FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Koroshetz, WJ Moskowitz, MA AF Koroshetz, WJ Moskowitz, MA TI Emerging treatments for stroke in humans SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID CEREBRAL-ARTERY OCCLUSION; CONJUGATED SUPEROXIDE-DISMUTASE; PROGRAMMED CELL-DEATH; ISCHEMIC THRESHOLDS; PROTEIN-SYNTHESIS; ENERGY-STATE; NITRIC-OXIDE; INJURY; BRAIN; RAT AB Ischaemic stroke causes loss of brain function in millions of people worldwide each year. Despite the enormity of the problem, no currently approved therapy reduces stroke size or neurological disability. This contrasts with a number of recently developed agents, reviewed here by Waiter Koroshetz and Michael Moskowitz, which limit infarct size in animal stroke models. Therapies that dissolve clot and restore blood flow, block excitatory neurotransmission, prevent the ischaemic inflammatory response or scavange free radicals have the potential to revolutionize stroke treatment if proven beneficial in ongoing, placebo-controlled clinical trials. Developments in the experimental arena continue to reinforce the need to characterize the pathophysiological stages leading to brain infarction and recovery. C1 MASSACHUSETTS GEN HOSP,STROKE & NEUROVASC REGULAT LAB,BOSTON,MA 02114. RP Koroshetz, WJ (reprint author), MASSACHUSETTS GEN HOSP,STROKE SERV,BOSTON,MA 02114, USA. RI Moskowitz, Michael/D-9916-2011 NR 66 TC 165 Z9 168 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUN PY 1996 VL 17 IS 6 BP 227 EP 233 DI 10.1016/0165-6147(96)10020-1 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UW153 UT WOS:A1996UW15300009 PM 8763201 ER PT J AU Bradshaw, PO Nelson, AG Fanton, JW Yates, T KaganHallet, KS AF Bradshaw, PO Nelson, AG Fanton, JW Yates, T KaganHallet, KS TI Effect of hyperbaric oxygenation on peripheral nerve regeneration in adult male rabbits SO UNDERSEA & HYPERBARIC MEDICINE LA English DT Article DE hyperbaric oxygenation; nerve regeneration; nerve crush injury ID INJURY; FIBERS AB Oxygen environments were used to study the regenerative effects of hyperbaric oxygen on crushed sciatic nerves in 30 adult male rabbits. Six different oxygen environments were used, and treatments were initiated 4 days post injury. Transmission electron microscopy and light microscopy were used to evaluate the regenerative morphology of crushed nerves. The morphology of crushed nerves after 7 wk of treatment with compressed oxygen at 202, 242, and 303 kPa resembled normal uncrushed nerves, with nerve fibers uniformly distributed throughout the section. The treatment groups receiving 202 kPa compressed air, 100% normobaric oxygen, or ambient air did not display morphologies similar to normal uncrushed nerve. The nerves in these animals were edematous and contained disarrayed nerve fibers. Myelination in the animals receiving 100% O-2 at high pressures resembled undamaged nerves. Collagen and blood vessels were more evident in the lower pressure/oxygen tension treatments than in the animals receiving 100% O-2 at higher pressures. The neurofilamentous material inside the crushed control axons was dense, whereas in the axons of animals treated with compressed O-2 it was loosely packed. These differences in morphology suggest that treatments consisting of 100% O-2, under pressure can accelerate a peripheral nerve's recovery from a crush injury. C1 LOUISIANA STATE UNIV,DEPT KINESIOL,BATON ROUGE,LA 70803. VET ADM MED CTR,DEPT NEUROPATHOL,SAN ANTONIO,TX. RP Bradshaw, PO (reprint author), USAF,SCH AEROSP MED,BROOKS AFB,TX 78235, USA. NR 20 TC 20 Z9 21 U1 2 U2 3 PU UNDERSEA & HYPERBARIC MEDICAL SOC INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1066-2936 J9 UNDERSEA HYPERBAR M JI Undersea Hyperb. Med. PD JUN PY 1996 VL 23 IS 2 BP 107 EP 113 PG 7 WC Marine & Freshwater Biology; Medicine, Research & Experimental SC Marine & Freshwater Biology; Research & Experimental Medicine GA UY285 UT WOS:A1996UY28500006 PM 8840479 ER PT J AU Jost, CA Ginsberg, D Kaelin, WG AF Jost, CA Ginsberg, D Kaelin, WG TI A conserved region of unknown function participates in the recognition of E2F family members by the adenovirus E4 ORF 6/7 protein SO VIROLOGY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; DNA-BINDING ACTIVITY; CELL-CYCLE REGULATION; COMPLEX-FORMATION; VIRAL ONCOPROTEINS; INFECTED CELLS; MYC PROMOTER; C-MYC; P107 AB 3E2F DNA-binding activity in vivo is due to heterodimer formation between members of the E2F and DP transcription factor families. The ability of these heterodimers to serve as transcriptional regulators is modulated by complex formation with additional proteins such as the products of the retinoblastoma gene and the adenovirus E4 ORF 6/7. Each of the E2F family members cloned to date contains a highly conserved region of unknown function, termed the marked box, which lies between their DNA binding and transactivation domains. Mutational analysis showed that the marked box contributed to the recognition of E2F family members by the E4 ORF 6/7 protein in vitro and in vivo. (C) 1996 Academic Press, Inc. C1 DANA FARBER CANC INST,DIV NEOPLAST DIS MECHANISMS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 81 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 1 PY 1996 VL 220 IS 1 BP 78 EP 90 DI 10.1006/viro.1996.0288 PG 13 WC Virology SC Virology GA UP568 UT WOS:A1996UP56800010 PM 8659131 ER PT J AU Calder, AJ Young, AW Perrett, DI Etcoff, NL Rowland, D AF Calder, AJ Young, AW Perrett, DI Etcoff, NL Rowland, D TI Categorical perception of morphed facial expressions SO VISUAL COGNITION LA English DT Article ID IDENTITY; EMOTION AB Using computer-generated line-drawings, Etcoff and Magee (1992) found evidence of categorical perception of facial expressions. We report four experiments that replicated and extended Etcoff and Magee's findings with photographic-quality stimuli. Experiments 1 and 2 measured identification of the individual stimuli falling along particular expression continua (e.g. from happiness to sadness) and discrimination of these stimuli with an ABX task in which stimuli A, B, and X were presented sequentially; subjects had to decide whether X was the same as A or B. Our identification data showed that each expression continuum was perceived as two distinct sections separated by a category boundary. From these identification data we were able to predict subjects' performance in the ABX discrimination task and to demonstrate better discrimination of cross-boundary than within-category pairs; that is, two faces identified as different expressions (e.g. happy and sad) were easier to discriminate than two faces of equal physical difference identified as the same expression (e.g. both happy). C1 UNIV DURHAM,DURHAM,ENGLAND. UNIV ST ANDREWS,ST ANDREWS KY16 9AJ,FIFE,SCOTLAND. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. RP Calder, AJ (reprint author), MRC,APPL PSYCHOL UNIT,15 CHAUCER RD,CAMBRIDGE CB2 2EF,ENGLAND. RI Young, Andy/G-2189-2011 OI Young, Andy/0000-0002-1202-6297 NR 22 TC 222 Z9 231 U1 4 U2 22 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 1350-6285 J9 VIS COGN JI Vis. Cogn. PD JUN PY 1996 VL 3 IS 2 BP 81 EP 117 DI 10.1080/713756735 PG 37 WC Psychology, Experimental SC Psychology GA VA584 UT WOS:A1996VA58400001 ER PT J AU Eck, MJ DhePaganon, S Trub, T Nolte, RT Shoelson, SE AF Eck, MJ DhePaganon, S Trub, T Nolte, RT Shoelson, SE TI Structure of the IRS-1 PTB domain bound to the juxtamembrane region of the insulin receptor SO CELL LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; SH2 DOMAIN; PROTEIN; RECOGNITION; BINDING AB Crystal structures of the insulin receptor substrate-1 (IRS-1) phosphotyrosine-binding (PTB) domain, alone and complexed with the juxtamembrane region of the insulin receptor, show how this domain recognizes phosphorylated ''NPXY'' sequence motifs. The domain is a 7-stranded beta sandwich capped by a C-terminal helix. The insulin receptor phosphopeptide fills an L-shaped cleft on the domain. The N-terminal residues of the bound peptide form an additional strand in the beta sandwich, stabilized by contacts with the C-terminal helix. These interactions explain why IRS-1 binds to the insulin receptor but not to NPXpY motifs in growth factor receptors. The PTB domains of IRS-1 and Shc share a common fold with pleckstrin homology domains. Overall, ligand binding by IRS-1 and Shc PTB domains is similar, but residues critical for phosphotyrosine recognition are not conserved. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02115. RP Eck, MJ (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,MOLEC MED LAB,BOSTON,MA 02115, USA. FU NIDDK NIH HHS [DK43123] NR 49 TC 238 Z9 240 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 31 PY 1996 VL 85 IS 5 BP 695 EP 705 DI 10.1016/S0092-8674(00)81236-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UP344 UT WOS:A1996UP34400010 PM 8646778 ER PT J AU Gardella, TJ Luck, MD Fan, MH Lee, CW AF Gardella, TJ Luck, MD Fan, MH Lee, CW TI Transmembrane residues of the parathyroid hormone (PTH)/PTH-related peptide receptor that specifically affect binding and signaling by agonist ligands SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; BETA-ADRENERGIC-RECEPTOR; TERNARY COMPLEX MODEL; EXPRESSION CLONING; MOLECULAR-CLONING; IDENTIFICATION; POLYPEPTIDE; CAMP AB Polar residues within the transmembrane domains (TMs) of G protein-coupled receptors have been implicated to be important determinants of receptor function. We have identified mutations at two polar sites in the TM regions of the rat parathyroid hormone (PTH)/PTH-related peptide receptor, Arg-233 in TM 2 and Gln-451 in TM 7, that caused 17-200-fold reductions in the binding affinity of the agonist peptide PTH-(1-34) without affecting the binding affinity of the antagonist/partial agonist PTH-(3-34). When mutations at the TM 2 and TM 7 sites were combined, binding affinity for PTH-(1-34) was restored to nearly that of the wild type receptor. The double mutant receptors, however, were completely defective in signaling cAMP or inositol phosphate production in response to PTH-(1-34) agonist ligand. The results demonstrate that Arg-233 and Gln-451 have important roles in determining agonist binding affinity and transmembrane signaling. Furthermore, the finding that residues in TM 2 and TM 7 are functionally linked suggests that the TM domain topology of the PTH/PTH-related peptide receptor may resemble that of receptors in the rhodopsin/beta-adrenergic receptor family, for which structural and mutagenesis data suggest interactions between TMs 2 and 7. C1 HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP MASSACHUSETTS GEN HOSP, DEPT MED, ENDOCRINE UNIT, BOSTON, MA 02114 USA. NR 44 TC 71 Z9 71 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 31 PY 1996 VL 271 IS 22 BP 12820 EP 12825 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN474 UT WOS:A1996UN47400022 PM 8662729 ER PT J AU Peraldi, P Hotamisligil, GS Buurman, WA White, MF Spiegelman, BM AF Peraldi, P Hotamisligil, GS Buurman, WA White, MF Spiegelman, BM TI Tumor necrosis factor (TNF)-alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEMATOPOIETIC-CELLS; FACTOR-ALPHA; EXPRESSION; PHOSPHORYLATION; MONOCYTOGENES; RESISTANCE; ADIPOCYTES; INFECTION AB Tumor necrosis factor (TNF)alpha plays a central role in the state of insulin resistance associated with obesity. It has previously been shown that one important mechanism by which TNF-alpha interferes with insulin signaling is through the serine phosphorylation of insulin receptor substrate-1 (IRS-1), which can then function as an inhibitor of the tyrosine kinase activity of the insulin receptor (IR), However, the receptors and the signaling pathway used by TNF-alpha that mediate the inhibition of IR activity are unknown. We show here that human TNF-alpha, which binds only to the murine p55 TNF receptor (TNFR), is as effective at inhibiting insulin-dependent tyrosine phosphorylation of IR and IRS-1 in adipocytes and myeloid 32D cells as murine TNF-alpha, which binds to both p55 TNFR and p75 TNFR. Likewise, antibodies that are specific agonists for p55 TNFR or p75 TNFR demonstrate that stimulation of p55 TNFR is sufficient to inhibit insulin signaling, though a small effect can also be seen with antibodies to p75 TNFR. Exogenous sphingomyelinase and ceramides, known to be formed by activat- ion of p55 TNFR, inhibit IR and IRS-1 tyrosine phosphorylation and convert IRS-1 into an inhibitor of IR tyrosine kinase in vitro. Myeloid 32D cells expressing LR and IRS-1 are sensitive to this inhibition, but cells expressing IR and IRS-2 are resistant, pointing to an important difference in the biological function between IRS-1 and IRS-2. These data strongly suggest that TNF-alpha inhibits insulin signaling via stimulation of p55 TNFR and sphingomyelinase activity, which results in the production of an inhibitory form of IRS-1. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. UNIV LIMBURG,DEPT SURG,6200 MD MAASTRICHT,NETHERLANDS. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. RI Peraldi, Pascal/O-4592-2016 OI Peraldi, Pascal/0000-0003-0205-9252 NR 41 TC 265 Z9 273 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 31 PY 1996 VL 271 IS 22 BP 13018 EP 13022 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN474 UT WOS:A1996UN47400053 PM 8662983 ER PT J AU Zhang, H Skinner, MM Sandberg, WS Wang, AHJ Terwilliger, TC AF Zhang, H Skinner, MM Sandberg, WS Wang, AHJ Terwilliger, TC TI Context dependence of mutational effects in a protein: The crystal structures of the V351, 147V and V351/147V gene V protein core mutants SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE X-ray crystallography; gene V protein; site-specific mutants; protein stability; filamentous phage ID CAVITY-CREATING MUTATIONS; HYDROPHOBIC CORE; STAPHYLOCOCCAL NUCLEASE; PACKING ARRANGEMENTS; STABILITY; LYSOZYME; BACTERIOPHAGE-T4; CONSEQUENCES; T4-LYSOZYME; ENERGETICS AB The basis for the context dependence of the effects of core mutations on protein stability was investigated by comparing the structures of three gene V protein mutants with that of the wild-type protein. We previously examined a ''swapped'' mutant in which core residues Va135 and Ile47 were simply reserved so that the mutant had no hydrophobicity change from the native protein. The swapped mutant was destabilized by 3 kcal/mol per gene V protein dimer relative to the wild-type protein, demonstrating that factors other than hydrophobicity must make substantial contributions to the effects of mutations on the stability of the protein. Here we have determined the structure of this swapped mutant (V35I/147V) as well as those of the two constituent mutants (V35I and 147V). We find that the structures of the mutant proteins are very similar to that of the wild-type protein except for the necessary addition or deletion of methylene groups and for slight positional shifts of atoms around each mutated residue. The structure of the double mutant is a composite of the structures of the two single mutants. In the mutant structures, the V35I mutation fills a cavity that exists in the wild-type protein and the 147V mutation creates a new cavity. The structures oi the mutants indicate further that the reason the V35I and 147V mutations do not have opposite effects on stability is that the cavity in the wild-type protein filled by the V35I mutation is not optimally shaped for accommodating the additional methylene group of the isoleucine. These results support the concepts that the details of core packing have substantial influence on the effects of core mutations on protein stability and that these packing effects are major determinants of the context dependence of core mutation effects on stability. (C) 1996 Academic Press Limited. C1 UNIV ILLINOIS,DIV BIOPHYS,URBANA,IL 61801. UNIV ILLINOIS,DEPT CELL & STRUCT BIOL,URBANA,IL 61801. LOS ALAMOS NATL LAB,DIV LIFE SCI,LOS ALAMOS,NM 87545. MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114. RI Terwilliger, Thomas/K-4109-2012 OI Terwilliger, Thomas/0000-0001-6384-0320 FU NIGMS NIH HHS [GM-38714, GM-41612] NR 52 TC 20 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 31 PY 1996 VL 259 IS 1 BP 148 EP 159 DI 10.1006/jmbi.1996.0309 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UM405 UT WOS:A1996UM40500014 PM 8648642 ER PT J AU Seol, W Choi, HS Moore, DD AF Seol, W Choi, HS Moore, DD TI An orphan nuclear hormone receptor that lacks a DNA binding domain and heterodimerizes with other receptors SO SCIENCE LA English DT Article ID RETINOIC ACID RECEPTORS; THYROID-HORMONE; RESPONSE ELEMENT; X-RECEPTOR; BETA-GENE; PROTEIN; ALPHA AB SHP is an orphan member of the nuclear hormone receptor superfamily that contains the dimerization and ligand-binding domain found in other;family members but lacks the conserved DNA binding domain. In the yeast two-hybrid system, SHP interacted with several conventional and orphan members of the receptor superfamily, including retinoid receptors, the thyroid hormone receptor, and the orphan receptor MB67. SHP also interacted directly with these receptors in vitro. In mammalian cells, SHP specifically inhibited transactivation by the superfamily members with which it interacted. These results suggest that SHP functions as a negative regulator of receptor-dependent signaling pathways. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. FU NIDDK NIH HHS [DK46546] NR 33 TC 362 Z9 373 U1 1 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 31 PY 1996 VL 272 IS 5266 BP 1336 EP 1339 DI 10.1126/science.272.5266.1336 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN472 UT WOS:A1996UN47200046 PM 8650544 ER PT J AU Yamatsuji, T Matsui, T Okamoto, T Komatsuzaki, K Takeda, S Fukumoto, H Iwatsubo, T Suzuki, N AsamiOdaka, A Ireland, S Kinane, TB Giambarella, U Nishimoto, I AF Yamatsuji, T Matsui, T Okamoto, T Komatsuzaki, K Takeda, S Fukumoto, H Iwatsubo, T Suzuki, N AsamiOdaka, A Ireland, S Kinane, TB Giambarella, U Nishimoto, I TI G protein-mediated neuronal DNA fragmentation induced by familial Alzheimer's disease-associated mutants of APP SO SCIENCE LA English DT Article ID AMYLOID PRECURSOR PROTEIN; MISSENSE MUTATION; ALPHA-SUBUNIT; GENE; CELLS; APOPTOSIS; INDUCTION; DEATH AB Missense mutations in the 595-amino acid form of the amyloid precursor protein (APP(695)) cosegregate with disease phenotype in families with dominantly inherited Alzheimer's disease. These mutations convert valine at position 642 to isoleucine, phenylalanine, or glycine. Expression of these mutant proteins, but not of normal APP(695), was shown to induce nucleosomal DNA fragmentation in neuronal cells. Induction of DNA fragmentation required the cytoplasmic domain of the mutants and appeared to be mediated by heterotrimeric guanosine triphosphate-binding proteins (G proteins). C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CARDIVASC RES CTR,DEPT MED,CHARLESTOWN,MA 02129. UNIV TOKYO,FAC PHARMACEUT SCI,DEPT NEUROPATHOL & NEUROSCI,BUNKYO KU,TOKYO 113,JAPAN. TAKEDA CHEM IND LTD,TSUKUBA,IBARAKI 30042,JAPAN. ONCOR INC,GAITHERSBURG,MD 20877. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PEDIAT,RENAL UNIT,CHARLESTOWN,MA 02129. NR 40 TC 204 Z9 208 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 31 PY 1996 VL 272 IS 5266 BP 1349 EP 1352 DI 10.1126/science.272.5266.1349 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN472 UT WOS:A1996UN47200050 PM 8650548 ER PT J AU Lohse, PA Szostak, JW AF Lohse, PA Szostak, JW TI Ribozyme-catalysed amino-acid transfer reactions SO NATURE LA English DT Article ID RNA AB THE 'RNA world' hypothesis proposes an early stage in the evolution of life in which both genomic and catalytic functions were fulfilled by RNA(1). The evolution of RNA-catalysed protein synthesis would have been a necessary step in the transition from such an RNA world to modern protein-dominated biology, For this to have been possible, RNA must be capable of catalysing amide-bond formation using acylated carrier RNA substrates as amino-acid donors. We have used in vitro selection and evolution to isolate ribozymes with acyl transferase activity from a pool of random RNA sequences. One of these acyl transferases with a 5'-amino group transfers an amino acid to itself in a reaction that we propose to be analogous to peptidyl transfer on the ribosome. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 10 TC 159 Z9 163 U1 2 U2 20 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAY 30 PY 1996 VL 381 IS 6581 BP 442 EP 444 DI 10.1038/381442a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN479 UT WOS:A1996UN47900056 PM 8632803 ER PT J AU Anzueto, A Baughman, RP Guntupalli, KK Weg, JG Wiedemann, HP Raventos, AA Lemaire, F Long, W Zaccardelli, DS Pattishall, EN AF Anzueto, A Baughman, RP Guntupalli, KK Weg, JG Wiedemann, HP Raventos, AA Lemaire, F Long, W Zaccardelli, DS Pattishall, EN TI Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID END-EXPIRATORY PRESSURE; SYNTHETIC SURFACTANT; SURVIVAL AB Background. Patients with acute respiratory distress syndrome (ARDS) have a deficiency of surfactant, Surfactant replacement improves physiologic function in such patients, and preliminary data suggest that it may improve survival. Methods. We conducted a prospective, multicenter, double-blind, randomized, placebo-controlled trial involving 725 patients with sepsis-induced ARDS. Patients were stratified according to the risk of death at base line (indicated by their score on the Acute Physiologic and Chronic Health Evaluation [APACHE III] index) and randomly assigned to receive either continuously administered synthetic surfactant (13.5 mg of dipalmitoylphosphatidylcholine per milliliter; 364 patients) or placebo (0.45 percent saline; 361 patients) in aerosolized form for up to five days. Results. The demographic and physiologic characteristics of the two treatment groups were similar at base line, The mean (+/-SD) age was 50+/-17 years in the surfactant group and 53+/-18 years in the placebo group, and the mean APACHE III scores at randomization were 70.4+/-25 and 70.5+/-25, respectively, Hemodynamic measures, measures of oxygenation, duration of mechanical ventilation, and length of stay in the intensive care unit did not differ significantly in the two groups. Survival at 30 days was 60 percent for both groups, Survival was similar in the groups when analyzed according to APACHE III score, cause of death, time of onset and severity of ARDS, presence or absence of documented sepsis, underlying disease, whether or not there was a do-not-resuscitate order, and medical center. Increased secretions were significantly more frequent in the surfactant group; the rates of other complications were similar in the two groups. Conclusions. The continuous administration of aerosolized synthetic surfactant to patients with sepsis-induced ARDS had no significant effect on 30-day survival, length of stay in the intensive care unit, duration of mechanical ventilation, or physiologic function. (C) 1996, Massachusetts Medical Society. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. OHIO UNIV,CINCINNATI,OH. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI. CLEVELAND CLIN,CLEVELAND,OH 44106. CONSORCI HOSP PARC TAVLI,SABADELL,SPAIN. HENRI MONDOR HOSP,PARIS,FRANCE. UNIV N CAROLINA,CHAPEL HILL,NC. GLAXO WELLCOME,RES TRIANGLE PK,NC. RP Anzueto, A (reprint author), S TEXAS VET HLTH CARE SYST,AUDIE L MURPHY MEM VET HOSP DIV,PULM DIS SECT 111E,SAN ANTONIO,TX 78284, USA. OI Wiedemann, Herbert/0000-0002-4587-4401 NR 36 TC 348 Z9 366 U1 0 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 30 PY 1996 VL 334 IS 22 BP 1417 EP 1421 DI 10.1056/NEJM199605303342201 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA UM493 UT WOS:A1996UM49300001 PM 8618579 ER PT J AU Ravindranath, Y Yeager, AM Chang, MN Steuber, CP Krischer, J GrahamPole, J Carroll, A Inoue, S Camitta, B Weinstein, HJ AF Ravindranath, Y Yeager, AM Chang, MN Steuber, CP Krischer, J GrahamPole, J Carroll, A Inoue, S Camitta, B Weinstein, HJ TI Autologous bone marrow transplantation versus intensive consolidation chemotherapy for acute myeloid leukemia in childhood SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; ACUTE NONLYMPHOBLASTIC LEUKEMIA; HIGH-DOSE CYTARABINE; 1ST REMISSION; MAINTENANCE THERAPY; PROGNOSTIC FACTORS; CHILDREN; INTENSIFICATION AB Background. The value of autologous bone marrow transplantation in the treatment of children with acute myeloid leukemia (AML) is unknown. We compared autologous bone marrow transplantation with intensive consolidation chemotherapy as treatments for children with AML in first remission. Methods. We induced remission with one course of daunorubicin, cytarabine, and thioguanine, followed by one course of high-dose cytarabine (3 g per square meter of body-surface area for six doses), Patients in remission after the second course of induction therapy were eligible for randomization, Between June 1988 and March 1993, 552 of 649 enrolled patients who could be evaluated (85 percent) entered remission, A total of 209 patients were not eligible for randomization; of the remaining 343 patients, 232 were randomly assigned to receive six courses of intensive chemotherapy (117 patients) or autologous transplantation (115 patients), Of the original 649 patients, 189, including 21 with Down's syndrome, were nonrandomly assigned to receive intensive chemotherapy. Results, The mean (+/-SE) rates of event-free survival and overall survival for the entire group at three years were 34+/-2.5 percent and 42+/-2.6 percent, respectively, For patients who were randomly assigned to one of the two treatment groups, the rates of event-free survival three years after randomization were not significantly different in the two groups when examined by intention-to-treat analysis: 36+/-5.8 percent for the intensive-chemotherapy group as compared with 38+/-6.4 percent for the autologous-transplantation group; and the relative risk of treatment failure for the chemotherapy group as compared with the autologous-transplantation group was 0.81 (P=0.20 by the log-rank test; 95 percent confidence interval, 0.58 to 1.12), Overall survival at three years followed a similar pattern. There was a lower relapse rate (31 percent vs, 58 percent, P<0.001) but a higher rate of treatment-related mortality (15 percent vs, 2.7 percent, P=0.005) in the group treated with autologous transplantation than in the intensive-chemotherapy group. The event-free survival at three years for the nonrandomized intensive-chemotherapy group was 39+/-5.1 percent, and for a contemporaneous group of patients each of whom received a histocompatible bone marrow transplant from a sibling, it was 52+/-8.0 percent. Conclusions. Treatment of children with AML in first remission with either autologous bone marrow transplantation or intensive chemotherapy prolongs event-free survival equally. (C) 1996, Massachusetts Medical Society. C1 CHILDRENS HOSP MICHIGAN, BARBARA ANN KARMANOS CANC INST, DETROIT, MI 48201 USA. WAYNE STATE UNIV, DETROIT, MI USA. EMORY UNIV, ATLANTA, GA 30322 USA. PEDIAT ONCOL GRP, STAT OFF, GAINESVILLE, FL USA. UNIV FLORIDA, DEPT STAT, GAINESVILLE, FL 32611 USA. TEXAS CHILDRENS HOSP, BAYLOR COLL MED, HOUSTON, TX 77030 USA. H LEE MOFFIT CANC CTR & RES INST, TAMPA, FL USA. UNIV FLORIDA, SHANDS TEACHING HOSP, GAINESVILLE, FL USA. UNIV ALABAMA, BIRMINGHAM, AL USA. HURLEY MED CTR, FLINT, MI USA. MED COLL WISCONSIN, MIDWEST CHILDRENS CANC CTR, MILWAUKEE, WI 53226 USA. CHILDRENS HOSP WISCONSIN, MILWAUKEE, WI 53201 USA. DANA FARBER CANC INST, BOSTON, MA 02115 USA. CHILDRENS HOSP, BOSTON, MA 02115 USA. FU NCI NIH HHS [CA-20549, CA-03161, CA-29691] NR 31 TC 193 Z9 196 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 30 PY 1996 VL 334 IS 22 BP 1428 EP 1434 DI 10.1056/NEJM199605303342203 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UM493 UT WOS:A1996UM49300003 PM 8618581 ER PT J AU Thadhani, R Pascual, M Bonventre, JV AF Thadhani, R Pascual, M Bonventre, JV TI Medical progress - Acute renal failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ACUTE TUBULAR-NECROSIS; CRITICALLY-ILL PATIENTS; PROXIMAL TUBULE; INTERSTITIAL NEPHRITIS; COMPLEMENT ACTIVATION; ADENINE-NUCLEOTIDES; DIALYSIS MEMBRANES; ARTERY STENOSIS; RISK-FACTORS; KIDNEY C1 MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. HARVARD MIT DIV HLTH SCI & TECHNOL,BOSTON,MA. FU NIDDK NIH HHS [DK-38452, DK-39773] NR 154 TC 1048 Z9 1098 U1 5 U2 28 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 30 PY 1996 VL 334 IS 22 BP 1448 EP 1460 DI 10.1056/NEJM199605303342207 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA UM493 UT WOS:A1996UM49300007 PM 8618585 ER PT J AU Yu, X White, LT Alpert, NM Lewandowski, ED AF Yu, X White, LT Alpert, NM Lewandowski, ED TI Subcellular metabolite transport and carbon isotope kinetics in the intramyocardial glutamate pool SO BIOCHEMISTRY LA English DT Article ID CITRIC-ACID CYCLE; C-13 NMR-SPECTROSCOPY; RAT-HEART; PYRUVATE-DEHYDROGENASE; FLUX AB The pathophysiological state of the cell must be translated into the mitochondria to meet the demands for oxidative energy production. Metabolite exchange across the mitochondrial membrane provides this communication and was observed with C-13 NMR spectroscopy of hearts oxidizing [2-C-13]-butyrate at normal or high cytosolic redox state, Previous NMR observations of C-13 turnover within the glutamate pool of intact tissues have indicated its relationship with metabolic flux through the tricarboxylic acid (TCA) cycle, but the direct influence of isotope exchange between the TCA cycle intermediates in the mitochondria and the cytosolic glutamate pool has been much less considered. This current study was designed to determine whether the physical transport of metabolites across the mitochondrial membrane of intact heart tissues could be discerned as a rate determinant for isotope turnover in the NMR-detectable glutamate pool, C-13 entry into glutamate provided measures of TCA cycle flux and the interconversion between mitochondrial intermediates and cytosolic glutamate. The influence of the malate-aspartate shuttle activity was examined by comparing two groups of hearts: one group oxidizing 2.5 mM [2-C-13]-butyrate (n = 5) and the other oxidizing 2.5 mM [2-C-13]butyrate in the presence of a lactate (2.5 mM)-induced elevation in the cytosolic redox to stimulate shuttle activity (n = 5), High redox state did not affect TCA cycle flux but increased the rate of interconversion between alpha-ketoglutarate and glutamate from 3.1 +/- 0.2 mu mol min(-1) (g dry)(-1) to 14.3 +/- 2.0. High resolution C-13 NMR spectra of tissue extracts confirmed that the exogenous lactate did not contribute as a carbon source for the formation of either the TCA cycle intermediates or glutamate, In both groups, over 95% of the acetyl-CoA was derived from the short-chain fatty acid butyrate, irrespective of the presence of lactate. Additional hearts perfused with unlabeled butyrate and [3-C-13]lactate showed no label entry into glutamate, but rather the formation of [3-C-13]alanine, indicating the net reverse flux through lactate dehydrogenase to increase NADH production. Thus, the addition of lactate served only to augment cytosolic redox state to drive the malate-aspartate shuttle, The dynamic-mode acquisition of C-13 NMR data from intact hearts, oxidizing [2-C-13]-butyrate with or without additional lactate, demonstrated the influence of malate-aspartate shuttle activity on the C-13 enrichment rates within glutamate. These data indicate metabolic communication between the mitochondria and cytosol in response to the physiological state of intact tissues. C1 MASSACHUSETTS GEN HOSP,NMR CTR,DEPT RADIOL,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NHLBI NIH HHS [R01HL49244] NR 22 TC 42 Z9 42 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 28 PY 1996 VL 35 IS 21 BP 6963 EP 6968 DI 10.1021/bi960199l PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UN288 UT WOS:A1996UN28800050 PM 8639648 ER PT J AU Ravichandran, KS Igras, V Shoelson, SE Fesik, SW Burakoff, SJ AF Ravichandran, KS Igras, V Shoelson, SE Fesik, SW Burakoff, SJ TI Evidence for a role for the phosphotyrosine-binding domain of Shc in interleukin 2 signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECEPTOR-BETA-CHAIN; IL-2 RECEPTOR; ACTIVATION; ASSOCIATION; TRANSDUCTION; LYMPHOCYTES; P56(LCK); KINASE AB Stimulation via the T-cell growth factor interleukin 2 (IL-2) leads to tyrosine phosphorylation of Shc, the interaction of Shc with Grb2, and the Ras GTP/GDP exchange factor, mSOS. Shc also coprecipitates with the IL-2 receptor (IG-2R), and therefore, may link IL-2R to Ras activation. We have further characterized the Shc-IL-2R interaction and have made the following observations. (i) Among the two phosphotyrosine-interaction domains present in Shc, the phosphotyrosine-binding (PTB) domain, rather than its SH2 domain, interacts with the tyrosine-phosphorylated IL-2R beta chain. Moreover, the Shc-PTB domain binds a phosphopeptide derived from the IL-2R beta chain (corresponding to residues surrounding Y338, SCFTNQGpYFF) with high affinity. (ii) In vivo, mutant IL-2R beta chains lacking the acidic region of IL-2R beta (which contains Y338) fail to phosphorylate Shc. Furthermore, when wild type or mutant Shc proteins that lack the PTB domain were expressed in the IL-2-dependent CTLL-2O cell line, an intact Shc-PTB domain was required for Shc phosphorylation by the IL-2R, which provides further support for a Shc-PTB-IL-2R interaction in vivo. (iii) PTB and SH2 domains of Shc associate with different proteins in IL-2- and T-cell-receptor-stimulated lysates, suggesting that Shc, through the concurrent use of its two different phosphotyrosine-binding domains, could assemble multiple protein complexes. Taken together, our in vivo and in vitro observations suggest that the PTB domain of Shc interacts with Y338 of the IL-2R and provide evidence for a functional role for the Shc-PTB domain in IL-2 signaling. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. ABBOTT LABS,DIV PHARMACEUT DISCOVERY,N CHICAGO,IL 60064. NR 42 TC 90 Z9 92 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 28 PY 1996 VL 93 IS 11 BP 5275 EP 5280 DI 10.1073/pnas.93.11.5275 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN253 UT WOS:A1996UN25300019 PM 8643566 ER PT J AU Debant, A SerraPages, C Seipel, K OBrien, S Tang, M Park, SH Streuli, M AF Debant, A SerraPages, C Seipel, K OBrien, S Tang, M Park, SH Streuli, M TI The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has separate rac-specific and rho-specific guanine nucleotide exchange factor domains SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GTPase; immunoglobulin; pleckstrin homology; protein tyrosine phosphorylation; spectrin-like repeats ID LIGHT CHAIN KINASE; FAMILY; IDENTIFICATION; EXPRESSION; ONCOGENE; SEQUENCE; SPECTRIN; REGION AB rho-like GTP binding proteins play an essential role in regulating cell growth and actin polymerization. These molecular switch are positively regulated by guanine nucleotide exchange factors (GEFs) that promote the exchange of GDP for GTP. Using the interaction-trap assay to identify candidate proteins that bind the cytoplasmic region of the LAR transmembrane protein tyrosine phosphatase (PTPase), we isolated a cDNA encoding a 2861-amino acid protein termed Trio that contains three enzyme domains: two functional GEF domains and a protein serine/threonine kinase (PSK) domain. One of the Trio GEF domains (Trio GEF-D1) has rac-specific GEF activity, while the other Trio GEF domain (Trio GEF-D2) has rho-specific activity. The C-terminal PSK domain is adjacent to an Ig-like domain and is most similar to calcium/calmodulin-dependent kinases, such as smooth muscle myosin light chain kinase which similarly contains associated Ig-like domains. Near the N terminus, Trio has four spectrin-like repeats that may play a role in intracellular targeting. Northern blot analysis indicates that Trio has a broad tissue distribution. Trio appears to be phosphorylated only on serine residues, suggesting that Trio is not a LAR substrate, but rather that it forms a complex with LAR. As the LAR PTPase localizes to the ends of focal adhesions, we propose that LAR and the Trio GEF/PSK may orchestrate cell-matrix and cytoskeletal rearrangements necessary for cell migration. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV TUMOR IMMUNOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. MIT, WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA. MIT, DEPT BIOL, CAMBRIDGE, MA 02142 USA. FU NCI NIH HHS [CA 55547] NR 43 TC 330 Z9 333 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 28 PY 1996 VL 93 IS 11 BP 5466 EP 5471 DI 10.1073/pnas.93.11.5466 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN253 UT WOS:A1996UN25300053 PM 8643598 ER PT J AU Kolluri, R Tolias, KF Carpenter, CL Rosen, FS Kirchhausen, T AF Kolluri, R Tolias, KF Carpenter, CL Rosen, FS Kirchhausen, T TI Direct interaction of the Wiskott-Aldrich syndrome protein with the GTPase Cdc42 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunodeficiency; small guanosine 5'-triphosphate binding protein; Rho family; cytoskeleton; actin ID LYMPHOCYTES-T; CELLS; LOCALIZATION; DXS255; KINASE; LOCUS AB Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency disorder with the most severe pathology in the T lymphocytes and platelets. The disease arises from mutations in the gene encoding the WAS protein. T lymphocytes of affected males with WAS exhibit a severe disturbance of the actin cytoskeleton, suggesting that the WAS protein could regulate its organization. We show here that WAS protein interacts with a member of the Rho family of GTPases, Cdc42. This interaction, which is guanosine 5'-triphosphate (GTP)-dependent, was detected in cell lysates, in transient transfections and with purified recombinant proteins. A weaker interaction was also detected with Rad using WAS protein from cell lysates. It was also found that different mutant WAS proteins from three affected males retained their ability to interact with Cdc42 and that the level of expression of the WAS protein in these mutants was only 2-5% of normal. Taken together these data suggest that the WAS protein might function as a signal transduction adaptor downstream of Cdc42, and in affected males, the cytoskeletal abnormalities may result from a defect in Cdc42 signaling. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP,DIV IMMUNOL,BOSTON,MA 02115. BETH ISRAEL HOSP,DIV SIGNAL TRANSDUCT,BOSTON,MA 02115. NR 35 TC 174 Z9 175 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 28 PY 1996 VL 93 IS 11 BP 5615 EP 5618 DI 10.1073/pnas.93.11.5615 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN253 UT WOS:A1996UN25300080 PM 8643625 ER PT J AU Lu, FM Lux, SE AF Lu, FM Lux, SE TI Constitutively active human Notch1 binds to the transcription factor CBF1 and stimulates transcription through a promoter containing a CBF1-responsive element SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RBPJ(k); TAN-1; signal transduction; Suppressor of Hairless ID EPSTEIN-BARR-VIRUS; DROSOPHILA-NOTCH; CELL-FATE; MOUSE HOMOLOG; PROTEINS; GENE; EXPRESSION; REPEATS; MELANOGASTER; RECEPTOR AB Notch is a transmembrane receptor that plays a critical role in cell fate determination. In Drosophila, Notch binds to and signals through Suppressor of Hairless. A mammalian homologue of Suppressor of Hairless, named CBF1 (or RBPJ(k)), is a ubiquitous transcription factor whose function in mammalian Notch signaling is unknown. To determine whether mammalian Notch can stimulate transcription through a CBF1-responsive element (RE), we cotransfected a CBF1-RE-containing chloramphenicol acetyltransferase reporter and N1(delta EC), a constitutively active form of human Notch1 lacking the extracellular domain, into DG75, COS-1, HeLa, and 293T cells, which all contain endogenous CBF1. N1(delta EC) dramatically increased chloramphenicol acetyltransferase activity in these cells, indicating functional coupling of Notch1 and CBF1. The activity was comparable to that produced by the Epstein-Barr virus protein EBNA2, a well-characterized, potent transactivator of CBF1. To test whether CBF1 and Notch1 interact physically, we tagged CBF1 with an epitope from the influenza virus hemagglutinin or with the N-terminal domain of gal4, and transfected the tagged CBF1 plus N1(delta EC) into COS-1 cells. Cell lysates were immunoprecipitated and immunoblotted with several anti-Notch1 antibodies [to detect N1(delta EC)] or with antibodies to hemagglutinin or gal4 (to detect CBF1). Each immunoprecipitate contained a complex of N1(delta EC) and CBF1. In summary, we find that the truncated, active form of human Notch1, N1(delta EC), binds CBF1 and activates transcription through a CBF1-RE-containing promoter. We conclude that CBF1 is a critical downstream protein in the human Notch1 signaling pathway. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. FU NHLBI NIH HHS [HL 32262]; NIDDK NIH HHS [DK 34083] NR 43 TC 65 Z9 69 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 28 PY 1996 VL 93 IS 11 BP 5663 EP 5667 DI 10.1073/pnas.93.11.5663 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UN253 UT WOS:A1996UN25300089 PM 8643633 ER PT J AU Barsky, AJ Delamater, BA Clancy, SA Antman, EM Ahern, DK AF Barsky, AJ Delamater, BA Clancy, SA Antman, EM Ahern, DK TI Somatized psychiatric disorder presenting as palpitations SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PRIMARY-CARE; SOMATOSENSORY AMPLIFICATION; TRANSIENT HYPOCHONDRIASIS; MENTAL-DISORDERS; PANIC DISORDER; DEPRESSION; ILLNESS; RECOGNITION; SYMPTOMS; ANXIETY AB Background: Psychiatric disorder is underdiagnosed in primary care practice, often because it is somatized and the patient reports only physical symptoms. Palpitations are among the symptoms that often are somatized. Methods: We studied prospectively 125 consecutive medical outpatients referred for ambulatory electrocardiographic monitoring to evaluate a chief complaint of palpitations. They completed an in-person research interview at the time of monitoring and a telephone follow-up interview 3 months later. The referring physicians completed questionnaires about their patients before receiving the results of the monitoring and again 3 months later. Results: Forty-three patients had clinically significant cardiac arrhythmias. Twenty-four (29%) of the remaining 82 patients had a current psychiatric disorder, and 20 of these patients (83%) had major depression or panic disorder. These patients were significantly younger and more disabled, somatized more, and had more hypochondriacal concerns about their health than did patients who had no psychiatric disorder. Their palpitations were more likely to last longer than 15 minutes, were accompanied by more ancillary symptoms, and were described as more intense. At 3-month follow-up, about 90% of the patients in both groups continued to experience palpitations. Symptoms of somatization, hypochondriacal concerns, and impairment of intermediate activities had improved in both groups, but remained higher in patients with psychiatric disorder than in patients without psychiatric disorder. During the follow-up interval, patients with psychiatric disorder had more emergency department visits. The physicians of patients with psychiatric disorder were more likely to ascribe the palpitations to anxiety or depression, and ordered fewer laboratory tests on them, but few patients who had not already been in psychiatric treatment were referred or started on psychotropic medication. Conclusions: Physicians are aware of a psychiatric component to the clinical presentation of palpitation, but this observation does not result in psychiatric treatment or referral in most cases. C1 BRIGHAM & WOMENS HOSP, DIV CARDIOVASC MED, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, PSYCHIAT SERV, BOSTON, MA 02114 USA. RP Barsky, AJ (reprint author), BRIGHAM & WOMENS HOSP, DIV PSYCHIAT, 75 FRANCIS ST, BOSTON, MA 02115 USA. NR 42 TC 10 Z9 11 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 27 PY 1996 VL 156 IS 10 BP 1102 EP 1108 DI 10.1001/archinte.156.10.1102 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UM685 UT WOS:A1996UM68500009 ER PT J AU Meissner, JD Brown, GA Mueller, WH Scheibe, RJ AF Meissner, JD Brown, GA Mueller, WH Scheibe, RJ TI Retinoic acid-mediated decrease of G(alpha S) protein expression: Involvement of G(alpha S) in the differentiation of HL-60 myeloid cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; HUMAN PITUITARY-TUMORS; ALPHA-SUBUNIT; TERATOCARCINOMA CELLS; GS-ALPHA; NUCLEAR RECEPTOR; ADENYLYL CYCLASE; PERTUSSIS-TOXIN; IDENTIFICATION; STIMULATION AB The amount of the heterotrimeric G protein subunit G(alpha>s) decreases after the induction of human myeloblastic leukemia HL-60 cells to become granulocyte-like cells in the presence of retinoic acid (RA). Compared to untreated control cells, HL-60 cells expressed decreased levels of G(alpha s) protein and mRNA levels after addition of RA to the cultures as shown by immunoblot and Northern blot analysis. The reduction of the G(alpha s) protein in HL-60 cells by antisense RNA expression was associated with (i) decreased cell doubling time; (ii) induction of a granulocyte-like phenotype; (iii) and expression of a surface marker characteristic of myeloid differentiation. Expression of a constitutively active mutant G(alpha s) (Q227L) in HL-60 cells blocked RA-induced differentiation. In contrast, treatment with forskolin, prostaglandin E(2), or 8-bromo-cyclic: AMP, which increase intracellular cyclic AMP (cAMP) levels, did not inhibit the RA-mediated differentiation process. No changes in cAMP levels occurred in response to Rk The present study provides insights into the involvement of G(alpha s) protein in growth regulation during differentiation of the human myeloid cell line HL-60. These data suggest that in HL-60 human myeloid cells RA-mediated decrease of G(alpha s) plays a critical role in the regulation of differentiation which is independent of intracellular cAMP. (C) 1996 Academic Press, Inc. C1 HANNOVER MED SCH,DEPT CLIN CHEM,ZENTRUM BIOCHEM,D-30623 HANNOVER,GERMANY. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 53 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 25 PY 1996 VL 225 IS 1 BP 112 EP 121 DI 10.1006/excr.1996.0162 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UM491 UT WOS:A1996UM49100012 PM 8635503 ER PT J AU Pratt, JC Weiss, M Sieff, CA Shoelson, SE Burakoff, SJ Ravichandran, KS AF Pratt, JC Weiss, M Sieff, CA Shoelson, SE Burakoff, SJ Ravichandran, KS TI Evidence for a physical association between the Shc-PTB domain and the beta(c) chain of the granulocyte-macrophage colony-stimulating factor receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-TRANSDUCTION; ACTIVATION; PROTEIN; INTERLEUKIN-3; REQUIRES; SUBUNIT AB Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates the growth and function of several myeloid cell types at different stages of maturation. The effects of GM-CSF are mediated through a high affinity receptor that is composed of two chains: a unique, ligand-specific alpha chain and a beta common chain (beta(c)) that is also a component of the receptors for interleukin 3 (IL-3) and IL-5, beta(c) plays an essential role in the transduction of extracellular signals to the nucleus through its recruitment of secondary messengers, Several downstream signaling events induced by GM CSF stimulation have been described, including activation of tyrosine kinases and tyrosine phosphorylation of cellular proteins (including beta(c)) and activation of the Ras/mitogen-activated protein kinase and the JAK/STAT pathways, A region within the beta(c) cytoplasmic tail (amino acids 517-763) has been reported to be necessary for tyrosine phosphorylation of the adapter protein, Shc, and for the subsequent GM-CSF-induced activation of Ras, In this paper, we describe a physical association between the tyrosine phosphorylated GM-CSF receptor (GMR)-beta(c) chain and Shc in vivo. Using a series of cytoplasmic truncation mutants of beta(c) and various mutant Shc proteins, we demonstrate that the N-terminal phosphotyrosine-binding (PTB) domain of Shc binds to a short region of beta(c) (amino acids 549-656) that contains Tyr(577). Addition of a specific phosphopeptide encoding amino acids surrounding this tyrosine inhibited the interaction between beta(c) and Shc. Moreover, mutation of a key residue within the phosphotyrosine binding pocket of the Shc-PTB domain abrogated its association with beta(c). These observations provide an explanation for the previously described requirement for Tyr(577) of beta(c) for GM-CSF-induced tyrosine phosphorylation of She and have implications for Ras activation through the GM-CSF, IL-3, and IL-5 receptors. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. UNIV MUNICH,CHILDRENS HOSP,DEPT PEDIAT,D-80337 MUNICH,GERMANY. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. FU NIAID NIH HHS [AI-17258] NR 32 TC 69 Z9 69 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 1996 VL 271 IS 21 BP 12137 EP 12140 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL660 UT WOS:A1996UL66000006 PM 8647804 ER PT J AU Recht, A Come, SE Henderson, IC Gelman, RS Silver, B Hayes, DF Shulman, LN Harris, JR AF Recht, A Come, SE Henderson, IC Gelman, RS Silver, B Hayes, DF Shulman, LN Harris, JR TI The sequencing of chemotherapy and radiation therapy after conservative surgery for early-stage breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article AB Background. Patients with early-stage breast cancer who are at substantial risk for systemic metastases are increasingly treated with breast-conserving therapy and adjuvant chemotherapy. However, the optimal sequencing of chemotherapy and radiation therapy is not clear. Methods. Two hundred forty-four patients with stage I or II breast cancer who were at substantial risk for distant metastases were randomly assigned to receive a 12-week course of chemotherapy either before or after radiation therapy. All had had breast-conserving surgery. The median length of follow-up in surviving patients was 58 months (range, 10 to 124). Results. The five-year actuarial rates of cancer recurrence at any site and of distant metastases in the radiotherapy-first group and the chemotherapy-first group were 38 percent and 31 percent (P = 0.17) and 36 percent and 25 percent (P = 0.05), respectively. Overall survival was 73 percent and 81 percent (P = 0.11), respectively. The five-year crude rates of first recurrence according to site in the radiotherapy-first and chemotherapy-first groups, respectively, were 5 percent and 14 percent for local recurrence and 32 percent and 20 percent for distant or regional recurrence or both, This difference in the pattern of recurrence was of borderline statistical significance (P = 0.07). Conclusions. This study suggests that for patients at substantial risk for systemic metastases, it is preferable to give a le-week course of chemotherapy followed by radiation therapy, rather than radiation therapy followed by chemotherapy. (C) 1996, Massachusetts Medical Society. C1 BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. BETH ISRAEL HOSP,JOINT CTR RADIAT THERAPY,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02215. DANA FARBER CANC INST,BREAST EVALUAT CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. DANA FARBER CANC INST,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 27 TC 289 Z9 302 U1 1 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 23 PY 1996 VL 334 IS 21 BP 1356 EP 1361 DI 10.1056/NEJM199605233342102 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UL251 UT WOS:A1996UL25100002 PM 8614420 ER PT J AU Asch, DA AF Asch, DA TI The role of critical care nurses in euthanasia and assisted suicide SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VOLUNTARY EUTHANASIA; ATTITUDES AB Background. Euthanasia and assisted suicide have received considerable attention recently in medical literature, public discussion, and proposed state legislation. Almost all the discussion in this area has focused on the role of physicians. However, nurses - especially critical care nurses - may be in a special position to understand the wishes of patients and to act on this understanding. Methods. I mailed a survey to 1600 critical care nurses in the United States, asking them to describe anonymously any requests from patients, family members or others acting for patients (surrogates), or physicians to perform euthanasia or assisted suicide, as well as their own practices. Results. Of the 1139 nurses who responded (71 percent), 852 said they practiced exclusively in intensive care units for adults in the United States. Of these 852 nurses, 141 (17 percent) reported that they had received requests from patients or family members to perform euthanasia or assist in suicide; 129 (16 percent of those for whom data were available) reported that they had engaged in such practices; and an additional 35 (4 percent) reported that they had hastened a patient's death by only pretending to provide life-sustaining treatment ordered by a physician. Some nurses reported engaging in these practices without the request or advance knowledge of physicians or others. The method of euthanasia most commonly described was the administration of a high dose of an opiate to a terminally ill patient. Conclusions. As public debate continues about euthanasia and assisted suicide, some critical care nurses in the United States are engaging in such practices. (C) 1995, Massachusetts Medical Society. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,CTR BIOETH,DIV GEN INTERNAL MED,PHILADELPHIA,PA 19104. NR 27 TC 160 Z9 164 U1 2 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 23 PY 1996 VL 334 IS 21 BP 1374 EP 1379 DI 10.1056/NEJM199605233342106 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UL251 UT WOS:A1996UL25100006 PM 8614424 ER PT J AU Perales, MA Skolnik, PR Lieberman, J AF Perales, MA Skolnik, PR Lieberman, J TI Effect of interleukin 12 on in vitro HIV type 1 replication depends on clinical stage SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; ACQUIRED IMMUNODEFICIENCY SYNDROME; HETERODIMERIC CYTOKINE; CYTOTOXIC ACTIVITY; INTERFERON-GAMMA; IMMUNE-RESPONSES; FACTOR NKSF; IL-12; PROLIFERATION AB CDS-depleted PBMCs from 20 HIV-l-seropositive donors were incubated in the presence of no cytokines, rIL-2, rIL-12, or both. HIV-1 replication, measured by culture supernatant p24 Ag, was increased to a comparable extent by either rIL-2 or rIL-12 in five of seven asymptomatic subjects and was not induced by either cytokine in the remaining two asymptomatic subjects. Recombinant IL-2 induced increased detectable p24 in cultures from 8 of 13 symptomatic subjects, but rIL-12 did only in cell lines from 5 symptomatic subjects and then only marginally. In IL-2 containing cultures from subjects with minor symptoms of HIV infection, the mean p24 Ag was 320 +/- 217 pg/ml versus 27 +/- 6 in IL-12-containing cultures (p = 0.03). When rIL-12 was added with rIL-2, p24 Ag levels were reduced fourfold compared to cultures from this group incubated with only rIL-2 (p = 0.03). Neither cytokine had much effect on viral replication in CD8-depleted PBMCs from subjects who had had a major AIDS infection, although the number of CD4 cells in four of six of those cultures was markedly reduced, IL,-4, IFN-gamma, and IL-10 production induced by exposure to IL-2 and/or IL-12 were also measured. In CDS-depleted cultures from all infected asymptomatic donors and from some symptomatic donors, addition of rIL-12 to rIL-2 decreased IL-4 and increased both IFN-gamma and IL-10 production, Cytokine-induced production of IL-4, IFN-gamma, and IL-10 was greater in cultures from asymptomatic donors than in cultures from symptomatic subjects, Our results suggest that IL,-12 immunotherapy may be complicated by enhancement of viral expression in asymptomatic individuals. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. TUFTS UNIV,NEW ENGLAND MED CTR,SCH MED,DIV GEOG MED & INFECT DIS,DEPT MED,BOSTON,MA 02111. TUPPER RES INST,BOSTON,MA 02111. RI Lieberman, Judy/A-2717-2015; OI PERALES, MIGUEL-ANGEL/0000-0002-5910-4571 FU NCI NIH HHS [T32CA0942]; NIAID NIH HHS [K08 AI01046, R01 AI33290] NR 40 TC 11 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 20 PY 1996 VL 12 IS 8 BP 659 EP 668 DI 10.1089/aid.1996.12.659 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UK286 UT WOS:A1996UK28600003 PM 8744576 ER PT J AU Reppert, SM Weaver, DR Ebisawa, T Mahle, CD Kolakowski, LF AF Reppert, SM Weaver, DR Ebisawa, T Mahle, CD Kolakowski, LF TI Cloning of a melatonin-related receptor from human pituitary SO FEBS LETTERS LA English DT Article DE melatonin; human pituitary; G protein-coupled receptor ID EXPRESSION AB We have cloned an orphan G protein-coupled receptor from a human pituitary cDNA library using a probe generated by PCR, The cDNA, designated H9, encodes a protein of 613 amino acids that is 45% identical at the amino acid level to the recently cloned human Mel(1a) and Mel(1b) melatonin receptors. Structural analyses of the encoded protein and its gene, along,vith phylogenetic analysis, further show that H9 is closely related to the G protein-coupled melatonin receptor family, Unusual features of the protein encoded by H9 include a lack of N-linked glycosylation sites and a carboxyl tail >300 amino acids long, H9 transiently expressed in COS-1 cells did not bind [I-125]melatonin or [H-3]melatonin, H9 mRNA is expressed in hypothalamus and pituitary, suggesting that the encoded receptor and its natural ligand are involved in neuroendocrine function. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02114. BRISTOL MYERS SQUIBB PHARMACEUT RES INST,CNS NEUROPHARMACOL,WALLINGFORD,CT 06492. UNIV TEXAS,CTR HLTH SCI,DEPT PHARMACOL,SAN ANTONIO,TX 78284. RP Reppert, SM (reprint author), MASSACHUSETTS GEN HOSP,LAB DEV CHRONOBIOL,JACKSON 1226,BOSTON,MA 02114, USA. FU NICHD NIH HHS [R37 HD14427] NR 21 TC 97 Z9 105 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 20 PY 1996 VL 386 IS 2-3 BP 219 EP 224 DI 10.1016/0014-5793(96)00437-1 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UM442 UT WOS:A1996UM44200028 PM 8647286 ER PT J AU Natowicz, MR Evans, JE Kelley, RI Moser, AB Watkins, PA Moser, HW AF Natowicz, MR Evans, JE Kelley, RI Moser, AB Watkins, PA Moser, HW TI Urinary bile acids and peroxisomal bifunctional enzyme deficiency SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE peroxisome; peroxisomal disease; bifunctional enzyme; bile acids; cholestanoates; cholestenoates ID BETA-OXIDATION SYSTEM; FAST-ATOM-BOMBARDMENT; ENOYL-COA HYDRATASE; 3-HYDROXYACYL-COA DEHYDROGENASE; MASS-SPECTROMETRY; RAT-LIVER; ZELLWEGER SYNDROME; INBORN-ERRORS; PROTEIN; TRIHYDROXYCHOLESTANAEMIA AB The biosynthesis of normal bile acids involves beta-oxidation of the 8-carbon sidechain of cholesterol, in addition to numerous modifications of the sterol nucleus. Because beta-oxidation of the sterol sidechain has been localized to the peroxisome, bile acid analysis has been suggested to be useful in the diagnostic evaluation of individuals suspected of having peroxisomal disorders. Although data from subjects with generalized peroxisomal disorders support this, few data exist regarding the bile acids in individuals having single peroxisomal beta-oxidation enzyme disorders. In this study, we analyzed the urinary bile acids from 12 patients with peroxisomal bifunctional protein deficiency using continuous flow fast atom bombardment mass spectrometry. All 12 patients had abnormal spectra, although their ion profiles and rank order of intensity of ions varied considerably. Ten of 12 individuals had abnormal spectra with presence of taurine-conjugated tetrahydroxycholestenoates, allowing a definite diagnosis of a peroxisomal beta-oxidation defect and a presumptive diagnosis of bifunctional protein deficiency; the other two cases were nondiagnostically abnormal. The strengths and limitations of urinary bile acid analysis for the diagnosis of peroxisomal beta-oxidation disorders are discussed. (C) 1996 Wiley-Liss, Inc. C1 MASSACHUSETTS GEN HOSP,SHRIVER CTR MENTAL RETARDAT,DIV MED GENET & BIOMED SCI,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. JOHNS HOPKINS UNIV,MED CTR,DEPT NEUROL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,MED CTR,DEPT PEDIAT,BALTIMORE,MD 21218. KENNEDY KRIEGER INST,BALTIMORE,MD. FU NICHD NIH HHS [HD 24061] NR 41 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 17 PY 1996 VL 63 IS 2 BP 356 EP 362 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA UP713 UT WOS:A1996UP71300007 PM 8725785 ER PT J AU Yamasaki, L Jacks, T Bronson, R Goillot, E Harlow, E Dyson, NJ AF Yamasaki, L Jacks, T Bronson, R Goillot, E Harlow, E Dyson, NJ TI Tumor induction and tissue atrophy in mice lacking E2F-1 SO CELL LA English DT Article ID TRANSCRIPTION FACTOR E2F; RETINOBLASTOMA PROTEIN; BINDING PROTEIN; GENE; EXPRESSION; CLONING; MOUSE; CELLS; SITE; TRANSACTIVATION AB The retinoblastoma tumor suppressor protein (pRB) is a transcriptional repressor that regulates gene expression by physically associating with transcription factors such as E2F family members. Although pRB and its upstream regulators are commonly mutated in human cancer, the physiological role of the pRB-E2F pathway is unknown. To address the function of E2F-1 and pRB/E2F-1 complexes in vivo, we have produced mice homozygous for a nonfunctional E2F-1 allele. Mice lacking E2F-1 are viable and fertile, yet experience testicular atrophy and exocrine gland dysplasia. Surprisingly, mice lacking E2F-1 develop a broad and unusual spectrum of tumors. Although overexpression of E2F-1 in tissue culture cells can stimulate cell proliferation and be oncogenic, loss of E2F-1 in mice results in tumorigenesis, demonstrating that E2F-1 also functions as a tumor suppressor. C1 MIT,CTR CANC RES,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. TUFTS UNIV,SCH VET MED,USDA,HUMAN NUTR RES CTR AGING,DEPT PATHOL,BOSTON,MA 02111. RP Yamasaki, L (reprint author), MASSACHUSETTS GEN HOSP,CTR CANC,BLDG 49,13TH ST,CHARLESTOWN,MA 02129, USA. FU NCI NIH HHS [CA64402, CA42063, CA60636] NR 75 TC 593 Z9 604 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 17 PY 1996 VL 85 IS 4 BP 537 EP 548 DI 10.1016/S0092-8674(00)81254-4 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UM415 UT WOS:A1996UM41500011 PM 8653789 ER PT J AU Field, SJ Tsai, FY Kuo, F Zubiaga, AM Kaelin, WG Livingston, DM Orkin, SH Greenberg, ME AF Field, SJ Tsai, FY Kuo, F Zubiaga, AM Kaelin, WG Livingston, DM Orkin, SH Greenberg, ME TI E2F-1 functions in mice to promote apoptosis and suppress proliferation SO CELL LA English DT Article ID TRANSCRIPTION FACTOR E2F; DNA-BINDING ACTIVITY; HUMAN MYC PROMOTER; RETINOBLASTOMA PROTEIN; CYCLIN-A; CELL-CYCLE; THYMIDINE KINASE; TRANS-ACTIVATION; S-PHASE; COMPLEX AB Members of the E2F transcription factor family (E2F-1-E2F-5) are believed to be critical positive regulators of cell cycle progression in eukaryotes although the in vivo functions of the individual E2Fs have not been elucidated. Mice were generated that lack E2F-1 and, surprisingly, these mice develop and reproduce normally. However, E2F-1(-/-) mice exhibit a defect in T lymphocyte development leading to an excess of mature T cells due to a maturation stage-specific defect in thymocyte apoptosis. As E2F-1(-/-) mice age they exhibit a second phenotype marked by aberrant cell proliferation. These findings suggest that while certain members of the E2F family may positively regulate cell cycle progression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation. C1 CHILDRENS HOSP,DIV NEUROSCI,BOSTON,MA 02115. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HOWARD HUGHES MED INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. DANA FARBER CANC INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK49216] NR 64 TC 653 Z9 662 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAY 17 PY 1996 VL 85 IS 4 BP 549 EP 561 DI 10.1016/S0092-8674(00)81255-6 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UM415 UT WOS:A1996UM41500012 PM 8653790 ER PT J AU Hansen, U AF Hansen, U TI Mechanisms of eukaryotic transcription: Surfaces, complexes, and contexts - (Cold Spring Harbor cancer cells meeting, August 30 September 3, 1995) SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. RP Hansen, U (reprint author), DANA FARBER CANC INST,DIV MOLEC GENET,44 BINNEY ST,RM B410,BOSTON,MA 02115, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAY 16 PY 1996 VL 1287 IS 1 BP 59 EP 62 DI 10.1016/0304-419X(96)00004-2 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA UP431 UT WOS:A1996UP43100003 PM 8639706 ER PT J AU Bao, JX Zervos, AS AF Bao, JX Zervos, AS TI Isolation and characterization of Nmi, a novel partner of Myc proteins SO ONCOGENE LA English DT Article DE Myc oncoproteins; transcription; two-hybrid screen ID C-MYC; INCREASED EXPRESSION; DNA-BINDING; MAX; GENE; TRANSFORMATION; RECOGNITION; SEQUENCE; CLONING; TARGET AB The Myc family of oncogenes is thought to play an important role In cell proliferation, differentiation, and neoplastic transformation. Although the structure and expression of Myc genes are well characterized, the function and biochemical properties of the Myc proteins are less well understood, Here, using a yeast genetic screen, we identified a novel gene, Nmi, that binds to N-myc and C-myc, It also interacts with other transcription factors in yeast. The carboxyl terminus of Nmi shows homology to an interferon-induced leucine zipper protein, IFP 35, whereas its amino terminus is homologous to a coiled-coil heptad repeat in the C. elegans protein, CEF59, Go-precipitation studies of Nmi with N-myc and C-myc confirmed the interaction in mammalian cells, Nmi mRNA is expressed at low levels in all fetal and adult human tissues tested, except brain, Among several cancer cell lines, high expression of Nmi was found in myeloid leukemias, which also express high levels of C-myc. Nmi gene is localized on human chromosome 22q13.3. Translocations of this region have been reported In some human leukemias. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. NR 45 TC 81 Z9 83 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY 16 PY 1996 VL 12 IS 10 BP 2171 EP 2176 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UP283 UT WOS:A1996UP28300016 PM 8668343 ER PT J AU Lau, JYN Davis, GL Prescott, LE Maertens, G Lindsay, KL Qian, KP Mizokami, M Simmonds, P Perrillo, RP Schiff, ER Bodenheimer, HC Balart, LA Regenstein, F Dienstag, JL Katkov, WN Tamburro, CH Goff, JS Everson, GT Goodman, Z Albrecht, J AF Lau, JYN Davis, GL Prescott, LE Maertens, G Lindsay, KL Qian, KP Mizokami, M Simmonds, P Perrillo, RP Schiff, ER Bodenheimer, HC Balart, LA Regenstein, F Dienstag, JL Katkov, WN Tamburro, CH Goff, JS Everson, GT Goodman, Z Albrecht, J TI Distribution of hepatitis C virus genotypes determined by line probe assay in patients with chronic hepatitis C seen at tertiary referral centers in the United States SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE hepatitis C viruses; genotype; hepatitis C; assay, line probe; serotyping ID SEQUENCE; REGION; VARIABILITY; INFECTION; DISTINCT; SUBTYPES; GENOMES AB Objective: To 1) verify the validity of a new line probe assay for hepatitis C virus (HCV) genotyping and 2) determine the distribution of HCV genotypes and the association between HCV genotype and clinical variables in patients with chronic hepatitis C seen in tertiary referral centers in the United States. Design: Retrospective cross-sectional analysis. Patients: 438 patients with chronic hepatitis C from 10 tertiary referral centers. Measurements: The validity of the line probe assay was first verified against a panel of serum specimens that had previously been characterized by six different HCV genotyping methods. Specimens from all 438 patients were then genotyped using this line probe assay. The associations between HCV genotype and clinical variables were examined using analysis of variance. Pairwise testing was used when the F test showed a statistically significant difference. Nonparametric alternatives were used for variables for which normality could not be assumed. Results: The line probe assay was quick and reproducible, and it showed good concordance with other tests. In our sample, the proportions of patients with HCV types 1, 2, 3, and 4 were 71.5%, 13.5%, 5.5%, and 1.1%, respectively. Subtypes la and Ib were seen in approximately equal proportions of patients with HCV type 1. Mixed infection was detected in 3.7% of specimens, and 4.8% of specimens either had negative results on polymerase chain reaction or could not be typed. A higher proportion of patients with HCV type 1 than of patients with HCV-type 1 had acquired HCV through transfusion of blood products (50% compared with 25%; P < 0.001). Patients with HCV type 1 also had a longer estimated duration of infection compared with patients with HCV type 3 (P = 0.004) and type 4 (P = 0.049). Disease activity did not differ among patients infected with HCV types 1, 2, or 3. Levels of viremia were similar in patients with HCV types 1, 2, or 3, but patients with HCV type 4 had a lower level of viremia than did patients with HCV type 1 (P = 0.047). Conclusions: The line probe assay can be used in patients with chronic HCV infection in the United States. In patients with chronic hepatitis C referred to tertiary centers in the United States, type 1 is the most common HCV genotype. Disease activity and viremia levels do not differ among patients chronically infected with HCV types 1, 2, or 3. C1 UNIV EDINBURGH,DEPT MICROBIOL,EDINBURGH EH8 9AG,MIDLOTHIAN,SCOTLAND. INNOGENET,B-9052 GHENT,BELGIUM. UNIV SO CALIF,DEPT MED,DIV GASTROINTESTINAL & LIVER DIS,LOS ANGELES,CA 90033. NAGOYA CITY UNIV,SCH MED,DEPT INTERNAL MED 2,NAGOYA,AICHI 467,JAPAN. VET AFFAIRS MED CTR,ST LOUIS,MO. UNIV MIAMI,MIAMI,FL 33152. RHODE ISL HOSP,PROVIDENCE,RI 02902. BROWN UNIV,PROVIDENCE,RI 02912. ALTON OCHSNER MED FDN & OCHSNER CLIN,NEW ORLEANS,LA 70121. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV LOUISVILLE,LOUISVILLE,KY 40292. UNIV COLORADO,DENVER,CO 80202. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. SCHERING PLOUGH CORP,RES INST,KENILWORTH,NJ 07033. RP Lau, JYN (reprint author), UNIV FLORIDA,J HILLIS MILLER HLTH CTR,DEPT MED,DIV GASTROENTEROL HEPATOL & NUTR,GAINESVILLE,FL 32610, USA. FU NCRR NIH HHS [5M01RR00082, M01RR01066, RR-00865] NR 36 TC 165 Z9 166 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 15 PY 1996 VL 124 IS 10 BP 868 EP & PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA UJ801 UT WOS:A1996UJ80100002 PM 8610915 ER PT J AU Faraone, SV Biederman, J Mick, E Wozniak, J Kiely, K Guite, J Ablon, JS Warburton, R Reed, E AF Faraone, SV Biederman, J Mick, E Wozniak, J Kiely, K Guite, J Ablon, JS Warburton, R Reed, E TI Attention deficit hyperactivity disorder in a multigenerational pedigree SO BIOLOGICAL PSYCHIATRY LA English DT Article C1 MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BROCKTON W ROXBURY VET AFFAIRS MED CTR,CAMBRIDGE,MA 02138. MASSACHUSETTS MENTAL HLTH CTR,BOSTON,MA 02115. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 7 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 1996 VL 39 IS 10 BP 906 EP 908 DI 10.1016/0006-3223(95)00194-8 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UJ097 UT WOS:A1996UJ09700013 PM 8860195 ER PT J AU Shivdasani, RA Orkin, SH AF Shivdasani, RA Orkin, SH TI The transcriptional control of hematopoiesis SO BLOOD LA English DT Review ID T-CELL LEUKEMIA; PU.1 REGULATES EXPRESSION; LEUCINE ZIPPER PROTEIN; GATA-BINDING PROTEINS; EMBRYONIC STEM-CELLS; LOOP-HELIX PROTEINS; DNA-BINDING; MOUSE EMBRYO; YOLK-SAC; ERYTHROID-DIFFERENTIATION C1 CHILDRENS HOSP,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. CHILDRENS HOSP,DANA FARBER CANC INST,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. HOWARD HUGHES MED INST,BOSTON,MA 02115. NR 175 TC 491 Z9 493 U1 4 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4025 EP 4039 PG 15 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900001 PM 8639758 ER PT J AU Rosenzweig, M Marks, DF Zhu, HH Hempel, D Mansfield, KG Sehgal, PK Kalams, S Scadden, DT Johnson, RP AF Rosenzweig, M Marks, DF Zhu, HH Hempel, D Mansfield, KG Sehgal, PK Kalams, S Scadden, DT Johnson, RP TI In vitro T lymphopoiesis of human and rhesus CD34(+) progenitor cells SO BLOOD LA English DT Article ID EARLY EVENTS; BONE-MARROW; THYMUS; PRECURSORS; LYMPHOCYTE; EXPRESSION; ANTIGENS; INVITRO AB Differentiation of hematopoietic progenitor cells into T lymphocytes generally occurs in the unique environment of the thymus, a feature that has hindered efforts to model this process in the laboratory. We now report that thymic stromal cultures from rhesus macaques can support T-cell differentiation of human or rhesus CD34(+) progenitor cells. Culture of rhesus or human CD34(+) bone marrow-derived cells depleted of CD3(+) lymphocytes on rhesus thymic stromal monolayers yielded CD3(+)CD4(+)CD8(+), CD3(+)CD4(+)CD8(-), and CD3(+)CD4(-)CD8(+) cells after 10 to 14 days. In addition to classical T lymphocytes, a discrete population of CD3(+)CD8(lo)CD16(+)CD56(+) cells was detected after 14 days in cultures inoculated with rhesus CD34(+) cells. CD3(+) T cells arising from these cultures were not derived from contaminating T cells present in the CD34(+) cells used to inoculate thymic stromal monolayers or from the thymic monolayers, as shown by labeling of cells with the lipophilic membrane dye PKH26. Expression of the recombinase activation gene RAG-2, which is selectively expressed in developing lymphocytes, was detectable in thymic cultures inoculated with CD34(+) cells but not in CD34(+) cells before thymic culture or in thymic stromal monolayers alone, Reverse transcriptase-polymerase chain reaction analysis of T cells derived from thymic stromal cultures of rhesus and human CD34(+) cells showed a polyclonal T-cell receptor repertoire. T-cell progeny derived from rhesus CD34(+) cells cultured on thymic stroma supported vigorous simian immunodeficiency virus replication in the absence of exogenous mitogenic stimuli. Rhesus thymic stromal cultures provide a convenient means to analyze T-cell differentiation in vitro and may be useful as a model of hematopoietic stem cell therapy for diseases of T cells, including acquired immunodeficiency syndrome. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV IMMUNOL,SOUTHBOROUGH,MA 01772. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV PATHOL,SOUTHBOROUGH,MA 01772. HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,DIV PRIMATE MED,SOUTHBOROUGH,MA 01772. HARVARD UNIV,DEACONESS HOSP,SCH MED,DIV HEMATOL ONCOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,CTR AIDS RES,BOSTON,MA. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA. FU NCRR NIH HHS [RR-00168, RR-00055]; NIAID NIH HHS [AI-36550] NR 28 TC 43 Z9 44 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4040 EP 4048 PG 9 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900002 PM 8639759 ER PT J AU Kawashima, I Zanjani, ED AlmaidaPorada, G Flake, AW Zeng, HQ Ogawa, M AF Kawashima, I Zanjani, ED AlmaidaPorada, G Flake, AW Zeng, HQ Ogawa, M TI CD34(+) human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; HUMAN BONE-MARROW; PROGENITOR CELLS; BLAST CELL; C-KIT; INUTERO; TRANSPLANTATION AB Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34(+) cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34(+) Kit(-), CD34(+) Kit(low), and CD34(+) Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34(+) Kit(low) cells showed signs of engraftment according to analysis of CD45(+) cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34(+) Kit(high) cells and two fetuses receiving CD34(+) Kit(-) cells failed to wshow evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34(+) Kit(low) cells exhibited signs of engraftment upon serial examination, Earlier, in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population. (C) 1996 by The American Society of Hematology. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. UNIV NEVADA,SCH MED,DEPT VET AFFAIRS MED CTR,RENO,NV 89557. FU NHLBI NIH HHS [HL52955]; NIDDK NIH HHS [DK/HL48714, DK32294] NR 22 TC 114 Z9 116 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4136 EP 4142 PG 7 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900014 PM 8639771 ER PT J AU Yamashita, T Wu, N Kupfer, G Corless, C Joenje, H Grompe, M DAndrea, AD AF Yamashita, T Wu, N Kupfer, G Corless, C Joenje, H Grompe, M DAndrea, AD TI Clinical variability of fanconi anemia (type C) results from expression of an amino terminal truncated fanconi anemia complementation group C polypeptide with partial activity SO BLOOD LA English DT Article ID READING FRAMES; FACC; GENE; CELLS; TRANSLATION; REGISTRY; MUTATION AB Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases, Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in a severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptide, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55, All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50, Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients. (C) 1996 by The American Society of Hematology. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. FREE UNIV AMSTERDAM,DEPT HUMAN GENET,AMSTERDAM,NETHERLANDS. OREGON HLTH SCI UNIV,DEPT MOLEC & MED GENET,PORTLAND,OR 97201. FU NHLBI NIH HHS [R01-HL5725] NR 36 TC 63 Z9 63 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 15 PY 1996 VL 87 IS 10 BP 4424 EP 4432 PG 9 WC Hematology SC Hematology GA UK879 UT WOS:A1996UK87900047 PM 8639804 ER PT J AU Ikezu, T Okamoto, T Komatsuzaki, K Matsui, T Martyn, JAJ Nishimoto, I AF Ikezu, T Okamoto, T Komatsuzaki, K Matsui, T Martyn, JAJ Nishimoto, I TI Negative transactivation of cAMP response element by familial Alzheimer's mutants of APP SO EMBO JOURNAL LA English DT Article DE amyloid precursor protein; cAMP response element; familial Alzheimer's disease; G(0)-dependent mechanism; memory formation ID AMYLOID PRECURSOR PROTEIN; APLYSIA SENSORY NEURONS; LONG-TERM FACILITATION; MISSENSE MUTATION; GROWTH-FACTOR; DISEASE; RECEPTOR; GENE; SPECIFICITY; ACTIVATION AB In familial Alzheimer's disease (FAD), missense point mutations V642I/F/G, which co-segregate, with the disease phenotype, have been disco,vered in amyloid precursor APP(695). Here, we report that three FAD mutants (FAD-APPs) negatively regulated the transcriptional activity of cAMP response element (CRE) by a G(0)-dependent mechanism, but expression of wildtype APP(695) had no effect on CRE. Experiments with various G alpha(s) chimeras demonstrated that Phe-APP coupled selectively to the C-terminus of G alpha(0). Again, wild-type APP(695) had no effect on its C-terminus, These data indicate that FAD-APPs are gain-of-function mutants of APP(695) that negatively regulate the CRE activity through G(0). This negative transactivation of CRE is the first biochemically analyzed signal evoked by the three FAD-APPs, but not by wild-type APP(695), in a whole-cell system, We discuss the significance of constitutive CRE suppression by FAD-APPs, which is potentially relevant to synaptic malplasticity or memory disorders. C1 MASSACHUSETTS GEN HOSP,SHRINERS HOSP CRIPPLED CHILDREN,DEPT ANESTHESIA,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. NR 41 TC 32 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAY 15 PY 1996 VL 15 IS 10 BP 2468 EP 2475 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UM406 UT WOS:A1996UM40600016 PM 8665854 ER PT J AU Du, W Vidal, M Xie, JE Dyson, N AF Du, W Vidal, M Xie, JE Dyson, N TI RBF, a novel RE-related gene that regulates E2F activity and interacts with cyclin E in Drosophila SO GENES & DEVELOPMENT LA English DT Article DE Drosophila; RB, E2F; S-phase; cyclin E; cell cycle ID TRANSCRIPTION FACTOR E2F; LARGE T-ANTIGEN; RETINOBLASTOMA PROTEIN; CELL-PROLIFERATION; MOLECULAR-CLONING; BINDING PROTEIN; EXPRESSION; P107; FAMILY; CDC2 AB Genetic studies have shown that cyclin E and dE2F are critical regulators of S-phase entry during Drosophila embryogenesis. Whereas the ectopic expression of cyclin E activates dE2F-dependent transcription, it has been proposed that cyclin E does not act directly on dE2F but targets a negative regulator of E2F activity. Such a regulator might be analogous to the family of RE-related proteins (pRB, p107, and p130) that associate with E2F in humans; however, extensive efforts have failed to find such homologs in Drosophila. We have developed a two-hybrid approach that allows transcription activators to be used as bait for interacting proteins. From a screen using Drosophila E2F (dE2F and dDP) as bait, we identified a novel gene, REP. RBF combines several of the structural features of pRB, p107, and p130, suggesting that it may have evolved from a common ancestor to the three human genes. RBF associates with dE2F and dDP in vivo and is a stoichiometric component of E2F DNA-binding complexes. RBF specifically repressed E2F-dependent transcription and suppressed the phenotype generated by ectopic expression of dE2F and dDP in the developing Drosophila eye. RBF was phosphorylated by a cyclin E-associated kinase in vitro, and loss-of-function cyclin E mutations enhanced an RBF overexpression phenotype, consistent with the idea that the biological activity of RBF is negatively regulated by endogenous cyclin E. The properties of RBF suggest that it is the intermediary factor that was proposed to allow cyclin E induction of E2F activity. These findings indicate that RBF plays a critical role in the regulation of cell proliferation in Drosophila and show that analogous pathways regulate S-phase entry in a diverse range of species. C1 MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. FU NIGMS NIH HHS [GM53203] NR 71 TC 190 Z9 193 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1996 VL 10 IS 10 BP 1206 EP 1218 DI 10.1101/gad.10.10.1206 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UP168 UT WOS:A1996UP16800004 PM 8675008 ER PT J AU Lee, MS Henry, M Silver, PA AF Lee, MS Henry, M Silver, PA TI A protein that shuttles between the nucleus and the cytoplasm is an important mediator of RNA export SO GENES & DEVELOPMENT LA English DT Article DE NPL3; poly(A)(+); RNA; nuclear export; shuttling; hnRNP ID MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; BINDING-PROTEINS; YEAST; TRANSPORT; RECOGNITION; MUTANT; FAMILY; CELL AB The connection between RNA and protein export from the nucleus was examined in the budding yeast Saccharomyces cerevisiae. NPL3 encodes an RNA-binding protein that shuttles in and out of the nucleus. Export of poly(A)(+) RNA has been shown previously to be blocked in npl3-1 mutants. To understand the role of Npl3p in RNA export, we have developed a novel assay that effectively uncouples nuclear protein export from reimport. With this assay, we show that Npl3p satisfies several of the predicted requirements for a protein carrier for mRNA export. Temperature-sensitive mutations in the RNA recognition motifs of Npl3p result in nuclear accumulation of poly(A)(+) RNA. One such mutation prevents nuclear export of Npl3p. Moreover, Npl3p export depends on ongoing RNA polymerase II transcription. Export ceases in either the presence of the RNA synthesis inhibitor thiolutin or in a temperature-sensitive RNA polymerase (rpb1) mutant. Together, these findings support a model in which Npl3p exits the nucleus in association with poly(A)(+) RNA, deposits the RNA in the cytoplasm, and is rapidly reimported for another cycle of export. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOLEC BIOL,BOSTON,MA 02115. NR 53 TC 235 Z9 237 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1996 VL 10 IS 10 BP 1233 EP 1246 DI 10.1101/gad.10.10.1233 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UP168 UT WOS:A1996UP16800006 PM 8675010 ER PT J AU Shea, DK Rutter, M Lucente, D McCormick, MK AF Shea, DK Rutter, M Lucente, D McCormick, MK TI Assignment of the p60 subunit of chromatin assembly factor I to chromosome 21q22.2 SO GENOMICS LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,MOLEC NEUROGENET UNIT,CHARLESTOWN,MA 02140. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02140. FU NINDS NIH HHS [NS32675] NR 6 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1996 VL 34 IS 1 BP 148 EP 150 DI 10.1006/geno.1996.0256 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UM824 UT WOS:A1996UM82400022 PM 8661039 ER PT J AU Rock, KL Clark, K AF Rock, KL Clark, K TI Analysis of the role of MHC class II presentation in the stimulation of cytotoxic T lymphocytes by antigens targeted into the exogenous antigen-MHC class I presentation pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HELPER-CELL; 3-CELL-TYPE CLUSTERS; MONOCLONAL-ANTIBODY; PRESENTING CELLS; VIRUS-INFECTION; KILLER-CELLS; RESPONSES; INVIVO; INDUCTION; COSTIMULATION AB By conjugation of proteins to beads, Ags can be selectively targeted into the MHC class I pathway of phagocytes in vivo and can stimulate CTL responses. Because phagocytes also present particulate Ag on MHC class II molecules, we examined whether these Ags stimulated concomitant CD4 T cell immunity. Although the priming of CD4 T cells with soluble OVA required adjuvants, particulate Ag was stimulatory when injected in saline. We next examined whether CD4 T tell responses played a role in the generation of CTL to particulate Ag. At low concentrations of Ag, OVA primed CTLs in wild-type mice but not in MHC class II-deficient animals, indicating that MHC class II presentation of Ag was essential for CTL generation. These data both support a model where CD4 T cells collaborate with CTLs as part of a three-cell interaction and identify a phagocyte as the third cell in this reaction. Interestingly, injection of higher concentrations of the same Ag primed equivalent CTL responses in both wild-type and MHC class II-deficient mice. These results indicate that a key variable in determining whether CTL generation is helper cell dependent or independent is the dose of immunogen. This may explain in part why CTL responses to abundant Ags, such as viruses, tend to be helper independent, while responses to less abundant Ags, such as minor histocompatibility Ags, require T helper cells. In addition, these results also point to the potential of using particulate Ags to prime or boost responses in settings with CD4 immunodeficiency. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Rock, KL (reprint author), DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 54 TC 76 Z9 76 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1996 VL 156 IS 10 BP 3721 EP 3726 PG 6 WC Immunology SC Immunology GA UJ341 UT WOS:A1996UJ34100019 PM 8621907 ER PT J AU Berman, JS Blumenthal, RL Kornfeld, H Cook, JA Cruikshank, WW Vermeulen, MW Chatterjee, D Belisle, JT Fenton, MJ AF Berman, JS Blumenthal, RL Kornfeld, H Cook, JA Cruikshank, WW Vermeulen, MW Chatterjee, D Belisle, JT Fenton, MJ TI Chemotactic activity of mycobacterial lipoarabinomannans for human blood T lymphocytes in vitro SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; BOVIS BCG; TUBERCULOSIS; STRAINS; MACROPHAGES; ACTIVATION; INHIBITOR; VIRULENT; INSULIN AB A crucial early event in tuberculosis is the ingestion of Mycobaterium tuberculosis (Mtb) by alveolar macrophages, Chemotactic factors released by infected macrophages are likely to initiate a granulomatous response, a key feature of host resistance to tuberculosis. To date, the role of mycobacterial products in regulating the granulomatous response has not been clearly defined. Here we report that the mycobacterial cell wall glycophospholipid lipoarabinomannan (LAM) could specifically induce human peripheral blood T cell chemotaxis in vitro. Both terminally mannosylated LAM isolated from Mtb and LAM lacking the terminal mannosyl units isolated from an avirulent mycobacterium could induce T cell migration in the absence of serum. in contrast, terminally mannosylated LAM isolated from Mycobacterium bovis BCC failed to induce T cell chemotaxis. These observations represent the first report that LAM is capable of directly inducing biologic responses in human T cells. Flow cytometry analysis revealed that CD4(+), CD8(+), and CD45RO(+) lymphocytes were present in the migrating cell populations at ratios similar to those found in nonmigrating cells. The chemotactic: response was found to require new protein synthesis, and could be blocked by inhibitors of protein tyrosine kinases at concentrations that did not affect random migration. Acyl groups at the reducing terminus of LAM appear to be required for the chemotactic activity of this mycobacterial glycolipid. Lastly, culture supernatants from human alveolar macrophages infected in vitro with a virulent strain of Mtb could induce T cell migration. Much of the migratory activity present in these supernatants could be blocked using a mAb against LAM, suggesting that LAM is one of the chemotactic factors released by Mtb-infected alveolar macrophages. C1 BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,BOSTON,MA 02129. COLORADO STATE UNIV,DEPT MICROBIOL,FT COLLINS,CO 80523. RI Belisle, John/B-8944-2017 OI Belisle, John/0000-0002-2539-2798 FU NHLBI NIH HHS [HL43510, HL51957] NR 42 TC 25 Z9 25 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1996 VL 156 IS 10 BP 3828 EP 3835 PG 8 WC Immunology SC Immunology GA UJ341 UT WOS:A1996UJ34100032 PM 8621920 ER PT J AU Hansen, RM Ryan, L Anderson, T Krzywda, B Quebbeman, E Benson, A Haller, DG Tormey, DC AF Hansen, RM Ryan, L Anderson, T Krzywda, B Quebbeman, E Benson, A Haller, DG Tormey, DC TI Phase III study of bolus versus infusion fluorouracil with or without cisplatin in advanced colorectal cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VENOUS INFUSION; PLUS CISPLATIN; LONG-TERM; 5-FLUOROURACIL; CHEMOTHERAPY; TRIAL AB Background: Phase II studies of fluorouracil (5-FU) administered by protracted intravenous infusion have suggested an improved response rate and decreased toxicity profile when compared with 5-FU given by bolus injection in patients with metastatic colorectal cancer, Additional studies have suggested further enhancement of infusion 5-FU activity when it is combined with low-dose weekly cisplatin administration, Purpose: This phase III study in adults with metastatic colorectal cancer was planned as a comparison of objective response rates, toxicity, and survival in patients receiving bolus versus protracted-infusion 5-FU with or without cisplatin, Methods: Four hundred ninety-seven previously untreated patients with advanced, measurable metastatic colorectal cancer were randomly assigned to receive treatment A (bolus 5-FU at 500 mg/m(2) for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m(2)), treatment B (bolus 5-FU at 500 mg/m(2) for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m(2), plus weekly cisplatin at 20 mg/m(2)), treatment C (5-FU at 300 mg/m(2) per day by continuous infusion), or treatment D (5-FU at 300 mg/m(2) per day by continuous infusion plus weekly cisplatin at 20 mg/m(2)), All drugs were administered intravenously, Enrollment in the trial occurred from August 1987 through December 1990, and follow-up was through September 1995, The Kaplan-Meier method was used to estimate overall and disease-free survival, and Cox regression models were used to assess the effects of patient characteristics on survival, All P values resulted from two-sided tests, Results: Objective tumor response was observed in 28 (18%) of 153 patients receiving treatment A, in 45 (28%) of 159 patients receiving treatment C (C versus A; P = .045), and in 47 (31%) of 153 patients receiving treatment D (D versus A; P = .016), Because of excessive toxicity, treatment B was discontinued after only 12 patients had begun treatment, Median time to disease progression was 5.1 months for patients in arm A compared with 6.2 and 6.5 months for patients in arms C and D, respectively (C versus A, P = .007; D versus A, P = .017), Patterns of toxic effects differed substantially among the treatment arms, Forty-five percent of the patients receiving bolus 5-FU alone (A) experienced grade 3-4 leukopenia, with two sepsis-related deaths, Hand-foot syndrome and mucositis were the major treatment-limiting toxic effects for patients in the two treatment arms involving infusion, Despite the improvement in response rates and time to disease progression with infusion 5-FU with or without cisplatin (C and D, respectively) (P = .003), the overall survival for the three groups (A, C, and D) was similar (P = .307), This mag have been due in part to a longer median survival time of 10.4 months for patients in arm A, compared with an anticipated survival of 7 months, Conclusion: 5-FU given as a continuous infusion produced a higher objective response rate, a modest prolongation in time to disease progression, and less life-threatening myelosuppression in patients than bolus 5-FU, Concomitant treatment with low-dose cisplatin caused added toxicity and complexity of treatment and did not provide a major clinical benefit, No statistically significant survival differences were observed among the three treatment groups. C1 DANA FARBER CANC INST,BOSTON,MA 02115. MED COLL WISCONSIN,MILWAUKEE,WI 53226. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. UNIV PENN,CTR CANC,PHILADELPHIA,PA 19104. AMC CANC RES CTR,DENVER,CO. RP Hansen, RM (reprint author), WAUKESHA MEM HOSP,REG CANC CTR,725 AMER AVE,WAUKESHA,WI 53188, USA. FU NCI NIH HHS [CA15488, CA21076, CA23318] NR 28 TC 104 Z9 105 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 15 PY 1996 VL 88 IS 10 BP 668 EP 674 DI 10.1093/jnci/88.10.668 PG 7 WC Oncology SC Oncology GA UK186 UT WOS:A1996UK18600012 PM 8627643 ER PT J AU Patel, R Snydman, DR Rubin, RH Ho, M Pescovitz, M Martin, M Paya, CV AF Patel, R Snydman, DR Rubin, RH Ho, M Pescovitz, M Martin, M Paya, CV TI Cytomegalovirus prophylaxis in solid organ transplant recipients SO TRANSPLANTATION LA English DT Article ID RENAL-TRANSPLANT; IMMUNE GLOBULIN; CONTROLLED TRIAL; LIVER-TRANSPLANTATION; ALLOGRAFT RECIPIENTS; RANDOMIZED TRIAL; VIRUS INFECTION; ORAL ACYCLOVIR; CMV INFECTION; DISEASE C1 MAYO CLIN,DIV INFECT DIS & INTERNAL MED,ROCHESTER,MN 55905. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02111. MASSACHUSETTS GEN HOSP,TRANSPLANTAT UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15261. INDIANA UNIV,MED CTR,DEPT SURG,TRANSPLANTAT SECT,INDIANAPOLIS,IN 46202. UNIV IOWA HOSP & CLIN,DEPT TRANSPLANTAT,IOWA CITY,IA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 58 TC 139 Z9 143 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY 15 PY 1996 VL 61 IS 9 BP 1279 EP 1289 DI 10.1097/00007890-199605150-00001 PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UL468 UT WOS:A1996UL46800001 PM 8629285 ER PT J AU Berson, EL AF Berson, EL TI Retinitis pigmentosa: Unfolding its mystery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RHODOPSIN GENE; FRIEDENWALD LECTURE; OCULAR FINDINGS; ONE FORM; MUTATIONS; PHOTORECEPTOR RP Berson, EL (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BERMAN GUND LAB STUDY RETINAL DEGENERAT,BOSTON,MA 02114, USA. NR 33 TC 87 Z9 88 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4526 EP 4528 DI 10.1073/pnas.93.10.4526 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500003 PM 8643437 ER PT J AU Xiao, ZX Ginsberg, D Ewen, M Livingston, DM AF Xiao, ZX Ginsberg, D Ewen, M Livingston, DM TI Regulation of the retinoblastoma protein-related protein p107 by G(1) cyclin-associated kinases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-PRODUCT; E2F; FAMILY; MEMBER; DOMAIN; BINDS; P130; CDK2; DNA AB p107 is a retinoblastoma protein-related phosphoprotein that, when overproduced, displays a growth inhibitory function. It interacts with and modulates the activity of the transcription factor, E2F-4. In addition, p107 physically associates with cyclin E-CDK2 and cyclin A-CDK2 complexes in late G(1) and at G(1)/S, respectively, an indication that cyclin-dependent kinase complexes may regulate, contribute to, and/or benefit from p107 function during the cell cycle. Our results show that p107 phosphorylation begins in mid Ct and proceeds through late G(1) and S and that cyclin D-associated kinase(s) contributes to this process. In addition, E2F-4 binds selectively to hypophosphorylated p107, and G(1) cyclin-dependent p107 phosphorylation leads to the dissociation of p107-E2F-4 complexes as well as inactivation of p107 G(1) blocking function. C1 DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 32 TC 97 Z9 97 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4633 EP 4637 DI 10.1073/pnas.93.10.4633 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500023 PM 8643455 ER PT J AU Swat, W Shinkai, Y Cheng, HL Davidson, L Alt, FW AF Swat, W Shinkai, Y Cheng, HL Davidson, L Alt, FW TI Activated ras signals differentiation and expansion of CD4(+)8(+) thymocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-CELL-RECEPTOR; BETA-CHAIN; TRANSGENIC MICE; PROTEIN; EXPRESSION; TRANSFORMATION; REARRANGEMENT; RESTORATION; INDUCTION; P21RAS AB We describe a novel approach to assay the ability of particular gene products to signal transitions in lymphocyte differention in vivo. The method involves transfection of test expression constructs into RAG-1-deficient embryonic stem cells, which are subsequently assayed by the RAG-2-deficient blastocyst complementation approach. We have used this method to demonstrate that expression of activated Ras in CD4(-)8(-) (double negative, DN) prothymocytes in vivo induces their differentiation into small CD4(+)8(+) (double postitive, DP) cortical thymocytes with accompanying expansion to normal thymocyte numbers, However, activated Ras expression in DP cells does not cause proliferation or maturation to CD4(+)8(-) or CD4(-)8(+) (single positive) thymocytes. Therefore, signaling through Ras is sufficient for promoting differentiation of DN to DP cells, but further differentiation requires the activity of additional signaling pathways. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP Swat, W (reprint author), CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115, USA. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 NR 50 TC 120 Z9 120 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4683 EP 4687 DI 10.1073/pnas.93.10.4683 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500032 PM 8643464 ER PT J AU Hollander, GA Castigli, E Kulbacki, R Su, M Burakoff, SJ GutierrezRamos, JC Geha, RS AF Hollander, GA Castigli, E Kulbacki, R Su, M Burakoff, SJ GutierrezRamos, JC Geha, RS TI Induction of alloantigen-specific tolerance by B cells from CD40-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ANTIGEN-PRESENTING CELLS; CD40 LIGAND; T-CELLS; ACTIVATION; EXPRESSION; SIGNAL; RECEPTOR; ANTIBODY; CTLA-4; B7/BB1 AB Interaction between CD40 on B cells and CD40 ligand molecules on T cells is pivotal for the generation of a thymus-dependent antibody response. Here ne show that B cells deficient in CD40 expression are unable to elicit the proliferation of allogeneic T cells in vitro. More importantly, mice immunized with CD40(-/-) B cells become tolerant to allogeneic major histocompatibility complex (MHC) antigens as measured by a mixed lymphocyte reaction and cytotoxic T-cell assay. The failure of CD40(-/-) B cells to serve as antigen presenting cells in vitro was corrected by the addition of anti-CD28 mAb. Moreover, lipopolysaccharide stimulation, which upregulates B7 expression, reversed the inability of CD40(-/-) B cells to stimulate an alloresponse in vitro and abrogated the capacity of these B cells to induce tolerance in vivo. These results suggest that CD40 engagement by CD40 ligand expressed on antigen-activated T cells is critical for the upregulation of B7 molecules on antigen-presenting B cells that subsequently deliver the costimulatory signals necessary for T-cell proliferation and differentiation. Our experiments suggest a novel strategy for the induction of antigen-specific tolerance in vivo. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PEDIAT,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. FU NCI NIH HHS [P01 CA39542-08A1]; NIAID NIH HHS [AI35714]; NICHD NIH HHS [HD17461] NR 25 TC 55 Z9 55 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 4994 EP 4998 DI 10.1073/pnas.93.10.4994 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500087 PM 8643517 ER PT J AU Forcione, DG Sands, B Isselbacher, KJ Rustgi, A Podolsky, DK Pillai, S AF Forcione, DG Sands, B Isselbacher, KJ Rustgi, A Podolsky, DK Pillai, S TI An increased risk of Crohn's disease in individuals who inherit class II DRB3(*)0301 allele SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inflammatory bowel disease; major histocompatibility complex; disease susceptibility; HLA class II genotyping ID INFLAMMATORY BOWEL-DISEASE; OLIGONUCLEOTIDE PROBES; ULCERATIVE-COLITIS; ANTIGENS; LESIONS; CELLS AB The role of inflammatory T cells in Crohn's disease suggests that inherited variations in major histocompatibility complex (MHC) class II genes may be of pathogenetic importance in inflammatory bowel disease, The absence of consistent and strong associations with MHC class II genes in Caucasian patients with inflammatory bowel disease probably reflects the use of less precise typing approaches and the failure to type certain loci by any means, A PCR-sequence-specific oligonucleotide-based approach was used to type individual alleles of the HLA class II DRB1, DRB3, DRB4, and DRB5 loci in 40 patients with ulcerative colitis, 42 Crohn's disease patients, and 93 ethnically matched healthy controls, Detailed molecular typing of the above alleles has previously not been reported in patients with inflammatory bowel disease, A highly significant positive association with the HLA-DRB3*0301 allele was observed in patients with Crohn's disease (P = 0.0004) but not in patients with ulcerative colitis, The relative risk for this association was 7.04, Other less significant HLA class II associations were also noted in patients with Crohn's disease. One of these associations involved the HLA-DRB1*1302 allele, which is known to be in linkage disequilibrium with HLA-DRB3*0301. These data suggest that a single allele of an infrequently typed HLA class II locus is strongly associated with Crohn's disease and that MHC class II molecules may be important in its pathogenesis. C1 MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,GASTROENTEROL UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. FU NIAID NIH HHS [AI-33507]; NIDDK NIH HHS [P30DK43351] NR 22 TC 51 Z9 53 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 14 PY 1996 VL 93 IS 10 BP 5094 EP 5098 DI 10.1073/pnas.93.10.5094 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UL255 UT WOS:A1996UL25500105 PM 8643533 ER PT J AU Sternini, C Su, D Arakawa, J DeGiorgio, R Rickman, DW Davis, BM Albers, KM Brecha, NC AF Sternini, C Su, D Arakawa, J DeGiorgio, R Rickman, DW Davis, BM Albers, KM Brecha, NC TI Cellular localization of Pan-trk immunoreactivity and trk(c) mRNA in the enteric nervous system SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE nerve growth factor; brain-derived neurotrophic factor; neurotrophin-3; tyrosine kinase receptor; gastrointestinal tract ID TYROSINE PROTEIN-KINASE; ADULT SENSORY NEURONS; GROWTH-FACTOR FAMILY; NEUROTROPHIC FACTOR; NEURAL CREST; MESSENGER-RNA; SUBSTANCE-P; RAT TRKC; PEPTIDE IMMUNOREACTIVITY; PROTOONCOGENE PRODUCT AB The members of the trk family of tyrosine receptor kinases, trk(A), trk(B), and trk(C), are the functional receptors for neurotrophins, a family of related neurotrophic factors. In this study, we investigated 1) the distribution of neurotrophin receptors in the developing and adult rat digestive tract with a pan-trk antibody that recognizes all known trks and 2) the cellular localization of trk-encoding mRNAs in the adult gut with single-stranded RNA probes specific for trh(A), trk(B), and trk(C). In the developing myenteric plexus, trk. immunoreactivity was present at embryonic day (ED) 14. Cells and fibers immunoreactive for trk could be visualized in the myenteric plexus at ED 16. At this age, dense staining was found in thick bundles of fibers in proximity to the myenteric plexus in the longitudinal muscle and in association with blood vessels in the mesentery. At ED 18, trk immunoreactivity was also seen in thin processes running from the myenteric plexus into the circular muscle, and in fibers and cells in intrapancreatic ganglia. By ED 20, immunoreactive staining was quite dense in both the myenteric and submucosal plexuses. At birth, virtually all enteric ganglia displayed strong trk immunoreactivity; the intensity of the staining at this age made it difficult to discern individual cells. During postnatal development, there was a decrease in cell body staining and an increase in the density of trk-containing fibers that became widely distributed to the gut wall and pancreas. The adult pattern of trk immunoreactivity was established between postnatal days 5 and 10. In adults, trk immunoreactivity was found in numerous enteric and intrapancreatic ganglion cells and in dense networks of fibers innervating all the layers of the gut, the pancreas, and vasculature. The trk(C) mRNA was expressed in adult enteric ganglion cells of both the myenteric and submucous plexus. By contrast, the trk(A) and trk(B) mRNAs could not be detected in enteric ganglia. Al three trk mRNAs were expressed in dorsal root ganglia, which were used as positive controls. The density and wide distribution of trk immunoreactivity together with its persistence in adulthood support the concept that neurotrophins play a broad role in the digestive system from development through adult Life, perhaps being involved in differentiation, phenotypic expression, and tissue maintenance. The presence of trk(C) mRNA in enteric neurons along with recent evidence that neurotrophin-3 plays a role in the development of the enteric nervous system suggest that trk(C) and neurotrophin-3 are a major neurotrophin system in the gastrointestinal tract. (C) 1996 Wiley-Liss, Inc. C1 UNIV CALIF LOS ANGELES,DEPT MED,DIGEST DIS RES CTR,CURE,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT NEUROBIOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST BRAIN RES,LOS ANGELES,CA 90024. UNIV KENTUCKY,MED CTR,DEPT ANAT & NEUROBIOL,LEXINGTON,KY 40536. UNIV KENTUCKY,MED CTR,DEPT PATHOL,LEXINGTON,KY 40536. RP Sternini, C (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIGEST DIS RES CTR,CURE,11301 WILSHIRE BLVD,BLDG 115,ROOM 203,LOS ANGELES,CA 90073, USA. OI De Giorgio, Roberto/0000-0003-0867-5873; Albers, Kathryn/0000-0003-4597-9323; Davis, Brian/0000-0002-4646-0569 FU NIDDK NIH HHS [DK 41301]; NINDS NIH HHS [NS 31826] NR 65 TC 30 Z9 30 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAY 13 PY 1996 VL 368 IS 4 BP 597 EP 607 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UH853 UT WOS:A1996UH85300010 PM 8744446 ER PT J AU Hurny, C Bernhard, J Coates, AS CastiglioneGertsch, M Peterson, HF Gelber, RD Forbes, JF Rudenstam, CM Simoncini, E Crivellari, D Goldhirsch, A Senn, HJ AF Hurny, C Bernhard, J Coates, AS CastiglioneGertsch, M Peterson, HF Gelber, RD Forbes, JF Rudenstam, CM Simoncini, E Crivellari, D Goldhirsch, A Senn, HJ TI Impact of adjuvant therapy on quality of life in women with node-positive operable breast cancer SO LANCET LA English DT Article ID OF-LIFE; RECEIVING END; CHEMOTHERAPY; TRIAL; ADJUSTMENT AB Background Adjuvant therapy for early breast cancer is effective but may be toxic. Our aim was to investigate the impact of the presence, timing, and duration of adjuvant chemotherapy on patients' perceptions of their quality of life (QL). Methods International Breast Cancer Study Group trial VI assessed adjuvant chemotherapy in 1475 premenopausal and perimenopausal patients, and trial VII assessed adjuvant tamoxifen or chemoendocrine therapy in 1212 postmenopausal patients with node-positive breast cancer. Patients were asked to complete a QL questionnaire-single-item linear analogue self-assessment scales measured physical wellbeing, mood, appetite, and perceived adjustment/coping. QL was assessed in this way at the beginning of treatment, 2 months after the start of treatment, every 3 months, and at 1 and 6 months after recurrence. Findings Baseline QL scores decreased as the number of involved axillary nodes increased (for example, mean mood score: 66.1 for women with one positive node, 66.4 for two to four positive nodes, 61.3 for five to nine positive nodes, and 59.1 for ten or more positive nodes; p=0.008 for trends), and were lower in patients with oestrogen-receptor-negative than in patients with oestrogen-receptor-positive tumours (61.4 vs 66.3, p=0.0009). AII treatment groups showed substantial improvement in QL scores during adjuvant therapy. Patterns of QL scores reflected presence, duration, and timing of cytotoxic treatment. Longer initial cytotoxic therapy delayed improvement in QL scores. Later cytotoxic therapy had transient adverse effects. Anticipation of future therapy also affected QL scores. Interpretation Overall, chemotherapy had a measurable adverse effect on QL, but this effect was transient and minor compared with patients' adaptation/coping after diagnosis and surgery. This finding should encourage patients and doctors to choose appropriate adjuvant therapy with less concern for initial toxicity. C1 ROYAL PRINCE ALFRED HOSP,DEPT MED ONCOL,CAMPERDOWN,NSW 2050,AUSTRALIA. UNIV BERN,INSELSPITAL,MED DIV LORY,CH-3010 BERN,SWITZERLAND. IBCSG,COORDINATING CTR,BERN,SWITZERLAND. HARVARD UNIV,SCH PUBL HLTH,DANA FARBER CANC INST,IBCSG STAT CTR,DIV BIOSTAT & EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. MATER MISERICORDIAE HOSP,HUNTER ONCOL CTR,WARATAH,NSW,AUSTRALIA. GOTHENBURG UNIV,SAHLGRENS HOSP,DEPT SURG,S-41345 GOTHENBURG,SWEDEN. SPEDALE CIVILLI,SERV ONCOL,FDN BERETTA,BRESCIA,ITALY. CTR RIFERIMENTO ONCOL,I-33081 AVIANO,ITALY. OSPED CIVICO,SERV ONCOL,LUGANO,SWITZERLAND. KANTONSSPITAL,ST GALLEN,SWITZERLAND. NR 32 TC 131 Z9 131 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 11 PY 1996 VL 347 IS 9011 BP 1279 EP 1284 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UK758 UT WOS:A1996UK75800007 PM 8622502 ER PT J AU Spiro, RG Zhu, Q Bhoyroo, V Soling, HD AF Spiro, RG Zhu, Q Bhoyroo, V Soling, HD TI Definition of the lectin-like properties of the molecular chaperone, calreticulin, and demonstration of its copurification with endomannosidase from rat liver Golgi SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-LINKED OLIGOSACCHARIDES; ALPHA-D-MANNOSIDASE; ENDOPLASMIC-RETICULUM; GLYCOPROTEIN-BIOSYNTHESIS; BINDING-PROTEIN; GLUCOSE; COMPLEX; CELLS; GLYCOSYLATION; MATURATION AB Calreticulin was identified by immunochemical and sequence analyses to be the higher molecular mass (60 kDa) component of the polypeptide doublet previously observed in a rat liver Golgi endomannosidase preparation obtained by chromatography on a Glc alpha 1-->3Man-containing matrix. The affinity for this saccharide ligand, which paralleled that of endomannosidase and was also observed with purified rat liver calreticulin, suggested that this chaperone has lectin-like binding properties. Studies carried out with immobilized calreticulin and a series of radiolabeled oligosaccharides derived from N-linked carbohydrate units revealed that interactions with this protein were limited to monoglucosylated polymannose components. Although optimal binding occurred with Glc(1)Man(9)GlcNAc, substantial interaction with calreticulin was retained after sequential trimming of the polymannose portion down to the Glc(1)Man(5)GlcNAc stage. The alpha 1-->6-mannose branch point of the oligosaccharide core, however, appeared to be essential for recognition as Glc(1)Man(4)GlcNAc did not interact with the calreticulin. The carbohydrate-peptide linkage region had no discernible influence on binding as monoglucosylated oligosaccharides in N-glycosidic linkage interacted with the chaperone to the same extent as in their unconjugated state. The immobilized calreticulin proved to be a highly effective tool for sorting out monoglucosylated polymannose oligosaccharides or glycopeptides from complex mixtures of processing intermediates. The copurification of calreticulin and endomannosidase from a Golgi fraction in comparable amounts and the strikingly similar saccharide specificities of the chaperone and the processing enzyme have suggested a tentative model for the dissociation through glucose removal of calreticulin-glycoprotein complexes in a post-endoplasmic reticulum locale; in this scheme, deglucosylation would be brought about by the action of endomannosidase rather than glucosidase II. C1 HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. UNIV GOTTINGEN,ZENTRUM INNERE MED,BIOCHEM ABT,D-3400 GOTTINGEN,GERMANY. RP Spiro, RG (reprint author), JOSLIN DIABET CTR,ELLIOTT P JOSLIN RES LAB,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [DK 17325, DK 17477] NR 51 TC 227 Z9 230 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 10 PY 1996 VL 271 IS 19 BP 11588 EP 11594 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ944 UT WOS:A1996UJ94400082 PM 8626722 ER PT J AU Pritchard, ML Saunders, AM Gaskell, PC Small, GW Conneally, PM Rosi, B Yamaoka, LH Roses, AD Haines, JL PericakVance, MA AF Pritchard, ML Saunders, AM Gaskell, PC Small, GW Conneally, PM Rosi, B Yamaoka, LH Roses, AD Haines, JL PericakVance, MA TI No association between very low density lipoprotein receptor (VLDL-R) and Alzheimer disease in American Caucasians SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer disease; very low density lipoprotein receptor gene; association; apolipoprotein-epsilon ID LINKAGE ANALYSIS; ALLELE AB The very low density lipoprotein receptor gene (VLDL-R) is a receptor for apolipoprotein-epsilon (APOE)-containing lipoproteins, and thus has been suggested as a possible risk factor for Alzheimer disease (AD). Recently, Okuizumi et al. [Nature Genet., 11 (1995) 207-209] reported an association between the 96 bp allele at the VLDL-R locus and AD in a Japanese population. The association resulted in a two-fold increase of risk that decreased with increasing age, We have examined this association in 316 Caucasian sporadic AD patients, comparing their findings to 160 Caucasian AD spouse controls. We also investigated 53 late-onset Caucasian AD families for association and linkage. Our data failed to confirm linkage and/or association to the VLDL-R locus. Stratification by age at onset or APOE genotype also failed to show significant results. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. INDIANA UNIV,DEPT MED GENET,INDIANAPOLIS,IN 46204. MASSACHUSETTS GEN HOSP,MOL NEUROGENET UNIT,BOSTON,MA. RI Haines, Jonathan/C-3374-2012 FU NIA NIH HHS [AG05128, U24 AG021886]; NINDS NIH HHS [NS26630, NS531153] NR 14 TC 26 Z9 26 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 MAY 10 PY 1996 VL 209 IS 2 BP 105 EP 108 DI 10.1016/0304-3940(96)12630-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UM747 UT WOS:A1996UM74700009 PM 8761993 ER PT J AU Xanthoudakis, S Viola, JPB Shaw, KTY Luo, C Wallace, JD Bozza, PT Curran, T Rao, A AF Xanthoudakis, S Viola, JPB Shaw, KTY Luo, C Wallace, JD Bozza, PT Curran, T Rao, A TI An enhanced immune response in mice lacking the transcription factor NFAT1 SO SCIENCE LA English DT Article ID ACTIVATED T-CELLS; CYCLOSPORINE-A; NUCLEAR FACTOR; GENE; IDENTIFICATION; LYMPHOCYTE; COMPLEX; DISEASE AB Transcription factors of the NFAT family are thought to play a major role in regulating the expression of cytokine genes and other inducible genes during the immune response. The role of NFAT1 was investigated by targeted disruption of the NFAT1 gene. Unexpectedly, cells from NFAT1(-/-) mice showed increased primary responses to Leishmania major and mounted increased secondary responses to ovalbumin in vitro. In an in vivo model of allergic inflammation, the accumulation of eosinophils and levels of serum immunoglobulin E were increased in NFAT1(-/-) mice. These results suggest that NFAT1 exerts a negative regulatory influence on the immune response. C1 ST JUDE CHILDRENS RES HOSP, DEPT DEV NEUROBIOL, MEMPHIS, TN 38105 USA. HOFFMANN LA ROCHE INC, DEPT CNS RES, NEUROGENET PROGRAM, NUTLEY, NJ 07110 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, DIV CELLULAR & MOLEC BIOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, HARVARD THORNDIKE LAB, BOSTON, MA 02115 USA. HARVARD UNIV, BETH ISRAEL HOSP,SCH MED,CHARLES A DANA RES INST, SCH MED, BOSTON, MA 02115 USA. RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011 OI Curran, Tom/0000-0003-1444-7551; FU NCI NIH HHS [CA42471, P30 CA21765]; NIGMS NIH HHS [GM46227] NR 54 TC 281 Z9 285 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAY 10 PY 1996 VL 272 IS 5263 BP 892 EP 895 DI 10.1126/science.272.5263.892 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK757 UT WOS:A1996UK75700065 PM 8629027 ER PT J AU Jacobson, AM AF Jacobson, AM TI Current concepts - The psychological care of patients with insulin-dependent diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID METABOLIC CONTROL; ADOLESCENTS; MANAGEMENT; DEPRESSION; CHILDREN; IDDM; INTERVENTIONS; PREVALENCE; EDUCATION; DISORDERS C1 HARVARD UNIV, SCH MED, DEPT PSYCHIAT, BOSTON, MA 02115 USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. FU NIDDK NIH HHS [DK 42315, DK 27845] NR 67 TC 89 Z9 93 U1 2 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 9 PY 1996 VL 334 IS 19 BP 1249 EP 1253 DI 10.1056/NEJM199605093341907 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA UJ054 UT WOS:A1996UJ05400007 PM 8606721 ER PT J AU Wood, PD Redmond, RW AF Wood, PD Redmond, RW TI Triplet state interactions between nucleic acid bases in solution at room temperature: Intermolecular energy and electron transfer SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID STRAND BREAK FORMATION; AQUEOUS-SOLUTION; LASER PHOTOLYSIS; PYRIMIDINE-BASES; PULSE-RADIOLYSIS; REDOX CHEMISTRY; QUANTUM YIELDS; 248 NM; DNA; NUCLEOSIDES AB This study aims to provide information on the fate of triplet energy in DNA by considering the triplet-mediated reactions which occur between nucleic acid bases in solution, at room temperature. Following sensitization of base triplet states by acetone, the subsequent photophysics and photochemistry are highly dependent on the nature of the nucleotide pair under study. By establishing the direction of triplet energy transfer between pairs of mononucleotides, the relative triplet energy ordering was determined under physiologically relevant conditions, i.e. aqueous solution at room temperature. This order (C > U > G > A > T) is in agreement with that previously reported which was obtained at 77 K in rigid media. The absolute value for TMP triplet energy has been estimated as 310 kJ mol(-1), based on triplet energy transfer studies involving acetophenone and 3-methoxyacetophenone. Determination of the triplet energy gaps between all mononucleotides, to within 1 kJ mol(-1), has allowed an estimation of the absolute values of CMP (321 kJ mol(-1)), UMP (320 kJ mol(-1)), GMP (317 kJ mol(-1)), and AMP (314 kJ mol(-1)). The energy gaps between the triplet states are smaller than those reported at low temperature. This allows triplet energy transfer equilibria to be established in which a significant proportion of both triplets is present, unless thymine is present, in which case the dominant process is triplet energy transfer to the thymine. In any purine/pyrimidine (not thymine) pair, electron transfer from purine to pyrimidine is significant, producing the purine radical cation, which rapidly deprotonates to give the neutral radical. This process is most efficient for the guanosine-uracil combination and our evidence suggests that it is the purine triplet state which initiates the electron transfer. In the guanosine-adenosine system, there is no evidence of electron transfer and net triplet energy transfer is low due to a small triplet energy gap. This results in a relatively high proportion of both triplet states being observed in the equilibrium. These results show that DNA photochemistry should be highly sequence dependent and may have significance regarding the existence of ''hot spots'' in DNA photoproduct formation. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 41 TC 81 Z9 82 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 8 PY 1996 VL 118 IS 18 BP 4256 EP 4263 DI 10.1021/ja954340+ PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA UK145 UT WOS:A1996UK14500005 ER PT J AU Raab, M Rudd, CE AF Raab, M Rudd, CE TI Hematopoietic cell phosphatase (HCP) regulates p56(LCK) phosphorylation and ZAP-70 binding to T cell receptor zeta chain SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROTEIN-TYROSINE KINASE; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; CD4 RECEPTOR; SH2 DOMAINS; MOTH-EATEN; ACTIVATION; P56LCK; MUTATIONS; COMPLEX AB Ligation of the T cell receptor complex and CD4 leads to activation of the protein tyrosine kinases p56(lck) and p59(fyn) resulting in phosphorylation of TcR zeta chain and the recruitment of ZAP-70. In this study, we have reconstituted p56(lck) phosphorylation of TcR zeta and ZAP-70 recruitment in heterologous cells and examined the role of the tyrosine phosphatase HCP in regulating the process. Both p56(lck) and p59(fyn) induce significant phosphorylation of TcR zeta. However, under conditions of comparable p56(lck) and p59(fyn) expression, p56(lck) was found to induce three to four fold greater in vivo phosphorylation of TcR zeta. HCP dephosphorylated p56(lck), ZAP-70 and the TcR zeta chain. Further, dephosphorylation of the different TcR zeta isoforms results in disruption of the interaction between TcR zeta and ZAP-70. These results indicate that HCP acts to negatively regulate signal transduction pathways in T cells. (C) 1996 Academic Press, Inc. C1 DANA FARBER CANC INST,DIV TUMOR IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 40 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 6 PY 1996 VL 222 IS 1 BP 50 EP 57 DI 10.1006/bbrc.1996.0696 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UJ625 UT WOS:A1996UJ62500009 PM 8630073 ER PT J AU Sun, XJ Pons, S Asano, T Myers, MG Glasheen, E White, MF AF Sun, XJ Pons, S Asano, T Myers, MG Glasheen, E White, MF TI The fyn tyrosine kinase binds Irs-1 and forms a distinct signaling complex during insulin stimulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-SRC ACTIVITY; HEMATOPOIETIC-CELLS; CATALYTIC ACTIVITY; SH3 DOMAINS; MUTANT MICE; RECEPTOR; PROTEIN; PHOSPHORYLATION; ASSOCIATION; EXPRESSION AB Irs-proteins link the receptors for insulin/IGF-1, growth hormones, and several interleukins and interferons to signaling proteins that contain Src homology-2 (SH2). To identify new Irs-1-binding proteins, we screened a mouse embryo expression library with recombinant [P-32]Irs-1, which revealed a specific association between p59(fyn) and Irs-1. The SH2 domain in p59(fyn) bound to phosphorylated Tyr(895) and Tyr(1172), which are located in YXX(L/I) motifs. Mutation of p59(fyn) at the COOH-terminal tyrosine phosphorylation site (Tyr(531)) enhanced its binding to Irs-1 during insulin stimulation. Binding experiments with various SH2 proteins revealed that Grb-2 was largely excluded from Irs-1 complexes containing p59(fyn), whereas Grb-2 and p85 occurred in the same Irs-1 complex, By comparison with the insulin receptor, p59(fyn) kinase phosphorylated a unique cohort of tyrosine residues in Irs-1. These results outline a role for p59(fyn) or other related Src-kinases during insulin and cytokine signaling. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,PROGRAM CELL & DEV BIOL,BOSTON,MA 02215. RI Pons , Sebastian/K-7794-2014 OI Pons , Sebastian/0000-0003-1027-0621 FU NIDDK NIH HHS [DK 43808, DK38712] NR 47 TC 104 Z9 105 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10583 EP 10587 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200027 PM 8631859 ER PT J AU Hu, E Liang, P Spiegelman, BM AF Hu, E Liang, P Spiegelman, BM TI AdipoQ is a novel adipose-specific gene dysregulated in obesity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PULMONARY SURFACTANT APOPROTEIN; RESPONSIVE GLUCOSE TRANSPORTER; MESSENGER-RNA CONTENT; TUMOR-NECROSIS-FACTOR; GROWTH FACTOR-I; 3T3-L1 CELLS; BINDING-PROTEIN; DIFFERENTIAL DISPLAY; ELECTRON-MICROSCOPY; CLASSICAL PATHWAY AB Adipose differentiation is accompanied by changes in cellular morphology, a dramatic accumulation of intracellular lipid and activation of a specific program of gene expression, Using an mRNA differential display technique, we have isolated a novel adipose cDNA, termed adipoQ. The adipoQ cDNA encodes a polypeptide of 247 amino acids with a secretory signal sequence at the amino terminus, a collagenous region (Gly-X-Y repeats), and a globular domain. The globular domain of adipoQ shares significant homology with subunits of complement factor Clq, collagen alpha 1(X), and the brain-specific factor cerebellin, The expression of adipoQ is highly specific to adipose tissue in both mouse and rat, Expression of adipoQ is observed exclusively in mature fat cells as the stromal-vascular fraction of fat tissue does not contain adipoQ mRNA. In cultured 3T3-F442A and 3T3-L1 preadipocytes, hormone-induced differentiation dramatically increases the level of expression for adipoQ, Furthermore, the expression of adipoQ mRNA is significantly reduced in the adipose tissues from obese mice and humans. Whereas the biological function of this polypeptide is presently unknown, the tissue-specific expression of a putative secreted protein suggests that this factor may function as a novel signaling molecule for adipose tissue. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MOLEC PHARMACOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK42539] NR 68 TC 1406 Z9 1488 U1 4 U2 42 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10697 EP 10703 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200045 PM 8631877 ER PT J AU Loh, C Shaw, KTY Carew, J Viola, JPB Luo, C Perrino, BA Rao, A AF Loh, C Shaw, KTY Carew, J Viola, JPB Luo, C Perrino, BA Rao, A TI Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLOSPORINE-A; LYMPHOCYTES-T; PHOSPHATASE-ACTIVITY; MESSENGER-RNA; ACTIVATION; PROTEIN; FK506; TARGET; FK-506; COMPLEXES AB NFAT1 (previously termed NFATp) is a cytoplasmic transcription factor involved in the induction of cytokine genes. We have previously shown that the dephosphorylation of NFAT1, accompanied by its nuclear translocation and increased DNA binding activity, is regulated by calcium- and calcineurin-dependent mechanisms, as each of these hallmarks of NFAT1 activation is elicited by ionomycin and blocked by the immunosuppressive drugs cyclosporin A and FK506 (Shaw, K. T.-Y., Ho, A. M., Raghavan, A., Kim, J., Jain, J., Park, J., Sharma, S., Rao, A., and Hogan, P. G. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 11205-11209). Here we show that the activation state of NFAT1 in T cells is remarkably sensitive to the level of calcineurin activity. Addition of cyclosporin A, even in the presence of ongoing ionomycin stimulation, results in rephosphorylation of NFAT1, its reappearance in the cytoplasm, and a return of its DNA binding activity to low levels. Similar effects are observed upon removal of ionomycin or addition of EGTA. We also demonstrate a direct interaction between calcineurin and NFAT1 that is consistent with a direct enzyme-substrate relation between these two proteins and that may underlie the sensitivity of NFAT1 activation to the level of calcineurin activity. The NFAT1-calcineurin interaction, which involves an N-terminal region of NFAT1 conserved in other NFAT family proteins, may provide a target for the design of novel immunosuppressive drugs. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MOL & CELLULAR BIOL,BOSTON,MA 02115. OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201. FU NCI NIH HHS [CA42471]; NIGMS NIH HHS [GM46227] NR 54 TC 242 Z9 248 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 3 PY 1996 VL 271 IS 18 BP 10884 EP 10891 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ342 UT WOS:A1996UJ34200072 PM 8631904 ER PT J AU Ishii, H Jirousek, MR Koya, D Takagi, C Xia, P Clermont, A Bursell, SE Kern, TS Ballas, LM Heath, WF Stramm, LE Feener, EP King, GL AF Ishii, H Jirousek, MR Koya, D Takagi, C Xia, P Clermont, A Bursell, SE Kern, TS Ballas, LM Heath, WF Stramm, LE Feener, EP King, GL TI Amelioration of vascular dysfunctions in diabetic rats by an oral PKC beta inhibitor SO SCIENCE LA English DT Article ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; RETINAL CIRCULATION; PHORBOL ESTERS; ANGIOTENSIN-II; GLUCOSE; AUTOPHOSPHORYLATION; MICROALBUMINURIA; STAUROSPORINE AB The vascular complications of diabetes mellitus have been correlated with enhanced activation of protein kinase C (PKC). LY333531, a specific inhibitor of the beta isoform of PKC, was synthesized and was shown to be a competitive reversible inhibitor of PKC beta(1) and beta(2), with a half-maximal inhibitory constant of similar to 5 nM; this value was one-fiftieth of that for other PKC isoenzymes and one-thousandth of that for non-PKC kinases. When administered orally, LY333531 ameliorated the glomerular filtration rate, albumin excretion rate, and retinal circulation in diabetic rats in a dose-responsive manner, in parallel with its inhibition of PKC activities. C1 BRIGHAM & WOMENS HOSP,DEPT MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. UNIV WISCONSIN,DEPT OPHTHALMOL,MADISON,WI 53706. SPHINX PHARMACEUT,DURHAM,NC 27707. RI Xia, Pu/G-3090-2010; Koya, Daisuke /J-3257-2014 OI Xia, Pu/0000-0003-4705-8878; FU NEI NIH HHS [EY05110-11]; NIDDK NIH HHS [P30 DK036836, DK36836] NR 36 TC 881 Z9 913 U1 1 U2 25 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 3 PY 1996 VL 272 IS 5262 BP 728 EP 731 DI 10.1126/science.272.5262.728 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UJ051 UT WOS:A1996UJ05100053 PM 8614835 ER PT J AU Brennick, J Mattia, A AF Brennick, J Mattia, A TI Strongyloides stercoralis Infestation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article RP Brennick, J (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 2 PY 1996 VL 334 IS 18 BP 1173 EP 1173 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UG831 UT WOS:A1996UG83100006 PM 8602184 ER PT J AU Ubel, PA DeKay, ML Baron, J Asch, DA AF Ubel, PA DeKay, ML Baron, J Asch, DA TI Cost-effectiveness analysis in a setting of budget constraints - Is it equitable? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEALTH-CARE PRIORITIES; OREGON AB Background. One of the promises of cost-effectiveness analysis is that it can demonstrate how to maximize health benefits attainable within a specific limited budget. Many people argue, however, that when there are budget limitations, the use of cost-effectiveness analysis leads to health care policies that are inequitable. Methods. We asked prospective jurors, medical ethicists, and experts in medical decision making to choose between two screening tests for a population at low risk for colon cancer. One test was more cost effective than the other but because of budget constraints was too expensive to be given to everyone in the population. With the use of the more effective test for only half the population, 1100 lives could be saved at the same cost as that of saving 1000 lives with the use of the less effective test for the entire population. Results. Fifty-six percent of the prospective jurors, 53 percent of the medical ethicists, and 41 percent of the experts in medical decision making recommended offering the less effective screening test to everyone, even though 100 more lives would have been saved by offering the more expensive test to only a portion of the population, Most of the study participants justified this recommendation on the basis of equity, A smaller number stated either that it was not politically feasible to offer a test to only half the population or that the additional benefit of the more expensive test (100 more lives saved) was too small to justify offering it to only a portion of the public. Conclusions. People place greater importance on equity than is reflected by cost-effectiveness analysis, Even many experts in medical decision making - those often responsible for conducting cost-effectiveness analyses - expressed discomfort with some of its implications, Basing health care priorities on cost effectiveness may not be possible without incorporating explicit considerations of equity into cost-effectiveness analyses or the process used to develop health care policies on the basis of such analyses. (C) 1996, Massachusetts Medical Society. C1 VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,LEONARD DAVIS INST HLTH ECON,PHILADELPHIA,PA 19104. UNIV PENN,WHARTON SCH,DEPT OPERAT & INFORMAT MANAGEMENT,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PSYCHOL,PHILADELPHIA,PA 19104. RP Ubel, PA (reprint author), UNIV PENN,SCH MED,DIV GEN INTERNAL MED,CTR BIOETH,3401 MKT ST,SUITE 320,PHILADELPHIA,PA 19104, USA. NR 21 TC 127 Z9 127 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 2 PY 1996 VL 334 IS 18 BP 1174 EP 1177 DI 10.1056/NEJM199605023341807 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA UG831 UT WOS:A1996UG83100007 PM 8602185 ER PT J AU Shoptaw, S Jarvik, ME Ling, W Rawson, RA AF Shoptaw, S Jarvik, ME Ling, W Rawson, RA TI Contingency management for tobacco smoking in methadone-maintained opiate addicts SO ADDICTIVE BEHAVIORS LA English DT Article ID MAINTENANCE AB Seventeen methadone-maintained cigarette smokers received 4 weeks of contingency management (CM) as a stop-smoking intervention. Results indicated that CM patients significantly reduced breath CO levels from baseline to completion of treatment and that 23.4% of patients maintained 1 week or more of continued smoking abstinence. Results indicated a link between smoking abstinence and reduced cocaine use, although not reduced opiate use, which raised questions about possible shared biological and psychological mechanisms for tobacco and cocaine use. C1 LOS ANGELES ADDICT TREATMENT RES CTR,LOS ANGELES,CA 90025. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. OI Shoptaw, Steven/0000-0002-3583-0026 NR 7 TC 76 Z9 77 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAY-JUN PY 1996 VL 21 IS 3 BP 409 EP 412 DI 10.1016/0306-4603(95)00066-6 PG 4 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA UL906 UT WOS:A1996UL90600012 PM 8883490 ER PT J AU Harrer, T Harrer, E Kalams, SA Elbeik, T Staprans, SI Feinberg, MB Cao, YZ Ho, DD Yilma, T Caliendo, AM Johnson, RP Buchbinder, SP Walker, BD AF Harrer, T Harrer, E Kalams, SA Elbeik, T Staprans, SI Feinberg, MB Cao, YZ Ho, DD Yilma, T Caliendo, AM Johnson, RP Buchbinder, SP Walker, BD TI Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY VIRUS TYPE-1; LYMPHOCYTES-T; INCUBATION PERIOD; FINE SPECIFICITY; HOMOSEXUAL MEN; BLOOD; AIDS; QUANTITATION; ANTIGENS AB Some individuals in well-defined cohorts have now been infected with HIV-1 for well over a decade and yet remain clinically asymptomatic with normal CD4 counts, To determine immunologic and virologic parameters in these individuals, we examined 10 persons from the San Francisco City Clinic with firmly documented infection of 11-15 years duration who had maintained stable CD4 counts above 500 cells/mu l. Our results indicate that long-term nonprogressors are a heterogeneous group with respect to viral load and HIV-l-specific immune responses, and that progression can occur even after 15 years of stable infection, However, in a subset of persons with the lowest viral loads and persistent nonprogressive infection, we detected strong CTL responses, whereas neutralizing antibody studies revealed weak to undetectable titers against a panel of 10 primary isolates, This study demonstrates that a vigorous irt vivo activated HIV-1-specific CTL response can be part of the host immune response in stable nonprogressive HIV-1 infection, and that circulating activated CTL can be detected in the setting of an extremely low viral load, These results also indicate that long-term nonprogressing HIV-1 infection does not require the presence of broadly cross-reactive neutralizing antibodies. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. UNIV CALIF SAN FRANCISCO,CTR AIDS RES,SAN FRANCISCO,CA 94141. GLADSTONE INST,SAN FRANCISCO,CA 94141. AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. UNIV CALIF DAVIS,DAVIS,CA 95616. DEPT PUBL HLTH,AIDS OFF,SAN FRANCISCO,CA 94140. RP Harrer, T (reprint author), MASSACHUSETTS GEN HOSP,AIDS RES CTR,BOSTON,MA 02114, USA. OI Elbeik, Tarek/0000-0001-5983-0867 FU NIAID NIH HHS [AI28568, AI30194] NR 34 TC 262 Z9 265 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1996 VL 12 IS 7 BP 585 EP 592 DI 10.1089/aid.1996.12.585 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UF722 UT WOS:A1996UF72200005 PM 8743084 ER PT J AU Roberts, CGP Meister, GE Jesdale, BM Lieberman, J Berzofsky, JA DeGroot, AS AF Roberts, CGP Meister, GE Jesdale, BM Lieberman, J Berzofsky, JA DeGroot, AS TI Prediction of HIV peptide epitopes by a novel algorithm SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL EPITOPES; MHC CLASS-II; SEROPOSITIVE INDIVIDUALS; NEF PROTEIN; REVERSE-TRANSCRIPTASE; SYNTHETIC PEPTIDES; FINE SPECIFICITY; ENVELOPE PROTEIN AB Identification of promiscuous or multideterminant T cell epitopes is essential for HIV vaccine development, however, current methods for T cell epitope identification are both cost intensive and labor intensive, We have developed a computer-driven algorithm, named EpiMer, which searches protein amino acid sequences for putative MHC class I- and/or class II-restricted T cell epitopes. This algorithm identifies peptides that contain multiple MHC-binding motifs from protein sequences, To evaluate the predictive power of EpiMer, the amino acid sequences of the HIV-1 proteins nef, gp160, gag p55, and tat were searched for regions of MHC-binding motif clustering, We assessed the algorithm's predictive power by comparing the EpiMer-predicted peptide epitopes to T cell epitopes that have been published in the literature, The EpiMer method of T cell epitope identification was compared to the standard method of synthesizing short, overlapping peptides and testing them for immunogenicity (overlapping peptide method), and to an alternate algorithm that has been used to identify putative T cell epitopes from primary structure (AMPHI). For the four HIV-1 proteins analyzed, the in vitro testing of EpiMer peptides for immunogenicity would have required the synthesis of fewer total peptides than either AMPHI or the overlapping peptide method, The EpiMer algorithm proved to be more efficient and more sensitive per amino acid than both the overlapping peptide method and AMPHI, The EpiMer predictions for these four HIV proteins are described, Since EpiMer-predicted peptides have the potential to bind to multiple MHC alleles, they are strong candidates for inclusion in a synthetic HIV vaccine. C1 BROWN UNIV,SCH MED,DIV BIOL & MED,TB HIV RES LAB,PROVIDENCE,RI 02912. HARVARD UNIV,MED CTR,CTR BLOOD RES,BOSTON,MA 02112. NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. MIRIAM HOSP,DEPT GEOG MED & CLIN IMMUNOL,PROVIDENCE,RI 02906. RI De Groot, Anne/B-6221-2013; Lieberman, Judy/A-2717-2015 OI De Groot, Anne/0000-0001-5911-1459; FU NCI NIH HHS [R08 CA01449]; NIAID NIH HHS [R01 AI35271, U19 AI36611] NR 86 TC 31 Z9 31 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY 1 PY 1996 VL 12 IS 7 BP 593 EP 610 DI 10.1089/aid.1996.12.593 PG 18 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UF722 UT WOS:A1996UF72200006 PM 8743085 ER PT J AU Nguyen, PL Zukerberg, LR Benedict, WF Harris, NL AF Nguyen, PL Zukerberg, LR Benedict, WF Harris, NL TI Immunohistochemical detection of p53, bcl-2, and retinoblastoma proteins in follicular lymphoma SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE p53; bcl-2; retinoblastoma protein; apoptosis; programmed cell death; cell cycle; lymphoma; follicle center; cytologic grade ID T(14-18) CHROMOSOMAL TRANSLOCATION; NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMAS; GENE-MUTATIONS; EXPRESSION; CANCER; PROGRESSION; ONCOGENE; PRODUCT AB Mutations of p53 have been suggested to be involved in the histologic transformation of follicular lymphoma, but the role of the retinoblastoma (RE) gene, another tumor suppressor gene, in lymphomagenesis has not been established. To determine the roles of these tumor suppressor genes and their relationship with the anti-apoptotic bcl-2 gene in follicle center lymphoma, the immunohistochemical expression of p53, bcl-2, and RE proteins was correlated with cytologic grade in 50 cases of follicular lymphoma, and the results were compared to 23 cases of diffuse large B-cell lymphoma. The results showed that only 2 of 25 grade 1 follicular lymphoma were p53-positive compared to 16 of 25 grade 3 cases (P <.0001). A significantly lower number (13 of 25) of grade 3 follicular lymphomas expressed bcl-2 compared to grade 1 cases (23 of 25) (P <.004). Eight of 14 bcl-2-negative follicular lymphomas expressed p53, compared with 10 of 36 bcl-2-positive cases (P = .1). Twenty-four of 25 grade 3 follicular lymphomas showed 2+ to 3+ staining for RE protein compared to 9 of 21 grade 1 cases (P <.0002). Expression of p53 protein correlates significantly with higher cytologic grade in follicular lymphoma, Similar to earlier studies of breast cancer and lymphoma, there appears to be an inverse relationship between p53 and bcl-2 expression in follicular lymphoma, Inactivation of the retinoblastoma gene does not seem to be involved in the histogenesis of follicle center lymphoma or diffuse large B-cell lymphoma. C1 BAYLOR COLL MED,CTR BIOTECHNOL,THE WOODLANDS,TX 77381. RP Nguyen, PL (reprint author), HARVARD UNIV,DEPT PATHOL,MASSACHUSETTS GEN HOSP,SCH MED,WARREN 2,32 FRUIT ST,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA54672] NR 31 TC 39 Z9 40 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1996 VL 105 IS 5 BP 538 EP 543 PG 6 WC Pathology SC Pathology GA UK278 UT WOS:A1996UK27800004 PM 8623759 ER PT J AU Sorensen, G Stoddard, A Hammond, SK Hebert, JR Avrunin, JS Ockene, JK AF Sorensen, G Stoddard, A Hammond, SK Hebert, JR Avrunin, JS Ockene, JK TI Double jeopardy: Workplace hazards and behavioral risks for craftspersons and laborers SO AMERICAN JOURNAL OF HEALTH PROMOTION LA English DT Article DE cancer prevention and control; worksites; health protection; health promotion; smoking; occupational health ID CIGARETTE-SMOKING; LUNG-CANCER; GUIDELINES; WORKSITE; SEX AB Purpose. To address three specific questions in a sample of craftspersons and laborers: (1) Do craftspersons and laborers exposed to workplace hazards have higher behavioral risks, such as smoking and high-fat diets, than those with few job risks? (2) Compared to workers with few job risks, do workers exposed to risks on the job have higher intentions to reduce their behavioral risks? (3) Does concern about the level of exposure to risks on the job increase workers' intentions to reduce behavioral risks? Design. A cross-sectional self-administered survey was conducted in participating worksites. Setting. Twenty-two predominantly manufacturing worksites in Massachusetts. Subjects. Craftspersons and laborers responding to the survey and employed in these 22 worksites (completion rate = 61%, N = 1841). Measures. By using standardized items, this survey measured self-reported exposure to workplace hazards, concern about job exposures, smoking status, fat and fiber intake, readiness to quit smoking, plans to reduce fat intake, plans to eat more fruits and vegetables, and sociodemographic variables. Results. Workers reporting exposure to chemical hazards on the job were significantly more likely to be smokers than were unexposed workers, even when results were controlled for gender. Compared with unexposed workers, smokers exposed to chemical hazards were significantly more likely to be thinking of quitting or taking action to quit, when results were controlled for gender, race, and education. Among workers exposed to occupational chemical hazards, concern about this exposure was significantly associated with intentions to decrease fat intake and increase fruit and vegetable intake, and, among men, intentions to quit smoking. Conclusions. Efforts aimed at integrating health promotion and health protection are needed to address simultaneously the job risks and personal risks these workers face. C1 HARVARD UNIV, SCH PUBL HLTH, BOSTON, MA 02115 USA. UNIV MASSACHUSETTS, SCH PUBL HLTH, AMHERST, MA 01003 USA. UNIV MASSACHUSETTS, SCH MED, WORCESTER, MA USA. RP CHILDRENS HOSP, DANA FARBER CANC INST, DIV CANC EPIDEMIOL & CONTROL, 44 BINNEY ST, BOSTON, MA 02115 USA. FU NCI NIH HHS [UOC CA51686] NR 28 TC 43 Z9 43 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-1171 EI 2168-6602 J9 AM J HEALTH PROMOT JI Am. J. Health Promot. PD MAY-JUN PY 1996 VL 10 IS 5 BP 355 EP 363 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UK778 UT WOS:A1996UK77800005 PM 10163305 ER PT J AU Jannsen, RK Murphy, CM Kendzierski, DL Brown, DH Carter, BL Furmaga, EM Schoen, MD Woker, DR AF Jannsen, RK Murphy, CM Kendzierski, DL Brown, DH Carter, BL Furmaga, EM Schoen, MD Woker, DR TI Ambulatory care certificate program for pharmacists SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE ambulatory care; certification; curriculum; department of veterans affairs; education, pharmaceutical; military; pharmaceutical care; pharmacists; United States Navy AB An ambulatory care certificate program tailored to meet the educational needs of Department of Veterans Affairs (VA) and Navy pharmacists is described. In 1992, the College of Pharmacy, University of Illinois at Chicago, worked with the VA and the Navy to design an ambulatory care certificate program for pharmacists in VA and Navy hospitals. The pilot course consisted of 103 hours of didactic and experiential education. The 10 didactic modules covered both disease manage ment and clinical skills. The experiential component incorporated pharmaceutical care steps as applied to therapeutic areas taught in the course. Although the pilot course met most of the original objectives, several unanticipated problems emerged, including distance learning issues, the number of hours for completing the course requirements, learner variance, the impact of institutional support on participants' academic success, participants' difficulty in assimilating education into practice, and difficulty with the clinical evaluation tool developed for the course. The course was modified over the next year to address these problems. Now in its fourth year, the course is offered nationally to the VA and the Department of Defense. In the first three years, 72 of 99 enrolled pharmacists completed the course. An ambulatory care certificate program helps Navy and TIA pharmacists develop patient care skills. C1 US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,PHARM SERV 119,HINES,IL 60141. VET AFFAIRS W SIDE MED CTR,CHICAGO,IL. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,DIV CLIN PHARM,HINES,IL 60141. UNIV ILLINOIS,COLL PHARM,DEPT PHARM PRACTICE,CHICAGO,IL 60680. UNIV ILLINOIS,ACAD PROGRAMS SECT,CHICAGO,IL 60680. UNIV ILLINOIS,COLL PHARM,DEPT PHARM PRACTICE & MED,CHICAGO,IL 60680. NR 7 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD MAY 1 PY 1996 VL 53 IS 9 BP 1018 EP 1023 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UJ488 UT WOS:A1996UJ48800015 PM 8744463 ER PT J AU Bruening, R Kwong, KK Vevea, MJ Hochberg, FH Cher, L Harsh, GR Niemi, PT Weisskoff, RM Rosen, BR AF Bruening, R Kwong, KK Vevea, MJ Hochberg, FH Cher, L Harsh, GR Niemi, PT Weisskoff, RM Rosen, BR TI Echo-planar MR determination of relative cerebral blood volume in human brain tumors: T1 versus T2 weighting SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE blood, volume; brain, magnetic resonance; brain, neoplasms; magnetic resonance, flow studies ID POSITRON EMISSION TOMOGRAPHY; CONTRAST AGENTS; HEMODYNAMICS; PREDICTION; SURVIVAL; GLIOMAS; FLOW; PET AB PURPOSE: Maps related to relative cerebral blood volume (rCBV) were generated with the use of the T1 effects produced by a low-dose bolus passage of gadopentetate dimeglumine. The T1 maps were evaluated in a tumor population and compared with rCBV maps obtained with T2-weighted measurements. METHODS: Imaging was performed in 19 patients with suspected intraaxial brain tumors. For the T1 rCBV maps, a low-dose bolus of contrast material was given during T1-weighted interleaved spin-echo echo-planar MR imaging. This was followed by a second injection during serial T2-weighted imaging for generation of the T2 rCBV maps. RESULTS: Among patients with low-grade lesions (n = 9), T1-based and T2-based rCBV maps showed comparably low rCBV in 7 subjects. In the other 2 patients, with confirmed tumor dedifferentiation, elevation of rCBV values was seen on maps obtained with both techniques. Among patients with high-grade tumors (n = 10), 4 had no evidence of recurrence and 6 did have tumor recurrence (confirmed by follow-up and positron emission tomography). In patients with the high-grade lesions exhibiting conventional contrast enhancement, lesions tended to have higher estimated values on T1 rCBV maps than on the T2 rCBV maps. CONCLUSION: Although the T1 rCBV maps showed less contrast as compared with the T2 rCBv maps, they provided diagnostic information that was comparable to the T2 rCBV maps in our series of 19 patients with primary brain tumors. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. FU NCI NIH HHS [5R01 CA 40303]; NHLBI NIH HHS [5R01 HL 39810]; NINDS NIH HHS [2 POINS 10828] NR 32 TC 86 Z9 87 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAY PY 1996 VL 17 IS 5 BP 831 EP 840 PG 10 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UL344 UT WOS:A1996UL34400003 PM 8733954 ER PT J AU Merchant, SN Gopen, Q AF Merchant, SN Gopen, Q TI A human temporal bone study of acute bacterial meningogenic labyrinthitis SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE acute bacterial meningogenic labyrinthitis; sensorineural hearing loss; cochlear aqueduct ID SENSORINEURAL HEARING-LOSS; PNEUMOCOCCAL MENINGITIS; DEXAMETHASONE THERAPY; CHILDREN; SEQUELA; INFANTS AB It is well established that sensorineural hearing loss (SNHL) is an important sequela of acute bacterial menin gitis. Previous human temporal bone histopathologic studies have suggested that such hearing loss is due to labyrinthitis. This study involved a detailed and systematic evaluation of the auditory and vestibular end-organs in 41 human temporal bones from patients with acute bacterial meningitis, aimed at describing the spectrum of histopathologic changes within the labyrinth, ascertaining likely routes for spread of infection from the meninges to the inner ear, and comparing the data from humans with those described in a rabbit model of meningogenic labyrinthitis. Our study revealed the following: (a) Suppurative labyrinthitis occurred in 20 (49%) bones. Of these 20 bones, the cochlea was affected in all, whereas the vestibular organs were involved in 10. Eosinophilic staining of inner ear fluids without the presence of inflammatory cells (so-called ''serous'' labyrinthitis) occurred in 14 of the remaining 21 bones. This staining occurred primarily within the vestibular system. Its significance and pathogenesis remains unknown; (b) Sensory and neural structures of the inner ear appeared intact in the majority of specimens, including bones with suppurative labyrinthitis and those with eosinophilic staining of inner ear fluids. This finding raises the possibility of preventing or reversing SNHL by therapeutic intervention. Spiral ganglion cells were severely degenerated in 12% of bones, Indicating a retrocochlear site of hearing loss in addition to the cochlea. This subset of patients may perform poorly after cochlear implantation; (c) It has been traditionally assumed that irreversible and permanent SNHL is caused by suppurative labyrinthitis, whereas reversible SNHL is caused by serous labyrinthitis. Our findings question the validity of these assumptions; (d) The data were consistent with the hypothesis that both the cochlear modiolus and cochlear aqueduct can serve as potential pathways for spread of infection from the meninges to the inner ear; (e) There were many similarities in the histopathology of the inner ear in humans when compared with the rabbit model of meningogenic labyrinthitis. A notable difference was that the cochlear aqueduct appeared to be the sole pathway for spread of infection in the rabbit, whereas in the human, both the modiolus and aqueduct were possible pathways. C1 HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. RP Merchant, SN (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [R01DC00079, T32DC00038] NR 29 TC 53 Z9 55 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD MAY PY 1996 VL 17 IS 3 BP 375 EP 385 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA UV040 UT WOS:A1996UV04000004 PM 8817013 ER PT J AU Raychowdhury, R Zheng, G Brown, D McCluskey, RT AF Raychowdhury, R Zheng, G Brown, D McCluskey, RT TI Induction of heymann nephritis with a gp330/megalin fusion protein SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ANTIGENIC COMPLEX; ALPHA-2-MACROGLOBULIN RECEPTOR; MEMBRANE GLYCOPROTEIN; BRUSH-BORDER; GP330; AUTOANTIBODIES; IDENTIFICATION; ANTIBODIES; BINDING; KIDNEY AB There is considerable evidence that glomerular deposits in Heymann nephritis, a rat model of membranous nephritis, result from shedding of immune complexes formed on podocytes and that the principal antigen is part of the extracellular domain of a cell surface glycoprotein receptor called gp330 or megalin. It has also been reported that the immunogen that induces Heymann nephritis is a complex formed between gp330 and the receptor-associated protein RAP, The recent elucidation of the primary structure of gp330 mates it possible to investigate the ability of defined portions of gp330, devoid of RAP, to induce Heymann nephritis. Irt the present study we show that a gp330-glutathione-S-transferase fusion protein, containing 137 amino acid residues (1114 to 1250) of the ectodomain, induces active Heymann nephritis and that heterologous antibodies against this fusion protein produce passive Heymann nephritis. By immunofluorescence, typical glomerular immunoglobulin deposits were found, but complement components were lacking and the rats did not develop proteinuria. In the active model, we obtained evidence indicating that the deposits contained portions of the ectodomain of gp330, including regions other than those of the fusion protein. Thus, the deposits were stained by polyclonal antibodies to gp330 and to the gp330 fusion protein, as well as by two monoclonal antibodies reactive with portions of the ectodomain of gp330, only one of which reacted with the fusion protein in vitro. Antibodies against the cytoplasmic domain of gp330 did not stain. Furthermore, we found that RAP was able to bind to gp330 in the glomerular deposits but not to the gp330 fusion protein in vitro. The results show that the region of gp330 spanning amino acid residues 1114 to 1250 contains peptides capable of inducting pathogenic antibodies of Heymann nephritis without a contributory role of RAP. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MED SERV,RENAL UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. FU NIDDK NIH HHS [DK-42956, DK-4630] NR 37 TC 38 Z9 40 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1996 VL 148 IS 5 BP 1613 EP 1623 PG 11 WC Pathology SC Pathology GA UJ473 UT WOS:A1996UJ47300028 PM 8623929 ER PT J AU Eisinger, DB Kumar, R Woodrow, R AF Eisinger, DB Kumar, R Woodrow, R TI Effect of lumbar orthotics on trunk muscle strength SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE back pain; lumbar corsets; back braces; trunk weakness AB Weakening of the trunk muscles is thought to be one disadvantage of prolonged lumbar orthotic use. This study examines weakness of the trunk flexor and extensor muscles in patients who are wearing lumbar orthotics for extended periods. Strength of the trunk flexor and trunk extensor muscles was tested in 24 individuals, using the Kinetic computer. Both concentric and eccentric forces were recorded. Pour groups of patients were studied. Group 1 (n = 6) consisted of patients with low back pain who had used a lumbar orthotic for a prolonged period of time. Group 2 (n = 6) consisted of hospital employees with no history of low back pain, who wore lumbar orthotics prophylactically, for back protection. Group 1C (n = 6) consisted of healthy controls, with no history of either back pain or lumbar orthotic use, who were individually age- and gender-matched to each patient in Group 1. Group 2C (n = 6) consisted of healthy controls matched in the same fashion to each patient in Group 2. After consultation with a statistician, statistical analysis was performed using the Wilcoxon's test. Nonparametric statistics were chosen because of the lack of evidence of a normal distribution of the parameters being studied. This analysis revealed significant weakness in concentric flexion (P = 0.0464), concentric extension (P = 0.0277), and eccentric extension (P = 0.0464) in Group 1 compared with matched controls in Group 1C. The only significant weakness compared with controls in Group 2 was in eccentric flexion (P = 0.0277). Trends were toward weakness in the orthotic users for the other motions studied, with a P value of less than 0.1 for eccentric extension. Prolonged use of lumbar orthotics may be associated with trunk muscle weakness in the population studied. Prescribers should continue to limit duration of use when possible and to consider strengthening exercises when prolonged use is anticipated. C1 UNIV CALIF LOS ANGELES,MULTICAMPUS PHYS MED & REHABIL RESIDENCY PROGRAM,LOS ANGELES,CA. RP Eisinger, DB (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PHYS MED & REHABIL SERV,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 12 TC 10 Z9 11 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAY-JUN PY 1996 VL 75 IS 3 BP 194 EP 197 DI 10.1097/00002060-199605000-00008 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA UT068 UT WOS:A1996UT06800006 PM 8663926 ER PT J AU Brand, SH Holtzman, EJ Scher, DA Ausiello, DA Stow, JL AF Brand, SH Holtzman, EJ Scher, DA Ausiello, DA Stow, JL TI Role of myristoylation in membrane attachment and function of G alpha(1-3) on Golgi membranes SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE G proteins; lipids; Golgi vesicles; membrane binding; immunostaining ID PROTEIN-ALPHA-SUBUNIT; HETEROTRIMERIC G-PROTEIN; GTP-BINDING PROTEINS; EPITHELIAL-CELLS; BETA-GAMMA; LIPID MODIFICATIONS; PALMITOYLATION; RECEPTOR; PROTEOGLYCAN; ASSOCIATION AB Heterotrimeric G protein a-subunits localized on the cytoplasmic face of Golgi membranes are involved in regulating vesicle trafficking and protein secretion. We investigated the role of myristoylation in attachment of the G alpha(i-3) subunit to Golgi membranes. G alpha(i-3) was epitope-tagged by insertion of a FLAG sequence at an NH2-terminal site predicted to interfere with myristoylation, and the resulting NT-alpha(i-3) construct was stably transfected and expressed in polarized epithelial LLC-PK1 cells. Metabolic labeling confirmed that the translation product of NT-alpha(i-3) was not myristoylated. In contrast to endogenous G alpha(i-3), which is tightly bound to Golgi membranes, the unmyristoylated FLAG-tagged NT-alpha(i-3) did not attach to membranes; it was localized by immunofluorescence in the cytoplasm of LLC-PK1 cells and was detected only in the cytosol fraction of cell homogenates. Pertussis toxin-dependent ADP-ribosylation was used to test the ability of NT-alpha(i-3) to interact with membrane-bound beta gamma-subunits. In both in vitro and in vivo assays, cytosolic NT-alpha(i-3) alone was not ADP-ribosylated, although in the presence of membranes it could interact with G beta gamma-subunits to form heterotrimers. The expression of NT-alpha(i-3) in LLC-PK1 cells altered the rate of basolateral secretion of sulfated proteoglycans, consistent with the demonstrated function of endogenous G alpha(i-3). These data are consistent with a model in which G alpha(i-3) utilizes NH2-terminal myristoylation to bind to Golgi membranes and to maximize its interaction with G beta gamma-subunits. Furthermore, our results show that stable attachment of G alpha(i-3) to Golgi membranes is not required for it to participate as a regulatory element in vesicle trafficking in the secretory pathway. C1 MASSACHUSETTS GEN HOSP, DEPT MED, RENAL UNIT, BOSTON, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, RENAL UNIT, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA. NR 36 TC 11 Z9 11 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1996 VL 270 IS 5 BP C1362 EP C1369 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UJ814 UT WOS:A1996UJ81400013 ER PT J AU Prat, AG Cantiello, HF AF Prat, AG Cantiello, HF TI Nuclear ion channel activity is regulated by actin filaments SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE nuclear transport; cytoskeleton; intracellular signaling ID ENDOPLASMIC-RETICULUM VESICLES; PORE COMPLEX; AMPHIBIAN OOCYTES; CARDIAC MYOCYTES; ENVELOPE; CELLS; POLYMERIZATION; ACTIVATION; MECHANISM; CYTOPLASM AB Actin filaments are novel second messengers involved in ion channel regulation. Because cytoskeletal components interact with the nuclear envelope, the actin cytoskeleton may also control nuclear membrane function. In this report, the patch-clamp technique was applied to isolated nuclei from amphibian A6 epithelial cells to assess the role of actin filaments on nuclear ion channel activity under nucleus-attached or -excised conditions. The most prevalent spontaneous nuclear ion channel species, 76% (n = 46), was cation selective and had a maximal single-channel conductance of similar to 420 pS. Nuclear ion channels also displayed multiple subconductance states, including channel activity of 26 pS that was frequently observed. Nuclear ion channel activity on otherwise quiescent patches was induced by either addition of the actin cytoskeleton disrupter cytochalasin D (CD; 5 mu g/ml, 60%, 3 of 5 patches) or actin (10-1,000 mu g/ml) to the bathing solution of nucleus-attached patches (59%, 13 of 22 patches). Actin also induced ion channel activity in quiescent excised inside-out patches from the nuclear envelope (80%, 4 of 5 patches). In contrast, addition of bovine serum albumin (10-1,000 mu g/ml) to the bathing solution of nucleus-attached patches was without effect on nuclear ion channel activity (5 of 5 patches). The monoclonal antibody MAb414, specific for nuclear pore complex proteins, completely prevented either spontaneous or cytosolic actin-induced nuclear ion channels under nucleus-attached conditions (4 of 4 patches) but not intranuclear actin-induced nuclear ion channels under excised inside-out conditions (3 of 3 patches). In nucleus-attached patches, channel activity was readily activated by addition of the G-actin-binding protein deoxyribonuclease I to nucleus-attached patches (56%, 5 of 9 patches) or further addition of the actin-cross-linker filamin in the presence of actin (57%, 4 of 7 patches). The data indicate that dynamic changes in actin filament organization may represent a novel mechanism to control nuclear function. C1 MASSACHUSETTS GEN HOSP EAST, RENAL UNIT, BOSTON, MA 02129 USA. HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02115 USA. NR 34 TC 24 Z9 24 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAY PY 1996 VL 270 IS 5 BP C1532 EP C1543 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UJ814 UT WOS:A1996UJ81400033 ER PT J AU Loo, DDF Sachs, G Prinz, C AF Loo, DDF Sachs, G Prinz, C TI Potassium and chloride currents in rat gastric enterochromaffin-like cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE exocytosis; acid secretion ID BOVINE CHROMAFFIN CELLS; PERITONEAL MAST-CELLS; ACID-SECRETION; HISTAMINE-RELEASE; ENDOCRINE-CELLS; OXYNTIC CELL; PATCH-CLAMP; K+ CHANNELS; CALCIUM; CONDUCTANCE AB The gastric enterochromaffin-like (ECL) cell secretes histamine in response to secretagogues (gastrin, acetylcholine) by calcium signaling-dependent exocytosis of intracellular vacuoles containing the hormone. ECL cells were isolated from rat fundic gastric mucosa by elutriation and density-gradient centrifugation. Currents across the plasma membrane were measured using whole cell patch-clamp methods. These cells had a low conductance of 0.5 nS and resting potential of -50 mV. Depolarization activated a K+ current that was blocked by Ba2+. Steady-state current in absence of K+ was due to Cl- because of the magnitude of the reversal potential and the effects of Cl- removal. Stimulation of secretion by gastrin, cholecystokinin octapeptide (CCK-8), and the phorbol ester 12-O-tetradecanoylphorbol 13-acetate activated the Cl- conductance with a time course similar to that of histamine release. Therefore the ECL cell maintains a high resting potential, largely due to K+ currents, and stimulation of secretion activates a Cl- current, perhaps deriving from the membrane of the secretory granule that fuses with the plasma membrane. The depolarization that ensues may activate the K+ current to maintain the membrane potential during exocytosis. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT PHYSIOL, CTR HLTH SCI, LOS ANGELES, CA 90095 USA. W LOS ANGELES VET AFFAIRS MED CTR, DEPT VET AFFAIRS, CTR ULCER RES & EDUC, CTR DIGEST DIS, LOS ANGELES, CA 90073 USA. NR 33 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAY PY 1996 VL 270 IS 5 BP G739 EP G745 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA UK342 UT WOS:A1996UK34200001 ER PT J AU Altshuler, LL Cohen, L Szuba, MP Burt, VK Gitlin, M Mintz, J AF Altshuler, LL Cohen, L Szuba, MP Burt, VK Gitlin, M Mintz, J TI Pharmacologic management of psychiatric illness during pregnancy: Dilemmas and guidelines SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID FLOPPY-INFANT SYNDROME; PRENATAL EXPOSURE; ANTIEPILEPTIC DRUGS; ANOREXIA-NERVOSA; ORAL CLEFTS; CONGENITAL-MALFORMATIONS; MATERNAL DIAZEPAM; PANIC DISORDER; VALPROIC ACID; WITHDRAWAL SYMPTOMS AB Objective: Given concerns about use of psychotropic medication during pregnancy, the authors reviewed the literature regarding the effects of prenatal exposure to psychotropic medications on fetal outcome. Method: A MEDLINE search of all articles written in English from 1966 to 1995 was performed to review information on the effects of psychotropic drug use during pregnancy on fetal outcome. Where sufficient data were available and when methodologically appropriate, meta-analyses were performed to assess risk of fetal exposure by psychotropic medication class. Results: Three primary effects are associated with medication use during pregnancy: 1) teratogenicity, 2) perinatal syndromes (neonatal toxicity), and 3) postnatal behavioral sequelae. For many drug classes there are substantial data regarding risk for teratogenicity. Tricyclic antidepressants do not seem to confer increased risk for organ dysgenesis. The available data indicate that first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies. However, the absolute risk of congenital malformations following prenatal exposure to most psychotropics is low. Conclusions: Exposure to certain psychotropic drugs in utero may increase the risk for some specific congenital anomalies, but the rate of occurrence of these anomalies even with the increased risk remains low. Use of psychotropic medications during pregnancy is appropriate in many clinical situations and should include thoughtful weighing of risk of prenatal exposure versus risk of relapse following drug discontinuation. The authors present disorder-based guidelines for psychotropic drug use during pregnancy and for psychiatrically ill women who wish to conceive. C1 UNIV CALIF LOS ANGELES,NEUROPSYCHIAT HOSP,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,CTR BEHAV SCI,LOS ANGELES,CA. UNIV PENN,SCH MED,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. RP Altshuler, LL (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT PSYCHIAT,B116-A12,11301 WILSHIRE BLVD,LOS ANGELES,CA 90075, USA. NR 219 TC 278 Z9 289 U1 5 U2 29 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1996 VL 153 IS 5 BP 592 EP 606 PG 15 WC Psychiatry SC Psychiatry GA UH921 UT WOS:A1996UH92100003 PM 8615404 ER PT J AU Asch, DA Hershey, JC Pauly, MV Patton, JP Jedrziewski, MK Mennuti, MT AF Asch, DA Hershey, JC Pauly, MV Patton, JP Jedrziewski, MK Mennuti, MT TI Genetic screening for reproductive planning: Methodological and conceptual issues in policy analysis SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CYSTIC-FIBROSIS; PRENATAL-DIAGNOSIS; PROGNOSTIC INFORMATION; TESTS; ATTITUDES; PROGRAM AB Objectives, This paper explores several critical assumptions and methodological issues arising in cost-effectiveness analyses of genetic screening strategies in the reproductive setting. Methods. Seven issues that arose in the development of a decision analysis of alternative strategies for cystic fibrosis carrier screening are discussed. Each of these issues required a choice in technique. Results, The presentations of these analyses frequently mask underlying assumptions and methodological choices. Often there is no best choice. In the case of genetic screening in the reproductive setting, these underlying issues often touch on deeply felt human values. Conclusions. Space limitations for published papers often preclude explaining such choices in detail; yet these decisions determine the way the results should be interpreted. Those who develop these analyses need to make sure that the implications of important assumptions are understood by the clinicians who will use them. At the same time, clinicians need to enhance their understanding of what these models truly mean and how they address underlying clinical, ethical, and economic issues. C1 UNIV PENN, SCH MED, DIV GEN INTERNAL MED, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, CTR BIOETH, PHILADELPHIA, PA 19104 USA. UNIV PENN, LEONARD DAVIS INST HLTH ECON, PHILADELPHIA, PA 19104 USA. UNIV PENN, WHARTON SCH, DEPT HLTH CARE SYST, PHILADELPHIA, PA 19104 USA. UNIV PENN, WHARTON SCH, DEPT OPERAT & INFORMAT MANAGEMENT, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, DEPT OBSTET & GYNECOL, PHILADELPHIA, PA 19104 USA. RP Asch, DA (reprint author), VET AFFAIRS MED CTR, DIV GEN INTERNAL MED, 317 RALSTON PENN CTR, 3615 CHESTNUT ST, PHILADELPHIA, PA 19104 USA. FU NHGRI NIH HHS [1-R011HG00616, 1-R011HG00621] NR 22 TC 17 Z9 17 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 1996 VL 86 IS 5 BP 684 EP 690 DI 10.2105/AJPH.86.5.684 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UK290 UT WOS:A1996UK29000016 PM 8629720 ER PT J AU Puig, S Dupuy, DE Sarmiento, A Boland, GW Grigoris, P Greene, R AF Puig, S Dupuy, DE Sarmiento, A Boland, GW Grigoris, P Greene, R TI Articular muscle of the knee: A muscle seldom recognized on MR imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. We studied the MR imaging characteristics of the articular muscle of the knee, an important but seldom recognized structure of the distal thigh and knee. SUBJECTS AND METHODS. We used a 1.5-T system to prospectively evaluate the articular muscle of the knee in five healthy volunteers (10 knees); then we retrospectively studied the knee examinations of 24 patients (30 knees). One reader made duplicate readings to prospectively assess the sagittal proton density-weighted and axial T1-weighted images of the healthy volunteers. Three independent readers retrospectively evaluated the sagittal proton density-weighted images of the 24 patients. RESULTS. The articular muscle of the knee was identified in 100% of prospective studies (10/10) and in 83% of retrospective studies (25/30). For the prospective study group, measurements (mean +/- SEM) were as follows: number of bundles, 2.4 +/- 0.68 (range, 1-4); length of uppermost bundle, 47.2 +/- 4.06 mm; width of origin, 8.6 +/- 0.79 mm; angle of origin, 11.4 degrees +/- 1.29 degrees; and cross-sectional bundle width, 19.8 +/- 2.05 mm(2). CONCLUSION. The articular muscle of the knee can usually be identified by MR imaging as an independent entity, separate from the great (vastus) muscle group. C1 HLTH CARE INT SCOTLAND LTD,DEPT RADIOL,CLYDEBANK G81 4DY,SCOTLAND. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02114. HLTH CARE INT SCOTLAND LTD,DEPT ORTHOPAED & MUSCULOSKELETAL DISORDERS,CLYDEBANK G81 4DY,SCOTLAND. RP Puig, S (reprint author), UNIV VIENNA,RADIODIAGNOST KLIN,WAHRINGER GURTEL 18-20,A-1090 VIENNA,AUSTRIA. OI Dupuy, Damian/0000-0003-0524-5982 NR 6 TC 8 Z9 8 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1996 VL 166 IS 5 BP 1057 EP 1060 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UF853 UT WOS:A1996UF85300009 PM 8615242 ER PT J AU Fan, CM Whitman, GJ Chew, FS AF Fan, CM Whitman, GJ Chew, FS TI Radiologic pathlogic conferences of the Massachusetts General Hospital - Necrotizing fasciitis of the scrotum (Fournier's gangrene) SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 5 TC 9 Z9 10 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAY PY 1996 VL 166 IS 5 BP 1164 EP 1164 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UF853 UT WOS:A1996UF85300029 PM 8615262 ER PT J AU Beyersdorf, SR Nania, JN Luna, GR AF Beyersdorf, SR Nania, JN Luna, GR TI Community medical response to the Fairchild mass casualty event SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the North-Pacific-Surgical-Association CY NOV 09-11, 1995 CL VICTORIA, CANADA SP N Pacific Surg Assoc ID INJURY SEVERITY; TRAUMA SCORE AB BACKGROUND: On June 20, 1994, a discharged serviceman with a psychiatric history opened fire with a MAC-90 assault rifle at Fairchild Air Force Base in Spokane, Washington, The attack killed 5 people and wounded 22. This report reviews the communication, triage, transport, injuries, and the community medical response to this mass casualty. METHODS: Data for the review were obtained from city-wide debriefing sessions, medical records, and evaluation forms from prehospital agencies. RESULTS: A total of 19 patients were triaged to four community hospitals, while 3 victims with comparatively minor injuries stayed at the Base hospital, All fatalities except a child in utero died at the scene. All victims surviving to hospital were discharged recovered from their injuries, Two patients were undertriaged, 1 of whom sustained a pelvic and buttock wound. CONCLUSIONS: Rapid triage was possible due to: (1) initial treatment by military medical personnel; (2) an established and practiced disaster plan; (3) the use of disaster packs and triage tags; (4) the immediate initiation of triage and transport; and (5) coordinated ground and air transport. C1 DEACONESS MED CTR,DEPT SURG,SPOKANE,WA. DEACONESS MED CTR,DEPT EMERGENCY MED,SPOKANE,WA. NR 12 TC 7 Z9 7 U1 0 U2 0 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAY PY 1996 VL 171 IS 5 BP 467 EP 470 DI 10.1016/S0002-9610(96)00005-0 PG 4 WC Surgery SC Surgery GA UP243 UT WOS:A1996UP24300006 PM 8651386 ER PT J AU Swerdlow, SH Zukerberg, LR Yang, WI Harris, NL Williams, ME AF Swerdlow, SH Zukerberg, LR Yang, WI Harris, NL Williams, ME TI The morphologic spectrum of non-Hodgkin's lymphomas with BCL1/cyclin D1 gene rearrangements SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article ID B-CELL LYMPHOMA; CHROMOSOME-11 BCL-1 LOCUS; CENTROCYTIC LYMPHOMA; LYMPHOCYTIC LYMPHOMAS; BREAKPOINTS; FEATURES; LEUKEMIA; CRITERIA AB BCL1/PRAD1 gene rearrangements involving the cyclin D1 gene are a feature of about 70% of centrocytic/mantle-cell lymphomas (CC/MCL) but are identified in only a small proportion of other B-cell non-Hodgkin's lymphomas. Of 37 lymphomas found to have BCL1/cyclin D1 (PRAD1, CCND1) gene rearrangements, 30 fit the morphologic and immunophenotypic criteria for typical CC/MCL. Seven cases with morphologic features atypical for CC/MCL were identified. CD5+ monoclonal B cells were documented in all these cases. Six cases were subsequently stained for cyclin D1 protein, and all showed nuclear positivity. Five cases had variably sized foci of cells with moderately abundant pale cytoplasm resembling parafollicular/monocytoid B cells, marginal zone cells, hairy cells, or even proliferation centers. Transformed-appearing cells were also present in some lymphomas. In one case, striking follicular colonization created a markedly nodular growth pattern mimicking a follicular lymphoma. A sixth case had a marked predominance of small, round lymphocytes at some sites, mimicking a small lymphocytic lymphoma. Five of these six cases also had areas more typical of CC/MCL. The seventh case was a CD5-positive splenic marginal zone-like lymphoma (SMZL) with plasmacytic differentiation and circulating villous lymphocytes consistent with a splenic lymphoma with villous lymphocytes (SLVL). These cases illustrate the morphologic spectrum of small B-cell lymphoid neoplasms that have BCL1/cyclin D1 gene rearrangements and overexpression of cyclin D1. Despite the BCL1 translocation and cyclin D1 overexpression, the splenic lymphoma with plasmacytic differentiation was definitely not a CC/MCL and fit the clinicopathologic entity of SMZL/SLVL. The other six cases are best considered CC/MCL variants based on a combined morphologic, immunophenotypic, and genotypic evaluation. Genotypic or immunophenotypic studies to identify cyclin DI rearrangements and overexpression, although not-pathognomonic, are useful in recognizing these variant CC/MCL cases, which can mimic almost any of the other well-described but more indolent low-grade B-cell lymphomas and leukemias. Some of the variant CC/MCL cases had features in common with the CD5+ cyclin D1 + SMZL/SLVL, suggesting a possible relationship between these two otherwise distinct entities. C1 UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV VIRGINIA,SCH MED,DEPT INTERNAL MED,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,SCH MED,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. NR 42 TC 83 Z9 84 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAY PY 1996 VL 20 IS 5 BP 627 EP 640 DI 10.1097/00000478-199605000-00009 PG 14 WC Pathology; Surgery SC Pathology; Surgery GA UG683 UT WOS:A1996UG68300009 PM 8619427 ER PT J AU Owens, DK Holodniy, M Garber, AM Scott, J Sonnad, S Moses, L Kinosian, B Schwartz, JS AF Owens, DK Holodniy, M Garber, AM Scott, J Sonnad, S Moses, L Kinosian, B Schwartz, JS TI Polymerase chain reaction for the diagnosis of HIV infection in adults - A meta-analysis with recommendations for clinical practice and study design SO ANNALS OF INTERNAL MEDICINE LA English DT Review DE human immunodeficiency virus; human immunodeficiency virus infections; polymerase chain reaction; meta-analysis; sensitivity and specificity ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; SERONEGATIVE HOMOSEXUAL MEN; INTRAVENOUS-DRUG-USERS; AT-RISK INDIVIDUALS; AMPLIFIED VIRAL-DNA; TYPE-1 INFECTION; PERIPHERAL-BLOOD; PROVIRAL DNA; GENE AMPLIFICATION AB Purpose: To do a meta-analysis of studies that have evaluated the sensitivity and specificity of polymerase chain reaction (PCR) assay for the diagnosis of human immunodeficiency virus (HIV) infection in adults. Evaluating the performance of PCR is difficult because in certain clinical situations, the sensitivity or specificity of PCR may exceed those of the current reference standard tests (enzyme immunoassay followed by confirmatory Western blot analysis). Therefore, an additional goal was to develop recommendations for 1) the design of future evaluative studies of PCR and 2) the use of PCR in persons with suspected HIV infection. Data Sources: Studies published between 1988 and 1994 that were identified in a search of 17 computer databases, including MEDLINE, and abstracts identified from conference proceedings. Study Selection: Studies were included if DNA amplification by PCR was done on peripheral blood mononuclear cells from adults. Ninety-six studies met the inclusion criteria. Data Extraction: Data were extracted independently by two reviewers. Study design was assessed independently by two investigators blinded to study results. Results: Reported sensitivities for PCR range from 10% to 100%, and specificities range from 40% to 100%. A summary receiver-operating characteristic curve based on all 96 studies has a maximum joint sensitivity and specificity (upper left point on the curve, where sensitivity equals specificity) of 97.0% to 98.1%. If the threshold value that defines a positive PCR result is chosen so that sensitivity is higher than 98.1%, specificity will decrease to less than 98.1%. Conversely, if the threshold value that defines a positive PCR result is chosen so that specificity is greater than 98.1%, sensitivity will decrease to less than 98.1%. If sensitivity and specificity are chosen to be equal, the corresponding false-positive rate is 1.9% to 3.0%. At the maximum joint sensitivity and specificity, the positive predictive value of PCR ranges from 34% to 85% as the prevalence of HIV increases from 1.0% to 10%. We identified seven areas in which study design could be modified to 1) reduce susceptibility to bias in estimates of the sensitivity and specificity of PCR and 2) to increase the generalizability of the study results. These modifications will also help to overcome methodologic problems created by the lack of a reference standard test. Conclusions: The PCR assay is not sufficiently accurate to be used for the diagnosis of HIV infection without confirmation. Use of PCR for the diagnosis of HIV in adults should be limited to situations in which antibody tests are known to be insufficient. Future studies of PCR performance should be sufficiently large and should use adequate reference standard tests and standardized methods for the performance of PCR. Specimens should be evaluated by persons blinded to clinical status and to the results of other diagnostic tests for HIV infection. C1 STANFORD UNIV,DEPT HLTH RES & POLICY,STANFORD,CA 94305. DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. UNIV PENN,PHILADELPHIA,PA 19104. RP Owens, DK (reprint author), VET AFFAIRS PALO ALTO HLTH CARE SYST,GEN INTERNAL MED SECT 111A,3801 MIRANDA AVE,PALO ALTO,CA 94304, USA. RI Garber, Alan/F-1476-2010 FU NIAID NIH HHS [AI27762-04]; PHS HHS [IIR91-044.A] NR 124 TC 41 Z9 42 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 1996 VL 124 IS 9 BP 803 EP & PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA UG254 UT WOS:A1996UG25400004 PM 8610949 ER PT J AU Soriano, SG Lipton, SA Wang, YMF Xiao, M Springer, TA GutierrezRamos, JC Hickey, PR AF Soriano, SG Lipton, SA Wang, YMF Xiao, M Springer, TA GutierrezRamos, JC Hickey, PR TI Intercellular adhesion molecule-1-deficient mice are less susceptible to cerebral ischemia - Reperfusion injury SO ANNALS OF NEUROLOGY LA English DT Article ID ENDOTHELIAL-CELLS; INFARCT VOLUME; EXPRESSION; RATS; ICAM-1 AB Neutrophil emigration is mediated by adhesion proteins that are highly expressed on the endothelial surface during inflammatory processes in the brain. Intercellular adhesion molecule-1 (CAM-1) is an inducible adhesion molecule that binds to leukocyte integrins and facilitates neutrophil adhesion and transendothelial migration. To study the role of ICAM-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in ICAM-1-deficient mice generated by gene targeting in embryonic stem cells. Transient focal ischemia was induced by occluding the left middle cerebral artery for 3 hours followed by a 21- or 45-hour reperfusion period. When compared with their wild-type littermates, ICAM-1-deficient mice were less susceptible to cerebral injury as demonstrated by a 5.6- or 7.8-foid reduction in infarction volume, respectively. These data support the premise that neutrophil adhesion in ischemic areas may be deleterious and that ICAM-1 deficiency reduces neurological damage after transient focal cerebral ischemia. C1 CHILDRENS HOSP,DEPT NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,PROGRAM NEUROSCI,BOSTON,MA 02115. RP Soriano, SG (reprint author), CHILDRENS HOSP,DEPT ANESTHESIA,300 LONGWOOD AVE,BOSTON,MA 02115, USA. RI tao, li/G-7956-2011 FU NHLBI NIH HHS [P01 HL148674-02]; PHS HHS [P01 H029587-04] NR 29 TC 150 Z9 163 U1 0 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1996 VL 39 IS 5 BP 618 EP 624 DI 10.1002/ana.410390511 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UK339 UT WOS:A1996UK33900010 PM 8619547 ER PT J AU Kass, ES Hillman, RE Zeitels, SM AF Kass, ES Hillman, RE Zeitels, SM TI Vocal fold submucosal infusion technique in phonomicrosurgery SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE laryngoscopy; microlaryngoscopy; phonosurgery; vocal cord; vocal fold; voice AB Phonomicrosurgery is optimized by maximally preserving the vocal fold's layered microstructure (laminae propriae). The technique of submucosal infusion of saline and epinephrine into the superficial lamina propria (SLP) was examined to delineate how, when, and why it was helpful toward this surgical goal. A retrospective review revealed that the submucosal infusion technique was used to enhance the surgery in 75 of 152 vocal fold procedures that were performed over the last 2 years. The vocal fold epithelium was noted to be adherent to the vocal ligament in 29 of the 75 cases: 19 from previous surgical scarring, 4 from cancer, 3 from sulcus vocalis, 2 from chronic hemorrhage, and 1 from radiotherapy. The submucosal infusion technique was most helpful when the vocal fold epithelium required resection and/or when extensive dissection in the SLP was necessary. The infusion enhanced the surgery by vasoconstriction of the microvasculature in the SLP, which improved visualization during cold-instrument tangential dissection. Improved visualization facilitated maximal preservation of the SLP, which is necessary for optimal pliability of the overlying epithelium. The infusion also improved the placement of incisions at the perimeter of benign, premalignant, and malignant lesions, and thereby helped preserve epithelium uninvolved by the disorder. C1 MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. NR 15 TC 23 Z9 27 U1 0 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD MAY PY 1996 VL 105 IS 5 BP 341 EP 347 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA UK597 UT WOS:A1996UK59700003 PM 8651626 ER PT J AU Tsai, TM Shea, BF Souney, PF Volinsky, FG Scavone, JM ONeill, S AF Tsai, TM Shea, BF Souney, PF Volinsky, FG Scavone, JM ONeill, S TI Effects of ofloxacin administration on the reliability of urine glucose testing SO ANNALS OF PHARMACOTHERAPY LA English DT Article AB OBJECTIVE: To study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0-4 hours postdose, and (3) pooled 4-8 hours postdose, Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0, 25, 50, 100, 200, 400, and 800 mu g/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSION: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations. C1 MASSACHUSETTS COLL PHARM & ALLIED HLTH SCI,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PHARM SERV,CLIN SERV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT EMERGENCY MED,BOSTON,MA 02114. NR 14 TC 0 Z9 0 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 1996 VL 30 IS 5 BP 469 EP 472 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UJ215 UT WOS:A1996UJ21500006 PM 8740325 ER PT J AU Sunahara, JF GoraHarper, ML Nash, KS AF Sunahara, JF GoraHarper, ML Nash, KS TI Possible erythromelalgia-like syndrome associated with nifedipine in a patient with Raynaud's phenomenon SO ANNALS OF PHARMACOTHERAPY LA English DT Article ID BROMOCRIPTINE; ERUPTION AB OBJECTIVE: To describe a patient who was diagnosed with Raynaud's phenomenon, was prescribed immediate-release nifedipine, and developed a possible erythromelalgia-like syndrome. CASE SUMMARY: A 24-year-old white woman with a history of esophageal spasms and Raynaud's phenomenon was prescribed nifedipine 10 mg po qid. Approximately 1 hour after the patient had taken the fourth dose of nifedipine, she experienced acute erythema and a burning sensation in her feet and lower limbs, light-headedness, and palpitations. Because of a reportedly abnormally low blood pressure, the patient took diphenhydramine 50 mg po and proceeded to the clinic. On arrival, abnormal vital signs were BP 140/48 mm Hg and HR 130 beats/min. Without any other medical intervention, approximately 30 minutes later her blood pressure and heart rate had returned to baseline at 122/60 mm Hg and 96 beats/min, respectively. The nifedipine was permanently discontinued and the patient's symptoms completely resolved over 24 hours. DISCUSSION: The characteristic symptoms of erythromelalgia include burning pain, increased skin temperature, and erythema of the extremities, usually to the feet, lower legs, and, less often, the hands. Erythromelalgia-like syndromes secondary to the administration of many medications have been reported. Several nifedipine-related reports describe an erythromelalgia-like syndrome similar to our reported case. CONCLUSIONS: Because the patient was not taking any other medications and the symptoms started with the administration of nifedipine and were relieved after its discontinuation, nifedipine was thought to be the cause of the erythromelalgia-like syndrome. C1 UNIV KENTUCKY HOSP,DRUG INFORMAT CTR,LEXINGTON,KY 40536. UNIV KENTUCKY,COLL PHARM,DEPT PHARM PRACTICE & SCI,LEXINGTON,KY. UNIV KENTUCKY,COLL PHARM,DEPT VET AFFAIRS,LEXINGTON,KY. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. NR 22 TC 12 Z9 12 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD MAY PY 1996 VL 30 IS 5 BP 484 EP 486 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UJ215 UT WOS:A1996UJ21500010 PM 8740329 ER PT J AU Fischer, CP Bode, BP Takahashi, K Tanabe, KK Souba, WW AF Fischer, CP Bode, BP Takahashi, K Tanabe, KK Souba, WW TI Glucocorticoid-dependent induction of interleukin-6 receptor expression in human hepatocytes facilitates interleukin-6 stimulation of amino acid transport SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 107th Annual Scientific Session of the Southern-Surgical-Association CY DEC 03-06, 1995 CL HOT SPRINGS, VA SP So Surg Assoc ID TUMOR-NECROSIS-FACTOR; ACUTE PHASE RESPONSE; GENE-EXPRESSION; RAT HEPATOCYTES; METABOLISM; GP130 AB Objective The authors studied the effects of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-LU) on glutamine and alanine transport in isolated human hepatocytes, They also evaluated the role of dexamethasone in modulating this response and its effects on the expression of the plasma membrane high-affinity IL-6 receptor. Summary Background Data Animal studies indicate that cytokines are important mediators of the increased hepatic amino acid uptake that occurs during cancer and sepsis, but studies in human tissues are lacking. The control of transport by cytokines and cytokine receptor expression in the liver may provide a mechanism by which hepatocytes can modulate amino acid availability during catabolic disease slates. Methods Human hepatocytes were isolated from wedge biopsy specimens and plated in 24-well trays. Interleukin-6 and TNf-alpha, in combination with the synthetic glucocorticoid dexamethasone, were added to hepatocytes in culture, and the transport of radiolabeled glutamine and alanine was measured. Fluorescent-activated cell sorter (FACS) analysis was used to study the effects of dexamethasone on IL-6 receptor number in the well-differentiated human hepatoma HepG2. Results Both IL-6 and TNF-alpha exerted a small stimulatory effect on alanine and glutamine transport. Dexamethasone alone did not alter transport rates, but pretreatment of cells augmented the effects of both cytokines on carrier-mediated amino acid uptake. Dexamethasone pretreatment and a combination of IL-6 and TNF-alpha resulted in a greater than twofold increase in transport activity. Fluorescent-activated cell sorter analysis demonstrated that dexamethasone induced a threefold increase in the expression of high-affinity IL-6 receptors. Conclusions Interleukin-6 and TNF-alpha work coordinately with glucocorticoids to stimulate amino acid uptake in human hepatocytes. Dexamethasone exerts a permissive effect on cytokine-mediated increases in transport by increasing IL-6 receptor expression on the cell surface. It is likely that this upregulation of IL-6 receptors ''primes'' human liver cells ?or subsequent stimulation by cytokines. The resulting increase in hepatic amino acid transport provides the liver with substrate to support key metabolic pathways during catabolic states. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. FU NCI NIH HHS [CA57690]; NIDDK NIH HHS [DK 40561-02] NR 29 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAY PY 1996 VL 223 IS 5 BP 610 EP 618 DI 10.1097/00000658-199605000-00017 PG 9 WC Surgery SC Surgery GA UJ977 UT WOS:A1996UJ97700032 PM 8651752 ER PT J AU Harpole, DH Richards, WG Herndon, JE Sugarbaker, DJ AF Harpole, DH Richards, WG Herndon, JE Sugarbaker, DJ TI Angiogenesis and molecular biologic substaging in patients with stage I non-small cell lung cancer SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 09-11, 1995 CL SAN ANTONIO, TX SP So Thorac Surg Assoc ID REGRESSION-MODELS; ADENOCARCINOMAS; RECURRENCE; METASTASIS; CARCINOMA AB Background. Although complete surgical resection remains the primary treatment for localized stage I non-small cell lung cancer, the cancer recurrence rate is 25% to 40%. If one could identify a subset of patients using molecular factors that contribute to tumor aggressiveness, one might improve prognosis in this group with additional treatment. High expression of angiogenesis factor viii has been associated with the presence of nodal metastases in breast cancer; here we examined its relation to survival with non-small cell lung cancer. Methods. We examined angiogenesis using immunohistochemistry on paraffin blocks of tumor from 275 consecutive patients with stage I non-small cell lung cancer, more than 68 months of follow-up, and a 64% 5-year survival. Angiogenesis was calculated from the microvessel number per ten 200 x microscope fields measured at the tumor periphery, in the center, and in the area of highest concentration. Results. Measurements in the central area were inconsistent due to prominent necrosis. However, microvessel number recorded at the periphery and at the ''hottest'' area correlated well (r(2) = 0.952; p = 0.001), and a significant survival advantage was noted for low-level expression at both areas (peripheral, p = 0.046; ''hottest'', p = 0.006). Multivariate survival analysis using angiogenesis, protooncogene erbB-2, tumor suppressor gene p53, and the proliferation marker KI-67 defined angiogenesis as the most significant prognostic factor in stage I lung cancer. Conclusions. This molecular biologic substaging system including angiogenesis for stage I non-small cell lung cancer is independent of routine histopathologic factors and revealed an additive adverse effect with expression of several biologic markers (5-year survival: no marker [n = 51] 81%, 1 marker [n = 82] 71%, 2 markers [n = 84] 54%, and 3 to 4 markers [n = 58] 49%; p = 0.0001). C1 DANA FARBER CANC INST,LUNG CANC RES LAB,THORAC ONCOL PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,BOSTON,MA. NR 20 TC 113 Z9 114 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAY PY 1996 VL 61 IS 5 BP 1470 EP 1476 DI 10.1016/0003-4975(96)00104-X PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UG909 UT WOS:A1996UG90900045 PM 8633961 ER PT J AU Huncharek, M Kelsey, K Mark, EJ Muscat, J Choi, N Carey, R Christiani, D AF Huncharek, M Kelsey, K Mark, EJ Muscat, J Choi, N Carey, R Christiani, D TI Treatment and survival in diffuse malignant pleural mesothelioma; A study of 83 cases from the Massachusetts General Hospital SO ANTICANCER RESEARCH LA English DT Article DE chemotherapy; surgery; survival; combined modality; asbestos AB The influence of treatment on clinical outcome in pleural mesothelioma (PM) is uncertain. We studied 83 patients with PM treated at our institution to evaluate the impact of treatment mortality on survival. Methods. Medical records of 83 patients with PM treated between 1978 and 1994 were reviewed The following data were tabulated for each patient; age, sex, date of diagnosis, history of asbestos exposure, smoking history, method of diagnosis histologic subtype, type of treatment and survival from diagnosis. Four treatment groups were analyzed; chemotherapy (C), surgery (S), combined modality (CM i.e. S + C with or without radiation therapy) and supportive care alone (SC). Survival curves were calculated and adjustment made for age. Survival curves were compared using Wilcoxon Chi-square analysis. Results. Seventy-one males and 12 females with a mean age of 67 years were analyzed Seventy-five percent were smokers and 74% reported definite or probable asbestos exposure Treatment groups did not vary according to smoking or asbestos history The CM group and SC groups contained similar proportions of patients with epithelial tumors (54% v 56%). Median survival for patients in the CM group was 23.9 months versus 4.5 months among those receiving SC (p < 0.01). Discussion. This analysis suggest prolonged survival among patients with PM receiving CM versus SC of single modality treatment. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,RADIOBIOL LAB,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02114. AMER HLTH FDN,DIV EPIDEMIOL,NEW YORK,NY 10017. MASSACHUSETTS GEN HOSP,DEPT MED ONCOL,BOSTON,MA 02114. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PULM & CRIT CARE MED,BOSTON,MA 02114. RP Huncharek, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. NR 11 TC 27 Z9 27 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 MAY-JUN PY 1996 VL 16 IS 3A BP 1265 EP 1268 PG 4 WC Oncology SC Oncology GA UR869 UT WOS:A1996UR86900033 PM 8702248 ER PT J AU Barchiesi, F Najvar, LK Luther, MF Scalise, G Rinaldi, MG Graybill, JR AF Barchiesi, F Najvar, LK Luther, MF Scalise, G Rinaldi, MG Graybill, JR TI Variation in fluconazole efficacy for Candida albicans strains sequentially isolated from oral cavities of patients with AIDS in an experimental murine candidiasis model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID RESISTANCE; HIV AB Four strains of Candida albicans, isolated from two patients with AIDS who had undergone prolonged fluconazole therapy for oral candidiasis, were studied in a model of disseminated murine candidiasis. Pre- and posttreatment isolates from each patient were genetically related, and the fluconazole MICs for the strains had increased significantly, from 0.25 to 32 mu g/ml for the strains isolated from patient 1 and from 1.0 to 16 mu g/ml for the strains isolated from patient 2. Mice were infected intravenously and were treated orally with fluconazole. For survival studies, mice were treated from day 1 to day 10 postinfection and were observed through day 30. The fluconazole dosages were as follows: 0.25, 0.5, 1.0, and 5.0 mg/kg of body weight twice a day. For tissue burden studies, two groups of mice (each group received fluconazole at 0.25 or 5.0 mg/kg) were treated from day 1 to day 7 and were sacrificed 1 day later for quantitative tissue cultures of the spleen and both kidneys. For pretreatment isolates from both patients, all fluconazole dosing regimens were effective at prolonging survival compared with the survival of the control groups. For posttreatment isolates, only fluconazole at 5.0 mg/kg was effective at prolonging survival. Both fluconazole dosing regimens used in the tissue burden studies significantly reduced the counts of the pretreatment isolate from patient 1 in the spleen and kidney, while fluconazole at 5.0 mg/kg was effective at reducing the counts of the posttreatment isolate, For both isolates from patient 2, only fluconazole at 5.0 mg/kg was effective at reducing the counts in the spleen and kidney. The study indicates that C. albicans mutation to resistance to fluconazole may play a critical role in fluconazole-refractory oral candidiasis in AIDS patients. C1 UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP Barchiesi, F (reprint author), UNIV ANCONA,OSPED UMBERTO 1,IST MALATTIE INFETT & MED PUBBL,LARGO CAPPELLI 1,I-60121 ANCONA,ITALY. NR 29 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1996 VL 40 IS 5 BP 1317 EP 1320 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UJ076 UT WOS:A1996UJ07600054 PM 8723495 ER PT J AU Rauch, SL vanderKolk, BA Fisler, RE Alpert, NM Orr, SP Savage, CR Fischman, AJ Jenike, MA Pitman, RK AF Rauch, SL vanderKolk, BA Fisler, RE Alpert, NM Orr, SP Savage, CR Fischman, AJ Jenike, MA Pitman, RK TI A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 10th Annual Meeting of the International-Society-for-Traumatic-Stress-Studies CY NOV 05-09, 1994 CL CHICAGO, IL SP Int Soc Traumat Stress Studies ID PSYCHOPHYSIOLOGICAL ASSESSMENT; COMBAT VETERANS; PANIC DISORDER; PET IMAGES; ANXIETY; MEMORY; TRAUMA; RELIABILITY; MECHANISMS; VALIDITY AB Background: Previous studies have used symptom provocation and positron emission tomography to delineate the brain systems that mediate various anxiety states. Using an analogous approach, the goal of this study was to measure regional cerebral blood flow changes associated with posttraumatic stress disorder (PTSD) symptoms. Methods: Eight patients with PTSD, screened as physiologically responsive to a script-driven imagery symptom provocation paradigm, were exposed sequentially to audiotaped traumatic and neutral scripts in conjunction with positron emission tomography. Heart rate and subjective measures of emotional state were obtained for each condition. Statistical mapping techniques were used to determine locations of significant brain activation. Results: Increases in normalized blood flow were found for the traumatic as compared with control conditions in right-sided limbic, paralimbic, and visual areas; decreases were found in left inferior frontal and middle temporal cortex. Conclusions: The results suggest that emotions associated with the PTSD symptomatic state are mediated by the limbic and paralimbic systems within the right hemisphere. Activation of visual cortex may correspond to the visual component of PTSD reexperiencing phenomena. C1 HARVARD UNIV, SCH MED, BOSTON, MA USA. MASSACHUSETTS GEN HOSP, DEPT PSYCHIAT, BOSTON, MA 02114 USA. VET AFFAIRS MED CTR, MANCHESTER, NH USA. FU NCI NIH HHS [5T32CA09362]; NIMH NIH HHS [MH01215, MH48559] NR 70 TC 565 Z9 576 U1 8 U2 26 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1996 VL 53 IS 5 BP 380 EP 387 PG 8 WC Psychiatry SC Psychiatry GA UJ819 UT WOS:A1996UJ81900001 PM 8624181 ER PT J AU Ling, W Wesson, DR Charuvastra, C Klett, CJ AF Ling, W Wesson, DR Charuvastra, C Klett, CJ TI A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HEROIN-ADDICTS; FOLLOW-UP; ABUSE AB Background: Buprenorphine is a partial agonist at the mu-opioid receptor that has been proposed as an alternative to traditional full agonist maintenance therapy for the treatment of opioid addiction. We report on a clinical trial in which the relative safety and efficacy of long-term fixed-dose buprenorphine maintenance was examined in comparison to low- and high-dose methadone maintenance. Methods: Two hundred twenty-five treatment-seeking opioid addicts (46 women, 179 men) were randomly assigned to receive, in a double-blind manner, either 8 mg/d of buprenorphine, 30 mg/d of methadone, or 80 mg/d of methadone maintenance over a 1-year period. Objective and subjective measures of efficacy (urine toxicology, retention, craving, and withdrawal symptoms) were examined at the study midpoint and at termination, and safety data were tabulated over the entire 52-week study period. Results: Patients assigned to high-dose methadone maintenance performed significantly better on measures of retention, opioid use, and opioid craving than either the low-dose methadone or the buprenorphine group at both 26-week and 52-week time points. Performance on these measures was virtually identical between the latter two groups. No serious adverse health effects attributable to buprenorphine were noted. Conclusions: Buprenorphine maintenance at 8 mg/d appears to be less than optimally efficacious under the conditions of the present study. Continued research is needed to reconcile these findings with the more positive results reported by other investigative groups. There are no apparent health risks associated with long-term buprenorphine maintenance at this dosage. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,BIOBEHAV SCI SUBST ABUSE PROGRAM,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,SUBST ABUSE TREATMENT PROGRAM,LOS ANGELES,CA 90073. SUMMIT MED CTR,MPI TREATMENT SERV,OAKLAND,CA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP Ling, W (reprint author), LOS ANGELES ADDICT TREATMENT RES CTR,10350 SANTA MONICA BLVD,STE 340,LOS ANGELES,CA 90025, USA. FU NIDA NIH HHS [R18 DA6082] NR 30 TC 259 Z9 261 U1 4 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1996 VL 53 IS 5 BP 401 EP 407 PG 7 WC Psychiatry SC Psychiatry GA UJ819 UT WOS:A1996UJ81900003 PM 8624183 ER PT J AU Biederman, J Faraone, S Milberger, S Guite, J Mick, E Chen, L Mennin, D Marrs, A Oullette, C Moore, P Spencer, T Norman, D Wilens, T Kraus, I Perrin, J AF Biederman, J Faraone, S Milberger, S Guite, J Mick, E Chen, L Mennin, D Marrs, A Oullette, C Moore, P Spencer, T Norman, D Wilens, T Kraus, I Perrin, J TI A prospective 4-year follow-up study of attention-deficit hyperactivity and related disorders SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PSYCHIATRIC STATUS; ACADEMIC UNDERACHIEVEMENT; LEARNING-DISABILITIES; FAMILIAL ASSOCIATION; CONDUCT DISORDER; CHILD-BEHAVIOR; ADHD CHILDREN; COMORBIDITY; BOYS; ADOLESCENTS AB Background: Previous cross-sectional data showed that children and adolescents with attention-deficit hyperactivity disorder (ADHD) are at increased risk of comorbid conduct, mood, and anxiety disorders as well as impairments in cognitive, social, family, and school functioning. However, longitudinal data were needed to confirm these initial impressions. Methods: Using DSM-III-R structured diagnostic interviews and raters blinded as to diagnosis, we reexamined psychiatric diagnoses at 1- and 4-year follow-ups in children with ADHD and controls. In addition, subjects were evaluated for cognitive, achievement, social, school, and family functioning. Results: Analyses of follow-up findings revealed significant differences between children with ADHD and controls in rates of behavioral, mood, and anxiety disorders, with these disorders increasing markedly from baseline to follow-up assessments. In addition, children with ADHD had significantly more impaired cognitive, family, school, and psychosocial functioning than did controls. Baseline diagnosis of conduct disorder predicted conduct disorder and substance use disorders at follow-up, major depression at baseline predicted major depression and bipolar disorder at follow-up, and anxiety disorders at baseline predicted anxiety disorders at follow-up. Conclusions: These results confirm and extend previous retrospective results indicating that children with ADHD are at high risk of developing a wide range of impairments affecting multiple domains of psychopathology such as cognition, interpersonal, school, and family functioning. These findings provide further support for the value of considering psychiatric comorbidity in both clinical assessment and research protocols involving children with ADHD. C1 MASSACHUSETTS GEN HOSP,DEPT CHILD PSYCHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. HARVARD UNIV,BROCKTON W ROXBURY VET AFFAIRS MED CTR,SCH MED,DEPT PSYCHIAT,BOSTON,MA. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD COMMUNITY HLTH PLAN,DEPT PSYCHIAT,BOSTON,MA. RP Biederman, J (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT ACC 725,PSYCHIAT SERV,FRUIT ST,BOSTON,MA 02114, USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 55 TC 441 Z9 453 U1 4 U2 35 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1996 VL 53 IS 5 BP 437 EP 446 PG 10 WC Psychiatry SC Psychiatry GA UJ819 UT WOS:A1996UJ81900008 PM 8624187 ER PT J AU Yannuzzi, LA Sorenson, JA Sobel, RS Daly, JR DeRosa, JT Seddon, JM Gragoudas, ES Puliafito, CA Gelles, E Gonet, R Burton, TC Culver, J Metzger, K Kalbfleisch, N Zarling, D Farber, MD Blair, N Stelmack, T Axelrod, A Waitr, SE Cross, A Rolnick, C Flom, T Haller, J Pusin, S Cassel, G Appelgate, CA Sperduto, RD Seigel, D Hiller, R Mowery, R Chew, E Tamboli, A Dunn, M Shamban, K Lento, D AF Yannuzzi, LA Sorenson, JA Sobel, RS Daly, JR DeRosa, JT Seddon, JM Gragoudas, ES Puliafito, CA Gelles, E Gonet, R Burton, TC Culver, J Metzger, K Kalbfleisch, N Zarling, D Farber, MD Blair, N Stelmack, T Axelrod, A Waitr, SE Cross, A Rolnick, C Flom, T Haller, J Pusin, S Cassel, G Appelgate, CA Sperduto, RD Seigel, D Hiller, R Mowery, R Chew, E Tamboli, A Dunn, M Shamban, K Lento, D TI Risk factors for central retinal vein occlusion - The eye disease case-control study group SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ALCOHOL-CONSUMPTION; HEART-DISEASE; CLASSIFICATION AB Objective: To identify possible risk factors for central retinal vein occlusion (CRVO). Design: Between May 1, 1986, and December 31, 1990, 258 patients with CRVO and 1142 controls were identified at five clinical centers. Data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. Results: An increased risk of CRVO was found in persons with systemic hypertension, diabetes mellitus, and open-angle glaucoma. Risk of CRVO decreased with increasing levels of physical activity and increasing levels of alcohol consumption. In women, risk of occlusion decreased with use of postmenopausal estrogens and increased with higher erythrocyte sedimentation rates. Cardiovascular disease, electrocardiographic abnormalities, history of treatment of diabetes mellitus, higher blood glucose levels, lower albumin-globulin ratios, and higher alpha(1)-globulin levels were associated with increased risk only for ischemic CRVO. Systemic hypertension was associated with increased risk for ischemic and nonischemic CRVO, but odds ratios were greater for the ischemic type. Conclusions: Our results suggest a cardiovascular risk profile for persons with CRVO, in particular, patients with the ischemic type. The findings reinforce recommendations to diagnose and treat systemic hypertension, advise patients to increase physical exercise, and consider use of exogenous estrogens in postmenopausal women. C1 NEI,DIV BIOMETRY & EPIDEMIOL,BETHESDA,MD 20892. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV ILLINOIS,CHICAGO,IL. JOHNS HOPKINS UNIV HOSP,WILMER EYE INST,BALTIMORE,MD. ORKAND CORP,COORDINATING CTR,SILVER SPRING,MD. PHOTOG READING CTR,BOSTON,MA. NR 31 TC 189 Z9 191 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 1996 VL 114 IS 5 BP 545 EP 554 PG 10 WC Ophthalmology SC Ophthalmology GA UJ223 UT WOS:A1996UJ22300005 ER PT J AU Berson, EL Remulla, JFC Rosner, B Sandberg, MA WeigelDiFranco, C AF Berson, EL Remulla, JFC Rosner, B Sandberg, MA WeigelDiFranco, C TI Evaluation of patients with retinitis pigmentosa receiving electric stimulation, ozonated blood, and ocular surgery in Cuba SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Objective: To evaluate the effect of intervention with electric stimulation, autotransfused ozonated blood, and ocular surgery, performed in Cuba, on the course of the common forms of retinitis pigmentosa. Design: Ocular evaluations over 6 to 8 months before and after intervention in Cuba. Setting: Evaluations performed at a US clinical research facility. Patients: Ten adult patients aged 25 to 67 years with retinitis pigmentosa. Main Outcome Measure: Visual acuity, visual field area, and electroretinogram (ERG) amplitude. Results: No significant change in visual acuity or visual field area was observed on average between preintervention and postintervention values over a 6- to 8-month interval. Mean 30-Hz cone ERG amplitude declined by 15.5% between preintervention and postintervention values (P=.006). When data on change in visual field area from 1 statistically significant outlier were excluded from the analysis, a significant decline of 12.9% in mean visual field area was observed (P=.025). Conclusions: These data support the conclusion that the intervention offered in Cuba provides no benefit to patients with retinitis pigmentosa as measured by visual acuity, visual field area, and ERG. The magnitudes of the mean declines observed in ERG amplitude and visual field area over a 6- to 8-month interval, relative to those reported in previous studies, raise the possibility that this intervention may worsen the course of the disease. RP Berson, EL (reprint author), HARVARD UNIV, MASSACHUSETTS EYE & EAR INFIRM, SCH MED, BERMAN GUND LAB, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 13 TC 20 Z9 21 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 1996 VL 114 IS 5 BP 560 EP 563 PG 4 WC Ophthalmology SC Ophthalmology GA UJ223 UT WOS:A1996UJ22300007 PM 8619765 ER PT J AU Rodriguez, A Calonge, M PedrozaSeres, M Akova, YA Messmer, EM DAmico, DJ Foster, CS AF Rodriguez, A Calonge, M PedrozaSeres, M Akova, YA Messmer, EM DAmico, DJ Foster, CS TI Referral patterns of uveitis in a tertiary eye care center SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; SYPHILIS; MANIFESTATIONS; TOXOPLASMOSIS; ANTERIOR; AIDS AB Objective: To analyze the referral patterns and diagnosis of uveitis during the past decade in a large tertiary eye center. Design: The records of 1237 patients with uveitis referred to the Immunology Service of the Massachusetts Eye and Ear Infirmary from 1982 to 1992 were classified and analyzed. Data regarding sex, race, nationality, referral site, ages at presentation and onset of uveitis, ocular involvement, clinical characteristics, ocular condition, and systemic disease associations were obtained. Results: The mean age at onset of uveitis was 37.2 years; the male-to-female ratio was 1:1.4. Most patients were white (85.8%), born in the United States (83.1%), and referred from within New England (84.7%). Anterior uveitis was most common (51.6%), followed by posterior uveitis (19.4%), panuveitis (16.0%), and intermediate uveitis (13.0%). Chronic (58.3%), nongranulomatous (77.7%), and noninfectious (83.1%) were the most frequent types of uveitis. The most common entities included idiopathic (34.9%), seronegative spondyloarthropathies (10.4%), sarcoidosis (9.6%), juvenile rheumatoid arthritis (5.6%), systemic lupus erythematosus (4.8%), Behcet's disease (2.5%), and the acquired immunodeficiency syndrome (2.4%). Conclusion: The appearance of new uveitic entities, such as the acute retinal necrosis syndrome, multifocal choroiditis and panuveitis, birdshot retinochoroidopathy, and acquired immunodeficiency syndrome-related uveitis, and the reemergence of the classic infectious causes of uveitis, tuberculosis and syphilis, have changed the way we approach the diagnosis and management of posterior and panuveitis at the Massachusetts Eye and Ear Infirmary. C1 UNIV VALLADOLID,INST APPL OPHTHALMOBIOL,VALLADOLID,SPAIN. RP Rodriguez, A (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA 02114, USA. RI Calonge, Margarita/K-2839-2014; OI Calonge, Margarita/0000-0001-8178-4836; Rodriguez-Garcia, Alejandro/0000-0002-1419-2109 NR 35 TC 184 Z9 196 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 1996 VL 114 IS 5 BP 593 EP 599 PG 7 WC Ophthalmology SC Ophthalmology GA UJ223 UT WOS:A1996UJ22300013 PM 8619771 ER PT J AU Wong, JJ Hartstein, ME Hoenig, J AF Wong, JJ Hartstein, ME Hoenig, J TI Adjustable suture technique for levator recession SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Objective: To determine whether an adjustable suture technique is clinically useful in levator recession surgery. Design: Consecutive clinical series. Setting: Inpatient hospital and ambulatory surgical center. Participants: Ten patients who were undergoing levator recession surgical procedures for correction of eyelid retraction constituted the group of subjects of this study. Outcome Measures: Outcome measures included margin-reflex Results: Postoperative margin-reflex distance and palpebral fissure measurements were within 0.5 mm of the desired eyelid position in 10 of 14 procedures and within 1 mm of the desired position in 12 of 14 procedures. Conclusion: Adjustable sutures may be a useful adjunct in levator recession surgery. C1 NEW ENGLAND EYE CTR,BOSTON,MA. TUFTS UNIV,SCH MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. NR 8 TC 0 Z9 0 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAY PY 1996 VL 114 IS 5 BP 620 EP 624 PG 5 WC Ophthalmology SC Ophthalmology GA UJ223 UT WOS:A1996UJ22300022 ER PT J AU Perrin, JM Greenspan, P Bloom, SR Finkelstein, D Yazdgerdi, S Leventhal, JM Rodewald, L Szilagyi, P Homer, CJ AF Perrin, JM Greenspan, P Bloom, SR Finkelstein, D Yazdgerdi, S Leventhal, JM Rodewald, L Szilagyi, P Homer, CJ TI Primary care involvement among hospitalized children SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID NEW-YORK-CITY; CHILDHOOD ASTHMA; SERVICES; POVERTY; RATES AB Objective: To examine relations between characteristics of a child's usual source of primary care and involvement of that source before and during hospitalization. Design: Medical record review of pediatric hospitalizations. Setting: All hospitals in Boston, Mass; New Haven, Conn; and Rochester, NY admitting children during the calendar years 1988 through 1990. Patients: The study included 1875 randomly selected pediatric hospitalizations for five diagnostic groups tie, asthma and other lower respiratory tract disease, abdominal pain [including appendicitis], meningitis [bacterial and viral], toxic ingestions, and head injury). Hospital records selected were limited to children aged between 1 month and 12 years and residing in the three study communities. Outcome Measures: Whether the primary care source examined the child before admission to the hospital, referred the child to the emergency department, or served as the in-hospital attending physician. Results: Of the medical charts reviewed, 85.7% identified primary care sources. Children in Rochester had higher rates of medical visits before admission (P<.04), referrals (P<.001), and in-hospital care provided by the primary care physician (P<.001, chi(2)) than children in Boston and New Haven. Patterns of primary care involvement also varied by source of care within cities, after controlling for income and severity of illness. Compared with children from Rochester community-based private practices, children in Boston receiving care from health centers, hospitals, or community-based private practices generally had 25% to 50% lower likelihood of positive findings on all primary care involvement measures. Children in New Haven receiving care from community-based private or hospital-based practices also had lower rates, but involvement rates were not higher when they received care from health centers. Other children in Rochester and children receiving care from health maintenance organizations in all cities demonstrated almost no significant differences compared with data from Rochester community practices. Conclusion: The source of primary care is associated with patterns of prehospital and hospital care among hospitalized children, although specific associations vary by city. C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,DEPT MED,BOSTON,MA 02115. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06510. UNIV ROCHESTER,DEPT PEDIAT,ROCHESTER,NY 14627. RP Perrin, JM (reprint author), MASSACHUSETTS GEN HOSP,CHILDRENS SERV,WACC 715,BOSTON,MA 02114, USA. FU AHRQ HHS [5RO1 HS 06060] NR 20 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAY PY 1996 VL 150 IS 5 BP 479 EP 486 PG 8 WC Pediatrics SC Pediatrics GA UJ619 UT WOS:A1996UJ61900007 PM 8620228 ER PT J AU Mithofer, K Warshaw, AL AF Mithofer, K Warshaw, AL TI Recurrent acute pancreatitis caused by afferent loop stricture after gastrectomy SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 103rd Scientific Session of the Western-Surgical-Association CY NOV 13-15, 1995 CL CHICAGO, IL SP W Surg Assoc ID OBSTRUCTION; APPEARANCE AB Afferent loop obstruction after gastrectomy and Billroth II gastrojejunostomy is only rarely diagnosed as the cause of recurrent acute pancreatitis. Three patients are described in whom afferent loop stricture after gastrectomy and Billroth II reconstruction manifested as recurrent pancreatitis 13 to 24 years after the initial procedure. Late onset, nonspecific symptoms, and other simultaneous gastrointestinal pathologic features promoted a chronic clinical course in all patients. Symptoms included acute abdominal pain, vomiting, jaundice, hyperamylasemia, weight loss, and anemia. A thorough history, barium examination, cholescintigraphy, and endoscopy were central in establishing the diagnosis. The pathogenesis of stricture formation is thought to be ischemic mucosal damage from intestinal crossclamping. Surgical decompression provided lasting relief of the symptoms. Afferent loop stricture should be considered in the differential diagnosis in patients with recurrent acute pancreatitis and previous gastrectomy with Billroth II reconstruction. C1 MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 23 TC 12 Z9 12 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD MAY PY 1996 VL 131 IS 5 BP 561 EP 565 PG 5 WC Surgery SC Surgery GA UK354 UT WOS:A1996UK35400035 PM 8624206 ER PT J AU Napoli, R Cittadini, A Chow, JC Hirshman, MF Smith, RJ Douglas, PS Horton, ES AF Napoli, R Cittadini, A Chow, JC Hirshman, MF Smith, RJ Douglas, PS Horton, ES TI Chronic growth hormone treatment in normal rats reduces post-prandial skeletal muscle plasma membrane GLUT1 content, but not glucose transport or GLUT4 expression and localization SO BIOCHEMICAL JOURNAL LA English DT Article ID INSULIN ACTION; CELLS AB Whether skeletal muscle glucose transport system is impaired in the basal, post-prandial state during chronic growth hormone treatment is unknown. The current study was designed to determine whether 4 weeks of human growth hormone (hGH) treatment (3.5 mg/kg per day) would impair glucose transport and/or the number of glucose transporters in plasma membrane vesicles isolated from hindlimb skeletal muscle of Sprague-Dawley rats under basal, post-prandial conditions. hGH treatment was shown to have no effect on glucose influx (V-max or K-m) determined under equilibrium exchange conditions in isolated plasma membrane vesicles. Plasma membrane glucose transporter number (R(o)) measured by cytochalasin B binding was also unchanged by hGH treatment. Consequently, glucose transporter turnover number (V-max/R(o)), a measure of average glucose transporter intrinsic activity, was similar in hGH-treated and control rats. hGH did not change GLUT4 protein content in whole muscle or in the plasma membrane, and muscle content of GLUT4 mRNA also was unchanged. In contrast, GLUT1 protein content in the plasma membrane fraction was significantly reduced by hGH treatment, This was associated with a modest, although not significant, decrease in muscle content of GLUT1 mRNA. In conclusion, high-dose hGH treatment for 4 weeks did not alter post-prandial skeletal muscle glucose transport activity, Neither the muscle level nor the intracellular localization of GLUT4 was changed by the hormone treatment. On the contrary, the basal post-prandial level of GLUT1 in the plasma membrane was reduced by hGH. The mRNA data suggest that this reduction might result from a decrease in the synthesis of GLUT1. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,BOSTON,MA. RI Cittadini, Antonio/I-8426-2012; OI Cittadini, Antonio/0000-0002-9905-9277; NAPOLI, Raffaele/0000-0002-3366-2321 FU NIDDK NIH HHS [DK36836, DK43038, R01-DK26317] NR 19 TC 14 Z9 14 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1996 VL 315 BP 959 EP 963 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK894 UT WOS:A1996UK89400038 PM 8645183 ER PT J AU Shen, TT Bogdanov, A Bogdanova, A Poss, K Brady, TJ Weissleder, R AF Shen, TT Bogdanov, A Bogdanova, A Poss, K Brady, TJ Weissleder, R TI Magnetically labeled secretin retains receptor affinity to pancreas acinar cells SO BIOCONJUGATE CHEMISTRY LA English DT Article ID IRON-OXIDE; MION AB Previously, we have developed a colloidal dextran-stabilized monocrystalline iron oxide nanocompound (MION-46) as a magnetic label for magnetic resonance imaging(MRI). In an effort to use this magnetic label to visualize pancreatic receptor function by MRI in vivo, we investigated the potential of secretin as a vector molecule. Secretin receptors, abundant on exocrine pancreas cells, recognize secretin through its amidated carboxyl terminal. In order to conjugate secretin to MION, we utilized the specific interaction between biotin and streptavidin, since direct conjugation of human secretin to MION has previously resulted in low yields and low affinity of the conjugate (unpublished results). Initially, we biotinylated the N-terminal primary amino group of secretin (60% yield). In a separate step, streptavidin (SA) was immobilized onto the surface dextran molecules of MION (79% yield) by reductive amination. Each secretin molecule was conjugated to one biotin molecule and each MION particle to an average of two SA molecules. The biotinylated secretin was then conjugated to MION through the biotin-streptavidin interaction (90% yield). The secretin-biotin-streptavidin-MION construct thus contained approximately two secretin molecules per MION. An in vitro competitive binding assay of pancreatic acinar cells demonstrated that the magnetically labeled secretin retained affinity to the secretin receptors. In vivo distribution studies in rats showed a significantly higher pancreatic accumulation of the secretin-biotin-streptavidin-MION construct as compared to the control group that had received unmodified MION. Our data indicate that bioactive peptides can be attached to dextran-coated iron oxide particles through the biotin-streptavidin interaction while retaining receptor affinity. Such target-specific agents have potential use in MR imaging to probe for a variety of receptor systems. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. FU NCI NIH HHS [R01 CA59649-01, 2RO1 CA 54886-OA, 5T32CA09502-10] NR 19 TC 35 Z9 39 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 1996 VL 7 IS 3 BP 311 EP 316 DI 10.1021/bc960003u PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA UN619 UT WOS:A1996UN61900005 PM 8816953 ER PT J AU Averboukh, L Douglas, SA Zhao, S Lowe, K Maher, J Pardee, AB AF Averboukh, L Douglas, SA Zhao, S Lowe, K Maher, J Pardee, AB TI Better gel resolution and longer cDNAs increase the precision of differential display SO BIOTECHNIQUES LA English DT Article ID MESSENGER-RNA C1 SMITHKLINE BEECHAM PHARMACEUT,KING OF PRUSSIA,PA 19406. GENOMYX,FOSTER CITY,CA. RP Averboukh, L (reprint author), CHILDRENS HOSP,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,44 BINNEY ST,BOSTON,MA 02115, USA. NR 6 TC 21 Z9 23 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1996 VL 20 IS 5 BP 918 EP 921 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UJ638 UT WOS:A1996UJ63800037 PM 8723942 ER PT J AU Suzuki, A Andrew, DP Gonzalo, JA Fukumoto, M Spellberg, J Hashiyama, M Takimoto, H Gerwin, N Webb, I Molineux, G Amakawa, R Tada, Y Wakeham, A Brown, J McNiece, I Ley, K Butcher, EC Suda, T GutierrezRamos, JC Mak, TW AF Suzuki, A Andrew, DP Gonzalo, JA Fukumoto, M Spellberg, J Hashiyama, M Takimoto, H Gerwin, N Webb, I Molineux, G Amakawa, R Tada, Y Wakeham, A Brown, J McNiece, I Ley, K Butcher, EC Suda, T GutierrezRamos, JC Mak, TW TI CD34-deficient mice have reduced eosinophil accumulation after allergen exposure and show a novel crossreactive 90-kD protein SO BLOOD LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; C DIRECTLY PHOSPHORYLATES; COLONY-FORMING CELLS; CD34+ MARROW-CELLS; L-SELECTIN; ENDOTHELIAL LIGAND; VASCULAR ADDRESSIN; PROGENITOR CELLS; STEM-CELLS; ANTIGEN AB CD34 is expressed on the surface of hematopoietic stem/progentior cells, stromal cells, and on the surface of high-endothelial venules (HEV). CD34 binds L-selectin, an adhesion molecule important for leukocyte rolling on venules and lymphocyte homing to peripheral lymph nodes (PLN). We generated CD34-deficient mutant animals through the use of homologous recombination. Wild-type and mutant animals showed no differences in lymphocyte binding to PLN HEV, in leukocyte rolling on venules or homing to PLN, in neutrophil extravasation into peritoneum in response to inflammatory stimulus, nor in delayed type hypersensitivity. Anti-L-selectin monoclonal antibody (MEL-14) also inhibited these immune responses similarly in both CD34-deficient and wildtype mice. However, eosinophil accumulation in the lung after inhalation of a model allergen, ovalbumin, is several-fold lower in mutant mice. We found no abnormalities in hematopoiesis in adult mice and interactions between mutant progenitor cells and a stromal cell line in vitro were normal. No differences existed in the recovery of progenitor cells after 5-fluorouracil treatment, nor in the mobilization of progenitor cells after granulocyte colony-stimulating factor treatment compared with wild-type animals. Surprisingly, although CD34 was not expressed in these mice, a portion of its 90-kD band crossreactive with MECA79 remained after Western blot. Thus, we have identified an additional molecule(s) that might be involved in leukocyte trafficking. These results indicate that CD34 plays an important role in eosinophil trafficking into the lung. (C) 1996 by The American Society of Hematology. C1 UNIV TORONTO, ONTARIO CANC INST, AMGEN INST, DEPT IMMUNOL, TORONTO, ON M5G 2C1, CANADA. AMGEN INC, BOULDER, CO USA. KYOTO UNIV, FAC MED, DEPT PATHOL 1, KYOTO, JAPAN. KUMAMOTO UNIV, SCH MED, INST MOL EMBRYOL & GENET, DEPT CELL DIFFERENTIAT, KUMAMOTO 860, JAPAN. HARVARD UNIV, SCH MED, CTR BLOOD RES INC, BOSTON, MA USA. AMGEN INC, THOUSAND OAKS, CA 91320 USA. UNIV VIRGINIA, HLTH SCI CTR, DEPT BIOMED ENGN, CHARLOTTESVILLE, VA USA. STANFORD UNIV, MED CTR, DEPT PATHOL, LAB IMMUNOL & VASC BIOL, STANFORD, CA 94305 USA. INST CANC RES, CHESTER BEATTY LABS, LEUKAEMIA RES FUND CTR, LONDON SW3 6JB, ENGLAND. RP Suzuki, A (reprint author), UNIV TORONTO, ONTARIO CANC INST,AMGEN INST,DEPT MED BIOPHYS, 620 UNIV AVE, SUITE 706, TORONTO, ON M5G 2C1, CANADA. RI Suda, Toshio/H-6761-2013 OI Suda, Toshio/0000-0001-7540-1771 FU NIGMS NIH HHS [GM 37734] NR 58 TC 114 Z9 116 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAY 1 PY 1996 VL 87 IS 9 BP 3550 EP 3562 PG 13 WC Hematology SC Hematology GA UH142 UT WOS:A1996UH14200003 PM 8611677 ER PT J AU Mauch, PM Kalish, LA Marcus, KC Coleman, CN Shulman, LN Krill, E Come, S Silver, B Canellos, GP Tarbell, NJ AF Mauch, PM Kalish, LA Marcus, KC Coleman, CN Shulman, LN Krill, E Come, S Silver, B Canellos, GP Tarbell, NJ TI Second malignancies after treatment for laparotomy staged IA-IIIB Hodgkin's disease: Long-term analysis of risk factors and outcome SO BLOOD LA English DT Article ID 2ND PRIMARY CANCERS; FOLLOW-UP; PROGNOSTIC FACTORS; RADIATION-THERAPY; ACUTE-LEUKEMIA; LUNG-CANCER; CHEMOTHERAPY; LYMPHOMA; RADIOTHERAPY; ASSOCIATION AB The survival of patients with Hodgkin's disease has dramatically improved over the past 30 years because of advances in treatment. However, concern for the risk of long-term complications has resulted in a number of trials to evaluate reduction of therapy. The consequences of these trials on recurrence, development of long-term complications, and survival remain unknown. One major consequence of successful treatment of Hodgkin's disease is the development of second malignant neoplasms. We sought to determine the factors most important for development of second tumors in pathologically staged and treated Hodgkin's disease patients followed for long intervals to provide background information for future clinical trials and guidelines for routine patient follow-up. Between April 1969 and December 1988, 794 patients with laparotomy staged (PS) IA-IIIB Hodgkin's disease were treated with radiation therapy (RT) alone or combined radiation therapy and chemotherapy (CT). There were 8,500 person-years of follow-up (average of 10.7 person-years per patient). Age and gender-specific incidence rates were multiplied by corresponding person-years of observation to obtain expected numbers of events. Observed to expected results were calculated by type of treatment, age at treatment, sex, and time after Hodgkin's disease. Absolute (excess) risk was expressed as number of excess cases per 10,000 person-years. Seventy-two patients have developed a second malignant neoplasm. Eight patients developed acute leukemia, 10 had non-Hodgkin's lymphoma (NHL), and 53 patients developed solid tumors at a median time of 5 years, 7.25 years, and 12.2 years, respectively, after Hodgkin's disease. One patient developed multiple myeloma 16.5 years after Hodgkin's disease. The relative risk (RR) of developing a second malignancy was 5.6. The absolute excess risk per 10,000 person-years (AR) of developing a second malignancy was 69.6 (7.0% excess risk per person per decade of follow-up). The highest RR occurred for the development of leukemia (RR = 66.2), however because of the low expected risk, the AR was only 9.3. The RR of solid tumors after Hodgkin's disease was lower (4.7); however, the AR was greater (49) than for acute leukemia. Among the solid tumors, breast, gastrointestinal, lung, and soft tissue cancers had the highest absolute excess risks. The risk for developing breast cancer after Hodgkin's disease was greatest in women who were under the age of 25 at treatment. The most significant risk factor for the development of both leukemia and solid tumors was the combined use of radiation therapy and chemotherapy. The RR following RT alone was 4.1 (AR = 51.1); for RT + CT (initially or at relapse) the RR was 9.75 (P < 0.05, nonoverlapping confidence limits, AR = 123.9). Survival following development of a second malignancy was poor in patients with leukemia, gastrointestinal tumors, lung cancer, and sarcoma. Survival from other malignancies including NHL and breast cancer was more encouraging. Second malignant neoplasms are a major cause of late morbidity and mortality following treatment for Hodgkin's disease. The most significant risk factor for the development of second tumors is the extent of treatment for Hodgkin's disease, Recommendations are presented for both prevention and early detection of these tumors. (C) 1996 by The American Society of Hematology. C1 BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT BIOSTAT,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. RP Mauch, PM (reprint author), DANA FARBER CANC INST,JOINT CTR RADIAT THERAPY,330 BROOKLINE AVE,BOSTON,MA 02215, USA. NR 55 TC 146 Z9 149 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1996 VL 87 IS 9 BP 3625 EP 3632 PG 8 WC Hematology SC Hematology GA UH142 UT WOS:A1996UH14200012 PM 8611686 ER PT J AU Liu, CN Lambert, JM Teicher, BA Blattler, WA OConnor, R AF Liu, CN Lambert, JM Teicher, BA Blattler, WA OConnor, R TI Cure of multidrug-resistant human B-cell lymphoma xenografts by combinations of anti-B4-blocked ricin and chemotherapeutic drugs SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; STANDARD REGIMEN CHOP; PHASE-I TRIAL; P-GLYCOPROTEIN; CYTO-TOXICITY; BLOCKED RICIN; TUMOR-CELLS; LEUKEMIA; VERAPAMIL; ADRIAMYCIN AB The CD-19-directed immunotoxin anti-B4-blocked ricin (anti-B4-bR) is currently in clinical trials for the treatment of B-cell malignancies, To explore the potential of using anti-B4-bR with chemotherapy protocols we tested the in vivo efficacy of the immunotoxin in combination with two multi-drug chemotherapeutic regimens in severe combined immunodeficient (SCID) mice bearing disseminated tumors of the multidrug-resistant human B-cell lymphoma Namalwa/mdr-1, In cytotoxicity studies in vitro, combinations of the immunotoxin with cisplatin produced supra-additive killing effects on both Namalwa and Namalwa/mdr-1 cells, whereas anti-B4-bR combined with 4-hydroperoxy-cyclophosphamide caused additive killing of both cell lines. In vivo cyclophosphamide, cisplatin, vincristine, doxorubicin, and etoposide as single agents, were effective in prolonging the survival of SCID mice burdened with the Namalwa tumor, whereas only cyclophosphamide and cisplatin were effective on Namalwa/mdr-1 tumors. Treatment of Namalwa/mdr-1-bearing mice with anti-B4-bR alone or with the drug combination CHOE (consisting of cyclophosphamide, vincristine, doxorubicin, and etoposide) alone increased the lifespan of the tumor-burdened mice by 58% and 73%, respectively. However, treatment with five daily bolus intravenous injections of anti-B4-bR followed by CHOE increased the lifespan by 173%, and 20% of the mice were cured, The drug combination CCE (cyclophosphamide, cisplatin, and etoposide) alone could increase the lifespan of the Namalwa/mdr-1 tumor-burdened mice by 129% compared with untreated controls, Combination therapy with anti-B4-bR and CCE produced long-term cures in 50% of the tumor-burdened mice. These results suggest that anti-B4-bR in combination with current multidrug regimens may constitute a highly efficacious modality for the treatment of drug-resistant B-cell malignancies. (C) 1996 by The American Society of Hematology. C1 DANA FARBER CANC INST,BOSTON,MA 02115. RP Liu, CN (reprint author), IMMUNOGEN INC,148 SIDNEY ST,CAMBRIDGE,MA 02139, USA. NR 48 TC 25 Z9 25 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1996 VL 87 IS 9 BP 3892 EP 3898 PG 7 WC Hematology SC Hematology GA UH142 UT WOS:A1996UH14200043 PM 8611717 ER PT J AU Parsons, SK Castellino, SM Lehmann, LE Eickhoff, CE Tarbell, NJ Sallan, SE Weinstein, HJ Billett, AL AF Parsons, SK Castellino, SM Lehmann, LE Eickhoff, CE Tarbell, NJ Sallan, SE Weinstein, HJ Billett, AL TI Relapsed acute lymphoblastic leukemia: Similar outcomes for autologous and allogeneic marrow transplantation in selected children SO BONE MARROW TRANSPLANTATION LA English DT Article DE allogeneic; autologous; relapsed ALL ID 2ND REMISSION; HOST DISEASE; TABLES; GRAFT AB The therapy of choice for relapsed childhood acute lymphoblastic leukemia is controversial, We retrospectively compared the outcome of 57 patients who received autologous bone marrow transplantation (BMT) with 17 patients who underwent allogeneic BMT for B cell lineage acute lymphoblastic leukemia after at least one marrow relapse. The allogeneic BMT cohort included only those who would also have been eligible for autologous BMT had they not had a matched sibling donor. Specifically, patients who were not in complete remission, those with T cell positive leukemia, t(9;22) or those with only an extramedullary relapse were excluded from both groups, Conditioning regimens included total body irradiation and chemotherapy. Age, white blood count at diagnosis, and duration of first and longest complete remissions were comparable for the two groups, The median follow-up of the event-free survivors was 4.8 years for those who received an autologous BMT (n = 26) and 4.6 years for those who received an allogeneic BMT (n = 8), The relapse rate was higher in the autologous BMT group and the incidence of nonleukemic deaths higher in the allogeneic BMT group. Event-free survival at 3 years was comparable for the two groups (47% +/- 7 vs 53% +/- 12, autologous vs allogeneic, respectively; P = 0.77), Based upon these findings, we concluded that the outcome for autologous BMT was equivalent to allogeneic BMT for relapsed childhood B cell lineage acute lymphoblastic leukemia in selected clinical situations. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. RP Parsons, SK (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 34183, 5K12 CA 01730, CA 06516] NR 28 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 1996 VL 17 IS 5 BP 763 EP 768 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA UK314 UT WOS:A1996UK31400016 PM 8733695 ER PT J AU Rimm, IJ Krenger, W Beland, JL Geller, MC DiSavino, E Yui, K Katsumata, M Ferrara, JLM AF Rimm, IJ Krenger, W Beland, JL Geller, MC DiSavino, E Yui, K Katsumata, M Ferrara, JLM TI TCR-beta transgenic mice fail to mediate a GVHR due to defects of allorecognition and subsequent IL-2 generation SO BONE MARROW TRANSPLANTATION LA English DT Article DE bone marrow transplantation; graft-versus-host disease; transgenic mice ID VERSUS-HOST DISEASE; T-CELL RECEPTORS; BONE-MARROW TRANSPLANTATION; MONOCLONAL-ANTIBODY; ACUTE GRAFT; ANTIGEN RECEPTOR; CHAIN; ALPHA; TOLERANCE; LEUKEMIA AB All T cells of TCR-beta transgenic mice bear a single TCR-beta chain and consequently the diversity of the TCR may be reduced by as much as one million-fold, Despite this limited diversity, many measures of lymphocyte function in these mice are normal, We have previously demonstrated that Lymphoid cells from TCR-beta mice are unable to mediate an intense graft-versus-host response (GVHR). In order to investigate the mechanism of this hyporesponsiveness, we studied in vivo allorecognition in diverse strains of TCR-beta mice, All tested strains of TCR-beta mice failed to mediate a substantial GVHR across multiple H-2 barriers, In addition, mixtures of cells from several strains of TCR-beta mice only generated mild GVHRs, Sensitive tests of in vitvo allorecognition show that lymphoid cells from TCR-beta mice respond less vigorously to alloantigen as measured both by decreased proliferation and decreased IL-2 production in a MLR, In addition, cells from TCR-beta mice fail to use exogenous IL-2 appropriately in their response to alloantigen. We conclude that the fixed TCR-beta chain causes a defective response to alloantigen, which is measured as decreased IL-2 generation and utilization, and that this abnormality results in a decreased GVHR. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RP Rimm, IJ (reprint author), DANA FARBER CANC INST,DIV PEDIAT ONCOL,DANA 1710B,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [P01 CA 39542]; NIAID NIH HHS [R01 AI 30018, R01 AI 36303] NR 49 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAY PY 1996 VL 17 IS 5 BP 835 EP 842 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA UK314 UT WOS:A1996UK31400027 PM 8733706 ER PT J AU Goto, T Marota, JJA Crosby, G AF Goto, T Marota, JJA Crosby, G TI Volatile anaesthetics antagonize nitrous oxide and morphine-induced analgesia in the rat SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthetics gases, nitrous oxide; anaesthetics volatile, halothane; anaesthetics volatile, isoflurane; analgesics opioid, morphine; interactions (drugs); rat ID SUB-MAC CONCENTRATIONS; ANESTHETIC REQUIREMENT; ENFLURANE MAC; HALOTHANE; ISOFLURANE; INHALATION; SUPPRESSION; NALOXONE; PRESSURE AB We reported previously that nitrous oxide induces pre-emptive analgesia that is partially antagonized by naloxone and totally antagonized by halothane. The aims of this study were to determine if halothane and isoflurane are similar in this respect and to examine if volatile anaesthetics antagonize the analgesic effect of exogenous opioids. We found that 75% nitrous oxide prolonged tail-flick latency by 37% and this analgesia was dose-dependently inhibited by halothane and, less effectively, by isoflurane. In contrast, morphine 1.25 mg kg(-1) i.v. also prolonged tail-flick latency by 35% but, unlike nitrous oxide-induced analgesia, this effect was attenuated only by high doses of halothane and was unaffected by isoflurane. Neither halothane nor isoflurane alone altered the tail-flick response. We conclude that both halothane and isoflurane dose-dependently antagonized nitrous oxide analgesia but antagonized morphine-induced analgesia to a lesser extent. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ANESTHESIA SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIA,BOSTON,MA 02114. NR 31 TC 25 Z9 25 U1 0 U2 0 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD MAY PY 1996 VL 76 IS 5 BP 702 EP 706 PG 5 WC Anesthesiology SC Anesthesiology GA UH212 UT WOS:A1996UH21200021 PM 8688273 ER PT J AU Muscat, JE Huncharek, M AF Muscat, JE Huncharek, M TI Dietary intake and the risk of malignant mesothelioma SO BRITISH JOURNAL OF CANCER LA English DT Article DE mesothelioma; diet; asbestos; carotenoids; lycopene; body weight ID LUNG-CANCER RISK; VEGETABLES; COLON AB A high consumption of fruit and vegetables reduces the risk of several types of cancer. There is little information on the association between dietary intake and mesothelioma. A hospital-based case-control study of 94 men and women with malignant mesothelioma and 64 control patients without cancer was conducted to determine the odds associated with consumption of carotenoid-containing fruits and vegetables. After statistical adjustment for occupational asbestos exposure, the odds ratio was 0.2 [95% confidence interval (CI) 0.1-0.8] for carrot consumption and 0.5 (95% Cl 0.2-1.4) for tomato consumption. However: the frequency of consuming other foods that have a high vitamin A or carotenoid content was not associated with a decreased risk of cancer. These results provide some justification for the hypothesis that provitamin A or beta-carotene may decrease the risk of mesothelioma. The body mass index was unrelated to the risk of mesothelioma. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. RP Muscat, JE (reprint author), AMER HLTH FDN,DIV EPIDEMIOL,320 E 43RD ST,NEW YORK,NY 10017, USA. FU NCI NIH HHS [CA-32617] NR 18 TC 18 Z9 18 U1 1 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1996 VL 73 IS 9 BP 1122 EP 1125 DI 10.1038/bjc.1996.215 PG 4 WC Oncology SC Oncology GA UG706 UT WOS:A1996UG70600017 PM 8624274 ER PT J AU Yamamoto, S PavanLangston, D Kinoshita, S Nishida, K Shimomura, Y Tano, Y AF Yamamoto, S PavanLangston, D Kinoshita, S Nishida, K Shimomura, Y Tano, Y TI Detecting herpesvirus DNA in uveitis using the polymerase chain reaction SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ACUTE RETINAL NECROSIS; VIRUS; DIAGNOSIS; AMPLIFICATION AB Background-Herpesviruses are involved in the pathogenesis of many ocular diseases including keratitis, iridocyclitis, and acute retinal necrosis syndrome. The rapid and accurate diagnosis of herpetic infections has become increasingly important with the rising incidence of immunosuppressive diseases. The purpose of this study was to evaluate the use of the polymerase chain reaction (PCR) to detect herpesvirus DNA in uveitis patients. Methods-Aqueous samples were aspirated from 11 patients with active uveitis of suspected viral origin. Using PCR, masked samples were assayed for herpes simplex virus (HSV), varicella tester virus (VZV), and cytomegalovirus (CMV) to assist in supporting the clinical diagnosis of viral aetiology. Masked controls included 10 aqueous humour specimens from normal patients undergoing cataract surgery and specimens from seven patients diagnosed with active non-viral uveitis - Behcet's disease, sarcoidosis, Fuchs' heterochromic iridocyclitis, or Harada's disease. Results-Ten of 11 cases clinically diagnosed as being of possible viral aetiology yielded aqueous PCR positive for a herpesvirus. Eight patients were PCR positive for amplified HSV DNA, of whom two had acute retinal necrosis, one had corneal endotheliitis, and five had recurrent iridocyclitis. VZV DNA was detected in one case of iridocyclitis, and CMV DNA in one case of chorioretinitis. Successful therapy was based on the PCR results. Ten normal aqueous specimens and the seven uveitis samples from cases not suspected of a viral aetiology were PCR negative for HSV, VZV, and CMV. Conclusion-These results demonstrate that detecting herpesvirus DNA in the aqueous humour is useful to support a clinical diagnosis of viral uveitis. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. KYOTO PREFECTURAL UNIV MED,KYOTO 602,JAPAN. RP Yamamoto, S (reprint author), OSAKA UNIV,SCH MED,DEPT OPHTHALMOL,2-2 YAMADAOKA,SUITA,OSAKA 565,JAPAN. NR 23 TC 50 Z9 55 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD MAY PY 1996 VL 80 IS 5 BP 465 EP 468 DI 10.1136/bjo.80.5.465 PG 4 WC Ophthalmology SC Ophthalmology GA UM864 UT WOS:A1996UM86400019 PM 8695570 ER PT J AU Gue, M Junien, JL Reeve, JR Rivier, J Grandt, D Tache, Y AF Gue, M Junien, JL Reeve, JR Rivier, J Grandt, D Tache, Y TI Reversal by NPY, PYY and 3-36 molecular forms of NPY and PYY of intracisternal CRF-induced inhibition of gastric acid secretion in rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE neuropeptide Y (NPY); peptide YY (PYY); sigma receptor; corticotropin-releasing factor (CRF); gastric acid secretion; central nervous system; pentagastrin ID CORTICOTROPIN-RELEASING FACTOR; NEUROPEPTIDE-Y; SIGMA-RECEPTORS; AUTORADIOGRAPHIC LOCALIZATION; PEPTIDE-YY; BRAIN-STEM; JO-1784; LIGAND; STRESS AB 1 The Y receptor subtype involved in the antagonism by neuropeptide Y (NPY) of intracisternal corticotropin-releasing factor (CRF)-induced inhibition of gastric acid secretion was studied in urethane-anaesthetized rats by use of peptides with various selectivity for Y-1, Y-2 and Y-3 subtypes: NPY, a Y-1, Y-2 and Y-3 agonist, peptide YY (PYY), a Y-1 and Y-2 agonist, [Leu(31), Pro(34)]-NPY, a Y-1 and Y-3 agonist, NPY(3-36) and PYY(3-36), highly selective Y-2 agonists and NPY(13-36) a weak Y-2 and Y-3 agonist. Peptides were injected intracisternally 10 min before intracisternal injection of CRF (10 mu g) and gastric acid secretion was measured by the flushed technique for 1 h before and 2 h after pentagastrin-(10 mu g kg(-1) h(-1), i.v.) infusion which started 10 min after CRF injection. 2 Intracisternal injection of CRF (10 mu g) inhibited by 56% gastric acid secretion stimulated by pentagastrin. Intracisternal injection of NPY and PYY (0.1-0.5 mu g) did not influence the acid response to pentagastrin but blocked CRF-induced inhibition of pentagastrin-stimulated acid secretion. NPY(3-36) (0.5 mu g) and PYY(3-36) (0.25 and 0.5 mu g) also completely blocked the inhibitory action of CRF on pentagastrin-stimulated acid secretion. 3 [Leu(31), Pro(34)]-NPY (0.5-5 mu g) and NPY(13-36) (0.5-5 mu g) injected intracisternally did not modify gastric acid secretion induced by pentagastrin or CRF inhibitory action. 4 The sigma antagonist, BMY 14802 (1 mg kg(-1) s.c.) did not influence the acid response to pentagastrin but prevented the antagonism by PW(3-36) (0.5 mu g) of the CRF antisecretory effect. 5 These results show that both PYY and NPY and the 3-36 forms of PYY and NPY are equipotent in blocking central CRF-induced inhibition of pentagastrin-stimulated gastric acid secretion. The structure activity profile suggests a mediation through Y-2 receptor subtype and the involvement of sigma binding sites. C1 W LOS ANGELES VET AFFAIRS MED CTR,CURE,DIGEST DIS RES CTR,DEPT MED,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,BRAIN RES INST,LOS ANGELES,CA 90073. JOUVEINAL RES INST,F-94260 FRESNES,FRANCE. SALK INST BIOL STUDIES,CLAYTON FDN LABS PEPTIDE BIOL,LA JOLLA,CA 92037. UNIV ESSEN GESAMTHSCH,DIV GASTROENTEROL,ESSEN,GERMANY. FU NIDDK NIH HHS [DK-33601, DK-41301]; NIMH NIH HHS [MH-00663] NR 38 TC 15 Z9 15 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 1996 VL 118 IS 2 BP 237 EP 242 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UL745 UT WOS:A1996UL74500007 PM 8735621 ER PT J AU Bodis, S Siziopikou, KP Schnitt, SJ Harris, JR Fisher, DE AF Bodis, S Siziopikou, KP Schnitt, SJ Harris, JR Fisher, DE TI Extensive apoptosis in ductal carcinoma in situ of the breast SO CANCER LA English DT Article DE screening mammography; necrosis; DCIS ID P53 PROTEIN; CELL-DEATH; INSITU; CANCER; FREQUENCY; INDUCTION AB BACKGROUND. More than 50% of breast ductal carcinomas in situ (DCIS) contain significant histologic necrosis, an important prognostic factor for determining recurrence and progression to invasive breast cancer. We have examined whether the mechanism of this spontaneous cell death might be apoptosis, a genetically encoded suicide pathway that may be triggered by various events including dysregulated cell proliferation. METHODS. Twenty-five untreated DCIS cases accessioned at our institution were examined for subtype, grade, and presence of apoptosis using two criteria: (1) cellular morphology (shrinkage, nuclear condensation, fragmentation, apoptotic bodies, and lack of inflammatory component); and (2) terminal transferase (TUNEL) staining of DNA fragmentation, a characteristic though less specific feature of apoptosis. Immunohistochemical staining was also carried out to assess whether wild-type p53, a regulator of apoptosis, was associated with this cell death. RESULTS. In all 19 cases with intraductal necrosis, cellular morphology was consistent with apoptotic death, despite its presence within sheets of ''geographic necrosis.'' Additionally, the identical regions were all strongly TUNEL-positive. No evidence of TUNEL staining was seen in 5 Grade I DCIS cases without intraductal necrosis. Immunohistochemical staining suggested that this apoptosis was independent of p53 mutational status. CONCLUSIONS. Extensive intraductal necrosis in DCIS is likely to represent apoptosis. However, it is unlikely that this apoptosis is regulated by p53. The apparently abundant apoptosis identified here, particularly in high grade DCIS, may be important in explaining why spontaneous cell death in DCIS is associated with a worse prognosis. (C) 1996 American Cancer Society. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DEPT PATHOL,BOSTON,MA. NR 33 TC 41 Z9 42 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1996 VL 77 IS 9 BP 1831 EP 1835 PG 5 WC Oncology SC Oncology GA UF719 UT WOS:A1996UF71900011 PM 8646681 ER PT J AU Fagundes, MA Zietman, AL Althausen, AF Coen, JJ Shipley, WU AF Fagundes, MA Zietman, AL Althausen, AF Coen, JJ Shipley, WU TI The management of spermatic cord sarcoma SO CANCER LA English DT Article DE sarcoma; spermatic cord; testicular neoplasms; radiation; orchiectomy ID SOFT-TISSUE SARCOMAS; LYMPH-NODE DISSECTION; PARATESTICULAR SARCOMAS; ADJUVANT CHEMOTHERAPY; MALIGNANT-TUMORS; RHABDOMYOSARCOMA; ADULTS; HEAD; NECK AB BACKGROUND, Between April 1963 and July 1991, 18 patients were treated for spermatic cord sarcoma. The histologic subtype distribution was: 7 leiomyosarcoma, 7 liposarcoma, 2 malignant fibrous histiocytoma, and 1 mesothelioma. METHODS, All patients underwent surgical resection: 16 radical orchiectomy and local excision. Nine were treated with orchiectomy alone, and 9 received adjuvant radiation. The radiation fields encompassed the ipsilateral iliac and inguinal lymph nodes, vas deferens, and hemiscrotum in 7 patients, and iliac and inguinal lymph nodes in 2 patients. RESULTS, The actuarial 5 and 8-year disease free survivals for the 18 patients were 77% and 58%, with an overall survival of 78% and 70%, respectively. The 5 and 8-year locoregional control rates were 82% and 61%. Five of 9 patients treated with surgery alone developed locoregional recurrence while none of the nine who had adjuvant radiation relapsed. The median follow-up for the irradiated group, however, was shorter (123 vs 63 months) and staging studies more complete. These potential biases are discussed. CONCLUSION, In this series, relapse was common after orchiectomy alone. Adjuvant radiation therapy may reduce the incidence of locoregional failure. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT UROL,GENITOURINARY ONCOL UNIT,BOSTON,MA. NR 25 TC 60 Z9 69 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1996 VL 77 IS 9 BP 1873 EP 1876 PG 4 WC Oncology SC Oncology GA UF719 UT WOS:A1996UF71900017 PM 8646687 ER PT J AU Zhou, GH Teicher, BA Frei, E AF Zhou, GH Teicher, BA Frei, E TI Postlabeling detection of DNA adducts of antitumor alkylating agents SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE postlabeling; alkylating agents; DNA adducts ID NITROGEN-MUSTARD INTERSTRAND; COMPLEXES INHIBIT REPAIR; OVARIAN-CANCER PATIENTS; CISPLATIN CHEMOTHERAPY; BLEOMYCIN TREATMENT; PLATINUM COMPLEXES; DAMAGE INVITRO; CROSS-LINKS; HUMAN-CELLS; CIS-DIAMMINEDICHLOROPLATINUM(II) AB The sensitivity for DNA adduct formation by antitumor alkylating agents (mechlorethamine, cisplatin and adozelesin) of the postlabeling technique and thin-layer chromatography was studied. Three DNAs were used: a double-stranded 20-bp oligonucleotide of defined sequence, calf thymus DNA and murine leukemia L1210 cellular DNA. With high concentrations of mechlorethamine, there was a marked decrease in normal dGp, a lesser decrease in dAp and dCp and no change in dTp. Using 2D mapping PEI-cellulose thin-layer chromatography analyses, it was found that six mechlorethamine: DNA adducts were produced after a short exposure to mechlorethamine. After an extended time at relatively high drug concentrations there was an alteration in the mechlorethamine: DNA adduct pattern that may reflect the conversion of monoadducts to crosslinked adducts. Similar observations were made with cisplatin and adozelesin. When murine leukemia L1210 cells were treated with 50 mu M mechlorethamine or 50 mu M cisplatin for 1 h, six or more mechlorethamine: DNA adducts and fire cisplatin: DNA adducts were detected. After allowing 6 h. for repair of potentially lethal damage, several adducts were no longer detectable and others appeared with diminished intensity. Nuclease P-1 dephosphorylates normal nucleotides at relatively low enzyme concentrations with variation depending upon the nucleotide. In general, considerably lower concentrations of nuclease P-1 were required to dephosphorylate the normal nucleotides than to dephosphorylate the antitumor alkylating agent: nucleotide adducts, thus allowing increased sensitivity of the postlabeling assay. The sensitivity of detection of antitumor alkylating agent: DNA adducts in DNA from treated L1210 cells approached one adduct per 10(7)-10(8) nucleotides. These results suggest that the postlabeling technique may be sufficiently sensitive and specific for the study of the clinically effective levels of antitumor alkylating agents. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [5P01-CA38493] NR 51 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1996 VL 38 IS 1 BP 71 EP 80 DI 10.1007/s002800050450 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA UB308 UT WOS:A1996UB30800012 PM 8603455 ER PT J AU Schatzkin, A Lanza, E Freedman, LS Tangrea, J Cooper, MR Marshall, JR Murphy, PA Selby, JV Shike, M Schade, RR Burt, W Kikendall, JW Cahill, J AF Schatzkin, A Lanza, E Freedman, LS Tangrea, J Cooper, MR Marshall, JR Murphy, PA Selby, JV Shike, M Schade, RR Burt, W Kikendall, JW Cahill, J TI The Polyp Prevention Trial I: Rationale, design, recruitment, and baseline participant characteristics SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLON CANCER; COLORECTAL-CANCER; DIETARY FIBER; EPIDEMIOLOGIC EVIDENCE; ADENOMATOUS POLYPS; UNITED-STATES; RISK; CARCINOGENESIS; SURVEILLANCE; MORTALITY AB The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial examining the effect of a low-fat (20% of total energy intake), high-fiber (18 g/1000 kcal), high-vegetable and -fruit (5-8 daily servings) dietary pattern on the recurrence of adenomatous polyps of the large bowel, precursors of most colorectal malignancies. Eligibility criteria include one or more adenomas removed within 6 months of randomization; complete nonsurgical polyp removal and complete colonic examination to the cecum at the qualifying colonoscopy; age 35 years or more; no history of colorectal cancer, inflammatory bowel disease, or large bowel resection; and satisfactory completion of a food frequency questionnaire and 4-day food record. Of approximately 38,277 potential participants with one or more polyps recently resected, investigators at eight clinical centers randomized 2,079 (5.4%; 1,037 in the intervention and 1,042 in the control arm) between June 1991 and January 1994, making the PPT the largest adenoma recurrence trial ever conducted. Of PPT participants, 35% are women and 10% are minorities. At study entry, participants averaged 61.4 Sears of age; 14% of them smoked, and 22% used aspirin. At the baseline colonoscopy, 35% of participants had two or more adenomas, and 29% had at least one large (greater than or equal to 1 cm) adenoma. Demographic, behavioral, dietary, and clinical characteristics are comparable across the two study arms. Participants have repeat colonoscopies after 1 (T-1) and 4 (T-4) years of follow-up. The primary end point is adenoma recurrence; secondary end points include number, size, location, and histology of adenomas. All resected lesions are reviewed centrally by gastrointestinal pathologists. The trial provides 90% power to detect a reduction of 24% in the annual adenoma recurrence rate. The primary analytic period, on which sample size calculations were based, is 3 years (T-1 to T-4), which permits a 1-year lag time for the intervention to work and allows a more definitive clearing of lesions at T-1, given that at least 10-15% of polyps may be missed at baseline, The final (T-4) colonoscopies are expected to be completed in early 1998. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. SUNY BUFFALO,SCH MED & BIOMED SCI,BUFFALO,NY. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,HINES,IL 60141. KAISER FDN RES INST,OAKLAND,CA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV UTAH,SALT LAKE CITY,UT. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. WESTAT CORP,ROCKVILLE,MD. RP Schatzkin, A (reprint author), NCI,DEPT HLTH & HUMAN SERV,PUBL HLTH SERV,NIH,BETHESDA,MD 20892, USA. NR 50 TC 82 Z9 84 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1996 VL 5 IS 5 BP 375 EP 383 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UJ727 UT WOS:A1996UJ72700009 PM 9162304 ER PT J AU Lanza, E Schatzkin, A BallardBarbash, R Clifford, DC Paskett, E Hayes, D Bote, E Caan, B Shike, M Weissfeld, J Slattery, M Mateski, D AF Lanza, E Schatzkin, A BallardBarbash, R Clifford, DC Paskett, E Hayes, D Bote, E Caan, B Shike, M Weissfeld, J Slattery, M Mateski, D TI The Polyp Prevention Trial II: Dietary intervention program and participant baseline dietary characteristics SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; SELF-EFFICACY; CANCER; VEGETABLES; FAT; QUESTIONNAIRE; REDUCTION; FIBER; FRUIT; RISK AB The Polyp Prevention Trial (PPT) is a multicenter randomized controlled trial to evaluate whether a low-fat, high-dietary fiber, high-fruit and -vegetable eating pattern will reduce the recurrence of adenomatous polyps of the large bowel. Men and women who had one or more adenomas removed recently were randomized into either the intervention (it = 1037) or control (it = 1042) arms, Food frequency questionnaire data indicate that PPT participants at the beginning of the trial consumed 36.8% of total energy from fat, 9.7 g of dietary fiber/1000 kcal, and 3.8 daily servings of fruits and vegetables, Baseline dietary characteristics, including intake of fat, fiber, and fruits and vegetables, as well as other macro- and micronutrients, were similar in the two study groups, The intervention participants receive extensive dietary and behavioral counseling to achieve the PPT dietary goals of 20% of total energy from fat, 18 g/1000 kcal of dietary fiber, and 5-8 daily servings (depending on total caloric intake) of fruits and vegetables, Control participants do not receive such counseling and are expected to continue their usual intake, Dietary intake in both groups is monitored annually using a 4-day food record (also completed at 6 months by intervention participants only) and a food frequency questionnaire, with a 10% random sample of participants completing an annual unscheduled 24-h telephone recall, Blood specimens are drawn and analyzed annually for lipids and carotenoids, This article provides details on the rationale and design of the PPT dietary intervention program and describes the participant baseline dietary intake data characteristics. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. SUNY BUFFALO,SCH MED & BIOMED SCI,BUFFALO,NY. US DEPT VET AFFAIRS,VET AFFAIRS EDWARD HINES JR HOSP,HINES,IL 60141. KAISER FDN RES INST,OAKLAND,CA. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV UTAH,SALT LAKE CITY,UT. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. WESTAT CORP,ROCKVILLE,MD. NR 52 TC 66 Z9 66 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 1996 VL 5 IS 5 BP 385 EP 392 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UJ727 UT WOS:A1996UJ72700010 PM 9162305 ER PT J AU Tamiya, T Ono, Y Wei, MX Mroz, PJ Moolten, FL Chiocca, EA AF Tamiya, T Ono, Y Wei, MX Mroz, PJ Moolten, FL Chiocca, EA TI Escherichia coli gpt gene sensitizes rat glioma cells to killing by 6-thioxanthine or 6-thioguanine SO CANCER GENE THERAPY LA English DT Article DE 6-thioxanthine; 6-thioguanine; retrovirus vector; brain tumor; neoplasm; gene transfer ID THYMIDINE KINASE GENES; MALIGNANT BRAIN-TUMORS; BEARING; THERAPY; SELECTION; INVIVO; LINE AB Genes that encode enzymes that convert inactive ''prodrugs'' into anticancer metabolites may be therapeutically useful against brain tumors. Unlike other genes tested to date in brain tumor models, the Escherichia coli gpt gene is unique in that it not only sensitizes cells to the prodrug 6-thioxanthine (6TX) but also encodes resistance to a different regimen (mycophenolic acid, xanthine, and hypoxanthine), thus providing a means to select for gpt-positive cells. In the present study, rat C6 glioma cells were infected with a retrovirus vector that transduces th is gene. A clonal line (C6GPT-7) was derived that exhibited significant 6TX susceptibility in vitro with an ID50 of 2.5 mu mol/L, whereas 50% growth inhibition of parental C6 cells was not achieved at concentrations tested (up to 50 mu mol/L). Th is line also exhibited significant sensitivity to 6-thioguanine (6TG), with an ID50 of 0.05 mu mol/L, whereas 50% growth inhibition of parental C6 cells was achieved at 0.5 mu mol/L. In a ''bystander'' assay, C6GPT-7 tumor cells efficiently transferred 6TX sensitivity to C6 cells at ratios as low as 1:9 (C6GPT-7:C6). This in vitro bystander effect was abrogated when C6GPT-7 and C6 cells were separated by a microporous membrane, suggesting that it was not mediated by highly diffusible metabolites. In vivo both 6TX and 6TG significantly inhibited the growth of subcutaneously transplanted C6GPT-7 cells but not that of C6 cells in athymic mice. In an intracerebral model, both 6TX and 6TG exhibited significant antiproliferative effects against tumors formed by C6GPT-7 cells. These findings provide a basis for exploring further gene therapy strategies based on in vivo transfer of the E coli gpt gene to provide chemosensitivity against 6TX and 6TG. C1 MASSACHUSETTS GEN HOSP, MOLEC NEUROGENET UNIT, DEPT NEUROL, CHARLESTOWN, MA 02129 USA. MASSACHUSETTS GEN HOSP, DEPT SURG, NEUROL SERV, CHARLESTOWN, MA 02129 USA. EDITH NOURSE ROGERS MEM VET ADM HOSP, RES DEPT, BEDFORD, MA 01730 USA. FU NINDS NIH HHS [NS24279] NR 26 TC 25 Z9 27 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 EI 1476-5500 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAY-JUN PY 1996 VL 3 IS 3 BP 155 EP 162 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA UN889 UT WOS:A1996UN88900003 PM 8725879 ER PT J AU Zhuang, ZP Vortmeyer, AO Mark, EJ Odze, R EmmertBuck, MR Merino, MJ Moon, H Liotta, LA Duray, PH AF Zhuang, ZP Vortmeyer, AO Mark, EJ Odze, R EmmertBuck, MR Merino, MJ Moon, H Liotta, LA Duray, PH TI Barrett's esophagus: Metaplastic cells with loss of heterozygosity at the APC gene locus are clonal precursors to invasive adenocarcinoma SO CANCER RESEARCH LA English DT Article ID CANCERS; AMPLIFICATION; DYSPLASIA; RECEPTOR; HST-1; RISK; P53 AB Adenocarcinoma in Barrett's esophagus is the second most rapidly increasing cancer in western society, The cause and pathogenesis are unknown, Although histological studies suggest that there is successive progression from metaplasia and dysplasia, with a high risk of subsequent invasive carcinoma, at present there is no direct evidence that metaplastic and dysplastic epithelia are clonal precursors of adenocarcinoma, We selected 12 esophagectomy specimens of Barrett's esophagus patients, which showed a spectrum of normal tissue, metaplasia, dysplasia, and invasive adenocarcinoma in each individual biopsy, We applied the microdissection technique to selectively procure microscopic tissue samples from H&E-stained slides for genetic evaluation using polymorphic markers flanking the APC gene locus, Identical APC gene alterations were found in the dysplastic and adenocarcinoma foci of all informative cases, The same changes were observed even in some metaplastic foci adjacent to dysplasia, Furthermore, clonality analysis of X-chromosome inactivation in female cases verified the same X-chromosome inactivation pattern in carcinoma, dysplasia, and metaplasia adjacent to dysplasia, No APC gene alterations were found in the normal epithelium and metaplasia distant from dysplasia, These data show for the first time that a tissue field of genotypic changes precedes the histopathological phenotypic changes of carcinoma in Barrett's esophagus syndrome, Our findings, in conjunction with the applied tissue microdissection technique, may help identify genotypic changes in patients with Barrett's esophagus before phenotypic changes occur, Therefore, genotyping of Barrett's metaplastic epithelium may supplement the histopathological evaluation of Barrett's esophagus. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. CATHOLIC UNIV SEOUL,MED COLL,SEOUL,SOUTH KOREA. NR 27 TC 88 Z9 90 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 1961 EP 1964 PG 4 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600002 PM 8616831 ER PT J AU Eng, C Mulligan, LM Healey, CS Houghton, C Frilling, A Raue, F Thomas, GA Ponder, BAJ AF Eng, C Mulligan, LM Healey, CS Houghton, C Frilling, A Raue, F Thomas, GA Ponder, BAJ TI Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma SO CANCER RESEARCH LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; PROTOONCOGENE AB Mutations in the RET proto-oncogene are associated with the pathogenesis of medullary thyroid carcinoma (MTC). In an attempt to understand this process, we examined microdissected subpopulations from MTC and multiple metastases from these tumors. Approximately 80% of sporadic MTCs had at least one subpopulation with the RET codon 918 mutation, which is a mutation previously detected in sporadic MTC as a somatic mutation and in multiple endocrine neoplasia type 2B as a germline mutation. However, the distribution of this mutation was nonhomogeneous, occurring only in subpopulations in most tumors and among subsets of multiple metastases, thus implying that although the codon 918 mutation could he an early event, it is not necessarily an early or essential event in tumorigenesis. This heterogeneity suggests either that the codon 918 mutation can arise as an event in progression within a metastatic clone or within a single tumor, or that MTC can be of polyclonal origin, Of significance, one of two multiple endocrine neoplasia type 2A MTCs carried a somatic mutation at codon 918, in addition to the RET mutation present in the germline, We found no correlation between the presence of other somatic genetic events, such as loss of heterozygosity on chromosome arms 1p and 22q, and RET mutation status in the various subpopulations of MTC. C1 UNIV CAMBRIDGE,ADDENBROOKES HOSP,CANC RES CAMPAIGN,HUMAN CANC GENET RES GRP,CAMBRIDGE CB2 2QQ,ENGLAND. UNIV CAMBRIDGE,ADDENBROOKES HOSP,DEPT HISTOPATHOL,CAMBRIDGE CB2 2QQ,ENGLAND. QUEENS UNIV,DEPT PATHOL,KINGSTON,ON K7L 3N6,CANADA. QUEENS UNIV,DEPT PAEDIAT,KINGSTON,ON K7L 3N6,CANADA. UNIV KRANKENHAUS HAMBURG,CHIRURG KLIN,W-2000 HAMBURG 20,GERMANY. UNIV HEIDELBERG,MED KLIN & POLIKLIN,INNERE MED ABT 1,D-69115 HEIDELBERG,GERMANY. RP Eng, C (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,DEPT MED,D920C,BOSTON,MA 02115, USA. OI Eng, Charis/0000-0002-3693-5145 NR 29 TC 118 Z9 124 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1996 VL 56 IS 9 BP 2167 EP 2170 PG 4 WC Oncology SC Oncology GA UG756 UT WOS:A1996UG75600038 PM 8616867 ER PT J AU Aguayo, SM Miller, Y Boose, D Holley, M Portanova, LB Schuyler, KD Kane, MA AF Aguayo, SM Miller, Y Boose, D Holley, M Portanova, LB Schuyler, KD Kane, MA TI Nonconstitutive expression of the gastrin-releasing peptide autocrine growth system in human small cell lung carcinoma NCI-H345 cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID BOMBESIN RECEPTOR SUBTYPES; CONSTITUTIVE EXPRESSION; LEUKEMIA-CELLS; EARLY SIGNALS; CANCER; BINDING; SECRETION; INVITRO; DENSITY; ASSAY AB Constitutive, unregulated autocrine growth is thought to be an important mechanism whereby cancer cells gain a proliferative advantage over nonmalignant cells. The question addressed here was whether the autocrine growth system for gastrin-releasing peptide (GRP) in human small cell lung carcinoma cells is, in fact, always expressed in a constitutive, unregulated fashion. Lag, rapid, and plateau growth states were defined for small cell lung carcinoma NCI-H345 cells based on periods during which they expressed different growth rates after plating as single cell suspensions. Immunoreactive GRP in the conditioned medium and in NCI-H345 cells harvested during each of these growth states, as well as cell DNA content, GRP mRNA expression, specific I-125-GRP uptake, specific I-125-GRP binding to solubilized membranes, and GRP and neuromedin B receptor mRNA expression by reverse transcription-PCR were analyzed. Maximal levels of GRP expression were observed during the lag growth state, with the highest concentration of immunoreactive GRP in the conditioned medium during the rapid growth state. Specific I-125-GRP uptake and binding were also highest during the lag growth state; however, GRP receptor mRNA did not significantly change. In contrast to prevailing concepts, these studies support the conclusion that the expression of the GRP autocrine growth system in NCI-H345 cells is indeed regulated. Furthermore, the components are maximally expressed before rapid growth begins, suggesting that other mechanisms are activated to support the actual proliferation. C1 UNIV COLORADO,HLTH SCI CTR,DENVER VET AFFAIRS MED CTR,DEPT MED,DIV PULM MED,DENVER,CO 80220. UNIV COLORADO,HLTH SCI CTR,DENVER VET AFFAIRS MED CTR,DIV MED ONCOL,DENVER,CO 80220. EMORY UNIV,SCH MED,DEPT MED,DIV PULM & CRIT CARE MED,ATLANTA,GA 30033. UNIV COLORADO,CTR CANC,DENVER,CO 80220. FU NCI NIH HHS [R29-CA44763, P50-CA58187]; NHLBI NIH HHS [R01-HL29891] NR 43 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1996 VL 7 IS 5 BP 563 EP 572 PG 10 WC Cell Biology SC Cell Biology GA UJ264 UT WOS:A1996UJ26400002 PM 8732666 ER PT J AU York, IA AF York, IA TI Immune evasion strategies of the herpesviruses SO CHEMISTRY & BIOLOGY LA English DT Article ID HUMAN CYTOMEGALOVIRUS; DOWN-REGULATION; EXPRESSION; ANTIGENS; SURFACE AB All viruses can deal with the immune response to some extent, and herpesviruses are exceptionally sophisticated in this ability. Recent work has uncovered some of the mechanisms by which herpesviruses subvert the antigen-presentation systems of their host cells. RP York, IA (reprint author), DANA FARBER CANC INST,DEPT LYMPHOCYTE BIOL,44 BINNEY ST,BOSTON,MA 02215, USA. OI York, Ian/0000-0002-3478-3344 NR 26 TC 10 Z9 11 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD MAY PY 1996 VL 3 IS 5 BP 331 EP 335 DI 10.1016/S1074-5521(96)90115-5 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UR743 UT WOS:A1996UR74300003 PM 8807861 ER PT J AU Kent, RL McDermott, PJ AF Kent, RL McDermott, PJ TI Passive load and angiotensin II evoke differential responses of gene expression and protein synthesis in cardiac myocytes SO CIRCULATION RESEARCH LA English DT Article DE angiotensin II; gene expression; protein synthesis; cardiac myocytes; cell culture ID ADULT FELINE CARDIOCYTES; STRETCH-INDUCED HYPERTROPHY; PRESSURE-OVERLOAD; HEART-CELLS; MAMMALIAN MYOCARDIUM; NA+-CA-2+ EXCHANGER; RAT-HEART; GROWTH; SYSTEM; CATECHOLAMINES AB This study introduced an improved model of loaded adult cardiocytes to address a proposed requirement for angiotensin II (Ang II) in the transduction pathway between load on the cardiac myocyte and its early anabolic responses of gene expression and acceleration of protein synthesis. The isolated cardiocytes were subjected to passive load by step increments of stretch and responded with proportional acceleration of protein synthesis in both adult and neonatal cardiocytes; this response was unaltered by 1 mu mol/L [Sar(1),Ile(8)]Ang II, an antagonist peptide to Ang II. Ang II from 1 nmol/L to 10 mu mol/L did not increase protein synthesis after 4 hours in adult cardiocytes nor at 100 nmol/L in neonatal cardiocytes. However, 100 nmol/L Ang II did increase [H-3]phenylalanine incorporation into neonatal cardiocyte protein by 10%, whereas passive load increased [H-3]phenylalanine incorporation into protein by 30%, which was not blocked by [Sar(1),Ile(8)]Ang II. Thus, the anabolic effect of load does not require Ang II to increase either 4-hour protein synthesis in both adult and neonatal cardiocytes or 24-hour [H-3]phenylalanine incorporation into neonatal cardiocytes. The genetic response of the cardiocyte to load was examined by assessing c-fos and Na+-Ca2+ exchanger mRNA levels, because these are rapidly expressed at the onset of cardiac pressure overload. The c-fos mRNA was increased fourfold within 1 hour after 100 nmol/L Ang II treatment of either adult or neonatal cardiocytes. This c-fos induction was blocked by [Sar(1),Ile(8)]Ang II. One hour after loading of adult cardiocytes, induction of c-fos expression was increased threefold; this was also blocked by [Sar(1),Ile(8)]Ang II. Thus, load-induced c-fos expression was Ang II dependent in adult cardiocytes. In contrast, exchanger mRNA levels were increased threefold 1 hour after loading of adult cardiocytes, but this increased expression was not blocked by [Sar(1),Ile(8)]Ang II. For additional comparison, c-fos expression was induced by Ang II and phorbol myristate acetate, which did not induce exchanger expression; conversely, exchanger expression was induced by veratridine, which did not increase c-fos expression. Thus, separate c-fos and exchanger expression pathways can be differentiated in adult cardiocytes. This study demonstrated that Ang II is not required for load to initiate the anabolic processes of accelerated protein synthesis or enhanced Na+-Ca2+ exchanger gene expression in cardiocytes; however, load induced c-fos expression is Ang II dependent. C1 MED UNIV S CAROLINA,GAZES CARDIAC RES INST,DIV CARDIOL,DEPT MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT PHARM & ANAT,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT CELL BIOL,CHARLESTON,SC 29425. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC. NR 51 TC 60 Z9 63 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1996 VL 78 IS 5 BP 829 EP 838 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA UH453 UT WOS:A1996UH45300011 PM 8620603 ER PT J AU Hallaq, Y Szczepiorkowski, ZM Teruya, J CluetteBrown, JE Laposata, M AF Hallaq, Y Szczepiorkowski, ZM Teruya, J CluetteBrown, JE Laposata, M TI Stability of plasma nonesterified arachidonate in healthy individuals in fasting and nonfasting states SO CLINICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; FREE FATTY-ACIDS; FLUORESCENCE DETECTION; ADIPOSE-TISSUE; QUANTIFICATION; METHYLATION; DIETARY; SERUM; WOMEN C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,DIV CLIN PATHOL,BOSTON,MA 02114. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 14 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1996 VL 42 IS 5 BP 771 EP 773 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA UJ253 UT WOS:A1996UJ25300022 PM 8653907 ER PT J AU Zhang, M Singh, RK Wang, MH Wells, A Siegal, GP AF Zhang, M Singh, RK Wang, MH Wells, A Siegal, GP TI Epidermal growth factor modulates cell attachment to hyaluronic acid by the cell surface glycoprotein CD44 SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE adhesion; CD44; EGF; EGF receptor; extracellular matrix; hyaluronic acid ID LYMPHOCYTE HOMING RECEPTOR; 3T3 CELLS; MONOCLONAL-ANTIBODIES; TUMOR INVASION; EGF; EXPRESSION; CANCER; VARIANTS; ANTIGEN; MATRIX AB Cell adhesion to and migration through extracellular matrices (ECM) are critical events in tumor invasion and metastasis, Previous work by us had demonstrated that signaling of epidermal growth factor receptor (EGFR) confers an oncogenic phenotype on NR6 cells and that these cells when transfected with hole EGFR demonstrate greater motility and invasiveness than cells carrying a carboxy-terminal truncated EGFR, Recently, a cell surface glycoprotein, CD44, has been implicated in cell-ECM adhesion involved in tumor cell migration, signal transduction, and metastasis, We investigated whether EGF regulates cellular interactions with ECM components, and in particular, hyaluronate, by modulating CD44 expression, In vitro cell attachment assays on hyaluronate-coated plates demonstrated similar basal level of binding (similar to 33%) for murine NR6 parental cells devoid of endogenous EGFR (P) or expressing wild-type EGFR (WT), while a time-dependent increase in binding was observed in WT cells stimulated with EGF, Additionally, utilizing monoclonal antibody blocking assays, CD44, but not EGFR, was shown to be directly involved in this' attachment, Both WT and P cells possessed equivalent 95 kDa bands on immunoblots, corresponding to CD44, The existence of CD44 mRNA was verified by RT-PCR using synthetic oligonucleotides in which a 1.1 kb cDNA was detected in both cell lines and confirmed by DNA sequencing, After 24-h exposure to exogenous EGF, an increase in CD44 protein and mRNA expression was found in WT cells, but not in P cells, supporting the contention that a functional EGFR signaling pathway is required for CD44 regulation, Thus, EGF stimulates cell binding to hyaluronate in vitro by regulating CD44 expression. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35233. UNIV ALABAMA,DEPT CELL BIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT SURG,BIRMINGHAM,AL 35294. UNIV ALABAMA,CELL ADHES & MATRIX RES CTR,BIRMINGHAM,AL. UNIV ALABAMA,CTR COMPREHENS CANC,BIRMINGHAM,AL 35294. BIRMINGHAM VET AFFAIRS MED CTR,BIRMINGHAM,AL. RI Siegal, Gene/A-8653-2009; OI Wells, Alan/0000-0002-1637-8150 NR 46 TC 22 Z9 22 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAY PY 1996 VL 14 IS 3 BP 268 EP 276 PG 9 WC Oncology SC Oncology GA UV508 UT WOS:A1996UV50800010 PM 8674281 ER PT J AU Strong, DM Friedlaender, GE Tomford, WW Springfield, DS Shives, TC Burchardt, H Enneking, WF Mankin, HJ AF Strong, DM Friedlaender, GE Tomford, WW Springfield, DS Shives, TC Burchardt, H Enneking, WF Mankin, HJ TI Immunologic responses in human recipients of osseous and osteochondral allografts SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FROZEN BONE ALLOGRAFTS; HLA-ALLOIMMUNIZATION; RANDOMIZED TRIAL; LYMPHOCYTE-B; REFRACTORINESS; PREVENTION; TRANSPLANTATION; TRANSFUSION AB A multiinstitutional study was carried out to evaluate immunologic responses for human recipients of massive frozen (-80 degrees C) osseous and osteochondral allografts, Allografts were used to reconstruct skeletal defects associated with a variety of traumatic degenerative and neoplastic disorders, Serum samples were obtained before surgery and from 1 month to 4 years after surgery. Sera were tested by microcytotoxicity against T cells from 60 donors for human leukocyte antigen Class I antibodies and against beta(2)-microglobulin treated B cells from 40 donors for human leukocyte antigen Class II antibodies, Panels were selected to represent the majority of known human leukocyte antigen specificities. Of the 84 cases evaluated, 62 (74%) received blood transfusions and 28 of 44 (64%) female recipients had been previously pregnant. Sensitization before transplant was shown in 33 of 84 (39%) patients. After grafting, 49 of 84 (58%) recipients showed evidence of sensitization to Class I antigens and 46 of 84 (55%) recipients showed evidence to sensitization to Class II antigens. Overall sensitization was 67%. C1 UNIV WASHINGTON,DEPT ORTHOPAED,SEATTLE,WA 98195. YALE UNIV,SCH MED,DEPT ORTHOPAED & REHABIL,NEW HAVEN,CT 06510. MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED,BOSTON,MA. UNIV FLORIDA,DEPT ORTHOPAED,GAINESVILLE,FL. MAYO CLIN & MAYO FDN,DEPT ORTHOPAED,ROCHESTER,MN 55905. PENN REG TISSUE BANK,SCRANTON,PA. RP Strong, DM (reprint author), PUGET SOUND BLOOD CTR & PROGRAM,NW TISSUE CTR,921 TERRY AVE,SEATTLE,WA 98104, USA. NR 50 TC 94 Z9 96 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 1996 IS 326 BP 107 EP 114 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UJ295 UT WOS:A1996UJ29500013 PM 8620630 ER PT J AU Krosnick, A AF Krosnick, A TI Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD MAY-JUN PY 1996 VL 18 IS 3 BP 359 EP 359 DI 10.1016/S0149-2918(96)80016-6 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UV992 UT WOS:A1996UV99200001 ER PT J AU Krosnick, A AF Krosnick, A TI Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD MAY-JUN PY 1996 VL 18 IS 3 BP 372 EP 372 DI 10.1016/S0149-2918(96)80018-X PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UV992 UT WOS:A1996UV99200003 ER PT J AU Krosnick, A AF Krosnick, A TI Editorial comment SO CLINICAL THERAPEUTICS LA English DT Editorial Material RP Krosnick, A (reprint author), JOSLIN DIABET CTR,BOSTON,MA 02215, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD MAY-JUN PY 1996 VL 18 IS 3 BP 391 EP 391 DI 10.1016/S0149-2918(96)80020-8 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UV992 UT WOS:A1996UV99200005 ER PT J AU GarciaAnoveros, J Corey, DP AF GarciaAnoveros, J Corey, DP TI Mechanosensation - Touch at the molecular level SO CURRENT BIOLOGY LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; NEURONS; GENE; MICROTUBULES AB The cloning of genes needed for gentle touch sensitivity in the nematode Caenorhabditis elegans has provided new molecular details about a proposed mechanosensory ion channel complex. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. RP GarciaAnoveros, J (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT NEUROL,WELLMAN 414,BOSTON,MA 02114, USA. OI Corey, David/0000-0003-4497-6016 NR 16 TC 19 Z9 36 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAY 1 PY 1996 VL 6 IS 5 BP 541 EP 543 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UL702 UT WOS:A1996UL70200019 PM 8805263 ER PT J AU Bhol, K Mohimen, A Neumann, R Yunis, J Foster, S Yunis, EJ Ahmed, AR AF Bhol, K Mohimen, A Neumann, R Yunis, J Foster, S Yunis, EJ Ahmed, AR TI Differences in the anti-basement membrane zone antibodies in ocular and pseudo-ocular cicatricial pemphigoid SO CURRENT EYE RESEARCH LA English DT Article DE anti-basement membrane zone antibody; autoantigen; cicatricial pemphigoid; immunoblot technique; MHC class II genes; pseudo or drug-related ocular cicatricial pemphigoid; human ID EPIDERMOLYSIS-BULLOSA-ACQUISITA; CIRCULATING AUTOANTIBODIES; CELL-LINES; IDENTIFICATION; VULGARIS; IMMUNOFLUORESCENT; PLAKOGLOBIN; AUTOIMMUNE; PATHOLOGY; DISTINCT AB Purpose. Ocular cicatricial pemphigoid (OCP) is a chronic autoimmune cicatrizing disease which affects the conjunctiva and other squamous epithelium, resulting in a scarring process. A similar process, limited only to the conjunctiva, observed in some patients using eye drops for the treatment of glaucoma, is called pseudo-ocular cicatricial pemphigoid (P-OCP). Immunofluorescence studies demonstrate deposition of immunoglobulins and complement components in the basement membrane zone (BMZ) of the conjunctiva and an anti-basement membrane zone antibody in the serum of patients. A striking association between OCP and MHC class II gene DQB1*0301 has been observed. The purpose of this study was to determine some of the differences in the binding of OCP and P-OCP sera to different lysate in an immunoblot assay, in an attempt to partially characterize the OCP and P-OCP antigens. Furthermore, we wanted to determine if the MHC class II gene association of P-OCP is similar to that of OCP. Methods. We studied sera from 11 patients with active ocular cicatricial pemphigoid and seven patients with pseudo-ocular cicatricial pemphigoid and controls. Indirect immunofluorescence (IIF) studies were done using monkey esophagus and salt split normal human skin as substrate. A sensitive immunoblot assay (IBA) was developed using normal human epidermis, dermis and conjunctiva as substrate. Typing for MHC class II genes was performed on eight pseudo-ocular cicatricial pemphigoid patients by dot-blot analysis and compared to 38 matched controls. Results. Weak staining of the basement membrane zone was observed in nine of ten ocular cicatricial pemphigoid sera and five of seven pseudo-ocular cicatricial pemphigoid sera in the IIF assay using monkey esophagus. Using salt split human skin as substrate, ten of eleven ocular cicatricial pemphigoid sera demonstrated low titer weak binding to the epidermal side of the split. No consistent pattern of staining was seen with pseudo-ocular cicatricial pemphigoid sera. Ten of the 11 ocular cicatricial pemphigoid sera demonstrated binding to 230, 205, 160 and 85 kDa proteins in the IBA using normal human epidermis and conjunctiva lysates. When the lysates were first reacted with BP sera and then immunoblotted with ocular cicatricial pemphigoid sera, the 230, 160, and 86 kDa bands disappeared, and only the 205 kDa band persisted. The sera of five of seven pseudo-ocular cicatricial pemphigoid patients bound to 290, 230, 205, 180, 97, and 85 kDa proteins in the epidermis and conjunctiva. However, the 230, 205, 180, and 85 kDa proteins are depleted when the lysates are first reacted with BP and ocular cicatricial pemphigoid sera. In the dermal lysate, the pseudo-ocular cicatricial pemphigoid sera recognize 400, 290, 150 and 45 kDa proteins. None of these are absorbed by BP, ocular cicatricial pemphigoid or pemphigus vulgaris or epidermolysis bullosa acquisita sera. The 290 kDa proteins identified in the dermis and epidermis are distinct from each other. No binding was seen with control sera with the 3 lysates. Statistically, dot-blot analysis did not demonstrate a significant increase in the frequency of the MHC DQB1*0301 gene. Conclusions. Patients with ocular cicatricial pemphigoid and pseudo-ocular cicatricial pemphigoid produce several autoantibodies. However, there are similarities and differences between them. The MHC class II genes associated with pseudo-ocular cicatricial pemphigoid are different from those with ocular cicatricial pemphigoid. This provides a new model system to study the immune abnormalities in idiopathic and drug-related organ specific autoimmunity. C1 CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH DENT MED,DEPT ORAL PATHOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA. DEPT OPHTHALMOL,BOSTON,MA. HARVARD UNIV,SCH MED,DEPT PATHOL,DANA FARBER CANC INST,DIV IMMUNOGENET,BOSTON,MA. FU NEI NIH HHS [EY08378]; NIDCR NIH HHS [DE09978] NR 49 TC 23 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 1996 VL 15 IS 5 BP 521 EP 532 DI 10.3109/02713689609000763 PG 12 WC Ophthalmology SC Ophthalmology GA UL417 UT WOS:A1996UL41700008 PM 8670753 ER PT J AU Coley, CM Eagle, KA AF Coley, CM Eagle, KA TI Preoperative assessment and perioperative management of cardiac ischemic risk in noncardiac surgery SO CURRENT PROBLEMS IN CARDIOLOGY LA English DT Review ID CORONARY-ARTERY DISEASE; PERIPHERAL VASCULAR-SURGERY; ABDOMINAL AORTIC-ANEURYSM; DOBUTAMINE STRESS ECHOCARDIOGRAPHY; SILENT-MYOCARDIAL-ISCHEMIA; TOTAL HIP-REPLACEMENT; NEW-YORK-STATE; DIPYRIDAMOLE-THALLIUM SCINTIGRAPHY; UNTREATED HYPERTENSIVE PATIENTS; EXERCISE TL-201 SCINTIGRAPHY C1 UNIV MICHIGAN,MED CTR,HEART CARE PROGRAM,ANN ARBOR,MI. RP Coley, CM (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114, USA. NR 324 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0146-2806 J9 CURR PROB CARDIOLOGY JI Curr. Probl. Cardiol. PD MAY PY 1996 VL 21 IS 5 BP 296 EP 382 PG 91 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UJ851 UT WOS:A1996UJ85100002 ER PT J AU Nelson, CE Morgan, BA Burke, AC Laufer, E DiMambro, E Murtaugh, LC Gonzales, E Tessarollo, L Parada, LF Tabin, C AF Nelson, CE Morgan, BA Burke, AC Laufer, E DiMambro, E Murtaugh, LC Gonzales, E Tessarollo, L Parada, LF Tabin, C TI Analysis of Hox gene expression in the chick limb bud SO DEVELOPMENT LA English DT Article DE Hox; limb; pattern; chick; Sonic hedgehog ID HOMEOBOX GENE; HOMEOTIC TRANSFORMATIONS; MOUSE EMBRYOS; PATTERN-FORMATION; RETINOIC ACID; XENOPUS; MORPHOGENESIS; TRANSGENE; EVOLUTION; PROTEIN AB The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Herd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Nora and Herd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Herd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Horn and Herd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3' genes are expressed in the fore limb bud while the 5' genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs, However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Herd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Herd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, hut depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg. C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOL EMBRYOL SECT,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,CTR DEV BIOL,DALLAS,TX 75235. RI Parada, luis/B-9400-2014; OI Laufer, Edward/0000-0002-4933-1017 NR 62 TC 375 Z9 384 U1 1 U2 19 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAY PY 1996 VL 122 IS 5 BP 1449 EP 1466 PG 18 WC Developmental Biology SC Developmental Biology GA UM558 UT WOS:A1996UM55800011 PM 8625833 ER PT J AU Dobens, L Raftery, L AF Dobens, L Raftery, L TI Establishing cell fates in an epithelial monolayer: Drosophila shortsighted demarcates a decapentaplegic sensitive boundary in anterior follicle cells during oogenesis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 CUTANEOUS BIOL RES CTR,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT DERMATOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY 1 PY 1996 VL 175 IS 2 BP 30 EP 30 PG 1 WC Developmental Biology SC Developmental Biology GA UK435 UT WOS:A1996UK43500086 ER PT J AU Almind, K Inoue, G Pedersen, O Kahn, CR AF Almind, K Inoue, G Pedersen, O Kahn, CR TI A common amino acid polymorphism in IRS-1 causes impaired insulin signaling: Evidence from transfection studies SO DIABETES LA English DT Meeting Abstract C1 JOSLIN DIABET CTR,BOSTON,MA 02215. STENO DIABET CTR,COPENHAGEN,DENMARK. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 1996 VL 45 SU 2 BP 570 EP 570 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ883 UT WOS:A1996UJ88300566 ER PT J AU Peterson, AE Maryniuk, MD AF Peterson, AE Maryniuk, MD TI Using a nutrition assessment to determine a nutrition prescription SO DIABETES EDUCATOR LA English DT Editorial Material RP Peterson, AE (reprint author), JOSLIN DIABET CTR,1 JOSLIN PL,BOSTON,MA 02215, USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC DIABETES EDUCATORS PI CHICAGO PA STE 1240, 444 NORTH MICHIGAN AVE, CHICAGO, IL 60611-3901 SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD MAY-JUN PY 1996 VL 22 IS 3 BP 205 EP & DI 10.1177/014572179602200303 PG 4 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA UL664 UT WOS:A1996UL66400003 PM 8788717 ER PT J AU Boner, G vanDyk, DJ Tan, MH Tan, J Ekstrand, A Koivisto, VA Groop, LC Groop, PH Lucas, A Romero, R Salinas, I Sanmarti, A Escobar, F EscobarJimenez, F CamposPastor, MM Mugoz, M Gomez, M Mangili, R Pozza, G Spotti, D Hansen, KW Christiansen, JS Klein, F Mogensen, CE Ziekenhuis, M vanDoorn, LG Spooren, PFMJ Cruickshank, JK Jervell, J Paus, PN Barnes, DJ Collins, A Viberti, GC Williams, G Nelstrop, GA Amorosa, L Anolik, JR Aronoff, SL Eubank, B Bailie, M Pelletier, L Blevins, T Charles, MA Perry, M Clarke, D Tomkey, D Einhorn, D Humphries, D Garber, AJ Haag, B Williams, E Hoy, W Watkins, M Kahkonen, D Kruger, D Kilo, C Laffel, L Golden, E Lodewick, P Lovinsky, D Mason, J Johnson, S McGill, J Schmidt, L Orlander, P Sorenson, K Raskin, P Hellenbrand, D Rosenblatt, S Schwartz, S Aufieri, J Sheehan, JP Ulchaker, M Skyler, JS Agramonte, R Starr, J Gagliastre, D Taylor, T Dawn, K Ward, WK Rigdon, M Cooper, M Gans, DJ AF Boner, G vanDyk, DJ Tan, MH Tan, J Ekstrand, A Koivisto, VA Groop, LC Groop, PH Lucas, A Romero, R Salinas, I Sanmarti, A Escobar, F EscobarJimenez, F CamposPastor, MM Mugoz, M Gomez, M Mangili, R Pozza, G Spotti, D Hansen, KW Christiansen, JS Klein, F Mogensen, CE Ziekenhuis, M vanDoorn, LG Spooren, PFMJ Cruickshank, JK Jervell, J Paus, PN Barnes, DJ Collins, A Viberti, GC Williams, G Nelstrop, GA Amorosa, L Anolik, JR Aronoff, SL Eubank, B Bailie, M Pelletier, L Blevins, T Charles, MA Perry, M Clarke, D Tomkey, D Einhorn, D Humphries, D Garber, AJ Haag, B Williams, E Hoy, W Watkins, M Kahkonen, D Kruger, D Kilo, C Laffel, L Golden, E Lodewick, P Lovinsky, D Mason, J Johnson, S McGill, J Schmidt, L Orlander, P Sorenson, K Raskin, P Hellenbrand, D Rosenblatt, S Schwartz, S Aufieri, J Sheehan, JP Ulchaker, M Skyler, JS Agramonte, R Starr, J Gagliastre, D Taylor, T Dawn, K Ward, WK Rigdon, M Cooper, M Gans, DJ TI Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria SO DIABETOLOGIA LA English DT Article DE microalbuminuria; diabetic nephropathy; angiotensin converting enzyme inhibition; insulin-dependent diabetes mellitus ID CONVERTING ENZYME-INHIBITION; INSULIN DEPENDENT DIABETICS; KIDNEY-FUNCTION; ANTIHYPERTENSIVE TREATMENT; URINARY ALBUMIN; ENALAPRIL; HYPERTENSION; PREVENTION; MELLITUS; THERAPY AB In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 of 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI): 31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril-treated group (-6.4 [-10.2--2.5] vs -1.4 [-5.3-2.6] ml . min(-1). 1.73 m(-2), p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects. C1 UNITED MED & DENT SCH, GUYS HOSP, METAB MED UNIT, LONDON SE1 9RT, ENGLAND. BEILINSON MED CTR, PETAH TIQWA, ISRAEL. HALIFAX INFIRM, HALIFAX, NS, CANADA. HELSINKI UNIV, CENT HOSP, HELSINKI, FINLAND. HOSP GERMANS TRIAS & PUJOL, BADALONA, SPAIN. HOSP UNIV GRANADA, GRANADA, SPAIN. IST SCI SAN RAFFAELE, MILAN, ITALY. KOMMUNEHOSP UNIV HOSP, AARHUS, DENMARK. MARIA ZIEKENHUIS TILBURG, TILBURG, NETHERLANDS. MED SPECTRUM TWENTE, ENSCHEDE, NETHERLANDS. NORTHWICK PK HOSP & CLIN RES CTR, HARROW HA1 3UJ, MIDDX, ENGLAND. SENTRALSYKEHUSET & AKERSHUS, NORDBYHAGEN, NORWAY. RIKSHOP OSLO, OSLO, NORWAY. UNITED MED & DENT SCH, GUYS HOSP, COORDINATING CTR, LONDON SE1 9RT, ENGLAND. UNITED MED & DENT SCH, GUYS HOSP, CENT LAB, LONDON SE1 9RT, ENGLAND. WATFORD DIST GEN HOSP, WATFORD, ENGLAND. ROBERT WOOD JOHNSON MED SCH, PISCATAWAY, NJ USA. ENDOCRINE ASSOCIATES DALLAS, DALLAS, TX USA. UNIV CONNECTICUT, CTR HLTH, STORRS, CT 06269 USA. AUSTIN DIAGNOST RES CTR, AUSTIN, TX USA. SHARP HLTH CARE DIABET RES CTR, SAN DIEGO, CA USA. METHODIST HOSP, HOUSTON, TX 77030 USA. BAYSTATE MED CTR, SPRINGFIELD, MA 01107 USA. LOVELACE FDN MED EDUC & RES, ALBUQUERQUE, NM 87108 USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. WASHINGTON UNIV, ST LOUIS, MO 63130 USA. UNIV TEXAS, HLTH SCI CTR, HOUSTON, TX USA. UNIV TEXAS, AUSTIN, TX 78712 USA. NEWPORT CLIN RES CTR, NEWPORT BEACH, CA USA. DIABET & GLANDULAR DIS CLIN, SAN ANTONIO, TX USA. N COAST INST DIABET & ENDOCRINOL, WESTLAKE, OH USA. JACKSON MED TOWERS, JACKSONVILLE, FL USA. WORCESTER DIABET METAB ASSOCIATES INC, WORCESTER, MA USA. GEORGETOWN UNIV HOSP, WASHINGTON, DC 20007 USA. PORTLAND DIABET CTR, PORTLAND, OR USA. RI Hoy, Wendy/A-7325-2010; Skyler, Jay/F-4211-2016; OI Hoy, Wendy/0000-0002-8405-1539; Mason, James/0000-0001-9210-4082; romero, ramon/0000-0001-9053-2649 NR 44 TC 141 Z9 142 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD MAY PY 1996 VL 39 IS 5 BP 587 EP 593 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UH678 UT WOS:A1996UH67800011 ER PT J AU Doria, A Lee, J Warram, JH Krolewski, AS AF Doria, A Lee, J Warram, JH Krolewski, AS TI Diabetes susceptibility at IDDM2 cannot be positively mapped to the VNTR locus of the insulin gene SO DIABETOLOGIA LA English DT Article DE insulin-dependent diabetes mellitus; insulin gene; tyrosine hydroxylase gene; VNTR; linkage disequilibrium ID REGION; MELLITUS AB An inconsistency has come to light between the conclusion of Lucassen et al. that IDDM2 (11p15.5) must lie within a 4.1 kilobase (kb) segment at the insulin (INS) locus and their own data showing statistically significant associations between insulin-dependent diabetes mellitus (IDDM) and markers beyond the boundaries of that segment. We present data from an independent study of 201 IDDM patients and 107 non-diabetic control subjects that also show significant association with a marker 5' of the INS locus. Patients and control subjects were genotyped at INS/ + 1140 A/C (a surrogate for the variable number tandem repeat (VNTR) polymorphism in the regulatory part of the INS gene) and a marker 5' of the tyrosine hydroxylase (TH) gene, TH/pINS500-RsaI, making it 10 kb 5' of the VNTR. Homozygotes for INS/ + 1140 allele ' + ' were significantly more frequent among IDDM patients than among control subjects (73 vs 45%, p < 0.001) giving an odds ratio of 3.3 (95% confidence interval (CI): 2.0-5.3). A very similar association was found for homozygotes for the TH/RsaI allele ' + ' (53 vs 31%, p < 0.001) giving an odds ratio of 2.6 (95% CI 1.6-4.2). By multilocus analysis, the TH/RsaI allele ' + ' identified a subset of INS/ + 1140 alleles ' + ' haplotypes that are more specifically associated with IDDM (odds ratio = 5.4, 95% CI 2.9-10.4) than allele + 1140 ' + ' as a whole. In conclusion, the segment of chromosome 11 that is associated with IDDM spans, at least, the INS and TH loci. No legitimate claim can be made that IDDM2 corresponds to the VNTR polymorphism at the INS locus until the correct boundaries for IDDM2 have been defined and other loci within them have been excluded as determinants of IDDM. C1 HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. RP Doria, A (reprint author), JOSLIN DIABET CTR,DIV RES,SECT EPIDEMIOL & GENET,1 JOSLIN PL,BOSTON,MA 02215, USA. FU NIDDK NIH HHS [P30-DK-36836] NR 25 TC 27 Z9 28 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 1996 VL 39 IS 5 BP 594 EP 599 DI 10.1007/BF00403307 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UH678 UT WOS:A1996UH67800012 PM 8739920 ER PT J AU Ura, S Araki, E Kishikawa, H Shirotani, T Todaka, M Isami, S Shimoda, S Yoshimura, R Matsuda, K Motoyoshi, S Miyamura, N Kahn, CR Shichiri, M AF Ura, S Araki, E Kishikawa, H Shirotani, T Todaka, M Isami, S Shimoda, S Yoshimura, R Matsuda, K Motoyoshi, S Miyamura, N Kahn, CR Shichiri, M TI Molecular scanning of the insulin receptor substrate-1 (IRS-1) gene in Japanese patients with NIDDM: Identification of five novel polymorphisms SO DIABETOLOGIA LA English DT Article DE insulin receptor substrate-1 (IRS-1); noninsulin-dependent diabetes mellitus; genetics; single-stranded conformation polymorphisms; insulin resistance; polymorphism ID DEPENDENT DIABETES-MELLITUS; SIGNAL TRANSDUCTION; MUTATION; PROTEIN; DEAFNESS; GLUCOSE; MUSCLE; CELLS; DNA AB Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a potential candidate for development of non-insulin-dependent diabetes mellitus (NIDDM). In this study, we have identified IRS-1 gene polymorphisms, evaluated their frequencies in Japanese subjects, and analysed the contribution of these polymorphisms to the development of NIDDM. The entire coding region of the IRS-1 gene of 94 subjects (47 NIDDM and 47 control subjects) was screened by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) analysis. Seven SSCP polymorphisms were identified. These corresponded to two previously identified polymorphisms [Gly(971)-->Arg (GGG-->AGG) and Ala(804) (GCA-->GCG)] as well as five novel polymorphisms [Pro(190)-->Arg (CCC-->CGC), Met(209)-->Thr (ATG-->ACG), Ser(809)-->Phe (TCT-->TTT), Leu(142) (CTT-->CTC), and Gly(625) (GGC-->GGT)]. Although the prevalence of each of these polymorphisms was not statistically different between NIDDM and control subjects, the prevalence of the four IRS-1 polymorphisms with an amino acid substitution together was significantly higher in NIDDM than in control subjects (23.4 vs 8.5%, p < 0.05), and two substitutions (Met(209)-->Thr and Ser(809)-->Phe) were found only in NIDDM patients. Equilibrium glucose infusion rates during a euglycaemic clamp in NIDDM and control subjects with the IRS-1 polymorphisms decreased by 29.5 and 22.0%, respectively on the average when compared to these in comparable groups without polymorphisms, although they were not statistically significant. Thus, IRS-1 polymorphisms may contribute in part to the insulin resistance and development of NIDDM in Japanese subjects; however, they do not account for the major part of the decrease in insulin-stimulated glucose uptake which is observed in subjects with clinically apparent NIDDM. C1 KUMAMOTO UNIV,SCH MED,DEPT METAB MED,KUMAMOTO 860,JAPAN. BRIGHAM & WOMENS HOSP,DEPT MED,DIV RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115. FU NIDDK NIH HHS [DK33201] NR 36 TC 53 Z9 53 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 1996 VL 39 IS 5 BP 600 EP 608 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UH678 UT WOS:A1996UH67800013 PM 8739921 ER PT J AU Warshaw, AL AF Warshaw, AL TI Ischemia- and reperfusion-related injury in pancreatitis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Editorial Material RP Warshaw, AL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,15 PARKHAM ST,WAC336,BOSTON,MA 02114, USA. NR 18 TC 18 Z9 18 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAY PY 1996 VL 41 IS 5 BP 821 EP 822 DI 10.1007/BF02091516 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UJ361 UT WOS:A1996UJ36100001 PM 8625748 ER PT J AU Teicher, BA Ara, G Emi, Y Kakeji, Y Ikebe, M Maehara, Y Buxton, D AF Teicher, BA Ara, G Emi, Y Kakeji, Y Ikebe, M Maehara, Y Buxton, D TI RSR13: Effects on tumor oxygenation and response to therapy SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE RSR13; tumor hypoxia; tumor oxygenation; radiation therapy ID FLUOSOL-DA 20-PERCENT; RAT MAMMARY-CARCINOMA; HEMOGLOBIN SOLUTION; BLOOD-FLOW; RADIATION RESPONSE; AFFINITY; RADIOSENSITIVITY; CARBOGEN; INVIVO; ENHANCEMENT AB RSR13, [2,4-[[(3,5-dimethylanilino)carbonyl] methyl] phenoxy]-2-methylpropionic acid], is a new allosteric effector of hemoglobin which causes hemoglobin to off-load oxygen more readily. Intravenous administration of RSR13 to rats bearing the 13762 mammary carcinoma resulted in a decrease in the hypoxic fraction (percent of pO(2) readings <5 mmHg) of the tumor that was dependent upon RSR13 dose and was maximal at 30 min after RSR13 administration. Breathing carbogen (95% oxygen/5% carbon dioxide) along with RSR13 administration markedly increased tumor oxygenation. Intravenous infusion of RSR13 (200 mg/kg) over 60 min resulted in maximal tumor oxygenation at 40 min into the infusion. By 30 min after completion of the infusion, tumor oxygenation had returned to baseline. RSR13 was very modestly cytotoxic to EMT-6 murine mammary carcinoma cells when administered to tumor-bearing animals in doses up to 500 mg/kg and was not toxic toward the bone marrow colony forming unit-granulocyte-macrophage (CFU-CM) from the same animals. Administration of RSR13 to animals bearing the Lewis lung carcinoma prior to each fraction of a fractionated radiation therapy regimen resulted in dose modification with dose-modifying factors up to 1.66. RSR13 administration also resulted in decreased numbers of lung metastases in these same animals. When RSR13 was administered on days P18, the modification of fractionated radiation remained the same but the number of lung metastases was decreased further. The combination of RSR13 with chemotherapy (cyclophosphamide, adriamycin, 5-fluorouracil, or cis-diamminedichloroplatinum II) resulted in 1.2-1.5-fold increases in the response of the primary tumor and marked decreases in lung metastases. In animals bearing the MB-49 bladder carcinoma, administration of RSR13 resulted in increased responses to both fractionated radiation therapy and chemotherapy and marked decreases in lung metastases. RSR13 was effective in decreasing the number of lung colonies formed by intravenously injected tumor cells if administered on the day prior to, on the same day as, or on the day after the tumor cells. Further investigation of this interesting new drug is warranted. (C) 1996 Wiley-Liss, Inc. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,DIV RADIAT BIOL,BOSTON,MA 02115. RP Teicher, BA (reprint author), DANA FARBER CANC INST,DIV CANC PHARMACOL,44 BINNET ST,BOSTON,MA 02115, USA. NR 43 TC 32 Z9 32 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD MAY PY 1996 VL 38 IS 1 BP 1 EP 11 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VF050 UT WOS:A1996VF05000001 ER PT J AU Mhashilkar, AM Agarwal, S Levin, R Marasco, WA AF Mhashilkar, AM Agarwal, S Levin, R Marasco, WA TI Genetic-based strategies for control of HIV-1: Tat and Rev as potential targets SO DRUG NEWS & PERSPECTIVES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; BY-PASSING IMMUNIZATION; TUMOR NECROSIS FACTOR; TRANS-ACTIVATOR GENE; VIRAL MESSENGER-RNA; ADENOASSOCIATED VIRUS; MUTATIONAL ANALYSIS; ANTIBODY FRAGMENTS; RETROVIRAL VECTORS C1 ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. NR 113 TC 2 Z9 2 U1 0 U2 1 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD MAY PY 1996 VL 9 IS 4 BP 220 EP 227 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UV378 UT WOS:A1996UV37800004 ER PT J AU Johnson, AL Bridgham, JT Witty, JP Tilly, JL AF Johnson, AL Bridgham, JT Witty, JP Tilly, JL TI Susceptibility of avian ovarian granulosa cells to apoptosis is dependent upon stage of follicle development and is related to endogenous levels of bcl-xlong gene expression SO ENDOCRINOLOGY LA English DT Article ID GALLUS-DOMESTICUS; ATRESIA; DEATH; HEN; FRAGMENTATION; THYMOCYTES; ZINC; DNA AB Studies were conducted to evaluate the susceptibility of avian ovarian granulosa cells to apoptosis when incubated in vitro and to relate this relative susceptibility to both the stage of follicle development from which granulosa cells were collected (atresia-prone vs. -resistant) and to the expression of a gene previously linked to the regulation of cell viability, bcl-xlong. Granulosa cells from slow growing, prehierarchal (4- to 8-mm diameter; atresia-prone) follicles were found to undergo rapid and progressively extensive apoptosis after incubation in defined medium for 6-24 h (P < 0.05 vs. unincubated controls). By contrast, cells from the largest preovulatory (F1) follicle, as well as from follicles most recently recruited into the follicle hierarchy (9- to 12-mm diameter), showed significantly less low molecular wt labeling at 6 h of incubation (P < 0.05 vs. 4- to 8-mm follicles). Furthermore, the amount of low molecular wt labeling did not significantly increase in cells from either stage of follicle development at 12 or 24 h of incubation (P > 0.05 vs. 6 h incubation). This biochemical indication of ongoing apoptosis in prehierarchal follicle granulosa cells was confirmed by an increased incidence of pyknotic nuclei detected by morphological analysis. Thus, increase susceptibility to apoptosis in incubated prehierarchal follicle granulosa cells is correlated with the high rate of follicle atresia that is known to occur at this stage of development in vivo. Recombinant human FSH (100 mIU) and transforming growth factor-alpha (3.3 nM) partially suppressed apoptosis in prehierarchal follicle granulosa cells after 6 h of incubation (by 46-57%; P < 0.05 vs. control), as did the cAMP analog, 8-Br-cAMP (1 mM; by 59%; P < 0.05). A single form of the bcl-2-related gene, bcl-x, was detected in hen ovarian tissues; this transcript corresponded to bcl-xlong, the death-suppressing form of bcl-x. The highest levels of bcl-xlong messenger RNA were found in granulosa tissue from preovulatory follicles, with significantly lower levels detected in prehierarchal follicle granulosa tissue (P < 0.05). Elevated expression of bcl-xlong in preovulatory follicles was correlated to increased resistance to the process of apoptosis, in, vitro, and the virtual absence of follicle atresia at this stage of development, in vivo. We conclude that there is a direct relationship between the inherent susceptibility of avian granulosa cells to apoptosis and the high rate of follicle atresia in follicles not yet selected into the preovulatory hierarchy. Moreover, our results are consistent with the proposal that the expression of death-suppressing genes, including bcl-xlong, is capable of rendering cells resistant to the process of apoptosis. The findings reported herein provide the foundation for a novel model with which to further elucidate molecular mechanisms related not only to the initiation of follicle atresia, but also events associated with the process of follicle selection. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,VINCENT CTR REPROD BIOL,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. RP Johnson, AL (reprint author), UNIV NOTRE DAME,DEPT BIOL SCI,NOTRE DAME,IN 46556, USA. FU NIA NIH HHS [R01-AG-12279]; NICHD NIH HHS [R55-HD-31188] NR 31 TC 89 Z9 95 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1996 VL 137 IS 5 BP 2059 EP 2066 DI 10.1210/en.137.5.2059 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UG636 UT WOS:A1996UG63600071 PM 8612548 ER PT J AU Shalev, A Meier, CA AF Shalev, A Meier, CA TI Peroxisome proliferator-activated receptors: A nuclear hormone receptor involved in adipocyte differentiation and lipid homeostasis SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DIV ENDOCRINE,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV GENET,BOSTON,MA 02115. NR 10 TC 6 Z9 6 U1 0 U2 1 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAY PY 1996 VL 134 IS 5 BP 541 EP 542 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UQ999 UT WOS:A1996UQ99900002 PM 8664970 ER PT J AU Meier, CA AF Meier, CA TI Leptin secretion and action: An update SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article RP Meier, CA (reprint author), MASSACHUSETTS GEN HOSP,DIV ENDOCRINE,WEL501,FRUIT ST,BOSTON,MA 02114, USA. NR 9 TC 16 Z9 16 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAY PY 1996 VL 134 IS 5 BP 543 EP 545 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UQ999 UT WOS:A1996UQ99900004 PM 8664972 ER PT J AU Mei, L Kachinsky, AM Seiden, JE Kuncl, RW Miller, JB Huganir, RL AF Mei, L Kachinsky, AM Seiden, JE Kuncl, RW Miller, JB Huganir, RL TI Differential expression of PTP1D, a protein tyrosine phosphatase with two SH2 domains, in slow and fast skeletal muscle fibers SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; HEAVY-CHAIN ISOFORMS; LOOP-HELIX PROTEINS; ACETYLCHOLINE-RECEPTOR; REGULATORY FACTORS; MYOGENIC PROGRAMS; GROWTH-FACTOR; KINASE-C; MYOSIN; PHOSPHORYLATION AB We show that PTP1D, a protein tyrosine phosphatase that contains two SH2 domains, is preferentially expressed in slow skeletal muscle fibers. Immunohistochemical staining using polyclonal antibodies against PTP1D demonstrated that PTP1D was expressed in a subpopulation of rodent muscle fibers. These fibers were identified as slow Type I fibers based on histochemical ATPase assays and slow myosin heavy chain expression. Northern and Western analyses showed that PTP1D levels were higher in predominantly slow muscles than in predominantly fast muscles. This differential expression of PTP1D in slow muscle fibers appeared by birth. In cultures of mouse myogenic cells, PTP1D was expressed after MyoD and myogenin and appeared in myotubes derived from embryonic, fetal, and postnatal myoblasts. Remarkably, PTP1D was organized into sarcomeres in a pattern coincident with myosin heavy chain, suggesting that PTP1D associates with a component of the thick filament. These results show that PTP1D is preferentially expressed in slow muscle fibers, We speculate that PTP1D may play a role in slow muscle fiber function and differentiation. (C) 1996 Academic Press, Inc. C1 MASSACHUSETTS GEN HOSP,NEUROMUSULAR LAB,BOSTON,MA 02129. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,NEUROMUSCULAR DIV,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT NEUROSCI,BALTIMORE,MD 21205. RP Mei, L (reprint author), UNIV VIRGINIA,SCH MED,DEPT PHARMACOL,CHARLOTTESVILLE,VA 22908, USA. RI Mei, Lin/G-8755-2012 FU NINDS NIH HHS [NS24418, NS34062] NR 76 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY 1 PY 1996 VL 224 IS 2 BP 379 EP 390 DI 10.1006/excr.1996.0148 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UJ210 UT WOS:A1996UJ21000018 PM 8612715 ER PT J AU Huang, SH Adamis, AP Wiederschain, DG Shima, DT Shing, Y Moses, MA AF Huang, SH Adamis, AP Wiederschain, DG Shima, DT Shing, Y Moses, MA TI Matrix metalloproteinases and their inhibitors in aqueous humor SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE tissue inhibitors of matrix metalloproteinases; extracellular matrix; collagenase inhibitor; DNA synthesis inhibitor; angiogenesis ID TRANSFORMING GROWTH-FACTOR; TISSUE INHIBITOR; FACTOR-BETA; COLLAGENASE INHIBITOR; GLAUCOMATOUS EYES; BOVINE CARTILAGE; ANGIOGENESIS; NEOVASCULARIZATION; PROLIFERATION; PURIFICATION AB Matrix metalloproteinase activity is the rate-limiting step in extracellular matrix degradation. One mechanism by which metalloproteinases are regulated is through the activity of their endogenous inhibitors, the tissue inhibitors of metalloproteinases. Since metalloproteinase activity is a key component of the angiogenic process and many anterior segment structures are largely avascular, we became interested in examining aqueous humor for the presence of metalloproteinases and their endogenous inhibitors. Using zymography, we have identified the presence of several metalloproteinases in normal aqueous humor. Treatment with 4-aminophenylmercuric acetate, an organomercurial which activates latent metalloproteinases, revealed that all metalloproteinases were in their active state. By Western blot analysis, normal aqueous humor was also found to contain at least two tissue inhibitors of metalloproteinases. Subsequent partial purification by two successive chromatographic steps revealed the presence of inhibitory activity against collagenase, endothelial cell DNA synthesis, and angiogenesis on the chick chorioallantoic membrane. The presence of metalloproteinases and their inhibitors in normal aqueous humor, a fluid which bathes avascular ocular structures, suggests that future studies should examine whether an imbalance in this protease/inhibitor family may contribute to the anterior chamber extracellular matrix alterations associated with diseases such as ocular neovascularization and glaucoma. (C) 1996 Academic Press Limited. C1 MASSACHUSETTS EYE & EAR INFIRM, DEPT OPHTHALMOL, BOSTON, MA 02114 USA. MASSACHUSETTS EYE & EAR INFIRM, CHILDRENS HOSP, DEPT SURG, SURG RES LAB, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, DEPT SURG, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, PROGRAM CELL & DEV BIOL, BOSTON, MA 02115 USA. NR 49 TC 31 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 1996 VL 62 IS 5 BP 481 EP 489 DI 10.1006/exer.1996.0058 PG 9 WC Ophthalmology SC Ophthalmology GA UN343 UT WOS:A1996UN34300003 PM 8759516 ER PT J AU Joseph, PM Witten, ML Burke, CH Hales, CA AF Joseph, PM Witten, ML Burke, CH Hales, CA TI The effects of chronic sidestream cigarette smoke exposure on eicosanoid production by tracheal epithelium SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE acrolein; eicosanoid; endotoxin; PGE(2); sidestream cigarette smoke; 6-keto-PGF(1 alpha); T chi B-2 ID PIG ISOLATED TRACHEA; ARACHIDONIC-ACID; PASSIVE SMOKING; SMOOTH-MUSCLE; PROSTAGLANDIN-E2 PRODUCTION; ENDOTHELIAL-CELLS; LUNG-CANCER; METABOLISM; ACROLEIN; RELEASE AB Environmental exposure to sidestream cigarette smoke (SSCS) has been associated with an increased incidence of pulmonary infection and bronchospasm. Chronic exposure to SSCS could modify the release of bronchoreactive eicosanoids by tracheal epithelium, the site of initial contact by lung with inhaled toxins. To assess this possibility, New Zealand white rabbits were placed in an environmental chamber flushed with 3 L of SSCS, 15 min/day for 20 days. Eighteen hours after the last exposure the animals were sacrificed and the tracheas were explanted. At 7 days, the epithelial cell outgrowths were exposed to media containing endotoxin (10 mu g/mL) or acrolein (50 mu M), an aldehyde commonly found in smoke, or to control media. After a 2-h exposure, media were assayed for eicosanoids by radioimmunoassay. PGE(2) was produced in epithelium from normal animals (5.7 +/- 1.3 ng/10(6) cells), and was not significantly different in SSCS-exposed epithelium. When incubated In medium containing acrolein, PGE(2) production increased significantly in SSCS-exposed epithelium (14.9 +/- 2.5, p < .05) but not in control groups. Endotoxin also increased PGE(2) production in SSCS-exposed cells (12.6 +/- 3.3 ng/10(6), p < .05). Baseline production of G-keto PGE(1 alpha) was 10.8 +/- 3.2 ng/10(6) cells In non-SSCS controls and did not change significantly in these cells with the addition of endotoxin or acrolein. In acrolein plus SSCS-exposed cells, 6-keto PGF(1 alpha) increased, in a dose-dependent manner, to 88.2 +/- 26.1 ng/10(6) (p < .05 compared to all normals, SSCS-exposed controls, and SSCS plus LPS). TxB(2) release in control, non-SSCS-exposed cells was 13.3 +/- 2.8 ng/10(6) cells and was significantly increased (p < .05) only in the SSCS plus acrolein group (60.7 +/- 16.2 ng/10(6) cells). The results indicate that even brief recurrent exposure to SSCS can change the production of cyclooxygenase products, particularly PGE(2), 6-keto PGF(1 alpha), and TxB(2). This may reflect art altered ability of SSCS-exposed tracheal epithelium to respond to environmental (e.g., acrolein) or bacterial (e.g., endotoxin) insults. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Joseph, PM (reprint author), MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,DEPT MED,FRUIT ST,BOSTON,MA 02114, USA. FU NHLBI NIH HHS [HL 07354, HL 368299] NR 53 TC 6 Z9 6 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD MAY-JUN PY 1996 VL 22 IS 3 BP 317 EP 335 DI 10.3109/01902149609031778 PG 19 WC Respiratory System SC Respiratory System GA UR046 UT WOS:A1996UR04600005 PM 8792124 ER PT J AU Sykes, M AF Sykes, M TI Immunobiology of transplantation SO FASEB JOURNAL LA English DT Article DE T cell; tolerance; T cell repertoire; chimerism; anergy; suppression; thymus; bone marrow transplantation ID T-CELLS; CLONAL ANERGY; TRANSGENIC MICE; HOST DISEASE; TOLERANCE; INDUCTION; LYMPHOCYTES; SUPPRESSION; MECHANISMS; ALLOGRAFTS AB Despite major advances resulting from the development of new immunosuppressive drugs in recent years, the field of clinical transplantation is currently limited by inadequate organ availability, chronic: rejection, and complications of chronic, nonspecific immunosuppressive therapy, Because of the organ shortage, extensive research has recently focused on the potential to use donors from other species, i.e., xenotransplantation, The best way to avoid the problems of chronic rejection and complications of immunosuppressive therapy, and to overcome the considerable immunologic barriers to xenotransplantation, would be to induce a state of systemic tolerance to the donor in the recipient, Recent developments in the understanding of mechanisms of central and peripheral T cell tolerance have led to new strategies for inducing tolerance in experimental models, some of which are already being evaluated clinically. RP Sykes, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NCI NIH HHS [CA64912]; NHLBI NIH HHS [HL49915] NR 69 TC 30 Z9 32 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAY PY 1996 VL 10 IS 7 BP 721 EP 730 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UN798 UT WOS:A1996UN79800006 PM 8635689 ER PT J AU Wershil, BK Furuta, GT Wang, ZS Galli, SJ AF Wershil, BK Furuta, GT Wang, ZS Galli, SJ TI Mast cell-dependent neutrophil and mononuclear cell recruitment in immunoglobulin E-induced gastric reactions in mice SO GASTROENTEROLOGY LA English DT Article ID CONNECTIVE-TISSUE-TYPE; TUMOR-NECROSIS-FACTOR; LATE PHASE REACTIONS; ALLERGIC DISEASES; FOOD ALLERGY; NU MICE; MOUSE; HYPERSENSITIVITY; INFILTRATION; PERITONITIS AB Background & Aims: Immunoglobulin (Ig) E-dependent reactions elicit an immediate response and can also result in a late-phase reaction that is characterized by the infiltration of leukocytes. This study assessed whether IgE-dependent late-phase responses can be elicited in the stomach wall of mice and examined the role of mast cells in this reaction, Methods: IgE-dependent gastric inflammation was elicited in genetically mast cell-deficient Kit(W)/Kit(W-v) mice, the congenic normal (+/+) mice, and mast cell-deficient Kit(W)/Kit(W-v) mice that had undergone local and selective reconstitution of gastric mast cell populations. Results: IgE-dependent gastric reactions were associated with mast cell degranulation and the infiltration of both neutrophils and mononuclear cells in normal mice, but no significant leukocyte infiltration was observed in mast cell-deficient Kit(W)/Kit(W-v) mice. By contrast, in mast cell-reconstituted Kit(W)/Kit(W-v) mice, IgE-dependent reactions were associated with the infiltration of neutrophils and mononuclear cells, Conclusions: These results show that late-phase reactions can occur during IgE-dependent gastric inflammation in the mouse and that the infiltration of both neutrophils and mononuclear cells that are observed during this reaction are mast cell dependent. C1 CHILDRENS HOSP,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BETH ISRAEL HOSP,DEPT PATHOL,DIV EXPTL PATHOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA/AI72074]; NIDDK NIH HHS [DK33506, DK1543] NR 27 TC 73 Z9 75 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1996 VL 110 IS 5 BP 1482 EP 1490 DI 10.1053/gast.1996.v110.pm8613053 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UH282 UT WOS:A1996UH28200019 PM 8613053 ER PT J AU Poplausky, MR Kaufman, JA Geller, SC Waltman, AC AF Poplausky, MR Kaufman, JA Geller, SC Waltman, AC TI Mesenteric venous thrombosis treated with urokinase via the superior mesenteric artery SO GASTROENTEROLOGY LA English DT Article ID LIVER-TRANSPLANTATION; COMPLICATIONS AB A 77-year-old man with a history of multiple surgically treated malignancies presented with increasing abdominal pain after eating. Computerized tomographic scan showed superior mesenteric vein and portal vein thrombosis. The patient was treated with selective superior mesenteric artery infusion of urokinase resulting in clinical improvement and near complete resolution of the mesenteric venous thrombosis. An underlying gastric malignancy was found and is believed to be the cause of the patient's hypercoagulable state. Direct infusion of urokinase into the superior mesenteric artery for treatment of mesenteric venous thrombosis is an alternative to surgery in selected patients and an alternative to the much more complicated delivery systems presently used. C1 MASSACHUSETTS GEN HOSP,DEPT VASC & INTERVENT RADIOL,BOSTON,MA 02114. NR 12 TC 69 Z9 79 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1996 VL 110 IS 5 BP 1633 EP 1635 DI 10.1053/gast.1996.v110.pm8613072 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UH282 UT WOS:A1996UH28200038 PM 8613072 ER PT J AU Doll, RF Crandall, JE Dyer, CA Aucoin, MM Smith, FI AF Doll, RF Crandall, JE Dyer, CA Aucoin, MM Smith, FI TI Comparison of promoter strengths on gene delivery into mammalian brain cells using AAV vectors SO GENE THERAPY LA English DT Article DE promoters; adeno-associated virus; transgene delivery ID ADENOASSOCIATED VIRUS; RAT-BRAIN; TRANSGENIC MICE; REP PROTEIN; EXPRESSION; INTEGRATION; OLIGODENDROCYTES; CULTURES; DNA AB Recent reports have suggested that delivery of genes flanked by AAV ITRs may be useful for gene therapy of diseases that involve the brain. We have compared the efficiency of gene expression in vitro in CNS-derived cells from four different promoters when the transgene is flanked by AAV ITRs, using both transfection via cationic liposomes, and infection via rAAV. The human cytomegalovirus (CMV) immediate-early enhancer/promoter, the SV40 early enhancer/promoter, the JC polyomavirus promoter, and the chicken beta(-)promoter coupled to the CMV enhancer were able to drive expression of the reporter gene beta-galactosidase in all tumor and primary brain cell cultures tested. Although the relative order of efficiency differed between cell types, the CMV promoter was always the strongest, generally by at least one order of magnitude. A comparison of the relative levels of expression seen between different cell types on transfection and infection suggest that not all CNS-derived cells are infected equally efficiently by rAAVs. High levels of expression were seen within 24 h of transgene delivery by either transfection or infection, dropping dramatically within days. All cell types and promoters showed the same decline, suggesting that transient expression by rep rAAVs may be efficient, but stable expression as detected in this system is a low frequency event. In vivo studies using the CMV promoter also suggest that although rep rAAVs are able to infect efficiently CNS cells and produce high levels of gene expression shortly after transduction, the majority of such infections do not lead to stable high-level expression of transgenes. C1 EUNICE KENNEDY SHRIVER CTR MENTAL RETARDAT INC,WALTHAM,MA 02154. HARVARD UNIV,SCH MED,DEPT NEUROL,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. FU NICHD NIH HHS [HD05515]; NIDDK NIH HHS [DK38381] NR 33 TC 39 Z9 39 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 1996 VL 3 IS 5 BP 437 EP 447 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA UK589 UT WOS:A1996UK58900009 PM 9156805 ER PT J AU Kim, JB Spiegelman, BM AF Kim, JB Spiegelman, BM TI ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism SO GENES & DEVELOPMENT LA English DT Article DE ADD1; bHLH-LZ transcription factor; adipocyte differentiation; dominant negative ADD1 ID ENHANCER-BINDING-PROTEIN; STEROL REGULATORY ELEMENT; LIPOPROTEIN RECEPTOR GENE; LEUCINE ZIPPER PROTEIN; DNA-BINDING; 3T3-L1 PREADIPOCYTES; ADIPOSE CONVERSION; CCAAT; MYC; TRANSCRIPTION AB Adipocyte determination and differentiation-dependent factor 1 (ADD1) is a member of the basic helix-loop-helix leucine zipper (bHLH-LZ) family of transcription factors that binds to two distinct DNA. sequences and has been associated with both adipocyte development and cholesterol homeostasis (where it has been termed SREBP1). To investigate the biological role of ADD1, we expressed wild-type and dominant negative forms of this protein with retroviral vectors in preadipocytes and nonadipogenic cells. A dominant-negative form of ADD1 with a point mutation in the DNA-binding domain sharply represses the differentiation of 3T3-L1 cells as observed morphologically or by the expression of adipocyte-specific mRNAs. When NIH-3T3 cells ectopically expressing ADD1 are cultured under hormonal conditions not favoring differentiation, they do not overtly differentiate but still activate expression of mRNAs for fatty acid synthase (FAS) and lipoprotein lipase (LPL), two key genes that regulate fatty acid metabolism. Under culture conditions permissive for differentiation including a PPAR activator, 15%-20% of the cells expressing ADD1 undergo adipogenesis while 2%-3% of cells containing a control vector differentiate. Simultaneous expression of ADD1 with PPAR gamma increases the transcriptional activity of this adipogenic nuclear hormone receptor, suggesting involvement of ADD1 in this pathway. These data indicate that ADD1 plays an important role in fat cell gene expression and differentiation, and suggest that it may function by augmenting a step in PPAR gamma-mediated transcription. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. FU NIDDK NIH HHS [DK31405] NR 50 TC 658 Z9 679 U1 2 U2 17 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 1 PY 1996 VL 10 IS 9 BP 1096 EP 1107 DI 10.1101/gad.10.9.1096 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UL248 UT WOS:A1996UL24800005 PM 8654925 ER PT J AU Kennedy, JW Caro, JF AF Kennedy, JW Caro, JF TI The ABCs of managing hyperthyroidism in the older patient SO GERIATRICS LA English DT Article ID THYROID-DISEASE; MANAGEMENT AB Hyperthyroidism in the older patient often presents with nonspecific symptoms, such as apathy, weight loss, and atrial fibrillation. General screening is not cost-effective, with the exception of two populations: women over age 40 with one or more nonspecific complaints and patients being admitted to a specialized geriatric unit. The sensitive TSH test is an excellent screen; a low TSH should be confirmed by an actual or estimated high free thyroxine test (FT4). The RAIU can help narrow the differential diagnosis. Radioiodine is the preferred treatment for the older patient with Graves' disease, the most common form of thyrotoxicosis. Graves must be differentiated from thyroiditis and toxic nodular goiters, as treatment regimens differ for each disorder. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,PHILADELPHIA,PA 19107. RP Kennedy, JW (reprint author), HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02115, USA. NR 20 TC 4 Z9 5 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 SN 0016-867X J9 GERIATRICS JI Geriatrics PD MAY PY 1996 VL 51 IS 5 BP 22 EP & PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA UJ880 UT WOS:A1996UJ88000004 PM 8621100 ER PT J AU Dignass, AU Stow, JL Babyatsky, MW AF Dignass, AU Stow, JL Babyatsky, MW TI Acute epithelial injury in the rat small intestine in vivo is associated with expanded expression of transforming growth factor alpha and beta SO GUT LA English DT Article DE epithelial restitution; proliferation; wound healing; phytohaemagglutinin; lectin; growth factors ID BEAN PHASEOLUS-VULGARIS; LECTIN-INDUCED LESIONS; RESTITUTION; INVITRO; INVIVO; MUCOSA; REPAIR; CELLS; DIFFERENTIATION; PROLIFERATION AB Background-Previous studies have shown the importance of transforming growth factors alpha and beta (TGF alpha and TGF beta) in modulating epithelial cell restitution after injury in vitro. Aim-To investigate the role of the growth factors TGF alpha and TGF beta after acute epithelial injury in vivo. Methods-An in vivo model of phytohaemagglutinin (PHA) induced acute epithelial injury in rat small intestine was used. Epithelial cell turnover was assessed by autoradiography and liquid scintillation counting of thymidine uptake. Expression of TGF alpha and TGF beta was assessed by immunohistochemistry. Results-An expansion of the proliferative compartment and increased turnover of intestinal epithelial cells was seen in rats with PHA induced intestinal epithelial injury. Expression of TGF alpha and TGF beta peptides was shown in both the epithelial cell and lamina propria compartment. Different patterns of TGF alpha and TGF beta expression were seen, however, within the epithelium of rats with acute intestinal injury compared with untreated controls, while the expression of these peptides within the lamina propria was not changed. Conclusions-These findings suggest that acute intestinal epithelial cell injury in vivo is associated with compensatory changes in expression of TGF alpha and TGF beta in the epithelial cell compartment, while the lamina propria does not seem to be significantly affected. C1 MASSACHUSETTS GEN HOSP,CTR STUDY INFLAMMATORY BOWEL DIS,NERPRC,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,RENAL UNIT,BOSTON,MA 02114. RP Dignass, AU (reprint author), UNIV ESSEN GESAMTHSCH,DEPT MED,DIV GASTROENTEROL,HUFELANDSTR 55,D-45122 ESSEN,GERMANY. FU NIDDK NIH HHS [DK 41557, DK 43351] NR 33 TC 56 Z9 56 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD MAY PY 1996 VL 38 IS 5 BP 687 EP 693 DI 10.1136/gut.38.5.687 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UM886 UT WOS:A1996UM88600010 PM 8707113 ER PT J AU Blacker, D AF Blacker, D TI Maintenance treatment of major depression: A review of the literature SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID RESEARCH DIAGNOSTIC-CRITERIA; RECURRENT DEPRESSION; LITHIUM-CARBONATE; DIFFERENTIAL RESPONSE; CONTINUATION THERAPY; UNIPOLAR DEPRESSION; AFFECTIVE-DISORDERS; DRUG-THERAPY; DOUBLE-BLIND; PSYCHOTHERAPY AB This review was undertaken to assess the indications for and efficacy of maintenance treatments for major depression. It was based on a search of the medical literature and a review of randomized clinical trials. The literature shows that antidepressant medications and, to a lesser extent, psychotherapy are both effective in preventing recurrence of major depression. Lithium and carbamazepine may also be effective. Antidepressant medications are probably more effective at full therapeutic doses than at the lower doses initially advised for maintenance treatment. Based on this review, maintenance treatment should be considered for any patient with recurrent major depression. It is clearly indicated in individuals with multiple frequent episodes. Patients with less-severe illness must weigh the risks and benefits of treatment in light of their earlier course and symptoms, the current impact of treatment, and the likely future impact of additional episodes. RP Blacker, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT 1499115,149 13TH ST,CHARLESTOWN,MA 02129, USA. FU NIMH NIH HHS [K21-MH01118] NR 52 TC 7 Z9 7 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1996 VL 4 IS 1 BP 1 EP 9 DI 10.3109/10673229609030517 PG 9 WC Psychiatry SC Psychiatry GA UN345 UT WOS:A1996UN34500001 PM 9384967 ER PT J AU Davidoff, S Mallya, GK Blacker, D AF Davidoff, S Mallya, GK Blacker, D TI Treatment of bipolar illness in an older, skeptical patient SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID DEPRESSIVE-ILLNESS; AFFECTIVE-DISORDER; MAJOR DEPRESSION; MANIA; AGE; UNIPOLAR; LINKAGE; FAMILY C1 HARVARD UNIV,SCH PUBL HLTH,SCH MED,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Davidoff, S (reprint author), MCLEAN HOSP,MAILMAN RES CTR,115 MILL ST,BELMONT,MA 02178, USA. NR 33 TC 1 Z9 1 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAY-JUN PY 1996 VL 4 IS 1 BP 39 EP 44 DI 10.3109/10673229609030520 PG 6 WC Psychiatry SC Psychiatry GA UN345 UT WOS:A1996UN34500004 PM 9384970 ER PT J AU Sorensen, G Stoddard, A Ockene, JK Hunt, MK Youngstrom, R AF Sorensen, G Stoddard, A Ockene, JK Hunt, MK Youngstrom, R TI Worker participation in an integrated health promotion health protection program: Results from the WellWorks project SO HEALTH EDUCATION QUARTERLY LA English DT Article ID CIGARETTE-SMOKING; WORKPLACE; WORKSITE; INTERVENTION; WELLNESS; SEX AB According to prior reports, blue-collar workers are less likely to participate in worksite health promotion programs than are white-collar workers, This study examined worker participation in the WellWorks worksite cancer prevention intervention, which integrated health promotion and health protection Analyses were conducted to assess relationships among participation in health promotion and health protection programs, and workers' perceptions of management changes to reduce potential occupational exposures. Results indicate that blue-collar workers were less likely to report participating in health promotion activities than white-collar workers. A significant association was observed between participation in nutrition- and exposure-related activities, suggesting that participation in programs to reduce exposures to occupational hazards might contribute to blue-collar workers' participation in health promotion activities, Furthermore, when workers were aware of changes their employer had made to reduce exposures to occupational hazards, they were more likely to participate in both smoking control and nutrition activities, even when controlling for job category. These findings have clear implications for future worksite cancer prevention efforts. C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV MASSACHUSETTS,SCH PUBL HLTH & HLTH SCI,DEPT BIOSTAT & EPIDEMIOL,AMHERST,MA 01003. UNIV MASSACHUSETTS,MED CTR,DIV PREVENT & BEHAV MED,WORCESTER,MA. DANA FARBER CANC INST,CTR COMMUNITY BASED RES,BOSTON,MA 02115. RP Sorensen, G (reprint author), DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,44 BINNEY ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [UO1 CA51686] NR 39 TC 66 Z9 66 U1 1 U2 10 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0195-8402 J9 HEALTH EDUC QUART JI Health Educ. Q. PD MAY PY 1996 VL 23 IS 2 BP 191 EP 203 DI 10.1177/109019819602300205 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UG138 UT WOS:A1996UG13800005 PM 8744872 ER PT J AU Melcher, JR AF Melcher, JR TI Cellular generators of the binaural difference potential in cat SO HEARING RESEARCH LA English DT Article DE auditory system; cochlear nucleus; spherical cell; superior olivary complex; kainic acid; lesion ID AUDITORY BRAIN-STEM; ANTEROVENTRAL COCHLEAR NUCLEUS; SUPERIOR OLIVARY COMPLEX; INDUCED NEURONAL LOSS; EVOKED-POTENTIALS; TRAPEZOID BODY; INFERIOR COLLICULUS; INTERAURAL TIME; RESPONSES ABRS; KAINIC ACID AB In humans, lateralization and fusion of binaurally presented clicks are correlated with the latency and amplitude of the binaural difference potential (BDP) (e.g., Furst et al., 1985). The BDP is derived by subtracting the brainstem auditory evoked potential (BAEP) for binaural stimulation from the sum of the BAEPs for left and right monaural stimulation. Our aim in this work was to determine the cellular generators of the BDP and thus identify cells that may be crucial for specific types of binaural sound processing. To this end, we injected kainic acid into the superior olivary complex (SOC) or the cochlear nucleus (CN) in cats and examined the effects of the resulting lesions on the click-evoked BDP. Lesions confined to the anterior anteroventral CN (AVCNa) substantially reduced the BDP, while lesions primarily involving mon posterior parts of the CN had little or no effect. BDP reductions occurred for lesions involving either high (> 10 kHz) or lower (< 10 kHz) characteristic frequency (CF) regions of the AVCNa (as well as the posterior CN). Lesions involving the SOC reduced the BDP and, in one case, eliminated the high-pass filtered (270 Hz cutoff) BDP. Combining these results with published information about the physiology and anatomy of auditory brainstem cells, we conclude that: (1) spherical cells in the AVCNa are essential for BDP production, (2) the earliest part of the BDP is generated by medial superior olive (MSG) principal cells which receive spherical cell inputs, (3) a later part is probably generated by the cellular targets of MSO principal cells and, (4) the cells involved in BDP generation have CFs above, as well as below, 10 kHz. Since humans, like cats, have a well-developed MSG, we suggest that the MSO may also be essential for BDP production in humans. Thus, perceptual correlates of the BDP, binaural fusion and click lateralization, apparently involve the MSO. C1 MIT,CAMBRIDGE,MA 02139. RP Melcher, JR (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [P01DC00119, P01 DC000119-260023, NIH-T32DC00006] NR 86 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1996 VL 95 IS 1-2 BP 144 EP 160 DI 10.1016/0378-5955(96)00032-9 PG 17 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA UR782 UT WOS:A1996UR78200014 PM 8793516 ER PT J AU Berglund, AM Benson, TE Brown, MC AF Berglund, AM Benson, TE Brown, MC TI Synapses from labeled type II axons in the mouse cochlear nucleus SO HEARING RESEARCH LA English DT Article DE auditory system; hearing; spiral ganglion neuron; outer hair cell; unmyelinated axon ID AUDITORY-NERVE FIBERS; DIFFERING SPONTANEOUS RATE; CENTRAL PROJECTIONS; SPIRAL GANGLION; HORSERADISH-PEROXIDASE; ADULT CATS; GUINEA-PIG; CELLS; BRANCHES; AFFERENT AB This study investigates the ultrastructure and central targets in the cochlear nucleus of axonal swellings of type II primary afferent neurons. Type II axons comprise only 5-10% of the ar;uns of the auditory nerve of mammals, but they alone provide the afferent innervation of the outer hail cells. In this study, type II axons were labeled with horseradish peroxidase, and serial-section electron microscopy was used to examine their swellings in: (1) the granule-cell lamina at its boundary with posteroventral cochlear nucleus, (2) the rostral anteroventral cochlear nucleus, and (3) the auditory nerve root. Only some (18%) of the type II terminal and en-passant swellings formed synapses. The synapses were asymmetric and contained clear round synaptic vesicles, suggesting that they are excitatory. Type II synapses were compared to those from type I fibers, the fibers providing the afferent innervation of the inner hair cells. Type II synapses tended to have slightly smaller and fewer synaptic vesicles had a greater proportion of the membrane apposition accompanied by a postsynaptic density, and often had densities that were discontinuous or 'perforated'. In all cochlear nucleus regions examined, the postsynaptic targets of type II synapses had characteristics of dendrites; in most cases these dendrites could not be traced to their cell bodies of origin. Some evidence suggests, however, that targets may include granule cells, spherical cells, and other cells in the nerve root. These results suggest afferent information from outer hair cells reaches diverse regions and targets within the cochlear nucleus. C1 HARVARD UNIV, SCH MED, DEPT OTOL & LARYNGOL, BOSTON, MA 02115 USA. BOSTON UNIV, DEPT BIOMED ENGN, BOSTON, MA 02215 USA. HARVARD UNIV, DIV HLTH SCI TECHNOL, CAMBRIDGE, MA 02138 USA. MIT, CAMBRIDGE, MA 02138 USA. RP Berglund, AM (reprint author), MASSACHUSETTS EYE & EAR INFIRM, EATON PEABODY LAB, 243 CHARLES ST, BOSTON, MA 02114 USA. FU NIDCD NIH HHS [DC00351, DC00119, DC00006] NR 49 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1996 VL 94 IS 1-2 BP 31 EP 46 DI 10.1016/0378-5955(95)00231-6 PG 16 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA UQ838 UT WOS:A1996UQ83800004 PM 8789809 ER PT J AU Quirk, DM Brugge, WR AF Quirk, DM Brugge, WR TI Choledocholithiasis: In quest of the stone SO HEPATOLOGY LA English DT Article ID ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; LAPAROSCOPIC CHOLECYSTECTOMY; DIAGNOSIS; CHOLANGIOGRAPHY; SONOGRAPHY; ULTRASOUND C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Quirk, DM (reprint author), MASSACHUSETTS GEN HOSP,DEPT MED,GASTROINTESTINAL UNIT,BOSTON,MA 02114, USA. NR 22 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 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1996 VL 23 IS 5 BP 1277 EP 1280 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UJ443 UT WOS:A1996UJ44300050 PM 8621165 ER PT J AU Doria, A Onuma, T Gearin, G Freire, MBS Warram, JH Krolewski, AS AF Doria, A Onuma, T Gearin, G Freire, MBS Warram, JH Krolewski, AS TI Angiotensinogen polymorphism M235T, hypertension, and nephropathy in insulin-dependent diabetes SO HYPERTENSION LA English DT Article DE genetics; insulin-dependent diabetes; nephropathy; angiotensinogen ID SODIUM-LITHIUM COUNTERTRANSPORT; DISEASE; SUSCEPTIBILITY; PREDISPOSITION; PRESSURE; MELLITUS AB The allele 235T (a threonine in place of a methionine at position 235) of angiotensinogen has been found to be associated with a predisposition to essential hypertension. We investigated whether this allele also confers increased susceptibility to nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). A group of 380 patients who had had IDDM for 15 to 20 years were genotyped at the angiotensinogen 235 locus. Included were 75 patients with normoalbuminuria (albumin excretion rate <30 mu g/min), two series of patients with microalbuminuria (n=30 and n=136), and two series with overt proteinuria (n=41 and n=98). Allele 235T frequency was higher among cases with microalbuminuria (0.41 in the two series combined) or overt proteinuria (0.40) than in the normoalbuminuria group (0.36). However, this difference was not statistically significant with this sample size (chi(2)=1.2, P=NS with 2 df). Under a recessive model, allele 235T homozygotes had a 1.6-fold risk of developing nephropathy relative to carriers of other genotypes, but this value was not significantly different from 1 (95% CI=0.8 to 3.5). The strength of the association did not improve after stratification by degree of glycemic control. With respect to the hypertension in these IDDM patients, no association with allele 235T was found. Allele 235T frequencies in normotensive and hypertensive individuals were 0.363 and 0.353, respectively, among normoalbuminuric IDDM individuals (chi(2)=0.01, P=NS) and 0.411 and 0.414 among microalbuminuric IDDM subjects (chi(2)=0.0, P=NS). We conclude that the angiotensinogen polymorphism M235T might influence susceptibility to nephropathy in insulin-dependent diabetes, but its effect, if any, is rather small and independent of hypertension. C1 JOSLIN DIABET CTR,SECT EPIDEMIOL & GENET,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NIDDK NIH HHS [R01-DK41526] NR 35 TC 54 Z9 54 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAY PY 1996 VL 27 IS 5 BP 1134 EP 1139 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UJ747 UT WOS:A1996UJ74700015 PM 8621207 ER PT J AU Wyatt, J Rizzo, J AF Wyatt, J Rizzo, J TI Ocular implants for the blind SO IEEE SPECTRUM LA English DT Article C1 HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. RP Wyatt, J (reprint author), MIT,ELECTR RES LAB,77 MASSACHUSETTS AVE,CAMBRIDGE,MA 02139, USA. NR 2 TC 85 Z9 89 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9235 J9 IEEE SPECTRUM JI IEEE Spectr. PD MAY PY 1996 VL 33 IS 5 BP 47 EP & DI 10.1109/6.490056 PG 7 WC Engineering, Electrical & Electronic SC Engineering GA UH993 UT WOS:A1996UH99300018 ER PT J AU Franc, NC Dimarcq, JL Lagueux, M Hoffmann, J Ezekowitz, RAB AF Franc, NC Dimarcq, JL Lagueux, M Hoffmann, J Ezekowitz, RAB TI Croquemort, a novel Drosophila hemocyte/macrophage receptor that recognizes apoptotic cells SO IMMUNITY LA English DT Article ID SCAVENGER RECEPTOR; MOLECULAR FLYPAPER; ANIMAL LECTINS; MACROPHAGES; DEATH; CD36; ATHEROSCLEROSIS; ENDOCYTOSIS; F4/80; EYE AB Programmed cell death is first observed at stage 11 of embryogenesis in Drosophila. The systematic removal of apoptotic cells is mediated by cells that are derived from the procephalic mesoderm and differentiate into macrophages. We describe a macrophage receptor for apoptotic cells. This receptor, croquemort (catcher of death), is a member of the CD36 superfamily. Croquemort-mediated phagocytosis represents the concept that phagocytosis evolved primarily as a cellular process for the removal of effete cells. Our findings support the idea that the primordial function of macrophages may have been in tissue modeling and that their adapted role is in host defense. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV INFECT DIS,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT PEDIAT,BOSTON,MA 02115. INST BIOL MOLEC & CELLULAIRE,CNRS,UNITE PROPRE RECH,F-67084 STRASBOURG,FRANCE. RP Franc, NC (reprint author), HARVARD UNIV,CHILDRENS HOSP,SCH MED,DIV HEMATOL,BOSTON,MA 02115, USA. RI Franc, Nathalie/C-2208-2009 NR 44 TC 242 Z9 249 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 1996 VL 4 IS 5 BP 431 EP 443 DI 10.1016/S1074-7613(00)80410-0 PG 13 WC Immunology SC Immunology GA UM678 UT WOS:A1996UM67800003 PM 8630729 ER PT J AU Tashima, KT Carroll, PA Rogers, MB Calderwood, SB AF Tashima, KT Carroll, PA Rogers, MB Calderwood, SB TI Relative importance of three iron-regulated outer membrane proteins for in vivo growth of Vibrio cholerae SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; TRANSCRIPTIONAL REGULATION; SUICIDE VECTOR; VIRULENCE GENE; FUR GENE; CLONING; CONSTRUCTION; SIDEROPHORE; SYSTEM; INVIVO AB Iron is an essential nutrient to support the growth of most bacterial species, However, iron is not easily available to microorganisms infecting mammalian hosts, because it is largely sequestered by iron-binding proteins, such as transferrin or lactoferrin, or complexed to heme, In response to environmental iron stress, Vibrio cholerae produces the siderophore vibriobactin as well as a number of iron-induced outer membrane proteins, Previous data on the role of iron acquisition systems for the intraintestinal growth Of mucosal pathogens such as V. cholerae are conflicting, In this report, we isolated mutants of V. cholerae with TnphoA fusions in each of viuA, hutA, and irgA, as well as strains mutant in each pair of these genes and all three simultaneously, to analyze the role of these iron-induced outer membrane protein receptors for in vivo growth of V. cholerae. The fusion between hutA and TnphoA in a single copy on the chromosome allowed the study of in vitro regulation of hutA in response to iron, fur, and irgB; transcription of hutA was tightly iron regulated (70-fold) and dependent on a functional Fur but did not require IrgB, To investigate the effects of mutations in these iron-induced outer membrane proteins on in vivo growth, we inoculated ileal loops in a rabbit model of infection, This avoids exposure of organisms to the potential killing effects of gastric acid, allows several logarithmic increases in growth in the in vivo environment, and facilitates direct comparison of multiple strains in the same animal to avoid any differences between animals, We grew each mutant to be tested in competition with the wild-type strain in the same loop, to provide an internal control, We confirmed that the inocula for these experiments were grown under conditions of iron stress prior to in vivo inoculation, by measuring the alkaline phosphatase activity of the iron-regulated fusion in each strain, The results confirmed that mutation of irgA produced a much more substantial in vivo growth defect than mutation of either hutA or viuA alone, Double mutants of irgA with either viuA or hutA, or the strain mutant in all three genes, showed an in vivo growth defect comparable to the strain mutant in irgA only, suggesting that mutation of irgA was the most relevant for in vivo growth, The strain mutant in both hutA and viuA was also markedly impaired for in vivo growth, suggesting that mutation of both of these iron uptake systems simultaneously can also produce a substantial in vivo growth defect. C1 MASSACHUSETTS GEN HOSP,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115. FU NIAID NIH HHS [AI34968] NR 36 TC 28 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1996 VL 64 IS 5 BP 1756 EP 1761 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UG365 UT WOS:A1996UG36500037 PM 8613388 ER PT J AU Gaebel, W Marder, S AF Gaebel, W Marder, S TI The acute episode in schizophrenia: Diagnosis, prognosis and treatment - Proceedings from a Lundbeck Symposium held in Copenhagen, 9-10 February 1996 - Introduction SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90024. RP Gaebel, W (reprint author), UNIV DUSSELDORF,DEPT PSYCHIAT,RHEIN LANDES & HSCH KLIN,BERG LANDSTR 2,D-40629 DUSSELDORF,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAY PY 1996 VL 11 SU 2 BP 1 EP 1 DI 10.1097/00004850-199605002-00001 PG 1 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UR527 UT WOS:A1996UR52700001 ER PT J AU Marder, SR AF Marder, SR TI Pharmacological treatment strategies in acute schizophrenia SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Lundbeck Symposium on the Acute Episode in Schizophrenia - Diagnosis, Prognosis and Treatment CY FEB 09-10, 1996 CL COPENHAGEN, DENMARK DE schizophrenia; antipsychotic; clozapine; risperidone; sertindole; olanzapine; seroquel ID DOUBLE-BLIND; HALOPERIDOL AB It may be helpful for clinicians to consider the management of schizophrenia as occurring in three different phases: an acute phase which lasts about 4-8 weeks, a resolving phase which lasts about 4-6 months and a stable phase which lasts as long as the patient remains in remission. During the acute phase, patients demonstrate active symptoms of schizophrenia. The goal of treatment during this phase is to reduce the most severe symptoms of the illness, particularly positive symptoms. Nearly all acute episodes should be treated with an antipsychotic medication. Moreover, drug treatment should occur as early in this phase as possible. Certain treatment principles should guide management: an antipsychotic drug and dose should be used that appropriately balances side effects and efficacy. Trial of the selected drug(s) should last at least 4-6 weeks before the medication is changed. Newer antipsychotics have clear advantages over older drugs in terms of side effects and efficacy. Greater use of these agents may improve the outcome in acute schizophrenia. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. RP Marder, SR (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,PSYCHIAT SERV 116A,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 24 TC 8 Z9 8 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAY PY 1996 VL 11 SU 2 BP 29 EP 34 DI 10.1097/00004850-199605002-00005 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UR527 UT WOS:A1996UR52700005 PM 8803657 ER PT J AU Gaebel, W Marder, S AF Gaebel, W Marder, S TI Conclusions and treatment recommendations for the acute episode in schizophrenia SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Lundbeck Symposium on the Acute Episode in Schizophrenia - Diagnosis, Prognosis and Treatment CY FEB 09-10, 1996 CL COPENHAGEN, DENMARK DE schizophrenia; acute episode; diagnosis; prognosis; treatment ID 2-YEAR FOLLOW-UP; EXPRESSED EMOTION; CONTROLLED TRIAL; 1ST-EPISODE SCHIZOPHRENIA; BEHAVIORAL INTERVENTION; FAMILY PSYCHOEDUCATION; COMMUNITY MANAGEMENT; MAINTENANCE THERAPY; SOCIAL-INTERVENTION; RELAPSE AB Interventions which reduce symptoms, vulnerability and stress on the one hand and improve psychosocial competence and quality of life on the other are essential components of a comprehensive treatment program in schizophrenia. Drug treatment of acute exacerbations which is adequate with respect to drug type, dose and treatment duration and takes risk/benefit measures into account is at the heart of these interventions and should be applied as early as possible. Subsequent neuroleptic treatment to prevent a relapse should be administered in accordance with established treatment guidelines. Drug treatment must be combined with psychosocial interventions, which should be properly adapted to the particular phase and stage of the illness. Implementation and coordination of various interventions require cooperation between therapists, institutions, the patient and the patient's family. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RP Gaebel, W (reprint author), UNIV DUSSELDORF,DEPT PSYCHIAT,RHEIN LANDES & HSCHKLIN BERG,BERG LANDSTR 2,D-40629 DUSSELDORF,GERMANY. NR 75 TC 1 Z9 1 U1 3 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD MAY PY 1996 VL 11 SU 2 BP 93 EP 100 DI 10.1097/00004850-199605002-00015 PG 8 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UR527 UT WOS:A1996UR52700015 PM 8803667 ER PT J AU Tan, KN Min, HK Pan, LY Ferrara, JLM Myrick, KV AF Tan, KN Min, HK Pan, LY Ferrara, JLM Myrick, KV TI Biological characteristics of an immunoregulatory activity secreted by an autoreactive CD4(+) T cell clone that suppresses autoimmune diabetes in non-obese diabetic mice SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE allogeneic mixed lymphocyte reaction; cytokine; insulin-dependent diabetes mellitus; non-obese diabetic mice; syngeneic mixed lymphocyte reaction; regulatory T lymphocyte ID MIXED-LYMPHOCYTE-REACTION; SYSTEMIC LUPUS-ERYTHEMATOSUS; BINDING PROTEIN; IFN-GAMMA; CYTOKINE; MOUSE; ACTIVATION; HEPARIN; ONSET; ABNORMALITIES AB We previously reported the generation and characterization of a panel of CD4(+) autoreactive T cell clones that suppress development of autoimmune diabetes in non-obese diabetic (NOD) mice, We showed that the protective capacity of the T cell clones correlates with secretion of an activity that potently inhibits allogeneic mixed lymphocyte reaction (allo-MLR). In this report, we describe the biological characteristics of the allo-MLR inhibitory activity (MLR-IA, short for mixed lymphocyte reaction inhibitory activity) secreted by the protective T cell clone, NOD-5, MLR-IA has little effect on initiation of proliferation in an allo-MLR, but it potently inhibits the maintenance and amplification of the proliferative response, MLR-IA is also capable of inhibiting concanavalin A (Con A)-stimulated splenic responder T cell proliferation, MLR-IA is reversible in vitro and is not restricted by MHC class I or II proteins, MLR-IA does not affect IL-2 receptor expression of responding T cells and has no effect on IL-2-dependent proliferation of CTLL-20 T cells, Partially purified MLR-IA inhibits IL-2 production in a primary allo-MLR, and decreases IFN-gamma production during secondary allo-MLR and Con A activation, whereas it enhances IL-4 production in both primary and secondary Con A activation, MLR-IA is not neutralized by combination of antibodies specific for transforming growth factor-beta, IL-10, tumor necrosis factor-alpha/beta or IFN-gamma suggestive of a novel activity, MLR-IA is ammonium sulfate precipitable, sensitive to protease digestion and is destroyed by boiling, indicating that a protein moiety is part of its active structure, Our work suggests that a potentially novel immunoregulatory activity, capable of inhibiting T lymphocyte proliferation and IFN-gamma production, and stimulating IL-4 production, may regulate development of autoimmune diabetes in NOD mice. C1 DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. RP Tan, KN (reprint author), DANA FARBER CANC INST,IMMUNOPATHOL LAB,ROOM D-1620A,44 BINNEY ST,BOSTON,MA 02115, USA. FU NIAID NIH HHS [R01 AI30018]; NIDDK NIH HHS [R01 DK46382] NR 49 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1996 VL 8 IS 5 BP 689 EP 699 DI 10.1093/intimm/8.5.689 PG 11 WC Immunology SC Immunology GA UN188 UT WOS:A1996UN18800007 PM 8671656 ER PT J AU Ara, G Teicher, BA AF Ara, G Teicher, BA TI Relationship of cellular energy parameters to cytotoxicity for AG-17, lonidamine and cyclocreatine in four human tumor cell lines SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE AG-17; lonidamine; cyclocreatine; mitochondrial; toxins; tyrphostin ID TYROSINE KINASE INHIBITORS; CREATINE-KINASE; ELECTRON-TRANSPORT; ALKYLATING-AGENTS; IN-VITRO; CANCER; GROWTH; INVITRO; MURINE; POTENTIATION AB The cytotoxicity and effect on cellular energy parameters of AG-17, lonidamine and cyclocreatine were examined in four human tumor cell lines: MCF-7 breast carcinoma, SW2 small cell lung carcinoma, A2058 melanoma and A2058-055, a subline of A2058 transfected with the creatine kinase gene. Although these cell lines had widely differing levels of creatine kinase activity, there were no differences in their sensitivity to cyclocreatine. The MCF-7 cells were most sensitive to AG-17 and to lonidamine with 90% cell killing by 50 mu M and 115 mu M of the drugs after 72 h exposure, respectively. The percent of coupled respiration in the cells was 60-70% in the absence of drug exposure and was decreased to 30-40% after 24 h of exposure to each of the drugs. Cytochrome C oxidase activity was decreased by 8- to 9-fold in the high creatine kinase expressing cell lines (SW2 and A2058-055) after exposure to AG-17 (250 mu M) for 24 h. Lonidamine (250 mu M) exposure decreased hexokinase activity in the cells to 30-40% of normal in 24 h. Extra-cellular lactate levels increased most markedly in the media of the MCF-7 and SW2 cells exposed to AG-17 (100 and 250 mu M) for 24 h. Although no specific enzymatic target was effected, cyclocreatine exposure resulted in a decrease in the ATP content of the cells, especially in the MCF-7 cells where ATP was decreased to 30% of normal upon 24 h exposure to the drug. These results provide a rationale for the use of these agents in combination with each other or in combination with cytotoxic anticancer therapies targeted on cellular DNA. C1 DANA FARBER CANC INST,BOSTON,MA 02115. NR 43 TC 7 Z9 7 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1996 VL 8 IS 5 BP 865 EP 873 PG 9 WC Oncology SC Oncology GA UF761 UT WOS:A1996UF76100005 PM 21544439 ER PT J AU DAmico, AV Propert, KJ AF DAmico, AV Propert, KJ TI Prostate cancer volume adds significantly to prostate-specific antigen in the prediction of early biochemical failure after external beam radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; prostate-specific antigen; prostate cancer volume; prognostic factors; radiation therapy ID ADENOCARCINOMA AB Purpose: A new clinical pretreatment quantity that closely approximates the true prostate cancer volume is defined. Methods and Materials: The cancer-specific prostate-specific antigen (PSA), PSA density, prostate cancer volume (V (Ca)), and the volume fraction of the gland involved with carcinoma (V (Ca)fx) were calculated for 227 prostate cancer patients managed definitively with external beam radiation therapy. 1. PSA density = PSA/ultrasound prostate gland volume 2. Cancer-specific PSA = PSA - [PSA from benign epithelial tissue] 3. V-Ca = Cancer-specific PSA/[PSA in serum per cm(3) of cancer] 4. V(Ca)fx = V-Ca/ultrasound prostate gland volume A Cox multiple regression analysis was used to-test whether any of these clinical pretreatment parameters added significantly to PSA in predicting early postradiation PSA failure. Results: The prostate cancer volume (p = 0.039) and the volume fraction of the gland involved by carcinoma (p = 0.035) significantly added to the PSA in predicting postradiation PSA failure, Conversely, the PSA density and the cancer-specific PSA did not add significantly (p > 0.05) to PSA in predicting postradiation PSA failure, The 20-month actuarial PSA failure-free rates for patients with calculated tumor volumes of less than or equal to 0.5 cm(3), 0.5-4.0 cm(3), and >4.0 cm(3) were 92, 80, and 47%, respectively (p = 0.00004). Conclusion: The volume of prostate cancer (V (Ca)) and the resulting volume fraction of cancer both added significantly to PSA in their ability to predict for early postradiation PSA failure. These new parameters may be used to select patients in prospective randomized trials that examine the efficacy of combining radiation and androgen ablative therapy in patients with clinically localized disease, who are at high risk for early postradiation PSA failure. C1 HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NR 22 TC 20 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 1996 VL 35 IS 2 BP 273 EP 279 DI 10.1016/0360-3016(95)02389-5 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UM703 UT WOS:A1996UM70300009 PM 8635933 ER PT J AU Shipley, WU AF Shipley, WU TI Translational research in bladder cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material RP Shipley, WU (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,GENITOURINARY ONCOL UNIT,BOSTON,MA 02114, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 1996 VL 35 IS 2 BP 411 EP 412 DI 10.1016/0360-3016(96)00141-1 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UM703 UT WOS:A1996UM70300027 PM 8635951 ER PT J AU Ljubimov, AV Burgeson, RE Butkowski, RJ Couchman, JR Wu, RR Ninomiya, Y Sado, Y Maguen, E Nesburn, AB Kenney, MC AF Ljubimov, AV Burgeson, RE Butkowski, RJ Couchman, JR Wu, RR Ninomiya, Y Sado, Y Maguen, E Nesburn, AB Kenney, MC TI Extracellular matrix alterations in human corneas with bullous keratopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 14-19, 1995 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE basement membrane; bullous keratopathy; corneal edema; extracellular matrix; immunocytochemistry ID RETROCORNEAL FIBROUS MEMBRANE; DESCEMETS-MEMBRANE; ENDOTHELIAL-CELLS; RABBIT CORNEA; TENASCIN; EXPRESSION; COLLAGEN; FIBRONECTIN; ANTERIOR; POSTERIOR AB Purpose. To uncover abnormalities of extracellular matrix (ECM) distribution in human corneas with pseudophakic and aphakic bullous keratopathy (PBK/ABK). Methods. Indirect immunofluorescence with antibodies to 27 ECM components was used on frozen sections of 14 normal and 20 PBK/ABK corneas. Results. Fibrillar deposits of an antiadhesive glycoprotein tenascin in the anterior and posterior stroma, epithelial basement membrane (BM), bullae and subepithelial fibrosis (SEF) areas, and posterior collagenous layer (PCL) were revealed in diseased corneas. Tenascin in midstroma, which was observed in some cases, correlated with decreased visual acuity. In normal central corneas, tenascin was never found. Other major ECM abnormalities in PBK/ABK corneas compared to normals included: discontinuous epithelial BM staining for laminin-1 (alpha 1 beta 1 gamma 1), entactin/nidogen and fibronectin; accumulation of fibronectin and alpha 1-alpha 2 type IV collagen on the endothelial face of the Descemet's membrane; and abnormal deposition of stromal ECM (tenascin, fibronectin, decorin, types I, III, V, VI, VIII, XII, XIV collagen) and BM components (type IV collagen, perlecan, bamacan, laminin-l, entactin-nidogen, fibronectin) in SEF areas and in PCL. Conclusions. This study provides a molecular description of an ongoing fibrosis on the epithelial, stromal, and endothelial levels in PBK/ABK corneas. These fibrotic changes may follow initial endothelial damage after cataract surgery, may be caused by the upregulation of fibrogenic cytokines, and may play a significant role in the progression of bullous keratopathy. C1 MASSACHUSETTS GEN HOSP,HARVARD CUTANEOUS BIOL RES CTR,BOSTON,MA. INCSTAR CORP,STILLWATER,MN. UNIV ALABAMA,DEPT CELL BIOL,BIRMINGHAM,AL 35294. OKAYAMA UNIV,SCH MED,OKAYAMA 700,JAPAN. SHIGEI MED RES INST,OKAYAMA,JAPAN. RP Ljubimov, AV (reprint author), UNIV CALIF LOS ANGELES,CEDARS SINAI MED CTR,MED SCH AFFILATE,OPHTHALMOL RES LABS,DAVIS 5069,LOS ANGELES,CA 90048, USA. RI Ljubimov, Alexander/E-5883-2013 FU NEI NIH HHS [EY10836]; NIAMS NIH HHS [AR36457]; NICHD NIH HHS [N01-HD-2-3144] NR 53 TC 99 Z9 100 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1996 VL 37 IS 6 BP 997 EP 1007 PG 11 WC Ophthalmology SC Ophthalmology GA UK690 UT WOS:A1996UK69000007 PM 8631643 ER PT J AU Uchimaru, K Endo, K Fujinuma, H Zukerberg, L Arnold, A Motokura, T AF Uchimaru, K Endo, K Fujinuma, H Zukerberg, L Arnold, A Motokura, T TI Oncogenic collaboration of the cyclin D1 (PRAD1, bcl-1) gene with a mutated p53 and an activated ras oncogene in neoplastic transformation SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE cyclin D1; transfection experiment; transformation; p53; ras ID BREAST-CANCER; CELLULAR-TRANSFORMATION; CANDIDATE ONCOGENE; PUTATIVE ONCOGENE; CHROMOSOME 11Q13; MAMMALIAN-CELLS; POOR PROGNOSIS; TUMOR-ANTIGEN; COAMPLIFICATION; EXPRESSION AB Cyclin D1 is one of the key regulators in G1 progression in the cell cycle and is also a candidate oncogene (termed PRAD1 or bcl-1) in several types of human tumors, We report a collaboration of the cyclin D1 gene with ras and a mutated form of p53 (p53-mt) in neoplastic transformation, Transfection of cyclin D1 alone or in combination with ras or with p53-mt was not sufficient for focus formation of rat embryonic fibroblasts. However, focus formation induced by co-transfection of ras and p53-mt was enhanced in the presence of the cyclin D1-expression plasmid, Co-transfection of ras- and p53-mt-transformants with the cyclin D1-expression plasmid resulted in reduced serum dependency in vitro. Furthermore, the transformants expressing exogenous cyclin D1 grew faster than those without the cyclin D1 plasmid when injected into nude mice, These observations strengthen the significance of cyclin D1 overexpression through gene rearrangement or gene amplification observed in human tumors as a step in multistep oncogenesis; deregulated expression of cyclin D1 may reduce the requirement for growth factors and may stimulate in vivo growth. C1 UNIV TOKYO,SCH MED,DEPT INTERNAL MED 4,BUNKYO KU,TOKYO 112,JAPAN. CHUGAI PHARMACEUT CO LTD,LAB BONE DIS,SHIZUOKA 412,JAPAN. MASSACHUSETTS GEN HOSP,LAB ENDOCRINE ONCOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NCI NIH HHS [CA55909] NR 36 TC 14 Z9 14 U1 0 U2 1 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD MAY PY 1996 VL 87 IS 5 BP 459 EP 465 PG 7 WC Oncology SC Oncology GA UP584 UT WOS:A1996UP58400009 PM 8641982 ER PT J AU Trujillo, JR Navia, BA Worth, T Lucey, DR McLane, MF Lee, TH Essex, M AF Trujillo, JR Navia, BA Worth, T Lucey, DR McLane, MF Lee, TH Essex, M TI High levels of anti-HIV-1 envelope antibodies in cerebrospinal fluid as compared to serum from patients with AIDS dementia complex SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE AIDS dementia complex; cerebrospinal fluid; HIV-1 gp120 antibodies ID CENTRAL-NERVOUS-SYSTEM; IMMUNODEFICIENCY VIRUS-INFECTION; BRAIN-BARRIER SYNTHESIS; HIV-1 INFECTION; HTLV-III; INTRATHECAL SYNTHESIS; V3 LOOP; ENCEPHALOPATHY; NEOPTERIN; PROTEIN AB The antibody response to the HIV-I envelope protein has not been well characterized in patients with AIDS dementia complex (ADC). We evaluated the frequency of antibodies against the HIV-1 envelope in cerebrospinal fluid (CSF) and serum from 21 persons with ADC and 10 symptom-free HIV-1-positive subjects using Western immunoblot with reducing and nonreducing buffer and radioimmunoprecipitation (RIP) analysis. RIP analysis revealed anti-envelope antibodies in all sera tested. Higher anti-envelope levels were observed in CSF than in serum of 12 of 21 ADC patients and only 1 of 10 symptom-free subjects (two-sided Fisher exact test, p < 0.05). All persons with moderate to severe ADC had higher anti-envelope levels in CSF than in sera (p < 0.005). CSF anti-gp120 antibodies were not as readily detected by Western blot analysis even under nonreduced conditions, suggesting that they are directed to conformational epitopes. Higher CSF anti-envelope antibodies appear to be more common in patients with ADC than in symptom-free HIV-1-positive subjects. This antibody pattern may serve as a marker for ADC and its progression. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT CANC BIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. WILFORD HALL USAF MED CTR,SAN ANTONIO,TX. FU NCI NIH HHS [CA09382, CA39805]; NHLBI NIH HHS [HL33774] NR 50 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY 1 PY 1996 VL 12 IS 1 BP 19 EP 25 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UK146 UT WOS:A1996UK14600003 PM 8624756 ER PT J AU Finkelstein, DM Williams, PL Molenberghs, G Feinberg, J Powderly, WG Kahn, J Dolin, R Cotton, D AF Finkelstein, DM Williams, PL Molenberghs, G Feinberg, J Powderly, WG Kahn, J Dolin, R Cotton, D TI Patterns of opportunistic infections in patients with HIV infection SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE opportunistic infections; Pneumocystis carinii pneumonia; Mycobacterium avium complex; cytomegalovirus infection; systemic mycosis; relative risk; prophylactic therapies; proportional hazards model ID IMMUNODEFICIENCY-VIRUS DISEASE; AVIUM COMPLEX INFECTION; ZIDOVUDINE AB The pattern of the development of opportunistic infections (OIs) in HIV-infected patients was evaluated, based on a cohort of 1.530 patients enrolled in two AIDS Clinical Trials Group anti-retroviral studies. We quantified the increase in risk of OIs associated with the occurrence of a previous OI, This assessment was based on the observed event rates of the more common AIDS-defining OIs: Pneumocystis carinii pneumonia (PCP), Mycobacterium avium complex (MAC), cytomegalovirus (CMV), and a systemic mycosis. Additionally, for each OI, we assessed the relative risks associated with a history of prior OIs, changes in CD4 levels, and baseline prognostic factors. We found that the occurrence of each of these OIs increased the risk of subsequent OIs, even after adjusting for the CD4 count. Specifically, the occurrence of PCP significantly increased the risk of MAC and CMV and somewhat increased the risk of systemic mycoses. Diagnosis with MAC was associated with an increased risk of subsequent CMV. whereas the occurrence of CMV increased the risk of MAC. Finally, once patients were diagnosed with a systemic mycosis, they were at a somewhat increased risk of subsequently developing MAC or CMV. Although current practice for determining the timing and initiation of prophylactic therapies relies chiefly on CD4 count, the occurrence of specific AIDS-defining OIs in patients with HIV infection should also be taken into account in making decisions regarding prophylaxis strategies. C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. WASHINGTON UNIV,ST LOUIS,MO. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. UNIV ROCHESTER,ROCHESTER,NY. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP Finkelstein, DM (reprint author), HARVARD UNIV,SCH PUBL HLTH,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. FU NIAID NIH HHS [U01-AI 25903-09, N0-AI 95030, U01-AI-27668-09] NR 15 TC 38 Z9 39 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY 1 PY 1996 VL 12 IS 1 BP 38 EP 45 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA UK146 UT WOS:A1996UK14600006 PM 8624759 ER PT J AU Lakey, CK Nicholas, PK Wolf, KA Leuner, JD AF Lakey, CK Nicholas, PK Wolf, KA Leuner, JD TI Health care and nursing in Romania SO JOURNAL OF ADVANCED NURSING LA English DT Article ID ABORTION; CHILDREN AB Health care and the nursing profession have been affected dramatically by political and socio-economic conditions in Romania, The Romanian Ministry of Health has recognized the health problems and barriers to care delivery which exist in the country, with several goals identified to improve the status of Romanian health care. This paper explores the critical issues which have impacted on health care and nursing in Romania. C1 MASSACHUSETTS GEN HOSP,INST HLTH PROFESS,GRAD PROGRAMME NURSING,BOSTON,MA 02114. NR 24 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-2402 J9 J ADV NURS JI J. Adv. Nurs. PD MAY PY 1996 VL 23 IS 5 BP 1045 EP 1049 DI 10.1046/j.1365-2648.1996.10826.x PG 5 WC Nursing SC Nursing GA UH329 UT WOS:A1996UH32900045 PM 8732535 ER PT J AU MerayoLloves, J Zhao, TZ Dutt, JE Foster, CS AF MerayoLloves, J Zhao, TZ Dutt, JE Foster, CS TI A new murine model of allergic conjunctivitis and effectiveness of nedocromil sodium SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE cytokines; hay fever conjunctivitis; histopathology; IgE; nedocromil sodium; ragweed ID MAST-CELL; OCULAR ANAPHYLAXIS; TRANSGENIC MICE; EOSINOPHILS; IL-4; DISEASE; RESPONSIVENESS; MODULATION; CYTOKINES; ANTIGEN AB Background: Allergic conjunctivitis is the most common atopic disease affecting the eye. To study the pathophysiology and effectiveness of antiallergic drugs, it is necessary to develop animal models that closely mimic human allergic conjunctivitis. Objective: The study was performed to develop an experimental murine model of ocular allergic conjunctivitis to an airborne allergen. Methods: SWR/J mice were divided into the following groups: group 1, untreated, experimental; group 2, phosphate-buffered saline-treated; group 3, nedocromil sodium-treated; and group 4, unmanipulated controls. Groups 1, 2, and 3 were exposed to ragweed by topical contact with the nasal and conjunctival mucosae. Allergic conjunctivitis was evaluated by scoring of clinical signs, serum IgE levels, and histologic findings. Results: Mice exposed to ragweed had clinicopathologic signs of allergic conjunctivitis and specific anti-ragweed IgE. Allergic conjunctivitis was modulated by nedocromil sodium. Treated mice had fewer clinical signs of allergy, lower levels of ragweed-specific IgE, reduction of conjunctival eosinophil infiltration, decrease in the number of intact and degranulating mast cells, and reduction of cytokine release. Conclusion: This is the first report of a murine model of allergic conjunctivitis to an airborne allergen that can be used to study the disease pathophysiology and its response to treatment. C1 HARVARD UNIV, SCH MED,DEPT OPHTHALMOL, MASSACHUSETTS EYE & EAR INFIRM,OCULAR IMMUNOL SER, BOSTON, MA 02115 USA. RP MerayoLloves, J (reprint author), HARVARD UNIV, SCH MED, DEPT OPHTHALMOL, MASSACHUSETTS EYE & EAR INFIRM, HILLES IMMUNOL LAB, BOSTON, MA 02115 USA. NR 47 TC 19 Z9 19 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 1996 VL 97 IS 5 BP 1129 EP 1140 DI 10.1016/S0091-6749(96)70268-3 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA UL261 UT WOS:A1996UL26100015 PM 8626992 ER PT J AU Morgan, BJ Crabtree, DC Puleo, DS Badr, MS Toiber, F Skatrud, JB AF Morgan, BJ Crabtree, DC Puleo, DS Badr, MS Toiber, F Skatrud, JB TI Neurocirculatory consequences of abrupt change in sleep state in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE arousal; sympathetic nervous system; non-rapid-eye-movement sleep ID SYMPATHETIC-NERVE ACTIVITY; BLOOD-PRESSURE; CARDIAC-OUTPUT; IMPEDANCE CARDIOGRAPHY; OBSTRUCTIVE APNEAS; AROUSAL AB The arterial pressure elevations that accompany sleep apneas may be caused by chemoreflex stimulation, negative intrathoracic pressure, and/or arousal. To assess the neurocirculatory effects of arousal alone, we applied graded auditory stimuli during non-rapid-eye-movement (NREM) sleep in eight healthy humans. We measured muscle sympathetic nerve activity (intraneural microelectrodes), electroencephalogram (EEG; C-4/A(1) and O-1/A(2)), arterial pressure (photoelectric plethysmography), heart rate (electrocardiogram), and stroke volume (impedance cardiography). Auditory stimuli caused abrupt increases in systolic and diastolic pressures (21 +/- 2 and 15 +/- 1 mmHg) and heart rate (11 +/- 2 beats/min). Cardiac output decreased (-10%). Stimuli that produced EEG evidence of arousal evoked one to two large bursts of sympathetic activity (316 +/- 46% of baseline amplitude). Stimuli that did not alter EEG frequency produced smaller but consistent presser responses even though no sympathetic activation was observed. We conclude that arousal from NREM sleep evokes a presser response caused by increased peripheral vascular resistance. Increased sympathetic outflow to skeletal muscle may contribute to, but is not required for, this vasoconstriction. The neurocirculatory effects of arousal may augment those caused by asphyxia during episodes of sleep-disordered breathing. C1 UNIV WISCONSIN,DEPT MED,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,MADISON,WI 53706. RP Morgan, BJ (reprint author), UNIV WISCONSIN,DEPT KINESIOL,1300 UNIV AVE,5175 MSC,MADISON,WI 53706, USA. NR 30 TC 109 Z9 111 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1996 VL 80 IS 5 BP 1627 EP 1636 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA UM254 UT WOS:A1996UM25400026 PM 8727549 ER PT J AU Harada, Y Wang, JT Doppalapudi, VA Willis, AA Jasty, M Harris, WH Nagase, M Goldring, SR AF Harada, Y Wang, JT Doppalapudi, VA Willis, AA Jasty, M Harris, WH Nagase, M Goldring, SR TI Differential effects of different forms of hydroxyapatite and hydroxyapatite tricalcium phosphate particulates on human monocyte macrophages in vitro SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID CRYSTALS; COLLAGENASE; CELLS; FIBROBLASTS; INDUCTION; SECRETION; CERAMICS AB A possible complication associated with the use of hydroxyapatite (HA) or HA/tricalcium phosphate (HA/TCP) coating on the surfaces of prosthetic devices used for dental and orthopedic implants is their potential to fragment and thus exist as wear debris. In contrast to the so-called osteoconductive properties of HA or HA/TCP coatings, in particulate form these materials may lead to an adverse pattern of cellular and tissue responses at the bone-implant interface. We have established an in vitro cell culture system to characterize the biologic and biochemical effects of various particulate materials. The present study demonstrates that the HA/TCP particles derived from different sintering temperatures exhibit differential effects on cultured human monocyte/macrophages (M/M). The HA/TCP particles dried at 110 degrees C were the most biologically active, stimulating significant release of interleukin 1 beta (IL-1 beta), IL-6, tumor necrosis factor alpha and prostaglandin E(2) (PGE(2)), products implicated as important mediators of inflammation in diverse pathologic conditions. Other particles, sintered at either 900 or 1200 degrees C, did not stimulate production of cytokines or PGE(2). HA/TCP particles from plasma-spray coatings also failed to release proinflammatory products. These results suggest that the biochemical and crystalline structural properties of particles markedly affects their capacity to modulate M/M function. This in vitro culture system should be useful in characterizing the specific physical and chemcial properties of HA or HA/TCP particulates that are responsible for stimulating proinflammatory cell responses. (C) 1996 John Wiley & Sons, Inc. C1 HARVARD UNIV,SCH MED,MED SERV,ARTHRITIS UNIT,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DEPT MED & ORTHOPAED SURG,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02114. GUNMA UNIV,SCH MED,DEPT ORTHOPAED SURG,GUNMA,JAPAN. NR 21 TC 78 Z9 85 U1 0 U2 4 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD MAY PY 1996 VL 31 IS 1 BP 19 EP 26 DI 10.1002/(SICI)1097-4636(199605)31:1<19::AID-JBM3>3.0.CO;2-T PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA UG002 UT WOS:A1996UG00200003 PM 8731145 ER PT J AU Mankin, HJ Mankin, CJ Simon, MA AF Mankin, HJ Mankin, CJ Simon, MA TI The hazards of the biopsy, revisited - For the members of the Musculoskeletal Tumor Society SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SOFT-TISSUE TUMORS; TRU-CUT BIOPSY; PRIMARY BONE; DIAGNOSIS AB In 1982, members of the Musculoskeletal Tumor Society representing sixteen centers for the treatment of bone and soft-tissue cancer, compiled data regarding the hazards associated with 329 biopsies of primary malignant musculoskeletal sarcomas, The investigation showed troubling rates of errors in diagnosis and technique, which resulted in complications and also adversely affected the care of the patients, These data were quite different when the biopsy had been carried out in a treatment center rather than in a referring institution, On the basis of these observations, the Society made a series of recommendations about the technical aspects of the biopsy and stated that, whenever possible, the procedure should be done in a treatment center rather than in a referring institution. In 1992, the Musculoskeletal Tumor Society decided to perform a similar study to determine whether the rates of complications, errors, and deleterious effects related to biopsy had changed, Twenty-five surgeons from twenty-one institutions submitted the cases of 597 patients, The results were essentially the same as those in the earlier study, The rate of diagnostic error for the total series (in which cases from referring institutions and treatment centers were combined) was 17.8 per cent. There was no significant difference in the rate of patients for whom a problem with the biopsy forced the surgeon to carry out a different and often more complex operation or to use adjunctive irradiation or chemotherapy (19.3 per cent in the current study, compared with 18 per cent in the previous one), There was also no significant difference in the percentage of patients who had a change in the outcome, such as the need for a more complex resection that resulted in disability, loss of function, local recurrence, or death, attributable to problems related to the biopsy (10.1 per cent in the current study, compared with 8.5 per cent in the 1982 study). Eighteen patients in the current study had an unnecessary amputation as a result of the biopsy, compared with fifteen in the previous study. Errors, complications, and changes in the course and outcome were two to twelve times greater (p < 0.001) when the biopsy was done in a referring institution instead of in a treatment center. RP Mankin, HJ (reprint author), MASSACHUSETTS GEN HOSP,ORTHOPAED SERV GR606,BOSTON,MA 02114, USA. NR 20 TC 311 Z9 328 U1 1 U2 8 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 1996 VL 78A IS 5 BP 656 EP 663 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UK141 UT WOS:A1996UK14100004 ER PT J AU Jupiter, JB Ring, D AF Jupiter, JB Ring, D TI A comparison of early and late reconstruction of malunited fractures of the distal end of the radius SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID COLLES FRACTURE AB We retrospectively evaluated the results for ten patients in whom a malaligned fracture of the distal end of the radius had been treated with early reconstruction (an average of eight weeks [range, six to fourteen weeks] after the injury) consisting of an osteotomy through the site of the fracture, autogenous cancellous iliac-crest bone-grafting, and internal fixation. The results for these patients were compared with those for ten patients in whom functional limitation after complete healing of a fracture of the distal end of the radius in a malreduced position had been treated,vith late reconstruction (an average of forty weeks [range, thirty to forty-eight weeks] after the injury) consisting of an osteotomy, corticocancellous bone-grafting, and internal fixation. The average duration of follow-up was forty-eight months (range, twenty to 120 months) after the early reconstructions and thirty-four months (range, twenty-four to forty-eight months) after the late reconstructions. After the early reconstructions, flexion of the wrist averaged 45 degrees; extension of the wrist, 52 degrees; pronation of the forearm, 79 degrees; and supination of the forearm, 77 degrees, compared with 42, 45, 77, and 68 degrees, respectively, after the late reconstructions. Grip strength averaged forty-two kilograms after the early reconstructions, compared with twenty-five kilograms after the late ones. One patient from each cohort had mild pain in the radiocarpal joint. According to the scale of Fernandez, there were seven excellent and three good results after the early reconstructions, and one excellent, seven good, and two fair results after the late reconstructions. Complications included a rupture of the extensor pollicis longus tendon twelve weeks after one of the early reconstructions, persistent pain at the donor site of the iliac-crest bone graft after a late reconstruction, and a delayed union that necessitated a second procedure after another late reconstruction. We believe that the results of early and late reconstruction of malunited fractures of the distal end of the radius are comparable. For patients who have radiographic characteristics that are predictive of persistent functional limitation, early reconstruction is technically easier and reduces the over-all period of disability. RP Jupiter, JB (reprint author), MASSACHUSETTS GEN HOSP,15 PARKMAN ST,ACC 527,BOSTON,MA 02114, USA. NR 32 TC 66 Z9 68 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 1996 VL 78A IS 5 BP 739 EP 748 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UK141 UT WOS:A1996UK14100014 PM 8642031 ER PT J AU Bergman, RJ Gazit, D Kahn, AJ Gruber, H Mcdougall, S Hahn, TJ AF Bergman, RJ Gazit, D Kahn, AJ Gruber, H Mcdougall, S Hahn, TJ TI Age-related changes in osteogenic stem cells in mice SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID BONE-MARROW; TRABECULAR BONE; INVITRO; DIFFERENTIATION; PROLIFERATION; DEXAMETHASONE; EXPRESSION; COLONIES; CULTURES; TISSUE AB Osteoblasts arise from partially differentiated osteogenic progenitor cells (OPCs) which in turn arise from undifferentiated marrow stromal mesenchymal stem cells (MSCs), It has been postulated that age-related defects in osteoblast number and function may be due to quantitative and qualitative stem cell defects, To examine this possibility, we compared osteogenic stern cell number and in vitro function in marrow cells from 4-month-old and 24-month-old male BALB/c mice, Histologic studies demonstrated that these mice undergo age-related bone loss resembling that seen in humans, In primary MSC cultures grown in media supplemented with 10 nM dexamethasone, cultures from older animals yielded an average of 41% fewer OPC colonies per given number of marrow cells plated (p < 0.001), This implies that for a given number of marrow cells there are fewer stem cells with osteogenic potential in older animals than there are in younger animals, The basal proliferative rate in cultures from older animals, as measured by H-3-thymidine uptake, was more than three times that observed in cultures from young animals (p < 0.005), However, the increase in proliferative response to serum stimulation was 10-fold in the younger cultures (p < 0.001) and insignificant (p < 0.4) in the older cultures, Colonies in both age groups became alkaline phosphatase positive at the same rate, and virtually all colonies were positive after 12 days of culture, Cultures from both age groups produced abundant type I collagen, These studies suggest that defects in the number and proliferative potential of MSCs may underlie age-related defects in osteoblast number and function. C1 HADASSAH MED CTR,SCH DENT,IL-91120 JERUSALEM,ISRAEL. UNIV CALIF SAN FRANCISCO,SCH DENT,SAN FRANCISCO,CA 94143. CAROLINAS MED CTR,ORTHOPED RES LAB,CHARLOTTE,NC 28203. RP Bergman, RJ (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,GRECC,W11G,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 38 TC 225 Z9 241 U1 3 U2 10 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAY PY 1996 VL 11 IS 5 BP 568 EP 577 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UG290 UT WOS:A1996UG29000003 PM 9157771 ER PT J AU Zinkl, GM Zuk, A van der Bijl, P van Meer, G Matlin, KS AF Zinkl, GM Zuk, A van der Bijl, P van Meer, G Matlin, KS TI An antiglycolipid antibody inhibits Madin-Darby canine kidney cell adhesion to laminin and interferes with basolateral polarization and tight junction formation SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EPITHELIAL MDCK CYSTS; PLASMA-MEMBRANE; A-CHAIN; MONOCLONAL-ANTIBODIES; SURFACE POLARITY; EXTRACELLULAR-MATRIX; GLYCOLIPID HAPTEN; LIPID-COMPOSITION; FORSSMAN ANTIGEN; GLYCOPROTEIN AB Epithelial cells polarize not only in response to cell-cell contacts, but also to contacts with a substratum composed of extracellular matrix molecules. To probe the role of specific matrix constituents in epithelial cell polarization, we investigated the effects of an adhesion-blocking mAb, 12B12, on initial polarization of MDCK cells. The 12B12 antibody, raised against whole MDCK cells, blocks adhesion to laminin by 65% but has no effect on adhesion of cells to collagen type I. Taking advantage of this antibody's function-blocking activity, as well as the fact that MDCK cells secrete laminin, the role of endogenous laminin in polarization was examined by plating cells on collagen-coated substrata in the presence of the antibody. Under these conditions, cell spreading was reduced 1.5 h after plating, and cells were flatter and had fewer microvilli after 24 h. Even though lateral cell membranes were closely apposed, transepithelial resistance in the presence of the antibody was significantly reduced relative to controls. When the polarization of specific apical and basolateral markers was examined both biochemically and immunocytochemically in the presence of the antibody, we observed that the apical marker polarized at normal rates while basolateral markers did not. Surprisingly, the 12B12 antibody was not directed against any known cell adhesion protein but reacted specifically with Forssman antigen, a glycosphingolipid. These results suggest that glycolipids may play a significant role in cell adhesion via laminin and in epithelial cell polarization. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, RENAL UNIT, BOSTON, MA 02129 USA. HARVARD UNIV, DEPT MED, SCH MED, BOSTON, MA 02129 USA. HARVARD UNIV, DIV MED SCI, SCH MED, PROGRAM BIOL & BIOMED SCI, BOSTON, MA 02129 USA. UNIV UTRECHT, SCH MED, DEPT CELL BIOL, 3584 CX UTRECHT, NETHERLANDS. UNIV UTRECHT, FAC VET MED,DEPT BASIC SCI,DIV BIOCHEM, INST BIOMEMBRANES, UTRECHT, NETHERLANDS. FU NIDDK NIH HHS [R01 DK46768, P01 DK38452] NR 81 TC 21 Z9 21 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD MAY PY 1996 VL 133 IS 3 BP 695 EP 708 DI 10.1083/jcb.133.3.695 PG 14 WC Cell Biology SC Cell Biology GA UK184 UT WOS:A1996UK18400018 PM 8636242 ER PT J AU Jenkins, BG Brouillet, E Chen, YCI Storey, E Schulz, JB Kirschner, P Beal, MF Rosen, BR AF Jenkins, BG Brouillet, E Chen, YCI Storey, E Schulz, JB Kirschner, P Beal, MF Rosen, BR TI Non-invasive neurochemical analysis of focus excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE magnetic resonance; spectroscopy; lactate; excitotoxicity; neurodegeneration; neuroprotection ID NUCLEAR MAGNETIC-RESONANCE; TOXIN 3-NITROPROPIONIC ACID; D-ASPARTATE RECEPTOR; CHRONIC PARKINSONISM; BRAIN METABOLISM; NMR-SPECTROSCOPY; RAT-BRAIN; NEUROTOXICITY; IMPAIRMENT; H-1-NMR AB Water-suppressed chemical shift magnetic resonance imaging was used to detect neurochemical alterations in vivo in neurotoxin-induced rat models of Huntington's and Parkinson's disease. The toxins were: N-methyl-4-phenylpyridinium (MPP(+)), aminooxyacetic acid (AOAA), 3-nitropropionic acid (3-NP), malonate, and azide. Local or systemic injection of these compounds caused secondary excitotoxic lesions by selective inhibition of mitochondrial respiration that gave rise to elevated lactate concentrations in the striatum. In addition decreased N-acetylaspartate (NAA) concentrations were noted at the lesion Site Over time. Measurements of lactate washout kinetics demonstrated that t(1/2) followed the order: 3-NP approximate to MPP(+) AOAA approximate to malonate which parallels the expected lifetimes of the neurotoxins based On their mechanisms of action. Further increases in lactate were also Caused by intravenous infusion of glucose. at least part of the excitotoxicity is mediated through indirect glutamate pathways because lactate production and lesion size were diminished using unilateral decortectomies (blockade of glutamatergic input) or glutamate antagonists (MK-801). Lesion size and lactate were also diminished by energy repletion with ubiquinone and nicotinamide. Lactate measurements determined by magnetic resonance agreed with biochemical measurements made using freeze clamp techniques. Lesion size as measured with MR, although larger by 30%, agreed well with lesion size determined histologically. These experiments provide evidence for impairment of intracellular energy metabolism leading to indirect excitotoxicity for all the compounds mentioned before and demonstrate the feasibility of small-volume metabolite imaging for in vivo neurochemical analysis. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,NEUROCHEM LAB,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA. RP Jenkins, BG (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,MGH NMR CTR,BLDG 149 13TH ST,BOSTON,MA 02129, USA. RI Schulz, Jorg/D-9786-2012; Brouillet, Emmanuel/B-4784-2014 OI Schulz, Jorg/0000-0002-8903-0593; Brouillet, Emmanuel/0000-0001-6322-7403 NR 43 TC 63 Z9 63 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1996 VL 16 IS 3 BP 450 EP 461 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA UF710 UT WOS:A1996UF71000011 PM 8621749 ER PT J AU Khurana, DS Buonanno, F Ebb, D Krishnamoorthy, KS AF Khurana, DS Buonanno, F Ebb, D Krishnamoorthy, KS TI The role of anticoagulation in idiopathic cerebral venous thrombosis SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID DURAL SINUS THROMBOSIS; CHILDREN; MRI RP Khurana, DS (reprint author), MASSACHUSETTS GEN HOSP,DEPT PEDIAT & NEUROL,BOSTON,MA 02114, USA. NR 17 TC 5 Z9 6 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 1996 VL 11 IS 3 BP 248 EP 250 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA UK384 UT WOS:A1996UK38400019 PM 8734033 ER PT J AU Hsi, ED Zukerberg, LR Yang, WI Arnold, A AF Hsi, ED Zukerberg, LR Yang, WI Arnold, A TI Cyclin D1/PRAD1 expression in parathyroid adenomas: An immunohistochemical study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BREAST-CANCER; RETINOBLASTOMA PROTEIN; CENTROCYTIC LYMPHOMA; CANDIDATE ONCOGENE; CHROMOSOME 11Q13; CELL-CYCLE; AMPLIFICATION; GENE; OVEREXPRESSION; COAMPLIFICATION AB The cyclin D1 (PRAD1) oncogene is rearranged with the PTH gene and is transcriptionally activated in a subset of parathyroid adenomas. Because of heterogeneity in rearrangement breakpoints, the true percentage of adenomas with cyclin D1 deregulation is unknown. Overexpression of the cyclin D1 protein in parathyroid adenomas appears to be a unifying consequence of all cyclin D1 gene rearrangements and can, therefore, be examined to more comprehensively identify adenomas in which cyclin D1 is pathogenetically important. We studied cyclin D1 expression in 65 parathyroid adenomas (from 64 patients), 51 normal parathyroid glands (from the same patients), and 4 parathyroid carcinoma specimens (from 3 patients) using a microwave-enhanced immunohistochemical method and affinity-purified cyclin D1 polyclonal antiserum. When available, data on adenoma mass, intact PTH level, and concurrent serum calcium level were also collected. Twelve of the 65 adenomas (18%) showed diffuse nuclear staining of approximately 30-70% of the tumor cells. All 51 normal glands were negative, except 1 gland that showed scattered cells (<10%) with positive nuclear staining. In addition, scattered positive cells were seen in the compressed rim of histologically normal parathyroid tissue surrounding 2 adenomas that were cyclin D1 negative. No significant differences in adenoma mass, intact PTH levels, or concurrent calcium levels were found between positive and negative tumors. Two of 4 parathyroid carcinoma specimens from 2 of 3 patients showed strong nuclear staining for cyclin D1. Overexpression of the cyclin D1 oncogene in 18% of our cases, due to the cyclin D1/PTH translocation and/or other mechanisms, suggests that overexpressed cyclin D1 plays a role in the pathogenesis of a much larger proportion of parathyroid adenomas than previously appreciated. Cyclin D1 overexpression is a feature of typical parathyroid adenomas and is not confined to unusually large, symptom-causing adenomas as had been suggested by early DNA studies. Although only three patients with parathyroid carcinoma were studied, two of the patients' tumors stained for cyclin D1, raising the possibility that; the frequency of cyclin D1 overexpression may be even greater in carcinomas. Cyclin D1 overexpression appears to highlight a central pathway in parathyroid neoplasia. C1 MASSACHUSETTS GEN HOSP, LAB ENDOCRINE ONCOL, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PATHOL, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. UNIV MICHIGAN, DEPT PATHOL, ANN ARBOR, MI 48109 USA. FU NIDDK NIH HHS [DK-11794] NR 32 TC 126 Z9 129 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 MAY PY 1996 VL 81 IS 5 BP 1736 EP 1739 DI 10.1210/jc.81.5.1736 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800014 PM 8626826 ER PT J AU Devlin, RD Bone, HG Roodman, GD AF Devlin, RD Bone, HG Roodman, GD TI Interleukin-6: A potential mediator of the massive osteolysis in patients with Gorham-Stout disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN MARROW CULTURES; HUMAN-BONE MARROW; CELLS; INVITRO; TUMORS AB Gorham-Stout disease (GSD) or massive osteolysis, is an extremely rare osteolytic condition that involves extensive locally aggressive resorption of bone. The etiology and pathophysiology are unknown, and the role of the osteoclast in GSD is unclear. We studied a patient with GSD who had massive resorption of his mandible, which extended to his maxilla, zygoma, right parietal region, and cranium. To investigate the cause of the extensive resorption, we tested the effects of the patient's serum, sampled early in the course of treatment and later after the osteolysis was stabilized, on the formation of osteoclastlike multinucleated cells (MNC) in cultures of normal human marrow. GSD serum (10%, vol/vol) markedly increased the number of MNC formed in these cultures compared to that in normal serum as well as stimulated the formation of resorption pits by these MNC on dentine slices. GSD serum, collected after further therapy, did not enhance the number of MNC formed in marrow cultures compared to that in normal serum. Elevated levels of interleukin-6 (IL-6) were detected in the earlier GSD serum that were 7 times the upper Limit of the normal range, and after further treatment, IL-6 levels fell to one quarter the pretreatment value. The levels of IL-1 beta, tumor necrosis factor-ct, transforming growth factor-alpha, PTH, and PTH-related peptide in pretreatment GSD serum were not increased. Moreover, the addition of neutralizing antibodies to IL-6 to the normal human bone marrow cultures effectively blocked the increase in MNC formation induced by active GSD serum. These data suggest that bone resorption in GSD patients is due to enhanced osteoclast activity, and that IL-6 may play a role in the increased bone resorption in GSD. C1 UNIV TEXAS, HLTH SCI CTR, SAN ANTONIO, TX 78284 USA. VET ADM MED CTR, SAN ANTONIO, TX USA. HENRY FORD HOSP, DETROIT, MI 48202 USA. FU NCI NIH HHS [CA-40035]; NIAMS NIH HHS [AR-39529, AR-40554] NR 31 TC 109 Z9 115 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 MAY PY 1996 VL 81 IS 5 BP 1893 EP 1897 DI 10.1210/jc.81.5.1893 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK198 UT WOS:A1996UK19800042 PM 8626854 ER PT J AU Uyemura, K Demer, LL Castle, SC Jullien, D Berliner, JA Gately, MK Warrier, RR Pham, N Fogelman, AM Modlin, RL AF Uyemura, K Demer, LL Castle, SC Jullien, D Berliner, JA Gately, MK Warrier, RR Pham, N Fogelman, AM Modlin, RL TI Cross-regulatory roles of interleukin (IL)-12 and IL-10 in atherosclerosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cytokine; highly oxidized LDL; minimally modified LDL; PCR; monocytes ID LOW-DENSITY-LIPOPROTEIN; INTERFERON-GAMMA-PRODUCTION; NECROSIS-FACTOR-ALPHA; T-CELL SUBSETS; MURINE LEISHMANIASIS; LYMPHOCYTES-T; MACROPHAGE ACTIVATION; ENDOTHELIAL-CELLS; CYTOKINE; EXPRESSION AB T cell cytokines are known to play a major role in determining protection and pathology in infectious disease. It has recently become clear that IL-12 is a key inducer of the type 1 T cell cytokine pattern characterized by production of IFN-gamma. Conversely, n-10 down-regulates IL-12 production and type 1 cytokine responses. We have investigated whether IL-12 and IL-10 might be involved in a chronic inflammatory reaction, atherosclerosis. In atherosclerotic plaques, we found strong expression of IFN-gamma but not IL-4 mRNAs as compared to normal arteries. IL-12 p40 mRNA and IL-12 p70 protein were also found to be abundant in atherosclerotic plaques. IL-12 was induced in monocytes in vitro in response to highly oxidized LDL but not minimally modified LDL. The cross-regulatory role of IL-10 was indicated by the expression of IL-10 in some atherosclerotic lesions, and the demonstration that exogenous rIL-10 inhibited LDL-induced IL-12 release. These data suggest that the balance between IL-12 and IL-10 production contributes to the level of immune-mediated tissue injury in atherosclerosis. C1 UNIV CALIF LOS ANGELES,DIV DERMATOL,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT GERIATR,LOS ANGELES,CA 90024. HOFFMANN LA ROCHE INC,DEPT INFLAMMAT AUTOIMMUNE DIS,NUTLEY,NJ 07110. RI Demer, Linda/I-5770-2013; JULLIEN, Denis/D-5654-2014; OI Demer, Linda/0000-0002-9618-6895; JULLIEN, Denis/0000-0002-2995-7928; Modlin, Robert/0000-0003-4720-031X FU NCRR NIH HHS [RR865]; NHLBI NIH HHS [HL-30568] NR 55 TC 300 Z9 307 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY 1 PY 1996 VL 97 IS 9 BP 2130 EP 2138 DI 10.1172/JCI118650 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UJ399 UT WOS:A1996UJ39900018 PM 8621803 ER PT J AU Steuber, CP Krischer, J Holbrook, T Camitta, B Land, V Sexauer, C Mahoney, D Weinstein, H AF Steuber, CP Krischer, J Holbrook, T Camitta, B Land, V Sexauer, C Mahoney, D Weinstein, H TI Therapy of refractory or recurrent childhood acute myeloid leukemia using amsacrine and etoposide with or without azacitidine: A pediatric oncology group randomized phase II study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; BONE-MARROW TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; MAINTENANCE THERAPY; CHILDREN; AMSA; 5-AZACYTIDINE; CANCER; ADULTS; INTENSIFICATION AB Purpose: A randomized study compared the combination of amsacrine (100 mg/m(2)/d on days 1 to 5) and etoposide (200 mg/m(2)/d on days 1 to 3) with the same two agents plus azacitidine (250 mg/m(2)/d on days 4 to 5) for the therapy of induction-resistant or relapsed childhood acute myeloid leukemia (AML). Patients and Methods: One hundred sixty-seven assessable children with AML who either had failed to respond to primary induction therapy (group 1, n = 41) or had relapsed (group 2, n = 126) were randomized. Results: Overall, there were 56 complete responses (34%; SE 4%). Among primary refractory patients (group 1), the complete response rate was higher with the three-drug regimen(18% v 53%, P = .03). In the relapsed patients (group 2), there was no difference in complete response rates related to treatment (31% v 35%, P = .3). There were 17 early deaths. The major toxicities for both regimens were myelosuppression and infection. Conclusion: The overall complete response rate of 34% in this patient population is indicative of effective antileukemic activity. For patients with relapsed leukemia, the addition of azacitidine to etoposide and amscacrine did not improve response. The suggested advantage of the three-drug regimen for induction failures warrants further investigation. (C) 1996 by American Society of Clinical Oncology. C1 BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. PEDIAT ONCOL GRP,STAT OFF,GAINESVILLE,FL. E CAROLINA UNIV,SCH MED,GREENVILLE,NC. MIDWEST CHILDRENS CANC CTR,MILWAUKEE,WI. WASHINGTON UNIV,MED CTR,ST LOUIS,MO. UNIV OKLAHOMA,HLTH SCI CTR,OKLAHOMA CITY,OK. DANA FARBER CANC INST,BOSTON,MA 02115. FU NCI NIH HHS [CA-15515, CA-03161, CA-29139] NR 34 TC 28 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 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 1521 EP 1525 PG 5 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300015 PM 8622066 ER PT J AU Perloff, M Norton, L Korzun, AH Wood, WC Carey, RW Gottlieb, A Aust, JC Bank, A Silver, RT Saleh, F Canellos, GP Perry, MC Weiss, RB Holland, JF AF Perloff, M Norton, L Korzun, AH Wood, WC Carey, RW Gottlieb, A Aust, JC Bank, A Silver, RT Saleh, F Canellos, GP Perry, MC Weiss, RB Holland, JF TI Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: A cancer and leukemia group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED TRIAL; THERAPY; METHOTREXATE; SENSITIVITY; ADRIAMYCIN; MODELS AB Purpose: To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen-vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)-in patients with stage II node-positive breast carcinoma. Methods: Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH. Results: Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens, VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040), For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years), This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients. Conclusion: Chemotherapy with crossover to escalating dose of VATH following CMFVP was well tolerated and effective, Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival, The observation that sensitivity to VATH is retained 50 long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of crossover designs in future trials of postoperative adjuvant chemotherapy regimens. (C) 1996 by American Society of Clinical Oncology. C1 NCI,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY. NEW YORK HOSP,CORNELL MED CTR,NEW YORK,NY 10021. MT SINAI HOSP,NEW YORK,NY 10029. SUNY SYRACUSE,HLTH SCI CTR,SYRACUSE,NY 13210. EMORY UNIV,SCH MED,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. DANA FARBER CANC INST,BOSTON,MA 02115. ONCOL ASSOCIATES SAN DIEGO,SAN DIEGO,CA. UNIV MISSOURI,ELLIS FISCHEL CANC CTR,COLUMBIA,MO. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. FU NCI NIH HHS [CA12449, CA07968, CA33601] NR 30 TC 49 Z9 49 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 1589 EP 1598 PG 10 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300025 PM 8622076 ER PT J AU Dreyfuss, AI Clerk, JR Norris, CM Rossi, RM Lucarini, JW Busse, PM Poulin, MD Thornhill, L Costello, R Posner, MR AF Dreyfuss, AI Clerk, JR Norris, CM Rossi, RM Lucarini, JW Busse, PM Poulin, MD Thornhill, L Costello, R Posner, MR TI Docetaxel: An active drug for squamous cell carcinoma of the head and neck SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-I; TAXOTERE RP-56976; INTRAVENOUS-INFUSION; TAXOL; CISPLATIN; CANCER; TRIAL; NSC-628503; ANALOG AB Purpose: We conducted a phase II study designed to evaluate activity, safety, and tolerability of docetaxel (Taxotere: Rhone-Poulene Rorer Pharmaceuticals Inc, Collegeville, PA) in patients with advanced, incurable, or recurrent squamous cell carcinoma of the head and neck (SCCHN) who herd not received prior palliative chemotherapy. Patients and Methods: Thirty-one patients with measurable, locoregional, of metastatic SCCHN were treated with docetaxel, administered at a dose of 100 mg/m(2) as a 1-hour intravenous (IV) infusion once every 21 days on an outpatient basis, All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. Prophylactic administration of growth factors or antiemetics was not permitted. Results: Thirty-one patients were treated. Twenty-nine patients; were assessable for response and 30 for toxicity. Four of 31 patients (13%) achieved complete response (CR), nine (29%) achieved partial response (PR), nine (29%) had stable disease (SD), and seven (23%) experienced progression of disease (PD). The major response rate was 42% (95% confidence interval [CI], 24% to 60%), The median duration of responses was 5 months (range, 2 to 14). The principal toxicity was leukopenia, which occurred with rapid onset and brief duration. Sixteen patients (53%) experienced nadir fever, and 13 required dose reduction. Hypersensitivity reactions occurred in four patients. Grade 3 peripheral neuropathy occurred in two patients; grade 2 or 3 fatigue occurred in six (20%) and 10 (33%), respectively. Minimal edema (grade 1) occurred in five patients (17%). Clinically significant mucositis, diarrhea, or dermatitis were not observed. Conclusion: Docetaxel has major activity against SCCHN. It appears to be well tolerated in this group of patients and can be safely administered on an outpatient basis. premedication with dexamethasone, cimetidine, and diphenhydramine is associated with a reduced incidence of significant edema, hypersensitivity reactions, and dermatologic toxicities. (C) 1996 by American Society of Clinical Oncology. C1 DANA FARBER CANC INST,HEAD & NECK ONCOL PROGRAM,BOSTON,MA 02115. NEW ENGLAND DEACONESS HOSP,DEPT OTOLARYNGOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. FU NCI NIH HHS [2PO1-CA19589-17] NR 37 TC 163 Z9 167 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 1672 EP 1678 PG 7 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300036 PM 8622087 ER PT J AU Offit, K Biesecker, BB Burt, RW Clayton, EW Garber, JE Kahn, MJE AF Offit, K Biesecker, BB Burt, RW Clayton, EW Garber, JE Kahn, MJE TI Statement of the American Society of Clinical Oncology: Genetic testing for cancer susceptibility SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article AB As the leading organization of physicians who treat people with cancer, the American Society of Clinical Oncology (ASCO) recognizes that cancer specialists must be fully informed of the range of issues involved in genetic testing for cancer risk. The newly discovered and still developing ability to identify individuals at highest risk for cancer holds the promise of improved prevention and early detection of cancers. It also poses potential medical, psychological, and other personal risks that must be addressed in the context of informed consent for genetic testing. ASCO firmly believes that any physician who offers genetic testing should be aware of, and able to communicate, the benefits and limits of current testing procedures, and the range of prevention and treatment options available to patients and their families. For these reasons, ASCO endorses the following principles: ASCO affirms the role of clinical oncologists in documenting a family history of cancer in their patients, providing counseling regarding familial cancer risk and options for prevention and early detection, and recognizing those families for which genetic testing may serve as an aid in counseling. To the greatest extent possible, genetic testing for cancer susceptibility should be performed in the setting of longterm outcome studies. ASCO endorses the formulation and implementation of a notional cooperative study/registry with appropriate confidentiality to define the clinical significance of mutations in known cancer susceptibility genes. ASCO is committed to providing educational opportunities for physicians concerning methods of quantitative cancer risk assessment, genetic testing, and pre- and post-test genetic counseling so that oncologists may more responsibly integrate genetic counseling and testing into the practice of clinical and preventive oncology. Oncologists must assure that informed consent has been given by the patient as an integral part of the process of genetic predisposition testing, whether such testing is offered on a clinical or research basis. ASCO recommends that cancer predisposition testing be offered only when: 1) the person has a strong family history of cancer or very early age of onset of disease; 2) the test can be adequately interpreted; and 3) the results will influence the medical management of the patient or family member. As clinical testing becomes more widely available, the Society encourages oncologists to utilize laboratories committed to the validation of testing methodologies, and to facilitate families' participation in long-term outcome studies. ASCO recommends that oncologists include in pre- and post-test counseling discussion of possible risks and benefits of cancer early detection and prevention modalities, which have presumed but unproven efficacy for individuals at the highest hereditary risk for cancer. ASCO endorses efforts to strengthen regulatory authority over laboratories that provide cancer predisposition tests that will be utilized to inform clinical decisions. These regulatory requirements should include appropriate oversight of the products used in genetic testing, interlaboratory comparisons of reference samples, as well as quality control mechanisms. ASCO endorses all efforts including legislation to prohibit discrimination by insurance companies or employers based on an individual's inherited susceptibility to cancer. All individuals at hereditary risk for cancer should have access to appropriate genetic testing and associated medical care, which should be covered by public and private third-party payers. ASCO endorses continued support of patient-oriented research to analyze the psychological impact of genetic testing of at-risk populations. C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV UTAH,SALT LAKE CITY,UT 84112. VANDERBILT UNIV,NASHVILLE,TN 37240. DANA FARBER CANC INST,BOSTON,MA 02115. NATL BREAST CANC COALIT,RICHMOND,VA. UNIV MICHIGAN,ANN ARBOR,MI 48109. UNIV TEXAS,MD ANDERSON CANCER CTR,HOUSTON,TX 77030. WASHINGTON UNIV,SCH MED,ST LOUIS,MO 63130. UNIV PENN,PHILADELPHIA,PA 19104. RP Offit, K (reprint author), AMER SOC CLIN ONCOL,225 REINEKERS LANE,SUITE 650,ALEXANDRIA,VA 22314, USA. NR 15 TC 450 Z9 453 U1 0 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 1730 EP 1736 PG 7 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300043 ER PT J AU Lin, A Longy, M Goldstein, A Mulvihill, J Ponder, B Tucker, M AF Lin, A Longy, M Goldstein, A Mulvihill, J Ponder, B Tucker, M TI Localization of Cowden's disease gene to chromosome 10022-23. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA 15260. INT BERGONIE,BORDEAUX,FRANCE. NCI,BETHESDA,MD 20892. UNIV CAMBRIDGE,CAMBRIDGE,ENGLAND. DANA FARBER CANC INST,BOSTON,MA 02115. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 2003 EP 2003 PG 1 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300054 ER PT J AU Kantoff, PW Conaway, M Winer, E Picus, J Vogelzang, NJ AF Kantoff, PW Conaway, M Winer, E Picus, J Vogelzang, NJ TI Hydrocortisone (HC) with or without mitoxantrone (M) in patients (pts) with hormone refractory prostate cancer (HRPC): Preliminary results from a prospective randomized cancer and leukemia group B study (9182) comparing chemotherapy to best supportive care. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. DUKE UNIV,MED CTR,DURHAM,NC 27706. WASHINGTON UNIV,MED CTR,ST LOUIS,MO 63130. UNIV CHICAGO,MED CTR,CHICAGO,IL 60637. CANC & LEUKEMIA GRP B,CHICAGO,IL. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1996 VL 14 IS 5 BP 2013 EP 2013 PG 1 WC Oncology SC Oncology GA UJ403 UT WOS:A1996UJ40300064 ER PT J AU DiazSiohl, JA Dogon, IL AF DiazSiohl, JA Dogon, IL TI Evaluation of adhesive bonding strength of Vitremer to dentin as variable substrate. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 CENT UNIV VENEZUELA,SCH DENT,OPERAT DEPT,CARACAS,VENEZUELA. FORSYTH DENT CTR,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1996 VL 75 IS 5 BP 1089 EP 1089 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VG926 UT WOS:A1996VG92600229 ER PT J AU Diaz, JA Siohl, IL AF Diaz, JA Siohl, IL TI Resistance evaluation of adhesive joints from Vitremer to variable dentin substrate. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 CENT UNIV VENEZUELA,SCH DENT,DEPT OPERAT DENT,CARACAS,VENEZUELA. FORSYTH DENT CTR,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1996 VL 75 IS 5 BP 1320 EP 1320 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VG926 UT WOS:A1996VG92601768 ER PT J AU Barsky, AJ Ahern, DK Bailey, D Delamater, BA AF Barsky, AJ Ahern, DK Bailey, D Delamater, BA TI Predictors of persistent palpitations and continued medical utilization SO JOURNAL OF FAMILY PRACTICE LA English DT Article DE palpitation; somatoform disorders; stress, psychological; health services; health services misuse; electrocardiography, ambulatory ID CHEST PAIN; TRANSIENT HYPOCHONDRIASIS; PSYCHOLOGICAL DISTRESS; LIFE EVENTS; ILLNESS; ANXIETY; HEALTH AB Background. The aim of this study was to determine the predictors of persistent palpitations and continued medical utilization in a sample of medical patients referred for ambulatory electrocardiographic monitoring. Methods. A prospective telephone follow-up was conducted with patients who had undergone ambulatory electrocardiographic monitoring 3 months earlier. At inception, patients completed in-person interviews and self-report questionnaires, assessing somatization, hypochondriacal attitudes, bodily amplification (high degree of sensitivity to bodily sensations), and two types of life stress (minor daily irritants and major life changes). At Follow-up, patients completed a structured interview about their clinical course, palpitations, and utilization of medical care during the interval. Results. At 3-month follow-up, 55 of the inception cohort of 67 patients were interviewed again. The mean severity of palpitations for the entire sample declined significantly, but 46 (83.6%) patients continued to experience their presenting symptoms. Stepwise multiple linear regression revealed that the interaction of bodily amplification and daily life stress at inception uniquely explained 10.0% of the variance in palpitation severity at follow-up. A four-step model composed of these two interaction terms and age and education level accounted for 21.4% of the variance in palpitations. The medical utilization findings are complementary in that the interaction of amplification and daily irritants at baseline predicted the number of unscheduled medical visits over the subsequent 3 months. The total number of ventricular premature contractions occurring during ambulatory monitoring was nor a significant predictor of palpitations. Conclusions. Palpitations are more persistent in persons who are both highly sensitive to bodily sensations and who experience a greater number of minor daily irritants. The existence of either predictor alone is not sufficient to perpetrate this functional somatic symptom; it requires the combination of these predictors. C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PSYCHIAT SERV,BOSTON,MA 02114. RP Barsky, AJ (reprint author), BRIGHAM & WOMENS HOSP,DIV PSYCHIAT,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [HL43216] NR 41 TC 20 Z9 21 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD MAY PY 1996 VL 42 IS 5 BP 465 EP 472 PG 8 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA UL123 UT WOS:A1996UL12300010 PM 8642363 ER PT J AU Hayward, LJ Brown, RH Cannon, SC AF Hayward, LJ Brown, RH Cannon, SC TI Inactivation defects caused by myotonia-associated mutations in the sodium channel III-IV linker SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE muscle; paralysis; familial; ion channels; human ID HYPERKALEMIC PERIODIC PARALYSIS; SITE-DIRECTED MUTAGENESIS; FUNCTIONAL EXPRESSION; CELLS; BETA-1-SUBUNIT; BRAIN AB Missense mutations in the skeletal muscle Na+ channel a subunit occur in several heritable forms of myotonia and periodic paralysis. Distinct phenotypes arise from mutations at two sites within the III-IV cytoplasmic loop: myotonia without weakness due to substitutions at glycine 1306, and myotonia plus weakness caused by a mutation at threonine 1313. Heterologous expression in HEK cells showed that substitutions at either site disrupted inactivation, as reflected by slower inactivation rates, shifts in steady-state inactivation, and larger a persistent Na+ currents. For Tl313M, however, the changes were an order of magnitude larger than any of three substitutions at G1306, and recovery from inactivation was hastened as well. Model simulations demonstrate that these functional differences have distinct phenotypic consequences. In particular, a large persistent Na+ current predisposes to paralysis due to depolarization-induced block of action potential generation. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. FU NIAMS NIH HHS [AR42703, AR41025]; NINDS NIH HHS [NS07340] NR 37 TC 96 Z9 96 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAY PY 1996 VL 107 IS 5 BP 559 EP 576 DI 10.1085/jgp.107.5.559 PG 18 WC Physiology SC Physiology GA UJ386 UT WOS:A1996UJ38600002 PM 8740371 ER PT J AU Kocher, MS Coombs, CJ Upton, J AF Kocher, MS Coombs, CJ Upton, J TI Actinomycetoma of the phalanx in an immunocompromised patient: A case report SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article RP Kocher, MS (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORTHOPAED SURG,FRUIT ST,BOSTON,MA 02135, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAY PY 1996 VL 21A IS 3 BP 515 EP 517 DI 10.1016/S0363-5023(96)80373-X PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA UM645 UT WOS:A1996UM64500035 PM 8724490 ER PT J AU McNamara, D DiSalvo, T Mathier, M Keck, S Semigran, M Dec, GW AF McNamara, D DiSalvo, T Mathier, M Keck, S Semigran, M Dec, GW TI Left ventricular dysfunction after heart transplantation: Incidence and role of enhanced immunosuppression SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID CORONARY-ARTERY DISEASE; ENDOMYOCARDIAL BIOPSY SPECIMENS; CARDIAC TRANSPLANTATION; NITRIC-OXIDE; VASCULAR REJECTION; INTERLEUKIN-2; RECIPIENTS; INTERFERON; CARDIOMYOPATHY; CONTRACTILITY AB Background: The purpose of this study was to examine the incidence, natural history, and outcome of left ventricular dysfunction in 102, consecutive heart transplant recipients. Left ventricular dysfunction (defined as a decline in the echocardiographic ejection fraction to < 0.45) occurred in 15 of 102 transplant recipients (16%) at a mean of 9.7 +/- 8.6 (standard deviation) months after transplantation. Methods: Diagnostic evaluation included right heart catheterization and endomyocardial biopsy in all patients and coronary angiography in 13 patients. Results: Four patients were found to have moderate cellular rejection (International Society for Heart and Lung Transplantation grade 2 or higher) and were treated with enhanced immunosuppression. Two patients had angiographically apparent coronary allograft vasculopathy: both died of electromechanical dissociation within 4 months. The remaining ten patients had no or mild cellular rejection (International Society for Heart and Lung Transplantation grade 0 or 1). Therapy in these ten patients included corticosteroids (n = 8), OKT3 (n = 5), and plasmapheresis (n = 2). Three patients died within 2 months of diagnosis, two from undetected severe coronary allograft vasculopathy and one from unrecognized constrictive pericarditis. The echocardiographic ejection fraction improved in the surviving patients after enhanced immunosuppressive therapy (0.33 to 0.53, p < 0.005). With the benefit of long-term clinical follow-up and autopsy data, the origins of left ventricular dysfunction in the 16 patients included moderate cellular rejection (n = 4), vascular rejection (n = 1), coronary allograft vasculopathy (n = 3), intercurrent cytomegalovirus injection (n = 1), constrictive. pericarditis (n = 1), and either mild or no evident rejection (n = 6). Survival of the 16 patients with left ventricular dysfunction was similar to that of the 86 patients without left ventricular dysfunction. Conclusions: The cause of left ventricular dysfunction after heart transplantation includes cellular rejection, vascular rejection, coronary allograft vasculopathy, cytomegalovirus infection, constrictive pericarditis, and unexplained mechanisms. Given the improvement in left ventricular function observed after empiric therapy with enhanced immunosuppression in patients with left ventricular dysfunction, immune-mediated phenomena may play an important pathogenic role. C1 MASSACHUSETTS GEN HOSP HEART FAILURE & CARDIAC TR,BOSTON,MA. NR 40 TC 22 Z9 22 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD MAY PY 1996 VL 15 IS 5 BP 506 EP 515 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA UP070 UT WOS:A1996UP07000010 PM 8771506 ER PT J AU Takabayashi, T Vannier, E Clark, BD Margolis, NH Dinarello, CA Burke, JF Gelfand, JA AF Takabayashi, T Vannier, E Clark, BD Margolis, NH Dinarello, CA Burke, JF Gelfand, JA TI A new biologic role for C3a and C3a desArg - Regulation of TNF-alpha and IL-1 beta synthesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 PRODUCTION; MONONUCLEAR-CELLS; HUMAN-MONOCYTES; MESSENGER-RNA; ANAPHYLATOXIN; C5A; COMPLEMENT; SEPSIS; PLASMA AB The complement activation products C3a and C3a desArg are generated in the course of trauma, infection, tissue injury, and ischemia. We have investigated the effects of C3a and C3a desArg on gene expression and protein synthesis of TNF-alpha and IL-1 beta in PBMC. Neither C3a nor C3a desArg alone induced detectable protein or mRNA levels for TNF-alpha and IL-1 beta. C3a modulated LPS-induced TNF-alpha and IL-1 beta synthesis. In nonadherent PBMC, C3a suppressed LPS-induced synthesis of TNF-alpha (20-71% decrease by 0.2-10 mu g/ml of C3a, p < 0.01) and IL-1 beta (19-57% decrease by 0.5-10 mu g/ml of C3a, p < 0.01), independently of endogenous production of PGE(2). C3a also suppressed LPS-induced mRNA levels for TNF-alpha and IL-1 beta. In contrast, in adherent PBMC, C3a at 5 to 20 mu g/ml enhanced LPS-induced TNF-alpha (75-188% increase, p < 0.001) and IL-1 beta (119-274% increase, p < 0.001) synthesis. C3a enhanced TNF-alpha and IL-1 beta mRNA levels in LPS-stimulated adherent cells. Furthermore, C3a desArg shared with C3a the ability to modulate LPS-induced mRNA and protein synthesis for TNF-alpha and IL-1 beta. These results suggest that C3a, thought to be proinflammatory, and C3a desArg, thought to be biologically inactive, are modulators of inflammation. Both C3a and C3a desArg may enhance cytokine synthesis by adherent monocytes at local inflammatory sites, while inhibiting the systemic synthesis of proinflammatory cytokines by circulating cells. C1 TUFTS UNIV NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. TUFTS UNIV,SCH MED,TUPPER RES INST,DEPT MED,BOSTON,MA 02111. HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. FU NIAID NIH HHS [AI-15614]; NIGMS NIH HHS [GM-50766, GM-21700] NR 36 TC 118 Z9 121 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1996 VL 156 IS 9 BP 3455 EP 3460 PG 6 WC Immunology SC Immunology GA UF742 UT WOS:A1996UF74200047 PM 8617973 ER PT J AU Brady, MT McGrath, N Brouwers, P Gelber, R Fowler, MG Yogev, R Hutton, N Bryson, YJ Mitchell, CD Fikrig, S Borkowsky, W Jimenez, E McSherry, G Rubinstein, A Wilfert, CM McIntosh, K Elkins, MM Weintrub, PS Bernstein, L Shliozberg, J Livingston, RA Vink, P Flautt, L Kline, MW Rayborn, T Kaul, A Lawrence, R Chandwani, S RubinHale, A KnoxBurke, K AlAttar, I Cooper, ER Pelton, SI Regan, AM Damon, B Young, B Nozyce, M Cihak, P Wiznia, A Chadwick, EG Silio, M Klauke, BJ Oleske, JM Colabelli, NB Connor, EM Gershon, A Pitt, J Shea, K Clark, P Cervia, JS Edelson, PJ SandersLaufer, D Hinds, GA Rakusan, TA Sever, J Herzog, K Ellaurie, M McKinney, RE Lane, BA Santacroce, S Nesheim, SR Sawyer, M Sarver, J Meadows, L Abrams, E Kanem, N Frere, M Urbano, R Ragni, MV Miller, B Carfagna, E Mendez, H Handlesman, E Difilippo, G Bergin, HF Shah, K Rao, S Villarica, NC Clintron, AA Hodes, D Barzelai, A Butler, L Heaton, S Gupta, A Ahern, L Munoz, J Li, K Bamji, M Kennedy, G Dummitt, M Pahwa, S Baksji, S Hunkler, JA Callaway, CC Crim, LB Diaz, C Rivera, C Flores, L Beauchamp, B Diaz, L Aguayo, R GarciaTrias, DE Frenkel, LD Gaur, S Scudder, RC Kechula, IM Lischner, HW Gregonis, SW Treston, CS Raphael, SA Carrer, MT Perez, L Berrios, Z Burchett, SK Melvin, AJ Corey, L Mohan, KM Grieco, M McKinley, G Rivera, J Moallen, H Schuller, G Pramberg, JC Alchediak, T VanDyke, RB Calligaro, D Church, J Deveikis, A Gilette, S Spector, SA Dankner, WM Instone, S Stangle, L Wara, DW Petru, A WilliamsHerman, D Baker, RC Siegel, R McOwen, N Robinson, J Wells, L Johnson, GM Rich, KC Hayani, K Turpin, D Sullivan, JL Luzuriaga, K Stechenberg, BW Robinson, JE Lim, W Dudek, V Mundorf, L Santucci, S Frenkel, L Lambert, JS Murante, B Scott, GB Gourley, J Mendoza, C Doyle, M Cantini, M AF Brady, MT McGrath, N Brouwers, P Gelber, R Fowler, MG Yogev, R Hutton, N Bryson, YJ Mitchell, CD Fikrig, S Borkowsky, W Jimenez, E McSherry, G Rubinstein, A Wilfert, CM McIntosh, K Elkins, MM Weintrub, PS Bernstein, L Shliozberg, J Livingston, RA Vink, P Flautt, L Kline, MW Rayborn, T Kaul, A Lawrence, R Chandwani, S RubinHale, A KnoxBurke, K AlAttar, I Cooper, ER Pelton, SI Regan, AM Damon, B Young, B Nozyce, M Cihak, P Wiznia, A Chadwick, EG Silio, M Klauke, BJ Oleske, JM Colabelli, NB Connor, EM Gershon, A Pitt, J Shea, K Clark, P Cervia, JS Edelson, PJ SandersLaufer, D Hinds, GA Rakusan, TA Sever, J Herzog, K Ellaurie, M McKinney, RE Lane, BA Santacroce, S Nesheim, SR Sawyer, M Sarver, J Meadows, L Abrams, E Kanem, N Frere, M Urbano, R Ragni, MV Miller, B Carfagna, E Mendez, H Handlesman, E Difilippo, G Bergin, HF Shah, K Rao, S Villarica, NC Clintron, AA Hodes, D Barzelai, A Butler, L Heaton, S Gupta, A Ahern, L Munoz, J Li, K Bamji, M Kennedy, G Dummitt, M Pahwa, S Baksji, S Hunkler, JA Callaway, CC Crim, LB Diaz, C Rivera, C Flores, L Beauchamp, B Diaz, L Aguayo, R GarciaTrias, DE Frenkel, LD Gaur, S Scudder, RC Kechula, IM Lischner, HW Gregonis, SW Treston, CS Raphael, SA Carrer, MT Perez, L Berrios, Z Burchett, SK Melvin, AJ Corey, L Mohan, KM Grieco, M McKinley, G Rivera, J Moallen, H Schuller, G Pramberg, JC Alchediak, T VanDyke, RB Calligaro, D Church, J Deveikis, A Gilette, S Spector, SA Dankner, WM Instone, S Stangle, L Wara, DW Petru, A WilliamsHerman, D Baker, RC Siegel, R McOwen, N Robinson, J Wells, L Johnson, GM Rich, KC Hayani, K Turpin, D Sullivan, JL Luzuriaga, K Stechenberg, BW Robinson, JE Lim, W Dudek, V Mundorf, L Santucci, S Frenkel, L Lambert, JS Murante, B Scott, GB Gourley, J Mendoza, C Doyle, M Cantini, M TI Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128) SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; CEREBROSPINAL-FLUID; ORAL ZIDOVUDINE; HIV INFECTION; AZT; ENCEPHALOPATHY; ABNORMALITIES; INFUSION; THERAPY; INFANTS AB The current dosage of zidovudine for children is 180 mg/m(2) every 6 h, To investigate whether a lower dosage was equally effective, human immunodeficiency virus (HIV)-infected children (3 months to 12 years) with mild to moderate symptoms were randomly assigned to receive either high-dose (180 mg/m(2)/dose) or low-dose (90 mg/m(2)/dose) zidovudine (double-blind), Treatments were compared with respect to neuropsychologic function, survival, clinical and laboratory evidence of disease progression, and safety and tolerance, Four hundred twenty-six HIV-infected children were enrolled; median time for receipt of study drug was 35 months, Zidovudine in either dose was well tolerated, with no difference in efficacy or tolerance by treatment group using any clinical or laboratory parameter, In children with mild to moderate disease, a reduction of zidovudine to 90 mg/m(2)/dose will result in substantial cost savings and should be the recommended dose. C1 OHIO STATE UNIV,COLL MED,DEPT PEDIAT & PREVENT MED,COLUMBUS,OH 43210. CHILDRENS HOSP,HIV PROGRAM,COLUMBUS,OH 43205. HARVARD UNIV,SCH MED,SCH PUBL HLTH,DANA FARBER CANC INST,STAT & DATA ANAL CTR,PED AI,BOSTON,MA. HARVARD UNIV,SCH MED,SCH PUBL HLTH,DANA FARBER CANC INST,DEPT PEDIAT BIOSTAT,BOSTON,MA. CHILDRENS HOSP,DIV INFECT DIS,BOSTON,MA. NCI,CLIN ONCOL PROGRAM,PEDIAT BRANCH,NEUROPSYCHOL GRP,BETHESDA,MD 20892. NIAID,DIV AIDS,PEDIAT MED BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD. CHILDRENS MEM HOSP,SECT PEDIAT & MATERNAL HIV INFECT,CHICAGO,IL 60614. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. UNIV MIAMI,DEPT PEDIAT,MIAMI,FL 33152. SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. NYU,DEPT PEDIAT,MED CTR,NEW YORK,NY 10016. ALBERT EINSTEIN COLL MED,DEPT PEDIAT,BRONX,NY 10467. ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10467. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,CHILDRENS HOSP NEW JERSEY,DEPT CLIN PEDIAT,NEWARK,NJ 07103. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27706. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. SAN JUAN CITY HOSP,DEPT PEDIAT,GUAYNABO,PR. RI Oleske, James/C-1951-2016 OI Oleske, James/0000-0003-2305-5605 FU NIAID NIH HHS [AI-25924] NR 36 TC 33 Z9 34 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1996 VL 173 IS 5 BP 1097 EP 1106 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UF867 UT WOS:A1996UF86700007 PM 8627060 ER PT J AU Damico, LA White, LT Yu, X Lewandowski, ED AF Damico, LA White, LT Yu, X Lewandowski, ED TI Chemical versus isotopic equilibrium and the metabolic fate of glycolytic end products in the heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE metabolism; hypoxia; lactate dehydrogenase; alanine aminotransferase; isotopes; glycolysis; nuclear magnetic resonance spectroscopy; carbon-13 ID PERFUSED RAT-HEART; CITRIC-ACID CYCLE; C-13 NMR; LACTATE; MITOCHONDRIAL; SPECTROSCOPY; MYOCARDIUM; PYRUVATE; ALANINE; STATE AB Recent studies of isotope exchange across lactate dehydrogenase (LDH) and alanine aminotransferase (AAT) in hearts call into question whether both reactions are in equilibrium. To compare the oxidative and non-oxidative fates of glycolytic end products, isolated rabbit hearts were perfused with 5 mM [2-C-13] glucose and 2.5 mM [3-C-13] pyruvate: with (n = 6) and without (n = 7) stimulation of pyruvate oxidation using dichloroacetate (DCA), and during normal perfusion or hypoxia (n = 7/n = 6, + / - DCA). C-13 NMR spectroscopy of intact hearts confirmed a steady-state enrichment level in both alanine and lactate. H-1- and C-13-NMR spectroscopy of tissue extracts identified the fractions of lactate, alanine and glutamate pools formed from each exogenous substrate. Glycolysis from glucose accounted for 22 +/- 7% of lactate formed and 10 +/- 2% of alanine formed in control hearts, and 16 +/- 2% lactate and 15 +/- 2% alanine in hypoxic hearts (mean +/- S.E.M.). In contrast, exogenous pyruvate formed 36 +/- 5% of the lactate pool, and 86 +/- 3% of the alanine pool in controls and 47 +/- 3% of lactate and of 67 +/- 3% alanine during hypoxia. [2-C-13] glucose did not contribute to oxidative energy production via the TCA cycle as determined from low C-13 enrichment of glutamate C5 from glucose (<2%), while [3-C-13] pyruvate accounted for 84 +/- 7% of labeled glutamate C4. Thus, exogenous pyruvate out-competed the metabolism of glucose, indicating low glycolytic activity. At 40 min, 96 +/- 2% of the total alanine was labeled from either glucose or pyruvate, confirming equilibrium at AAT. However, only 55 +/- 10% of total lactate was labeled, suggesting that the LDH reaction is not in rapid equilibrium within the myocardium. (C) 1996 Academic Press Limited C1 HARVARD UNIV, SCH MED,MASSACHUSETTS GEN HOSP,DEPT RADIOL, NUCL MAGNET RESONANCE CTR, CHARLESTOWN, MA 02129 USA. FU NHLBI NIH HHS [R01HL49244] NR 24 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 1996 VL 28 IS 5 BP 989 EP 999 DI 10.1006/jmcc.1996.0092 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA UM585 UT WOS:A1996UM58500017 PM 8762037 ER PT J AU He, Q Cahill, CJ Spiro, MJ AF He, Q Cahill, CJ Spiro, MJ TI Suspension culture of differentiated rat heart myocytes on non-adhesive surfaces SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE cardiac myocytes; differentiated state; dedifferentiation; suspension culture; myosin; cell viability; MTT; myocardial endothelial cells ID ADULT CARDIAC MYOCYTES; CALCIUM-TOLERANT MYOCYTES; LONG-TERM CULTURE; CELL-CULTURE; MUSCLE CELL; CARDIOMYOCYTES; FOLLICLES; POLARITY; COLLAGEN; DNA AB Cardiac myocytes isolated from adult rat ventricles have been maintained in a stable, differentiated state for prolonged periods by the use of suspension culture on hydrophobic tissue culture inserts or agarose-coated plates. The success of this procedure depends on the use of low-serum media to prevent myocyte-myocyte interaction and proliferation of any residual endothelial cells. Myocytes cultured in this manner retain many of their structural characteristics, suggesting that maintenance of their elongated irregular shape is not dependent on interaction with extracellular matrix. They also exclude trypan blue, can be vitally stained by the uptake and reduction of the tetrazolium dye MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide], synthesize myosin and when returned to adhesive surfaces are capable of attachment and attendant dedifferentiation. Stability of the myocytes in suspension permits their use in co-culture experiments; specifically, myocytes separated from endothelial cells by the hydrophobic membrane of the tissue culture insert stimulated proliferation of the latter cells, suggesting this to be a useful system for studying myocyte-endothelial cell interaction. (C) 1996 Academic Press Limited C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA USA. JOSLIN DIABET CTR, BOSTON, MA 02215 USA. HARVARD UNIV, SCH MED, DEPT BIOL CHEM, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL31315] NR 31 TC 3 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 1996 VL 28 IS 5 BP 1177 EP 1186 DI 10.1006/jmcc.1996.0108 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA UM585 UT WOS:A1996UM58500033 PM 8762053 ER PT J AU Hsu, DW Louis, DN Efird, JT HedleyWhyte, ET AF Hsu, DW Louis, DN Efird, JT HedleyWhyte, ET TI Use of Ki-67 (MIB-1) immunoreactivity in differentiating grade II and grade III gliomas. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 2 EP 2 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300014 ER PT J AU Louis, DN Rosenberg, JE Ueki, K Lisle, DK Burwick, JA AF Louis, DN Rosenberg, JE Ueki, K Lisle, DK Burwick, JA TI The chromosome 19Q glioma tumor suppressor gene: Further mapping and cloning efforts. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 4 EP 4 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300016 ER PT J AU Paulus, W Baur, I Reeves, SA AF Paulus, W Baur, I Reeves, SA TI beta 1-integrins mediate diffuse brain invasion of glioma cells in vivo. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV ZURICH HOSP,CH-8091 ZURICH,SWITZERLAND. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 7 EP 7 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300019 ER PT J AU Chen, TY Vonsattel, JP Wells, J Kowall, NW Bird, E McKee, A AF Chen, TY Vonsattel, JP Wells, J Kowall, NW Bird, E McKee, A TI Immunocytochemical and genotypic distinctions among 3 variants of Pick's lobar atrophy. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 VAMC,BEDFORD,MA. BOSTON UNIV,SCH MED,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MCLEAN BRAIN TISSUE RESOURCE CTR,BELMONT,MA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 11 EP 11 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300023 ER PT J AU Ma, MJ Vonsattel, JP HedleyWhyte, ET AF Ma, MJ Vonsattel, JP HedleyWhyte, ET TI Argyrophilic glial cytoplasmic inclusions in progressive supranuclear palsy - Sensitive and specific detection by Bielschowsky stain. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 15 EP 15 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300027 ER PT J AU GomezIsla, T Hollister, R West, H Mui, S Growdon, JH Petersen, RC Parisi, JE Hyman, BT AF GomezIsla, T Hollister, R West, H Mui, S Growdon, JH Petersen, RC Parisi, JE Hyman, BT TI Neuronal loss in Alzheimer's disease: Relation to tangles, plaques, and apolipoprotein E. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. MAYO CLIN,ROCHESTER,MN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 47 EP 47 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300059 ER PT J AU Kowall, NW Beal, MF Brown, RH Beckman, JS Volicer, L Ferrante, RJ AF Kowall, NW Beal, MF Brown, RH Beckman, JS Volicer, L Ferrante, RJ TI Localization of multiple histochemical markers of oxidative injury in projection neurons in Alzheimer cortex. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 VAMC,BEDFORD,MA. BOSTON UNIV,BOSTON,MA 02215. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 53 EP 53 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300065 ER PT J AU Xia, MQ Qin, SX McNamara, M Hyman, BT AF Xia, MQ Qin, SX McNamara, M Hyman, BT TI Type B IL-8 receptor (IL-8RB) in neuritic plaques of Alzheimer's disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. LEUKOSITE INC,CAMBRIDGE,MA 02142. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 56 EP 56 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300068 ER PT J AU Page, K Tanzi, RE Hyman, BT AF Page, K Tanzi, RE Hyman, BT TI The expression of Alzheimer's disease chromosome 14Q24.3 gene presenilin-1(PS1) in rat brain and in response to excitotoxic brain injury. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 58 EP 58 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300070 ER PT J AU Newell, KL Young, AB HedleyWhyte, ET Vonsattel, JP AF Newell, KL Young, AB HedleyWhyte, ET Vonsattel, JP TI Huntington's disease and progressive supranuclear palsy in an 80 year-old man. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,SCH MED,MCLEAN HOSP,BOSTON,MA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 128 EP 128 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300140 ER PT J AU Sohn, YK Bloch, KD Wands, JR Filippov, G Aquino, L delaMonte, SM AF Sohn, YK Bloch, KD Wands, JR Filippov, G Aquino, L delaMonte, SM TI Aberrant ceNOS expression correlates with Fas- and p53-related apoptosis in neurodegenerative diseases. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 130 EP 130 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300142 ER PT J AU Kelley, LM HedleyWhyte, ET Wheelock, T Ma, MJ Zhao, Y Bird, ED Vonsattel, JP AF Kelley, LM HedleyWhyte, ET Wheelock, T Ma, MJ Zhao, Y Bird, ED Vonsattel, JP TI A rapid, reliable method of obtaining outstanding histological sections from fresh or formalin-fixed brain tissue using liquid nitrogen vapor. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. HARVARD UNIV,SCH MED,MCLEAN HOSP,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 132 EP 132 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300144 ER PT J AU delaMonte, SM Carlson, RI Brown, NV Wands, JR AF delaMonte, SM Carlson, RI Brown, NV Wands, JR TI Profiles of neuronal thread protein expression in Alzheimer's disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1996 VL 55 IS 5 BP 156 EP 156 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA UK933 UT WOS:A1996UK93300168 ER PT J AU Palfi, SP Ferrante, RJ Brouillet, E Beal, MF Dolan, R Guyot, MC Peschanski, M Hantraye, P AF Palfi, SP Ferrante, RJ Brouillet, E Beal, MF Dolan, R Guyot, MC Peschanski, M Hantraye, P TI Chronic 3-nitropropionic acid treatment in baboons replicates the cognitive and motor deficits of Huntington's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; basal ganglia; caudate nucleus; frontal cortex; baboon; 3-nitropropionic acid; object retrieval detour task; cognitive behavior; motor behavior; apomorphine testing ID SCAN INVESTIGATIONS; ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM; TOMOGRAPHIC SCAN; OBJECT RETRIEVAL; CAUDATE-PUTAMEN; PRIMATE MODEL; HUMAN INFANTS; IMPAIRMENT; MONKEYS AB We showed recently that chronic administration of the mitochondrial inhibitor 3-nitropropionic acid (3NP) in primates produces various dyskinetic movements and dystonic postures associated with selective striatal lesions displaying many similarities with the pathological features of Huntington's disease (HD). In the present study, we examined whether such a toxic treatment could also induce frontal-type deficits similar to those observed in HD patients. Cognitive performances of 3NP-treated and control baboons were compared using the object retrieval detour task (ORDT), a test designed to assess the functional integrity of the frontostriatal pathway in human and nonhuman primates. During the same time, the motor function of each animal was assessed under spontaneous ''no drug'' conditions, and time-sampled neurological observations were used after apomorphine administration. A significant impairment in the ORDT was observed in the 3NP animals after 3-6 weeks of treatment, occurring in the absence of spontaneous abnormal movements but in the presence of apomorphine-inducible dyskinesias. Prolonged 3NP treatment resulted in the progressive appearance of spontaneous abnormal movements. Histological evaluation of these animals showed selective bilateral caudate-putamen lesions with sparing of the cerebral cortex, notably the prefrontal cortex. The present study demonstrates that chronic 3NP treatment replicates in primates the basic pathophysiological triad of HD, including spontaneous abnormal movements, progressive striatal degeneration, and a frontostriatal syndrome of cognitive impairment. C1 CEA DSV, URA CEA CNRS 1285, SERV HOSP FREDERIC JOLIOT, DRIPP, F-91401 ORSAY, FRANCE. FAC MED, INSERM U421, F-94010 CRETEIL, FRANCE. VET ADM MED CTR, GERIATR RES EDUC & CLIN CTR UNIT, BEDFORD, MA 01730 USA. BOSTON UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02118 USA. MASSACHUSETTS GEN HOSP, DEPT NEUROL, NEUROCHEM LAB, BOSTON, MA 02114 USA. RI Brouillet, Emmanuel/B-4784-2014 OI Brouillet, Emmanuel/0000-0001-6322-7403 NR 48 TC 164 Z9 171 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY 1 PY 1996 VL 16 IS 9 BP 3019 EP 3025 PG 7 WC Neurosciences SC Neurosciences & Neurology GA UF711 UT WOS:A1996UF71100015 PM 8622131 ER PT J AU Ogilvy, CS Carter, BS Kaplan, S Rich, C Crowell, RM AF Ogilvy, CS Carter, BS Kaplan, S Rich, C Crowell, RM TI Temporary vessel occlusion for aneurysm surgery: Risk factors for stroke in patients protected by induced hypothermia and hypertension and intravenous mannitol administration SO JOURNAL OF NEUROSURGERY LA English DT Article DE intracranial aneurysm; temporary arterial occlusion; cerebral ischemia; cerebral infarction ID SOMATOSENSORY EVOKED-POTENTIALS; ISCHEMIC NEURONAL INJURY; CORTICAL BLOOD-FLOW; CEREBRAL ANEURYSM; ARTERIAL-OCCLUSION; BRAIN TEMPERATURE; MANAGEMENT; ANESTHESIA; RUPTURE; DISEASE AB Temporary vessel occlusion is an effective technique used by microvascular surgeons to facilitate dissection and permanent clipping of cerebral aneurysms; however, several questions remain regarding the overall safety of this technique. To identify technical and patient-specific risk factors for perioperative stroke, the authors examined a series of patients in whom induced hypertension and mild hypothermia and intravenous mannitol administration were used as protection during temporary vessel occlusion for aneurysm clipping. The study comprises a nonconcurrent prospective analysis of 132 consecutive aneurysm clippings performed with the aid of temporary vascular occlusion and a specific antiischemic anesthetic protocol at the Massachusetts General Hospital from 1991 to 1993. Factors studied included duration of the temporary clip application, number of occlusive episodes, patient age and neurological status, presence of preoperative subarachnoid hemorrhage (SAH), and intraoperative aneurysm rupture (''forced'' temporary clipping), as well as whether proximal vessel occlusion or complete aneurysm trapping was used. In a univariate analysis, patient age, intraoperative aneurysm rupture. temporary clipping lasting more than 20 minutes, clipping between the 4th and 10th day after SAH, and multiple clipping episodes were all significantly associated with stroke outcome. Multivariate logistic regression revealed that intraoperative aneurysm rupture (relative risk 5.6, p = 0.02) and a duration of temporary clip application that lasted more than 20 minutes (relative risk 9.4, p = 0.04) were independently associated with stroke outcome. Overall, 5.2% of the patients had postoperative clinical strokes. Based on their findings the authors conclude that temporary clipping is a safe adjunct to aneurysm surgery, particularly when the duration of clipping is short. C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Ogilvy, CS (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,VBK 710,BOSTON,MA 02114, USA. NR 27 TC 111 Z9 119 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1996 VL 84 IS 5 BP 785 EP 791 DI 10.3171/jns.1996.84.5.0785 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UG540 UT WOS:A1996UG54000011 PM 8622152 ER PT J AU Barker, FG Jannetta, PJ Babu, RP Pomonis, S Bissonette, DJ Jho, HD AF Barker, FG Jannetta, PJ Babu, RP Pomonis, S Bissonette, DJ Jho, HD TI Long-term outcome after operation for trigeminal neuralgia in patients with posterior fossa tumors SO JOURNAL OF NEUROSURGERY LA English DT Article DE trigeminal neuralgia; microvascular decompression; brain neoplasm; posterior fossa tumor ID CEREBELLOPONTINE ANGLE; EPIDERMOID TUMORS; HEMIFACIAL SPASM; MICROVASCULAR DECOMPRESSION; GLOSSOPHARYNGEAL NEURALGIA; FACIAL-PAIN; MENINGIOMAS; COMPRESSION; DIAGNOSIS; SECONDARY AB During a 20-year period, 26 patients with typical symptoms of trigeminal neuralgia were found to have posterior fossa tumors at operation. These cases included 14 meningiomas. eight acoustic neurinomas, two epidermoid tumors, one angiolipoma, and one ependymoma. The median patient age was 60 years and 69% of the patients were women. Sixty-five percent of the symptoms were left sided. The median preoperative duration of symptoms was 5 years. The distribution of pain among the three divisions of the trigeminal nerve was similar to that found in patients with trigeminal neuralgia who did not have tumors; however, more divisions tended to be involved in the tumor patients. The mean postoperative follow-up period was 9 years. At operation, the root entry zone of the trigeminal nerve was examined for vascular cross-compression in 21 patients. Vessels compressing the nerve at the root entry zone were observed in all patients examined. Postoperative pain relief was frequent and long lasting. Using Kaplan-Meier methods the authors estimated excellent relief in 81% of the patients 10 years postoperatively, with partial relief in an additional 4%. C1 UNIV PITTSBURGH,DEPT NEUROL SURG,PITTSBURGH,PA 15260. RP Barker, FG (reprint author), MASSACHUSETTS GEN HOSP,NEUROSURG SERV,WARREN 905,FRUIT ST,BOSTON,MA 02114, USA. NR 76 TC 60 Z9 61 U1 0 U2 5 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAY PY 1996 VL 84 IS 5 BP 818 EP 825 DI 10.3171/jns.1996.84.5.0818 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UG540 UT WOS:A1996UG54000015 PM 8622156 ER PT J AU Narula, J Petrov, A ODonnell, SM Ditlow, C Pieslak, I Dilley, J Chen, F Khaw, BA AF Narula, J Petrov, A ODonnell, SM Ditlow, C Pieslak, I Dilley, J Chen, F Khaw, BA TI Gamma imaging of atherosclerotic lesions: The role of antibody affinity in in vivo target localization SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE antibody; atherosclerosis; radionuclide imaging; smooth muscle cells ID SMOOTH-MUSCLE CELLS; MONOCLONAL-ANTIBODY; PROLIFERATION; EVOLUTION AB Background. Monoclonal antibodies are attractive agents for noninvasive localization of various cardiovascular disorders. Because proliferating intimal smooth muscle cells are important components of atherosclerotic lesions, radiolabeled antibody Z2D3 specific for proliferating smooth muscle cells has been used for immunoscintigraphic localization of experimental atherosclerotic lesions. This study was undertaken to assess the role of antibody affinity in optimization of immunoscintigraphic localization of these lesions. Z2D3 belongs to the immunoglobulin (Ig) M class of antibodies. For immunoscintigraphic studies, attempts were made to prepare F(ab')(2) or Fab fragments from the parent cell line. Fragmentation of Z2D3-IgM or its two subclones (B7 and 2B12) was not possible; therefore the parent hybridoma line was subjected to class switching. Cell lines 5C5 and 3E5 secreted antibody of the IgG(1) subclass. The Z2D3-IgG(1) antibodies were enzymatically digested to provide F(ab')(2). Because of a tenfold loss of immunoreactivity of these class-switched antibodies, the parent clone was subsequently genetically engineered to obtain a mouse/human chimeric antibody with human IgG(1) constant region. F(ab')(2) of Z2D3-73.30 chimeric antibody retained the immunoreactivity relative to the original Z2D3-IgM. Radiolabeled murine and chimeric F(ab')(2) fragments were used to assess the role of affinity in gamma scintigraphic visualization of experimental atherosclerotic lesions. Methods and Results. Experimental atherosclerotic lesions were induced in 19 rabbits by abdominal aortic balloon deendothelialization followed by a hyperlipidemic diet for 12 weeks, In-111-labeled chimeric high-affinity Z2D3 F(ab')(2) fragments (In-111-Hi.aff Z2D3) were administered in four animals, Uptake was compared with In-111-labeled F(ab')(2) of nonspecific human IgG(1) (n = 4), murine low-affinity Z2D3-5C5 (In-111-Lo.aff Z2D3; n = 4), nonspecific murine IgG(1) monoclonal antibodies (n = 4), and I-123-labeled murine low-affinity Z2D3-3E5 (n = 3). Atherosclerotic lesions were visualized 48 hours after administration of the chimeric Hi.aff-Z2D3 antibody in all animals. Lesions were not visualized in rabbits injected with Lo.aff-Z2D3 or murine or human nonspecific antibodies. Mean percent injected dose per gram in the lesion was significantly higher with the In-111-Hi.aff-Z2D3 (0.112% +/- 0.024%) compared with In-111-Lo.aff-Z2D3 (0.037% +/- 0.005%; p = 0.03), human nonspecific (0.027% +/- 0.004%; p = 0.01), or murine nonspecific antibodies (0.006% +/- 0.001%; p = 0.0004). Nonspecific activity in unballooned thoracic aortic segments (normal) was comparable in the In-111-Hi.aff-Z2D3 (0.019 +/- 0.003) and the In-111-Lo.aff-Z2D3 (0.011% +/- 0.005%; p = 0.3) antibodies, The lesion activities of the Lo.aff-Z2D3 labeled with In-111 (0.037 +/- 0.005) or I-123 (0.034 +/- 0.007; p = 0.71) were similar regardless of the radioisotopes used for labeling. Conclusions. Our study demonstrates that the specificity of an antibody for the target antigen in the atheroma is a necessary condition for in vivo targeting. However, high enough affinity of an antibody is an essential component for noninvasive diagnostic visualization of experimental atherosclerotic lesions. C1 NORTHEASTERN UNIV,MASSACHUSETTS GEN HOSP,CTR DRUG TARGETING & ANAL,BOSTON,MA 02115. SCOTGEN BIOPHARMACEUT INC,MENLO PK,CA. NR 29 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD MAY-JUN PY 1996 VL 3 IS 3 BP 231 EP 241 DI 10.1016/S1071-3581(96)90037-9 PG 11 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA UU893 UT WOS:A1996UU89300006 PM 8805743 ER PT J AU Narula, J Elmaleh, DR Petrov, A Babich, J Zamecnik, PC Rapoport, E Fischman, AJ Khaw, BA AF Narula, J Elmaleh, DR Petrov, A Babich, J Zamecnik, PC Rapoport, E Fischman, AJ Khaw, BA TI Evaluation of upregulation of adenosine receptors on proliferating smooth muscle cells allows instant noninvasive localization of atherosclerotic lesions. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 4 EP 4 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500004 ER PT J AU Rubin, RH Baltimore, D Chen, B Wilkinson, RA Fischman, AJ AF Rubin, RH Baltimore, D Chen, B Wilkinson, RA Fischman, AJ TI Determination of tissue distribution of CD4 lymphocytes by immunoscintigraphy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MIT,CAMBRIDGE,MA 02139. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 87 EP 87 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500087 ER PT J AU Fischman, AJ Bonab, AA Babich, JW Alpert, NM Rauch, SL Elmaleh, DR Shoup, TM Rubin, RH AF Fischman, AJ Bonab, AA Babich, JW Alpert, NM Rauch, SL Elmaleh, DR Shoup, TM Rubin, RH TI Pet analysis of 5HT2 receptor occupancy in healthy volunteers treated with the novel antipsychotic agent, ziprasidone. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 123 EP 123 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500123 ER PT J AU Glass, EC Nelleman, P Hines, H Mandelkern, MA Blahd, WH AF Glass, EC Nelleman, P Hines, H Mandelkern, MA Blahd, WH TI Initial coincidence imaging experience with a SPECT/PET dual head camera. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA. ADAC LABS,MILPITAS,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 203 EP 203 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500203 ER PT J AU Madras, BK Livni, E Elmaleh, DR Fischman, AJ Brownell, AL AF Madras, BK Livni, E Elmaleh, DR Fischman, AJ Brownell, AL TI PET imaging of cocaine binding sites on the dopamine transporter: An application for cocaine medications development. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,BOSTON,MA. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 251 EP 251 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500251 ER PT J AU Brownell, AL Jenkins, B Burns, L Tatter, S Elmaleh, DR Livni, E Deacon, T Brownell, GL Isacson, O AF Brownell, AL Jenkins, B Burns, L Tatter, S Elmaleh, DR Livni, E Deacon, T Brownell, GL Isacson, O TI Using of PET and MRS techniques to evaluate neural degeneration and graft survival in primate Parkinson disease model. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA. MCLEAN HOSP,BELMONT,MA 02178. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 254 EP 254 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500254 ER PT J AU Vural, I Narula, J Torchilin, VP Khaw, BA AF Vural, I Narula, J Torchilin, VP Khaw, BA TI Preservation of hypoxic cardiomyocyte viability up to 5 days by antimyosin liposome membrane sealing therapy: Verification by 3-H thymidine uptake studies SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 415 EP 415 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500415 ER PT J AU Barbarics, E Croop, JM Kronauge, JF Cohen, D Davison, A Jones, AG AF Barbarics, E Croop, JM Kronauge, JF Cohen, D Davison, A Jones, AG TI In-vivo accumulation and modulation of Tc-99m-MIBI in multidrug-resistant tumors. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. SANDOZ RES INST,E HANOVER,NJ. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 461 EP 461 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500461 ER PT J AU Silverman, DHS Munakata, JA Hoh, CK Mandelkern, MA Mayer, EA AF Silverman, DHS Munakata, JA Hoh, CK Mandelkern, MA Mayer, EA TI Regional cerebral activity in normal and pathologic perception of visceral pain. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 482 EP 482 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500482 ER PT J AU Alpert, NM Berdichevsky, D Levin, Z Morris, ED Fischman, AJ AF Alpert, NM Berdichevsky, D Levin, Z Morris, ED Fischman, AJ TI An automated system for multimodality image segmentation, registration and fusion. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 490 EP 490 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500490 ER PT J AU Frohlich, DEC Chen, JL Kehoe, K VandenAbbeele, AD AF Frohlich, DEC Chen, JL Kehoe, K VandenAbbeele, AD TI Hilar uptake on gallium-67 imaging following CHOP chemotherapy for NHL SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 617 EP 617 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500550 ER PT J AU Babich, JW Ferrill, K Graham, W Fischman, AJ AF Babich, JW Ferrill, K Graham, W Fischman, AJ TI Optimization of Sn(II)-mannitol formulation for Tc-99m-labeling of hydrazinonicotinamide-conjugated peptides. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 632 EP 632 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500565 ER PT J AU Schmidt, U Carles, MC Hajjar, RJ Narula, J DiSalvo, TG Semigran, MJ Dec, GW Khaw, BA AF Schmidt, U Carles, MC Hajjar, RJ Narula, J DiSalvo, TG Semigran, MJ Dec, GW Khaw, BA TI Sarcoplasmic reticulum calcium ATPase is inhibited by auto-antibodies present in dilated cardiomyopathy patients. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 633 EP 633 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500566 ER PT J AU Babich, JW Ferrill, K Rose, DJ Graham, W Maresca, K Zubieta, J Fischman, AJ AF Babich, JW Ferrill, K Rose, DJ Graham, W Maresca, K Zubieta, J Fischman, AJ TI Pyridinethiols and pyrimidinethiols (PT) as coligands for Tc-99M labeled hydrazinonicotinamide (HYNIC) conjugated peptides SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. SYRACUSE UNIV,SYRACUSE,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 670 EP 670 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500603 ER PT J AU Huggins, GS Skopicki, HA Abraham, SA Alpert, NM Fischman, AJ Gewirtz, H AF Huggins, GS Skopicki, HA Abraham, SA Alpert, NM Fischman, AJ Gewirtz, H TI Maximal microvascular dilator capacity assessed by PET N-3 ammonia in myocardial regions with normal flow reserve is abnormal in patients with stable IHD. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 704 EP 704 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500637 ER PT J AU Rammohan, R Petrov, A Haider, N Vural, I Pak, CYK Narula, J Khaw, BA AF Rammohan, R Petrov, A Haider, N Vural, I Pak, CYK Narula, J Khaw, BA TI Subnuclear localization of Tc-99m glucarate in necrotic myocardium. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. MTTI,MALVERN,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 808 EP 808 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500695 ER PT J AU Callahan, RJ Barrow, SA Abrams, MJ Rubin, RH Fischman, AJ AF Callahan, RJ Barrow, SA Abrams, MJ Rubin, RH Fischman, AJ TI Biodistribution and dosimetry of technetium-99m-hydrazino nicotinamide IgG, comparison with indium-111-DTPA-IgG SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE technetium-99m-HYNIC-IgG; indium-111-DTPA-IgG; dosimetry ID POLYCLONAL IGG; FOCAL SITES; BACTERIAL-INFECTION; IMMUNOGLOBULIN; INFLAMMATION; LOCALIZATION AB The biological behavior of human polyclonal immunoglobulin G (IgG), radiolabeled with Tc-99m via. a nicotinyl hydrazine derivative (Tc-99m-HYNIC-IgG), was evaluated in normal human subjects. Methods: Initial biodistribution and dosimetry studies were performed in six normal male volunteers. Additionally, (TC)-T-99m-IgG and In-111-DTPA-IgG were co-injected into six subjects and scintillation camera images were acquired at 6 and 18 hr later and serial blood and urine samples were collected. Biodistribution of both radiopharmaceuticals were measured by region of interest analysis. In the dual-injection group, images were crossover-corrected. Results: All subjects tolerated injection of the radiolabeled IgG preparations without apparent ill effects, Biodistribution of the two antibody preparations were remarkably similar with an increase in liver and abdominal activity for the In-111 preparation. Linear correlation of the tissue-to-blood ratios of Tc-99m and In-111-labeled IgG was observed at both times (r(2) > 0.98). The slopes of the regression line were 0.97 and 0.76 at 6 and 18 hr, respectively. The beta phase of the blood clearance of Tc-99m-HYNIC-IgG Was significantly delayed (p < 0.01) compared with In-111-IgG (t(1/2): 51.9 +/- 6.5 versus 35.3 +/- 3.4 hr). In contrast, the volumes of distribution and urinary excretions of the radiopharmaceuticals were not significantly different. Conclusion: These studies establish that the biodistribution of Tc-99m-HYNIC-IgG in normal human subjects is nearly identical to In-111-DTPA-lgG. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,DIV NUCL MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CLIN INVEST UNIT,MED SERV,BOSTON,MA 02114. JOHNSON MATTHEY PHARMACEUT RES,W CHESTER,PA. HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. NR 17 TC 18 Z9 20 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 BP 843 EP 846 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UK883 UT WOS:A1996UK88300037 PM 8965158 ER PT J AU Callahan, RJ Bogdanov, AA Barrow, SA Brady, TJ Fischman, AJ Weissleder, R AF Callahan, RJ Bogdanov, AA Barrow, SA Brady, TJ Fischman, AJ Weissleder, R TI Initial clinical trial of a synthetic copolymer kit for blood pool imaging. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 906 EP 906 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500792 ER PT J AU Wernikoff, R Gewirtz, H AF Wernikoff, R Gewirtz, H TI Misleading estimates of small-lesion detectability in phantom studies of Tl-201 myocardial perfusion (TL) SPECT. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 967 EP 967 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500853 ER PT J AU Callahan, RJ Correia, JA Bonab, AA Graham, W Babich, JW Fischman, AJ AF Callahan, RJ Correia, JA Bonab, AA Graham, W Babich, JW Fischman, AJ TI Comparison of human and animal data based radiation absorbed dose estimates for positron radiopharmaceuticals used in drug development. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1030 EP 1030 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500916 ER PT J AU Fischman, AJ Babich, JW Alpert, NM Vincent, J Callahan, RJ Correia, JA Rubin, RH AF Fischman, AJ Babich, JW Alpert, NM Vincent, J Callahan, RJ Correia, JA Rubin, RH TI Pharmacokinetics of F-18 trovafloxacin in normal and E-coli infected rabbits studied with PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. PFIZER INC,GROTON,CT 06340. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1076 EP 1076 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500962 ER PT J AU Carter, EA Tompkins, RG Babich, JW Fischman, AJ AF Carter, EA Tompkins, RG Babich, JW Fischman, AJ TI Accumulation of Tc-99m chemotactic peptides in chronic intestinal inflammation. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1077 EP 1077 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500963 ER PT J AU Carter, EA Tompkins, RG Babich, JW Fischman, AJ AF Carter, EA Tompkins, RG Babich, JW Fischman, AJ TI Severe trauma increases Tc-99m chemotactic peptide accumulation in lung: Comparison with In-111 WBC's. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1078 EP 1078 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500964 ER PT J AU Callahan, RJ Achong, DM Wilkinson, RA Dragotakes, SC Fischman, AJ AF Callahan, RJ Achong, DM Wilkinson, RA Dragotakes, SC Fischman, AJ TI Can filtration improve the bone marrow imaging properties of Tc-99m sulfur colloid? SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1079 EP 1079 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500965 ER PT J AU Hsu, H Yu, YM Tompkins, RG Correia, JA Young, VR Burke, JF Alpert, NM Fischman, AJ AF Hsu, H Yu, YM Tompkins, RG Correia, JA Young, VR Burke, JF Alpert, NM Fischman, AJ TI Measurement of regional hepatic blood flow with [O-15]water and pet in dogs SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1098 EP 1098 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62500984 ER PT J AU Arthur, IE Kehoe, K VandenAbbeele, AD AF Arthur, IE Kehoe, K VandenAbbeele, AD TI Thallium-201 scintigraphy in low grade non-Hodgkin's lymphoma. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DIV ONCOL NUCL MED,DANA FARBER CANC INST,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1154 EP 1154 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501040 ER PT J AU VandenAbbeele, AD Slavin, SA AF VandenAbbeele, AD Slavin, SA TI Classification of upper extremity lymphedema [LED] via lymphoscintigraphy [LS]. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV NUCL MED,DANA FARBER CANC INST,BOSTON,MA. HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,DIV SURG,BOSTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1170 EP 1170 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501056 ER PT J AU Elmaleh, D Petrov, A Narula, J Babich, J Zamecnik, PC Rapoport, E Fischman, AJ Khaw, BA AF Elmaleh, D Petrov, A Narula, J Babich, J Zamecnik, PC Rapoport, E Fischman, AJ Khaw, BA TI Tc-99m N-myc antisense for imaging of human breast tumor hosted in SCID mice: Comparison with indium-111-103D2 antibody. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NORTHEASTERN UNIV,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1202 EP 1202 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501088 ER PT J AU Rabito, CA Cosimi, AB Lee, J Farrell, ML Pascual, M AF Rabito, CA Cosimi, AB Lee, J Farrell, ML Pascual, M TI Combined use of renal scan end ambulatory renal monitor (ARM) to evaluate renal function of original transplanted kidneys after simultaneous cadaver kidney and pancreas transplant (CKPT). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1996 VL 37 IS 5 SU S BP 1307 EP 1307 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL625 UT WOS:A1996UL62501193 ER PT J AU Li, KK Stephens, WL Gliklich, R AF Li, KK Stephens, WL Gliklich, R TI Reconstruction of the severely atrophic edentulous maxilla using Le Fort I osteotomy with simultaneous bone graft and implant placement SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID IMMEDIATE ENDOSSEOUS IMPLANTS; OSSEOINTEGRATED IMPLANTS; ALVEOLAR RIDGE; JAW AB Purpose: This study evaluated the outcome of patients who underwent simultaneous Le Fort I osteotomy, an interpositional bone graft, and implant placement for reconstruction of the severely atrophic edentulous maxilla, Patients and Methods: Twenty patients operated by the same surgeon were included in the study, Patients were followed annually with clinical and radiographic examinations for an average of 33 months, Results: One hundred thirty-nine implants were initially inserted in the bone grafts at the time of Le Fort I osteotomy, Twenty-five implants (18%) failed to osseointegrate, Seventeen of the 25 implants lost were from three patients, The most significant prognostic factor appeared to be the thickness of the atrophic maxillary ridge, Twelve of the 20 patients completed prosthetic restoration, with an average follow-up of 21 months after loading, No implants were lost after loading, and all prostheses have remained stable, Conclusions: This method of reconstruction of the severely atrophic maxilla achieves an implant survival rate of 82% while correcting the unfavorable maxillomandibular relationship commonly seen in these patients. C1 BRIGHAM & WOMENS HOSP,DEPT DENT ORAL & MAXILLOFACIAL SURG,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA. RP Li, KK (reprint author), MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL HEAD & NECK SURG,HARVARD SCH DENT MED,BOSTON,MA 02114, USA. NR 22 TC 44 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 1996 VL 54 IS 5 BP 542 EP 546 DI 10.1016/S0278-2391(96)90626-6 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UJ199 UT WOS:A1996UJ19900002 PM 8632236 ER PT J AU Ohlendorf, C Tomford, WW Mankin, HJ AF Ohlendorf, C Tomford, WW Mankin, HJ TI Chondrocyte survival in cryopreserved osteochondral articular cartilage SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID MICROSCOPY AB Fluorescent staining techniques were used in combination with confocal and conventional fluorescent microscopy to determine the location of viable chondrocytes in frozen and thawed osteochondral articular cartilage. The results showed that cell survival was confined to the superficial layer of the cartilage matrix. The addition of a cryopreservative agent (dimethyl sulfoxide) increased chondrocyte survival but only in the same layer. There was no evidence of cell survival in the middle or deep layers of the cartilage with or without the use of dimethyl sulfoxide. Under the conditions employed in this study, chondrocyte survival in a cryopreserved osteochondral allograft appears to be limited to the superficial layer of the articular cartilage. C1 MASSACHUSETTS GEN HOSP,ORTHOPAED RES LABS,BOSTON,MA 02114. FU NIAMS NIH HHS [AR-21896] NR 7 TC 113 Z9 119 U1 1 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 1996 VL 14 IS 3 BP 413 EP 416 DI 10.1002/jor.1100140311 PG 4 WC Orthopedics SC Orthopedics GA UT655 UT WOS:A1996UT65500010 PM 8676254 ER PT J AU Thielen, RJ Fangon, NB Frazer, A AF Thielen, RJ Fangon, NB Frazer, A TI 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-iodobenzamido]ethyl]pipe razine and 4-(2'-methoxyphenyl)-1-[2'-[N-(2''-pyridinyl)-p-fluorobenzamido]ethyl]pi perazine, two new antagonists at pre- and postsynaptic serotonin-1A receptors SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DORSAL RAPHE NUCLEUS; 5-HT1A RECEPTOR; RAT-BRAIN; 5-HT(1A) RECEPTORS; IN-VIVO; PHARMACOLOGICAL CHARACTERIZATION; DIFFERENTIAL PROJECTIONS; HIPPOCAMPAL MEMBRANES; SELECTIVE ANTAGONIST; MOLECULAR-CLONING AB p-MPPI [4-(2'-methoxyphenyl)-1-[2'-[N-(2 ''-pyridinyl)-p-iodobenzamido]ethyl]piperazine] and p-MPPF [4-(2'-methoxyphenyl)-1-[2'-[N-(2 ''-pyridinyl)-p-fluorobenzamido]ethyl]piperazine] competitively antagonized 5-HT1A receptor activation in the rat, as measured by hypothermia, forepaw treading and 5-HT turnover; they exhibited no partial agonist activity on any of these measures. When given i.p., p-MPPI and p-MPPF dose-dependently antagonized the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) (0.5 mg/kg), with approximate ID50 of 5 and 3 mg/kg, respectively. The inhibitory effect caused by a fixed dose of pMPPI (6 mg/kg) or p-MPPF (3 mg/kg) was surmounted by higher doses of 8-OH-DPAT. pMPPI and p-MPPF also attenuated the hypothermia induced by gepirone. Forepaw treading caused by 8-OH-DPAT (2 mg/kg) in reserpine-pretreated rats (1 mg/kg, s.c., 18-24 hr before the experiment) was dose-dependently antagonized by p-MPPI and p-MPPF with approximate ID50 of 3 and 0.7 mg/kg, respectively. p-MPPI also antagonized forepaw treading induced by 5-methoxy-N,N,-dimethyltryptamine (5-MeODMT) (5 mg/kg) and this antagonism was competitively overcome by higher doses of 5-methoxy-N,N,-dimethyltryptamine. p-MPPI and p-MPPF were able to antagonize the 8-OH-DPAT-(0.5 mg/kg) induced reduction in the 5-HIAA/5-HT ratio, a measure of 5-HT turnover in the hippocampus or striatum. No hypothermia or reciprocal forepaw treading was produced by either drug when given at doses as high as 10 mg/kg. Neither p-MPPI nor p-MPPF (10 mg/kg) given alone significantly altered the ratio of 5-HIAA/5-HT in the hippocampus or striatum. Also, binding of [H-3]p-MPPF to hippocampal membranes was unaltered by the addition of 100 mu M guanylyl-imidodiphosphate to the incubation medium. In conclusion, pMPPI and p-MPPF behave, in vivo, as competitive antagonists of both postsynaptic 5-HT1A receptors and somatodendritic 5-HT1A autoreceptors. C1 AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO,TX 78284. RP Thielen, RJ (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT PHARMACOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NIMH NIH HHS [MH48125, MH29094] NR 67 TC 44 Z9 44 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1996 VL 277 IS 2 BP 661 EP 670 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UJ953 UT WOS:A1996UJ95300013 PM 8627543 ER PT J AU Stiel, H Teuchner, K Paul, A Leupold, D Kochevar, IE AF Stiel, H Teuchner, K Paul, A Leupold, D Kochevar, IE TI Quantitative comparison of excited state properties and intensity-dependent photosensitization by rose bengal SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE photosensitization; excited states; non-linear absorption ID LASER FLASH-PHOTOLYSIS; CELL ACETYLCHOLINESTERASE; QUANTUM YIELD; PHOTOCHEMISTRY; EXCITATION; MOLECULES; LIFETIME AB A quantitative (multistep) excitation-deactivation model of rose bengal (RE) has been developed which includes energy and electron transfer to oxygen and the possibility of photoproduct formation via higher excited triplet-singlet states. The model is based on previous measurements of non-linear absorption (NLA) and emission of RE with piccosecond pulses at 532 nm and on NLA measurements with nanosecond pulses. A coupled rate equation and photon transport equation approach for non-linear light-matter interaction is used. The resulting term scheme with all relevant excited state parameters confirms that (i) in the first excited state of RE, relevant absorption at 532 nm takes place only in the triplet, and (ii) the previously reported intensity dependence of RE-sensitized enzyme inhibition is well modelled by the intensity-dependent RB-T-1 population and (as the main process) subsequent energy transfer to form singlet oxygen. C1 MASSACHUSETTS GEN HOSP, WELLMAN LABS PHOTOMED, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RP Stiel, H (reprint author), MAX BORN INST NICHTLINEARE OPT & KURZZEITSPEKTROS, POSTFACH 1107, D-12474 BERLIN, GERMANY. OI Paul, Andrea/0000-0003-2849-4754 FU NIGMS NIH HHS [GM 30 155] NR 24 TC 21 Z9 21 U1 1 U2 10 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 MAY PY 1996 VL 33 IS 3 BP 245 EP 254 DI 10.1016/1011-1344(95)07248-9 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UU693 UT WOS:A1996UU69300009 PM 8683400 ER PT J AU Almendral, D Waller, SG Talamo, JH AF Almendral, D Waller, SG Talamo, JH TI Assessment of ablation zone centration after photorefractive keratectomy using a vector center of mass formula SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID CORNEAL TOPOGRAPHY; SURGERY; MYOPIA; PUPIL AB BACKGROUND: Adequate centration of keratorefractive surgical procedures is essential for a successful outcome, An accurate technique to mathematically describe the centration and topography of the ablation zone after photorefractive keratectomy (PRK) would be valuable in assessing the effects of these variables on subsequent visual results, METHODS: A vector center of mass formula and computerized videokeratography were used to study the postoperative treatment zone centration and topography of 17 consecutive highly myopic patients (-6.00 to 12.00 diopters [D]). Each had undergone PRK using either a single 6.0 mm (n=11) or three-stepped ablation zone (n=6), with good visual results, RESULTS: Calculations disclosed mean ablation zone decentration relative to the pupil center for all patients to be 0.20 +/- 0.16 mm using the vector center of mass formula, Areas of uniform central corneal dioptric power (mean diameter 3.4 +/- 0.8 mm) and surrounding transition zones of declining dioptric power (mean slope 1.61 +/- 0.44 D/mm) were also determined, CONCLUSION: A new vector center of dioptric power distribution that analyzes centration and transition zone topography offers a rigorous but straightforward means to assess the effects of refractive corneal surgery procedures on central corneal topography. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,CORNEA SERV,BOSTON,MA 02114. NR 14 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 J9 J REFRACT SURG JI J. Refractive Surg. PD MAY-JUN PY 1996 VL 12 IS 4 BP 483 EP 491 PG 9 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA UP190 UT WOS:A1996UP19000012 PM 8771544 ER PT J AU Toth, TL Awwad, JT Veeck, LL Jones, HW Muasher, SJ AF Toth, TL Awwad, JT Veeck, LL Jones, HW Muasher, SJ TI Suppression and flare regimens of gonadotropin-releasing hormone agonist - Use in women with different basal gonadotropin values in an in vitro fertilization program SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE gonadotropins; fertilization in vitro ID FOLLICLE-STIMULATING-HORMONE; INVITRO FERTILIZATION; OVARIAN STIMULATION; LONG PROTOCOL; CYCLE DAY-3; INDUCTION; OVULATION; COMBINATION; PITUITARY AB OBJECTIVE: To evaluate the suppression and flare regimens of gonadotropin-releasing hormone agonist (GnRH-a) in ovarian hyperstimulation in women with variable basal gonadotropin values in an in vitro fertilization (IVF) program. STUDY DESIGN: A retrospective study comparing the initiation of GnRH-a in the midluteal phase of the preceding cycle (suppression protocol) and follicular phase of the stimulated cycle (flare protocol) in women with basal follicle-stimulating hormone (FSH) vales < 15 mIU/mL and greater than or equal to 15 mIU/mL. RESULTS: The pregnancy rate per initiated cycle and implantation rate for women with basal FSH levels greater than or equal to 15 mIU/mL were 20.4% and 9.8% in flare GnRH-a cycles and 11.7% and 3.5%, respectively, in suppression GnRH-a cycles. Comparing the percent differences in clinical pregnancy and implantation rates between both protocols for women with different basal FSH values, pregnancy outcome was significantly greater in the flare protocol in women with values greater than or equal to 15 mIU/mL (P < .001). Individualization of the stimulation protocol by retrospective sorting of women undergoing IVF with respect to their basal gonadotropin levels significantly improved clinical pregnancy (P < .05) and implantation rates (P < .05) and reduced the cancellation rate (P < .05). CONCLUSION: The flare regimen with GnRH-a is a useful alternative for controlled ovarian hyperstimulation in women with elevated basal FSH values (greater than or equal to 15 mIU/mL) undergoing IVF. C1 EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT OBSTET & GYNECOL,NORFOLK,VA. RP Toth, TL (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,VINCENT MEM OBSTET & GYNECOL SERV,BOSTON,MA 02114, USA. NR 25 TC 29 Z9 31 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA P.O. DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAY PY 1996 VL 41 IS 5 BP 321 EP 326 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UP065 UT WOS:A1996UP06500006 PM 8725756 ER PT J AU Park, J Gowin, KM Schumacher, HR AF Park, J Gowin, KM Schumacher, HR TI Steroid sparing effect of methotrexate in relapsing polychondritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE steroid sparing; methotrexate; relapsing polychondritis ID ANTI-CD4 MONOCLONAL-ANTIBODY; CYCLOSPORINE-A; INVOLVEMENT AB Relapsing polychondritis is a rare inflammatory disorder causing recurrent inflammatory reactions in the cartilaginous structures. It often worsens as prednisone is tapered. We describe 3 biopsy proven patients with relapsing polychondritis in whom methotrexate was useful as a steroid sparing agent in the management of auricular chondritis. C1 VET AFFAIRS MED CTR,ARTHRIT IMMUNOL CTR,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NR 12 TC 22 Z9 24 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 1996 VL 23 IS 5 BP 937 EP 938 PG 2 WC Rheumatology SC Rheumatology GA UJ948 UT WOS:A1996UJ94800027 PM 8724312 ER PT J AU Hubert, JF Panish, PT Chure, DJ Prostak, KS AF Hubert, JF Panish, PT Chure, DJ Prostak, KS TI Chemistry, microstructure, petrology, and diagenetic model of Jurassic dinosaur bones, Dinosaur National Monument, Utah SO JOURNAL OF SEDIMENTARY RESEARCH LA English DT Article ID POROSITY; CRYSTALLIZATION; PERMEABILITY; EVOLUTION; COLLAGEN; ORIGIN; SAND AB The fossil-bone mineral in dinosaurs from the Morrison Formation is well-crystallized, stoichiometric francolite, The closely packed, subparallel francolite crystals have equidimensional cross sections mostly 10-40 nm wide. In contrast, crystallites in unaltered mammal bone tissue are poorly crystallized, nonstoichiometric carbonate hydroxyapatite, a few nanometers thick, and plate-, rod or needle-shaped. The diagenetic francolite crystals are elongated in the c axis direction, as are bone-tissue crystallites. Along permeable cracks, francolite crystals grew to 250 nm wide. Compared to unaltered crystallites in mammal bones, the francolite has higher concentrations of Ba, Ce, Cr, F, La, Mn, Ni, Pb, Rb, Sr, Th, U, V, and Y, and perhaps Zr. Na and Mg are lower in concentration. Diagenetic francolite grew from groundwater enriched in ions from silicic ashes in the Brushy Basin Member and from dissolution of bone-tissue crystallites. After burial, francolite grew on crystallite seeds, filling the space formerly occupied by collagen, perhaps half the tissue volume, and dissolved crystallites. The micron-scale structures such as Haversian canals and laminae are preserved because the diagenetic francolite retains the orientations of the seeds. The laminae, 1-10 mu m thick, commonly preserve an orthogonal plywood structure. The diagenetic growth of francolite during this type of bone fossilization implies that oxygen isotopic ratios measured in dinosaur bones, even those that appear fresh and unaltered, may dominantly reflect groundwater temperature rather than dinosaur body temperature. Trace element concentrations in the francolite may reflect groundwater composition rather than dinosaur diet. Pore-filling cements precipitated in the sands and bones at shallow burial depths, as evidenced by the 35-52% minus cement porosities of the sandstones and numerous uncompacted oversize pores filled by cements. Gypsum and calcite were precipitated from shallow alkaline groundwater. As the groundwater became increasingly dominated by ions from silicic ash, argentite, chalcopyrite, native gold, native silver, tiemannite, and uraninite replaced areas of bone a few microns to tens of microns in size along cracks. A thin chlorite crust commonly mantled francolite crystals along bone cracks and lined openings in bones and sandstones. Pervasive precipitation of a chalcedony crust followed, with pseudomorphs of chalcedony after gypsum. In larger cancellous openings, the remaining space was filled by the various forms of silica. The bones are brown due to goethite filled cracks that cut pore-filling minerals. C1 DINOSAUR NATL MONUMENT,JENSEN,UT 84035. FORSYTH DENT CTR,BOSTON,MA 02115. RP Hubert, JF (reprint author), UNIV MASSACHUSETTS,DEPT GEOSCI,AMHERST,MA 01003, USA. NR 55 TC 79 Z9 82 U1 2 U2 9 PU SEPM-SOC SEDIMENTARY GEOLOGY PI TULSA PA 1731 E 71ST STREET, TULSA, OK 74136-5108 SN 1073-130X J9 J SEDIMENT RES JI J. Sediment. Res. PD MAY PY 1996 VL 66 IS 3 BP 531 EP 547 PN A PG 17 WC Geology SC Geology GA UL269 UT WOS:A1996UL26900013 ER PT J AU Ravicz, ME Rosowski, JJ Voigt, HF AF Ravicz, ME Rosowski, JJ Voigt, HF TI Sound-power collection by the auditory periphery of the mongolian gerbil Meriones unguiculatus .2. External-ear radiation impedance and power collection SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MIDDLE-EAR; INPUT IMPEDANCE; TRANSFORMATION; LOCALIZATION; SENSITIVITY; EARDRUM; MODELS; PINNA; FIELD; CAT AB Acoustic power flow into the external and middle ear of gerbil is computed from acoustic measurements and models of the external ear and used to predict the behavioral auditory threshold. The external-ear radiation impedance from the tympanic ring Z(E) measured in six gerbil ears with a calibrated acoustic source at frequencies from 10 Hz to 18 kHz is mass dominated below about 8 kHz, with a mean mass of 2720 kg/m(4). Z(E) shows resonant behavior near 8 and 14 kHz. The frequency dependence of Z(E) is Similar to that measured in cat, chinchilla, and models of the human external ear, but the mass and the resonant frequencies are higher. The power utilization ratio (PUR) computed from Z(E) and measurements of the middle-ear input impedance Z(T) presented previously [Ravicz et al., J. Acoust. Soc. Am. 92, 157-177 (1992)] suggests that appreciable power is transmitted to the middle ear only above 1.5 kHz. Mathematical external-ear models, consisting of tube segments and conical hems that include Viscous and thermal losses, were developed from anatomical dimensions to match Z(E) over the entire frequency range of measurement. The radiation efficiency eta(R), computed from the models is near unity only above 12 kHz and falls to 10(-5) as frequency decreases to 10 Hz. Predictions of the mean pressure gain from an external diffuse sound field to the tympanic membrane resemble measurements in another gerbilline species. The effective area of the ear in a diffuse sound field at the tympanic membrane EA(TM)(DF) computed from PUR and eta(R) approaches the anatomical area of the pinna opening, 71 mm(2), above 1.5 kHz and the geometric limit of lambda(z)/4 pi determined by the wavelength lambda above 12 kHz but decreases sharply below 1.5 kHz to 0.002 mm(2) at 10 Hz. The diffuse-field sound pressure required to deliver 5X10(-17) W to the middle ear between 10 Hz and 18 kHz resembles the behavioral auditory threshold [Ryan, J. Acoust. Soc. Am. 54, 1222-1226 (1976)]. This result supports the idea that the cochlea acts as a power detector at the auditory threshold. (C) 1996 Acoustical Society of America. C1 BOSTON UNIV,DEPT BIOMED ENGN,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT OTOL & LARYNGOL,BOSTON,MA 02115. MIT,ELECTR RES LAB,CAMBRIDGE,MA 02139. BOSTON UNIV,DEPT OTOLARYNGOL,BOSTON,MA 02215. RP Ravicz, ME (reprint author), MASSACHUSETTS EYE & EAR INFIRM,EATON PEABODY LAB AUDITORY PHYSIOL,243 CHARLES ST,BOSTON,MA 02114, USA. RI Voigt, Herbert/I-2068-2015 OI Voigt, Herbert/0000-0002-0476-6594 FU NIDCD NIH HHS [R01 DC00194, DC00310, DC01099, R01 DC000194] NR 57 TC 20 Z9 20 U1 0 U2 3 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 1996 VL 99 IS 5 BP 3044 EP 3063 DI 10.1121/1.414793 PG 20 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA UK253 UT WOS:A1996UK25300044 PM 8642116 ER PT J AU Greene, RW Biederman, J Faraone, SV Ouellette, CA Penn, C Griffin, SM AF Greene, RW Biederman, J Faraone, SV Ouellette, CA Penn, C Griffin, SM TI Toward a new psychometric definition of social disability in children with attention-deficit hyperactivity disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; social disability; psychiatric comorbidity ID ADJUSTMENT INVENTORY; SOCIOMETRIC STATUS; ADHD CHILDREN; COMORBIDITY; ADOLESCENTS; MECHANISMS; INTERVIEW; VALIDITY; PATTERNS; CONDUCT AB Objective: To investigate a new mechanism for identifying social disability in children with attention-deficit hyperactivity disorder (ADHD), employing psychometric methodology used in defining learning disabilities. Method: Two groups of index children were examined: 140 children with ADHD (referred from both psychiatric and pediatric sources) and 120 non-ADHD comparison children. Subjects were defined as socially disabled if they had a value greater than 1.65 on a standardized discrepancy score between observed and expected scores on a measure of social functioning (with expected scores derived as a function of the child's estimated Full Scale IQ). Children identified as socially disabled were compared with non-socially disabled probands on psychopathology, familiality, cognitive functioning, school history, and treatment history. Results: Using this psychometric approach, 22% of the ADHD probands qualified as socially disabled, whereas none of the comparison probands qualified (p less than or equal to .001). Socially disabled ADHD probands were significantly more impaired than were non-socially disabled ADHD probands in global and specific measures of social functioning and patterns of psychiatric comorbidity. Conclusions: The psychometrically defined construct of social disability may identify children with ADHD who are at very high risk for severe social dysfunction and whose course and prognosis may vary from those of other children with ADHD. This subgroup of children with ADHD may be at heightened risk for poor outcome, and their identification may facilitate the development of clinical interventions aimed at ameliorating their specific difficulties. C1 MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,JOINT PROGRAM PEDIAT PSYCHOPHARMACOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. BROCKTON VA MED CTR,PSYCHIAT SERV,BROCKTON,MA. RP Greene, RW (reprint author), MASSACHUSETTS GEN HOSP,CHILD PSYCHIAT SERV,PEDIAT PSYCHOPHARMACOL UNIT,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 42 TC 97 Z9 99 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1996 VL 35 IS 5 BP 571 EP 578 DI 10.1097/00004583-199605000-00011 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UG542 UT WOS:A1996UG54200011 PM 8935203 ER PT J AU Faraone, SV AF Faraone, SV TI Genetic influence on parent-reported attention-related problems in a Norwegian general population twin sample - Discussion SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material ID DEFICIT DISORDER; HYPERACTIVITY C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,MASSACHUSETTS MENTAL HLTH CTR,CAMBRIDGE,MA 02138. HARVARD UNIV,INST PSYCHIAT EPIDEMIOL & GENET,BOSTON,MA 02115. RP Faraone, SV (reprint author), MASSACHUSETTS GEN HOSP,PEDIAT PSYCHOPHARMACOL UNIT,PSYCHIAT SERV,ACC 725,15 PARKMAN ST,BOSTON,MA 02114, USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1996 VL 35 IS 5 BP 596 EP 598 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UG542 UT WOS:A1996UG54200014 ER PT J AU Prince, JB Wilens, TE Biederman, J Spencer, TJ Wozniak, JR AF Prince, JB Wilens, TE Biederman, J Spencer, TJ Wozniak, JR TI Clonidine for sleep disturbances associated with attention-deficit hyperactivity disorder: A systematic chart review of 62 cases SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit hyperactivity disorder; clonidine; sleep disturbances; children; adolescents ID PLACEBO-CONTROLLED EVALUATION; CHILDREN; METHYLPHENIDATE; ADD; ADOLESCENTS; PATTERNS; SYMPTOMS AB Objective: Children and adolescents with attention-deficit hyperactivity disorder (ADHD), with or without psychostimulant treatment, frequently suffer from sleep disturbances. This report evaluates the use of clonidine in the treatment of sleep disturbances associated with ADHD. Method: A systematic search of a computerized database in an outpatient pediatric psychopharmacology unit of patients treated with clonidine for ADHD-associated sleep disturbances (N = 62; 42 children and 20 adolescents) was performed. Patients were rated retrospectively about the type and severity of sleep disturbances at baseline and after treatment with clonidine. Results: A majority of patients (85%) treated with clonidine for ADHD-associated sleep disturbances were considered to be much to very much improved by the National Institute of Mental Health global assessment of improvement (sleep). Nighttime clonidine doses ranged from 50 to 800 mu g (mean +/- SEM; 157 +/- 14 mu g), and subjects received clonidine for 35.5 +/- 3.5 months. There was no association between response and age group, gender, comorbidity, or concurrent pharmacotherapy. Children and adolescents with ADHD with baseline, medicine-induced, or medicine-exacerbated sleep disturbances responded equally well to clonidine treatment. Mild adverse effects were reported in 19 subjects (31%). Conclusions: These findings suggest that clonidine may be an effective agent for sleep disturbances associated with ADHD, or its treatment, and warrant further controlled investigations. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 40 TC 93 Z9 94 U1 1 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAY PY 1996 VL 35 IS 5 BP 599 EP 605 DI 10.1097/00004583-199605000-00014 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UG542 UT WOS:A1996UG54200015 PM 8935206 ER PT J AU Lee, PK Dover, JS AF Lee, PK Dover, JS TI Recurrent exacerbation of acne by granulocyte colony-stimulating factor administration SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,DIV DERMATOL,BOSTON,MA 02215. RP Lee, PK (reprint author), MASSACHUSETTS GEN HOSP,DEPT DERMATOL,ACC 489,32 FRANCIS ST,BOSTON,MA 02114, USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1996 VL 34 IS 5 BP 855 EP 856 DI 10.1016/S0190-9622(96)90045-6 PN 1 PG 2 WC Dermatology SC Dermatology GA UJ212 UT WOS:A1996UJ21200024 PM 8632088 ER PT J AU Buhac, J Bhol, K Padilla, T Foster, CS Ahmed, AR AF Buhac, J Bhol, K Padilla, T Foster, CS Ahmed, AR TI Coexistence of pemphigus vulgaris and ocular cicatricial pemphigoid SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CELL AB We describe the case of a patient with both pemphigus vulgaris limited to the oral cavity and ocular cicatricial pemphigoid. The diagnoses were established by means of histopathologic examination and direct and indirect immunofluorescence studies and confirmed by immunoblot analysis of serum, Treatment with dapsone resulted in a prolonged remission of the ocular cicatricial pemphigoid. The pemphigus vulgaris has remained localized to the oral cavity and has responded to sublesional corticosteroid injections. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,UVEITIS & IMMUNOL SERV,BOSTON,MA. BOSTON UNIV,SCH MED,DEPT DERMATOL,BOSTON,MA 02118. FU NEI NIH HHS [EY 08739]; NIDCR NIH HHS [DE 09978] NR 13 TC 15 Z9 15 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1996 VL 34 IS 5 BP 884 EP 886 DI 10.1016/S0190-9622(96)90071-7 PN 2 PG 3 WC Dermatology SC Dermatology GA UJ757 UT WOS:A1996UJ75700004 PM 8621820 ER PT J AU Otley, CC Momtaz, K AF Otley, CC Momtaz, K TI Induction of Darier-White disease with UVB radiation in a clinically photo-insensitive patient SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Combination UVA/UVB radiation and UVB radiation alone have been shown to induce the lesions of Darier-White disease. However, 6% of patients with Darier-White disease claim that sunlight ameliorates their condition. We performed an unblinded, side-by-side controlled trial of UVB, UVA, and combination UVB/UVA phototherapy in a patient with historically photoameliorated Darier-White disease to determine whether phototherapy was beneficial, to determine whether phototherapy-related heat was detrimental, and to confirm, with appropriate controls, the action spectrum of the disease. Phototherapy with radiation in the UVB but not UVA spectrum evoked Darier-White disease in this patient, both clinically and histologically. UVB radiation was capable of inducing Darier-White disease in vivo in spite of a history of photoamelioration, whereas UVA radiation alone and the heat associated with phototherapy in our protocol had no effect on the disease. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,BOSTON,MA. NR 10 TC 6 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 1996 VL 34 IS 5 BP 931 EP 934 DI 10.1016/S0190-9622(96)90083-3 PN 2 PG 4 WC Dermatology SC Dermatology GA UJ757 UT WOS:A1996UJ75700016 PM 8621832 ER PT J AU Gaissert, HA Mathisen, DJ Moncure, AC Hilgenberg, AD Grillo, HC Wain, JC AF Gaissert, HA Mathisen, DJ Moncure, AC Hilgenberg, AD Grillo, HC Wain, JC TI Survival and function after sleeve lobectomy for lung cancer SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID BRONCHOGENIC-CARCINOMA AB Between 1962 and 1991, 72 patients (mean age 63.4 years) underwent sleeve lobectomy for primary lung cancer, Thirty-seven patients had adequate lung function and 35 were deemed unsuitable for pneumonectomy on the basis of inadequate pulmonary reserve (n = 31) or cardiac risk factors (n = 4), Squamous cell carcinomas (68%) and adenocarcinomas (26%) predominated. Upper lobectomy was performed in 48 patients, lower and middle lobectomy in 13, and right upper and middle bilobectomy in 11, Hospital mortality was 4% (3/72) and compares with a hospital mortality of 9% in 56 consecutive pneumonectomies between 1986 and 1990, Major complications occurred in 11% (bronchopleural fistula 1, persistent atelectasis 4, pneumonia 4), Adjusted actuarial survival after sleeve lobectomy at 1 and 5 years was 84% and 42%, compared with 76% and 44% after pneumonectomy, Five-year survival after lower and middle lobectomy in 13 patients (52%) was similar to that after upper lobectomy (46%), suggesting that in carefully selected patients the concept of sleeve lobectomy can be applied to all pulmonary lobes, N1 disease and compromised lung function were associated with lower survival (N1 38% vs N0 57%; compromised 20% vs adequate 55%), Comparison of preoperative and postoperative lung function and quantitative ventilation-perfusion isotope studies substantiated the preservation of pulmonary function in this group of patients. Sleeve lobectomy is the procedure of choice for anatomically suitable carcinomas or when reduced pulmonary reserve precludes extensive resection. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,GEN THORAC SURG UNIT,BOSTON,MA 02114. NR 13 TC 73 Z9 78 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 1996 VL 111 IS 5 BP 948 EP 953 DI 10.1016/S0022-5223(96)70369-0 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UK884 UT WOS:A1996UK88400009 PM 8622318 ER PT J AU Fischer, CP Bode, BP Souba, WW AF Fischer, CP Bode, BP Souba, WW TI Starvation and endotoxin act independently and synergistically to coordinate hepatic glutamine transport SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Association-for-the-Surgery-of-Trauma / 13th Annual Meeting of the Trauma-Association-of-Canada CY SEP 27-30, 1995 CL HALIFAX, CANADA SP Amer Assoc Surg Trauma, Trauma Assoc Canada ID AMINO-ACID-TRANSPORT; RAT-LIVER; METABOLISM; HEPATOCYTES; ARGININE; SYSTEM; IMMUNE AB Objective: Because hepatic glutamine transport is markedly enhanced during critical illness, we tested the hypothesis that nutrient starvation and endotoxemia act coordinately to augment transport activity, Design: Fed or starved (48 hours) rats received Escherichia coli endotoxin (LPS, 10 mg/kg of body weight, intraperitoneally) or saline before hepatocyte isolation for measurement of glutamine transport, Materials and Methods: Hepatocytes were isolated from fed or fasted rats 4 hours after LPS treatment, [H-3]glutamine uptake was measured and normalized to cellular protein, Data (mean +/- standard deviation, three separate determinations) were analyzed by Student's t test and analysis of variance. Main Results: Starvation induced a 1.6-fold increase in glutamine transport, while LPS treatment of fed rats increased transport activity 2.6-fold, Treatment of fasted animals with LPS induced a sixfold increase in glutamine transport, Kinetically, this effect in endotoxemic starved rats was mediated by both an increase in System N V-max and the induction of a high affinity System A amino acid carrier which transports glutamine, Conclusions: Starvation and endotoxemia regulate hepatocyte glutamine transport independently and synergistically, This hepatic response provides glutamine and other amino acids to support key metabolic pathways in the liver during critical illness. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG, DIV SURG ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG, NUTR SUPPORT UNIT, BOSTON, MA 02114 USA. FU NIDDK NIH HHS [1 P30 DK40561-02] NR 30 TC 21 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-5282 EI 1529-8809 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAY PY 1996 VL 40 IS 5 BP 688 EP 693 DI 10.1097/00005373-199605000-00002 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA UK405 UT WOS:A1996UK40500002 PM 8614065 ER PT J AU Whelan, NL Subramanian, R Jin, J Keith, IM AF Whelan, NL Subramanian, R Jin, J Keith, IM TI Intramyocardial arterial cushions of coronary vessels in animals and humans: Morphology, occurrence and relation to heart disease SO JOURNAL OF VASCULAR RESEARCH LA English DT Article DE coronary arteries; intimal cushions; smooth muscle; ultrastructure; heart disease ID ATHEROSCLEROSIS AB The existence of coronary endoarterial cushions (CEC) in the human heart as nonpathological, functional entities has been debated, and CEC have been sparsely reported in animals. Arterial cushions are localized thickenings that protrude into the lumen of specific arteries, We have identified CEC in the rhesus monkey, dog, sheep, goat, pig, rabbit and rat, and in the human heart, Two distinct types are described: the ovoid CEC arranged singly, in pairs, or in groups of three to four, and the less common polypoid CEC seen primarily in humans. The highest incidence of CEC in rabbits and humans was in the left ventricle in arteries 150-488 mu m in diameter. Light and electron microscopy demonstrated intimal location with smooth muscle cells surrounded by ground substance, collagen and elastin fibers in a highly organized pattern. Nerve fibers identified by their immunoreactivity with antiserum to the vasodilatory calcitonin-gene-related peptide contacted the CEC along the tunica media and were occasionally seen within CEC, Arrangement and histological composition of CEC suggest a role in the regulation of local blood now and myocardial perfusion. In human hearts, the CEC density index correlated highly with the degree of heart disease. In subjects with high heart disease rating, increased connective tissue, lipid-like infiltration and calcification was seen within CEC, and foam cells were present in CEC of obese rabbits. This suggests that CEC in coronary arteries could be predisposed sites of atherosclerosis, and that injured CEC can cause coronary artery spasm and ischemia. We conclude that CEC occur in animals and humans as innervated intimal smooth muscle cushions that might have a role in myocardial perfusion and heart disease. C1 UNIV WISCONSIN,SCH VET MED,DEPT COMPARAT BIOSCI,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT PATHOL,MADISON,WI. FU NCRR NIH HHS [2 507 RR05912-05] NR 53 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD MAY-JUN PY 1996 VL 33 IS 3 BP 209 EP 224 DI 10.1159/000159149 PG 16 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA UQ124 UT WOS:A1996UQ12400003 PM 8924519 ER PT J AU Wall, C Arakawa, GK AF Wall, C Arakawa, GK TI Model that relates canal-ocular to otolith-ocular responses SO JOURNAL OF VESTIBULAR RESEARCH-EQUILIBRIUM & ORIENTATION LA English DT Article DE vestibulo-ocular reflex; model; otoliths; central vestibular function; velocity storage integrator ID SQUIRREL-MONKEY; PHYSIOLOGY; ORGANS; FORCE AB Rotation about the vertical stimulates primarily the horizontal semicircular canals and produces compensatory horizontal nystagmus whose slow component velocity response during constant velocity can be approximated as having a simple exponential decay time constant, T-VOR. Constant velocity Saw rotation about a horizontal axis stimulates both the horizontal canals and the otolith organs, producing two additional nystagmus components thought to be of otolithic origin: a steady component called bias and a periodic component known as modulation, We tested a group of 7 human subjects using rotation about each of these axes. We found a strong, negative correlation (r = 0.956) between these individuals' dominant time constants, T-VOR, and the magnitude of their modulation components, Canal and otolith signals originate from different parts of the same endorgan and travel separately to the vestibular nucleus, The reflexive eye movements in response to these inputs are thought to be the result of additional processing by the central vestibular and ocular motor systems. Thus, the source of these strongly correlated otolith-ocular and canal-ocular reflex components could logically be due to common factors affecting peripheral transduction or to a subsequent common central processing step. Using anatomical measurements of human vestibular end organs, biophysical endorgan models, and models of central vestibular processes, we examined the alternatives to determine which was the most likely, Correlations were not found between T-VOR and the anatomical data or between the T-VOR and the biophysical model elements, However, modifications of the velocity storage integrator of Raphan to incorporate either a highpass filter (HPF) or a lowpass filter input for otolith modulation signals allowed for the desired strong negative correlation between T-VOR and modulation. We argue in favor of the HPF configuration because it better explains the tendency for the modulation component to increase in amplitude as the modulation frequency is increased, Ire the above mentioned representation of the central processing of vestibular afferent inputs, we conclude that the modulation component input to the vestibuloocular reflex is within the indirect pathway, but it is ''down stream'' from the velocity storage integrator. RP Wall, C (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02114, USA. FU NIDCD NIH HHS [DC 00290] NR 15 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0957-4271 J9 J VESTIBUL RES-EQUIL JI J. Vestib. Res.-Equilib. Orientat. PD MAY-JUN PY 1996 VL 6 IS 3 BP 159 EP 171 PG 13 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA UJ528 UT WOS:A1996UJ52800002 PM 8744524 ER PT J AU Stubdal, H Zalvide, J DeCaprio, JA AF Stubdal, H Zalvide, J DeCaprio, JA TI Simian virus 40 large T antigen alters the phosphorylation state of the RB-related proteins p130 and p107 SO JOURNAL OF VIROLOGY LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; SV40 LARGE-T; TRANSCRIPTION FACTOR E2F; ADENOVIRUS E1A PROTEINS; LARGE TUMOR-ANTIGEN; TRANSFORMATION-GOVERNING SEQUENCE; HUMAN CYCLIN-A; VIRAL ONCOPROTEINS; SEPARATE DOMAINS; PRODUCT AB p130 and p107 are nuclear phosphoproteins related to the retinoblastoma gene product (pRb). pRb, p107, and p130 each undergo cell cycle-dependent phosphorylation, form complexes with the E2F family of transcription factors, and associate with oncoproteins of DNA tumor viruses, including simian virus 40 (SV40) large T antigen (TAg) and adenovirus E1A protein. The results of recent studies with mouse embryo fibroblasts (MEFs) lacking the retinoblastoma gene (Rb-1) have suggested that p130 and p107 may be important targets for SV40 large TAg-mediated transformation (J. B. Christensen and M. J. Imperiale, J. Virol. 65:39453948, 1995; J. Zalvide and J. A. DeCaprio, Mel. Cell. Biol. 15:58005810, 1995). In this report, we demonstrate that the expression of TAg affects the phosphorylation state of p130 and p107. In cells expressing wild-type TAg, only un(der)phosphorylated p130 and p107 were detected. To determine the domains within TAg that contribute to this effect on the phosphorylation of p130, we performed transient expression assays. While transiently expressed p130 was apparently phosphorylated normally, only un(der)phosphorylated p130 was detected when p130 was coexpressed with TAg. Using this assay, we found that the first 147 amino acids of TAg were sufficient to alter the phosphorylation state of p130. Within this region, the LXCXE domain of TAg, required for binding to the retinoblastoma family of proteins, was necessary but not sufficient to affect p130 phosphorylation. Residues within the first 82 amino acids of TAg were also required. TAg with mutations in the N terminus retained the ability to efficiently associate with p130 but did not affect its phosphorylation state. This demonstrates that the effect of SV40 TAg on p130 is not simply the result of binding and suggests that TAg has a novel effect on p130 and p107 that differs from its effect on pRb. C1 DANA FARBER CANC INST,DIV NEOPLAST DIS MECH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 72 TC 85 Z9 86 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 2781 EP 2788 PG 8 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700013 PM 8627752 ER PT J AU OBrien, WA SumnerSmith, M Mao, SH Sadeghi, S Zhao, JQ Chen, IY AF OBrien, WA SumnerSmith, M Mao, SH Sadeghi, S Zhao, JQ Chen, IY TI Anti-human immunodeficiency virus type 1 activity of an oligocationic compound mediated via gp120 V3 interactions SO JOURNAL OF VIROLOGY LA English DT Article ID SYNCYTIUM-INDUCING PHENOTYPE; RECOMBINANT SOLUBLE CD4; LONG TERMINAL REPEAT; ENVELOPE GLYCOPROTEIN; SULFATED POLYSACCHARIDES; DEXTRAN SULFATE; TRANS-ACTIVATION; GENE-EXPRESSION; BINDING-SITE; CELL TROPISM AB An oligocationic peptide compound (ALX40-4C) was developed for consideration in the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This compound was designed to mimic the basic domain of the HIV-1 transactivation protein, Tat, and will competitively,inhibit Tat binding to its specific RNA hairpin target (TAR [transactivation region]), found at the 5' end of all HIV-1 transcripts. Blocking Tat-TAR interactions can abrogate HIV-1 replication. ALX40-4C was shown to inhibit replication of HIV-1(NL4-3) in a range of cell types, including primary cells and transformed cell lines, by as much as 10(4)-fold. In some experiments, virus rescue was not possible even after removal of ALX40-4C from the cultures. Strain-dependent resistance has been demonstrated for all antiretroviral agents tested; therefore, we tested for variable sensitivity to ALX40-4C. The cloned primary strains, HIV-1(JR-CSF) and HIV-1(JR-FL,) ALX40-4C inhibition. Unexpectedly, determinants for efficient ALX40-4C inhibition were mapped by using recombinant virus strains to the V3 region of gp120 and were shown to act at early events in viral replication, which include viral entry. If entry and reverse transcription are bypassed by transfection, a more modest, virus strain-independent inhibition is shown; this inhibition is likely due to blocking of Tat-TAR interaction.'Thus, the highly basic oligocationic Tat inhibitor ALX40-4C appears to interfere with initial virus-target cell interactions which involve HIV-1 gp120 V3 determinants, most efficiently for T-cell line-adapted strains. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. ALLELIX BIOPHARMACEUT INC,MISSISSAUGA,ON,CANADA. RP OBrien, WA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DEPT MED,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NIAID NIH HHS [AI 29894] NR 67 TC 73 Z9 73 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 2825 EP 2831 PG 7 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700017 PM 8627756 ER PT J AU Lu, YC Brosio, P Lafaile, M Li, J Collman, RG Sodroski, J Miller, CJ AF Lu, YC Brosio, P Lafaile, M Li, J Collman, RG Sodroski, J Miller, CJ TI Vaginal transmission of chimeric simian human immunodeficiency viruses in rhesus macaques SO JOURNAL OF VIROLOGY LA English DT Article ID LANGERHANS CELLS; LYMPHOCYTE SUBSETS; INFECTION; MONKEYS; HIV-1; MACROPHAGES; CERVIX; SIV; DNA AB Chimeric simian/human immunodeficiency viruses (SHIVs) that express the env genes derived from distinct HIV type 1 (HIV-1) isolates were tested for the ability to infect rhesus macaques following intravaginal inoculation. SHIVs containing either the HIV-1 HXBc2 or the HIV-1 89.6 envelope glycoproteins were capable of replicating in intravenously inoculated rhesus macaques. However, intravaginal inoculation of animals with these two SHIVs resulted in infection only with the SHIV containing the HIV-1 89.6 glycoprotein. Thus, properties conferred by the envelope glycoproteins in the chimeric virus affect the ability of particular SHIVs to initiate a systemic infection following vaginal inoculation. These results provide indirect support for the hypothesis that the selection of specific viral variants occurs in the genital tracts of individuals exposed to HIV by sexual contact. C1 UNIV CALIF DAVIS,CALIF REG PRIMATE RES CTR,VIROL & IMMUNOL UNIT,DAVIS,CA 95616. UNIV CALIF DAVIS,SCH VET MED,DEPT PATHOL MICROBIOL & IMMUNOL,DAVIS,CA 95616. INST VIRUS RES,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,HUMAN RETROVIRUS LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. UNIV PENN,SCH MED,DEPT MICROBIOL,PHILADELPHIA,PA 19104. FU NIAID NIH HHS [AI33832, AI35478, AI35545] NR 29 TC 69 Z9 71 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 3045 EP 3050 PG 6 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700043 PM 8627782 ER PT J AU Reimann, KA Li, JT Voss, G Lekutis, C TennerRacz, K Racz, P Lin, WY Montefiori, DC LeeParritz, DE Lu, YC Collman, RG Sodroski, J Letvin, NL AF Reimann, KA Li, JT Voss, G Lekutis, C TennerRacz, K Racz, P Lin, WY Montefiori, DC LeeParritz, DE Lu, YC Collman, RG Sodroski, J Letvin, NL TI An env gene derived from a primary human immunodeficiency virus type 1 isolate confers high in vivo replicative capacity to a chimeric simian human immunodeficiency virus in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; MOLECULAR CLONE; HTLV-III; INFECTION; HIV-1; NEUTRALIZATION; ANTIBODIES; COMPLEMENT; RETROVIRUS; MACAQUES AB To explore the roles played by specific human immunodeficiency virus type 1 (HIV-1) genes in determining the in vivo replicative capacity of AIDS viruses, we have examined the replication kinetics and virus-specific immune responses in rhesus monkeys following infection with two chimeric simian/human immunodeficiency viruses (SHIVs). These viruses were composed of simian immunodeficiency virus STVmac239 expressing HIV-1 env and the associated auxiliary HIV-1 genes tat, vpu, and rev. Virus replication was assessed during primary infection of rhesus monkeys by measuring plasma SIVmac p27 levels and by quantifying virus replication in lymph nodes using in situ hybridization. SHTV-HXBc2, which expresses the HIV-1 env of a T-cell-tropic, laboratory-adapted strain of HIV-1 (HXBc2), replicated well in rhesus monkey peripheral blood leukocytes (PBL) in vitro but replicated only to low levels when inoculated in rhesus monkeys. In contrast, SHTV-89.6 was constructed with the HIV-1 env gene of a T-cell- and macrophage-tropic clone of a patient isolate of HIV-1 (89.6). This virus replicated to a lower level in monkey PBL in vitro but replicated to a higher degree in monkeys during primary infection. Moreover, monkeys infected with SHTV-89.6 developed an inversion in the PBL CD4/CD8 ratio coincident with the clearance of primary viremia. The differences in the in vivo consequences of infection by these two SHIVs could not be explained by differences in the immune responses elicited by these viruses, since infected animals had comparable type-specific neutralizing antibody titers, proliferative responses to recombinant HTV-1 gp120, and virus-specific cytolytic effector T-cell responses. With the demonstration that a chimeric SHIV can replicate to high levels during primary infection in rhesus monkeys, this model can now be used to define genetic determinants of HIV-1 pathogenicity. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. BERNHARD NOCHT INST TROP MED,DEPT PATHOL,D-20359 HAMBURG,GERMANY. BERNHARD NOCHT INST TROP MED,KORBER LAB,D-20359 HAMBURG,GERMANY. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. HARVARD UNIV,SCH MED,NEW ENGLAND REG PRIMATE RES CTR,SOUTHBOROUGH,MA 01772. INST VIRUS RES,CAMBRIDGE,MA 02138. UNIV PENN,SCH MED,DIV PULM & CRIT CARE,PHILADELPHIA,PA 19104. RP Reimann, KA (reprint author), BETH ISRAEL HOSP,DIV VIRAL PATHOGENESIS,RE 113,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NCI NIH HHS [CA-50139]; NIAID NIH HHS [AI-20729, AI-33832] NR 40 TC 222 Z9 225 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1996 VL 70 IS 5 BP 3198 EP 3206 PG 9 WC Virology SC Virology GA UF247 UT WOS:A1996UF24700061 PM 8627800 ER PT J AU Davis, KM Fish, LC Minaker, KL Elahi, D AF Davis, KM Fish, LC Minaker, KL Elahi, D TI Atrial natriuretic peptide levels in the elderly: Differentiating normal aging changes from disease SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID CONGESTIVE-HEART-FAILURE; VENTRICULAR EJECTION FRACTION; SUPRAVENTRICULAR TACHYCARDIA; PLASMA-CONCENTRATIONS; BLOOD-PRESSURE; POLYPEPTIDE; AGE; RELIABILITY; HORMONE; INDEX AB Background. Atrial natriuretic peptide (ANP) levels increase with advancing age and in patients with cardiac dysfunction. Previous studies have failed to differentiate the elevated ANP levels of normal aging from those of cardiac disease. Methods. To differentiate the increased ANP levels seen in normal aging from that of disease, tasting supine ANP was measured in healthy young (n=24), healthy old (n=90), and clinically stable bu cardiovascularly diseased old (n=269) residents of a life care facility. ANP levels were correlated with physical exam findings, blood chemistries, measures of physical and cognitive function, and medications. Results. ANP levels were almost fourfold higher in the healthy elderly than in the young (11.4+/-1.1 (SEM) vs 3+/-0.3 pmol/L. p <.01), and two-and-one half times higher in the cardiovascular-diseased elderly than the healthy elderly (29+/-1.9 vs 11.4+/-1.1 pmol L. p <.01). An ANP value of 21 pmol L has a sensitivity of 83% and specificity of 52% in distinguishing those elders classified as healthy from those classified as having chronic cardiovascular disease. ANP levels had positive univariate correlation with age (even from 70 to 102 years) an systolic blood pressure. ANP rose progressively with increasing numbers of markers of cardiovascular comorbidity. ANP was higher in subjects with jugular venous pressure 10 cm, presence of a third heart sound, peripheral edema, artificial cardiac pacemaker, atrial arrhythmias, and in those taking digoxin diuretics, or nitrates. On multivariate analysis independent predictors of ANP levels were in descending order, nitrates, age, diuretics, and atrial arrhythmias. Conclusion. These data suggest that ANP levels greater than 21 pmol L are associated with cardiovascular comorbidity in a clinically stable elderly cohort. C1 HARVARD UNIV,SCH MED,DIV AGING,CAMBRIDGE,MA 02138. HEBREW REHABIL CTR AGED,BOSTON,MA 02131. MASSACHUSETTS GEN HOSP,BEACON HH GERIATR HLTH PRACTICE,BOSTON,MA 02114. VET AFFAIRS MED CTR,GRECC,BALTIMORE,MD. RP Davis, KM (reprint author), N MISSISSIPPI MED CTR,GERIATR SERV,DEPT GERIATR,830 S GLOSTER ST,TUPELO,MS 38801, USA. FU NCRR NIH HHS [RR-0132]; NIA NIH HHS [AG-04390, AG-00599] NR 37 TC 20 Z9 20 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 1996 VL 51 IS 3 BP M95 EP M101 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VN555 UT WOS:A1996VN55500009 PM 8630708 ER PT J AU DAndrea, DM CoupayeGerard, B Kleyman, TR Foster, MH Madaio, MP AF DAndrea, DM CoupayeGerard, B Kleyman, TR Foster, MH Madaio, MP TI Autoantibodies interact directly with distinct glomerular and vascular cell surface antigens SO KIDNEY INTERNATIONAL LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; FORM IMMUNE DEPOSITS; V-REGION SEQUENCES; DNA ANTIBODIES; MURINE LUPUS; ACETYLCHOLINE-RECEPTOR; MONOCLONAL-ANTIBODY; MYASTHENIA-GRAVIS; CROSS-REACTIVITY; RAT-KIDNEY AB We have identified monoclonal anti-DNA antibodies derived from lupus prone MRL-lpr/lpr mice that produce glomerular immune deposits and nephritis after passive transfer to normal mice. Particularly noteworthy is that the location of immune deposition varied among nephritogenic Ig, and this was associated with distinctive histologies and clinical disease profiles. Although their autoantigen binding properties differed, they were highly cross-reactive, in a manner similar to Ig deposited in glomeruli of lupus mice. This antigen binding profile was also typical of other previously described nephritogenic autoantibodies that bound directly to glomerular antigens to initiate immune deposit formation. In this study, we questioned whether ligation of different glomerular antigens by individual autoantibodies could contribute to the observed differences in the location of immune deposits. To examine this possibility, monoclonal anti-DNA antibodies (IgG2a) that produced glomerular immune deposits in different locations were evaluated. H221 produced mesangial, intracapillary (that is, intraluminal or within the capillary lumen) and subendothelial deposits associated with heavy proteinuria, whereas H147 produced mesangial, subendothelial and linear basement membrane deposits associated with proliferative glomerulonephritis. Initially, the capacity of H221 and H147 to bind directly to glomerular and vascular cell surfaces was evaluated. As demonstrated by FAGS, H221 bound preferentially to mesangial cells whereas H147 bound preferentially to endothelial cells. To identify possible target cell surface antigens, Western blots, immunoprecipitation of surface labeled cells, and 2D gel electrophoresis were employed. H221 reacted with a 108 kDa protein on mesangial cells not identified by H147, whereas H147 reacted with a 45 kDa protein on endothelial cells not identified by H221. These results support the hypothesis that some nephritogenic lupus autoantibodies initiate immune deposit formation through direct interaction with glomerular antigens. Furthermore, they suggest that the site of immune deposition is determined by both antigen binding properties of the relevant antibody and the location of its target ligand within the glomerulus. In a given individual, therefore, the predominant autoantibody-glomerular antigen interaction may influence the morphologic and clinical phenotype expressed. Variation in the predominant interaction may also contribute to variations in disease expression among individuals with lupus nephritis. C1 UNIV PENN,DEPT MED,RENAL ELECTROLYTE & HYPERTENS DIV,PHILADELPHIA,PA 19104. UNIV PENN,DEPT PHYSIOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,PHILADELPHIA,PA. FU NIAID NIH HHS [AI 27915]; NIDDK NIH HHS [DK 45191, DK 33694] NR 47 TC 68 Z9 70 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1996 VL 49 IS 5 BP 1214 EP 1221 DI 10.1038/ki.1996.175 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA UF620 UT WOS:A1996UF62000005 PM 8731084 ER PT J AU Mayadas, TN Mendrick, DL Brady, HR Tang, T Papayianni, A Assmann, KJM Wagner, DD Hynes, RO Cotran, RS AF Mayadas, TN Mendrick, DL Brady, HR Tang, T Papayianni, A Assmann, KJM Wagner, DD Hynes, RO Cotran, RS TI Acute passive anti-glomerular basement membrane nephritis in P-selectin-deficient mice SO KIDNEY INTERNATIONAL LA English DT Article ID IMMUNE-COMPLEX NEPHRITIS; HETEROLOGOUS PHASE; GBM NEPHRITIS; PLATELETS; PROTEIN; MOUSE AB P-selectin present on surfaces of activated endothelium and platelets mediates neutrophil-endothelial and neutrophil-platelet interactions. The role of P-selectin in vivo was examined in a model of acute passive anti-GEM nephritis in P-selectin-deficient and wild-type mice which was induced by intravenous injection of anti-GEM serum. There were two major differences between P-selectin-deficient and wild-type mice. Firstly, mutant mice had approximately two fold more glomerular PMNs and albuminuria than wild-type animals at the peak of neutrophil influx and proteinuria. Secondly, Lipoxin A(4) (LXA(4)), an eicosanoid which inhibits leukocyte-endothelial adhesion in vitro, and is generated primarily by transcellular biosynthetic routes during P-selectin-mediated platelet-PMN interaction [1], was approximately 60% of wild type levels in nephritic kidneys of P-selectin-deficient mice. Injection of wild-type platelets into P-selectin-null mice restored LXA(4) to wild-type levels. The corresponding PMN influx approximated PMN levels in wild-type mice receiving platelets but urine albuminuria remained higher. Although these two P-selectin-dependent events cannot be directly linked, our results point to the importance of considering both platelet and endothelial P-selectin in determining the cellular events in inflammation. C1 BROCKTON W ROXBURY VET AFFAIRS MED CTR,DEPT MED,DIV RENAL,BOSTON,MA. MIT,CTR CANC RES,BOSTON,MA. UNIV NIJMEGEN HOSP,DEPT PATHOL,NIJMEGEN,NETHERLANDS. HOWARD HUGHES MED INST,COCONUT GROVE,FL 33133. RP Mayadas, TN (reprint author), HARVARD UNIV,SCH MED,BRIGHAM & WOMENS HOSP,DEPT PATHOL,VASC RES DIV,CTR BLOOD RES,BOSTON,MA 02115, USA. FU NHLBI NIH HHS [P01 HL36028]; NIDDK NIH HHS [DK44380]; NINDS NIH HHS [NS33296] NR 25 TC 79 Z9 80 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1996 VL 49 IS 5 BP 1342 EP 1349 DI 10.1038/ki.1996.190 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA UF620 UT WOS:A1996UF62000020 PM 8731099 ER PT J AU Tallon, S Berdud, I Hernandez, A Concepcion, HT Almaden, Y Torres, A MartinMalo, A Felsenfeld, AJ Aljama, P Rodriguez, M AF Tallon, S Berdud, I Hernandez, A Concepcion, HT Almaden, Y Torres, A MartinMalo, A Felsenfeld, AJ Aljama, P Rodriguez, M TI Relative effects of PTH and dietary phosphorus on calcitriol production in normal and azotemic rats SO KIDNEY INTERNATIONAL LA English DT Article ID CHRONIC-RENAL-FAILURE; PARATHYROID-HORMONE; SERUM CONCENTRATION; VITAMIN-D; 1,25-DIHYDROXYVITAMIN-D; HYPERPARATHYROIDISM; MODERATE; INSUFFICIENCY; METABOLISM; PHOSPHATE AB In moderate renal failure, the serum calcitriol level is influenced by the stimulatory effect of high PTH and the inhibitory action of phosphorus retention. Our goal was to evaluate the relative effect that high PTH levels and increased dietary phosphorus had on calcitriol production in normal rats (N) and rats with moderate renal failure (Nx). Normal and Nx (3/4 nephrectomy) rats were divided into two groups: (1) rats with intact parathyroid glands (IPTG) and (2) parathyroidectomized rats in which PTH was replaced (PTHR) by the continuous infusion of rat 1-34 PTH, 0.022 mu g/hr/100 g body wt, using a miniosmotic Alzet pump. To test the effect of dietary phosphorus, rats received either a moderate (MPD, 0.6% P) or a high phosphorus (HPD, 1.2%) diet for 14 days. The experimental design included pair-fed N and Nx rats with either IPTG or PTHR. Serum calcitriol and PTH levels in N rats fed a MPD were 69 +/- 3 and 40 +/- 5 pg/ml, respectively. In Nx rats on a MPD, serum calcitriol levels decreased only if hyperparathyroidism was not allowed to occur (76 +/- 4 vs. 62 +/- 4 pg/ml in Nx-IPTG-MPD and Nx-PTHR-MPD groups respectively, P < 0.05). Even in N rats on a HPD, high PTH levels (67 +/- 8 pg/ml in the N-IPTG-HPD group) were required to maintain normal serum calcitriol levels (69 +/- 4 vs. 56 +/- 6 pg/ml in Nx-IPTG-HPD and Nx-PTHR-HPD groups, respectively; P < 0.05). In Nx rats on a HPD, the development of secondary hyperparathyroidism (286 +/- 19 pg/ml in the Nx-IPTG-HPD group) prevented a decrease in serum calcitriol levels (68 +/- 7 pg/ml). In contrast, serum calcitriol levels were low in the Nx-PTHR-HPD group (52 +/- 4 pg/ml, P < 0.05), which were deprived of the adaptative increase in endogenous PTH production. In conclusion, our results in rats indicate that in moderate renal failure, an elevated PTH level maintains calcitriol production and overcomes the inhibitory action of phosphorus retention. C1 UNIV CORDOBA,HOSP REINA SOFIA,UNIDAD INVEST,E-14004 CORDOBA,SPAIN. UNIV CORDOBA,HOSP REINA SOFIA,SERV NEFROL,E-14004 CORDOBA,SPAIN. HOSP UNIV CANARIAS,SERV NEFROL,TENERIFE,SPAIN. HOSP UNIV CANARIAS,UNIDAD INVEST,TENERIFE,SPAIN. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. W LOS ANGELES VA MED CTR,DEPT MED,LOS ANGELES,CA. RI Rodriguez, teresa/H-5452-2011 NR 26 TC 36 Z9 36 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 1996 VL 49 IS 5 BP 1441 EP 1446 DI 10.1038/ki.1996.203 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA UF620 UT WOS:A1996UF62000033 PM 8731112 ER PT J AU Zeitels, SM AF Zeitels, SM TI Laser versus cold instruments for microlaryngoscopic surgery SO LARYNGOSCOPE LA English DT Article ID CLINICAL EXPERIENCE; CO2-LASER; CARCINOMA AB Controversy has arisen concerning the merits of the CO2 laser in microlaryngoscopic surgery because of the potentially harmful effects that the injudicious application of the laser could have on voice production. In an effort to develop a logical approach to instrument selection, the author examined the use of both cold instruments and the CO2 laser in the treatment of various beni,sn and malignant lesions, A retrospective review of 307 microlaryngeal procedures performed over a 3-year period revealed that 263 (86%) were glottal and 44 (14%) were supraglottal. Of the 263 glottal procedures, 203 (77%) employed cold instruments alone and 60 (23%) used both cold instruments and the CO2 laser, The laser was used to assist in all 44 supraglottal procedures, Therefore, 203 (66%) of 307 procedures were done with cold instruments alone, and 104 (34%) of 307 procedures were performed using the CO2 laser with cold instruments, Lesions were stratified on the basis of pathology and size, as well as surgical approach, A primary phonomicrosurgical principle in glottal surgery is to maximally preserve the vocal fold's layered microstructure (laminae propria and epithelium), Precise tangential dissection was necessary for achieving this goal, For limited lesions, this dissection was best accomplished with cold instruments alone, The CO2 laser facilitated hemostatic surgical dissection for all supraglottal lesions and for selected larger glottal lesions in which bleeding would obscure visualization of the microanatomy of the musculomembranous vocal fold. C1 HARVARD UNIV, SCH MED, DEPT OTOLARYNGOL, BOSTON, MA 02115 USA. VET AFFAIRS MED CTR, OTOLARYNGOL SECT, BOSTON, MA USA. RP Zeitels, SM (reprint author), MASSACHUSETTS EYE & EAR INFIRM, DEPT OTOLARYNGOL, 243 CHARLES ST, BOSTON, MA 02114 USA. NR 40 TC 44 Z9 44 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 1996 VL 106 IS 5 BP 545 EP 552 DI 10.1097/00005537-199605000-00006 PN 1 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UT403 UT WOS:A1996UT40300005 PM 8628079 ER PT J AU Gilbert, RJ Daftary, S Woo, P Seltzer, S Shapshay, SM Weisskoff, RM AF Gilbert, RJ Daftary, S Woo, P Seltzer, S Shapshay, SM Weisskoff, RM TI Echo-planar magnetic resonance imaging of deglutitive vocal fold closure: Normal and pathologic patterns of displacement SO LARYNGOSCOPE LA English DT Article ID GLOTTIC CLOSURE; PHARYNGEAL AB Abnormalities of vocal fold closure during deglutition predispose to aspiration due to impairment of airway protection. Conventional assessment of deglutitive vocal fold motion with laryngoscopy does not permit visualization through a complete adduction-abduction cycle. We determined spatiotemporal patterns of deglutitive vocal fold adduction through echo-planer magnetic resonance imagining in 15 normal volunteers and 6 patients with vocal paralysis. In normal volunteers, deglutitive vocal fold adduction was synchronized with laryngeal elevation, with complete vocal fold closure at the apex. Patients with unilateral vocal paralysis demonstrated reduced elevation and medial movement of the involved vocal fold. At maximal laryngeal elevation the uninvolved vocal fold attained a position superior to the paralyzed fold, resulting in level differences and an interglottic gap. Patients with bilateral vocal fold paralysis demonstrated reduced elevation and medial movement of both vocal folds. These findings indicated that normal and abnormal patterns of vocal fold displacement can be distinguished noninvasively through the use of echo-planar imaging. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. ST ELIZABETHS MED CTR,BOSTON,MA. TUFTS UNIV,SCH MED,DEPT OTOLARYNGOL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. RP Gilbert, RJ (reprint author), NUCL MAGNET RESONANCE CTR,DEPT RADIOL,149 13TH ST,CHARLESTOWN,MA 02114, USA. NR 15 TC 18 Z9 18 U1 0 U2 1 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAY PY 1996 VL 106 IS 5 BP 568 EP 572 DI 10.1097/00005537-199605000-00009 PN 1 PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UT403 UT WOS:A1996UT40300008 PM 8628082 ER PT J AU Yu, M Honoki, K Andersen, J Paietta, E Nam, DK Yunis, JJ AF Yu, M Honoki, K Andersen, J Paietta, E Nam, DK Yunis, JJ TI MLL tandem duplication and multiple splicing in adult acute myeloid leukemia with normal karyotype SO LEUKEMIA LA English DT Article DE MLL; tandem duplication; acute leukemia; karyotype; prognosis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BRITISH COOPERATIVE GROUP; 11Q23 TRANSLOCATIONS; DROSOPHILA-TRITHORAX; GENE; DOMAIN; T(4-11)(Q21-Q23); REARRANGEMENTS; CLASSIFICATION; PROTEINS AB Rearrangement of the MLL (myeloid-lymphoid or mixed-lineage leukemia) gene through a reciprocal chromosomal translocation is found in 5% of adult acute myeloid (AML) and 10% of pediatric acute lymphoid (ALL) leukemia. More than 25 different reciprocal chromosomal translocations, with an 11q23 breakpoint, fuse the MLL gene (also named ALL-I, HRX and Htrx1) to a second partner gene. These leukemias have poor prognosis and frequently have a monocytic, lymphoid or biphenotypic (myeloid and lymphoid) antigen expression in blast cells. Approximately 20-30% of patients diagnosed as having adult de novo AML have normal chromosomes by metaphase analysis and the majority of these patients have good prognosis. With the use of reverse transcriptase-polymerase chain reaction (RT-PCR) technique and Southern blot analysis, we found that seven of 34 such patients (21%) had a tandem partial duplication of exons 2 to 6 or 2 to 8 of the MLL gene. These seven patients showed a median survival of 2.7 months, compared to a 6.8 months median survival for all other patients in the study. If confirmed on a large series of patients, our findings may help differentiate AML with normal karyotype and poor prognosis from those with normal karyotype and a more favorable prognosis. C1 THOMAS JEFFERSON UNIV,DEPT PATHOL ANAT & CELL BIOL,DIV CANC BIOL,PHILADELPHIA,PA 19107. DANA FARBER CANC INST,BOSTON,MA 02115. ALBERT EINSTEIN COLL MED,CTR CANC,BRONX,NY 10467. RI Honoki, Kanya/C-8814-2009 FU NCI NIH HHS [CA51664] NR 40 TC 48 Z9 49 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 1996 VL 10 IS 5 BP 774 EP 780 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA UP256 UT WOS:A1996UP25600005 PM 8656671 ER PT J AU Simon, JS Deshmukh, G Couch, FJ Merajver, SD Weber, BL VanVooren, P Tissil, F Szpirer, J Szpirer, C Alper, SL Jacob, HJ Brosius, FC AF Simon, JS Deshmukh, G Couch, FJ Merajver, SD Weber, BL VanVooren, P Tissil, F Szpirer, J Szpirer, C Alper, SL Jacob, HJ Brosius, FC TI Chromosomal mapping of the rat Slc4a family of anion exchanger genes, Ae1, Ae2, and Ae3 SO MAMMALIAN GENOME LA English DT Article ID PCR-ANALYZED MICROSATELLITES; MESSENGER-RNA; LOCI C1 UNIV MICHIGAN,DEPT INTERNAL MED,ANN ARBOR,MI 48109. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. VET ADM MED CTR,ANN ARBOR,MI 48109. FREE UNIV BRUSSELS,DEPT BIOL MOLEC,B-1640 RHODE ST GENESE,BELGIUM. BETH ISRAEL HOSP,MOL MED UNIT,BOSTON,MA 02215. BETH ISRAEL HOSP,RENAL UNIT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NHLBI NIH HHS [HL-18575] NR 26 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1996 VL 7 IS 5 BP 380 EP 382 DI 10.1007/s003359900109 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UM129 UT WOS:A1996UM12900013 PM 8661729 ER PT J AU Reue, K Xia, YR Shi, VW Cohen, RD Welch, C Lusis, AJ AF Reue, K Xia, YR Shi, VW Cohen, RD Welch, C Lusis, AJ TI Localization of mouse peroxisome proliferator-activated receptor gamma on chromosome 6 SO MAMMALIAN GENOME LA English DT Article ID CLONING; MEMBER; LIVER C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90095. RP Reue, K (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,BLDG 113,ROOM 312,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. FU NHLBI NIH HHS [HL28481] NR 10 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD MAY PY 1996 VL 7 IS 5 BP 390 EP 391 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UM129 UT WOS:A1996UM12900018 PM 8661743 ER PT J AU Mauceri, T Biggs, PJ Beatty, J Doppke, K Gall, K Hong, L Leong, J Lo, YC Rosenthal, SR Russell, MD AF Mauceri, T Biggs, PJ Beatty, J Doppke, K Gall, K Hong, L Leong, J Lo, YC Rosenthal, SR Russell, MD TI A method for predicting the variation of the depth of maximum dose in shaped electron fields SO MEDICAL PHYSICS LA English DT Article ID LINEAR-ACCELERATOR; OUTPUT FACTORS; DOSIMETRY RP Mauceri, T (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,DIV RADIAT BIOPHYS,BOSTON,MA 02114, USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 1996 VL 23 IS 5 BP 695 EP 697 DI 10.1118/1.597716 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UL576 UT WOS:A1996UL57600012 PM 8724742 ER PT J AU Waters, GS Caplan, D AF Waters, GS Caplan, D TI Processing resource capacity and the comprehension of garden path sentences SO MEMORY & COGNITION LA English DT Article ID WORKING MEMORY; INDIVIDUAL-DIFFERENCES AB Three experiments explored the relationship between verbal working memory capacity and the comprehension of garden path sentences. In Experiment 1, subjects with high, medium, and low working memory spans made acceptability judgments about garden path and control sentences under whole sentence and rapid serial visual presentation (RSVP) conditions. There were no significant differences between subjects with different working memory spans in the comprehension of garden path sentences in either condition. In Experiments 2A and 2B, subjects with high and low working memory spans were tested on the same materials at three RSVP rates. There were no significant differences between subjects with different working memory spans in the magnitude of the effect of garden path sentences at any presentation rate. The results suggest that working memory capacity, as measured by the Daneman and Carpenter (1980) reading span task, is not a major determinant of individual differences in the processing of garden path sentences. C1 MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. RP Waters, GS (reprint author), MCGILL UNIV, SCH COMMUN SCI & DISORDERS, 1266 PINE AVE W, MONTREAL, PQ H3G 1A8, CANADA. FU NIA NIH HHS [AG09661] NR 23 TC 62 Z9 66 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-502X J9 MEM COGNITION JI Mem. Cogn. PD MAY PY 1996 VL 24 IS 3 BP 342 EP 355 DI 10.3758/BF03213298 PG 14 WC Psychology, Experimental SC Psychology GA UH518 UT WOS:A1996UH51800007 PM 8718768 ER PT J AU Adrogue, HJ Pena, J Comstock, JP AF Adrogue, HJ Pena, J Comstock, JP TI Glyburide increases the secretion, tissue uptake, and action of insulin in conscious normal dogs SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CULTURED RAT HEPATOCYTES; SULFONYLUREAS; HYPERINSULINEMIA; GLIPIZIDE; BINDING; METABOLISM; RECEPTORS; THERAPY; INVIVO AB The action of glyburide on glucose homeostasis involves pancreatic and extrapancreatic mechanisms. The relative importance of each of these processes in the hypoglycemic response to sustained administration of glyburide is unknown. In addition, the effect of this drug on the hepatic extraction of insulin is controversial. This investigation uses direct techniques in conscious normal dogs to examine the impact of glyburide therapy (2.5 mg twice daily for 4 weeks) on glucose homeostasis. Preparatory surgery included placement of Doppler flow probes on hepatic vessels and insertion of catheters in carotid artery, portal vein, hepatic vein, and renal vein. After recovery from surgery, animals underwent an intravenous glucose tolerance test ([IGTT] 0.3 g . kg(-1) intravenous glucose bolus) and an insulin infusion clamp test ([IICT] 2 mU . kg(-1). min(-1) intravenous insulin during 150 minutes) followed by glyburide therapy. After 4 weeks, the IGTT and IICT were repeated. Glyburide increased the insulin secretory response during the late phase of the IGTT and augmented glucose clearance during the IICT, Hepatic extraction of insulin was also stimulated by glyburide, We conclude that the hypoglycemic action of long-term glyburide administration involves stimulation of both insulin secretion by the pancreas and glucose disposal by peripheral tissues. In addition, glyburide augments the extraction of insulin by the liver, and such an effect might prevent the development of sustained high levels of insulin in blood perfusing peripheral tissues. (C) 1996 by W.B. Saunders Company. C1 DEPT VET AFFAIRS MED CTR,ENDOCRINE SECT,DEPT MED,HOUSTON,TX 77030. BAYLOR COLL MED,HOUSTON,TX 77030. RP Adrogue, HJ (reprint author), DEPT VET AFFAIRS MED CTR,RENAL SECT 111,DEPT MED,2002 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 31 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 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAY PY 1996 VL 45 IS 5 BP 579 EP 586 DI 10.1016/S0026-0495(96)90027-X PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ864 UT WOS:A1996UJ86400007 PM 8622600 ER PT J AU Baish, JW Gazit, Y Berk, DA Nozue, M Baxter, LT Jain, RK AF Baish, JW Gazit, Y Berk, DA Nozue, M Baxter, LT Jain, RK TI Role of tumor vascular architecture in nutrient and drug delivery: An invasion percolation-based network model SO MICROVASCULAR RESEARCH LA English DT Article ID BLOOD-FLOW; MICROVASCULAR ARCHITECTURE; SOLID TUMORS; TISSUE; PRESSURE; OXYGEN; ADENOCARCINOMA; DIFFUSION; GROWTH; MICE AB Delivery of diffusible nutrients and drugs in tissues is limited in part by the distance over which substances must diffuse between the vascular space and the surrounding tissues and by upstream losses prior to local delivery by the blood. By examining the fractal behavior of two-dimensional vascular networks in the murine dorsal skinfold chamber preparation, we have identified distinct architectural features of normal and tumor vascular networks that lead to fundamentally different transport behavior. Normal capillaries which are relatively straight and regularly spaced are well modeled by the widely used Krogh cylinder model. In contrast, the fractal dimensions of tumor vascular networks suggest that the tortuous vessels and wide range of avascular spaces found in tumors are better represented by invasion percolation, a well-known statistical growth process governed by local substrate properties. Based on these observations, we have constructed a percolation-based model of tumor vascular growth that enables us to predict the effects of network architecture on transport. We find that the number of avascular spaces in tumors scales with the size of the spaces so that there will exist a few large avascular spaces and many smaller avascular spaces between vessels. We also End that the tortuosity of the vessels, as reflected by the elevated minimum path dimension, produces regions of locally flow-limited transport and reduces flow through the tumor as a whole. Our model helps to explain the long-standing paradox that tumor vasculature has a higher geometrical resistance than normal vasculature despite increases in vessel diameter. A comparison to oxygenation measurements in normal and tumor tissues shows that our model predicts the architectural obstacles to transport in tumors more accurately than the Krogh cylinder model. Our results suggest that clinical interventions that yield more regular vascular geometry may be useful as a supplement to those that improve arterial availability or decrease rates of consumption by the tissue. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,STEELE LAB,DEPT RADIAT ONCOL,BOSTON,MA 02114. MIT,HARVARD MIT DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. RI Berk, David/A-4863-2012 OI Berk, David/0000-0002-3855-6886 FU NCI NIH HHS [CA-56591] NR 48 TC 158 Z9 161 U1 1 U2 26 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD MAY PY 1996 VL 51 IS 3 BP 327 EP 346 DI 10.1006/mvre.1996.0031 PG 20 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UK977 UT WOS:A1996UK97700005 PM 8992232 ER PT J AU Oliva, E Young, RH AF Oliva, E Young, RH TI Clear cell adenocarcinoma of the urethra: A clinicopathologic analysis of 19 cases SO MODERN PATHOLOGY LA English DT Article DE clear cell carcinoma; neoplasm; urethra ID FEMALE URETHRA; PAPILLARY ADENOCARCINOMA; NEPHROGENIC ADENOMA; CARCINOMA; DIVERTICULUM; BLADDER; ORIGIN; WOMEN; TUMOR AB Nineteen clear cell adenocarcinomas of the urethra, 18 from women and one from a man, are described. The patients ranged from 35 to 80 years of age (average, 58 yrs). The clinical presentation and gross findings were similar to those of urethral carcinomas, except that 12 tumors, all from women, arose within a urethral diverticulum. On microscopic examination, the neoplasms exhibited the classic triad of tubulocystic, papillary, and diffuse patterns that characterize this tumor. The tumors had tbe typical cytologic features of dear cell adenocarcinoma, including hobnail cells, flattened cells, and cells with abundant clear cytoplasm. Nuclear pleomorphism was typically at least moderate and was marked in almost half the specimens. Mitotic figures were easily found in almost all the specimens. These cytologic features should aid in distinction of this carcinoma from the benign nephrogenic adenoma, although one of our patients was initially misdiagnosed as having the latter. Immunostaining for prostate-specific antigen and prostatic acid phosphatase was performed on 13 tumors, and all were negative. Follow-up is available for 13 patients. Six of them had no evidence of recurrence up to 10 years postoperatively. Four patients died of disease from 5 months to 42 months postoperatively. Three additional patients have had recurrence but were alive up to 6.5 years after presentation. We conclude that urethral clear cell adenocarcinoma occurs in adults, and in women in the great majority of cases; has a particular association with a urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; probably does not arise by malignant transformation of nephrogenic adenoma; is usually readily distinguished from the latter because of greater cytologic atypicality and mito tic activity; and does not stain for prostate-specific antigen or prostatic acid phosphatase. C1 MASSACHUSETTS GEN HOSP,DEPT PEDIAT,JAMES HOMER WRIGHT PATHOL LABS,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. NR 53 TC 45 Z9 45 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD MAY PY 1996 VL 9 IS 5 BP 513 EP 520 PG 8 WC Pathology SC Pathology GA UK455 UT WOS:A1996UK45500008 PM 8733766 ER PT J AU Tsukada, J Waterman, WR Koyama, Y Webb, AC Auron, PE AF Tsukada, J Waterman, WR Koyama, Y Webb, AC Auron, PE TI A novel STAT-like factor mediates lipopolysaccharide, interleukin 1 (IL-1), and IL-6 signaling and recognizes a gamma interferon activation site-like element in the IL1B gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN PROINTERLEUKIN-1-BETA GENE; TYROSINE PHOSPHORYLATION; DNA-SEQUENCES; GROWTH-FACTOR; EXPRESSION; RECEPTOR; CELLS; CLONING; TRANSCRIPTION; INDUCIBILITY AB Binding of many cytokines to their cognate receptors immediately activates Jak tyrosine kinases and their substrates, STAT (signal transducers and activators of transcription) DNA-binding proteins, The DNA binding targets of STATs are sequence elements related to the archetypal gamma interferon activation site, GAS, However, association of interleukin 1 (IL-1) with Jak-STAT signaling has remained unresolved, We now report an element termed LILRE (lipopolysaccharide [LPS] and IL-l-responsive element) in the human prointerleukin 1 beta gene (IL1B) which can be immediately induced by either lipopolysaccharide (LPS) or IL-1 protein to bind a tyrosine-phosphorylated protein. This LPS- and IL-1-induced factor (LIL factor) is recognized by an antibody raised against the N terminus of Stat1, but not by those specific for either the C terminus of Stat1 or any other GAS-binding STAT, Phosphotyrosine (P-Tyr) specifically inhibits formation of the LIL factor-DNA complex, suggesting the importance of P-Tyr for the DNA-binding activity, as has been found for all STAT dimers, Analysis of DNA-binding specificity demonstrates that the LIL factor possesses a novel GAS-like binding activity that contrasts with those of other STATs in a requirement for a G residue at position 8 (TTCCTGAGA), Further investigation has revealed that IL-6, but neither IL-4 nor gamma interferon, activates the LIL factor. Thus, the existence of such a STAT-like factor (IL-Stat) relates the LPS and IL-1 signaling pathway to other cytokine receptor signaling pathways via the activation of STATs, Moreover, the unique DNA-binding specificity and antigenicity of this factor suggest that LPS, IL-1, and IL-6 may use a common signaling pathway. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. WELLESLEY COLL,DEPT BIOL SCI,WELLESLEY,MA 02181. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02129. FU NCI NIH HHS [CA68544]; NIAID NIH HHS [AI27850]; NIAMS NIH HHS [AR03564] NR 48 TC 74 Z9 74 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2183 EP 2194 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900032 PM 8628285 ER PT J AU Antonetti, DA Algenstaedt, P Kahn, CR AF Antonetti, DA Algenstaedt, P Kahn, CR TI Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTORS; TYROSINE KINASES; SH2 DOMAINS; PI3-KINASE; ASSOCIATE; PROTEINS; CLONING; CDNA; GENE; P85 AB We have identified two novel alternatively spliced forms of the p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase by expression screening of a human skeletal muscle library with phosphorylated baculovirus-produced human insulin receptor substrate 1, One form is identical to p85 alpha throughout the region which encodes both Src homology 2 (SH2) domains and the inter-SH2 domain/p110 binding region but diverges in sequence from p85 alpha on the 5' side of nucleotide 953, where the entire break point cluster gene and SH3 regions are replaced by a unique 34-amino-acid N terminus, This form has an estimated molecular mass of similar to 53 M)a and has been termed p85/AS53. The second form is identical to p85 and p85/AS53 except for a 24-nucleotide insert between the SH2 domains that results in a replacement of aspartic acid 605 with nine amino acids, adding two potential serine phosphorylation sites in the vicinity of the known serine autophosphorylation site (Ser-608), Northern (RNA) analyses reveal a wide tissue distribution of p85 alpha, whereas p85/AS53 is dominant in skeletal muscle and brain, and the insert isoforms are restricted to cardiac muscle and skeletal muscle. Western blot (immunoblot) analyses using an anti-p85 polyclonal antibody and a specific anti-p85/AS53 antibody confirmed the tissue distribution of p85/AS53 protein and indicate a similar to 7-fold higher expression of p85/AS53 protein than of p85 in skeletal muscle, Both p85 and p85/AS53 bind to p110 in coprecipitation experiments, but p85 alpha itself appears to have preferential binding to insulin receptor substrate 1 following insulin stimulation, These data indicate that the gene for the p85 alpha regulatory subunit of PI 3-kinase can undergo tissue-specific alternative splicing. Two novel splice variants of the regulatory subunit of PI 3-kinase are present in skeletal muscle, cardiac muscle, and brain; these variants may have important functional differences in activity and may play a role in tissue-specific signals such as insulin-stimulated glucose transport or control of neurotransmitter secretion or action. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. FU NIDDK NIH HHS [DK33201, DK45935] NR 42 TC 105 Z9 109 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2195 EP 2203 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900033 PM 8628286 ER PT J AU Yenush, L Fernandez, R Myers, MG Grammer, TC Sun, XJ Blenis, J Pierce, JH Schlessinger, J White, MF AF Yenush, L Fernandez, R Myers, MG Grammer, TC Sun, XJ Blenis, J Pierce, JH Schlessinger, J White, MF TI The Drosophila insulin receptor activates multiple signaling pathways but requires insulin receptor substrate proteins for DNA synthesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT HEMATOPOIETIC-CELLS; PHOSPHATIDYLINOSITOL 3'-KINASE; TYROSINE PHOSPHORYLATION; IRS-1; KINASES; TRANSDUCTION; ASSOCIATION; BINDS; GRB2 AB The Drosophila insulin receptor (DIR) contains a 368-amino-acid COOH-terminal extension that contains several tyrosine phosphorylation sites in YXXM motifs, This extension is absent from the human insulin receptor but resembles a region in insulin receptor substrate (IRS) proteins which binds to the phosphatidylinositol (PI) 3-kinase and mediates mitogenesis, The function of a chimeric DIR containing the human insulin receptor binding domain (hDIR) was investigated in 32D cells, which contain few insulin receptors and no IRS proteins. Insulin stimulated tyrosine autophosphorylation of the human insulin receptor and hDIR, and both receptors mediated tyrosine phosphorylation of She and activated mitogen-activated protein kinase, IRS-1 was required by the human insulin receptor to activate PI 3-kinase and p70(s6k), whereas hDIR associated with PI 3-kinase and activated p70(s6k) without IRS-I, However, both receptors required IRS-1 to mediate insulin-stimulated mitogenesis. These data demonstrate that the DIR possesses additional signaling capabilities compared with its mammalian counterpart but still requires IRS-1 for the complete insulin response in mammalian cells. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,PROGRAM BIOMED & BIOL SCI,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02215. NYU,MED CTR,DEPT PHARMACOL,NEW YORK,NY 10016. NIH,LAB CELL & MOL BIOL,BETHESDA,MD 20892. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NCI NIH HHS [CA46595]; NIDDK NIH HHS [DK43808, DK38712] NR 41 TC 62 Z9 62 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1996 VL 16 IS 5 BP 2509 EP 2517 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UG299 UT WOS:A1996UG29900066 PM 8628319 ER PT J AU Offermanns, S IidaKlein, A Segre, GV Simon, MI AF Offermanns, S IidaKlein, A Segre, GV Simon, MI TI G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID EXPRESSION CLONING; MOLECULAR-CLONING; ADENYLYL-CYCLASE; G-PROTEINS; SIGNAL-TRANSDUCTION; BETA-GAMMA; RAT; SUBUNITS; ACTIVATION; CDNA AB The PTH/PTH-related peptide (PTHrP) receptor and the calcitonin receptor mediate the action of their physiological ligands by activating two different effecters, adenylyl cyclase and phospholipase C. Whereas regulation of adenylyl cyclase via both receptors is thought to involve the G protein G(s), it is not known whether activation of phospholipase C results from coupling of the receptors to G(q) family members or whether beta gamma-subunits released from receptor-activated G(s) lead to phospholipase C activation. To elucidate the mechanism of this type of dual signaling, we reconstituted the signal transduction of the PTH/PTHrP and the calcitonin receptor in COS-7 and HEK293 cells. In COS-7 cells expressing the receptor alone, addition of the respective ligands resulted in the accumulation of cAMP and inositol phosphates. When cells were cotransfected with the cDNAs of receptor and different alpha-subunits of the G(q) family (G alpha(q), G alpha(11), G alpha(14), G alpha(15), and G alpha(16)), a severalfold increase in the ligand-dependent inositol phosphate production could be observed, indicating that the receptors functionally interacted with all alpha-subunits of the G alpha(q) family. Additionally, whereas PTH treatment of HEK293 cells coexpressing both the PTH/PTHrP receptor and G alpha(q), increased both second messengers, the same treatment in cells expressing the PTH/PTHrP receptor alone increased only cAMP. Under all conditions tested, activation of phospholipase C via the PTH/PTHrP and calcitonin receptor required higher ligand concentrations than receptor-mediated adenylyl cyclase activation. Our data strongly support the idea that dual signaling of the PTH/PTHrP and calcitonin receptors is due to the activation of different G proteins belonging to the G(s) and G(q) families. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,ENDOCRINE UNIT,BOSTON,MA 02114. RP Offermanns, S (reprint author), CALTECH,DIV BIOL 14775,PASADENA,CA 91125, USA. FU NIDDK NIH HHS [DK-47034, DK-11794]; NIGMS NIH HHS [GM-34236] NR 43 TC 79 Z9 80 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1996 VL 10 IS 5 BP 566 EP 574 DI 10.1210/me.10.5.566 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK448 UT WOS:A1996UK44800010 PM 8732687 ER PT J AU Aparicio, CL Berthiaume, F Chang, CC Yarmush, ML AF Aparicio, CL Berthiaume, F Chang, CC Yarmush, ML TI Tumor necrosis factor-alpha (TNF-alpha) induces a reversible, time- and dose-dependent adhesion of progenitor T cells to endothelial cells SO MOLECULAR IMMUNOLOGY LA English DT Article DE tumor necrosis factor-alpha; interleukin-1; endothelial cell; progenitor T cell; FTF1 cell; cell-cell adhesion ID GROWTH-FACTOR-BETA; INVITRO INDUCTION; SURFACE-MARKERS; CD8 EXPRESSION; MOUSE EMBRYOS; THYMUS; LYMPHOCYTES; MOLECULES; THYMOCYTES; MIGRATION AB Recent in vivo studies suggest that tumor necrosis factor-alpha (TNF-alpha) is involved in the development of the thymus. We postulated that this inflammatory mediator could regulate the influx of progenitor T cells into the thymus. Using an in vitro static adhesion system, we found that TNF-alpha increases the adhesion of a murine progenitor T cell line (FTF1) to a bovine aortic endothelial cell line (1F8), human umbilical vein endothelial (HUVE) cells, and a murine arterial endothelial (MAE) cell line. TNF-alpha treatment of the 1F8 cells resulted in a time- and dose-dependent increase in the adherence of FTF1 cells. Adherence increased during the first 6 hr of treatment with TNF-alpha concentrations ranging from 10(-11) to 10(-9) M. Maximal adherence (6 hr treatment with 10(-10) M of TNF-alpha) was approximately 4.5-fold larger than that of untreated monolayers. A slow decrease in adherence, down to approximately 2-fold at 48 hr, was observed beyond 12 hr of TNF-alpha treatment; in contrast, removal of TNF-alpha after 6 hr of continued stimulation caused the adherence to return to pre-stimulation levels within 24-30 hr. Adhesion of FTF1 cells to TNF-alpha-treated 1F8 cells was almost completely blocked by a monoclonal antibody against murine CD49d (very late antigen-4) expressed on FTF1 cells. TNF-alpha-induced adhesion of FTF1 cells to MAE cells was also blocked by monoclonal antibodies against murine CD49d and CD106 (vascular cell adhesion molecule-1). These results support the notion that local secretion of TNF-alpha could modulate the dynamics of adhesion of progenitor T cells to the thymic endothelium. Copyright (C) 1996 Elsevier Science Ltd. C1 RUTGERS STATE UNIV,DEPT CHEM & BIOCHEM ENGN,PISCATAWAY,NJ 08855. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,SURG SERV,BOSTON,MA 02114. SHRINERS BURNS INST,BOSTON,MA 02114. NR 53 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAY-JUN PY 1996 VL 33 IS 7-8 BP 671 EP 680 DI 10.1016/0161-5890(96)00013-2 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA VA418 UT WOS:A1996VA41800011 PM 8760279 ER PT J AU Rothenberg, ME Ownbey, R Mehlhop, PD Loiselle, PM vandeRijn, M Bonventre, JV Oettgen, HC Leder, P Luster, AD AF Rothenberg, ME Ownbey, R Mehlhop, PD Loiselle, PM vandeRijn, M Bonventre, JV Oettgen, HC Leder, P Luster, AD TI Eotaxin triggers eosinophil-selective chemotaxis and calcium flux via a distinct receptor and induces pulmonary eosinophilia in the presence of interleukin 5 in mice SO MOLECULAR MEDICINE LA English DT Article ID BASOPHILS; MIGRATION; CELLS AB Background: Understanding the processes that control selective eosinophilia is of fundamental importance in a variety of human diseases (e.g., allergies, parasitic infections, malignancy). Interleukin 5, an eosinophil-specific growth and activating factor, and eotaxin appear to collaborate in this process. Eotaxin is a recently described chemotactic factor that belongs to the C-C (or beta) chemokine family and has been implicated in animal and human eosinophilic inflammatory states. We have recently reported the molecular characterization of murine eotaxin and now report the biological properties of purified recombinant murine eotaxin in vitro and in vivo in the presence or absence of interleukin 5 (IL-5) in mice. Materials and Methods: Murine eotaxin was expressed in bacteria and purified by affinity chromatography and HPLC. Activity was tested in vitro by examining chemotactic and calcium flux responses of purified murine leukocytes. Additionally, desensitization of calcium flux responses to other chemokines, eosinophil survival assays, and basophil histamine release were examined. Finally, eotaxin was delivered to wild-type or IL-5 transgenic mice and the host response was examined. Results: Eotaxin had activity only when the recombinant molecule had the native mature amino terminus and contained the first 25 amino acids of the mature protein. It was active in vitro at an effective concentration between 10 and 100 ng/ml in both chemotaxis and calcium nux assays toward eosinophils, but not macrophages or neutrophils. Furthermore, intranasal or subcutaneous application of eotaxin selectively recruited large numbers of eosinophils into the mouse lung and skin, respectively, only in the presence of interleukin 5. Macrophage inflammatory protein-1 alpha, a related C-C chemokine active on eosinophils, and eotaxin were not able to cross-desensitize. Eotaxin had no affect on the in vitro survival of eosinophils and did not induce basophil histamine release. Conclusions: Mouse eotaxin is an eosinophil specific chemoattractant that has a markedly enhanced effect in vivo in the presence of another eosinophil selective cytokine IL-5, and utilizes a signal transduction receptor pathway that is distinct from that utilized by macrophage inflammatory protein-1 alpha. This data suggests that the development of tissue eosinophilia in vivo involves a two-step mechanism elicited by interleukin 5 and eotaxin. C1 HARVARD UNIV,INFECT DIS UNIT,MASSACHUSETTS GEN HOSP,SCH MED,CHARLESTOWN,MA 02129. HARVARD UNIV,RENAL UNIT,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA. CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA. CHILDRENS HOSP,DIV IMMUNOL,BOSTON,MA. UNIV PENN MED SYST,DEPT PATHOL & LAB MED,PHILADELPHIA,PA. NR 42 TC 153 Z9 153 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY PY 1996 VL 2 IS 3 BP 334 EP 348 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UQ243 UT WOS:A1996UQ24300009 PM 8784786 ER PT J AU Rollins, BJ AF Rollins, BJ TI Monocyte chemoattractant protein 1 a potential regulator of monocyte recruitment in inflammatory disease SO MOLECULAR MEDICINE TODAY LA English DT Review ID ATHEROSCLEROTIC LESIONS; RECEPTOR-BINDING; GROWTH-FACTOR; EXPRESSION; INTERLEUKIN-8; PURIFICATION; RESIDUES; CLONING; CELLS AB The appearance of specific types of leukocytes in inflammatory infiltrates may be governed by cell-specific chemoattractants called chemokines. In particular, monocyte chemoattractant protein 1 (MCP-1) has been implicated in diseases characterized by monocyte-rich infiltrates, including atherosclerosis, rheumatoid arthritis and multiple sclerosis. While we are beginning to understand the structural determinants that govern the activities of MCP-1 in vitro, we know much less about its physiological functions in vivo and its pathogenetic role in disease. However, recent data from genetically modified mice have begun to place MCP-1 in a central position in monocyte trafficking and activation. RP Rollins, BJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,D930,44 BINNEY ST,BOSTON,MA 02115, USA. NR 35 TC 301 Z9 304 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 1357-4310 J9 MOL MED TODAY JI Mol. Med. Today PD MAY PY 1996 VL 2 IS 5 BP 198 EP 204 DI 10.1016/1357-4310(96)88772-7 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UK240 UT WOS:A1996UK24000009 PM 8796888 ER PT J AU Yu, XJ Waeber, C Castanon, N Scearce, K Hen, R Macor, JE Chaveau, J Moskowitz, MA AF Yu, XJ Waeber, C Castanon, N Scearce, K Hen, R Macor, JE Chaveau, J Moskowitz, MA TI 5-carboxamido-tryptamine, CP-122,288 and dihydroergotamine but not sumatriptan, CP-93,129, and serotonin-5-O-carboxymethyl-glycyl-tyrosinamide block dural plasma protein extravasation in knockout mice that lack 5-hydroxytryptamine(1B) receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID MATER; RAT; MECHANISMS; LEAKAGE; SUBTYPE; BRAIN AB We studied the dural plasma protein extravasation response after unilateral electrical stimulation of the trigeminal ganglion in mice lacking serotonin 5-HT1B (5-HT1D beta) receptors by modifying a technique previously described in rats or guinea pigs. We investigated the inhibitory effects of six 5-HT1 receptor agonists in this model: 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP-93,129), sumatriptan, serotonin-5-O-carboxymethylglycyl-tyrosinamide (GTI), 5-methylaminosulfonylmethyl-3-(N-methylpyrrolidin-2R-ylmethyl)-1H-indole (CP-122,288), 5-carboxamido-tryptamine (5-CT), and dihydroergotamine. The plasma extravasation response did not differ between wild-type and mutant after vehicle injection. The potency of sumatriptan, CP-122,288, CP-93,129, and 5-CT in wild-type mice was similar to that previously reported for rats. CP-122,288 (1 nmol kg), 5-CT (1 nmol/kg), and dihydroergotamine (72 nmol/kg) inhibited plasma protein extravasation within dura mater after electrical trigeminal ganglion stimulation in both wild-type and knockout mice, which suggests that these agonists act predominantly via receptors other than 5-HT1B. Unlike in wild-type mice, CP-93,129 (1.4 mu mol/kg), a specific 5-HT1B receptor agonist, had no effect in knockout mice. The same held true for sumatriptan (0.7 mu mol/kg) and GTI (0.6 mu mol/kg). These results suggest that CP-93,129, sumatriptan, and GTI exert their effects via 5-HT1B (5-HT1D beta) receptors in mice. C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. COLUMBIA UNIV,CTR NEUROL BEHAV,NEW YORK,NY 10032. IMMUNOTECH SA,MARSEILLE,FRANCE. PFIZER INC,DIV CENT RES,GROTON,CT 06340. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NINDS NIH HHS [NS21558] NR 29 TC 44 Z9 44 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAY PY 1996 VL 49 IS 5 BP 761 EP 765 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UK004 UT WOS:A1996UK00400001 PM 8622623 ER PT J AU Reaume, AG Elliott, JL Hoffman, EK Kowall, NW Ferrante, RJ Siwek, DF Wilcox, HM Flood, DG Beal, MF Brown, RH Scott, RW Snider, WD AF Reaume, AG Elliott, JL Hoffman, EK Kowall, NW Ferrante, RJ Siwek, DF Wilcox, HM Flood, DG Beal, MF Brown, RH Scott, RW Snider, WD TI Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury SO NATURE GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; MUTATIONS AB The discovery that some cases of familial amyotrophic lateral sclerosis (FALS) are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) has focused much attention on the function of SOD1 as related to motor neuron survival. Here we describe the creation and characterization of mice completely deficient for this enzyme. These animals develop normally and show no overt motor deficits by 6 months in age. Histological examination of the spinal cord reveals no signs of pathology in animals 4 months in age. However Cu/Zn SOD-deficient mice exhibit marked vulnerability to motor neuron loss after axonal injury. These results indicate that Cu/Zn SOD is not necessary for normal motor neuron development and function but is required under physiologically stressful conditions following injury. C1 WASHINGTON UNIV,SCH MED,DEPT NEUROL,CTR STUDY NERVOUS SYST INJURY,ST LOUIS,MO 63110. VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,BEDFORD,MA. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,CECIL B LAB NEUROMUSCULAR RES,BOSTON,MA 02114. RP Reaume, AG (reprint author), CEPHALON INC,DEPT MOLEC BIOL,145 BRANDYWINE PKWY,W CHESTER,PA 19380, USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NIA NIH HHS [AG05681, AG12922-01]; NINDS NIH HHS [1P0 1NS31248-03] NR 23 TC 828 Z9 847 U1 1 U2 29 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1996 VL 13 IS 1 BP 43 EP 47 DI 10.1038/ng0596-43 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA UH430 UT WOS:A1996UH43000014 PM 8673102 ER PT J AU Manome, Y Wen, PY Dong, YH Tanaka, T Mitchell, BS Kufe, DW Fine, HA AF Manome, Y Wen, PY Dong, YH Tanaka, T Mitchell, BS Kufe, DW Fine, HA TI Viral vector transduction of the human deoxycytidine kinase cDNA sensitizes glioma cells to the cytotoxic effects of cytosine arabinoside in vitro and in vivo SO NATURE MEDICINE LA English DT Article ID HIGH-DOSE 1-BETA-D-ARABINOFURANOSYLCYTOSINE; ACUTE MYELOCYTIC-LEUKEMIA; HUMAN ADENOVIRUS TYPE-5; DNA POLYMERASE; GENE-TRANSFER; RAT MODEL; ARA-C; ADRIAMYCIN; TRANSPORT; TOXICITY AB Cytosine arabinoside (ara-C) is a cytidine analog that incorporates into replicating DNA and induces lethal DNA strand breaks. Although ara-C is a potent antitumor agent for hematologic malignancies, it has only minimal activity against most solid tumors. The rate-limiting step in intracellular ara-C activation is phosphorylation of the prodrug by deoxycytidine kinase (dCK). The present results demonstrate that both retroviral and adenoviral vector-mediated transduction of the dCK cDNA results in marked sensitization of glioma cell lines to the cytotoxic effects of ara-C in vitro. We also demonstrate that ara-C treatment of established intradermal and intracerebral gliomas transduced with dCK results in significant antitumor effects in vivo. These data suggest that viral vector transduction of the dCK gene followed by treatment with ara-C represents a new chemosensitization strategy for cancer gene therapy. C1 DANA FARBER CANC INST,DIV CANC PHARMACOL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV NEUROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27599. NR 35 TC 100 Z9 102 U1 0 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1996 VL 2 IS 5 BP 567 EP 573 DI 10.1038/nm0596-567 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UJ230 UT WOS:A1996UJ23000041 PM 8616717 ER PT J AU Schwartz, MW Peskind, E Raskind, M Boyko, EJ Porte, D AF Schwartz, MW Peskind, E Raskind, M Boyko, EJ Porte, D TI Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans SO NATURE MEDICINE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; INSULIN; BRAIN; TRANSPORT AB The adipocyte hormone, leptin (OB protein), is proposed to be an ''adiposity signal'' that acts in the brain to lower food intake and adiposity(1-5). As plasma leptin levels are elevated in most overweight individuals, obesity may be associated with leptin resistance(6,7). To investigate the mechanisms underlying brain leptin uptake and to determine whether reduced uptake may contribute to leptin resistance, we measured immunoreactive leptin levels in plasma and cerebrospinal fluid (CSF) of 53 human subjects. Leptin concentrations in CSF were strongly correlated to the plasma level in a nonlinear manner (r = 0.92; P = 0.0001). Like levels in plasma, CSF leptin levels were correlated to body mass index (r = 0.43; P = 0.001), demonstrating that plasma leptin enters human cerebrospinal fluid in proportion to body adiposity. However, the efficiency of this uptake (measured as the CSF:plasma leptin ratio) was lower among those in the highest as compared with the lowest plasma leptin quintile (5.4-fold difference). We hypothesize that a saturable mechanism mediates CSF leptin transport, and that reduced efficiency of brain leptin delivery among obese individuals with high plasma leptin levels results in apparent leptin resistance. C1 UNIV WASHINGTON,SCH MED,DEPT PSYCHIAT & BEHAV SCI,EDUC & CLIN CTR,SEATTLE,WA 98105. UNIV WASHINGTON,SCH MED,DEPT GERIATR RES,EDUC & CLIN CTR,SEATTLE,WA 98105. VET AFFAIRS PUGET SOUND HLTH CARE SYST,SEATTLE,WA 98108. RP Schwartz, MW (reprint author), UNIV WASHINGTON,SCH MED,DEPT MED,SEATTLE,WA 98105, USA. RI Schwartz, Michael/H-9950-2012 FU NIA NIH HHS [AG 05136]; NIDDK NIH HHS [DK 12829]; NINDS NIH HHS [NS 32273] NR 18 TC 697 Z9 707 U1 2 U2 20 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1996 VL 2 IS 5 BP 589 EP 593 DI 10.1038/nm0596-589 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UJ230 UT WOS:A1996UJ23000046 PM 8616722 ER PT J AU Abraham, EH Vos, P Kahn, J Grubman, SA Jefferson, DM Ding, I Okunieff, P AF Abraham, EH Vos, P Kahn, J Grubman, SA Jefferson, DM Ding, I Okunieff, P TI Cystic fibrosis hetero- and homozygosity is associated with inhibition of breast cancer growth SO NATURE MEDICINE LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; ANTICANCER ACTIVITIES; ADENINE-NUCLEOTIDES; ANIMAL-MODEL; GENE; CELLS; MICE AB Cystic fibrosis (CF) is the most common lethal recessive genetic disease of the Caucasian population. Although reports of cancer frequency in CF have emphasized an elevated observed-to-expected ratio of 6.5 for digestive tract cancers, these studies also show a significantly decreased observed-to-expected ratio for other malignancies including breast cancer. The cystic fibrosis transmembrane conductance regulator (CFTR) functions as an ATP channel(1-3). We found that heterozygous and homozygous CFTR knockout mice had elevated blood ATP concentrations. Elevated extracellular ATP is known to inhibit tumor growth in vivo and in vitro(4-7). Using double mutant mice created by F-2 generation crosses of CFTR knockout and nude mice, we observed reduced breast tumor implantability in CFTR homozygous nude animals. Decreased tumor growth rate was observed in both CFTR heterozygous and homozygous nude animals. Extracellular ATP reduced human tumor cell growth rate in vitro, and a breast transfected with human CFTR that had high extracellular ATP concentrations in vitro correspondingly had a slower growth rate in vivo. The results suggest that both CFTR heterozygosity and homozygosity suppress breast cancer growth and that elevated extracellular ATP can account for this phenomenon. C1 MASSACHUSETTS GEN HOSP,DEPT RADIAT ONCOL,BOSTON,MA 02114. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT PHYSIOL & PEDIAT,BOSTON,MA 02111. RP Abraham, EH (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 42 Z9 42 U1 1 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAY PY 1996 VL 2 IS 5 BP 593 EP 596 DI 10.1038/nm0596-593 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UJ230 UT WOS:A1996UJ23000047 PM 8616723 ER PT J AU Pronovost, PH Brady, HR Gunning, ME Espinoza, O Rennke, HG AF Pronovost, PH Brady, HR Gunning, ME Espinoza, O Rennke, HG TI Clinical features, predictors of disease progression and results of renal transplantation in fibrillary/immunotactoid glomerulopathy SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Article DE amyloid; cryoglobulinaemia fibrils; fibrillary glomerulonephritis; fibrillary glomerulopathy; glomerulonephritis; immunotactoid glomerulopathy; kidney diseases; lymphoma; leukaemia; multiple myeloma; transplantation ID NONAMYLOIDOTIC FIBRILLARY GLOMERULOPATHY; IMMUNOTACTOID GLOMERULOPATHY; MONOCLONAL GAMMOPATHY; NEPHROTIC SYNDROME; GLOMERULONEPHRITIS; DEPOSITS; PATIENT; AMYLOIDOSIS; ENTITY; IMMUNOFLUORESCENCE AB Background. The clinical manifestations of fibrillary-immunotactoid glomerulopathy are still being appreciated. It is unclear whether fibrillary-immunotactoid glomerulopathy represents two distinct clinicopathological entities, fibrillary glomerulopathy (FG) immunotactoid glomerulopathy (ITG), or a single disease with different ultrastructural variants. Methods. To address these issues, we analysed the clinical features of 186 patients with fibrillary-immunotactoid glomerulopathy referred to our institutions (25 patients) or reported in the literature (161 patients). In separate analyses, patients were subclassified as having either fibrillary glomerulopathy (FG) or immunotactoid glomerulopathy (ITG) according to fibril diameter (FG less than or equal to 30 nm, ITG>30 nm) or arrangement (FG, random; ITG, focally organized). Results. Proteinuria (FG similar to 100%, ITG similar to 100%), nephrotic syndrome( FG similar to 71%, ITG similar to 82%), haematuria (FG similar to 71%, ITG similar to 64%), hypertension (FG similar to 67%, ITG similar to 45%), and renal insufficiency (FG similar to 54%, ITG similar to 42%) were frequent clinical correlates of both FG and ITG, irrespective of the ultrastructural criteria for diagnosis. Twenty-five patients presenting to our institutions (24 FG, 1 ITG) were divided into three groups based on rate of decline of GFR (mean slope of 1/serum creatinine versus time: group 1 -0.103+/-0.238; group 2 0.121+/-0.040; group 3 0.466+/-0.318) in an attempt to identify clinical predictors of progression at presentation. Rapid progressors (Group 3) had an increased incidence of nephrotic syndrome and tended to have higher blood pressure than patients with milder disease, but did not differ from other groups in age, prevalence of haematuria or degree of renal insufficiency. The number of patients requiring dialysis was 0/10 in group 1, 2/6 in group 2, and 2/4 in group 3 over a follow-up period of 47+/-46, 55+/-32, and 19+/-19 months respectively; two predialysis deaths being recorded in group 3. Four patients received five renal allografts (one patient being transplanted twice) and were followed for 4-11 years. Whereas recurrence of FG was documented in three allografts undergoing post-transplant biopsy, the rate of deterioration of GFR was invariably slower in allografts than native kidneys (mean slope of 1/Cr versus time: 0.036+/-0.01 versus 0.301+/-0.18 respectively). The strength of association between FG-ITG and lymphoproliferative malignancy varied depending on whether patients with monoclonal-gammopathy-associated fibrillary deposits were included or excluded from the analysis. Conclusions. We contend that patients presenting with Congo-red-negative fibrillary deposits on renal biopsy should be evaluated carefully for monoclonal gammopathy and cryoglobulins, but that there is insufficient published data, as yet, to justify subclassification of FG and ITG as distinct clinicopathological entities. Indeed, we argue that it remains to be determined if FG-ITG represents a unique condition or a forme fruste of cryoglobulin- or monoclonal-gammopathy-associated renal disease. Although the optimal treatment for FG-ITG has not been determined, renal transplantation appears an attractive option in patients with end-stage renal failure. C1 UNIV DUBLIN TRINITY COLL,MATER MISERICORDIAE HOSP,DEPT MED,DUBLIN 7,IRELAND. BRIGHAM & WOMENS HOSP,DEPT MED,DIV RENAL,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,JOSLIN DIABET CTR,RENAL DIV,BOSTON,MA 02215. NR 39 TC 68 Z9 73 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD MAY PY 1996 VL 11 IS 5 BP 837 EP 842 PG 6 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA UM770 UT WOS:A1996UM77000020 ER PT J AU Harr, SD Hollister, RD Hyman, BT AF Harr, SD Hollister, RD Hyman, BT TI Glycogen synthase kinase 3 alpha and 3 beta do not colocalize with neurofibrillary tangles SO NEUROBIOLOGY OF AGING LA English DT Article DE glycogen synthase kinase; Alzheimer's disease; neurofibillary tangles; tau; kinase; hippocampus ID RABBIT SKELETAL-MUSCLE; DEPENDENT PROTEIN PHOSPHATASE; PAIRED HELICAL FILAMENTS; ALZHEIMER-LIKE STATE; TAU-PROTEIN; ACTIVATING FACTOR; DISEASE; PHOSPHORYLATION; LOCALIZATION; PURIFICATION AB Glycogen synthase kinase (GSK) 3 alpha and 3 beta are two proline-directed serine/threonine kinases that have been shown in vitro to hyperphosphorylate tau, and therefore, may contribute to neurofibillary tangle (NFT) formation in Alzheimer's disease (AD). We report here that, in the human hippocampal formation of both control and AD individuals, GSK 3 alpha and 3 beta are immunohistochemically localized to neurons within the presubiculum > CA1, CA3, and CA4 subfields of the hippocampus, layers III > II > IV, V, VI of entorhinal cortex, and occasional neurons in layers III, V, and VI of temporal neocortex. By contrast, NFTs occur primarily in CA1, subiculum, layers II and IV of entorhinal cortex, and layers II, III, and V of temporal neocortex. The presubiculum and other subfields are frequently spared. Thus, localization of GSK 3 alpha. and GSK 3 beta does not correspond to the expected pattern of neuronal vulnerability to NFT formation in AD. Interpreted within the limitations of immunohistochemical detection, these results argue against a major role of GSK 3 alpha or GSK 3 beta in NFT formation in AD. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. FU NIA NIH HHS [AG11337, AG08487] NR 29 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD MAY-JUN PY 1996 VL 17 IS 3 BP 343 EP 348 DI 10.1016/0197-4580(96)00025-5 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA UN895 UT WOS:A1996UN89500003 PM 8725894 ER PT J AU Brooks, BR AF Brooks, BR TI Clinical epidemiology of amyotrophic lateral sclerosis SO NEUROLOGIC CLINICS LA English DT Review ID MOTOR-NEURON-DISEASE; LONGITUDINAL GOMPERTZIAN ANALYSIS; DETERMINISTIC MORTALITY DYNAMICS; PARKINSONISM-DEMENTIA; UNITED-STATES; MOTONEURON DISEASE; MULTIPLE-SCLEROSIS; ANTECEDENT EVENTS; RISING MORTALITY; RISK-FACTORS AB The introduction of palliative therapies in amyotrophic lateral sclerosis (ALS) will alter the epidemiology of ALS as it is known now. Although incidence rates will remain unchanged in the near future, prevalence rates will likely increase dramatically. Better understanding of the age-specific presentation of motor neuron diseases worldwide will shed light on the vexing questions concerning the variable incidence rates in some countries and apparent incidence gradients in North America and Europe. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR, NEUROL SERV, MADISON, WI 53705 USA. GREAT LAKES VET INTEGRATED SERV NETWORK, MADISON, WI USA. UNIV WISCONSIN, SCH MED, MADISON, WI USA. RP Brooks, BR (reprint author), UNIV WISCONSIN HOSP & CLIN, ALS CLIN RES CTR, 600 HIGHLAND AVE, CSC H6-558, MADISON, WI 53792 USA. FU NCRR NIH HHS [M01RR03186] NR 297 TC 42 Z9 44 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 EI 1557-9875 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 1996 VL 14 IS 2 BP 399 EP + DI 10.1016/S0733-8619(05)70264-4 PG 0 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UM723 UT WOS:A1996UM72300012 PM 8827179 ER PT J AU Morens, DM Grandinetti, A Waslien, CI Park, CB Ross, GW White, LR AF Morens, DM Grandinetti, A Waslien, CI Park, CB Ross, GW White, LR TI Case-control study of idiopathic Parkinson's disease and dietary vitamin E intake SO NEUROLOGY LA English DT Article ID EPIDEMIOLOGY; HAWAII; MEN AB A nested case-control study of 84 incident cases of patients with idiopathic Parkinson's disease (PD) detected by June 30, 1994 and 336 age-matched control subjects, compared previously-documented intake of total dietary vitamin E and of selected vitamin E-containing foods, All study subjects had been followed for 27 to 30 years after diet recording in the 8,006-man Honolulu Heart Study cohort. We determined PD outcomes by periodic cohort re-examination and neurologic testing, private physician reports, examination of O'ahu neurologists' office records, and continual death certificate and hospital discharge diagnosis surveillance. Data on vitamin E intake, obtained from three dietary data sets at the time of cohort enrollment (1965 to 1968), included a food-frequency questionnaire and a 24-hour photograph-assisted dietary recall administered by trained dietitians. Although absence of PD was significantly associated with prior consumption of legumes (adjusted OR = 0.27, 95% CI 0.09 to 0.78), a dietary variable preselected for high vitamin E content, neither food categories nor quartiles nor continuous variables of vitamin E consumption were significantly associated with PD occurrence, Though consistent with prior reports of PD protection afforded by legumes, and with speculation on the possible benefits of dietary or supplemental vitamin E in preventing PD, these preliminary data do not conclusively document a beneficial effect of dietary vitamin E on PD occurrence. C1 UNIV HAWAII,SCH PUBL HLTH,DEPT PUBL HLTH,HONOLULU,HI 96822. UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI 96822. NIA,NIH,EAST WEST CTR,HONOLULU,HI. NIA,NIH,NAT HAWAII HLTH PROGRAM,HONOLULU,HI. NIA,NIH,QUEENS MED CTR,HONOLULU,HI. NIA,NIH,US DEPT VET AFFAIRS,HONOLULU,HI. NIA,NIH,HONOLULU ASIA AGING STUDY,HONOLULU,HI. FU NINDS NIH HHS [NS 30371] NR 34 TC 48 Z9 48 U1 0 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAY PY 1996 VL 46 IS 5 BP 1270 EP 1274 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA UK628 UT WOS:A1996UK62800014 PM 8628465 ER PT J AU Hyman, SE AF Hyman, SE TI Addiction to cocaine and amphetamine SO NEURON LA English DT Review C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,LAB MOL & DEV NEUROSCI,BOSTON,MA 02114. NR 18 TC 173 Z9 173 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD MAY PY 1996 VL 16 IS 5 BP 901 EP 904 DI 10.1016/S0896-6273(00)80111-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UN480 UT WOS:A1996UN48000003 PM 8630246 ER PT J AU Panahian, N Yoshida, T Huang, PL HedleyWhyte, ET Dalkara, T Fishman, MC Moskowitz, MA AF Panahian, N Yoshida, T Huang, PL HedleyWhyte, ET Dalkara, T Fishman, MC Moskowitz, MA TI Attenuated hippocampal damage after global cerebral ischemia in mice mutant in neuronal nitric oxide synthase SO NEUROSCIENCE LA English DT Article DE global ischemia; nitric oxide; neurotoxicity; neuronal NOS gene ID TRANSIENT FOREBRAIN ISCHEMIA; BILATERAL HEMISPHERIC ISCHEMIA; INDUCED BRAIN-DAMAGE; 2-VESSEL OCCLUSION; RAT; INJURY; HYPOTHERMIA; GERBILS; MODEL; HALOTHANE AB To address the importance of nitric oxide or its reaction products as mediators of neurotoxicity in brain, tissue injury was assessed after transient global ischemia in mice rendered mutant in the gene for neuronal nitric oxide synthase. Halothane-anesthetized wild type and mutant mice were subjected to temporary occlusion of the basilar plus both carotid arteries for 5 or 10 min followed by three days of reperfusion. Hippocampal injury, assessed both by qualitative grading and by cell counting in the CA1 subregion, was Significantly less in the mutant mice group after 5 or 10 min of ischemia. Mutant mice exhibited a lower mortality (P < 0.01), less weight loss, more normal grooming and spontaneous motor activity and better grasping in the 10 min group. There were no obvious differences in cerebrovascular anatomy or hemodynamics between wild type and mutant mice. The data suggest that a deficiency of neuronal nitric oxide synthase confers increased resistance to transient global cerebral ischemia, and support the suggestion that selective neuronal nitric oxide synthase inhibitors might reduce tissue injury associated with global cerebral ischemia. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT SURG,STROKE & NEUROVASC REGULAT SECT NEUROSU,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,DEPT NEUROL,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,CARDIOVASC RES CTR,BOSTON,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PATHOL,BOSTON,MA 02129. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [NS 10828, NS 33335-01, NS 64361] NR 72 TC 137 Z9 141 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1996 VL 72 IS 2 BP 343 EP 354 DI 10.1016/0306-4522(95)00563-3 PG 12 WC Neurosciences SC Neurosciences & Neurology GA UF982 UT WOS:A1996UF98200005 PM 8737405 ER PT J AU Eisenberg, E Vos, BP Strassman, AM AF Eisenberg, E Vos, BP Strassman, AM TI The peripheral antinociceptive effect of morphine in a rat model of facial pain SO NEUROSCIENCE LA English DT Article DE opioid receptors; formalin test; vibrissal pad; pain behavior ID RECEPTORS MEDIATING ANTINOCICEPTION; FORMALIN TEST; OPIOID RECEPTORS; INFLAMMATORY PAIN; MICE; DISSOCIATION; NOCICEPTION; INVOLVEMENT; BRADYKININ; ACTIVATION AB The present study compared the peripheral and systemic antinociceptive effect of morphine on formalin-induced facial pain behavior in the rat. Formalin (5%, 50 mu l) was injected subcutaneously into the vibrissal pad of adult rats (250-300 g). Morphine sulfate at doses of 100-1000 mu g was subcutaneously injected locally (same area) or systemically (in the neck), 30 min before, or simultaneously with, formalin. The typical biphasic face grooming response, consisting of an early phasic phase (0-6 min) and a delayed tonic phase (12-42 min), displayed by control animals, was suppressed by both local and systemic administration of morphine; this effect was dose dependent. However, the suppression of the early phase with local morphine administration 30 min before formalin could be significantly greater (49-52%) than with systemic administration, depending on the dose used. Administration of local morphine simultaneously with formalin produced up to 34% reduction in the early and an additional 32% reduction of the late phases of Face grooming, compared to systemic injections. Local injection of naloxone (10 mu g) almost completely reversed the antinociceptive effect of 1000 mu g of morphine (early phase 85 +/- 7%, late phase 100 +/- 26% reduction), whereas the same dose of naloxone applied systemically (i.p.) produced only partial reversal (early phase 29 +/- 16%, late phase 36 +/- 1% reduction). This study further indicates that locally administered morphine can exert an analgesic effect superior to systemic administration in the case of inflammatory and non-inflammatory pain through a peripheral site of action. These results support the clinical use of peripheral opioid administration in the treatment of human painful conditions. C1 MASSACHUSETTS GEN HOSP, DEPT NEUROL, BOSTON, MA 02115 USA. HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, DEPT ANESTHESIA, BOSTON, MA 02115 USA. RAMBAM MED CTR, PAIN RELIEF CLIN, IL-35254 HAIFA, ISRAEL. NR 35 TC 54 Z9 55 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1996 VL 72 IS 2 BP 519 EP 525 DI 10.1016/0306-4522(95)00565-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA UF982 UT WOS:A1996UF98200020 PM 8737420 ER PT J AU Moskowitz, MA Waeber, C AF Moskowitz, MA Waeber, C TI Migraine enters the molecular era SO NEUROSCIENTIST LA English DT Article DE trigeminovascular system; 5-HT1D receptors ID RAT DURA-MATER; GENE-RELATED PEPTIDE; PLASMA-PROTEIN EXTRAVASATION; TRIGEMINAL NUCLEUS CAUDALIS; GUINEA-PIG BRAIN; BLOOD-VESSELS; SUBSTANCE-P; SPREADING DEPRESSION; VASCULAR HEADACHES; CEREBRAL-ARTERIES AB Migraine headache is the first neurological condition treatable by a drug targeted to a specific receptor binding site. Originally viewed as a disorder of brain blood vessels, migraine may have as its biological basis a disturbance in brain function. Regarding therapy, recent molecular data document that 5-HT1D receptors on primary afferent fibers are coupled to inhibition of neuropeptide release, blockade of neurogenic inflammation, and c-fos expression within the trigeminal nucleus caudalis after noxious meningeal stimulation in experimental animals. The 5-HT1D alpha receptor subtype (as opposed to the 5-HT1D beta receptor) has emerged as an important therapeutic target aimed at blocking trigeminal nerve fibers without constricting vascular smooth muscle. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROSURG,STROKE & NEUROVASCULAR REGULAT LAB,CHARLESTOWN,MA 02129. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT NEUROL,CHARLESTOWN,MA 02129. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 58 TC 8 Z9 8 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD MAY PY 1996 VL 2 IS 3 BP 191 EP 200 DI 10.1177/107385849600200314 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VX113 UT WOS:A1996VX11300014 ER PT J AU Chen, JJ Peters, R Saha, P Lee, P Theodoras, A Pagano, M Wagner, G Dutta, A AF Chen, JJ Peters, R Saha, P Lee, P Theodoras, A Pagano, M Wagner, G Dutta, A TI A 39 amino acid fragment of the cell cycle regulator p21 is sufficient to bind PCNA and partially inhibit DNA replication in vivo SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DEPENDENT KINASES; POLYMERASE-DELTA; NUCLEAR ANTIGEN; PROTEIN; SUBUNIT; INVITRO; P53; RPA AB The cell cycle regulator p21 interacts with and inhibits the DNA replication and repair factor proliferating cell nuclear antigen (PCNA). We have defined a 39 amino acid fragment of p21 which is sufficient to bind PCNA with high affinity (Kd 10-20 nM). This peptide can inhibit DNA replication in vitro and microinjection of a GST fusion protein containing this domain inhibited S phase in vivo. Despite its high affinity for PCNA, the free 39 amino acid peptide does not have a well-defined structure, as judged from circular dichroism and nuclear magnetic resonance measurements, suggesting an induced fit mechanism for the PCNA-p21 interaction. The association of the small peptide with PCNA was thermolabile, suggesting that portions of p21 adjoining the minimal region of contact stabilize the interaction. In addition, a domain containing 67 amino acids from the N-terminus of PCNA was defined as both necessary and sufficient for binding to p21. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT PATHOL,DIV MOLEC ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MITOTIX INC,CAMBRIDGE,MA 02139. RI Dutta, Anindya/P-3203-2016 FU NCI NIH HHS [R01 CA060499, CA60499, R01 CA060499-02S1] NR 41 TC 67 Z9 73 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 1 PY 1996 VL 24 IS 9 BP 1727 EP 1733 DI 10.1093/nar/24.9.1727 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UL787 UT WOS:A1996UL78700020 PM 8649992 ER PT J AU McHenry, CR Azar, T Ramahi, AJ Collins, PL AF McHenry, CR Azar, T Ramahi, AJ Collins, PL TI Monomicrobial necrotizing fasciitis complicating pregnancy and puerperium SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB Background: Necrotizing fasciitis is an uncommon, rapidly progressive, life-threatening infection involving the subcutaneous tissue and fascia. Usually, it is a synergistic polymicrobic infection that occurs in patients with coexisting factors predisposing them to bacterial inoculation and the spread of infection. Cases: We report a monomicrobial variant of necrotizing fasciitis affecting three otherwise healthy pregnant or postpartum women. The necrotizing fasciitis involved either the lower extremity or the abdominal wall. The causative bacteria were Steptococcus pyogenes (two cases) and Staphylococcus aureus (one). All patients presented with an acute fulminant infection, including one woman who died from overwhelming sepsis. Conclusion: These cases raise a question about the possible role of increased bacterial virulence and the immunologic changes of pregnancy as potential predisposing factors in the development of necrotizing fasciitis. C1 CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,SCH MED,DEPT OBSTET & GYNECOL,CLEVELAND,OH 44109. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. RP McHenry, CR (reprint author), CASE WESTERN RESERVE UNIV,METROHLTH MED CTR,SCH MED,DEPT SURG,2500 METROHLTH DR,CLEVELAND,OH 44109, USA. NR 8 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1996 VL 87 IS 5 BP 823 EP 826 PN 2 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UG785 UT WOS:A1996UG78500010 PM 8677102 ER PT J AU Kasahara, N Sibayan, SA Montenegro, MH Simmons, RB Smith, TJ AF Kasahara, N Sibayan, SA Montenegro, MH Simmons, RB Smith, TJ TI Corneal incision phacoemulsification and internal bleb revision SO OPHTHALMIC SURGERY AND LASERS LA English DT Article ID TRABECULECTOMY AB BACKGROUND AND OBJECTIVE: Cataract extraction in filtered eyes often leads to decreased outflow and, eventually, to bleb failure. The authors describe a surgical technique that promotes preservation of the filtering bleb. PATIENTS AND METHODS: The authors retrospectively reviewed 19 eyes of 19 consecutive patients who underwent corneal incision phacoemulsification and simultaneous internal revision of the previous filtering bleb. RESULTS: The mean follow-up time was 13.6 +/- 7.6 months. Visual acuity improved in all patients (89.4% achieved 20/40 or better). No significant difference was noted between preoperative and postoperative intraocular pressures and astigmatism The bleb was preserved in 89.4% of the eyes at the time of the last follow-up. CONCLUSIONS: This surgical technique proved to be safe and yielded good results. C1 NEW ENGLAND EYE RES FDN,BOSTON,MA. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. SCHEPENS EYE RES INST,BOSTON,MA. RI Kasahara, Niro/N-8865-2014 OI Kasahara, Niro/0000-0003-4101-0304 NR 15 TC 5 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD MAY PY 1996 VL 27 IS 5 BP 361 EP 366 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA UM393 UT WOS:A1996UM39300005 PM 8860602 ER PT J AU Weissgold, DJ Maguire, AM Brucker, AJ AF Weissgold, DJ Maguire, AM Brucker, AJ TI Management of postoperative Acremonium endophthalmitis SO OPHTHALMOLOGY LA English DT Article ID INTRAOCULAR-LENS IMPLANTATION; CANDIDA-PARAPSILOSIS ENDOPHTHALMITIS; FUNGAL ENDOPHTHALMITIS; AMPHOTERICIN-B; PSEUDOPHAKIC ENDOPHTHALMITIS; FLUCONAZOLE; DIAGNOSIS; INFECTION; THERAPY AB Purpose: Four patients presented after cataract surgery with delayed-onset endophthalmitis caused by Acremonium kiliense with in vitro sensitivity to amphotericin B. In all patients, ocular infection was recalcitrant to single-dose intravitreous amphotericin B injection. The authors reviewed the management of endophthalmitis caused by A. kiliense and presented treatment recommendations. Methods: The authors retrospectively evaluated a cluster of four patients with delayed-onset postoperative endophthalmitis after phacoemulsification with posterior chamber intraocular lens implantation. All patients underwent vitreous sampling, intravitreous injection of amphotericin B, and systemic administration of fluconazole. Pars plana vitrectomy was performed in all patients for management of either primary(1 eye) or persistent infection (3 eyes). Two patients with persistent infection also underwent surgical explanation of their posterior chamber intraocular lens. Results: Worsening infection developed in three of three eyes that underwent vitireous aspiration with intravitreous injection of 5 mu g amphotericin B. These patients subsequently responded to vitrectomy followed by additional intravitreous amphotericin B injection. One eye underwent primary vitrectomy and intravitreous injection of 7.5 mu g amphotericin B. Although treatment of the initial infection was successful, fungal keratitis developed in this patient 3 months after presentation. Visual outcome was variable, ranging from visual acuity of 20/25 to no light perception with follow-up of 2 years. Epidemiologic investigation suggested a common environmental source for the A. kiliense organisms. Conclusions: Single-dose administration of intravitreous amphotericin a was inadequate treatment for fungal endophthalmitis caused by A. kiliense. Vitrectomy with repeated intravitreous administration of amphotericin B may be necessary to eradicate intraocular infection caused by this organism. C1 UNIV PENN,SCHEIE EYE INST,DEPT OPHTHALMOL,PHILADELPHIA,PA 19104. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. NR 39 TC 23 Z9 23 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1996 VL 103 IS 5 BP 749 EP 756 PG 8 WC Ophthalmology SC Ophthalmology GA UL481 UT WOS:A1996UL48100015 PM 8637683 ER PT J AU Tamesis, RR Rodriguez, A Christen, WG Akova, YA Messmer, E Foster, CS AF Tamesis, RR Rodriguez, A Christen, WG Akova, YA Messmer, E Foster, CS TI Systemic drug toxicity trends in immunosuppressive therapy of immune and inflammatory ocular disease SO OPHTHALMOLOGY LA English DT Article ID LOW-DOSE METHOTREXATE; RHEUMATOID-ARTHRITIS; LIVER HISTOLOGY; AZATHIOPRINE; COMPLICATIONS; CYCLOPHOSPHAMIDE; HEPATOTOXICITY; CHLORAMBUCIL; CYCLOSPORIN; BIOPSIES AB Purpose: To compare the relative toxicities of six systemic immunosuppressive drugs and systemic corticosteroids used to treat patients with severe ocular inflammatory disease and to identify factors influencing their occurrence. Methods: The authors reviewed the clinical records of 602 patients with ocular inflammatory disease treated with immunosuppressive drug therapy and/or systemic corticosteroids for adverse systemic effects while undergoing therapy. Proportional hazards regression analysis was performed to identify demographic and clinical factors that influence the occurrence of drug toxicity in these patients. Results: Immunosuppressive drug treatment was more likely to result in discontinuation of therapy because of toxic side effects than was corticosteroid treatment. However, unlike many of the side effects of corticosteroid treatment, the side effects of immunosuppressive therapy were reversible with reduction in dosage or discontinuation of the drug. Gastrointestinal symptoms and hematologic abnormalities accounted for the majority of reported side effects of the immunosuppressive medications. Neuropsychiatric and endocrine side effects were common in patients taking prednisone. In 17 patients treated with prednisone, pathologic fractures developed, which involved the hips and the spine. Female sex and age older than 60 years also were identified as factors associated with intolerance to drug therapy in the authors' study population. Race and type of systemic and ocular disease were not significant factors influencing tolerance to drug therapy. Conclusion: These findings suggest that when properly administered and monitored for adverse effects, most immunosuppressive agents used in the current study have similar risk profiles with relatively few serious therapeutic mishaps and largely reversible side effects. In contrast, corticosteroids can result in permanent disabilities as a result of long-term treatment. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,DEPT OPHTHALMOL,IMMUNOL & UVEITIS SERV,BOSTON,MA 02114. UNIV NEBRASKA,MED CTR,DEPT OPHTHALMOL,OMAHA,NE. OI Rodriguez-Garcia, Alejandro/0000-0002-1419-2109 NR 41 TC 38 Z9 41 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 1996 VL 103 IS 5 BP 768 EP 775 PG 8 WC Ophthalmology SC Ophthalmology GA UL481 UT WOS:A1996UL48100017 PM 8637685 ER PT J AU Townsend, JC AF Townsend, JC TI Pharmaceutical formulary for the primary care optometrist in a hospital and medical center SO OPTOMETRY AND VISION SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Optometry CY DEC 11, 1994 CL SAN DIEGO, CA SP Amer Acad Optometry RP Townsend, JC (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD MAY PY 1996 VL 73 IS 5 BP 328 EP 333 DI 10.1097/00006324-199605000-00011 PG 6 WC Ophthalmology SC Ophthalmology GA UP279 UT WOS:A1996UP27900011 PM 8771588 ER PT J AU Kung, DS Kaban, LB AF Kung, DS Kaban, LB TI Supratarsal fold incision for approach to the superior lateral orbit SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID FRACTURES AB Objective. To report and evaluate the use of the supratarsal fold incision for access to the lateral and superior orbit. Design. This is a retrospective evaluation of seven patients with zygomatic and orbital fractures who underwent repair with the supratarsal fold incision used to expose the frontozygomatic region or supraorbital rim. Data were obtained by review of hospital charts, radiographs, and by clinical examination. Results. Excellent exposure and access were obtained because of the proximity of the incision to the lateral and superior orbit. Mobility of the eyelid tissue allowed for atraumatic manipulation and retraction. All fractures were adequately reduced by clinical acid radiographic examination without complication. Conclusion. The supratarsal fold incision is a versatile incision for access to the zygomaticofrontal suture and supraorbital rim. In addition to providing excellent exposure, it produces a superb cosmetic result with a scar well-hidden in the skin folds of the upper eyelid. RP Kung, DS (reprint author), MASSACHUSETTS GEN HOSP,DEPT ORAL & MAXILLOFACIAL SURG,WARREN 1201,BOSTON,MA 02114, USA. NR 17 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAY PY 1996 VL 81 IS 5 BP 522 EP 525 DI 10.1016/S1079-2104(96)80040-0 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UM139 UT WOS:A1996UM13900007 PM 8734696 ER PT J AU Olsen, WA Li, BUK Lloyd, M Korsmo, H AF Olsen, WA Li, BUK Lloyd, M Korsmo, H TI Heterogeneity of intestinal lactase activity in children: Relationship to lactase-phlorizin hydrolase messenger RNA abundance SO PEDIATRIC RESEARCH LA English DT Article ID ADULT-TYPE HYPOLACTASIA; RAT INTESTINE; EXPRESSION; RABBIT; BIOSYNTHESIS; ENTEROCYTES; DEFICIENCY; ENZYME; AGE AB Despite extensive study in both humans and nonhuman mammals the mechanisms which regulate intestinal lactase activity, particularly during development, are incompletely understood. Our previous studies of human adults are consistent with an important role of lactase-phlorizin hydrolase (LPH) mRNA abundance in determining the lactase persistence/nonpersistence phenotypes. Our intent in the present study was to determine the role of LPH mRNA in the regulation of lactase in children. We therefore studied duodenal mucosal biopsies from 39 children undergoing diagnostic upper endoscopy in whom significant small intestinal and nutritional disease was excluded. We found no relationship between the level of LPH mRNA and lactase enzymatic activity. Our observations suggest the importance of posttranscriptional mechanisms in lactase regulation in human children. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,GASTROENTEROL RES LAB,MADISON,WI 53705. OHIO STATE UNIV,COLUMBUS CHILDRENS HOSP,DEPT PEDIAT,COLUMBUS,OH 43205. FU NIDDK NIH HHS [R-29-DK45785] NR 36 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD MAY PY 1996 VL 39 IS 5 BP 877 EP 881 DI 10.1203/00006450-199605000-00023 PG 5 WC Pediatrics SC Pediatrics GA UG001 UT WOS:A1996UG00100023 PM 8726245 ER PT J AU Wharton, RH Levine, KR Buka, S Emanuel, L AF Wharton, RH Levine, KR Buka, S Emanuel, L TI Advance care planning for children with special health care needs: A survey of parental attitudes SO PEDIATRICS LA English DT Article DE advance directives; parents; chronic illness; decision making ID LIFE-SUSTAINING TREATMENT; MEDICAL-CARE; BAD-NEWS; PREFERENCES; DIAGNOSIS; PERCEPTIONS; PROXY AB Objectives. This study explored parental attitudes about their interactions with their children's providers when decision making involved critical life situations. We evaluated parents' attitudes regarding the following questions: What was the parents' understanding of their children's health care issues, and what was the parental perception of the professionals' understanding of their children and of themselves? Who should be the principal decision makers for the children? What was the parents' knowledge about advance directives? Did parents want to participate in a process of advance planning to assist with critical life decision making for their children? Methods. We surveyed all parents attending a conference sponsored by the Massachusetts Department of Public Health for parents of children with special needs. The questionnaire was provided to all parents attending the conference. An announcement was made at the conference requesting parental participation. The 76 respondents constitute a convenience sample of patents of children with special needs sufficient for this preliminary stage of investigation. Results. Of 177 parents attending the conference, 76 (43%) completed the questionnaire. Eighty-eight percent of the participants strongly agreed that they understood their children's conditions. Twenty-one percent stated that they had sufficient understanding of their children's future medical needs, and 21% thought that they had a sufficient understanding of their children's developmental potential. Ninety-nine percent of parents strongly agreed that physicians should share information with parents no matter how serious or potentially upsetting. Ninety-four percent of those parents who thought that their children's physicians understood their own needs also thought that the physicians understood their children's needs. In contrast, only half (55%) of those parents who thought the physicians did not understand their needs thought the physicians understood their children's needs. Ninety-two percent of parents who thought that the physicians understood their needs agreed that the physicians would make the best decisions in crises versus 60% of those who did not think the physicians understood their needs. Seventy-four percent stated that they would consider written guidelines for their children that dealt with critical life situations. All parents who thought their children's conditions were not understood wanted written guidelines. Of those parents who had thought their children would not survive (15 parents), 94% wanted written guidelines. All seven parents who had been told their children would not survive wanted written guidelines. Conclusions. Parents in this study were generally satisfied with care being provided to their children. Nevertheless, the results clearly suggest goals that could lead to improved capacity for parents and providers to make critical life decisions for and with children. First, physicians must understand the needs of parents to be able to make decisions that would be in the children's best interests. Second, parents should participate fully in critical life decisions for their children and should use written guidelines to assist with the process of these critical life decisions. Our findings strongly support the development of a longitudinal process, initiated early after the onset or discovery of illness and maintained longitudinally throughout the course of a child's illness, to help parents and providers work together in this vital area of health care to children. C1 SPAULDING REHABIL HOSP,DEPT PSYCHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,SERV PEDIAT,BOSTON,MA 02114. HARVARD UNIV,SCH PUBL HLTH,DEPT MATERNAL & CHILD HLTH,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV MED ETH,BOSTON,MA. CHILDRENS HOSP,DEPT PSYCHOL,BOSTON,MA 02115. RP Wharton, RH (reprint author), SPAULDING REHABIL HOSP,DEPT CHILD & ADOLESCENT MED,125 NASHUA ST,BOSTON,MA 02114, USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 35 TC 43 Z9 45 U1 2 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 1996 VL 97 IS 5 BP 682 EP 687 PG 6 WC Pediatrics SC Pediatrics GA UH758 UT WOS:A1996UH75800013 PM 8628607 ER PT J AU Demetri, GD AF Demetri, GD TI The emergence of peripheral blood progenitor cells to support intensive chemotherapy for patients with breast cancer SO PHARMACOTHERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; THERAPY AB Increasing evidence supports the hypothesis that ''dose'' is critical to the clinical outcomes of cytotoxic chemotherapy for patients with breast cancer. Clinical trials continue to investigate whether higher doses of chemotherapy lead to proportionate improvements in the outcomes of patients. Delivery of dose-intensive chemotherapy has been facilitated by technological advancements in supportive care. Improved antiemetics have led to increased patient tolerance of the most acute symptoms of aggressive chemotherapeutic dosing. Chemotherapy-induced myelosuppression may be minimized in a lineage-specific manner by appropriate use of hematopoietic cytokines such as filgrastim (granulocyte colony-stimulating factor), sargramostim (granulocyte-macrophage colony-stimulating factor), and/or epoetin alfa (erythropoietin). However, cumulative myelotoxicity occurs with dose-intensive chemotherapy over multiple cycles despite adjunctive cytokine support. Additionally no cytokine has yet been demonstrated to support platelet production to any clinically significant degree although several regulators of platelet production (such as thrombopoietin, IL-6, and IL-11) are in clinical trials. Many cytokines can induce the mobilization of hematopoietic progenitor and stem cells from the bone marrow into the circulating blood pool, where these cells may be harvested. Clinical use of these cytokine-mobilized peripheral blood progenitor cells (also known as PBPCs or, commonly as blood stem cells) has documented the effectiveness of these cells to reconstitute multilineage blood production following very high-dose chemotherapy. The ease with which PBPCs can be collected and their reproducible clinical effectiveness to support patients through intensive treatment protocols have led to a virtual elimination of bone marrow as the source of cellular support for myeloablative chemotherapy in many transplant centers. Novel investigative approaches are also possible with PBPCs. In this review. the historical background of PBPCs is summarized, and the potential benefits (including economic advantages) of PBPCs to support dose-intensive chemotherapy for treating breast cancer are discussed. While dose intensification of breast cancer chemotherapy to the degree requiring PBPC support remains controversial and, in most centers, investigational, there is no doubt that PBPCs are an effective adjunct to the hematopoietic support of patients undergoing transplant-level cytotoxic treatments. Further study will undoubtedly lead to increased use of PBPCs in novel treatments for patients with breast cancer and other solid tumors. RP Demetri, GD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED ONCOL,DIV CANC PHARMACOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 14 TC 4 Z9 4 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAY-JUN PY 1996 VL 16 IS 3 BP S94 EP S100 PN 2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UM606 UT WOS:A1996UM60600003 PM 8726588 ER PT J AU Cahalin, LP AF Cahalin, LP TI Heart failure SO PHYSICAL THERAPY LA English DT Article DE exercise; heart failure; rehabilitation ID LEFT-VENTRICULAR DYSFUNCTION; POSITIVE AIRWAY PRESSURE; SKELETAL-MUSCLE; MYOCARDIAL-INFARCTION; EXERCISE PERFORMANCE; DILATED CARDIOMYOPATHY; CARDIAC REHABILITATION; EJECTION FRACTION; CORONARY PATIENTS; SLEEP-APNEA AB Congestive heart failure (CHF) affects more than 2 million Americans and requires greater than 900,000 hospitalizations each year. The incidence of CHF is increasing because of the increasing age of the American population and tile use of newer medications and technologies that have increased survival at the expense of increased morbidity. Physical therapists are treating many patients who have varying degrees of CHF. Recent research has demonstrated the importance of exercise conditioning in patients with CHF. This article will review the pathophysiology, compensatory mechanisms, and signs and symptoms of CHF as well as provide a discussion of the role of physical therapy in the treatment of patients with CHF. RP Cahalin, LP (reprint author), MASSACHUSETTS GEN HOSP,PHYS THERAPY SERV,BIGELOW 858,BOSTON,MA 02114, USA. NR 83 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD MAY PY 1996 VL 76 IS 5 BP 516 EP 533 PG 18 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA UM477 UT WOS:A1996UM47700008 PM 8637939 ER PT J AU Mirza, N AF Mirza, N TI Otitis externa - Management in the primary care office SO POSTGRADUATE MEDICINE LA English DT Article AB Although mild cases of otitis externa often respond quickly to appropriate therapy, primary care physicians need to be alert to more severe infection, particularly in diabetic and immunocompromised patients. In these cases, uncomplicated infection may progress to deep invasion of bone and become potentially fatal if cranial nerves are affected. prompt referral to an otolaryngologist is recommended. C1 UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. RP Mirza, N (reprint author), VET AFFAIRS MED CTR,OTOLARYNGOL SECT,UNIV & WOODLAND AVE,PHILADELPHIA,PA 19104, USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAY PY 1996 VL 99 IS 5 BP 153 EP & PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA UK847 UT WOS:A1996UK84700017 PM 8650083 ER PT J AU Mandell, R Packman, S Laframboise, R Golbus, MS Schmidt, K Workman, L Saudubray, JM Shih, VE AF Mandell, R Packman, S Laframboise, R Golbus, MS Schmidt, K Workman, L Saudubray, JM Shih, VE TI Use of amniotic fluid aiming acids in prenatal testing for argininosuccinic aciduria and citrullinaemia SO PRENATAL DIAGNOSIS LA English DT Article DE prenatal diagnosis; argininosuccinic aciduria; citrullinaemia; urea cycle disorder; inborn error of metabolism ID DIAGNOSIS; RISK AB Prenatal testing of 12 pregnancies at risk for argininosuccinic aciduria due to argininosuccinate lyase (ASAL) deficiency and three pregnancies at risk for citrullinaemia due to argininosuccinate synthatase (ASAS) deficiency was performed by metabolite detection in amniotic fluid and measurement of enzyme activity in uncultured and cultured chorionic tissue and in cultured amniocytes. From our data and those of previous studies, amniotic fluid argininosuccinate measurement alone is clearly a reliable and rapid diagnostic test for both severe and mild ASAL deficiency if maternal ASAL deficiency can be excluded. For prenatal diagnosis of ASAS deficiency, however, both measurement of the amniotic fluid citrulline level and enzyme assay should be employed. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02129. UNIV SAN FRANCISCO,DEPT PEDIAT,DIV GENET,SAN FRANCISCO,CA 94117. CHU LAVAL,LAVAL,PQ G1V 4G2,CANADA. UNIV CALIF SAN FRANCISCO,DEPT OBSTET GYNECOL & REPROD SCI,SAN FRANCISCO,CA 94143. HOP NECKER ENFANTS MALAD,CLIN GENET,DEPT PEDIAT,F-75743 PARIS,FRANCE. FU NCRR NIH HHS [5-MO1-RR-01271]; NINDS NIH HHS [NS05096] NR 21 TC 9 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAY PY 1996 VL 16 IS 5 BP 419 EP 424 DI 10.1002/(SICI)1097-0223(199605)16:5<419::AID-PD872>3.0.CO;2-7 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA UR368 UT WOS:A1996UR36800005 PM 8843999 ER PT J AU Brees, DK Hutchison, FN Cole, GJ Williams, JC AF Brees, DK Hutchison, FN Cole, GJ Williams, JC TI Differential effects of diabetes and glomerulonephritis on glomerular basement membrane composition SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID EXTRACELLULAR-MATRIX SYNTHESIS; PASSIVE HEYMANN NEPHRITIS; MESSENGER-RNA LEVELS; HEPARAN-SULFATE; IV COLLAGEN; PROTEINS; NEPHROPATHY; COMPONENTS; GLYCOSAMINOGLYCANS; PROTEOGLYCANS AB The hallmark of renal diseases involving the glomerulus is the presence of proteinuria. While the routes of pathogenesis of proteinuria have not been established, alterations in the barrier function of the glomerular basement membrane (GEM) have been implicated, We evaluated the effect of streptozotocin diabetes and passive Heymann nephritis (PHN) over time on the macromolecular composition of rat GEM to determine if changes in composition correlate with proteinuria. Six to twelve rats from each group (control, diabetic, and PHN) were sacrificed 1, 5, 28, 56, or 84 days after induction of disease, Identical amounts of GEM were subjected to a sequential extraction procedure, and type IV collagen, entactin, laminin, fibronectin, and anionic charge content were quantitated in the extracts. Type IV collagen and entactin content did not change with time or disease, Both laminin and fibronectin contents increased with time in GEM in all groups, but this increase was significantly greater in diabetic GEM. A significant decrease in anionic charge content of GBM coincided with the onset of albuminuria at Day 28 in diabetes, but no change was seen in PHN, In diabetic rats, the increase in laminin content over control preceded the onset of albuminuria, while the increase in fibronectin was not apparent until after albuminuria was present, In PHN, no differences in type IV collagen, entactin, laminin, fibronectin, or anionic charge content of GEM were found compared with control, even though profound albuminuria was evident from Day 5 through 84, Thus, while alterations in laminin and fibronectin content may contribute to the loss of glomerular permselectivity in streptozotocin diabetes, such changes apparently are not involved in PHN. C1 MED UNIV S CAROLINA,DEPT ANAT & CELL BIOL,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29425. RALPH H JOHNSON VET AFFAIRS MED CTR,CHARLESTON,SC 29425. OHIO STATE UNIV,CTR BIOTECHNOL,COLUMBUS,OH 43210. INDIANA UNIV,SCH MED,DEPT ANAT,INDIANAPOLIS,IN 46202. OI Williams, James/0000-0001-6665-6596 FU NIDDK NIH HHS [DK 43186, DK 39023] NR 42 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAY PY 1996 VL 212 IS 1 BP 69 EP 77 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UG751 UT WOS:A1996UG75100009 PM 8618954 ER PT J AU Garan, H AF Garan, H TI A perspective on the ESVEM trial and current knowledge: Sotalol should not be the first-line agent in the management of ventricular arrhythmias SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID ANTIARRHYTHMIC AGENTS; TACHYARRHYTHMIAS; FIBRILLATION; TACHYCARDIA; EFFICACY; SAFETY RP Garan, H (reprint author), MASSACHUSETTS GEN HOSP, CARDIAC UNIT, BULBA 036, 32 FRUIT ST, BOSTON, MA 02114 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-0620 EI 1873-1740 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAY-JUN PY 1996 VL 38 IS 6 BP 455 EP 456 DI 10.1016/S0033-0620(96)80009-0 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UN550 UT WOS:A1996UN55000004 PM 8638026 ER PT J AU Garan, H AF Garan, H TI A perspective on the ESVEM trial and current knowledge: Catheter ablation for ventricular tachyarrhythmias SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID TACHYCARDIA; EFFICACY; DISEASE; ORIGIN; SITE RP Garan, H (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BULBA 036,32 FRUIT ST,BOSTON,MA 02114, USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAY-JUN PY 1996 VL 38 IS 6 BP 457 EP 462 DI 10.1016/S0033-0620(96)80010-7 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UN550 UT WOS:A1996UN55000005 PM 8638027 ER PT J AU Miotto, K Compton, P Ling, W Conolly, M AF Miotto, K Compton, P Ling, W Conolly, M TI Diagnosing addictive disease in chronic pain patients SO PSYCHOSOMATICS LA English DT Article ID NON-MALIGNANT PAIN; PSYCHIATRIC-DISORDERS; COCAINE ABUSERS; MEDICATION; MANAGEMENT; THERAPY; ALCOHOLICS; COMMUNITY; ONSET; WOMEN AB As opiate therapy is increasingly accepted for the management of chronic pain, the consultation-liaison psychiatrist is often challenged to diagnose and provide treatment recommendations for addictive disease in chronic pain patients. Reviewed are the defining characteristics of addiction within the context of chronic pain, and the interesting commonalities between addictive disease and chronic pain. Guidelines for assessment of addiction in patients with chronic pain are presented, as are suggestions for the management of these concurrent disorders. Underlying this review is a belief that opiates should not be withheld from persons with chronic pain, even in the presence of addictive disease. C1 UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. LOS ANGELES ADDICT TREATMENT RES CTR,LOS ANGELES,CA. W LOS ANGELES VET AFFAIRS MED CTR,DIV PSYCHIAT,SUBST ABUSE SERV,LOS ANGELES,CA. UNIV CALIF LOS ANGELES,DEPT ANESTHESIOL,LOS ANGELES,CA 90024. NR 66 TC 47 Z9 50 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1996 VL 37 IS 3 BP 223 EP 235 PG 13 WC Psychiatry; Psychology SC Psychiatry; Psychology GA UG788 UT WOS:A1996UG78800001 PM 8849499 ER PT J AU Greenberg, DB AF Greenberg, DB TI Mindhunter: Inside the FBI's elite serial crime unit - Douglas,J, Olshaker,M SO PSYCHOSOMATICS LA English DT Book Review RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,LAW & PSYCHIAT SERV,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1996 VL 37 IS 3 BP 302 EP 304 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA UG788 UT WOS:A1996UG78800012 ER PT J AU Greenberg, DB AF Greenberg, DB TI Homicide: A psychiatric perspective - Malmquist,CP SO PSYCHOSOMATICS LA English DT Book Review RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,LAW & PSYCHIAT SERV,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1996 VL 37 IS 3 BP 302 EP 304 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA UG788 UT WOS:A1996UG78800010 ER PT J AU Greenberg, DB AF Greenberg, DB TI Bad men do what good men dream: A forensic psychiatrist illuminates the darker side of human behavior - Simon,RI SO PSYCHOSOMATICS LA English DT Book Review RP Greenberg, DB (reprint author), MASSACHUSETTS GEN HOSP,LAW & PSYCHIAT SERV,BOSTON,MA 02114, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 1996 VL 37 IS 3 BP 302 EP 304 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA UG788 UT WOS:A1996UG78800011 ER PT J AU Held, KD Sylvester, FC Hopcia, KL Biaglow, JE AF Held, KD Sylvester, FC Hopcia, KL Biaglow, JE TI Role of Fenton chemistry in thiol-induced toxicity and apoptosis SO RADIATION RESEARCH LA English DT Article ID CONTAINING RADIOPROTECTOR DITHIOTHREITOL; RADICAL-MEDIATED TOXICITY; GLUTATHIONE REDOX CYCLE; HAMSTER OVARY CELLS; HYDROGEN-PEROXIDE; MAMMALIAN-CELLS; ENDOTHELIAL-CELLS; CYTO-TOXICITY; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION AB Under certain conditions, many radioprotective thiols can be toxic, causing loss of colony-forming ability in cultured mammalian cells in a biphasic fashion whereby the thiols are not toxic at high or low concentrations of the drug, but cause decreased clonogenicity at intermediate (0.2-1.0 mM) drug levels. This symposium paper summarizes our studies using dithiothreitol (DTT) as a model thiol to demonstrate the role of Fenton chemistry in thiol toxicity. The toxicity of DTT in V79 cells has several characteristics: it is dependent on the medium used during exposure of cells to the drug; the toxicity is decreased or prevented by addition of catalase exogenously, but superoxide dismutase has no effect; the toxicity is increased by addition of copper, either free or derived from ceruloplasmin in serum; and the toxicity can be modified intracellularly by altering glucose availability or pentose cycle activity. Thus the data are consistent with a mechanism whereby DTT oxidation produces H2O2 in a reaction catalyzed by metals, predominantly copper, followed by reaction of H2O2 in a metal-catalyzed Fenton reaction to produce the ultimate toxic species, (OH)-O-.. Studies comparing 12 thiols have shown that the magnitude of cell killing and pattern of dependence on thiol concentration vary among the different agents, with the toxicity depending on the interplay between the rates of two reactions: thiol oxidation and the reaction between the thiol and the H2O2 produced during the thiol oxidation. The addition of other metals, e.g. Zn2+, and metal chelators, e.g. EDTA, can also alter DTT toxicity by altering the rates of thiol oxidation or the Fenton reaction. Recent studies have shown that in certain cell lines thiols can also cause apoptosis in a biphasic pattern, with little apoptosis at low or high drug concentrations but greatly increased apoptosis levels at intermediate (similar to 3 mM) thiol concentrations. There appears to be a good correlation between those thiols that cause loss of clonogenicity and those that induce apoptosis, suggesting similar mechanisms may be involved in both end points. However, thiol-induced apoptosis is nor prevented by addition of exogenous catalase. These observations are discussed in relation to the possible role of Fenton chemistry in induction of apoptosis by thiols. (C) 1996 by Radiation Research Society C1 UNIV PENN,DEPT RADIAT ONCOL,PHILADELPHIA,PA 19104. RP Held, KD (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA 02114, USA. FU NCI NIH HHS [CA42167, CA44982, CA18614] NR 81 TC 79 Z9 80 U1 1 U2 6 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1996 VL 145 IS 5 BP 542 EP 553 DI 10.2307/3579272 PG 12 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA UH191 UT WOS:A1996UH19100003 PM 8619019 ER PT J AU Biaglow, JE Held, KD Manevich, Y Tuttle, S Kachur, A Uckun, F AF Biaglow, JE Held, KD Manevich, Y Tuttle, S Kachur, A Uckun, F TI Role of guanosine triphosphate in ferric ion-linked Fenton chemistry SO RADIATION RESEARCH LA English DT Article ID CONTAINING RADIOPROTECTOR DITHIOTHREITOL; RADICAL-MEDIATED TOXICITY; IONIZING-RADIATION; CELLULAR-RESPONSE; HYDROGEN-PEROXIDE; ELECTRON-TRANSFER; MAMMALIAN-CELLS; PENTOSE CYCLE; OXYGEN; MECHANISMS AB We measured the production of reactive hydroxyl radical (OH.) by Fe2+ itself or complexed with nucleotide triphosphates or tripolyphosphate (TPP). Coumarin-3-carboxylic acid (3-CCA) reacts with the OH. produced by Fe2+, Fe3+ or Cu2+ plus ascorbate and with various iron complexes. We measured in real time the increased fluorescence of 3-CCA after hydroxylation to 7-hydroxy-coumarin-3-carboxylic acid (7-OHCCA). Phosphate-buffered solutions do not affect the yield of Fe2+-linked OH. as do other organic buffer solutions. Our results show that guanosine triphosphate enhances the Fe2+-linked production of OH.. We also tested inosine triphosphate, adenosine triphosphate and xanthine triphosphate for their capacity to produce OH. with Fe2+. Inosine triphosphate is the most effective nucleotide in the production of OH.. However, the Fe2+-mediated yield of OH. is greater in the presence of TPP compared to the nucleotide triphosphates. Organic buffers as well as the purine and ribose portion of nucleotides compete for OH. and decrease the yield of fluorescent 7-OHCCA. We also decreased the yield of OH. by adding guanosine to the Fe2+/TPP-generating system. Adenosine, ribose and deoxyribose also react with Fete-generated OH.. The decreased yield of 7-OHCCA occurs because the ribose and purine part of the molecule reacts with OH.. The maximal production of reactive OH., compared to all nucleotides and phosphates tested, occurs with a ratio of 2 TPP/Fe2+ complex. In conclusion, the real-time measurement of the production of fluorescent 7-OHCCA provides a convenient means for measuring chemically generated OH.. The TPP/Fe2+-generating mixture, in the presence of 3-CCA, can be used to study the scavenging ability of other competing molecules. (C) 1996 by Radiation Research Society C1 MASSACHUSETTS GEN HOSP, DEPT RADIAT ONCOL, BOSTON, MA 02114 USA. HARVARD UNIV, BOSTON, MA 02114 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. RP UNIV PENN, DEPT BIOCHEM BIOPHYS & RADIAT ONCOL, PHILADELPHIA, PA 19104 USA. FU NCI NIH HHS [CA 56679, CA 44982] NR 68 TC 19 Z9 21 U1 1 U2 3 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1996 VL 145 IS 5 BP 554 EP 562 DI 10.2307/3579273 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA UH191 UT WOS:A1996UH19100004 PM 8619020 ER PT J AU Halpern, HJ Yu, C Peric, M Barth, ED Karczmar, GS River, JN Grdina, DJ Teicher, BA AF Halpern, HJ Yu, C Peric, M Barth, ED Karczmar, GS River, JN Grdina, DJ Teicher, BA TI Measurement of differences in pO(2) in response to perfluorocarbon carbogen in FSa and NFSa murine fibrosarcomas with low-frequency electron paramagnetic resonance oximetry SO RADIATION RESEARCH LA English DT Article ID SPIN LABEL; TUMOR RADIOSENSITIVITY; INVIVO MEASUREMENTS; RADIATION RESPONSE; HYPOXIC CELLS; OXYGEN; SENSITIVITY; MISONIDAZOLE; SPECTROSCOPY; PARAMETERS AB We have used very low-frequency electron paramagnetic resonance (EPR) oximetry to measure the change in oxygen concentration (Delta pO(2)) due to change in breathing atmosphere in FSa and NFSa fibrosarcomas implanted in the legs of C3H mice infused with perfluoro-octylbromine (PFOB). Measurements in each tumor were made before and after the administration of the high-density (47% v/v) perfluorocarbon PFOB, perflubron (Alliance pharmaceutical Corporation, San Diego, CA). Measurements in each tumor were also made, after the administration of the PFOB, both before (PFOB/air) and after the administration of carbogen (95% O-2 + 5% CO2, PFOB/carbogen). Large changes (Delta pO(2)) relative to PFOB/air oxygenation were seen with the administration of PFOB/carbogen. No significant difference in oxygen concentration was seen between air-breathing mice with and without PFOB. The mean Delta pO(2) for FSa tumors was 13 +/- 6 torr, while the mean for NFSa fibrosarcomas was 28 +/- 7 torr. There were such large intertumor differences that the trend toward a smaller change in the more hypoxic FSa tumors was not significant (P = 0.13). This paper describes a novel method of measuring differences in oxygenation in tumor tissues. The results of such measurements indicate large differences in pO(2) response to different breathing atmospheres in PFOB-infused tumors of similar histology. The intertumor Delta pO(2) differences may correlate with differences in radiation response. (C) 1996 by Radiation Research Society C1 UNIV CHICAGO,DEPT RADIOL,CHICAGO,IL 60637. ARGONNE NATL LAB,CTR MECHANIST BIOL & BIOTECHNOL,ARGONNE,IL 60439. DANA FARBER CANC INST,BOSTON,MA 02115. RP Halpern, HJ (reprint author), UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA-50679, CA-66132] NR 41 TC 33 Z9 33 U1 0 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1996 VL 145 IS 5 BP 610 EP 618 DI 10.2307/3579280 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA UH191 UT WOS:A1996UH19100011 PM 8619027 ER PT J AU Greenes, RA Bauman, RA AF Greenes, RA Bauman, RA TI The era of health care reform and the information superhighway - Implications for radiology SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article AB Radiology is undergoing dramatic change, along with the rest of the health care system, in its mode of organization, financing, and delivery. Information technology is becoming central to health care delivery and will enable a higher degree of integration of imaging practice with the rest of the health care system. Radiology will need to address the requirements for achieving this integration to continue to be successful in the future. C1 HARVARD UNIV, SCH MED, DEPT RADIOL, BOSTON, MA 02115 USA. MASSACHUSETTS GEN HOSP, DEPT RADIOL, BOSTON, MA 02114 USA. RP Greenes, RA (reprint author), BRIGHAM & WOMENS HOSP, DECIS SYST GRP, 75 FRANCIS ST, BOSTON, MA 02115 USA. FU NLM NIH HHS [LM 04572, N01-LM-4-3512, LM 07092] NR 11 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 1996 VL 34 IS 3 BP 463 EP + PG 0 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UN664 UT WOS:A1996UN66400002 PM 8657866 ER PT J AU Bauman, RA AF Bauman, RA TI Reporting and communications SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID PROCESSING SYSTEM; COMPUTER; LANGUAGE AB The history and the status of the use of computers in radiologic reporting and communications are reviewed. The Likely future demands for faster reporting, outcomes assessment, and assembling and using data to optimize the trade-offs between the studies done and their cost are considered. Likely future approaches for radiology in meeting these demands also are discussed. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 55 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 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 1996 VL 34 IS 3 BP 597 EP & PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UN664 UT WOS:A1996UN66400009 PM 8657873 ER PT J AU Goldberg, MA AF Goldberg, MA TI Teleradiology and telemedicine SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Review ID SPATIAL-RESOLUTION REQUIREMENTS; OPERATING CHARACTERISTIC ANALYSIS; DIGITAL CHEST RADIOGRAPHY; OBSERVER PERFORMANCE; DIAGNOSTIC-ACCURACY; WORKSTATION IMAGES; HARD-COPY; FILM; RADIOLOGY; DISPLAY AB This article provides a historical perspective as well as an update on the current state of teleradiology and telemedicine in the United States. Technical implementation issues are discussed and enabling technologies are described. Considerations that impact network design are outlined including data transmission, data compression, applicable standards, and bandwidth requirements. Reimbursement, medicolegal, Licensure, and regulatory issues related to the delivery of teleradiology and other telemedicine services are reviewed. Insight is provided into the role of teleradiology and telemedicine in a changing health care environment. C1 HARVARD UNIV,SCH MED,DEPT RADIOL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 102 TC 51 Z9 55 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAY PY 1996 VL 34 IS 3 BP 647 EP & PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UN664 UT WOS:A1996UN66400012 PM 8657876 ER PT J AU Sorensen, AG Buonanno, FS Gonzalez, RG Schwamm, LH Lev, MH HuangHellinger, FR Reese, TG Weisskoff, RM Davis, TL Suwanwela, N Can, U Moreira, JA Copen, WA Look, RB Finklestein, SP Rosen, BR Koroshetz, WJ AF Sorensen, AG Buonanno, FS Gonzalez, RG Schwamm, LH Lev, MH HuangHellinger, FR Reese, TG Weisskoff, RM Davis, TL Suwanwela, N Can, U Moreira, JA Copen, WA Look, RB Finklestein, SP Rosen, BR Koroshetz, WJ TI Hyperacute stroke: Evaluation with combined multisection diffusion-weighted and hemodynamically weighted echo-planar MR imaging SO RADIOLOGY LA English DT Article; Proceedings Paper CT 1995 RSNA Scientific Assembly CY NOV 26-DEC 01, 1995 CL CHICAGO, IL SP Radiol Soc N Amer DE blood vessels, MR; brain, infarction; brain, MR; gadolinium; magnetic resonance (MR), diffusion study; magnetic resonance (MR), vascular studies ID FOCAL CEREBRAL-ISCHEMIA; CONTRAST AGENTS; BLOOD-VOLUME; BRAIN; INFARCTION; TISSUE; HUMANS; FLOW; CATS AB PURPOSE: To evaluate acute stroke with conventional, multisection diffusion-weighted (DW), and hemodynamically weighted (HW) magnetic resonance (MR) imaging. MATERIALS AND METHODS: The three MR imaging techniques were performed in 11 patients within 10 hours of the onset of acute hemiparesis. The volume of DW and HW abnormalities were compared with infarct volumes depicted at initial and/or follow-up MR or computed tomography (CT). RESULTS: Findings at DW and HW imaging were abnormal in nine of the 11 patients, despite normal findings at initial CT and/or MR. In all nine patients, infarcts were depicted at follow-up CT or MR. The DW abnormality was generally smaller and the HW abnormality was generally larger than the infarct volume determined at subsequent imaging. In the two patients with normal findings at DW and HW imaging, symptoms resolved completely within 1-48 hours. CONCLUSION: Different aspects of hyperacute cerebral ischemia are depicted at DW and HW imaging before infarction is depicted at conventional MR or CT. These techniques may improve stroke diagnosis and may contribute to advances in treatment. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. RP Sorensen, AG (reprint author), MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114, USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NCI NIH HHS [P01-CA48729, R01-CA40303] NR 44 TC 559 Z9 576 U1 0 U2 7 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1996 VL 199 IS 2 BP 391 EP 401 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UG011 UT WOS:A1996UG01100017 PM 8668784 ER PT J AU DeSanctis, JT Bramson, RT Blickman, JG AF DeSanctis, JT Bramson, RT Blickman, JG TI Can clinical parameters help reliably predict the onset of acute intracranial hemorrhage in infants receiving extracorporeal membrane oxygenation? SO RADIOLOGY LA English DT Article DE brain, hemorrhage; extracorporeal membrane oxygenation; infants, newborn, cardiovascular system; infants, newborn, respiratory system; ultrasound (US), in infants and children AB PURPOSE: To determine whether clinical parameters can be used to help predict the onset of acute intracranial hemorrhage (ICH) in infants receiving extracorporeal membrane oxygenation (ECMO). MATERIALS AND METHODS: The authors retrospectively reviewed cranial sonograms and intensive care unit data for 53 neonates treated with ECMO for intractable cardiorespiratory insufficiency. Thirty-nine boys and 14 girls were treated between February 1988 and June 1993. Gestational age ranged from 34 to 43.5 weeks (mean, 39.2 weeks). Birth weights ranged from 2,200 to 4,650 g (mean, 3,310 g). Multiple clinical variables were subjected to statistical analysis. RESULTS: There were 38 patients without ICH, 10 with early ICH (within 72 hours after cannulation), and five with late ICH (more than 72 hours after cannulation). Analysis with bivariate scatterplots revealed almost complete overlap in the clinical parameters for patients in these three categories. Thus, use of individual variables to predict acute ICH was impractical. CONCLUSION: No clinical parameters helped adequately distinguish patients who developed ICH from those who did not. C1 MASSACHUSETTS GEN HOSP,DIV PEDIAT IMAGING,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 10 TC 10 Z9 10 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1996 VL 199 IS 2 BP 429 EP 432 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UG011 UT WOS:A1996UG01100022 PM 8668789 ER PT J AU Bennett, GL Bromley, B Benacerraf, BR AF Bennett, GL Bromley, B Benacerraf, BR TI Agenesis of the corpus callosum: Prenatal detection usually is not possible before 22 weeks of gestation SO RADIOLOGY LA English DT Article DE corpus callosum, agenesis; fetus, central nervous system; pregnancy, US ID SONOGRAPHY; FREQUENCY AB PURPOSE: To determine whether agenesis of the corpus callosum can be diagnosed prenatally with standard ultrasonographic (US) evaluation before 22 weeks of gestation. MATERIALS AND METHODS: Initial scans obtained on or before 22 weeks and follow-up scans obtained in the third trimester were selected from all cases of agenesis of the corpus callosum diagnosed prenatally at the authors' laboratory. Follow-up was attained by means of review of the medical records and included imaging, karyotype, and clinical outcome. RESULTS: Among 15 fetuses with callosal agenesis confirmed by means of third-trimester scans, 10 had completely normal US scans at 16-22 weeks and five had other US abnormalities. Isolated callosal agenesis was identified in six children with normal development (except one with polydactyly). Among the others, four were developmentally delayed, three died, and two others had abnormal karyotype. CONCLUSION: Standard second-trimester US before 22 weeks of gestation may not show isolated callosal agenesis. Fetuses with this abnormality can have normal second-trimester scans and develop abnormal US findings in the third trimester. C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02114. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. RI Forkel, Stephanie/A-4018-2011 OI Forkel, Stephanie/0000-0003-0493-0283 NR 20 TC 37 Z9 40 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1996 VL 199 IS 2 BP 447 EP 450 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UG011 UT WOS:A1996UG01100025 PM 8668792 ER PT J AU MayoSmith, WW Dawson, SL Mauceri, T Mueller, PR AF MayoSmith, WW Dawson, SL Mauceri, T Mueller, PR TI Attenuation effects of biliary endoprostheses on therapeutic radiation SO RADIOLOGY LA English DT Article DE bile ducts, stents and prostheses; bile ducts, stenosis or obstruction; radiations, measurement; therapeutic radiology AB Seven commercially available biliary stents were tested to determine if they caused any clinically important attenuation of therapeutic radiation. Attenuation effects were evaluated in models of brachytherapy (iridium-192 source) and external beam radiation therapy (cobalt-60 source), with use of parameters that mimicked those used in patient treatment for biliary neoplasms. No stent demonstrated clinically important attenuation or scatter of therapeutic radiation, so local dosimetry was not affected. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT ABDOMINAL & INTERVENT RADIOL,BOSTON,MA. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,BOSTON,MA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 1996 VL 199 IS 2 BP 571 EP 572 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UG011 UT WOS:A1996UG01100048 PM 8668815 ER PT J AU Williams, DM Grubbs, BG ParkSnyder, S Rank, RG Bonewald, LF AF Williams, DM Grubbs, BG ParkSnyder, S Rank, RG Bonewald, LF TI Activation of latent transforming growth factor beta during Chlamydia trachomatis-induced murine pneumonia SO RESEARCH IN MICROBIOLOGY LA English DT Article DE cytokine; TGF beta; immunosuppression; Chlamydia trachomatis; RT/PCR; Northern blot; active and latent TGF beta; beta 1 and beta 2 isoforms ID NECROSIS FACTOR-ALPHA; TGF-BETA; EXTRACELLULAR-MATRIX; HUMAN MACROPHAGES; GAMMA-INTERFERON; LYMPHOCYTES-B; HOST DEFENSE; ROLE INVIVO; EXPRESSION; MOUSE AB Transforming growth factor beta (TGF beta) is a multifunctional cytokine with potentially important roles in both host defence and immunopathogenesis. Latent, but more importantly, active TGF beta was significantly elevated in bronchiolar lavage fluid from lungs of mice infected with murine Chlamydia trachomatis. Induction of both latent and active TGF beta in these infected animals was highest at day two after infection (2 to 4-fold) compared with day 15 (1 to 2-fold). Both active and latent TGF beta 1 and TGF beta 2 isoforms were detected. Quantitative reverse transcription polymerase chain reaction (RT-PCR) assay showed a slight but significant increase in PCR product for TGF beta 1, but Northern analysis for TGF beta 1 in lung tissue was not significantly different between treatment groups. No significant change was observed for TGF beta 2 mRNA by RT-PCR. The increase in active and latent TGF beta in these lung lavages from mice infected with C. trachomatis appears to be primarily post-transcriptionally regulated. C1 AUDIE L MURPHY MEM VET ADM MED CTR, DEPT MED, SAN ANTONIO, TX 78284 USA. UNIV ARKANSAS MED SCI HOSP, DEPT MICROBIOL & IMMUNOL, LITTLE ROCK, AR 72205 USA. RP Williams, DM (reprint author), UNIV TEXAS, HLTH SCI CTR, DEPT MED, DIV INFECT DIS, 7703 FLOYD CURL DR, SAN ANTONIO, TX 78284 USA. FU NIAID NIH HHS [AI 22380] NR 47 TC 10 Z9 10 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD MAY PY 1996 VL 147 IS 4 BP 251 EP 262 DI 10.1016/0923-2508(96)81385-4 PG 12 WC Microbiology SC Microbiology GA UD859 UT WOS:A1996UD85900005 PM 8763612 ER PT J AU Cros, D Triggs, WJ AF Cros, D Triggs, WJ TI Guillain-Barre syndrome: Clinical neurophysiologic studies SO REVUE NEUROLOGIQUE LA English DT Article; Proceedings Paper CT International Meeting of the French-Society-of-Neurology - Immune-Mediated Polyneuropathies CY JUN 08-09, 1995 CL PARIS, FRANCE SP French Soc Neurol ID INFLAMMATORY DEMYELINATING POLYNEUROPATHY; ACUTE AXONAL FORM; CONDUCTION BLOCK; ELECTRODIAGNOSTIC ABNORMALITIES; CAMPYLOBACTER-JEJUNI; ANTI-GM1 ANTIBODIES; DEGENERATION; NEUROPATHY; RESPONSES; DISORDERS AB Guillain-Barre syndrome is a well-defined clinical entity corresponding to primary inflammatory demyelinating lesions of peripheral nerves and spinal roots in the majority of cases seen in Western Europe and North America. Documentation of conduction abnormalities characteristic of demyelination in the context of rapidly developing weakness confirms the clinical diagnosis of acute inflammatory demyelinating polyradiculoneuropathy. These abnormalities include(1) conduction block, (2) markedly prolonged distal latencies, (3) marked slowing of motor conduction velocities, and (4) absent or impersistent F responses. Other abnormalities are of ambiguous significance : (1) low amplitude compound muscle responses, (2) absent sensory nerve potentials, (3) reduction in the maximum EMG recruitment pattern, which may all (1, 2, and 3) indicate conduction block or axonal degeneration, and (4) fibrillation potentials due to breakdown of motor axons, a frequent non-specific effect of primary inflammatory demyelination, A Guillain-Barre va riant due to immune-mediated primary axonal degeneration has also been recently described. RP Cros, D (reprint author), MASSACHUSETTS GEN HOSP,DEPT NEUROL,EMG UNIT,BIGELOW 12,BOSTON,MA 02114, USA. NR 55 TC 7 Z9 7 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0035-3787 J9 REV NEUROL JI Rev. Neurol. PD MAY PY 1996 VL 152 IS 5 BP 339 EP 343 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA UX502 UT WOS:A1996UX50200007 PM 8881426 ER PT J AU Walker, WH Habener, JF AF Walker, WH Habener, JF TI Role of transcription factors CREB and CREM in cAMP-regulated transcription during spermatogenesis SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID BINDING PROTEIN CREB; CELL-INTERACTIONS; GENE; ACTIVATOR; MULTIPLE; EXPRESSION; TESTIS; EXON; AUTOREGULATION; VERSATILITY AB The cAMP response element binding protein (CREB) and the cAMP-responsive element modulator (CREM) ave cyclically expressed at high levels during spermatogenesis. Cyclical expression of CREB and CREM in germ and somatic Sertoli cells correlates with the fluctuations in cAMP signaling induced by the pituitary gonadotropic hormones FSH and LH both during sexual maturation of the testis and during the 12-day cycles of spermatogenesis that occur in the adult testis. CREB and CREM are expressed at different rimes during the spermatogenic cycle, undergo programmed sequential switches from activator to repressor isoforms by mechanisms of alternative exon splicing and promoter usage, and are autoregulated by cAMP signaling in opposing directions. cAMP response elements located in the promoter of the CREB gene upregulate the expression of activator CREBs, whereas cAMP autoregulatory response elements in the internal promoter of the CREM gene induce expression of repressor CREM isoforms. The complex mechanisms for the regulation of the expression of CREB and CREM in the testis appear to reflect critical adaptations for regulating key target genes essential for the development of germ cells. RP Walker, WH (reprint author), HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,MOLEC ENDOCRINOL LAB,MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 37 TC 58 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAY-JUN PY 1996 VL 7 IS 4 BP 133 EP 138 DI 10.1016/1043-2760(96)00035-5 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UM539 UT WOS:A1996UM53900003 PM 18406739 ER PT J AU Yamada, K Seebach, JD DerSimonian, H Sachs, DH AF Yamada, K Seebach, JD DerSimonian, H Sachs, DH TI Human anti-pig T-cell mediated cytotoxicity SO XENOTRANSPLANTATION LA English DT Article DE xenograft; MHC; miniature swine; human; NK cell; T-cell; CTL ID PRESENTING CELLS; MOUSE; SURFACE AB Miniature swine have a variety of advantages as potential donors for human xenotransplantation, including size, physiological similarities, and breeding characteristics. To investigate the nature of the human anti-pig xenogeneic cellular response, we performed standard Cr-51-release cell-mediated lympholysis (CML) experiments. The major histocompatibility complex (MHC) allele specificity of the xenogeneic cellular response was tested on porcine target cells of three distinct homozygous MHC haplotypes (SLA(aa), SLA(cc), SLA(dd)) and three intra-MHC recombinant haplotypes (SLA(ii), SLA(gg), SLA(kk)), Obtained from our herd of partially inbred miniature swine. After stimulation with irradiated porcine peripheral blood mononuclear cells (PBMC) of SLA(aa) haplotype, a strong nonspecific cytotoxic response of the bulk culture against xenogeneic targets of all three haplotypes was observed. However, SLA allele specificity could be demonstrated after T cell enrichment, and mapping experiments revealed predominantly SLA class I restriction of xenoreactive cytotoxic T lymphocytes (CTLs), although some class II restriction was also observed. The experiments were repeated in the presence of anti-T cell monoclonal antibodies, anti-CD3 (OKT3), anti-CD2 (35.1), anti-CD4 (OKT4), or anti-CD8 (OKT8). The bulk xenogeneic CML was not inhibited by any of the anti-T cell antibodies tested. However, after T cell-enrichment, lysis of porcine targets was significantly inhibited by anti-CD3 or anti-CD8 antibody and partially inhibited by anti-CD2 antibody. In comparable assays, the human allogeneic CML was blocked by anti-CD3 and anti-CD8, but not by anti-CD2 or anti-CD4 antibodies. Finally, the cytotoxic activity of A3b3, a human CD4(+) T-cell clone, was tested. A3b3 lysed xenogeneic targets of SLA(aa) haplotype, but not SLA(cc) or allogeneic targets, and was inhibited by anti-CD4, anti-CD2, and anti-CD3 antibodies, but not by anti-CD8. With the aid of intra-MHC recombinant haplotypes, the xenogeneic CML reactivity of A3b3 was mapped to SLA class II, suggesting direct xenogeneic recognition of porcine MHC class II antigens by human T cells. Thus, the human anti-pig cell-mediated cytotoxic response is similar in magnitude to comparable allogeneic responses, and involves both SLA class I and class II restricted T-cell mediated cytotoxicity, as well as additional nonspecific killing, possibly by NK cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 20 TC 35 Z9 35 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 1996 VL 3 IS 2 BP 179 EP 187 DI 10.1111/j.1399-3089.1996.tb00136.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA UR915 UT WOS:A1996UR91500002 ER PT J AU Seebach, JD Yamada, K McMorrow, IM Sachs, DH DerSimonian, H AF Seebach, JD Yamada, K McMorrow, IM Sachs, DH DerSimonian, H TI Xenogeneic human anti-pig cytotoxicity mediated by activated natural killer cells SO XENOTRANSPLANTATION LA English DT Article DE xenograft; NK cell; MHC miniature swine; human; T-cell; CTL ID LYMPHOCYTES; XENOTRANSPLANTATION; RESPONSES; REJECTION AB Even if hyperacute rejection, which is mediated by human natural antibodies (nAb) and complement, could be prevented, xenoreactive human anti-pig cellular responses may lead to delayed and/or chronic xenograft rejection. Among the cell populations participating in such rejection, Mt cells have been proposed as an important component. In this study we report the in vitro cytotoxic activity of natural killer (NK) cells obtained from healthy human donors against porcine target cells. Freshly isolated peripheral blood mononuclear cells (PBMC) and purified NK cells (CD16+/CD56+, CD3-, CD20-, CD33-) exhibited little or no cytotoxic activity when tested on porcine phytohemagglutinin (PHA)-stimulated lymphoblasts or bone marrow- or aortic-derived endothelial cell lines in the presence of serum-free medium. Killing was considerably higher in the presence of human decomplemented plasma, containing xenoreactive nAb, or purified Gal(alpha 1,3)Gal-reactive antibodies, suggesting that antibody dependent cell-mediated cytotoxicity (ADCC) mediated by NK cells is an important mechanism involved in xenogeneic cytotoxicity. After incubation of human PBMC for 6 days in the presence of irradiated xenogeneic porcine or allogeneic stimulator cells, or in the presence of exogenous interleukin 2 (IL-2), the cytotoxic activity of the bulk cultures as well as that of isolated NK cells (separated from stimulated bulk cultures) against xenogeneic targets increased considerably, and corresponded to an increased NK-specific lysis of K562 target cells. Cell surface staining and flow cytometry showed that CD16+/CD56+, CD3- NK cells composed ca. 25% of short-term (6 days) xenogeneic, allogeneic, or IL-2 stimulated bulk cultures. In summary, these data suggest that, in contrast to allogeneic cell-mediated killing, xenogeneic human anti-porcine cytotoxicity includes an important contribution from NK cells. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,BOSTON,MA 02129. NR 34 TC 88 Z9 88 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 1996 VL 3 IS 2 BP 188 EP 197 DI 10.1111/j.1399-3089.1996.tb00137.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA UR915 UT WOS:A1996UR91500003 ER PT J AU Garg, HG Siebert, JW Garg, A Neame, PJ AF Garg, HG Siebert, JW Garg, A Neame, PJ TI Inseparable iduronic acid-containing proteoglycan PG((IdoA)) preparations of human skin and post-burn PG scar tissues: Evidence for elevated levels of ((IdoA))-I in hypertrophic scar by N-terminal sequencing SO CARBOHYDRATE RESEARCH LA English DT Article DE skin; proteoglycan, iduronic acid containing; scar, hypertrophic ID DERMATAN SULFATE PROTEOGLYCANS; PROTEODERMATAN SULFATE; ARTICULAR-CARTILAGE; PIG SKIN; DECORIN; BIGLYCAN; PURIFICATION; EXPRESSION; BONE; CDNA AB Hypertrophic scarring is characterized by disordered collagen fibrils. In order to determine whether this is, in part, a result of changes in the population of proteoglycans that are thought to be involved in regulation of collagen fibril formation, we have compared PGs from post-burn normal and hypertrophic scar tissue, as well as from human dermis and epidermis. Efforts to separate the two major iduronic acid-containing proteoglycans, decorin [PG((IdoA))-II] and biglycan [PG((IdoA))-I], for quantitation were not successful. The different N-terminal sequences of these two iduronic acid-containing proteoglycans PG((IdoA))-I and -II were utilized to estimate the relative amounts in the above PG((IdoA)) preparations. Normal scar, dermis and epidermis were all found to contain primarily decorin with low (<10%) levels of biglycan relative to decorin. In contrast, iduronic acid-containing proteoglycans from hypertrophic scar were found to be approximately 30% biglycan [PG((IdoA))-I]. This may be a proximal cause of altered collagen fibrils, or may result in alterations in the sequestration of growth factors, which then results in changes in collagen that effect the appearance of the scar. (C) 1996 Elsevier Science Ltd. C1 HARVARD UNIV,SCH MED,SHRINERS BURN INST,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NYU,MED CTR,INST RECONSTRUCT PLAST SURG,NEW YORK,NY 10016. UNIV S FLORIDA,SHRINERS HOSP CRIPPLED CHILDREN,ORTHOPED RES LABS,TAMPA,FL 33612. UNIV S FLORIDA,DEPT BIOCHEM & MOLEC BIOL,TAMPA,FL 33612. RP Garg, HG (reprint author), MASSACHUSETTS GEN HOSP E,PULM RES LAB,BLDG 149,13TH ST,BOSTON,MA 02129, USA. NR 22 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD APR 30 PY 1996 VL 284 IS 2 BP 223 EP 228 DI 10.1016/0008-6215(95)00403-3 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA UJ266 UT WOS:A1996UJ26600007 PM 8653721 ER PT J AU Suda, T Vu, Q Callahan, R VanRooijen, N Schneeberger, EE AF Suda, T Vu, Q Callahan, R VanRooijen, N Schneeberger, EE TI Effect of IFN-gamma and dexamethasone on dendritic cell (DC) traffic to the lung. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. VRIJE UNIV AMSTERDAM,AMSTERDAM,NETHERLANDS. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 44 EP 44 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100274 ER PT J AU VanCott, JL Chatfield, SN Hone, D Pascual, DW Hohmann, E Kiyono, H McGhee, JR AF VanCott, JL Chatfield, SN Hone, D Pascual, DW Hohmann, E Kiyono, H McGhee, JR TI Immunity of attenuated Salmonella vaccine vectors in IFN-gamma knockout (GKO) mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,LONDON,ENGLAND. UNIV MARYLAND,CVD,BALTIMORE,MD. MONTANA STATE UNIV,BOZEMAN,MT 59717. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 114 EP 114 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100346 ER PT J AU Diacovo, TG Puri, KD Warnock, RA Springer, TA vonAndrian, UH AF Diacovo, TG Puri, KD Warnock, RA Springer, TA vonAndrian, UH TI P-selectin binding to an endothelial L-selectin ligand: A common pathway of activated platelet and leukocyte recruitment SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 172 EP 172 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100401 ER PT J AU Suzuki, H Shinkai, Y Love, PE Alt, FW Singer, A AF Suzuki, H Shinkai, Y Love, PE Alt, FW Singer, A TI Commitment of immature thymocytes to the CD4(+) T cell lineage independent of clonotypic TCR chains SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. CHILDRENS HOSP,DEPT GENET & PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. RI Shinkai, Yoichi/N-3909-2014 OI Shinkai, Yoichi/0000-0002-6051-2484 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 262 EP 262 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100492 ER PT J AU Tsitsikov, EN GutierrezRamos, JC Geha, RS AF Tsitsikov, EN GutierrezRamos, JC Geha, RS TI Characterization of CD81/TAPA-1 deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CHILDRENS HOSP,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 287 EP 287 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100517 ER PT J AU Ryan, LK Golenbock, DT Day, BW Wu, J Vermeulen, MW AF Ryan, LK Golenbock, DT Day, BW Wu, J Vermeulen, MW TI Proinflammatory cytokine production by C3H/HEJ mouse alveolar (AM), peritoneal (PM), and bone marrow (BM) macrophages stimulated with LPS, interferon-gamma (IFN) and taxol. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US EPA,RES TRIANGLE PK,NC 27711. BOSTON UNIV,SCH MED,BOSTON,MA 02118. UNIV PITTSBURGH,PITTSBURGH,PA 15238. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 293 EP 293 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100525 ER PT J AU Pahlavani, MA Harris, MD Richardson, A AF Pahlavani, MA Harris, MD Richardson, A TI Effect of caloric restriction and aging on transcriptional regulation of IL-2 gene in rat lymphocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. AUDIE L MURPHY MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 315 EP 315 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100545 ER PT J AU Beland, JL Kozlow, W Adler, H Rimm, JJ AF Beland, JL Kozlow, W Adler, H Rimm, JJ TI HSV-1 infection after allogeneic murine bone marrow transplantation: A model of post-transplant immunodeficiency. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DFCI,DEPT PEDIAT,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 356 EP 356 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100586 ER PT J AU Yang, XF Weber, GF Kozak, CA Cantor, H AF Yang, XF Weber, GF Kozak, CA Cantor, H TI Cloning of bcl-x gamma, a new bcl-x isoform that is preferentially expressed in CD4+ T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOPATHOL,BOSTON,MA 02115. NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 412 EP 412 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100643 ER PT J AU Wyss, DF Choi, JS Li, J Knoppers, MH Willis, KJ Arulanandam, ARN Smolyar, A Reinherz, EL Wagner, G AF Wyss, DF Choi, JS Li, J Knoppers, MH Willis, KJ Arulanandam, ARN Smolyar, A Reinherz, EL Wagner, G TI Conformation and function of the N-linked glycan in the adhesion domain of human CD2 SO FASEB JOURNAL LA English DT Meeting Abstract C1 PROCEPT INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT BIOL CHEM MOL PHARMACOL & MED,BOSTON,MA 02115. DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. NR 0 TC 2 Z9 2 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 497 EP 497 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100726 ER PT J AU Jones, R Jacobson, M Beaumont, E Lipson, M AF Jones, R Jacobson, M Beaumont, E Lipson, M TI Co-localization of alpha-smooth muscle actin and smooth muscle myosin filaments in microvascular cells in pulmonary hypertension (PH): Contractile phenotype regulation SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 01267. MASSACHUSETTS GEN HOSP,BOSTON,MA 01267. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 783 EP 783 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101012 ER PT J AU Moro, O Bello, Y Ohnuma, M Wakita, K Tajima, M Lerner, E AF Moro, O Bello, Y Ohnuma, M Wakita, K Tajima, M Lerner, E TI The cutaneous vasodilator maxadilan is a specific PACAP type I receptor agonist. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA 02129. HARVARD UNIV,SCH MED,CHARLESTOWN,MA 02129. SHISEIDO LIFE SCI LAB,KANAGAWA,JAPAN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 828 EP 828 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101056 ER PT J AU Sunday, ME Mu, Q Fishman, M Hatzis, D AF Sunday, ME Mu, Q Fishman, M Hatzis, D TI Neuroendocrine (NE) cell hyperplasia and non-NE tumors in transgenic mice with V-HA-RAS driven by the calcitonin promoter. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 846 EP 846 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101076 ER PT J AU Adler, H Beland, JL Kozlow, W Kobzik, L Brewer, J Martin, TR Rimm, IJ AF Adler, H Beland, JL Kozlow, W Kobzik, L Brewer, J Martin, TR Rimm, IJ TI Characterization of the pulmonary inflammatory response to murine herpes simplex virus-type 1 (HSV-1) infection. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DANA FARBER CANC INST,DEPT PED,PULM DIV,DIV PED HEM ONC,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1071 EP 1071 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101303 ER PT J AU Gould, D Auchincloss, H AF Gould, D Auchincloss, H TI Direct versus indirect pathways in allograft rejection. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1126 EP 1126 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101356 ER PT J AU vonAndrian, UH AF vonAndrian, UH TI Murine lymph node venules express two distinct functional L-selectin ligands. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1144 EP 1144 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101372 ER PT J AU Fors, BP Goodarzi, K vonAdrian, UH AF Fors, BP Goodarzi, K vonAdrian, UH TI L-selectin shedding is independent of its subsurface structures and topography. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1157 EP 1157 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101386 ER PT J AU Anand, A Bloch, K Kradin, R AF Anand, A Bloch, K Kradin, R TI Nitric oxide (NO) secretion by alveolar macrophages (AM) is effectively inhibited by anti-intercellular adhesion molecule (ICAM)-1. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1172 EP 1172 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101400 ER PT J AU Castigli, E Hollander, G Kulbacki, R Su, M Burakoff, S GutierrezRamos, J Geha, R AF Castigli, E Hollander, G Kulbacki, R Su, M Burakoff, S GutierrezRamos, J Geha, R TI Induction of alloantigen-specific tolerance by B cells from CD40-deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1212 EP 1212 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101443 ER PT J AU Russell, H Rock, K Hermel, E Monaco, JJ AF Russell, H Rock, K Hermel, E Monaco, JJ TI The absence or reduced expression of the H2-DM alpha in class II processing defective mouse mutant cell lines SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV CINCINNATI,HOWARD HUGHES MED INST,CINCINNATI,OH 45267. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1221 EP 1221 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101450 ER PT J AU Luk, JM Springer, TA AF Luk, JM Springer, TA TI Expression of an extracellular domain or soluble leukocyte integrin beta-2 subunit (sCD18) and its functional implication. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. CASE WESTERN RESERVE UNIV,DEPT PEDIAT,CLEVELAND,OH 44106. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1312 EP 1312 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101539 ER PT J AU Lu, CF Springer, TA AF Lu, CF Springer, TA TI The alpha subunit cytoplasmic domain regulates adhesive activity and alpha beta subunit dimerization of LFA-1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1322 EP 1322 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101550 ER PT J AU Toth, I Lazar, G Bridges, KR AF Toth, I Lazar, G Bridges, KR TI Novel role of vitamin C as regulator of PKC alpha gene SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,MASSACHUSETTS GEN HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1336 EP 1336 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101565 ER PT J AU Kolhekar, AS Keutmann, HT Eipper, BA AF Kolhekar, AS Keutmann, HT Eipper, BA TI Assignment of disulfide bonds in peptidylglycine alpha-hydroxylating monooxygenase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1358 EP 1358 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101588 ER PT J AU Vadlamudi, RK Joung, I Strominger, JL Shin, J AF Vadlamudi, RK Joung, I Strominger, JL Shin, J TI p62, a phosphotyrosine independent ligand of p56Lck SH2 domain interacts with ubiquitin SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1505 EP 1505 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101736 ER PT J AU Gerszten, RE Ding, HT Dichek, DA Gimbrone, MA Luscinskas, FW Rosenzweig, A AF Gerszten, RE Ding, HT Dichek, DA Gimbrone, MA Luscinskas, FW Rosenzweig, A TI Adhesion of memory lymphocytes to VCAM-1 transduced endothelial cells under flow SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. BRIGHAM & WOMENS HOSP,DIV VASC RES,BOSTON,MA 02115. GLADSTONE INST,SAN FRANCISCO,CA 94141. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1624 EP 1624 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101854 ER PT J AU Suh, WK Mitchell, EK Yang, Y Peterson, PA Waneck, GL Williams, DB AF Suh, WK Mitchell, EK Yang, Y Peterson, PA Waneck, GL Williams, DB TI MHC class I molecules form ternary complexes with calnexin and TAP and undergo peptide-regulated interaction with TAP via their extracellular domains. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TORONTO,TORONTO,ON M5S 1A8,CANADA. RW JOHNSON PHARMACEUT RES INST,SAN DIEGO,CA 92121. MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1745 EP 1745 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86101973 ER PT J AU Zhao, ZS Schaffer, P Cantor, H AF Zhao, ZS Schaffer, P Cantor, H TI Molecular mimicry between a virus and self-antigen leading to autoimmune disease. SO FASEB JOURNAL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV IMMUNOPATHOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV MOLEC GENET,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MICROBIOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1779 EP 1779 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102009 ER PT J AU Hagenbaugh, A Sharma, S Aranda, R Cheroutre, H Moore, K Dubinett, S Kronenberg, M AF Hagenbaugh, A Sharma, S Aranda, R Cheroutre, H Moore, K Dubinett, S Kronenberg, M TI Altered immune function in IL-10 transgenic mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,DEPT MICRO & IMMUN,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,WADSWORTH PULM IMMUN LAB,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,DEPT GASTROENTEROL,LOS ANGELES,CA 90073. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1781 EP 1781 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102010 ER PT J AU Bani, L Moreau, JL David, D Demaison, C Sun, K Nakarai, T Saluucci, O Chouaib, S Ritz, J Theze, J AF Bani, L Moreau, JL David, D Demaison, C Sun, K Nakarai, T Saluucci, O Chouaib, S Ritz, J Theze, J TI Evidence for differential expression of the beta and gamma subunits of the IL-2 receptor in human lymphomononuclear cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. INST GUSTAVE ROUSSY,PARIS,FRANCE. INST PASTEUR,PARIS,FRANCE. RI Chouaib, Salem/F-7939-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1884 EP 1884 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102114 ER PT J AU Kim, S Vermeulen, MW Alleva, D Kornfeld, H Fenton, MJ AF Kim, S Vermeulen, MW Alleva, D Kornfeld, H Fenton, MJ TI Nitric oxide and IFN-production by human macrophages infected with M-tuberculosis SO FASEB JOURNAL LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,CTR PULM,BOSTON,MA 02118. MASSACHUSETTS GEN HOSP,PULM & CRIT CARE UNIT,CHARLESTOWN,MA 02129. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1945 EP 1945 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102176 ER PT J AU Pero, SC Wakshull, E Mackin, WM Auron, PE Adams, DS AF Pero, SC Wakshull, E Mackin, WM Auron, PE Adams, DS TI PGG-glucan activates the transcription factor nuclear factor IL6 (NF-IL6) in a murine monocytic cell line SO FASEB JOURNAL LA English DT Meeting Abstract C1 ALPHA BETA TECHNOL INC,WORCESTER,MA 01605. WORCESTER POLYTECH INST,DEPT BIOL BIOTECHNOL,WORCESTER,MA 01609. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1952 EP 1952 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102180 ER PT J AU Adams, DS Pero, SC Mackin, WM Auron, PE Wakshull, E AF Adams, DS Pero, SC Mackin, WM Auron, PE Wakshull, E TI PGG-glucan activates a nuclear factor-kappa B (NF-kappa B)-like transcription factor in a murine monocytic cell line SO FASEB JOURNAL LA English DT Meeting Abstract C1 ALPHA BETA TECHNOL INC,WORCESTER,MA 01605. WORCESTER POLYTECH INST,DEPT BIOL BIOTECHNOL,WORCESTER,MA 01609. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 1953 EP 1953 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102183 ER PT J AU Saban, R Wershil, B HaakFrendscho, M DeBoer, D Zine, M Bjorling, DE AF Saban, R Wershil, B HaakFrendscho, M DeBoer, D Zine, M Bjorling, DE TI Differential responses of tracheal and bladder segments isolated from control and mast cell - Deficient mice to antigen challenge following actively and passively sensitization. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV WISCONSIN,SMOOTH MUSCLE LAB,MADISON,WI 53706. MASSACHUSETTS GEN HOSP,COMBINED PROGRAM PEDIAT GASTROINTESTINAL NUTR,BOSTON,MA 02129. PROMEGA CORP,MADISON,WI 53711. UNIV WISCONSIN,DEPT MED SCI,MADISON,WI 53706. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2111 EP 2111 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102342 ER PT J AU Khandekar, S Naylor, J Kern, P Newcomb, J LeClair, K Bettencourt, B Brauer, P Profy, A Jones, B AF Khandekar, S Naylor, J Kern, P Newcomb, J LeClair, K Bettencourt, B Brauer, P Profy, A Jones, B TI Bimolecular interactions between T-cell receptor (TCR), superantigens and class II MHC analyzed by surface plasmon resonance (SPR) biosensor. SO FASEB JOURNAL LA English DT Meeting Abstract C1 PROCEPT INC,CAMBRIDGE,MA 02139. DANA FARBER CANC INST,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2134 EP 2134 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102363 ER PT J AU Liu, J Brewer, GA Auron, PE Vermeulen, MW AF Liu, J Brewer, GA Auron, PE Vermeulen, MW TI Structural analysis of 3'-untranslated regions (3'-UTR) of human TNF-alpha and IL-1 beta mRNA, and their interactions with RNA-binding proteins. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27157. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2365 EP 2365 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102594 ER PT J AU Hsu, HC Zhou, T Young, PY Martin, F Mountz, JD AF Hsu, HC Zhou, T Young, PY Martin, F Mountz, JD TI CD2-FAS transgene increases T cell immune response and elevates amyloidosis in the kidney of aged CD-1 mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ALABAMA,BIRMINGHAM,AL 35294. BIRMINGHAM VAMC,BIRMINGHAM,AL 35294. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2451 EP 2451 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102678 ER PT J AU King, PD Sadra, A Han, A SunderPlassman, R Reinherz, E Dupont, B AF King, PD Sadra, A Han, A SunderPlassman, R Reinherz, E Dupont, B TI Activation of the Tec family kinase EMT/ITK by CD2 stimulation of Jurkat leukemia cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2584 EP 2584 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102814 ER PT J AU Arulanandam, ARN McGregor, MJ Wyss, DF Wagner, G Willis, K Pallai, P Jones, B Reinherz, EL AF Arulanandam, ARN McGregor, MJ Wyss, DF Wagner, G Willis, K Pallai, P Jones, B Reinherz, EL TI A refined model for the docking topology of the CD2-CD58 interaction. SO FASEB JOURNAL LA English DT Meeting Abstract C1 PROCEPT INC,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH MED,DEPT BIO CHEM MOL PHARMACOL & MED,BOSTON,MA. DANA FARBER CANC INST,IMMUNOBIOL LAB,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2617 EP 2617 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102843 ER PT J AU Noble, A Cantor, H AF Noble, A Cantor, H TI CD8(+) T cell suppression of anti-sheep erythrocyte IgM responses is dependent on Qa-1 expression by activated B cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,DIV IMMUNOPATHOL,BOSTON,MA 02115. RI Noble, Alistair/E-9473-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2644 EP 2644 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86102874 ER PT J AU KovacsovicsBankowski, M Rock, KL AF KovacsovicsBankowski, M Rock, KL TI Particulate antigens enter a cytosolic pathway for MHC class I presentation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. CHU VAUDOIS,DEPT INTERNAL MED,CH-1011 LAUSANNE,SWITZERLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP 2821 EP 2821 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86103046 ER PT J AU Szostak, JW Bartel, D Hager, A Das, A Lohse, P AF Szostak, JW Bartel, D Hager, A Das, A Lohse, P TI Isolation of new ribozymes form pools of random sequences. SO FASEB JOURNAL LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,DEPT BIOL MOLEC,BOSTON,MA 02114. NR 0 TC 2 Z9 2 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP C1 EP C1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100050 ER PT J AU Kolodner, R AF Kolodner, R TI Mismatch repair and cancer susceptibility. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP D13 EP D13 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100013 ER PT J AU Gijon, M Qiu, Z Kyriakis, J Leslie, C AF Gijon, M Qiu, Z Kyriakis, J Leslie, C TI Activation of Jun kinases and p38 in macrophages and phosphorylation of cytosolic phospholipase(2). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA 02129. NR 0 TC 4 Z9 4 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP L19 EP L19 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100109 ER PT J AU Choudhury, GG Karamitsos, C Gentilini, A Abboud, HE AF Choudhury, GG Karamitsos, C Gentilini, A Abboud, HE TI Phosphatidylinositol 3 kinase (PI 3 K) regulates glomerular mesangial cell chemotaxis and proliferation: Involvement of mitogen activated protein kinase (MAPK) dependent and independent pathways. SO FASEB JOURNAL LA English DT Meeting Abstract C1 AUDIE L MURPHY MEM VET ADM MED CTR,DEPT MED & GERIATR,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 30 PY 1996 VL 10 IS 6 BP P50 EP P50 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UK861 UT WOS:A1996UK86100209 ER PT J AU Yonemura, Y Ku, H Hirayama, F Souza, LM Ogawa, M AF Yonemura, Y Ku, H Hirayama, F Souza, LM Ogawa, M TI Interleukin 3 or interleukin 1 abrogates the reconstituting ability of hematopoietic stem cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hematopoiesis; growth factors ID BLOOD CD34+ CELLS; PROGENITOR CELLS; EXVIVO EXPANSION; GROWTH-FACTORS; KIT-LIGAND; DIFFERENTIATION; PROLIFERATION; COLONIES; CULTURE; IL-6 AB Because of their known myelopoietic activities, both interleukin (IL)-3 and IL-1 are often used in combination with other cytokines for in vitro (ex vivo) expansion of stem cells. We have investigated the effects of IL-3 and IL-1 on in vitro expansion of murine hematopoietic stem cells with long-term engraftment capabilities, using a highly purified progenitor population. Lineage-negative, Ly-6A/E(+), c-kit(+) bone marrow cells from male mice were cultured in suspension in the presence of stem cell factor, IL-6, IL-11, and erythropoietin with or without IL-3 or IL-1. Kinetic studies revealed an exponential increase in total nucleated cells and about 10-fold enhancement of nucleated cells by IL-3 during the initial 10 days. Addition of IL-3 hastened the development but significantly suppressed the peak production of colony-forming cells. Addition of IL-1 also significantly suppressed the numbers of colony-forming cells. The reconstituting ability of the cultured cells was tested by transplanting the expanded male cells into lethally irradiated female mice, The cells expanded from enriched cells in the absence of IL-3 and IL-1 revealed engraftment at 2, 4, 5, and 6 months, whereas addition of IL-3 or IL-1 to the cultures significantly reduced the reconstituting ability. The results suggest that these cytokines mag. have a modulatory role on the self-renewal of stem cells and further indicate that the use of IL-3 and IL-1 for in vitro expansion of human stem cells needs to be cautiously evaluated. C1 RALPH H JOHNSON DEPT VET AFFAIRS MED CTR,CHARLESTON,SC 29401. AMGEN INC,THOUSAND OAKS,CA 91320. RP Yonemura, Y (reprint author), MED UNIV S CAROLINA,DEPT MED,CHARLESTON,SC 29401, USA. FU NIDDK NIH HHS [DK/HL48714, DK32294] NR 32 TC 161 Z9 163 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 1996 VL 93 IS 9 BP 4040 EP 4044 DI 10.1073/pnas.93.9.4040 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK557 UT WOS:A1996UK55700057 PM 8633013 ER PT J AU Shi, CW Lee, WS He, Q Zhang, D Fletcher, DL Newell, JB Haber, E AF Shi, CW Lee, WS He, Q Zhang, D Fletcher, DL Newell, JB Haber, E TI Immunologic basis of transplant-associated arteriosclerosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mutant mice; homologous recombination; immune deficiency; allogeneic vascular transplantation ID OP OP MOUSE; CARDIAC ALLOGRAFTS; CHAIN GENE; T-CELLS; MICE; DEFICIENT; OSTEOPETROSIS; REJECTION; MUTATION; DISEASE AB Although immunosuppressive therapy minimizes the risk of graft failure due to acute rejection, transplant-associated arteriosclerosis of the coronary arteries remains a significant obstacle to the long-term survival of heart transplant recipients. The participation of specific inflammatory cell types in the genesis of this lesion was examined in a mouse model in which carotid arteries were transplanted across multiple histocompatibility barriers into seven mutant strains with immunologic defects. An acquired immune response-with the participation of CD4(+) (helper) T cells, humoral antibody, and macrophages-was essential to the development of the concentric neointimal proliferation and luminal narrowing characteristic of transplant arteriosclerosis. CD8(+) (cytotoxic) T cells and natural killer cells were not involved in the process. Arteries allografted into mice deficient in both T-cell receptors and humoral antibody showed almost no neointimal proliferation, whereas those grafted into mice deficient only in helper T cells, humoral antibody, or macrophages developed small neointimas. These small neointimas and the large neointimas of arteries grafted into control animals contained a similar number of inflammatory cells; however, smooth muscle cell number and collagen deposition were diminished in the small neointimas. Also, the degree of inflammatory reaction in the adventitia did not correlate with the size of the neointima. Thus, the reduction in neointimal size in arteries allografted into mice deficient in helper T cells, humoral antibody, or macrophages may be accounted for by a decrease in smooth muscle cell migration or proliferation. C1 HARVARD UNIV,SCH PUBL HLTH,CARCIOVASC BIOL LAB,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CARDIAC COMP CTR,BOSTON,MA 02114. NR 29 TC 178 Z9 180 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 1996 VL 93 IS 9 BP 4051 EP 4056 DI 10.1073/pnas.93.9.4051 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK557 UT WOS:A1996UK55700059 PM 8633015 ER PT J AU Brachmann, RK Vidal, M Boeke, JD AF Brachmann, RK Vidal, M Boeke, JD TI Dominant-negative p53 mutations selected in yeast hit cancer hot spots SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR GENE; PROTEIN PHOSPHATASE; SYSTEM; OCCUR AB Clinically important mutant p53 proteins may be tumorigenic through a dominant-negative mechanism or due to a gain-of-function. Examples for both hypotheses have been described; however, it remains unclear to what extent they apply to TP53 mutations in general. Here it is shown that the mutational spectrum of dominant-negative p53 mutants selected in a novel yeast assay correlates tightly with p53 mutations in cancer. Two classes of dominant-negative mutations are described; the more dominant one affects codons that are essential for the stabilization of the DNA-binding surface of the p53 core domain and for the direct interaction of p53 with its DNA binding sites. These results predict that the vast majority of TP53 mutations leading to cancer do so in a dominant-negative fashion. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21287. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. NR 34 TC 123 Z9 129 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 1996 VL 93 IS 9 BP 4091 EP 4095 DI 10.1073/pnas.93.9.4091 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK557 UT WOS:A1996UK55700066 PM 8633021 ER PT J AU Lane, MA Baer, DJ Rumpler, WV Weindruch, R Ingram, DK Tilmont, EM Cutler, RG Roth, GS AF Lane, MA Baer, DJ Rumpler, WV Weindruch, R Ingram, DK Tilmont, EM Cutler, RG Roth, GS TI Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE aging; Macaca mulatta; locomotor activity; circadian rhythm; heart rate ID DIETARY RESTRICTION; FOOD RESTRICTION; METABOLIC-RATE; DEOXYRIBONUCLEIC-ACID; ENERGY-METABOLISM; FISCHER-344 RATS; MICE; ADULT; VARIABLES; LONGEVITY AB Many studies of caloric restriction (CR) in rodents and lower animals indicate that this nutritional manipulation retards aging processes, as evidenced by increased longevity, reduced pathology, and maintenance of physiological function in a more youthful state. The anti-aging effects of CR are believed to relate, at least in part, to changes in energy metabolism. We are attempting to determine whether similar effects occur in response to CR in nonhuman primates. Core (rectal) body temperature decreased progressively with age from 2 to 30 years in rhesus monkeys fed ad lib (controls) and is reduced by approximate to 0.5 degrees C in age-matched monkeys subjected to 6 years of a 30% reduction in caloric intake. A short-term (1 month) 30% restriction of 2.5-year-old monkeys lowered subcutaneous body temperature by 1.0 degrees C. Indirect calorimetry showed that 24-hr energy expenditure was reduced by approximately 24% during short-term CR. The temporal association between reduced body temperature and energy expenditure suggests that reductions in body temperature relate to the induction of an energy conservation mechanism during CR. These reductions in body temperature and energy expenditure are consistent with findings in rodent studies in which aging rate was retarded by CR, now strengthening the possibility that CR may exert beneficial effects in primates analogous to those observed in rodents. C1 USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,DIET & HUMAN PERFORMANCE LAB,BELTSVILLE,MD 20705. UNIV WISCONSIN,SCH MED,DEPT MED,MADISON,WI 53706. WILLIAM S MIDDLETON MEM VET ADM MED CTR,CTR GERIATR RES EDUC & CLIN,MADISON,WI 53706. RP Lane, MA (reprint author), NIA,MOLEC PHYSIOL & GENET SECT,NATHAN W SHOCK LABS,GERONTOL RES CTR,NIH,BAYVIEW MED CTR,BALTIMORE,MD 21224, USA. NR 43 TC 204 Z9 207 U1 0 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 1996 VL 93 IS 9 BP 4159 EP 4164 DI 10.1073/pnas.93.9.4159 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK557 UT WOS:A1996UK55700078 PM 8633033 ER PT J AU Roberts, RW Crothers, DM AF Roberts, RW Crothers, DM TI Prediction of the stability of DNA triplexes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE van't Hoff enthalpy; free energy; cytosine repulsion; nearest neighbor ID HELIX FORMATION; DUPLEX STABILITY; BASE-SEQUENCE; AFFINITY; RNA; OLIGONUCLEOTIDE; THERMODYNAMICS; INTERCALATION; SPECIFICITY; RECOGNITION AB We present rules that allow one to predict the stability of DNA pyrimidine . purine . pyrimidine (Y . R . Y) triple helices on the basis of the sequence. The rules were derived from van't Hoff analysis of 23 oligonucleotide triplexes tested at a variety of pH values. To predict the enthalpy of triples formation (Delta H degrees), a simple nearest-neighbor model was found to be sufficient. However, to accurately predict the free energy of the triples (Delta G degrees), a combination model consisting of five parameters was needed. These parameters were (i) the Delta G degrees for helix initiation, (ii) the Delta G degrees for adding a T-A . T triple, (iii) the Delta G degrees for adding a C+-G . C triple, (iv) the penalty for adjacent C bases, and (v) the pH dependence of the C+-G . C triple's stability. The fitted parameters are highly consistent with thermodynamic data from the basis set, generally predicting both Delta H degrees and Delta G degrees to within the experimental error. Examination of the parameters points out several interesting features. The combination model predicts that C+-G . C triples are much more stabilizing than T-A . T triples below pH 7.0 and that the stability of the former increases approximate to 1 kcal/mol per pH unit as the pH is decreased. Surprisingly though, the most stable sequence is predicted to be a CT repeat, as adjacent C bases partially cancel the stability of one another. The parameters successfully. predict t(m) values from other laboratories, with some interesting exceptions. C1 YALE UNIV,DEPT CHEM,NEW HAVEN,CT 06511. RP Roberts, RW (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 36 TC 62 Z9 62 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 1996 VL 93 IS 9 BP 4320 EP 4325 DI 10.1073/pnas.93.9.4320 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UK557 UT WOS:A1996UK55700108 PM 8633063 ER PT J AU Matthews, RT Beal, MF AF Matthews, RT Beal, MF TI Increased 3-nitrotyrosine in brains of Apo E-deficient mice SO BRAIN RESEARCH LA English DT Article DE peroxynitrite Alzheimer's disease; apolipoprotein E; oxidative stress ID APOLIPOPROTEIN-E; NITRIC-OXIDE; PEROXYNITRITE; SUPEROXIDE; DISEASE AB Apolipoprotein E (Apo-E) is linked to the pathogenesis of Alzheimer's disease. Apo-E deficient mice have increased lipid peroxidation in plasma; In the present study we examined two markers of oxidative stress in brains of Apo-E deficient mice. The ratios of 2,3 and 2,5 dihydroxybenzoic acid (DHBA)/salicylate, an index of hydroxyl radical generation, were unchanged except for an increase in 2,5-DHBA/salicylate in the cerebellum. 3-Nitrotyrosine is a marker for nitration of proteins produced by peroxynitrite. Concentrations of 3-nitrotyrosine were significantly increased in the cerebral cortex, hippocampus, brainstem and cerebellum of Apo-E deficient mice. These results suggest the Apo-E may modulate oxidative stress produced by peroxynitrite. C1 MASSACHUSETTS GEN HOSP,NEUROCHEM LAB,NEUROL SERV,BOSTON,MA 02114. HARVARD UNIV,MG3 MED SCH,BOSTON,MA 02114. FU NIA NIH HHS [P50 AGO 5134, P01 AG11337] NR 20 TC 51 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 APR 29 PY 1996 VL 718 IS 1-2 BP 181 EP 184 DI 10.1016/0006-8993(95)01576-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UP226 UT WOS:A1996UP22600024 PM 8773783 ER PT J AU Murphy, B Auchincloss, H Carpenter, CB Sayegh, MH AF Murphy, B Auchincloss, H Carpenter, CB Sayegh, MH TI T cell recognition of xeno-MHC peptides during concordant xenograft rejection SO TRANSPLANTATION LA English DT Article ID HISTOCOMPATIBILITY COMPLEX ALLOPEPTIDES; ANTIGEN-PRESENTING CELLS; ALLOGRAFTS; RESPONSES; MOUSE; TRANSPLANTATION; INDUCTION; TOLERANCE; SKIN; RAT AB T cell recognition of xenoantigens is likely to play a key role in rejection of xenografts surviving hyperacute and delayed xenograft rejection, but the mechanisms of how this might occur are unknown, We used synthetic rat class II MHC peptides to study the role of the indirect pathway, where processed xenogeneic MHC antigens are presented in the context of self MHC, in a concordant xenograft rejection model in vivo, Mice of four different strains, BALB/c, B10.A, CBA/ca, and C57BL/6j, were immunized with a mixture of rat class II MHC 25-mer xenopeptides representing the full-length sequence of the beta chain hypervariable domain of either RT1.D-u (DR and I-E like) or RT1.B-u (DQ and I-A like) of the Wistar-Furth (WF) (RT1(u)) rat, Draining lymph node cells were capable of recognizing and proliferating to specific class II xeno-MHC peptides, The immunogenicity of the different peptides varied with the responder mouse strain, Responder T cells were CD4(+), and were inhibited by anti-I-A and anti-I-E antibodies, We then examined the proliferative response of T cells from B10.A primed by WF skin or vascularized cardiac xenografts to the class II MHC xenopeptides, when presented by naive B10.A splenic antigen-presenting cells, These T cells were capable of proliferating to the same xeno-MHC peptides shown to be immunogenic by immunization, These data confirm the occurrence of self-restricted T cell recognition of xeno-MHC peptides in xenograft rejection, and provide the rationale for further investigating the role of the indirect pathway of recognition in xenotransplantation. C1 BRIGHAM & WOMENS HOSP,LAB IMMUNOGENET & TRANSPLANTAT,DEPT MED,DIV RENAL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA. FU NIAID NIH HHS [NSRA AI 09071, R29 AI 349965, R01 AI33100] NR 30 TC 28 Z9 28 U1 2 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 27 PY 1996 VL 61 IS 8 BP 1133 EP 1137 DI 10.1097/00007890-199604270-00001 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UJ003 UT WOS:A1996UJ00300001 PM 8610405 ER PT J AU Kochevar, IE Lambert, CR Lynch, MC Tedesco, AC AF Kochevar, IE Lambert, CR Lynch, MC Tedesco, AC TI Comparison of photosensitized plasma membrane damage caused by singlet oxygen and free radicals SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE photosensitization; singlet oxygen; free radical; plasma membrane; photodynamic therapy; membrane potential; proline transport; lipid oxidation ID MOUSE LYMPHOMA-CELLS; PHOTODYNAMIC THERAPY; ROSE-BENGAL; CHROMOPHORE; DEPOLARIZATION; DEGENERATION; ACTIVATION; APOPTOSIS; DYES AB The efficiency and selectivity of photosensitized damage to membrane functions may be influenced strongly by the identity of the initial reactive species formed by the photosensitizer. To test this possibility, a phorosensitizer, rose bengal (RE), was used that resides in the plasma membrane and which generates singlet molecular oxygen (O-1(2).) upon excitation with visible light, and radicals plus O-1(2). upon excitation with UV radiation. With this approach, O-1(2). and radicals are formed at the same locations in the plasma membrane. The response of three plasma membrane functions, namely, proline transport, membrane potential, and membrane impermeability to charged dye molecules, was assessed. The efficiencies of the responses in the presence and absence of oxygen were compared per photon absorbed by RE at two wavelengths; 355 nm (UV excitation) and 532 nm (visible excitation). The efficiency of oxygen removal before irradiation was assessed by measuring the RE tripler lifetime. The three membrane functions were inhibited more efficiently at 355 nm than at 532 nm in the presence of oxygen indicating that the radicals are more effective at initiating damage to membrane components than O-1(2). The ratio of photosensitized effects at the two wavelengths in the presence of oxygen was the same for two membrane functions but not for the third suggesting that O-1(2). and radicals initiate a common mechanistic pathway for damage to some membrane functions but not to others. Removing oxygen reduced the efficiency of 355 nm-induced photosensitization by factors of 1.4 to 7. The sensitivity of the three membrane functions to O-1(2).-initiated damage varied over a factor of 50 whereas radical initiated damage only varied by a factor of 15. In summary, these results indicate that radicals and O-1(2). formed at the same locations in the plasma membrane vary in their efficiency and specificity for membrane damage but may, in some cases, operate by a common secondary damage mechanism in the presence of oxygen. RP Kochevar, IE (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114, USA. RI Tedesco, Antonio/B-7584-2012 OI Tedesco, Antonio/0000-0003-4198-9321 FU NIGMS NIH HHS [R01 GM30755] NR 30 TC 42 Z9 44 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD APR 26 PY 1996 VL 1280 IS 2 BP 223 EP 230 DI 10.1016/0005-2736(95)00297-9 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UN360 UT WOS:A1996UN36000008 PM 8639697 ER PT J AU Yang, X Goncalves, J Gabuzda, D AF Yang, X Goncalves, J Gabuzda, D TI Phosphorylation of Vif and its role in HIV-1 replication SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-KINASE-C; GAG GENE-PRODUCTS; REV PROTEIN; ANTIRETROVIRAL ACTIVITY; INFECTED-CELLS; DNA-SYNTHESIS; VPU-PROTEIN; CEM CELLS; SOR GENE AB Vif is a 23-kDa protein encoded by human immunodeficiency virus, type 1 (HIV-1) which is important for virion infectivity. Here, we describe the phosphorylation of HIV-1 Vif and its role in HIV-1 replication. In vivo studies demonstrated that Vif is highly phosphorylated on serine and threonine residues. To identify phosphorylation sites and characterize the Vif kinase(s), Vif was expressed in Escherichia coli and purified for use as a substrate in in vitro kinase assays. The purified Vif protein was phosphorylated in vitro on serine and threonine residues by a kinase(s) present in both cytosol and membrane fractions. Phosphorylation of Vif was stimulated by phorbol 12-myristate 13-acetate and inhibited by staurosporine and hypericin, a drug with potent anti-HIV activity. The Vif kinase(s) was resistant to inhibitors of protein kinase C, cAMP-dependent kinase, and cGMP-dependent kinase, suggesting that it is distinct from these enzymes. To identify the phosphorylation sites, P-32-labeled Vif was digested by V8 protease and the peptides were resolved by reverse-phase high performance liquid chromatography. Radioactive peptide sequencing identified three phosphorylation sites within the C terminus, Ser(144), Thr(155), and Thr(188). Two-dimensional tryptic phosphopeptide mapping indicated that these sites are also phosphorylated in vivo. Both Ser(144) and Thr(188) are contained in the recognition motifs (R/KXXS*/T* and R/KXXXS*/T*) used by serine/threonine protein kinases such as cGMP-dependent kinase and PKC. Ser(144) is present in the motif SLQXLA, which is the most highly conserved sequence among all lentivirus Vif proteins. Mutation of Ser(144) to alanine resulted in loss of Vif activity and >90% inhibition of HIV-1 replication. These studies suggest that phosphorylation of Vif by a serine/threonine protein kinase(s) plays an important role in regulating HIV-1 replication and infectivity. C1 HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DIV HUMAN RETROVIROL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT PATHOL, BOSTON, MA 02115 USA. HARVARD UNIV, SCH MED, DEPT NEUROL, BOSTON, MA 02115 USA. RI iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, M2B /B-5277-2014; Goncalves, Joao/B-2013-2008 OI Goncalves, Joao/0000-0002-1245-3715 FU NIAID NIH HHS [AI36186, AI28691, AI33837] NR 55 TC 92 Z9 95 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD APR 26 PY 1996 VL 271 IS 17 BP 10121 EP 10129 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG257 UT WOS:A1996UG25700043 PM 8626571 ER PT J AU Jenden, DJ Scremin, OU Roch, M Li, G AF Jenden, DJ Scremin, OU Roch, M Li, G TI The influence of aging on whole body choline release and clearance SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT Scientific Festschrift on Cholinergic and Related Mechanisms in Aging and Disease - A Tribute to Donald J Jenden, MD CY NOV 17-18, 1995 CL UNIV CALIF LOS ANGELES, LOS ANGELES, CA SP Loyola Univ Chicago Stritch Sch Med, Neurosci & Aging Inst HO UNIV CALIF LOS ANGELES DE choline release; choline clearance; hypoxia; age; deuterium labelling; pharmacokinetics AB We have confirmed that hypoxia elicits a substantial rise in blood choline levels in young adult rats. An intravenous infusion of tracer quantities of [H-2(4)]-Ch, serial measurements of blood [H-2(0)]-Ch and [H-2(4)]-Ch, and a simple pharmacokinetic model were used to assess the bidirectional nux of choline between the central pool and peripheral pools before, during and after a period of imposed hypoxia, in rats ranging fi-om 56 to 780 days of age. The results indicate that the age-dependence of the hypercholinemic response to hypoxia is predominantly due to an increase in the amount of choline released in response to hypoxia, and that changes in its clearance are relatively unimportant. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90095. W LOS ANGELES VET AFFAIRS MED CTR,GERIATR RES & EDUC CLIN CTR,LOS ANGELES,CA 90073. RP Jenden, DJ (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT PHARMACOL,LOS ANGELES,CA 90095, USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 26 PY 1996 VL 58 IS 22 BP 2003 EP 2009 DI 10.1016/0024-3205(96)00191-9 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UH285 UT WOS:A1996UH28500014 PM 8637430 ER PT J AU Scremin, OU Jenden, DJ AF Scremin, OU Jenden, DJ TI Cholinergic control of cerebral blood flow in stroke, trauma and aging SO LIFE SCIENCES LA English DT Article; Proceedings Paper CT Scientific Festschrift on Cholinergic and Related Mechanisms in Aging and Disease - A Tribute to Donald J Jenden, MD CY NOV 17-18, 1995 CL UNIV CALIF LOS ANGELES, LOS ANGELES, CA SP Loyola Univ Chicago Stritch Sch Med, Neurosci & Aging Inst HO UNIV CALIF LOS ANGELES DE cerebrovascular circulation; acetylcholine; choline; brain injuries; aging ID ALZHEIMERS-DISEASE; RAT-BRAIN; PLASMA CHOLINE; ACETYLCHOLINE; METABOLISM; DEMENTIA; VASODILATATION; AUTOREGULATION; STIMULATION; TURNOVER AB Enhancing the availability of endogenous acetylcholine by inhibition of cholinesterase with physostigmine, eptastigmine or soman at sub-toxic doses increases cerebral blood flow (CBF) and the response of this variable to changes in PaCO2. These effects are not correlated with metabolic activation, suggesting that the function of the cholinergic vasodilatation is not merely to supply metabolic substrates. Since choline (Ch) can exchange between blood and the brain extracellular milieu the stage is set for possible feedback interactions between ACh synthesis and CBF. A negative feedback of CBF on ACh synthesis under conditions of a negative arteriovenous (A-V) difference for Ch across cerebral capillaries may contribute to stabilize CBF in ischemia. Eptastigmine and physostigmine significantly improve perfusion in experimental models of focal cerebral ischemia and traumatic brain injury respectively. During the short periods of time in which the A-V difference for Ch across the brain is positive, a positive feedback between cerebral free Ch and CBF may enhance the ability of the brain to recover Ch from the circulation for synthesis of membrane phospholipids. A loss of cholinergic cerebrovascular control may thus impair the survival of all cells within the CNS and contribute to the pathophysiology of dementia. Perhaps the view that the loss of cholinergic cells is the end point of Alzheimer's dementia could be modified to state that a cholinergic deficit may be the starting point of a decline in cerebral phospholipid turnover and cell membrane renewal that could lead to a generalized deterioration of cerebral function. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT MOLEC & MED PHARMACOL,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,SCH MED,DEPT BIOMATH,LOS ANGELES,CA 90073. RP Scremin, OU (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,GERIATR RES & EDUC CLIN CTR,11301 WILSHIRE BLVD,LOS ANGELES,CA 90073, USA. NR 44 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 26 PY 1996 VL 58 IS 22 BP 2011 EP 2018 DI 10.1016/0024-3205(96)00192-0 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UH285 UT WOS:A1996UH28500015 PM 8637431 ER PT J AU Schacter, DL Savage, CR Alpert, NM Rauch, SL Albert, MS AF Schacter, DL Savage, CR Alpert, NM Rauch, SL Albert, MS TI The role of hippocampus and frontal cortex in age-related memory changes: A PET study SO NEUROREPORT LA English DT Article DE positron emission tomography; memory; aging; hippocampal formation; frontal lobes ID PREFRONTAL CORTEX; DYSFUNCTION; RETRIEVAL; NETWORKS; AMNESIA AB THE purpose of this study was to examine neuroanatomical correlates of explicit retrieval of episodic memories in older and young adults. We used an experimental paradigm that allowed us to separate the effort involved in attempting to retrieve a recently studied word from the actual recollection of the item. Both older and younger adults showed hippocampal blood flow increases in association with recollection of a studied word. Lo contrast, younger but not older adults showed bilateral blood increases in anterior prefrontal cortex during retrieval attempts: older adults showed more posterior frontal lobe activations during attempted retrieval. We conclude that the hippocampus activations may reflect a commonality in the way that older and younger adults remember past events, whereas differences in frontal activation may reflect age-related changes in their retrieval strategies. C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02129. HARVARD UNIV,SCH MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02129. RP Schacter, DL (reprint author), HARVARD UNIV,DEPT PSYCHOL,33 KIRKLAND ST,CAMBRIDGE,MA 02138, USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441-06]; NIMH NIH HHS [MH01215, MH01230] NR 25 TC 170 Z9 172 U1 2 U2 9 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD APR 26 PY 1996 VL 7 IS 6 BP 1165 EP 1169 DI 10.1097/00001756-199604260-00014 PG 5 WC Neurosciences SC Neurosciences & Neurology GA VK184 UT WOS:A1996VK18400014 PM 8817525 ER PT J AU Barker, FG Jannetta, PJ Bissonette, DJ Larkins, MV Jho, HD AF Barker, FG Jannetta, PJ Bissonette, DJ Larkins, MV Jho, HD TI The long-term outcome of microvascular decompression for trigeminal neuralgia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RETROGASSERIAN GLYCEROL RHIZOTOMY; PARTIAL SENSORY RHIZOTOMY; HEMIFACIAL SPASM; MANAGEMENT; EXPERIENCE; INJECTION; GANGLION AB Background. Several surgical procedures to treat trigeminal neuralgia (tic douloureux) are available, but most reports provide only short-term follow-up information. Methods. We describe the long-term results of surgery in 1185 patients who underwent microvascular decompression of the trigeminal nerve for medically intractable trigeminal neuralgia, The outcome of the procedure was assessed prospectively with annual questionnaires. Results. Of the 1185 patients who underwent microvascular decompression during the 20-year study period, 1155 were followed for 1 year or more after the operation, The median follow-up period was 6.2 years, Most postoperative recurrences of tic took place in the first two years after surgery, Thirty percent of the patients had recurrences of tie during the study period, and 11 percent underwent second operations for the recurrences. Ten years after surgery, 70 percent of the patients (as determined by Kaplan-Meier analysis) had excellent final results - that is, they were free of pain without medication for tie. An additional 4 percent had occasional pain that did not require long-term medication, Ten years after the procedure, the annual rate of the recurrence of tic was less than 1 percent, Female sex, symptoms lasting more than eight years, venous compression of the trigeminal-root entry zone, and the lack of immediate postoperative cessation of tic were significant predictors of eventual recurrence, Having undergone a previous ablative procedure did not lessen a patient's likelihood of having a cessation of tic after microvascular decompression, but the rates of burning and aching facial pain, as reported on the last follow-up questionnaire, were higher if a trigeminal-ganglion lesion had been created with radiofrequency current before microvascular decompression. Major complications included two deaths shortly after the operation (0.2 percent) and one brain-stem infarction (0.1 percent), Sixteen patients (1 percent) had ipsilateral hearing loss. Conclusions. Microvascular decompression is a safe and effective treatment for trigeminal neuralgia, with a high rate of long-term success. (C) 1996, Massachusetts Medical Society. C1 MASSACHUSETTS GEN HOSP,NEUROL SERV,BOSTON,MA 02114. UNIV PITTSBURGH,DEPT NEUROL SURG,PITTSBURGH,PA 15260. SW OHIO NEUROSURG,PIQUA,OH. NR 39 TC 597 Z9 636 U1 7 U2 22 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 25 PY 1996 VL 334 IS 17 BP 1077 EP 1083 DI 10.1056/NEJM199604253341701 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UG457 UT WOS:A1996UG45700001 PM 8598865 ER PT J AU Emanuel, EJ Daniels, E AF Emanuel, EJ Daniels, E TI Oregon's physician-assisted suicide law - Provisions and problems SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID DEPRESSION; CARE; ILL RP Emanuel, EJ (reprint author), DANA FARBER CANC INST,CTR OUTCOMES & POLICY RES STUDIES,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115, USA. NR 17 TC 27 Z9 27 U1 5 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 22 PY 1996 VL 156 IS 8 BP 825 EP 829 DI 10.1001/archinte.156.8.825 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA UF803 UT WOS:A1996UF80300001 PM 8774200 ER PT J AU Gelber, RD Cole, BF Goldhirsch, A Rose, C Fisher, B Osborne, CK Boccardo, F Gray, R Gordon, NH Bengtsson, NO Sevelda, P AF Gelber, RD Cole, BF Goldhirsch, A Rose, C Fisher, B Osborne, CK Boccardo, F Gray, R Gordon, NH Bengtsson, NO Sevelda, P TI Adjuvant chemotherapy plus tamoxifen compared with tamoxifen alone for postmenopausal breast cancer: Meta-analysis of quality-adjusted survival SO LANCET LA English DT Article ID TRIAL; LIFE AB Background Adjuvant tamoxifen for early breast cancer provides an improvement in relapse-free (RFS) and overall survival (OS), especially for older women. We carried out a meta-analysis to find out whether the benefit of adding chemotherapy to tamoxifen outweighs its costs in terms of toxic effects for postmenopausal patients. Methods The meta-analysis of quality-adjusted survival was based on data from 3920 patients aged 50 years or older with node-positive breast cancer randomly assigned in nine trials that compared combination chemotherapy plus tamoxifen with tamoxifen alone. The nine trials were included in the worldwide overview conducted by the early breast. cancer trialists' collaborative group (EBCTCG). The quality-adjusted time without symptoms or toxicity (Q-TWiST) method was used to provide treatment comparisons incorporating differences in quality of life associated with subjective toxic effects of treatment and symptoms of disease relapse. Findings Within 7 years of follow-up the modest benefit of increased RFS and OS for patients who received chemotherapy just balanced the costs in terms of acute toxic side-effects. Chemotherapy-treated patients gained an average of 5 . 4 months of RFS and 2 months of OS (neither statistically significant), but had to receive cytotoxic treatment for between 2 and 24 months to achieve these gains. No values of preference weights for time spent undergoing chemotherapy and time after relapse gave significantly more Q-TWiST with chemotherapy plus tamoxifen than with tamoxifen alone. Interpretation Within 7 years of follow-up, adjuvant significant advantage in relapse-free survival, but the effect on overall survival was not significant. The question of whether the observed benefit for chemotherapy outweighs the costs in terms of toxic effects demands an answer before the regimen is used for all postmenopausal patients who require adjuvant systemic therapy. Our evaluation of chemotherapy effectiveness in postmenopausal patients was based on a meta-analysis of quality-adjusted survival. We analysed data from all trials on combination chemotherapy plus tamoxifen versus tamoxifen alone included in the EBCTCG overview update. Treatment effects were estimated exclusively for patients aged 50 years or older. We provided an additional type of analysis that incorproated features of quality of life into the treatment comparison. C1 HARVARD UNIV,SCH MED,SCH PUBL HLTH,DANA FARBER CANC INST,CTR OUTCOMES & POLICY RES,BOSTON,MA 02115. BROWN UNIV,DEPT COMMUNITY HLTH,PROVIDENCE,RI 02912. BROWN UNIV,DIV APPL MATH,PROVIDENCE,RI 02912. OSPED CIV,DIV ONCOL,LUGANO,SWITZERLAND. ODENSE UNIV HOSP,DIV ONCOL R,DK-5000 ODENSE,DENMARK. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15260. UNIV TEXAS,HLTH SCI CTR,DEPT MED,SAN ANTONIO,TX 78284. IST NAZL RIC CANC,I-16132 GENOA,ITALY. RADCLIFFE INFIRM,CLIN TRIAL SERV UNIT,OXFORD OX2 6HE,ENGLAND. CASE WESTERN RESERVE UNIV,UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. REG SJUKHUSET,DEPT ONCOL,UMEA,SWEDEN. UNIV HOSP,VIENNA,AUSTRIA. RP Gelber, RD (reprint author), HARVARD UNIV,SCH MED,SCH PUBL HLTH,DANA FARBER CANC INST,DIV BIOSTAT,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA-06516] NR 31 TC 98 Z9 99 U1 0 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 20 PY 1996 VL 347 IS 9008 BP 1066 EP 1071 DI 10.1016/S0140-6736(96)90277-9 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UG042 UT WOS:A1996UG04200010 PM 8602056 ER PT J AU Huncharek, M Kelsey, K Muscat, J Christiani, D AF Huncharek, M Kelsey, K Muscat, J Christiani, D TI Parental cancer and genetic predisposition in malignant pleural mesothelioma: A case-control study SO CANCER LETTERS LA English DT Article DE familial clustering; pleural mesothelioma; genetic predisposition ID FAMILIAL MESOTHELIOMA AB Familial clustering of pleural mesothelioma (PM) has been previously reported suggesting that genetic factors (predisposition) may be involved in PM. We studied parental cancer history in a cohort of 39 cases of PM and 259 age matched controls to assess the possible influence of family history on PM risk. Cases consisted of 39 patients with PM treated at our institution between 1978 and 1993, An age frequency matched control group (by 5-year age groups) consisted of 259 subjects who were spouses or friends of patients undergoing resection of primary lung cancer. Data were obtained by interview of controls and interview of the patient or next of kin (usually spouse) for cases. The following data were obtained using a standard questionnaire and medical record review; age, sex, date of diagnosis, history of asbestos exposure, smoking history, method of diagnosis, histologic subtype, type of treatment, parental cancer history and tumor type. Cases and control frequency of parental cancer and site specific tumor frequency were compared using chi-square analysis. Twenty-eight (71%) cases reported a parental history of cancer versus 114 (44%) in the control group (P < 0.01). Gastrointestinal malignancies were the predominant tumor type among parents of cases, i.e. 11 cases (40%) versus 25% of controls (P < 0.01). No other tumor site showed an increased frequency among cases. These data suggest a possible role for family history in the development of PM. Genetic predisposition may be important in the etiology of this tumor. C1 HARVARD UNIV,SCH PUBL HLTH,OCCUPAT HLTH PROGRAM,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,RADIOBIOL LAB,BOSTON,MA 02115. AMER HLTH FDN,DIV EPIDEMIOL,NEW YORK,NY 10017. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT PULM & CRIT CARE MED,BOSTON,MA. RP Huncharek, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT RADIAT ONCOL,COX B,BOSTON,MA 02114, USA. NR 10 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 19 PY 1996 VL 102 IS 1-2 BP 205 EP 208 DI 10.1016/0304-3835(96)04172-9 PG 4 WC Oncology SC Oncology GA UB974 UT WOS:A1996UB97400027 PM 8603371 ER PT J AU Takahashi, K Stamenkovic, I Cutler, M Dasgupta, A Tanabe, KK AF Takahashi, K Stamenkovic, I Cutler, M Dasgupta, A Tanabe, KK TI Keratan sulfate modification of CD44 modulates adhesion to hyaluronate SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MELANOMA CELL MOTILITY; MONOCLONAL-ANTIBODIES; COLORIMETRIC ASSAY; COLON CARCINOMAS; ACID BINDING; I COLLAGEN; RECEPTOR; IDENTIFICATION; PROTEOGLYCAN; MOLECULE AB CD44 alternative splicing has been implicated in the regulation of CD44 function, CD44 undergoes significant posttranslational modification in all cells, but the functional consequences of these modifications are poorly understood, In the current study, we have demonstrated that keratan sulfate modification of CD44 significantly modulates its ability to bind to hyaluronate. We observed naturally occurring differences in CD44 keratan sulfate substitution between two clonal variants of the KM12 human colon carcinoma cell line. CD44 on the highly metastatic KM12L4 clone is more heavily substituted with keratan sulfate than CD44 on the poorly metastatic KM12C6 clone, Moreover, CD44H on KM112L4 bound to hyaluronate poorly compared to CD44H on KM12C6, Removal of keratan sulfate from CD44 greatly enhanced CD44-mediated cell adhesion to hyaluronate. Removal of keratan sulfate from CD44H-immunoglobulin fusion proteins also enhanced their adhesion to hyaluronate, The influence of glycosaminoglycan substitution on CD44 function was specific to keratan sulfate substitution; treatment to remove chondroitin sulfate, heparan sulfate, or hyaluronate did not affect CD44-mediated cell adhesion to hyaluronate, Use of site-directed CD44H cDNA mutants with arginine changed to alanine at position 41 indicated that keratan sulfate modification of CD44 modulates hyaluronate adhesion through its B loop domain. These findings suggest that keratan sulfate modification of CD44 may play an important regulatory role in the broad spectrum of biological processes attributed to CD44, including normal development, tumor progression, and lymphocyte function. C1 MASSACHUSETTS GEN HOSP,DIV SURG ONCOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,DIV MED ONCOL,BOSTON,MA 02114. FU NCI NIH HHS [CA55735, CA64454]; NIDDK NIH HHS [DK433351] NR 43 TC 72 Z9 72 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 19 PY 1996 VL 271 IS 16 BP 9490 EP 9496 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG044 UT WOS:A1996UG04400051 PM 8621620 ER PT J AU Igarashi, P Whyte, DA Li, K Nagami, GT AF Igarashi, P Whyte, DA Li, K Nagami, GT TI Cloning and kidney cell-specific activity of the promoter of the murine renal Na-K-Cl cotransporter gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL-CELLS; RAT-TISSUES; EXPRESSION; PROTEINS AB The murine Nkcc2/Slc12a1 gene encodes a bumetanide sensitive Na-K-Cl cotransporter that is expressed exclusively in the kidney in the thick ascending limb of the loop of Henle, Nuclear run-off assays demonstrated that kidney-specific expression of Nkcc2 was due, at least in part, to kidney-specific gene transcription, To begin study of the gene promoter, a genomic clone that contained 13.5 kilobases of the 5'-flanking region of Nkcc2 was isolated. A single transcription initiation site was located 1330 base pairs (bp) upstream of the start codon. The sequence of the proximal 5'-flanking region contained typical eukaryotic promoter elements including a TATA box, two CCAAT boxes, and an initiator, A (G-A)(28) (C-T)(28) microsatellite and consensus binding sites for hepatocyte nuclear factor 1, cAMP-response element binding protein, CCAAT/enhancer-binding proteins, and basic helix-loop-helix proteins, were also identified, To functionally express the promoter, 2255 bp of the proximal 5'-flanking region was ligated to a luciferase reporter gene and transfected into thick ascending limb (TAL) cells, a stable cell line derived from microdissected loops of Henle of the Tg(SV40E)Bri7 mouse. TAL cells exhibited furosemide-sensitive Na-K(NH4+)-Cl cotransport activity and endogenously expressed the 5.0-kilobase Nkcc2 transcript. Luciferase activity was 130-fold greater following transfection into TAL cells compared with transfection into cells that did not express Nkcc2 (NIH 3T3 fibroblasts). Deletion analysis revealed that promoter activity in TAL cells was similar in constructs extending from the transcription initiation site to -1529 to -469, whereas further deletion to -190 resulted in a 76% decrease in activity, We conclude that the Nkcc2 promoter exhibits kidney cell-specific activity. Regulatory elements required for maximal promoter activity are located in a 280-bp DNA segment that contains consensus binding sites for several transcription factors expressed in the kidney. C1 YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06520. W LOS ANGELES DEPT VET AFFAIRS,MED CTR,MED & RES SERV,LOS ANGELES,CA 90073. RP Igarashi, P (reprint author), YALE UNIV,SCH MED,NEPHROL SECT,DEPT INTERNAL MED,333 CEDAR ST,NEW HAVEN,CT 06520, USA. OI Igarashi, Peter/0000-0001-8698-1185 FU NIDDK NIH HHS [R01 DK-44122, R01 DK-42921, T32 DK-07276] NR 43 TC 84 Z9 83 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 19 PY 1996 VL 271 IS 16 BP 9666 EP 9674 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG044 UT WOS:A1996UG04400073 PM 8621642 ER PT J AU Song, KS Li, SW Okamoto, T Quilliam, LA Sargiacomo, M Lisanti, MP AF Song, KS Li, SW Okamoto, T Quilliam, LA Sargiacomo, M Lisanti, MP TI Co-purification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains - Detergent-free purification of caveolae membranes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-GOLGI-NETWORK; ROUS-SARCOMA VIRUS; PLASMA-MEMBRANE; EPITHELIAL-CELLS; COMPONENT; VESICLES; SIGNAL; TRANSFORMATION; MOLECULES; TYROSINE AB Caveolae are plasma membrane specializations that have been implicated in signal transduction. Caveolin, a 21-24-kDa integral membrane protein, is a principal structural component of caveolae membranes in vivo, G protein alpha subunits are concentrated in purified preparations of caveolae membranes, and caveolin interacts directly with multiple G protein alpha subunits, including G(s), G(o), and G(i2). Mutational or pharmacologic activation of G, subunits prevents the interaction of caveolin with G(alpha) proteins, indicating that inactive G(alpha) subunits preferentially interact with caveolin, Here, we show that caveolin interacts with another well characterized signal transducer, Ras, Using a detergent-free procedure for purification of caveolin-rich membrane domains and a polyhistidine tagged form of caveolin, we find that Has and other classes of lipid-modified signaling molecules co-fractionate and co-elute with caveolin, The association of Ras with caveolin was further evaluated using two distinct in vitro binding assays, Wild-type H-Ras interacted with glutathione S-transferase (GST)-caveolin fusion proteins but not with GST alone. Using a battery of GST fusion proteins encoding distinct regions of caveolin, Ras binding activity was localized to a 41-amino acid membrane proximal region of the cytosolic N-terminal domain of caveolin, In addition, reconstituted caveolin-rich membranes (prepared with purified recombinant caveolin and purified lipids) interacted with a soluble form of wild-type H-Ras but failed to interact with mutationally activated soluble H-Ras (G12V), Thus, a single amino acid change (G12V) that constitutively activates Ras prevents or destabilizes this interaction, These results clearly indicate that (i) caveolin is sufficient to recruit soluble Ras onto lipid membranes and (ii) membrane-bound caveolin preferentially interacts with inactive Ras proteins, In direct support of these in vitro studies, we also show that recombinant overexpression of caveolin in intact cells is sufficient to functionally recruit a nonfarnesylated mutant of Ras (C186S) onto membranes, overcoming the normal requirement for lipid modification of has. Taken together, these observations suggest that caveolin may function as a scaffolding protein to localize or sequester certain caveolin-interacting proteins, such as wild-type Ras, within caveolin-rich microdomains of the plasma membrane. C1 WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,SHRINERS HOSP CRIPPLED CHILDREN,DEPT ANESTHESIA,BOSTON,MA 02114. INDIANA UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOL,INDIANAPOLIS,IN 46202. RI Lisanti, Michael/C-6866-2013; Quilliam, Lawrence/B-6447-2015 FU NCI NIH HHS [CA-63139]; NIGMS NIH HHS [GM-50443] NR 59 TC 852 Z9 863 U1 2 U2 22 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 19 PY 1996 VL 271 IS 16 BP 9690 EP 9697 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG044 UT WOS:A1996UG04400076 PM 8621645 ER PT J AU Cannistra, SA Niloff, JM AF Cannistra, SA Niloff, JM TI Medical progress - Cancer of the uterine cervix SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SQUAMOUS-CELL CARCINOMA; HUMAN PAPILLOMAVIRUS TYPE-16; GYNECOLOGIC-ONCOLOGY-GROUP; IMMUNODEFICIENCY-VIRUS INFECTION; TERM FOLLOW-UP; RADIATION-THERAPY; STAGE-IB; INTRAEPITHELIAL NEOPLASIA; RADICAL HYSTERECTOMY; PELVIC EXENTERATION C1 BETH ISRAEL HOSP,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA. RP Cannistra, SA (reprint author), DANA FARBER CANC INST,DEPT MED,DIV MED ONCOL,44 BINNEY ST,BOSTON,MA 02115, USA. NR 101 TC 206 Z9 218 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 18 PY 1996 VL 334 IS 16 BP 1030 EP 1038 DI 10.1056/NEJM199604183341606 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA UE733 UT WOS:A1996UE73300006 PM 8598842 ER PT J AU Liberthson, RR AF Liberthson, RR TI Current concepts - Sudden death from cardiac causes in children and young adults SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID MITRAL-VALVE PROLAPSE; CARDIOVASCULAR-DISEASE; UNEXPECTED DEATH; KAWASAKI DISEASE; NATURAL DEATH; CARDIOMYOPATHY; CHILDHOOD; ADOLESCENCE; PROGNOSIS; ANEURYSMS C1 HARVARD UNIV,SCH MED,BOSTON,MA. RP Liberthson, RR (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,BOSTON,MA 02114, USA. NR 53 TC 275 Z9 287 U1 1 U2 7 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 18 PY 1996 VL 334 IS 16 BP 1039 EP 1044 DI 10.1056/NEJM199604183341607 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UE733 UT WOS:A1996UE73300007 PM 8598843 ER PT J AU Mulholland, K Suara, RO Siber, G Roberton, D Jaffar, S NJie, J Baden, L Thompson, C Anwaruddin, R Dinan, L Glezen, WP Francis, N Fritzell, B Greenwood, BM AF Mulholland, K Suara, RO Siber, G Roberton, D Jaffar, S NJie, J Baden, L Thompson, C Anwaruddin, R Dinan, L Glezen, WP Francis, N Fritzell, B Greenwood, BM TI Maternal immunization with Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine in the Gambia SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEMOPHILUS-INFLUENZAE; PREGNANT-WOMEN; CAPSULAR POLYSACCHARIDE; SERUM ANTIBODIES; CHILDREN; INFANTS; MENINGITIS; PROTECTION AB Objective.-To evaluate maternal responses to Haemophilus influenzae type b (Hib) polysaccharide-tetanus protein conjugate vaccine (polyribosylribitol phosphate-tetanus or PRP-T) given to pregnant Gambian women, the transplacental transfer of antibody, and the effect of maternal immunization on infant responses to the vaccine. Design.-An open, randomized immunogenicity study. Setting.-A busy urban health center in The Gambia. Study participants.-A total of 451 pregnant women enrolled during the third trimester of pregnancy. Intervention.-Study participants were randomized to three groups. In one group, mothers were given PRP-T during the third trimester and their infants were given PRP-T at 2, 3, and 4 months of age, In the second group, mothers received PRP-T and infants were given inactivated poliovirus vaccine. In the third group, mothers received meningococcal A and C vaccine, and their infants received PRP-T. Main Outcome Measures.-Anti-PRP antibody measurements of maternal, cord, and infant blood. Results.-Vaccinated women had a marked increase in total anti-PRP antibody (geometric mean titer, 9.0 mu g/mL), which was greatest in women in their first or second pregnancy, Previous tetanus vaccination during the same pregnancy and high concentrations of antitetanus antibody were associated with lower anti-PRP responses. In infants of PRP-T recipients, cord blood anti-PRP IgG concentrations were 61% of simultaneous maternal concentrations, In vaccinated infants of vaccinated mothers, geometric mean anti-PRP antibody concentrations at birth, 2 months of age, and 5 months of age were 1.92, 0.35, and 2.84 mu g/mL, respectively, while in vaccinated infants of unvaccinated mothers, the corresponding concentrations were 0.29, 0.12, and 3.91 mu g/mL. At 2 months of age, 60% of infants of vaccinated mothers and 26% of infants of unvaccinated mothers had anti-PRP antibody concentrations considered to be protective (>0.15 mu g/mL). Conclusions.-In areas where much invasive Hib disease occurs in infants younger than 6 months, maternal immunization may help to reduce the risk of Hib disease in infants too young for immunization. C1 MRC LABS,FAJARA,GAMBIA. DANA FARBER CANC INST,BOSTON,MA 02115. UNIV ADELAIDE,DEPT PAEDIAT,ADELAIDE,SA 5001,AUSTRALIA. BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. CHARING CROSS & WESTMINSTER MED SCH,DEPT HISTOPATHOL,LONDON W6 8RF,ENGLAND. PASTEUR MERIEUX SERUMS & VACCINS,MARNES COQUETTE,FRANCE. FU NIAID NIH HHS [AI 15126] NR 36 TC 42 Z9 43 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 17 PY 1996 VL 275 IS 15 BP 1182 EP 1188 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UE625 UT WOS:A1996UE62500030 PM 8609686 ER PT J AU Zhu, Y Carroll, M Papa, FR Hochstrasser, M DAndrea, AD AF Zhu, Y Carroll, M Papa, FR Hochstrasser, M DAndrea, AD TI DUB-1, a deubiquitinating enzyme with growth-suppressing activity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cytokines; interleukin 3; ubiquitin; cell cycle ID DIFFERENTIAL DISPLAY; BETA-SUBUNIT; TRE ONCOGENE; RECEPTOR; CLONING; COMPLEX; PRODUCT; SIGNAL; FAMILY AB Cytokines regulate cell growth by inducing the expression of specific target genes. Using the differential display method, we have cloned a cytokine-inducible immediate early gene, DUE-I (for deubiquitinating enzyme), DUE-I is related to members of the UBP superfamily of deubiquitinating enzymes, which includes the oncoprotein Tre-2. A glutathione S-transferase-DUB-1 fusion protein cleaved ubiquitin from a ubiquitin-beta-galactosidase protein. When a conserved cysteine residue of DUE-I, required for ubiquitin specific thiol protease activity, was mutated to serine (C60S), deubiquitinating activity was abolished, Continuous expression of DUE-I from a steroid-inducible promoter induced growth arrest in the G(1) phase of the cell cycle, Cells arrested by DUE-I expression remained viable and resumed proliferation upon steroid withdrawal, Our results suggest that DUE-I regulates cellular growth by modulating either the ubiquitin-dependent proteolysis or the ubiquitination state of an unknown growth regulatory factor(s). C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,CELLULAR & MOL BIOL DIV,BOSTON,MA 02115. UNIV CHICAGO,DEPT BIOCHEM & MOLEC BIOL,CHICAGO,IL 60637. FU NIDDK NIH HHS [R01 DK43889-01]; NIGMS NIH HHS [GM46904] NR 44 TC 145 Z9 149 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 1996 VL 93 IS 8 BP 3275 EP 3279 DI 10.1073/pnas.93.8.3275 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UF740 UT WOS:A1996UF74000023 PM 8622927 ER PT J AU Verchere, CB DAlessio, DA Palmiter, RD Weir, GC BonnerWeir, S Baskin, DG Kahn, SE AF Verchere, CB DAlessio, DA Palmiter, RD Weir, GC BonnerWeir, S Baskin, DG Kahn, SE TI Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE non-insulin-dependent diabetes mellitus; insulin; glucose ID SECRETORY GRANULES; DIABETES-MELLITUS; GLUCOSE-TOLERANCE; INSULIN; PEPTIDE; PROTEIN; LOCALIZATION; SUSCEPTIBILITY; LANGERHANS; FIBRILS AB Pancreatic islet amyloid deposits are a characteristic pathologic feature of non-insulin-dependent diabetes mellitus and contain islet amyloid polypeptide (IAPP; amylin), We used transgenic mice that express human IAPP in pancreatic beta cells to explore the potential role of islet amyloid in the pathogenesis of non-insulin-dependent diabetes mellitus, Extensive amyloid deposits were observed in the pancreatic islets of approximate to 80% of male transgenic mice >13 months of age. Islet amyloid deposits were rarely observed in female transgenic mice (11%) and were never seen in nontransgenic animals, Ultrastructural analysis revealed that these deposits were composed of human IAPP-immunoreactive fibrils that accumulated between beta cells and islet capillaries. Strikingly, approximately half of the mice with islet amyloid deposits were hyperglycemic (plasma glucose >11 mM). In younger (6- to 9-month-old) male transgenic mice, islet amyloid deposits were less commonly observed but were always associated with severe hyperglycemia (plasma glucose >22 mM). These data indicate that expression of human IAPP in beta cells predisposes male mice to the development of islet amyloid and hyperglycemia. The frequent concordance of islet amyloid with hyperglycemia in these mice suggests an interdependence of these two conditions and supports the hypothesis that islet amyloid may play a role in the development of hyperglycemia. C1 UNIV WASHINGTON,DEPT MED,DIV METAB ENDOCRINOL & NUTR,SEATTLE,WA 98195. UNIV WASHINGTON,HOWARD HUGHES MED INST,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOL STRUCT,SEATTLE,WA 98195. JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. RP Verchere, CB (reprint author), VET AFFAIRS MED CTR,MAIL STOP 151,1660 S COLUMBIAN WAY,SEATTLE,WA 98108, USA. OI Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [DK-12829, DK-17047, DK-35816] NR 34 TC 200 Z9 200 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 1996 VL 93 IS 8 BP 3492 EP 3496 DI 10.1073/pnas.93.8.3492 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UF740 UT WOS:A1996UF74000064 PM 8622964 ER PT J AU Kotkow, KJ Orkin, SH AF Kotkow, KJ Orkin, SH TI Complexity of the erythroid transcription factor NF-E2 as revealed by gene targeting of the mouse p18 NF-E2 locus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic stem cells; globin gene expression; maf proteins ID DOMINANT CONTROL REGION; LEUCINE ZIPPER PROTEIN; MAF ONCOGENE; V-MAF; EXPRESSION; CELLS; EXTRACTION; LETHALITY; ENCODES; DOMAIN AB High-level globin-expression in erythroid precursor cells depends on the integrity of NF-E2 recognition sites, transcription factor AP-1-like protein-binding motifs, located in the upstream regulatory regions of the alpha- and beta-globin loci, The NF-E2 transcription factor, which recognizes these sites, is a heterodimer consisting of (i) p45 NF-E2 (the larger subunit), a hematopoietic-restricted basic leucine zipper protein, and (ii) a widely expressed basic leucine zipper factor, p18 NF-E2, the smaller subunit, p18 NF-E2 protein shares extensive homology with the maf protooncogene family, To determine an in vivo role for p18 NF-E2 protein me disrupted the p18 NF-E2-encoding gene by homologous recombination in murine embryonic stem cells and generated p18 NF-E2(-/-) mice, These mice are indistinguishable from littermates throughout all phases of development and remain healthy in adulthood, Despite the absence of expressed p18 NF-E2, DNA-binding activity with the properties of the NF-E2 heterodimer is present in fetal liver erythroid cells of p18 NF-E2(-/-) mice, We speculate that another member of the maf basic leucine zipper family substitutes for the p18 subunit in a complex with p45 NF-E2. Thus, p18 NF-E2 per se appears to be dispensable in vivo. C1 HOWARD HUGHES MED INST,BOSTON,MA 02115. RP Kotkow, KJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV HEMATOL ONCOL,CHILDRENS HOSP,DEPT PEDIAT,BOSTON,MA 02115, USA. NR 31 TC 37 Z9 38 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 1996 VL 93 IS 8 BP 3514 EP 3518 DI 10.1073/pnas.93.8.3514 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UF740 UT WOS:A1996UF74000068 PM 8622968 ER PT J AU Bodor, J Spetz, AL Strominger, JL Habener, JF AF Bodor, J Spetz, AL Strominger, JL Habener, JF TI cAMP inducibility of transcriptional repressor ICER in developing and mature human T lymphocytes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE; DNA-BINDING; EXPRESSION; GENE; CREM; INTERLEUKIN-2; ACTIVATION; DIRECTS; ELEMENT; CELLS AB Stimulation of the cAMP-dependent signaling pathway exerts an inhibitory effect on the proliferation and effector functions of T cells. The ability of T cells to form high intracellular levels of cAMP is acquired during development in the human thymus and is retained by the majority of mature peripheral T lymphocytes. Here we show that elevated cAMP levels in T cells correlate with the expression of the potent transcriptional repressor ICER (inducible cAMP early repressor) previously described in the hypothalamic-pituitary-gonadal axis, Further, in transcriptional assays in vivo, ICER inhibits calcineurin-mediated expression of the interleukin 2 promoter as well as Tax-mediated transactivation of the human T-lymphotropic virus type I (HTLV-I) promoter. Thus, the induction of ICER in T cells may play an important role in the cAMP-induced quiescence and the persistent latency of HTLV-I. C1 MASSACHUSETTS GEN HOSP,MOLEC ENDOCRINOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,HOWARD HUGHES MED INST,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV TUMOR VIROL,BOSTON,MA 02114. RI Spetz, Anna-Lena/C-3543-2016 OI Spetz, Anna-Lena/0000-0003-3964-9512 FU NCI NIH HHS [CA 47554]; NIDDK NIH HHS [DK25532] NR 28 TC 71 Z9 73 U1 3 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 16 PY 1996 VL 93 IS 8 BP 3536 EP 3541 DI 10.1073/pnas.93.8.3536 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UF740 UT WOS:A1996UF74000072 PM 8622971 ER PT J AU Kang, JX Leaf, A AF Kang, JX Leaf, A TI Evidence that free polyunsaturated fatty acids modify Na+ channels by directly binding to the channel proteins SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cardiac myocytes; omega-3 and omega-6 fatty acids; ion channel; receptor; antiarrhythmics ID SMOOTH-MUSCLE CELLS; ARACHIDONIC-ACID; SODIUM-CHANNELS; POTASSIUM CHANNELS; CARDIAC-CELLS; NMDA RECEPTOR; K+ CHANNELS; MYOCYTES; CURRENTS AB The effects of free polyunsaturated fatty acids (PUFA) on the binding of ligands to receptors on voltage-sensitive Na+ channels of neonatal rat cardiac myocytes were assessed, The radioligand was [benzoyl-2,5-H-3] batrachotoxinin A 20 alpha-benzoate ([H-3]BTXB), a toxin that binds to the Na+ channel, The PUFA that have been shown to be antiarrhythmic, including eicosapentaenoic acid (EPA; C20:5n-3), docosahexaenoic acid (DHA; C22:6n-3), eicosatetraynoic acid (ETYA), linolenic acid (C18:3n-3), and linoleic acid (C18:2n-6), inhibited [H-3]BTXB binding in a dose-dependent fashion with IC50 values of 28-35 mu M, whereas those fatty acids that have no antiarrhythmic effects including saturated fatty acid (stearic acid; C18:0), monounsaturated fatty acid (oleic acid; C18:1n-9), and EPA methyl ester did not have a significant effect an [H-3]BTXB binding. Enrichment of the myocyte membrane with cholesterol neither affected [H-3]BTXB binding when compared with control cells nor altered the inhibitory effects of PUFA on [H-3]BTXB binding. Scatchard analysts of [H-3]BTXB binding showed that EPA reduced the maximal binding without altering the K-d for [H-3]BTXB binding, indicating allosteric inhibition, The inhibition by EPA of [H-3] BTXB binding was reversible (within 30 min) when delipidated bovine serum albumin was added, The binding of the PUFA to this site on the Na+ channel is reversible and structure-specific and occurs at concentrations close to those required for apparent antiarrhythmic effects and a blocking effect on the Na+ current, suggesting that binding of the PUFA at this site relates to their antiarrhythmic action. C1 HARVARD UNIV, SCH MED, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, BOSTON, MA 02114 USA. BROCKTON VET AFF MED CTR, BROCKTON, MA USA. W ROXBURY VET AFF MED CTR, BOSTON, MA 02132 USA. FU NIDDK NIH HHS [R01-DK 38165] NR 34 TC 138 Z9 145 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 APR 16 PY 1996 VL 93 IS 8 BP 3542 EP 3546 DI 10.1073/pnas.93.8.3542 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UF740 UT WOS:A1996UF74000073 PM 8622972 ER PT J AU Keuthen, NJ Savage, CR OSullivan, RL Brown, HD Shera, DM Cyr, P Jenike, MA Baer, L AF Keuthen, NJ Savage, CR OSullivan, RL Brown, HD Shera, DM Cyr, P Jenike, MA Baer, L TI Neuropsychological functioning in trichotillomania SO BIOLOGICAL PSYCHIATRY LA English DT Article DE trichotillomania; hairpulling; neuropsychology; obsessive-compulsive spectrum disorder ID OBSESSIVE-COMPULSIVE DISORDER; CEREBRAL GLUCOSE-METABOLISM; PERFORMANCE; DISEASE C1 MASSACHUSETTS GEN HOSP,DEPT PSYCHIAT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. HARVARD UNIV,DEPT PSYCHOL,CAMBRIDGE,MA 02138. SOLVAY PHARMACEUT CO,ATLANTA,GA. NR 21 TC 28 Z9 29 U1 9 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1996 VL 39 IS 8 BP 747 EP 749 DI 10.1016/0006-3223(95)00613-3 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UG772 UT WOS:A1996UG77200011 PM 8731464 ER PT J AU Kingston, RE Bunker, CA Imbalzano, AN AF Kingston, RE Bunker, CA Imbalzano, AN TI Repression and activation by multiprotein complexes that alter chromatin structure SO GENES & DEVELOPMENT LA English DT Review ID RNA POLYMERASE-II; CHROMOSOME-BINDING-SITES; NUCLEOSOME CORE PARTICLE; YEAST ALPHA-2 REPRESSOR; MYC TRANSGENIC MICE; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATION; DROSOPHILA-MELANOGASTER; HISTONE ACETYLATION; BITHORAX COMPLEX C1 HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. RP Kingston, RE (reprint author), MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114, USA. NR 148 TC 387 Z9 393 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 1996 VL 10 IS 8 BP 905 EP 920 DI 10.1101/gad.10.8.905 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UJ343 UT WOS:A1996UJ34300001 PM 8608939 ER PT J AU Brun, RP Tontonoz, P Forman, BM Ellis, R Chen, J Evans, RM Spiegelman, BM AF Brun, RP Tontonoz, P Forman, BM Ellis, R Chen, J Evans, RM Spiegelman, BM TI Differential activation of adipogenesis by multiple PPAR isoforms SO GENES & DEVELOPMENT LA English DT Article DE adipogenic activity; PPAR isoforms; nuclear hormone receptor; adipose tissue; gene expression; differentiation ID ENHANCER-BINDING-PROTEIN; ADIPOSE CELL-DIFFERENTIATION; HORMONE RECEPTOR SUPERFAMILY; GENE-EXPRESSION; PEROXISOME-PROLIFERATOR; FATTY-ACIDS; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; MOUSE; IDENTIFICATION AB Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor expressed predominantly in adipose tissue, where it plays a central role in the control of adipocyte gene expression and differentiation. Because there are two additional PPAR isoforms, PPAR alpha and PPAR delta, and these are also expressed at some level in certain adipose depots, we have compared directly the adipogenic potential of all three receptors. Ectopically expressed PPAR gamma powerfully induces adipogenesis at a morphological and molecular level in response to a number of PPAR gamma activators. PPAR alpha is less adipogenic but is able to induce significant differentiation in response to strong PPAR alpha activators. Expression and activation of PPAR delta did not stimulate adipogenesis. Of the three PPARs, only PPAR gamma can cooperate with C/EBP alpha in the promotion of adipogenesis. To begin to investigate the functional basis for the differential adipogenic activity of the PPAR isoforms, we have examined their ability to bind to several PPAR DNA response sequences. Compared with PPAR alpha and PPAR delta, PPAR gamma shows preferential binding to two well-characterized regulatory sequences derived from a fat-specific gene, ARE6 and ARE7. These data strongly suggest that PPAR gamma is the predominant receptor regulating adipogenesis; however, they also suggest that PPAR alpha may play a role in differentiation of certain adipose depots in response to a different set of physiologic activators or in certain disease states. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. SALK INST BIOL STUDIES,GENE EXPRESS LAB,LA JOLLA,CA 92037. HOWARD HUGHES MED INST,GENE EXPRESS LAB,LA JOLLA,CA 92037. NR 48 TC 348 Z9 354 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 1996 VL 10 IS 8 BP 974 EP 984 DI 10.1101/gad.10.8.974 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UJ343 UT WOS:A1996UJ34300006 PM 8608944 ER PT J AU Ramirez, G AF Ramirez, G TI Evidence-based medicine: The cochrane collaboration SO HOSPITAL PRACTICE LA English DT Editorial Material RP Ramirez, G (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,SAN ANTONIO COCHRANE CTR,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD APR 15 PY 1996 VL 31 IS 4 BP 11 EP & PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA UF106 UT WOS:A1996UF10600001 PM 8609178 ER PT J AU Saidman, SL Fitzpatrick, D Mann, M Comerford, C Drew, L Marrari, M Duquesnoy, R AF Saidman, SL Fitzpatrick, D Mann, M Comerford, C Drew, L Marrari, M Duquesnoy, R TI HLA class II antibodies in highly sensitized patients awaiting renal transplantation SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR 15 PY 1996 VL 47 IS 1-2 BP O709 EP O709 PG 1 WC Immunology SC Immunology GA UM455 UT WOS:A1996UM45500710 ER PT J AU Castano, L Calvo, B Deulofeut, R Bagley, D Bilbao, JR Alper, CA AF Castano, L Calvo, B Deulofeut, R Bagley, D Bilbao, JR Alper, CA TI HLA class II and III typing in Basque type I diabetics SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 HOSP CRUCES,BILBAO,SPAIN. CTR BLOOD RES,BOSTON,MA 02115. RI Castano, Luis/C-3084-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR 15 PY 1996 VL 47 IS 1-2 BP P835 EP P835 PG 1 WC Immunology SC Immunology GA UM455 UT WOS:A1996UM45500837 ER PT J AU Goldfeld, A Alosco, S Thim, S Cohen, M McKenzie, FE Marshall, W Pesavento, P Salazar, M Delgado, J Turbay, D Yunis, E AF Goldfeld, A Alosco, S Thim, S Cohen, M McKenzie, FE Marshall, W Pesavento, P Salazar, M Delgado, J Turbay, D Yunis, E TI HLA-DQ polymorphism and haplotype diversity associated with tuberculosis in Cambodia SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 DANA FARBER CANC INST,BOSTON,MA 02115. USA AMER RED CROSS,DEDHAM,MA. CAMBODIAN HLTH COMM,PHNOM PENH,CAMBODIA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR 15 PY 1996 VL 47 IS 1-2 BP P674 EP P674 PG 1 WC Immunology SC Immunology GA UM455 UT WOS:A1996UM45500676 ER PT J AU Yunis, JJ Yunis, EJ Deulofeut, R Salazar, M Ossa, H Yunis, E AF Yunis, JJ Yunis, EJ Deulofeut, R Salazar, M Ossa, H Yunis, E TI Unusual high frequencies for class II allele and haplotypes of the Guambiano, Paez and Ingano (Inga) tribes of Colombia may indicate a common ancestral origin. SO HUMAN IMMUNOLOGY LA English DT Meeting Abstract C1 UNIV NATL COLOMBIA, INST GENET, SANTA FE DE BOGOTA, 02115, COLOMBIA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA USA. USA AMER RED CROSS, BLOOD SERV, DEDHAM, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 EI 1879-1166 J9 HUM IMMUNOL JI Hum. Immunol. PD APR 15 PY 1996 VL 47 IS 1-2 BP P697 EP P697 PG 1 WC Immunology SC Immunology GA UM455 UT WOS:A1996UM45500698 ER PT J AU Natesan, M RaziWolf, Z Reiser, H AF Natesan, M RaziWolf, Z Reiser, H TI Costimulation of IL-4 production by murine B7-1 and B7-2 molecules SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; ADDITIONAL LIGAND; COUNTER-RECEPTOR; ANTIGEN PROVIDES; CTLA-4; EXPRESSION; SIGNAL; CD28 AB We have examined the capacity of murine B7-1 and B7-2 to costimulate the production of IL-4 by murine CD4(+) T lymphocytes. Cloned and freshly isolated T cells were incubated with the anti-CD3 mAb 145-2C11 in the presence of Chinese hamster ovary (CHO) cells that stably express murine B7-1 and B7-2 at comparable levels, IL-4 protein levels were measured in culture supernatants by the CT.4S bioassay, and levels of IL-4 mRNA were determined by semiquantitative reverse transcription-PCR. Both B7-1- and B7-2-transfected CHO cells, but not CHO control transfectants, were able to costimulate IL-4 production, Similarly, both B7-1 and B7-2 could up-regulate IFN-gamma mRNA levels. Cell fractionation experiments on freshly isolated CD4(+) T lymphocytes revealed that the costimulatory potential of B7-1 and B7-2 for IL-4 production was restricted to CD44(high) T cells, i.e., the subpopulation that contains recently activated and memory cells, CD44(low), naive CD4(+) T lymphocytes, could only be induced to produce IL-4 by repeated stimulation with B7 transfectants. In summary, we have not detected qualitative differences in the capacities of murine B7-1 and B7-2 to induce IL-4 production. The results of our experiments, therefore, argue against the recent hypothesis that precursor Th cells are directed toward the Th2 phenotype by B7-2 and toward the Th1 phenotype by B7-1. C1 DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI-35297, AI-33679] NR 45 TC 76 Z9 76 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1996 VL 156 IS 8 BP 2783 EP 2791 PG 9 WC Immunology SC Immunology GA UE192 UT WOS:A1996UE19200019 PM 8609397 ER PT J AU Vidard, L KovacsovicsBankowski, M Kraeft, SK Chen, LB Benacerraf, B Rock, KL AF Vidard, L KovacsovicsBankowski, M Kraeft, SK Chen, LB Benacerraf, B Rock, KL TI Analysis of MHC class II presentation of particulate antigens by B lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECOGNITION; LISTERIA-MONOCYTOGENES; MACROPHAGES; MOLECULES; HETEROGENEITY; PHAGOLYSOSOMES; MYCOBACTERIUM; ESTABLISHMENT; COMPARTMENTS; HYBRIDOMAS AB To generate Ab responses to most protein Ags, B cells must first degrade proteins in endocytic compartments and then display antigenic peptides bound to MHC class II molecules. T helper lymphocytes recognize these complexes and stimulate the B cell to synthesize Ab. Although Ab play a key role in host defense against bacteria, it is believed that B cells are incapable of internalizing particulate Ags. However, we find that B lymphoblastoid cell lines and LPS-activated B lymphocytes can present particulate Ag up to 10(5)-fold more efficiently compared with soluble Ag. Moreover, particulate Ags are presented efficiently by unstimulated B cells when they bind to surface Ig. In comparison to B cells, macrophages in general presented particulate Ags 10-to 1000-fold more efficiently and could also present Ag from particles of a much wider range of sizes. We document by ultrastructural and immunofluorescence analysis that B lymphoblastoid cell lines bind and internalize these particles. The internalization and presentation of the particulate Ag is inhibited by cytochalasin B. In contrast, a similar morphologic analysis of normal lymphocytes demonstrated that while Ag beads are bound to the cell surface, they are internalized only rarely. These results suggest there may be both surface and intracellular pathways for the presentation of particulate Ags by B cells. Interestingly, for both macrophages and B cells, the epitopes generated from particulate and soluble Ags were not identical quantitatively or qualitatively, indicating that there are differences in how these forms of Ag are processed and presented. C1 DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CELLULAR & MOL BIOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. FU NCI NIH HHS [CA46967]; NIAID NIH HHS [AI20248, AI31337] NR 46 TC 94 Z9 95 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 1996 VL 156 IS 8 BP 2809 EP 2818 PG 10 WC Immunology SC Immunology GA UE192 UT WOS:A1996UE19200022 PM 8609400 ER PT J AU Dawson, VL Kizushi, VM Huang, PL Snyder, SH Dawson, TM AF Dawson, VL Kizushi, VM Huang, PL Snyder, SH Dawson, TM TI Resistance to neurotoxicity in cortical cultures from neuronal nitric oxide synthase-deficient mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE nitric oxide; nitric oxide synthase; glutamate; NMDA; toxicity; ischemia ID NADPH-DIAPHORASE; GLUTAMATE NEUROTOXICITY; GLUCOSE DEPRIVATION; SELECTIVELY RESISTANT; STRIATAL NEURONS; NMDA RECEPTORS; CELL-CULTURES; L-ARGININE; SUPEROXIDE; INJURY AB In addition to its functions as a neuronal messenger molecule, nitric oxide (NO) has also been implicated in playing a major role in ischemic damage and glutamate neurotoxicity. Using primary cortical cultures from transgenic neuronal NO synthase (NOS) null (nNOS(-)) mice, we definitively establish NO as a mediator of NMDA and hypoxic neurotoxicity. Neurotoxicity elicited by NMDA is markedly attenuated in nNOS(-) cortical cultures compared with wild-type cultures. The NOS inhibitor nitro-L-arginine is neuroprotective in wild-type but not nNOS(-) cultures, confirming the role of nNOS-derived NO in glutamate neurotoxicity. Confirming that the nNOS(-) cultures lack NMDA-stimulated nNOS activity, NMDA did not stimulate the formation of cGMP in nNOS(-) cultures, but markedly elevates cGMP in wild-type cultures. Both wild-type and nNOS(-) cultures are sensitive to toxicity induced by NO donors, indicating that pathways stimulated by NO that result in neuronal cell death are still intact in the transgenic mice. Superoxide dismutase is neuroprotective against NMDA and NO neurotoxicity in both wild-type and nNOS(-) cultures, highlighting the importance of superoxide anion in subsequent neuronal damage. The unknown cellular factors that endow differential resistance to NMDA neurotoxicity and differential susceptibility to quisqualate neurotoxicity remain intact in the nNOS(-) cultures, because the response of somatostatin-immunopositive neurons in nNOS(-) cultures to high-dose NMDA and low-dose quisqualate is identical to the response of NOS-immunopositive neurons in the wild-type cultures. There is no difference in susceptibility to kainate neurotoxicity between nNOS(-) and wild-type cultures and only a modest resistance to quisqualate neurotoxicity, confining observations that NO-mediated neurotoxicity is associated primarily with activation of the NMDA receptor. The nNOS(-) cultures are markedly protected from 60 min of combined oxygen-glucose deprivation neurotoxicity compared with wild-type cultures. Wild-type cultures are protected from neuronal cell death by the NMDA receptor antagonist MK-801 and the NOS inhibitor L-nitroarginine methyl ester, but not its inactive stereoisomer D-nitroarginine methyl ester. nNOS(-) cultures were not additionally protected. These data confirm that activation of NMDA receptors and production of NO are primary mediators of neuronal damage after ischemic insult. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21287. MASSACHUSETTS GEN HOSP,CARDIOVASC RES CTR,BOSTON,MA 02129. OI Dawson, Valina/0000-0002-2915-3970 FU NINDS NIH HHS [NS01578, NS33142, NS33277] NR 68 TC 303 Z9 312 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 1996 VL 16 IS 8 BP 2479 EP 2487 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UD671 UT WOS:A1996UD67100006 PM 8786424 ER PT J AU Hjalmars, U Kulldorff, M Gustafsson, G Nagarwalla, N AF Hjalmars, U Kulldorff, M Gustafsson, G Nagarwalla, N TI Childhood leukaemia in Sweden: Using GIS and a spatial scan-statistic for cluster detection SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Conference on Statistics and Computing in Disease Clustering CY JUL 21-22, 1994 CL UNIV BRITISH COLUMBIA, VANCOUVER, CANADA SP BioMedware, Elect Power Res Inst, Natl Canc Inst HO UNIV BRITISH COLUMBIA ID ACUTE LYMPHOBLASTIC-LEUKEMIA; BRITAIN; POWER AB The study of disease clustering is becoming increasingly common in the field of medical epidemiology. There is great public concern and numerous reports on perceived clusters of various diseases, with cancers, and especially leukaemia, being the most commonly studied. We present a population based study on acute childhood leukaemia in Sweden 1973-1993, illustrating the possibility of a system for full-scale spatial epidemiological study design. The aim of the study is to test a large set of childhood leukaemia cases for the presence of geographical clusters. Necessary prerequisites, in the form of extensive population and disease data, a tool for geographical spatial analysis and a proper statistical method were fulfilled. No significant clusters were found. C1 NCI,BIOMETRY BRANCH,DCPC,BETHESDA,MD 20892. UNIV UPPSALA,DEPT STAT,S-75120 UPPSALA,SWEDEN. KAROLINSKA INST,REG ONCOL CTR,S-10401 STOCKHOLM,SWEDEN. HARVARD UNIV,SCH DENT MED,DEPT ORAL PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP Hjalmars, U (reprint author), OSTERSUND CENT HOSP,DEPT PAEDIAT,S-83183 OSTERSUND,SWEDEN. RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 NR 26 TC 86 Z9 89 U1 2 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 1996 VL 15 IS 7-9 BP 707 EP 715 DI 10.1002/(SICI)1097-0258(19960415)15:7/9<707::AID-SIM242>3.3.CO;2-W PG 9 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UG357 UT WOS:A1996UG35700004 PM 9132898 ER PT J AU Nagarwalla, N AF Nagarwalla, N TI A scan statistic with a variable window SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Conference on Statistics and Computing in Disease Clustering CY JUL 21-22, 1994 CL UNIV BRITISH COLUMBIA, VANCOUVER, CANADA SP BioMedware, Elect Power Res Inst, Natl Canc Inst HO UNIV BRITISH COLUMBIA ID APPROXIMATIONS; PROBABILITIES; CLUSTERS AB Given N points or events occurring according to some probability distribution in the unit interval (0, 1), the simple scan statistic is defined to be the maximum number of points in any sub-interval of length d. In many areas, as in epidemiology, it is used to test the null hypothesis that the events are random, against the alternative that they cluster within some window of fixed width d. Since d must be chosen without snooping at the data, the test restricts the alternative to clusters of a fixed size. In this paper, we propose a scan statistic with a variable window, whose size does not need to be chosen a priori. This test is the generalized likelihood ratio test for a uniform null distribution against an alternative of non-random clustering which allows for clusters of variable width. A simple algorithm for the implementation of the method is given and applied to birth defects data previously analysed by a simple scan statistic. C1 HARVARD UNIV,SCH MED,CTR BLOOD RES,BOSTON,MA 02115. RP Nagarwalla, N (reprint author), HARVARD UNIV,SCH DENT MED,DEPT ORAL PATHOL,800 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 14 TC 29 Z9 29 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD APR 15 PY 1996 VL 15 IS 7-9 BP 845 EP 850 DI 10.1002/(SICI)1097-0258(19960415)15:7/9<845::AID-SIM254>3.3.CO;2-O PG 6 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA UG357 UT WOS:A1996UG35700016 PM 9132910 ER PT J AU Love, RB Conhaim, RL Harms, BA AF Love, RB Conhaim, RL Harms, BA TI Effects of University of Wisconsin and Euro-Collins solutions on interstitial pulmonary edema in isolated rat lungs SO TRANSPLANTATION LA English DT Article ID UW SOLUTION; PRESERVATION; HYPOPROTEINEMIA; TRANSPLANTATION; SHEEP AB Macromolecules are present in lung preservation solutions to limit liquid filtration out of the pulmonary circulation and minimize pulmonary edema. We tested the effectiveness of these molecules by measuring interstitial edema in rat lungs perfused with macromolecular solutions (University of Wisconsin [UW] solution and Euro-Collins solution supplemented with modified pentastarch [pentafraction, PEN]), or with solutions that lacked macromolecules (UW solution without PEN and Euro-Collins solution.) The lungs were inflated with air and perfused with one of the test solutions, then rapidly frozen and prepared for histological analysis. From tissue sections, we measured cross-sectional areas of pulmonary arteries and veins, and also measured cross-sectional areas of interstitial spaces surrounding arteries and veins. We then calculated the interstitium-to-vessel cross-sectional area ratio. In lungs perfused with macromolecular solutions these ratios were 0.09 +/ -0.15 and 0.53 +/- 0.56 (mean +/- SD) for UW solution and Euro-Collins solution with PEN, respectively (P less than or equal to 0.05). In lungs perfused with solutions that lacked macromolecules, area ratios were 0.48 +/- 0.88 and 1.95 +/- 1.82 for UW solution without PEN and Euro-Collins solution, respectively (P less than or equal to 0.05). Solutions containing PEN caused less interstitial expansion than their counterparts that lacked it, but UW solution without PEN caused interstitial expansion equal to that of Euro-Collins solution with PEN. We conclude that macromolecules limit edema formation, but other constituents of UW solution limit edema formation also. C1 WILLIAM S MIDDLETON MEM VET ADM MED CTR,DEPT SURG,MADISON,WI 53705. UNIV WISCONSIN,DEPT SURG,MADISON,WI 53705. FU NHLBI NIH HHS [HL49985, HL46236] NR 13 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 1996 VL 61 IS 7 BP 1014 EP 1018 DI 10.1097/00007890-199604150-00005 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UF704 UT WOS:A1996UF70400005 PM 8623178 ER PT J AU Hansen, H Svensson, U Zhu, JW Laviola, L Giorgino, F Wolf, G Smith, RJ Riedel, H AF Hansen, H Svensson, U Zhu, JW Laviola, L Giorgino, F Wolf, G Smith, RJ Riedel, H TI Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; GROWTH FACTOR-I; PROTEIN; PHOSPHORYLATION; BINDING; SUBSTRATE-1; SPECIFICITY; EXPRESSION; TRUNCATION; SUBUNIT AB Grb10 is a member of a recently identified family of adapter proteins that are thought to play a role in receptor tyrosine kinase-mediated signal transduction. We identified and isolated the Grb10 SH2 domain based on its interaction with the intracellular domain of the insulin receptor beta-subunit using the yeast two-hybrid system, The interaction was specific for the insulin receptor and the insulin-like growth factor-1 receptor, and it required a catalytically active receptor kinase domain and an intact Grb10 SH2 domain. Glutathione S-transferase fusion proteins containing the Grb10 SH2 domain associated in an insulin-dependent manner with insulin receptors from cell lysates and with purified insulin receptors. Go-precipitation experiments revealed the association of cellular Grb10 with hormone-stimulated insulin receptors in cell extracts. The Grb10 SH2 domain did not bind to an insulin receptor lacking 43 amino acids at the carboxyl terminus, and it exhibited highest affinity for a phosphopeptide containing Tyr(P)-1322. Unlike p85 and Syp, which also bind to Tyr(P)-1322, Grb10 was not found to associate with insulin receptor substrate-1, These results suggest that Grb10 is a novel insulin receptor interactive protein and provide direct evidence for an insulin receptor substrate-1-independent function of the insulin receptor carboxyl terminus in protein binding. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,MOLEC BIOL SECT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,METAB SECT,BOSTON,MA 02215. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,SECT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02215. RI Giorgino, Francesco/K-7262-2016; OI Giorgino, Francesco/0000-0001-7372-2678; Laviola, Luigi/0000-0001-8860-5845 FU NIDDK NIH HHS [DK36836, DK43038] NR 43 TC 88 Z9 89 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 12 PY 1996 VL 271 IS 15 BP 8882 EP 8886 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UE730 UT WOS:A1996UE73000061 PM 8621530 ER PT J AU Ponton, A Clement, MV Stamenkovic, I AF Ponton, A Clement, MV Stamenkovic, I TI The CD95 (APO-1/Fas) receptor activates NF-kappa B independently of its cytotoxic function SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article AB Engagement of the CD95 (APO-1/Fas) receptor induces apoptosis in a variety of cell types, However, the nature of the cytotoxic signal and the intermediate messenger molecules remain to be elucidated, In an effort to understand CD95-mediated signaling, we assessed possible changes in the DNA binding activity of NF-kappa B as a result of CD95 engagement in various tumor cells, By performing electrophoresis mobility shift assays, we show that CD95 can stimulate the DNA binding activity of NF-kappa B in a variety of cells, irrespective of their sensitivity or resistance to CD95-mediated cytotoxicity, Moreover, deletion of 37 carboxyl-terminal residues from the cytoplasmic domain of CD95, which abrogates CD95-mediated apoptosis, only marginally affects NF-kappa KB activation. Taken together, these observations indicate that CD95 has a function that involves activation of NF-kappa B and that appears to be unrelated to its role as an inducer of apoptotic cell death. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,DEPT PATHOL,MED SCH & PATHOL RES,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,CTR CANC,BOSTON,MA 02129. FU NCI NIH HHS [CA55735]; NIGMS NIH HHS [GM/AI48614] NR 23 TC 127 Z9 128 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 12 PY 1996 VL 271 IS 15 BP 8991 EP 8995 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UE730 UT WOS:A1996UE73000076 PM 8621545 ER PT J AU Yu, CE Oshima, J Fu, YH Wijsman, EM Hisama, F Alisch, R Matthews, S Nakura, J Miki, T Ouais, S Martin, GM Mulligan, J Schellenberg, GD AF Yu, CE Oshima, J Fu, YH Wijsman, EM Hisama, F Alisch, R Matthews, S Nakura, J Miki, T Ouais, S Martin, GM Mulligan, J Schellenberg, GD TI Positional cloning of the Warner's syndrome gene SO SCIENCE LA English DT Article ID VARIEGATED TRANSLOCATION MOSAICISM; WERNERS SYNDROME; XERODERMA-PIGMENTOSUM; FIBROBLAST-CULTURES; PUTATIVE HELICASES; DNA HELICASE; REPAIR; RECOMBINATION; CHROMOSOME-8; LYMPHOCYTES AB Werner's syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as WRN) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients. C1 VET AFFAIRS PUGET SOUND HLTH CARE SYST,CTR GERIATR RES EDUC & CLIN,SEATTLE,WA 98108. UNIV WASHINGTON,DEPT NEUROL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PHARMACOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. UNIV WASHINGTON,DIV MED GENET,DEPT MED,SEATTLE,WA 98195. DARWIN MOLEC CORP,BOTHELL,WA 98021. YALE UNIV,SCH MED,DEPT NEUROL,NEW HAVEN,CT 06510. DAMASCUS CITY HOSP,ENDOCRINOL SECT,DAMASCUS,SYRIA. OSAKA UNIV,SCH MED,DEPT GERIATR MED,SUITA,OSAKA 565,JAPAN. FU NIA NIH HHS [P01 AG01751, R01 AG12019, T32 AG00057] NR 58 TC 1235 Z9 1262 U1 0 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 12 PY 1996 VL 272 IS 5259 BP 258 EP 262 DI 10.1126/science.272.5259.258 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UE729 UT WOS:A1996UE72900039 PM 8602509 ER PT J AU Colas, P Cohen, B Jessen, T Grishina, I McCoy, J Brent, R AF Colas, P Cohen, B Jessen, T Grishina, I McCoy, J Brent, R TI Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2 SO NATURE LA English DT Article ID BINDING; LIBRARY; LIGANDS AB A NETWORK of interacting proteins controls the activity of cyclin-dependent kinase 2 (Cdk2) (refs 1, 2) and governs the entry of higher eukaryotic cells into S phase. Analysis of this and other genetic regulatory networks would be facilitated by intracellular reagents that recognize specific targets and inhibit specific network connections. We report here the expression of a combinatorial library of constrained 20-residue peptides displayed by the active-site loop of Escherichia coli thioredoxin, and the use of a two-hybrid system to select those that bind human Cdk2. These peptide aptamers were designed to mimic the recognition function of the complementarity-determining regions of immunoglobulins. The aptamers recognized different epitopes on the Cdk2 surface with equilibrium dissociation constant in the nanomolar range; those tested inhibited Cdk2 activity. Our results show that peptide aptamers bear some analogies with monoclonal antibodies, with the advantages that they are isolated together with their coding genes, that their small sizes should allow their structures to be solved, and that they are designated to function inside cells. C1 MASSACHUSETTS GEN HOSP,DEPT BIOL MOLEC,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. GENET INST INC,CAMBRIDGE,MA 02142. NR 26 TC 291 Z9 302 U1 0 U2 20 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD APR 11 PY 1996 VL 380 IS 6574 BP 548 EP 550 DI 10.1038/380548a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UE663 UT WOS:A1996UE66300056 PM 8606778 ER PT J AU Stanton, RC Papanicolaou, N Haupert, GT Nickeleit, V Mark, EJ AF Stanton, RC Papanicolaou, N Haupert, GT Nickeleit, V Mark, EJ TI A 69-year-old man with progressive renal failure and the abrupt onset of dyspnea - Atheroembolism of the kidneys and lungs. Nephrosclerosis. (Renal-artery stenosis, bilateral) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHOLESTEROL EMBOLIZATION; PULMONARY-EDEMA; PREVALENCE; HEMATURIA; DISEASE C1 DEACONESS HOSP,BOSTON,MA. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. RP Stanton, RC (reprint author), JOSLIN DIABET CTR,JOINT DIV NEPHROL,BOSTON,MA 02215, USA. NR 32 TC 2 Z9 2 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 11 PY 1996 VL 334 IS 15 BP 973 EP 979 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA UD596 UT WOS:A1996UD59600008 ER PT J AU Poteat, HT Ramstedt, U Yoon, S Dardik, M Terwilliger, E Sodroski, JG AF Poteat, HT Ramstedt, U Yoon, S Dardik, M Terwilliger, E Sodroski, JG TI Cyclic AMP-mediated growth arrest is associated with increased expression of human T cell leukemia virus type I structural and transforming genes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LONG TERMINAL REPEAT; PROTEIN-KINASE-A; TRANS-ACTIVATOR; HTLV-I; SPASTIC PARAPARESIS; ENHANCER ELEMENT; NUCLEAR FACTOR; LYMPHOCYTES; SEQUENCE; TRANSACTIVATION AB The effect of increased intracellular cyclic AMP levels on gene expression of the human T cell leukemia virus type I (HTLV-I) provirus was examined, Induction of infected cells to produce elevated levels of cyclic AMP was associated with specific increases in viral surface antigen expression, protein synthesis, p24 release into the supernatant, and RNA levels. The patterns of HTLV-I proviral gene expression observed support results from transfection experiments regarding the function of Tax, Rex, and cyclic AMP in HTLV-I gene regulation. As evidenced by thymidine incorporation, treatment of the infected cells to produce cyclic AMP caused reversible growth arrest. The data indicate that HTLV-I RNA and protein synthesis can proceed at an elevated level in the absence of cell growth, Sustained increases in the intracellular level of cyclic AMP may represent a method for enriching cell cultures in HTLV-I proteins. C1 DANA FARBER CANC INST,DIV HUMAN RETROVIROL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. RP Poteat, HT (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. FU NCI NIH HHS [CA 36974]; NIAID NIH HHS [AI 28691] NR 34 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR 10 PY 1996 VL 12 IS 6 BP 527 EP 533 DI 10.1089/aid.1996.12.527 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UD625 UT WOS:A1996UD62500009 PM 8679308 ER PT J AU Dong, YH Wen, P Manome, Y Parr, M Hirshowitz, A Chen, L Hirschowitz, EA Crystal, R Weichselbaum, R Kufe, DW Fine, HA AF Dong, YH Wen, P Manome, Y Parr, M Hirshowitz, A Chen, L Hirschowitz, EA Crystal, R Weichselbaum, R Kufe, DW Fine, HA TI In vivo replication-deficient adenovirus vector-mediated transduction of the cytosine deaminase gene sensitizes glioma cells to 5-fluorocytosine SO HUMAN GENE THERAPY LA English DT Article ID COLORECTAL-CARCINOMA; 5-FLUOROURACIL; TUMORS; SYSTEM AB Viral vector-mediated transfer of chemosensitization genes represents a promising new approach to the treatment of cancer. Previous reports have demonstrated that transfection of the bacterial cytosine deaminase (cd) gene into mammalian cells can sensitize them to the otherwise nontoxic nucleoside, 5-fluorocytosine (5-FC). We now report that a replication-deficient adenovirus vector that transduces the ed gene (Ad.CMV-cd) highly sensitizes 9L gliosarcoma cells to 5-FC, and that gene transduction is associated with a potent bystander effect that is not dependent on direct cell-to-cell contact. Stereotactic injection of Ad.CMV-cd into established rat gliomas, followed by systemic administration of 5-FC in vivo, results in prolongation of survival. C1 HARVARD UNIV,DIV CANC PHARMACOL,DANA FARBER CANC INST,SCH MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,DIV NEUROL,SCH MED,BOSTON,MA 02115. CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. UNIV CHICAGO,SCH MED,DEPT RADIOTHERAPY,CHICAGO,IL 60637. NR 23 TC 72 Z9 77 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR 10 PY 1996 VL 7 IS 6 BP 713 EP 720 DI 10.1089/hum.1996.7.6-713 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA UG397 UT WOS:A1996UG39700003 PM 8919593 ER PT J AU Rohatgi, R Bartel, DP Szostak, JW AF Rohatgi, R Bartel, DP Szostak, JW TI Kinetic and mechanistic analysis of nonenzymatic, template-directed oligoribonucleotide ligation SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID TETRAHYMENA RIBOZYME REACTION; PHOSPHORYL TRANSFER; ADENOSINE; PHOSPHATE; RNA; CATALYSIS; CLEAVAGE; COORDINATION; TRIPHOSPHATE; HYDROLYSIS AB The role of divalent cations in the mechanism of pyrophosphate-activated, template-directed oligoribonucleotide ligation has been investigated. The dependence of the reaction rate on Mg2+ concentration suggests a kinetic scheme in which a Mg2+ ion must bind before ligation can proceed. Mn2+, Ca2+, Sr2+, and Ba2+ can also catalyze the reaction. Although Pb2+ and Zn2+ do not catalyze the reaction in the absence of other divalent ions, they significantly modulate the reaction rate when added in the presence of Mg2+, With Pb2+ stimulating the reaction (up to 65-fold) and Zn2+ inhibiting the reaction. The logarithm of the ligation rate increases linearly, with slope of 0.95, as a function of pH, indicating that the reaction involves a single critical deprotonation step. The ligation rates observed with the different divalent metal ion catalysts (Mn2+ > Mg2+ > Ca2+ > Sr2+ = Ba2+) vary inversely with the pK(a) values of their bound water molecules. The pH profile and these relative ligation rates suggest a mechanism in which a metal-bound hydroxide ion located near the ligation junction promotes catalysis, most likely by deprotonation of the hydroxyl nucleophile. The effects of changing either the leaving group or the attacking hydroxyl, together with the large Delta S-double dagger value for oligonucleotide ligation (about -20 eu), are consistent with an associative transition state. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 43 TC 71 Z9 71 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 10 PY 1996 VL 118 IS 14 BP 3332 EP 3339 DI 10.1021/ja953712b PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA UE656 UT WOS:A1996UE65600002 PM 11539267 ER PT J AU Rohatgi, R Bartel, DP Szostak, JW AF Rohatgi, R Bartel, DP Szostak, JW TI Nonenzymatic, template-directed ligation of oligoribonucleotides is highly regioselective for the formation of 3'-5' phosphodiester bonds SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RNA-POLYMERASE; CATALYSIS; OLIGOGUANYLATES; MODEL AB We have found that nonenzymatic, template-directed ligation reactions of oligoribonucleotides display high selectivity for the formation of 3'-5' rather than 2'-5' phosphodiester bonds. Formation of the 3'-5'-linked product is favored regardless of the metal ion catalyst or the leaving group, and for several different ligation junction sequences. The degree of selectivity depends on the leaving group: the ratio of 3'-5' -to 2'-5'-linked products was 10-15:1 when the 5'-phosphate was activated as the imidazolide, and 60-80:1 when the 5'-phosphate was activated by formation of a 5'-triphosphate. Comparison of oligonucleotide ligation reactions with previously characterized single nucleotide primer extension reactions suggests that the strong preference for 3'-5'-linkages in oligonucleotide ligation is primarily due to the occurrence of ligation within the context of an extended Watson-Crick duplex. The ability of RNA to correctly self-assemble by template-directed ligation is an intrinsic consequence of its chemical structure and need not be imposed by an external catalyst (i.e., an enzyme polymerase); RNA therefore provides a reasonable structural basis for a self-replicating system in a prebiological world. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NR 23 TC 70 Z9 71 U1 0 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 10 PY 1996 VL 118 IS 14 BP 3340 EP 3344 DI 10.1021/ja9537134 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA UE656 UT WOS:A1996UE65600003 PM 11539268 ER PT J AU Moradpour, D Schauer, JI Zurawski, VR Wands, JR Boutin, RH AF Moradpour, D Schauer, JI Zurawski, VR Wands, JR Boutin, RH TI Efficient gene transfer into mammalian cells with cholesteryl-spermidine SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA; COMPLEXES; GROWTH AB The naturally occurring polyamine spermidine was covalently conjugated with cholesterol, resulting in a novel cationic compound that mediates efficient gene transfer into mammalian cells. Using reporter plasmids coding for firefly luciferase and beta-galactosidase, a simple procedure was developed allowing highly reproducible and efficient transient and stable transfection of HuH-7 cells. Transfection efficiency could be further increased when a fusogenic peptide derived from the influenza virus hemagglutinin HA2 aminoterminal sequence was included in the cholesteryl-spermidine-DNA complex. Cholesteryl-spermidine (Transfectall) represents a novel cationic compound for efficient transfection of cultured cells in vitro and has the potential to be used for gene transfer in vivo. (C) 1996 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,MOLEC HEPATOL LAB,MASSACHUSETTS GEN HOSP,CANC CTR,BOSTON,MA. APOLLON INC,MALVERN,PA 19355. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666, AA-08169] NR 20 TC 44 Z9 46 U1 0 U2 6 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 5 PY 1996 VL 221 IS 1 BP 82 EP 88 DI 10.1006/bbrc.1996.0549 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UF049 UT WOS:A1996UF04900016 PM 8660349 ER PT J AU Reedquist, KA Fukazawa, T Panchamoorthy, G Langdon, WY Shoelson, SE Druker, BJ Band, H AF Reedquist, KA Fukazawa, T Panchamoorthy, G Langdon, WY Shoelson, SE Druker, BJ Band, H TI Stimulation through the T cell receptor induces Cbl association with Crk proteins and the guanine nucleotide exchange protein C3G SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE; ZETA-CHAIN; LEUCINE ZIPPER; V-CBL; ONCOGENE; BINDING; DOMAIN; IDENTIFICATION; CD4 AB We and others have recently identified Cbl, the protein product of the c-cbl protooncogene, as an early tyrosine kinase substrate upon T cell activation and have shown that Cbl forms in vivo complexes with Src family tyrosine kinases, Grb2 adaptor protein, and the p85 subunit of PI-3 kinase. Here we show that Cbl associates with all three forms of the human Crk protein, predominantly CrkL, following T cell receptor activation of Jurkat T cells. Association between Cbl and Crk proteins was confirmed in normal human peripheral blood-derived T cells. In vitro, Cbl was able to interact with the Crk SH2 domain but not the SH3 domain. A phosphopeptide corresponding to a potential Crk SH2 domain-binding motif in Cbl (pYDVP) specifically inhibited binding between Cbl and Crk SH2 domain. Anti-Cbl antibody completely immunodepleted the CrkL-associated 120-kDa phosphotyrosyl polypeptide, suggesting that the recently described p130(cas)-related Crk-associated p116 of T cells may be Cbl. Consistent with this possibility, the 4F4 antibody used to characterize the p116 polypeptide cross-reacted with Cbl protein when it was resolved on one- or two-dimensional gels. CrkL was constitutively associated with a substantial amount of the guanine nucleotide exchange protein C3G, and a fraction of the C3G protein was coimmunoprecipitated with Cbl in activated Jurkat T cells. These results suggest the possibility that Cbl may participate in a signaling pathway that regulates guanine nucleotide exchange on small G-proteins in T cells. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,LYMPHOCYTE BIOL SECT,DIV RHEUMATOL & IMMUNOL,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,JOSLIN DIABET CTR,DEPT MED,BOSTON,MA 02115. UNIV WESTERN AUSTRALIA,QUEEN ELIZABETH II MED CTR,DEPT PATHOL,NEDLANDS,WA 6009,AUSTRALIA. OREGON HLTH SCI UNIV,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. FU NIAMS NIH HHS [AR36308] NR 57 TC 161 Z9 163 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 1996 VL 271 IS 14 BP 8435 EP 8442 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UD600 UT WOS:A1996UD60000083 PM 8626543 ER PT J AU Scully, R Ganesan, S Brown, M DeCaprio, JA Cannistra, SA Feunteun, J Schnitt, S Livingston, DM AF Scully, R Ganesan, S Brown, M DeCaprio, JA Cannistra, SA Feunteun, J Schnitt, S Livingston, DM TI Location of BRCA1 in human breast and ovarian cancer cells SO SCIENCE LA English DT Article C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. INST GUSTAVE ROUSSY,F-94805 VILLEJUIF,FRANCE. BETH ISRAEL HOSP,BOSTON,MA 02115. RP Scully, R (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. RI Myles, Brown/B-6906-2008; Scully, Ralph/F-5008-2013; OI Brown, Myles/0000-0002-8213-1658 NR 4 TC 208 Z9 213 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 5 PY 1996 VL 272 IS 5258 BP 123 EP 125 DI 10.1126/science.272.5258.123 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UD597 UT WOS:A1996UD59700055 PM 8600523 ER PT J AU Zhu, JG Guo, SZ Beggs, AH Maruyama, T Santarius, T Dashner, K Olsen, N Wu, JK Black, P AF Zhu, JG Guo, SZ Beggs, AH Maruyama, T Santarius, T Dashner, K Olsen, N Wu, JK Black, P TI Microsatellite instability analysis of primary human brain tumors SO ONCOGENE LA English DT Article DE brain neoplasms; polymerase chain reaction; microsatellite markers; loss of heterozygosity; replication errors; microsatellite instability ID COLORECTAL-CANCER; GENETIC INSTABILITY; MUTATIONS; CARCINOMA; HOMOLOG; REPEAT; COLON; LOCUS; DNA AB Microsatellite instability, as shown by the presence of additional alleles or shifts of electrophoretic mobility at simple sequence tandem repeat loci, has been demonstrated in hereditary and sporadic colorectal tumors and many other tumor types. To study microsatellite instability in human brain tumors, we examined a total of 144 sporadic neoplasms. These included 33 astrocytic tumors, 23 oligodendrogliomas, six gangliogliomas, 41 meningiomas, 10 vestibular schwannomas and 31 pituitary adenomas. Di-, tri- and tetranucleotide repeat microsatellite markers localized on chromosome 4 and 9, X, 13 and 22, respectively, were used to assess whether instability was a significant aspect of their abnormal chromosomal pattern. Instability of microsatellite markers was detected in four oligodendrogliomas (17.4%), one pituitary adenoma (3.2%), one meningioma (2.4%), one astrocytic tumor (3.0%) and not at all in gangliogliomas and schwannomas. Therefore, our results suggest that the microsatellite instability which occurs in colorectal cancers with defective mismatch repair is infrequent in many types of human brain tumors and that the lower level of instability observed in brain tumors may be reflective of other mechanisms of genetic instability. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CHILDRENS HOSP,DANA FARBER CANC INST,NEUROSURG LABS,BOSTON,MA 02115. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CHILDRENS HOSP,DANA FARBER CANC INST,BRAIN TUMOR CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,CHILDRENS HOSP,DIV GENET,BOSTON,MA 02115. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT NEUROSURG,BOSTON,MA 02111. OI Beggs, Alan/0000-0001-8818-0568 NR 43 TC 48 Z9 48 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 4 PY 1996 VL 12 IS 7 BP 1417 EP 1423 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UF076 UT WOS:A1996UF07600005 PM 8622857 ER PT J AU Lambert, CR Kochevar, IE AF Lambert, CR Kochevar, IE TI Does rose bengal triplet generate superoxide anion? SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SINGLET OXYGEN; ELECTRON TRANSFER; QUANTUM YIELD; LIGHT C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,DEPT DERMATOL,WELLMAN LABS PHOTOMED,BOSTON,MA 02114. NR 19 TC 42 Z9 43 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 3 PY 1996 VL 118 IS 13 BP 3297 EP 3298 DI 10.1021/ja9600800 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA UD464 UT WOS:A1996UD46400032 ER PT J AU RaziWolf, Z Hollander, GA Reiser, H AF RaziWolf, Z Hollander, GA Reiser, H TI Activation of CD4(+) T lymphocytes from interleukin 2-deficient mice by costimulatory B7 molecules SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL ACTIVATION; MONOCLONAL-ANTIBODY; MURINE LYMPHOCYTES; COUNTER-RECEPTOR; ANTIGEN PROVIDES; CTLA-4; CD28; COMPLEX; LIGAND; SIGNAL AB Interleukin 2 (IL-2)-deficient (IL-2(-/-)) mice develop hemolytic anemia and chronic inflammatory bowel disease. Importantly, the induction of disease in IL-2-deficient mice is critically dependent on CD4(+) T cells. We have studied the requirements of T cells from IL-2 deficient mice for costimulation with B7 antigens, Stable B7-1 or B7-2 chinese hamster ovary (CHO) cell transfectants could synergize with anti-CD3 monoclonal antibody (mAb) to induce the proliferation of CD4(+) T cells from IL-2(-/-) mutant mice. Further mechanistic studies established that B7-induced activation resulted in surface expression of the gamma chain of the IL-2 receptor, B7-induced proliferation occurred independently of IL-4 and was largely independent of the common gamma chain of the IL-2, IL-4, IL-7, IL-9, and IL-15 receptors. Finally, anti-B7-2 but not anti-B7-1 mAb was able to inhibit the activation of IL-2(-/-) T cells induced by anti-CD3 mAb in the presence of syngeneic antigen-presenting cells, The results of our experiments Indicate that IL-2(-/-) CD4(+) T cells remain responsive to B7 stimulation and raise the possibility that B7 antagonists have a role in the prevention/treatment of inflammatory bowel disease. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. DANA FARBER CANC INST,DIV LYMPHOCYTE BIOL,BOSTON,MA 02115. DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. FU NIAID NIH HHS [AI-33679] NR 44 TC 29 Z9 29 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 2 PY 1996 VL 93 IS 7 BP 2903 EP 2908 DI 10.1073/pnas.93.7.2903 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UD375 UT WOS:A1996UD37500053 PM 8610140 ER PT J AU Finley, RL Thomas, BJ Zipursky, SL Brent, R AF Finley, RL Thomas, BJ Zipursky, SL Brent, R TI Isolation of Drosophila cyclin D, a protein expressed in the morphogenetic furrow before entry into S phase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cyclin-dependent kinase; two-hybrid; interaction trap ID CELL-CYCLE; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; CDC25 HOMOLOG; CLN FUNCTION; YEAST; EMBRYOGENESIS; GENE; KINASE; TWINE AB During Drosophila development, nuclear and cell divisions are coordinated in response to developmental signals. In yeast and mammalian cells, signals that control cell division regulate the activity of cyclin-dependent kinases (Cdks) through proteins such as cyclins that interact with the Cdks. Here we describe two Drosophila cyclins identified from a set of Cdk-interacting proteins. One, cyclin J, is of a distinctive sequence type; its exclusive maternal expression pattern suggests that it may regulate oogenesis or the early nuclear divisions of embryogenesis. The other belongs to the D class of cyclins, previously identified in mammalian cells. We show that Drosophila cyclin D is expressed in early embryos and in imaginal disc cells in a pattern that anticipates cell divisions. Expression in the developing eye disc at the anterior edge of the morphogenetic furrow suggests that cyclin D acts early, prior to cyclin E, in inducing G(1)-arrested cells to enter S phase. Our results also suggest that, although cyclin D may be necessary, its expression alone is not sufficient to initiate the events leading to S phase. C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT GENET,BOSTON,MA 02115. UNIV CALIF LOS ANGELES,DEPT BIOL CHEM,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,HOWARD HUGHES MED INST,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOLEC BIOL,LOS ANGELES,CA 90024. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 42 TC 73 Z9 74 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 2 PY 1996 VL 93 IS 7 BP 3011 EP 3015 DI 10.1073/pnas.93.7.3011 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UD375 UT WOS:A1996UD37500073 PM 8610160 ER PT J AU Pahlavani, MA Harris, MD AF Pahlavani, MA Harris, MD TI The age-related changes in DNA binding activity of AP-1, NF-kappa B, and OCT-1 transcription factors in lymphocytes from rats SO AGE LA English DT Article ID CD4+ T-CELLS; C-FOS; ANTIGEN RECEPTOR; OLD MICE; ACTIVATION; GENES; EXPRESSION; PROTEINS; ELEMENT; YOUNG AB The effect of aging on the induction of the ubiquitous transcription factors AP-1, NF-kappa B, and OCT-1 by concanavalin A (conA) was studied in nuclear extracts from spleen lymphocytes isolated from young (6 mo) and old (24 mo) male Fischer 344 rats. The induction of AP-1, NF-kappa B, and OCt-1 DNA binding activities were significantly lower (35 to 60%) in nuclear extracts from spleen lymphocytes isolated from old rats compared to nuclear extracts from spleen lymphocytes isolated from young rats. Because the transcription factor AP-1 consists of heterodimers of Fos and Jun oncoproteins, the induction of c-fos and c-jun expression (mRNA levels) by conA stimulated lymphocytes was measured using northern blot analysis. ConA induction of c-fos mRNA but not c-jun mRNA decreased approximately 70% with age. Therefore, the age-related decrease in the induction of AP-1 transcription factor appears to arise from alterations in c-fos expression. C1 UNIV TEXAS,HLTH SCI CTR,DEPT PHYSIOL,SAN ANTONIO,TX 78284. RP Pahlavani, MA (reprint author), AUDIE L MURPHY MEM VET ADM MED CTR,GRECC 182,7400 MERTON MINTER BLVD,SAN ANTONIO,TX 78284, USA. NR 45 TC 12 Z9 12 U1 0 U2 0 PU AMER AGING ASSOC PI CHESTER PA 2129 PROVIDENCE AVENUE, CHESTER, PA 19013 SN 0161-9152 J9 AGE JI Age PD APR PY 1996 VL 19 IS 2 BP 45 EP 54 DI 10.1007/BF02434070 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VG835 UT WOS:A1996VG83500002 ER PT J AU Gorski, NP Nouraldin, H Dube, DM Preffer, FI Dombkowski, DM Villa, EM Lewandrowski, KB Weiss, RD Hufford, C Laposata, M AF Gorski, NP Nouraldin, H Dube, DM Preffer, FI Dombkowski, DM Villa, EM Lewandrowski, KB Weiss, RD Hufford, C Laposata, M TI Reduced fatty acid ethyl ester synthase activity in the white blood cells of alcoholics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; alcoholism; ethanol; fatty acids; natural killer cells ID NONOXIDATIVE ETHANOL-METABOLISM; RECEPTOR GENE; ASSOCIATION; PANCREAS AB Purpose: Fatty acid ethyl esters (FAEEs), esterification products of ethanol and fatty acids, have been implicated as mediators of ethanol-induced organ damage. It has been shown that FAEE synthase, the enzyme responsible for the formation of FAEE, is present selectively in the organs commonly damaged by ethanol abuse. Recently, we have made the observation that FAEEs are also present in the serum after ethanol ingestion. The current study was performed to determine whether cellular elements of the blood and/or plasma are capable of synthesizing FAEEs from fatty acids and ethanol. Materials and Methods: Heparinized blood samples were collected from 10 healthy volunteers, and the red blood cells, platelets, plasma, and several white blood cell populations were assayed for FAEE synthase activity. Blood samples from control subjects and individuals admitted to an alcoholic detoxification unit at a local hospital were also assayed for FAEE synthase activity. Results: We observed that the FAEE synthase activity is present in whole blood, primarily within white blood cells. Fractionation of the white blood cells revealed that the lymphocyte-monocyte fraction isolated using Ficoll-hypaque contained similar to 3.5-fold higher activity than the granulocyte fraction. The cell type that contained the highest FAEE synthase activity (1220 pmol/hr/10(6) cells) was the natural killer (NK) cell population. B cells contained similar to 40% of the enzyme activity found in NK cells, and the B-cell activity was slightly greater than that found in CD4(+) and CD8(+) T cells. Having shown that FAEE synthase exists in a blood cell, we subsequently demonstrated that alcoholic individuals have approximately half the white blood cell FAEE synthase activity of that found in normal controls. We also demonstrated that white blood cell FAEE synthase could be induced nearly 2-fold upon ingestion of 2 oz of scotch whiskey for 6 days. The enzyme activity returned to baseline levels despite ingestion of 2 oz of scotch whiskey/day for 3 additional days. Conclusions: These data indicate that ethanol ingestion results in increased FAEE production, particularly by NK cells. FAEE synthesis after ethanol ingestion may explain the presence of FAEE in the serum. The lower enzyme activity observed in white blood cells of alcoholics from a detoxification center may be the result of years of ethanol abuse or it may be that alcoholics congenitally have low levels of FAEE synthase. If the latter is true, this finding may explain in part the genetic predisposition of many alcoholic individuals to ethanol abuse. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DIV CLIN LABS,BOSTON,MA 02114. MCLEAN HOSP,ALCOHOL & DRUG ABUSE PROGRAM,BELMONT,MA 02178. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA. FU NIDDK NIH HHS [R01 DK37454, R01 DK43159] NR 23 TC 35 Z9 35 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1996 VL 20 IS 2 BP 268 EP 274 DI 10.1111/j.1530-0277.1996.tb01639.x PG 7 WC Substance Abuse SC Substance Abuse GA UE737 UT WOS:A1996UE73700011 PM 8730217 ER PT J AU Isselbacher, EM Siu, SC Weyman, AE Picard, MH AF Isselbacher, EM Siu, SC Weyman, AE Picard, MH TI Absence of Q waves after thrombolysis predicts more rapid improvement of regional left ventricular dysfunction SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; LONG-TERM PROGNOSIS; THERAPY; REPERFUSION; DIAGNOSIS; SURVIVAL; TRIALS; EXTENT; SIZE AB Although the natural history of regional left ventricular (LV) dysfunction after Q-wave and non-a-wave myocardial infarction (MI) was well defined in the prethrombolytic era, the functional and structural implications of the absence of Q waves after thrombolysis are less clear, Echocardiography was performed within 48 hours of admission (entry) in 86 patients treated with thrombolysis for their first MI. The extent of abnormal wall motion (AWM; square centimeters) and LV endocardial surface area index (ESA(i); square centimeters per square meters) were quantified by using a previously validated echocardiographic endocardial surface-mapping technique. Electrocardiography (EGG) performed at 48 hours after thrombolysis was used to classify patients into groups with (Q; n = 70) and without (non-Q; n = 16) Q waves, All patients in the Q group had regional LV dysfunction on initial echocardiogram compared with 69% of those in the non-Q group (p < 0.001), When the patients in the non-Q group without AWM were excluded from analysis, there was no significant difference in the extent of AWM between the Q and non-Q groups, Among those patients with AWM on entry, follow-up echocardiography at 6 to 12 weeks demonstrated a significant reduction in extent of AWM for both the Q and non-Q groups, However, the fractional change in AWM was significantly greater in the non-Q than in the Q group (-0.74 +/- 0.28 vs -0.29 +/- 0.44; p < 0.02), with a trend toward less AWM at follow-up in the non-Q than in the Q group. The mean ESA(i) was not significantly different between the two groups at entry or at follow-up, In conclusion, failure to develop Q waves after thrombolysis predicts a lower likelihood of developing regional LV dysfunction and, when such dysfunction is present, predicts a greater degree of recovery. RP Isselbacher, EM (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC ULTRASOUND LAB,VBK-508,32 FRUIT ST,BOSTON,MA 02114, USA. OI Picard, Michael/0000-0002-9264-3243 NR 35 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 1996 VL 131 IS 4 BP 649 EP 654 DI 10.1016/S0002-8703(96)90266-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UE421 UT WOS:A1996UE42100003 PM 8721634 ER PT J AU Weissman, NJ Levangie, MW Guerrero, JL Weyman, AE Picard, MH AF Weissman, NJ Levangie, MW Guerrero, JL Weyman, AE Picard, MH TI Effect of beta-blockade on dobutamine stress echocardiography SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; PRESSURE-VOLUME; PERICARDIUM; PERFORMANCE; TOMOGRAPHY; INFUSION AB Dobutamine is an effective pharmacologic stress used in conjunction with echocardiography because of its beta-agonist properties, Concurrent beta-blockade might after this effectiveness; however, current clinical experience has been variable. The purpose of this study is to determine whether concurrent beta-blockade alters the ability of a dobutamine stress echocardiogram to detect a fixed coronary stenosis by preventing the onset of a wall motion abnormality or by altering the dose at which the wall motion abnormality appears, Paired dobutamine stress tests with and without beta-blockade (esmolol 500 mu g/kg initial bolus, 100 mu g/kg/min infusion) were performed in a canine model (n = 8) with a fixed single-vessel coronary stenosis, Heart rate, systolic pressure, proximal left anterior descending coronary flow, myocardial thickening (by sonomicrometry), and left ventricular area change (by epicardial echocardiography) were monitored. Simultaneous beta-blockade resulted in (1) a delayed and diminished increase in hemodynamic parameters (peak heart rate 164.1 +/- 22.3 without beta-blockade vs 110.1 +/- 28.9 beats/min with beta-blockade, p < 0.001, and peak systolic blood pressure 137.9 +/- 26.8 mm Hg without beta-blockade vs 107.3 +/- 15.3 mm Hg with beta-blockade, p = 0.01), (2) an elimination of the physiologic effects of low-dose (5 and 10 mu g/kg/min) dobutamine (-0.7% +/- 16.7% change in myocardial thickening from baseline with beta-blockade, p = NS), and (3) an elimination or alteration in timing of inducible wall motion abnormalities caused by severe coronary artery stenoses (mean termination dose 28.8 +/- 9.9 with beta-blockade vs 15.6 +/- 6.1 mu g/kg/min without beta-blocker, p < 0.01), The findings in this canine model suggest that the competitive antagonist markedly attenuates the ability of dobutamine stress echocardiography to detect a significant coronary lesion and may a Iter its ability to detect viable myocardium at low-dose testing. Further clinical studies to determine the sensitivity of dobutamine stress echocardiography in the presence of beta-blockers and to establish protocol standards are necessary. C1 MASSACHUSETTS GEN HOSP,CARDIAC UNIT,CARDIAC ULTRASOUND LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI Guerrero, Jorge/I-3666-2015 OI Guerrero, Jorge/0000-0003-4315-7318 NR 19 TC 12 Z9 12 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 1996 VL 131 IS 4 BP 698 EP 703 DI 10.1016/S0002-8703(96)90273-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UE421 UT WOS:A1996UE42100010 PM 8721641 ER PT J AU Paul, SD OGara, PT Mahjoub, ZA DiSalvo, TG ODonnell, CJ Newell, JB VillarrealLevy, G Smith, AJC Kondo, NI Cararach, M Ferrer, L Eagle, KA AF Paul, SD OGara, PT Mahjoub, ZA DiSalvo, TG ODonnell, CJ Newell, JB VillarrealLevy, G Smith, AJC Kondo, NI Cararach, M Ferrer, L Eagle, KA TI Geriatric patients with acute myocardial infarction: Cardiac risk factor profiles, presentation, thrombolysis, coronary interventions, and prognosis SO AMERICAN HEART JOURNAL LA English DT Article ID MORTALITY; HEART; AGE; THERAPY; DISEASE AB Elderly patients have a higher mortality after acute myocardial infarction (MI) yet are treated less aggressively than younger patients, To determine (1) the risk-factor profiles, (2) presentation, (3) management, and (4) hospital outcomes for the elderly (greater than or equal to 75 years) compared with middle aged (66 to 74 years) and younger (less than or equal to 65 years) patients in the 1990s, we studied 561 consecutive patients with acute MI, Compared with younger patients, the elderly more frequently had congestive heart failure (40% vs 14%; p < 0.00001) and non-Q wave infarctions (76% vs 56%; p < 0.005), received thrombolysis (9% vs 34%; p < 0.0001), and underwent catheterization (35% vs 73%; p < 0.00001), percutaneous transluminal coronary angioplasty (9% vs 31%; p < 0.0002), and coronary artery bypass grafting (5% vs 15%; p < 0.03) less frequently, Those who did not receive thrombolysis all had contraindications, Mortality was higher in the elderly (19% vs 5%; p < 0.004), especially among those who did not receive thrombolysis (20% vs 7%; p < 0.03), Multivariate predictors of mortality included age, and congestive heart failure, In addition, when clinical course and management variables were considered, use of the intraaortic balloon pump was a predictor of mortality, whereas undergoing coronary angiography was a negative predictor (relative risk, 0.3; 95% confidence intervals, 0.1 to 0.6). C1 UNIV MICHIGAN,MED CTR,DEPT MED,DIV CARDIOL,ANN ARBOR,MI 48109. RP Paul, SD (reprint author), MASSACHUSETTS GEN HOSP,CARDIAC UNIT,DEPT MED,ELLISON 908,BOSTON,MA 02114, USA. NR 22 TC 54 Z9 54 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 1996 VL 131 IS 4 BP 710 EP 715 DI 10.1016/S0002-8703(96)90275-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UE421 UT WOS:A1996UE42100012 PM 8721643 ER PT J AU Rivera, JM Vandervoort, P Mele, D Weyman, A Thomas, JD AF Rivera, JM Vandervoort, P Mele, D Weyman, A Thomas, JD TI Value of proximal regurgitant jet size in tricuspid regurgitation SO AMERICAN HEART JOURNAL LA English DT Article ID DIMENSIONAL DOPPLER ECHOCARDIOGRAPHY; SYSTEMIC BLOOD-FLOW; VALVULAR REGURGITATION; MITRAL REGURGITATION; AORTIC-INSUFFICIENCY; VOLUME FLOW; REAL-TIME; QUANTIFICATION; VALIDATION; CONVERGENCE AB Recent studies have shown good agreement between proximal regurgitant jet size obtained with transthoracic color flow mapping and regurgitant fraction in patients with mitral regurgitation, To evaluate this in patients with tricuspid regurgitation, we analyzed 40 patients in sinus rhythm, 16 with free jets and 24 with impinging jets, comparing proximal jet size (millimeters) with parameters derived from the Doppler two-dimensional echocardiographic method (regurgitant fraction) and the flow-convergence method (peak flow rate, effective regurgitant orifice area, and momentum). Good agreement was noted between peak flow rate (r = 0.80, p < 0.001), momentum (r = 0.80, p < 0.001), and effective regurgitant orifice area (r = 0.78, p < 0.001), with proximal jet size measured in the apical four-chamber view in patients with free jets. The average of jet proximal size in three planes also had good correlation with peak flow rate (r = 0.75, p < 0.001), regurgitant fraction, momentum, and effective regurgitant orifice area (r = 0.74, p < 0.001), In patients with impinging jet!;, agreement was fair between effective regurgitant orifice (r = 0.65, p < 0.001), peak flow rate (0.65, p < 0.001), anti momentum (r = 0.62, p < 0.001) with mean jet proximal size. Jet proximal size obtained with transthoracic color flow mapping is a good semiquantitative tool for measuring tricuspid regurgitation in free jets that correlates well with established measures of the severity and with new parameters available from analysis of the proximal acceleration field, In patients with eccentrically directed wall jets, the correlation weakens but still appears clinically significant. C1 HOSP LA FE,CTR INVEST CARDIOCIRULATORIA,E-46009 VALENCIA,SPAIN. CLEVELAND CLIN FDN,DEPT CARDIOL,CLEVELAND,OH 44195. OSPED CIVILE,DEPT CARDIOL,FERRARA,ITALY. MASSACHUSETTS GEN HOSP,DEPT CARDIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RI rivera, miguel/D-5026-2014 NR 30 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 1996 VL 131 IS 4 BP 742 EP 747 DI 10.1016/S0002-8703(96)90281-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UE421 UT WOS:A1996UE42100018 PM 8721649 ER PT J AU Rodriguez, AE Fernandez, M Santaera, O Larribau, M Bernardi, V Castano, H Palacios, IF AF Rodriguez, AE Fernandez, M Santaera, O Larribau, M Bernardi, V Castano, H Palacios, IF TI Coronary stenting in patients undergoing percutaneous transluminal coronary angioplasty during acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID THROMBOLYTIC THERAPY; IMMEDIATE ANGIOPLASTY; CARDIOGENIC-SHOCK; CLOSURE; STREPTOKINASE; RESTENOSIS AB Although coronary stenting has been useful in the treatment of patients with suboptimal results, abrupt closure, and threatening occlusion after percutaneous transluminal coronary angioplasty (PTCA), its use in patients with acute myocardial infarction (AMI) is controversial because of the presence of intracoronary thrombus. In this study intracoronary stenting was used to treat suboptimal results and complications in 30 patients (35 lesions) undergoing PTCA during AMI. There were 28 men and 2 women, mean age 58 +/- 12 years. Thirteen patients (43%) had undergone rescue PTCA because of unsuccessful thrombolysis. Four patients had Killip's grade IV, 5 Killip's grade III, and 21 Killip's grade less than or equal to 2 heart failure. Stents were placed in the 35 lesions because of suboptimal result (n = 19), early loss (n = 9), abrupt closure (n = 2), and coronary dissection with threatening occlusion (n = 5). All stents were deployed successfully. In-hospital complications included 1 in-hospital death (3.0%); no patient required emergency coronary artery bypass graft surgery. One patient (3.0%) developed abrupt closure and was successfully treated with PTCA and intracoronary thrombolysis. Vascular complications requiring blood transfusion developed in 3 of 30 patients (10%). At 11.8 months (range 4 to 24) follow-up, there were no deaths or myocardial infarction. One patient underwent coronary artery bypass grafting. The remaining patients were free of angina at follow-up. Thus, intracoronary stents can be used successfully to treat both suboptimal results and complications occurring in patients undergoing PTCA during AMI. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CARDIAC UNIT,BOSTON,MA 02114. ANCHORENA HOSP,CARDIAC UNIT,BUENOS AIRES,DF,ARGENTINA. OTAMENDI HOSP,CARDIAC UNIT,BUENOS AIRES,DF,ARGENTINA. NR 30 TC 50 Z9 51 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 1996 VL 77 IS 9 BP 685 EP 689 DI 10.1016/S0002-9149(97)89200-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UF239 UT WOS:A1996UF23900003 PM 8651117 ER PT J AU Lo, CW Kleinman, RE AF Lo, CW Kleinman, RE TI Infant formula, past and future: Opportunities for improvement SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Genetic Engineering - Opportunities and Challenges in Infant Nutrition CY DEC 01-04, 1994 CL PALM BEACH, FL SP Wyeth Ayerst Int Inc, Wyeth Ayerst Res DE genetic engineering; antibodies; cytokines; growth factors ID SECRETORY IMMUNOGLOBULIN-A; MILK-FEEDING PATTERNS; UNITED-STATES; BREAST-MILK; BRONCHOPULMONARY DYSPLASIA; INFECTIONS; PROTECT; GROWTH; CELLS; AGE AB Infant formulas provide nutritional support to healthy infants that promotes growth and development equivalent to that in healthy infants fed human milk. Formula-fed infants are not as well protected against infections, and there remain infants whose health, growth, and development may not be supported optimally by either the formulas currently available or human milk. Some infants may be better supported by genetically engineered formulas that contain immunity-enhancing antibodies or antigens. Formulas that contain cytokines promoting epithelial cell growth and integrity may be protective against necrotizing enterocolitis. Formulas containing proteins with genetically excluded allergenic epitopes or formulas with tolerogenic peptides may be useful in treating allergic diseases or suppressing the development of autoimmune disorders later in life. Formulas with genetically engineered biologically active substances might increase the absorption of nutrients in infants with compromised absorption or digestion, enhance host immunity and mucosal integrity, and, potentially, militate or protect against the risk of disease. C1 MASSACHUSETTS GEN HOSP, COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR, BOSTON, MA 02114 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, BOSTON, MA 02115 USA. NR 45 TC 5 Z9 6 U1 0 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 1996 VL 63 IS 4 BP 646 EP 650 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UC185 UT WOS:A1996UC18500030 ER PT J AU Wong, TY Suster, S Cheek, RF Mihm, MC AF Wong, TY Suster, S Cheek, RF Mihm, MC TI Benign cutaneous adnexal tumors with combined folliculosebaceous, apocrine, and eccrine differentiation - Clinicopathologic and immunohistochemical study of eight cases SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE skin adnexal neoplasms; combined differentiation; divergent differentiation ID HAIR MATRIX DIFFERENTIATION; SWEAT GLAND TUMORS; SEBACEOUS DIFFERENTIATION; SKIN; CARCINOMA; ADENOMA; PROTEIN; POROMA AB Benign cutaneous adnexal tumors displaying divergent differentiation are rare, with very few well-documented cases reported in the literature. We describe eight cases of benign adnexal tumors showing a variable combination of eccrine, apocrine, and folliculosebaceous differentiation. Clinically, all tumors presented as solitary, slowly enlarging dermal or subcutaneous nodules located in the head and neck and the extremities. Histologically, they were characterized by well-circumscribed, unencapsulated nodules composed of a lobular proliferation of epithelial cells displaying a spectrum of trichogenic, sebaceous, apocrine, and eccrine differentiation. The histological spectrum included lobules and trabeculae of basaloid cells with glandular and ductal elements, well-formed folliculosebaceous units, primitive follicles, and foci of tricholemmal keratinization. Immunohistochemical evaluation in four cases showed similar cytokeratin, carcinoembryonic antigen, and epithelial membrane antigen staining profiles as those reported for sweat gland adenomas; in addition, focal S-100 protein positivity and GCDFP-15 positivity could also be demonstrated, suggesting eccrine-apocrine differentiation. The tumors were most frequently confused histologically with other adnexal neoplasms, including sebaceoma, sebaceous adenoma, basal cell carcinoma, chondroid syringoma, and trichoepithelioma. The present series highlights the capability for multidirectional differentiation of pluripotential germinal cells in the dermis and serves to underscore the difficulties occasionally encountered in the classification of benign skin adnexal neoplasms. C1 BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA. MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. MT SINAI MED CTR,ARKADI M RYWLIN DEPT PATHOL & LAB MED,MIAMI BEACH,FL 33140. UNIV MIAMI,SCH MED,MIAMI BEACH,FL. ALBANY MED COLL,DEPT DERMATOL,ALBANY,NY. NR 31 TC 32 Z9 34 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD APR PY 1996 VL 18 IS 2 BP 124 EP 136 DI 10.1097/00000372-199604000-00004 PG 13 WC Dermatology SC Dermatology GA UH672 UT WOS:A1996UH67200004 PM 8739986 ER PT J AU Nathan, DM Dunn, FL Bruch, J McKitrick, C Larkin, M Haggan, C LavinTompkins, J Norman, D Rogers, D Simon, D AF Nathan, DM Dunn, FL Bruch, J McKitrick, C Larkin, M Haggan, C LavinTompkins, J Norman, D Rogers, D Simon, D TI Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID MANAGEMENT; INJECTION; DELIVERY; GLUCOSE; TRIAL AB PURPOSE: TO examine the mechanism of the decreased frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous intensive therapy. PATIENTS AND METHODS: Eight subjects with insulin-dependent diabetes mellitus (IDDM), enrolled in an implantable insulin pump study, were admitted to the General Clinical Research Center and on 2 separate days were given either a dose of preprandial insulin chosen to maintain normoglycemia for a standard (450 kcal, 50% carbohydrate) breakfast or 1.75 times the dose. The two doses were administered subcutaneously (by syringe or with an external pump) during one inpatient admission and by implantable pump (intraperitoneally, n = 6; or intravenously, n = 2) during a separate admission. Blood glucose, plasma-free insulin, and neurocognitive function were measured for 4 hours after the meal. RESULTS: Subcutaneous administration resulted in 7 episodes of hypoglycemia (2 with the usual dose and 5 with the 1.75-fold dose), defined as blood glucose less than 50 mg/dL; implantable pump treatment resulted in only 2 episodes, both with the 1.75-fold dose (P <0.05, Fisher's two-tailed test for implantable versus subcutaneous). Compared with subcutaneous delivery, implantable pump therapy provided significantly lower insulin levels during the final 2 hours after administration of the usual dose and the 1.75-fold dose (P <0.005). In addition to the decreased frequency of hypoglycemia, implantable pump therapy resulted in significantly lower area under the glycemia curve during the first 120 minutes with the 1.75-fold dose compared with subcutaneous administration. CONCLUSIONS: The lower frequency of severe hypoglycemia with intensive therapy administered by implantable pump therapy is explained by the more rapid clearance of insulin delivered intraperitoneally or intravenously compared with intensive subcutaneous injection regimens. The lower frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous therapy demonstrated in clinical trials is confirmed by this study, in which we attempted to induce hypoglycemia. C1 MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT PSYCHOL, BOSTON, MA USA. HARVARD UNIV, SCH MED, BOSTON, MA USA. DUKE UNIV, MED CTR, DIV METAB ENDOCRINOL & NUTR, DURHAM, NC USA. RP Nathan, DM (reprint author), MASSACHUSETTS GEN HOSP, DIABET UNIT, DIABET RES CTR, BOSTON, MA 02114 USA. FU NCRR NIH HHS [M01-RR-30, RR01066] NR 27 TC 44 Z9 45 U1 0 U2 2 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 APR PY 1996 VL 100 IS 4 BP 412 EP 417 DI 10.1016/S0002-9343(97)89516-2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UD080 UT WOS:A1996UD08000007 PM 8610727 ER PT J AU Hamberg, LM Hunter, GJ Halpern, EF Hoop, B Gazelle, GS Wolf, GL AF Hamberg, LM Hunter, GJ Halpern, EF Hoop, B Gazelle, GS Wolf, GL TI Quantitative high-resolution measurement of cerebrovascular physiology with slip-ring CT SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article DE animal studies; cerebral blood flow; computed tomography; technique ID CEREBRAL BLOOD-FLOW; COMPUTED-TOMOGRAPHY; VOLUME AB PURPOSE: To implement and validate spiral slip-ring CT for use in cerebrovascular studies. METHODS: Continuous data were acquired from an experimental, first-pass, iodine contrast, bolus study by unidirectional X-ray tube rotation, and images were reconstructed at 100-millisecond intervals. Functional maps of cerebral blood volume (CBV) and cerebral blood flow (CBF) were constructed with voxel-by-voxel gamma variate fitting. Reproducibility studies, different injection volumes and sites, and CO2 challenge were applied to verify the technique. RESULTS: Average absolute cortical gray and white matter and basal ganglia results were reproducible within +/-0.8 mL/100 g for CBV and +/-20 mL/100 g per minute for CBF. CBV response to changing arterial CO2 tension was significant only in cortical gray matter and basal ganglia; CBF response was significant in gray and white matter, as well as in the basal ganglia. CONCLUSION: Functional CT and constructed functional maps provide an optimal, high-resolution tool with which to visualize cerebrovascular parameters and their changes. C1 MASSACHUSETTS GEN HOSP,CTR IMAGING & PHARMACEUT RES,DEPT RADIOL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,MED SERV,PULM & CRIT CARE UNIT,BOSTON,MA 02114. NR 19 TC 51 Z9 70 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD APR PY 1996 VL 17 IS 4 BP 639 EP 650 PG 12 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UF801 UT WOS:A1996UF80100005 PM 8730182 ER PT J AU DAmico, DJ Brazitikos, PD Marcellino, GR Finn, SM Hobart, JL AF DAmico, DJ Brazitikos, PD Marcellino, GR Finn, SM Hobart, JL TI Initial clinical experience with an erbium:YAG laser for vitreoretinal surgery SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL VITREOUS MEMBRANES; INTRAOCULAR ABLATIVE PHOTODECOMPOSITION; ER-YAG; EXCIMER; RABBITS; TISSUE; 193-NM AB PURPOSE: We tested the efficacy of an erbium:YAG laser for maneuvers in patients undergoing vitreoretinal surgery. METHODS: An erbium:YAG laser equipped with a flexible fiberoptic and interchangeable 20-gauge endoprobes of various tip configurations ranging from 100 to 365 mu m was used for specific maneuvers in 13 patients referred for vitreoretinal surgery for diabetic traction detachment, proliferative vitreoretinopathy, retinal detachment with posterior break, and epimacular membrane. The following maneuvers were performed: (1) transection of elevated vitreous membranes, (2) incision of epiretinal membranes, (3) drainage and relaxing retinotomy, (4) transection of subretinal membranes, (5) noncontact ablation of epiretinal membranes in air-filled eyes, (6) ablation of lens remnants, (7) posterior capsulotomy, (8) iris surgery, and (9) retinal vascular coagulation. RESULTS: Forty-eight defined maneuvers were performed with energy levels ranging from 0.2 to 5.0 mJ and repetition rates of 2 to 30 Hz. Transection of elevated membranes, subretinal membranes, and retinotomies were easily performed. Fourteen incisions into vascularized epiretinal membranes in diabetic traction detachment surgery demonstrated a fine margin of coagulation that permitted hemostatic incision, Retinal breaks were created during one of these incisions. Lens remnant ablation, posterior capsulotomy, and iris tissue removal were successful, with a single complication consisting of damage to the posterior surface of an intraocular lens during a pars plana posterior capsulotomy accomplished by means of a side-firing probe, Epiretinal membrane ablations in air-filled eyes were effectively performed in a gradual fashion without hemorrhage. CONCLUSIONS: The erbium:YAG laser offers precise and effective tissue cutting and removal in vitreoretinal maneuvers. Further study will deter mine the role of this technology in vitreoretinal surgery. C1 HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,LASER RES LAB,DEPT OPHTHALMOL,BOSTON,MA 02114. COHERENT INC,PALO ALTO,CA. RP DAmico, DJ (reprint author), HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,RETINA SERV,243 CHARLES ST,BOSTON,MA 02114, USA. NR 27 TC 31 Z9 31 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 1996 VL 121 IS 4 BP 414 EP 425 PG 12 WC Ophthalmology SC Ophthalmology GA UD610 UT WOS:A1996UD61000008 PM 8604735 ER PT J AU Xie, LY Leung, A Segre, GV Yamamoto, I AbouSamra, AB AF Xie, LY Leung, A Segre, GV Yamamoto, I AbouSamra, AB TI Downregulation of the PTH/PTHrP receptor by vitamin D-3 in the osteoblast-like ROS 17/2.8 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE parathyroid hormone; parathyroid hormone-related peptide; dihydroxyvitamin D-3 ID PARATHYROID-HORMONE RECEPTORS; INTRACELLULAR FREE CALCIUM; OSTEOGENIC-SARCOMA CELLS; TUMOR-NECROSIS-FACTOR; PROTEIN KINASE-C; ADENYLATE-CYCLASE; DOWN-REGULATION; OSTEOSARCOMA CELLS; GUANINE-NUCLEOTIDE; CYCLIC-AMP AB Effects of 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] on the expression of the parathyroid hormone (PTH)/PTH-related peptide (rP) receptor protein and mRNA in ROS 17/2.8 cells were studied. Treatment of ROS 17/2.8 cells with 1,25(OH)(2)D-3 caused time- and dose-dependent suppression of PTH/PTHrP receptor number and immunoreactivity. The effects required more than 24 h of incubation with 1,25(OH)(2)D-3 and were maximal by 72 h. The cells did not recover their PTH/PTHrP receptors even after 4 days of treatment with control medium. Treatment with low concentrations of 1,25(OH)(2)D-3 (0.1 M) dramatically decreased the PTH/PTHrP receptor mRNA levels, which were maximal after 24 h of incubation. The half-life of the PTH/PTHrP receptor transcript, 6-8 h, was similar in control and 1,25(OH)(2)D-3-treated cells, suggesting that 1,25(OH)(2)D-3 acts in controlling transcription of the PTH/PTHrP receptor gene but does not change the degradation rate of the PTH/PTHrP receptor transcripts. These data indicate that 1,25(OH)(2)D-3 has a potent inhibitory effect on the expression of the PTH/PTHrP receptor protein and mRNA in ROS 17/2.8 cells. C1 MASSACHUSETTS GEN HOSP, ENDOCRINE UNIT, BOSTON, MA 02114 USA. HARVARD UNIV, SCH MED, BOSTON, MA 02114 USA. RI Leung, Albert/H-6030-2013 NR 30 TC 25 Z9 25 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 APR PY 1996 VL 270 IS 4 BP E654 EP E660 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA UE561 UT WOS:A1996UE56100017 PM 8928773 ER PT J AU Hocker, M Zhang, ZS Fenstermacher, DA Tagerud, S Chulak, M Joseph, D Wang, TC AF Hocker, M Zhang, ZS Fenstermacher, DA Tagerud, S Chulak, M Joseph, D Wang, TC TI Rat histidine decarboxylase promoter is regulated by gastrin through a protein kinase C pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE L-histidine ID ENTEROCHROMAFFIN-LIKE CELLS; PHORBOL-MYRISTATE ACETATE; ANDROGEN-BINDING PROTEIN; MASTOCYTOMA P-815 CELLS; ACID-SECRETION; ENDOCRINE-CELLS; GENE-EXPRESSION; REPORTER GENE; HISTAMINE; IDENTIFICATION AB The enzyme L-histidine decarboxylase (HDC; EC 4.1.1.22), which converts L-histidine to histamine, plays a key role in the regulation of acid secretion. In the rat and human stomach, the peptide hormone gastrin appears to be one of the main regulators of HDC expression. In rats, marked elevation of gastric HDC mRNA abundance was observed within 12 h after induction of hypergastrinemia by a single injection of the proton-pump blocker omeprazole. In situ hybridization revealed that HDC expression occurred in the basal third of gastric glands where enterochromaffin-like cells are localized. To study the regulation of HDC gene transcription, 1,291 nucleotides of the 5'-flanking region of the rat HDC gene and the noncoding portion of exon 1 were cloned and sequenced. Gastrin and cholecystokinin (CCK) octapeptide equipotently stimulated the transcriptional activity of the rat HDC promoter three- to fourfold, and deletion analysis revealed the presence of a gastrin response element within 201 nucleotides upstream of the translational start site. Time-course studies revealed maximal activation of the HDC promoter after 12-36 h. Direct stimulation of protein kinase C (PKC) with the phorbol ester phorbol 12-myristate 13-acetate (PMA) substantially elevated rat HDC promoter activity, whereas induction of Ca2+-dependent signaling pathways with thapsigargin was without effect. Downregulation or blockade of PKC abolished the effects of gastrin and PMA on the HDC promoter. These data indicate that stimulation of the CCK-B/gastrin receptor activates the rat HDC promoter in a time- and dose-dependent fashion and that this effect is primarily mediated via a PKC-dependent signaling pathway. Use of HDC as a model gene will allow further investigation of the intracellular pathways that are involved in gastrin-dependent gene regulation. C1 MASSACHUSETTS GEN HOSP, GASTROINTESTINAL UNIT, BOSTON, MA 02114 USA. MASSACHUSETTS GEN HOSP, DEPT MED, BOSTON, MA 02114 USA. UNIV N CAROLINA, CURRICULUM GENET & MOLEC BIOL, CHAPEL HILL, NC 27599 USA. UNIV N CAROLINA, SCH MED, DEPT PEDIAT, CHAPEL HILL, NC 27599 USA. FU NIDDK NIH HHS [R01-DK-48077, R01-DK-21744] NR 54 TC 46 Z9 46 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 1996 VL 270 IS 4 BP G619 EP G633 PG 15 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA UE563 UT WOS:A1996UE56300010 PM 8928792 ER PT J AU Tanaka, R Barnes, MA Cooper, G Zile, MR AF Tanaka, R Barnes, MA Cooper, G Zile, MR TI Effects of anisosmotic stress on cardiac muscle cell length, diameter, area, and sarcomere length SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE osmolarity; stiffness; cat; rat; adult; mammal ID SCANNING ACOUSTIC MICROSCOPY; VENTRICULAR MYOCYTES; SKELETAL-MUSCLE; OSMOTIC COMPRESSION; PASSIVE STIFFNESS; HEART-CELLS; VOLUME; FORCE; FROG; TENSION AB The purpose of this study was to examine the effects of anisosmotic stress on adult mammalian cardiac muscle cell (cardiocyte) size. Cardiocyte size and sarcomere length were measured in cardiocytes isolated from 10 normal rats and 10 normal cats. Superfusate osmolarity was decreased from 300 +/- 6 to 130 +/- 5 mosM and increased to 630 +/- 8 mosM. Cardiocyte size and sarcomere length increased progressively when osmolarity was decreased, and there were no significant differences between cat and rat cardiocytes with respect to percent change in cardiocyte area or diameter; however, there were significant differences in cardiocyte length (2.8 +/- 0.3% in cat vs. 6.1 +/- 0.3% in rat, P < 0.05) and sarcomere length (3.3 +/- 0.3% in cat vs. 6.4 +/- 0.3% in rat, P < 0.05). To determine whether these species-dependent differences in length were related to diastolic interaction of the contractile elements or differences in relative passive stiffness, cardiocytes were subjected to the osmolarity gradient 1) during treatment with 7 mM 2,3-butanedione monoxime (BDM), which inhibits cross-bridge interaction, or 2) after pretreatment with 1 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), a bivalent Ca2+ chelator. Treatment with EGTA or BDM abolished the differences between cat and rat cardiocytes. Species-dependent differences therefore appeared to be related to the degree of diastolic cross-bridge association and not differences in relative passive stiffness. In conclusion, the osmolarity vs. cell size relation is useful in assessing the cardiocyte response to anisosmotic stress and may in future studies be useful in assessing changes in relative passive cardiocyte stiffness produced by pathological processes. C1 MED UNIV S CAROLINA, DEPT MED, DIV CARDIOL, GAZES CARDIAC RES INST, CHARLESTON, SC 29425 USA. RALPH H JOHNSON DEPT VET AFFAIRS MED CTR, CHARLESTON, SC 29425 USA. NR 48 TC 9 Z9 9 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 APR PY 1996 VL 270 IS 4 BP H1414 EP H1422 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA UE416 UT WOS:A1996UE41600035 ER PT J AU Ikegami, M Ueda, T Hull, W Whitsett, JA Mulligan, RC Dranoff, G Jobe, AH AF Ikegami, M Ueda, T Hull, W Whitsett, JA Mulligan, RC Dranoff, G Jobe, AH TI Surfactant metabolism in transgenic mice after granulocyte macrophage-colony stimulating factor ablation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE alveolar proteinosis; surfactant protein A; dipalmitoylphosphatidylcholine; biological half-life; phospholipids; granulocyte macrophage-colony stimulating deficient ID PULMONARY SURFACTANT; RABBIT LUNG; II CELLS; RAT LUNG; ALVEOLAR; PHOSPHATIDYLCHOLINE; SECRETION; CLEARANCE; PROTEIN AB Mice made granulocyte macrophage-colony stimulating factor (GM-CSF)-deficient by homologous recombination maintain normal steady-state hematopoiesis but have an alveolar accumulation of surfactant lipids and protein that is similar to pulmonary alveolar proteinosis in humans. We asked how GM-CSF deficiency alters surfactant metabolism and function in mice. Alveolar and lung tissue saturated phosphatidylcholine (Sat PC) were increased six- to eightfold in 7- to 9-wk-old GM-CSF-deficient mice relative to controls. Incorporation of radiolabeled palmitate and choline into Sat PC was higher in GM-CSF deficient mice than control mice, and no loss of labeled Sat PC occurred from the lungs of GM-CSF-deficient mice. Secretion of radiolabeled Sat PC to the alveolus was similar in GM-CSF-deficient and control mice. Labeled Sat PC and surfactant protein A (SP-A) given by tracheal instillation were cleared rapidly in control mice, but there was no measurable loss from the lungs of GM-CSF-deficient mice. The function of the surfactant from GM-CSF-deficient mice was normal when tested in preterm surfactant-deficient rabbits. GM-CSF deficiency results in a catabolic defect for Sat PC and SP-A. C1 UNIV CALIF LOS ANGELES, HARBOR MED CTR, SCH MED, TORRANCE, CA 90502 USA. CHILDRENS HOSP, DIV PULM BIOL, CINCINNATI, OH 45229 USA. MIT, WHITEHEAD INST BIOMED RES, CAMBRIDGE, MA 02142 USA. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. FU NHLBI NIH HHS [HL-28623, HL-51832]; NICHD NIH HHS [HD-11932] NR 32 TC 134 Z9 135 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 1996 VL 270 IS 4 BP L650 EP L658 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA UE408 UT WOS:A1996UE40800021 PM 8928826 ER PT J AU Barquist, E Bonaz, B Martinez, V Rivier, J Zinner, MJ Tache, Y AF Barquist, E Bonaz, B Martinez, V Rivier, J Zinner, MJ Tache, Y TI Neuronal pathways involved in abdominal surgery-induced gastric ileus in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE corticotropin-releasing factor; capsaicin; splanchnic afferent; c-fos; paraventricular nucleus of the hypothalamus; nucleus of the solitary tract; supraoptic nucleus; locus ceruleus ID CORTICOTROPIN-RELEASING FACTOR; SPINAL-CORD; GASTROINTESTINAL TRANSIT; PARAVENTRICULAR NUCLEUS; SUPRAOPTIC NUCLEI; SENSORY NEURONS; CAPSAICIN; CRF; INHIBITION; HYPOTHALAMUS AB The 20-min rate of gastric emptying of a noncaloric solution and c-fos expression detected by immunohistochemistry in the brain were monitored 3 h after abdominal surgery performed under 10-min enflurane anesthesia in rats. Abdominal surgery (laparotomy and 1-min manipulation of the cecum) decreased gastric emptying from 60.8 +/- 3.4 to 25.9 +/- 3.4%. Capsaicin applied to the celiac/superior mesenteric ganglia 2 wk before the experiment reduced the delay in gastric emptying induced by abdominal surgery (46.3 +/- 3.4%), whereas perivagal capsaicin application had no effect (23.6 +/- 7.9%). The corticotropin-releasing factor (CRF) antagonist [D-Phe(12),Nle(21,38),C(alpha)MeLeu(37)]CRF-(12-41) injected intracisternally (10-20 pg) prevented postoperative gastroparesis induced by surgery, while having no effect on basal gastric emptying. Abdominal surgery increased the number of Fos-positive cells in brain nuclei regulating autonomic outflow: the nucleus of the solitary tract, locus ceruleus, paraventricular nucleus, and supraoptic nucleus of the hypothalamus. These data indicate that; capsaicin-sensitive splanchnic afferent fibers and activation of CRF receptors in the brain are part of the neuronal circuitry mediating gastric stasis 3 h after abdominal surgery. C1 W LOS ANGELES VET AFFAIRS MED CTR, CTR ULCER RES & EDUC, DIGEST DIS RES CTR, LOS ANGELES, CA 90073 USA. SALK INST BIOL STUDIES, CLAYTON FDN LABS, LA JOLLA, CA 92038 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, DEPT SURG, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, BRAIN RES INST, LOS ANGELES, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-33061, DK-41301]; NIMH NIH HHS [MH-00663] NR 37 TC 84 Z9 86 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 1996 VL 270 IS 4 BP R888 EP R894 PG 7 WC Physiology SC Physiology GA UD269 UT WOS:A1996UD26900024 PM 8967419 ER PT J AU Li, XP Abdi, K Rawn, J Mackay, CR Mentzer, SJ AF Li, XP Abdi, K Rawn, J Mackay, CR Mentzer, SJ TI LFA-1 and 1-selectin regulation of recirculating lymphocyte tethering and rolling on lung microvascular endothelium SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID MEMORY T-CELLS; LEUKOCYTE ADHESION; L-SELECTIN; MIGRATION PATHWAYS; FLOW; HYDROETHIDINE; MECHANISMS; RECEPTOR; CALCEIN; LIGAND AB Recirculating lymphocytes migrate into areas of lung inflammation by binding to microvascular endothelium and transmigrating into extravascular tissue. In this report, we examined the multiple-step paradigm using a unique system: recirculating lymphocytes from sheep peripheral lymphatics adhering to activated lung microvascular endothelium in conditions of physiologic flow. Video microscopy demonstrated that recirculating lymphocytes formed abrupt adhesions, without requisite rolling, on the lung microvascular endothelial cells. Lymphocyte velocity was unchanged within 100 ms of the development of firm adhesions. To dissect the adhesion mechanism, the lymphocytes were pretreated with anti-LFA-1 or anti-L-selectin monoclonal antibody (mAb). Both mAb decreased the incidence of firm adhesions. The mechanism of this inhibition was investigated using time-lapse topographic reconstructions of cell movement after pretreatment with mAb. Time-lapse analysis of the movement of lymphocytes pretreated with anti-LFA-1 mAb suggested that abortive adhesion was manifested by a characteristic saltatory movement and a sustained reduction in cell velocity (rolling) to < 25 mu m/s. In contrast, abortive adhesions of lymphocytes pretreated with anti-L-selectin mAb demonstrated transient arrest (tethering) but minimal rolling before resumption of baseline velocity in the flow stream. These observations provide insights into selectin and integrin regulation of lymphocyte transmigration into the lung. Further, the results of mAb inhibition suggest that the mechanism of lymphocyte migration may have some unique features not observed in studies of neutrophil transmigration. C1 BRIGHAM & WOMENS HOSP,DIV THORAC SURG,IMMUNOPHYSIOL LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. LEUKOSITE INC,CAMBRIDGE,MA. RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NHLBI NIH HHS [HL47078] NR 46 TC 34 Z9 35 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1996 VL 14 IS 4 BP 398 EP 406 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA UE207 UT WOS:A1996UE20700013 PM 8600945 ER PT J AU Fan, KT Whitman, GJ Chew, FS AF Fan, KT Whitman, GJ Chew, FS TI Enterohemorrhagic Escherichia coli colitis SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02114. NR 4 TC 3 Z9 3 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1996 VL 166 IS 4 BP 788 EP 788 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UB521 UT WOS:A1996UB52100007 PM 8610550 ER PT J AU Tirman, PFJ Feller, JF Palmer, WE Carroll, KW Steinbach, LS Cox, I AF Tirman, PFJ Feller, JF Palmer, WE Carroll, KW Steinbach, LS Cox, I TI The Buford complex - A variation of normal shoulder anatomy: MR arthrographic imaging features SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID GLENOID LABRUM; TEARS; INSTABILITY AB OBJECTIVE. The purpose of this study was to show the MR arthrographic imaging features of a normal anatomic variation of the shoulder: the absence of the anterior superior labrum and the presence of a ''cordlike'' middle glenohumeral ligament, which together are known as the Buford complex. MATERIALS AND METHODS. We retrospectively analyzed the MR arthrographic examinations of 10 patients with arthroscopically proven Buford complexes. RESULTS. MR arthrographic examinations showed an absent anterior superior labrum and an associated cordlike middle glenohumeral ligament in all patients, No contiguous tear of the superior labrum or anterior inferior labrum was evident. Originally, this variation was mistakenly diagnosed as a labral avulsion in two of the 10 patients, Also, a differential diagnosis of a superior labral tear was mistakenly offered for four patients. CONCLUSION. An absent anterior superior labrum and an associated cordlike middle glenohumeral ligament represent the normal variation that is known as the Buford complex rather than an avulsed labrum, This normal variation may be mistaken for a detached labrum. C1 DEPT VET AFFAIRS,DAVID GRAND USAF MED CTR,TRAVIS AFB,CA 94535. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA 02114. VET ADM MED CTR,SAN FRANCISCO,CA 94121. ST FRANCIS XAVIER CABRINI HOSP,MELBOURNE,VIC 3144,AUSTRALIA. RP Tirman, PFJ (reprint author), SAN FRANCISCO MAGNET RESONANCE CTR,3333 CALIF ST,STE 105,SAN FRANCISCO,CA 94118, USA. NR 18 TC 58 Z9 59 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1996 VL 166 IS 4 BP 869 EP 873 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UB521 UT WOS:A1996UB52100022 PM 8610565 ER PT J AU Provenzale, JM Mukherji, S Allen, NB Castillo, M Weber, AW AF Provenzale, JM Mukherji, S Allen, NB Castillo, M Weber, AW TI Orbital involvement by Wegener's granulomatosis: Imaging findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID SURFACE-COIL MR; ANTICYTOPLASMIC AUTOANTIBODIES; OCULAR MANIFESTATIONS; EXPERIENCE; PSEUDOTUMOR; LESIONS AB OBJECTIVE. The purpose of this study was to define patterns of Wegener's granulomatosis (WG) orbital disease involvement. SUBJECTS AND METHODS. We evaluated the orbital examinations of 14 WG patients (CT for nine, MR imaging for three, and both CT and MR imaging for two) for the number of involved orbits, intraconal or extraconal location, involvement of the orbital apex, sinus involvement, bony erosion, and optic nerve compression. MR images were analyzed for signal characteristics and enhancement patterns. RESULTS. We found orbital disease to be unilateral in 12 patients (86%) and bilateral in two patients (14%) (total of 16 orbits). In 11 orbits (69%), coexistent orbital and sinus diseases with bony erosion were present. Orbital disease without sinus disease was seen in five orbits (31%). Intraorbital disease distribution was as follows: solely extraconal-seven orbits (44%) (four with involvement of muscle); intraconal with muscular involvement-one orbit (6%); combined intra- and extraconal-seven orbits (44%); and primarily orbital apex-one orbit (6%). Involvement of the apex was seen in six orbits. The WG mass was hypointense relative to orbital fat on three standard T2-weighted MR images. We saw homogeneous MR contrast enhancement in all four orbits studied on enhanced T1-weighted images. CONCLUSION. Intraorbital WG involvement is usually accompanied by paranasal sinus disease. A hypointense signal on T2-weighted MR images is helpful in suggesting the diagnosis. C1 UNIV N CAROLINA,DEPT RADIOL,CHAPEL HILL,NC 27599. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. MASSACHUSETTS EYE & EAR INFIRM,DEPT RADIOL,BOSTON,MA 02143. RP Provenzale, JM (reprint author), DUKE UNIV,MED CTR,DEPT RADIOL,BOX 3808,DURHAM,NC 27710, USA. NR 26 TC 41 Z9 42 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1996 VL 166 IS 4 BP 929 EP 934 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UB521 UT WOS:A1996UB52100033 PM 8610576 ER PT J AU Keel, SB Zukerberg, L GraemeCook, F Compton, CC AF Keel, SB Zukerberg, L GraemeCook, F Compton, CC TI A pancreatic endocrine tumor arising within a serous cystadenoma of the pancreas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pancreatic endocrine tumor; serous cystadenoma; cystic neoplasm of the pancreas; microcystic adenoma ID CELL-CARCINOMA; MALIGNANCY; ENTITY; CYSTADENOCARCINOMA AB We report a pancreatic endocrine tumor arising within an otherwise benign pancreatic serous cystadenoma in a 47-year-old woman with a history of lupus treated by steroids. She presented 10 years before resection with epigastric pain and intermittent jaundice. Histologic and immunohistochemical studies showed that the solid endocrine component was composed of small, uniform cells with stippled nuclei, which were chromogranin A positive. The surrounding cystic component was lined by periodic acid Schiffs-positive, diastase-digestable cells containing glycogen. To the best of our knowledge, this is the first case of a serous cystadenoma of the pancreas that contains a well defined pancreatic endocrine tumor reported in the English literature. C1 HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. RP Keel, SB (reprint author), MASSACHUSETTS GEN HOSP,DEPT PATHOL,JAMES HOMER WRIGHT PATHOL LABS,15 FRUIT ST,BOSTON,MA 02114, USA. NR 18 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 1996 VL 20 IS 4 BP 471 EP 475 DI 10.1097/00000478-199604000-00010 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA UC900 UT WOS:A1996UC90000010 PM 8604814 ER PT J AU Huszar, M Fanburg, JC Dickersin, GR Kirshner, JJ Rosenberg, AE AF Huszar, M Fanburg, JC Dickersin, GR Kirshner, JJ Rosenberg, AE TI Retroperitoneal malignant meningioma - A light microscopic, immunohistochemical, and ultrastructural study SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE malignant meningioma; ectopic; retroperitoneum ID PULMONARY MENINGIOMA; SOFT-TISSUE; FEATURES; TUMORS AB Malignant meningiomas are uncommon and rarely occur outside the central nervous system. We describe herein a morphologically unusual malignant neoplasm that arose in the retroperitoneum of a 25-year-old woman. The tumor was composed of sheets of epithelioid cells that were frequently arranged in prominent whorls. By electron microscopy, the neoplastic cells had long, tapering cell processes that formed numerous interdigitations; many junctions including desmosomes; and abundant intermediate filaments. Immunohistochemistry showed that the tumor cells expressed vimentin, keratin, and epithelial membrane antigen. Based on these findings, the neoplasm was classified as a malignant meningioma. According to our review of the literature, this is the first reported occurrence of a primary retroperitoneal meningothelial neoplasm and the second reported case of an ectopic meningioma that was malignant. C1 MASSACHUSETTS GEN HOSP,DEPT PATHOL,BOSTON,MA 02114. CHAIM SHEBA MED CTR,DEPT PATHOL,TEL HASHOMER,ISRAEL. ARMED FORCES INST PATHOL,SOFT TISSUE BRANCH,WASHINGTON,DC 20306. HARVARD UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02115. HEMATOL ONCOL ASSOCIATES CENT NEW YORK,SYRACUSE,NY. NR 38 TC 21 Z9 24 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 1996 VL 20 IS 4 BP 492 EP 499 DI 10.1097/00000478-199604000-00014 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA UC900 UT WOS:A1996UC90000014 PM 8604818 ER PT J AU Tobias, MD Pilla, MA Rogers, C Jobes, DR AF Tobias, MD Pilla, MA Rogers, C Jobes, DR TI Lidocaine inhibits blood coagulation: Implications for epidural blood patch SO ANESTHESIA AND ANALGESIA LA English DT Article ID POSTDURAL PUNCTURE HEADACHE; PLATELET-AGGREGATION; THROMBELASTOGRAPHY AB Lidocaine in the epidural space, through inhibitory effects upon coagulation, may contribute to inefficacy of epidural autologous blood patch (EBP). This study was undertaken to evaluate the effect of achievable epidural concentrations of lidocaine on blood coagulation as a step in testing this hypothesis. Ex vivo blood coagulation using whole blood (n = 20) was studied with computerized thrombelastography (TEG). Each blood specimen was exposed to serial dilutions of lidocaine hydrochloride or saline to form end-concentrations of 0.0 mM, 2.3 mM, 4.6 mM, 9.2 mM, 18.5 mM, and 36.9 mM lidocaine. Statistical analysis using analysis of variance for repeated measures revealed that the three highest lidocaine concentrations tested caused hypocoagulable and/or fibrinolytic changes as compared with controls. Achievable epidural admixtures of lidocaine and whole blood will impair coagulation. Therefore, residual lidocaine in the epidural space may contribute to failures of immediate or early EBP. C1 UNIV PENN,SCH MED,DEPT ANESTHESIA,PHILADELPHIA,PA 19104. MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,CAMBRIDGE,MA. ST ANDREWS COLL,BERRIEN SPRINGS,MI. NR 19 TC 33 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 1996 VL 82 IS 4 BP 766 EP 769 DI 10.1097/00000539-199604000-00016 PG 4 WC Anesthesiology SC Anesthesiology GA UC482 UT WOS:A1996UC48200016 PM 8615495 ER PT J AU Alikhani, S Alfille, PH AF Alikhani, S Alfille, PH TI Right-sided double lumen tubes: Does clinical confirmation ensure proper fiberoptic positioning? SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 1996 VL 82 IS 4 SU S BP SCA81 EP SCA81 PG 1 WC Anesthesiology SC Anesthesiology GA UD164 UT WOS:A1996UD16400081 ER PT J AU Ong, BC Nathan, N Lynch, KE Johnson, S DAmbra, MN AF Ong, BC Nathan, N Lynch, KE Johnson, S DAmbra, MN TI Serum protein C (an intrinsic anticoagulant) activity drops prior to institution of cardiopulmonary bypass well below levels expected from hemodilution alone SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 1996 VL 82 IS 4 SU S BP SCA9 EP SCA9 PG 1 WC Anesthesiology SC Anesthesiology GA UD164 UT WOS:A1996UD16400009 ER PT J AU Dershwitz, M Hoke, JF Rosow, CE Michalowski, P Connors, PM Muir, KT Dienstag, JL AF Dershwitz, M Hoke, JF Rosow, CE Michalowski, P Connors, PM Muir, KT Dienstag, JL TI Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease SO ANESTHESIOLOGY LA English DT Article DE analgesics, opioids, GR90291, remifentanil; anesthetics, intravenous, remifentanil; liver, disease; pharmacodynamics; pharmacokinetics ID GI87084B; CIRRHOSIS; SURGERY AB Background: Remifentanil, a new p-opioid agonist with an extremely short duration of action, is metabolized by circulating and tissue esterases; therefore, its clearance should be relatively unaffected by changes in hepatic or renal function. This study was designed to determine whether severe hepatic disease affects the pharmacokinetics or pharmacodynamics of remifentanil. Methods: Ten volunteers with chronic, stable, severe hepatic disease and awaiting liver transplantation and ten matched controls were enrolled. Each subject was given a 4-h infusion of remifentanil. The first five pairs received 0.0125 mu g . kg(-1). min(-1) for 1 h followed by 0.025 mu g . kg(-1). min(-1) for 3 h; the second five pairs received double these Infusion rates. During and after the infusion, arterial blood was obtained for pharmacokinetic analyses, and the ventilatory response to a hypercarbic challenge was assessed. Simultaneous pharmacokinetic and pharmacodynamic analyses were performed. The pharmacokinetics were described using a one-compartment intravenous infusion model, and ventilatory depression was modelled using the inhibitory E(max) model. The pharmacokinetics of the metabolite GR90291 were determined using noncompartmental methods. Results: There were no differences in any of the pharmacokinetic parameters for remifentanil or GR90291 between the two groups, The subjects with liver disease were more sensitive to the ventilatory depressant effects of remifentanil. The EC(50) values (the remifentanil concentrations determined from simultaneous pharmacokinetic/pharmacodynamic analyses to depress carbon dioxide-stimulated minute ventilation by 50%) in the control and hepatic disease groups were 2.52 ng/ml(95% confidence interval 2.07-2.97 ng/ml) and 1.56 ng/ml(9596 confidence interval 1.37-1.76 ng/ml), respectively. Conclusions: The pharmacokinetics of remifentanil and GR90291 are unchanged In persons with severe, chronic liver disease. Such patients may be more sensitive to the ventilatory depressant effects of remifentanil, a finding of uncertain clinical significance, considering the extremely short duration of action of the drug. C1 HARVARD UNIV,SCH MED,BOSTON,MA. GLAXO GRP RES LTD,RES INST,DEPT CLIN PHARMACOL,RES TRIANGLE PK,NC. MASSACHUSETTS GEN HOSP,DEPT MED,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. RP Dershwitz, M (reprint author), MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,BOSTON,MA 02114, USA. NR 17 TC 109 Z9 119 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 1996 VL 84 IS 4 BP 812 EP 820 DI 10.1097/00000542-199604000-00008 PG 9 WC Anesthesiology SC Anesthesiology GA UD614 UT WOS:A1996UD61400008 PM 8638835 ER PT J AU Yang, HS Goudsouzian, N Martyn, JAJ AF Yang, HS Goudsouzian, N Martyn, JAJ TI Pseudocholinesterase-mediated hydrolysis is superior to neostigmine for reversal of mivacurium-induced paralysis in vitro SO ANESTHESIOLOGY LA English DT Article DE antagonists, anticholinesterase (neostigmine), cholinesterases, pseudocholinesterase; drug metabolism, mivacurium, succinylcholine; interactions, drug, cholinesterases-mivacurium, cholinesterases-succinylcholine, mivacurium-neostigmine; neuromuscular relaxants, mivacurium, succinylcholine ID NEUROMUSCULAR BLOCKADE; PLASMA CHOLINESTERASE; ANTICHOLINESTERASES; SUCCINYLCHOLINE; PYRIDOSTIGMINE AB Background: The metabolic hydrolysis of mivacurium (and succinylcholine) is markedly impaired in the presence of hereditary or acquired defects of pseudocholinesterase. Clinical reports are conflicting as to the utility of anticholinesterases, in the reversal of mivacurium paralysis. In the current study, the role of exogenous cholinesterases and/or of anticholinesterase, neostigmine, in the reversal of deep mivacurium-induced paralysis, was studied. The rat phrenic-diaphragm preparation, in a fixed volume of Krebs solution, was chosen to eliminate the confounding effects on the dissipation of neuromuscular effects caused by hydrolysis, elimination, and redistribution of the drug. Methods: In the phrenic-diaphragm preparation, mivacurium was administered to obtain >90% single twitch inhibition. Single twitch responses (0.1 Hz) were monitored for 60 min, after which the response to train-of-four stimulation was tested. The reversal of mivacurium by 0.5, 1.0, or 2.0 units/ml of (true) acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase and by neostigmine, 0.1, 1.0, or 10.0 mu g/ml was tested. The efficacy of human plasma cholinesterase, 1 unit/ml in combination with each of the above neostigmine concentrations, also was examined. The reversal of succinylcholine-induced paralysis by the acetylcholinesterase, bovine pseudocholinesterase, or human plasma cholinesterase (1 unit/ml) alone and in the presence of neostigmine (10.0 mu g/ml) was additionally tested as a positive control, A train-of-four ratio > 0.75 was considered adequate reversal. Results: Acetylcholinesterase was a poor hydrolyzer of mivacurium, as bioassayed by reversal of paralysis. Bovine pseudocholinesterase In concentrations of 0.5 and 1.0 units/ml did not effectively reverse single twitch and train-of-four responses by 60 min, but bovine pseudocholinesterase (2 units/ml) and all concentrations of human plasma cholinesterase did. Neostigmine alone, tested at all concentrations, was an incomplete reversal drug. Clinical or therapeutic concentrations (0.1 and 1.0 mu g/ml) of neostigmine did not, but pharmacologic concentrations (10 mu g/ml) did interfere with the efficacy of human plasma cholinesterase (1 unit/ml). Bovine pseudocholinesterase and human plasma cholinesterase equally reversed the effects of succinylcholine but acetylcholinesterase did not, whereas the addition of 10 mu g/ml neostigmine to the enzymes inhibited the reversal of succinylcholine. Conclusions: Human plasma cholinesterase will reverse mivacurium more effectively than bovine pseudocholinesterase, but both will effectively reverse succinylcholine. Acetylcholinesterase has no effects on either relaxant. The anticholinesterase neostigmine was an incomplete reversal drug. Pharmacologic concentrations of anticholinesterases do, while clinical or therapeutic concentrations do not, completely inhibit the metabolic activity of pseudocholinesterases. C1 MASSACHUSETTS GEN HOSP,DEPT ANESTHESIA,ANESTHESIA SERV,CLIN & BIOCHEM PHARMACOL LAB,BOSTON,MA 02114. HARVARD UNIV,SCH MED,DEPT ANAESTHESIOL,BOSTON,MA. SHRINERS BURNS INST,BOSTON,MA. FU NIGMS NIH HHS [R01 GM31569-13] NR 40 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 1996 VL 84 IS 4 BP 936 EP 944 DI 10.1097/00000542-199604000-00022 PG 9 WC Anesthesiology SC Anesthesiology GA UD614 UT WOS:A1996UD61400022 PM 8638849 ER PT J AU Leaf, DA Kleinman, MT AF Leaf, DA Kleinman, MT TI Acute exposure to carbon monoxide does not affect plasma lipids, lipoproteins, and apolipoproteins SO ANGIOLOGY LA English DT Article AB Study objectives: To examine the effects of acute exposure to carbon monoxide and hypoxia on plasma lipids, lipoproteins, and apolipoproteins. Design: Random-order assignment to blinded, inhaled exposures of carbon monoxide and hypoxia. Setting: Research laboratory of ambulatory subjects. Subjects: 10 elderly, male nonsmokers with chronic stable angina. Intervention: Random-order two-hour inhaled exposure to clean air at sea level, carbon monoxide at sea level, carbon monoxide at high altitude, and clean air at high altitude. Measurements: Fasting plasma lipids, lipoproteins, and apolipoproteins before and after exposures. Results: No differences were noted between fasting plasma lipid, lipoprotein, or apolipoprotein levels before and after exposures. Conclusion: Acute exposure to carbon monoxide and high altitude does not affect fasting plasma lipid, lipoprotein, or apolipoprotein levels. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF IRVINE,DEPT COMMUNITY & ENVIRONM MED,IRVINE,CA 92717. RP Leaf, DA (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,DIV GEN INTERNAL MED 691111G,WILSHIRE & SAWTELLE BLVD,LOS ANGELES,CA 90073, USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 SN 0003-3197 J9 ANGIOLOGY JI Angiology PD APR PY 1996 VL 47 IS 4 BP 337 EP 341 DI 10.1177/000331979604700403 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA UF257 UT WOS:A1996UF25700003 PM 8619505 ER PT J AU Villareal, MS Klaustermeyer, WB Hahn, TJ Gordon, EH AF Villareal, MS Klaustermeyer, WB Hahn, TJ Gordon, EH TI Osteoporosis in steroid-dependent asthma SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; BONE LOSS; THERAPY; COMPLICATIONS; DISEASE AB Background: Patients on prolonged corticosteroid therapy are at risk of developing osteoporosis. Some patients with severe asthma are difficult to wean off corticosteroids and are therefore at risk of developing bony complications due to steroids. Objective: The purpose of this study was to examine the relationship of cumulative steroid dosage and duration of therapy with osteoporosis. Methods: We obtained bone mineral density studies using dual photon absorptiometry, and radiographs of the lumbar spine of 16 steroid-dependent patients with asthma. Patients with conditions affecting bone metabolism were excluded. Results: We studied 16 male steroid-dependent patients with asthma who received 4 to 41 grams equivalent dose of prednisone over a period of 1 to 15 years. The overall prevalence rate for abnormal age-matched bone mineral density was 50%. Abnormal bone mineral density was more commonly noted in the lumbar spine (38%) than in the femoral neck (19%). The lowest dose of corticosteroid associated with a decrease in bone mineral density was a cumulative steroid dose of 5.6 equivalent grams-prednisone. Conclusion: Prolonged corticosteroid therapy can cause significant osteoporosis among male patients with steroid-dependent asthma. Bone loss due to corticosteroid therapy occurs at different rates at different bony sites. C1 UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,ALLERGY & IMMUNOL SECT IIIR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,W LOS ANGELES VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,LOS ANGELES,CA 90073. NR 19 TC 21 Z9 21 U1 1 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD APR PY 1996 VL 76 IS 4 BP 369 EP 372 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA UF806 UT WOS:A1996UF80600012 PM 8612121 ER PT J AU Gelber, RD AF Gelber, RD TI Gemcitabine for pancreatic cancer: How hard to look for clinical benefit? An American perspective SO ANNALS OF ONCOLOGY LA English DT Editorial Material C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. RP Gelber, RD (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 9 TC 15 Z9 15 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 1996 VL 7 IS 4 BP 335 EP 337 PG 3 WC Oncology SC Oncology GA UT903 UT WOS:A1996UT90300012 PM 8805922 ER PT J AU Chen, NT Butler, PEM Hooper, DC May, JW AF Chen, NT Butler, PEM Hooper, DC May, JW TI Bacterial growth in saline implants: In vitro and in vivo studies SO ANNALS OF PLASTIC SURGERY LA English DT Article ID TISSUE EXPANDERS; BREAST IMPLANTS; INFECTION AB The survival of bacteria was evaluated in custom-made saline breast implants with integral injection ports in vitro and in 10 New Zealand White rabbits for Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Serratia marcescens. Pseudomonas and Serratia survived in vitro in saline-filled implants and multiplied 24-fold and 22-fold, respectively, from the initial inocula of 300 colony-forming units per cubic centimeter in 21 days. Serratia alone survived in saline implants placed on the dorsum of rabbits, proliferated 80-fold in 7 days, and tapered to 10-fold at the end of 3 weeks. Chemical analysis revealed the presence of glucose in fluid from the implants in the animal study (mean, 1.2 mg per deciliter; standard error of mean [SEM], 0.6) after 21 days and from human subjects (mean, 3.8 mg per deciliter; SEM, 1.0) after 8 months to 10 years. Senatia incubated in human breast implant fluid samples proliferated 7-fold to 30-fold greater than in the saline control in a nonaerated environment. We conclude that some bacteria are able to proliferate in saline in breast implants. Furthermore, their survival may be facilitated by a substance (i.e., glucose) that diffuses across the implant outer shell. C1 MASSACHUSETTS GEN HOSP,DIV PLAST & RECONSTRUCT SURG,DEPT SURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT MED,INFECT DIS UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. NR 13 TC 16 Z9 16 U1 1 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD APR PY 1996 VL 36 IS 4 BP 337 EP 341 DI 10.1097/00000637-199604000-00001 PG 5 WC Surgery SC Surgery GA UE564 UT WOS:A1996UE56400001 PM 8728573 ER PT J AU Souba, WW Tanabe, KK Gadd, MA Smith, BL Bushman, MS AF Souba, WW Tanabe, KK Gadd, MA Smith, BL Bushman, MS TI Attitudes and opinions toward surgical research - A survey of surgical residents and their chairpersons SO ANNALS OF SURGERY LA English DT Article AB Objective To learn more about how research in academic surgery is viewed by surgical residents and their chairpersons. Summary Background Data There is a general perception that a productive experience in a basic science laboratory is an important prerequisite for a successful career in academic surgery. Methods An anonymous mail survey of 189 surgical residents entering the laboratory and their chairpersons (n = 81) was done. Questions included how a laboratory was chosen by the resident, the importance of a basic science laboratory experience as a prerequisite to an academic career, and the perceived goal or goals of the laboratory experience: Data were analyzed by chi square analysis. Results The response rate from each group was excellent (80% response for residents, 90% from chairpersons). Of the residents surveyed, 78% were men and 22% were women; 51% entered the laboratory after 2 years of clinical training and 34% after 3 years; 84% did their research at their home institution and 91% worked in a surgeon's laboratory; 51% were scheduled to be in the laboratory for 1 year, 41% for 2 years, and 7% for 3 years. Two thirds of the residents were salaried by the surgery department. Both residents (70%) and chairpersons (86%) felt that the best surgical journal was Annals of Surgery. Both groups ranked Science as the top basic science journal. Twenty-four percent of the residents felt their peers offered the best advice in choosing a laboratory compared to 0% of the chairpersons (p < 0.01); chairpersons felt they themselves or the program director were better advisors (chairpersons, 44%, vs. residents, 27%; p < 0.01). Chairpersons believed that the principal investigators' previous success with residents was the major factor in determining in which laboratory to work; the residents placed more value on their interest in the project. Eighty-nine percent of women requested to go into the laboratory versus 66% of men (p < 0.05). Half of the chairpersons and residents believed the faculty felt pressure on them to get grants; however, 71% of postgraduate year (PGY) residents who were PGY3 sensed this pressure compared to 44% of the PGY2 residents (p < 0.01). Being in debt did not adversely influence the decision of 77% of these residents to do research. The residents felt more so than did their chairpersons that basic science research was necessary to be a successful academic surgeon (p < 0.01). Conclusions Although there are some differences in opinions between surgical residents and surgical chairpersons about the value and purpose of basic science research, these differences should be embraced and serve to enhance openness and discussion. Overall, surgical residents viewed the research experience away from clinical surgery as a positive one. The main reason for going into the laboratory was because of a genuine interest in the scientific method and the academic mission. RP Souba, WW (reprint author), HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP,DEPT SURG,DIV SURG ONCOL,COX BLDG,ROOM 626,BOSTON,MA 02114, USA. NR 10 TC 26 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD APR PY 1996 VL 223 IS 4 BP 377 EP 383 DI 10.1097/00000658-199604000-00006 PG 7 WC Surgery SC Surgery GA UE698 UT WOS:A1996UE69800006 PM 8633916 ER PT J AU Vlahakes, GJ AF Vlahakes, GJ TI Management of pulmonary hypertension and right ventricular failure: Another step forward SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 HARVARD UNIV,SCH MED,DEPT SURG,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 7 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 1996 VL 61 IS 4 BP 1051 EP 1052 DI 10.1016/0003-4975(96)00019-7 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UD082 UT WOS:A1996UD08200002 PM 8607653 ER PT J AU DeBoer, DA Margolis, ML Livornese, D Bell, KA Livolsi, VA Bavaria, JE AF DeBoer, DA Margolis, ML Livornese, D Bell, KA Livolsi, VA Bavaria, JE TI Pulmonary venous aneurysm presenting as a middle mediastinal mass SO ANNALS OF THORACIC SURGERY LA English DT Article AB A large mediastinal mass in a 43-year-old man was proven at thoracotomy to comprise a right superior pulmonary vein aneurysm. Intraoperative transesophageal echocardiography was useful in defining the abnormality. Pulmonary venous aneurysm appears to represent an extremely rare but surgically correctable addition to the differential diagnosis of middle mediastinal masses. C1 HOSP UNIV PENN,DEPT CARDIOTHORAC SURG,PHILADELPHIA,PA 19104. HOSP UNIV PENN,DEPT PATHOL,PHILADELPHIA,PA 19104. VET AFFAIRS MED CTR,DEPT MED,DIV PULM,PHILADELPHIA,PA. NR 3 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 1996 VL 61 IS 4 BP 1261 EP 1262 DI 10.1016/0003-4975(95)00980-9 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA UD082 UT WOS:A1996UD08200064 PM 8607703 ER PT J AU Doern, GV Ferraro, MJ Brueggemann, AB Ruoff, KL AF Doern, GV Ferraro, MJ Brueggemann, AB Ruoff, KL TI Emergence of high rates of antimicrobial resistance among viridans group streptococci in the United States SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID NEUTROPENIC PATIENTS; SUSCEPTIBILITIES; ENDOCARDITIS; LEUKEMIA; MITIS AB Three hundred fifty-two blood culture isolates of viridans group streptococci obtained from 43 U,S, medical centers during 1993 and 1994 were characterized, Included were 48 isolates of ''Streptococcus milleri,'' 219 S. mitis isolates, 29 S, salivarius isolates, and 56 S. sanguis isolates, High-level penicillin resistance (MIG, greater than or equal to 4.0 mu g/ml) was noted among 13.4% of the strains; for 42.9% of the strains, penicillin MICs were 0.25 to 2.0 mu g/ml (i,e,, intermediate resistance), In general, amoxicillin was slightly more active than penicillin, The rank order of activity for five cephalosporins versus viridans group streptococci was cefpodoxime = ceftriaxone > cefprozil = cefuroxime much greater than cephalexin, The percentages of isolates resistant (MIC, greater than or equal to 2 mu g/ml) to these agents were 15, 17, 18, 20, and 96, respectively, The rates of resistance to erythromycin, tetracycline, and trimethoprimsulfamethoxazole were 12 to 38%, Resistance to either chloramphenicol or ofloxacin was uncommon (i,e., <1%). In general, among the four species, S, mitis was the most resistant and ''S, milleri'' was the most susceptible. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. RP Doern, GV (reprint author), UNIV MASSACHUSETTS,MED CTR,CLIN MICROBIOL LABS,55 LAKE AVE N,WORCESTER,MA 01655, USA. NR 15 TC 197 Z9 205 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1996 VL 40 IS 4 BP 891 EP 894 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA UD248 UT WOS:A1996UD24800012 PM 8849246 ER PT J AU Armstrong, ML Stuppy, DJ Gabriel, DC Anderson, RR AF Armstrong, ML Stuppy, DJ Gabriel, DC Anderson, RR TI Motivation for tattoo removal SO ARCHIVES OF DERMATOLOGY LA English DT Article ID SWITCHED RUBY-LASER; DOSE-RESPONSE AB Background and Design: Motivational issues surrounding tattoo removal are important to understand because tattooing is flourishing, thus creating many requests for tattoo removal. A descriptive study and a 67-item survey were used to examine characteristics of tattooed patients seeking laser therapy for tattoo removal. The setting was the Laser Dermatology Center, Massachusetts General Hospital in Boston, a large metropolitan ambulatory clinic. Patients queried were 64 tattooed males and 41 tattooed females between the ages of 17 and 62 years with a wide variety of vocational and professional occupations. We assessed risk factors surrounding tattooing decisions and experiences that might later influence their motivation to have the tattoos removed by laser therapy. Results: Motivation, treatment, and cost, in terms of money, pain, and risk of disfigurement all entered into the decision making to have the tattoos removed. Strong elements of purchase and possesion risks were documented as well as an improved sense of self and maturity. The patient's maturation was in contrast to the notion of a waiting room filled with ill-behaved stereotypical tattooed individuals. Most participants impulsively obtained their tattoos for internal expectations of self-identity at an early age and were still internally motivated to dissociate from the past and improve self-identity. Conclusions: Poor decision making and subsequent personal regret seem to be frequent motivations for tattoo removal, thus viable methods and accessibility to tattoo removal programs are important. In addition, educational programs for adolescents about tattooing to reduce risks and promote dissuasion should be implemented. C1 MASSACHUSETTS GEN HOSP, DEPT DERMATOL, BOSTON, MA 02114 USA. TEXAS TECH UNIV, HLTH SCI CTR, SCH NURSING, LUBBOCK, TX 79430 USA. UNIV TEXAS, SCH NURSING, ARLINGTON, TX 76019 USA. MASSACHUSETTS GEN HOSP, LASER DEPT CTR, BOSTON, MA 02114 USA. NR 30 TC 37 Z9 37 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 1996 VL 132 IS 4 BP 412 EP 416 DI 10.1001/archderm.132.4.412 PG 5 WC Dermatology SC Dermatology GA UE213 UT WOS:A1996UE21300006 PM 8629844 ER PT J AU Lucarelli, MJ Ceisler, EJ Talamo, JH Jakobiec, FA AF Lucarelli, MJ Ceisler, EJ Talamo, JH Jakobiec, FA TI Complex choristoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID EPIBULBAR RP Lucarelli, MJ (reprint author), MASSACHUSETTS EYE & EAR INFIRM,243 CHARLES ST,BOSTON,MA 02114, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 1996 VL 114 IS 4 BP 498 EP 499 PG 2 WC Ophthalmology SC Ophthalmology GA UD951 UT WOS:A1996UD95100029 PM 8602797 ER PT J AU Cook, MW Levin, LA Joseph, MP Pinczower, EF AF Cook, MW Levin, LA Joseph, MP Pinczower, EF TI Traumatic optic neuropathy - A meta-analysis SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID FACIAL FRACTURES; BLINDNESS; INJURY AB Background: The management of traumatic optic neuropathy remains controversial. Reports of improvement have been published after observation alone, treatment with corticosteroids, and surgical decompression. Objective: To systematically review the published literature about traumatic optic neuropathy using a meta-analysis. Methods: We performed a retrospective literature review of case series and case reports of traumatic optic neuropathy. These include all English language cases and selected non-English language cases for which patient data were available. The cases were organized into four grades based on visual acuity and the locations and type of fracture. Grade 1 included patients with visual acuity greater than 20/200 in the affected eye and without a posterior orbit fracture; grade 2, patients with visual acuity between 20/200 and light perception; grade 3, patients without light perception or with a nondisplaced posterior orbital fracture and remaining vision; and grade 4, patients with no light perception and a displaced posterior orbital fracture. A meta-analysis was performed, analyzing for each case the recovery of visual acuity for treatment, fracture pattern, and grade. Results: The recovery of vision in treated patients was significantly better than the recovery in patients receiving no treatment. No significant difference in improvement was found among patients treated with corticosteroids alone, with surgical decompression alone, or with corticosteroids and surgical decompression. Recovery was related to the severity of initial injury, as reflected in the grading system. A trend was noted for better improvement of visual acuity in patients without orbital fractures than those with orbital fractures, and also in patients with anterior orbital fractures than in patients with posterior orbital fractures. Conclusions: Treatment with corticosteroids, extracranial decompression, or both, is better than no treatment of traumatic optic neuropathy. Because the data are insufficient Co determine whether corticosteroids, surgery, or use of both treatments is most effective, the findings of the ongoing International Optic Nerve Trauma Study should prove valuable. The standardized grading system we developed is a useful tool for comparing studies and treatment protocols. C1 UNIV WASHINGTON,MED CTR,DEPT OTOLARYNGOL HEAD & NECK SURG,SEATTLE,WA 98195. UNIV HOSP CLIN,DEPT OPHTHALMOL,MADISON,WI. MASSACHUSETTS EYE & EAR INFIRM,DEPT OTOLARYNGOL,BOSTON,MA 02114. NR 22 TC 109 Z9 126 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD APR PY 1996 VL 122 IS 4 BP 389 EP 392 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA UE212 UT WOS:A1996UE21200005 PM 8600923 ER PT J AU Rattner, DW DelCastillo, CF Brugge, WR Warshaw, AL AF Rattner, DW DelCastillo, CF Brugge, WR Warshaw, AL TI Defining the criteria for local resection of ampullary neoplasms SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 76th Annual Meeting of the New-England-Surgical-Society CY SEP 30-OCT 01, 1995 CL MONTREAL, CANADA SP New England Surg Soc ID VILLOUS TUMORS; VATER; CARCINOMA; ENDOSONOGRAPHY; PAPILLA AB Objective: To delineate factors determined preoperatively, which predict successful local resection of ampullary neoplasms. Design: Retrospective review of case series of the authors' experience from 1988 through 1995. The median follow-up of patients with malignancies was 29 months. Setting: Tertiary care university teaching hospital. Patients: Twenty-seven patients underwent surgery. The decision to perform either an ampullectomy or pancreaticoduodenectomy (PD) was based on the size of the lesion, the presence of a ''field defect'' tie, familial polyposis), depth of invasion determined by preoperative endoscopic ultrasound, and extent of pancreatic and bile duct involvement seen on endoscopic retrograde cholangiopancreatography. Interventions: Fourteen patients underwent ampullectomy, 12 patients underwent PD, and one patient had a retroperitoneal node biopsy performed without resection of the primary tumor. Main Outcome Measures: Resectability, morbidity, and mortality. Results: Depth of invasion was accurately determined in nine of 12 patients studied by preoperative endoscopic ultrasound. Preoperative endoscopic biopsy specimens were obtained in 21 patients and were inaccurate in seven of 21 cases. The length of stay following local resection was 10.5+/-3.7 days vs 15.4+/-5.8 days following PD (P=.02). One patient died following PD, and there were no deaths following ampullectomy. Six of 12 patients undergoing PD had postoperative complications vs two of 14 patients undergoing local resection. Conclusions: Ampullectomy is the procedure of choice for resecting benign lesions smaller than 3 cm, small neuroendocrine tumors, and T1 carcinomas of the ampulla. While endoscopic ultrasonography is helpful in identifying stage T1 lesions suitable for local resection, no preoperative test proved accurate enough to substitute for clinical judgment and intraoperative pathological confirmation. C1 MASSACHUSETTS GEN HOSP,GASTROINTESTINAL UNIT,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA. RP Rattner, DW (reprint author), MASSACHUSETTS GEN HOSP,DEPT SURG,BOSTON,MA 02114, USA. NR 25 TC 93 Z9 99 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1996 VL 131 IS 4 BP 366 EP 371 PG 6 WC Surgery SC Surgery GA UD953 UT WOS:A1996UD95300005 PM 8615720 ER PT J AU Ozeki, S Ohtsuru, A Seto, S Takeshita, S Yano, H Nakayama, T Ito, M Yokota, T Nobuyoshi, M Segre, GV Yamashita, S Yano, K AF Ozeki, S Ohtsuru, A Seto, S Takeshita, S Yano, H Nakayama, T Ito, M Yokota, T Nobuyoshi, M Segre, GV Yamashita, S Yano, K TI Evidence that implicates the parathyroid hormone-related peptide in vascular stenosis - Increased gene expression in the intima of injured rat carotid arteries and human restenotic coronary lesions SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE PTH/PTHrP receptor; restenosis; atherectomy; neointimal formation; PTHrP ID SMOOTH-MUSCLE CELLS; MESSENGER RIBONUCLEIC-ACIDS; OSTEOBLAST-LIKE CELLS; PROTEIN GENE; FREE CALCIUM; ANGIOPLASTY; PROLIFERATION; RECEPTOR; ATHEROSCLEROSIS; HYPERCALCEMIA AB Proliferation of vascular smooth muscle cells (VSMCs) is considered to be one key event underlying the pathophysiology of restenosis after angioplasty. The parathyroid hormone-related peptide (PTHrP) and its receptor, a local autocrine and paracrine regulator of cellular growth in a variety of normal cell types, have been reported in the vicinity of VSMCs. To investigate how PTHrP might be involved in the process of neointimal formation after balloon angioplasty, we examined PTHrP expression in balloon-denuded rat carotid arteries and human coronary arteries that had been retrieved by directional atherectomy. In rat carotid arteries, the RNase protection assay and in situ hybridization demonstrated that PTHrP mRNA expression increased fourfold to sixfold 1 to 7 days after denudation and continued for 28 days, coincident with downregulation of PTH/PTHrP receptor mRNA expression. In situ hybridization and immunohistochemistry revealed that PTHrP expression in balloon-denuded carotid arteries was mainly localized to the neointima. To confirm the involvement of the PTHrP in human coronary artery restenotic lesions, immunohistochemical analysis of human coronary atherectomy specimens (23 primary and 10 restenotic lesions) was then performed. The number of intimal cells that expressed PTHrP protein was significantly higher in restenotic (407 +/- 53 cells/mm(2); range, 143 to 739) than in stable angina (50 +/- 12 cells/mm(2); range, 18 to 132; P<.05) or unstable angina (129 +/- 16 cells/mm(2); range, 21 to 232; P<.05) specimens. These data demonstrate that PTHrP gene expression in VSMCs markedly increases during neointimal formation, supporting the hypothesis that PTHrP may play an important role in vascular stenosis as a regulator of VSMC proliferation. C1 NAGASAKI UNIV,SCH MED,INST ATOM DIS,DEPT CELL PHYSIOL,NAGASAKI 852,JAPAN. NAGASAKI UNIV,SCH MED,INST ATOM DIS,DEPT PATHOL,NAGASAKI 852,JAPAN. NAGASAKI UNIV,SCH MED,INST ATOM DIS,DEPT INTERNAL MED 3,NAGASAKI 852,JAPAN. KOKURA MEM HOSP,KITAKYUSHU,FUKUOKA,JAPAN. MASSACHUSETTS GEN HOSP,ENDOCRINE UNIT,BOSTON,MA 02114. OI Yamashita, Shunichi/0000-0001-6399-6261 NR 44 TC 41 Z9 41 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD APR PY 1996 VL 16 IS 4 BP 565 EP 575 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA UF802 UT WOS:A1996UF80200010 PM 8624779 ER PT J AU Sugerman, PB Savage, NW AF Sugerman, PB Savage, NW TI Exfoliative cytology in clinical oral pathology SO AUSTRALIAN DENTAL JOURNAL LA English DT Article DE exfoliative cytology; oral mucosa; oral carcinoma; oral screening ID ORTHO-TOLUIDINE; CANCER; SMEARS AB Exfoliative cytology is a rapid, non-invasive procedure for assessing dysplastic change within the oral epithelium. The indications for oral exfoliative cytology are reviewed and a technique for cell collection and smear examination is presented. The value of exfoliative cytology in oral cancer screening programmes as a public health measure is discussed. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,CUTANEOUS BIOL RES CTR,CAMBRIDGE,MA 02138. NR 29 TC 23 Z9 26 U1 0 U2 1 PU AUSTRALIAN DENTAL ASSN INC PI NORTH SYDNEY NSW PA 116 PACIFIC HIGHWAY, NORTH SYDNEY NSW 2060, AUSTRALIA SN 0045-0421 J9 AUST DENT J JI Aust. Dent. J. PD APR PY 1996 VL 41 IS 2 BP 71 EP 74 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UH944 UT WOS:A1996UH94400001 PM 8670036 ER PT J AU OBrien, CP Childress, AR McElgin, W Mozley, PD Fitzgerald, J Reivich, M AF OBrien, CP Childress, AR McElgin, W Mozley, PD Fitzgerald, J Reivich, M TI Brain imaging correlates of cue-induced cocaine craving SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV PENN,DEPT VET AFFAIRS MED CTR,ADDICT TREATMENT RES CTR,PHILADELPHIA,PA 19104. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 36 EP 36 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300032 ER PT J AU Jenike, MA AF Jenike, MA TI Neurosurgical procedures for refractory OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 HARVARD UNIV,SCH MED,DEPT PSYCHIAT,CAMBRIDGE,MA 02138. MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 42 EP 42 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300038 ER PT J AU Young, AS Nuechterlein, KH Mintz, J Ventura, J Gitlin, M Liberman, RP AF Young, AS Nuechterlein, KH Mintz, J Ventura, J Gitlin, M Liberman, RP TI Suicidal ideation and behavior in recent-onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 75 EP 75 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300071 ER PT J AU New, AS Yehuda, R Steinberg, B Trestman, RL Mitropoulou, V Coccaro, EF Siever, LJ AF New, AS Yehuda, R Steinberg, B Trestman, RL Mitropoulou, V Coccaro, EF Siever, LJ TI Self-reported abuse and biological measures in personality disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY 10029. MED COLL HOSP,PHILADELPHIA,PA 19129. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 121 EP 121 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300117 ER PT J AU Zale, C New, AS Trestman, RL Mitropoulou, V Siever, L AF Zale, C New, AS Trestman, RL Mitropoulou, V Siever, L TI Serum cholesterol and impulsive aggressive behavior in personality disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 122 EP 122 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300118 ER PT J AU Serby, M Kalkstein, D Aryan, M Schmeidler, J AF Serby, M Kalkstein, D Aryan, M Schmeidler, J TI An analysis of olfactory deficits in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. BRONX VET ADM MED CTR,BRONX,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 175 EP 175 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300171 ER PT J AU McGurk, SR Green, MF Wirshing, WC Ames, D Marshall, BD Marder, SR AF McGurk, SR Green, MF Wirshing, WC Ames, D Marshall, BD Marder, SR TI The effects of risperidone vs haloperidol on spatial working memory in treatment-resistant schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,CAMARILLO RES CTR,LOS ANGELES,CA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 245 EP 245 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300237 ER PT J AU Roitman, SEL Keefe, RSE Dupre, RL Siever, LJ AF Roitman, SEL Keefe, RSE Dupre, RL Siever, LJ TI Visuospatial working memory in schizotypal personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY. DUKE UNIV,MED CTR,DURHAM,NC 27710. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 266 EP 266 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300258 ER PT J AU vanGorp, WG Altshuler, LL Dixon, W Theberge, DC AF vanGorp, WG Altshuler, LL Dixon, W Theberge, DC TI Cognitive impairment in euthymic patients with bipolar affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. UNIV CALIF LOS ANGELES,MED CTR,LOS ANGELES,CA 90024. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 277 EP 277 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300269 ER PT J AU Kirrane, R Trestman, R Mitropoulou, V Cornblatt, B Siever, L AF Kirrane, R Trestman, R Mitropoulou, V Cornblatt, B Siever, L TI Effects of amphetamine on cognitive impairment in schizotypal personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 MT SINAI MED CTR,NEW YORK,NY 10029. BRONX VET ADM MED CTR,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 280 EP 280 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300272 ER PT J AU Flach, KA Gerhardt, GA Freedman, R Adler, LE AF Flach, KA Gerhardt, GA Freedman, R Adler, LE TI Sensory gating in a computer model of the CA3 neural network of the hippocampus SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. DENVER VAMC,DENVER,CO. RI Moxon, Karen/K-7407-2012 OI Moxon, Karen/0000-0002-5790-097X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 1996 VL 39 IS 7 BP 446 EP 446 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UE893 UT WOS:A1996UE89300431 ER EF