less helpful in this context. Copyright (C) 2000 by W.B. Saunders Company. C1 Univ Mainz, Dept Pathol, D-55101 Mainz, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Emory Univ Hosp, Dept Pathol, Atlanta, GA 30322 USA. RP Kommoss, F (reprint author), Univ Mainz, Dept Pathol, D-55101 Mainz, Germany. NR 37 TC 64 Z9 64 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 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2000 VL 31 IS 9 BP 1055 EP 1061 DI 10.1053/hupa.2000.16237 PG 7 WC Pathology SC Pathology GA 355ZK UT WOS:000089418300009 PM 11014571 ER PT J AU Cronin, CT Keel, SB Grabbe, J Schuler, JG AF Cronin, CT Keel, SB Grabbe, J Schuler, JG TI Adult rhabdomyoma of the extremity: A case report and review of the literature SO HUMAN PATHOLOGY LA English DT Review DE adult rhabdomyoma; sarcoma; skeletal muscle neoplasm; extremity; pathology ID EXTRA-CARDIAC RHABDOMYOMA; ELECTRON-MICROSCOPY; LIGHT; HISTOCHEMISTRY; TUMOR; NECK AB The adult rhabdomyoma is a rare, benign skeletal muscle neoplasm that usually occurs in the head and neck. A case report of an adult rhabdomyoma arising in the thigh is presented with a review of the literature. This is the first case of an extremity adult rhabdomyoma to be reported. It is also the largest at 13 centimeters. Distinction from a highly differentiated rhabdomyosarcoma is important. Recent chromosomal studies suggest that the adult rhabdomyoma is a true neoplasm. Total resection is curative but the lesion may recur if incompletely excised. Copyright (C) 2000 by W.B. Saunders Company. C1 Mt Auburn Hosp, Dept Surg, Cambridge, MA 02238 USA. Cambridge Hosp, Dept Surg, Cambridge, MA 02139 USA. Cambridge Hosp, Dept Pathol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Schuler, JG (reprint author), Mt Auburn Hosp, Dept Surg, 330 Mt Auburn St, Cambridge, MA 02238 USA. NR 28 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 2000 VL 31 IS 9 BP 1074 EP 1080 DI 10.1053/hupa.2000.9783 PG 7 WC Pathology SC Pathology GA 355ZK UT WOS:000089418300012 PM 11014574 ER PT J AU Fowler, DJ Nicolaides, KH Miell, JP AF Fowler, DJ Nicolaides, KH Miell, JP TI Insulin-like growth factor binding protein-1 (IGFBP-1): a multifunctional role in the human female reproductive tract SO HUMAN REPRODUCTION UPDATE LA English DT Article DE female reproductive tract; IGFBP-1; intrauterinegrowth restriction; polycystic ovarian syndrome; pre-eclampsia ID ENDOMETRIAL STROMAL CELLS; HUMAN GRANULOSA-CELLS; POLYCYSTIC OVARIAN SYNDROME; I IGF-I; PLACENTAL PROTEIN-12; AMNIOTIC-FLUID; FACTOR BINDING-PROTEIN-1; CIRCULATING LEVELS; TRANSGENIC MICE; GENE-EXPRESSION AB Insulin-like growth factor-1 (IGFBP-1) is particularly important in human female reproductive physiology, where it is involved with other factors in a complex system which regulates menstrual cycles, puberty, ovulation, decidualization, implantation and fetal growth. This has implications for clinical obstetrics and gynaecology, where there is evidence for a pathophysiological role for IGPBP-1 in pre-eclampsia, intrauterine growth restriction, polycystic ovarian syndrome and trophoblast and endometrial neoplasms. C1 Kings Coll Hosp London, Dept Obstet & Gynaecol, Harris Birthright Res Ctr Fetal Med, London, England. Guys Kings & St Thomas Med Sch, Dept Med, London, England. RP Fowler, DJ (reprint author), Massachusetts Gen Hosp, Genet Unit, 55 Fruit St,Warren 801, Boston, MA 02114 USA. EM djfowler@partners.org NR 94 TC 57 Z9 61 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1355-4786 EI 1460-2369 J9 HUM REPROD UPDATE JI Hum. Reprod. Update PD SEP-OCT PY 2000 VL 6 IS 5 BP 495 EP 504 DI 10.1093/humupd/6.5.495 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 362YK UT WOS:000089805700010 PM 11045880 ER PT J AU Marro, ML Scremin, OU Jordan, MC Huynh, L Porro, F Roos, KP Gajovic, S Baralle, FE Muro, AF AF Marro, ML Scremin, OU Jordan, MC Huynh, L Porro, F Roos, KP Gajovic, S Baralle, FE Muro, AF TI Hypertension in beta-adducin-deficient mice SO HYPERTENSION LA English DT Article DE hypertension, genetic; adducin; mice, knockout; echocardiography; cytoskeleton; telemetry; electrocardiography ID HUMAN ALPHA-ADDUCIN; BLOOD-PRESSURE; GENETIC-HYPERTENSION; JAPANESE POPULATION; POINT MUTATIONS; POLYMORPHISM; ASSOCIATION; PROTEIN; LINKAGE; LOCUS AB Polymorphic variants of the cytoskeletal protein adducin have been associated with hypertension in humans and rats. However, the direct role of this protein in modulating arterial blood pressure has never been demonstrated. To assess the effect of beta-adducin on blood pressure, a beta-adducin-deficient mouse strain (-/-) was studied and compared with wild-type controls (+/+). Aortic blood pressure was measured in nonanesthetized, freely moving animals with the use of telemetry implants. It is important to note that these mice have at least 98% of C57B1/6 genetic background, with the only difference from wild-type animals being the beta-adducin mutation. We found statistically significant higher levels of systolic blood pressure (mm Hg) (mean+/-SE values: -/-: 126.94+/-1.14, n=5; +/+: 108.06+/-2.34, n=6; P less than or equal to 0.0001), diastolic blood pressure (-/-: 83.54+/-1.07; +/+: 74.87+/-2.23; P less than or equal to 0.005), and pulse blood pressure (-/-: 43.32+/-1.10; +/+: 33.19+/-1.96; P less than or equal to 0.001) in beta-adducin-deficient mice. Western blot analysis showed that as a result of the introduced genetic modification, beta-adducin was not present in heart protein extracts from -/- mice. Consequently, this deficiency produced a sharp decrease of alpha-adducin and a lesser reduction in gamma-adducin levels. However, we found neither cardiac remodeling nor modification of the heart function in these animals. This is the first report showing direct evidence that hypertension is triggered by a mutation in the adducin gene family. C1 Int Ctr Genet Engn & Biotechnol, I-34012 Trieste, Italy. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. Vet Affairs GLA Healthcare Syst, Los Angeles, CA USA. Univ Zagreb, Sch Med, Dept Histol & Embryol, Zagreb 41001, Croatia. RP Muro, AF (reprint author), Int Ctr Genet Engn & Biotechnol, Padriciano 99, I-34012 Trieste, Italy. RI Muro, Andres/K-3156-2016 OI Muro, Andres/0000-0002-9628-0494 NR 24 TC 28 Z9 28 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2000 VL 36 IS 3 BP 449 EP 453 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 354MG UT WOS:000089333800025 PM 10988280 ER PT J AU VanSickle, DP Cooper, RA Boninger, ML AF VanSickle, DP Cooper, RA Boninger, ML TI Road loads acting on manual wheelchairs SO IEEE TRANSACTIONS ON REHABILITATION ENGINEERING LA English DT Article DE design; forces; instrumentation; modeling; moments; wheelchairs ID SURFACE; DESIGN AB A barrier to performing more in-depth analyzes during the wheelchair design process is a lack of dynamic reaction force and moment data, and the instrumentation to collect this data. Instrumentation was developed to collect the dynamic force and moment data. New data collections methodologies and analysis techniques were implemented to facilitate computer-aided-engineering fur wheelchair designs. Data were collected during standardized wheelchair fatigue tests, while driving over a simulated road course within a laboratory, and while driving in the community. Seventeen subjects participated in this study. Based upon the three test conditions, a pseudo-statistical distribution of the force and moment data at both a easter and rear wheel was developed. The key parameters describing the distribution and the extremums of the data (minima and maxima) were compared using analysis of variance. The results showed that the force and moment distributions and extreme values were similar for the both sets of human trials (i.e,, simulated road course and field trials). However, the standardized testing (i.e., wheelchair fatigue testing) differed from both human trials. The force/moment data gathered during this study are suitable for inputs in finite element analysis and dynamic modeling. Our results suggest that the fatigue tests should be modified to change the magnitude and increase the frequency of the forces and moments imparted on the wheelchair. The data reported from this study can be used to improve wheelchair standards and to facilitate computer-aided-engineer in wheelchair design. C1 VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Div PM&R, Pittsburgh, PA 15261 USA. RP VanSickle, DP (reprint author), VA Pittsburgh Healthcare Syst, VA Rehabil Res & Dev Ctr, Human Engn Res Labs, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 33 TC 14 Z9 14 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1063-6528 J9 IEEE T REHABIL ENG JI IEEE Trans. Rehabil. Eng. PD SEP PY 2000 VL 8 IS 3 BP 371 EP 384 DI 10.1109/86.867879 PG 14 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 354NN UT WOS:000089336700012 PM 11001517 ER PT J AU DiGiovine, CP Cooper, RA DiGiovine, MM Boninger, ML Robertson, RN AF DiGiovine, CP Cooper, RA DiGiovine, MM Boninger, ML Robertson, RN TI Frequency analysis of kinematics of racing wheelchair propulsion SO IEEE TRANSACTIONS ON REHABILITATION ENGINEERING LA English DT Article DE cutoff frequency; frequency analysis; kinematics; motion analysis; racing wheelchair propulsion ID SPINAL-CORD INJURY; ERGOMETER; EFFICIENCY; CHILDREN; ADULTS AB The purpose of this study was to describe the frequency content of racing wheelchair propulsion motion data. The selection of the filter corner frequency in previous kinematic analyses of manual wheelchair propulsion was commonly based on gait literature. An estimate of the frequency separating the signal and the noise was determined to make recommendations for low-pass digital filters, The global (noncoordinate specific) cutoff frequency was 6 Hz. The directional cutoff frequencies were 5.1, 3.9, and 5.6 Hz, in the anterior-posterior, superior-inferior and medial-lateral directions, respectively. Recommendations for the corner frequencies of low-pass Butterworth digital filters based on the cutoff frequency are higher than the corner frequencies used in previous studies of manual wheelchair propulsion kinematic data, This study provides a foundation for the data reduction of manual wheelchair propulsion kinematic data that is independent of gait literature. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Human Engn Res Lab, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Div PM&R, Pittsburgh, PA 15261 USA. RP DiGiovine, CP (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. RI DiGiovine, Carmen/E-2982-2011; OI Boninger, Michael/0000-0001-6966-919X NR 33 TC 6 Z9 6 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1063-6528 J9 IEEE T REHABIL ENG JI IEEE Trans. Rehabil. Eng. PD SEP PY 2000 VL 8 IS 3 BP 385 EP 393 DI 10.1109/86.867880 PG 9 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 354NN UT WOS:000089336700013 PM 11001518 ER PT J AU Ishido, S Choi, JK Lee, BS Wang, CY DeMaria, M Johnson, RP Cohen, GB Jung, JU AF Ishido, S Choi, JK Lee, BS Wang, CY DeMaria, M Johnson, RP Cohen, GB Jung, JU TI Inhibition of natural killer cell-mediated cytotoxicity by kaposi's sarcoma-associated herpesvirus K5 protein SO IMMUNITY LA English DT Article ID MHC CLASS-I; ACTIN-BINDING PROTEIN-280; HEAVY-CHAINS FREE; NK CELLS; CYTOPLASMIC DOMAIN; DNA-SEQUENCES; FILAMIN; LINE; IDENTIFICATION; RECEPTORS AB Kaposi's sarcoma-associated herpesvirus (KSHV) K3 and K5 proteins dramatically downregulate MHC class I molecules. However, although MHC class I downregulation may protect KSHV-infected cells from cytotoxic T lymphocyte recognition, these cells become potential targets for natural killer (NK) cell-mediated lysis. We now show that K5 also downregulates ICAM-1 and B7-2, which are ligands for NK cell-mediated cytotoxicity receptors. As a consequence, K5 expression drastically inhibits NK cell-mediated cytotoxicity. Conversely, de novo expression of B7-2 and ICAM-1 resensitizes the W-expressing cells to NK cell-mediated cytotoxicity. This is a novel viral immune evasion strategy where KSHV K5 achieves immune avoidance by downregulation of cellular ligands for NK cell-mediated cytotoxicity receptors. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Tumor Virol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. RP Jung, JU (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Tumor Virol, Southborough, MA 01772 USA. FU NCI NIH HHS [CA82057, CA31363, CA86841] NR 61 TC 185 Z9 190 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2000 VL 13 IS 3 BP 365 EP 374 DI 10.1016/S1074-7613(00)00036-4 PG 10 WC Immunology SC Immunology GA 359NF UT WOS:000089616400009 PM 11021534 ER PT J AU Pahlavani, MA Vargas, DM AF Pahlavani, MA Vargas, DM TI The effect of a ceramide analog, N-acetylsphingosine on the induction of proliferation and IL-2 synthesis in T cells from young and old F344 rats SO IMMUNOPHARMACOLOGY LA English DT Article DE ceramide; T cell activation; IL-2; apoptosis; rat; aging ID SIGNAL-TRANSDUCTION; CELLULAR SENESCENCE; INDUCED APOPTOSIS; OXIDATIVE STRESS; PHOSPHOLIPASE-D; AGE; ACTIVATION; EXPRESSION; SPHINGOMYELINASES; MICE AB Ceramide is a physiological mediator of extracellular signals that control various cellular functions, including proliferation and apoptosis. In the present study, we examined the effects of cell-permeable ceramide analog, N-acetyl-sphingosine (C-2-ceramide) on the induction of proliferation and interleukin-2 (IL-2) synthesis in T cells from young and old rats. Splenic T cells from 6- and 24-month-old Fischer 344 rats were treated with C-2-ceramide and then incubated with anti-CD3 antibody for 24 or 48 h. The induction of proliferation and IL-2 production by anti-CD3 was significantly (P < 0.001) lower in T cells from old rats compared to T cells from young rats. C-2-ceramide treatment resulted in suppression of proliferation and IL-2 production in a concentration-dependent manner. The suppressive effect of C-2-ceramide on proliferation and IL-2 production was greater in T cells from old rats than T cells from young rats, We investigated whether this decreased responsiveness was due to induction of program cell death (apoptosis) and found that there was a significant increase in DNA fragmentation in C-2-ceramide treated and anti-CD3 stimulated T cells from both young and old rats. The increase in DNA fragmentation was paralleled with an increase in caspase-3 activation, C-2-ceramide-induced caspase-3 activation and DNA fragmentation was significantly (P < 0.5) higher in stimulated T cells from old rats compared to stimulated T cells from young rats. These results suggest that the sphingomyelin-ceramide signaling pathway may play an important regulatory role in the well-documented age-related decline in immune function, (C) 2000 Elsevier Science B.V. All rights reserved. C1 Audie L Murphy Mem Vet Hosp, Geriatr Res Educ & Clin Ctr 182, 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 Hosp, Geriatr Res Educ & Clin Ctr 182, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG00677, AG14088] NR 49 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0162-3109 J9 IMMUNOPHARMACOLOGY JI Immunopharmacology PD SEP PY 2000 VL 49 IS 3 BP 345 EP 354 DI 10.1016/S0162-3109(00)00254-X PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 358QK UT WOS:000089568600013 PM 10996032 ER PT J AU Califano, JV Kitten, T Lewis, JP Macrina, FL Fleischmann, RD Fraser, CM Duncan, MJ Dewhirst, FE AF Califano, JV Kitten, T Lewis, JP Macrina, FL Fleischmann, RD Fraser, CM Duncan, MJ Dewhirst, FE TI Characterization of Porphyromonas gingivalis insertion sequence-like element ISPg5 SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; PATHOGENICITY ISLANDS; GENE; TRANSPOSITION; IS1126; IDENTIFICATION; EVOLUTION; VIRULENCE; BACTERIA; FAMILY AB Porphyromonas gingivalis, a black-pigmented, gram-negative anaerobe, is found in periodontitis lesions, and its presence in subgingival plaque significantly increases the risk for periodontitis. In contrast to many bacterial pathogens, P. gingivalis strains display considerable variability, which is likely due to genetic exchange and intragenomic changes. To explore the latter possibility, we have studied the occurrence of insertion sequence (IS)-like elements in P. gingivalis W83 by utilizing a convenient and rapid method of capturing IS-like sequences and through analysis of the genome sequence of P. gingivalis strain W83. We adapted the method of Matsutani et al. (S. Matsutani, H. Ohtsubo, Y. Maeda, and E. Ohtsubo, J. Mol. Biol. 196:445-455, 1987) to isolate and clone rapidly annealing DNA sequences characteristic of repetitive regions, within a genome. We show that in P. gingivalis strain W83, such sequences include (i) nucleotide sequence with homology to tRNA genes, (ii) a previously described IS element, and (iii) a novel IS-like element. Analysis of the P. gingivalis genome sequence for the distribution of the least used tetranucleotide, CTAG, identified regions in many of the initial 218 contigs which contained CTAG clusters. Examination of these CTAG clusters led to the discovery of 11 copies of the same novel IS-like element identified by the repeated sequence capture method of Matsutani et al. This new 1,512-bp IS-like element, designated ISPg5, has features of the IS3 family of IS elements. When a recombinant plasmid containing much of ISPg5 was used in Southern analysis of several P. gingivalis strains, including clinical isolates, diversity among strains was apparent. This suggests that ISPg5 and other IS elements may contribute to strain diversity and can be used for strain fingerprinting. C1 Virginia Commonwealth Univ, Sch Dent, Dept Periodont, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Philips Inst Oral & Craniofacial Mol Biol, Richmond, VA 23298 USA. Inst Genome Res, Rockville, MD 20850 USA. Forsyth Inst, Boston, MA 02115 USA. RP Califano, JV (reprint author), Virginia Commonwealth Univ, Sch Dent, Dept Periodont, Med Coll Virginia Campus, Richmond, VA 23298 USA. OI Fraser, Claire/0000-0003-1462-2428 FU NIDCR NIH HHS [DE 12082, DE04224] NR 45 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2000 VL 68 IS 9 BP 5247 EP 5253 DI 10.1128/IAI.68.9.5247-5253.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 346KM UT WOS:000088870200057 PM 10948151 ER PT J AU Rorty, M Yager, L Buckwalter, JG Rossotto, E Guthrie, D AF Rorty, M Yager, L Buckwalter, JG Rossotto, E Guthrie, D TI Development and validation of the parental intrusiveness rating scale among bulimic and comparison women SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article; Proceedings Paper CT 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc DE parental intrusiveness; Parental Intrusiveness Rating Scale; disturbed relationships ID NERVOSA; ABUSE AB Objective: Based on hypotheses generated dr,ring clinical interviews with 80 women with a lifetime history of bulimia nervosa (BN), we designed an instrument for assessing the extent to which, women with BN report parental intrusiveness and breakdown of appropriate role boundaries during their adolescent development. Method: Through an iterative process of item generation and scale administration, the Parental Intrusiveness Rating Scale (PIRS), consisting of 20 maternal items and 20 paternal items, was developed. Maternal subscales include Invasion of Privacy, Jealousy and Competition, and Overconcern with the Daughter's Eating, Weight, and Shape. Paternal subscales include Invasion of Privacy Seductiveness, and Overconcern with the Daughter's Eating, Weight, and Shape. We validated the instrument using a subset of die above BN and comparison women (ns = 55 and 33, respectively), as well as an independent sample of women with BN and college com parison subjects (ns = 31 and 540, respectively). Results: Parental intrusiveness scores were significantly positively correlated with disturbed relationships in the family of origin of our initial cohort. Reliability analyses, both test-retest and item-scale correlations, revealed adequate to strong statistical associations in the combined sample. Conclusion: The PIRS promises to enrich our understanding of problematic parental behaviors among women who develop BN and allows us to broaden the conceptualization of familial risk factors for this disorder. (C) 2000 by John Wiley &Sons, Inc. C1 Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA. Univ So Calif, Sch Med, Dept Gerontol, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. RP Yager, L (reprint author), Univ New Mexico, Sch Med, Dept Psychiat, 2400 Tucker NE, Albuquerque, NM 87131 USA. NR 23 TC 2 Z9 2 U1 1 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2000 VL 28 IS 2 BP 188 EP 201 DI 10.1002/1098-108X(200009)28:2<188::AID-EAT8>3.0.CO;2-X PG 14 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 335JP UT WOS:000088240600008 PM 10897081 ER PT J AU Rorty, M Yager, J Rossotto, E Buckwalter, G AF Rorty, M Yager, J Rossotto, E Buckwalter, G TI Parental intrusiveness in adolescence recalled by women with a history of bulimia nervosa and comparison women SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article; Proceedings Paper CT 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-23, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc DE intrusive parental behavior; Parental Intrusiveness Rating Scale; adolescence ID SEXUAL ABUSE; MOTHERS; GIRLS AB Objective: To learn if women with a lifetime history of bulimia nervosa (BN) report more intrusive parental behavior during adolescence than their nonclinical peers, and to provide further validation of the Parental Intrusiveness Rating Scale (PIRS). Method: We administered the PIRS to 86 women with a lifetime history of BN and 573 comparison subjects and examined between-group differences. Results: Relative to the comparison group, lifetime BN subjects reported higher levels of parental intrusiveness, specifically maternal invasion of privacy, maternal jealousy and competition, paternal seductiveness, and maternal and paternal overconcern with the daughter's eating, weight, and shape. There were no between-group differences in paternal invasion of privacy. In exploratory analyses with the comparison sample, Caucasian women reported greater maternal jealousy and competition than Asian American/Pacific Islander women, but there were no other differences. Conclusion: These results support clinical observations of high levels of parental intrusiveness in the adolescent experiences of women who develop BN. Nonclinical women of diverse ethnic backgrounds report largely equivalent experiences. (C) 2000 by John Wiley & Sons, Inc. C1 Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA. W Los Angeles Vet Adm Med Ctr, Dept Psychiat, Los Angeles, CA USA. Univ So Calif, Sch Med, Dept Gerontol, Los Angeles, CA USA. RP Yager, J (reprint author), Univ New Mexico, Sch Med, Dept Psychiat, 2400 Tucker NE, Albuquerque, NM 87131 USA. NR 25 TC 26 Z9 27 U1 0 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD SEP PY 2000 VL 28 IS 2 BP 202 EP 208 DI 10.1002/1098-108X(200009)28:2<202::AID-EAT9>3.0.CO;2-G PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 335JP UT WOS:000088240600009 PM 10897082 ER PT J AU Snow, KK Seddon, JM AF Snow, KK Seddon, JM TI Age-related eye diseases: Impact of hormone replacement therapy, and reproductive and other risk factors SO INTERNATIONAL JOURNAL OF FERTILITY AND WOMENS MEDICINE LA English DT Review DE age-related macular degeneration; cataract; estrogen; hormones; postmenopausal women; reproductive factors; review article; risk factors; visual impairment (108 references) ID BEAVER DAM EYE; SENILE MACULAR DEGENERATION; CORONARY HEART-DISEASE; BLUE-MOUNTAINS EYE; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; LENS OPACITIES; BREAST-CANCER; VENOUS THROMBOEMBOLISM AB In Western countries, age-related macular degeneration is the leading cause of legal blindness in the population over 60 years of age, and cataract is the leading cause of visual impairment worldwide. Because postmenopausal women are living longer, they have a greater probability of developing a variety of age-related visual disorders. As the population ages, the physical and emotional toll of these ailments, as well as the burden on the health care system, will escalate. Currently, interventional therapy for age-related macular degeneration is limited to a small subpopulation of patients who can benefit from laser treatment, whereas surgery is the only effective treatment for cataract. The need for other therapeutic options and preventive measures remains a major challenge for the future. Studies among women have suggested that exposure to estrogens is associated with a reduction in risk of developing ocular diseases associated with aging. This article addresses the epidemiology of age-related macular degeneration and cataract, focusing on the specific risks for women, and discusses factors that may influence development or progression of these visual disorders. C1 Massachusetts Eye & Ear Infirm, Epidemiol Unit, Boston, MA 02114 USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Seddon, JM (reprint author), Massachusetts Eye & Ear Infirm, Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. NR 107 TC 11 Z9 11 U1 0 U2 1 PU MEDICAL SCIENCE PUBLISHING INT INC PI PORT WASHINGTON PA 405 MAIN ST, PORT WASHINGTON, NY 11050 USA SN 1069-3130 J9 INT J FERTIL WOMEN M JI Int. J. Fertil. Womens Med. PD SEP-OCT PY 2000 VL 45 IS 5 BP 301 EP 313 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 370UG UT WOS:000165140300001 PM 11092701 ER PT J AU Leybovich, LB Dogan, N Sethi, A AF Leybovich, LB Dogan, N Sethi, A TI A modified technique for RF-LCF interstitial hyperthermia SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE hyperthermia; radiofrequency; localized; interstitial; concomitant AB To provide uniform heating of a tumour, it is necessary to establish sufficient volumetric control of power deposition. The interstitial Radio-Frequency Localized Current Field (RF-LCF) technique may provide such control when segmented electrodes are used. The length of segments is equal to 1-1.5 cm. Each segment is connected to a separate power source. However, this technique requires an additional implant for interstitial radiotherapy, because the lumen of segmented electrodes is filled with wires necessary to connect each segment to a separate power source. In this work, a modified method of implant that allows delivery of sequential and concomitant controlled thermoradiotherapy was investigated. In this method, each segmented electrode is surrounded by four continuous electrodes. Continuous electrodes pass through vertices of 1.5 x 1.5 cm square and a segmented electrode passes through the centre of the square. The distance between segmented and continuous electrodes is 1.06 cm. The electric field induced between an electrically interacting segment and continuous electrodes is concentrated primarily between this segment and its projection on continuous electrodes. Therefore, control of temperature distribution achieved with a modified implant is similar to that achieved with an implant containing only segmented electrodes. For temperature control during treatment, plastic catheters are inserted at a 0.5 cm distance from each segmented electrode. Temperature is monitored using multisensor temperature probes. The continuous electrodes are also used for placement of radioactive sources. The lateral distance between radioactive sources is equal to 1.5 cm. Besides allowing a sequential and concomitant thermoradiotherapy, the modified method is simpler to implement because it uses several fold less amount of segmented electrodes and power sources. C1 Loyola Univ, Stritch Sch Med, Dept Radiat Oncol, Div Med Phys, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 61103 USA. RP Leybovich, LB (reprint author), Loyola Univ, Stritch Sch Med, Dept Radiat Oncol, Div Med Phys, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 14 TC 2 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD SEP PY 2000 VL 16 IS 5 BP 405 EP 413 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 352PC UT WOS:000089226200002 PM 11001574 ER PT J AU Dewhirst, FE Fox, JG Mendes, EN Paster, BJ Gates, CE Kirkbride, CA Eaton, KA AF Dewhirst, FE Fox, JG Mendes, EN Paster, BJ Gates, CE Kirkbride, CA Eaton, KA TI 'Flexispira rappini' strains represent at least 10 Helicobacter taxa SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE Helicobacter; 'Flexispira rappini'; rRNA; phylogeny ID SP-NOV; LABORATORY MICE; LARGE-BOWEL; BACTERIUM; CAMPYLOBACTER; BACTEREMIA; PHYLOGENY; ABORTION; GASTROENTERITIS; COLITIS AB 'Flexispira rappini' is a provisional name given to Cram-negative, microaerophilic, motile, spindle-shaped micro-organisms with spiral periplasmic fibres and bipolar tufts of sheathed flagella. Several investigators, including Kirkbride, Romero, and Archer isolated strains possessing this morphology. Previously, the phylogenetic position of three 'Flexispira rappini' strains was determined by 16S rRNA sequencing, which indicated that flexispira were members of the genus Helicobacter. As more organisms with 'F, rappini' morphology were isolated, it became apparent that there were multiple Helicobacter taxa with this distinctive morphology. The purpose of this study was to examine a collection of 36 'F. rappini' strains from diverse habitats by using 16S rRNA sequence analysis. The strains fell into 10 taxa, each possibly representing a novel Helicobacter species. Two of these flexispira taxa were previously named, by us, Helicobacter bills and Helicobacter trogontum. Currently, none of the flexispira taxa contains enough phenotypically and genotypically characterized strains to be formally named 'Helicobacter rappinii'. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. MIT, Div Comparat Med, Cambridge, MA 02319 USA. UFMG, Fac Med, PRO, Div Lab Med, BR-30130100 Belo Horizonte, MG, Brazil. S Dakota State Univ, Dept Vet Sci, Brookings, SD 57007 USA. Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 10374, DE 08303, DE 11443] NR 34 TC 52 Z9 54 U1 0 U2 3 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD SEP PY 2000 VL 50 BP 1781 EP 1787 PN 5 PG 7 WC Microbiology SC Microbiology GA 361HN UT WOS:000089717800010 PM 11034487 ER PT J AU Ye, HQQ Maeda, M Yu, FSX Azar, DT AF Ye, HQQ Maeda, M Yu, FSX Azar, DT TI Differential expression of MT1-MMP (MMP-14) and collagenase III (MMP-13) genes in normal and wounded rat corneas SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID TYPE-1 MATRIX METALLOPROTEINASE; MT-MMPS; TUMOR INVASION; GELATINASE-B; LOCALIZATION; CELLS; METASTASIS; FAMILY; KERATECTOMY; ARTHRITIS AB PURPOSE. Several members of the matrix metalloproteinase (MMP) group have been identified in the rat cornea during corneal mound healing. The aim of the present study was to identify additional members of the MMP gene family in the rat cornea and localize the expression of membrane type-1 matrix metalloproteinase (MT1-MMP; MMP-14) and collagenase III (MMP-13) in normal and wounded corneas. METHODS. Adult rats underwent laser keratectomy on the right eye. Unwounded left eyes were normal controls. Corneas were collected and processed at different times post-wounding. Reverse transcription-polymerase chain reaction (RT-PCR) and DNA sequencing were used to discover the MMP genes expressed in the corneas, In situ hybridization was performed to localize the mRNA expression of MMP-14 and MMP-13. RESULTS. MMP-13 mRNA was detected in epithelial cells of wounded corneas, but not in normal controls; MMP-14 was found in both normal and wounded corneas, MMP-14 mRNA was expressed predominantly in the stromal keratocytes and rarely in the basal epithelial cells in normal and wounded corneas. MMP-13 mRNA was localized exclusively to basal cells of the epithelium at the wounded area from 6 hours to 3 days after wounding. CONCLUSIONS. MMP-14 and MMP-13 expression in rat corneas parallels that of gelatinases A and B, respectively. MMP-13 may play an important role in the gelatinase B-associated proteolytic cascade that allows rapid turnover of the extracellular matrix (ECM) components during corneal wound healing. MMP-14 may contribute to removing abnormal ECM components through activation of gelatinase A in rat corneas. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea Serv, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu FU NEI NIH HHS [EY10101] NR 31 TC 87 Z9 88 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2000 VL 41 IS 10 BP 2894 EP 2899 PG 6 WC Ophthalmology SC Ophthalmology GA 350FA UT WOS:000089089100010 PM 10967042 ER PT J AU Dryja, TP McEvoy, JA McGee, TL Berson, EL AF Dryja, TP McEvoy, JA McGee, TL Berson, EL TI Novel rhodopsin mutations Gly114Val and Gln184Pro in dominant retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID STRAND CONFORMATION POLYMORPHISM; STATIONARY NIGHT BLINDNESS; POINT MUTATIONS; GENE; FAMILIES AB PURPOSE. To identify mutations in the rhodopsin gene in North American patients with autosomal dominant retinitis pigmentosa (ADRP) and to measure the proportion of cases with rhodopsin mutations. METHODS. Single-strand conformation polymorphism (SSCP) analysis and direct genomic sequencing were used to evaluate the coding region and intron splice sites of the rhodopsin gene for mutations in 91 unrelated patients. RESULTS. Nineteen patients heterozygously carried a missense change in the rhodopsin gene (six with Pro23His, two with Pro347Leu, and one each with Thr17Met, Phe45Leu, Gly51Arg, Gly89Asp, Gly114Val, Arg135Trp, Pro171Leu, Gln184Pro, Phe220Leu, Ser297Arg, and Pro347Thr). All these missense changes were previously reported as causes for ADRP except for Gly114Val. Gln184Pro, and Phe220Leu, which were evaluated further by examining the relatives of index patients. The Gly114Val and Gln184Pro alleles cosegregated with ADRP as expected if they were pathogenic. Phe220Leu did not, indicating that it is not a cause of ADRP. CONCLUSIONS. Summation of the results of cases in this study with those of 272 unrelated cases of ADRP previously evaluated by our group shows that 90 of 363 (25%) of cases were caused by rhodopsin mutations. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RP Dryja, TP (reprint author), 243 Charles St, Boston, MA 02114 USA. EM dryja@helix.mgh.harvard.edu FU NEI NIH HHS [EY00169, EY11655, EY08683] NR 19 TC 63 Z9 69 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2000 VL 41 IS 10 BP 3124 EP 3127 PG 4 WC Ophthalmology SC Ophthalmology GA 350FA UT WOS:000089089100041 PM 10967073 ER PT J AU Swartz, MN AF Swartz, MN TI Eliminating tuberculosis: Opportunity knocks twice SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Swartz, MN (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD FAL PY 2000 VL 17 IS 1 BP 39 EP 42 PG 4 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA 397RJ UT WOS:000166709100035 ER PT J AU Ma, QF Anderson, DJ Fritzsch, B AF Ma, QF Anderson, DJ Fritzsch, B TI Neurogenin 1 null mutant ears develop fewer, morphologically normal hair cells in smaller sensory epithelia devoid of innervation SO JARO LA English DT Article DE proneuronal genes; ear development; ganglion cell development; inner ear efferents; bHLH genes ID INNER-EAR; NERVOUS-SYSTEM; CHICK-EMBRYOS; MICE; GANGLIA; NEURONS; EXPRESSION; EFFERENTS; FIBERS; TRKB AB The proneuronal gene neurogenin 1 (ngn1) is essential for development of the inner-ear sensory neurons that are completely absent in ngn1 null mutants. Neither afferent, efferent, nor autonomic nerve fibers were detected in the ears of ngn1 null mutants. We suggest that efferent and autonomic fibers are lost secondarily to the absence of afferents. In this article we show that ngn1 null mutants develop smaller sensory epithelia with morphologically normal hair cells. In particular, the saccule is reduced dramatically and forms only a small recess with few hair cells along a duct connecting the utricle with the cochlea. Hair cells of newborn ngn1 null mutants show no structural abnormalities, suggesting that embryonic development of hair cells is independent of innervation. However, the less regular pattern of dispersal within sensory epithelia may be caused by some effects of afferents or to the stunted growth of the sensory epithelia. Tracing of facial and state-acoustic nerves in control and ngn1 null mutants showed that only the distal, epibranchial, placode-derived sensory neurons of the geniculate ganglion exist in mutants. Tracing further showed that these geniculate ganglion neurons project exclusively to the solitary tract. In addition to the normal complement of facial branchial and visceral motoneurons, ngn1 null mutants have some trigeminal motoneurons and contralateral inner-ear efferents projecting, at least temporarily, through the facial nerve. These data suggest that some neurons in the brainstem (e.g., inner-ear efferents, trigeminal motoneurons) require afferents to grow along and redirect to ectopic cranial nerve roots in the absence of their corresponding sensory roots. C1 Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. CALTECH, Pasadena, CA 91125 USA. RP Fritzsch, B (reprint author), Creighton Univ, Dept Biomed Sci, 2500 Calif Plaza, Omaha, NE 68178 USA. OI Fritzsch, Bernd/0000-0002-4882-8398 FU NIDCD NIH HHS [2P01 DC00215-14A1] NR 53 TC 175 Z9 182 U1 1 U2 6 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO JI JARO PD SEP PY 2000 VL 1 IS 2 BP 129 EP 143 DI 10.1007/sl01620010017 PG 15 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 425FA UT WOS:000168279000003 PM 11545141 ER PT J AU Trujillo, JR Goletiani, NV Bosch, I Kendrick, C Rogers, RA Trujillo, EB Essex, M Brain, JD AF Trujillo, JR Goletiani, NV Bosch, I Kendrick, C Rogers, RA Trujillo, EB Essex, M Brain, JD TI T-tropic sequence of the V3 loop is critical for HIV-1 infection of CXCR4-positive colonic HT-29 epithelial cells SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1V3; CXCR4; colonic cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; GALACTOSYL CERAMIDE; TYPE-1 INFECTION; AIDS VIRUS; RECEPTOR; DOMAIN; GP120; ENTRY; LINE; PHENOTYPE AB Some colonic and neuronal cells which are CD4(-) but galactosyl ceramide-positive are susceptible to infection with HIV-1. We have previously shown that the T-cell tropic V3 loop of HIV-1 gp120 serves as a primary viral determinant for infectivity of CD4- neuronal cells. However, the nature of the V3 loop of HIV-1 needed for infection and the V3 loop's interaction with coreceptors on colonic epithelial cells have not been fully analyzed. By using HIV-1 molecular clones, we show that the T-cell tropic V3 domain is critical for HIV-1 infection of colonic HT-29 epithelial cells. Because T-cell tropic HIV-1 can use CXCR4 as a coreceptor in T cells, we set out to determine the role of CXCR4 during infection of HT-29 cells. Using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunostaining, we show that these epithelial cells of colonic origin express the chemokine receptor CXCR4. Importantly, antibody against CXCR4 or a neutralizing antibody against HIV-1 gp120 V3 loop blocks T-cell tropic HIV-1 entry into MT-29 cells. These data indicate that the V3 loop of HIV-1 and the chemokine receptor CXCR4 are both critical for HIV-1 infection of colonic MT-29 epithelial cells. An HIV-1 T-tropic virus may be responsible for the infection of human colonic epithelial cells in vivo. C1 Harvard Univ, Sch Publ Hlth, Physiol Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Metab Support Serv, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Trujillo, JR (reprint author), Harvard Univ, Sch Publ Hlth, Physiol Program, Dept Environm Hlth, 665 Huntington Ave,1-1304, Boston, MA 02115 USA. FU NCI NIH HHS [CA39805]; NHLBI NIH HHS [P01 HL43510] NR 48 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD SEP 1 PY 2000 VL 25 IS 1 BP 1 EP 10 DI 10.1097/00126334-200009010-00001 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 373FB UT WOS:000165276800001 PM 11064498 ER PT J AU Stein, MD Cunningham, WE Nakazono, T Asch, S Turner, BJ Crystal, S Andersen, RM Zierler, S Bozzette, SA Shapiro, TF AF Stein, MD Cunningham, WE Nakazono, T Asch, S Turner, BJ Crystal, S Andersen, RM Zierler, S Bozzette, SA Shapiro, TF CA HIV Cost Serv Utilization Study Co TI Care of vaginal symptoms among HIV-infected women SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE vaginal symptoms; gynecologic manifestations; vaginitis; sexually transmitted diseases ID IMMUNODEFICIENCY-VIRUS INFECTION; NATIONAL PROBABILITY SAMPLES; LOW-PREVALENCE DISEASES; NORTH-AMERICAN WOMEN; BACTERIAL VAGINOSIS; SERVICES UTILIZATION; UNITED-STATES; ASSOCIATION; HEALTH; FLORA AB Objective: Gynecologic disease is common in HIV-infected women. We examine the sociodemographic, clinical, and provider factors associated with the care of women with vaginal symptoms. Methods: Women enrolled in the HIV Cost and Services Utilization Study (HCSUS), a nationally representative probability sample of HIV-infected adults, were interviewed between January 1996 and April 1997. Women with vaginal symptoms who sought medical attention were asked, "Did your health care provider examine your vaginal area?" Women were also asked if they received medication for their symptoms. Results: Among 154 women with vaginal symptoms, 127 sought care for their symptoms. Of those who sought care, 48% saw a gynecologist and 52% sought care from nongynecologists, most often their usual HIV care provider. Women who saw a gynecologist for their symptoms were more likely to have received a pelvic examination (92% versus 76%; p = .06) and vaginal fluid collection (98% versus 88%; p = .06) than those who saw their regular HIV provider. Fifteen percent of women received medication for their symptoms without having a pelvic examination; gynecologists were less likely to prescribe without an examination (8% versus 21%; p = .12). Conclusion: Gynecologists are more likely to provide adequate care of vaginal symptoms among HIV-infected women than nongynecologists who were HIV care providers. This specialty difference is consistent with quality of care studies for other medical conditions, but the potential gynecologic complications of inadequate evaluation and treatment warrants further investigation. C1 Brown Univ, Div Gen Med, Providence, RI 02912 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Div Gen Med & Hlth Serv Res, Los Angeles, CA USA. W Los Angles Vet Affairs Hosp, Los Angeles, CA USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Rutgers State Univ, Inst Hlth, AIDS Res Grp, New Brunswick, NJ 08903 USA. Brown Univ, Sch Med, Dept Community Hlth, Providence, RI 02912 USA. RAND Corp, Hlth Sci Program, Santa Monica, CA USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. RP Stein, MD (reprint author), Rhode Isl Hosp, Div Gen Internal Med, 593 Eddy St, Providence, RI 02903 USA. NR 27 TC 3 Z9 3 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD SEP 1 PY 2000 VL 25 IS 1 BP 51 EP 55 DI 10.1097/00126334-200009010-00007 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 373FB UT WOS:000165276800007 PM 11064504 ER PT J AU Bowden, CL Lecrubier, Y Bauer, M Goodwin, G Greil, W Sachs, G von Knorring, L AF Bowden, CL Lecrubier, Y Bauer, M Goodwin, G Greil, W Sachs, G von Knorring, L TI Maintenance therapies for classic and other forms of bipolar disorder SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article; Proceedings Paper CT 1st International Exchange on Bipolar Disorders Meeting (IEBD) CY FEB 01-04, 1998 CL BARCELONA, SPAIN DE rapid cycling bipolar disorder; maintenance treatment; divalproex sodium; lithium; carbamazepine; neuroleptics ID MANIC-DEPRESSIVE ILLNESS; PRELIMINARY DOUBLE-BLIND; TERM LITHIUM TREATMENT; PROSPECTIVE FOLLOW-UP; PROPHYLACTIC LITHIUM; CONTROLLED TRIAL; MOOD DISORDERS; I DISORDER; CARBAMAZEPINE; EFFICACY AB The progressive, episodic and chronic nature of bipolar disorder dictates the need for lifelong pharmacological maintenance treatment in the majority of patients. Prophylaxis should be considered after a single episode of severe mania or after more than one episode of hypomania in bipolar II disorder, although some clinicians now consider an episode of either sufficient to warrant maintenance therapy. Lithium is efficacious as maintenance therapy, but is not as highly effective as early studies initially suggested (abrupt discontinuation of lithium probably increased placebo relapse figures). Rates of premature discontinuation of lithium are high. Divalproex sodium is used frequently in the USA and Canada for long-term treatment for bipolar disorder but an insufficient number of controlled trials have been published to assess adequately its role. Carbamazepine is also employed in maintenance treatment. Randomized studies indicate it is superior to placebo but somewhat less effective than lithium. Augmentation of any of these drugs with another mood stabilizer, an antipsychotic, or electroconvulsive therapy appears to be effective, although there are few controlled studies. Design issues that need consideration in order to achieve meaningful data are discussed. A severe manifestation of bipolar disorder is rapid cycling. It is often induced by antidepressants, although this association frequently goes unrecognized. Patients with a rapid cycling course of illness are difficult to treat effectively. Although rapid cycling is often associated with poor response to lithium, there have been no randomized, controlled treatment studies. Based on open studies and expert panel recommendations, the International Exchange on Bipolar Disorder (LEBD) recommended initial treatment with divalproex sodium, with subsequent addition of other mood stabilizers, antipsychotics or thyroid supplementation as necessary. Combination treatments are frequently required for optimal response in these patients. (C) 2000 Elsevier Science B.V. All lights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Hosp La Salpetriere, Paris, France. Mental Hlth & Behav Sci Serv, Providence, RI USA. Univ Oxford, Dept Psychiat, Oxford, England. Psychiat Privatklin Sanatorium, Zurich, Switzerland. Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. Univ Uppsala Hosp, Dept Psychiat, S-75185 Uppsala, Sweden. RP Bowden, CL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI von Knorring, Lars/D-2125-2010 NR 81 TC 24 Z9 24 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP PY 2000 VL 59 SU 1 BP S57 EP S67 DI 10.1016/S0165-0327(00)00179-8 PG 11 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 401PA UT WOS:000166935400005 PM 11121827 ER PT J AU Binkley, KE Davis, A AF Binkley, KE Davis, A TI Clinical, biochemical, and genetic characterization of a novel estrogen-dependent inherited form of angioedema SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE hereditary angioedema; estrogen; Cl inhibitor ID HEREDITARY ANGIONEUROTIC-EDEMA; FACTOR-XII; C1 INHIBITOR; ORAL-CONTRACEPTIVES; WOMEN AB Background: Two genetic forms of hereditary angioedema (HAE) are currently recognized. Both are transmitted in an autosomal dominant manner and are characterized by recurrent episodes of localized angioedema. Involvement of the gut leads to episodes of severe abdominal pain, and laryngeal involvement can lead to airway obstruction and even death. One type results from heterozygosity for a nonexpressed C1 inhibitor allele, and the other results from heterozygosity for a nonfunctional C1 inhibitor allele. Objective: This report identifies a third type of HAE, with a unique estrogen-dependent phenotype. Methods: Detailed medical histories were obtained from family members, and a pedigree was constructed to ascertain the mode of inheritance. Determination of serum complement factors, C1 inhibitor protein, C1 inhibitor function, coagulation factor XII, plasma prekallikrein, high molecular weight kininogen, and selected DNA sequences were performed in affected members by using standard assays. Results: Episodes of angioedema were clinically indistinguishable from those associated with previously described forms of HAE; however, these occurred only during pregnancy or the use of exogenous estrogens. Patients were otherwise asymptomatic, except for one patient who had acetyl salicylic acid/nonsteroidal anti-inflammatory drug-related angioedema later in life. History was available for members spanning 4 generations, and affected individuals were identified in 3 generations. Of 46 family members, phenotype could be determined in 13 members. Seven were affected, and 6 were not. One male of undetermined phenotype was an obligate carrier. The unique estrogen-dependent nature of the phenotype means that the status of several members in the third and fourth generation remains unknown. The disorder appears to be transmitted in an autosomal dominant fashion, although other modes of inheritance cannot be excluded entirely. C1 inhibitor protein, C1 inhibitor function, C2, C4, C1q, coagulation factor XII, prekallikrein, and high molecular kininogen were normal in 3 affected family members during asymptomatic periods. DNA sequencing revealed no abnormality in 3 patients in the coding region of the gene encoding C1 inhibitor or in the 5' flanking regions of the genes encoding C1 inhibitor and factor XII, Conclusions: This family appears to have a novel form of inherited angioedema that does not result from CI inhibitor deficiency or dysfunction, The phenotype is uniquely estrogen dependent. Implications for diagnosis and treatment are discussed. Further studies are required to define the exact nature of the genetic abnormality involved. C1 Univ Toronto, St Michaels Hosp, Div Clin Immunol & Allergy, Toronto, ON M5B 1W8, Canada. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Binkley, KE (reprint author), 30 St Clair Ave W,Suite 201, Toronto, ON M4V 3A1, Canada. FU NICHD NIH HHS [HD22082, HD337327] NR 23 TC 148 Z9 150 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2000 VL 106 IS 3 BP 546 EP 550 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 356YN UT WOS:000089471900019 PM 10984376 ER PT J AU Conhaim, RL Rodenkirch, LA Watson, KE Harms, BA AF Conhaim, RL Rodenkirch, LA Watson, KE Harms, BA TI Acellular hemoglobin solution enters compressed lung capillaries more readily than red blood cells SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE DCLHb; blood substitutes; plasma volume expanders; pulmonary microcirculation; pulmonary perfusion; zone I lung ID PULMONARY VASCULAR PERFUSION; LIGHT-MICROSCOPY; ELECTRON; ZONE-1 AB High lung inflation pressures compress alveolar septal capillaries, impede red cell transit, and interfere with oxygenation. However, recently introduced acellular hemoglobin solutions may enter compressed lung capillaries more easily than red blood cells. To test this hypothesis, we perfused isolated rat lungs with fluorescently labeled diaspirin cross-linked hemoglobin (DCLHb; 10%) and or autologous red cells (hematocrit, 20). Septal capillaries were compressed by setting lung inflation pressure above vascular pressures (zone 1). Examination by confocal microscopy showed that DCLHb was distributed throughout alveolar septa. Furthermore, this distribution was not affected by adding red blood cells to the perfusate. We estimated the maximum acellular hemoglobin mass within septa to be equivalent to that of 15 red blood cells. By comparison, we found an average of 2.7 +/- 4.6 red cells per septum in zone 1. These values increased to 30.4 +/- 25.8 and 50.4 +/- 22.1 cells per septum in zones 2 and 3, respectively. We conclude that perfusion in zone 1 with a 10% acellular hemoglobin solution may increase the hemoglobin concentration per septum up to fivefold compared with red cell perfusion. C1 William S Middleton Mem Vet Hosp, Dept Surg, Madison, WI 53705 USA. Univ Wisconsin, Dept Surg, Madison, WI 53705 USA. RP Conhaim, RL (reprint author), William S Middleton Mem Vet Hosp, Dept Surg, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NHLBI NIH HHS [HL49985] NR 20 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD SEP PY 2000 VL 89 IS 3 BP 1198 EP 1204 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 352DX UT WOS:000089200200044 PM 10956369 ER PT J AU Eto, H Yoon, SS Bode, BP Kamidono, S Makino, K Saya, H Nakamura, H Tanabe, KK AF Eto, H Yoon, SS Bode, BP Kamidono, S Makino, K Saya, H Nakamura, H Tanabe, KK TI Mapping and regulation of the tumor-associated epitope recognized by monoclonal antibody RS-11 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSITIONAL CELL CARCINOMAS; O-LINKED GLYCOSYLATION; BREAST-CANCER; INTERMEDIATE FILAMENTS; EXPRESSION PATTERNS; MOLECULAR-CLONING; HUMAN KERATIN-18; CYTOKERATIN; ANTIGEN; PHOSPHORYLATION AB We have previously described a rat monoclonal antibody, RS-ll, which recognizes a tumor-associated antigen common to several species. In the present study, we have cloned and characterized the antigen recognized by RS-11, We screened a phage expression library prepared from HeLa cDNA and identified a clone that reacts with RS-ll, DNA sequence analysis revealed that this clone contains sequences of keratin 18 (nucleotides 568-1196). We constructed several glutathione S-transferase fusion proteins and synthetic peptides based on this DNA sequence analysis and examined their reactivity with RS-ll to accurately map the RS-ll epitope. We determined that the epitope resides within a region of seven amino acids on the alpha-helix 2B domain of keratin 18 in which two amino acids (Leu(366) and Lys(370)) are completely conserved among intermediate filaments as well as other keratin members that are immunoreactive with RS-ll, These two residues are sequentially discontinuous but spatially adjacent, The RS-ll epitope is constitutively present in human primary cultured hepatocytes; however, its immunoreactivity with RS-11 is upregulated by malignant transformation or stimulation with either epidermal growth factor or transforming growth factor alpha. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Kobe Univ, Sch Med, Dept Urol, Kobe, Hyogo 650, Japan. Kumamoto Univ, Sch Med, Dept Tumor Genet & Biol, Kumamoto 860, Japan. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Cox 626, Boston, MA 02114 USA. RI Saya, Hideyuki/J-4325-2013 FU NCI NIH HHS [CA64454, CA71345]; NIDDK NIH HHS [DK43351] NR 42 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 1 PY 2000 VL 275 IS 35 BP 27075 EP 27083 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 351EL UT WOS:000089144800056 PM 10801882 ER PT J AU Chin, KR Kharrazi, FD Miller, BS Mankin, HJ Gebhardt, MC AF Chin, KR Kharrazi, FD Miller, BS Mankin, HJ Gebhardt, MC TI Osteochondromas of the distal aspect of the tibia or fibula - Natural history and treatment SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: There is little information on the natural history or treatment of osteochondromas arising from the distal aspect of either the tibia or the fibula. It is believed that there is a risk of deformation of the ankle if these exostoses are left untreated or if the physis or neurovascular structures are injured during operative intervention. Methods: We reviewed the records of twenty-three patients who had been treated for osteochondroma of the distal aspect of the tibia or fibula between 1980 and 1996. Four of the patients had hereditary multiple cartilaginous exostoses. There were seventeen male and six female patients, and the average age at the time of presentation was sixteen years (range, eight to forty-eight years). Results: Preoperative radiographs showed evidence of plastic deformation of the fibula in eleven patients who had a large osteochondroma. Four patients elected not to have an operation. The tumor was excised in nineteen patients. Postoperatively, all nineteen patients had a Musculoskeletal Tumor Society score of 100 percent for function of the lower extremity with pain-free symmetrical and unrestricted motion of the ankle at the latest follow-up examination. Partial remodeling of the tibia and fibula gradually diminished the asymmetry of the ankles in all nineteen operatively managed patients; however; the remodeling was most complete in the younger patients. Pronation deformities of the ankle did not change after excision of the tumor. Complications of operative treatment included four recurrences (only three of which were symptomatic), one sural neuroma, one superficial wound infection, and one instance of growth arrest of the distal aspects of the tibia and fibula. Conclusions: Osteochondromas of the distal and lateral aspects of the tibia were more often symptomatic than those of the distal aspect of the fibula; they most commonly occurred in the second decade of life with ankle pain, a palpable mass, and unrestricted ankle motion. Untreated or partially excised lesions in skeletally immature patients may become larger and cause plastic deformation of the tibia and fibula and a pronation deformity of the ankle. Ideally operative intervention should be delayed until skeletal maturity, but, in symptomatic patients, partial excision preserving the physis may be necessary for the relief of symptoms and the prevention of progressive ankle deformity. However, partial excision is associated with a high rate of recurrence, so a close follow-up is required. Skeletally mature patients who are symptomatic mag require excision of the tumor. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Serv, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Chin, KR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Oncol Serv, Gray Bldg,Room 606,55 Fruit St, Boston, MA 02114 USA. NR 25 TC 29 Z9 32 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD SEP PY 2000 VL 82A IS 9 BP 1269 EP 1278 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 354BC UT WOS:000089309100007 PM 11005518 ER PT J AU Aarts, MM Guo, J Bringhurst, R Henderson, JE AF Aarts, MM Guo, J Bringhurst, R Henderson, JE TI PTHrP rescues serum-deprived chondrocytes from apoptosis by promoting quiescence through mechanisms linked to translational control. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Sir Mortimer B Davis Jewish Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA F469 BP S232 EP S232 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400380 ER PT J AU Aikawa, T Segre, GV Lee, K AF Aikawa, T Segre, GV Lee, K TI FGF2 inhibits chondrocytic proliferation by activating retinoblastoma protein (Rb) through inducing p21 and inactivation of cdk-2. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Endocrine Unit, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SA131 BP S257 EP S257 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400473 ER PT J AU Allemann, F Yates, KE Glowacki, J AF Allemann, F Yates, KE Glowacki, J TI Preservation of chondroblastic gene expression signature in 3D culture devices. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M042 BP S468 EP S468 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401336 ER PT J AU Bastepe, M Lane, AH Juppner, H AF Bastepe, M Lane, AH Juppner, H TI Pseudohypoparathyroidism-type Ib in a patient with paternal uniparental disomy/maternal deletion of chromosome 20q. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Endocrine Unit, Boston, MA USA. SUNY Stony Brook, Dept Pediat, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU119 BP S360 EP S360 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400892 ER PT J AU Bringhurst, FR Singh, R AF Bringhurst, FR Singh, R TI Activation of phospholipase D by transfected PTH/PTHrP receptors in LLCPK1 cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SA462 BP S319 EP S319 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400724 ER PT J AU Calvi, LM Sims, NA Knight, MC Hunzelman, JL Saxton, JM Giovannetti, A Baron, R Kronenberg, HM Schipani, E AF Calvi, LM Sims, NA Knight, MC Hunzelman, JL Saxton, JM Giovannetti, A Baron, R Kronenberg, HM Schipani, E TI In vivo targeted expression of a constitutively active PTH/PTHrP receptor has differential effects on trabecular and cortical bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1079 BP S158 EP S158 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400080 ER PT J AU Chung, U Wei, W Schipani, E McMahon, A Kronenberg, H AF Chung, U Wei, W Schipani, E McMahon, A Kronenberg, H TI Indian hedgehog couples chondrogenesis to osteogenesis in endochondral bone development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1216 BP S192 EP S192 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400217 ER PT J AU Chung, U Wei, W Schipani, E Hunzelman, J Weinstein, L Kronenberg, H AF Chung, U Wei, W Schipani, E Hunzelman, J Weinstein, L Kronenberg, H TI In vivo function of stimulatory G protein (Gs) in the growth plate. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NIH, NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1149 BP S175 EP S175 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400150 ER PT J AU Cole, JA Bringhurst, F AF Cole, JA Bringhurst, F TI PTH and P42/P44 MAPK activation in OK cells and LLC-PK1 cells expressing different densities of the human PTH1 receptor (PTH1R). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Missouri, Columbia, MO USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SA452 BP S318 EP S318 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400718 ER PT J AU Divieti, P Juppner, H Bringhurst, FR AF Divieti, P Juppner, H Bringhurst, FR TI Ligand determinants of binding to skeletal receptors specific for the carboxyl-terminus of intact PTH(1-84). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU466 BP S444 EP S444 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401239 ER PT J AU Divieti, P Hamirani, S Bringhurst, FR AF Divieti, P Hamirani, S Bringhurst, FR TI Intact PTH(1-84) induces apoptosis in PTH1R(-/-) osteocytic cells via the carboxyl-terminal PTH receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA F457 BP S232 EP S232 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400378 ER PT J AU Gao, Y Segre, GV AF Gao, Y Segre, GV TI Bone cell-specific overexpression of constitutively active G alpha q suppresses osteoblastic differentiation and results in dwarfism and osteoporosis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1001 BP S139 EP S139 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400002 ER PT J AU Gensure, RC Gardella, TJ Juppner, H AF Gensure, RC Gardella, TJ Juppner, H TI Sites of interaction between the carboxy-terminus of PTHrP(1-36) and the PTH/PTHrP receptor. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M460 BP S565 EP S565 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401751 ER PT J AU Ghosh-Choudhury, N Ghosh-Choudhury, G Woodruff, K Bsoul, S Nishimura, R Qi, W Celeste, A Abboud, S AF Ghosh-Choudhury, N Ghosh-Choudhury, G Woodruff, K Bsoul, S Nishimura, R Qi, W Celeste, A Abboud, S TI Identification of a Smad binding element (SBE) in BMP-3 responsive CSF-1 gene promoter: A mechanism of BMP-2-mediated transregulation of osteoclastogenesis during bone remodeling. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, GRECC, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Osaka Univ, Suita, Osaka, Japan. Genet Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA F027 BP S203 EP S203 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400263 ER PT J AU Gori, F Demay, MB AF Gori, F Demay, MB TI Identification of a novel BMP-2 regulated gene in an in vitro model of endochondral bone formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU036 BP S340 EP S340 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400809 ER PT J AU Guo, J Chung, U Bringhurst, RF Kronenberg, HM AF Guo, J Chung, U Bringhurst, RF Kronenberg, HM TI Failure of phospholipase C activation via the PTH/PTHrP receptor leads to abnormalities in embryonic bone development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1053 BP S152 EP S152 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400054 ER PT J AU Hershey, CL Weilbaecher, KN Takemoto, CM Horstmann, M Young, T Price, E Fisher, DE AF Hershey, CL Weilbaecher, KN Takemoto, CM Horstmann, M Young, T Price, E Fisher, DE TI Age-related roles for microphthalmia (Mitf) and TFE3 during osteoclast development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M243 BP S514 EP S514 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401535 ER PT J AU Hoare, SRJ Gardella, TJ Usdin, TB AF Hoare, SRJ Gardella, TJ Usdin, TB TI Measuring ligand affinity for the G-protein-coupled and uncoupled states of the parathyroid hormone 1 (PTH1) receptor: Implications for the development of therapeutic ligands. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SA461 BP S319 EP S319 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400723 ER PT J AU Jones, G Byford, V Sakai, Y Demay, M AF Jones, G Byford, V Sakai, Y Demay, M TI Dramatic reduction of 1,25-(OH)(2)D-3 catabolism in keratinocytes from VDR-null mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Queens Univ, Kingston, ON, Canada. Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1172 BP S181 EP S181 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400173 ER PT J AU Jonsson, KB Mannstadt, M Ljunggren, O Juppner, H AF Jonsson, KB Mannstadt, M Ljunggren, O Juppner, H TI Aqueous extracts from tumors causing oncogenic osteomalacia inhibit phosphate-uptake and stimulate cAMP accumulation in opossum kidney cells: Evidence that both activities are related to distinct molecules. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Uppsala Univ, Dept Med Sci, Uppsala, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU104 BP S356 EP S356 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400877 ER PT J AU Kacena, MA Shivdasani, RA Gundberg, CM White, DW Chen, Y Orkin, SH Horowitz, MC AF Kacena, MA Shivdasani, RA Gundberg, CM White, DW Chen, Y Orkin, SH Horowitz, MC TI NF-E2 and GATA-1 deficient mice, new models of bone formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. Dana Farber Canc Inst, Boston, MA USA. Millennium Pharmaceut, Cambridge, MA USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1048 BP S151 EP S151 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400049 ER PT J AU Kobayashi, T Chung, U Katagiri, T Goad, D Lanske, B Kronenberg, HM AF Kobayashi, T Chung, U Katagiri, T Goad, D Lanske, B Kronenberg, HM TI Mice with decreased expression of PTH/PTHrP receptor exhibit novel growth plate phenotype. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M459 BP S565 EP S565 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401750 ER PT J AU Kobayashi, T Chung, U Katagiri, T Goad, D Lanske, B Kronenberg, HM AF Kobayashi, T Chung, U Katagiri, T Goad, D Lanske, B Kronenberg, HM TI Loss of PTH/PTHrP receptor signaling in osteoblasts increases bone mass. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1046 BP S150 EP S150 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400047 ER PT J AU Kondo, H Guo, J Bringhurst, FR AF Kondo, H Guo, J Bringhurst, FR TI PTH regulates expression of ODF and OPG by different signaling pathway in murine marrow stromal cells. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU470 BP S445 EP S445 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401243 ER PT J AU Kuizon, BD Salusky, IB Sanchez, CP Cambay, E Jueppner, H Goodman, WG AF Kuizon, BD Salusky, IB Sanchez, CP Cambay, E Jueppner, H Goodman, WG TI Diminished angiogenesis and delayed chondrocyte apoptosis in growth plate cartilage of calcium-supplemented rats with renal failure. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Wisconsin, Sch Med, Madison, WI USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M041 BP S467 EP S467 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401335 ER PT J AU Li, Y Deng, W Liang, Y Shimizu, K Chen, W AF Li, Y Deng, W Liang, Y Shimizu, K Chen, W TI Cathepsin K-deficient mice exhibit osteopetrosis, craniofacial dysphasia, and acroosteolysis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU227 BP S386 EP S386 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401000 ER PT J AU MacLean, HE Schipani, E Zhang, P Kronenberg, HM AF MacLean, HE Schipani, E Zhang, P Kronenberg, HM TI Characterizing the role of the cyclin dependent kinase inhibitor p57(Kip2) in growth plate chondrocytes in vivo. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Jewish Med & Res Ctr, Cell Biol Program, Denver, CO USA. Natl Jewish Med & Res Ctr, Dept Pharmacol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1188 BP S185 EP S185 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400189 ER PT J AU Motyckova, G Weilbaecher, K Fisher, DE AF Motyckova, G Weilbaecher, K Fisher, DE TI Microphthalmia and TFE3 transcription factors regulate cathepsin K expression in osteoclasts. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU226 BP S386 EP S386 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400999 ER PT J AU Peters, JH Carsons, S McDougall, S Yoshida, M Ko, F Hahn, TJ AF Peters, JH Carsons, S McDougall, S Yoshida, M Ko, F Hahn, TJ TI Characterization of N-terminal sequence-containing species of fibronectin in synovial fluid in osteoarthritis and rheumatoid arthritis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Sacramento VA Med Ctr, Mather, CA USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. W Los Angeles VA Healthcare Ctr, GRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU059 BP S345 EP S345 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400832 ER PT J AU Qian, J Colbert, MC Witte, DP Gruenstein, EI Lanske, B Kronenberg, HM Clemens, TL AF Qian, J Colbert, MC Witte, DP Gruenstein, EI Lanske, B Kronenberg, HM Clemens, TL TI Abrupt mid-gestational death of mice lacking the PTH/PTHrP receptor: Evidence for a role of PTHrP in cardiovascular development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Cincinnati, Div Endocrinol, Cincinnati, OH USA. Childrens Hosp, Med Ctr, Div Mol Cardiovasc Biol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Div Pathol, Cincinnati, OH 45229 USA. Univ Cincinnati, Cincinnati, OH USA. Max Planck Inst Biochem, D-82152 Martinsried, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1108 BP S165 EP S165 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400109 ER PT J AU Reichel, H Roth, HJ Krug, A Gao, P Schmidt-Gayk, H John, MR AF Reichel, H Roth, HJ Krug, A Gao, P Schmidt-Gayk, H John, MR TI Correlation between a novel assay for full-length parathyroid hormone (PTH), intact PTH, tartrate-resistant acid phosphatase and bone alkaline phosphatase in adult hemodialysis patients. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Nephrol Ctr, Villingen Schwenningen, Germany. Lab Grp, Heidelberg, Germany. Scantibodies Lab, Santee, CA USA. Harvard Univ, Sch Med, Endocrine Unit, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU485 BP S448 EP S448 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401258 ER PT J AU Sakai, Y Demay, MB AF Sakai, Y Demay, MB TI Failure of anagen initiation in vitamin D receptor knockout mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA F503 BP S233 EP S233 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400384 ER PT J AU Shimizu, M Petroni, B Potts, JT Gardella, TJ AF Shimizu, M Petroni, B Potts, JT Gardella, TJ TI Evidence for functional interactions between residues in the 15-20 region of PTH and the region of the PTH-1 receptor containing the transmembrane domains and extracellular loops. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M463 BP S566 EP S566 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401754 ER PT J AU Shimizu, M Carter, PH Gardella, TJ AF Shimizu, M Carter, PH Gardella, TJ TI Analyzing the interaction between the N-terminal domain of PTH and the core region of the PTH-1 receptor using tethered PTH/PTH-1 receptor constructs. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1150 BP S176 EP S176 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400151 ER PT J AU Shin, HI Paola, D Bringhurst, FR Taga, T Suda, T Kronenberg, H AF Shin, HI Paola, D Bringhurst, FR Taga, T Suda, T Kronenberg, H TI gp130 is necessary for full PTH-induced osteoclastic differentiation and activation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02115 USA. Tokyo Med & Dent Univ, Tokyo, Japan. Showa Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA F237 BP S218 EP S218 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400323 ER PT J AU Soegiarto, DW Kiachopoulos, S Schipani, E Barkey, W Juppner, H Lanske, BK AF Soegiarto, DW Kiachopoulos, S Schipani, E Barkey, W Juppner, H Lanske, BK TI Early lethality of PTH/PTHrP receptor (-/-) mice is only partially rescued by expressing a constitutively active "Jansen" receptor (H223R mutant) under the control of the type II collagen promoter. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Max Planck Inst Biochem, D-82152 Martinsried, Germany. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1187 BP S185 EP S185 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400188 ER PT J AU Sooy, K Melzi, R Demay, MB AF Sooy, K Melzi, R Demay, MB TI Characterization of a silencer motif in the rat osteocalcin gene. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU167 BP S372 EP S372 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400940 ER PT J AU Tawfeek, HA Oian, F Abou-Samra, AB AF Tawfeek, HA Oian, F Abou-Samra, AB TI Phosphorylation-deficient PTH/PTHrP receptors are more sensitive to PTH stimulation than the wild type receptors SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M462 BP S566 EP S566 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401753 ER PT J AU Vallarta-Ast, N Krueger, D Binkley, N AF Vallarta-Ast, N Krueger, D Binkley, N TI Bone mass measurement of the proximal femur and ultadistal radius best identifies osteoporosis in male veterans. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 William S Middleton Mem Vet Adm Med Ctr, Dept Radiol, Madison, WI 53705 USA. Univ Wisconsin, Inst Aging, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SA347 BP S299 EP S299 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400644 ER PT J AU Weilbaecher, K Motyckova, G Takemoto, C Hemesath, T Huber, W Wells, A Hershey, C Xu, Y Fisher, DE AF Weilbaecher, K Motyckova, G Takemoto, C Hemesath, T Huber, W Wells, A Hershey, C Xu, Y Fisher, DE TI A helix-loop-helix transcription factor family links M-CSF signaling to osteoclast development. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Decode Genet, Reykjavik, Iceland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA F259 BP S220 EP S220 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400330 ER PT J AU Whitfield, JF Isaacs, RJ Chakravarthy, BR MacLean, S Morley, P Willick, GE Divieti, P Bringhurst, FR AF Whitfield, JF Isaacs, RJ Chakravarthy, BR MacLean, S Morley, P Willick, GE Divieti, P Bringhurst, FR TI Stimulation of protein kinase C activity by N-terminally truncated fragments of hPTH-(1-34) in cells expressing human PTH receptors. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU473 BP S446 EP S446 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401246 ER PT J AU William, L Abou-Samra, AB AF William, L Abou-Samra, AB TI SP1 and MAZ activate the U3 promoter of the rat parathyroid hormone/parathyroid hormone-related peptide receptor gene. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA M169 BP S497 EP S497 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898401462 ER PT J AU Woodland, ML Chafe, LL McDonald, KR Demay, MB Kovacs, CS AF Woodland, ML Chafe, LL McDonald, KR Demay, MB Kovacs, CS TI Ablation of the VDR minimally affects fetal-placental calcium metabolism and placental calcitropic gene expression. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Mem Univ Newfoundland, Fac Med, St Johns, NF, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA 1170 BP S181 EP S181 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400171 ER PT J AU Yamaguchi, DT Makhijani, N Tomin, E McDougall, S Lane, JM Hahn, TJ AF Yamaguchi, DT Makhijani, N Tomin, E McDougall, S Lane, JM Hahn, TJ TI Immunohistochemical localization of angiogenic growth factors and chemokines in fracture repair. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare System, GRECC, Los Angeles, CA USA. VA Greater Los Angeles Healthcare System, Res Serv, Los Angeles, CA USA. Hosp Special Surg, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU140 BP S365 EP S365 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400913 ER PT J AU Yates, KE Mizuno, S Glowacki, J AF Yates, KE Mizuno, S Glowacki, J TI Representational difference analysis of chondroinduced human dermal fibroblasts reveals upregulated cellular and cytoskeletal components. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Skeletal Biol Res Ctr, Charlestown, MA USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2000 VL 15 SU 1 MA SU041 BP S341 EP S341 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 346YJ UT WOS:000088898400814 ER PT J AU Ingelmo, C Frame, LH AF Ingelmo, C Frame, LH TI Mechanism for site-dependent differences in the shape of the resetting response curve in fixed barrier reentry SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE resetting response curves; reentry; site dependence; excitable gap; tachycardia; interval-dependent conduction; resetting ID VENTRICULAR-TACHYCARDIA; TRANSIENT ENTRAINMENT; TRICUSPID RING; EXCITABLE GAP; TERMINATION; CIRCUIT; INVITRO; MODEL AB Site Dependence of Resetting Response Curves. Introduction: We investigated whether the site of stimulation within a reentrant circuit affects the resetting response curve (RRC), RRCs are used to characterize the excitable gap of reentrant circuits, including the duration of the fully excitable gap and the presence of partially excitable tissue. Methods and Results: We reset proximal and distal to a site of interval-dependent conduction (IDC) in canine in vitro atrial tricuspid rings. Adjustable reentry allowed changes in the cycle length and direction of reentry, In nine preparations we reset 26 tachycardias, In the 16 tachycardias with one site of IDC, RRCs were significantly different when stimulating distal and proximal to a site of interval-dependent conduction. For the distal, curves, the duration of the eat portion was 42 +/- 26 msec greater (P < 0.001), the slope of the increasing portion was 0.20 +/- 0.17 less (P < 0.02), and the increase in the return cycle was 14 +/- 9 msec less (P < 0.001). These differences resulted from early activation of the site of IDC by the antidromic premature impulse when stimulating from distal sites. As a result, the coupling interval of the orthodromic impulse at the site of IDC was the same or greater than at the stimulation site. In 10 tachycardias with multiple sites of IDC, significant differences in the resetting responses did not occur even when the antidromic impulse penetrated one site of IDC. Conclusion: In a fixed anatomic barrier reentrant circuit with one site of IDC, resetting distal to this site misrepresents the properties of the excitable gap of the entire circuit. C1 Vet Affairs Med Ctr, Cardiol Sect, Philadelphia, PA 19104 USA. Univ Penn, Div Cardiovasc, Philadelphia, PA 19104 USA. RP Frame, LH (reprint author), Vet Affairs Med Ctr, Cardiol Sect, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL38386] NR 15 TC 5 Z9 5 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2000 VL 11 IS 9 BP 981 EP 989 DI 10.1111/j.1540-8167.2000.tb00170.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 356QH UT WOS:000089453600005 PM 11021468 ER PT J AU Trinkaus-Randall, V Kewalramani, R Payne, J Cornell-Bell, A AF Trinkaus-Randall, V Kewalramani, R Payne, J Cornell-Bell, A TI Calcium signaling induced by adhesion mediates protein tyrosine phosphorylation and is independent of pHi SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CORNEAL EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; INTRACELLULAR PH; HUMAN-PLATELETS; F-ACTIN; INTEGRIN; TRANSDUCTION; FIBROBLASTS; PP125(FAK) AB Our goal was to evaluate early signaling events that occur as epithelial cells make initial contact with a substrate and to correlate them with phosphorylation. The corneal epithelium was chosen to study signaling events that occur with adhesion because it represents a simple system in which the tissue adheres to a basal lamina, is avascular, and is bathed by a rear Film in which changes in the local Environment are hypothesized to alter signaling. To perform these experiments we developed a novel adhesion assay to capture the changes in intracellular Ca2+ and pH that occur as a cell makes its initial contact with a substrate. The first transient cytosolic Ca2+ peak was detected only as the cell made contact with the substrate and was demonstrated using fluorimetric assays combined with live cell imaging. We demonstrated that this transient Ca2+ peak always preceded a cytoplasmic alkalization. When the intracellular environment was modified, the initial response was altered. Pretreatment with 1,2-bis(o-aminophenoxy)ethane-N,N,N'N'-tetraacctic acid (BAPTA), an intracellular chelator, inhibited Ca2+ mobilization, whereas benzamil altered the duration of the oscillations. Thapsigargin caused an initial Ca2+ release followed by a long attenuated response. An inositol triphosphate analog induced a large initial response, whereas heparin inhibited Ca2+ oscillations. Inhibitors of tyrosine phosphorylation did not alter the initial mobilization of cytosolic Ca-2 but clearance of cytosolic Ca2+ was inhibited. Exposing corneal epithelial cells to BAPTA, benzamil, or thapsigargin also attenuated the phosphorylation of the focal adhesion protein paxillin. However, although heparin inhibited Ca2+ oscillations, it did not alter phosphorylation of paxillin. These studies demonstrate that the initial contact that a cell makes with a substrate modulates the intracellular environment, and that changes in Ca2+ mobilization can alter later signaling events such as the phosphorylation of specific adhesion proteins. These findings may have implications for wound repair and development. J. Cell. Physiol. 184:385-399, 2000. (C) 2000 Wiley-Liss, Inc. C1 Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Viatech Cognetix, Ivoryton, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Trinkaus-Randall, V (reprint author), Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. FU NEI NIH HHS [EY06000]; NIEHS NIH HHS [ES08470] NR 38 TC 14 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD SEP PY 2000 VL 184 IS 3 BP 385 EP 399 DI 10.1002/1097-4652(200009)184:3<385::AID-JCP14>3.0.CO;2-7 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 339RV UT WOS:000088492400014 PM 10911371 ER PT J AU Namura, S Nagata, I Kikuchi, H Andreucci, M Alessandrini, T AF Namura, S Nagata, I Kikuchi, H Andreucci, M Alessandrini, T TI Serine-threonine protein kinase Akt does not mediate ischemic tolerance after global ischemia in the gerbil SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE Akt; PI 3-kinase; ischemic preconditioning; global ischemia; gerbil ID PHOSPHORYLATION; ADENOSINE; DAMAGE; SIGNAL; BRAIN AB The protein kinase Akt/PKB has been implicated in antiapoptosis and neuronal survival. The authors now show that Akt is phosphorylated in the hippocampus during the early reperfusion period after 3.5 minutes bilateral carotid artery occlusion (BCAO) in the gerbil. Repeated sublethal ischemia induces ischemic tolerance, which is known as ischemic preconditioning. Ischemic preconditioning does not affect the amount of Akt protein, but rather decreases the phosphorylation of Akt at Ser-473 after 10 minutes reperfusion after 3.5 minutes BCAO. These results suggest that although Akt may play a role in neuronal survival after ischemia, it may not play a role in isehemic tolerance by preconditioning. C1 Natl Cardiovasc Ctr, Res Inst, Stroke & Brain Protect Lab, Suita, Osaka 5658565, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Med Serv,Renal Unit, Charlestown, MA 02129 USA. RP Namura, S (reprint author), Natl Cardiovasc Ctr, Res Inst, Stroke & Brain Protect Lab, 5-7-1 Fujishirodai, Suita, Osaka 5658565, Japan. NR 17 TC 37 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2000 VL 20 IS 9 BP 1301 EP 1305 DI 10.1097/00004647-200009000-00004 PG 5 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 349XA UT WOS:000089069800004 PM 10994851 ER PT J AU Zaharchuk, G Yamada, M Sasamata, M Jenkins, BG Moskowitz, MA Rosen, BR AF Zaharchuk, G Yamada, M Sasamata, M Jenkins, BG Moskowitz, MA Rosen, BR TI Is all perfusion-weighted magnetic resonance imaging for stroke equal? The temporal evolution of multiple hemodynamic parameters after focal ischemia in rats correlated with evidence of infarction SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE focal ischemia; cerebral blood volume; CBF; MRI; microvasculature ID CEREBRAL BLOOD-VOLUME; POSITRON-EMISSION-TOMOGRAPHY; ARTERY OCCLUSION; CONTRAST AGENT; CEREBROVASCULAR-DISEASE; TRANSVERSE RELAXATION; WATER DIFFUSION; MR-ANGIOGRAPHY; TRANSIT-TIME; FLOW AB Although perfusion-weighted imaging techniques are increasingly used to study stroke, no particular hemodynamic variable has emerged as a standard marker for accumulated ischemic damage. To better characterize the hemodynamic signature of infarction, the authors have assessed the severity and temporal evolution of ischemic hemodynamics in a middle cerebral artery occlusion model in the rat. Cerebral blood flow (CBF) and total and microvascular cerebral blood volume (CBV) changes were measured with arterial spin labeling and steady-state susceptibility contrast magnetic resonance imaging (MRI), respectively, and analyzed in regions corresponding to infarcted and spared ipsilateral tissue, based on 2,3,5-triphenyltetrazolium chloride histology sections after 24 hours ischemia. Spin echo susceptibility contrast was used to measure microvascular-weighted CBV, which had a maximum sensitivity for vessels with radii between 4 and 30 mu m. Serial measurements between 1 and 3 hours after occlusion showed no change in CBF (22 +/- 20% of contralateral, mean +/- SD) or in total CBV (78 +/- 13% of contralateral) in regions destined to infarct. However, microvascular CBV progressively declined from 72 +/- 5% to 64 +/- 11% (P < 0.01) during this same period. Microvascular CBV changes with time were entirely due to decreases in subcortical infarcted zones (from 73 +/- 9% to 57+/-14%, P < 0.001) without changes in the cortical infarcted territory. The hemodynamic variables showed differences in magnitude and temporal response, and these changes varied based on histologic outcome and brain architecture. Such factors should be considered when designing imaging studies for human stroke. C1 Harvard Univ, Harvard Mit Div Hlth Sci & Technol, Sch Med, Boston, MA USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Stroke & Neurovasc Regulat Lab, Charlestown, MA USA. RP Zaharchuk, G (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med MEB486, 1 Robert Wood Johnson Pl, New Brunswick, NJ 08903 USA. RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [R0I-HL39810]; NIDA NIH HHS [5 PO1-DA09467]; NINDS NIH HHS [R01-NS35258-01] NR 58 TC 34 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2000 VL 20 IS 9 BP 1341 EP 1351 DI 10.1097/00004647-200009000-00009 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 349XA UT WOS:000089069800009 PM 10994856 ER PT J AU Lin, SH Vincent, A Shaw, T Maynard, KI Maiese, K AF Lin, SH Vincent, A Shaw, T Maynard, KI Maiese, K TI Prevention of nitric oxide-induced neuronal injury through the modulation of independent pathways of programmed cell death SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE apoptosis; cysteine proteases; DNA fragmentation; hippocampal neurons; nicotinamide; phosphatidylserine ID INTRACELLULAR PH; ENDONUCLEASE ACTIVITY; CHOLINE LEVELS; APOPTOSIS; NICOTINAMIDE; BRAIN; PHOSPHATIDYLSERINE; INHIBITION; DNA; RAT AB Neuronal injury may be dependent upon the generation of the free radical nitric oxide (NO) and the subsequent induction of programed cell death (PCD). Although the nature of this injury may be both preventable and reversible, the underlying mechanisms that mediate PCD are not well understood. Using the agent nicotinamide as an investigative tool in primary rat hippocampal neurons, the authors examined the ability to modulate two independent components of PCD, namely the degradation of genomic DNA and the early exposure of membrane phosphatidylserine (PS) residues. Neuronal injury was determined through trypan blue dye exclusion, DNA fragmentation, externalization of membrane PS residues, cysteine protease activation, and the measurement of intracellular pH (pH(i)). Exposure to the NO donors SIN-1 and NOC-9 (300 mu mol/L) alone rapidly increased genomic DNA fragmentation from 20 +/- 4% to 71 +/- 5% and membrane PS exposure from 14 neuroprotective concentration of nicotinamide (12.5 mmol/L) consistently maintained DNA integrity and prevented the progression of membrane PS exposure. Posttreatment paradigms with nicotinamide at 2, 4, and 6 hours after NO exposure further demonstrated the ability of this agent to prevent and reverse neuronal PCD. Although not dependent upon pH,, neuroprotection by nicotinamide was linked to the modulation of two independent components of neuronal PCD through the regulation of caspase 1 and caspase 3-like activities and the DNA repair enzyme poly(ADP-ribose) polymerase. The current work lays the foundation for the development of therapeutic strategies that may not only prevent the course of PCD, bur may also offer the ability for the repair of neurons that have been identified through the loss of membrane asymmetry for subsequent destruction. C1 Wayne State Univ, Sch Med, Dept Neurol, Lab Cellular & Mol Cerebral Ischemia, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Ctr Mol Med & Genet,Ctr Mol & Cellular Toxicol, Detroit, MI 48201 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Boston, MA USA. RP Maiese, K (reprint author), Wayne State Univ, Sch Med, Dept Neurol, Lab Cellular & Mol Cerebral Ischemia, 8C-1 UHC,4201 St Antoine, Detroit, MI 48201 USA. NR 34 TC 92 Z9 96 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 2000 VL 20 IS 9 BP 1380 EP 1391 DI 10.1097/00004647-200009000-00013 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 349XA UT WOS:000089069800013 PM 10994860 ER PT J AU Biederman, J Mick, E Spencer, TJ Wilens, TE Faraone, SV AF Biederman, J Mick, E Spencer, TJ Wilens, TE Faraone, SV TI Therapeutic dilemmas in the pharmacotherapy of bipolar depression in the young SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PREPUBERTAL CHILDREN; DISORDER; MANIA; ADOLESCENTS; MISTAKEN; SYMPTOMS; FAMILY; ONSET; ADHD AB Pediatric bipolar disorder is commonly mixed with co-occurring symptoms of major depression and mania, Knowledge has begun to accumulate on the treatment of the mania component, but limited information is available to guide the therapeutic approach to bipolar depression. To this end, we reviewed the medical charts of 59 patients with diagnosis of DSM-III-R bipolar disorder from an outpatient pediatric psychopharmacology clinic. Multivariate methods were used to model the probability of improvement and relapse at each visit of clinical follow-up, Serotonin-specific antidepressants were significantly associated with both an increased rate of improvement of bipolar depression-relative risk = 6.7 (1.9-23.6); p = 0.003-and a significantly greater probability of relapse of manic symptomatology-relative risk = 3.0 (1.2-7.8); p = 0.02, Although mood stabilizers improved manic symptomatology, they had no demonstrable effect on the symptoms of bipolar depression. Despite the increased risk of mood destabilization, serotonin-specific antidepressants did not interfere with the antimanic effects of mood stabilizers. Because bipolar youth commonly come to clinical practice with depression, these results underscore the importance of assessing a lifetime history of bipolar disorder in making treatment decisions in depressed youth. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. RP Biederman, J (reprint author), Pediat Psychopharmacol Unit, ACC 725,15 Parkman St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 18 TC 67 Z9 68 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 2000 VL 10 IS 3 BP 185 EP 192 DI 10.1089/10445460050167296 PG 8 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 361MW UT WOS:000089727700005 PM 11052408 ER PT J AU Prince, JB Wilens, TE Biederman, J Spencer, TJ Millstein, R Polisner, DA Bostic, JQ AF Prince, JB Wilens, TE Biederman, J Spencer, TJ Millstein, R Polisner, DA Bostic, JQ TI A controlled study of nortriptyline in children and adolescents with attention deficit hyperactivity disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DOUBLE-BLIND; DEFICIT/HYPERACTIVITY DISORDER; TRICYCLIC ANTIDEPRESSANTS; SUDDEN-DEATH; DESIPRAMINE; PLACEBO; ADULTS; METHYLPHENIDATE; SAMPLE; COMORBIDITY AB Objectives: To study the efficacy and tolerability of nortriptyline (NT) in the treatment of pediatric attention deficit hyperactivity disorder (ADHD). Methodology: Subjects were outpatient children and adolescents with ADHD ascertained from clinical referrals. Subjects were enrolled in a 6-week open study in which NT was titrated to 2 mg/kg/day as tolerated over 2 weeks. Using either a 30% reduction in the ADHD rating scale or a score of 1 or 2 on the Clinical Global Impression (CGI) scale for ADHD improvement, responders to treatment were then randomized into a 3-week, controlled discontinuation phase. During this phase, subjects either continued on their current dose of NT or were tapered to placebo under double-blind conditions. Subjects were monitored for symptoms of ADHD, oppositionality, anxiety, and depression. Results: Of the 35 subjects enrolled in the study, 32 completed the open phase and 23 completed the discontinuation phase. The mean dose of NT was 80 mg (1.8 mg/kg/day), resulting in a serum level of 81 ng/ml. At the conclusion of the open 6-week study, NT was related to a significant reduction in ADHD (p < 0.001) and oppositional symptoms (p < 0.001). At the conclusion of the discontinuation phase, the 12 subjects randomized to NT had significantly lower scores on the DSM-IV ADHD symptom checklist than those 11 subjects randomized to placebo (31 versus 21; t = 2.2; p < 0.04). No significant adverse events were observed, and children were noted to have weight gain during the trial. Conclusions: These data suggest that NT is effective in reducing symptoms not only of ADHD but also of oppositionality. This group of children and adolescents tolerated robust dosing of NT well, with few clinical or cardiovascular adverse events. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Consolidated Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Prince, JB (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Consolidated Dept Psychiat, ACC 725, Boston, MA 02114 USA. NR 49 TC 52 Z9 53 U1 3 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 2000 VL 10 IS 3 BP 193 EP 204 DI 10.1089/10445460050167304 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 361MW UT WOS:000089727700006 PM 11052409 ER PT J AU Bostic, JQ Biederman, J Spencer, TJ Wilens, TE Prince, JB Monuteaux, MC Sienna, M Polisner, DA Hatch, M AF Bostic, JQ Biederman, J Spencer, TJ Wilens, TE Prince, JB Monuteaux, MC Sienna, M Polisner, DA Hatch, M TI Pemoline treatment of adolescents with attention deficit hyperactivity disorder: A short-term controlled trial SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID MINIMAL BRAIN-DYSFUNCTION; DOUBLE-BLIND; PSYCHIATRIC STATUS; CHILDREN; ADULTS; METHYLPHENIDATE; ADHD; STIMULANTS; THERAPY; PLACEBO AB Background: Despite the increased recognition of attention deficit hyperactivity disorder (ADHD) in adolescents, few controlled studies have assessed treatments for this age group. Adolescent issues, such as embarrassment at receiving medication at school and experimentation with abusable substances, have accelerated efforts to find effective, well-tolerated treatments beyond traditional stimulants. Pemoline has been found effective for treating both children and adults with ADHD but has not been evaluated in adolescents with ADHD. Methods: Twenty-one adolescents (mean age 14 years old) diagnosed with ADHD by structured and clinical interviews participated in a 10-week, double-blind crossover design study of pemoline. Dosing was optimized with robust doses up to 3 mg/kg/day in one to two doses. Clinical evaluations of ADHD, depression, anxiety, and oppositional defiant disorder (ODD) symptoms were assessed weekly. Results: Adolescents with ADHD exhibited a marked response to pemoline treatment relative to placebo on the ADHD rating scale (p = 0.001), with an average reduction of 3.02 points per week of treatment. Sixty percent of adolescents responded to pemoline, compared to 11% treated with placebo. This response was independent of gender or lifetime psychiatric comorbidity. Pemoline was well tolerated, with patients averaging 2.88 mg/kg/day in two doses per day, with a mean dose at end of follow-up of 181.1 mg (SD 45.6, range 112.5-262.5 mg). Side effects were mild, and no adverse hepatic events occurred. Conclusions: These findings resemble those reported in children and adults with ADHD. This trial suggests pemoline is well tolerated and effective in adolescents and may be a particularly useful ADHD treatment for adolescents. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Bostic, JQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, WAC 725, Boston, MA 02114 USA. NR 60 TC 19 Z9 19 U1 3 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 2000 VL 10 IS 3 BP 205 EP 216 DI 10.1089/10445460050167313 PG 12 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 361MW UT WOS:000089727700007 PM 11052410 ER PT J AU Wilens, TE Biederman, J Wong, J Spencer, TJ Prince, JB AF Wilens, TE Biederman, J Wong, J Spencer, TJ Prince, JB TI Adjunctive donepezil in attention deficit hyperactivity disorder youth: Case series SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; DOUBLE-BLIND; ADULTS; NICOTINE; ADOLESCENTS; PERFORMANCE; CHILDREN; SMOKING; PLACEBO; TRIAL AB Despite well-documented improvement in attention deficit hyperactivity disorder (ADHD) in youths with the available single and combined pharmacologic agents, a number of youths remain with residual symptomatology causing impairment in multiple domains. Recent work has suggested a potential cognitive-enhancing role of cholinergic agents in ADHD. We describe five cases of ADHD youths aged 8-17 years being treated for ADHD with the acetylcholinesterase inhibitor donepezil (Aricept(R)), all of whom demonstrated improvement. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Boston, MA 02114 USA. FU NIMH NIH HHS [MH01175A] NR 24 TC 30 Z9 30 U1 2 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 2000 VL 10 IS 3 BP 217 EP 222 DI 10.1089/10445460050167322 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 361MW UT WOS:000089727700008 PM 11052411 ER PT J AU Mick, E Biederman, J Jetton, J Faraone, SV AF Mick, E Biederman, J Jetton, J Faraone, SV TI Sleep disturbances associated with attention deficit hyperactivity disorder: The impact of psychiatric comorbidity and pharmacotherapy SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT/HYPERACTIVITY DISORDER; CHILDREN; METHYLPHENIDATE; PATTERNS; BEHAVIOR; DESIPRAMINE; ADD AB Objective: To estimate the relative risk of sleep problems associated with attention deficit hyperactivity disorder (ADHD), its pharmacotherapy, and its comorbid psychopathology, Method: Standard sleep questionnaires were used to assess sleep problems and characteristics in ADHD (n = 122) and non-ADHD (n = 105) comparison youths. Results: ADHD was associated with 10 of 19 sleep problems assessed. However, after controlling for psychiatric comorbidity and pharmacotherapy with stimulants, the majority of these differences were no longer evident, Rather, treatment with stimulants and comorbidity with anxiety and behavior disorders were significantly associated with sleep disturbances. Positive family history of ADHD was associated with none of the sleep problems assessed here after adjusting for age, psychiatric comorbidity, and treatment with anti-ADHD medication, Conclusions: Although subjective sleep difficulties are common in ADHD youths, they are frequently accounted for by comorbidity and pharmacotherapy, Furthermore, the lack of an association between a positive family history of ADHD and sleep difficulties suggests that ADHD is not a misdiagnosis of the consequences of disruption of normal sleep. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Sch Med, Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA USA. Massachusetts Hlth Ctr, Boston, MA USA. RP Mick, E (reprint author), Pediat Psychopharmacol Res, 15 Parkman St,ACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 38 TC 85 Z9 85 U1 2 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD FAL PY 2000 VL 10 IS 3 BP 223 EP 231 DI 10.1089/10445460050167331 PG 9 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 361MW UT WOS:000089727700009 PM 11052412 ER PT J AU Krishnamoorthy, KS Soman, TB Takeoka, M Schaefer, PW AF Krishnamoorthy, KS Soman, TB Takeoka, M Schaefer, PW TI Diffusion-weighted imaging in neonatal cerebral infarction: Clinical utility and follow-up SO JOURNAL OF CHILD NEUROLOGY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Child-Neurology-Society CY OCT 29-NOV 03, 1997 CL PHOENIX, ARIZONA SP Child Neurol Soc ID ACUTE STROKE; MR; BRAIN; ISCHEMIA; THROMBOSIS; ASPHYXIA; NEWBORN; EDEMA; WATER AB We describe the clinical utility of echo-planar diffusion-weighted imaging in neonatal cerebral infarction. Eight full-term neonates aged 1 to 8 days referred for neonatal seizures were studied. Patients were followed for a mean of 17 months with detailed neurologic examinations at regular intervals. Head computed tomography (CT) and conventional magnetic resonance (MRI) and diffusion-weighted images were obtained. Percent lesion contrast was evaluated for 19 lesions on T-2-weighted and diffusion-weighted images. Follow-up conventional MRIs were obtained in seven patients. The findings on diffusion-weighted imaging were correlated with CT and conventional MRI findings as well as with short-term neurodevelopmental outcome. Four patients had focal cerebral infarctions, Four patients had diffuse injury consistent with hypoxic-ischemic encephalopathy. Percent lesion contrast of all 19 lesions was significantly higher on diffusion-weighted images when compared with T-2-weighted images. In five patients, there were lesions visualized only with diffusion-weighted imaging. In all patients, there was increased lesion conspicuity and better definition of lesion extent on the diffusion-weighted images compared with the CT and T-2-weighted MR images. In seven of eight patients follow-up imaging confirmed prior infarctions. Short-term neurologic outcome correlated with the extent of injury seen on the initial diffusion-weighted imaging scans for all patients. Diffusion-weighted imaging is useful in the evaluation of acute ischemic brain injury and seizure etiology in neonates. In the acute setting, diffusion-weighted imaging provides information not available on CT and conventional MRI. This information correlates with short-term clinical outcome. C1 Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Pediat Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Krishnamoorthy, KS (reprint author), Massachusetts Gen Hosp, Dept Neurol, Pediat Neurol Unit, VBK 731,32 Fruit St, Boston, MA 02114 USA. NR 31 TC 29 Z9 31 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD SEP PY 2000 VL 15 IS 9 BP 592 EP 602 DI 10.1177/088307380001500905 PG 11 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 356ZP UT WOS:000089474300005 PM 11019790 ER PT J AU Hayes, FJ AF Hayes, FJ TI Editorial: Testosterone - Fountain of youth or drug of abuse? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CLINICAL-RESEARCH CENTER; HYPOGONADAL MEN; AGE; PHARMACOKINETICS; REPLACEMENT; METABOLISM; STRENGTH; DISEASE; SITE C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM Hayes.Frances@MGH.Harvard.edu NR 18 TC 17 Z9 17 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2000 VL 85 IS 9 BP 3020 EP 3023 DI 10.1210/jc.85.9.3020 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351NZ UT WOS:000089166200005 PM 10999779 ER PT J AU Hayes, FJ Seminara, SB Decruz, S Boepple, PA Crowley, WF AF Hayes, FJ Seminara, SB Decruz, S Boepple, PA Crowley, WF TI Aromatase inhibition in the human male reveals a hypothalamic site of estrogen feedback SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; RECEPTOR-IMMUNOREACTIVE CELLS; MESSENGER-RIBONUCLEIC-ACID; CLINICAL-RESEARCH CENTER; ALPHA-KNOCKOUT MOUSE; SEX STEROID CONTROL; LUTEINIZING-HORMONE; TYROSINE-HYDROXYLASE; CLOMIPHENE CITRATE; DEFICIENT MEN C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Fruit St, Boston, MA 02114 USA. EM hayes.frances@mgh.harvard.edu FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [U54 HD029164, P30 HD028138, R01 HD015788, R01-HD15788-15, U54 HD028138]; NIDDK NIH HHS [DK-07028-24] NR 71 TC 136 Z9 140 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2000 VL 85 IS 9 BP 3027 EP 3035 DI 10.1210/jc.85.9.3027 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351NZ UT WOS:000089166200007 PM 10999781 ER PT J AU Pinzone, JJ Katznelson, L Danila, DC Pauler, DK Miller, CS Klibanski, A AF Pinzone, JJ Katznelson, L Danila, DC Pauler, DK Miller, CS Klibanski, A TI Primary medical therapy of micro- and macroprolactinomas in men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LONG-TERM; HYPERPROLACTINEMIC MALES; CLINICAL CHARACTERISTICS; CABERGOLINE TREATMENT; GONADAL-FUNCTION; PROLACTINOMAS; BROMOCRIPTINE AB The presentation and long-term therapeutic responses of PRL-secreting pituitary tumors in men have been only partially studied. Gender-specific differences in tumor size at clinical presentation and possible differences in tumor biology in men compared to women make it important to determine treatment outcomes of male patients with prolactinomas. We performed a retrospective review of men with prolactinomas medically managed at Massachusetts General Hospital between 1980 and 1997. We identified 46 male patients with prolactinomas managed with medical therapy alone. Twelve patients had microadenomas, defined as a serum PRL level greater than 15 ng/mL and a normal pituitary scan or a tumor smaller than 1 cm. Thirty-four patients had macroprolactinomas, defined by a serum PRL greater than 200 ng/mL and pituitary adenoma larger than 1 cm. Bromocriptine, quinagolide, and/or cabergoline were administered as medical therapy. AU patients had at least one follow-up visit, and the most recent serum PRL measurement after initiating dopamine agonist therapy was reported. Baseline clinical characteristics for patients with macroprolactinomas and microprolactinomas showed a larger proportion of patients with macroprolactinomas reporting a history of headache (74% vs. 0%), whereas the prevalence of sexual dysfunction and testosterone deficiency was similar between the two groups. Median serum PRL at presentation was 99 ng/mL, (range, 16-385 ng/mL) vs. 1415 ng/mL (range, 387-67,900 ng/mL), in the microprolactinoma and macroprolactinoma groups, respectively. A normal PRL level was achieved in a similar percentage of men with microprolactinomas vs, macroprolaetinomas (83% vs. 79%, respectively). Although the majority of patients in both groups were treated with bromocriptine, a comparable number of patients with microprolactinomas vs. macroprolactinomas achieved a normal PRL level with cabergoline therapy. The response rates for bromocriptine and cabergoline were similar in both groups. No patient with a microprolactinoma required hormone replacement therapy, in contrast to patients with macroprolactinomas, who required thyroid, testosterone, and/or glucocorticoid replacement therapy. No patient had evidence of an increase in tumor size during therapy. In summary, me investigated the clinical presentation and treatment outcome in men with prolactinomas. We found that normalization of serum PRL levels occurs in approximately 80% of men with prolactinomas. Of importance, dopamine agonist administration yielded similar biochemical remission rates in men with microprolactinomas and macroprolactinomas. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01-RR-01066] NR 16 TC 75 Z9 82 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2000 VL 85 IS 9 BP 3053 EP 3057 DI 10.1210/jc.85.9.3053 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351NZ UT WOS:000089166200011 PM 10999785 ER PT J AU Schneyer, AL Fujiwara, T Fox, J Welt, CK Adams, J Messerlian, GM Taylor, AE AF Schneyer, AL Fujiwara, T Fox, J Welt, CK Adams, J Messerlian, GM Taylor, AE TI Dynamic changes in the intrafollicular inhibin/activin/follistatin axis during human follicular development: Relationship to circulating hormone concentrations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the Endocrine-Society CY JUN 12-16, 1999 CL SAN DIEGO, CA SP Endocrine Soc ID HUMAN MENSTRUAL-CYCLE; ACTIVIN-A; OVARIAN-FOLLICLES; INHIBIN B; POLYCYSTIC OVARIES; DIMERIC INHIBIN; ANTRAL FLUID; IN-VITRO; FOLLISTATIN; WOMEN AB Previous studies of normal human ovaries suggest that inhibins, activins, and follistatin (FS) are produced in a stage-specific pattern indicative of intraovarian, autocrine/paracrine roles in regulating follicle development. However, these studies relied largely on surgical specimens and thus include little information about the menstrual cycle stage or dominant follicle status at the time follicles or ovaries were obtained. The purpose of this study was to 1) determine the pattern of intrafollicular hormone biosynthesis across antral follicle development in normal women, 2) compare hormone concentrations in dominant and nondominant follicles from the same ovary, and 3) examine the relationship between dominant follicle hormone content and circulating hormone levels. Intrafollicular estradiol, progesterone, and inhibin A concentrations increased significantly with follicle size or maturity, whereas significant inverse relationships were observed for androstenedione and the androstenedione/estradiol (A:E) ratio. In contrast, neither inhibin B, activin A, nor free FS Varied consistently with size or maturity. Estradiol, progesterone, and inhibin A levels and A:E ratio were significantly lower in nondominant follicles, compared to the dominant follicle aspirated from the same ovary. Although intrafollicular and serum concentrations of each hormone followed the same general pattern as follicles develop, the human follicular fluid/serum gradients changed during the follicular phase and were different for estradiol and inhibin A, suggesting the presence of stage-specific differences in pharmacodynamics. These results are consistent with the hypothesis that the orderly transition from an activin-dominant to an inhibin A/FS-dominant microenvironment is critical for dominant follicle development. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet Gynecol, Boston, MA 02114 USA. Brown Univ, Women & Infants Hosp, Dept Pathol & Lab Med, Providence, RI 02903 USA. RP Schneyer, AL (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Natl Ctr Infertil Res, BHX-5, Boston, MA 02114 USA. EM schneyer.alan@mgh.harvard.edu OI Welt, Corrine/0000-0002-8219-5504; Messerlian, Geralyn/0000-0002-9440-3411 FU NICHD NIH HHS [P30-HD-23138, U54-HD-29164] NR 34 TC 63 Z9 66 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2000 VL 85 IS 9 BP 3319 EP 3330 DI 10.1210/jc.85.9.3319 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351NZ UT WOS:000089166200054 PM 10999828 ER PT J AU Marino, M Chiovato, L Mitsiades, N Latrofa, F Andrews, D Tseleni-Balafouta, S Collins, AB Pinchera, A McCluskey, RT AF Marino, M Chiovato, L Mitsiades, N Latrofa, F Andrews, D Tseleni-Balafouta, S Collins, AB Pinchera, A McCluskey, RT TI Circulating thyroglobulin transcytosed by thyroid cells is complexed with secretory components of its endocytic receptor megalin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SERUM THYROGLOBULIN; HEYMANN NEPHRITIS; FOLLICLE CELLS; GENE FAMILY; GP330; PROTEIN; IDENTIFICATION; GP330/MEGALIN; TRANSPORT; CLONING AB After its endocytosis from the colloid, some thyroglobulin (Tg) is transcytosed intact across thyrocytes, accounting in part for its presence in the circulation. We previously showed that megalin (gp330), an endocytic Tg receptor, mediates apical to basolateral Tg transcytosis. Here we investigated whether a portion of megalin remains combined with Tg after its transcytosis, using studies with cultured thyroid cells and in, vivo observations. FRTL-5 cells, a rat thyroid cell line, cultured on filters in dual chambers form tight junctions and exhibit features of polarity, with expression of megalin exclusively on the upper (apical) surface. After the addition of unlabeled Tg to the upper chamber and incubation at 37 C, some Tg was transcytosed intact across FRTL-5 cells into the lower chamber. Two antimegalin ectodomain antibodies precipitated transcytosed Tg in fluids collected from the lower chamber. After the addition of Tg to surface-biotinylated FRTL-5 cells, an anti-Tg antibody and the two antimegalin ectodomain antibodies precipitated high molecular mass biotinylated material in fluids collected from the lower chamber, corresponding to much of the megalin ectodomain, as well as smaller amounts of lower molecular mass material. The results indicate that Tg transcytosed across FRTL-5 cells remains complexed with megalin ectodomain components, which we refer to as megalin secretory components. In aminotriazole-treated rats, which develop increased megalin-mediated Tg transcytosis, antimegalin antibodies precipitated some of the Tg in the serum. Tg was also precipitated by antimegalin antibodies in sera from patients with Graves' disease, in which we found increased megalin expression on the apical surface of thyrocytes. In contrast, in thyroidectomized patients with metastatic papillary thyroid carcinoma, in whom Tg is directly secreted by neoplastic thyroid cells into the circulation rather than transcytosed, serum Tg was not precipitated by antimegalin antibodies. The detection of Tg-megalin complexes may help identify the source of serum Tg in patients with thyroid diseases. C1 Univ Pisa, Dept Endocrinol, I-56100 Pisa, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. Univ Athens, Dept Pathol, Athens 10554, Greece. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56100 Pisa, Italy. EM m.marino@endoc.med.unipi.it OI Latrofa, Francesco/0000-0003-0297-5904 FU PHS HHS [46301] NR 38 TC 15 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2000 VL 85 IS 9 BP 3458 EP 3467 DI 10.1210/jc.85.9.3458 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 351NZ UT WOS:000089166200075 PM 10999849 ER PT J AU Rosen, ED Spiegelman, BM AF Rosen, ED Spiegelman, BM TI Peroxisome proliferator-activated receptor gamma ligands and atherosclerosis: ending the heartache SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID LOW-DENSITY-LIPOPROTEIN; ZUCKER FATTY RATS; PPAR-GAMMA; INSULIN SENSITIVITY; GENE-EXPRESSION; OXIDIZED LDL; TROGLITAZONE; DIFFERENTIATION; MACROPHAGES; RESISTANCE C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 32 TC 52 Z9 52 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 SEP PY 2000 VL 106 IS 5 BP 629 EP 631 DI 10.1172/JCI10909 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 351VN UT WOS:000089179000005 PM 10974014 ER PT J AU Wu, CJ Yang, XF McLaughlin, S Neuberg, D Canning, C Stein, B Alyea, EP Soiffer, RJ Dranoff, G Ritz, J AF Wu, CJ Yang, XF McLaughlin, S Neuberg, D Canning, C Stein, B Alyea, EP Soiffer, RJ Dranoff, G Ritz, J TI Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; MINOR HISTOCOMPATIBILITY ANTIGENS; CHRONIC MYELOID-LEUKEMIA; DONOR LYMPHOCYTE INFUSION; CYTOTOXIC T-LYMPHOCYTES; TYROSINE KINASE RAFTK; CEREBELLAR DEGENERATION; TUMOR-ANTIGEN; J-KAPPA AB The effectiveness of donor-lymphocyte infusion (DLI) for treatment of relapsed chronic myelogenous leukemia (CML) after allogeneic bone marrow transplantation is a clear demonstration of the graft-versus-leukemia (GVL) effect. T cells are critical mediators of GVL, but the antigenic targets of this response are unknown. To determine whether patients who respond to DLI also develop B-cell immunity to CML-associated antigens, we analyzed sera from three patients with relapsed CML who achieved a complete molecular remission after infusion of donor T cells. Sera from these individuals recognized 13 distinct gene products represented in a CML-derived cDNA library. Two proteins, J kappa-recombination signal-binding protein (RBP-J kappa) and related adhesion focal tyrosine kinase (RAFTK), were recognized by sera from three of 19 DLI responders. None of these antigens were recognized by sera from healthy donors or patients with chronic graft-versus-host disease. Four gene products were recognized by sera from CML patients treated with hydroxyurea and nine were detected by sera from CML patients who responded to IFN-a. Antibody titers specific for RAFTK, but not for RBP-JK, were found to be temporally associated with the response to DLI. These results demonstrate that patients who respond to DLI generate potent antibody responses to CML-associated antigens, suggesting the development of coordinated T- and B-cell immunity. The characterization of B cell-defined antigens may help identify clinically relevant targets of the GVL response in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NIAID NIH HHS [AI-29530, P01 AI029530, U19 AI029530] NR 58 TC 90 Z9 93 U1 0 U2 0 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 SEP PY 2000 VL 106 IS 5 BP 705 EP 714 DI 10.1172/JCI10196 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 351VN UT WOS:000089179000015 PM 10974024 ER PT J AU Cangi, MG Cukor, B Soung, P Signoretti, S Moreira, G Ranashinge, M Cady, B Pagano, M Loda, M AF Cangi, MG Cukor, B Soung, P Signoretti, S Moreira, G Ranashinge, M Cady, B Pagano, M Loda, M TI Role of the Cdc25A phosphatase in human breast cancer SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CYCLIN-DEPENDENT KINASES; CELL-CYCLE; G(1)/S TRANSITION; INHIBITOR P27; S-PHASE; ACTIVATION; PROLIFERATION; PHOSPHORYLATION; EVENTS AB The phosphatase Cdc25A plays an important role in cell cycle regulation by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases, and it has been shown to transform diploid murine fibroblasts in cooperation with activated Ras. Here we show that Cdc25A is overexpressed in primary breast tumors and that such overexpression is correlated with higher levels of cyclin-dependent kinase 2 (Cdk2) enzymatic activity in vivo. Furthermore, in the breast cancer cell line MCF-7, Cdc25A activity is necessary for both the activation of Cdk2 and the subsequent induction of S-phase entry. Finally, in a series of small (< 1 cm) breast carcinomas, overexpression of Cdc25A was found in 47% of patients and was associated with poor survival. These data suggest that overexpression of Cdc25A contributes to the biological behavior of primary breast tumors and that both Cdc25A and Cdk2 are suitable therapeutic targets in early-stage breast cancer. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Brown Univ, Sch Med, Dept Surg, Providence, RI 02912 USA. NYU Med Ctr, Dept Pathol, New York, NY 10016 USA. Kaplan Comprehens Canc Ctr, New York, NY USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Dana 740B, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA076584, P30 CA016087, P30CA16087, R01CA81755]; NIGMS NIH HHS [R01 GM057587, R01GM57587] NR 26 TC 147 Z9 152 U1 0 U2 4 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 SEP PY 2000 VL 106 IS 6 BP 753 EP 761 DI 10.1172/JCI9174 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 355MW UT WOS:000089390300008 PM 10995786 ER PT J AU Kurihara, T Brough, DE Kovesdi, I Kufe, DW AF Kurihara, T Brough, DE Kovesdi, I Kufe, DW TI Selectivity of a replication-competent adenovirus for human breast carcinoma cells expressing the MUC1 antigen SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MONOCLONAL-ANTIBODY DF3; VIRUS THYMIDINE KINASE; TUMOR-CELLS; GENE-EXPRESSION; ANTITUMORAL EFFICACY; BRAIN-TUMORS; CANCER CELLS; P53 STATUS; THERAPY; MUTANT AB The DF3/MUC1 gene is aberrantly overexpressed in human breast and other carcinomas. Previous studies have demonstrated that the DF3/MUC1I promoter/enhancer confers selective expression of diverse transgenes in MUC1-positive breast cancer cells. In this study, we show that an adenoviral vector (Ad.DF3-E1) in which the DF3/MUC1 promoter drives expression ofE1A selectively replicates in MUC1-positive breast cancer cells. We also show that Ad.DF3-E1 infection of human breast tumor xenografts in nude mice is associated with inhibition of tumor growth. In contrast to a replication-incompetent adenoviral vector that infects along the injection track, Ad.DF3-E1 infection was detectable throughout the tumor xenografts. To generate an Ad.DF3-E1 vector with the capacity for incorporating therapeutic products, we inserted the cytomegalovirus (CMV) promoter upstream of the TNF cDNA. Infection with Ad.DF3-E1/CMV-TNF was associated with selective replication and production of TNF in cells that express MUC1. Moreover, treatment of MUC1-positive, but not MUC1-negative, xenografts with a single injection of Ad.DF3-E1/CMV-TNF was effective in inducing stable tumor regression These findings demonstrate that the DF3/MUC1 promoter confers competence for selective replication of Ad.DF3-E1 in MUC1-positive breast tumor cells, and that the antitumor activity of this vector is potentiated by integration of the TNF cDNA. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. GenVec Inc, Gaithersburg, MD USA. RP Kufe, DW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Kovesdi, Imre/0000-0002-0322-3969 NR 36 TC 181 Z9 192 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2000 VL 106 IS 6 BP 763 EP 771 DI 10.1172/JCI9180 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 355MW UT WOS:000089390300009 PM 10995787 ER PT J AU Iwen, PC Tarantolo, SR Sutton, DA Rinaldi, MG Hinrichs, SH AF Iwen, PC Tarantolo, SR Sutton, DA Rinaldi, MG Hinrichs, SH TI Cutaneous infection caused by Cylindrocarpon lichenicola in a patient with acute myelogenous leukemia SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID FUSARIUM AB Cylindrocarpon lichenicola is a saprophytic soil fungus which has rarely been associated with human disease. We report the first case of localized invasive cutaneous infection caused by this fungus in a 53-year-old male from the rural midwestern United States with relapsed acute myelogenous leukemia. On admission for induction chemotherapy, the patient was noted to have an abrasive laceration between the fourth and fifth metacarpophalangeal joints and on the dorsum of the right hand, which progressed to frank ulceration following chemotherapy. A biopsy provided an initial diagnosis of an invasive fungal infection consistent with aspergillosis based on the histopathological appearance of the mold in tissue. Multiple positive fungal cultures which were obtained from the biopsied tissue were subsequently identified by microscopic and macroscopic characteristics to be C. lichenicola. The infection resolved following marrow regeneration, aggressive debridement of the affected tissue, and treatment with amphotericin B. This case extends the conditions associated with invasive disease caused by C. lichenicola. C1 Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Iwen, PC (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 986495 Nebraska Med Ctr, Omaha, NE 68198 USA. NR 20 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2000 VL 38 IS 9 BP 3375 EP 3378 PG 4 WC Microbiology SC Microbiology GA 350RG UT WOS:000089114500040 PM 10970386 ER PT J AU Bauer, KA AF Bauer, KA TI Venous thromboembolism in malignancy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID DEEP-VEIN THROMBOSIS; CANCER C1 Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Bauer, KA (reprint author), Harvard Univ, Sch Med, Boston VA Healthcare Syst, Boston, MA 02115 USA. NR 10 TC 12 Z9 14 U1 0 U2 2 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 SEP PY 2000 VL 18 IS 17 BP 3065 EP 3067 PG 3 WC Oncology SC Oncology GA 349GX UT WOS:000089038300001 PM 10963634 ER PT J AU Krop, IE Wieczorek, TJ Mayer, RJ AF Krop, IE Wieczorek, TJ Mayer, RJ TI Case 3. Metastatic ovarian cancer simulating colon cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CYTOKERATIN-20; CARCINOMA C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Krop, IE (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP PY 2000 VL 18 IS 17 BP 3189 EP 3192 PG 4 WC Oncology SC Oncology GA 349GX UT WOS:000089038300017 PM 10963649 ER PT J AU Ximenez-Fyvie, LA Haffajee, AD Som, S Thompson, M Torresyap, G Socransky, SS AF Ximenez-Fyvie, LA Haffajee, AD Som, S Thompson, M Torresyap, G Socransky, SS TI The effect of repeated professional supragingival plaque removal on the composition of the supra- and subgingival microbiota SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE microbiology; periodontal health; periodontal disease; supragingival plaque; subgingival plaque; periodontal pathogens; bacteria; DNA probes; treatment ID NON-SURGICAL TREATMENT; PERIODONTAL-DISEASE; BACTERIAL-COLONIZATION; BARRIER MATERIAL; MICROFLORA; POCKETS; REGENERATION AB Background, aims: The purpose of the present investigation was to determine the effect of weekly professionally administered supragingivaI plaque removal on the composition of the supra and subgingival microbiota. Methods: 18 adult subjects with periodontitis who had been treated and were in a maintenance phase of therapy were clinically and microbiologically monitored at baseline, 3, 6 and 12 months. After the baseline visit, the subjects received scaling and root planing followed by professional supragingival plaque removal every week for 3 months. Clinical measures of plaque accumulation, bleeding on probing (BOP), gingival redness, suppuration, pocket depth and attachment level were made at 6 sites per tooth at each visit. Separate supra (N=1804) and subgingival (N = 1804) plaque samples were taken from the mesial aspect of all teeth excluding third molars in each subject at each time point and evaluated for their content of 40 bacterial taxa using checkerboard DNA-DNA hybridization. Significance of changes in mean counts, prevalence and proportions of bacterial species over time in both supra and subgingival samples were determined using the Quads test and adjusted for multiple comparisons. Results: Mean % of sites exhibiting plaque, gingival redness and BOP were significantly reduced during the course of the study. Significant decreases in mean counts were observed in both supra and subgingival samples. Mean total DNA probe counts (x 10(5), +/- SEM) at baseline, 3, 6 and 12 months were: 133 +/- 19, 95 +/- 25, 66 +/- 6, 41 +/- 6 (p<0.001) for supragingival samples and 105 +/- 22, 40' +/- 10, 19 +/- 4 13 +/- 3 (p<0.001) for subgingival samples. Mean counts of 22 of 40 and 34 of 40 species tested were significantly reduced in the supra and subgingival samples respectively over the monitoring period. For example, mean counts of Porphyromonas gingivalis x 10(5) at baseline, 3, 6 and 12 months in the subgingival plaque samples were 2.0 +/- 0.4, 0.5 +/- 0.2, 0.6 +/- 0.3, 0.3 +/- 0.1 (p<0.001); Bacteroides forsythus 2.0+/-0.6, 0.4+/-0.1, 0.4+/-0.2, 0.1+/-0.2 (p<0.001); Treponema denticola 3.4 +/- 1.1, 0.8 +/- 0.3, 0.4 +/- 0.2, 0.3 +/- 0.3 (p<0.01). Similar reductions were seen in supragingival plaque samples. While counts were markedly reduced by professional plaque removal, the proportion and prevalence of the 40 test species were marginally affected. Conclusions: weekly professional supragingival plaque removal profoundly diminished counts of both supra- and subgingival species creating a microbial profile comparable to that observed in periodontal health. This profile was maintained at the final monitoring visit, 9 months after completion of therapy. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-04881, DE-10977, DE-12108] NR 36 TC 69 Z9 75 U1 0 U2 10 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 2000 VL 27 IS 9 BP 637 EP 647 DI 10.1034/j.1600-051x.2000.027009637.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 345UP UT WOS:000088833800003 PM 10983597 ER PT J AU Ximenez-Fyvie, LA Haffajee, AD Socransky, SS AF Ximenez-Fyvie, LA Haffajee, AD Socransky, SS TI Comparison of the microbiota of supra- and subgingival plaque in health and periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE microbiology; periodontal health; periodontal disease; supragingival plaque; subgingival plaque; periodontal pathogens; bacteria; DNA probes ID ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; BACTEROIDES-FORSYTHUS; VIRULENCE FACTORS; PERIODONTOPATHOGENS; GINGIVALIS; GINGIVITIS AB Background, aims: The purpose of the present investigation was to compare the microbial composition of supra and subgingival plaque in 22 periodontally healthy (mean age 32 +/- 16 years) and 23 adult periodontitis subjects (mean age 51 +/- 14 years). Methods: A total of 2358 supra and separately subgingival plaque samples were collected from the mesial aspect of all teeth excluding 3rd molars in each subject. Samples were examined for the presence and levels of 40 bacterial taxa using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments including dichotomous measures of gingival redness, bleeding on probing, plaque accumulation and suppuration, as well as duplicate measures of pocket depth and attachment level, were made at 6 sites per tooth, Mean counts (x10(5)), % DNA probe count and % sites colonized for each species were determined separately for supra and subgingival samples in each subject and then averaged across subjects in the 2 clinical groups. Significance of differences between healthy and periodontitis subjects was determined using the Mann-Whitney test and adjusted for multiple comparisons. Results: Mean total DNA probe counts (x10(5), +/-SEM) for healthy and periodontitis subjects in supragingival plaque were 72.1 +/- 11 and 132 +/- 17.5, respectively (p<0.01), and in subgingival plaque 22.1 +/- 6.6 and 100.3 +/- 18.4, (p<0.001). Porphyromonas gingivalis, Bacteroides forsythus and Treponema denticola could be detected in supragingival plaque samples of both healthy and periodontitis subjects. Actinomyces species were the dominant taxa in both supra- and subgingival plaque from healthy and periodontitis subjects. 4 Actinomyces species accounted for 63.2% of supragingival and 47.2% of subgingival plaque in healthy subjects and 48.1% and 37.8% in periodontitis subjects respectively. Increased proportions of P. gingivalis, B. forsythus, and species of Prevotella, Fusobacterium, Campylobacter and Treponema were detected subgingivally in the periodontitis subjects. P. gingivalis, B, forsythus and T. denticola were significantly more prevalent in both supra- and subgingival plaque samples from periodontitis subjects. Conclusions: The main differences between supra and subgingival plaque as well as between health and disease were in the proportions and to some extent levels of Actinomyces, "orange" and "red" complex species. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-04881, DE-10977, DE-12108] NR 24 TC 245 Z9 260 U1 4 U2 28 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD SEP PY 2000 VL 27 IS 9 BP 648 EP 657 DI 10.1034/j.1600-051x.2000.027009648.x PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 345UP UT WOS:000088833800004 PM 10983598 ER PT J AU Guille, C Sachs, GS Ghaemi, SN AF Guille, C Sachs, GS Ghaemi, SN TI A naturalistic comparison of clozapine, risperidone, and olanzapine in the treatment of bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIPSYCHOTIC AGENTS; DOUBLE-BLIND; MANIA; SCHIZOPHRENIA; HALOPERIDOL; OBESITY; OUTPATIENTS; TRIAL AB Background: Our purpose was to evaluate the overall efficacy and tolerability of novel antipsychotic medications for patients with bipolar disorder type I. Method: A retrospective study of the Massachusetts General Hospital Bipolar Clinic database was carried out to identify 50 consecutive treatment trials in patients with DSM-IV bipolar disorder type I who had received adjunctive treatment with risperidone, olanzapine, or clozapine, along with standard mood stabilizers. The treatment charts of those patients (N = 42) were re viewed for details of adverse effects, tolerability, and efficacy of medication. Results: Overall results indicated equivalent efficacy in novel antipsychotic treatments according to change in Clinical Global Impressions scale score. Levels of extrapyramidal symptoms were similar in all groups and occurred in 12/42 patients (28.6%). Prolactin-related side effects were not observed in any patients. There were no cases of affective switch or worsening of mania. Substantial weight gain of more than 10 lb (4.5 kg) was significantly greater in patients treated with olanzapine. Conclusion: These results suggest that the efficacy and tolerability of risperidone, olanzapine, and clozapine are similar in patients with bipolar disorder. One major differentiation factor of these drugs appears to be weight- gain, particularly between olanzapine and risperidone. This may, in part, also be related to the need to use mood-stabilizing agents, like lithium or divalproex sodium, which may potentiate the weight-gain effect of novel antipsychotics. C1 Harvard Univ, Dept Psychiat, Psychopharmacol Program, Cambridge Hosp,Med Sch, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Psychiat, Bipolar Res Program, Boston, MA 02114 USA. RP Ghaemi, SN (reprint author), Harvard Univ, Dept Psychiat, Psychopharmacol Program, Cambridge Hosp,Med Sch, 1493 Cambridge St, Cambridge, MA 02139 USA. NR 35 TC 74 Z9 75 U1 3 U2 5 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2000 VL 61 IS 9 BP 638 EP 642 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 359RN UT WOS:000089626000003 PM 11030483 ER PT J AU Kleespies, PM AF Kleespies, PM TI Behavioral emergencies and crises: An overview SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Editorial Material ID PATIENT SUICIDAL-BEHAVIOR; NATIONAL SURVEY; PSYCHOLOGY; PSYCHIATRY; THERAPIST; PROGRAMS; STRESS C1 VA Boston Healthcare Syst, Psychiat Serv 116B, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kleespies, PM (reprint author), VA Boston Healthcare Syst, Psychiat Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. NR 18 TC 3 Z9 3 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2000 VL 56 IS 9 BP 1103 EP 1108 DI 10.1002/1097-4679(200009)56:9<1103::AID-JCLP1>3.0.CO;2-L PG 6 WC Psychology, Clinical SC Psychology GA 349ZU UT WOS:000089076200001 PM 10987686 ER PT J AU Kleespies, PM Dettmer, EL AF Kleespies, PM Dettmer, EL TI An evidence-based approach to evaluating and managing suicidal emergencies SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE suicide; behavioral emergency; suicidal emergency; suicide evaluation ID BORDERLINE PERSONALITY-DISORDER; SAN-DIEGO SUICIDE; RISK-FACTORS; COMPLETED SUICIDE; VIETNAM VETERANS; PSYCHOLOGICAL AUTOPSY; PSYCHIATRIC-PATIENTS; BEHAVIOR; SCHIZOPHRENIA; ALCOHOLISM AB This article presents a framework for making suicide risk estimations, as well as recommendations for the management of suicidal emergencies, that are useful to the practitioner. It provides a review, of existing empirical data concerning factors significantly related to acute suicidal behaviors within high-risk diagnoses. Findings across studies are categorized into risk profiles (as proposed by Clark & Fawcett. 1992) that are meant to aid the clinician in the application of recent research. The profiles are intended as templates in development and clearly require continual updating and clarification as new studies are completed. The article then addresses related management issues such as the importance of viewing risk factors within a comprehensive suicide assessment and the impact of possible negative therapist reactions when working with high-risk patients. (C) 2000 John Wiley & Sons, Inc. C1 VA Boston Healthcare Syst, Psychiat Serv 116B, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kleespies, PM (reprint author), VA Boston Healthcare Syst, Psychiat Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. NR 85 TC 17 Z9 17 U1 5 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2000 VL 56 IS 9 BP 1109 EP 1130 PG 22 WC Psychology, Clinical SC Psychology GA 349ZU UT WOS:000089076200002 PM 10987687 ER PT J AU Kleespies, PM Hughes, DH Gallacher, FP AF Kleespies, PM Hughes, DH Gallacher, FP TI Suicide in the medically and terminally ill: Psychological and ethical considerations SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE suicide; terminally ill; medically ill; ethics ID PHYSICIAN-ASSISTED SUICIDE; MENTAL-HEALTH PROFESSIONALS; GENERAL-PRACTITIONERS; TREATMENT DECISIONS; PRIMARY-CARE; DIGNITY ACT; DEPRESSION; DEATH; LIFE; HIV AB For the clinician who works in a behavioral-medicine or primary-care setting, this article presents the association between medical illness and suicide. Specific illnesses such as HIV/AIDS, cancers of the brain and nervous system, and multiple sclerosis all are associated with an increased risk of suicide. Rates of major depression rise with increasing rates of serious medical illness; however, depression and associated suicidal ideation tend to be undertreated in the medically ill. When medical illness becomes terminal, the clinician's patient may be confronted with difficult end-of-life decisions. Great concern exists in the United States about the ethics of end-of-life decision making and the issue of physician-assisted suicide, The latter part of this article examines the terminally ill patient's right to refuse life-sustaining treatments or to have death hastened according to the principle of the "double effect." it also reviews psychologists' apparent acceptance of the concept of rational suicide, as well as assisted suicide under certain conditions; and offers several caveats. A reexamination of psychology's role, standards, and principles with respect to rational suicide is recommended. (C) 2000 John Wiley a Sons, Inc. C1 VA Boston Healthcare Syst, Psychiat Serv 116B, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kleespies, PM (reprint author), VA Boston Healthcare Syst, Psychiat Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. NR 69 TC 18 Z9 18 U1 2 U2 11 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2000 VL 56 IS 9 BP 1153 EP 1171 DI 10.1002/1097-4679(200009)56:9<1153::AID-JCLP4>3.0.CO;2-Y PG 19 WC Psychology, Clinical SC Psychology GA 349ZU UT WOS:000089076200004 PM 10987689 ER PT J AU Trezza, GR Popp, SM AF Trezza, GR Popp, SM TI The substance user at risk of harm to self or others: Assessment and treatment issues SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE substance use; suicide; violence ID SAN-DIEGO SUICIDE; COMPLETED SUICIDE; DOMESTIC VIOLENCE; MARITAL VIOLENCE; MENTAL-HEALTH; LIFETIME RISK; ALCOHOL; ABUSE; SCHIZOPHRENIA; DIAGNOSES AB This article is divided into two main sections, one discussing suicide and substance use. and the other describing substance use and various forms of violent behavior toward others, including sexual assault and domestic violence. In each section, issues regarding prevalence of harm to self and others in substance users, clinical assessment and treatment. etiologic factors, definitional problems, and research needs are discussed. Substance use appears to be associated strongly with both violence toward self and violence toward others, but the exact nature of these relationships is somewhat unclear. (C) 2000 John Wiley & Sons, Inc. C1 Boston Univ, Sch Med, Boston VA Med Ctr, Boston, MA 02118 USA. Tufts Univ, Sch Med, Medford, MA 02155 USA. RP Trezza, GR (reprint author), VA Boston Healthcare Syst, Psychiat Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. NR 51 TC 11 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD SEP PY 2000 VL 56 IS 9 BP 1193 EP 1205 DI 10.1002/1097-4679(200009)56:9<1193::AID-JCLP6>3.0.CO;2-G PG 13 WC Psychology, Clinical SC Psychology GA 349ZU UT WOS:000089076200006 PM 10987691 ER PT J AU Caterina, J Shi, J Sun, X Qian, Q Yamada, S Liu, Y Krakora, S Bartlett, JD Yamada, Y Engler, JA Birkedal-Hansen, H Simmer, JP AF Caterina, J Shi, J Sun, X Qian, Q Yamada, S Liu, Y Krakora, S Bartlett, JD Yamada, Y Engler, JA Birkedal-Hansen, H Simmer, JP TI Cloning, characterization, and expression analysis of mouse enamelysin SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE MMP-20; amelogenin; ameloblast; odontoblast ID MATRIX METALLOPROTEINASES; AMELOGENIN; PROTEINS; TOOTH AB Enamelysin is a recently isolated member of the matrix metalloproteinase (MMP) family of extracellular matrix (ECM)-degrading enzymes. Here we describe the isolation and characterization of the mouse enamelysin cDNA. Expression of mouse enamelysin was detectable only in ameloblasts and odontoblasts of developing teeth. Characterization of mouse enamelysin demonstrated that it is highly conserved in both its sequence content and pattern of expression relative to the porcine, human, and bovine homologues previously described. C1 Natl Inst Dent & Craniofacial Res, Matrix Metalloprot Unit, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat Dent, San Antonio, TX 78284 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. RP Caterina, J (reprint author), Natl Inst Dent & Craniofacial Res, Matrix Metalloprot Unit, 30 Convent Dr,MSC 4380, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA13148]; NIDCR NIH HHS [DE08228, DE10631, R29 DE012098] NR 17 TC 20 Z9 21 U1 0 U2 0 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 SEP PY 2000 VL 79 IS 9 BP 1697 EP 1703 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 359GV UT WOS:000089603900010 PM 11023266 ER PT J AU Trehan, M AF Trehan, M TI The use of antimalarials in dermatology SO JOURNAL OF DERMATOLOGICAL TREATMENT LA English DT Article DE Antimalarials; chloroquine; hydroxychloroquine; quinacrine ID SYSTEMIC LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; HYDROXYCHLOROQUINE TREATMENT; BRITISH-EXPERIENCE; RHEUMATOID-ARTHRITIS; HEALTHY-VOLUNTEERS; RETINAL TOXICITY; ANTI-MALARIALS; OCULAR SAFETY; HUMAN-MILK C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Trehan, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 77 TC 1 Z9 2 U1 1 U2 2 PU MARTIN DUNITZ LTD PI LONDON PA LIVERY HOUSE, 7-9 PRATT ST, LONDON NW1 0AE, ENGLAND SN 0954-6634 J9 J DERMATOL TREAT JI J. Dermatol. Treat. PD SEP PY 2000 VL 11 IS 3 BP 185 EP 194 DI 10.1080/09546630050517351 PG 10 WC Dermatology SC Dermatology GA 365HL UT WOS:000089945800010 ER PT J AU Calvi, LM Schipani, E AF Calvi, LM Schipani, E TI The PTH/PTHrP receptor in Jansen's metaphyseal chondrodysplasia SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Review ID HORMONE-RELATED PEPTIDE; HYPERFUNCTIONING THYROID ADENOMAS; ENDOCHONDRAL BONE-FORMATION; MALE PRECOCIOUS PUBERTY; PARATHYROID-HORMONE; THYROTROPIN-RECEPTOR; AUTOSOMAL-DOMINANT; BLOMSTRAND-CHONDRODYSPLASIA; SOMATIC MUTATIONS; INDIAN HEDGEHOG C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schipani, E (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. OI Calvi, Laura Maria/0000-0001-6969-239X FU NIAMS NIH HHS [AR-44855]; NIDDK NIH HHS [DK-07028] NR 64 TC 25 Z9 26 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD SEP PY 2000 VL 23 IS 8 BP 545 EP 554 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 357LY UT WOS:000089504200011 PM 11021773 ER PT J AU Dretler, SP AF Dretler, SP TI Ureteroscopy for proximal ureteral calculi: Prevention of stone migration SO JOURNAL OF ENDOUROLOGY LA English DT Article ID MANAGEMENT AB Background: The cephalad migration of proximal ureteral calculi accounts for a high percentage of ureteroscopic failures, Patients and Methods: A balloon on a wire is a single-channel 0.038-inch hollow guidewire with a low-profile balloon, which is inflatable to 12F. Forty-two consecutive patients with proximal ureteral calculi underwent ureteroscopy with the aid of this device. Results: Twenty-nine patients had successful placement of the balloon on a wire above the stone. Of those 29 patients, 26 became stone free with a single procedure. Conclusion: The balloon on a wire is a useful tool to aid in the prevention of proximal ureteral stone migration during ureteroscopy and to minimize the number of secondary procedures. In addition, it appears to be cost-effective. C1 Massachusetts Gen Hosp, Kidney Stone Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Dretler, SP (reprint author), Wang Ambulatory Care Ctr, 15 Parkman St,Suite 486, Boston, MA 02114 USA. NR 4 TC 26 Z9 33 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD SEP PY 2000 VL 14 IS 7 BP 565 EP 567 DI 10.1089/08927790050152159 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 356FM UT WOS:000089433400013 PM 11030537 ER PT J AU Stewart, L Ponce, R Oesterle, AL Griffiss, JM Way, LW AF Stewart, L Ponce, R Oesterle, AL Griffiss, JM Way, LW TI Pigment gallstone pathogenesis: Slime production by biliary bacteria is more important than beta-glucuronidase production SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 16-19, 1999 CL ORLANDO, FLORIDA SP Soc Surg Alimentary Tract DE gallstones; bacterial slime; glycocalyx; beta-glucuronidase ID COMMON BILE-DUCT; UNCONJUGATED BILIRUBIN; BLOCKAGE; BIOFILM; ENDOPROSTHESES; CHOLELITHIASIS; DISEASE; STENTS; MODEL; PH AB Pigment stones are thought to form as a result of deconjugation of bilirubin by bacterial beta -glucuronidase, which results in precipitation of calcium bilirubinate. Calcium bilirubinate is then aggregated into stones by an anionic glycoprotein. Slime (glycocalyx), an anionic glycoprotein produced by bacteria causing foreign body infections, has been implicated in the formulation of the precipitate that blocks biliary stents. We previously showed that bacteria are present within the pigment portions of gallstones and postulated a bacterial role in pigment stone formation through beta -glucuronidase or slime production. Ninety -one biliary bacterial isolates from 61 patients and 12 control stool organisms were tested for their production of beta -glucuronidase and slime. The average slime production was 42 for biliary bacteria and 2.5 for stool bacteria (P < 0.001). Overall, 73% of biliary bacteria and 8% of stool bacteria produced slime (optical density >3). In contrast, only 38% of biliary bacteria produced beta -glucuronidase. Eighty-two percent of all patients, 90% of patients with common bile duct (CBD) stones, 100% of patients with primary CBD stones, and 93% of patients with biliary tubes had one or more bacterial species in their stones that produced slime. By comparison, only 47% of all patients, 60% of patients with CBD stones, 62 of patients with primary CBD stones, and 50% of patients with biliary T tubes had one or more bacteria that produced beta- glucuronidase. Most biliary bacteria produced slime, and slime production correlated better than beta -glucuronidase production did with stone formation and the presence of biliary tubes or stents. Patients with primary CBD stones and biliary tubes had the highest incidence of slime production. These findings suggest that bacterial slime is important in gallstone formation and the blockage of biliary tubes. C1 Univ Calif San Francisco, Vet Adm Med Ctr, Dept Surg, Surg Serv 112, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Microbiol, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Stewart, L (reprint author), Univ Calif San Francisco, Vet Adm Med Ctr, Dept Surg, Surg Serv 112, 4150 Clement St, San Francisco, CA 94121 USA. NR 28 TC 22 Z9 26 U1 0 U2 1 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD SEP-OCT PY 2000 VL 4 IS 5 BP 547 EP 553 DI 10.1016/S1091-255X(00)80100-6 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 418XJ UT WOS:000167919400017 PM 11077333 ER PT J AU Herrlinger, U Pechan, PA Jacobs, AH Woiciechowski, C Rainov, NG Fraefel, C Paulus, W Reeves, SA AF Herrlinger, U Pechan, PA Jacobs, AH Woiciechowski, C Rainov, NG Fraefel, C Paulus, W Reeves, SA TI HSV-1 infected cell proteins influence tetracycline-regulated transgene expression SO JOURNAL OF GENE MEDICINE LA English DT Article ID HERPES-SIMPLEX VIRUS; INDUCIBLE GENE-EXPRESSION; IMMEDIATE-EARLY PROTEINS; TYPE-1 LATE GENE; MAMMALIAN-CELLS; ADENOVIRUS VECTOR; AMPLICON VECTORS; TRANSCRIPTIONAL ACTIVATION; REPLICATION-COMPETENT; ALPHA PROTEIN-ICP27 AB Background This study investigates elements of herpes simplex virus type 1 (HSV-1) which influence transgene expression in tetracycline-regulated expression systems. Methods Different HSV-1 mutants were used to infect Vero cells that had been transfected with plasmids containing the luciferase gene under the control of tet-off or tet-on tetracycline-regulation systems. Results The baseline level of luciferase expression was elevated after infection with HSV-1 mutants lacking one or more immediate early genes encoding transactivating factors: ICP27, ICP4 and ICP0. With the tet-off system, not only was baseline expression elevated, but there was a complete loss of induction upon removal of tet when this regulatory system was brought into the cell by infection with helper virus-free amplicon vectors. Elevation of luciferase expression was also observed upon infection with the same HSV-1 mutants following transfection with a plasmid containing only a CMV minimal promoter driving luciferase (pUHC13-3). Only one HSV mutant (14H Delta 3), which bears a disruption in the transactivation domain of VP16 and is deleted for both ICP4 genes, did not increase baseline luciferase expression after transfection of pUHC13-3. The disregulating effects were dependent on virus dose and were not influenced by treatment with interferon (IFN)-alpha, which suppresses viral gene expression. Additional assays involving cotransfection of pUHC13-3 with a plasmid encoding of the HSV-1 transactivating factor ICP4 revealed that ICP4 was the most potent inducer of gene expression from the tetO/CMV minimal promoter. Conclusion These results indicate that proteins encoded in the HSV-1 genome, especially the transactivating immediate early gene products (ICP4, ICP27 and ICP0) and the VP16 tegument protein can activate the tetO/minimal CMV promoter and thereby interfere with the integrity of tetracycline-regulated transgene expression. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Univ Tubingen, Dept Neurol, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Serv Neurol, Mol Neuogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Univ Cologne, Dept Neurol, Cologne, Germany. Humboldt Univ, Dept Neurosurg, Berlin, Germany. Univ Halle Wittenberg, Dept Neurosurg, Halle, Germany. Univ Zurich, Inst Virol, Zurich, Switzerland. Univ Munster, Inst Neuropathol, D-4400 Munster, Germany. RP Herrlinger, U (reprint author), Univ Tubingen, Dept Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. NR 71 TC 16 Z9 17 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD SEP-OCT PY 2000 VL 2 IS 5 BP 379 EP 389 DI 10.1002/1521-2254(200009/10)2:5<379::AID-JGM126>3.0.CO;2-G PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 360KU UT WOS:000089667500010 PM 11045432 ER PT J AU Mahoney, JE Eisner, J Havighurst, T Gray, S Palta, M AF Mahoney, JE Eisner, J Havighurst, T Gray, S Palta, M TI Problems of older adults living alone after hospitalization SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hospitalization; risk factors; activities of daily living; socioeconomic factors; support; aged ID ACUTE MEDICAL ILLNESS; NURSING-HOME; FUNCTIONAL STATUS; SOCIAL SUPPORT; RISK-FACTORS; CARE; DEPRESSION; DECLINE; INSTITUTIONALIZATION; ADMISSION AB OBJECTIVE: To describe functional deficits among older adults living alone and receiving home nursing following medical hospitalization, and the association of living alone with lack of functional improvement and nursing home utilization 1 month after hospitalization. DESIGN: Secondary analysis of a prospective cohort study. PARTICIPANTS: Consecutive sample of patients age 65 and over receiving home nursing following medical hospitalization, Patients were excluded for new diagnosis of myocardial infarction or stroke in the previous 2 months, diagnosis of dementia if living alone, or nonambulatory status. Of 613 patients invited to participate, 312 agreed. MEASUREMENTS: One week after hospitalization, patients were assessed in the home for demographic information, medications, cognition, and self-report of prehospital and current mobility and function in activities of daily living (ADLs) and independent activities of daily living (IADLs). One month later, patients were asked about current function and nursing home utilization. The outcomes were lack of improvement in ADL function and nursing home utilization 1 month after hospitalization. RESULTS: One hundred forty-one (45%) patients lived alone. After hospital discharge, 40% of those living alone and 62% of those living with others had at least 1 ADL dependency (P = .0001). Patients who were ADL dependent and lived alone were 3.3 (95% confidence interval [95% CI], 1.4 to 7.6) times less likely to improve in ADLs and 3.5 (95% CI, 1.0 to 11.9) times more likely to be admitted to a nursing home in the month after hospitalization. CONCLUSION: Patients who live alone and receive home nursing after hospitalization are less likely to improve in function and more likely to be admitted to a nursing home, compared with those who live with others. More intensive resources may be required to continue community living and maximize independence. C1 William S Middleton Mem Vet Hosp, GRECC Serv, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Univ Wisconsin, Inst Aging, Madison, WI USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Univ Wisconsin, Sch Med, Dept Prevent Med, Madison, WI USA. RP Mahoney, JE (reprint author), William S Middleton Mem Vet Hosp, GRECC Serv, 2500 Overlook Terrace, Madison, WI 53705 USA. FU NIA NIH HHS [K08AG00623] NR 38 TC 28 Z9 30 U1 2 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2000 VL 15 IS 9 BP 611 EP 619 DI 10.1046/j.1525-1497.2000.06139.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 362QZ UT WOS:000089790900001 PM 11029674 ER PT J AU Rosenfeld, KE Wenger, NS Kagawa-Singer, M AF Rosenfeld, KE Wenger, NS Kagawa-Singer, M TI End-of-life decision making - A qualitative study of elderly individuals SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE advance care planning; aged; decision making; life-sustaining treatment; physician-patient relations; proxy; terminal care ID CARDIOPULMONARY-RESUSCITATION; INTENSIVE-CARE; BREAST-CANCER; ILL PATIENTS; PREFERENCES; SURVIVAL; AGE; CHOICES; OLDER; DEATH AB OBJECTIVE: To identify the desired features of end-of-life medical decision making from the perspective of elderly individuals. DESIGN: Qualitative study using in-depth interviews and analysis from a phenomenologic perspective. SETTING: A senior center and a multilevel retirement community in Los Angeles. PARTICIPANTS: Twenty-one elderly informants (mean age 83 years) representing a spectrum of functional status and prior experiences with end-of-life decision making. MAIN RESULTS: Informants were concerned primarily with the outcomes of serious illness rather than the medical interventions that might be used, and defined treatments as desirable to the extent they could return the patient to his or her valued life activities. Advanced age was a relevant consideration in decision making, guided by concerns about personal losses and the meaning of having lived a "full life." Decisionmaking authority was granted both to physicians (for their technical expertise) and family members (for their concern for the patient's interests), and shifted from physician to family as the patient's prognosis for functional recovery became grim. Expressions of care, both by patients and family members, were often important contributors to end-of-life treatment decisions. CONCLUSIONS: These findings suggest that advance directives and physician-patient discussions that focus on acceptable health states and valued life activities may be better suited to patients' end-of-Life care goals than those that focus on specific medical interventions, such as cardiopulmonary resuscitation. We propose a model of collaborative surrogate decision making by families and physicians that encourages physicians to assume responsibility for recommending treatment plans, including the provision or withholding of specific life-sustaining treatments, when such recommendations are consistent with patients' and families' goals for care. C1 Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth & Asian Amer Studies, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Rosenfeld, KE (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Div Gen Internal Med 111G, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 41 TC 107 Z9 107 U1 4 U2 14 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2000 VL 15 IS 9 BP 620 EP 625 DI 10.1046/j.1525-1497.2000.06289.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 362QZ UT WOS:000089790900002 PM 11029675 ER PT J AU Brandenburg, JA Marrie, TJ Coley, CM Singer, DE Obrosky, DS Kapoor, WN Fine, MJ AF Brandenburg, JA Marrie, TJ Coley, CM Singer, DE Obrosky, DS Kapoor, WN Fine, MJ TI Clinical presentation, processes and outcomes of care for patients with pneumococcal pneumonia SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE pneumonia; pneumococcal; outcomes ID COMMUNITY-ACQUIRED PNEUMONIA; RESISTANT STREPTOCOCCUS-PNEUMONIAE; HOSPITALIZED-PATIENTS; BACTEREMIA; MORTALITY; SURVEILLANCE; ETIOLOGY; SWEDEN AB OBJECTIVE: To describe the presentation, resolution of symptoms, processes of care, and outcomes of pneumococcal pneumonia, and to compare features of the bacteremic and nonbacteremic forms of this illness. DESIGN:A prospective cohort study, SETTING: Five medical institutions in 3 geographic locations. PARTICIPANTS: Inpatients and outpatients with community-acquired pneumonia (CAP), MEASUREMENTS: Sociodemographic characteristics, respiratory and nonrespiratory symptoms, and physical examination findings were obtained from interviews or chart review. Severity of illness was assessed using a validated prediction rule for short-term mortality in CAP, Pneumococcal pneumonia was categorized as bacteremic; nonbacteremic, pure etiology; or nonbacteremic, mixed etiology, MAIN RESULTS: One hundred fifty-eight (6.9%) of 2,287 patients (944 outpatients, 1,343 inpatients) with CAP had pneumococcal pneumonia. Sixty-five (41%) of the 158 with pneumococcal pneumonia were bacteremic: 74 (47%) were nonbacteremic with S, pneumoniae as sole pathogen: and 19 (12%) were nonbacteremic with S. pneumoniae as one of multiple pathogens. The pneumococcal bacteremia sate for outpatients was 2.6% and for inpatients it was 6.6%. Cough, dyspnea, and pleuritic pain were common respiratory symptoms. Hemopytsis occurred in 16% to 22% of the patients. A large number of nonrespiratory symptoms were noted. Bacteremic patients were less likely than nonbacteremic patients to have sputum production and myalgias (60% vs 82% and 33% vs 57%, respectively; P < .01 for both), more likely to have elevated blood urea nitrogen and serum creatinine levels, and more Likely to receive pencillin therapy. Half of bacteremic patients were in the low risk category for short-term mortality (groups I to III), similar to the nonbacteremic patients. None of the 32 bacteremic patients in risk groups I to III died, while 7 of 23 (30%) in risk group V died, Intensive care unit admissions and pneumonia-related mortality were similar between bacteremic and nonbacteremic groups. although 46% of the bacteremic group had respiratory failure compared with 32% and 37% for the other groups. The nonbacteremic pure etiology patients returned to household activities faster than bacteremic patients. Symptoms frequently persisted at 30 days: cough (50%); dyspnea (53%): sputum production (48%); pleuritic pain (13%); and fatigue (63%). CONCLUSIONS: There were few differences in the presentation of bacteremic and nonbacteremic pneumococcal pneumonia, About half of bacteremic pneumococcal pneumonia patients were at low risk for mortality. Symptom resolution frequently was slow. C1 St Francis Med Ctr, Pittsburgh, PA USA. Harvard Community Hlth Plan, Boston, MA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Div Gen Med, Dept Med, Pittsburgh, PA USA. Dalhousie Univ, Halifax, NS, Canada. Victoria Gen Hosp, Dept Med, Div Infect Dis, Halifax, NS B3H 2Y9, Canada. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Med Serv, Boston, MA 02114 USA. RP Marrie, TJ (reprint author), Walter C Mackenzie Hlth Sci Ctr, Dept Med, 2F1-30,8440 112 St, Edmonton, AB T6G 2R7, Canada. FU AHRQ HHS [R01 HS-06468] NR 31 TC 45 Z9 45 U1 2 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2000 VL 15 IS 9 BP 638 EP 646 DI 10.1046/j.1525-1497.2000.04429.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 362QZ UT WOS:000089790900005 PM 11029678 ER PT J AU Covinsky, KE AF Covinsky, KE TI Bringing a generalist approach to the problems of older patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID FUNCTIONAL OUTCOMES; ILL; GERIATRICS; SYMPTOMS; CARE C1 San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Covinsky, KE (reprint author), San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD SEP PY 2000 VL 15 IS 9 BP 673 EP 674 DI 10.1046/j.1525-1497.2000.00719.x PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 362QZ UT WOS:000089790900010 PM 11029683 ER PT J AU Morrill, JA Cannon, SC AF Morrill, JA Cannon, SC TI COOH-terminal truncated alpha(1s) subunits conduct current better than full-length dihydropyridine receptors SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE Ca2+ channels; skeletal muscle; Xenopus oocyte expression; cut-open oocyte voltage clamp; gating charge movement ID MAMMALIAN SKELETAL-MUSCLE; CALCIUM CHANNELS; CHARGE MOVEMENT; CA2+ CHANNEL; BETA-SUBUNIT; FIBERS; EXPRESSION; ACTIVATION; KINETICS; ALPHA-1 AB Skeletal muscle dihydropyridine (DHP) receptors function both as voltage-activated Ca2+ channels and as voltage sensors for coupling membrane depolarization to release of Ca2+ from the sarcoplasmic reticulum. In skeletal muscle, the principal or alpha(1S) subunit occurs in full-length (similar to 10% of total) and post-transcriptionally truncated (similar to 90%) forms, which has raised the possibility that the two functional roles are subserved by DHP receptors comprised of different sized oils subunits. We tested the functional properties of each form by injecting oocytes with cRNAs coding for full-length (alpha(1S)) or truncated (alpha(1S Delta C)) alpha subunits. Both translation products were expressed in the membrane, as evidenced by increases in the gating charge (Q(max) 80-150 pC). Thus, oocytes provide a robust expression system for the study of gating charge movement in arts, unencumbered by contributions from other voltage-gated channels or the complexities of the transverse tubules. As in recordings from skeletal muscle, for heterologously expressed channels the peak inward Ba2+ currents were small relative to Q(max). The truncated alpha(1S Delta C) protein, however, supported much larger ionic currents than the full-length product. These data raise the possibility that DHP receptors containing the more abundant, truncated form of the oils subunit conduct the majority of the L-type Ca2+ current in skeletal muscle. Our data also suggest that the carboxyl terminus of the oils subunit modulates the coupling between charge movement and channel opening. C1 Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Neurosci Program, Boston, MA 02115 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, Dept Nephrol, EDR 413,Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R37 AR042703, AR42703, R01 AR042703] NR 32 TC 9 Z9 9 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD SEP PY 2000 VL 116 IS 3 BP 341 EP 348 DI 10.1085/jgp.116.3.341 PG 8 WC Physiology SC Physiology GA 352XR UT WOS:000089245100003 PM 10962012 ER PT J AU Conigliaro, J Kraemer, K McNeil, M AF Conigliaro, J Kraemer, K McNeil, M TI Screening and identification of older adults with alcohol problems in primary care SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID CAGE QUESTIONNAIRE; USE DISORDERS; ELDERLY VETERANS; UNITED-STATES; SELF-REPORTS; TEST AUDIT; ABUSE; CONSUMPTION; DRINKING; DRINKERS AB Primary care physicians can anticipate encountering more elderly patients with alcohol problems since this population is increasing and the prevalence of alcohol problems has been stable. Brief screening tools, originally developed and validated among younger adults, may not be appropriate in the elderly. Therefore, specific validation studies and the development of elderly specific instruments have been reported. The specific goals of this report are to (1) review available screening tools for alcohol problems, (2) summarize elderly focused studies, and (3) provide recommendations for use in primary care. Using a variety of standards, the CAGE (Cut down, Annoyed, Guilty, and Eye opener) is the most consistent brief screen, but its threshold may need to be adjusted in the elderly. The Michigan Alcoholism Screening Test-Geriatric Version includes elderly-specific consequences, but its length may hinder routine use even in shortened form. Finally, the Alcohol Use Disorders Identification Test, although less sensitive than the CAGE, can also capture problem drinkers. Efforts are needed to include elderly-specific consequences and meaningful consumption thresholds in a brief, easily applied screen. C1 VA Pittsburgh Hlth Care Syst, Sect Gen Internal Med 11E120, Ctr Hlth Serv Res, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Div Gen Med, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Conigliaro, J (reprint author), VA Pittsburgh Hlth Care Syst, Sect Gen Internal Med 11E120, Ctr Hlth Serv Res, 11A,Univ Dr C, Pittsburgh, PA 15240 USA. FU NIAAA NIH HHS [5K08-AA00235] NR 61 TC 35 Z9 37 U1 1 U2 4 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD FAL PY 2000 VL 13 IS 3 BP 106 EP 114 PG 9 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 353FU UT WOS:000089264800002 PM 11001132 ER PT J AU Schonfeld, L Dupree, LW Dickson-Fuhrmann, E Royer, CM McDermott, CH Rosansky, JS Taylor, S Jarvik, LF AF Schonfeld, L Dupree, LW Dickson-Fuhrmann, E Royer, CM McDermott, CH Rosansky, JS Taylor, S Jarvik, LF TI Cognitive-behavioral treatment of older veterans with substance abuse problems SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article AB The authors describe the initial cohort of participants in the GET SMART program, an age-specific, outpatient program for older veterans with substance abuse problems. Chief among the program's services is a relapse-prevention intervention consisting of 16 weekly group sessions using cognitive-behavioral (CB) and self-management approaches. Group sessions begin with analysis of substance use behavior to determine high-risk situations for alcohol or drug use, followed by a series of modules to teach coping skills for coping with social pressure, being at home and alone, feelings of depression and loneliness, anxiety and tension, anger and frustration, cues for substance use, urges (self-statements), and slips or relapses. Of the first 110 admissions, more than one-third were homeless, which is indicative of the severity of psychosocial distress of the patients, and more than one-third used illicit drugs. A total of 49 patients completed CB treatment groups and 61 dropped out of treatment. At 6-month follow-up, program completers demonstrated much higher rates of abstinence compared to noncompleters. The results suggest that CB approaches work well with older veterans with significant medical, social, and drug use problems. C1 Univ S Florida, Louis De La Porte Florida Mental Hlth Inst, Dept Aging & Mental Hlth, Tampa, FL 33612 USA. VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, GET SMART Team, Los Angeles, CA USA. RP Schonfeld, L (reprint author), Univ S Florida, Louis De La Porte Florida Mental Hlth Inst, Dept Aging & Mental Hlth, Tampa, FL 33612 USA. NR 15 TC 25 Z9 25 U1 2 U2 9 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD FAL PY 2000 VL 13 IS 3 BP 124 EP 129 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 353FU UT WOS:000089264800004 PM 11001134 ER PT J AU Royer, CM Dickson-Fuhrmann, E McDermott, CH Taylor, S Rosansky, JS Jarvik, LF AF Royer, CM Dickson-Fuhrmann, E McDermott, CH Taylor, S Rosansky, JS Jarvik, LF TI Portraits of change: Case studies from an elder-specific addiction program SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article AB The authors describe two case histories of patients served by the GET SMART program that provide a glimpse of typical client substance abuse histories and their remarkable journeys of change. An age-specific outpatient program for older veterans with illicit drug and alcohol dependence, the GET SMART program uses individualized and group treatment interventions in an environment of collaboration, respect, and hope. The program employs the stages of change framework and a clinical framework that includes cognitive-behavioral and motivational interviewing approaches. C1 VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, GET SMART Program, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, UPBEAT Program, Los Angeles, CA 90073 USA. RP Royer, CM (reprint author), VA Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, GET SMART Program, Los Angeles, CA 90073 USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD FAL PY 2000 VL 13 IS 3 BP 130 EP 133 PG 4 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 353FU UT WOS:000089264800005 PM 11001135 ER PT J AU Kubota, T Miyagishima, M Alvarez, RJ Kormos, R Rosenblum, WD Demetris, AJ Semigran, MJ Dec, GW Holubkov, R McTiernan, CF Mann, DL Feldman, AM McNamara, DM AF Kubota, T Miyagishima, M Alvarez, RJ Kormos, R Rosenblum, WD Demetris, AJ Semigran, MJ Dec, GW Holubkov, R McTiernan, CF Mann, DL Feldman, AM McNamara, DM TI Expression of proinflammatory cytokines in the failing human heart: Comparison of recent-onset and end-stage congestive heart failure SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; DILATED CARDIOMYOPATHY; INTERLEUKIN-6; MYOCARDIUM AB Background: Plasma levels of proinflammatory cytokines, including tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, are elevated in patients with congestive heart failure (CHF). Recent studies suggest that the failing human heart is a source of proinflammatory cytokines in the end-stage failing heart. However, the relevance of plasma levels to those of the myocardium remains undefined. We sought to compare cytokine expression in early and end-stage CHF, and to evaluate the correlation of tissue expression to plasma levels. Methods: Two patient populations were studied: patients with recent-onset CHF, all with symptoms less than 6 months (n = 17, duration of symptoms 2.1 +/- 1.6 months, range of New York Heart Association (NYHA) 1 to 3), and end-stage heart-failure patients (n = 7) who underwent left-ventricular assist-device (LVAD) implantation (Duration of symptoms 47.1 +/- 28.0 months, all NYHA class 4). Plasma levels of TNF-alpha and IL-6 proteins were evaluated by an Enzyme-Linked Immuno-Sorbent Assay (ELISA), while myocardial levels of cytokine transcripts were assessed by ribonuclease (Rnase) protection assay. Results: In patients with end-stage heart failure, TNF-alpha and IL-6 were increased in the plasma-as well as in the myocardium (plasma: TNF- alpha = 7.7 +/- 2.3 pg/ml, IL-6 = 45.0 +/- 47.1 pg/ml; myocardium: TNF-alpha = 0.31 +/- 0.15% of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, IL-6 = 1.56 +/- 1.54%). In contrast, despite elevated plasma levels of TNF-alpha and IL-6, the myocardium of patients with the recent onset of symptoms demonstrated minimal expression of TNF-alpha and IL-6 messenger ribonucleic acid (mRNA) (plasma: TNF-alpha = 4.3 +/- 1.7 pg/ml, IL-6 = 3.3 +/- 1.8 pg/ml; myocardium: TNF-alpha = 0.13 +/- 0.04%, IL-6 = 0.02 +/- 0.04%). Plasma levels of TNF-alpha were significantly correlated with those in the myocardium when both populations were combined. (r = 0.69, p < 0.001) Conclusions: Cytokines are expressed in the myocardium in end-stage heart failure to a much greater degree than in patients with the recent-onset of symptoms. This suggests that induction of cytokines in the myocardium is a relatively late event in the pathogenesis of CHF. Furthermore, plasma levels of TNF-alpha correlates with mRNA expression in the myocardium and thus may serve as an appropriate marker of myocardial cytokine activation. Whether the production of cytokines in the failing human heart precedes the elevation of cytokines in the plasma remains undefined. Therefore, we studied expression of TNF-alpha and IL-6 in the myocardium as well as in the plasma in patients with early and end-stage CHF. The results have demonstrated that cytokines are expressed in the myocardium in end-stage heart failure to a much greater degree than in patients with the recent onset of symptoms. This suggests that induction of cytokines in the myocardium is a relatively late event in the pathogenesis of CHF. C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, UPMC Hlth Syst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Surg, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Div Transplant Pathol, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Vet Adm Med Ctr, Dept Med, Cardiol Sect, Houston, TX 77211 USA. Baylor Coll Med, Houston, TX 77030 USA. RP McNamara, DM (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, UPMC Hlth Syst, 200 Lothrop St,558 Scaife Hall, Pittsburgh, PA 15213 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 12 TC 77 Z9 79 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD SEP PY 2000 VL 19 IS 9 BP 819 EP 824 DI 10.1016/S1053-2498(00)00173-X PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 357PA UT WOS:000089509000001 PM 11008069 ER PT J AU Bhol, KC Dans, MJ Simmons, RK Foster, CS Giancotti, FG Ahmed, AR AF Bhol, KC Dans, MJ Simmons, RK Foster, CS Giancotti, FG Ahmed, AR TI The autoantibodies to alpha(6)beta(4) integrin of patients affected by ocular cicatricial pemphigoid recognize predominantly epitopes within the large cytoplasmic domain of human beta(4) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASEMENT-MEMBRANE; LUPUS-ERYTHEMATOSUS; ANTIBODIES; HEMIDESMOSOMES; ADHESION; SUBUNIT; IMMUNOFLUORESCENCE; PROTEINS; ANTIGEN; ASSOCIATION AB This study was undertaken to characterize the antigenic determinants recognized by the autoantibodies of patients with ocular cicatricial pemphigoid (OCP), OCP is a subepithelial, blistering, autoimmune disease that mainly affects the conjunctiva and other mucous membranes. We previously demonstrated that a cDNA clone, isolated from a keratinocyte expression library by using immunoaffinity-purified OCP autoantibody, encoded the cytoplasmic domain of beta (4) integrin subunit, Our subsequent studies showed that sera from all the OCP patients that were tested recognize the human beta (4) integrin subunit, To identify the prevalent epitopes of the anti-beta (4) autoantibodies of OCP, we have used cell lines transfected with vectors encoding a wild-type beta (4) subunit, a tailless beta (4) subunit, or a beta (4) subunit lacking the extracellular domain. Nontransfected cell lines were used as controls. Lysates from these cell lines were analyzed with OCP sera, IgG fractions from OCP sera, and immunoaffinity-purified OCP autoantibodies. Abs to extracellular and cytoplasmic domains of human beta (4) integrin were used as positive controls, whereas normal human sera and normal human IgG fractions were used as negative controls. The reactivity of OCP Abs was determined by using immunoblotting, immunoprecipitation, and FAGS analysis. The results of this study indicate that OCP sera, OCP Ige fractions, and immunoaffinity-purified OCP autoantibodies react with the intracellular and not the extracellular domain of human beta (4) integrin subunit. In vitro cell culture experiments demonstrated that OCP autoantibody binds to the cytoplasm of the cells. The relevance of these findings to the pathogenesis of OCP is discussed. C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Cellular Biochem & Biophys, New York, NY 10021 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med, 188 Longwood Ave, Boston, MA 02115 USA. FU NEI NIH HHS [R01 EY08379] NR 35 TC 32 Z9 32 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2000 VL 165 IS 5 BP 2824 EP 2829 PG 6 WC Immunology SC Immunology GA 390MF UT WOS:000166299300063 PM 10946315 ER PT J AU Bryant, AE Chen, RYZ Nagata, Y Wang, Y Lee, CH Finegold, S Guth, PH Stevens, DL AF Bryant, AE Chen, RYZ Nagata, Y Wang, Y Lee, CH Finegold, S Guth, PH Stevens, DL TI Clostridial gas gangrene. I. Cellular and molecular mechanisms of microvascular dysfunction induced by exotoxins of Clostridium perfringens SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 1st American-Society-for-Microbiology Conference on Microbes, Haemostasis, and Vascular Biology CY MAR, 1998 CL GALVESTON, TEXAS SP Amer Soc Microbiol ID PHOSPHOLIPASE-C; ALPHA-TOXIN; ACTIVATED PLATELETS; ENDOTHELIAL-CELLS; EXPRESSION; LEUKOCYTES; FLOW AB Mechanisms responsible for the rapid tissue destruction in gas gangrene are not well understood. To examine the early effects of Clostridium perfringens exotoxins on tissue perfusion, a rat model of muscle blood flow was developed. Intramuscular injection of a clostridial toxin preparation containing both phospholipase C (PLC) and theta-toxin caused a rapid (1-2 min) and irreversible decrease in blood how that paralleled formation of activated platelet aggregates in venules and arterioles. Later (20-40 min), aggregates contained fibrin and leukocytes, and neutrophils accumulated along vascular walls. Flow cytometry confirmed that these clostridial toxins or recombinant PLC induced formation of P-selectin-positive platelet aggregates. Neutralization of PLC activity in the clostridial toxin preparation completely abrogated human platelet responses and reduced perfusion deficits. It is concluded that tissue destruction in gas gangrene is related to profound attenuation of blood how initiated by activation of platelet responses by PLC. C1 Vet Affairs Med Ctr, Infect Dis Sect, Boise, ID 83702 USA. Univ Idaho, Dept Microbiol, Moscow, ID 83843 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Anesthesiol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Bryant, AE (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, Bldg 45,500 W Ft St, Boise, ID 83702 USA. NR 28 TC 48 Z9 50 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 2000 VL 182 IS 3 BP 799 EP 807 DI 10.1086/315756 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 355LH UT WOS:000089386800020 PM 10950774 ER PT J AU Bryant, AE Chen, RYZ Nagata, Y Wang, Y Lee, CH Finegold, S Guth, PH Stevens, DL AF Bryant, AE Chen, RYZ Nagata, Y Wang, Y Lee, CH Finegold, S Guth, PH Stevens, DL TI Clostridial gas gangrene. II. Phospholipase C-induced activation of platelet gpIIbIIIa mediates vascular occlusion and myonecrosis in Clostridium perfringens gas gangrene SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th European Workshop on Bacterial Protein Toxins CY JUN, 1999 CL STE MAXIME, FRANCE ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; WHOLE-BLOOD; FIBRINOGEN; ADHESION; TOXIN; GLYCOPROTEIN; EXPRESSION; CD11B/CD18; SELECTIN; MAC-1 AB Clostridium perfringens gas gangrene is a fulminant infection, and radical amputation re mains the single best treatment. It has been hypothesized that rapid tissue destruction is related to tissue hypoxia secondary to toxin-induced vascular obstruction, and previous studies demonstrated that phospholipase C (PLC) caused a rapid and irreversible decrease in skeletal muscle blood flow that paralleled the formation of intravascular aggregates of activated plate lets, fibrin, and leukocytes, In this study, flow cytometry demonstrated that PLC stimulated platelet/neutrophil aggregation in a gpIIbIIIa-dependent fashion. Pretreatment of animals with heparin or depletion of leukocytes reduced blood-flow deficits, and aggregate formation caused by PLC. It is concluded that fulminant tissue destruction in gas gangrene results from profound attenuation of blood dow caused by PLC-induced, gpIIbIIIa-mediated formation of heterotypic platelet/polymorphonuclear leukocyte aggregates. Therapeutic strategies that target gpIIbIIIa may prevent vascular occlusion, maintain tissue viability, and provide an alternative to radical amputation for patients with this infection. C1 Vet Affairs Med Ctr, Infect Dis Sect, Boise, ID 83702 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Anesthesiol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Bryant, AE (reprint author), Vet Affairs Med Ctr, Infect Dis Sect, Bldg 45,500 W Ft St, Boise, ID 83702 USA. NR 28 TC 50 Z9 50 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 2000 VL 182 IS 3 BP 808 EP 815 DI 10.1086/315757 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 355LH UT WOS:000089386800021 PM 10950775 ER PT J AU Ge, YM Ezzell, RM Warren, HS AF Ge, YM Ezzell, RM Warren, HS TI Localization of endotoxin in the rat intestinal epithelium SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MULTIPLE-ORGAN-FAILURE; ESCHERICHIA-COLI; BACTERIAL TRANSLOCATION; CELLULAR-DISTRIBUTION; LIPOPOLYSACCHARIDE; EXCRETION; CYTOKINE; ENTEROCYTES; CLEARANCE; SURVIVAL AB High levels of circulating lipopolysaccharide (LPS) cause intestinal inflammation and increased permeability to bacteria and toxins. To better understand the effects of LPS on the gut, confocal microscopy and immunofluorescence staining were used to examine the distribution of LPS in the rat intestine after intravenous or enteral administration. LPS was localized in macrophages in the lamina propria from 1 h to >28 days after intravenous injection. LPS was also detected in the epithelial cells from 8 h to 7 days after injection. In contrast, LPS administered enterally was found in the gut lumen in close proximity to the mucosa but was not detected in enterocytes at any time. The concentration of LPS in enterocytes near the villus tip provides a mechanism for the clearance of endotoxin, by the turnover and shedding of LPS-containing enterocytes into the gut lumen, that has not been previously described. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Res Lab,Dept Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit,Dept Pediat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit,Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Warren, HS (reprint author), Massachusetts Gen Hosp East, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI28943]; NIDDK NIH HHS [DK43351] NR 32 TC 17 Z9 17 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 2000 VL 182 IS 3 BP 873 EP 881 DI 10.1086/315784 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 355LH UT WOS:000089386800029 PM 10950783 ER PT J AU Zollner, TM Beschmann, HA Ludwig, R von Andrian, UH Kaufmann, R Podda, M AF Zollner, TM Beschmann, HA Ludwig, R von Andrian, UH Kaufmann, R Podda, M TI Cyclosporine A and FK506 inhibit the expression and function of the cutaneous lymphocyte-associated antigen (CLA) on T cells via alpha(1,3)-fucosyltransferase VII SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Frankfurt, Dept Dermatol, D-6000 Frankfurt, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2000 VL 115 IS 3 BP 533 EP 533 PG 1 WC Dermatology SC Dermatology GA 350KR UT WOS:000089100300131 ER PT J AU Podda, M Beschmann, HA von Andrian, UH Kaufmann, R Zollner, TM AF Podda, M Beschmann, HA von Andrian, UH Kaufmann, R Zollner, TM TI Peroxynitrite induces the expression of cutaneous lymphocyte-associated antigen (CLA) via alpha(1,3)-fucosyltransferase VII on human T cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Frankfurt, Dept Dermatol, D-6000 Frankfurt, Germany. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP PY 2000 VL 115 IS 3 BP 562 EP 562 PG 1 WC Dermatology SC Dermatology GA 350KR UT WOS:000089100300304 ER PT J AU Arozullah, A Henderson, W Khuri, S Daley, J AF Arozullah, A Henderson, W Khuri, S Daley, J TI Variation in risk-adjusted hospital rates of postoperative pulmonary complications. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 Univ Illinois, Coll Med, Chicago, IL USA. Hines Cooperat Studies Program, Hines, IL USA. Boston VA Healthcare System, W Roxbury, MA USA. Massachusetts Gen Hosp, Partners Healthcare, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 2000 VL 48 IS 5 MA 130 BP 255A EP 255A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 349GW UT WOS:000089038200142 ER PT J AU Bodennec, J Koul, O Aguado, I Brichon, G Zwingelstein, G Portoukalian, J AF Bodennec, J Koul, O Aguado, I Brichon, G Zwingelstein, G Portoukalian, J TI A procedure for fractionation of sphingolipid classes by solid-phase extraction on aminopropyl cartridges SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ceramides; sphingosine; dihydrosphingosine; phytosphingosine; neutral glycosphingolipids; sphingomyelin; ceramide 1-phosphate; sphingosine 1-phosphate; sulfatides; solid-phase extraction ID THIN-LAYER CHROMATOGRAPHY; SPHINGOSINE 1-PHOSPHATE; RAPID SEPARATION; FATTY-ACIDS; BIOLOGICAL SAMPLES; LIPID CLASSES; POLAR LIPIDS; CERAMIDES; SILICA; CELLS AB Solid-phase extraction (SPE) methods are easy, rapid, and reliable. Their growing popularity is in part due to their operational simplicity and cost reduction in solvents, and partly because they are easier to automate, Sphingolipids are implicated in various cellular events such as growth, differentiation, and apoptosis, However, their separation by small SPE cartridges has attracted limited attention. Here we describe an SPE procedure on aminopropyl cartridges that by sequential elution allows the separation elf a lipid mixture into free ceramides, neutral glycosphingolipids, neutral phospholipids (sphingomyelin), and a fraction containing the acidic phospholipids and phosphorylated sphingoid bases, phosphoceramides and sulfatides, Individual components are obtained in high yield and purity. We applied the procedure to obtain data on separation of [H-3]myristic acid-labeled sphingolipids from fish gills, and from human melanoma tumor tissue. Individual lipids in the SPE fractions were identified by chromatography on several high-performance thin-layer chromatography (HPTLC) systems. The chromatographic behavior of free sphingoid bases is also reported. C1 Univ Lyon 1, Inst Michel Pacha, F-83500 La Seyne Sur Mer, France. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA 02452 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02214 USA. Massachusetts Gen Hosp, Boston, MA 02214 USA. Univ Lyon 1, Fac Med Lyon Sud, Lab Tumor Glycobiol, F-69921 Oullins, France. RP Bodennec, J (reprint author), Univ Lyon 1, Inst Michel Pacha, F-83500 La Seyne Sur Mer, France. NR 40 TC 68 Z9 71 U1 5 U2 22 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2000 VL 41 IS 9 BP 1524 EP 1531 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 355VF UT WOS:000089408700018 PM 10974060 ER PT J AU Benner, T Reimer, P Erb, G Schuierer, G Heiland, S Fischer, C Geens, V Sartor, K Forsting, M AF Benner, T Reimer, P Erb, G Schuierer, G Heiland, S Fischer, C Geens, V Sartor, K Forsting, M TI Cerebral MR perfusion imaging: First clinical application of a 1 M gadolinium chelate (Gadovist 1.0) in a double-blinded randomized dose-finding study SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT 6th Scientific Meeting and Exhbiition of the International-Society-for-Magnetic-Resonance-in-Medicine CY 1998 CL SYDNEY, AUSTRALIA SP Internat Soc Magnet Resonance Med DE magnetic resonance imaging; cerebral perfusion; paramagnetic contrast media; gadolinium chelate ID BLOOD-VOLUME; COMPUTED-TOMOGRAPHY; CONTRAST AGENT; STEADY-STATE; GADOBUTROL; BRAIN; FLOW; ISCHEMIA; QUANTIFICATION; VASCULARITY AB The purpose of this study was to evaluate efficacy and safety of the 1 M gadolinium chelate Gadovist 1.0 for assessment of cerebral hemodynamics with dynamic susceptibility contrast-enhanced magnetic resonance (AM) imaging. Eighty-nine patients with carotid artery stenosis or cerebral infarcts were included in this multicenter, double-blinded study using five dose groups from 0.1 to 0.5 mmol/kg. Imaging was performed with 1-T scanners using a T2*-weighted fast low-angle shot (FLASH) sequence. Dose-dependent changes in quantitative and qualitative parameters describing signal-time curves and relative regional cerebral blood volume maps were Investigated. For safety evaluation, vital signs, clinical and laboratory tests, and adverse events were assessed. The quantitative measurements revealed an optimal dose of 0.4 mmol/kg. The qualitative evaluation revealed that the required qualitative assessment for clinical purposes was already reached at a dose of 0.3 mmol/kg. No significant changes in vital signs and laboratory tests were found. No serious adverse events were observed. The combined results revealed the dose of 0.3 mmol/kg as the diagnostically adequate dose given the gradient-echo sequence and field strength used. Gadovist 1.0 has been shown to be a safe and well-tolerated contrast agent. (C) 2000 Willey-Liss, Inc. C1 Univ Heidelberg, Sch Med, Dept Neuroradiol, D-69120 Heidelberg, Germany. RP Benner, T (reprint author), Massachusetts Gen Hosp, NMR Ctr, Charlestown Navy Yard,Bldg 149 13th St, Charlestown, MA 02129 USA. RI Forsting, Michael/C-6925-2013 NR 45 TC 31 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2000 VL 12 IS 3 BP 371 EP 380 DI 10.1002/1522-2586(200009)12:3<371::AID-JMRI1>3.0.CO;2-3 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 477QE UT WOS:000171295100001 PM 10992303 ER PT J AU Syngal, S Fox, EA Eng, C Kolodner, RD Garber, JE AF Syngal, S Fox, EA Eng, C Kolodner, RD Garber, JE TI Sensitivity and specificity of clinical criteria for hereditary non-polyposis colorectal cancer associated mutations in MSH2 and MLH1 SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE hereditary non-polyposis colorectal cancer; MSH2; MLH1 ID NONPOLYPOSIS COLON-CANCER; MICROSATELLITE INSTABILITY; HOMOLOG; GENE; HNPCC; FAMILIES; RECEPTOR AB Background and aims-There are multiple criteria for the clinical diagnosis of hereditary non-polyposis colorectal cancer (HNPCC). The value of several of the newer proposed diagnostic criteria in identifying subjects with mutations in HNPCC associated mismatch repair genes has not been evaluated, and the performance of the different criteria have not been formally compared with one another. Methods-We classified 70 families with suspected hereditary colorectal cancer (excluding familial adenomatous polygosis) by several existing clinical criteria for HNPCC, including the Amsterdam criteria, the Modified Amsterdam criteria, the Amsterdam II criteria, and the Bethesda criteria. The results of analysis of the mismatch repair genes MSH2 and MLH1 by full gene sequencing were available for a proband with colorectal neoplasia in each family. The sensitivity and specificity of each of the clinical criteria for the presence of MSH2 and MLH1 mutations were calculated. Results-Of the 70 families, 28 families fulfilled the Amsterdam criteria, 39 fulfilled the Modified Amsterdam Criteria, 34 fulfilled the Amsterdam II criteria, and 56 fulfilled at least one of the seven Bethesda Guidelines for the identification of HNPCC patients. The sensitivity and specificity of the Amsterdam criteria were 61% (95% CI 43-79) and 67% (95% CI 50-85). The sensitivity of the Modified Amsterdam and Amsterdam II criteria were 72% (95% CI 58-86) and 78% (95% CI 64-92), respectively. Overall, the most sensitive criteria for identifying families with pathogenic mutations were the Bethesda criteria, with a sensitivity of 94% (95% CI 88-100); the specificity of these criteria was 25% (95% CI 14-36). Use of the first three criteria of the Bethesda guidelines only was associated with a sensitivity of 94% and a specificity of 49% (95% CI 34-64). Conclusions-The Amsterdam criteria for HNPCC are neither sufficiently sensitive nor specific for use as a sole criterion for determining which families should undergo testing for MSN2 and MLH1 mutations. The Modified Amsterdam and the Amsterdam II criteria increase sensitivity, but still miss many families with mutations. The most sensitive clinical criteria for identifying subjects with pathogenic MSN2 and MLH1 mutations were the Bethesda Guidelines; a streamlined version of the Bethesda Guidelines may be more specific and easier to use in clinical practice. C1 Dana Farber Canc Inst, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Ludwig Inst Canc Res, La Jolla, CA USA. RP Syngal, S (reprint author), Dana Farber Canc Inst, Div Gastroenterol, 44 Binney St, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 NR 24 TC 169 Z9 178 U1 0 U2 3 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2000 VL 37 IS 9 BP 641 EP 645 DI 10.1136/jmg.37.9.641 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 353WQ UT WOS:000089298800001 PM 10978352 ER PT J AU Pless, M Rizzo, JF Lamkin, JC Lessell, S AF Pless, M Rizzo, JF Lamkin, JC Lessell, S TI Concordance of bilateral temporal artery biopsy in giant cell arteritis SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article DE giant cell arteritis; temporal arteritis; temporal artery biopsy ID DIAGNOSIS AB Objective: To determine whether the diagnostic sensitivity of bilateral temporal artery biopsy is superior to that of unilateral biopsy in cases of suspected temporal arteritis. Materials and Methods: A retrospective analysis of the results of 60 bilateral temporal artery biopsies examined in an ophthalmic pathology laboratory. Results: The histopathologic diagnosis in 13% of the biopsy pairs was discordant. There was a 5% chance of obtaining a positive biopsy result on the side opposite an initially negative biopsy result. Conclusions: Bilateral temporal artery biopsy is 5% more likely than unilateral biopsy to detect the characteristic histopathologic findings in patients with temporal arteritis. C1 Univ Pittsburgh, Inst Eye & Ear, Med Ctr, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Pless, M (reprint author), Inst Eye & Ear, Dept Ophthalmol, 203 Lothrop St, Allsburgh, PA 15221 USA. NR 10 TC 48 Z9 48 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2000 VL 20 IS 3 BP 216 EP 218 DI 10.1097/00041327-200020030-00012 PG 3 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 408BP UT WOS:000167306900012 PM 11001198 ER PT J AU Lessell, S AF Lessell, S TI Bilateral temporal artery biopsies in giant cell arteritis SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Lessell, S (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 3 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD SEP PY 2000 VL 20 IS 3 BP 220 EP 221 PG 2 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 408BP UT WOS:000167306900014 PM 11001200 ER PT J AU Atwood, CS Scarpa, RC Huang, XD Moir, RD Jones, WD Fairlie, DP Tanzi, RE Bush, AI AF Atwood, CS Scarpa, RC Huang, XD Moir, RD Jones, WD Fairlie, DP Tanzi, RE Bush, AI TI Characterization of copper interactions with Alzheimer amyloid beta peptides: Identification of an attomolar-affinity copper binding site on amyloid beta 1-42 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE human amyloid beta peptide; copper; affinity; stoichiometry; Alzheimer's disease; binding affinity method; chelators ID A-BETA; CEREBROSPINAL-FLUID; TRACE-ELEMENTS; HYDROGEN-PEROXIDE; SERUM ZINC; DISEASE; BRAIN; PROTEIN; AGGREGATION; IMBALANCES AB Cu and Zn have been shown to accumulate in the brains of Alzheimer's disease patients. We have previously reported that Cu2+ and Zn2+ bind amyloid beta (A beta), explaining their enrichment in plaque pathology. Here we detail the stoichiometries and binding affinities of multiple cooperative Cu2+-binding sites on synthetic A beta 1-40 and A beta 1-42. We have developed a ligand displacement technique (competitive metal capture analysis) that uses metal-chelator complexes to evaluate metal ion binding to A beta, a notoriously self-aggregating peptide. This analysis indicated that there is a very-high-affinity Cu2+-binding site on A beta 1-42 (log K-app = 17.2) that mediates peptide precipitation and that the tendency of this peptide to self-aggregate in aqueous solutions is due to the presence of trace Cu2+ contamination (customarily similar to 0.1 mu M). In contrast, A beta 1-40 has much lower affinity for Cu2+ at this site (estimated log K-app = 10.3), explaining why this peptide is less self-aggregating. The greater Cu2+-binding affinity of A beta 1-42 compared with A beta 1-40 is associated with significantly diminished negative cooperativity, The role of trace metal contamination in inducing A beta precipitation was confirmed by the demonstration that A beta peptide (10 mu M) remained soluble for 5 days only in the presence of high-affinity Cu2+-selective chelators. C1 Massachusetts Gen Hosp, Dept Psychiat, Lab Oxidat Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Lab Oxidat Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Genet & Aging Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld, Australia. RP Bush, AI (reprint author), Massachusetts Gen Hosp E, Ctr Neurosci, Lab Oxidat Biol, Genet & Aging Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Jones, Walton/A-2417-2011; Fairlie, David/F-8865-2014; Bush, Ashley/A-1186-2007 OI Jones, Walton/0000-0001-8642-627X; Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [R29AG12686] NR 50 TC 448 Z9 458 U1 4 U2 47 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 SEP PY 2000 VL 75 IS 3 BP 1219 EP 1233 DI 10.1046/j.1471-4159.2000.0751219.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 346JY UT WOS:000088868500037 PM 10936205 ER PT J AU Libby, RT Champliaud, MF Claudepierre, T Xu, Y Gibbons, EP Koch, M Burgeson, RE Hunter, DD Brunken, WJ AF Libby, RT Champliaud, MF Claudepierre, T Xu, Y Gibbons, EP Koch, M Burgeson, RE Hunter, DD Brunken, WJ TI Laminin expression in adult and developing retinae: Evidence of two novel CNS laminins SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retina; synapse; matrix; photoreceptor; interphotoreceptor matrix; laminin ID CONGENITAL MUSCULAR-DYSTROPHY; CENTRAL-NERVOUS-SYSTEM; S-LAMININ; MESSENGER-RNA; NEUROMUSCULAR-JUNCTION; RAT RETINA; INSITU HYBRIDIZATION; FILAMENT PROTEIN; SYNAPTIC CLEFT; SCHWANN-CELLS AB Components of the extracellular matrix exert myriad effects on tissues throughout the body. In particular, the laminins, a family of heterotrimeric extracellular glycoproteins, have been shown to affect tissue development and integrity in such diverse organs as the kidney, lung, skin, and nervous system. Of these, we have focused on the roles that laminins play in the differentiation and maintenance of the nervous system. Here, we examine the expression of all known laminin chains within one component of the CNS, the retina. We find seven laminin chains-alpha 3, alpha 4, alpha 5, beta 2, beta 3, gamma 2, and gamma 3-outside the retinal basement membranes. Anatomically, these chains are coexpressed in one or both of two locations: the matrix surrounding photoreceptors and the first synaptic layer where photoreceptors synapse with retinal interneurons. Biochemically, four of these chains are coisolated from retinal extracts in two independent complexes, confirming that two novel heterotrimers-alpha 4 beta 2 gamma 3 and alpha 5 beta 2 gamma 3-are present in the retinal matrix. During development, all four of these chains, along with components of laminin 5 (the alpha 3, beta 3, and gamma 2 chains) are also expressed at sites at which they could exert important effects on photoreceptor development. Together, these data suggest the existence of two novel laminin heterotrimers in the CNS, which we term here laminin 14 (composed of the alpha 4, beta 2, and gamma 3 chains) and laminin 15 (composed of the alpha 5, beta 2, and gamma 3 chains), and lead us to hypothesize that these laminins, along with laminin 5, may play roles in photoreceptor production, stability, and synaptic organization. C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Hunter, DD (reprint author), Tufts Univ, Sch Med, Dept Neurosci SC6, 136 Harrison Ave, Boston, MA 02111 USA. OI Libby, Richard/0000-0003-2844-7632 FU NEI NIH HHS [R01 EY012676, R01 EY012676-01A1] NR 64 TC 203 Z9 209 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 2000 VL 20 IS 17 BP 6517 EP 6528 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 348VJ UT WOS:000089006900024 PM 10964957 ER PT J AU Chapman, PH Curtin, HD Cunningham, MJ AF Chapman, PH Curtin, HD Cunningham, MJ TI An unusual pterygopalatine meningocele associated with neurofibromatosis Type 1 - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE meningocele; Meckel's cave; neurofibromatosis; meningitis; cavernous sinus; pterygopalatine fossa ID CLASSIFICATION; PATIENT AB The authors describe an unusual meningocele of the lateral wall of the cavernous sinus and the anterior skull base in a young patient with typical stigmata of neurofibromatosis Type 1 (NF1). This lesion was discovered during evaluation for recurrent meningitis. It represented an anterior continuation of Meckel's cave into a large cerebrospinal fluid space within the lateral wall of the cavernous sinus, extending extracranially through an enlarged superior orbital fissure into the pterygopalatine fossa adjacent to the nasal cavity. It was successfully obliterated, via an intradural middle fossa approach, with fat packing and fenestration into the subarachnoid space. This meningocele most likely represents a variant of cranial nerve dural ectasia occasionally seen in individuals with NF1. It has as its basis the same mesodermal defect responsible for the more common sphenoid wing dysplasia and spinal dural ectasias identified with this condition. Involvement of the trigeminal nerve with expansion of the lateral wall of cavernous sinus has not been reported previously. The authors surmise, however, that it may be present in some cases of orbital meningocele associated with sphenoid wing dysplasia. C1 Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Otolaryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chapman, PH (reprint author), Massachusetts Gen Hosp, Div Neurosurg, 55 Fruit St,GRB 502, Boston, MA 02114 USA. NR 16 TC 9 Z9 9 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD SEP PY 2000 VL 93 IS 3 BP 480 EP 483 DI 10.3171/jns.2000.93.3.0480 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 347VX UT WOS:000088950800015 PM 10969948 ER PT J AU August, M Faquin, WC Troulis, M Kaban, LB AF August, M Faquin, WC Troulis, M Kaban, LB TI Differentiation of odontogenic keratocysts from nonkeratinizing cysts by use of fine-needle aspiration biopsy and cytokeratin-10 staining SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID JAW LESIONS; DIAGNOSIS; EXPRESSION; EPITHELIUM; ANTIGEN; TUMORS; CELLS AB Purpose: In this study, the efficacy of fine-needle aspiration biopsy (FNAB) and cytokeratin 10 immunocytochemical staining to differentiate odontogenic keratocysts (OKC) from dentigerous and other nonkeratinizing cysts was evaluated. Patients and Methods: This was a prospective study of 18 FNABs of odontogenic cystic lesions performed at the Massachusetts General Hospital between 1995 and 1998. A consistent and standardized technique was used to obtain the cytologic material. Immunocytochemistry was performed on destained smears by using a monoclonal antibody against cytokeratin 10. Identical immunohistochemical methods were applied to the final surgical specimen, and results were compared. Results: Cells of 10 of 18 FNABs showed a markedly positive immunoreaction to anti-cytokeratin 10, supporting a diagnosis of OKC. In all 10 cases, the diagnosis was confirmed by histology. Six of 18 cases showed an absence of staining and were interpreted as anti-cytokeratin 10 negative. In the 2 remaining cases, there were occasional squamous cells on the smear with weak anti-cytokeratin 10 uptake. The overall pattern was negative, and these were interpreted as nonkeratinizing cysts. In all 8 of these cases, the diagnosis of OKC was excluded based on the immunocytochemistry, and the final histologic diagnoses were: dentigerous cyst (n = 4) and radicular cyst (n = 4). Conclusions: The combination of FNAB with immunocytochemical determination of cytokeratin 10 expression by sampled epithelial cells was 100% accurate in distinguishing an OKC from a nonkeratinizing odontogenic cyst in this series. The technique allows for early diagnosis and rational surgical planning. (C) 2000 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP August, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, WRN 1201,32 Fruit St, Boston, MA 02114 USA. NR 23 TC 35 Z9 37 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2000 VL 58 IS 9 BP 935 EP 940 DI 10.1053/joms.2000.8731 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 352RG UT WOS:000089231200002 PM 10981972 ER PT J AU Seldin, EB AF Seldin, EB TI An in vitro study of the accuracy of a new protocol for planning distraction osteogenesis of the mandible SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. RP Seldin, EB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD SEP PY 2000 VL 58 IS 9 BP 990 EP 991 DI 10.1053/joms.2000.8741 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 352RG UT WOS:000089231200014 ER PT J AU Costigan, M Woolf, CJ AF Costigan, M Woolf, CJ TI Pain: Molecular mechanisms SO JOURNAL OF PAIN LA English DT Article; Proceedings Paper CT Neurobiology Working Group Conference on Pain - New Targets-New Treatments CY OCT 21, 1999 CL BOCA RATON, FLORIDA DE pain; neuropathic; inflammatory; plasticity; DRG; dorsal horn ID PRIMARY SENSORY NEURONS; RAT SPINAL-CORD; PROGRESSIVE TACTILE HYPERSENSITIVITY; PERIPHERAL-NERVE INJURY; INFLAMMATORY PAIN; DORSAL HORN; CAPSAICIN-RECEPTOR; SUBSTANTIA-GELATINOSA; SYNAPTIC CURRENTS; NEUROPATHIC PAIN AB Our understanding of chronic inflammatory and neuropathic pain at the molecular and cellular level has developed at an extraordinary rate in recent years. Inflammatory, or neuropathic, neuronal plasticity describes the process by which the neurons involved in pain transmission are converted from a state of normosensitivity to one in which they are hypersensitive. Here we summarize current theories on somatosensory neuroplasticity in a molecular context, highlighting key receptors, ion channels, and signal molecules involved. We also suggest new possibilities for drug design, based on the rational targeting of these molecular players. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Costigan, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, 149 13th St,Room 4309, Boston, MA 02129 USA. NR 57 TC 111 Z9 116 U1 0 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD FAL PY 2000 VL 1 IS 3 SU 1 BP 35 EP 44 DI 10.1054/jpai.2000.9818 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 358BU UT WOS:000089538000007 PM 14622841 ER PT J AU Kaihara, S Kim, S Kim, BS Mooney, DJ Tanaka, K Vacanti, JP AF Kaihara, S Kim, S Kim, BS Mooney, DJ Tanaka, K Vacanti, JP TI Survival and function of rat hepatocytes cocultured with nonparenchymal cells or sinusoidal endothelial cells on biodegradable polymers under flow conditions SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE hepatocyte transplantation; nonparenchymal cell; sinusoidal endothelial cell; flow culture ID LIVER-CELLS; TRANSPLANTATION; STIMULATION; CULTURE; GROWTH; DIFFERENTIATION; CULTIVATION; MAINTENANCE; SPONGES AB Background/Purpose: The authors have investigated hepatocyte transplantation using biodegradable polymer scaffolds as a possible treatment of end-stage liver disease. The purpose of this study was to investigate the survival rate and function of hepatocytes alone or cocultured with other cell types on 3-dimensional biodegradable polymers for 7 days under continuous flow conditions in vitro. Methods: Hepatocytes (group 1, n = 8), hepatocytes with nonparenchymal cells (group 2, n = 7), or hepatocytes with sinusoidal endothelial cells (group 3, n = 6) were isolated from Lewis rats and seeded onto the polymer scaffolds. The polymer devices subsequently were placed under continuous flow conditions for 7 days. Albumin production from the constructs was measured each day, and urea nitrogen synthesis was examined on day 7. The devices also were examined by histology at day 7. Results: Histology results showed the presence of numerous viable hepatocytes on polymer devices, with no differences in hepatocyte viability between the 3 groups. Albumin secretion in the culture medium gradually decreased by day 7. There also were no significant differences in albumin production or urea nitrogen synthesis between the 3 groups at day 7. Conclusions: Hepatocytes could survive on the 3-dimensional polymer scaffolds under flow conditions for 7 days, and albumin secretion and urea synthesis of hepatocytes were seen at day 7. Nonparenchymal cells acid sinusoidal endothelial cells had no measurable effect on hepatocyte function in our continuous flow culture system. J Pediatr Surg 35:1287-1290. Copyright (C) 2000 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Kyoto Univ, Fac Med, Dept Transplant Immunol, Kyoto, Japan. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dept Urol, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 1157,55 Fruit St, Boston, MA 02114 USA. RI Kim, Byung-Soo/O-2352-2013 NR 20 TC 30 Z9 30 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD SEP PY 2000 VL 35 IS 9 BP 1287 EP 1290 DI 10.1053/jpsu.2000.9298 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 351FF UT WOS:000089146600003 PM 10999680 ER PT J AU Gonzalez, S Vibhagool, C Sherwood, M Flotte, TJ Kollias, N AF Gonzalez, S Vibhagool, C Sherwood, M Flotte, TJ Kollias, N TI The phototoxicity of photodynamic therapy may be suppressed or enhanced by modulation of the cutaneous vasculature SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE vascular modulation; benzoporphyrin derivative; skin phototoxicity; erythema; UVB radiation; epinephrine-iontophoresis ID SKIN; PHOTOSENSITIZERS AB In photodynamic therapy, the threshold for light induced toxicity depends on the drug concentration and the light dose. This study was aimed to show for vascular photosensitizers that the toxicity threshold on normal tissue may be predictably modified by modulation of the cutaneous vasculature. Albino rabbits were injected with 1.0 mg/kg of a vascular photosensitizer, benzoporphyrin derivative monoacid ring-a. The threshold light dose for toxicity to normal skin was determined at an absorption maximum of the drug (694 nm), 1 h after drug injection. The cutaneous vasculature was dilated by prior skin exposure to ultraviolet radiation or was constricted by iontophoretic application of epinephrine. Threshold toxicity was determined clinically and by assessing the effective concentration of hemoglobin in the skin by diffuse reflectance spectroscopy (DRS). Tissue samples that received threshold doses were investigated with light and electron microscopy. The toxicity threshold increased by 3.2+/-0.9 (mean+/-S.D.) following vasoconstriction and decreased by 3.6+/-0.8 following vasodilation, compared to control sites. Light and electron microscopy showed similar findings at threshold for both vasodilated and vasoconstricted sites. Therefore vascular modulation may be used to predictably enhance or suppress the level of phototoxicity of normal skin. (C) 2000 Elsevier Science S.A. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. RP Kollias, N (reprint author), Johnson & Johnson Consumer Prod Worldwide, 199 Grandview Rd, Skillman, NJ 08558 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD SEP PY 2000 VL 57 IS 2-3 BP 142 EP 148 DI 10.1016/S1011-1344(00)00089-0 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 383HK UT WOS:000165876900009 PM 11154080 ER PT J AU Smith, SR Wingenfeld, SA Hilsenroth, MJ Reddy, LA LeBuffe, PA AF Smith, SR Wingenfeld, SA Hilsenroth, MJ Reddy, LA LeBuffe, PA TI The use of the Devereux Scales of Mental Disorders in the assessment of attention-deficit/hyperactivity disorder and conduct disorder SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article; Proceedings Paper CT Midwinter Meeting of the Society-for-Personality-Assessment CY FEB, 1998 CL BOSTON, MASSACHUSETTS SP Soc Personal Assessment DE conduct disorder; hyperactivity disorders; attention deficit; Devereux Scales ID CHILD-BEHAVIOR CHECKLIST; DEFICIT HYPERACTIVITY DISORDER; RATING-SCALE; DIAGNOSTIC EFFICIENCY; PSYCHIATRIC DIAGNOSES; SCHOOL FORM; PREVALENCE; VALIDITY; STUDENTS; ADHD AB The present study was designed to gather validity data on the Devereux Scales of Mental Disorders (DSMD) for distinguishing among children and adolescents with Attention-Deficit/Hyperactivity Disorder (ADHD; N = 32), Conduct Disorder (CD; N = 34), or no clinical diagnosis (NC; N = 65). Three types of indicators were compared: (nj DSMD scale, composite, and total scores, (b) the number of ADHD or CD-related items endorsed, and (c) diagnostic efficiency statistics (e.g., sensitivity, positive and negative predictive power). The clinical groups did not differ significantly from each other, but both were significantly higher than the NC group on all DSMD scales. Moreover, there were significant differences between the ADHD and the CD groups on the number of respective ADHD and CD-related items endorsed. A cut-off-of seven to eight items yielded the best discrimination between the two diagnostic groups. Diagnostic efficiency statistics indicate that the DSMD may be effective at differentiating between similar disruptive behavior disorders. C1 Univ Arkansas, Fayetteville, AR 72701 USA. La Trobe Univ, Bundoora, Vic 3083, Australia. Fairleigh Dickinson Univ, Rutherford, NJ 07070 USA. Devereux Fdn, Bryn Mawr, PA 19010 USA. RP Smith, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,WACC 812, Boston, MA 02114 USA. NR 41 TC 3 Z9 3 U1 4 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD SEP PY 2000 VL 22 IS 3 BP 237 EP 255 DI 10.1023/A:1007510216543 PG 19 WC Psychology, Clinical SC Psychology GA 349JV UT WOS:000089042700002 ER PT J AU Mischoulon, D Burger, JK Spillmann, MK Worthington, JJ Fava, M Alpert, JE AF Mischoulon, D Burger, JK Spillmann, MK Worthington, JJ Fava, M Alpert, JE TI Anemia and macrocytosis in the prediction of serum folate and vitamin B12 status, and treatment outcome in major depression SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE anemia; B12; depression; folate; macrocytosis ID ALCOHOL-RELATED ILLNESS; FOLIC-ACID; PLASMA FOLATE; COBALAMIN DEFICIENCY; PSYCHIATRIC-PATIENTS; CELL FOLATE; HOMOCYSTEINE; PREVALENCE AB Background: Folate and B12 deficiencies may result in macrocytic anemia, and are common in major depression; hypofolatemia may result in poorer antidepressant response. We wished to determine whether anemia or macrocytosis predict hypofolatemia, low B12, or refractoriness to antidepressants. Methods: After obtaining serum folate, B12, and hematological indices, 213 depressed adults were treated with fluoxetine 20 mg/ day. Amelioration of depressive symptoms was measured. Results: Neither macrocytosis nor anemia predicted low serum folate/B12, or antidepressant refractoriness. Among 39 patients with hypofolatemia, none had macrocytosis; 28% had low HCT; 41% had low RBC. Among 25 patients with low B12, none had macrocytosis; 24% had low HCT; 28% had low RBC. Among non-responders, 3% had macrocytosis; 24% had low HCT; 25% had low RBC. Conclusion: Anemia and macrocytosis should not be used to predict folate or B12 deficiencies, or refractoriness to antidepressants. Measurement of folate and B12 should be considered when evaluating treatment refractoriness. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WAC-812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [MH-48483] NR 43 TC 13 Z9 14 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD SEP PY 2000 VL 49 IS 3 BP 183 EP 187 DI 10.1016/S0022-3999(00)00158-6 PG 5 WC Psychiatry SC Psychiatry GA 382QF UT WOS:000165833200003 PM 11110989 ER PT J AU Berkowitz, RS AF Berkowitz, RS TI Recent advances in the understanding of reproductive malignancies - A new section SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Editorial Material DE genital neoplasms; female C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD SEP PY 2000 VL 45 IS 9 BP 691 EP 691 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 359UB UT WOS:000089629500001 PM 11027077 ER PT J AU Schorge, JO Goldstein, DP Bernstein, MR Berkowitz, RS AF Schorge, JO Goldstein, DP Bernstein, MR Berkowitz, RS TI Recent advances in gestational trophoblastic disease SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE trophoblastic neoplasms; hydatidiform moles; gestational trophoblastic disease ID COMPLETE HYDATIDIFORM MOLE; TUMOR-SUPPRESSOR GENE; NORMAL PLACENTA; RISK-FACTORS; MATRIX METALLOPROTEINASES; P53 GENE; EXPRESSION; CHORIOCARCINOMA; PREGNANCY; CHEMOTHERAPY AB Recent advances have increased our understanding of gestational trophoblastic disease, and epidemiologic studies have demonstrated that there are important differences in risk factors for complete and partial mole. Complete moles are now increasingly being diagnosed in the first trimester, affecting their clinical presentation and pathologic characteristics. While important advances have been made in chemotherapy, it is note recognized that etoposide is associated with a risk of second tumors. Several studies have advanced understanding of the molecular biology of gestational trophoblastic disease, and this is important for the eventual development of new and innovative therapy. C1 Harvard Univ, Sch Med,New England Trophoblast Dis Ctr, Dana Farber Canc Inst,Gillette Ctr Womens Canc, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med,New England Trophoblast Dis Ctr, Dana Farber Canc Inst,Gillette Ctr Womens Canc, Div Gynecol Oncol,Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. NR 60 TC 15 Z9 21 U1 1 U2 1 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD SEP PY 2000 VL 45 IS 9 BP 692 EP 700 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 359UB UT WOS:000089629500002 PM 11027078 ER PT J AU Gall, G Pagano, ME Desmond, MS Perrin, JM Murphy, JM AF Gall, G Pagano, ME Desmond, MS Perrin, JM Murphy, JM TI Utility of psychosocial screening at a school-based health center SO JOURNAL OF SCHOOL HEALTH LA English DT Article ID PEDIATRIC SYMPTOM CHECKLIST; MENTAL-HEALTH; MANAGED CARE; SERVICES; COMMUNITY; PSYCHOPATHOLOGY; PREVALENCE; MORBIDITY; DIAGNOSIS; EPSDT AB School-based health centers (SBHC) have substantial potential to improve the recognition and treatment of adolescents' mental health problems. This study was undertaken as a quality improvement project to evaluate utility of the Pediatric Symptom Checklist when completed by youth (PSC-Y) among 383 adolescents seen at a SBHC. and the extent to which identification of psychosocial dysfunction and referral to mental health services improved academic functioning. Adolescents identified by the PSC-Y were significantly more likely to be insured by Medicaid, be a teen-age parent and to have higher rates of absenteeism and tardiness in comparison to those not identified. Adolescents identified with the PSC-Y who were referred to mental health services significantly decreased their rates of absences and tardiness. Study results provide support for the utility of psychosocial screening and referral in the SBHC environment in facilitating recognition and treatment of adolescent mental health problems and improving student academic functioning. C1 Clin Serv Sch Hlth Program, Boston, MA 02118 USA. Northwestern Univ, Dept Human Dev, Evanston, IL USA. Chelsea High Sch Student Hlth Ctr, Chelsea, MA USA. Massachusetts Gen Hosp, Chelsea Hlth Care Ctr, Chelsea, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. RP Gall, G (reprint author), Clin Serv Sch Hlth Program, 1010 Mass Ave, Boston, MA 02118 USA. FU NIAAA NIH HHS [L30 AA014994, K01 AA015137]; NIDDK NIH HHS [R03 DK062937-01] NR 30 TC 50 Z9 51 U1 0 U2 1 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD SEP PY 2000 VL 70 IS 7 BP 292 EP 298 PG 7 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 348UG UT WOS:000089004400003 PM 10981284 ER PT J AU Apreleva, M Parsons, IM Warner, JJP Fu, FH Woo, SLY AF Apreleva, M Parsons, IM Warner, JJP Fu, FH Woo, SLY TI Experimental investigation of reaction forces at the glenohumeral joint during active abduction SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID SHOULDER; MOTION AB Reaction forces at the glenohumeral joint counterbalance the mass moment of the upper extremity during shoulder motion and are directly related to the activity of muscles across the joint. Because stability of the glenohumeral joint depends on compression of the humeral head into the glenoid, reaction forces constitute an important aspect of shoulder biomechanics. The objective of this study was to measure reaction forces at the glenohumeral joint during active scapula plane abduction. Furthermore, to clarify the relationship between the deltoid and supraspinatus muscles throughout abduction, this study investigated the effect of 4 variations of applied muscle forces on the magnitude and direction of glenohumeral reaction forces. We used a dynamic shoulder testing apparatus equipped with a forcemoment sensor to directly measure reaction Forces. Joint reaction forces increased throughout abduction and peaked at approximately 90 degrees for all testing conditions. The largest reaction forces occurred when the ratio of applied forces favored the supraspinatus tendon, whereas simulated paralysis of the supraspinatus resulted in a significant decrease in joint compression. There were no differences in direction of the reaction Force between testing conditions. The results of this study indicate that the magnitude of glenohumeral joint reaction Forces varies according to the ratio of forces between the supraspinatus and deltoid muscles. Thus, conditions characterized by either deltoid or supraspinatus dysfunction may result in abnormal loading mechanics at the glenohumeral joint. Understanding the relationship between rotator cuff function and glenohumeral reaction forces will aid in clarifying the importance of muscular activity to shoulder stability and strength as it relates to compression of the humeral head. C1 Univ Pittsburgh, Dept Orthopaed Surg, Musculoskeletal Res Ctr, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Woo, SLY (reprint author), Univ Pittsburgh, Dept Orthopaed Surg, Musculoskeletal Res Ctr, POB 71199, Pittsburgh, PA 15213 USA. NR 25 TC 38 Z9 42 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD SEP-OCT PY 2000 VL 9 IS 5 BP 409 EP 417 DI 10.1067/mse.2000.106321 PG 9 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 371HB UT WOS:000165171900009 PM 11075325 ER PT J AU Bridgeford, D Arciniegas, DB Batkis, M Sandberg, E Beresford, TP AF Bridgeford, D Arciniegas, DB Batkis, M Sandberg, E Beresford, TP TI Methylphenidate treatment of neuropsychiatric symptoms of central and extrapontine myelinolysis SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID CENTRAL PONTINE MYELINOLYSIS; TRAUMATIC BRAIN INJURY; MANIFESTATIONS AB Objective: Previous reports describe the presentation and course of the neurobehavioral manifestations cf central and extrapontine myelinolysis; as of yet, however, there are no specific recommendations far treatment of these problems. We offer the first report of successful treatment. Method: We describe a 55-year-old man with chronic alcoholism who developed central and extrapontine myelinolysis following an episode of heavy drinking and rapid correction of hyponatremia The patient acutely developed motor, cognitive, emotional and behavioral problems best accounted for by central pontine and bilateral striatal myelinolysis. These neuropsychiatric symptoms were treated with methylphenidate over the course of I month in an off-on-off-on fashion. The Neuropsychiatric Inventory and other tests were used to assess treatment response. Results: Marked improvements in the patient's neuropsychiatric status were noted only during treatment with methylphenidate. Conclusions: Methylphenidate effectively reversed the neuropsychiatric symptoms associated with the patient's demyelinating lesions. We discuss possible underlying mechanisms of both symptom formation and treatment effect. C1 Denver Vet Affairs Med Ctr, Psychiat Serv 116, Denver, CO 80220 USA. RP Bridgeford, D (reprint author), Denver Vet Affairs Med Ctr, Mental Hlth Serv, 1055 Clermont St, Denver, CO 80220 USA. RI Arciniegas, David/A-3792-2009 NR 21 TC 5 Z9 6 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD SEP PY 2000 VL 61 IS 5 BP 657 EP 660 PG 4 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 358KU UT WOS:000089557900004 PM 11022803 ER PT J AU Baskaran, H Yarmush, ML Berthiaume, F AF Baskaran, H Yarmush, ML Berthiaume, F TI Dynamics of tissue neutrophil sequestration after cutaneous burns in rats SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE burns; neutrophil; rat; adhesion; vascular permeability ID THERMAL-INJURY; MONOCLONAL-ANTIBODY; MYELOPEROXIDASE ACTIVITY; BACTERIAL TRANSLOCATION; VASCULAR INJURY; DEPENDENT LUNG; P-SELECTIN; BLOOD-FLOW; NECROSIS; SKIN AB Background. Neutrophil recruitment in organs after bumps may cause local vascular damage, which can be reduced by agents blocking neutrophil adhesion to the vascular wall. Because these agents may increase susceptibility to infection, it is important to characterize the dynamics of neutrophil sequestration in order to optimize an eventual anti-adhesion therapy. Materials and methods. Rats were scald burned over 20 or 40% of their total body surface area (TBSA) and saline resuscitated. Sham controls were used. Myeloperoxidase (MPO) activity was measured in lungs, liver, kidney, gut, and burned skin up to 1 week postburn. Extravascular accumulation of I-125-labeled bovine serum albumin (I-125-BSA) was measured at 12 h postburn. Results. MPO activity in lungs, liver, and kidney was increased within 3 h postburn and returned to normal within 24-48 h. Peak MPO levels occurred at 6-12 h postburn and were similar for both burn sizes. No MPO increase was observed in gut. MPO levels in burned skin did not increase before 6 h, peaked at 24 h, decreased at 48 h, but remained elevated for up to 7 days. Neutrophil recruitment in lungs and liver was cofirmed histochemically. No neutrophils were found in kidneys. Extravascular I-125-BSA was increased in lungs, liver, kidneys, and gut, in the 40% TBSA group only. Conclusions. Neutrophil sequestration in remote organs is a transient phenomenon while neutrophil homing into the wound site is sustained. Neutrophil accumulation dynamics are independent of burn size, although a minimum size is required to trigger vascular damage, Temporary early anti-adhesion therapy to reduce lung and liver neutrophil sequestration with little impact on neutrophil homing into the burn wound may be possible. (C) 2000 Academic Press. C1 Shriners Hosp Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA 02114 USA. RP Berthiaume, F (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. NR 52 TC 44 Z9 48 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 SEP PY 2000 VL 93 IS 1 BP 88 EP 96 DI 10.1006/jsre.2000.5955 PG 9 WC Surgery SC Surgery GA 353PT UT WOS:000089285200013 PM 10945948 ER PT J AU Solomon, V Madihally, S Yarmush, M Toner, M AF Solomon, V Madihally, S Yarmush, M Toner, M TI Insulin suppresses the increased activities of lysosomal cathepsins and ubiquitin conjugation system in burn-injured rats SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE burn; insulin; muscle; cathepsins; ubiquitin; proteasome; chymotrpsin-like activity; protein degradation ID MUSCLE PROTEIN-SYNTHESIS; SKELETAL-MUSCLE; DEGRADATION; BREAKDOWN; PATHWAY; HYPERINSULINEMIA; STIMULATION; TURNOVER; ENZYME AB Background. Burn injure results in increased rate of skeletal muscle protein degradation, In vitro studies on incubated muscles indicate that increased rate of protein degradation is due to activation of multiple proteolytic systems, but the supporting evidence is of an indirect nature. The present study was carried out to investigate the role of various lysosomal cathepsins, ubiquitin conjugation, and proteasome systems in accelerated proteolysis, and the effect of insulin in burn-induced muscle wasting syndrome. Materials and methods. Fifteen to twenty percent total body surface area scald burn injury was inflicted on the shaved dorsum of young growing rats. Insulin-treated rats received a daily single subcutaneous injection for 3 days (0.25-1.0 U/day). The rate of ubiquitin conjugation to endogenous proteins and exogenously added I-125-lysozyme and the activities of various proteases were measured in muscle homogenates. Results. Burn injury resulted in increased rate of ubiquitin conjugation to endogenous proteins and I-125-lysozyme. Activities of cathepsins B, C, H, and L, were also up-regulated following burn injury. When the burn-injured rats were treated with insulin, the increased rate of ubiquitin conjugation and cathepsin activities mere suppressed to the control levels. Conclusions. The increased ubiquitin conjugation and lysosomal cathepsins contribute to accelerated protein degradation in burn-injured rats and insulin suppresses the muscle protein degradation at least in part by suppressing the activities of lysosomal cathepsins and of ubiquitin conjugation system. (C) 2000 Academic Press. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. RI Madihally, Sundararajan/D-9285-2012 OI Madihally, Sundararajan/0000-0001-7498-5760 NR 30 TC 19 Z9 20 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 SEP PY 2000 VL 93 IS 1 BP 120 EP 126 DI 10.1006/jsre.2000.5958 PG 7 WC Surgery SC Surgery GA 353PT UT WOS:000089285200017 PM 10945952 ER PT J AU Huang, GT Rosowski, JJ Puria, S Peake, WT AF Huang, GT Rosowski, JJ Puria, S Peake, WT TI A noninvasive method for estimating acoustic admittance at the tympanic membrane SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MIDDLE-EAR; REFLECTANCE TYMPANOMETRY; SPATIAL-DISTRIBUTION; ENERGY REFLECTANCE; INPUT IMPEDANCE; SOUND PRESSURE; CAT; TRANSMISSION; FREQUENCIES; COEFFICIENT AB The acoustic admittance at the tympanic membrane (TM), Y-TM, describes the linear acoustic properties of the ear. Here, a noninvasive measurement procedure is developed fur estimating Y-TM in intact ears. The method consists of (1) measuring the admittance in the ear canal Y-EC with a commercially available earphone-and-microphone system, and (2) estimating Y-TM via uniform-tube approximation of the space between the measurement point and the TM. The dimensions of this space are estimated from Y-EC via an area-estimation algorithm [Keefe et al., J. Acoust. Sec. Am. 91, 470 (1992)] and measurements made with controlled static pressures in the canal. Measurements in artificial loads are used to test the accuracy of the measurement system and to determine sources of error. For accurate admittance measurements: (1) extension of the microphone tube medially beyond the earphone's port is necessary for frequencies above 2 kHz: (2) the acoustic system must be calibrated in known loads with diameters within 15% of the canal diameter, because the source's output characteristics vary with load diameter. The method is applied to intact ears of anesthetized domestic cats; for frequencies below 5 kHz, the estimated Y-TM in four ears have features that are similar to those of previous measurements made at the cat TM. Sources of error include nonuniform waves generated at the earphone's narrow port, inaccuracy in estimation of canal dimensions, irregular geometry of the canal, and earphone-microphone cross talk. (C) 2000 Acoustical Society of America. [S0001-4466(00)00409-4]. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Huang, GT (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. NR 62 TC 29 Z9 29 U1 0 U2 6 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2000 VL 108 IS 3 BP 1128 EP 1146 DI 10.1121/1.1287024 PN 1 PG 19 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 352RD UT WOS:000089230900023 PM 11008815 ER PT J AU Huang, GT Rosowski, JJ Puria, S Peake, WT AF Huang, GT Rosowski, JJ Puria, S Peake, WT TI Tests of some common assumptions of ear-canal acoustics in cats SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MIDDLE-EAR; REFLECTANCE TYMPANOMETRY; SPATIAL-DISTRIBUTION; TYMPANIC MEMBRANE; SOUND PRESSURE; IMPEDANCE; FREQUENCIES; COEFFICIENT; ADULTS; INPUT AB The accuracy of ear-canal admittance and reflectance as measures of the ear's properties depends on the acoustic effects of the canal. Here, measurements of acoustic admittance at different canal locations in domestic cats are used to test three common assumptions. (I) Can a uniform-tube model of the canal represent spatial variations in admittance? Data from cats support this assumption for frequencies below 3 kHz, where the admittance inferred at the tympanic membrane (TM) based on a uniform-tube model differs by less than 3 dB in magnitude and 0.07 periods in angle from the admittance measured at the TM; for higher frequencies greater differences occur. (2) Do large static air pressures in the canal make the middle ear rigid without affecting the properties of the canal space? The measurements reported indicate that large negative static pressures reduce the low-frequency compliance of the cat middle ear to about 10% of the compliance of the canal air volume. Static displacements of the: acoustic probe, TM, and canal walls with static pressure may affect estimates of the canal volume and middle-ear compliance by as much as 15% to 20%. (3) Is the acoustic-reflectance magnitude constant with position along the canal? Reflectance data from cat ear canals generally support this idea, except within a frequency region near 0.5 kHz for which there is evidence of energy loss. These results demonstrate that noninvasive measurements in the canal describe middle-ear acoustic properties to within tolerances that depend on the effects of the canal. (C) 2000 Acoustical Society of America. [S0001 -4966(00)00509-9]. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Huang, GT (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. NR 42 TC 15 Z9 15 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD SEP PY 2000 VL 108 IS 3 BP 1147 EP 1161 DI 10.1121/1.1287025 PN 1 PG 15 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 352RD UT WOS:000089230900024 PM 11008816 ER PT J AU Campos, VB Dierickx, CC Farinelli, WA Lin, TYD Manuskiatti, W Anderson, RR AF Campos, VB Dierickx, CC Farinelli, WA Lin, TYD Manuskiatti, W Anderson, RR TI Hair removal with an 800-nm pulsed diode laser SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MODE RUBY-LASER AB Background and Objective: Laser hair removal is a relatively new procedure. Our purpose was to study the efficacy and safety of a high-power, pulsed diode laser array for removing unwanted hair. Methods: A total of 38 subjects were treated with a prototype of the 800-nm diode laser system. Fluences ranging from 10 to 40 J/cm(2) (mean, 33.4 J/cm(2)) were used and 1 to 4 treatments (mean, 2.7) were performed. Evaluation of hair loss was performed at least 4 months after the last treatment (mean, 8.7 months) by a blinded assessment of clinical photographs. Results: A total of 59% of the subjects had only sparse hair regrowth at the final follow-up. Higher fluences and multiple treatments produced greater long-term efficacy Transient pigmentary changes occurred in 29% of the subjects and were more common in darker skin types IV to VI (P = .047). Conclusion: The 800-nm diode laser is an efficient and safe technique for hair reduction. Adverse pigmentary effects occur, but are transient. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol Wellman Labs Photomed, Boston, MA USA. RP Anderson, RR (reprint author), Wellman Labs Photomed, 50 Blossom St,Bartlett Extens 6, Boston, MA 02114 USA. NR 17 TC 58 Z9 63 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2000 VL 43 IS 3 BP 442 EP 447 DI 10.1067/mjd.2000.107239 PG 6 WC Dermatology SC Dermatology GA 349AX UT WOS:000089022600003 PM 10954655 ER PT J AU Movsowitz, HD Levine, RA Hilgenberg, AD Isselbacher, EM AF Movsowitz, HD Levine, RA Hilgenberg, AD Isselbacher, EM TI Transesophageal echocardiographic description of the mechanisms of aortic regurgitation in acute type A aortic dissection: Implications for aortic valve repair SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ASCENDING AORTA; SURGICAL-MANAGEMENT; COMPOSITE-GRAFT; MARFAN-SYNDROME; A DISSECTION; FOLLOW-UP; INSUFFICIENCY; PRESERVATION; ANEURYSMS; DIAGNOSIS AB OBJECTIVES The purpose of this study was to use transesophageal echocardiography (TEE) to define the mechanisms of aortic regurgitation (AR) in acute type A aortic dissection so as to assist the surgeon in identifying patients with mechanisms of AR suitable for valve preservation. BACKGROUND Significant AR frequently complicates acute type A aortic dissection necessitating either aortic valve repair or replacement at the time of aortic surgery. Although direct surgical inspection can identify intrinsically normal leaflets suitable for repair, it is preferable for the surgeon to correlate aortic valve function with the anatomy prior to thoracotomy. METHODS We studied 50 consecutive patients with acute type A aortic dissection in whom preoperative TEE findings were considered by the surgeons in planning aortic valve surgery. Six patients did not undergo surgery (noncandidacy or refusal) and one patient had had a prior aortic valve replacement and therefore was excluded from the analysis. RESULTS Twenty-seven patients had no or minimal AR and 22 had moderate or severe AR. In all, there were 16 with intrinsically normal leaflets who had AR due to one or more correctable aortic valve lesion: incomplete leaflet closure due to leaflet tethering in a dilated aortic root ill 7; leaflet prolapse due to disrupted leaflet attachments in 8; and dissection flap prolapse through the aortic valve orifice in 5. Of these 16 patients, 15 had successful aortic valve repair whereas just 1 underwent aortic valve replacement after a complicated intraoperative course (unrelated to the aortic valve). Nine patients underwent aortic valve replacement for nonrepairable abnormalities, including Marfan's syndrome in four, bicuspid aortic valve in four, and aortitis in one. In patients undergoing aortic valve repair, follow-up transthoracic echocardiography at a median of three months revealed no or minimal residual ARI and clinical follow-up at a median of 23 months showed that none required aortic valve replacement. CONCLUSIONS When significant AR complicates acute type PI aortic dissection, TEE can define the severity and mechanisms of AR and can assist the surgeon in identifying patients in whom valve repair is likely to be successful. (C) 2000 by the American College of Cardiology. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 15 Parkman St,ACC 469, Boston, MA 02114 USA. NR 34 TC 62 Z9 66 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 SEP PY 2000 VL 36 IS 3 BP 884 EP 890 DI 10.1016/S0735-1097(00)00766-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 351HQ UT WOS:000089152100035 PM 10987615 ER PT J AU Ferrell, BA Josephson, K Norvid, P Alcorn, H AF Ferrell, BA Josephson, K Norvid, P Alcorn, H TI Pressure ulcers among patients admitted to home care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pressure sores; decubitus; home care ID LONG-TERM-CARE; BRADEN-SCALE; SORE RISK; PREVENTIVE INTERVENTIONS; PREDICTIVE-VALIDITY; MULTISITE; COST AB CONTEXT: Pressure ulcers are an understudied problem in home care. OBJECTIVE: To determine the prevalence of pressure ulcers among patients admitted to home care services, describe the demographic and health characteristics associated with pressure ulcers in this setting, and identify the percentage of these patients at risk for developing pressure ulcers. DESIGN: Cross-sectional survey of patients on admission to home care agencies. SETTING: Forty-one home care agencies in 14 states. PATIENTS: A consecutive sample of 3048 patients admitted March 1 through April 30, 1996 (86% of all admissions). Subjects had a mean age of 75 years; 63% were female and 85% white. MAIN OUTCOME MEASURES: Demographic, social, and clinical characteristics, functional status (Katz activities of daily living scale and Lawton instrumental activities of daily living scale), mental status (Katzman Short Memory-Orientation-Concentration test), pressure ulcer risk (Braden Scale), pressure ulcer status (Bates-Jensen Pressure Ulcer Status Tool), and a checklist of pressure-reducing devices and wound care products being used. RESULTS: In the total sample of 3048 patients, 9.12% had pressure injuries: 37.4% had more than one ulcer and 14.0% had three or more ulcers. Considering the worst ulcer for each subject, 40.3% had Stage II and 27% had Stage III or IV injuries. Characteristics associated with pressure ulcers included recent institutional discharge, functional impairment, incontinence, and having had a previous ulcer. About 30% of subjects were at risk for new pressure ulcers. Pressure-relieving devices and other wound care strategies appeared to be underutilized and often indiscriminately applied. CONCLUSIONS: There is substantial need for pressure ulcer prevention and treatment in home care settings. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr & Gerontol, Los Angeles, CA 90095 USA. LaGrange Mem Hosp, LaGrange, IL USA. Total Renal Res Inc, Minneapolis, MN USA. RP Ferrell, BA (reprint author), Univ Calif Los Angeles, Sch Med, Div Geriatr, 10945 Le Conte Ave, Los Angeles, CA 90095 USA. NR 24 TC 39 Z9 40 U1 3 U2 4 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 SEP PY 2000 VL 48 IS 9 BP 1042 EP 1047 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 351PR UT WOS:000089167800002 PM 10983902 ER PT J AU Deckersbach, T Savage, CR Phillips, KA Wilhelm, S Buhlmann, U Rauch, SL Baer, L Jenike, MA AF Deckersbach, T Savage, CR Phillips, KA Wilhelm, S Buhlmann, U Rauch, SL Baer, L Jenike, MA TI Characteristics of memory dysfunction in body dysmorphic disorder SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE body dysmorphic disorder; dysmorphophobia; neuropsychology; executive functioning; memory ID OBSESSIVE-COMPULSIVE DISORDER; POSITRON-EMISSION-TOMOGRAPHY; SYMPTOM PROVOCATION; ANXIETY DISORDERS; IMAGINED UGLINESS AB Although body dysmorphic disorder (BDD) is receiving increasing empirical attention, very little is known about neuropsychological deficits in this disorder. The current study investigated the nature of memory dysfunction in BDD, including the relationship between encoding strategies and verbal and nonverbal memory performance. We evaluated 17 patients with BDD and 17 healthy controls using the Rey-Osterrieth Complex Figure Test (RCFT) and the California Verbal Learning Test (CVLT). BDD patients differed significantly from healthy controls on verbal and nonverbal learning and memory indices. Multiple regression analyses revealed that group differences in free recall were statistically mediated by deficits in organizational strategies in the BDD cohort. These findings are similar to patterns previously observed in obsessive-compulsive disorder (OCD), suggesting a potential relationship between OCD and BDD. Studies in both groups have shown that verbal and nonverbal memory deficits are affected by impaired strategic processing. C1 Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, Charlestown, MA 02129 USA. Harvard Med Sch, Boston, MA USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Brown Univ, Sch Med, Butler Hosp, Providence, RI 02912 USA. RP Savage, CR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Cognit Neurosci Grp, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH01230] NR 42 TC 88 Z9 89 U1 3 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD SEP PY 2000 VL 6 IS 6 BP 673 EP 681 DI 10.1017/S1355617700666055 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 352XK UT WOS:000089244500005 PM 11011514 ER PT J AU D'Amico, AV Whittington, R Malkowicz, B Schnall, M Schultz, D Cote, K Tomaszewski, JE Wein, A AF D'Amico, AV Whittington, R Malkowicz, B Schnall, M Schultz, D Cote, K Tomaszewski, JE Wein, A TI Endorectal magnetic resonance imaging as a predictor of biochemical outcome after radical prostatectomy in men with clinically localized prostate cancer SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatectomy; magnetic resonance imaging; prostatic neoplasms; prostate-specific antigen ID BEAM RADIATION-THERAPY; RETROPUBIC PROSTATECTOMY; PATHOLOGICAL FINDINGS; DISEASE RECURRENCE; ANTIGEN; PROGRESSION; NOMOGRAM; FAILURE; STAGE; RISK AB Purpose: Endorectal magnetic resonance imaging (MRI) of the prostate is sometimes performed before radical prostatectomy but to our knowledge its role for predicting outcome after radical prostatectomy is not yet established. We evaluated the clinical usefulness of endorectal MRI for predicting time to prostate specific antigen (PSA) failure after radical prostatectomy in 1,025 consecutive men with clinically localized or PSA detected prostate cancer. Our analysis controlled for PSA level, biopsy Gleason score, clinical T stage and percent of positive biopsies. Materials and Methods: Using Cox regression analysis we prospectively assessed time to PSA failure to determine the role of endorectal MRI in predicting PSA outcome after radical prostatectomy at our institution, where an expert prostate magnetic resonance radiologist is available. The main outcome measure was actuarial freedom from PSA failure. Results: Endorectal MRI did not add clinically meaningful information in 834 of our 1,025 cases (81%) after accounting for the prognostic value of PSA, biopsy Gleason score, clinical T stage and percent of positive biopsies. However, this modality provided a clinically and statistically relevant stratification of 5-year PSA outcome in the remaining 191 patients at intermediate risk, based on established prognostic factors. Specifically when endorectal MRI was interpreted as indicating extracapsular versus organ confined disease the relative risk of PSA failure was 3.6 (95% confidence interval 2.0 to 6.3), and 5-year actuarial freedom from PSA failure was 33% versus 72% (p <0.0001). Conclusions: Despite expert radiological interpretation endorectal MRI had potential clinical value in less than 20% of the cases in our study after accounting for established prognostic factors. While further study of the value of this modality for predicting clinical outcome after radical prostatectomy should be performed in this select cohort, routine use of endorectal MRI cannot be justified based on these data. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Millersville Univ, Dept Math, Millersville, PA 17551 USA. RP D'Amico, AV (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RI Schnall, Mitchell/D-1149-2009 NR 19 TC 61 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD SEP PY 2000 VL 164 IS 3 BP 759 EP 763 DI 10.1016/S0022-5347(05)67297-7 PN 1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 343BP UT WOS:000088682100044 PM 10953141 ER PT J AU Goldberg, SN Solbiati, L Halpern, EF Gazelle, GS AF Goldberg, SN Solbiati, L Halpern, EF Gazelle, GS TI Variables affecting proper system grounding for radiofrequency ablation in an animal model SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE animal model; radiofrequency (RF) ablation ID EXPERIENCE; METASTASES; ELECTRODES; TUMORS AB PURPOSE: The authors sought to determine which factors contribute to excessive thermal deposition and burns at the grounding pad site after high-current percutaneous, image-guided radiofrequency (RF) ablation, MATERIALS AND METHODS: Radiofrequency (1,000-2,000 mA) was applied for 10 minutes with use of an internally-cooled electrode placed into in vivo pig livers (n = 88), In separate experiments, the number of pads (1, 2, or 4), orientation of pads (horizontal, vertical, or diagonal), and distance between the pads and the electrode (10-50 cm) of mesh or foil grounding pads (12.5 x 8 cm; 100 cm(2)) were varied. Thermistors measured skin surface temperatures during ablation, Pathologic analysis of skin changes was performed. RESULTS: Temperature elevations at the grounding pad were observed for every trial, with a temperature elevation greater than or equal to 12 degrees C (as high as 45 degrees C) observed in 60 of 88 trials (68.2%). Temperatures at the grounding site pad were dependent on all variables studied, including the grounding pad surface area, the amount of current deposited in the liver, the orientation of the pad, and the pad's distance from the electrode. Second-degree burns were seen with temperatures exceeding 47 degrees C and third-degree burns were observed when a temperature greater than or equal to 52 degrees C was noted. For a given set of RF parameters, reduced heating was observed for trials in which foil grounding pads were used (P < .001), Grounding pad burns did not occur at 2,000 mA (maximum generator output) when four foil pads were placed horizontally greater than or equal to 25 cm from the electrode. CONCLUSIONS: High-current RF ablation can induce severe burns at the grounding pad site if inadequate precautions are taken. To minimize the risk of burns, multiple large-surface-area foil pads should be placed on well-prepared skin and oriented with the longest surface edge facing the RF electrode. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Osped Gen, Dept Radiol, Busto Arsizio, Italy. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. OI Solbiati, Luigi/0000-0002-3109-1449 NR 27 TC 66 Z9 70 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD SEP PY 2000 VL 11 IS 8 BP 1069 EP 1075 DI 10.1016/S1051-0443(07)61341-4 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 352EE UT WOS:000089200900019 PM 10997473 ER PT J AU Chang, DW Chan, A Forse, RA Abbott, WM AF Chang, DW Chan, A Forse, RA Abbott, WM TI Enabling sutureless vascular bypass grafting with the exovascular sleeve anastomosis SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID AORTIC-SURGERY; TRIAL AB Purpose: We describe a technique for end-to-end sleeve anastomosis that may enable minimally invasive bypass grafting and characterize the tensile strength, stenosis rate, durability, and healing of the anastomosis. Method: An anastomotic device assembly consisting of a cable tie-type band with mobile teeth elements is mounted on the outer surface of a polytetrafluoroethylene graft. The graft is drawn over the artery resulting in a sleeve of vessel within the graft. As the band is tightened over an intraluminal obturator, the independently mobile anchoring teeth are driven through the graft into the artery. The tensile strength of the anastomosis was compared with sutured anastomosis during in vitro studies using cadaveric human femoral arteries. For in vivo studies on pigs and goats, we used a proximal exovascular sleeve anastomosis along with a distal sutured aortic anastomosis. Survival animals were studied by angiogram postoperatively and at the time of explantation. Results: In vitro studies showed no difference in maximal tensile strength between sutured and exovascular anastomoses (10.5 +/- 2.7 lb vs 10.2 +/- 3.0 lb, P = .83). However, loss of continuous graft to artery interface occurred at lower loads in the sutured anastomoses (6.5 +/- 0.6 lb, P < .05). In total, all 24 pigs tested in nonsurvival or survival settings sustained a successful and leakproof anastomosis. Of the 13 nonsurvival cases, maximal epinephrine-induced hypertension sustained over 15 minutes (peak systolic blood pressure > 210-250 mm Hg) was tolerated without leakage in a subgroup of five animals (100%). All 11 survival pigs had no pseudoaneurysms or stenosis relative to sutured control anastomoses at 6 week explantation (8.2 +/- 1.25 mm vs 8.5 +/- 1.6 mm, P = .21). The three long-term survival goats had no pseudoaneurysm or stenosis after 40 weeks. Histologic examination confirmed healing of the aorta to graft with minimal neointimal hyperplasia. Conclusion: Exovascular sutureless anastomosis appears comparable to sutured anastomosis in stenosis rate, healing, and durability, with some advantages in tensile strength and rapidity of application. C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Ctr Minimally Invas Surg, Boston, MA USA. RP Abbott, WM (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, WAC 458,15 Parkman St, Boston, MA 02114 USA. NR 13 TC 8 Z9 8 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD SEP PY 2000 VL 32 IS 3 BP 524 EP 530 DI 10.1067/mva.2000.107770 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 352QV UT WOS:000089230100024 PM 10957659 ER PT J AU Clarke, P Meintzer, SM Gibson, S Widmann, C Garrington, TP Johnson, GL Tyler, KL AF Clarke, P Meintzer, SM Gibson, S Widmann, C Garrington, TP Johnson, GL Tyler, KL TI Reovirus-induced apoptosis is mediated by TRAIL SO JOURNAL OF VIROLOGY LA English DT Article ID INFLUENZA-VIRUS INFECTION; PROGRAMMED CELL-DEATH; NECROSIS-FACTOR-ALPHA; FAS; ACTIVATION; PATHWAY; MODULATION; EXPRESSION; INHIBITION; RECEPTORS AB Members of the tumor necrosis factor (TNF) receptor superfamily and their activating ligands transmit apoptotic signals in a variety of systems. We now show that the binding of TNF-related, apoptosis-inducing ligand (TRAIL) to its cellular receptors DR5 (TRAILR2) and DR4 (TRAILR1) mediates reovirus-induced apoptosis. Anti-TRAIL antibody and soluble TRAIL receptors block reovirus-induced apoptosis by preventing TRAIL-receptor binding. In addition, reovirus induces both TRAIL release and an increase in the expression of DR5 and DR4 in infected cells. Reovirus-induced apoptosis is also blocked following inhibition of the death receptor-associated, apoptosis-inducing molecules FADD (for LAS-associated death domain) and caspase 8. We propose that reovirus infection promotes apoptosis via the expression of DR5 and the release of TRAIL from infected cells. Virus-induced regulation of the TRAIL apoptotic pathway defines a novel mechanism for virus-induced apoptosis. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Natl Jewish Ctr Immunol & Resp Med, Program Mol Signal Transduct, Denver, CO 80206 USA. Natl Jewish Ctr Immunol & Resp Med, Div Basic Sci, Denver, CO 80206 USA. RP Tyler, KL (reprint author), Denver VA Med Ctr, Dept Neurol 127, 1066 Clermont St, Denver, CO 80220 USA. RI Widmann, Christian/N-9851-2013; OI Widmann, Christian/0000-0002-6881-0363; Gibson, Spencer/0000-0003-0119-732X; Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1RO1AG14071]; NIGMS NIH HHS [R01 GM030324, GM30324, R37 GM030324] NR 31 TC 146 Z9 155 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2000 VL 74 IS 17 BP 8135 EP 8139 DI 10.1128/JVI.74.17.8135-8139.2000 PG 5 WC Virology SC Virology GA 346JD UT WOS:000088866500050 PM 10933724 ER PT J AU Chen, HM Engelman, A AF Chen, HM Engelman, A TI Characterization of a replication-defective human immunodeficiency virus type 1 att site mutant that is blocked after the 3 ' processing step of retroviral integration SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL-DNA ENDS; PREINTEGRATION COMPLEXES; ESCHERICHIA-COLI; PROTEIN INVITRO; SEQUENCE; RECOMBINATION; CLEAVAGE; TERMINI; HIV-1; IDENTIFICATION AB Two activities of retroviral integrase, 3' processing and DNA strand transfer, are required to integrate viral cDNA into a host cell chromosome. Integrase activity has been analyzed in vitro using purified protein and recombinant DNA substrates that model the U3 and U5 ends of viral cDNA or by using viral preintegration complexes (PICs) that form during virus infection. Numerous studies have investigated changes in integrase or viral DNA for effects on both 3' processing and DNA strand transfer activities using purified protein, but similar analyses have not been carried out using PICs. Here, we analyzed PICs from human immunodeficiency virus type 1 (HIV-1) strain 604del, an integration-defective mutant lacking 26 bp of U5, and revE1, a revertant of 604del containing an additional 19-bp deletion, for levels of 3' processing activity that occurred in infected cells and for levels of in vitro DNA strand transfer activity. Whereas revE1 supported one-third to one-half of the level of wild-type DNA strand transfer activity, the level of 604del DNA strand transfer activity was undetectable. Surprisingly, integrase similarly processed the 3' ends of 604del and revE1 in vivo. We therefore conclude that 604del is blocked in its ability to replicate in cells after the 3' processing step of retroviral integration. Whereas Western blotting showed that wild-type, revE1, and 604del PICs contained similar levels of integrase protein, Mu-mediated PCR footprinting revealed only minimal protein-DNA complex formation at the ends of 604del cDNA. We propose that 604del is replication defective because proteins important for DNA strand transfer activity do not stably associate with this cDNA after in vivo 3' processing by integrase. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39394, R01 AI039394, R37 AI039394] NR 40 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2000 VL 74 IS 17 BP 8188 EP 8193 DI 10.1128/JVI.74.17.8188-8193.2000 PG 6 WC Virology SC Virology GA 346JD UT WOS:000088866500057 PM 10933731 ER PT J AU Kaur, A Hale, CL Ramanujan, S Jain, RK Johnson, RP AF Kaur, A Hale, CL Ramanujan, S Jain, RK Johnson, RP TI Differential dynamics of CD4(+) and CD8(+) T-lymphocyte proliferation and activation in acute simian immunodeficiency virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; PRIMARY IMMUNE-RESPONSE; HIV-1 INFECTION; IN-VIVO; CELL PROLIFERATION; NUCLEAR ANTIGEN; RHESUS MACAQUES; TELOMERE LENGTH; TURNOVER; KI-67 AB Although lymphocyte turnover in chronic human immunodeficiency virus and simian immunodeficiency virus (SN) infection has been extensively studied, there is little information on turnover in acute infection. We carried out a prospective kinetic analysis of lymphocyte proliferation in 13 rhesus macaques inoculated with pathogenic SN. A short-lived dramatic increase in circulating Ki-67(+) lymphocytes observed at 1 to 4 weeks was temporally related to the onset of SIV replication. A 5- to 10-fold increase in Ki-67(+) CD8(+) T lymphocytes and a 2- to 3-fold increase in Ki-67(+) CD3(-) CD8(+) natural killer cells accounted for >85% of proliferating lymphocytes at peak proliferation. In contrast, there was little change in the percentage of Ki-67(+) CD4(+) T lymphocytes during acute infection, although transient increases in Ki-67(-) and Ki-67(+) CD4(+) T lymphocytes expressing CD69, Fas, and HLA-DR were observed, A two- to fourfold decline in CD4(+) T lymphocytes expressing CD25 and CD69 was seen later in SIV infection, The majority of Ki-67(+) CD8(+) T lymphocytes were phenotypically CD45RA(-) CD49d(hi) Fas(hi) CD25(-) CD69(-) CD28(-) HLA-DR- and persisted at levels twofold above baseline 6 months after SIV infection. Increased CD8(+) T-lymphocyte proliferation was associated with cell expansion, paralleled the onset of SIV-specific cytotoxic T-lymphocyte activity, and had an oligoclonal component. Thus, divergent patterns of proliferation and activation are exhibited by CD4(+) and CD8(+) T lymphocytes in early SIV infection and may determine how these cells are differentially affected in AIDS. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Kaur, A (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, 1 Pinehill Dr, Southborough, MA 01772 USA. FU NCI NIH HHS [F32 CA083248]; NCRR NIH HHS [P51 RR000168, RR00168, K26 RR000168]; NIAID NIH HHS [AI43890, R01 AI043890, AI38559] NR 45 TC 52 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2000 VL 74 IS 18 BP 8413 EP 8424 DI 10.1128/JVI.74.18.8413-8424.2000 PG 12 WC Virology SC Virology GA 347ML UT WOS:000088933700024 PM 10954541 ER PT J AU Altfeld, MA Trocha, A Eldridge, RL Rosenberg, ES Phillips, MN Addo, MM Sekaly, RP Kalams, SA Burchett, SA McIntosh, K Walker, BD Goulder, PJR AF Altfeld, MA Trocha, A Eldridge, RL Rosenberg, ES Phillips, MN Addo, MM Sekaly, RP Kalams, SA Burchett, SA McIntosh, K Walker, BD Goulder, PJR TI Identification of dominant optimal HLA-B60-and HLA-B61-restricted cytotoxic T-lymphocyte (CTL) epitopes: Rapid characterization of CTL responses by enzyme-linked immunospot assay SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HLA CLASS-I; HIV-1 INFECTION; SEROPOSITIVE INDIVIDUALS; VACCINE DEVELOPMENT; SLOW PROGRESSORS; FINE SPECIFICITY; VIREMIA; ASSOCIATION; HEPATITIS AB Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte (CTL) responses play a major role in the antiviral immune response, but the relative contribution of CTL responses restricted by different HLA class I molecules is less well defined. HLA-B60 or the related allele B61 is expressed in 10 to 20% of Caucasoid populations and is even more highly prevalent in Asian populations, but yet no CTL epitopes restricted by these alleles have been defined. Here we report the definition of five novel HLA-B60-restricted HIV-1-specific CTL epitopes, using peripheral blood mononuclear cells in enzyme-linked immunospot (Elispot) assays and using CTL clones and lines in cytolytic assays. The dominant HLA-B60-restricted epitope, Nef peptide KEKG GLEGL, was targeted by all eight subjects with B60 and also by both subjects with B61 studied. This study additionally establishes the utility of the Elispot assay as a more rapid and efficient method of defining novel CTL epitopes. This approach will help to define new CTL epitopes that may play an important role in the immune control of HIV-1. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada. RP Goulder, PJR (reprint author), CNY, MGH E, 149 13th St,5th Floor, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI39966, AI46995, R37 AI028568, U01 AI048023, R01 AI028568, R01 AI030914, R01 AI039966, R01 AI046995, AI28568] NR 45 TC 81 Z9 82 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2000 VL 74 IS 18 BP 8541 EP 8549 DI 10.1128/JVI.74.18.8541-8549.2000 PG 9 WC Virology SC Virology GA 347ML UT WOS:000088933700038 PM 10954555 ER PT J AU Cromwell, MA Veazey, RS Altman, JD Mansfield, KG Glickman, R Allen, TM Watkins, DI Lackner, AA Johnson, RP AF Cromwell, MA Veazey, RS Altman, JD Mansfield, KG Glickman, R Allen, TM Watkins, DI Lackner, AA Johnson, RP TI Induction of mucosal homing virus-specific CD8(+) T lymphocytes by attenuated simian immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC ACTIVITY; RHESUS-MONKEYS; SIV INFECTION; MACAQUES; VACCINE; TYPE-1; PROTECTION; MEMORY; CELLS; MAMU-A-ASTERISK-01 AB Induction of virus-specific T-cell responses in mucosal as well as systemic compartments of the immune system is likely to be a critical feature of an effective AIDS vaccine. We investigated whether virus-specific CD8(+) lymphocytes induced in rhesus macaques by immunization with attenuated simian immunodeficiency virus (SIV), an approach that is highly effective in eliciting protection against mucosal challenge, express the mucosa-homing receptor alpha 4 beta 7 and traffic to the intestinal mucosa. SIV-specific CD8(+) T cells expressing alpha 4 beta 7 were detected in peripheral blood and intestine of macaques infected with attenuated SIV. In contrast, virus-specific T cells in blood of animals immunized cutaneously by a combined DNA-modified vaccinia virus Ankara regimen did not express alpha 4 beta 7. These results demonstrate the selective induction of SIV-specific CD8+ T lymphocytes expressing alpha 4 beta 7 by a vaccine approach that replicates in mucosal tissue and suggest that induction of virus-specific lymphocytes that are able to home to mucosal sites may be an important characteristic of a successful AIDS vaccine. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Pathol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Primate Med, Southborough, MA 01772 USA. Emory Univ, Sch Med, Emory Vaccine Ctr Yerkes, Atlanta, GA 30322 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Johnson, RP (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Immunol, 1 Pine Hill Dr,POB 9102, Southborough, MA 01772 USA. FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [AI43045, AI43044, P01 AI043045]; NIDDK NIH HHS [R01 DK050550] NR 31 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2000 VL 74 IS 18 BP 8762 EP 8766 DI 10.1128/JVI.74.18.8762-8766.2000 PG 5 WC Virology SC Virology GA 347ML UT WOS:000088933700063 PM 10954580 ER PT J AU Royall, DR Chiodo, LK Polk, MJ AF Royall, DR Chiodo, LK Polk, MJ TI Correlates of disability among elderly retirees with "subclinical" cognitive impairment SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 52nd Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 19-23, 1999 CL SAN FRANCISCO, CALIFORNIA SP Gerontol Soc Amer ID MINI-MENTAL-STATE; ALZHEIMERS-DISEASE; GLUCOSE-UTILIZATION; UNAWARENESS; DYSFUNCTION; FEATURES; DEMENTIA; DEFICITS AB Background We assessed the effects of impaired Executive Control Function (ECF) on Instrumental Activities of Daily Living (IADL) and level of tare among noninstitutionalized elderly retirees with "subclinical" cognitive impairment. Methods. Subjects (N = 561; age 78.2 +/- 5.0 years) were residents of a single, 1500 bed, continuing care retirement community. Subjects were examined for cognitive impairment using the Executive Interview (EXIT25), Mini-Mental State Examination (MMSE), and an executive clock-drawing task (CLOX). The CLOX is divided into executively sensitive (CLOX1) and simple constructional (CLOX2) subtests. Results. Residents in congregate high-rises (n = 301) differed significantly From those in independent-living apartments (n = 260) with respect to age, gender, percent living alone, EXIT25, CLOX1, MMSE, and CLOX2 scores (all P < .03). Only differences in ECF measures persisted after adjusting for age and living alone (p < .004). The EXIT25 (P < .006) and CLOX2 (p = .02) were associated with the use of prostheses. The differences in EXIT25 scores persisted after adjusting for level and living alone (p = .01). All instruments distinguished residents with impairment in IADLs. However, only CLOX2 (p < .001), EXIT25 (p < .001), and age (p < .001) made significant independent contributions. Conclusions. ECF has statistically significant effects on level of care and IADL impairment, even among noninstitutionalized retirees. This emergent disability is not well detected by traditional global cognitive measures. Evaluation and treatment may he delayed unless ECF measures are employed. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Syst, Audie L Murphy Div GRECC, Dept Pharmacol, San Antonio, TX USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 48 TC 88 Z9 88 U1 3 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2000 VL 55 IS 9 BP M541 EP M546 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 373WC UT WOS:000165312200017 PM 10995053 ER PT J AU Felsenfeld, AJ Jara, A Avedian, G Kleeman, CR AF Felsenfeld, AJ Jara, A Avedian, G Kleeman, CR TI Effects of fasting, feeding, and bisphosphonate administration on serum calcitriol levels in phosphate-deprived rats SO KIDNEY INTERNATIONAL LA English DT Article DE hypercalcemia; parathyroid hormone; dietary phosphate; metabolism ID PHOSPHORUS DEPRIVATION; DIETARY PHOSPHORUS; PARATHYROID-HORMONE; BONE-RESORPTION; GROWTH-HORMONE; 1,25-DIHYDROXYVITAMIN-D CONCENTRATIONS; D METABOLISM; IN-VITRO; CALCIUM; DEPLETION AB Background. In a recent study, we showed in phosphate deprived rats that morning feeding decreased serum phosphate and increased serum calcium values as compared with similar rats: fasted overnight, and high doses of bisphosphonates did not reduce the magnitude of hypercalcemia. In the present study, we evaluated in phosphate-deprived rats whether serum calcitriol values were: (I) affected by the differences in serum phosphate induced by morning feeding and overnight fasting, (2) correlated with changes in serum phosphate levels, and (3) influenced by bisphosphonate administration. Methods. Four groups of rats were studied: (I) low-phosphate diet (LPD; P < 0.05%), (2) LPD + the bisphosphonate pamidronate (APD): (3) normal diet (ND: P 0.6%), and (4) ND + APD, Both diets contained 0.6% calcium. In rats receiving APD, high doses (0.8 mg/kg) were given subcutaneously four times during the study. On day 11, rats were sacrificed after an overnight fast or two to four hours after morning feeding. Results. In the fed phosphate-deprived rats (LPD and LPD + APD), serum phosphate levels were less (P < 0.05) and serum calcium levels were greater (P < 0.05) than in similar rats fasted overnight. In rats on the ND (ND and ND + APD), no differences were observed between fed and fasted rats. In phosphate-deprived rats, serum calcitriol levels were greater (LPD, P < 0.05) or tended to be greater (LPD + APD, P = 0.10) in the fed than in the fasted groups. In APD-treated rats. serum calcitriol values were greater than in rats not given APD whether rats were (I) fed or fasted, or (2) on an LPD dr ND. An inverse correlation was present between serum phosphate and serum calcitriol (r = -0.58, P = 0.001). In a stepwise regression model in which serum calcitriol was the dependent variable and independent variables were APD administration and serum calcium, phosphate, ind PTH. serum phosphate (r = 0.003) had an inverse and APD (P < 0.001) administration a direct effect on serum calcitriol (r(2) = 0.59). Conclusion. Calcitriol synthesis is rapidly inducible in rats during chronic phosphate deprivation, and the increase in serum calcitriol values is best attributed to feeding-induced decreases in serum phosphate. APD administration independently increases serum calcitriol levels in rats on normal and phosphate-deprived diets. Finally, whether our results in the rat are applicable to the clinical setting should be evaluated because in previous human studies of dietary phosphate restriction, serum calcitriol measurements were performed the morning after an overnight fast. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 49 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2000 VL 58 IS 3 BP 1016 EP 1022 DI 10.1046/j.1523-1755.2000.00259.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 351KE UT WOS:000089155700010 PM 10972666 ER PT J AU Jara, A Felsenfeld, AJ Bover, J Kleeman, CR AF Jara, A Felsenfeld, AJ Bover, J Kleeman, CR TI Chronic metabolic acidosis in azotemic rats on a high-phosphate diet halts the progression of renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE bone; calcium; parathyroid hormone; hyperphosphatemia; chronic renal failure; diet; mineral metabolism ID BODY PROTEIN-DEGRADATION; D-DEFICIENT RATS; PARATHYROID-HORMONE; INORGANIC-PHOSPHATE; BONE HISTOMORPHOMETRY; CALCIUM-TRANSPORT; ION HOMEOSTASIS; FAILURE; PHOSPHORUS; HYPERPARATHYROIDISM AB Background. Hyperphosphatemia and metabolic acidosis are general features of advanced chronic renal failure (RF), and each may affect mineral metabolism. The goal of the present study was to evaluate the effect of chronic metabolic acidosis on the development of hyperparathyroidism and bone disease in normal and azotemic rats on a high-phosphate diet. Our assumption that the two groups of azotemic rats (acid-loaded vs. non-acid-loaded) would have the same degree of renal failure at the end of the study proved to be incorrect. Methods. Four groups of rats receiving a high-phosphate (1.2%), normal-calcium (0.6%) diet for 30 days were studied: (I) normal (N); (2) normal + acid (N + Ac) in which 1.5% ammonium chloride (NH4Cl) was added to the drinking water to induce acidosis; (3) RF, 5/6 nephrectomized rats; and (4) RF + acid (RF + Ac) in which 0.75% NH4Cl was added to the drinking water of 5/6 nephrectomized rats to induce acidosis. Results. At sacrifice, the arterial pH and serum bicarbonate were lowest in the RF + Ac group and were intermediate in the N + Ac group. Serum creatinine (0.76 +/- 0.08 vs. 1.15 +/- 0.08 mg/dL), blood urea nitrogen (52 +/- 8 vs. 86 +/- 13 mg/dL), parathyroid hormone (PTH; 180 +/- 50 vs. 484 +/- 51 pg/mL), and serum phosphate (7.46 +/- 0.60 vs. 12.87 +/- 1.4 mg/dL) values were less (P < 0.05), and serum calcium (9.00 +/- 0.28 vs. 7.75 +/- 0.25 mg/dL) values were greater (P < 0.05) in the RF + Ac group than in the RF group. The fractional excretion of phosphate (FEp) was greater (P < 0.05) in the two azotemic groups than in the two nonazotemic groups. In the azotemic groups, the FEp was similar even though PTH and serum phosphate values were less in the RF + Ac than in the RF group. NH4Cl-induced acidosis produced hypercalciuria in the N + Ac and RF + Ac groups. When acid-loaded (N + Ac and RF + Ac) and non-acid-loaded (N and RF) rats were combined as separate groups, serum phosphate and PTH values were less for a similarly elevated serum creatinine value in acid-loaded than in non-acid-loaded rats. Finally, the osteoblast surface was less in the N + Ac group than in the other groups. However, in the acid-loaded azotemic group (RF + Ac), the osteoblast surface was not reduced. Conclusions. The presence of chronic metabolic acidosis in 5/6 nephrectomized rats on a high-phosphate diet (I) protected against the progression of RF, (2) enhanced the renal clearance of phosphate, (3) resulted in a lesser degree of hyperparathyroidism, and (4) did not reduce the osteoblast surface. The combination of metabolic acidosis and phosphate loading may protect against the progression of RF and possibly bone disease because the harmful effects of acidosis and phosphate loading may be counterbalanced. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Felsenfeld, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 85 TC 38 Z9 38 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2000 VL 58 IS 3 BP 1023 EP 1032 DI 10.1046/j.1523-1755.2000.00260.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 351KE UT WOS:000089155700011 PM 10972667 ER PT J AU Aiello, LP Wong, JS AF Aiello, LP Wong, JS TI Role of vascular endothelial growth factor in diabetic vascular complications SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 4th Hyonam Kidney Laboratory International Symposium on Diabetic Kidney Disease Research - Where do We Stand at the Turn of the Century CY FEB 11-13, 2000 CL SEOUL, SOUTH KOREA SP Int Soc Nephrol, AstraZeneca, Baxter Korea, Boryung Pharmaceut Co Lt, Choogwae Pharma Corp, Gambro Korea, Hanwha Grp, Lilly Korea Ltd, MSD Korea Ltd DE growth factors; angiogenesis; diabetic vascular complications ID ACUTE MYOCARDIAL-INFARCTION; FACTOR MESSENGER-RNA; PERMEABILITY FACTOR; FACTOR VEGF; TYROSINE KINASE; RETINAL NEOVASCULARIZATION; GENE-THERAPY; IN-VIVO; SIGNAL-TRANSDUCTION; HYPOXIC REGULATION AB Background. Much of the morbidity and mortality associated with diabetes mellitus predominantly reflects its deleterious effects on microcirculation and macrocirculation. During the past few years, rapid advancement has been made in our understanding of the mechanisms and molecules involved in the pathogonesis of diabetic microvasculopathy. This is particularly true with regard to retinal vascular disease and the role of the angiogenesis- and vasopermeability-inducing molecule, vascular endothelial growth factor (VEGF). Methods. Biochemical studies in many relevant cell types have been performed. Effects of VEGF action and inhibition have been evaluated in animals. Interventions that block the biochemical pathways initiated by VEGF have been tested both in culture and in animals. Human clinical trials have begun. Results. VEGF induces vascular endothelial cell proliferation, migration and vasopermeability in many cells and tissues. In vivo, VEGF has been identified as a primary initiator of proliferative diabetic retinopathy, and as a potential mediator of nonproliferative retinopathy. In addition, VEGF has been implicated in the development of neuropathy and nephropathy in the patient with diabetes. In patients with diabetes and coronary artery or peripheral vascular disease, VEGF may induce development of cardiac and limb vascular collateralization, respectively. Many biochemical processes mediating these actions have now been elucidated. Conclusions. VEGF appears to play a central role in mediating diabetic vasculopathy in many organs. Improved understanding of the molecular mechanisms underlying these processes has permitted development of novel therapeutic interventions, several of which are now in human clinical trials. These scientific advances and various implications for the future care of vasculopathy associated with diabetes will be discussed. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Vasc Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. NR 86 TC 16 Z9 16 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2000 VL 58 SU 77 BP S113 EP S119 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 348PV UT WOS:000088994800018 ER PT J AU Leehey, DJ Singh, AK Alavi, N Singh, R AF Leehey, DJ Singh, AK Alavi, N Singh, R TI Role of angiotensin II in diabetic nephropathy SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT 4th Hyonam Kidney Laboratory International Symposium on Diabetic Kidney Disease Research - Where do We Stand at the Turn of the Century CY FEB 11-13, 2000 CL SEOUL, SOUTH KOREA SP Int Soc Nephrol, AstraZeneca, Baxter Korea, Boryung Pharmaceut Co Lt, Choogwae Pharma Corp, Gambro Korea, Hanwha Grp, Lilly Korea Ltd, MSD Korea Ltd DE diabetes; angiotensin; glucose; matrix ID HUMAN MESANGIAL CELLS; VASCULAR-PERMEABILITY FACTOR; ENDOTHELIAL GROWTH-FACTOR; MESSENGER-RNA EXPRESSION; CONVERTING ENZYME-INHIBITION; FACTOR-BETA; GLUCOSE; RAT; MATRIX; SYSTEM AB Considerable evidence suggests that the intrarenal renin-angiotensin system plays an important role in diabetic nephropathy. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor blockers (ARBs) can attenuate progressive glomerulosclerosis in disease models and can slow disease progression in humans. Because agents that interfere with Ang II action may decrease glomerular injury without altering glomerular pressures, it has been suggested that Ang II has direct effects on glomerular cells to induce sclerosis independent of its hemodynamic actions. To study nonhemodynamic effects of Ang II on matrix metabolism, many investigators have used cell culture systems. Glucose and Ang II have been shown to produce similar effects on renal cells in culture. For instance, incubation of mesangial cells in high-glucose media or in the presence of Ang II stimulates matrix protein synthesis and inhibits degradative enzyme (e.g., collagenase, plasmin) activity. Glucose and Ang II also can inhibit proximal tubule proteinases. Glucose increases expression of the angiotensinogen gene in proximal tubule cells and Ang II production in primary mesangial cell culture, which indicates that high glucose itself can activate the renin-angiotensin system. The effects of glucose and Ang II on mesangial matrix metabolism may be mediated by transforming growth factor-beta (TGF-beta). Exposure of mesangial cells to glucose or Ang II increases TGF-beta expression and secretion. Their effects on matrix metabolism can be blocked by anti-TGF-beta antibody or ARBs such as losartan, which also prevents the glucose-induced increment in TGF-beta secretion. Taken together, these findings support the hypothesis that the high-glucose milieu of diabetes increases Ang II production by renal, and especially, mesangial cells, which results in stimulation of TGF-beta 1 secretion, leading to increased synthesis and decreased degradation of matrix proteins, thus producing matrix accumulation. This may be an important mechanism linking hyperglycemia and Ang II in the pathogenesis of diabetic nephropathy. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Sch Med, Maywood, IL 60153 USA. Hektoen Inst Med Res, Chicago, IL 60612 USA. Westside Vet Affairs Hosp, Chicago, IL USA. RP Leehey, DJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 62 TC 56 Z9 64 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2000 VL 58 SU 77 BP S93 EP S98 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 348PV UT WOS:000088994800015 ER PT J AU Rauch, SD Zurakowski, D Bloch, DB Bloch, KJ AF Rauch, SD Zurakowski, D Bloch, DB Bloch, KJ TI Anti-heat shock protein 70 antibodies in Meniere's disease SO LARYNGOSCOPE LA English DT Article DE Meniere's disease; heat shock protein 70 (HSP70); antibodies to HSP70 ID SENSORINEURAL HEARING-LOSS; IONIC VOLUME MARKER; MEASURED IN-VIVO; INNER-EAR; ENDOLYMPHATIC HYDROPS; SERUM ANTIBODIES; HEAT-SHOCK-PROTEIN-70; AUTOANTIBODIES; HSP70; SAC AB Objectives: To determine the prevalence of anti-heat shock protein 70 (anti-HSP70) antibodies in patients with Meniere's disease and healthy subjects and to probe the relationship between antibody status and clinical features of Meniere's disease. Study Design: Prospective cohort study of consecutive consenting patients with Meniere's disease. Methods: Serum samples were obtained prospectively from 134 patients with Meniere's disease and 124 blood donors. Serial samples were taken at 3-month intervals in 38 of 134 patients with Meniere's disease. Demographic data and clinical characterization of vestibular and auditory status were acquired with each sample. Serum was assayed for anti-HSP70 antibodies by Western blot using bovine renal extract, recombinant bovine HSP70, and recombinant human HSP70 antigens. Results: Immunoreactivity against bovine renal extract HSP70 was found in 38% of patients with Meniere's disease, compared with 25% of blood donors (P < .04). Reactivity with recombinant antigens was not significantly different between patients with Meniere's disease and healthy control subjects. Patients with Meniere's disease who reacted with all three antigens were more likely to have simultaneously active hearing and balance symptoms (P = .03). Neither univariate nor multivariate statistical analysis established any other association between serological findings and clinical features of Meniere's disease. Tests performed on serial samples of patients with Meniere's disease also showed no association of positive or negative test results with changes in clinical course. Conclusions: Because of the high prevalence of anti-HSP70 antibodies in healthy subjects and the very limited association of anti-HSP70 antibody status with clinical features or course of Meniere's disease, we conclude that, at present, the detection of anti-HSP70 antibodies by Western blotting offers little clinically useful information in Meniere's disease. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Div Res Comp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Arthrit Unit, Gen Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Allergy & Clin Immunol Unit, Gen Med Serv, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC02831] NR 50 TC 22 Z9 23 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD SEP PY 2000 VL 110 IS 9 BP 1516 EP 1521 DI 10.1097/00005537-200009000-00020 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 350XW UT WOS:000089127800019 PM 10983953 ER PT J AU Stone, ME AF Stone, ME TI A woman's guide to sleep: Guaranteed solutions for a good night's rest. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD SEP 1 PY 2000 VL 125 IS 14 BP 243 EP 243 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 350FD UT WOS:000089089400209 ER PT J AU Barnett, GO Chueh, HC AF Barnett, GO Chueh, HC TI Laboratory of computer science, Massachusetts General Hospital: Four decades of medical informatics SO M D COMPUTING LA English DT Editorial Material C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Barnett, GO (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD SEP-OCT PY 2000 VL 17 IS 5 BP 19 EP 22 PG 4 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 358TH UT WOS:000089572900014 PM 11050854 ER PT J AU D'Amato, RM D'Aquila, RT Wein, LM AF D'Amato, RM D'Aquila, RT Wein, LM TI Management of antiretroviral therapy for HIV infection: Analyzing when to change therapy SO MANAGEMENT SCIENCE LA English DT Article DE AIDS; stochastic modeling; censored measurements; Slepian's inequality ID PLASMA; SUPPRESSION; VIRUS; RNA AB We analyze two joint decisions in the management of HIV-infected patients on antiretroviral therapy: how frequently to measure a patient's virus level, and when to switch therapy. The underlying stochastic model captures the initial suppression and eventual rebound of the virus level in the blood of a typical HIV-infected patient undergoing treatment. We consider two classes of policies: a viral load policy, which triggers a change in therapy when the current virus level divided by the smallest level achieved thus far exceeds a prespecified threshold, and a proactive policy, which is similar to the viral load policy but also switches drugs at a prespecified time if no evidence of viral rebound has been seen. We find approximate analytical expressions for the probability of switching before the virus reaches its nadir (minimum value) and the mean delay in detection of viral rebound (i.e., the time interval from when the viral nadir occurs until the switch in therapy). Numerical results show that the proactive policy outperforms (i.e., a smaller detection delay for a given probability of prenadir switching) the viral load policy and recent recommendations by an expert AIDS panel, and may delay the onset of multidrug resistance in a significant proportion of patients who experience drug failure. C1 RAND Corp, Santa Monica, CA 90407 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA 02129 USA. MIT, Alfred P Sloan Sch Management, Cambridge, MA 02139 USA. RP D'Amato, RM (reprint author), RAND Corp, Santa Monica, CA 90407 USA. NR 27 TC 4 Z9 4 U1 1 U2 10 PU INST OPERATIONS RESEARCH MANAGEMENT SCIENCES PI LINTHICUM HTS PA 901 ELKRIDGE LANDING RD, STE 400, LINTHICUM HTS, MD 21090-2909 USA SN 0025-1909 J9 MANAGE SCI JI Manage. Sci. PD SEP PY 2000 VL 46 IS 9 BP 1200 EP 1213 DI 10.1287/mnsc.46.9.1200.12235 PG 14 WC Management; Operations Research & Management Science SC Business & Economics; Operations Research & Management Science GA 360BJ UT WOS:000089646300004 ER PT J AU Ubel, PA Nord, E Gold, M Menzel, P Prades, JLP Richardson, J AF Ubel, PA Nord, E Gold, M Menzel, P Prades, JLP Richardson, J TI Improving value measurement in cost-effectiveness analysis SO MEDICAL CARE LA English DT Article DE cost-effectiveness analysis; quality-adjusted life-years; person tradeoff; rationing; disability; quality of life; ethics ID PERSON-TRADE-OFF; HEALTH-CARE PRIORITIES; UTILITY ANALYSIS; PREFERENCES; QUALITY; OREGON; EQUITY; QALYS; LIFE; DISCRIMINATION AB OBJECTIVE. Before cost-effectiveness analysis (CEA) tan fulfill its promise as a tool to guide health care allocation decisions, the method of incorporating societal values into CEA may need to be improved. DESIGN. The study design was a declarative exposition of potential fallacies in the theoretical underpinnings of CEA. Two values held by many people-preferences for giving priority to severely ill patients and preferences to avoid discrimination against people who have limited treatment potential because of disability or chronic illness-that are not currently incorporated into CEA are discussed. CONCLUSIONS. Traditional CEA, through the measurement of quality-adjusted life years (QALYs), is constrained because of a "QALY trap." If, for example, saving the life of a person with paraplegia is equally valuable as saving the life of a person without paraplegia, then current QALY methods force us to conclude that curing paraplegia brings no benefit. Basing cost-effectiveness measurement on societal values rather than QALYs may allow us to better capture public rationing preferences, thereby escaping the QALY trap. CEA can accommodate a wider range of such societal values about fairness in its measurements by amending its methodology. C1 Univ Penn, Div Gen Internal Med, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Vet Affairs Med Ctr, Sch Med, Philadelphia, PA 19104 USA. Natl Publ Hlth Inst, Oslo, Norway. CUNY, Sch Med, New York, NY USA. Pacific Lutheran Univ, Dept Philosophy, Tacoma, WA 98447 USA. Pompeu Fabra Univ, Dept Econ, Barcelona, Spain. Pompeu Fabra Univ, Ctr Hlth Econ, Barcelona, Spain. RP Ubel, PA (reprint author), Univ Penn, Div Gen Internal Med, Sch Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. RI pinto prades, jose luis/B-7069-2008 OI pinto prades, jose luis/0000-0002-9684-3410 NR 52 TC 35 Z9 35 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2000 VL 38 IS 9 BP 892 EP 901 DI 10.1097/00005650-200009000-00003 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 348GD UT WOS:000088976400003 PM 10982111 ER PT J AU Deyo, RA Cherkin, DC Weinstein, J Howe, J Ciol, M Mulley, AG AF Deyo, RA Cherkin, DC Weinstein, J Howe, J Ciol, M Mulley, AG TI Involving patients in clinical decisions - Impact of an interactive video program on use of back surgery SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Society-for-the-Study-of-Lumbar-Spine CY JUN 21, 1999 CL KONA, HAWAII SP Int Soc Study Lumbar Spine DE herniated disk; spinal stenosis; lumbar spine surgery; patient education; shared decision making ID LUMBAR SPINAL STENOSIS; NONSURGICAL MANAGEMENT; 1-YEAR OUTCOMES; MEDICAL-CARE; PAIN; SCIATICA; DISK; COMPLICATIONS; REOPERATIONS; DISABILITY AB BACKGROUND. Back surgery rates are rapidly rising in the United States. This surgery is usually elective, so patient preferences are important in the treatment decision. OBJECTIVES. The objective of this study was to determine the impact on outcomes and surgical choices of an interactive, diagnosis-specific videodisk program for informing patients about treatment choices, RESEARCH DESIGN. This was a randomized, controlled trial at 2 sites comparing the interactive video plus a booklet with the booklet alone. SUBJECTS. Elective surgery candidates (n = 393) included 171 patients with herniated disks, 110 with spinal stenosis, and 112 with other diagnoses. MEASURES. Mailed questionnaires were used to assess outcomes and satisfaction; surgery rates were determined by questionnaires and automated records. RESULTS. Symptom and functional outcomes at 3 months and 1 year were similar between study groups. The overall surgery rate was 22% lower in the videodisk group (26% versus 33%, P = 0.08). Among patients with herniated disks, those in the video group underwent significantly less surgery (32% versus 47%, P = 0.05 by Kaplan-Meier test). Among patients with spinal stenosis, surgery rates in the video group were higher (39% for the video group, 29% for the booklet group; P = 0.4). There was little effect on patient satisfaction, but patients in the video group felt better informed. CONCLUSIONS. The program appears to facilitate decision making and may help to ensure informed consent. For patients with herniated disks, it reduced the surgery rate without diminishing patient outcomes. Its impact on costs of care depends on the proportion of patients with various diagnoses and on local surgery rates. C1 Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98103 USA. Univ Washington, Dept Med, Seattle, WA 98103 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98103 USA. Univ Washington, Dept Family Med, Seattle, WA 98103 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Grp Hlth Cooperat Puget Sound, Sect Neurol Surg & Neurol, Seattle, WA 98101 USA. Univ Iowa, Dept Orthopaed Surg, Iowa City, IA USA. Dartmouth Hitchcock Med Ctr, Hanover, NH USA. Dartmouth Med Sch, Hanover, NH USA. Harvard Univ, Sch Med, Div Gen Med, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Deyo, RA (reprint author), Univ Washington, Ctr Cost & Outcomes Res, 146 N Canal St,Suite 300, Seattle, WA 98103 USA. FU AHRQ HHS [HS 08079] NR 36 TC 109 Z9 109 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 2000 VL 38 IS 9 BP 959 EP 969 DI 10.1097/00005650-200009000-00009 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 348GD UT WOS:000088976400009 PM 10982117 ER PT J AU Shearman, LP Jin, XW Lee, CG Reppert, SM Weaver, DR AF Shearman, LP Jin, XW Lee, CG Reppert, SM Weaver, DR TI Targeted disruption of the mPer3 gene: Subtle effects on circadian clock function SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SUPRACHIASMATIC NUCLEUS; PERIOD HOMOLOGS; FIRING RHYTHMS; EXPRESSION; LIGHT; PROTEIN; TRANSCRIPTION; LOOP; DBP; COMPLEX AB Neurons in the mammalian suprachiasmatic nucleus (SCN) contain a cell-autonomous circadian clock that is based on a transcriptional-translational feedback loop. The basic helix-loop-helix-PAS proteins CLOCK and BMAL1 are positive regulators and drive the expression of the negative regulators CRY1 and CRY2, as well as PER1, PER2, and PER3, To assess the role of mouse PER3 (mPER3) in the circadian timing system, we generated mice with a targeted disruption of the mPer3 gene. Western blot analysis confirmed the absence of mPER3-immunoreactive proteins in mice homozygous for the targeted allele. mPer1, rnPer2, mCry1, and BmalI RNA rhythms in the SCN did not differ between mPER3-deficient and wild-type mice, Rhythmic expression of mPer1 and mPer2 RNAs in skeletal muscle also did not differ between mPER3-deficient and wild-type mice, mPer3 transcripts were rhythmically expressed in the SCN and skeletal muscle of mice homozygous for the targeted allele, but the level of expression of the mutant transcript was lower than that in wild-type controls. Locomotor activity rhythms in mPER3-deficient mice were grossly normal, but the circadian cycle length was significantly (0.5 h) shorter than that in controls. The results demonstrate that mPer3 is not necessary for circadian rhythms in mice. C1 Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Weaver, DR (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, GRJ 1226, Boston, MA 02114 USA. FU NHLBI NIH HHS [T32 HL007901, HL07901]; NICHD NIH HHS [HD14227]; NIMH NIH HHS [F32 MH012067]; NINDS NIH HHS [NS39303, R01 NS039303] NR 39 TC 192 Z9 200 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2000 VL 20 IS 17 BP 6269 EP 6275 DI 10.1128/MCB.20.17.6269-6275.2000 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343RZ UT WOS:000088716500009 PM 10938103 ER PT J AU Moores, SL Selfors, LM Fredericks, J Breit, T Fujikawa, K Alt, FW Brugge, JS Swat, W AF Moores, SL Selfors, LM Fredericks, J Breit, T Fujikawa, K Alt, FW Brugge, JS Swat, W TI Vav family proteins couple to diverse cell surface receptors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; GTP EXCHANGE FACTOR; NF-KAPPA-B; TYROSINE PHOSPHORYLATION; PROTOONCOGENE PRODUCT; T-CELL; SIGNALING PATHWAY; RHO-FAMILY; KINASE SYK; SH2 DOMAIN AB Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple,vith similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation, Integrin-induced tyrosine phosphorylation of Vav proteins was net detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NF kappa B dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 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 Pediat, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA078773, CA78773]; NHLBI NIH HHS [P01 HL59561, P01 HL059561]; NIAID NIH HHS [R01 AI020047, R37 AI020047, AI20047] NR 55 TC 110 Z9 112 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2000 VL 20 IS 17 BP 6364 EP 6373 DI 10.1128/MCB.20.17.6364-6373.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343RZ UT WOS:000088716500019 PM 10938113 ER PT J AU Phelan, ML Schnitzler, GR Kingston, RE AF Phelan, ML Schnitzler, GR Kingston, RE TI Octamer transfer and creation of stably remodeled nucleosomes by human SWI-SNF and its isolated ATPases SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; YEAST SWI/SNF COMPLEX; HISTONE OCTAMER; GLUCOCORTICOID RECEPTOR; RNA-POLYMERASE; IN-VITRO; CHROMATIN; DISRUPTION; ACTIVATION; ARRAYS AB Chromatin remodeling complexes help regulate the structure of chromatin to facilitate transcription, The multisubunit human (h) SWI-SNF complex has been shown to remodel mono- and polynucleosome templates in an ATP-dependent manner. The isolated hSWI-SNF ATPase subunits BRG1 and hBRM also have these activities. The intact complex has been shown to produce a stable remodeled dimer of mononucleosomes as a product. Here we show that the hSWI-SNF ATPases alone can also produce this product. In addition, we show that hSWI-SNF and its ATPases have the ability to transfer histone octamers from donor nucleosomes to acceptor DNA. These two reactions are characterized and compared. Our results are consistent with both products of SWI-SNF action being formed as alternative outcomes of a single remodeling mechanism. The ability of the isolated ATPase subunits to catalyze these reactions suggests that these subunits play a key role in determining the mechanistic capabilities of the SWI-SNF family of remodeling complexes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Kingston, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. NR 43 TC 81 Z9 82 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2000 VL 20 IS 17 BP 6380 EP 6389 DI 10.1128/MCB.20.17.6380-6389.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 343RZ UT WOS:000088716500021 PM 10938115 ER PT J AU Gabai, VL Yaglom, JA Volloch, V Meriin, AB Force, T Koutroumanis, M Massie, B Mosser, DD Sherman, MY AF Gabai, VL Yaglom, JA Volloch, V Meriin, AB Force, T Koutroumanis, M Massie, B Mosser, DD Sherman, MY TI Hsp72-mediated suppression of c-Jun N-terminal kinase is implicated in development of tolerance to caspase-independent cell death SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASES; STRESS-INDUCED APOPTOSIS; HEAT-SHOCK PROTEIN-70; EXPRESSION CASSETTE; HSP70; THERMOTOLERANCE; GENE; PATHWAY; JNK; OVEREXPRESSION AB Pretreatment with mild heat shock is known to protect cells from severe stress (acquired thermotolerance). Here we addressed the mechanism of this phenomenon by using primary human fibroblasts. Severe heat shock (45 degrees C, 75 min) of the fibroblasts caused cell death displaying morphological characteristics of apoptosis; however, it was caspase independent. This cell death process was accompanied by strong activation of Akt, extracellular signal-regulated kinase 1 (ERK1) and ERK2, p38, and c-Jun N-terminal (JNK) kinases. Suppression of Akt or ERK1 and -2 kinases increased cell thermosensitivity. In contrast, suppression of stress kinase JNK rendered cells thermoresistant. Development of thermotolerance was not associated with Akt or ERK1 and -2 regulation, and inhibition of these kinases did not reduce acquired thermotolerance. On the other hand, acquired tolerance to severe heat shock was associated with downregulation of JNK. Using an antisense-RNA approach, we found that accumulation of the heat shock protein Hsp72 is necessary for JNK downregulation and is critical for thermotolerance. The capability of naive cells to withstand moderate heat treatment also appears to be dependent on the accumulation of Hsp72 induced by this stress. Indeed, exposure to 45 degrees C for 45 min caused only transient JNK activation and was nonlethal, while prevention of Hsp72 accumulation prolonged JNK activation and led to massive cell death. We also found that JNK activation by UV irradiation, interleukin-1, or tumor necrosis factor was suppressed in thermotolerant cells and that Hsp72 accumulation was responsible for this effect. Hsp72-mediated suppression of JNK is therefore critical for acquired thermotolerance and may play a role in tolerance to other stresses. C1 Boston Biomed Res Inst, Watertown, MA 02472 USA. Tufts Univ, Medford, MA 02155 USA. Massachusetts Gen Hosp, Charlestown, MA USA. Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada. Med Radiol Res Ctr, Obninsk, Russia. RP Sherman, MY (reprint author), Boston Biomed Res Inst, 64 Grove St, Watertown, MA 02472 USA. RI Gabai, Vladimir/I-1650-2013; OI Force, Thomas/0000-0002-0450-8659 NR 46 TC 123 Z9 128 U1 3 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2000 VL 20 IS 18 BP 6826 EP 6836 DI 10.1128/MCB.20.18.6826-6836.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348HH UT WOS:000088979100020 PM 10958679 ER PT J AU Kriauciunas, KM Myers, MG Kahn, CR AF Kriauciunas, KM Myers, MG Kahn, CR TI Cellular compartmentalization in insulin action: Altered signaling by a lipid-modified IRS-1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; ACTIVATED PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE KINASE-ACTIVITY; RECEPTOR SUBSTRATE-1; 3T3-L1 ADIPOCYTES; SERINE/THREONINE PHOSPHORYLATION; PP70(S6K) ACTIVATION; GLUT4 TRANSLOCATION; AKT PROTOONCOGENE; PDGF RECEPTOR AB While most receptor tyrosine kinases signal by recruiting SH2 proteins directly to phosphorylation sites on their plasma membrane receptor, the insulin receptor phosphorylates intermediary IRS proteins that are distributed between the cytoplasm and a state of loose association with intracellular membranes. To determine the importance of this distribution to IRS-1-mediated signaling, we constructed a prenylated, constitutively membrane-bound IRS-1 by adding the COOH-terminal 9 amino acids from p21(ras), including the CAAX motif, to IRS-1 (IRS-CAAX) and analyzed its function in 32D cells expressing the insulin receptor. IRS-CAAX migrated more slowly on sodium dodecyl sulfate-polyacrylamide gel electrophoresis than did IRS-1 and demonstrated increased levels of serine/threonine phosphorylation, Insulin-stimulated tyrosyl phosphorylation of IRS-CAAX was slightly decreased, while IRS-CAAX-mediated phosphatidylinositol 3'-kinase (PI3'-kinase) binding and activation were decreased by approximately 75% compared to those for wild-type IRS-1. Similarly, expression of IRS-CAAX desensitized insulin stimulated [H-3]thymidine incorporation into DNA by about an order of magnitude compared to IRS-1. By contrast, IRS-CAAX-expressing cells demonstrated increased signaling by mitogen-activated protein kinase, Akt, and p70(S6) kinase in response to insulin. Hence, tight association with the membrane increased IRS-1 serine phosphorylation and reduced coupling between the insulin receptor, PI3'-kinase, and proliferative signaling while enhancing other signaling pathways. Thus, the correct distribution of IRS-1 between the cytoplasm and membrane compartments is critical to the normal balance in the network of insulin signaling. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 31036, DK 33201, R01 DK031036, R37 DK031036, R01 DK033201] NR 63 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2000 VL 20 IS 18 BP 6849 EP 6859 DI 10.1128/MCB.20.18.6849-6859.2000 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 348HH UT WOS:000088979100022 PM 10958681 ER PT J AU Sullivan, BM Harrison-Lavoie, KJ Marshansky, V Lin, HY Kehrl, JH Ausiello, DA Brown, D Druey, KM AF Sullivan, BM Harrison-Lavoie, KJ Marshansky, V Lin, HY Kehrl, JH Ausiello, DA Brown, D Druey, KM TI RGS4 and RGS2 bind coatomer and inhibit COPI association with Golgi membranes and intracellular transport SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HETEROTRIMERIC G-PROTEINS; ADP-RIBOSYLATION FACTOR; GTPASE-ACTIVATING PROTEIN; DILYSINE RETRIEVAL MOTIFS; LLC-PK1 EPITHELIAL-CELLS; TRIMERIC G-PROTEINS; ENDOPLASMIC-RETICULUM; ALPHA-SUBUNITS; COATED VESICLES; WD-REPEAT AB COPI, a protein complex consisting of coatomer and the small GTPase ARF1, is an integral component of some intracellular transport carriers. The association of COPI with secretory membranes has been implicated in the maintenance of Golgi integrity and the normal functioning of intracellular transport in eukaryotes. The regulator of G protein signaling, RGS4, interacted with the COPI subunit beta'-COP in a yeast two-hybrid screen. Both recombinant RGS4 and RGS2 bound purified recombinant beta'-COP in vitro. Endogenous cytosolic RGS4 from NG108 cells and RGS2 from HEK293T cells cofractionated with the COPI complex by gel filtration. Binding of beta'-COP to RGS4 occurred through two dilysine motifs in RGS4, similar to those contained in some aminoglycoside antibiotics that are known to bind coatomer. RGS4 inhibited COPI binding to Golgi membranes independently of its GTPase-accelerating activity on G(i alpha). In RCS4-transfected LLC-PK1 cells, the amount of COPI in the Golgi region was considerably reduced compared with that in wild-type cells, but there was no detectable difference in the amount of either Golgi-associated ARF1 or the integral Golgi membrane protein giantin, indicating that Golgi integrity was preserved. In addition, RGS4 expression inhibited trafficking of aquaporin 1 to the plasma membrane in LLC-PK1 cells and impaired secretion of placental alkaline phosphatase from HEK293T cells. The inhibitory effect of RGS4 in these assays was independent of GTPase-accelerating activity but correlated with its ability to bind COPI. Thus, these data support the hypothesis that these RGS proteins sequester coatomer in the cytoplasm and inhibit its recruitment onto Golgi membranes, which may in turn modulate Golgi-plasma membrane or intra-Golgi transport. C1 NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Program Membrane Biol, Renal Unit, Charlestown, MA 02129 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. NIAID, B Cell Mol Immunol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Druey, KM (reprint author), NIAID, Mol Signal Transduct Sect, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. OI Kehrl, John/0000-0002-6526-159X FU NIDDK NIH HHS [P01 DK038452, DK38452] NR 68 TC 21 Z9 23 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3992 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 2000 VL 11 IS 9 BP 3155 EP 3168 PG 14 WC Cell Biology SC Cell Biology GA 355LU UT WOS:000089387800024 PM 10982407 ER PT J AU Okamura, H Aramburu, J Garcia-Rodriguez, C Viola, JPB Raghavan, A Tahiliani, M Zhan, XL Qin, J Hogan, PG Rao, A AF Okamura, H Aramburu, J Garcia-Rodriguez, C Viola, JPB Raghavan, A Tahiliani, M Zhan, XL Qin, J Hogan, PG Rao, A TI Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity SO MOLECULAR CELL LA English DT Article ID PHOSPHORYLATION SITES; SIGNAL-TRANSDUCTION; NUCLEAR EXPORT; CALCINEURIN; CELLS; ACTIVATION; DOMAIN; IDENTIFICATION; TRANSLOCATION; BROMODOMAIN AB NFAT transcription factors are highly phosphorylated proteins that are regulated by the calcium-dependent phosphatase calcineurin. We show by mass spectrometry that NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain, thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), cause full exposure of a nuclear localization signal (NLS), and promote transcriptional activity. An inducible phosphorylation site in the transactivation domain contributes to transcriptional activity. Our data suggest that dephosphorylation promotes NFAT1 activation by increasing the probability of an active conformation, in a manner analogous to that by which depolarization increases the open probability of voltage-gated ion channels. This conformational switch paradigm may explain modification-induced functional changes in other heavily phosphorylated proteins. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Baylor Coll Med, VErna & Mars McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Cellular & Mol Biol, Houston, TX 77030 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Aramburu, J/G-8991-2014; OI Aramburu, J/0000-0001-9279-9523; Viola, Joao/0000-0002-0698-3146 FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI40127] NR 45 TC 301 Z9 308 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD SEP PY 2000 VL 6 IS 3 BP 539 EP 550 DI 10.1016/S1097-2765(00)00053-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 358VV UT WOS:000089578600004 PM 11030334 ER PT J AU Gaubatz, S Lindeman, GJ Ishida, S Jakoi, L Nevins, JR Livingston, DM Rempel, RE AF Gaubatz, S Lindeman, GJ Ishida, S Jakoi, L Nevins, JR Livingston, DM Rempel, RE TI E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control SO MOLECULAR CELL LA English DT Article ID CELL-CYCLE INHIBITION; RETINOBLASTOMA-PROTEIN; GROWTH SUPPRESSION; TRANSCRIPTION FACTORS; EXPRESSION PATTERNS; FAMILY; PRB; ACCUMULATION; P16(INK4A); P107 AB E2F transcription factors are major regulators of cell proliferation. The diversity of the E2F family suggests that individual members perform distinct functions in cell cycle control. E2F4 and E2F5 constitute a defined subset of the family. Until now, there has been little understanding of their individual biochemical and biological functions. Here, we report that simultaneous inactivation of E2F4 and E2F5 in mice results in neonatal lethality, suggesting that they perform overlapping functions during mouse development. Embryonic fibroblasts isolated from these mice proliferated normally and reentered from Go with normal kinetics compared to wild-type cells. However, they failed to arrest in G1 in response to p16(INK4a). Thus, E2F4 and E2F5 are dispensable for cell cycle progression but necessary for pocket protein-mediated G1 arrest of cycling cells. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Dept Genet, Durham, NC 27710 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 41 TC 176 Z9 179 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD SEP PY 2000 VL 6 IS 3 BP 729 EP 735 DI 10.1016/S1097-2765(00)00071-X PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 358VV UT WOS:000089578600022 PM 11030352 ER PT J AU Bruce, JL Hurford, RK Classon, M Koh, J Dyson, N AF Bruce, JL Hurford, RK Classon, M Koh, J Dyson, N TI Requirements for cell cycle arrest by p16(INK4a) SO MOLECULAR CELL LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; CDK4 AMPLIFICATION; FAMILY PROTEINS; T-LYMPHOCYTES; P107; P130; INHIBITION; PRB; PHOSPHORYLATION AB Analysis of tumor-derived mutations has led to the suggestion that p16(INK4a), cyclin D1, cdk4, and the retinoblastoma protein (pRB) are components of a regulatory pathway that is inactivated in most tumor cells. Cell cycle arrest induced by p16(INK4a), inhibitor of cyclin D-dependent kinases, requires pRB, and it has been proposed that this G1 arrest is mediated by pRB-E2F repressor complexes. By comparing the properties of primary mouse embryonic fibroblasts specifically lacking pRB-family members, we find that PRE is insufficient for a p16(INK4a)-induced arrest. In addition to pRB, a second function provided by either p107 or p130, two pRB-related proteins, is required for p16(INK4a) to block DNA synthesis. We infer that p16(INK4a)-induced arrest is not mediated exclusively by pRB, but depends on the nonredundant functions of at least two pRB-family members. C1 Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Oncol Mol Lab, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA64402] NR 57 TC 92 Z9 94 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD SEP PY 2000 VL 6 IS 3 BP 737 EP 742 DI 10.1016/S1097-2765(00)00072-1 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 358VV UT WOS:000089578600023 PM 11030353 ER PT J AU Mahajan-Miklos, S Rahme, LG Ausubel, FM AF Mahajan-Miklos, S Rahme, LG Ausubel, FM TI Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts SO MOLECULAR MICROBIOLOGY LA English DT Review ID PSEUDOMONAS-AERUGINOSA; CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; PROTEIN; GENES; PATHOGENESIS; MACROPHAGES; SECRETION; APOPTOSIS; MODEL AB Several strains of the human opportunistic pathogen Pseudomonas aeruginosa infect plants, nematodes and insects. Our laboratory has developed a multihost pathogenesis system based on the P, aeruginosa clinical isolate PA14, in which non-mammalian hosts are used to screen directly for virulence-attenuated mutants. The majority of PA14 mutants isolated using non-mammalian hosts also displayed reduced virulence in a burned mouse model. Surprisingly, only a few host-specific ari ru fence facto rs were identified, and many of the P. aeruginosa mutants were attenuated in virulence in all the hosts. These studies illustrate the extensive conservation in the virulence mechanisms used by P. aeruginosa to infect evolutionarily diverged hosts, and validate the multihost method of screening for virulence factors relevant to mammalian pathogenesis, Through the use of genetically tractable hosts, the multihost pathogenesis model also provides tools for elucidating host responses and dissecting the fundamental molecular interactions that underlie bacterial pathogenesis. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Microbia Inc, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 10, Boston, MA 02114 USA. NR 35 TC 124 Z9 131 U1 1 U2 9 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2000 VL 37 IS 5 BP 981 EP 988 DI 10.1046/j.1365-2958.2000.02056.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 356BK UT WOS:000089424000001 PM 10972817 ER PT J AU Zietman, AL AF Zietman, AL TI The case for neoadjuvant androgen suppression before radiation therapy SO MOLECULAR UROLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Neoadjuvant Hormonal Therapy for Prostate Cancer CY MAR 17-18, 2000 CL CAMBRIDGE, MASSACHUSETTS ID PROSTATE-CANCER; HORMONE-THERAPY; IN-VIVO; CARCINOMA; TUMOR; DEPRIVATION; RADIOTHERAPY; WITHDRAWAL AB Neoadjuvant androgen suppression (NAS) can reduce the number of tumor clonogens prior to radiation, thus increasing the tumor control probability, Also, NAS may sensitize tumor cells to radiation if cell kill by both modalities follows a common pathway. The timing and sequence of NAS and radiation are important, with radiation being most effective if given at the point of maximal tumor regression. The biologic rationale for NAS + radiation has been reinforced by results from randomized trials, in particular RTOG 8610, However, many murine adenocarcinomas respond to androgen deprivation by a reduction in the proliferation rate and arrest in G(0), and in vitro data suggest that this arrest may interfere with radiation-induced cell killing. The mechanism of cell killing after low-dose-rate radiation (brachytherapy) may be different from that after high-dose-rate treatment, There are no reported experimental data assessing the interaction of NAS and brachytherapy to determine whether the combination offers a theoretical advantage or is potentially deleterious. Whether we understand the mechanism or not, clinical trials seem to support a positive interaction of NAS with external-beam radiation, but we have only begun to explore the timing and sequence that will provide the maximal effect. It cannot be assumed that the same advantage will hold with brachytherapy. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Sch Med, 100 Blossom St,Cox 3, Boston, MA 02114 USA. RI huang, hongqi/N-1473-2014 NR 24 TC 6 Z9 6 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 2000 VL 4 IS 3 BP 203 EP 208 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 364UY UT WOS:000089912400027 PM 11062375 ER PT J AU Krane, RJ AF Krane, RJ TI Urinary incontinence after treatment for localized prostate cancer SO MOLECULAR UROLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Neoadjuvant Hormonal Therapy for Prostate Cancer CY MAR 17-18, 2000 CL CAMBRIDGE, MASSACHUSETTS ID RADICAL RETROPUBIC PROSTATECTOMY; COLLAGEN INJECTION THERAPY; BULBOURETHRAL SLING PROCEDURE; INTRINSIC SPHINCTERIC DEFICIENCY; EXTERNAL-BEAM RADIATION; QUALITY-OF-LIFE; URODYNAMIC EVALUATION; CONTINENCE; PRESERVATION; EXPERIENCE AB The incidence of incontinence after radical prostatectomy has ranged from 0 to 57% depending on the series and the type of incontinence considered, When total incontinence (not minimal stress incontinence) is reported, the average incidence is no more than 5%. This figure will increase with age, and in most series, approximately 10% of patients around the age of 70 will have total incontinence postoperatively. Preservation of continence after radical prostatectomy depends largely on the preservation of the distal urethral smooth-muscle sphincteric mechanism, which begins at the pelvic floor and ends at the prostatourethral junction. Newer techniques that attempt to increase postoperative continence include not cutting the puboprostatic ligaments and attempting to preserve as much striated muscle as possible along the length of the remaining urethra. Patients who are incontinent for 6 months after the surgery with no evidence of improvement will probably not become continent on their own. Therefore, some type of therapy should be considered. The options are periurethral injection of a bulking agent, implantation of an artificial sphincter, and, most recently, a bulbourethral sling procedure. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP Krane, RJ (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. NR 44 TC 17 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1091-5362 J9 MOL UROL JI Mol. Urol. PD FAL PY 2000 VL 4 IS 3 BP 279 EP 286 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 364UY UT WOS:000089912400045 PM 11062385 ER PT J AU Mathews, ES Scrivani, SJ AF Mathews, ES Scrivani, SJ TI Percutaneous stereotactic radiofrequency thermal rhizotomy for the treatment of trigeminal neuralgia SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article DE radiofrequency thermal rhizotomy; surgical treatment; facial pain ID FACIAL-PAIN; GAMMA-KNIFE; RADIOSURGERY; LESIONS; THERMOCOAGULATION; COMPRESSION; ETIOLOGY; GANGLION; ROOT AB Background: Trigeminal neuralgia (TN) is the most common cephalic neuralgia in people over the age of fifty, with a mean incidence of 4 per 100,000. Percutaneous stereotactic differential radiofrequency thermal rhizotomy (RTR) is a well-recognized surgical treatment for TN. The purpose of this study was to evaluate a management algorithm for TN and to evaluate the effectiveness of RTR for TN after failure of pharmacologic management. Methods: Two hundred and fifty-eight (258) patients underwent RTR from 1991-1996 and were prospectively evaluated. These patients were characterized by age, sex, side of the face and division(s) involved. Patients were evaluated for pain relief, recurrence requiring or not requiring re-operation, and the type and rate of complications. They were followed by serial clinical evaluation and telephone interview. Patients were grouped according to results: (A) Successful Result - excellent or good pain relief; (B) Unsuccessful Result - fair, poor or no pain relief. The RTR group was compared to historical controls. Follow-up ranged from 12-80 months (mean = 38 months). Results: At early follow-up (defined as median postoperative period up to 6 months), pain relief that was excellent or good (successful results) occurred in 224/258 (87%). At long-term follow-up (> 6 months) recurrence of tic pain required re-operation in 31 patients (12%). In 37 patients (14%), recurrence of tic pain did not require re-operation. Dysesthesia developed in 20 patients (8%); corneal analgesia developed in 8 patients (3%). "Anesthesia dolorosa" developed in 5 patients (2%) and was medically managed. At the conclusion of the long-term follow-up period, 214/258 patients (83%) had excellent to good pain relief(successful result). There were no mortalities, no significant morbidity and a low rate of minor complications. Conclusion: With the use of this specific diagnostic and management algorithm, patients with TN can be successfully managed with RTR. C1 Columbia Presbyterian Med Ctr, Dept Oral & Maxillofacial Surg, New York, NY 10032 USA. Massachusetts Gen Hosp, Craniofacial Pain Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Scrivani, SJ (reprint author), Columbia Presbyterian Med Ctr, Dept Oral & Maxillofacial Surg, HP-8,622 W 168th St, New York, NY 10032 USA. NR 57 TC 27 Z9 36 U1 0 U2 0 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 USA SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD SEP PY 2000 VL 67 IS 4 BP 288 EP 299 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 352TT UT WOS:000089234500006 PM 11021779 ER PT J AU Lindblad-Toh, K Tanenbaum, DM Daly, MJ Winchester, E Lui, WO Villapakkam, A Stanton, SE Larsson, C Hudson, TJ Johnson, BE Lander, ES Meyerson, M AF Lindblad-Toh, K Tanenbaum, DM Daly, MJ Winchester, E Lui, WO Villapakkam, A Stanton, SE Larsson, C Hudson, TJ Johnson, BE Lander, ES Meyerson, M TI Loss-of-heterozygosity analysis of small-cell lung carcinomas using single-nucleotide polymorphism arrays SO NATURE BIOTECHNOLOGY LA English DT Article ID HUMAN GENOME; CANCER; IDENTIFICATION; ALLELOTYPE; TUMORS; 3P AB Human cancers arise by a combination of discrete mutations and chromosomal alterations. Loss of heterozygosity (LOH) of chromosomal regions bearing mutated tumor suppressor genes is a key event in the evolution of epithelial and mesenchymal tumors'. Global patterns of LOH can be understood through allelotyping of tumors with polymorphic genetic markers(2), Simple sequence length polymorphisms (SSLPs, or microsatellites) are reliable genetic markers for studying LOH3, but only a modest number of SSLPs are used in LOH studies because the genotyping procedure is rather tedious. Here, we report the use of a highly parallel approach to genotype large numbers of single-nucleotide polymorphisms (SNPs) for LOH, in which samples are genotyped for nearly 1,500 loci by performing 24 polymerase chain reactions (PCR), Fooling the resulting amplification products and hybridizing the mixture to a high-density oligonucleotide array(4). We characterize the results of LOH analyses on human small-cell lung cancer (SCLC) and control DNA samples by hybridization. We show that the patterns of LOH are consistent with those obtained by analysis with both SSLPs(5) and comparative genomic hybridization (CGH), whereas amplifications rarely are detected by the SNP array. The results validate the use of SNP array hybridization for tumor studies. C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 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 Pathol, Boston, MA 02115 USA. Karolinska Hosp, CMM, Dept Mol Med, S-17176 Stockholm, Sweden. McGill Univ, Ctr Hlth, Montreal Genome Ctr, Montreal, PQ, Canada. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Lander, ES (reprint author), MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. RI Meyerson, Matthew/E-7123-2012; Lui, Weng-Onn/G-6703-2013 OI Lui, Weng-Onn/0000-0003-4717-4473 FU NCI NIH HHS [5T34CA72320-03]; NHGRI NIH HHS [HG01806] NR 16 TC 206 Z9 217 U1 0 U2 13 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 SEP PY 2000 VL 18 IS 9 BP 1001 EP 1005 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 350AN UT WOS:000089078300032 PM 10973224 ER PT J AU Cummings, DE Schwartz, MW AF Cummings, DE Schwartz, MW TI Melanocortins and body weight: a tale of two receptors SO NATURE GENETICS LA English DT Editorial Material ID OBESITY; LEPTIN; MICE AB The phenotypes of mice lacking melanocortin-3 (Mcr3) and melanocortin4 receptors (Mc4r) demonstrate that these isoforms reduce body weight through distinct and complementary mechanisms. Mc4r regulates food intake and possibly energy expenditure, whereas Mc3r influences feed efficiency and the partitioning of fuel stores into fat. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. Harborview Med Ctr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 NR 18 TC 46 Z9 51 U1 0 U2 3 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 SEP PY 2000 VL 26 IS 1 BP 8 EP 9 DI 10.1038/79223 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 350AK UT WOS:000089078000005 PM 10973234 ER PT J AU Altshuler, D Hirschhorn, JN Klannemark, M Lindgren, CM Vohl, MC Nemesh, J Lane, CR Schaffner, SF Bolk, S Brewer, C Tuomi, T Gaudet, D Hudson, TJ Daly, M Groop, L Lander, ES AF Altshuler, D Hirschhorn, JN Klannemark, M Lindgren, CM Vohl, MC Nemesh, J Lane, CR Schaffner, SF Bolk, S Brewer, C Tuomi, T Gaudet, D Hudson, TJ Daly, M Groop, L Lander, ES TI The common PPAR gamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes SO NATURE GENETICS LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; MISSENSE MUTATION; SULFONYLUREA RECEPTOR; GENE; MELLITUS; NIDDM; RESISTANCE; SUBSTITUTION; OBESITY; DISEQUILIBRIUM AB Genetic association studies are viewed as problematic and plagued by irreproducibility(1). Many associations have been reported for type 2 diabetes(2-17), but none have been confirmed in multiple samples and with comprehensive controls. We evaluated 16 published genetic associations to type 2 diabetes and related sub-phenotypes using a family-based design to control for population stratification, and replication samples to increase power. We were able to confirm only one association, that of the common Pro12Ala polymorphism in peroxisome proliferator-activated receptor-gamma (PPAR gamma) with type 2 diabetes. By analysing over 3.000 individuals, we found a modest (1.25-fold) but significant (P=0.002) increase in diabetes risk associated with the more common proline allele (similar to 85% frequency). Moreover. our results resolve a controversy about common variation in PPAR gamma. An initial study found a threefold effect(12). but four of five subsequent publications(18-22) failed to confirm the association. All six studies are consistent with the odds ratio we describe. The data implicate inherited variation in PPAR gamma in the pathogenesis of type 2 diabetes. Because the risk allele occurs at such high frequency, its modest effect translates into a large population attributable risk-influencing as much as 25% of type 2 diabetes in the general population. C1 MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Univ Lund, Malmo Univ Hosp, Wallenberg Lab, Dept Endocrinol, Malmo, Sweden. McGill Univ, Ctr Hlth, Res Inst, Montreal Genome Ctr, Montreal, PQ, Canada. Univ Helsinki, Cent Hosp, Dept Internal Med, Helsinki, Finland. Chicoutimi Hosp, Chicoutimi, PQ, Canada. MIT, Dept Biol, Cambridge, MA USA. RP Lander, ES (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011 OI Altshuler, David/0000-0002-7250-4107; FU Wellcome Trust [090532] NR 38 TC 1254 Z9 1305 U1 6 U2 37 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 SEP PY 2000 VL 26 IS 1 BP 76 EP 80 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 350AK UT WOS:000089078000022 PM 10973253 ER PT J AU Wong, KK Chang, S Weiler, SR Ganesan, S Chaudhuri, J Zhu, CM Artandi, SE Rudolph, KL Gottlieb, GJ Chin, L Alt, FW DePinho, RA AF Wong, KK Chang, S Weiler, SR Ganesan, S Chaudhuri, J Zhu, CM Artandi, SE Rudolph, KL Gottlieb, GJ Chin, L Alt, FW DePinho, RA TI Telomere dysfunction impairs DNA repair and enhances sensitivity to ionizing radiation SO NATURE GENETICS LA English DT Article ID STRAND BREAK REPAIR; V(D)J RECOMBINATION; MAMMALIAN-CELLS; LIGASE-IV; CHROMOSOME BREAKAGE; STEM-CELLS; MICE; KU; IDENTIFICATION; PROTEINS AB Telomeres are specialized nucleoprotein complexes that serve as protective caps of linear eukaryotic chromosomes. Loss of telomere function is associated with rampant genetic instability and loss of cellular viability and renewal potential. The telomere also participates in processes of chromosomal repair, as evidenced by the 'capture' or de novo synthesis of telomere repeats at double-stranded breaks(1-4) and by the capacity of yeast telomeres to serve as repositories of essential components of the DNA repair machinery, particularly those involved in non-homologous end-joining(5-7) (NHEJ). Here we used the telomerase-deficient mouse. null for the essential telomerase RNA gene (Terc). to assess the role of telomerase and telomere function on the cellular and organismal response to ionizing radiation. Although the loss of telomerase activity per se had no discernable impact on the response to ionizing radiation, the emergence of telomere dysfunction in late-generation Terc(-/-) mice imparted a radiosensitivity syndrome associated with accelerated mortality. On the cellular level, the gastrointestinal crypt stem cells and primary thymocytes showed increased rates of apoptosis, and mouse embryonic fibroblasts (MEFs) showed diminished dose-dependent clonogenic survival. The radiosensitivity of telomere dysfunctional cells correlated with delayed DNA break repair kinetics, persistent chromosomal breaks and cytogenetic profiles characterized by complex chromosomal aberrations and massive fragmentation. Our findings establish a intimate relationship between functionally intact telomeres and the genomic. cellular and organismal response to ionizing radiation. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 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, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. Quest Diagnost Inc, Anat Pathol, Teterboro, NJ USA. Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NIA NIH HHS [K08 AG001019]; NIAMS NIH HHS [K08AR02104-01]; NICHD NIH HHS [R01HD 34880, R01HD28317] NR 30 TC 225 Z9 241 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2000 VL 26 IS 1 BP 85 EP 88 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 350AK UT WOS:000089078000024 PM 10973255 ER PT J AU Hong, SE Shugart, YY Huang, DT Shahwan, SA Grant, PE Hourihane, JOB Martin, NDT Walsh, CA AF Hong, SE Shugart, YY Huang, DT Shahwan, SA Grant, PE Hourihane, JOB Martin, NDT Walsh, CA TI Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations SO NATURE GENETICS LA English DT Article ID NEURONAL MIGRATION; CORTICAL DEVELOPMENT; VLDL RECEPTOR; REELIN GENE; PROTEIN; EXPRESSION; SEQUENCE; ENCODES; CORTEX; MICE AB Normal development of the cerebral cortex requires long-range migration of cortical neurons from proliferative regions deep in the brain. Lissencephaly ("smooth brain." from "lissos," meaning smooth, and "encephalos," meaning brain) is a severe developmental disorder in which neuronal migration is impaired, leading to a thickened cerebral cortex whose normally folded contour is simplified and smooth. Two identified lissencephaly genes(1-3) do not account for all known cases(4), and additional lissencephaly syndromes have been described(5). An autosomal recessive form of lissencephaly (LCH) associated with severe abnormalities of the cerebellum, hippocampus and brainstem maps to chromosome 7q22, and is associated with two independent mutations in the human gene encoding reelin (RELN). The mutations disrupt splicing of RELN cDNA, resulting in low or undetectable amounts of reelin protein. LCH parallels the reeler mouse mutant (Reln(rl)). in which Rein mutations cause cerebellar hypoplasia, abnormal cerebral cortical neuronal migration and abnormal axonal connectivity(6,7). RELN encodes a large (388 kD) secreted proteins that acts on migrating cortical neurons by binding to the very low density lipoprotein receptor (VLDLR), the apolipoprotein E receptor 2 (ApoER2; refs 9-11), alpha 3 beta 1 integrin(12) and protocadherins(13). Although reelin was previously thought to function exclusively in brain, some humans with RELN mutations show abnormal neuromuscular connectivity and congenital lymphoedema, suggesting previously unsuspected functions for reelin in and outside of the brain. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Div Neurogenet, Boston, MA 02115 USA. Johns Hopkins Univ, Ctr Inherited Dis Res, Baltimore, MD USA. Riyadh Armed Forces Hosp, Dept Pediat, Riyadh, Saudi Arabia. Riyadh Armed Forces Hosp, Dept Neurosci, Riyadh, Saudi Arabia. Massachusetts Gen Hosp, Dept Radiol, Serv Neuroradiol, Boston, MA 02114 USA. Kent & Canterbury Hosp, Dept Pediat, Canterbury, Kent, England. RP Walsh, CA (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Div Neurogenet, Boston, MA 02115 USA. FU NINDS NIH HHS [P01 NS39404, R01 NS35129, R01 NS38097] NR 28 TC 466 Z9 489 U1 2 U2 10 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 SEP PY 2000 VL 26 IS 1 BP 93 EP 96 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 350AK UT WOS:000089078000026 PM 10973257 ER PT J AU Bagley, J Sawada, T Wu, Y Iacomini, J AF Bagley, J Sawada, T Wu, Y Iacomini, J TI A critical role for interleukin 4 in activating alloreactive CD4T cells SO NATURE IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; ALLOGRAFT-REJECTION; ANTIGEN; IL-4; CD28; MICE; TRANSPLANTATION; COSTIMULATION; EXPRESSION; TOLERANCE AB To generate antigen-specific responses, T cells and antigen presenting cells (APCs) must physically associate with each other and elaborate soluble factors that drive the full differentiation of each cell type. Immediately after T cell activation, CD4 T cells can produce both interferon gamma (IFN-gamma) and interleukin 4 (IL-4) before polarization into distinct T helper subsets. Inhibition of IL-4 during mixed allogeneic lymphocyte culture resulted in a defect in the ability of APCs to generate sufficient costimulatory signals for activation of alloreactive T cells. In vivo, a deficiency in IL-4 production inhibited the activation of alloreactive IL-2-, IL-4- and IFN-gamma-producing CD4 T cells in mice challenged with allogeneic skin grafts, resulting in prolonged skin graft survival.-rhus, production of IL-4 by CD4 T cells helps activate alloreactive T cells by affecting APC function. C1 Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI43619] NR 27 TC 40 Z9 40 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2000 VL 1 IS 3 BP 257 EP 261 DI 10.1038/79811 PG 5 WC Immunology SC Immunology GA 363BY UT WOS:000089815100026 PM 10973285 ER PT J AU Kluwe, L Mautner, V Parry, DM Jacoby, LB Baser, M Gusella, J Davis, K Stavrou, D MacCollin, M AF Kluwe, L Mautner, V Parry, DM Jacoby, LB Baser, M Gusella, J Davis, K Stavrou, D MacCollin, M TI The parental origin of new mutations in neurofibromatosis 2 SO NEUROGENETICS LA English DT Article DE parental origin; neurofibromatosis 2; allele loss; mosaicism ID GERM-LINE MUTATIONS; NF2 GENE; TYPE-2 NEUROFIBROMATOSIS; SPORADIC MENINGIOMAS; DINUCLEOTIDE REPEAT; RETINOBLASTOMA GENE; SOMATIC MUTATIONS; TUMOR-SUPPRESSOR; PATERNAL ORIGIN; SCHWANNOMAS AB Neurofibromatosis 2 (NF2) is an autosomal dominant disorder characterized by schwannomas and meningiomas that develop after inactivation of both copies of the NF2 gene. Approximately half of all patients with NF2 have unaffected parents and the disease results from new mutations at the NF2 locus. Loss of heterozygosity (LOH) in tumor specimens due to deletions covering the normal NF2 allele can be used to infer the haplotypes surrounding underlying mutations and determine the allelic origin of new mutations. We studied 71 sporadic NF2 patients using both LOH and pedigree analysis and compared the parental origin of the new mutation with the underlying molecular change. In the 45 informative individuals, 31 mutations (69%) mere of paternal and 14 (31%) were of maternal origin (P=0.016). Comparison with corresponding constitutional mutations revealed no correlation between parental origin and the type or location of the mutations. However, in 4 of 6 patients with somatic mosaicism the NF2 mutation was of maternal origin. A slight parent of origin effect on severity of disease was found. Further clinical and molecular studies are needed to determine the basis of these unexpected observations. C1 Univ Hamburg, Hosp Eppendorf, Dept Neurosurg, Lab Brain Tumor Biol, D-20246 Hamburg, Germany. Gen Hosp Ochsnezoll, Dept Neurol, Hamburg, Germany. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Hamburg, Hosp Eppendorf, Dept Neuropathol, D-20246 Hamburg, Germany. RP Kluwe, L (reprint author), Univ Hamburg, Hosp Eppendorf, Dept Neurosurg, Lab Brain Tumor Biol, Martinistr 52, D-20246 Hamburg, Germany. FU NCI NIH HHS [CA51410] NR 48 TC 19 Z9 20 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD SEP PY 2000 VL 3 IS 1 BP 17 EP 24 DI 10.1007/s100480000088 PG 8 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 362BP UT WOS:000089759000003 PM 11085592 ER PT J AU Thannickal, TC Moore, RY Nienhuis, R Ramanathan, L Gulyani, S Aldrich, M Cornford, M Siegel, JM AF Thannickal, TC Moore, RY Nienhuis, R Ramanathan, L Gulyani, S Aldrich, M Cornford, M Siegel, JM TI Reduced number of hypocretin neurons in human narcolepsy SO NEURON LA English DT Article ID CANINE NARCOLEPSY; OREXIN; HYPOTHALAMUS; HAPLOTYPE; SYSTEMS; GENE AB Murine and canine narcolepsy can be caused by mutations of the hypocretin (Hcrt) (orexin) precursor or Hcrt receptor genes. In contrast to these animal models, most human narcolepsy is not familial, is discordant in identical twins, and has not been linked to mutations of the Hcrt system. Thus, the cause of human narcolepsy remains unknown. Here we show that human narcoleptics have an 85%-95% reduction in the number of Hcrt neurons. Melanin-concentrating hormone (MCH) neurons, which are intermixed with Hcrt cells in the normal brain, are not reduced in number, indicating that cell loss is relatively specific for Hcrt neurons. The presence of gliosis in the hypocretin cell region is consistent with a degenerative process being the cause of the Hcrt cell loss in narcolepsy. C1 Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, N Hills, CA 91343 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. FU NHLBI NIH HHS [HL41370, HL6029C]; NINDS NIH HHS [NS14610] NR 28 TC 1063 Z9 1087 U1 8 U2 48 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP PY 2000 VL 27 IS 3 BP 469 EP 474 DI 10.1016/S0896-6273(00)00058-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 359FR UT WOS:000089601300011 PM 11055430 ER PT J AU Yoo, AS Cheng, I Chung, S Grenfell, TZ Lee, H Pack-Chung, E Handler, M Shen, J Xia, WM Tesco, G Saunders, AJ Ding, K Frosch, MP Tanzi, RE Kim, TW AF Yoo, AS Cheng, I Chung, S Grenfell, TZ Lee, H Pack-Chung, E Handler, M Shen, J Xia, WM Tesco, G Saunders, AJ Ding, K Frosch, MP Tanzi, RE Kim, TW TI Presenilin-mediated modulation of capacitative calcium entry SO NEURON LA English DT Article ID AMYLOID-BETA-PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; OPERATED HTRP3 CHANNELS; CA2+ ENTRY; IN-VIVO; INTRACELLULAR CA2+; PRECURSOR PROTEIN; SENILE PLAQUES; MUTATION N141I; T-LYMPHOCYTES AB We studied a novel function of the presenilins (PS1 and PS2) in governing capacitative calcium entry (CCE), a refilling mechanism for depleted intracellular calcium stores. Abrogation of functional PS1, by either knocking out PS1 or expressing inactive PS1, markedly potentiated CCE, suggesting a role for PS1 in the modulation of CCE. In contrast, familial Alzheimer's disease (FAD)-linked mutant PS1 or PS2 significantly attenuated CCE and store depletion-activated currents. While inhibition of CCE selectively increased the amyloidogenic amyloid beta peptide (Ap42), increased accumulation of the peptide had no effect on CCE. Thus, reduced CCE is most likely an early cellular event leading to increased A beta 42 generation associated with FAD mutant presenilins. Our data indicate that the CCE pathway is a novel therapeutic target for Alzheimer's disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Sungkyunkwan Univ, Sch Med, Dept Physiol, Suwon 440746, South Korea. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Kim, TW (reprint author), Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, 630 W 168th St,P&S 14-511, New York, NY 10032 USA. EM twk16@columbia.edu RI xia, weiming/E-5465-2016; OI xia, weiming/0000-0002-7463-3295; Yoo, Andrew/0000-0002-0304-3247 FU NIA NIH HHS [AG05845, AG15379, AG18026] NR 81 TC 211 Z9 216 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD SEP PY 2000 VL 27 IS 3 BP 561 EP 572 DI 10.1016/S0896-6273(00)00066-0 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 359FR UT WOS:000089601300019 PM 11055438 ER PT J AU Chan, AW Tarbell, NJ Black, PM Louis, DN Frosch, MP Ancukiewicz, M Chapman, P Loeffler, JS AF Chan, AW Tarbell, NJ Black, PM Louis, DN Frosch, MP Ancukiewicz, M Chapman, P Loeffler, JS TI Adult medulloblastoma: Prognostic factors and patterns of relapse SO NEUROSURGERY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 24-29, 1998 CL PHOENIX, ARIZONA SP Amer Soc Therapeut Radiol & Oncol DE adult; medulloblastoma; posterior fossa; primitive neuroectodermal tumor; radiation; surgery ID RADIATION-THERAPY; CEREBELLAR MEDULLOBLASTOMA; PHASE-III; SURVIVAL; CHILDREN; FAILURE; CHEMOTHERAPY; IRRADIATION; MANAGEMENT; TRIAL AB OBJECTIVE: To determine the patterns of relapse and the prognostic factors for adult medulloblastomas treated in the magnetic resonance imaging era. METHODS: Between 1986 and 1996, 32 adult patients (age, greater than or equal to 16 yr) with medulloblastomas confined to the craniospinal axis were treated in our institutions. Twenty cases involved classic histological features and 12 involved the desmoplastic variant. The Chang staging distribution was as follows: T1, 2; T2, 17; T3, 10; T4, 3; M0, 24; M1, 1; M2, 4; M3, 3. Brainstem invasion was present in nine patients. Lesions were midline in 13 cases and lateral in 19. Resection was complete in 17 cases, subtotal in 6, and partial in 5, with biopsy only in 4 cases. All patients received postoperative radiotherapy, with median doses of 36 Cy to the entire craniospinal axis and 55 Cy to the posterior fossa. Twenty-four patients received chemotherapy (20 before radiotherapy, 3 after radiotherapy, and 1 before and after radiotherapy). RESULTS: With a median follow-up period of 5.4 years, 17 patients experienced recurrences. At 5 and 8 years, overall survival rates were 83 and 45% and disease-free survival rates were 57 and 40%, respectively. The 5- and 8-year posterior fossa control rates were 67 and 59%, respectively. Twenty-nine percent of all relapses occurred more than 5 years after treatment. The posterior fossa was the most common site of relapses. In univariate analyses, factors adversely affecting posterior fossa control were less than complete resection (P < 0.001), the presence of brainstem invasion (P = 0.02), and the use of chemotherapy (P = 0.03). The overall radiotherapy duration was marginally significant in predicting posterior fossa control, with 5-year posterior fossa control rates of 81 and 49% for durations of less than 48 days and 48 days or more, respectively (P = 0.06). In a multivariate analysis, complete resection was predictive of improved posterior fossa control (P = 0.02) and disease-free survival (P = 0.02) rates, Of the eight low-risk patients who received radiotherapy alone, three experienced recurrences in the bone as the only site of relapse. CONCLUSION: Late relapse is common among adult patients with medulloblastomas, and long-term follow-up monitoring is important. Because of the high risk of systemic failure among the low-risk patients treated with radiotherapy alone, the role of chemotherapy for this group of patients needs to be further investigated. Complete resection, the absence of brainstem invasion, and an overall radiotherapy duration of less than 48 days are important prognostic factors. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. NR 37 TC 105 Z9 111 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD SEP PY 2000 VL 47 IS 3 BP 623 EP 631 DI 10.1097/00006123-200009000-00018 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 349GJ UT WOS:000089037100036 PM 10981749 ER PT J AU Vaish, NK Fraley, AW Szostak, JW McLaughlin, LW AF Vaish, NK Fraley, AW Szostak, JW McLaughlin, LW TI Expanding the structural and functional diversity of RNA: analog uridine triphosphates as candidates for in vitro selection of nucleic acids SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-POLYMERASES; 5'-TRIPHOSPHATES; DERIVATIVES; NUCLEOTIDE; NUCLEOSIDE; FIDELITY; SEQUENCE; ALPHA AB Two analog uridine triphosphates tethering additional functionality, one a primary amino group and the second a mercapto group, were prepared and tested for their compatibility with in vitro RNA selection procedures. 5-(3-Aminopropyl)uridine triphosphate (UNH2) as a uridine substitute was a more effective substrate for T7 RNA polymerase than 5-(2-mercaptoethyl)uridine triphosphate (USH), However, both functioned in transcription assays of 100 nt templates to generate RNA transcripts in quantities sufficient to initiate RNA selection procedures. Transcription of RNA pools with T7 RNA polymerase and UNH2 or USH occurred with efficiencies of 43 and 29%, respectively, of the values obtained for native UTP transcription. In addition, the transcribed RNA containing roughly 25% UNH2 residues exhibited better substrate properties for SuperScript(TM) II RNase H reverse transcriptase than did RNA transcripts containing similar to 25% of the USH analog, With either analog, both transcription and reverse transcription proceeded with high fidelity for insertion of the analog residue. C1 Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, Boston, MA 02114 USA. RP McLaughlin, LW (reprint author), Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. NR 33 TC 45 Z9 45 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 1 PY 2000 VL 28 IS 17 BP 3316 EP 3322 DI 10.1093/nar/28.17.3316 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 350AU UT WOS:000089078900016 PM 10954600 ER PT J AU Taylor, AE AF Taylor, AE TI Insulin-lowering medications in polycystic ovary syndrome SO OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID OBESE WOMEN; METFORMIN THERAPY; P450C17-ALPHA ACTIVITY; DIABETES-MELLITUS; INDUCED OVULATION; GRANULOSA-CELLS; NORMAL MENSES; LEAN WOMEN; RESISTANCE; TROGLITAZONE AB Polycystic ovary syndrome (PCOS), one of the most common clinical abnormalities, is associated with infertility, obesity, and metabolic dysfunction. A significant proportion of obese and lean women with PCOS have greater insulin resistance than is expected. Resistance is accompanied by a defect in insulin secretion, and recent studies have documented a dramatically high rate of diabetes mellitus and impaired glucose tolerance in this population of women. Medications that reduce serum insulin levels have been administered to women with PCOS to study the role of hyperinsulinemia in the pathophysiology and treatment of PCOS. This article presents the evidence for hyperinsulinemia and insulin resistance in women and reviews the therapeutic reponse to insulin-lowering agents. Recommendations are made for further research and the use of new agents in the treatment of PCOS. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Taylor, AE (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. NR 37 TC 27 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8545 J9 OBSTET GYN CLIN N AM JI Obstet. Gynecol. Clin. N. Am. PD SEP PY 2000 VL 27 IS 3 BP 583 EP + DI 10.1016/S0889-8545(05)70157-1 PG 14 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 350AW UT WOS:000089079200009 PM 10958005 ER PT J AU Chuang, HY Schwartz, J Tsai, SY Lee, MLT Wang, JD Hu, H AF Chuang, HY Schwartz, J Tsai, SY Lee, MLT Wang, JD Hu, H TI Vibration perception thresholds in workers with long term exposure to lead SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE blood lead; neuropathy; vibration perception threshold ID NERVE-CONDUCTION VELOCITY; VIBROTACTILE THRESHOLD; BATTERY WORKERS; NEUROPATHY; TAIWAN; MOTOR AB Objectives-To evaluate the impact of long term occupational exposure to lead on function of the peripheral nervous system as reflected by vibration perception threshold (VPT), measured with a portable vibrameter. Methods-217 Workers in a lead battery factory were required to have an annual blood lead measurement during each of the 5 years preceding this study. All were invited to take the VPT test. A total of 206 workers were studied. The associations were analysed between VPTs and current blood lead concentration, mean concentration of blood lead over the past 5 years, maximum blood lead concentration during the past 5 years, index of cumulative blood lead (ICL), time weighted index of cumulative blood lead (TWICL), and percentage of lifespan spent at work in the plant, as well as the other potential confounders. Ordinary multiple regressions, generalised additive models, and hockey stick regression analyses were used to explore the potential existence of a threshold effect of blood lead variables on VPT. Results-VPT at a frequency of 220 Hz ranged from 6 to 100 (10(-2) g, or 0.098 m/s(2)) with a mean (SD) of 19.8 (14.2) for the feet and from 4 to 43 with a mean (SD) of 10.2 (6.1) for the hands. The five variables of exposure to lead were all significantly correlated with VPT of the feet but not the hands. In multiple linear regression analyses, the mean of the blood lead concentrations and the TWICL were significantly associated with VPT of the feet. The relation between VPT of the feet and mean blood lead was shown to be a J shaped curve with a generalised additive model and local smoothing technique. In the hockey stick regression, evidence was found of a threshold effect at a mean blood lead concentration of 31 mu g/dl. Above this threshold it was estimated that each increase of 1 mu g/dl mean blood lead over 5 years would increase VPT of the feet by 0.29 (10(-2) g) or 0.028 m/s(2) (at a frequency of 220 Hz) with other potential confounders held constant. Conclusion-This study suggests that measurement of vibration sensory threshold is a relatively effective tool for detecting lead neuropathy in field studies, and that lead might cause sensory neuropathy with an effect threshold corresponding to a 5 year mean blood lead concentration of 31 mu g/dl. C1 Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, Taipei 10018, Taiwan. Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan. Kaohsiung Med Univ Hosp, Dept Occupat Med, Kaohsiung 807, Taiwan. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Tzu Ai Gen Hosp, Dept Neurol, Shi Lo, Yu Lin County, Taiwan. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Wang, JD (reprint author), Natl Taiwan Univ, Coll Publ Hlth, Inst Occupat Med & Ind Hyg, 1 Sect 1 Jen Ai Rd, Taipei 10018, Taiwan. RI Chuang, Hung-Yi/C-9143-2009 OI Chuang, Hung-Yi/0000-0002-8321-8720 FU NIEHS NIH HHS [ES-00002] NR 35 TC 24 Z9 24 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 2000 VL 57 IS 9 BP 588 EP 594 DI 10.1136/oem.57.9.588 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 345KK UT WOS:000088815000003 PM 10935939 ER PT J AU Hsu, WC Green, JP Spilker, MH Rubin, PAD AF Hsu, WC Green, JP Spilker, MH Rubin, PAD TI Primary placement of a titanium motility post in a porous polyethylene orbital implant - Animal model with quantitative assessment of fibrovascular ingrowth and vascular density SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID HYDROXYAPATITE; COMPLICATIONS; PARTICLES; RABBITS AB Purpose: To determine whether a Medpor porous polyethylene orbital implant, at the time of initial orbital implant surgery, will tolerate the insertion of a titanium screw on the anterior surface of the implant. Methods: Twelve New Zealand white rabbits were enucleated and implanted with a porous polyethylene orbital implant. At the time of enucleation, the porous polyethylene orbital implants were drilled, and titanium motility coupling posts were inserted. The motility coupling posts were inserted at two projection heights (2 or 3 mm) and either covered within Tenon capsule/conjunctiva (eight implants) or left exposed (four implants). Rabbits were killed at 6 or 12 weeks. Clinical tissue tolerance, histologic response to the motility coupling post, and vascular density of the porous polyethylene orbital implant were evaluated. Results: The motility coupling posts were well tolerated, and extrusion or migration of the motility coupling post did not occur. The average percentage cross-sectional area of the implant occupied by fibrovascular tissue at 6 and 12 weeks was 76.3% and 97.5%, respectively. In comparing the vascular density (number of vessels per square millimeter) in the porous polyethylene orbital implant within a 1-mm zone immediately surrounding the motility coupling post, no significant difference between this zone and the vascular density found within its entire corresponding annulus was found at either 6 or 12 weeks. Conclusions: During the 6- and 12-week observation periods, all implanted motility coupling posts demonstrated favorable tissue tolerance and stable interfaces with surrounding tissues. The extent of fibrovascular tissue ingrowth and vascular density verify that initial screw insertion does not adversely affect the healing process after porous polyethylene orbital implant implantation. Thus, primary placement of the motility coupling post may obviate the need for a secondary surgical procedure. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), 243 Charles St, Boston, MA 02114 USA. NR 18 TC 17 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD SEP PY 2000 VL 16 IS 5 BP 370 EP 379 DI 10.1097/00002341-200009000-00011 PG 10 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 355KE UT WOS:000089384200011 PM 11021387 ER PT J AU Mankarious, LA Goetinck, PF AF Mankarious, LA Goetinck, PF TI Growth and development of the human cricoid cartilage: An immunohistochemical analysis of the maturation sequence of the chondrocytes and surrounding cartilage matrix SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID HUMAN LARYNX AB OBJECTIVE: The goal was to determine maturational changes in the human cricoid cartilage. STUDY DESIGN: The study involved immunohistochemical staining of collagen II (a marker of proliferating chondrocytes), matrilin-1 (a marker of post-proliferative chondrocytes), and collagen X (a marker of hypertrophic chondrocytes). Specimens included uninjured human cricoid cartilages at 18 and 41 weeks' gestation and 1, 4, and 13 years postpartum. RESULTS: This study demonstrated that type II collagen peaks in concentration at approximately 41 weeks' gestation. Matrilin-1 is present in progressively lower concentration in the central core of the cricoid ring, but the peripheries of the ring contain the protein in relatively high concentration. Type X collagen is not expressed in the age groups tested. CONCLUSIONS: These biochemical markers lend further support to a chondrocyte proliferative phase that slows between 1 and 4 years of age. Chondrocytes then enter a phase histologically similar to the hypertrophic phase but are biochemically different than hypertrophic chondrocytes destined for endochondral ossification. C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol Anat & Cellular Biol, Boston, MA USA. RP Mankarious, LA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2000 VL 123 IS 3 BP 174 EP 178 DI 10.1067/mhn.2000.107529 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 352KQ UT WOS:000089214800004 PM 10964286 ER PT J AU Zirkle, M Bhattacharyya, N AF Zirkle, M Bhattacharyya, N TI Predictors of airway intervention in angioedema of the head and neck 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 26-29, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Acad Otolaryngol Head & Neck Surg ID CONVERTING ENZYME-INHIBITORS; LIFE-THREATENING ANGIOEDEMA; ACE-INHIBITORS; MANAGEMENT; EXPERIENCE; EDEMA AB OBJECTIVE: Records of patients presenting with angioedema of the head and neck were analyzed to determine clinical factors that predict the need for airway intervention. METHODS: A review of patients with angioedema of the head and neck over a IO-year period was conducted. Data were collected regarding demographics, cause of edema, and sites of involvement. A logistic regression model was used to ascertain whether any clinical variables were significant in predicting the need for airway intervention. RESULTS: Review of 138 charts with an admitting diagnosis of angioedema yielded 66 cases of angioedema of the head and neck in 48 patients. Twenty-three (34.8%) patients required airway intervention. Logistic regression identified increasing age and angioedema involving the oral cavity/oropharynx as predictors of airway intervention; involvement of other sites, cause, and sex were not predictive. CONCLUSION: Location of edema and patient age predict which patients with angioedema of the head and neck are likely to require airway intervention. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 333 Longwood Ave, Boston, MA 02115 USA. NR 13 TC 11 Z9 12 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2000 VL 123 IS 3 BP 240 EP 245 DI 10.1067/mhn.2000.107515 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 352KQ UT WOS:000089214800016 PM 10964298 ER PT J AU Siegel, NS Bradford, CR AF Siegel, NS Bradford, CR TI Fibromatosis of the head and neck: A challenging lesion SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review ID DESMOID TUMORS; AGGRESSIVE FIBROMATOSIS; RADIATION-THERAPY; LOCAL-CONTROL; CHEMOTHERAPY; TAMOXIFEN; RADIOTHERAPY; MANAGEMENT; PATTERNS; DRUGS AB Fibromatosis is a histologically benign fibrous neoplasm that arises from the musculoaponeurotic tissues of the body. It can have significant morbidity when it occurs in the head and neck region because of the proximity of vital structures. This review article considers the etiology, demographics, pathology natural history, and various treatment modalities for this lesion. Therapeutic guidelines are provided. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Univ Michigan, Sch Med, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI USA. RP Siegel, NS (reprint author), 825 Washington St,Suite 310, Norwood, MA 02062 USA. NR 63 TC 13 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2000 VL 123 IS 3 BP 269 EP 275 DI 10.1067/mhn.2000.107456 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 352KQ UT WOS:000089214800021 PM 10964303 ER PT J AU Davis, PJ Reeves, JL Hastie, BA Graff-Radford, SB Naliboff, BD AF Davis, PJ Reeves, JL Hastie, BA Graff-Radford, SB Naliboff, BD TI Depression determines illness conviction and pain impact: A structural equation modeling analysis SO PAIN MEDICINE LA English DT Article DE headache; orofacial pain; factor analysis; structural equation modeling; MMPI-2; MPI; BDI; VAS; depression ID LOW-BACK-PAIN; CHRONIC MUSCULOSKELETAL PAIN; VISUAL ANALOG SCALE; PSYCHOLOGICAL-FACTORS; COPING STRATEGIES; HEADACHE PATIENTS; CLUSTER-ANALYSIS; MMPI PROFILES; CONVERSION-V; INVENTORY AB Objective. The present study sought to derive an algorithm using factor analysis and structural equation modeling (SEM) to describe headache and orofacial pain patients using measures of behavioral and psychological functioning. This investigation further examined whether the underlying factor structure differed in 3 presumed distinct diagnostic categories: myofascial, neuropathic, and neurovascular pain. Design. The Minnesota Multiphasic Personality Inventory-2 ((MMPI-2), Multidimensional Pain Inventory (MPI), Beck Depression Inventory-II (BDI-II), and visual analog scale for functional limitation (VAS-FL) were administered to the subjects. A split group design was used. Exploratory factor analysis (EFA) was used to describe distinct factor domains in the first group. Confirmatory factor analysis (CFA) using SEM tested this structure in the second group and described causal relationships between the revealed (latent) factors. Analysis of variance (ANOVA) was used to test for differences in demographic variables and diagnostic group factor structure. Setting. The Pain Center is a comprehensive, multidisciplinary pain medicine program at Cedars Sinai Medical Center, Los Angeles, California. Subjects. Three hundred and ninety (N = 390) subjects were assigned to 1 of 3 diagnostic categories: myofascial pain syndrome, neuropathic pain, or neurovascular pain. Results. EFA revealed a 3-factor solution. The factors were labeled Depression, Illness Conviction, and Pain Impact, reflecting the content of their respective variables with highest loadings. CFA using SEM validated the 3-factor solution, and further revealed that Depression was a critical causal factor determining Illness Conviction and Pain Impact. No causal relationship was observed between Illness Conviction and Pain Impact. ANOVA found no differences in demographics. No difference in factor structure emerged for the 3 diagnostic categories. Conclusions. Analysis derived a 3-factor solution. The factors were Pain Impact, Illness Conviction, and Depression. SEM revealed the critical causal pathway showing that Depression determined Illness Conviction and Pain Impact. We conclude that the main target for pain treatment is depression. No differences in factor structure were found for the 3 diagnostic categories of myofascial, neuropathic, or neurovascular pain. This suggests that psychological processes are similar in chronic headache and orofacial pain patients despite their presumed distinct underlying pathophysiological mechanisms. SME is a powerful methodology to construct causal models that has been underutilized in the pain literature. C1 Alliant Univ, Fresno, CA USA. Univ Calif Los Angeles, Sch Dent, Sect Oral Med & Orofacial Pain, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Pain Ctr, Los Angeles, CA USA. Behav Med Network, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. W Los Angeles VA Hlth Care Ctr, Los Angeles, CA USA. RP Reeves, JL (reprint author), Behav Med Network, POB 18157, Beverly Hills, CA 90209 USA. NR 64 TC 16 Z9 18 U1 2 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD SEP PY 2000 VL 1 IS 3 BP 238 EP 246 DI 10.1046/j.1526-4637.2000.00032.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 425EW UT WOS:000168278600007 PM 15101890 ER PT J AU Rosado, KE Pitt, MJ Siegal, GP AF Rosado, KE Pitt, MJ Siegal, GP TI Osteoblastoma: A mimic of osteosarcoma SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Article DE bone tumor; neoplasm of bone; osteoblastoma; osteosarcoma ID OSTEOID OSTEOMA; PSEUDOMALIGNANT OSTEOBLASTOMA; BENIGN OSTEOBLASTOMA; CLASSIFICATION; FEATURES; SARCOMAS AB Osteoblastoma, a bone-forming neoplasm without metastatic potential, can be mistaken histologically for various benign and malignant primary neoplasms of bone or mimic nonneoplastic conditions, including osteoid osteoma, giant cell tumor of bone, aneurysmal bone cyst, and chondroblastoma [1]. The most important diagnostic distinction is to distinguish osteoblastoma from osteosarcoma. Although both lesions usually have characteristic clinical, radiologic, and histologic findings, in certain cases the distinction between both can be difficult. This is complicated by lesions that morphologically and biologically appear to exist at the interface between the two. In this review, we describe the characteristics of osteoblastomas and review criteria that can prove helpful in the distinction among the various pathologic entities. C1 Univ Alabama, Dept Pathol, Div Anat Pathol, Birmingham, AL 35233 USA. Univ Alabama, Dept Radiol, Birmingham, AL 35233 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35233 USA. Univ Alabama, Dept Surg, Birmingham, AL 35233 USA. Birmingham VAMC, Birmingham, AL USA. RP Siegal, GP (reprint author), Univ Alabama, Dept Pathol, Div Anat Pathol, 506 Kracke Bldg, Birmingham, AL 35233 USA. RI Siegal, Gene/A-8653-2009 NR 39 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD SEP PY 2000 VL 19 IS 5 BP 305 EP 322 PG 18 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 374EW UT WOS:000165332300002 ER PT J AU Kilpatrick, SE Abdul-Karim, FW Renner, JB King, TS Klein, MJ Rosenberg, AE Steiner, GC Bullough, PG Schiller, AL Dorfman, HD AF Kilpatrick, SE Abdul-Karim, FW Renner, JB King, TS Klein, MJ Rosenberg, AE Steiner, GC Bullough, PG Schiller, AL Dorfman, HD TI Interobserver variability among expert orthopedic pathologists for diagnosis, histologic grade, and determination of the necessity for chemotherapy in osteosarcoma SO PEDIATRIC PATHOLOGY & MOLECULAR MEDICINE LA English DT Article DE histologic grade; osteosarcoma ID MALIGNANT FIBROUS HISTIOCYTOMA; FINE-NEEDLE ASPIRATION; OSTEO-SARCOMA; MESENCHYMAL CHONDROSARCOMA; SOFT-TISSUE; BONE; EXPERIENCE; TERMINOLOGY; MELANOMA; VARIANT AB Eight expert orthopedic pathologists voluntarily reviewed the clinicoradiologic and histologic data from 12 selected cases coded as osteosarcoma over the past seven years ( procured from a total of 40 cases) from the files of the University of North Carolina and Wake Forest University. The study sample was chosen to include a full spectrum of histologic grades and subtypes including conventional, low-grade central, chondroblastoma-like, osteoblastoma-like, small cell, telangiectatic, parosteal, and periosteal variants. Participants were asked to render a diagnosis, provide a histologic grade (if applicable), and offer an opinion as to whether the patient could benefit from chemotherapy. Uniform agreement regarding the diagnosis of osteosarcoma was observed in 7 cases (58 hr %), including the most common, conventional subtypes, and the telangiectatic, parosteal, and periosteal variants. Among the remaining 5 cases, the consensus majority (greater than or equal to4) also was osteosarcoma. However, additional diagnoses ranged from osteoblastoma to high-grade osteosarcoma in two tumors, mesenchymal chondrosarcoma versus small cell osteosarcoma in one, fibrosarcoma and malignant fibrous histiocytoma versus fibroblastic osteosarcoma in another, and clear cell chondrosarcoma versus chondroblastoma versus chondroblastic osteosarcoma in a fifth. Among osteosarcoma diagnoses, histologic grading rang ed from low- to high-grade osteosarcoma in 6 tumors (50%). Regarding the necessity for chemotherapy, there was disagreement from at least one consultant in 7 cases (58 hr %). Evaluation of the intraclass correlation coefficient revealed modest agreement with respect to histologic grade and therapy but poor agreement for diagnosis, the latter reflecting the wide range of diagnoses in a minority of cases. Interobserver variability exists among expert orthopedic pathologists for determining the diagnosis, histologic grade, and necessity of chemotherapy in less common forms of osteosarcoma. A more objective histologic grading and scoring system for osteosarcoma should be established, followed by multi-institutional studies assessing the usefulness of the system as it relates to the necessity of chemotherapy and survival. C1 Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ Hosp Cleveland, Dept Pathol, Cleveland, OH 44106 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NYU, Hosp Joint Dis, Dept Pathol, New York, NY 10003 USA. Hosp Special Surg, Dept Pathol, New York, NY 10021 USA. Montefiore Hosp, Dept Pathol, Bronx, NY USA. RP Kilpatrick, SE (reprint author), Univ N Carolina, Dept Pathol & Lab Med, CB 7525,Brinkhous Bullitt Bldg, Chapel Hill, NC 27599 USA. NR 38 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1522-7952 J9 PEDIATR PATHOL MOL M JI Pediatr. Pathol. Mol. Med. PD SEP PY 2000 VL 19 IS 5 BP 337 EP 358 PG 22 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 374EW UT WOS:000165332300004 ER PT J AU Sipols, AJ Stuber, GD Klein, SN Higgins, MS Figlewicz, DP AF Sipols, AJ Stuber, GD Klein, SN Higgins, MS Figlewicz, DP TI Insulin and raclopride combine to decrease short-term intake of sucrose solutions SO PEPTIDES LA English DT Article DE insulin; dopamine; rats; food intake; reward ID DOPAMINE TRANSPORTER; FOOD-INTAKE; ENDOCRINE REGULATION; MESOLIMBIC DOPAMINE; MESSENGER-RNA; CORN-OIL; RATS; TRANSMISSION; BEHAVIOR; REWARD AB We have previously reported that the hormone insulin can modulate synaptic function of dopamine neurons. To evaluate whether insulin can alter performance of a task which is dependent on intact dopaminergic signaling, we tested rats in a five minute lick rate task, with a range of concentrations of sucrose or oil solutions. Rats received either ip (t - 15 min) saline or the D2 receptor antagonist raclopride (50 mug/kg), and intraventricular (t - 4 h) saline or insulin (5 mU). Although ineffective on its own, insulin combined with raclopride treatment resulted in significant suppression of sucrose lick rates compared to the saline/saline group. The overall results are consistent with our hypothesis that insulin may modify performance in tasks that are dependent on dopaminergic signaling. (C) 2000 Elsevier Science Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Seattle, WA 98108 USA. Latvian State Univ, Fac Med, Inst Clin & Expt Med, LV-1063 Riga, Latvia. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Div Endocrinol & Metab, 1660 So Columbian Way, Seattle, WA 98108 USA. RI Stuber, Garret/E-1160-2011 FU NIDDK NIH HHS [DK40963]; NINDS NIH HHS [T32 NS007431] NR 35 TC 29 Z9 31 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD SEP PY 2000 VL 21 IS 9 BP 1361 EP 1367 DI 10.1016/S0196-9781(00)00279-5 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 371WJ UT WOS:000165202000008 PM 11072123 ER PT J AU De Giorgio, R Arakawa, J Wetmore, CJ Sternini, C AF De Giorgio, R Arakawa, J Wetmore, CJ Sternini, C TI Neurotrophin-3 and neurotrophin receptor immunoreactivity in peptidergic enteric neurons SO PEPTIDES LA English DT Article DE nerve growth factor; neurotrophins; tyrosine kinase receptor; peptide-containing neurons; enteric nervous system ID NERVE GROWTH-FACTOR; TYROSINE PROTEIN-KINASE; FETAL-RAT GUT; GUINEA-PIG; SYSTEM DEVELOPMENT; ENDOCRINE-CELLS; SMALL-INTESTINE; SUBSTANCE-P; TRK FAMILY; IN-VITRO AB In the rat small intestine, neurotrophin-3 immunoreactivity was identified in ganglion cells and in processes mostly innervating the mucosa and occasionally the muscle layer and vasculature. The vast majority of neurotrophin-3 immunoreactive neurons contained vasoactive intestinal polypeptide (VIP), but not substance P or related tachykinin (SP/TK). Neurotrophin receptors visualized by pan-trk immunoreactivity were found in numerous ganglion cells of both plexuses and in nerve processes in the intestinal wall. Pan-trk submucosal neurons contained VIP (36%) or SP/TK-IR (47%). Pan-trk myenteric neurons contained VIP-IR (57%) or SP/TK (27%). Our data suggest that neurotrophin-3 and neurotrophin receptors may be involved in the maintenance of enteric neuronal circuits, transmission and phenotypic expression. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Bologna, Dept Internal Med & Gastroenterol, Bologna, Italy. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Neurobiol, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. RP Sternini, C (reprint author), VACLAHS, CURE Bldg 115,Rm 224,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM csternin@ucla.edu OI De Giorgio, Roberto/0000-0003-0867-5873 FU NIDDK NIH HHS [DK41301, DK51455] NR 43 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD SEP PY 2000 VL 21 IS 9 BP 1421 EP 1426 DI 10.1016/S0196-9781(00)00286-2 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 371WJ UT WOS:000165202000015 PM 11072130 ER PT J AU Bergeron, B AF Bergeron, B TI The loyalty effect SO PHYSICIAN AND SPORTSMEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD SEP PY 2000 VL 28 IS 9 BP A44 EP A44 PG 1 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA 354CR UT WOS:000089312700017 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Mandibular augmentation SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID RECONSTRUCTION; SURGERY; ANGLE AB Porous polyethylene implants are available that are designed to augment the mandibular ramus and body. They can be used to increase the bigonial distance in patients with normal mandibular anatomy who desire an increase in lower facial width. When used in combination with extended chin implants, they can camouflage the skeletal contour inadequacies associated with class II mandibular deficiency. The implants are placed through intraoral incisions and fixed with titanium screws. In a clinical experience with 11 patients over 6 years, this technique has proven to be safe and effective. C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Plast Surg, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, WACC-453, Boston, MA 02114 USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD SEP PY 2000 VL 106 IS 3 BP 697 EP 706 DI 10.1097/00006534-200009030-00030 PG 10 WC Surgery SC Surgery GA 347JM UT WOS:000088925700029 PM 10987481 ER PT J AU Simopoulos, AP Leaf, A Salem, N AF Simopoulos, AP Leaf, A Salem, N TI Workshop Statement on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT Workshop on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids CY APR 07-09, 1999 CL BETHESDA, MARYLAND SP NIAAA, NIH, Off Dietary Supplements, Ctr Genet Nutrit & Hlth, Int Soc Study Fatty Acids & Lipids C1 Ctr Genet Nutr & Hlth, Washington, DC USA. Massachusetts Gen Hosp, Charlestown, MA USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Simopoulos, AP (reprint author), Ctr Genet Nutr & Hlth, Washington, DC USA. NR 0 TC 135 Z9 145 U1 1 U2 21 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD SEP PY 2000 VL 63 IS 3 BP 119 EP 121 DI 10.1054/plef.2000.0176 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 369GV UT WOS:000165058300002 PM 10991764 ER PT J AU Saxena, S Rauch, SL AF Saxena, S Rauch, SL TI Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; GLUCOSE METABOLIC RATES; FRONTAL-SUBCORTICAL CIRCUITS; BASAL GANGLIA; TOURETTES-SYNDROME; FDG-PET; NEUROPSYCHIATRIC DISORDERS; SUBTHALAMIC NUCLEUS; EXTERNAL PALLIDUM AB Advances in neuroimaging have led to a greater understanding of the neurobiology of obsessive-compulsive disorder, providing strong evidence that its pathophysiology involves abnormal functioning along specific frontal-subcortical brain circuits. An updated review and analysis of the functional neuroimaging studies, including single photon emission computed tomography, positron emission tomography, magnetic resonance spectroscopy, and functional magnetic resonance imaging, is provided. Also reviewed is the basic science literature on the functional neuroanatomy of corticobasal gangliathalamocortical circuits, and this information is integrated with neuroimaging data in obsessive-compulsive disorder to present a theoretic model of brain mediation of obsessive-compulsive disorder symptoms and response to treatment. Functional neuroimaging studies indicate that obsessive-compulsive disorder symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits that may be caused by an imbalance of tone between direct and indirect striatopallidal pathways. Serotonergic drugs may ameliorate obsessive-compulsive disorder symptoms by changing the relative balance of tone through the indirect versus direct orbitofrontal-subcortical pathways, with therapy decreasing activity in the overall circuit that exists in the symptomatic state. C1 Univ Calif Los Angeles, Obsess Compuls Disorder Res Program, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Psychiat Neuroimaging Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Saxena, S (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, 300 UCLA Med Plaza, Los Angeles, CA 90095 USA. FU NIMH NIH HHS [R01 MH53565-01A1] NR 100 TC 404 Z9 417 U1 14 U2 65 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 2000 VL 23 IS 3 BP 563 EP + DI 10.1016/S0193-953X(05)70181-7 PG 25 WC Psychiatry SC Psychiatry GA 349UN UT WOS:000089064100008 PM 10986728 ER PT J AU O'Sullivan, RL Mansueto, CS Lerner, EA Miguel, EC AF O'Sullivan, RL Mansueto, CS Lerner, EA Miguel, EC TI Characterization of trichotillomania - A phenomenological model with clinical relevance to obsessive-compulsive spectrum disorders SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID BODY DYSMORPHIC DISORDER; OLFACTORY REFERENCE SYNDROME; TOURETTES DISORDER; BASAL GANGLIA; HAIR PULLERS; NEUROPSYCHIATRIC DISORDERS; REPETITIVE BEHAVIORS; SKIN PICKING; COMORBIDITY; CHILDHOOD AB Trichotillomania is a complex condition, the behavioral hallmark of which is clinically significant and psychologically distressing hair pulling. Although DSM-IV defines trichotillomania as an impulse control disorder, clinical experience and empiric data suggest that trichotillomania is a heterogeneous condition that shares phenomenologic similarities with many conditions, often termed obsessive-compulsive spectrum disorders, characterized by repetitive behavior or thoughts. A selective overview of trichotillomania is presented as context for presentation of a synthetic heuristic clinical assessment model, emphasizing phenomenologic assessment of trichotillomania, which expands on several previous lines of phenomenologic research. The assessment model is applied to several other clinical conditions often regarded as being on a continuum of obsessive-compulsive spectrum disorders, including Tourette syndrome, skin picking, body dysmorphic disorder, obsessive-compulsive disorder, and olfactory reference syndrome. The authors have found this approach clinically useful as a means by which clinicians can organize complex clinical information on frequently overlapping disorders in a systematic way. Also, it is intended to generate additional inquiry into putative pathophysiologic commonalties among obsessive-compulsive spectrum disorders based on a phenomenologic, as opposed to a categorical, approach. C1 Behav Therapy Ctr Greater Washington, Silver Spring, MD 20901 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Neurosci Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Bowie State Univ, Dept Psychol, Bowie, MD 20715 USA. Univ Sao Paulo, Fac Med, Psiquiatra Hosp Clin, Sao Paulo, Brazil. RP Mansueto, CS (reprint author), Behav Therapy Ctr Greater Washington, 11227 Lockwood Dr, Silver Spring, MD 20901 USA. RI Miguel, Euripedes/B-2871-2008; Citations, TLC SAB/C-4006-2011 NR 95 TC 25 Z9 25 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 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD SEP PY 2000 VL 23 IS 3 BP 587 EP + PG 20 WC Psychiatry SC Psychiatry GA 349UN UT WOS:000089064100009 PM 10986729 ER PT J AU Jones, L Brazel, D Peskind, ER Morelli, T Raskind, MA AF Jones, L Brazel, D Peskind, ER Morelli, T Raskind, MA TI Group therapy program for African-American veterans with posttraumatic stress disorder SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT 4th African-American Conference on Posttraumatic Stress Disorder CY SEP 13, 1999 CL WASHINGTON, D.C. ID ISSUES AB A Vet Center's group therapy treatment program for African-American veterans with posttraumatic stress disorder (PTSD) has met regularly and expanded since it was established in 1984, Program attributes described by participants as particularly helpful include facilitating open communication of thoughts and feelings among African-American men; providing support for coping with the intrapsychic, social, and economic effects of racism; increasing knowledge about the causes, consequences, and treatment of PTSD; and decreasing emotional and social isolation. The program appears to be a useful treatment for African-American veterans with PTSD. C1 VA Puget Sound Healthcare Syst, Mental Hlth Serv S116, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Hawaii, Honolulu, HI 96822 USA. RP Jones, L (reprint author), VA Puget Sound Healthcare Syst, Mental Hlth Serv S116, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 10 TC 6 Z9 8 U1 1 U2 3 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 SEP PY 2000 VL 51 IS 9 BP 1177 EP 1179 DI 10.1176/appi.ps.51.9.1177 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 350MK UT WOS:000089105100017 PM 10970924 ER PT J AU Maisto, SA Conigliaro, J McNeil, M Kraemer, K Kelley, ME AF Maisto, SA Conigliaro, J McNeil, M Kraemer, K Kelley, ME TI An empirical investigation of the factor structure of the AUDIT SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID DIAGNOSTIC INTERVIEW SCHEDULE; ALCOHOL-USE DISORDERS; DEPENDENCE AB This study investigated the Alcohol Use Disorders Identification Test's (AUDIT) factor structure and psychometric properties. The factor structure was derived from a sample of 7,035 men and women primary care patients. A principal components analysis identified 2 factors in the AUDIT data and was supported in a confirmatory factor analysis (CFA). The 2 factors were Dependence/Consequences and Alcohol Consumption. The CFA also provided support for a 3-factor model whose factors (Alcohol Consumption, Alcohol Dependence, and Related Consequences) matched those proposed by the AUDIT'S developers. Psychometric indexes were determined by use of the baseline and 12-month follow-up data of 301 men and women who entered a clinical trial. The results showed that the 2 factors had good reliability. Validity tests supported the interpretation of what the 2 factors measure, its implications for relationships to other variables, and the comparability of the 2- and 3-factor models. C1 Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA USA. RP Maisto, SA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. FU NIAAA NIH HHS [5K08-AA00235, AA1029] NR 19 TC 81 Z9 84 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD SEP PY 2000 VL 12 IS 3 BP 346 EP 353 DI 10.1037//1040-3590.12.3.346 PG 8 WC Psychology, Clinical SC Psychology GA 356JG UT WOS:000089439700016 PM 11021159 ER PT J AU Alterman, AI McDermott, PA Cook, TG Cacciola, JS McKay, JR McLellan, AT Rutherford, MJ AF Alterman, AI McDermott, PA Cook, TG Cacciola, JS McKay, JR McLellan, AT Rutherford, MJ TI Generalizability of the clinical dimensions of the Addiction Severity Index to nonopioid-dependent patients SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article AB Clinical dimensions (CDs) for the Addiction Severity Index recently have been established for application among opioid-dependent patients in methadone treatment (P. A. McDermott et al., 1996). This article examines the generalizability of the CDs to other substance-dependent patients. A sample of 2,027 adult nonopioid-dependent patients was identified; it comprised 581 primarily cocaine-dependent, 544 primarily alcohol-dependent, and 803 polydrug-dependent patients and 99 patients who were dependent on other varied drugs. Generality of dimensions was assessed through confirmatory components analysis, structural congruence, internal consistency, and variance partitioning in higher order factoring. The CDs were found generalizable overall and to specific nonopioid-dependent subgroups, and across patient gender and age, and to African American and White patients. Preliminary concurrent and predictive validity data supported the CD structure. C1 Univ Penn, Treatment Res Ctr, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Grad Sch Educ, Philadelphia, PA 19104 USA. Univ Washington, Alcohol & Drug Inst, Seattle, WA 98195 USA. RP Alterman, AI (reprint author), Univ Penn, Treatment Res Ctr, Sch Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA-05858, DA060142, DA05186] NR 16 TC 17 Z9 18 U1 1 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2000 VL 14 IS 3 BP 287 EP 294 DI 10.1037//0893-164X.14.3.287 PG 8 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 352JW UT WOS:000089212600007 PM 10998954 ER PT J AU Hauser, P Soler, R Reed, S Kane, R Gulati, M Khosla, J Kling, MA Valentine, AD Meyers, CA AF Hauser, P Soler, R Reed, S Kane, R Gulati, M Khosla, J Kling, MA Valentine, AD Meyers, CA TI Prophylactic treatment of depression induced by interferon-alpha SO PSYCHOSOMATICS LA English DT Article ID THERAPY; MOOD C1 Baltimore VA Med Ctr, Joint VA Univ Mood Disorders Programs, Psychiat Serv, Baltimore, MD 21201 USA. Portland VA Med Ctr, Dept Psychiat, Portland, OR USA. Univ Maryland, Med Ctr, Dept Psychiat, Baltimore, MD 21201 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. RP Baltimore VA Med Ctr, Joint VA Univ Mood Disorders Programs, Psychiat Serv, 10 N Greene St, Baltimore, MD 21201 USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 12 TC 44 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD SEP-OCT PY 2000 VL 41 IS 5 BP 439 EP 441 DI 10.1176/appi.psy.41.5.439 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 349CD UT WOS:000089025500011 PM 11015632 ER PT J AU Keuthen, NJ Niaura, RS Borrelli, B Goldstein, M DePue, J Murphy, C Gastfriend, D Reiter, SR Abrams, D AF Keuthen, NJ Niaura, RS Borrelli, B Goldstein, M DePue, J Murphy, C Gastfriend, D Reiter, SR Abrams, D TI Comorbidity, smoking behavior and treatment outcome SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE nicotine dependence; comorbidity; smoking cessation ID DIAGNOSTIC INTERVIEW SCHEDULE; SMOKING CESSATION; MAJOR DEPRESSION; NICOTINE DEPENDENCE; YOUNG-ADULTS; PSYCHIATRIC-DISORDERS; WITHDRAWAL SYMPTOMS; PREVALENCE; SCHIZOPHRENIA; ANXIETY AB Background: A sizeable sector of the population continues to smoke cigarettes despite our efforts to prevent and treat this addiction. We explored the relationships between lifetime comorbidity, psychiatric symptomatology, smoking behavior and treatment outcome to better understand vulnerability to smoking and treatment response. Methods: One hundred and twenty smokers at two sites were enrolled in a multicenter, double-blind, randomized, 10-week smoking cessation trial with fluoxetine and behavioral treatment. The Structured Clinical Interview for DSM-III-R and Hamilton Depression Rating Scale were administered prior to treatment initiation. Self-report measures were used to assess psychiatric symptoms throughout treatment and during a 6-month follow-up period. Results: Overall 62.3% of our sample were diagnosed with a lifetime mood, anxiety or substance use disorder despite stringent study exclusion criteria. Lifetime comorbidity was shown to be related to higher smoking rates and nicotine dependence, depressed mood and greater self-report of anxiety and stress. Lifetime comorbidity, however, alone or in combination with treatment condition, failed to predict treatment outcome (at posttreatment or follow-up). Baseline depression scores (Beck Depression Inventory, BDI) were related to treatment outcome only for smokers without a positive history of any psychiatric disorder or depression, with lower BDI scores more frequent in those who were abstinent. Conclusions: High prevalence rates of lifetime psychiatric illness and substance use disorders are reported for chronic smokers. Subsyndromal psychiatric symptoms may play a role in smoking behavior in combination with diagnosable disorders. Clinicians need to carefully assess both psychiatric diagnoses and symptoms in chronic smokers to optimize patient-treatment matching. Copyright (C) 2000 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Miriam Hosp, Div Behav & Prevent Med, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Keuthen, NJ (reprint author), Massachusetts Gen Hosp E, 149 13th St,9th Floor, Charlestown, MA 02129 USA. EM keuthen@psych.mgh.harvard.edu NR 38 TC 29 Z9 29 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD SEP-OCT PY 2000 VL 69 IS 5 BP 244 EP 250 DI 10.1159/000012403 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 348XW UT WOS:000089012600004 PM 10965289 ER PT J AU Bogdanov, AA Simonova, M Weissleder, R AF Bogdanov, AA Simonova, M Weissleder, R TI Engineering membrane proteins for nuclear medicine: Applications for gene therapy and cell tracking SO QUARTERLY JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE membrane proteins; genetic engineering; technetium; radionuclide imaging ID GREEN-FLUORESCENT PROTEIN; SIGNAL RECOGNITION PARTICLE; VIRUS THYMIDINE KINASE; POSITRON-EMISSION-TOMOGRAPHY; SINGLE-CHAIN FV; ENDOPLASMIC-RETICULUM; IN-VIVO; NEUTRAL ENDOPEPTIDASE-24.11; MONOCLONAL-ANTIBODIES; SYNTHETIC PEPTIDES AB Nuclear Imaging techniques such as PET and SPECT imaging are expected to play major roles in evaluating the efficacy of in vivo gene therapy. In particular, the quantification of vector delivery and imaging the efficacy of gem expression are of key interests in testing new treatment paradigms and in designing novel vectors. In this review article we illustrate how nuclear imaging can be used to image novel cell-surface expressed fusion proteins and how this strategy can be used to probe for phenotypic changes Ln genetically manipulated cells. Since the described approach uses new fusion proteins, typically not present on eukaryotic cells, such "artificial receptors" can be designed to bind radioisotopes currently In clinical use. The described fusion proteins consist of 1) a binding domain such as a peptide based chelator that binds Tc-99m oxotechnetate and 2) a membrane anchoring domain. A variety of fusion proteins have been tested so far and the most promising one to date consists of a metallothionein (Mr)-derived C-terminal peptide fused to a type II membrane protein markers containing the N-terminal membrane anchoring domain of neutral endopeptidase (PEP). Cell-surface expression of MT in transfected cells has been demonstrated using monoclonal antibodies in vitro. Both in vitro and in vivo transchelation experiments have confirmed expression of Tc-99m-binding sites Ln eukaryotic cells. We expect the described approach to evolve into a useful strategy to "tag" transfected cells with Tc-99m and thus assessing efficiency of gene delivery and expression. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Bogdanov, AA (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [5RO1 CA74424-01]; NINDS NIH HHS [5RO1 NS35258-03] NR 74 TC 14 Z9 14 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 0392-0208 J9 Q J NUCL MED JI Q. J. Nucl. Med. PD SEP PY 2000 VL 44 IS 3 BP 224 EP 235 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 339GX UT WOS:000088470200003 PM 11105587 ER PT J AU Pisano, ED Cole, EB Hemminger, BM Yaffe, MJ Aylward, SR Maidment, ADA Johnston, RE Williams, MB Niklason, LT Conant, EF Fajardo, LL Kopans, DB Brown, ME Pizer, SM AF Pisano, ED Cole, EB Hemminger, BM Yaffe, MJ Aylward, SR Maidment, ADA Johnston, RE Williams, MB Niklason, LT Conant, EF Fajardo, LL Kopans, DB Brown, ME Pizer, SM TI Image processing algorithms for digital mammography: A pictorial essay SO RADIOGRAPHICS LA English DT Article DE breast radiography; images, display; images, processing; radiography, digital AB Digital mammography systems allow manipulation of fine differences in image contrast by means of image processing algorithms. Different display algorithms have advantages and disadvantages for the specific tasks required in breast imaging-diagnosis and screening. Manual intensity windowing can produce digital mammograms very similar to standard screen-film mammograms but is limited by its operator dependence. Histogram-based intensity windowing improves the conspicuity of the lesion edge, but there is loss of detail outside the dense parts of the image. Mixture-model intensity windowing enhances the visibility of lesion borders against the fatty background, but the mixed parenchymal densities abutting the lesion may be lost. Contrast-limited adaptive histogram equalization can also provide subtle edge information but might degrade performance in the screening setting by enhancing the visibility of nuisance information. Unsharp masking enhances the sharpness of the borders of mass lesions, but this algorithm may make even an indistinct mass appear more circumscribed. Peripheral equalization displays lesion details well and preserves the peripheral information in the surrounding breast, but there may be flattening of image contrast in the nonperipheral portions of the image. Trex processing allows visualization of both lesion detail and breast edge information but reduces image contrast. C1 Univ N Carolina, Dept Radiol, Chapel Hill, NC 27514 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27514 USA. Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27514 USA. Univ Toronto, Dept Med Imaging, Toronto, ON, Canada. Thomas Jefferson Univ, Dept Radiol, Philadelphia, PA 19107 USA. Univ Virginia, Dept Radiol, Charlottesville, VA USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pisano, ED (reprint author), Univ N Carolina, Dept Radiol, 101 Manning Dr, Chapel Hill, NC 27514 USA. EM etpisano@med.unc.edu OI Cole, Elodia/0000-0002-2301-7468; Hemminger, Bradley/0000-0003-0558-8862 FU NCI NIH HHS [R01-CA60193-05, R01-CA75145-01A1, R01-CA6019] NR 7 TC 79 Z9 80 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD SEP-OCT PY 2000 VL 20 IS 5 BP 1479 EP 1491 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 481FR UT WOS:000171509700025 PM 10992035 ER PT J AU Weber, AL AF Weber, AL TI Radiologic evaluation of the neck - Preface SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2000 VL 38 IS 5 BP XV EP XV DI 10.1016/S0033-8389(05)70212-8 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363MY UT WOS:000089840300001 ER PT J AU Weber, AL Siciliano, A AF Weber, AL Siciliano, A TI CT and MR imaging evaluation of neck infections with clinical correlations SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID JUGULAR-VEIN-THROMBOSIS; CERVICAL TUBERCULOUS LYMPHADENITIS; ACUTE SUPPURATIVE THYROIDITIS; COMPUTED-TOMOGRAPHY; SPACE INFECTIONS; RETROPHARYNGEAL ABSCESS; DIFFERENTIAL-DIAGNOSIS; NECROTIZING FASCIITIS; THOROTRAST GRANULOMA; SUPRAHYOID NECK AB infection of the neck is a common clinical problem in all age groups, especially children and young adults. The clinical symptoms and signs are often suggestive of the diagnosis. Imaging studies including CT and MR imaging are frequently required to confirm the diagnosis but more importantly to localize the infectious process and search for and delineate an abscess cavity. Ultrasound has also been used in the evaluation of superficial neck infections, especially to determine fluid accumulation. Conventional films consisting of an anteroposterior and lateral view were the examination before the introduction of CT in 1972. Conventional films can still be used for a preliminary survey, especially of the retropharyngeal space when there is a question of a retropharyngeal phlegmon or abscess. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Fed Rio de Janeiro, Hop Univ Clementino Fraga Filho, Rio De Janeiro, Brazil. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 111 TC 22 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2000 VL 38 IS 5 BP 941 EP + DI 10.1016/S0033-8389(05)70214-1 PG 29 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363MY UT WOS:000089840300003 PM 11054962 ER PT J AU Sakai, O Curtin, HD Romo, LV Som, PM AF Sakai, O Curtin, HD Romo, LV Som, PM TI Lymph node pathology - Benign proliferative, lymphoma, and metastatic disease SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID CERVICAL ADENOPATHY; CT MANIFESTATIONS; THYROID-CARCINOMA; PAROTID CYSTS; AIDS PATIENTS; NECK-CANCER; MR FINDINGS; HEAD; LYMPHADENOPATHY; CALCIFICATION AB The evaluation of cervical lymph nodes is one of the main indications for performing CT and MR imaging of the neck. Imaging may be done for evaluation of an unknown neck mass, but more commonly the neck is imaged to evaluate potential metastasis from a known mucosal malignancy. CT and MR imaging characteristics of both malignant and nonmalignant nodal diseases are reviewed and the differential diagnosis of nodal pathologies for specific imaging findings are discussed. A recently proposed imaging-based nodal classification for metastatic nodal diseases from head and neck cancer is also described. C1 Jichi Med Sch & Hosp, Dept Radiol, Minami Kawachi, Tochigi 3290498, Japan. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Mt Sinai Sch Med, Dept Radiol, New York, NY USA. Mt Sinai Sch Med, Dept Otolaryngol, New York, NY USA. RP Sakai, O (reprint author), Jichi Med Sch & Hosp, Dept Radiol, 3311-1 Yakushiji, Minami Kawachi, Tochigi 3290498, Japan. NR 56 TC 50 Z9 66 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2000 VL 38 IS 5 BP 979 EP + DI 10.1016/S0033-8389(05)70216-5 PG 21 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363MY UT WOS:000089840300005 PM 11054964 ER PT J AU Lev, S Lev, MH AF Lev, S Lev, MH TI Imaging of cystic lesions SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID NECK MASS; CHILDREN; MANAGEMENT; CT AB Cystic masses of the neck include a wide array of developmental lesions. Mimics include necrotic lymphadenopathy and neoplasms. A multimodality imaging approach is necessary for optimal lesion characterization and preoperative planning. Proper assessment requires an analysis of lesion morphology, and an understanding of cross-sectional, compartmental anatomy. C1 Nassau Cty Med Ctr, Dept Radiol, E Meadow, NY 11554 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lev, S (reprint author), Nassau Cty Med Ctr, Dept Radiol, 2201 Hempstead Turnpike, E Meadow, NY 11554 USA. NR 24 TC 24 Z9 26 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2000 VL 38 IS 5 BP 1013 EP + DI 10.1016/S0033-8389(05)70218-9 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363MY UT WOS:000089840300007 PM 11054966 ER PT J AU Rabinov, JD AF Rabinov, JD TI Imaging of salivary gland pathology SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID DUCT CARCINOMA; PAROTID-GLAND; CT; MR AB Calcifications in the salivary glands may occur in calculi, chronic infection or inflammation, phleboliths, lymph nodes, chronic hematoma, amyloidosis, and tumors including pleomorphic adenomas, schwannomas, and mucoepidermoid cancers. This article discusses the different types of salivary gland conditions and the best methods of imaging for diagnosis. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. RP Rabinov, JD (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Gray 2,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 15 Z9 15 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2000 VL 38 IS 5 BP 1047 EP + DI 10.1016/S0033-8389(05)70220-7 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363MY UT WOS:000089840300009 PM 11054968 ER PT J AU Weber, AL Montandon, C Robson, CD AF Weber, AL Montandon, C Robson, CD TI Neurogenic tumors of the neck SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PERIPHERAL-NERVE SHEATH; PARAPHARYNGEAL SPACE; HUMAN NEUROBLASTOMAS; SCHWANNOMAS; NEUROFIBROMATOSIS; DIAGNOSIS; PROGNOSIS; BLASTOMA; STAGE; HEAD AB This article describes the CT and MR imaging findings, including clinical manifestations, of neurogenic and neuroblastic tumors of the neck. The relationship to neurofibromatosis and the multiple endocrine neoplasia syndrome are discussed. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02117 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Clin Imagem, Dept Radiol, Goiania, Go, Brazil. RP Weber, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02117 USA. OI Robson, Caroline/0000-0001-5592-249X NR 40 TC 28 Z9 29 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 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD SEP PY 2000 VL 38 IS 5 BP 1077 EP + DI 10.1016/S0033-8389(05)70222-0 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 363MY UT WOS:000089840300011 PM 11054970 ER EF