FN Thomson Reuters Web of Science™ VR 1.0 PT J AU SAITO, K CROWLEY, JS MARKEY, SP HEYES, MP AF SAITO, K CROWLEY, JS MARKEY, SP HEYES, MP TI A MECHANISM FOR INCREASED QUINOLINIC ACID FORMATION FOLLOWING ACUTE SYSTEMIC IMMUNE STIMULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBROSPINAL-FLUID; KYNURENIC ACID; INDOLEAMINE 2,3-DIOXYGENASE; L-TRYPTOPHAN; RAT-BRAIN; 3-HYDROXYANTHRANILIC ACID; NEUROACTIVE KYNURENINES; IMMUNODEFICIENCY VIRUS; INDOLEAMINE-2,3-DIOXYGENASE; QUANTIFICATION AB Mechanisms for increased levels of quinolinic acid (QUIN) following systemic immune stimulation were investigated. In gerbils, systemic administration of pokeweed mitogen (PWM) increased plasma and cerebrospinal fluid QUIN levels, while plasma kynurenic acid levels were decreased and cerebrospinal fluid kynurenic acid levels were unchanged. PWM also increased the QUIN concentrations of brain and systemic tissues. In slices of spleen, lung, liver, duodenum, and kidney, PWM caused marked increases in [C-13(6)]QUIN formation from L-[C-13(6)]tryptophan (but not from [C-13(6)anthranilic acid). PWM also increased QUIN excretion in the urine and enhanced the formation and excretion of [C-13(6)]QUIN following an intraperitoneal injection Of L-[C-13(6)]tryptophan. Indoleamine-2,3-dioxygenase activity was increased in the brain, kidney, lung, spleen, and duodenum while hepatic L-tryptophan-2,3-dioxygenase activity was reduced, data consistent with in vitro L-kynurenine formation from L-tryptophan. Kynurenine-3-hydroxylase activity was increased in the duodenum, lung, and spleen, but not in the brain, kidney, or liver. Kynureninase activity was increased in the brain, lung, and duodenum, but not in the spleen, kidney, or liver. 3-Hydroxyanthranilate-3,4-dioxygenase activity was unchanged in the brain, lung, and liver. No change in kynurenine aminotransferase activity was observed in the brain or lung, while liver kynurenine aminotransferase activity was reduced. We conclude that increased activities of kynurenine pathway enzymes in various tissues following systemic immune stimulation, in conjunction with macrophage infiltration of the affected tissue, provide a mechanism to account for increased concentrations of QUIN. RP SAITO, K (reprint author), NIMH,ANALYT BIOCHEM SECT,CLIN SCI LAB,BETHESDA,MD 20892, USA. NR 46 TC 145 Z9 146 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 JUL 25 PY 1993 VL 268 IS 21 BP 15496 EP 15503 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500029 PM 8340378 ER PT J AU WASHKO, PW WANG, YH LEVINE, M AF WASHKO, PW WANG, YH LEVINE, M TI ASCORBIC-ACID RECYCLING IN HUMAN NEUTROPHILS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COULOMETRIC ELECTROCHEMICAL DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; DEHYDROASCORBIC ACID; DIABETES-MELLITUS; HYDROGEN-PEROXIDE; FREE-RADICALS; PLASMA; LEUKOCYTES; PROTECTION; SUPEROXIDE AB Ascorbic acid (vitamin C) accumulation in activated human neutrophils is increased as much as 10-fold above the mM concentrations present in normal neutrophils. Internal concentrations as high as 14 mM are achieved when external vitamin is at physiologic concentration. The mechanism is by oxidation of external vitamin to dehydroascorbic acid, preferential transmembrane translocation of dehydroascorbic acid, and intracellular reduction to ascorbic acid within minutes. These data indicate that vitamin C accumulation is enhanced in activated human neutrophils and that human neutrophils utilize and recycle oxidized external vitamin C under physiologic conditions. C1 NIDDKD,CELL BIOL & BIOCHEM SECT,CELL BIOL & GENET LAB,BLDG 8,RM 415,BETHESDA,MD 20892. NR 40 TC 191 Z9 194 U1 1 U2 5 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 JUL 25 PY 1993 VL 268 IS 21 BP 15531 EP 15535 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500034 PM 8340380 ER PT J AU STERNEMARR, R GUREVICH, VV GOLDSMITH, P BODINE, RC SANDERS, C DONOSO, LA BENOVIC, JL AF STERNEMARR, R GUREVICH, VV GOLDSMITH, P BODINE, RC SANDERS, C DONOSO, LA BENOVIC, JL TI POLYPEPTIDE VARIANTS OF BETA-ARRESTIN AND ARRESTIN3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADRENERGIC-RECEPTOR KINASE; GTP-BINDING PROTEIN; S-ANTIGEN; PINEAL-GLAND; SIGNAL TRANSDUCTION; MONOCLONAL-ANTIBODY; SEQUENCE-ANALYSIS; ADENYLYL CYCLASE; CDNA CLONES; RHODOPSIN AB Retinal arrestin (S-antigen) inactivates the photo-transduction cascade by binding to light-activated phosphorylated rhodopsin and thereby ''arresting'' coupling to the G protein transducin. Beta-arrestin (betaarr), a ubiquitous arrestin homolog, acts analogously to desensitize the beta2-adrenergic receptor by disrupting G(s) receptor interaction. In an attempt to identify additional ''arrestins'' which might regulate the multitude of G protein-coupled receptors, we have isolated two bovine brain cDNAs which encode polypeptide variants of an arrestin homolog which we have designated arrestin3 (arr3). The open reading frames of these two cDNAs are identical except that the long form, arr3L, contains an 11-amino-acid insert between residues 361 and 362. Arr3 is more closely related to bovine betaarr (78% identity) than to bovine visual arrestin (56% identity). Polymerase chain reaction amplification of RNA and immunoblotting of lysates with an arr3-specific antibody suggest that the short form, arr3S, is the major form of arr3 in all bovine tissues and that it is most abundant in the spleen. Furthermore, polymerase chain reaction amplification of betaarr mRNA indicates that in several tissues (lung, liver, spleen, and pituitary), the major form of betaarr lacks 8 amino acids which are present in brain betaarr. Immunoblotting with an antibody which recognizes betaarr and arr3 with equal sensitivity demonstrates that betaarr (either the long or the short polypeptide) is the major arrestin in all (non-photoreceptor bearing) tissues examined. These observations suggest that in some tissues, as many as four arrestin homolog variants may play a role in the regulation of G protein-coupled receptors. C1 JEFFERSON CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA 19107. WILLS EYE HOSP & RES INST,DIV RES,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,PHILADELPHIA,PA 19107. NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. RI Gurevich, Vsevolod/A-3236-2008 OI Gurevich, Vsevolod/0000-0002-3950-5351 FU NEI NIH HHS [EY5095]; NHLBI NIH HHS [HL45964]; NIGMS NIH HHS [GM44944] NR 57 TC 118 Z9 122 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 JUL 25 PY 1993 VL 268 IS 21 BP 15640 EP 15648 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500049 PM 8340388 ER PT J AU HAMEL, CP TSILOU, E PFEFFER, BA HOOKS, JJ DETRICK, B REDMOND, TM AF HAMEL, CP TSILOU, E PFEFFER, BA HOOKS, JJ DETRICK, B REDMOND, TM TI MOLECULAR-CLONING AND EXPRESSION OF RPE65, A NOVEL RETINAL-PIGMENT EPITHELIUM-SPECIFIC MICROSOMAL PROTEIN THAT IS POSTTRANSCRIPTIONALLY REGULATED IN-VITRO SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING PROTEIN; SEQUENCE-ANALYSIS; BOVINE RETINA; CELLS; IDENTIFICATION; DIFFERENTIATION; 11-CIS-RETINYL; NITROCELLULOSE; PURIFICATION; TRANSLATION AB Studies reported previously from this laboratory have shown that microsomal membranes of the vertebrate retinal pigment epithelium (RPE) contain an RPE-specific 65-kDa protein, RPE65, which bears the determinant recognized by the strictly tissue-specific monoclonal antibody RPE9, and which is developmentally regulated (Hamel, C. P., Tsilou, E., Harris, E., Pfeffer, B. A., Hooks, J. J., Detrick, B., and Redmond, T. M. (1993) J. Neurosci. Res. 34, 414-425). Microsequencing of 17 tryptic and chymotryptic peptides obtained from the in situ digestion of the RPE65 blotted on nitrocellulose yielded primary sequences that were used to generate oligonucleotide probes. An 84-nucleotide guessmer was used to isolate two clones from a bovine RPE lambdaZap II cDNA library. Rapid amplification of cDNA ends was used to complete the 5' and 3' ends, resulting in a 3,115-base pair composite cDNA. The open reading frame encodes a novel protein of 533 amino acid residues with a computed molecular weight of 60,940. This protein does not match any other sequence in the data bases. The 231 amino acids obtained from peptide sequencing match 43% of the amino acid sequence deduced from the cDNA. The protein has a calculated pI of 6.41 and is not predicted to have any transmembrane segments. The open reading frame expressed in Escherichia coli has an apparent molecular weight identical to that of the native protein and is recognized by the monoclonal antibody RPE9, further corroborating its validity. Northern blot analysis detected a major mRNA species of 3.15 kilobases for RPE65, as well as shorter species, only in RPE and not in other tissues (including other ocular tissues). Cultured RPE cells (7 weeks in primary culture) contained RPE65 mRNA in amounts equivalent to fresh RPE. Such cells, however, contained no immunodetectable RPE65. The possible structure of this RPE-specific protein and hypotheses for the absence of translation in vitro are discussed. C1 NEI, RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 339, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NEI, IMMUNOL & VIROL LAB, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, MED CTR, DEPT PATHOL, WASHINGTON, DC 20037 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 49 TC 222 Z9 228 U1 0 U2 4 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 JUL 25 PY 1993 VL 268 IS 21 BP 15751 EP 15757 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500064 PM 8340400 ER PT J AU AGARWAL, A SALEM, P ROBBINS, KC AF AGARWAL, A SALEM, P ROBBINS, KC TI INVOLVEMENT OF P72(SYK), A PROTEIN-TYROSINE KINASE, IN FC-GAMMA RECEPTOR SIGNALING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; T-CELL; CROSS-LINKING; ZETA-CHAIN; MONOCLONAL-ANTIBODIES; HUMAN-MONOCYTES; SRC FAMILY; U937 CELLS; PHOSPHORYLATION; ACTIVATION AB Previous studies have demonstrated that multichain immune recognition receptors, such as the T-cell receptor, signal their occupancy by inducing tyrosine phosphorylation of cellular protein substrates. Type I and II receptors for the Fc portion of IgG are single-chain immune recognition receptors having external, trans-membrane, and cytoplasmic domains. In the present study, we have investigated the possibility that, upon engagement, Fcgamma receptors induce protein-tyrosine phosphorylation. Our findings reveal increased phosphorylation of a number of proteins on tyrosine residues after cross-linking of either high (FcgammaRI) or low (FcgammaRII) affinity receptors expressed on HL60 cells. Engagement of FcgammaRII induced rapid tyrosine phosphorylation that decayed to basal levels by 40 min. In contrast, phosphorylation induced by FcgammaRI cross-linking was more delayed, peaking at 5-10 min, and returning to basal levels by 60 min. Kinase assays of cellular proteins immunoprecipitated from lysates of activated cells by antibody to phosphotyrosine revealed phosphorylation of a 72-kDa molecule that was not present in lysates of resting cells. This phosphoprotein was identified as p72syk by immunoprecipitation with antibodies directed against two different regions of the syk gene product. Immunoprecipitation with antibodies against p72syk followed by immunoblotting with anti-phosphotyrosine antibodies revealed an activation-dependent tyrosine phosphorylation of p72syk. Thus, our present findings demonstrate induction of protein-tyrosine phosphorylation following engagement of monomeric immune recognition receptors and identify p72syk as a tyrosine kinase substrate involved in signaling by FcgammaRI and FcgammaRII. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NR 37 TC 137 Z9 137 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 JUL 25 PY 1993 VL 268 IS 21 BP 15900 EP 15905 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500082 PM 8340414 ER PT J AU KYRIAKIS, JM FORCE, TL RAPP, UR BONVENTRE, JV AVRUCH, J AF KYRIAKIS, JM FORCE, TL RAPP, UR BONVENTRE, JV AVRUCH, J TI MITOGEN REGULATION OF C-RAF-1 PROTEIN-KINASE ACTIVITY TOWARD MITOGEN-ACTIVATED PROTEIN KINASE-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; THREONINE TYROSINE KINASE; ERK-1 GENE-PRODUCT; MAP KINASE; SIGNAL TRANSDUCTION; RAF-1 KINASE; S6 KINASE; PHOSPHORYLATION; INSULIN; SERINE AB The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. PDGF-, epidermal groth factor-, and insulin-stimulated P-32-c-Raf-1 yield very similar, complex tryptic P-32-peptide maps, wherein only 2 of 10 P-32-peptides appear entirely de novo after growth factor addition. Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic P-32-peptides, all of which comigrate with tryptic P-32-peptides derived from c-Raf-1 labeled in situ. Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate P-32-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely. C1 MASSACHUSETTS GEN HOSP,DIABET UNIT,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP,MED SERV,CARDIOL UNIT,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. OI Force, Thomas/0000-0002-0450-8659 FU NIDDK NIH HHS [DK38452, DK01986]; NIGMS NIH HHS [GM46577] NR 40 TC 97 Z9 97 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 JUL 25 PY 1993 VL 268 IS 21 BP 16009 EP 16019 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN305 UT WOS:A1993LN30500096 PM 8340422 ER PT J AU BERGAN, R CONNELL, Y FAHMY, B NECKERS, L AF BERGAN, R CONNELL, Y FAHMY, B NECKERS, L TI ELECTROPORATION ENHANCES C-MYC ANTISENSE OLIGODEOXYNUCLEOTIDE EFFICACY SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CELLULAR UPTAKE; HEMATOPOIETIC-CELLS; OLIGONUCLEOTIDE; INHIBITION; PROLIFERATION; EXPRESSION; LEUKEMIA; DELIVERY; GROWTH AB Obtaining high transfection efficiencies and achieving appropriate intracellular concentrations and localization are two of the most important barriers to the implementation of gene targeted therapy. The efficiency of endogenous uptake of oligodeoxynucleotides (ODNs) varies from cell type to cell type and may be a limiting factor of antisense efficacy. The use of electroporation to obtain high intracellular concentrations of a synthetic ODN in essentially 100% of viable cells is described. It is also shown that the transfected ODNs initially localize to the nucleus and remain there for at least 48 hours. The cellular trafficking of electroporated ODNs is shown to be an energy dependent process. Targeting of the c-myc proto-oncogene of U937 cells by electroporation of phosphorothloate-modified ODNs results in rapid and specific suppression of this gene at ODN concentrations much lower than would otherwise be required. This technique appears to be applicable to a variety of cell types and may represent a powerful new investigative tool as well as a promising approach to the ex vivo treatment of hematologic disorders. RP BERGAN, R (reprint author), NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892, USA. NR 31 TC 101 Z9 101 U1 1 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 JUL 25 PY 1993 VL 21 IS 15 BP 3567 EP 3573 DI 10.1093/nar/21.15.3567 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ083 UT WOS:A1993LQ08300032 PM 8346033 ER PT J AU SILVER, J MAUDRU, T FUJITA, K REPASKE, R AF SILVER, J MAUDRU, T FUJITA, K REPASKE, R TI AN RT-PCR ASSAY FOR THE ENZYME-ACTIVITY OF REVERSE-TRANSCRIPTASE CAPABLE OF DETECTING SINGLE VIRIONS SO NUCLEIC ACIDS RESEARCH LA English DT Note RP SILVER, J (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. OI Silver, Jonathan/0000-0001-9231-6368 NR 1 TC 103 Z9 103 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 JUL 25 PY 1993 VL 21 IS 15 BP 3593 EP 3594 DI 10.1093/nar/21.15.3593 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ083 UT WOS:A1993LQ08300048 PM 7688457 ER PT J AU LAND, CE TOKUNAGA, M TOKUOKA, S NAKAMURA, N AF LAND, CE TOKUNAGA, M TOKUOKA, S NAKAMURA, N TI EARLY-ONSET BREAST-CANCER IN A-BOMB SURVIVORS SO LANCET LA English DT Letter ID FAMILIES C1 RADIAT EFFECTS RES FDN,NAGASAKI,JAPAN. KAGOSHIMA CITY HOSP,KAGOSHIMA,JAPAN. RADIAT EFFECTS RES FDN,HIROSHIMA 730,JAPAN. RP LAND, CE (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 46 Z9 46 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 24 PY 1993 VL 342 IS 8865 BP 237 EP 237 DI 10.1016/0140-6736(93)92324-M PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LN622 UT WOS:A1993LN62200034 PM 8100952 ER PT J AU KALINEC, F KACHAR, B AF KALINEC, F KACHAR, B TI INHIBITION OF OUTER HAIR CELL ELECTROMOTILITY BY SULFHYDRYL SPECIFIC REAGENTS SO NEUROSCIENCE LETTERS LA English DT Article DE OUTER HAIR CELL; ELECTROMOTILITY; SH-REAGENT; GUINEA PIG ID MEMBRANE; MECHANISM; TRANSPORT AB Mammalian outer hair cells can change length at acoustic frequencies when they are electrically stimulated. It was postulated that these length changes depend on electromechanical transduction based on voltage dependent conformational changes in a membrane motor protein. In this report, we describe the effect of various sulfhydryl (SH)-specific reagents on the OHC electromotility. p-Chloromercuriphenylsulfonate (pCMPS), in addition to other mercurials that can react with well-protected SH-groups in proteins, inhibits this electromechanical transduction process. In contrast, N-ethylmaleimide and diamide, SH-reagents that only react with exposed SH-groups, showed no effect. These results suggest that one or more reactive SH-groups are present in a functionally important and protected region of the electromechanical transduction protein. Such reactivity can be utilized to identify and characterize this novel membrane motor. C1 NIDCD,CELLULAR BIOL LAB,BLDG 10,ROOM 5D55,BETHESDA,MD 20892. NR 19 TC 22 Z9 23 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 JUL 23 PY 1993 VL 157 IS 2 BP 231 EP 234 DI 10.1016/0304-3940(93)90744-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA LR741 UT WOS:A1993LR74100027 PM 8233059 ER PT J AU SWAIN, MG VERGALLA, J BERGASA, NV JONES, EA AF SWAIN, MG VERGALLA, J BERGASA, NV JONES, EA TI SYMPATHETIC-NERVES, BUT NOT THE ADRENAL-GLAND, CONTRIBUTE TO ELEVATED PLASMA-LEVELS OF MET-ENKEPHALIN IN RATS WITH ACUTE CHOLESTATIC HEPATITIS SO REGULATORY PEPTIDES LA English DT Article DE ENDOGENOUS OPIOID; CRYPTIC ENKEPHALIN; SYMPATHETIC NERVE ID METHIONINE ENKEPHALIN; OPIOID-PEPTIDES; DISEASE; STRESS; BRAIN AB Met-enkephalin is known to circulate in human and animal plasma in low levels. However, the source(s) of plasma met-enkephalin have not been completely elucidated. It has been proposed that the adrenal gland, sympathetic nerves, pancreas and the gut might be implicated. Recently, markedly elevated levels of met-enkephalin have been documented in the presence of liver disease. To investigate potential sources of met-enkephalin in liver disease, rats with acute cholestatic hepatitis 24 h after gavage with alpha naphthylisothiocyanate (ANIT) 100 mg/kg were studied. Plasma met-enkephalin levels were determined by radioimmunoassay in plasma samples from normal, adrenalectomized, or chemically sympathectomized animals. In control rats, ANIT treatment resulted in a striking 8.7-fold increase in systemic venous met-enkephalin levels (inferior vena cava) (P less-than-or-equal-to 0.0005) and a significant increase in peptidase-derived met-enkephalin levels (determined after trypsin/carboxypeptidase B digestion of plasma samples) (P less-than-or-equal-to 0.05). ANIT-treatment also resulted in a 5.6-fold increase in portal vein met-enkephalin levels (P less-than-or-equal-to 0.005). Portal vein met-enkephalin levels were only 1.2-fold higher than IVC levels in ANIT-treated rats (P less-than-or-equal-to 0.05). Plasma activities of the two main enkephalin degrading enzymes, aminopeptidase and enkephalinase, were similar in control and ANIT-treated rats. Chemical sympathectomy, prior to ANIT treatment, decreased the elevation in inferior vena caval met-enkephalin levels by 35% (P less-than-or-equal-to 0.005). Adrenalectomy did not alter ANIT-induced increases in circulating met-enkephalin levels (pNS). Therefore, elevated systemic plasma met-enkephalin levels in rats with ANIT-induced acute cholestatic hepatitis: (i) are in part derived from secretion by sympathetic nerves, (ii) do not appear to be due to increased secretion by the adrenal gland or increased delivery from the portal circulation, and (iii) may arise in part from met-enkephalin derived from circulating precursor forms. RP SWAIN, MG (reprint author), NIDDK,LIVER DIS SECT,BLDG 10,RM 4D-52,BETHESDA,MD 20892, USA. NR 25 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 23 PY 1993 VL 46 IS 3 BP 535 EP 542 DI 10.1016/0167-0115(93)90254-6 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA LN629 UT WOS:A1993LN62900004 PM 8210512 ER PT J AU THOMAS, LA AF THOMAS, LA TI WOMEN IN SCIENCE 93 - A FEMALE STYLE SO SCIENCE LA English DT Letter RP THOMAS, LA (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 23 PY 1993 VL 261 IS 5120 BP 409 EP 409 DI 10.1126/science.261.5120.409 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LN623 UT WOS:A1993LN62300004 PM 17770004 ER PT J AU OMICHINSKI, JG CLORE, GM SCHAAD, O FELSENFELD, G TRAINOR, C APPELLA, E STAHL, SJ GRONENBORN, AM AF OMICHINSKI, JG CLORE, GM SCHAAD, O FELSENFELD, G TRAINOR, C APPELLA, E STAHL, SJ GRONENBORN, AM TI NMR STRUCTURE OF A SPECIFIC DNA COMPLEX OF ZN-CONTAINING DNA-BINDING DOMAIN OF GATA-1 SO SCIENCE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; ERYTHROID TRANSCRIPTION FACTOR; RESTRAINED MOLECULAR-DYNAMICS; PUTATIVE ZINC FINGER; OVERHAUSER ENHANCEMENT MEASUREMENTS; 3-DIMENSIONAL SOLUTION STRUCTURE; INTERPROTON DISTANCE RESTRAINTS; NITROGEN REGULATORY GENE; DOUBLE-HELICAL FRAGMENTS; CRYSTAL-STRUCTURE AB The three-dimensional solution structure of a complex between the DNA binding domain of the chicken erythroid transcription factor GATA-1 and its cognate DNA site has been determined with multidimensional heteronuclear magnetic resonance spectroscopy. The DNA binding domain consists of a core which contains a zinc coordinated by four cysteines and alpha carboxyl-terminal tail. The core is composed of two irregular antiparallel beta sheets and an ot helix, followed by a long loop that leads into the carboxyl-terminal tail. The amino-terminal part of the core, including the helix, is similar in structure, although not in sequence, to the amino-terminal zinc module of the glucocorticoid receptor DNA binding domain. In the other regions, the structures of these two DNA binding domains are entirely different. The DNA target site in contact with the protein spans eight base pairs. The helix and the loop connecting the two antiparallel beta sheets interact with the major groove of the DNA. The carboxyl-terminal tail, which is an essential determinant of specific binding, wraps around into the minor groove. The complex resembles a hand holding a rope with the palm and fingers representing the protein core and the thumb, the carboxyl-terminal tail. The specific interactions between GATA-1 and DNA in the major groove are mainly hydrophobic in nature, which accounts for the preponderance of thymines in the target site. A large number of interactions are observed with the phosphate backbone. C1 NIDDKD,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 99 TC 376 Z9 381 U1 0 U2 10 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 23 PY 1993 VL 261 IS 5120 BP 438 EP 446 DI 10.1126/science.8332909 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LN623 UT WOS:A1993LN62300027 PM 8332909 ER PT J AU YAMASHITA, S HISATAKE, K KOKUBO, T DOI, K ROEDER, RG HORIKOSHI, M NAKATANI, Y AF YAMASHITA, S HISATAKE, K KOKUBO, T DOI, K ROEDER, RG HORIKOSHI, M NAKATANI, Y TI TRANSCRIPTION FACTOR TFIIB SITES IMPORTANT FOR INTERACTION WITH PROMOTER-BOUND TFIID SO SCIENCE LA English DT Article ID RNA POLYMERASE-II; INITIATION; SELECTION; COMPLEX; DOMAIN AB Transcription initiation factor TFIIB recruits RNA polymerase II to the promoter subsequent to interaction with a preformed TFIID-promoter complex. The domains of TFIIB required for binding to the TFIID-promoter complex and for transcription initiation have been determined. The carboxyl-terminal two-thirds of TFIIB, which contains two direct repeats and two basic residue repeats, is sufficient for interaction with the TFIID-promoter complex. An extra 84-residue amino-terminal region, with no obvious known structural motifs, is required for basal transcription activity. Basic residues within the second basic repeat of TFIIB are necessary for stable interaction with the TFIID-promoter complex, whereas the basic character of the first basic repeat is not. Functional roles of other potential structural motifs are discussed in light of the present study. C1 NINCDS,BETHESDA,MD 20892. ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. NIDCD,NEUROCHEM LAB,BETHESDA,MD 20892. UNIV TOKYO,INST APPL MICROBIOL,BUNKYO KU,TOKYO 113,JAPAN. FU NCI NIH HHS [CA42567]; NIAID NIH HHS [AI27397]; NIGMS NIH HHS [GM45258] NR 16 TC 49 Z9 49 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 23 PY 1993 VL 261 IS 5120 BP 463 EP 466 DI 10.1126/science.8332911 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LN623 UT WOS:A1993LN62300033 PM 8332911 ER PT J AU FAUCI, AS PANTALEO, G EMBRETSON, J HAASE, AT AF FAUCI, AS PANTALEO, G EMBRETSON, J HAASE, AT TI VIRAL BURDEN AND HIV DISEASE - REPLY SO NATURE LA English DT Letter C1 UNIV MINNESOTA, DEPT MICROBIOL, MINNEAPOLIS, MN 55455 USA. RP FAUCI, AS (reprint author), NIAID, BETHESDA, MD 20892 USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 8 TC 6 Z9 6 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 22 PY 1993 VL 364 IS 6435 BP 291 EP 292 DI 10.1038/364291b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LN570 UT WOS:A1993LN57000035 ER PT J AU ZHANG, XF SETTLEMAN, J KYRIAKIS, JM TAKEUCHISUZUKI, E ELLEDGE, SJ MARSHALL, MS BRUDER, JT RAPP, UR AVRUCH, J AF ZHANG, XF SETTLEMAN, J KYRIAKIS, JM TAKEUCHISUZUKI, E ELLEDGE, SJ MARSHALL, MS BRUDER, JT RAPP, UR AVRUCH, J TI NORMAL AND ONCOGENIC P21(RAS) PROTEINS BIND TO THE AMINO-TERMINAL REGULATORY DOMAIN OF C-RAF-1 SO NATURE LA English DT Article ID S6 KINASE-II; XENOPUS OOCYTES; SIGNAL TRANSDUCTION; SUPPRESSOR ACTIVITY; RAS-P21 GTPASE; RAS; ACTIVATION; SERINE; RAF-1; GROWTH AB In higher eukaryotes, the Ras and Raf-1 proto-oncoproteins transduce growth and differentiation signals initiated by tyrosine kinases. The Ras polypeptide and the amino-terminal regulatory domain of Raf-1(residues 1-257) are shown to interact, directly in vitro and in a yeast expression system. Raf-1(1-257) binds GTP-Ras in preference to GDP-Ras, and inhibits Ras-GAP activity. Mutations in and around the Ras effector domain impair Ras binding to Raf-1(1-257) and Ras transforming activity in parallel. C1 HARVARD UNIV,SCH MED,DIABET UNIT,149 13TH ST,BOSTON,MA 02129. HARVARD UNIV,SCH MED,MED SERV,BOSTON,MA 02129. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP E,CTR CANC,BOSTON,MA 02129. BAYLOR COLL MED,DEPT BIOCHEM,HOUSTON,TX 77030. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. INDIANA UNIV,SCH MED,DEPT MED,HEMATOL ONCOL SECT,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. NR 48 TC 758 Z9 765 U1 0 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 22 PY 1993 VL 364 IS 6435 BP 308 EP 313 DI 10.1038/364308a0 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LN570 UT WOS:A1993LN57000047 PM 8332187 ER PT J AU WENGER, NK SPEROFF, L PACKARD, B AF WENGER, NK SPEROFF, L PACKARD, B TI CARDIOVASCULAR HEALTH AND DISEASE IN WOMEN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORONARY-ARTERY DISEASE; CONGENITAL HEART-DISEASE; MYOCARDIAL PERFUSION SCINTIGRAPHY; VENOUS THROMBOEMBOLIC DISEASE; QUALITY-OF-LIFE; FOLLOW-UP; EXERCISE-ELECTROCARDIOGRAPHY; PERIPARTUM CARDIOMYOPATHY; VALVE-REPLACEMENT; BYPASS-SURGERY C1 OREGON HLTH SCI UNIV, DEPT OBSTET & GYNECOL, PORTLAND, OR 97201 USA. NHLBI, BETHESDA, MD 20892 USA. RP WENGER, NK (reprint author), EMORY UNIV, SCH MED, DEPT MED, DIV CARDIOL, 69 BUTLER ST SE, ATLANTA, GA 30303 USA. NR 140 TC 479 Z9 488 U1 0 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 22 PY 1993 VL 329 IS 4 BP 247 EP 256 DI 10.1056/NEJM199307223290406 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA LM682 UT WOS:A1993LM68200006 PM 8316269 ER PT J AU GOLLAN, J KALSER, S HOOFNAGLE, J FERGUSON, J HALL, W BRAY, E AF GOLLAN, J KALSER, S HOOFNAGLE, J FERGUSON, J HALL, W BRAY, E TI NIH CONSENSUS CONFERENCE ON LAPAROSCOPIC CHOLECYSTECTOMY - ARE REFORMS NECESSARY - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH,BETHESDA,MD 20892. RP GOLLAN, J (reprint author), BRIGHAM & WOMENS HOSP,BOSTON,MA 02115, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 JUL 21 PY 1993 VL 270 IS 3 BP 321 EP 321 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LM435 UT WOS:A1993LM43500016 ER PT J AU PETTIT, GR CICHACZ, ZA GAO, F HERALD, CL BOYD, MR AF PETTIT, GR CICHACZ, ZA GAO, F HERALD, CL BOYD, MR TI ISOLATION AND STRUCTURE OF THE REMARKABLE HUMAN CANCER CELL-GROWTH INHIBITORS SPONGISTATIN-2 AND SPONGISTATIN-3 FROM AN EASTERN INDIAN OCEAN-SPONGIA SP SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID CYTOTOXIC METABOLITES; INVIVO ACTIVITY; BRYOSTATIN-1; INVITRO AB A black Spongia SP. in the Porifera class Demospongiae had been found to contain two new and exceptionally potent cell (human cancer) growth inhibitors named spongistatins 2 (1b) and 3 (1c). C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. NR 18 TC 110 Z9 111 U1 1 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0022-4936 J9 J CHEM SOC CHEM COMM JI J. Chem. Soc.-Chem. Commun. PD JUL 21 PY 1993 IS 14 BP 1166 EP 1168 DI 10.1039/c39930001166 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA LN193 UT WOS:A1993LN19300031 ER PT J AU ENG, C LI, FP ABRAMSON, DH ELLSWORTH, RM WONG, FL GOLDMAN, MB SEDDON, J TARBELL, N BOICE, JD AF ENG, C LI, FP ABRAMSON, DH ELLSWORTH, RM WONG, FL GOLDMAN, MB SEDDON, J TARBELL, N BOICE, JD TI MORTALITY FROM 2ND TUMORS AMONG LONG-TERM SURVIVORS OF RETINOBLASTOMA SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NON-OCULAR CANCER; BILATERAL RETINOBLASTOMA; HUMAN SARCOMAS; OSTEO-SARCOMA; SUSCEPTIBILITY GENE; MALIGNANT NEOPLASMS; NONOCULAR TUMORS; BONE SARCOMAS; EXPRESSION; DELETION AB Background: Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. Purpose: We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. Methods: A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. Results: Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). Conclusions: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. Implications: Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer. C1 NCI,RADIAT EPIDEMIOL BRANCH,EPN 408,6130 EXECUT BLVD,ROCKVILLE,MD 20852. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV MED ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. BOSTON CHILDRENS HOSP,JOINT CTR RADIAT THERAPY,BOSTON,MA. HARVARD UNIV,SCH MED,BOSTON,MA 02115. MASSACHUSETTS EYE & EAR INFIRM,BOSTON,MA 02114. CORNELL UNIV,MED CTR,NEW YORK HOSP,CTR OPHTHALM ONCOL,NEW YORK,NY 10021. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. RI Wong, Fuhin/M-8360-2013; OI Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [N01CP85604, N01CPO5609] NR 54 TC 376 Z9 382 U1 0 U2 9 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 JUL 21 PY 1993 VL 85 IS 14 BP 1121 EP 1128 DI 10.1093/jnci/85.14.1121 PG 8 WC Oncology SC Oncology GA LM449 UT WOS:A1993LM44900011 PM 8320741 ER PT J AU HUNTER, CP REDMOND, CK CHEN, VW AUSTIN, DF GREENBERG, RS CORREA, P MUSS, HB FORMAN, MR WESLEY, MN BLACKLOW, RS KURMAN, RJ DIGNAM, JJ EDWARDS, BK SHAPIRO, S AF HUNTER, CP REDMOND, CK CHEN, VW AUSTIN, DF GREENBERG, RS CORREA, P MUSS, HB FORMAN, MR WESLEY, MN BLACKLOW, RS KURMAN, RJ DIGNAM, JJ EDWARDS, BK SHAPIRO, S TI BREAST-CANCER - FACTORS ASSOCIATED WITH STAGE AT DIAGNOSIS IN BLACK-AND-WHITE WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POSITIVE AXILLARY NODES; AMERICAN-COLLEGE; SELF-EXAMINATION; UNITED-STATES; PATIENT CHARACTERISTICS; PROGESTERONE-RECEPTOR; SOCIOECONOMIC-STATUS; RACIAL-DIFFERENCES; NATIONAL SURVEY; BODY SIZE AB Background: Numerous studies have reported differences in cancer staging at diagnosis and in survival between Black and White patients with breast cancer. Utilizing data obtained from the National Cancer Institute's (NCI's) Black/White Cancer Survival Study for the period 1985-1986, a new study is presented here that systematically examines multiple explanatory factors (e.g., lack of mammograms) associated with these cancer-staging differences. Purpose: We evaluated within a single study the relationship of selected demographic, lifestyle, antecedent medical experiences, and health care acces s factors to cancer staging at diagnosis in Black and White breast cancer patients. Methods: Data utilized in this population-based cohort study of 1222 eligible women (649 Black and 573 White) newly diagnosed for the period 1985-1986 with histologically confirmed primary breast cancer were obtained from the NCI's Black/White Cancer Survival Study. Sources of data included abstracts of hospital medical records, central review of histology slides by a study consultant pathologist, and patient interviews obtained from three metropolitan areas: Atlanta, New Orleans, and San Francisco-Oakland. Within each area, 70% of all Black incident cases were randomly selected, and a sample of White cases, frequency matched by age groups (20-49 years, 50-64 years, and 65-79 years), was selected for comparison. Stage of breast cancer at diagnosis was classified according to the international tumor-lymph node-metastases (TNM) system. Statistical models utilized in this study included the log-linear and polychotomous logistic regression with multiple predictor variables. Results: Factors associated with cancer staging were differentially expressed in Blacks and Whites. Indicators of access to health care, a lack of mammograms, and an increased body mass index significantly (P<.02) contributed to stage differences in Blacks, whereas income was marginally associated (P = .06) with stage for Whites only. Nuclear grade, having a breast examination by a physician, and a history of patient delay explained approximately 50% of the excess risk for stage III-IV Cancer versus stage I-II(N0) cancer among Blacks compared with Whites (odds ratio- reduction from 2.19 to 1.68). Conclusion: These findings suggest that no single factor or group of factors can explain more than half of the race-stage differences noted in this study with respect to Black and White breast cancer patients. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. CTR DIS PREVENT & EPIDEMIOL,OREGON HLTH DIV,PORTLAND,OR. EMORY UNIV,SCH PUBL HLTH,OFF DEAN,ATLANTA,GA 30322. WAKE FOREST UNIV,CTR COMPREHENS CANC,WINSTON SALEM,NC 27109. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. UNIV PARIS 06,DEPT BIOSTAT,F-75230 PARIS 05,FRANCE. LOUISIANA STATE UNIV,MED CTR,DEPT PATHOL,NEW ORLEANS,LA 70112. RP HUNTER, CP (reprint author), NIH,OFF RES WOMENS HLTH,FED BLDG,RM 6A-09,BETHESDA,MD 20892, USA. NR 42 TC 171 Z9 173 U1 2 U2 6 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 JUL 21 PY 1993 VL 85 IS 14 BP 1129 EP 1137 DI 10.1093/jnci/85.14.1129 PG 9 WC Oncology SC Oncology GA LM449 UT WOS:A1993LM44900012 PM 8320742 ER PT J AU PASTAN, I LOVELACE, E RUTHERFORD, AV KUNWAR, S WILLINGHAM, MC PEEHL, DM AF PASTAN, I LOVELACE, E RUTHERFORD, AV KUNWAR, S WILLINGHAM, MC PEEHL, DM TI PR1 - A MONOCLONAL-ANTIBODY THAT REACTS WITH AN ANTIGEN ON THE SURFACE OF NORMAL AND MALIGNANT PROSTATE CELLS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID ADENOCARCINOMAS; CARCINOMA; LINE AB Background: The principal treatment for prostate cancer is surgery; prostate cancer is resistant to the common anticancer drugs. The only useful therapy for metastases involves diminishing testosterone levels by orchiectomy or administration of drugs, either of which may increase survival time. One approach to prostate cancer treatment is to use a monoclonal antibody (MAb) to target cytotoxic substances to these cancer cells. The MAbs available either do not react uniformly with prostate cancer cells or react with normal tissues. Thus, a new MAb is needed. Purpose: The goal of this study was to isolate an MAb that reacts with an antigen present on the surface of prostate cancer cells. Methods: A strain of prostate cancer cells was isolated from a prostate cancer specimen, grown for 2-4 weeks in short-term culture, and used to immunize BALB/c mice. Hybridomas were then prepared by using spleen cells from the immunized mice. One hybridoma produced an MAb (PR1) that reacted with prostate cancers. Results: MAb PR1 is an IgM(kappa) subtype that reacts uniformly with the surface of most (25 of 26) adenocarcinomas of the prostate. It also reacts with the surface antigen on normal prostate epithelial cells and on cells from benign prostatic hyperplasia. MAb PR1 reacts with a limited number of normal tissues including a subset of principal cells located in the collecting ducts of the kidney. Conclusion: We conclude that MAb PR1 reacts with a differentiation antigen present in normal prostate and that this antigen continues to be expressed on almost all adenocarcinomas of the prostate. Implications: This antibody may be useful for the diagnosis of or therapy for prostate cancer. C1 STANFORD UNIV,MED CTR,DEPT UROL,STANFORD,CA 94305. MED UNIV S CAROLINA,DEPT PATHOL & LAB MED,DIV ANAT PATOL,CHARLESTON,SC 29425. RP PASTAN, I (reprint author), NCI,DIV CANC BIOL DIAGN & CTR,MOLEC BIOL LAB,BLDG 37,RM 4E16,BETHESDA,MD 20892, USA. NR 22 TC 17 Z9 17 U1 0 U2 0 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 JUL 21 PY 1993 VL 85 IS 14 BP 1149 EP 1154 DI 10.1093/jnci/85.14.1149 PG 6 WC Oncology SC Oncology GA LM449 UT WOS:A1993LM44900014 PM 7686582 ER PT J AU BELL, DA TAYLOR, JA PAULSON, DF ROBERTSON, CN MOHLER, JL LUCIER, GW AF BELL, DA TAYLOR, JA PAULSON, DF ROBERTSON, CN MOHLER, JL LUCIER, GW TI GENETIC RISK AND CARCINOGEN EXPOSURE - A COMMON INHERITED DEFECT OF THE CARCINOGEN-METABOLISM GENE GLUTATHIONE-S-TRANSFERASE M1 (GSTM1) THAT INCREASES SUSCEPTIBILITY TO BLADDER-CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TRANS-STILBENE OXIDE; LUNG-CANCER; URINARY-BLADDER; DNA ADDUCTS; CLASS-MU; IDENTIFICATION; LEUKOCYTES; PHENOTYPE; SMOKING; MARKER AB Background: Numerous studies have associated bladder cancer with exposure to carcinogens present in tobacco smoke and other environmental or occupational exposures. Approximately 50% of all humans inherit two deleted copies of the GSTM1 gene which encodes for the carcinogen-detoxification enzyme glutathione S-transferase M1. Recent findings suggest that the GSTM1 gene may modulate the internal dose of environmental carcinogens and thereby affect the risk of developing bladder cancer. Purpose: We investigated whether the absence of the GSTM1 gene affects bladder cancer risk and whether there are racial differences in GSTM1 genotype frequency. Methods: Using a polymerase chain reaction (PCR)-based method, we examined the frequency of the homozygous deleted genotype (GSTM1 0/0) in 229 patients with transitional cell carcinoma of the bladder and 211 control subjects who were enrolled from the Urology Clinics at Duke University Medical Center and the University of North Carolina Hospitals. Control subjects were urology clinic patients who primarily presented with benign prostatic hypertrophy or impotence, who had no history of any cancer other than nonmelanoma skin cancer, and who were frequency matched to case patients on race, sex, and age (10-year age intervals). In order to explore racial differences in GSTM1 gene frequency, genotype was also determined in a community-based sample of 466 paid, healthy, unrelated volunteers from Durham and Chapel Hill, N.C. The presence or absence of the GSTM1 gene locus was determined by using a differential PCR, a semiquantitative technique in which multiple genes are coamplified. Results: Overall, the GSTM1 0/0 genotype conferred a 70% increased risk of bladder cancer (odds ratio [OR] = 1.7; 95% confidence interval [CI] = 1.2-2.5; P = .004). Absence of the GSTM1 gene encoding the glutathione S-transferase M1 enzyme significantly increased risk to persons with exposure to the carcinogens in tobacco smoke (OR = 1.8; 95% CI = 1.2-3.0; P = .01) but poses little increased risk to persons without such exposure. Persons with smoking exposure of more than 50 pack-years who had the GSTM1 0/0 genotype had a sixfold greater risk relative to persons in the lowest risk group (i.e., nonsmokers who were GSTM1 +/+ or +/0). In the pooled clinic control and community sample groups (677 individuals), the GSTM1 0/0 genotype occurred less frequently among Blacks (35%) than among Whites (49%, P<.001). Conclusions: These findings support a protective role for the GSTM1 gene in bladder cancer. From these findings, it is estimated that 25% of all bladder cancer may be attributable to the at-risk GSTM1 0/0 genotype. C1 NIEHS,EPIDEMIOL BRANCH,MD A3-02,POB 12233,RES TRIANGLE PK,NC 27709. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA HOSP,CHAPEL HILL,NC. DUKE UNIV,MED CTR,DURHAM,NC 27710. RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; taylor, jack/0000-0001-5303-6398 NR 34 TC 605 Z9 630 U1 2 U2 16 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 JUL 21 PY 1993 VL 85 IS 14 BP 1159 EP 1164 DI 10.1093/jnci/85.14.1159 PG 6 WC Oncology SC Oncology GA LM449 UT WOS:A1993LM44900016 PM 8320745 ER PT J AU BUNN, PA WHANGPENG, J GAZDAR, AF MINNA, JD CARNEY, D AF BUNN, PA WHANGPENG, J GAZDAR, AF MINNA, JD CARNEY, D TI KARYOTYPIC DERIVATION OF H9 CELL-LINE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID LYMPHOMAS C1 NCI,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75230. MATER MISERICORDIAE HOSP,DUBLIN,IRELAND. RP BUNN, PA (reprint author), UNIV COLORADO,CTR CANC,4200 E 9TH AVE,BOX B188,DENVER,CO 80262, USA. NR 6 TC 3 Z9 3 U1 0 U2 0 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 JUL 21 PY 1993 VL 85 IS 14 BP 1168 EP 1168 DI 10.1093/jnci/85.14.1168 PG 1 WC Oncology SC Oncology GA LM449 UT WOS:A1993LM44900017 PM 8320746 ER PT J AU FANSLER, TD NOSSAL, R AF FANSLER, TD NOSSAL, R TI PHOTON-CORRELATION AND SCATTERING - INTRODUCTION BY THE FEATURE EDITORS SO APPLIED OPTICS LA English DT Editorial Material AB This feature issue brings together fourteen papers, most of which were presented at the Eighth Topical Meeting on Photon Correlation and Scattering (Boulder, Colorado, 24-26 August 1992). Research areas represented here include dynamic light scattering; laser velocimetry; diffusing-wave spectroscopy and imaging in multiply-scattering media; fundamental analyses of measurement sensitivity and accuracy; and development of new instrumentation, procedures, and data analysis algorithms. The common theme that unites these diverse topics is the idea of exploiting the statistical properties of scattered light to probe structure or motion in complex systems. C1 NIH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BETHESDA, MD 20892 USA. RP FANSLER, TD (reprint author), GM CORP, CTR RES & DEV, DEPT THERMOSCI, WARREN, MI 48090 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0003-6935 J9 APPL OPTICS JI Appl. Optics PD JUL 20 PY 1993 VL 32 IS 21 BP 3811 EP 3812 PG 2 WC Optics SC Optics GA LN837 UT WOS:A1993LN83700001 PM 20830010 ER PT J AU DOLAN, ME PEGG, AE MOSCHEL, RC GRINDEY, GB AF DOLAN, ME PEGG, AE MOSCHEL, RC GRINDEY, GB TI EFFECT OF O6-BENZYLGUANINE ON THE SENSITIVITY OF HUMAN COLON-TUMOR XENOGRAFTS TO 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA (BCNU) SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ALKYLATING-AGENTS; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; CROSS-LINKING; DNA; MODULATION; CANCER; CELLS; CHLOROETHYLNITROSOUREA; CARCINOGENESIS AB A number of trials were conducted to determine the effect of O6-benzylguanine pretreatment on the sensitivity of human colon tumor xenografts to the antitumor effects of 1,3-bis(2-chloroethyl)-1-nitrosourea 1-nitrosourea (BCNU). O6-Benzylguanine has been shown to inactivate the DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), which is primarily responsible for resistance to alkylnitrosoureas including BCNU. Colon tumor xenografts carried in nude mice were analyzed for their AGT content, and tumors with low, intermediate and high levels were chosen for further study. The AGT activity of HC-1, GC-3, VRC-5 and CX-1 human colon tumor xenografts was 16, 113, 180 and 367 fmol/mg protein, respectively. Treatment of mice consisted of vehicle alone, 6.25 to 50 mg/kg BCNU administered alone or BCNU (6.25 to 25 mg/kg) 1 hr after 120 mg/kg O6-benzylguanine on days 7 and 14 post-inoculation. Toxicity studies revealed that pretreatment with O6-benzylguanine increased the toxicity of BCNU, requiring administration of about 4-fold less drug. The growth of the VRC-5 tumor at day 42 post-inoculation was inhibited by 39% following treatment with 12.5 mg/kg BCNU alone and 92% when BCNU was combined with O6-benzylguanine pretreatment. The combination of O6-benzylguanine and BCNU (12.5 mg/kg) at day 42 resulted in an inhibition of HC-1 and CX-1 tumor growth by 84 and 72%, whereas BCNU alone inhibited growth by 54 and 14%, respectively. Therefore, the degree to which the antitumor effect of BCNU was increased by O6-benzylguanine pretreatment was dependent on the AGT activity, with a greater effect in tumors of intermediate or high activity. These data suggest that there is a role for O6-benzylguanine combined with BCNU in the treatment of human colon tumors. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PHARMACOL,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. LILLY RES LAB,INDIANAPOLIS,IN 46285. RP DOLAN, ME (reprint author), UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,MC 2115,5841 S MARYLAND,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA18137, CA47228, N01-CO-74101] NR 28 TC 73 Z9 75 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 20 PY 1993 VL 46 IS 2 BP 285 EP 290 DI 10.1016/0006-2952(93)90416-T PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LP958 UT WOS:A1993LP95800013 PM 8347150 ER PT J AU DRISCOLL, PC ALTMAN, JD BONIFACE, JJ SAKAGUCHI, K REAY, PA OMICHINSKI, JG APPELLA, E DAVIS, MM AF DRISCOLL, PC ALTMAN, JD BONIFACE, JJ SAKAGUCHI, K REAY, PA OMICHINSKI, JG APPELLA, E DAVIS, MM TI 2-DIMENSIONAL NUCLEAR-MAGNETIC-RESONANCE ANALYSIS OF A LABELED PEPTIDE BOUND TO A CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE CLASS-II MHC; PROTEIN-PEPTIDE COMPLEX; ISOTOPE-EDITED NMR SPECTROSCOPY; C-13-LABELING; PH DEPENDENCE ID MULTIPLE QUANTUM COHERENCE; CHEMICAL-SHIFTS; MHC; PROTEINS; BINDING; PROTON; NMR; CONFORMATION; RECOGNITION; SPECTROSCOPY C1 STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. NCI,CELL BIOL LAB,BETHESDA,MD 20892. STANFORD UNIV,HOWARD HUGHES MED INST,STANFORD,CA 94305. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RP DRISCOLL, PC (reprint author), UNIV OXFORD,DEPT BIOCHEM,S PARKS RD,OXFORD OX1 3QU,ENGLAND. RI Driscoll, Paul/B-8007-2010 OI Driscoll, Paul/0000-0002-4124-6950 NR 35 TC 21 Z9 21 U1 0 U2 2 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 JUL 20 PY 1993 VL 232 IS 2 BP 342 EP 350 DI 10.1006/jmbi.1993.1394 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ985 UT WOS:A1993LQ98500003 PM 8393933 ER PT J AU NEWCOMB, WW TRUS, BL BOOY, FP STEVEN, AC WALL, JS BROWN, JC AF NEWCOMB, WW TRUS, BL BOOY, FP STEVEN, AC WALL, JS BROWN, JC TI STRUCTURE OF THE HERPES-SIMPLEX VIRUS CAPSID - MOLECULAR COMPOSITION OF THE PENTONS AND THE TRIPLEXES SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HERPES SIMPLEX VIRUS; CAPSID STRUCTURE; PENTON COMPOSITION; CRYOELECTRON MICROSCOPY; SCANNING TRANSMISSION ELECTRON MICROSCOPY ID TRANSMISSION ELECTRON-MICROSCOPY; CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; EQUINE HERPESVIRUS-1; BACTERIOPHAGE-LAMBDA; SURFACE LATTICE; SIMIAN VIRUS-40; PROTEIN; IDENTIFICATION; LOCALIZATION C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. FU NIGMS NIH HHS [GM34036] NR 57 TC 204 Z9 206 U1 0 U2 9 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 JUL 20 PY 1993 VL 232 IS 2 BP 499 EP 511 DI 10.1006/jmbi.1993.1406 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ985 UT WOS:A1993LQ98500015 PM 8393939 ER PT J AU OLSON, WK MARKY, NL JERNIGAN, RL ZHURKIN, VB AF OLSON, WK MARKY, NL JERNIGAN, RL ZHURKIN, VB TI INFLUENCE OF FLUCTUATIONS ON DNA CURVATURE - A COMPARISON OF FLEXIBLE AND STATIC WEDGE MODELS OF INTRINSICALLY BENT DNA SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE B-DNA; CURVATURE; DOUBLE HELIX; FLEXIBILITY; WEDGE MODEL ID DOUBLE-HELICAL DNA; RANDOM-FLIGHT CHAIN; CURVED DNA; B-DNA; KINETOPLAST DNA; BASE SEQUENCE; EXCLUDED-VOLUME; POLYMER-CHAINS; ELECTROPHORETIC MOBILITY; ANISOTROPIC FLEXIBILITY C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP OLSON, WK (reprint author), RUTGERS UNIV,DEPT CHEM,WRIGHT RIEMAN LABS,NEW BRUNSWICK,NJ 08903, USA. RI Jernigan, Robert/A-5421-2012 FU NCI NIH HHS [N01-CO-74102]; NIGMS NIH HHS [GM20861] NR 114 TC 126 Z9 129 U1 1 U2 6 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 JUL 20 PY 1993 VL 232 IS 2 BP 530 EP 551 DI 10.1006/jmbi.1993.1409 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LQ985 UT WOS:A1993LQ98500018 PM 8345522 ER PT J AU KOVAC, P AF KOVAC, P TI DISACCHARIDE AND TRISACCHARIDE GLYCOSYL DONORS FOR THE SYNTHESIS OF FRAGMENTS OF THE O-SPECIFIC ANTIGEN OF SHIGELLA-DYSENTERIAE TYPE-1 SO CARBOHYDRATE RESEARCH LA English DT Article ID REPEATING-UNIT; LIPOPOLYSACCHARIDE; OLIGOSACCHARIDES; POLYSACCHARIDE; THIOGLYCOSIDES; DERIVATIVES; ACTIVATION; BROMINE; INSITU; CHAIN AB Methyl O-(2,4-di-O-benzoyl-3-0-bromoacetyl-alpha-L-rhamnopyranosyl)-(l --> 3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranoside was treated with dichloromethyl methyl ether and ZnCl2 to give O-(2,4-di-O-ben-zoyl-3-0-bromoacetyl-alpha-L-rhamnopyranosyl)-(l --> 3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl chloride. Similar treatment of methyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoXY-alpha-D-glucopyranosyl)-(l --> 3)-2,4-di-0-benzoyl-alpha-L-rhamnopyranoside (13) gave crystalline O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-gluco-pyranosyl)-(l --> 3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl chloride (14), which was also obtained by treatment of methyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxoy-alpha-D-glucopyranosyl)-(l --> 3)-2,4-di-0-benzoyl-1-thio-alpha-L-rhamnopyranoside (12) with chlorine. In contrast to the conversion 12 --> 14, which was stereospecific, the reaction of methyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-glucopyranosyl)-(l --> 3)-(O-2,4-di-O-benzoYl-alpha-L-rhamnopyranosyl)-(l --> 3)-2,4-di-O-benzoyl-1-thio-alpha-L-rhamnopyranoside with chlorine gave a mixture of the corresponding alpha- (16) and beta- (17) glycosyl chlorides. Condensation of the mixed chlorides 16 and 17 with 1,3,4,6-tetra-0-acetyl-alpha-D-galactopyranose, followed by reduction-acetylation of the product, gave a fully protected derivative of the tetrasaccharide alpha-D-Glc pNAc-(1 --> 3)-alpha-L-Rha p-(l --> 3)-alpha-L-Rha p-(l --> 2)-alpha-D-Gal p. RP KOVAC, P (reprint author), NIDDK,BETHESDA,MD 20892, USA. NR 18 TC 12 Z9 12 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL 19 PY 1993 VL 245 IS 2 BP 219 EP 231 DI 10.1016/0008-6215(93)80073-N PG 13 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA LN590 UT WOS:A1993LN59000004 PM 7690306 ER PT J AU AIDA, K MOORE, R NEGISHI, M AF AIDA, K MOORE, R NEGISHI, M TI CLONING AND NUCLEOTIDE-SEQUENCE OF A NOVEL, MALE-PREDOMINANT CARBOXYLESTERASE IN MOUSE-LIVER SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE CARBOXYLESTERASE; NUCLEOTIDE SEQUENCE; CDNA SEQUENCE; ES-MALE; (MOUSE LIVER) ID ENDOPLASMIC-RETICULUM; MULTIGENE FAMILY; CDNA CLONING; ESTERASE; PROTEINS; EXPRESSION AB As a family of serine-dependent enzymes, the carboxylesterases (EC 3.1.1.1) demonstrate a broad substrate specificity. Mouse carboxylesterases comprise at least 20 genetically distinct loci. We cloned a full-length cDNA for a novel mouse carboxylesterase, Es-male which was expressed predominantly in,male livers. This carboxylesterase consisted of 554 amino acid residues, and exhibited 43% and 42% similarities to the known mouse esterases Es-22 and pEs-N, respectively. Es-male contained a C-terminal ER-retention signal PEEL, indicating that it may be a microsomal carboxylesterase. C1 NIEHS,REPROD & DEV TOXICOL LAB,PHARMACOGENET SECT,RES TRIANGLE PK,NC 27709. NR 18 TC 34 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JUL 18 PY 1993 VL 1174 IS 1 BP 72 EP 74 DI 10.1016/0167-4781(93)90093-S PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LN651 UT WOS:A1993LN65100009 PM 7916639 ER PT J AU ICHIKAWA, H JACOBOWITZ, DM SUGIMOTO, T AF ICHIKAWA, H JACOBOWITZ, DM SUGIMOTO, T TI CALRETININ-IMMUNOREACTIVE NEURONS IN THE TRIGEMINAL AND DORSAL-ROOT GANGLIA OF THE RAT SO BRAIN RESEARCH LA English DT Article DE CALRETININ; CARBONIC ANHYDRASE; TACHYKININ; TRIGEMINAL GANGLION; DORSAL ROOT GANGLION; RAT ID CARBONIC-ANHYDRASE ACTIVITY; CALCIUM-BINDING PROTEIN; PRIMARY SENSORY NEURONS; GENE-RELATED PEPTIDE; VASOACTIVE INTESTINAL POLYPEPTIDE; PERIPHERAL NERVOUS-SYSTEM; SUBSTANCE-P; HORSERADISH-PEROXIDASE; IMMUNOHISTOCHEMICAL LOCALIZATION; RETROGRADE TRANSPORT AB The cell body size of primary neurons were measured in the trigeminal (TG) and lumbar dorsal root ganglia (DRG) monochrome-stained for calretinin (CR)-like immunoreactivity. A trichrome stain for CR, carbonic anhydrase (CA) and tachykinin (TK) was also employed to estimate possible overlap of cellular distribution of these substances. In the DRG, the cell size spectrum of CR-positive cells was clearly bimodal; a greater proportion (84.1%) of CR-positive cells was distributed in the range greater-than-or-equal-to 800 mum2 with a mode between 1,500-1,600 mum2, while a smaller proportion (14.8%) < 700 mum2 with a mode of 400-500 mum2 . They were evenly distributed throughout the DRG. Although CR-positive TG neurons were smaller than similar DRG neurons, a bimodal distribution pattern remained unchanged. 94.6% of CR-positive cells measured 100-1,400 mum2 with peak ranges of 200-300 mum2 and 400-500 mum2. Most of CR-positive cells in the ophthalmic division were 400 mum2 or larger and small CR-positive cells ( < 400 mum2) were concentrated in the maxillary and mandibular divisions. Most of CR-positive DRG cells showed CA activity (76.5%), while those with TK-immunoreactivity were rare (7.2%). In the TG, 38.4% of CR-positive cells were TK-positive. They were mostly smaller than 800 mum2. On the other hand, CA was detected in 43.4% of CR-positive TG cells. Most of the TG cells co-expressing CR and CA were 400 mum2 or larger. Simultaneous co-expression of TK and CA by the CR-positive cells was negligible. The cell bodies co-expressing CR and TK were more or less concentrated in the maxillary and mandibular divisions of the TG. The results suggest that CR-positive DRG cells are mostly proprioceptive, whereas similar TG cells include many small primary neurons innervating the visceral mucosa. C1 OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT 2,2-5-1 SHIKATA CHO,OKAYAMA 700,JAPAN. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 42 TC 36 Z9 36 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 JUL 16 PY 1993 VL 617 IS 1 BP 96 EP 102 DI 10.1016/0006-8993(93)90618-W PG 7 WC Neurosciences SC Neurosciences & Neurology GA LL526 UT WOS:A1993LL52600014 PM 7690667 ER PT J AU LIS, J WU, C AF LIS, J WU, C TI PROTEIN TRAFFIC ON THE HEAT-SHOCK PROMOTER - PARKING, STALLING, AND TRUCKING ALONG SO CELL LA English DT Review ID RNA POLYMERASE-II; TRANSCRIPTIONAL ACTIVATION DOMAIN; DNA-BINDING; NUCLEOSOMAL TEMPLATES; MOLECULAR-CLONING; FACTOR CONTAINS; GENE; INVITRO; EXPRESSION; ELONGATION C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. RP LIS, J (reprint author), CORNELL UNIV,BIOCHEM MOLEC & CELL BIOL SECT,ITHACA,NY 14850, USA. NR 42 TC 335 Z9 341 U1 1 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 16 PY 1993 VL 74 IS 1 BP 1 EP 4 DI 10.1016/0092-8674(93)90286-Y PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LN625 UT WOS:A1993LN62500001 PM 8334697 ER PT J AU FUKUYAMA, R RAPOPORT, SI AF FUKUYAMA, R RAPOPORT, SI TI A MONOCLONAL-ANTIBODY, RAISED AGAINST RAT EMBRYO HIPPOCAMPUS, IDENTIFIES A NUCLEAR-PROTEIN ENRICHED IN HIPPOCAMPAL AND OTHER NEURONS OF THE ADULT-RAT BRAIN SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE HIPPOCAMPUS; PC12 CELL; EMBRYOGENESIS; HISTOCHEMISTRY; ALZHEIMERS DISEASE ID CELL-ADHESION; GENES; ORIGIN; EXPRESSION; ANTIGENS; DISEASE; FAMILY; HORN; TIME AB We report characteristics of a monoclonal antibody (MAb) produced by immunizing mice against rat embryo hippocampus, and its cellular distribution in the brains of adult and embryonic rats. This antibody, designated as MAb 4A4, brightly stained granular and pyramidal neurons of the adult rat hippocampus, as well as some cortical neurons. Also, MAb 4A4 labeled granular and Purkinje cells of the cerebellum with less intensity. While glial cells were labeled relatively faintly. At embryonic day 18 in the rat, most brain neurons, primitive neuroepithelium, connective tissues and glia were labeled with this antibody, indicating that the expression of 4A4 antigen is regulated developmentally. The 4A4 antigen appeared to be localized to the nucleus of cells except in choroid plexus in which the focal membrane staining was observed. The nuclear localization of 4A4 antigen was further confirmed by the staining of cultured cell lines with MAb 4A4. Western blot analysis demonstrated a single band of the 4A4 antigen from cultured cells, with an apparent molecular weight of 220 kDa. Both the molecular weight and the distribution of the 4A4 antigen in the embryonic and adult rat brain and cultured cells suggest that this antigen is a novel nonhistone nuclear type, which is preferentially expressed in neurons of the rodent brains and is under developmental regulation. RP FUKUYAMA, R (reprint author), NIA, NEUROSCI LAB, BLDG 10, ROOM 6C103, BETHESDA, MD 20892 USA. NR 38 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JUL 16 PY 1993 VL 74 IS 1 BP 127 EP 132 DI 10.1016/0165-3806(93)90092-O PG 6 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA LN331 UT WOS:A1993LN33100016 ER PT J AU CHEH, AM CHADHA, A SAYER, JM YEH, HJC YAGI, H PANNELL, LK JERINA, DM AF CHEH, AM CHADHA, A SAYER, JM YEH, HJC YAGI, H PANNELL, LK JERINA, DM TI STRUCTURES OF COVALENT NUCLEOSIDE ADDUCTS FORMED FROM ADENINE, GUANINE, AND CYTOSINE BASES OF DNA AND THE OPTICALLY-ACTIVE BAY-REGION 3,4-DIOL 1,2-EPOXIDES OF BENZ[A]ANTHRACENE SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID BENZOPYRENE 7,8-DIOL 9,10-EPOXIDES; DIOL-EPOXIDE; ACID; ALKYLATION; IDENTIFICATION; DERIVATIVES; GUANOSINE; PRODUCTS; OXIDE AB Chemical structures of the principal covalent adducts formed from DNA upon reaction in vitro with the four optically active 3,4-diol 1,2-epoxides of benz[a]anthracene have been elucidated at the nucleoside level. In addition to adducts formed by cis and trans addition of the exocyclic amino groups of deoxyadenosine (dA) and deoxyguanosine (dG) and a trans deoxycytidine (dC) adduct, chemical characterization of a deglycosylated N-7 dG adduct formed in DNA by trans opening of the (4S,3R)-diol (2R,1S)-epoxide isomer is reported. Relative stereochemistries of the adducts (cis versus trans opening of the epoxides by the exocyclic amino groups) were deduced from the coupling constants of the methine protons of the tetrahydro benzo rings of the acetylated derivatives. Adducts having (S)-configuration at the attachment site on the hydrocarbon moiety have CD spectra that exhibit a positive band at 250-260 nm and a negative band at longer wavelengths, whereas (R)-configuration at this center gives rise to CD spectra with bands of approximately equal intensity and opposite sign. This allowed assignment of cis versus trans addition to the chiral epoxides for adducts that were not generated in sufficient quantity to obtain NMR spectra. Analysis of the patterns of adducts derived from benz[a]anthracene, benzo[c]phenanthrene, and benzo[a]pyrene shows that the comparative tumorigenicities of the diol epoxide isomers of each hydrocarbon do not correlate well with the extent of adduct formation, the ratio of cis versus trans addition to the epoxide, the propensity for forming adducts at dC or the N-7 position of dG, or the ratio of adduct formation at dA versus dG, although tumorigenicity may correlate with the ability to form dG adducts with (S)-configuration at the N-substituted benzylic carbon, especially those arising from trans addition to the epoxide. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. NR 43 TC 35 Z9 36 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUL 16 PY 1993 VL 58 IS 15 BP 4013 EP 4022 DI 10.1021/jo00067a039 PG 10 WC Chemistry, Organic SC Chemistry GA LV424 UT WOS:A1993LV42400039 ER PT J AU HAMER, DH HU, S MAGNUSON, VL HU, N PATTATUCCI, AML AF HAMER, DH HU, S MAGNUSON, VL HU, N PATTATUCCI, AML TI A LINKAGE BETWEEN DNA MARKERS ON THE X-CHROMOSOME AND MALE SEXUAL ORIENTATION SO SCIENCE LA English DT Article ID GENETICALLY COMPLEX TRAITS; AFFECTED RELATIVE PAIRS; MALE HOMOSEXUALITY; STRATEGIES; IDENTITY; POWER; POLYMORPHISM; RFLP; MEN AB The role of genetics in male sexual orientation was investigated by pedigree and linkage analyses on 114 families of homosexual men. Increased rates of same-sex orientation were found in the maternal uncles and male cousins of these subjects, but not in their fathers or paternal relatives, suggesting the possibility of sex-linked transmission in a portion of the population. DNA linkage analysis of a selected group of 40 families in which there were two gay brothers and no indication of nonmaternal transmission revealed a correlation between homosexual orientation and the inheritance of polymorphic markers on the X chromosome in approximately 64 percent of the sib-pairs tested. The linkage to markers on Xq28, the subtelomeric region of the long arm of the sex chromosome, had a multipoint lod score of 4.0 (P = 10(-5)), indicating a statistical confidence level of more than 99 percent that at least one subtype of male sexual orientation is genetically influenced. RP HAMER, DH (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 51 TC 452 Z9 465 U1 19 U2 197 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 16 PY 1993 VL 261 IS 5119 BP 321 EP 327 DI 10.1126/science.8332896 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM678 UT WOS:A1993LM67800027 PM 8332896 ER PT J AU BRUNGER, AT CLORE, GM GRONENBORN, AM SAFFRICH, R NILGES, M AF BRUNGER, AT CLORE, GM GRONENBORN, AM SAFFRICH, R NILGES, M TI ASSESSING THE QUALITY OF SOLUTION NUCLEAR-MAGNETIC-RESONANCE STRUCTURES BY COMPLETE CROSS-VALIDATION SO SCIENCE LA English DT Article ID DISTANCE GEOMETRY; 3-DIMENSIONAL STRUCTURE; MACROMOLECULAR STRUCTURES; PROTEIN CONFORMATIONS; MOLECULAR-DYNAMICS; TRYPSIN-INHIBITOR; REFINEMENT; SPECTROSCOPY; CONSTRAINTS; RESTRAINTS AB Structure determination of macromolecules in solution by nuclear magnetic resonance (NMR) spectroscopy involves the fitting of atomic models to the observed nuclear Over-hauser effect (NOE) data. Complete cross-validation has been used to define reliable and unbiased criteria for the quality of solution NMR structures. The method is based on the partitioning of NOE data into test sets and the cross-validation of statistical quantities for each of the test sets. A high correlation between cross-validated measures of fit, such as distance bound violations and NMR R values, and the quality of solution NMR structures was observed. Less complete data resulted in poorer satisfaction of the cross-validated measures of fit. Optimization of cross-validated measures of fit will likely produce solution NMR structures with maximal information content. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. YALE UNIV,DEPT MOLEC BIOPHYS & BIOCHEM,NEW HAVEN,CT 06511. EUROPEAN MOLEC BIOL LAB,W-6900 HEIDELBERG,GERMANY. RP BRUNGER, AT (reprint author), YALE UNIV,HOWARD HUGHES MED INST,NEW HAVEN,CT 06511, USA. RI Clore, G. Marius/A-3511-2008; Nilges, Michael/E-4803-2011; OI Clore, G. Marius/0000-0003-3809-1027; Nilges, Michael/0000-0002-1451-8092; Saffrich, Rainer/0000-0002-0547-4550 NR 43 TC 136 Z9 136 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 16 PY 1993 VL 261 IS 5119 BP 328 EP 331 DI 10.1126/science.8332897 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM678 UT WOS:A1993LM67800028 PM 8332897 ER PT J AU THOMAS, JD SIDERAS, P SMITH, CIE VORECHOVSKY, I CHAPMAN, V PAUL, WE AF THOMAS, JD SIDERAS, P SMITH, CIE VORECHOVSKY, I CHAPMAN, V PAUL, WE TI COLOCALIZATION OF X-LINKED AGAMMAGLOBULINEMIA AND X-LINKED IMMUNODEFICIENCY GENES SO SCIENCE LA English DT Article ID B-CELLS; IMMUNE-DEFICIENCY; LYMPHOCYTES-B; SRC GENE; 5' EXONS; C-SRC; MICE; MUTATION; PROTEIN; MOUSE AB Mice that bear the X-linked immunodeficiency (xid) mutation have a B lymphocyte-specific defect resulting in an inability to make antibody responses to polysaccharide antigens. A backcross of 1114 progeny revealed the colocalization of xid with Bruton's agammaglobulinemia tyrosine kinase (btk) gene, which is implicated in the human immune deficiency, X-linked agammaglobulinemia. Mice that carry xid have a missense mutation that alters a highly conserved arginine near the amino-terminus of the btk protein, Btk. Because this region of Btk lies outside any obvious kinase domain, the xid mutation may define another aspect of tyrosine kinase function. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. KAROLINSKA INST,NOVUM,CTR BIOTECHNOL,S-14157 HUDDINGE,SWEDEN. UMEA UNIV,APPL CELL & MOLEC BIOL UNIT,S-90187 UMEA,SWEDEN. NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,DEPT MOLEC BIOL,BUFFALO,NY 14263. FU NHGRI NIH HHS [HG00277]; NIGMS NIH HHS [GM33160] NR 40 TC 527 Z9 529 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 JUL 16 PY 1993 VL 261 IS 5119 BP 355 EP 358 DI 10.1126/science.8332900 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM678 UT WOS:A1993LM67800037 PM 8332900 ER PT J AU RAWLINGS, DJ SAFFRAN, DC TSUKADA, S LARGAESPADA, DA GRIMALDI, JC COHEN, L MOHR, RN BAZAN, JF HOWARD, M COPELAND, NG JENKINS, NA WITTE, ON AF RAWLINGS, DJ SAFFRAN, DC TSUKADA, S LARGAESPADA, DA GRIMALDI, JC COHEN, L MOHR, RN BAZAN, JF HOWARD, M COPELAND, NG JENKINS, NA WITTE, ON TI MUTATION OF UNIQUE REGION OF BRUTONS TYROSINE KINASE IN IMMUNODEFICIENT XID MICE SO SCIENCE LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; B-CELLS; LYMPHOCYTES-B; BONE-MARROW; CHROMOSOME; EXPRESSION; GENE AB The cytoplasmic tyrosine kinase, Bruton's tyrosine kinase (Btk, formerly bpk or atk), is crucial for B cell development. Loss of kinase activity results in the human immunodeficiency, X-linked agammaglobulinemia, characterized by a failure to produce B cells. In the murine X-linked immunodeficiency (XID), B cells are present but respond abnormally to activating signals. The Btk gene, btk, was mapped to the xid region of the mouse X chromosome by interspecific backcross analysis. A single conserved residue within the amino terminal unique region of Btk was mutated in XID mice. This change in xid probably interferes with normal B cell signaling mediated by Btk protein interactions. C1 UNIV CALIF LOS ANGELES,HOWARD HUGHES MED INST,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT MICROBIOL & MOLEC GENET,LOS ANGELES,CA 90024. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. DNAX RES INST MOLEC & CELLULAR BIOL INC,MOLEC & CELLULAR BIOL RES INST,PALO ALTO,CA 94304. RI Bazan, J. Fernando/B-4562-2010; Largaespada, David/C-9832-2014 FU NCI NIH HHS [N01-CO-74101]; NIAMS NIH HHS [AR36834] NR 40 TC 698 Z9 705 U1 3 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 16 PY 1993 VL 261 IS 5119 BP 358 EP 361 DI 10.1126/science.8332901 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM678 UT WOS:A1993LM67800038 PM 8332901 ER PT J AU MAUTNER, GC MAUTNER, SL CANNON, RO HUNSBERGER, SA ROBERTS, WC AF MAUTNER, GC MAUTNER, SL CANNON, RO HUNSBERGER, SA ROBERTS, WC TI CLINICAL FACTORS USEFUL IN PREDICTING AORTIC-VALVE STRUCTURE IN PATIENTS GREATER-THAN-40 YEARS OF AGE WITH ISOLATED VALVULAR AORTIC-STENOSIS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB A number of reports have described the frequency of coronary arterial narrowing in patients with valvular aortic stenosis. No published reports have examined the structure of the stenotic aortic valve in adults and related the valve structure to variables, including coronary arterial narrowing, useful in predicting that structure. One hundred eighty-eight patients having aortic valve replacement for isolated valvular aortic stenosis were studied. All patients were >40 years of age at the time of aortic valve replacement, all had coronary angiograms preoperatively, and of 182 patients (97%) measurements of serum total cholesterol had been obtained and 184 (98%) had body mass index calculated. The structure of the operatively excised valve was classified as unicuspid or bicuspid (congenitally malformed), or tricuspid aortic valve. A logistic regression model was developed that found 4 factors (age, serum total cholesterol, angiographic coronary artery disease and body mass index) to be predictive of aortic valve structure: (1) Patients with at least 3 or all 4 factors high or present (i.e., age >65 years, serum total cholesterol >200 mg/dl, body mass index >29 kg/m2 and coronary artery disease) had a low probability (10 to 29%) of having a congenitally malformed valve; (2) patients with at least 3 or all 4 factors low or absent (i.e., age less-than-or-equal-to 65 years, serum total cholesterol less-than-or-equal-to 200 mg/dl, body mass index less-than-or-equal-to 29 kg/m2, and no coronary artery disease) had a high probability (72 to 90%) of having a congenitally malformed valve. Thus, the morphology of the operatively excised stenotic aortic valve can be predicted with knowledge of the age, serum total cholesterol, body mass index and coronary artery status of the patient. C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. RP MAUTNER, GC (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 4 TC 38 Z9 39 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 JUL 15 PY 1993 VL 72 IS 2 BP 194 EP 198 DI 10.1016/0002-9149(93)90159-A PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LL185 UT WOS:A1993LL18500014 PM 8328383 ER PT J AU PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V PANZA, JA MAUREA, S BONOW, RO AF PERRONEFILARDI, P BACHARACH, SL DILSIZIAN, V PANZA, JA MAUREA, S BONOW, RO TI REGIONAL SYSTOLIC FUNCTION, MYOCARDIAL BLOOD-FLOW AND GLUCOSE-UPTAKE AT REST IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; CORONARY-ARTERY DISEASE; COMPUTED-TOMOGRAPHY; N-13 AMMONIA; CHEST PAIN; IDENTIFICATION; METABOLISM; FLUORODEOXYGLUCOSE; ABNORMALITIES; QUANTITATION AB Decreased 18fluorodeoxyglucose (FDG) uptake and blood flow at rest in the ventricular septum, as compared with the lateral wall, have been reported in mildly symptomatic patients with hypertrophic cardiomyopathy (HC). To assess whether regional metabolic heterogeneity in patients with HC is related to heterogeneous regional systolic function, 10 symptomatic patients (mean age 36 +/- 17 years) with HC and no coronary artery disease underwent positron emission tomography with oxygen-15-water and FDG, and nuclear magnetic resonance imaging at rest to assess regional anatomy and systolic function. Regional absolute blood flow was similar between the ventricular septum and lateral wall. In contrast, FDG activity was significantly greater in the lateral wall than in the septum (1,023 +/- 588 vs 767 +/- 388 nCi/ml, respectively; p < 0.01). However, regional systolic wall thickening was also significantly greater in the lateral wall than in the septum (5.3 +/- 4.3 vs 2.4 +/- 4.0 mm, respectively; p < 0.001). Patients were then divided into group A (n = 5) with similar regional wall thickening in the septum and lateral wall, and group B (n = 5) with greater thickening in the lateral wall than in the septum. In both groups, regional blood flow was similar between the septum and lateral wall. However, the regional septal-to-lateral FDG activity ration was 0.97 +/- 0.31 in group A, and 0.74 +/- 0.25 in group B (p < 0.01); the ratio in group A did not differ from that in 5 normal subjects (1.02 +/- 0.58). Thus, myocardial blood flow is normal at rest in patients with HC and no coronary artery disease; the heterogeneity in regional glucose uptake is parallel to that of regional systolic function and does not necessarily represent a metabolic abnormality at the cellular level. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT NUCL MED,CTR CLIN,BETHESDA,MD 20892. NR 26 TC 32 Z9 32 U1 0 U2 1 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 JUL 15 PY 1993 VL 72 IS 2 BP 199 EP 204 DI 10.1016/0002-9149(93)90160-E PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LL185 UT WOS:A1993LL18500015 PM 8328384 ER PT J AU DOMANSKI, MJ CUNNION, RE FERNICOLA, DJ ROBERTS, WC AF DOMANSKI, MJ CUNNION, RE FERNICOLA, DJ ROBERTS, WC TI FATAL COR-PULMONALE CAUSED BY EXTENSIVE TUMOR EMBOLI IN THE SMALL PULMONARY-ARTERIES WITHOUT EMBOLI IN THE MAJOR PULMONARY-ARTERIES OR METASTASES IN THE PULMONARY PARENCHYMA SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID DIAGNOSIS C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP DOMANSKI, MJ (reprint author), NHLBI,CLIN TRIALS BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 12 Z9 13 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 JUL 15 PY 1993 VL 72 IS 2 BP 233 EP 234 DI 10.1016/0002-9149(93)90168-C PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LL185 UT WOS:A1993LL18500023 PM 8328392 ER PT J AU DEMORAIS, SMF SCHWEIKL, H BLAISDELL, J GOLDSTEIN, JA AF DEMORAIS, SMF SCHWEIKL, H BLAISDELL, J GOLDSTEIN, JA TI GENE STRUCTURE AND UPSTREAM REGULATORY REGIONS OF HUMAN CYP2C9 AND CYP2C18 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MEPHENYTOIN HYDROXYLATION; HUMAN CYTOCHROME-P-450; DRUG-METABOLISM; RAT-LIVER; EXPRESSION; POLYMORPHISM; SUBFAMILY; TOLBUTAMIDE; ELEMENTS; PROTEIN C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. RI Goldstein, Joyce/A-6681-2012; Schweikl, Helmut/C-2998-2013 NR 22 TC 65 Z9 67 U1 0 U2 2 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 JUL 15 PY 1993 VL 194 IS 1 BP 194 EP 201 DI 10.1006/bbrc.1993.1803 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LM603 UT WOS:A1993LM60300028 PM 8333835 ER PT J AU QUON, MJ ZARNOWSKI, MJ GUERREMILLO, M SIERRA, MD TAYLOR, SI CUSHMAN, SW AF QUON, MJ ZARNOWSKI, MJ GUERREMILLO, M SIERRA, MD TAYLOR, SI CUSHMAN, SW TI TRANSFECTION OF DNA INTO ISOLATED RAT ADIPOSE-CELLS BY ELECTROPORATION - EVALUATION OF PROMOTER ACTIVITY IN TRANSFECTED ADIPOSE-CELLS WHICH ARE HIGHLY RESPONSIVE TO INSULIN AFTER ONE-DAY IN CULTURE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EXPRESSION; GENE; ADIPOCYTES; TIME RP QUON, MJ (reprint author), NIDDKD,DIABET BRANCH,BETHESDA,MD 20892, USA. RI Quon, Michael/B-1970-2008; OI Quon , Michael /0000-0002-5289-3707 NR 18 TC 70 Z9 70 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 JUL 15 PY 1993 VL 194 IS 1 BP 338 EP 346 DI 10.1006/bbrc.1993.1825 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LM603 UT WOS:A1993LM60300050 PM 8392839 ER PT J AU GLENNON, MC SHEARS, SB AF GLENNON, MC SHEARS, SB TI TURNOVER OF INOSITOL PENTAKISPHOSPHATES, INOSITOL HEXAKISPHOSPHATE AND DIPHOSPHOINOSITOL POLYPHOSPHATES IN PRIMARY CULTURED-HEPATOCYTES SO BIOCHEMICAL JOURNAL LA English DT Article ID MAMMARY-TUMOR CELLS; RAT-LIVER; MYOINOSITOL 1,3,4,5,6-PENTAKISPHOSPHATE; PHOSPHATES; TETRAKISPHOSPHATES; METABOLISM; 1,3,4-TRISPHOSPHATE; PHOSPHORYLATION; IDENTIFICATION; PURIFICATION AB We have used a non-transformed cell model, the primary cultured hepatocyte, to explore the turnover of inositol hexakisphosphate, multiple isomers of inositol pentakisphosphate and two novel diphosphoinositol polyphosphates. All of these compounds gradually accumulated radioactivity throughout a 70 h period of labelling with [H-3]inositol. However, a rapid metabolic rate was revealed upon inhibition of diphosphoinositol polyphosphate biphosphatase(s) with 1 mM fluoride for 40 min: this treatment elevated levels of [H-3]diphosphoinositol polyphosphates up to 10-fold, indicating that their cellular pools were normally turning over at least 10 times every 40 min. This was accompanied by a turnover of about 10 % of the pool of inositol hexakisphosphate. Control experiments established that 200 nM vasopressin brought about a typical activation of phospholipase C in hepatocytes after 62 h of primary culture. This agonist treatment did not affect steady-state levels of [H-3]inositol pentakisphosphates, [H-3]inositol hexakisphosphate or [H-3]diphosphoinositol polyphosphates. However, prolonged treatment of hepatocytes with 2 muM thapsigargin reduced steady-state levels of [H-3]diphosphoinositol polyphosphates by 50-70 %. This effect of thapsigargin was also observed in the presence of fluoride, indicating that thapsigargin inhibited the rate of synthesis of diphosphoinositol polyphosphates. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INOSITOL LIPID SECT,RES TRIANGLE PK,NC 27709. NR 29 TC 82 Z9 83 U1 0 U2 4 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 15 PY 1993 VL 293 BP 583 EP 590 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LP713 UT WOS:A1993LP71300043 PM 8343137 ER PT J AU BODINE, DM SEIDEL, NE ZSEBO, KM ORLIC, D AF BODINE, DM SEIDEL, NE ZSEBO, KM ORLIC, D TI IN-VIVO ADMINISTRATION OF STEM-CELL FACTOR TO MICE INCREASES THE ABSOLUTE NUMBER OF PLURIPOTENT HEMATOPOIETIC STEM-CELLS SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; C-KIT RECEPTOR; PERIPHERAL-BLOOD; GROWTH-FACTOR; PROGENITOR CELLS; SI-LOCUS; LIGAND; MOUSE; RECONSTITUTION; MARROW C1 AMGEN CORP,THOUSAND OAKS,CA. NEW YORK MED COLL,VALHALLA,NY 10595. RP BODINE, DM (reprint author), NHLBI,CLIN HEMATOL BRANCH,BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 45 TC 103 Z9 105 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 JUL 15 PY 1993 VL 82 IS 2 BP 445 EP 455 PG 11 WC Hematology SC Hematology GA LN186 UT WOS:A1993LN18600013 PM 7687160 ER PT J AU YANUCK, M CARBONE, DP PENDLETON, CD TSUKUI, T WINTER, SF MINNA, JD BERZOFSKY, JA AF YANUCK, M CARBONE, DP PENDLETON, CD TSUKUI, T WINTER, SF MINNA, JD BERZOFSKY, JA TI A MUTANT P53 TUMOR-SUPPRESSOR PROTEIN IS A TARGET FOR PEPTIDE-INDUCED CD8+ CYTOTOXIC T-CELLS SO CANCER RESEARCH LA English DT Note ID TOXIC LYMPHOCYTES-T; LUNG-CANCER; ANTIGEN; GENE; RECOGNITION; DETERMINANT; EXPRESSION; PROTECTION; EPITOPES; FREQUENT AB Cytotoxic T-lymphocytes (CTL) recognize processed peptide fragments of any endogenous protein, after these peptides are carried to the cell surface by class I major histocompatibility molecules. Thus, a tumor antigen does not have to be expressed as an intact protein on the cell surface to be recognizable by CTL. However, mutant oncogene products have not yet been shown to be targets of CD8+ CTL. Here, we generate p53-specific CD8+ CTL by immunizing BALB/c mice with spleen cells pulsed with a peptide, corresponding to a 21-amino acid sequence encompassing a point mutation (135 Cys to Tyr) in the mutant p53 gene product from a human lung carcinoma. The mutation created a new K(d) class I molecule binding motif sequence, and the determinant recognized was mapped to this motif and presented by the K(d) class I molecule. The wild type peptide, without the mutation, was not recognized. Importantly, the CTL killed specifically BALB/c fibroblasts transfected with the mutant p53 gene and endogenously expressing the mutant protein, but not control fibroblasts or ones transfected with a different human mutant p53 gene. Thus, endogenously synthesized mutant p53, at levels found in tumors, can render cells targets for specific CTL, and these CTL can be generated by peptide immunization. These findings point the way toward an approach to selective immunotherapy against tumors. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. RP YANUCK, M (reprint author), NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BLDG 10,ROOM 6B-12,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA57856, CA58220] NR 31 TC 149 Z9 149 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1993 VL 53 IS 14 BP 3257 EP 3261 PG 5 WC Oncology SC Oncology GA LM677 UT WOS:A1993LM67700011 PM 7686815 ER PT J AU BOYER, JC THOMAS, DC MAHER, VM MCCORMICK, JJ KUNKEL, TA AF BOYER, JC THOMAS, DC MAHER, VM MCCORMICK, JJ KUNKEL, TA TI FIDELITY OF DNA-REPLICATION BY EXTRACTS OF NORMAL AND MALIGNANTLY TRANSFORMED HUMAN-CELLS SO CANCER RESEARCH LA English DT Article ID SPONTANEOUS MUTATION-RATES; NUCLEAR EXTRACTS; DIPLOID HUMAN; MISMATCH CORRECTION; HUMAN-FIBROBLASTS; POLYMERASE-BETA; G.T MISPAIRS; LIFE-SPAN; INVITRO; REPAIR AB To test the hypothesis that a mutator phenotype may be associated with carcinogenesis (L. A. Loeb, Cancer Res., 51: 3074-3079, 1991), we have compared the fidelity of double-stranded DNA replication and the efficiency of mismatch repair in extracts from normal diploid and malignantly transformed human cells. Included was a diploid fibroblast strain and its transformed derivative, as well as a second diploid fibroblast strain and HeLa cells. The fidelity of DNA replication by cytoplasmic extracts in the presence of simian virus 40 large tumor antigen (SV40 T-antigen) was measured using a forward mutagenesis assay. The replicated DNA consisted of double-stranded M13 mp2 DNA containing the SV40 origin of replication and the lacZalpha complementation gene as a target sequence for scoring mutations. T-antigen-dependent replication was detected in all cell extracts, with those from transformed cells having the greatest activity. No differences in replication fidelity were detected between normal and transformed cell extracts. Using a heteroduplex containing a G.G mispair, we also detected mismatch repair activity in the cell extracts, including efficient repair in extracts from malignantly transformed cells. While these data do not eliminate the possibility that a mutator phenotype may be associated with carcinogenesis, they do suggest that genetic instability associated with transformation does not involve reduced fidelity of replication of undamaged DNA or reduced mismatch repair efficiency. C1 NIEHS, MOLEC GENET LAB, E3-01, POB 122233, RES TRIANGLE PK, NC 27709 USA. MICHIGAN STATE UNIV, DEPT MICROBIOL, CARCINOGENESIS LAB, E LANSING, MI 48824 USA. MICHIGAN STATE UNIV, DEPT BIOCHEM, E LANSING, MI 48824 USA. FU NCI NIH HHS [CA21253] NR 50 TC 26 Z9 26 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1993 VL 53 IS 14 BP 3270 EP 3275 PG 6 WC Oncology SC Oncology GA LM677 UT WOS:A1993LM67700014 PM 8391921 ER PT J AU WEI, SJC CHANG, RL BHACHECH, N CUI, XX MERKLER, KA WONG, CQ HENNIG, E YAGI, H JERINA, DM CONNEY, AH AF WEI, SJC CHANG, RL BHACHECH, N CUI, XX MERKLER, KA WONG, CQ HENNIG, E YAGI, H JERINA, DM CONNEY, AH TI DOSE-DEPENDENT DIFFERENCES IN THE PROFILE OF MUTATIONS INDUCED BY (+)-7R,8S-DIHYDROXY-9S,10R-EPOXY-7,8,9,10-TETRAHYDROBENZO(A)PYRENE IN THE CODING REGION OF THE HYPOXANTHINE (GUANINE) PHOSPHORIBOSYLTRANSFERASE GENE IN CHINESE-HAMSTER V-79 CELLS SO CANCER RESEARCH LA English DT Article ID DIPLOID HUMAN FIBROBLASTS; DIASTEREOMERIC BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; OPTICAL ENANTIOMERS; 7,8-DIOL 9,10-EPOXIDES; SEQUENCE SPECIFICITY; EXCISION REPAIR; SHUTTLE VECTOR; RAS ONCOGENES; DIOL EPOXIDE; HPRT GENE AB Chinese hamster V-79 cells were exposed to a high dose (0.30-0.48 muM; 32% cell survival), an intermediate dose (0.04-0.10 muM; 100% cell survival) or a low dose (0.01-0.02 muM; 97% cell survival) of (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene [(+)-BPDE] which is the ultimate carcinogenic metabolite of benzo(a)pyrene. The mutation frequency for cells treated with dimethyl sulfoxide vehicle or with low, intermediate or high doses of (+)-BPDE were 1, 10, 52 or 514 8-azaguanine-resistant colonies/10(5) survivors, respectively. Independent 8-azaguanine-resistant clones were isolated, and complementary DNAs were prepared by reverse transcription. The coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene was amplified by the polymerase chain reaction and sequenced. Altogether, 368 (+)-BPDE-induced mutant clones were examined. At all doses, base substitutions were the most prevalent mutations observed (about 72% of the mutant clones), followed by exon deletions (about 26% of the mutant clones) and frame-shift mutations (about 6% of the mutant clones). At the high cytotoxic dose, 7 of 120 base substitutions occurred at AT base pairs (6%) and 113 at GC base pairs (94%). At the intermediate noncytotoxic dose, 20 of 82 base substitutions occurred at AT base pairs (24%) and 62 at GC base pairs (76%). At the low noncytotoxic dose, 27 of 76 base substitutions were at AT base pairs (36%) and 49 were at GC base pairs (64%). The results indicated that decreasing the dose of (+)-BPDE decreased the proportion of mutations at GC base pairs and increased the proportion of mutations at AT base pairs. As the dose of (+)-BPDE was decreased, there was a dose-dependent decrease in the proportion of GC-->TA transversions from 69% to 42% of the base substitutions) and a dose-dependent increase in the proportion of AT-->CG transversions (from 1% to 25% of the base substitutions). The data also indicated dose-dependent differences in (+)-BPDE-induced exon deletions and hot spots for base substitutions at GC and AT base pairs. Although more than 99% of the (+)-BPDE-induced mutations at guanine occurred on the nontranscribed strand of DNA, (+)-BPDE-induced mutations at adenine occurred on both the transcribed and nontranscribed strands. The ratio of mutations at adenine on the transcribed strand to mutations at adenine on the nontranscribed strand was 35:19 in (+)-BPDE-treated V-79 cells. These observations suggest different mechanisms of mutation induction at GC and AT base pairs and/or differences in repair mechanisms for premutagenic lesions at GC and AT base pairs. Several nucleotide sequences with frequent (+)-BPDE-induced mutations targeted at guanines in the coding region of the HPRT gene were identified. These included AGGGGGGC, TGGA, AGGA, TGGT, AGGC, TGGGA, AGGGA, and TGGGGA. Seventy % of all base substitution mutations targeted at guanine were on these sequences. (+)-BPDE-induced mutations in ras motifs (corresponding to ras codons 12, 13, 61) in the coding region of the HPRT gene were more commonly observed than by chance. C1 NIDDKD,BIOORGAN CHEM LAB,OXIDAT MECHANISMS SECT,BETHESDA,MD 20892. RP WEI, SJC (reprint author), RUTGERS UNIV,COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,CANC RES LAB,PISCATAWAY,NJ 08855, USA. FU NCI NIH HHS [CA49756] NR 38 TC 115 Z9 117 U1 0 U2 2 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 JUL 15 PY 1993 VL 53 IS 14 BP 3294 EP 3301 PG 8 WC Oncology SC Oncology GA LM677 UT WOS:A1993LM67700018 PM 8324741 ER PT J AU PRIMUS, FJ FINCH, MD MASCI, AM SCHLOM, J KASHMIRI, SVS AF PRIMUS, FJ FINCH, MD MASCI, AM SCHLOM, J KASHMIRI, SVS TI SELF-REACTIVE ANTIBODY EXPRESSION BY HUMAN CARCINOMA-CELLS ENGINEERED WITH MONOCLONAL-ANTIBODY GENES SO CANCER RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; LYMPHOCYTE-T DIFFERENTIATION; CELLULAR CYTO-TOXICITY; ACTIVATED KILLER-CELLS; MURINE TUMOR; GAMMA-INTERFERON; EFFECTOR-CELLS; FC-RECEPTORS; FACTOR-ALPHA AB The purpose of this study was to determine if human colon cancer cells transduced with monoclonal antibody (MAb) genes become sensitive to immune destruction through coexpression of both the MAb and its reactive antigen. Murine retroviral expression vectors were constructed with the heavy or light chain genes of an anti-human colon carcinoma MAb, D612, that mediates antibody-dependent cell-mediated cytotoxicity (ADCC). Transduction of D612 MAb genes into the D612 antigen-positive (>95%) human colon carcinoma cell line, LS-174T, was carried out by sequential cocultivation with PA317 packaging cells producing infectious virions containing the light or heavy chain expression vectors. Six cultures survived drug selection, two of which were found to have elevated levels of both light and heavy immunoglobulin chain activity in their supernatants. IgG secretion levels (24 h) were 1-2 ng/1 x 10(6) cells. Low but definite antigen reactivity was also present in supernatants obtained from these LS-174T transductants. Immunocytochemical staining of transduced tumor cells revealed that >95% of the cells were positive for IgG expression. Thus, LS-174T transductants were capable of producing both the D612 MAb and D612-reactive antigen. Analysis of transductants by flow cytometry further revealed that >95% of the cells had murine immunoglobulin on their surfaces. ADCC mediated by human natural killer cells against nontransduced tumor cells was observed when the latter cells were cocultivated in the presence of transductants producing both D612 heavy and light chains but not in the presence of tumor cells transduced with light chain only. LS-174T cells transduced with both D612 heavy and light chain genes were more sensitive to cytotoxicity mediated by natural killer cells than were light chain gene only transductants. ADCC contributed to the greater sensitivity of the former transductants to cytotoxicity based on its inhibition by anti-FcRgammaIII antibody. Thus, these studies demonstrate that tumor cells transduced with genes encoding for MAbs that can participate in ADCC reactions are able to sensitize nontransduced tumor cells to immune destruction as well as to direct killer cells against themselves. These studies may lead to a new immunotherapeutic approach for the treatment of cancer based on MAb gene therapy. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP PRIMUS, FJ (reprint author), CITY HOPE NATL MED CTR,BECKMAN RES INT,DIV IMMUNOL,1450 E DUARTE RD,DUARTE,CA 91010, USA. FU NCI NIH HHS [CA33572] NR 54 TC 13 Z9 13 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 JUL 15 PY 1993 VL 53 IS 14 BP 3355 EP 3361 PG 7 WC Oncology SC Oncology GA LM677 UT WOS:A1993LM67700027 PM 8324746 ER PT J AU SEFTOR, REB SEFTOR, EA STETLERSTEVENSON, WG HENDRIX, MJC AF SEFTOR, REB SEFTOR, EA STETLERSTEVENSON, WG HENDRIX, MJC TI THE 72 KDA TYPE-IV COLLAGENASE IS MODULATED VIA DIFFERENTIAL EXPRESSION OF ALPHA-V-BETA-3-INTEGRIN AND ALPHA-5-BETA-1-INTEGRIN DURING HUMAN-MELANOMA CELL INVASION SO CANCER RESEARCH LA English DT Article ID BASEMENT-MEMBRANE; TUMOR INVASION; MONOCLONAL-ANTIBODIES; FIBRONECTIN RECEPTOR; SIGNAL TRANSDUCTION; TISSUE INHIBITOR; HUMAN AMNION; ADHESION; INTEGRIN; METALLOPROTEINASES AB We have recently reported that concomitant with an increase in invasiveness, there is an increase in the expression and secretion of the matrix-degrading 72 kDa gelatinase A/type IV collagenase (MMP-2) in a moderately invasive human melanoma cell line (A375M) upon perturbation of the alpha(v)beta3, classic vitronectin receptor. In the present study, we have extended these observations to include a highly invasive and metastatic melanoma cell line (C8161) which expresses a comparable amount of the alpha5beta1 integrin (classic fibronectin receptor), but very little alpha(v)beta3 integrin on its surface. When perturbed with an anti-alpha5beta1 antibody, C8161 cells are 89% more invasive in vitro, and express and secrete increased levels of the gelatinase A. These changes were not elicited using antibodies to the alpha(v)beta3 integrin. In addition, a 73% increase in invasion of C8161 cells through a fibronectin-enhanced matrix occurred, which could be abrogated by neutralizing antibodies to gelatinase A. Furthermore, we attempted to transiently mimic the invasive phenotype of the C8161 cells by diminishing the alpha(v)beta3 integrin from the A375M cell surface through fluorescence-activated cell sorting selection or deoxynojirimycin treatment, and found these cells to be 30-50% more invasive than the parental population. These data suggest that alternative modulation and signaling events could be involved in melanoma tumor cell invasion as a result of the differential expression of integrins, and strictly cataloging the presence of these integrins is but an initial step in the analysis of their functional activity. C1 UNIV ARIZONA,DEPT ANAT,TUCSON,AZ 85724. UNIV ARIZONA,ARIZONA CANC CTR,TUCSON,AZ 85724. NCI,PATHOL LAB,BETHESDA,MD 20892. RP SEFTOR, REB (reprint author), UNIV ARIZONA,DEPT OPHTHALMOL,TUCSON,AZ 85724, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [NCI CA-54984, NCI CA-59702] NR 39 TC 157 Z9 157 U1 0 U2 2 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 JUL 15 PY 1993 VL 53 IS 14 BP 3411 EP 3415 PG 5 WC Oncology SC Oncology GA LM677 UT WOS:A1993LM67700036 PM 7686818 ER PT J AU OKUNIEFF, P HOECKEL, M DUNPHY, EP SCHLENGER, K KNOOP, C VAUPEL, P AF OKUNIEFF, P HOECKEL, M DUNPHY, EP SCHLENGER, K KNOOP, C VAUPEL, P TI OXYGEN-TENSION DISTRIBUTIONS ARE SUFFICIENT TO EXPLAIN THE LOCAL RESPONSE OF HUMAN BREAST-TUMORS TREATED WITH RADIATION ALONE SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE HYPOXIA; RADIATION THERAPY; ADENOCARCINOMA; RADIATION SENSITIZER ID HYPERBARIC-OXYGEN; HYPOXIC CELLS; BLOOD-FLOW; P-31 NMR; RADIOTHERAPY; CARCINOMA; THERAPY; INVIVO; TISSUE; MICROENVIRONMENT AB Purpose: Several factors are known to influence the probability of tumor control after radiation. These include tumor oxygen tension distribution, glutathione content, intrinsic radiation sensitivity, rate of repopulation, tumor size, physician skill, etc. The relative impact of oxygen on human tumor response is unknown. The purpose of this analysis is to determine to what extent the observed shape of the radiation response curve for human tumors can be predicted by the tumor oxygenation status. Methods and Materials: The radiation dose response curve for patients treated with radiation alone for breast cancer was calculated based on pooled data. Tumor control rates as a function of radiation dose were fitted to a probit curve. Twenty-two women with breast cancer in Mainz (Germany) and at Stanford University had pO2 measurements made of their tumors. An average of 87 +/- 58 (range 21 to 300) measurements were made from each patient. Hypoxia was assumed to be a purely dose modifying factor with a maximum oxygen enhancement ratio of 2.5. Assuming patients are treated with daily radiation doses of 2 Gy, the breast cancer alpha/beta ratio is 10 Gy, tumors have a mean of 10(8) stem cells, and using the linear quadratic formula for modelling surviving fraction, it was possible to estimate tumor control probability. Results: Tumor oxygenation was an extremely important modifier of the shape of the dose response curve and alone was sufficient to account for the slope of the observed dose response curve for human breast carcinoma. Tumor size distribution had a smaller effect on the shape and the slope of the dose response curve. Two models of radiation induced reoxygenation were tested, one that allowed full reoxygenation to the baseline state between the daily radiation fractions and another with no reoxygenation between fractions. The clinical data fell between these two models in accordance with the expected incomplete reoxygenation between treatments. Conclusion: The results support the conclusion that in human breast carcinoma, oxygen tension distribution is a critical modifier of radiation treatment response. C1 UNIV MAINZ,INST PHYSIOL & PATHOPHYSIOL,W-6500 MAINZ 1,GERMANY. STANFORD UNIV,DEPT RADIAT ONCOL,STANFORD,CA 94305. UNIV MAINZ,DEPT OBSTET & GYNECOL,W-6500 MAINZ 1,GERMANY. RP OKUNIEFF, P (reprint author), NCI,RADIAT ONCOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA13311, CA48096] NR 34 TC 127 Z9 133 U1 0 U2 2 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 JUL 15 PY 1993 VL 26 IS 4 BP 631 EP 636 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA LP361 UT WOS:A1993LP36100009 PM 8330993 ER PT J AU FATHI, Z BENYA, RV SHAPIRA, H JENSEN, RT BATTEY, JF AF FATHI, Z BENYA, RV SHAPIRA, H JENSEN, RT BATTEY, JF TI THE 5TH TRANSMEMBRANE SEGMENT OF THE NEUROMEDIN-B RECEPTOR IS CRITICAL FOR HIGH-AFFINITY NEUROMEDIN-B BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOMBESIN RECEPTOR; LIGAND-BINDING; EXTRACELLULAR DOMAIN; CELLS; IDENTIFICATION; ACTIVATION; CLONING AB The two bombesin receptor subtypes, neuromedin B (NMB-R) and gastrin releasing peptide (GRP-R) receptors, bind their respective ligands with high affinity. To identify molecular components mediating high affinity NMB binding, four mutant receptors were constructed, in which different parts of the NMB-R were replaced with the corresponding regions of the GRP-R. When stably expressed in Balb 3T3 fibroblasts, all four NMB-R/GRP-R chimeras were functional and showed NMB-induced stimulation of inositol phosphate (IP) formation. Results of I-125-[D-Tyr0]NMB displacement assays using unlabeled NMB for competition indicated that high affinity NMB binding was determined by amino acid sequences in transmembrane domain V (TM-V) of the NMB-R. To identify which amino acid(s) in TM-V of NMB-R contributed to high affinity NMB binding, four additional NMB-R mutants were constructed where non-conserved amino acids in TM-V of NMB-R were replaced by the corresponding GRP-R amino acids. Three of the mutations, TyrPheLeu220-222 --> PheTyrVal, Ile230 --> Val, and His234 --> Phe, did not affect high affinity NMB binding. The Ile216 --> Ser substitution, however, abolished high affinity NMB binding and severely impaired the ability of the mutant receptor to stimulate NMB-dependent inositol phosphate formation. These results suggest that Ile216 in TM-V of NMB-R may be critical for high affinity NMB binding. C1 NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,RM 5D02,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NR 24 TC 41 Z9 41 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 JUL 15 PY 1993 VL 268 IS 20 BP 14622 EP 14626 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL759 UT WOS:A1993LL75900017 PM 8392057 ER PT J AU JUNG, G FUKUI, Y MARTIN, B HAMMER, JA AF JUNG, G FUKUI, Y MARTIN, B HAMMER, JA TI SEQUENCE, EXPRESSION PATTERN, INTRACELLULAR-LOCALIZATION, AND TARGETED DISRUPTION OF THE DICTYOSTELIUM MYOSIN ID HEAVY-CHAIN ISOFORM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACANTHAMOEBA-CASTELLANII; HOMOLOGOUS RECOMBINATION; CELL MOTILITY; GENE; DISCOIDEUM; CHEMOTAXIS; CLONING; ACTIN; IA; IB AB The complete sequence of the Dictyostelium myosin ID (DMID) heavy chain isoform has been determined from cDNA and genomic clones. Like the DMIB isoform characterized previously, the DMID isoform is up-regulated during starvation-induced chemotatic aggregation, and its 124-kDa heavy chain contains the tail domain sequences that correspond to both the membrane and second actin-binding sites. An antibody that is specific for the DMID isoform was found to stain the actin-rich pseudopods at the leading edge of migrating cells. Protein microsequencing data reveals that the myosin I isoform localized to leading edge pseudopods in a previous study (Fukui, Y., Lynch, T. J., Brzeska, H., and Korn, E. D. (1989) Nature 341, 328-33 1) was DMIB, indicating that DMID and DMIB also colocalize and that both should influence the dynamics of actin-rich cortical structures. This and other data indicate that the DMID and DMIB isoforms are closely related and are distinct from the DMIA and DMIE isoforms, which possess truncated tail domains and are not up-regulated during chemotactic aggregation. Cells in which the DMID gene was rendered nonfunctional by targeted gene disruption do not show obvious behavioral defects, suggesting that another myosin I isoform(s) (possibly DMIB) might compensate for DMID. Finally, Southern blot data indicate that Dictyostelium may contain as many as nine myosin I isoforms. C1 NHLBI,CELL BIOL LAB,9000 ROCKVILLE PIKE,3-B1-22,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,DEPT CELL MOLEC & STRUCT BIOL,CHICAGO,IL 60611. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 48 TC 83 Z9 86 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 JUL 15 PY 1993 VL 268 IS 20 BP 14981 EP 14990 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL759 UT WOS:A1993LL75900067 PM 8325874 ER PT J AU LEE, FJS MOSS, J AF LEE, FJS MOSS, J TI AN RNA-BINDING PROTEIN GENE (RBP1) OF SACCHAROMYCES-CEREVISIAE ENCODES A PUTATIVE GLUCOSE-REPRESSIBLE PROTEIN CONTAINING 2 RNA RECOGNITION MOTIFS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING; NUCLEOTIDE-SEQUENCE; CONSENSUS SEQUENCE; PARTICLE CONTAINS; SNRNP PROTEIN; SEX-LETHAL; DROSOPHILA; YEAST; EXPRESSION; DOMAIN AB A gene, termed RNA-binding protein (RBP1), was cloned from Saccharomyces cerevisiae. RBP1 contains an open reading frame of 2016 nucleotides that encodes a 672-amino acid protein with a calculated M(r) of approximately 75,000. Southern blots of genomic DNA from wild-type and RBP1-disrupted strains were consistent with the presence of homologous genes. RNA blots revealed a major 2.7-kb RNA band and two minor bands of 1.5 and 1.1 kb. The sequence of the putative RBP1 protein contains two copies of an RNA recognition motif, two glutamine stretches, an asparagine-rich region, a methionine-rich region, and two long potential alpha-helixes. In addition, recombinant RBP1 fusion protein can bind to RNA and single-stranded DNA but not double-stranded DNA. RBP1 is a glucose-repressible gene. Disruption of RBP1 increased cell growth rate in the early log phase. Overexpression of RBP1 or reduction in its translation by expression of antisense RNA decreased or increased the cell growth rate, respectively. From these observations, we infer that RBP1 may be involved in growth regulation, possibly through its participation in RNA metabolism. RP NHLBI, CELLULAR METAB LAB, ROOM 5N-307, BLDG 10, BETHESDA, MD 20892 USA. OI LEE, FANG-JEN/0000-0002-2167-2426 NR 60 TC 25 Z9 27 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1993 VL 268 IS 20 BP 15080 EP 15087 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL759 UT WOS:A1993LL75900079 PM 8325883 ER PT J AU HEMRIC, ME LU, FWM SHRAGER, R CAREY, J CHALOVICH, JM AF HEMRIC, ME LU, FWM SHRAGER, R CAREY, J CHALOVICH, JM TI REVERSAL OF CALDESMON BINDING TO MYOSIN WITH CALCIUM-CALMODULIN OR BY PHOSPHORYLATING CALDESMON SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CALDESMON; PROTEIN-KINASE-C; CHICKEN GIZZARD CALDESMON; INTACT HUMAN-PLATELETS; LIGHT-CHAIN KINASE; ATPASE ACTIVITY; HEAVY-MEROMYOSIN; SKELETAL-MUSCLE; CROSS-LINKING; F-ACTIN AB Caldesmon, an actin-binding protein from smooth muscle and non-muscle cells, has previously been shown to bind stoichiometrically to smooth muscle myosin in an ATP-dependent manner. We now show quantitatively the effects of Ca2+-calmodulin and phosphorylation on the binding of caldesmon to myosin. Ca2+-calmodulin reduces the binding of caldesmon to myosin with the same effectiveness as it does the binding of caldesmon to actin. However, Ca2+-calmodulin is ineffective in antagonizing the binding of the purified myosin-binding region of caldesmon to myosin. These and other results suggest that Ca2+-calmodulin binding to the COOH-terminal region of caldesmon is responsible for reversal of binding to myosin. Phosphorylation of the NH2-terminal region of caldesmon by the co-purifying kinase, calmodulin-dependent protein kinase II, weakens but does not eliminate the binding of caldesmon to smooth muscle myosin. Finally, phosphorylation of smooth muscle myosin by smooth muscle myosin light chain kinase has no effect on the binding of caldesmon to myosin. Since Ca2+-calmodulin and phosphorylation of caldesmon weaken the binding of caldesmon to both actin and myosin, these events may be coordinately regulated. C1 E CAROLINA UNIV,SCH MED,DEPT BIOCHEM,GREENVILLE,NC 27858. NIH,BETHESDA,MD 20892. OI Chalovich, Joseph/0000-0002-1243-4055 FU NIAMS NIH HHS [AR35216, R01 AR035216] NR 62 TC 25 Z9 25 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 JUL 15 PY 1993 VL 268 IS 20 BP 15305 EP 15311 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL759 UT WOS:A1993LL75900109 PM 8325900 ER PT J AU GIESE, T ALLISON, JP DAVIDSON, WF AF GIESE, T ALLISON, JP DAVIDSON, WF TI FUNCTIONALLY ANERGIC LPR AND GLD B220(+) T-CELL RECEPTOR (TCR)-ALPHA/BETA(+) DOUBLE-NEGATIVE T-CELLS EXPRESS CD28 AND RESPOND TO COSTIMULATION WITH PHORBOL-MYRISTATE ACETATE AND ANTIBODIES TO CD28 AND THE TCR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; INTERLEUKIN-2 GENE-EXPRESSION; MURINE LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; SURFACE-ANTIGEN; LPR/LPR MICE; LYT-2+ CELLS; ACTIVATION ANTIGEN-B7; MATURE THYMOCYTES; INTERFERON-GAMMA AB Mice homozygous for lpr and gld develop lymphadenopathy characterized by the progressive accumulation of an unusual population of CD4-, CD8-, CD2-, IL-2R- double-negative (DN) T cells that express reduced levels of TCR-alpha/beta, high levels of CD45 (B220) and Ly-6C and variable levels of CD69. These cells are refractory to most stimuli, including staphylococcal entertoxins and cross-linking of the TCR, Ly-6C, and CD69. For normal T cells, the binding of ligand to the TCR alone is insufficient to induce a proliferative response and can result in the induction of a state of prolonged anergy. Efficient stimulation is dependent on the delivery of a second or costimulatory signal. Recently it was reported that CD28 can provide costimulatory signals to T cells and, that these signals can prevent anergy induction in T cell clones. We investigated the possibility that lpr and gld DN T cells are unresponsive because they fail to transduce signals via CD28. These studies showed that highly purified B220+ TCR-alpha/beta+ DN T cells expressed high levels of CD28, responded weakly to stimulation with PMA and anti-CD28 mAb and quite strongly to PMA, anti-CD28 antibody and high concentrations of immobilized anti-TCR-alpha/beta antibodies. The latter stimulus also induced low levels of expression of CD2 and IL-2R and secretion of modest amounts of IL-2. Although DN T cells proliferated and secreted IL-2, these responses differed qualitatively and quantitatively from those of +/+ and lpr B220- T cells. Consistent with its effects on normal T cells, cyclosporin A partially inhibited the response of DN T cells to TCR cross-linking and CD28 ligation. Studies of synergism between CD28-, Ly-6C-, and CD69-mediated signals revealed that ligation of CD28 enhanced the proliferative response induced by cross-linking of Ly-6C or CD69 on +/+, lpr and gld B220- T cells but had no effect on the unresponsiveness of DN T cells to these stimuli. Ligation of CD28 did not reverse the unresponsiveness of DN T cells to SEB and had only a weak synergistic effect on the response of B220- T cells. Together, these observations suggest that the mechanisms leading to immunosuppression of DN T cells are complex and appear to involve abnormalities in signal transduction via the TCR and CD28 and possibly via Ly-6C and CD69 as well. C1 NCI,GENET LAB,BETHESDA,MD 20892. UNIV CALIF BERKELEY,CANC RES LAB,BERKELEY,CA 94720. UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,DIV IMMUNOL,BERKELEY,CA 94720. NR 71 TC 32 Z9 32 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 JUL 15 PY 1993 VL 151 IS 2 BP 597 EP 609 PG 13 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600006 PM 7687618 ER PT J AU ISHIDA, Y CHUSED, TM AF ISHIDA, Y CHUSED, TM TI LACK OF VOLTAGE-SENSITIVE POTASSIUM CHANNELS AND GENERATION OF MEMBRANE-POTENTIAL BY SODIUM-POTASSIUM ATPASE IN MURINE T-LYMPHOCYTES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ION CHANNELS; PUMP; CELLS; EXPRESSION; DEPENDENCE; GRADIENTS AB Voltage sensitive K+ channels, which are responsible for generation of membrane potential in most cells, are functionally absent in about one-third of peripheral murine T cells and greatly reduced in the rest as shown by resistance of their membrane potential to changes in extracellular potassium concentration and failure of K+ channel dependent volume regulation. Despite the absence of voltage- sensitive K+ channels, the membrane potential of peripheral T cells is between -60 and -70 mV, the same as thymocytes. A total of 40 to 70 mV of the membrane potential of peripheral T cells is produced by the direct electrogenic action of the asymmetric Na+K+ ATPase pump because the cells are depolarized by ouabain, an inhibitor of the pump, removal of extracellular potassium or reduction of temperature. The residual, ouabain-resistant membrane potential, is sensitive to the K+ channel blocker, quinine, and thus due to electrodiffusion through K+ channels. Na+ and K+ turnover, and sensitivity to ouabain, are the same in peripheral T cells and thymocytes. The predominant mechanism of membrane potential generation changes during T lymphocyte differentiation from electrodiffusion in the thymus to electrogenic in peripheral T cells and back to electrodiffusion upon peripheral cell activation. C1 NIAID,IMMUNOL LAB,TW 2,RM 69,BETHESDA,MD 20892. NR 38 TC 36 Z9 36 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 JUL 15 PY 1993 VL 151 IS 2 BP 610 EP 620 PG 11 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600007 PM 8393035 ER PT J AU SCHWEIGHOFFER, T TANAKA, Y TIDSWELL, M ERLE, DJ HORGAN, KJ LUCE, GEG LAZAROVITS, AI BUCK, D SHAW, S AF SCHWEIGHOFFER, T TANAKA, Y TIDSWELL, M ERLE, DJ HORGAN, KJ LUCE, GEG LAZAROVITS, AI BUCK, D SHAW, S TI SELECTIVE EXPRESSION OF INTEGRIN ALPHA-4-BETA-7 ON A SUBSET OF HUMAN CD4(+) MEMORY T-CELLS WITH HALLMARKS OF GUT-TROPHISM SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE HOMING RECEPTOR; MONOCLONAL-ANTIBODY; LEUKOCYTE ADHESION; ENDOTHELIAL-CELLS; DIFFERENTIAL EXPRESSION; MIGRATION PATHWAYS; ACTIVATION ANTIGEN; IMMUNE-SYSTEM; 3 DISTINCT; MOLECULES AB Human memory CD4+ T lymphocytes are heterogenous in expression of integrins; one subset has the unexpected phenotype beta(low)alpha4high. We demonstrate that this subset is unique among CD4+ cells in expression of high levels of alpha4beta7, detected by a distinctive mAb Act-1. Alpha4beta7 is involved in binding to both fibronectin and vascular cell adhesion molecule-1; Act-1 blocks cell binding to the former and augments binding to the latter. Act-1 expression marks a subset of memory cells that, unlike the predominant circulating memory cell, has up-regulated beta7 rather than beta1. Their phenotype is distinct from that described for skin-homing T cells and is fully consistent with that described for gut-homing T cells. Differential adhesion capacity of this subset is verified by selective binding to FN and vascular cell adhesion molecule-1 in a beta1-independent fashion. Thus, alpha4beta7 detected on this subset of circulating normal T cells fits the expectations for a gut-homing receptor. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,CTR LUNG BIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,SAN FRANCISCO,CA 94143. UNIV WESTERN ONTARIO,UNIV HOSP,MULTIPLE ORGAN TRANSPLANT SERV,LONDON N6A 5A5,ONTARIO,CANADA. BECTON DICKINSON,SAN JOSE,CA. RP SCHWEIGHOFFER, T (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL07185]; NIAMS NIH HHS [AR60684] NR 52 TC 227 Z9 229 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 JUL 15 PY 1993 VL 151 IS 2 BP 717 EP 729 PG 13 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600018 PM 7687621 ER PT J AU SMYTH, MJ ORTALDO, JR AF SMYTH, MJ ORTALDO, JR TI MECHANISMS OF CYTOTOXICITY USED BY HUMAN PERIPHERAL-BLOOD CD4(+) AND CD8(+) T-CELL SUBSETS - THE ROLE OF GRANULE EXOCYTOSIS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOLYTIC LYMPHOCYTES-T; PROTEIN GENE-EXPRESSION; MEDIATED CYTO-TOXICITY; ANTIGEN-SPECIFIC CD4+; SERINE ESTERASE; LYTIC ACTIVITY; DNA FRAGMENTATION; 9TH COMPONENT; KILLER-CELLS; CLONES AB The broad lytic properties of high buoyant density CD4+ and CD8+ T cell subsets were examined by activating these populations with anti-CD3 mAb and IL-2 for 1 to 5 days and testing their cytotoxic activity against various target cells. The effects of a variety of metabolic inhibitors and anti-TNF antibodies were examined to distinguish several different mechanisms of cytotoxicity used by CD4+ and CD8+ T cell effectors isolated from human PBL. In particular, activated CD4+ and CD8+ T cells were cytotoxic when redirected by an anti-nitrophenyl (NP)-anti-CD3 mAb heteroconjugate against NP-modified nucleated target cells (TC) and anucleated SRBC and also lysed L929 in a TNF-alpha-dependent manner. CD4+ and CD8+ T cells displayed distinct pathways of antibody-redirected lysis against NP-EL4, yet common mechanisms of SRBC redirected lysis by CD4+ and CD8+ effectors were implied by a similar pattern of sensitivity to cholera toxin, cyclosporin A (CsA), and EGTA. CsA inhibited CD4+ and CD8+ T cell redirected lysis of SRBC, but not EL4, suggesting that T cells redirectedly lyse nucleated and anucleated TC by different mechanisms. Cholera toxin, CsA, or EGTA pretreatment also significantly inhibited their release of alpha-N-benzyloxycarbonyl-L-lysine-thiobenzylester-esterase activity suggesting that degranulation of CD4+ and CD8+ effectors may be a critical step in their redirected lysis of SRBC. Overall, these findings suggested that activated human PBL CD4+ or CD8+ effectors can lyse TC by at least three distinct mechanisms: 1) a CsA-sensitive redirected lysis of SRBC that correlates with exocytosis and presumably occurs via membrane lesions; 2) a CsA-insensitive redirected lysis of NP-modified nucleated TC that does not appear to involve exocytosis and is metabolically distinct in activated CD4+ and CD8+ T cell effectors; and 3) a direct TNF-dependent lysis of TNF-sensitive TC. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. RP SMYTH, MJ (reprint author), AUSTIN HOSP,AUSTIN RES INST,CELLULAR CYTOTOX LAB,KRONHEIMER BLDG,STUDLEY RD,HEIDELBERG,VIC 3084,AUSTRALIA. RI Smyth, Mark/H-8709-2014 OI Smyth, Mark/0000-0001-7098-7240 NR 40 TC 21 Z9 21 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 JUL 15 PY 1993 VL 151 IS 2 BP 740 EP 747 PG 8 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600020 PM 8101537 ER PT J AU HAKIMI, J HA, VC LIN, P CAMPBELL, E GATELY, MK TSUDO, M PAYNE, PW WALDMANN, TA GRANT, AJ TSIEN, WH SCHNEIDER, WP AF HAKIMI, J HA, VC LIN, P CAMPBELL, E GATELY, MK TSUDO, M PAYNE, PW WALDMANN, TA GRANT, AJ TSIEN, WH SCHNEIDER, WP TI HUMANIZED MIK-BETA-1, A HUMANIZED ANTIBODY TO THE IL-2-RECEPTOR BETA-CHAIN THAT ACTS SYNERGISTICALLY WITH HUMANIZED ANTI-TAC SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR MONOCLONAL-ANTIBODY; HUMAN IL-2 RECEPTOR; VERSUS-HOST DISEASE; T-CELL LEUKEMIA; INTERLEUKIN-2 RECEPTOR; RENAL-TRANSPLANTATION; ALLOGRAFT SURVIVAL; DISTINCT; EXPRESSION; BINDS AB Mikbeta1 is a mouse mAb directed at the beta-subunit of the human IL-2R (Tac) that inhibits IL-2 binding and inhibits IL-2 induction of large granular lymphocytes (LGL). Mikbeta1 alone does not inhibit IL-2-induced T-cell proliferation, but acts synergistically with anti-Tac to inhibit IL-2-induced proliferation of activated T cells. To evaluate these effects for possible therapy in humans, we constructed two humanized Mikbeta1 antibodies by combining the complementarity-determining regions of the murine antibody with human framework and constant regions. Compared with murine Mikbeta1, the two humanized Mikbeta1 antibodies, which differ in their degree of humanization, had similar affinities for IL-2Rbeta. The murine Mikbeta1 and one of the humanized Mikbeta1 antibodies were equivalent in competing for IL-2 binding to IL-2Rbeta and inhibiting IL-2 induction of LGL cytotoxicity. The activity of the second humanized antibody was significantly reduced. The three Mikbeta1 antibodies act synergistically to varying degrees with humanized anti-Tac to prevent IL-2-induced proliferation of activated T cells. This capacity to synergize paralleled their abilities to inhibit IL-2 binding. In addition, both humanized antibodies directed antibody-dependent cell-mediated cytotoxicity. We hope that humanized Mikbeta1 in combination with humanized anti-Tac will provide a new immunosuppressive therapy for the treatment of autoimmune diseases, graft-versus-host disease, and prevention of allograft rejection. C1 PROT DESIGN LABS INC,MT VIEW,CA 94043. KYOTO KASURA HOSP,KYOTO,JAPAN. NCI,METAB BRANCH,BETHESDA,MD 20892. RP HAKIMI, J (reprint author), HOFFMANN LA ROCHE INC,ROCHE RES CTR,INFLAMMAT & AUTOIMMUNE DIS,340 KINGSLAND ST,NUTLEY,NJ 07110, USA. NR 36 TC 46 Z9 52 U1 1 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 JUL 15 PY 1993 VL 151 IS 2 BP 1075 EP 1085 PG 11 WC Immunology SC Immunology GA LN986 UT WOS:A1993LN98600053 PM 8335891 ER PT J AU KOLCH, W HEIDECKER, G KOCHS, G HUMMEL, R VAHIDI, H MISCHAK, H FINKENZELLER, G MARME, D RAPP, UR AF KOLCH, W HEIDECKER, G KOCHS, G HUMMEL, R VAHIDI, H MISCHAK, H FINKENZELLER, G MARME, D RAPP, UR TI PROTEIN KINASE-C-ALPHA ACTIVATES RAF-1 BY DIRECT PHOSPHORYLATION SO NATURE LA English DT Article AB THE kinase Raf-1 can be activated by treatment of cells with mitogens and by the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA) (reviewed in refs 1,2). Activated Raf-1 triggers a protein kinase cascade by direct phosphorylation of MAP kinase kinase3-5, resulting in phosphorylation of ternary complex factor6 and Jun7,8 by MAP kinase. Here we investigate the molecular mechanism and biological consequences of PKCalpha-mediated Raf-1 activation in NIH3T3 fibroblasts. PKCalpha directly phosphorylates and activates Raf-1 both in vitro and in vivo. PKCalpha induces Raf-1 phosphorylation at several sites, including a serine residue at position 499. Mutation of serine at this position or at residue 259 does not abrogate Raf-1 stimulation by a combination of Ras plus the src tyrosine kinase Lck, but severely impedes Raf-1 activation by PKCalpha. Consistent with such a direct interaction is the observation that Raf-1 and PKCalpha cooperate in the transformation of NIH3T3 cells. The Ser499 phosphorylation site is necessary for this synergism. C1 GODECKE AG,BIOL RES,W-7800 FREIBURG,GERMANY. NCI,FCRDC,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV FREIBURG,GOEDECKE AG,INST MOLEC CELL BIOL,W-7800 FREIBURG,GERMANY. NCI,GENET LAB,BETHESDA,MD 20892. RI Mischak, Harald/E-8685-2011; OI Kolch, Walter/0000-0001-5777-5016 NR 19 TC 1197 Z9 1208 U1 1 U2 14 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 15 PY 1993 VL 364 IS 6434 BP 249 EP 252 DI 10.1038/364249a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM683 UT WOS:A1993LM68300061 PM 8321321 ER PT J AU CLOS, J RABINDRAN, S WISNIEWSKI, J WU, C AF CLOS, J RABINDRAN, S WISNIEWSKI, J WU, C TI INDUCTION TEMPERATURE OF HUMAN HEAT-SHOCK FACTOR IS REPROGRAMMED IN A DROSOPHILA CELL ENVIRONMENT SO NATURE LA English DT Article ID BINDING AB HEAT shock factor (HSF)1,2, the transcriptional activator of eukaryotic heat shock genes, is induced to bind DNA by a monomer to trimer transition involving leucine zipper interactions3,4. Although this mode of regulation is shared among many eukaryotic species, there is variation in the temperature at which HSF binding activity is induced. We investigated the basis of this variation by analysing the response of a human HSF expressed in Drosophila cells and Drosophila HSF expressed in human cells. We report here that the temperature that induces DNA binding and trimerization of human HSF in Drosophila was decreased by approximately 10-degrees-C to the induction temperature for the host cell, whereas Drosophila HSF expressed in human cells was constitutively active. The results indicate that the activity of HSF in vivo is not a simple function of the absolute environmental temperature. C1 NCI,BIOCHEM LAB,BLDG 37,RM 4C-09,BETHESDA,MD 20892. NR 16 TC 66 Z9 66 U1 2 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 15 PY 1993 VL 364 IS 6434 BP 252 EP 255 DI 10.1038/364252a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM683 UT WOS:A1993LM68300062 PM 8321322 ER PT J AU GRAZIOSI, C PANTALEO, G BUTINI, L DEMAREST, JF SAAG, MS SHAW, GM FAUCI, AS AF GRAZIOSI, C PANTALEO, G BUTINI, L DEMAREST, JF SAAG, MS SHAW, GM FAUCI, AS TI KINETICS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) DNA AND RNA-SYNTHESIS DURING PRIMARY HIV-1 INFECTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EXPRESSION; AMPLIFICATION; LYMPHOCYTES; ZIDOVUDINE; VIREMIA; PLASMA; BLOOD; CELLS; AIDS AB HIV-1 replication and viral burden in peripheral blood mononuclear cells (PBMC) have been reported to be high in primary infection but generally very low during the prolonged period of clinical latency. It is uncertain precisely when this transition occurs during the HIV-1 infection and what the relationship is between the changes in HIV-1 replication versus the clearance of infected cells in the overall control of viral replication. In the present study, the kinetics of viral burden (i.e., frequency of HIV-1-infected cells) and replication during primary and early-chronic infection were analyzed in PBMC of four acutely infected individuals. High frequencies of HiV-1-infected cells and high levels of virus replication were observed in PBMC after primary HIV-1 infection. Down-regulation of virus replication in PBMC was observed in all four patients coincident with the emergence of HIV-1-specific immune responses. Other parameters of virus replication, such as circulating plasma p24 antigen and plasma viremia showed similar kinetics. In contrast, a significant decline in viral burden in PBMC was observed in only one of four patients. These results indicate that the down-regulation in the levels of virus replication associated with the clinical transition from acute to chronic infection does not necessarily reflect a reduction in viral burden, thus suggesting the involvement of additional factors. Identification of these factors will be important in elucidating the host mechanisms involved in the early control of HIV-1 infection and disease. C1 UNIV ANCONA,DEPT INTERNAL MED,I-60100 ANCONA,ITALY. UNIV ALABAMA,DEPT MED,DIV HEMATOL ONCOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,DIV INFECT DIS,BIRMINGHAM,AL 35294. RP GRAZIOSI, C (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 27 TC 113 Z9 113 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 JUL 15 PY 1993 VL 90 IS 14 BP 6405 EP 6409 DI 10.1073/pnas.90.14.6405 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100007 PM 8341646 ER PT J AU HAYES, JJ WOLFFE, AP AF HAYES, JJ WOLFFE, AP TI PREFERENTIAL AND ASYMMETRIC INTERACTION OF LINKER HISTONES WITH 5S DNA IN THE NUCLEOSOME SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CORE HISTONES; CHROMATIN; RESOLUTION; OCTAMER; GENE; RNA; H-1; PARTICLE; COMPLEX AB We establish that linker histones H1 and H5 bind preferentially to a Xenopus borealis somatic 5S RNA gene associated with an octamer of core histones rather than to naked 5S DNA. This preferential binding requires free linker DNA to either side of the nucleosome core. Incorporation of a single linker histone molecule into the nucleosome protects an additional 20 bp of linker DNA from micrococcal nuclease digestion. This additional DNA is asymmetrically distributed with respect to the nucleosome core. Incorporation of linker histones causes no change to the cleavage of DNA in the nucleosome by hydroxyl radical or DNase I. RP HAYES, JJ (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA. NR 37 TC 138 Z9 138 U1 1 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 JUL 15 PY 1993 VL 90 IS 14 BP 6415 EP 6419 DI 10.1073/pnas.90.14.6415 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100009 PM 8341648 ER PT J AU ANDREWS, SB GALLANT, PE LEAPMAN, RD SCHNAPP, BJ REESE, TS AF ANDREWS, SB GALLANT, PE LEAPMAN, RD SCHNAPP, BJ REESE, TS TI SINGLE KINESIN MOLECULES CROSSBRIDGE MICROTUBULES IN-VITRO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SCANNING TRANSMISSION ELECTRON MICROSCOPY; MOLECULAR STRUCTURE; CYTOSKELETON ID CRYO-ELECTRON MICROSCOPY; BOVINE BRAIN KINESIN; MONOCLONAL-ANTIBODY; HEAVY-CHAIN; IDENTIFICATION; MOTILITY; PROTEINS; FREEZE AB Kinesin is a cytoplasmic motor protein that moves along microtubules and can induce microtubule bundling and sliding in vitro. To determine how kinesin mediates microtubule interactions, we determined the shapes and mass distributions of squid brain kinesin, taxol-stabilized microtubules (squid and bovine), and adenosine 5'-[beta,gamma-imido]triphosphate-stabilized kinesin-microtubule complexes by high-resolution metal replication and by low-temperature, low-dose dark-field scanning transmission electron microscopy of unfixed, directly frozen preparations. Mass mapping by electron microscopy revealed kinesins loosely attached to the carbon support as asymmetrical dumbbell-shaped molecules, 40-52 nm long, with a mass of 379 +/- 15 kDa. The mass distribution and shape of these molecules suggest that these images represent kinesin in a shortened conformation. Kinesin-microtubule complexes were organized as bundles of linearly arrayed microtubules, stitched together at irregular intervals by crossbridges typically less-than-or-equal-to 25 nm long. The crossbridges had a mass of 360 +/- 15 kDa, consistent with one kinesin per crossbridge. These results suggest that kinesin has a second microtubule binding site in addition to the known site on the motor domain of the heavy chain; this second site may be located near the C terminus of the heavy chains or on the associated light chains. Thus, kinesin could play a role in either crosslinking or sliding microtubules. C1 NINCDS,NEUROBIOL LAB,BLDG 36,ROOM 2A-29,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT CELLULAR & MOLEC PHYSIOL,BOSTON,MA 02115. NR 31 TC 31 Z9 31 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 JUL 15 PY 1993 VL 90 IS 14 BP 6503 EP 6507 DI 10.1073/pnas.90.14.6503 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100027 PM 8341662 ER PT J AU DALPORTO, J JOHANSEN, TE CATIPOVIC, B PARFIIT, DJ TUVESON, D GETHER, U KOZLOWSKI, S FEARON, DT SCHNECK, JP AF DALPORTO, J JOHANSEN, TE CATIPOVIC, B PARFIIT, DJ TUVESON, D GETHER, U KOZLOWSKI, S FEARON, DT SCHNECK, JP TI A SOLUBLE DIVALENT CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX MOLECULE INHIBITS ALLOREACTIVE T-CELLS AT NANOMOLAR CONCENTRATIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TOXIC LYMPHOCYTES-T; ANTIGEN; PEPTIDE; RECOGNITION; RECEPTOR; HLA-A2; MHC; AFFINITY AB Genetically engineered or chemically purified soluble monovalent major histocompatibility complex (MHC) molecules, which have previously been used to study T cells, have not blocked cytotoxic T-cell responses. Here we describe a genetically engineered divalent class I MHC molecule which inhibits lysis of target cells by alloreactive cytotoxic T cells. This protein, H-2K(b)/IgG, was generated as a fusion protein between the extracellular domains of a murine class I polypeptide, H-2K(b), and an immunoglobulin heavy chain polypeptide. The chimeric protein has serological and biochemical characteristics of both the MHC and IgG polypeptides. Nanomolar concentrations of H-2K(b)/IgG inhibited lysis of H-2K(b)-expressing target cells not only by alloreactive H-2K(b)-specific T-cell clones but also by alloreactive H-2K(b)-specific primary T-cell cultures. A direct binding assay showed high-affinity binding between the H-2K(b)/IgG molecule and an H-2K(b)-specific alloreactive T-cell clone. Unlabeled H-2K(b)/IgG displaced I-125-labeled H-2K(b)/IgG from T cells with an IC50 of 1.2 nM. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV MOLEC RHEUMATOL,BALTIMORE,MD 21224. UNIV COPENHAGEN,RIGSHOSP,DEPT CLIN CHEM,DK-6321 COPENHAGEN,DENMARK. NIH,IMMUNOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CLIN IMMUNOL,BALTIMORE,MD 21224. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 32 TC 110 Z9 111 U1 1 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 JUL 15 PY 1993 VL 90 IS 14 BP 6671 EP 6675 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100061 PM 8341685 ER PT J AU XU, NZ BRADLEY, L AMBDUKAR, I GUTKIND, JS AF XU, NZ BRADLEY, L AMBDUKAR, I GUTKIND, JS TI A MUTANT ALPHA-SUBUNIT OF G(12) POTENTIATES THE EICOSANOID PATHWAY AND IS HIGHLY ONCOGENIC IN NIH-3T3 CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARACHIDONIC-ACID RELEASE; SWISS 3T3 CELLS; RECEPTOR SUBTYPES; G-PROTEINS; TRANSFORMATION; MITOGENESIS; ACTIVATION; GENES AB The discovery of GTPase-inhibiting mutations in genes for alpha subunits of G(s) or G(i2) in certain human endocrine tumors has raised the possibility that heterotrimeric guanine nucleotide-binding regulatory proteins (G proteins) might contribute to neoplastic disease. Expression of GTPase-deficient alpha(s) or alpha(i2). polypeptides in rodent fibroblasts increases or decreases cAMP, respectively, and induces certain alterations in cell growth but only a few of the phenotypic changes associated with cellular transformation. In contrast, an analogous mutation in the alpha subunit of G(q), which activates phosphatidylinositol (PI)-specific phospholipase C, is fully oncogenic. However, activated alpha(q) is cytotoxic and several orders of magnitude less potent as an oncogene than certain G protein-coupled receptors. Thus, G proteins other than those inducing PI hydrolysis might possess high transforming efficiency. In the present study, we explored the G12 family of G proteins for their oncogenic potential. Our results show that whereas overexpression of wild-type alpha12 in NIH 3T3 cells is itself weakly transforming, an activated alpha12 behaves as a remarkably potent oncogene. Transformation by alpha12 correlates with alterations in the eicosanoid pathway but not with PI-specific phospholipase C or other G protein-linked second messengers. C1 NIDR,CELLULAR DEV & ONCOL LAB,MOLEC SIGNALLING GRP,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 30 TC 160 Z9 160 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 JUL 15 PY 1993 VL 90 IS 14 BP 6741 EP 6745 DI 10.1073/pnas.90.14.6741 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100075 PM 8393576 ER PT J AU BIVIN, DB KUBOTA, S PEARLSTEIN, R MORALES, MF AF BIVIN, DB KUBOTA, S PEARLSTEIN, R MORALES, MF TI ON HOW A MYOSIN TRYPTOPHAN MAY BE PERTURBED SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FLUORESCENCE; INDOLE AB A well-known indication that a nucleotide has bound to myosin is the enhancement of the fluorescence of a specific tryptophan in the ''subfragment 1'' segment of the protein. Empirically the effect has been enormously useful in myosin enzymology. But beyond an early suggestion that it arises from a purine-tryptophan charge-transfer complex, the mechanism of the effect has not been considered. Here we consider the alternative that it arises from an ionizable group (either another residue or the phosphate of the nucleotide) whose proximity to the tryptophan is altered by substrate binding. We study this possibility by studying the interaction of an ionizable residue and tryptophan when both are incorporated in a diketopiperazine structure. The geometry of the situation is inferred from molecular mechanics simulations. Unexpectedly, the best explanation seems to be that the field of the imposed charge, acting across space, affects events in the excited state of the indole. C1 PENINSULA CO,BELMONT,CA 94002. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP BIVIN, DB (reprint author), UNIV PACIFIC,DEPT PHYSIOL,2155 WEBSTER ST,SAN FRANCISCO,CA 94115, USA. FU NHLBI NIH HHS [HL-44200] NR 26 TC 20 Z9 20 U1 0 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 JUL 15 PY 1993 VL 90 IS 14 BP 6791 EP 6795 DI 10.1073/pnas.90.14.6791 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100085 PM 8341700 ER PT J AU BALDWIN, ET BHAT, TN GULNIK, S HOSUR, MV SOWDER, RC CACHAU, RE COLLINS, J SILVA, AM ERICKSON, JW AF BALDWIN, ET BHAT, TN GULNIK, S HOSUR, MV SOWDER, RC CACHAU, RE COLLINS, J SILVA, AM ERICKSON, JW TI CRYSTAL-STRUCTURES OF NATIVE AND INHIBITED FORMS OF HUMAN CATHEPSIN-D - IMPLICATIONS FOR LYSOSOMAL TARGETING AND DRUG DESIGN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ASPARTIC PROTEASE; N-LINKED OLIGOSACCHARIDE; PEPSTATIN-A ID ASPARTIC PROTEINASES; PORCINE PEPSIN; ENZYME; RESOLUTION; COMPLEX; BRAIN; SELECTIVITY; GENERATION; MOLECULES; PROTEASE AB Cathepsin D (EC 3.4.23.5) is a lysosomal protease suspected to play important roles in protein catabolism, antigen processing, degenerative diseases, and breast cancer progression. Determination of the crystal structures of cathepsin D and a complex with pepstatin at 2.5 angstrom resolution provides insights into inhibitor binding and lysosomal targeting for this two-chain, N-glycosylated aspartic protease. Comparison with the structures of a complex of pepstatin bound to rhizopuspepsin and with a human renin-inhibitor complex revealed differences in subsite structures and inhibitor-enzyme interactions that are consistent with affinity differences and structure-activity relationships and suggest strategies for fine-tuning the specificity of cathepsin D inhibitors. Mutagenesis studies have identified a phosphotransferase recognition region that is required for oligosaccharide phosphorylation but is 32 angstrom distant from the N-domain glycosylation site at Asn-70. Electron density for the crystal structure of cathepsin D indicated the presence of an N-linked oligosaccharide that extends from Asn-70 toward Lys-203, which is a key component of the phosphotransferase recognition region, and thus provides a structural explanation for how the phosphotransferase can recognize apparently distant sites on the protein surface. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,AIDS VACCINE PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 40 TC 207 Z9 210 U1 2 U2 12 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 JUL 15 PY 1993 VL 90 IS 14 BP 6796 EP 6800 DI 10.1073/pnas.90.14.6796 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM681 UT WOS:A1993LM68100086 PM 8393577 ER PT J AU PIANTADOSI, S GAIL, MH AF PIANTADOSI, S GAIL, MH TI A COMPARISON OF THE POWER OF 2 TESTS FOR QUALITATIVE INTERACTIONS SO STATISTICS IN MEDICINE LA English DT Article AB 'Qualitative' or 'crossover' interactions arise when a new treatment, compared with a control treatment, is beneficial in some subsets of patients and harmful in other subsets. We present a new range test for crossover interactions and compare it with the likelihood ratio test developed by Gail and Simon. The range test has greater power when the new treatment is harmful in only a few subsets, whereas the likelihood ratio test has greater power when the new treatment is harmful in several subsets. We provide power tables for both tests to facilitate sample size calculations for designing experiments to detect qualitative interactions and for interpreting the results of clinical trials. C1 NCI,DIV CANC ETIOL,EPIDEMIOL METHODS SECT,ROCKVILLE,MD 20892. RP PIANTADOSI, S (reprint author), JOHNS HOPKINS UNIV HOSP,CTR ONCOL,550 N BROADWAY,SUITE 1103,BALTIMORE,MD 21205, USA. NR 11 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 15 PY 1993 VL 12 IS 13 BP 1239 EP 1248 PG 10 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 LM813 UT WOS:A1993LM81300004 PM 8210823 ER PT J AU KARP, JE BRODER, S AF KARP, JE BRODER, S TI ONCOLOGY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CANCER; DISOMY RP KARP, JE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 16 TC 0 Z9 0 U1 0 U2 0 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 JUL 14 PY 1993 VL 270 IS 2 BP 237 EP 239 DI 10.1001/jama.270.2.237 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA LL368 UT WOS:A1993LL36800032 PM 8315746 ER PT J AU PRUSS, D WOLFFE, AP AF PRUSS, D WOLFFE, AP TI HISTONE DNA CONTACTS IN A NUCLEOSOME CORE CONTAINING A XENOPUS 5S RIBOSOMAL-RNA GENE SO BIOCHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR-IIIA; PRIMARY ORGANIZATION; CROSS-LINKING; RNA GENE; CHROMATIN; PARTICLES; COMPLEX; RESOLUTION; OCTAMER; REGION AB We describe histone-DNA cross-linking in a nucleosome core containing a Xenopus borealis somatic 5S rRNA gene. Histones H3 and H4 are cross-linked to DNA within 30 bp to either side of the dyad axis. Histones H2A/H2B and H3 are cross-linked to DNA where it enters and exits, wrapping around the histone octamer. These latter interactions extend for 80 bp to one side of the dyad axis of the nucleosome core, including the entire binding site for transcription factor TFIIIA. These extensive interactions with linker DNA might account for inhibition of TFIIIA binding and also might assist in the folding of internucleosomal DNA within the chromatin fiber. C1 NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892. NR 35 TC 51 Z9 51 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 JUL 13 PY 1993 VL 32 IS 27 BP 6810 EP 6814 DI 10.1021/bi00078a002 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN442 UT WOS:A1993LN44200002 PM 8334114 ER PT J AU MCTIGUE, MA DAVIES, JF KAUFMAN, BT KRAUT, J AF MCTIGUE, MA DAVIES, JF KAUFMAN, BT KRAUT, J TI CRYSTAL-STRUCTURES OF CHICKEN LIVER DIHYDROFOLATE-REDUCTASE - BINARY THIONADP+ AND TERNARY THIONADP+.BIOPTERIN COMPLEXES SO BIOCHEMISTRY LA English DT Article ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; NUCLEAR MAGNETIC-RESONANCE; LACTOBACILLUS-CASEI; ESCHERICHIA-COLI; BACILLUS-STEAROTHERMOPHILUS; ALCOHOL-DEHYDROGENASE; LACTATE-DEHYDROGENASE; COENZYME ANALOGS; WILD-TYPE; BINDING AB The role of the 3'-carboxamide substituent of NADPH in the reduction of pteridine substrates as catalyzed by dihydrofolate reductase (EC 1.5.1.3, DHFR) has been investigated by determining crystal structures at 2.3 angstrom of chicken liver DHFR in a binary complex with oxidized thionicotinamide adenine dinucleotide (thioNADP+) and in a ternary complex with thioNADP+ and biopterin. These structures are isomorphous with those previously reported for chicken liver DHFR [Volz, K. W., Matthews, D. A., Alden, R. A., Freer, S. T ., Hansch, C., Kaufman, B. T., & Kraut, J. (1982) J. Biol. Chem. 257, 2528-2536]. ThioNADPH, which has a 3'-carbothioamide substituent in place of a 3'-carboxamide, functions very poorly as a coenzyme for DHFR [Williams, T. J., Lee, T. K., & Dunlap, R. B. (1977) Arch. Biochem. Biophys. 181, 569-579; Stone, S. R., Mark, A., & Morrison, J. F. (1984) Biochemistry 23, 4340-4346]. Comparisons show that, while NADP+ and NADPH bind to DHFR with the pyridine ring and 3'-carboxamide coplanar, the thioamide group is twisted by 23-degrees from the pyridine plane in both the binary and ternary complexes. This twist appears to be due to steric conflict between the thioamide sulfur atom and both the pyridine ring at C4 and the adjacent protein backbone at Ala-9. It results in an unfavorably close contact between the sulfur and the biopterin pteridine ring (0.9 angstrom less than the van der Waals separation) which, on the basis of there fined structure, greatly destabilizes the binding of biopterin. We infer that the thioamide in this position interferes with the transfer of a hydride ion from thioNADPH to the pteridine substrate by impeding movement of the coenzyme pyridine ring and substrate pteridine ring toward one another in the transition state. Thus, the planar conformation of the nicotinamide of NADPH when bound to DHFR appears to minimize steric repulsion during substrate binding to the holoenzyme complex and during transition-state formation. C1 UNIV CALIF SAN DIEGO,DEPT CHEM,LA JOLLA,CA 92093. NIDDK,BETHESDA,MD 20205. FU NCI NIH HHS [CA 17374]; NIGMS NIH HHS [GM07313] NR 63 TC 24 Z9 25 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 13 PY 1993 VL 32 IS 27 BP 6855 EP 6862 DI 10.1021/bi00078a008 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN442 UT WOS:A1993LN44200008 PM 8334118 ER PT J AU FORD, PC WINK, DA STANBURY, DM AF FORD, PC WINK, DA STANBURY, DM TI AUTOXIDATION KINETICS OF AQUEOUS NITRIC-OXIDE SO FEBS LETTERS LA English DT Review DE NITRIC OXIDE; DIOXYGEN; AUTOXIDATION; KINETICS; GENOTOXICITY; CYTOTOXICITY; BIOREGULATION ID RELAXING FACTOR; OXIDATION; RELEASE AB Reports on the kinetics of the autoxidation of aqueous nitric oxide are discussed. It is concluded that the correct rate law is -d[NO]/dt = 4k(aq)[NO]2[O2] with k(aq) = 2 x 10(6) M-2 . s-1 at 25-degrees-C and that a recent report of a rate law zero order in NO is incorrect. C1 NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. AUBURN UNIV,DEPT CHEM,AUBURN,AL 36849. RP FORD, PC (reprint author), UNIV CALIF SANTA BARBARA,DEPT CHEM,SANTA BARBARA,CA, USA. RI Ford, Peter/D-1826-2011 OI Ford, Peter/0000-0002-5509-9912 NR 15 TC 323 Z9 327 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 12 PY 1993 VL 326 IS 1-3 BP 1 EP 3 DI 10.1016/0014-5793(93)81748-O PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LM174 UT WOS:A1993LM17400001 PM 8325356 ER PT J AU KEMPNER, ES AF KEMPNER, ES TI MOVABLE LOBES AND FLEXIBLE LOOPS IN PROTEINS - STRUCTURAL DEFORMATIONS THAT CONTROL BIOCHEMICAL-ACTIVITY SO FEBS LETTERS LA English DT Review DE ENZYME; REACTION RATE; STRUCTURE FUNCTION; DOMAIN ID TRIOSEPHOSPHATE ISOMERASE; LACTATE-DEHYDROGENASE; CONFORMATIONAL CHANGE; BINDING; COMPLEX; SUBUNIT; MOTION; LIPASE; VIRUS; INHIBITOR AB Two classes of protein whose structure is modified by small ligands are reviewed. Proteins of one group contain two massive domains joined by a flexible link; in response to small molecules, the two lobes approach and enclose the ligand. In the other, a short segment of amino acids moves as a flexible loop over the ligand which often is trapped in a non-aqueous environment. Biochemical reaction rates are altered dramatically by these movements. RP KEMPNER, ES (reprint author), NIAMSD,PHYS BIOL LAB,BLDG 6,ROOM 120,BETHESDA,MD 20892, USA. NR 30 TC 71 Z9 72 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 12 PY 1993 VL 326 IS 1-3 BP 4 EP 10 DI 10.1016/0014-5793(93)81749-P PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LM174 UT WOS:A1993LM17400002 PM 8325386 ER PT J AU MISCHAK, H GOODNIGHT, J HENDERSON, DW OSADA, S OHNO, S MUSHINSKI, JF AF MISCHAK, H GOODNIGHT, J HENDERSON, DW OSADA, S OHNO, S MUSHINSKI, JF TI UNIQUE EXPRESSION PATTERN OF PROTEIN-KINASE-C -THETA - HIGH MESSENGER-RNA LEVELS IN NORMAL MOUSE TESTES AND IN T-LYMPHOCYTIC CELLS AND NEOPLASMS SO FEBS LETTERS LA English DT Article DE PROTEIN KINASE-C; ISOENZYME; EXPRESSION; LYMPHOCYTE; TESTIS; LYMPHOMA; SKELETAL MUSCLE ID PHORBOL ESTERS; HEMATOPOIETIC-CELLS; FAMILY; NPKC; ACTIVATION; ZETA; PKC; FIBROBLASTS; CLONING; CALCIUM AB A 2.2-kb cDNA that contains the entire coding region of mouse protein kinase C-theta (PKC-theta) was cloned from skeletal muscle mRNA using reverse transcription and the polymerase chain reaction (PCR). This clone was used as a probe to study the expression of this PKC isoform in normal and transformed hemopoietic cells and other normal tissues. By far the highest steady-state level of PKC-theta mRNA was found as a 2.8-kb transcript on a Northern blot of poly(A)+ RNA from testes. High levels were also found in skeletal muscle, spleen, T lymphomas and purified normal T lymphocytes, but these tissues and cells expressed two transcripts, 3.3 kb and 3.8 kb. Lower levels of similar size transcripts were found in normal brain, B lymphocytes and B-lymphocytic tumors and cell lines. C1 NCI,GENET LAB,MOLEC GENET SECT,BLDG 37,RM 2B04,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. YOKOHAMA CITY UNIV,SCH MED,DEPT MOLEC BIOL,KANAZAWA KU,YOKOHAMA 236,JAPAN. RI Mischak, Harald/E-8685-2011 NR 26 TC 42 Z9 42 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 JUL 12 PY 1993 VL 326 IS 1-3 BP 51 EP 55 DI 10.1016/0014-5793(93)81759-S PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LM174 UT WOS:A1993LM17400012 PM 8325388 ER PT J AU SHARMA, Y GOPALAKRISHNA, A BALASUBRAMANIAN, D FAIRWELL, T KRISHNA, G AF SHARMA, Y GOPALAKRISHNA, A BALASUBRAMANIAN, D FAIRWELL, T KRISHNA, G TI STUDIES ON THE INTERACTION OF THE DYE, STAINS-ALL, WITH INDIVIDUAL CALCIUM-BINDING DOMAINS OF CALMODULIN SO FEBS LETTERS LA English DT Article DE CALCIUM-BINDING DOMAIN; CALMODULIN EF-HAND MOTIF; STAINS-ALL; CIRCULAR DICHROISM ID TROPONIN-C; TRIFLUOPERAZINE BINDING; CA-2+-BINDING PROTEINS; CONFORMATIONAL-CHANGES; BRAIN CALMODULIN; ION BINDING; SITE-III; EF-HAND; CRYSTALLINS; TRYPTOPHAN AB We show that the calcium-mimic dye, Stains-all, is a convenient probe to study the structural features of the individual calcium-binding sites of calmodulin (CaM) and related calcium-binding proteins (CaBP). These peptides bind the dye in their calcium-binding sites, and induce a circular dichroism (CD) band in the bound dye in the 620 nm (J band) region, which is abolished upon the addition of calcium. Replacement of Asp by Asn in the +x position of the weaker calcium-binding site (site I of CaM) abolishes the dye binding, while the same change in the higher affinity site IV attenuates the binding of the dye and does not abolish it. Replacement of Tyr in site IV with Trp does not distort the geometry, although it increases the dye binding affinity. C1 NHLBI,CHEM PHARMACOL LAB,DRUG TISSUE INTERACT SECT,BLDG 10,RM 8N107,BETHESDA,MD 20892. CTR CELLULAR & MOLEC BIOL,HYDERABAD 500007,INDIA. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 33 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 12 PY 1993 VL 326 IS 1-3 BP 59 EP 64 DI 10.1016/0014-5793(93)81761-N PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LM174 UT WOS:A1993LM17400014 PM 8325390 ER PT J AU CHUANG, AJ KILLAM, KF CHUANG, RY RICE, WG SCHAEFFER, CA MENDELEYEV, J KUN, E AF CHUANG, AJ KILLAM, KF CHUANG, RY RICE, WG SCHAEFFER, CA MENDELEYEV, J KUN, E TI INHIBITION OF THE REPLICATION OF NATIVE AND 3'-AZIDO-2',3'-DIDEOXY-THYMIDINE (AZT)-RESISTANT SIMIAN IMMUNODEFICIENCY VIRUS (SIV) BY 3-NITROSOBENZAMIDE SO FEBS LETTERS LA English DT Article DE AZT-RESISTANT SIV; 6-NITROSOBENZAMIDE; ANTIVIRAL; ZINC FINGER; ANTI-AIDS ID REVERSE-TRANSCRIPTASE; HTLV-III; POLYMERASE; RETROVIRUS; MACAQUES; INVITRO; AGENTS; AIDS; AZT AB The 3-nitrosobenzamide (NOBA) drug abolishes SIV replication sharply at 20 muM concentration when CEM x 174 cells are preincubated for 1 h with the drug prior to viral infection. Treatment of CEM x 174 cells with 20 muM NOBA resulted in the inhibition of the synthesis of the DNA sequence coding for the gag gene, as determined by the PCR technique. Cell viability was directly proportional to the antiviral action of NOBA. Replication of AZT-resistant SIV 23740 in MMU 23740 cells in vitro was suppressed by NOBA in a concentration-dependent manner without significant effects on cell viability. Reverse transcriptase activity of SIV(max)239 was unaffected by NOBA up to 800 muM concentration. Preincubation of two SIV strains with NOBA completely abolished their infectivity in human PHA-PBL cells. Replication of two strains of SIV in PHA-PBL cells was also inhibited by NOBA. C1 SAN FRANCISCO STATE UNIV,ROMBERG TIBURON CTR,OCTAMER RES FDN,POB 855,TIBURON,CA 94920. UNIV CALIF DAVIS,SCH MED,DEPT MED PHARMACOL & TOXICOL,DAVIS,CA 95616. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,ANTIVIRAL DRUG MED LAB,FREDERICK,MD 21702. SAN FRANCISCO STATE UNIV,ROMBERG TIBURON CTR,ENVIRONM TOXICOL & CHEM LAB,TIBURON,CA 94920. FU NCI NIH HHS [N01-CO-7402]; NIDA NIH HHS [NIDA DA05901] NR 18 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 12 PY 1993 VL 326 IS 1-3 BP 140 EP 144 DI 10.1016/0014-5793(93)81778-X PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LM174 UT WOS:A1993LM17400031 PM 8325360 ER PT J AU RUGGIERO, M PAZZAGLI, C RIGACCI, S MAGNELLI, L RAUGEI, G BERTI, A CHIARUGI, VP PIERCE, JH CAMICI, G RAMPONI, G AF RUGGIERO, M PAZZAGLI, C RIGACCI, S MAGNELLI, L RAUGEI, G BERTI, A CHIARUGI, VP PIERCE, JH CAMICI, G RAMPONI, G TI NEGATIVE GROWTH-CONTROL BY A NOVEL LOW MR PHOSPHOTYROSINE PROTEIN PHOSPHATASE IN NORMAL AND TRANSFORMED-CELLS SO FEBS LETTERS LA English DT Article DE PHOSPHATASE; ONCOGENE; NEOPLASIA; INOSITOL LIPID ID CYTOSOLIC ACID-PHOSPHATASE; TYROSINE PHOSPHATASES; BOVINE HEART; RECEPTOR; EXPRESSION; LIVER; GENE; OVEREXPRESSION; DIACYLGLYCEROL; PURIFICATION AB Having determined the complete amino acid sequence of a cytosolic phosphatase purified from bovine liver, we studied the role of this enzyme (referred to as 'PTPase') in the control of cell proliferation. We used NIH/3T3 fibroblasts, both normal and transformed by the oncogenes v-erbB, v-src, and v-raf. a synthetic gene coding for PTPase was transfected into, and overexpressed in, normal and transformed NIH/3T3 cells with resulting inhibition of cell growth. Inhibition of proliferation correlated with the level of foreign PTPase; growth in soft apr was also inhibited in transformants overexpressing the enzyme. However, PTPase overexpression did not inhibit the rapid turnover of inositol lipids stimulated by platelet-derived growth factor. We conclude that this novel PTPase is active on cell type-specific signalling substrates that control normal and transformed fibroblast proliferation. C1 UNIV FLORENCE,DEPT BIOCHEM SCI,I-50134 FLORENCE,ITALY. NCI,LCMB,BETHESDA,MD 20892. RP RUGGIERO, M (reprint author), UNIV FLORENCE,INST GEN PATHOL,VIALE MORGAGNI 50,I-50134 FLORENCE,ITALY. NR 27 TC 41 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 12 PY 1993 VL 326 IS 1-3 BP 294 EP 298 DI 10.1016/0014-5793(93)81811-D PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LM174 UT WOS:A1993LM17400064 PM 8100784 ER PT J AU BENCHEKROUN, MN SINHA, BK ROBERT, J AF BENCHEKROUN, MN SINHA, BK ROBERT, J TI DOXORUBICIN-INDUCED OXYGEN-FREE RADICAL FORMATION IN SENSITIVE AND DOXORUBICIN-RESISTANT VARIANTS OF RAT GLIOBLASTOMA CELL-LINES SO FEBS LETTERS LA English DT Article DE ANTHRACYCLINE; ELECTRON SPIN RESONANCE SPECTROSCOPY; FREE RADICAL; ANTICANCER DRUG; REDOX ACTIVATION; LIPID PEROXIDATION ID TUMOR-CELLS; CYTOTOXICITY; GLUTATHIONE; ADRIAMYCIN; REDUCTION; EXPLAIN; TISSUE; ASSAY AB We have studied the formation of hydroxyl radical (OH.) induced by doxorubicin in a series of doxorubicin- or vincristine-selected variants of C6 rat glioblastoma cells in culture by electron-spin resonance spectroscopy using 5,5-dimethyl-1-pyrroline-1-oxide as a spin trap. Wild-type cells, sensitive to doxorubicin, exhibited in the presence of this drug a concentration-dependent OH' formation which could be inhibited by preincubation with superoxide dismutase, catalase or an antibody against cytochrome P450-reductase. In highly doxorubicin-resistant cells, OH. formation was reduced to about 20% of the level obtained in sensitive cells. In cells presenting a very low level of resistance to doxorubicin or in cells selected with vincristine, both presenting a pure multidrug-resistant phenotype, OH' formation was identical to that obtained in sensitive cells. In cells of intermediate resistance or in revertant cells, intermediate levels of OH' formation were obtained. Protection against OH' formation and action can be identified at the levels of superoxide dismutase and glutathione peroxidase activities, which are both enhanced in the resistant cells. C1 UNIV BORDEAUX 2,DEPT BIOCHIM MED & BIOL MOLEC,146 RUE LEO SAIGNAT,F-33076 BORDEAUX,FRANCE. NCI,BIOCHEM MOLEC PHARMACOL SECT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. FDN BERGONIE,BIOCHIM & PHARMACOL,F-33076 BORDEAUX,FRANCE. NR 15 TC 0 Z9 0 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 JUL 12 PY 1993 VL 326 IS 1-3 BP 295 EP 298 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LM174 UT WOS:A1993LM17400068 ER PT J AU MURPHY, MR SHIMIZU, M ROTH, SY DRANGINIS, AM SIMPSON, RT AF MURPHY, MR SHIMIZU, M ROTH, SY DRANGINIS, AM SIMPSON, RT TI DNA-PROTEIN INTERACTIONS AT THE SACCHAROMYCES-CEREVISIAE ALPHA-2-OPERATOR IN-VIVO SO NUCLEIC ACIDS RESEARCH LA English DT Article ID YEAST ALPHA-2 REPRESSOR; MATING TYPE LOCUS; SACCHAROMYCES-CEREVISIAE; CELL-TYPE; TRANSCRIPTIONAL REGULATOR; OPERATOR; GENE; MAT-ALPHA-1; EXPRESSION; BINDING AB Two homodimeric proteins, alpha2 and MCM1, are required to repress transcription of a-cell type specific genes in haploid yeast alpha-cells. In vitro studies by others of the interactions of these proteins with operator DNA have suggested that MCM1 binds to the middle and alpha2 to the ends of the 31 bp operator. We have previously shown that alpha2 organizes chromatin structure adjacent to the operator; in the presence of alpha2 repressor, a precisely positioned nucleosome abuts the operator in both minichromosomes and the genome. We present in vivo footprinting evidence consistent with occupancy of the operator by MCM1 in both a- and alpha-cells and by alpha2 repressor in alpha-cells. Interestingly, our in vivo results differ from previous in vitro work in detail. In contrast to the broad block of reagent accessibility to DNA by the factors seen in vitro, we find a pattern of strand-specific protection or augmented reactivity in vivo. The in vivo results are consistent with genetic data concerning transcriptional regulation of a-cell specific genes and corroborate the crystallographic data of others. C1 NIDDKD,CELLULAR & DEV BIOL LAB,BLDG 6,ROOM B1-28,BETHESDA,MD 20892. NR 28 TC 26 Z9 26 U1 0 U2 0 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 JUL 11 PY 1993 VL 21 IS 14 BP 3295 EP 3300 DI 10.1093/nar/21.14.3295 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN960 UT WOS:A1993LN96000021 PM 8341604 ER PT J AU ROBERTS, JW HOEG, JM MOURADIAN, MM LINFANTE, I CHASE, TN AF ROBERTS, JW HOEG, JM MOURADIAN, MM LINFANTE, I CHASE, TN TI IATROGENIC HYPERLIPEMIA WITH G(M1) GANGLIOSIDE SO LANCET LA English DT Letter C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. RP ROBERTS, JW (reprint author), NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892, USA. NR 2 TC 9 Z9 9 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 10 PY 1993 VL 342 IS 8863 BP 115 EP 115 DI 10.1016/0140-6736(93)91316-E PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LL789 UT WOS:A1993LL78900041 PM 8100881 ER PT J AU ABI-DARGHAM, A LARUELLE, M LIPSKA, B JASKIW, GE WONG, DT ROBERTSON, DW WEINBERGER, DR KLEINMAN, JE AF ABI-DARGHAM, A LARUELLE, M LIPSKA, B JASKIW, GE WONG, DT ROBERTSON, DW WEINBERGER, DR KLEINMAN, JE TI SEROTONIN 5-HT3 RECEPTORS IN SCHIZOPHRENIA - A POSTMORTEM STUDY OF THE AMYGDALA SO BRAIN RESEARCH LA English DT Article DE SEROTONIN(3) RECEPTOR; SCHIZOPHRENIA; ANTIPSYCHOTIC TREATMENT; AMYGDALA; [H-3]LY278584 ID HUMAN-BRAIN; RECOGNITION SITES; AUTORADIOGRAPHIC LOCALIZATION; H-3 LY278584; RAT; DOPAMINE; BINDING; IDENTIFICATION; RELEASE; SYSTEM AB Alterations in density of some serotonin receptor sites (5-HT1A receptors, 5-HT2 receptors and 5-HT uptake sites) have been reported in Postmortem studies of brain obtained from subjects with schizophrenia, suggesting a disturbance in serotonergic transmission in schizophrenia, The purpose of the present study is to investigate [H-3]-LY278584 binding to serotonin 5-HT3 receptors in postmortem samples of amygdala from schizophrenic and matched control subjects. As all of the schizophrenic patients but none of the controls had been treated with neuroleptics, we first investigated in rodents the effects of short-term and long-term haloperidol administration on limbic 5-HT3 receptors, and we found no effects. No differences in the maximum number of 5-HT3 binding sites (B(max)) or equilibrium dissociation constant (K(d)) between schizophrenics and controls were found in amygdala. This study does not support the presence of an alteration of 5-HT3 receptors in amygdala in schizophrenic patients. C1 ST ELIZABETH HOSP, NIMH,CTR NEUROSCI,IRP,CLIN BRAIN DISORDERS BRANCH, NEUROPATHOL SECT, WASHINGTON, DC 20032 USA. LIGAND PHARMACEUT, SAN DIEGO, CA 92121 USA. ELI LILLY & CO, LILLY RES LAB, INDIANAPOLIS, IN 46285 USA. NR 39 TC 18 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JUL 9 PY 1993 VL 616 IS 1-2 BP 53 EP 57 DI 10.1016/0006-8993(93)90191-O PG 5 WC Neurosciences SC Neurosciences & Neurology GA LL219 UT WOS:A1993LL21900008 PM 8358629 ER PT J AU HAUGER, RL IRWIN, MR LORANG, M AGUILERA, G BROWN, MR AF HAUGER, RL IRWIN, MR LORANG, M AGUILERA, G BROWN, MR TI HIGH INTRACEREBRAL LEVELS OF CRH RESULT IN CRH RECEPTOR DOWN-REGULATION IN THE AMYGDALA AND NEUROIMMUNE DESENSITIZATION SO BRAIN RESEARCH LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; AMYGDALA; ANTERIOR PITUITARY; CORTICOTROPIN-RELEASING HORMONE RECEPTOR; ADRENOCORTICOTROPIN HORMONE; CORTICOSTERONE; CELLULAR IMMUNITY ID CORTICOTROPIN-RELEASING-FACTOR; FACTOR-LIKE IMMUNOREACTIVITY; SYMPATHETIC NERVOUS-SYSTEM; ARGININE VASOPRESSIN; PARAVENTRICULAR NUCLEUS; DIFFERENTIAL REGULATION; IMMOBILIZATION STRESS; PITUITARY RECEPTORS; RAT-BRAIN; ADRENALECTOMY AB Corticotropin-releasing hormone (CRH) acts at the pituitary level to increase ACTH secretion and, within the central nervous system, to stimulate the sympathoadrenomedullary axis and behavioral activity. In addition, the central administration of CRH has been reported to reduce cellular immunity in the periphery. This study investigated the temporal relationship between CRH receptor regulation and the changes in splenic natural killer (NK) cell and pituitary-adrenocortical hormone responses to a single intracisternal (IC) CRH challenge (acute CRH) 24 h after chronic CRH pretreatment (5 nmol/day IC CRH for 4 days). Chronic CRH significantly decreased by 44.2 +/- 7.8% (P < 0.01) the CRH receptor concentration (beta(max)) in the amygdala. In contrast, the CRH receptor concentration of the anterior pituitary in the chronic CRH group was similar to the pituitary CRH receptor concentration in chronic saline controls. The immunoreactive-CRH concentration of the amygdala measured 24 h after the last IC CRH injection was not different from brain CRH levels in controls receiving chronic saline pretreatment. Consequently, the downregulation of amygdala CRH receptors occurred after transient increases in intracerebral CRH levels and did not result from ex vivo receptor occupancy by residual exogenous CRH sequestrated in brain tissue at the time of the CRH binding assay. Pretreatment with chronic CRH completely abolished the ability of a central CRH injection to suppress splenic NK activity; whereas, pituitary-adrenal responses to a superimposed acute CRH challenge were not significantly altered by chronic CRH pretreatment. These results suggest that the desensitization of the brain processes mediating CRH-induced suppression of splenic NK cytotoxicity is temporally correlated with CRH receptor downregulation in the amygdala but independent of pituitary-adrenal activation. These findings represent the first in vivo demonstration of homologous downregulation of extrahypothalamic CRH receptors and provide further evidence for the role of central CRH in the modulation of immune function. C1 UNIV CALIF SAN DIEGO,SAN DIEGO VET AFFAIRS MED CTR,DEPT MED,LA JOLLA,CA 92093. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. RP HAUGER, RL (reprint author), UNIV CALIF SAN DIEGO,VET AFFAIRS MED CTR,DEPT PSYCHIAT 0603,9500 GILMAN DR,LA JOLLA,CA 92093, USA. RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 FU NHLBI NIH HHS [HL 37716]; NIMH NIH HHS [NIMH MH 44275-03] NR 49 TC 47 Z9 48 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 9 PY 1993 VL 616 IS 1-2 BP 283 EP 292 DI 10.1016/0006-8993(93)90219-D PG 10 WC Neurosciences SC Neurosciences & Neurology GA LL219 UT WOS:A1993LL21900036 PM 8395304 ER PT J AU OVIEDO, A GLOWA, J HERKENHAM, M AF OVIEDO, A GLOWA, J HERKENHAM, M TI CHRONIC CANNABINOID ADMINISTRATION ALTERS CANNABINOID RECEPTOR-BINDING IN RAT-BRAIN - A QUANTITATIVE AUTORADIOGRAPHIC STUDY SO BRAIN RESEARCH LA English DT Article DE TETRAHYDROCANNABINOL; CANNABIDIOL; CP-55,940; CATALEPSY; TOLERANCE; AUTORADIOGRAPHY ID ADENYLATE-CYCLASE; LOCALIZATION; H-3-DELTA9-TETRAHYDROCANNABINOL; PHARMACOLOGY; CANNABIDIOL; TOLERANT; INVIVO; DRUGS AB The active ingredient of marijuana is (-)-DELTA9-tetrahydrocannabinol (DELTA9-THC). DELTA9-THC and other natural and synthetic cannabinoids such as CP-55,940 inhibit spontaneous activity and produce catalepsy in animals in a receptor-mediated fashion. Tolerance develops to the motor effects of DELTA9-THC after repeated administration. To test the hypothesis that tolerance is mediated by changes in cannabinoid receptor binding characteristics, we used quantitative in vitro autoradiography of [H-3]CP-55,940 binding to striatal brain sections from rats treated either chronically or acutely with DELTA9-THC, CP-55,940, or the inactive natural cannabinoid cannabidiol. In the chronic condition, rats were given daily i.p. injections of DELTA9-THC (10 mg/kg), cannabidiol (10 mg/kg), or CP-55,940 (1, 3, or 10 mg/kg) for 2 weeks and sacrificed 30 min after the last injection. In the acute condition, animals received a single dose (10 mg/kg) prior to sacrifice. Rats developed tolerance to the inhibitory effects of DELTA9-THC and CP-55,940, assayed in an open field on days 1, 7, and 14. Cannabidiol had no effect on behavior. Densitometry of [H-3]CP-55,940 binding to brain sections showed that DELTA9-THC- and CP-55,940-treated animals had homogeneous decreases in binding in all structures measured at the selected striatal level. Cannabidiol had no effect on binding. Analysis of binding parameters showed that alterations in the acute condition were attributed to changes in affinity (K(D)), whereas the major changes in the chronic condition were attributed to a lowering of capacity (B(max)). The effects in the 1, 3, and 10 mg/kg CP-55,940 conditions were dose-dependent and paralleled the behavioral data showing that the animals given the highest dose developed the greatest degree of tolerance. The data suggest that tolerance to cannabinoids results at least in part from agonist-induced receptor down-regulation. C1 NIMH, FUNCT NEUROANAT SECT, NIMH BLDG 36, ROOM 2D15, BETHESDA, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 55 TC 133 Z9 135 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 9 PY 1993 VL 616 IS 1-2 BP 293 EP 302 DI 10.1016/0006-8993(93)90220-H PG 10 WC Neurosciences SC Neurosciences & Neurology GA LL219 UT WOS:A1993LL21900037 PM 8395305 ER PT J AU HEIDBREDER, CA GOLDBERG, SR SHIPPENBERG, TS AF HEIDBREDER, CA GOLDBERG, SR SHIPPENBERG, TS TI THE KAPPA-OPIOID RECEPTOR AGONIST U-69593 ATTENUATES COCAINE-INDUCED BEHAVIORAL SENSITIZATION IN THE RAT SO BRAIN RESEARCH LA English DT Note DE COCAINE; U-69593; KAPPA-OPIOID; LOCOMOTOR ACTIVITY; STEREOTYPY ID NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; MOTIVATIONAL PROPERTIES; BINDING-SITES; BRAIN; OPIATE; DYNORPHIN; PEPTIDES; LIGAND; PLACE AB The effects of treatment with the selective kappa-opioid receptor agonist U-69593 upon cocaine-induced changes in locomotor activity and stereotypy were examined in rats. U-69593 (0.16 mg/kg s1.c.) administered either acutely or chronically attenuated both the motor stimulant effect and stereotypy produced by an acute injection of cocaine (20 mg/kg i.p.). Daily cocaine treatment resulted in sensitization to both effects of cocaine. In contrast, no such sensitized responses were seen in animals which had received U-69593 either prior to or in conjunction with daily cocaine treatment. These data demonstrate that activation of kappa-opioid receptors attenuates the acute and chronic effects of cocaine on locomotor activity and stereotypy. Given the inhibitory effects ascribed to both exogenous and endogenous kappa-opioid agonists upon dopamine release in the mesolimbic dopaminergic system, it is suggested that this action may underlie the observed effects of U-69593 on cocaine-induced changes in locomotor activity and stereotypy. C1 NIDA,BEHAV PHARMACOL & GENET SECT,PRECLIN PHARMACOL LAB,POB 5180,BALTIMORE,MD 21224. NR 30 TC 116 Z9 116 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 9 PY 1993 VL 616 IS 1-2 BP 335 EP 338 DI 10.1016/0006-8993(93)90228-F PG 4 WC Neurosciences SC Neurosciences & Neurology GA LL219 UT WOS:A1993LL21900045 PM 8395306 ER PT J AU BERNART, MW KASHMAN, Y TISCHLER, M CARDELLINA, JH BOYD, MR AF BERNART, MW KASHMAN, Y TISCHLER, M CARDELLINA, JH BOYD, MR TI BERSHACOLONE, AND UNPRECEDENTED DITERPENE CYCLOBUTENE FROM MAPROUNEA-AFRICANA SO TETRAHEDRON LETTERS LA English DT Article ID SECONDARY MOLD METABOLITES; FUNGUS LAURILIA-SULCATA; NATURAL-PRODUCTS; HIV-1 AB The organic extract of Maprounea africana was found to contain bershacolone (1), which was defined by spectral methods as a unique diterpene containing a cyclobutene ring within a novel carbon skeleton. C1 NCI,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 10 TC 10 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUL 9 PY 1993 VL 34 IS 28 BP 4461 EP 4464 DI 10.1016/0040-4039(93)88059-R PG 4 WC Chemistry, Organic SC Chemistry GA LM538 UT WOS:A1993LM53800010 ER PT J AU WISTOW, G AF WISTOW, G TI PROTEIN-STRUCTURE AND INTRONS SO NATURE LA English DT Letter RP WISTOW, G (reprint author), NEI,MOLEC STRUCT & FUNCT SECT,BETHESDA,MD 20892, USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 8 PY 1993 VL 364 IS 6433 BP 107 EP 108 DI 10.1038/364107b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LL367 UT WOS:A1993LL36700029 PM 7686630 ER PT J AU GURALNIK, JM LAND, KC BLAZER, D FILLENBAUM, GG BRANCH, LG AF GURALNIK, JM LAND, KC BLAZER, D FILLENBAUM, GG BRANCH, LG TI EDUCATIONAL STATUS AND ACTIVE LIFE EXPECTANCY AMONG OLDER BLACKS AND WHITES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ALAMEDA COUNTY; UNITED-STATES; NATURAL DEATH; MORTALITY; COMPRESSION; PREDICTORS; MORBIDITY; DISEASE; ELDERS; RISK AB Background and Methods. Persons of low socioeconomic status are known to have reduced life expectancy. In a study of the relation of socioeconomic status to disability-free or active life expectancy among older persons, we analyzed prospectively gathered data on 2219 blacks and 1838 whites who were 65 years of age or older in the Piedmont region of North Carolina. We defined disability as the inability to perform independently one or more basic functional activities such as walking, bathing, dressing, eating, and using the toilet. For subgroups defined by sex, race, and education, statistical models were used to estimate, for persons at each year of age, the probability of transition from not being disabled or being disabled at base line to not being disabled, being disabled, or having died one year later. These transition probabilities were then entered into increment-decrement life tables to generate estimates of total, active, and disabled life expectancy (with total life expectancy equal to active life expectancy plus disabled life expectancy). Results. Sixty-five-year-old black men had a lower total life expectancy (11.4 years) and active life expectancy (10 years) than white men (total life expectancy, 12.6 years; active life expectancy, 11.2 years), although the differences were reduced after we controlled for education. The estimates for 65-year-old black women (total life expectancy, 18.7 years; active life expectancy, 15.9 years) were similar to those for white women. Black men and women 75 years old and older had higher values for total life expectancy and active life expectancy than whites, and the differences were larger after stratification for education. Education had a substantially stronger relation to total life expectancy and active life expectancy than did race. At the age of 65, those with 12 or more years of education had an active life expectancy that was 2.4 to 3.9 years longer than the values for those with less education in all the four subgroups defined by sex and race. Overall, the subgroups with longer total life expectancy and active life expectancy also lived more years with a disability. Conclusions. Among older blacks and whites, the level of education, a measure of socioeconomic status, has a greater effect than race on total life expectancy and active life expectancy. C1 DUKE UNIV,DEPT SOCIOL,DURHAM,NC 27706. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27710. BOSTON UNIV,SCH MED,BOSTON,MA 02118. ABT ASSOCIATES INC,CAMBRIDGE,MA 02138. RP GURALNIK, JM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,RM 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-1-2102] NR 47 TC 334 Z9 335 U1 1 U2 10 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 JUL 8 PY 1993 VL 329 IS 2 BP 110 EP 116 DI 10.1056/NEJM199307083290208 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA LL196 UT WOS:A1993LL19600008 PM 8510687 ER PT J AU TRACHTENBERG, AI ORAVEC, L AF TRACHTENBERG, AI ORAVEC, L TI THE LAW AND CONTROL OF TUBERCULOSIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP TRACHTENBERG, AI (reprint author), NIDA,ROCKVILLE,MD 20857, USA. NR 3 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 JUL 8 PY 1993 VL 329 IS 2 BP 136 EP 137 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LL196 UT WOS:A1993LL19600022 PM 8510696 ER PT J AU SWEDO, SE LENANE, MC LEONARD, HL AF SWEDO, SE LENANE, MC LEONARD, HL TI LONG-TERM TREATMENT OF TRICHOTILLOMANIA (HAIR PULLING) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CLOMIPRAMINE RP SWEDO, SE (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 4 TC 45 Z9 47 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 JUL 8 PY 1993 VL 329 IS 2 BP 141 EP 142 DI 10.1056/NEJM199307083290220 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LL196 UT WOS:A1993LL19600035 PM 8510704 ER PT J AU HATCH, EE BRACKEN, MB AF HATCH, EE BRACKEN, MB TI CAFFEINE USE DURING PREGNANCY - HOW MUCH IS SAFE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 YALE UNIV,SCH MED,NEW HAVEN,CT 06510. RP HATCH, EE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 4 TC 3 Z9 3 U1 0 U2 0 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 JUL 7 PY 1993 VL 270 IS 1 BP 46 EP 47 DI 10.1001/jama.270.1.46 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LK366 UT WOS:A1993LK36600017 PM 8357378 ER PT J AU LILLIEBLANTON, M ANTHONY, JC SCHUSTER, CR AF LILLIEBLANTON, M ANTHONY, JC SCHUSTER, CR TI RACE AND CRACK COCAINE - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIDA,BALTIMORE,MD. RP LILLIEBLANTON, M (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218, USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 JUL 7 PY 1993 VL 270 IS 1 BP 46 EP 46 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LK366 UT WOS:A1993LK36600016 ER PT J AU MILLS, JL GRAUBARD, BI BROWN, ZA SIMPSON, JL HOLMES, LB AF MILLS, JL GRAUBARD, BI BROWN, ZA SIMPSON, JL HOLMES, LB TI CAFFEINE USE DURING PREGNANCY - HOW MUCH IS SAFE - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NCI,BETHESDA,MD 20892. UNIV WASHINGTON,SCH MED,SEATTLE,WA 98195. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. RP MILLS, JL (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 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 JUL 7 PY 1993 VL 270 IS 1 BP 47 EP 48 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LK366 UT WOS:A1993LK36600019 ER PT J AU DROLLER, MJ ANDERSON, JR BECK, JC BREMNER, WJ EVANS, K GRAY, M KEENEY, AH LANZISERA, PJ LIAO, WC RICHARDSON, DW ROHNER, TJ SHORTLIFFE, LD TURNER, WR ZITRIN, A HALL, WH AF DROLLER, MJ ANDERSON, JR BECK, JC BREMNER, WJ EVANS, K GRAY, M KEENEY, AH LANZISERA, PJ LIAO, WC RICHARDSON, DW ROHNER, TJ SHORTLIFFE, LD TURNER, WR ZITRIN, A HALL, WH TI IMPOTENCE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 NIH, OFF MED APPLICAT RES,FED BLDG,ROOM 618, 7550 WISCONSIN AVE, BETHESDA, MD 20892 USA. MT SINAI MED CTR, DEPT UROL, NEW YORK, NY 10029 USA. UNIV NEBRASKA, MED CTR, DEPT PREVENT & SOCIETAL MED, OMAHA, NE 68105 USA. UNIV CALIF LOS ANGELES, SCH MED, MULTICAMPUS PROGRAM GERIATR MED & GERONTOL, LOS ANGELES, CA USA. VET AFFAIRS MED CTR, SEATTLE, WA USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. KAISER PERMANENTE, DEPT UROL, DALLAS, TX USA. GEORGIA STATE UNIV, SCH NURSING, ALPHARETTA, GA USA. AMER FDN UROL DIS, BALTIMORE, MD USA. HENRY FORD HLTH SCI CTR, DEPT PSYCHIAT, PSYCHOL INTERNSHIP PROGRAM, DETROIT, MI USA. RES TRIANGLE INST, CTR EPIDEMIOL & MED STUDIES, RES TRIANGLE PK, NC 27709 USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT CARDIOL, RICHMOND, VA 23298 USA. PENN STATE UNIV, MILTON S HERSHEY MED CTR, COLL MED, DIV UROL, HERSHEY, PA 17033 USA. STANFORD UNIV, PACKARD CHILDRENS HOSP, SCH MED, DEPT UROL, STANFORD, CA 94305 USA. MED UNIV S CAROLINA, DEPT UROL, CHARLESTON, SC 29425 USA. NYU, SCH MED, NEW YORK, NY 10003 USA. NR 0 TC 1268 Z9 1293 U1 3 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 7 PY 1993 VL 270 IS 1 BP 83 EP 90 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA LK366 UT WOS:A1993LK36600029 ER PT J AU SOLOMON, D AF SOLOMON, D TI SCREENING FOR CERVICAL-CANCER - PROSPECTS FOR THE FUTURE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material RP SOLOMON, D (reprint author), NCI,DIV CANC BIOL DIAG & CTR,BLDG 10,RM 2A19,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 12 Z9 13 U1 0 U2 0 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 JUL 7 PY 1993 VL 85 IS 13 BP 1018 EP 1019 DI 10.1093/jnci/85.13.1018 PG 2 WC Oncology SC Oncology GA LK823 UT WOS:A1993LK82300001 PM 8515480 ER PT J AU ROUZER, CA THOMPSON, EJ SKINNER, TL HEAVNER, PA BARTOLINI, WP MITCHELL, K KURZ, E SMITH, RH MICHEJDA, CJ AF ROUZER, CA THOMPSON, EJ SKINNER, TL HEAVNER, PA BARTOLINI, WP MITCHELL, K KURZ, E SMITH, RH MICHEJDA, CJ TI AN UNEXPECTED PATHWAY FOR THE METABOLIC-DEGRADATION OF 1,3-DIALKYL-3-ACYLTRIAZENES SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID ALKYLATING-AGENTS; DECOMPOSITION; 1,3-DIALKYLTRIAZENES; TRIALKYLTRIAZENES; TRIAZENES; PRODUCTS; RATES; DNA AB In the presence of NADPH, rat liver microsomes catalyzed the degradation of a series of 1,3-dialkyl-3-acyltriazenes, and the extent of the reaction was correlated with compound lipophilicity. In the case of two methylcarbamoyltriazenes, 1-(2-chloroethyl)-3-benzyl-3-(methylcarbamoyl)triazene (CBzM) and 1-(2-chloroethyl)-3-methyl-3-(methylcarbamoyl)triazene (CMM), microsomal metabolites were isolated. Identification of the CBzM metabolites as 1-(2-chloroethyl)-3-benzyl-3-(hydroxymethylcarbamoyl) triazene and 1-(2-chloroethyl)-3-benzyl-3-carbamoyltriazene, and the CMM metabolite as 1-(2-chloroethyl)-3-methyl-3-(hydroxymethylcarbamoyl)triazene indicated that the first metabolic step involves hydroxylation of the methylcarbamoyl substituent. Detailed studies of the metabolism of CBzM indicated that the K(m) for the reaction was 84 muM, and that metabolism was more efficient if microsomes were prepared from male than from female rats. During prolonged incubation, the metabolites of CBzM were also degraded. The degradation of CBzM and its metabolites was inhibited by SKF-525A and metyrapone, suggesting the involvement of a cytochrome P450 isozyme, and supporting the hypothesis that the process is oxidative rather than hydrolytic in both cases. Metabolic oxidation represents an alternative pathway to chemical or enzymatic hydrolysis for the in vivo decomposition of methylcarbamoyl)triazenes. This mechanism may ultimately explain the antitumor efficacy and low acute toxicity of selected compounds. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC ASPECTS DRUG DESIGN SECT,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP ROUZER, CA (reprint author), WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157, USA. FU NCI NIH HHS [N01-CO-74101] NR 23 TC 4 Z9 4 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 6 PY 1993 VL 46 IS 1 BP 165 EP 173 DI 10.1016/0006-2952(93)90361-Y PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LP955 UT WOS:A1993LP95500021 PM 8347127 ER PT J AU FREDERICO, LA KUNKEL, TA SHAW, BR AF FREDERICO, LA KUNKEL, TA SHAW, BR TI CYTOSINE DEAMINATION IN MISMATCHED BASE-PAIRS SO BIOCHEMISTRY LA English DT Article ID DEOXYRIBONUCLEIC-ACID; ESCHERICHIA-COLI; IMINO PROTON; DNA; EXCHANGE; REPAIR; EFFICIENCIES; DEPURINATION; DUPLEXES AB The rate of deamination of cytosine in mismatched base pairs has been determined. Incubation of M13mp2 nicked heteroduplex DNA molecules containing T.C or C.C mispairs in the lacZ alpha-complementation gene results in deamination of cytosine to uracil, producing T.U or C.U mispairs. Strands which have undergone deamination at the target site to produce uracil will yield dark blue plaque revertants, while all other strands yield faint blue or colorless plaque phenotypes upon transfection of an ung- alpha-complementation Escherichia coli host strain. Rate constants were calculated from the reversion frequencies for several different heteroduplexes incubated at either 60 or 37-degrees-C. For the 60-degrees-C incubations, the hydrolytic deamination rate constants for mispairs in three different local sequence environments ranged from 8 x 10(-10) to 40 x 10(-10) s-1. For incubations at 37-degrees-C, the rate constants were between 0.4 x 10(-10) and 1.3 x 10(-10) sec-1. At both temperatures and for all mispairs, these rate constants are significantly greater than deamination rate constants in properly matched Watson-Crick G.C base pairs and are similar to those constants determined for cytosine deamination in single-stranded DNA. Since deamination most likely occurs via a single-stranded intermediate, the data suggest that, at 37-degrees-C, the T.C and C.C mispairs exhibit from 20% to 100% single-stranded character. We conclude that cytosine residues involved in a mispair in DNA are 1-2 orders of magnitude more prone to deaminate to uracil than are cytosines in double-stranded DNA. These studies underscore the importance of Watson-Crick base-pairing interactions in maintaining the genetic integrity of DNA. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. DUKE UNIV,PM GROSS CHEM LAB,DEPT CHEM,DURHAM,NC 27708. FU NCI NIH HHS [CA 44709] NR 22 TC 63 Z9 64 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 6 PY 1993 VL 32 IS 26 BP 6523 EP 6530 DI 10.1021/bi00077a005 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN434 UT WOS:A1993LN43400005 PM 8329382 ER PT J AU KUNZ, BC MUCZYNSKI, KA WELSH, CF STANLEY, SJ TSAI, SC ADAMIK, R CHANG, PP MOSS, J VAUGHAN, M AF KUNZ, BC MUCZYNSKI, KA WELSH, CF STANLEY, SJ TSAI, SC ADAMIK, R CHANG, PP MOSS, J VAUGHAN, M TI CHARACTERIZATION OF RECOMBINANT AND ENDOGENOUS ADP-RIBOSYLATION FACTORS SYNTHESIZED IN SF9 INSECT CELLS SO BIOCHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING PROTEIN; CHOLERA-TOXIN; EXPRESSION VECTORS; BOVINE BRAIN; ADENYLATE-CYCLASE; MYRISTIC ACID; GTP; COFACTOR; MYRISTYLATION; PURIFICATION AB ADP-ribosylation factors (ARFs) are a family of highly conserved, 20-kDa guanine nucleotide-binding proteins that participate in protein trafficking and enhance cholera toxin-catalyzed ADP-ribosylation. ARF 2 from bovine retinal cDNA was expressed in Sf9 insect cells using recombinant baculovirus and compared to the major insect cell ARF (Sf9 ARF) and to recombinant ARF 2 expressed in Escherichia coli (E. coli rARF 2). The 150000g supernatant and particulate fractions of freeze-thawed, recombinant ARF 2 baculovirus-infected cells contained immunoreactive proteins of 20 and 21 kDa at significantly higher levels than were found in uninfected cells. Infected Sf9 cells incorporated [H-3]myristate only into the 20-kDa protein. Sf9 cell recombinant ARF 2 (Sf9 rARF 2) and Sf9 ARF were separated by isoelectric focusing or ion-exchange chromatography and identified by microsequencing of HPLC-purified tryptic peptides. Sf9 ARF displayed considerable sequence identity to mammalian class I ARFs. Both Sf9 ARF and Sf9 rARF 2 stimulated in a GTP-dependent manner cholera toxin-catalyzed ADP-ribosylation. The K(a) for GTP of Sf9 ARF was, however, significantly lower than that of Sf9 rARF 2 or E. coli rARF 2. Myristoylation did not significantly affect the ability of ARF 2 to enhance cholera toxin-catalyzed ADP-ribosylation or the K(a) for GTP. Despite the sequence identities and the fact that both were synthesized in insect cells, the endogenous Sf9 ARF was functionally different from Sf9 rARF 2. C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. NR 39 TC 8 Z9 8 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 6 PY 1993 VL 32 IS 26 BP 6643 EP 6648 DI 10.1021/bi00077a017 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN434 UT WOS:A1993LN43400017 PM 8392366 ER PT J AU ARCHER, SJ VINSON, VK POLLARD, TD TORCHIA, DA AF ARCHER, SJ VINSON, VK POLLARD, TD TORCHIA, DA TI SECONDARY STRUCTURE AND TOPOLOGY OF ACANTHAMOEBA PROFILIN-I AS DETERMINED BY HETERONUCLEAR NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY SO BIOCHEMISTRY LA English DT Article ID LARGER PROTEINS; PHYSARUM-POLYCEPHALUM; N-15-LABELED PROTEINS; PHOSPHOLIPASE-C; N-15 NMR; ACTIN; C-13; ASSIGNMENTS; COHERENCE; GELSOLIN AB The protein profilin binds to both actin and the head groups of poly(phosphoinositide)s and may regulate both actin assembly and the phosphoinositide signaling pathway. As a first step in understanding the activity of profilin at the molecular level, we have determined the secondary structure of Acanthamoeba profilin I in solution using multidimensional, heteronuclear NMR spectroscopy. Using a combination of triple-resonance (H-1, C-13, N-15) experiments, we obtained virtually complete backbone and side-chain resonance assignments based solely on scalar couplings. 3D and 4D NOESY experiments were then used to determine the secondary structure and global fold of Acanthamoeba profilin I. The central feature of the protein structure is a five-stranded antiparallel beta-sheet flanked by three helices and a short two-stranded antiparallel beta-sheet. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. FU NIGMS NIH HHS [GM-35171, GM13620] NR 38 TC 25 Z9 26 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 JUL 6 PY 1993 VL 32 IS 26 BP 6680 EP 6687 DI 10.1021/bi00077a022 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN434 UT WOS:A1993LN43400022 PM 8329394 ER PT J AU POWERS, R GARRETT, DS MARCH, CJ FRIEDEN, EA GRONENBORN, AM CLORE, GM AF POWERS, R GARRETT, DS MARCH, CJ FRIEDEN, EA GRONENBORN, AM CLORE, GM TI THE HIGH-RESOLUTION, 3-DIMENSIONAL SOLUTION STRUCTURE OF HUMAN INTERLEUKIN-4 DETERMINED BY MULTIDIMENSIONAL HETERONUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY SO BIOCHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; HUMAN GROWTH-HORMONE; POTATO CARBOXYPEPTIDASE INHIBITOR; INTERPROTON DISTANCE RESTRAINTS; IMMUNOGLOBULIN BINDING DOMAIN; MULTIPLE QUANTUM COHERENCE; STREPTOCOCCAL PROTEIN-G; BOUND WATER-MOLECULES; NMR-SPECTROSCOPY; LARGER PROTEINS AB The high-resolution three-dimensional solution structure of recombinant human interleukin-4 (IL-4), a protein of approximately 15 kDa which plays a key role in the regulation of B and T lymphocytes, has been determined using three- and four-dimensional heteronuclear NMR spectroscopy. The structure is based on a total of 2973 experimental NMR restraints, comprising 2515 approximate interproton distance restraints, 102 distance restraints for 51 backbone hydrogen bonds, and 356 torsion angle restraints. A total of 30 structures was calculated by means of hybrid distance geometry-simulated annealing, and the atomic rms distribution about the mean coordinate positions for residues 8-129 is 0.44 +/- 0.03 angstrom for the backbone atoms, 0.83 +/- 0.03 angstrom for all atoms, and 0.51 +/- 0.04 angstrom for all atoms excluding disordered side chains. The N- and C-terminal residues (1-7 and 130-133, respectively) appear to be disordered. The structure of IL-4 is dominated by a left-handed four-helix bundle with an unusual topology comprising two overhand connections. The linker elements between the helices are formed by either long loops, small helical turns, or short strands. The latter include a mini anti-parallel beta-sheet. A best fit superposition of the NMR structure of IL-4 with the 2.25 angstrom resolution crystal structure [Wlodawer, A., Pavlovsky, A., & Gutschina, A. (1992) FEBS Lett. 309, 59-64] yields a backbone atomic rms difference of 1.37 angstrom which can be mainly attributed to tighter packing of the helices in the crystal structure. This is indicated by an approximately 20% reduction in the axial separation of three pairs of helices (alpha(A)-alpha(C), alpha(A)-alpha(D), and alpha(C)-alpha(D)) in the crystal structure relative to the NMR structure and may reflect the greater flexibility of the molecule in solution which is reduced in the crystal due to intermolecular contacts. Comparison of the NMR structure of IL-4 with the X-ray structures of two other related proteins, granulocyte-macrophage colony stimulating factor [Diedrichs, K., Boone, T., & Karplus, P. A. (1992) Science 254, 1779-1782] and human growth hormone [de Vos, A. M., Ultsch, M., & Kossiakoff, A. A. (1992) Science 255, 306-312], that bind to the same hematopoietic superfamily of cell surface receptors reveals a remarkably similar topological fold, despite the absence of any significant overall sequence identity, and substantial differences in the relative lengths of the helices, the lengths and the nature of the various connecting elements, and the pattern and number of disulfide bridges. Indeed, the C(alpha) atom coordinates of 72 and 79 residues of IL-4 can be superimposed on the C(alpha) coordinates of granulocyte-macrophage colony stimulating factor and human growth hormone with rms differences of approximately 1.7 and 2.0 angstrom, respectively. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. IMMUNEX CORP,SEATTLE,WA 98101. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 98 TC 122 Z9 124 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 6 PY 1993 VL 32 IS 26 BP 6744 EP 6762 DI 10.1021/bi00077a030 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN434 UT WOS:A1993LN43400030 PM 8329398 ER PT J AU CHEN, KH WIDEN, SG WILSON, SH HUANG, KP AF CHEN, KH WIDEN, SG WILSON, SH HUANG, KP TI IDENTIFICATION OF A NUCLEAR-PROTEIN BINDING-ELEMENT WITHIN THE RAT-BRAIN PROTEIN-KINASE-C GAMMA PROMOTER THAT IS RELATED TO THE DEVELOPMENTAL CONTROL OF THIS GENE SO FEBS LETTERS LA English DT Article DE PROTEIN KINASE-C GAMMA GENE; DEVELOPMENTAL REGULATION; DNA BINDING PROTEIN ID TRANSCRIPTION FACTOR; INVITRO TRANSCRIPTION; 5'-FLANKING REGION; DNA-BINDING; 1ST INTRON; CYCLIC-AMP; ENHANCER; SEQUENCE; EXPRESSION; INDUCTION AB Protein kinase C gamma (PKC gamma) is a brain-specific isozyme expressed at a high level in the adult but not in the fetal or newborn rat. At least seventeen nuclear protein binding sites within the 5'-flanking region extending from - 1612 to +243 had been identified by DNase I footprinting analysis and gel mobility shift assays. Among them, one site, GAATTAATAGG, at -669 to -679 is protected from DNase I digestion by nuclear protein from newborn but not from the adult rat brain. The levels of this binding protein, as determined by gel mobility shift assay, were found inversely related to the levels of PKC gamma in rat brain at different stages of development. These results suggest that this particular binding site may participate in the developmental regulation of PKC gamma gene. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,ROOM 6A-36,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 35 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 5 PY 1993 VL 325 IS 3 BP 210 EP 214 DI 10.1016/0014-5793(93)81075-B PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LK454 UT WOS:A1993LK45400011 PM 8319805 ER PT J AU ADACHI, Y COPELAND, TD HATANAKA, M OROSZLAN, S AF ADACHI, Y COPELAND, TD HATANAKA, M OROSZLAN, S TI NUCLEOLAR TARGETING SIGNAL OF REX PROTEIN OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I SPECIFICALLY BINDS TO NUCLEOLAR SHUTTLE PROTEIN-B-23 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MESSENGER-RNA; HTLV-I; TRANS-ACTIVATION; GENE-EXPRESSION; SEQUENCES; IDENTIFICATION; P40X; PHOSPHORYLATION; LOCALIZATION AB Rex protein, the post-transcriptional regulator of human T-cell leukemia virus type I, is located predominantly in the cell nucleolus and is associated with the cytoplasmic accumulation of unspliced and singly spliced viral mRNAs. The N-terminal 19-amino acid segment of Rex has been identified as the nucleolar targeting signal (NOS) and shown to be important for Rex function. To study the molecular interaction between the NOS region of Rex and its binding host protein(s) in the nucleolus, we chemically synthesized a functional NOS peptide (wild type) and mutant NOS peptides. Fluorescein isothiocyanate-conjugated functional NOS peptide was rapidly taken up by human cells and was transported to the nucleolus. Using affinity chromatography, we identified nucleolar protein B-23 as the major protein that binds to NOS. We also identified two highly acidic regions of B-23 (amino acids 120-132 and 161-188) as acceptor regions for NOS. Previous experiments have suggested that B-23 functions as a shuttle protein for the nucleolar transport of ribosomal components. Our results suggest that B-23 may also serve as a shuttle for the import of Rex from the cytoplasm to the nucleolus coupled to the export of viral mRNAs containing the Rex-responsive element. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,PROT STRUCT GRP,FREDERICK,MD 21702. KYOTO UNIV,INST VIRUS RES,SAKYO KU,KYOTO 606,JAPAN. FU NCI NIH HHS [N01-CO-74101] NR 47 TC 103 Z9 109 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 JUL 5 PY 1993 VL 268 IS 19 BP 13930 EP 13934 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500026 PM 8314759 ER PT J AU SAKATA, SF SHELLY, LL RUPPERT, S SCHUTZ, G CHOU, JY AF SAKATA, SF SHELLY, LL RUPPERT, S SCHUTZ, G CHOU, JY TI CLONING AND EXPRESSION OF MURINE S-ADENOSYLMETHIONINE SYNTHETASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE AMINOTRANSFERASE GENE; DNA-BINDING; CYCLIC-AMP; RAT-LIVER; ARABIDOPSIS-THALIANA; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; STRUCTURAL GENE; MESSENGER-RNA; TRANSCRIPTION AB Mice homozygous for chromosomal deletions at or around the albino locus on chromosome 7 express reduced levels of a group of liver genes. Here, we report the isolation and characterization of cDNA and genomic clones encoding one of the affected genes, the mouse adult liver S-adenosylmethionine (AdoMet) synthetase. This enzyme catalyzes the synthesis of AdoMet, which functions in transmethylation and transsulfuration. Mouse AdoMet synthetase cDNA is 3232 base pairs (bp) in length and contains an open reading frame that encodes an enzymatically active polypeptide of 396 amino acids. The mouse AdoMet synthetase shares 98 and 96% amino acid sequence identity with the adult liver enzyme in the rat and human, respectively. AdoMet synthetases possess the consensus ATP-binding motif Gly-X-Gly-X-X-Gly and a putative ATP-binding Lys residue at conserved locations. As an initial step toward understanding the control of AdoMet synthetase gene expression, we characterized the complete transcription unit of this gene. The AdoMet synthetase gene spans approximately 18 kilobases and consists of nine exons ranging from 78 to 1920 bp. The transcription initiation site was demonstrated by rapid amplification of cDNA ends and confirmed by primer extension studies. A putative TATA box is located at -28 to -23 bp upstream of the transcription start site. The cis-acting DNA elements in the 5'-flanking region of the AdoMet synthetase gene that drive chloramphenicol acetyltransferase gene expression in mouse hepatocytes were identified by transient expression assays. The -365 to -2-bp DNA region upstream of the transcription start site of the AdoMet synthetase gene contains promoter elements, and the -518 to -366-bp DNA region might be involved in negative gene regulation. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,RM 95242,BETHESDA,MD 20892. GERMAN CANC RES CTR,INST CELL & TUMOR BIOL,W-6900 HEIDELBERG,GERMANY. NR 59 TC 51 Z9 53 U1 1 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 JUL 5 PY 1993 VL 268 IS 19 BP 13978 EP 13986 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500033 PM 8314764 ER PT J AU WADA, N CHOU, JY AF WADA, N CHOU, JY TI CHARACTERIZATION OF UPSTREAM ACTIVATION ELEMENTS ESSENTIAL FOR THE EXPRESSION OF GERM-CELL ALKALINE-PHOSPHATASE IN HUMAN CHORIOCARCINOMA CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; GENE-EXPRESSION; BINDING-FACTOR; DNA-BINDING; CACCC-BOX; SEQUENCE; PROMOTER; SP1; PHOSPHATIDYLINOSITOL; TRANSFECTION AB Expression of the germ cell alkaline phosphatase is a highly regulated process tied to malignant transformation of the human placenta. Human choriocarcinoma cells (malignant trophoblasts) express primarily the germ cell alkaline phosphatase gene and only low or nondetectable levels of the placental alkaline phosphatase normally found in the human placenta. Here, we show that nucleotides -156 to -1 region relative to the gene transcription start site (+1) contain cis-acting DNA elements that direct germ cell alkaline phosphatase expression in choriocarcinoma cells. Within the minimal activator region, at least three nuclear protein-binding sites, I (-63/-44), II (-87/-67), and III (-136/-103), were identified by DNase I footprinting analysis. All three sites are GC-rich. Sites I and II contain a sequence known to bind the transcription factor AP-2; the AP-2 site in site II overlaps a consensus motif for the transcription factor Sp1. Gel retardation experiments showed that similar nuclear protein factor(s) in JEG-3 choriocarcinoma cells bind to all three sites, with highest affinity to sites I and II. Site-directed mutagenesis that prevents binding of nuclear proteins to either site I or II, or both sites I and II, resulted in the loss of factor binding and reduced activator activity. The germ cell alkaline phosphatase promoter that contains an intact binding site III but altered sites I and II had little activator activity, suggesting that protein-protein interaction is important for germ cell alkaline phosphatase gene activation. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,RM 9S242,BETHESDA,MD 20892. NR 49 TC 16 Z9 16 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 JUL 5 PY 1993 VL 268 IS 19 BP 14003 EP 14010 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500036 PM 8314767 ER PT J AU DEBINSKI, W PURI, RK KREITMAN, RJ PASTAN, I AF DEBINSKI, W PURI, RK KREITMAN, RJ PASTAN, I TI A WIDE-RANGE OF HUMAN CANCERS EXPRESS INTERLEUKIN-4 (IL4) RECEPTORS THAT CAN BE TARGETED WITH CHIMERIC TOXIN COMPOSED OF IL4 AND PSEUDOMONAS EXOTOXIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUSION PROTEIN; RECOMBINANT IMMUNOTOXIN; ESCHERICHIA-COLI; ANIMAL TOXICITY; TUMOR-CELLS; CYTOTOXICITY; AERUGINOSA; SEQUENCES; CARCINOMA; DOMAINS AB A chimeric toxin has been constructed by fusion of a gene encoding human interleukin 4 (hIL4) to a gene encoding a mutant form of Pseudomonas exotoxin A (PE) which cannot bind to its receptors (PE4E). The chimeric gene was expressed in Escherichia coli where large amounts of the chimeric toxin, hIL4-PE4E, was produced. Purified hIL4-PE4E was very cytotoxic to cancer cell lines of both hematopoietic and solid tumor origin. In the HUT 102 T cell leukemia and Daudi B cell lymphoma cell lines, protein synthesis was inhibited by 50% (ID50) at a hIL4-PE4E concentration of 2 and 7 ng/ml (25 and 86 pM, respectively). hIL4-PE4E was also very cytotoxic to cell lines derived from carcinomas of the colon, breast, stomach, liver, adrenals, and prostate, as well as melanoma and epidermoid carcinoma, indicating that hIL4 receptors are widely expressed on human malignancies. We also found that human phytohemagglutinin- activated peripheral blood lymphocytes were extremely sensitive to hIL4-PE4E with an ID50 of 0.2 ng/ml (2.5 pM). The cytotoxic action of hIL4-PE4E was specific because it was blocked by an excess of hIL4 and not of human interleukin 2. In addition, hIL4-PE4ED553, an enzymatically inactive form of the chimeric toxin, was not cytotoxic. These results suggest that the hIL4 receptor may be a target for therapy in malignant and immunologic disorders using hIL4 chimeric toxin. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPIES,BETHESDA,MD 20892. NR 32 TC 68 Z9 68 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 JUL 5 PY 1993 VL 268 IS 19 BP 14065 EP 14070 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500044 PM 8314773 ER PT J AU DIAMOND, AM CHOI, IS CRAIN, PF HASHIZUME, T POMERANTZ, SC CRUZ, R STEER, CJ HILL, KE BURK, RF MCCLOSKEY, JA HATFIELD, DL AF DIAMOND, AM CHOI, IS CRAIN, PF HASHIZUME, T POMERANTZ, SC CRUZ, R STEER, CJ HILL, KE BURK, RF MCCLOSKEY, JA HATFIELD, DL TI DIETARY SELENIUM AFFECTS METHYLATION OF THE WOBBLE NUCLEOSIDE IN THE ANTICODON OF SELENOCYSTEINE TRANSFER RNA[SER]SEC SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHROMATOGRAPHY-MASS-SPECTROMETRY; TRANSFER-RNA; ESCHERICHIA-COLI; MAMMALIAN-CELLS; INSERTS SELENOCYSTEINE; RIBOSE METHYLATION; SEQUENCE-ANALYSIS; AMINO-ACID; GENE; UGA AB We reported previously that the presence of selenium in culture media of mammalian cells influences both the steady-state levels and distributions of two tRNA isoacceptors involved in the insertion of selenocysteine into protein in response to certain UGA codons. In this study, we demonstrate an increase in the levels of these isoacceptors in rats fed a selenium-adequate diet compared to animals fed a selenium-deficient diet, as well as a shift in the relative distribution toward the tRNA which elutes later from an RPC-5 column. These effects were found to occur in a tissue-specific manner. Both selenocysteine tRNAs were isolated from rat liver, sequenced, analyzed by mass spectrometry, and shown to differ only by ribose 2'-O-methylation of 5-methylcarboxymethyluridine that occurs in the wobble position of the anticodon. This modified nucleoside has been documented previously only in yeast tRNA while the corresponding 2'-O-methylribose derivative has not been observed. The structure of these nucleosides was established by mass spectrometry and confirmed by chemical synthesis. Although the role of methylation of the wobble nucleotide is not known, the differences in elution properties from RPC-5 columns are consistent with other experimental observations indicating that a change in tRNA conformation accompanies this methylation. C1 VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,NASHVILLE,TN 37232. UNIV MINNESOTA,MED CTR,DEPT MED,MINNEAPOLIS,MN 55455. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. UNIV UTAH,DEPT MED CHEM,SALT LAKE CITY,UT 84112. RP DIAMOND, AM (reprint author), UNIV CHICAGO,DEPT RADIAT & CELLULAR ONCOL,CHICAGO,IL 60637, USA. FU NCI NIH HHS [R01 CA54364]; NIEHS NIH HHS [R01 ES02497]; NIGMS NIH HHS [R01 GM29812] NR 45 TC 93 Z9 93 U1 0 U2 5 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 JUL 5 PY 1993 VL 268 IS 19 BP 14215 EP 14223 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500064 PM 8314785 ER PT J AU ROTROSEN, D YEUNG, CL KATKIN, JP AF ROTROSEN, D YEUNG, CL KATKIN, JP TI PRODUCTION OF RECOMBINANT CYTOCHROME-B558 ALLOWS RECONSTITUTION OF THE PHAGOCYTE NADPH OXIDASE SOLELY FROM RECOMBINANT PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; RESPIRATORY BURST; HUMAN-NEUTROPHILS; PLASMA-MEMBRANE; EXPRESSION; COMPONENT; BACULOVIRUS; ACTIVATION; CLONING; SUBUNIT AB Phagocytic white blood cells contain a multicomponent oxidase that generates microbicidal products by catalyzing electron transfer from NADPH to molecular oxygen. Activation of this oxidase requires interactions of a unique membrane flavocytochrome with the cytosolic proteins p47phox, p67phox, and p21Rac. This flavocytochrome, designated cytochrome b558, is a heteromer comprising a 22-kDa alpha-subunit (p22phox) and a glycosylated almost-equal-to 91-kDa beta-subunit (gp91phox). Cytochrome b558 was expressed in Sf9 insect cells coinfected with recombinant baculoviruses carrying cDNAs for p22phox and gp91phox. Membranes of these cells contained a b-type cytochrome with a dithionite-reduced minus oxidized difference spectrum similar to that of neutrophil cytochrome b558. The recombinant cytochrome b558 beta-subunit was heterogeneously N-glycosylated as demonstrated by its susceptibility to cleavage with endoglycosidases F and H. In contrast to the neutrophil cytochrome b558, a portion of the N-linked oligosaccharide was of the high mannose type. Recombinant cytochrome b558 supported superoxide production in a cell-free assay containing recombinant p47phox, p67phox, and p21Rac. The enzymatic turnover of the partially purified recombinant cytochrome b558 and neutrophil cytochrome b558 were similar (almost-equal-to 100-160 mol of superoxide generated/s/mol of cytochrome heme, range of two experiments) and the native and recombinant cytochromes showed similar requirements for NADPH and exogenous FAD. These studies represent the first reconstitution of the NADPH oxidase solely from recombinant proteins and define a model system to explore the structure and function of cytochrome b558. RP ROTROSEN, D (reprint author), NIAID,HOST DEF LAB,BLDG 10,RM 11N112,BETHESDA,MD 20892, USA. NR 36 TC 75 Z9 75 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 JUL 5 PY 1993 VL 268 IS 19 BP 14256 EP 14260 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500070 PM 8314788 ER PT J AU GENTRY, D BENGRA, C IKEHARA, K CASHEL, M AF GENTRY, D BENGRA, C IKEHARA, K CASHEL, M TI GUANYLATE KINASE OF ESCHERICHIA-COLI K-12 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACTERIOPHAGE-T7 RNA-POLYMERASE; NUCLEOTIDE-SEQUENCE; OMEGA SUBUNIT; RECG LOCUS; SPOT GENE; DNA; CLONING; RECOMBINATION; PURIFICATION; EXPRESSION AB We have identified the gene gmk, in the same operon as rpoZ, spoT, and recG at about 82 minutes on the Escherichia coli chromosome. The gmk (GMP kinase) gene encodes a peptide of 23,592 Da, possessing extensive similarity to the amino acid sequence of guanylate kinase from yeast. To confirm that gmk truly encodes guanylate kinase and to explore some of its enzymatic features, we have overproduced the product of gmk and purified it to homogeneity. Unlike guanylate kinases purified from eukaryotic sources, E. coli guanylate kinase is multimeric, and ionic conditions dictate its protomeric state; under low ionic conditions it appears to be a tetramer while under high ionic conditions it is a dimer. Kinetic analysis reveals that guanylate kinase, again, unlike eukaryotic guanylate kinases, binds GMP cooperatively and that the observed cooperativity changes with ionic strength. These results indicate that, despite extensive sequence similarity to its eukaryotic counterparts, E. coli guanylate kinase is structurally and enzymatically different. RP GENTRY, D (reprint author), NICHHD,MOLEC GENET LAB,MOLEC REGULAT LAB,BLDG 6B,RM 3B-316,BETHESDA,MD 20892, USA. NR 32 TC 43 Z9 45 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 JUL 5 PY 1993 VL 268 IS 19 BP 14316 EP 14321 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500078 PM 8390989 ER PT J AU HEPLER, JR KOZASA, T SMRCKA, AV SIMON, MI RHEE, SG STERNWEIS, PC GILMAN, AG AF HEPLER, JR KOZASA, T SMRCKA, AV SIMON, MI RHEE, SG STERNWEIS, PC GILMAN, AG TI PURIFICATION FROM SF9 CELLS AND CHARACTERIZATION OF RECOMBINANT GQ-ALPHA AND G11-ALPHA - ACTIVATION OF PURIFIED PHOSPHOLIPASE-C ISOZYMES BY G-ALPHA SUBUNITS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BINDING REGULATORY PROTEINS; EPIDERMAL GROWTH-FACTOR; ESCHERICHIA-COLI; BETA-GAMMA; IMMUNOLOGICAL IDENTIFICATION; PERTUSSIS TOXIN; BOVINE BRAIN; 2 FORMS; EXPRESSION; RECEPTOR AB Members of the G(qalpha) subfamily of heterotrimeric guanine nucleotide-binding proteins (G proteins) activate phospholipase C (PLC). The complementary DNAs (cDNAs) for the G protein alpha subunits G(qalpha) and G11alpha were expressed in insect (Sf9) cells using recombinant baculovirus. Active, nonaggregated, and membrane-associated protein was generated only when the alpha subunit cDNA was expressed together with cDNAs encoding G protein beta and gamma subunits. Recombinant alpha subunits (rG(qalpha) and rG11alpha) were purified by three-step procedures, as was a PLC-activating alpha subunit(s) endogenous to Sf9 cells. Guanosine 5'-3-(thio)triphosphate (GTPgammaS) activated rG(qalpha) and rG11alpha with an apparent K0.5 of 30 muM; similarly high concentrations of the nucleotide were required to observe [S-35]GTPgammaS binding to rG(qalpha). Activated rG(qalpha) and rG11alpha each stimulated all three isoforms of purified PLC-beta with the rank order of potency PLC-beta1 = PLC-beta3 greater-than-or-equal-to PLC-beta2; both alpha subunits also stimulated PLC-beta1 and PLC-beta3 to a much greater extent (10-fold) than they did PLC-beta2. In contrast, activated rG(qalpha) and rG11alpha failed to stimulate either PLC-delta1 or PLCg-gamma1. Recombinant G(ialpha1), G(ialpha2), G(ialpha3), G(oalpha(A)), G(salpha), and G(zalpha) all failed to stimulate any of the isoforms of PLC. The apparent affinities of rG(qalpha) and rG11alpha for PLC-beta1 and their capacities to activate the enzyme were similar to values observed for purified brain G(qalpha/11alpha). Purified brain betagamma subunits also stimulated the three isoforms of PLC-beta. The capacities of rG(qalpha) and rG11alpha to activate PLC-beta1 and PLC-beta3 greatly exceeded those of betagamma, whereas G(qalpha), G11alpha and betagamma were roughly equiefficacious with PLC-beta2; the alpha subunits were more potent than betagamma in all cases. The effects of alpha and betagamma together were nonadditive for both PLC-beta1 and PLC-beta2. These results demonstrate that G(qalpha) and G11alpha specifically and selectively stimulate beta isoforms of PLC and confirm the idea that these members of the G(qalpha) subfamily of G proteins are physiological regulators of this signaling pathway. C1 UNIV TEXAS,SW MED CTR,DEPT PHARMACOL,5323 HARRY HINES BLVD,DALLAS,TX 75235. CALTECH,DEPT BIOL,PASADENA,CA 91125. NATL HEART LUNG & BLOOD INST,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM31954, GM34236, GM34497] NR 62 TC 248 Z9 250 U1 1 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 JUL 5 PY 1993 VL 268 IS 19 BP 14367 EP 14375 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LJ825 UT WOS:A1993LJ82500084 PM 8314796 ER PT J AU DASGUPTA, S MUKHOPADHYAY, G PAPP, PP LEWIS, MS CHATTORAJ, DK AF DASGUPTA, S MUKHOPADHYAY, G PAPP, PP LEWIS, MS CHATTORAJ, DK TI ACTIVATION OF DNA-BINDING BY THE MONOMERIC FORM OF THE P1 REPLICATION INITIATOR REPA BY HEAT-SHOCK PROTEINS DNAJ AND DNAK SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ESCHERICHIA-COLI; PLASMID P1; DNA REPLICATION; DNA PROTEIN INTERACTIONS ID REPRESSOR-OPERATOR INTERACTION; ESCHERICHIA-COLI; PLASMID REPLICATION; BACTERIOPHAGE-LAMBDA; NUCLEOPROTEIN STRUCTURES; RNA-POLYMERASE; PURIFICATION; ORIGIN; GRPE; RECONSTITUTION C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NIH,NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RI Papp, Peter/A-6907-2013 NR 39 TC 47 Z9 47 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 JUL 5 PY 1993 VL 232 IS 1 BP 23 EP 34 DI 10.1006/jmbi.1993.1367 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN044 UT WOS:A1993LN04400005 PM 8331660 ER PT J AU MACK, JW STEVEN, AC STEINERT, PM AF MACK, JW STEVEN, AC STEINERT, PM TI THE MECHANISM OF INTERACTION OF FILAGGRIN WITH INTERMEDIATE FILAMENTS - THE IONIC ZIPPER HYPOTHESIS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE KERATIN; INTERMEDIATE FILAMENTS; FILAGGRIN; MACROFIBRILS ID MOUSE EPIDERMAL-CELLS; SOLID-STATE NMR; KERATIN FILAMENTS; PROFILAGGRIN GENE; GLOBULAR-PROTEINS; COILED-COIL; SEQUENCE; DYNAMICS; DIVERSITY; INVITRO C1 NIAMSK,SKIN BIOL BRANCH,BLDG 6,ROOM 425,BETHESDA,MD 20892. NIAMSK,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 63 TC 75 Z9 77 U1 0 U2 0 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 JUL 5 PY 1993 VL 232 IS 1 BP 50 EP 66 DI 10.1006/jmbi.1993.1369 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LN044 UT WOS:A1993LN04400007 PM 7687298 ER PT J AU SOUQUET, PJ CHAUVIN, F BOISSEL, JP CELLERINO, R CORMIER, Y GANZ, PA KAASA, S PATER, JL QUOIX, E RAPP, E TUMARELLO, D WILLIAMS, J WOODS, BL BERNARD, JP AF SOUQUET, PJ CHAUVIN, F BOISSEL, JP CELLERINO, R CORMIER, Y GANZ, PA KAASA, S PATER, JL QUOIX, E RAPP, E TUMARELLO, D WILLIAMS, J WOODS, BL BERNARD, JP TI POLYCHEMOTHERAPY IN ADVANCED NON-SMALL-CELL LUNG-CANCER - A METAANALYSIS SO LANCET LA English DT Article ID RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; SUPPORTIVE CARE; CARCINOMA; CISPLATIN; VINDESINE AB We did a meta-analysis of all published polychemotherapy vs supportive care clinical trials in patients with non-resectable non small cell lung cancer. 7 studies with more than 700 patients were selected. We used the number of deaths at 3, 6, 9, 12, and 18 months as the endpoints because we were unable to obtain all the individual data. Our analysis showed a reduction in mortality during the first 6 months with polychemotherapy. Although small, this increase in survival, together with an improved quality of life, suggests that polychemotherapy should be recommended for patients with non-resectable non small cell lung cancer. C1 UNITE PHARMACOL CLIN, LYON, FRANCE. HOP LAVAL, CTR PNEUMOL, QUEBEC CITY, PQ, CANADA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA USA. CTR HOSP STRASBOURG, SERV PNEUMOL, STRASBOURG, FRANCE. ROYAL N SHORE HOSP, DEPT CLIN ONCOL, SYDNEY, AUSTRALIA. TOM BAKER CANC CLIN, CALGARY, AB, CANADA. SOUTHAMPTON GEN HOSP, CRC, SOUTHAMPTON SO9 4XY, HANTS, ENGLAND. UNIV ANCONA, ONCOL CLIN, I-60100 ANCONA, ITALY. NORWEGIAN RADIUM HOSP, OSLO 3, NORWAY. QUEENS UNIV, NCI, CANADA CLIN TRIALS GRP, KINGSTON K7L 3N6, ONTARIO, CANADA. RP SOUQUET, PJ (reprint author), CTR HOSP LYON SUD, SERV PNEUMOL, F-69310 PIERRE BENITE, FRANCE. NR 19 TC 462 Z9 468 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD JUL 3 PY 1993 VL 342 IS 8862 BP 19 EP 21 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA LK985 UT WOS:A1993LK98500011 PM 8100290 ER PT J AU GINSBERG, L ATACK, JR RAPOPORT, SI GERSHFELD, NL AF GINSBERG, L ATACK, JR RAPOPORT, SI GERSHFELD, NL TI REGIONAL SPECIFICITY OF MEMBRANE INSTABILITY IN ALZHEIMERS-DISEASE BRAIN SO BRAIN RESEARCH LA English DT Note DE ALZHEIMERS DISEASE; MEMBRANE; LIPID BILAYER INSTABILITY; NEURODEGENERATION; CRITICAL TEMPERATURE ID PROTEIN AB We report an inherent tendency towards the destabilisation of cellular membranes in Alzheimer's disease (AD) brain. This tendency is a natural consequence of abnormal membrane lipid composition, which has previously been documented in AD. Membrane destabilisation may contribute to AD pathogenesis in its own right and may also facilitate amyloid beta-protein deposition, which is potentially neurotoxic. The instability was found to co-localise selectively with areas of neurodegeneration in AD brain, thereby possibly accounting for the focal pathology observed in this disorder. C1 NATL INST ARTHRITIS & MUSCULOSKELETAL & SKIN DIS,PHYS BIOL LAB,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. RI Ginsberg, Lionel/C-8704-2009 NR 10 TC 38 Z9 38 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 2 PY 1993 VL 615 IS 2 BP 355 EP 357 DI 10.1016/0006-8993(93)90050-W PG 3 WC Neurosciences SC Neurosciences & Neurology GA LK262 UT WOS:A1993LK26200023 PM 8364743 ER PT J AU SMITH, CA GRUSS, HJ DAVIS, T ANDERSON, D FARRAH, T BAKER, E SUTHERLAND, GR BRANNAN, CI COPELAND, NG JENKINS, NA GRABSTEIN, KH GLINIAK, B MCALISTER, IB FANSLOW, W ALDERSON, M FALK, B GIMPEL, S GILLIS, S DIN, WS GOODWIN, RG ARMITAGE, RJ AF SMITH, CA GRUSS, HJ DAVIS, T ANDERSON, D FARRAH, T BAKER, E SUTHERLAND, GR BRANNAN, CI COPELAND, NG JENKINS, NA GRABSTEIN, KH GLINIAK, B MCALISTER, IB FANSLOW, W ALDERSON, M FALK, B GIMPEL, S GILLIS, S DIN, WS GOODWIN, RG ARMITAGE, RJ TI CD30 ANTIGEN, A MARKER FOR HODGKINS LYMPHOMA, IS A RECEPTOR WHOSE LIGAND DEFINES AN EMERGING FAMILY OF CYTOKINES WITH HOMOLOGY TO TNF SO CELL LA English DT Article ID TUMOR-NECROSIS-FACTOR; NERVE GROWTH-FACTOR; STERNBERG-REED CELLS; GENETIC-LINKAGE MAP; MONOCLONAL-ANTIBODIES; EXPRESSION CLONING; MOLECULAR-CLONING; IL-1 RECEPTOR; SURFACE; DISEASE AB CD30 is a surface marker for neoplastic cells of Hodgkin's lymphoma and shows sequence homology to members of the tumor necrosis factor (TNF) receptor superfamily. Using a chimeric probe consisting of the extracellular domain of CD30 fused to truncated immunoglobulin heavy chains, we expression cloned the cDNA cognate from the murine T cell clone 7B9. The encoded protein is a 239 amino acid type II membrane protein whose C-terminal domain shows significant homology to TNFalpha, TNFbeta, and the CD40L. Cross-hybridization to an induced peripheral blood T cell cDNA library yielded the human homolog, which is 72% identical at the amino acid level. The recombinant human ligand enhances the proliferation of CD3-activated T cells yet induces differential responses, including cell death, in several CD30+ lymphoma-derived clones. The human and murine genes map to 9q33 and the proximal region of chromosome 4, respectively. C1 ADELAIDE CHILDRENS HOSP INC,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA 5006,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP SMITH, CA (reprint author), IMMUNEX RES & DEV CORP,51 UNIV ST,SEATTLE,WA 98101, USA. RI Sutherland, Grant/D-2606-2012 FU NCI NIH HHS [N01-CO-74101] NR 62 TC 465 Z9 471 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD JUL 2 PY 1993 VL 73 IS 7 BP 1349 EP 1360 DI 10.1016/0092-8674(93)90361-S PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LL209 UT WOS:A1993LL20900010 PM 8391931 ER PT J AU MOZES, E KOHN, LD HAKIM, F SINGER, DS AF MOZES, E KOHN, LD HAKIM, F SINGER, DS TI RESISTANCE OF MHC CLASS-I-DEFICIENT MICE TO EXPERIMENTAL SYSTEMIC LUPUS-ERYTHEMATOSUS SO SCIENCE LA English DT Article ID T-CELLS; INDUCTION; IDIOTYPE AB Experimental systemic lupus erythematosus (SLE) can be induced in mice by immunization with a human monoclonal antibody to DNA that bears a common idiotype (16/6Id). These mice generate antibodies to 16/6Id, antibodies to DNA, and antibodies directed against nuclear antigens. Subsequently, manifestations of SLE develop, including leukopenia, proteinuria, and immune complex deposits in the kidney. In contrast, after immunization with 16/6Id, mice lacking major histocompatibility complex (MHC) class I molecules generated antibodies to 16/6Id but did not generate antibodies to DNA or to nuclear antigen. Furthermore, they did not develop any of the above clinical manifestations. These results reveal an unexpected function of MHC class I in the induction of autoimmune SLE. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 13 TC 99 Z9 99 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 JUL 2 PY 1993 VL 261 IS 5117 BP 91 EP 93 DI 10.1126/science.8316860 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK434 UT WOS:A1993LK43400038 PM 8316860 ER PT J AU MUEGGE, K VILA, MP DURUM, SK AF MUEGGE, K VILA, MP DURUM, SK TI INTERLEUKIN-7 - A COFACTOR FOR V(D)J REARRANGEMENT OF THE T-CELL RECEPTOR BETA-GENE SO SCIENCE LA English DT Article ID MURINE INTERLEUKIN-7; RECOMBINATION; RAG-1; IL-7; THYMOCYTES; REGION AB The diversity of the T cell receptor repertoire is generated by rearrangement of gene elements in immature thymocytes. To identify a thymic signal that induces this rearrangement, a variety of agents were tested for their ability to induce rearrangement of the T cell receptor beta gene in suspensions of thymocytes from mouse embryos at day 14 of gestation. Of 16 agents tested, only interleukin-7 (IL-7) induced V(D)J gene rearrangement and sustained expression of the RAG-1 and RAG-2 genes, which are known to control rearrangement. These data implicate IL-7, a cytokine that is abundantly expressed in embryonic thymus, in driving gene rearrangement during early T cell development. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702. RP MUEGGE, K (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 25 TC 194 Z9 194 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 2 PY 1993 VL 261 IS 5117 BP 93 EP 95 DI 10.1126/science.7686307 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK434 UT WOS:A1993LK43400039 PM 7686307 ER PT J AU LEE, JW MARQUEZ, VE LEWIN, NE BLUMBERG, PM AF LEE, JW MARQUEZ, VE LEWIN, NE BLUMBERG, PM TI SYNTHESIS OF 2 RIGID DIACYLGLYCEROL ANALOGS HAVING A PERHYDRO FURO[3,4-B]FURAN BIS-GAMMA-BUTYROLACTONE SKELETON .2. SO TETRAHEDRON LETTERS LA English DT Article AB The stereoselective synthesis of two rigid diacylglycerol analogues starting from L-arabinose is described. The construction of the desired bicyclic bis-butyrolactone structure was accomplished via intramolecular radical cyclization. Both compounds (3a and 3b) showed poor binding affinity for PK-C. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. NR 9 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUL 2 PY 1993 VL 34 IS 27 BP 4313 EP 4316 DI 10.1016/S0040-4039(00)79337-3 PG 4 WC Chemistry, Organic SC Chemistry GA LK759 UT WOS:A1993LK75900012 ER PT J AU LEE, JW MARQUEZ, VE BAHADOR, A KAZANIETZ, MG BLUMBERG, PM AF LEE, JW MARQUEZ, VE BAHADOR, A KAZANIETZ, MG BLUMBERG, PM TI SYNTHESIS OF 2 RIGID DIACYLGLYCEROL ANALOGS HAVING A PERHYDRO FURO[3,2-B] FURAN BIS-GAMMA-BUTYROLACTONE SKELETON .3. SO TETRAHEDRON LETTERS LA English DT Article AB The stereoselective synthesis of two new bis-gamma-butyrolactones starting from 1,2:5,6-di-O-isopropylidene-alpha-D-allofuranose was completed in 22 steps. One of the isomers (3a) showed very good binding affinity towards protein kinase C. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,MOLEC MECH TUMOR PROMOT SECT,BETHESDA,MD 20892. NR 4 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD JUL 2 PY 1993 VL 34 IS 27 BP 4317 EP 4320 DI 10.1016/S0040-4039(00)79338-5 PG 4 WC Chemistry, Organic SC Chemistry GA LK759 UT WOS:A1993LK75900013 ER PT J AU MEASSO, G ZAPPALA, G CAVARZERAN, F CROOK, TH ROMANI, L PIROZZOLO, FJ GRIGOLETTO, F AMADUCCI, LA MASSARI, D LEBOWITZ, BD AF MEASSO, G ZAPPALA, G CAVARZERAN, F CROOK, TH ROMANI, L PIROZZOLO, FJ GRIGOLETTO, F AMADUCCI, LA MASSARI, D LEBOWITZ, BD TI RAVENS COLORED PROGRESSIVE MATRICES - A NORMATIVE STUDY OF A RANDOM SAMPLE OF HEALTHY-ADULTS SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article DE NORMAL AGING; NONVERBAL INTELLIGENCE; NORMATIVE VALUES ID MEMORY; IMPAIRMENT; AGE AB Raven's Colored Progressive Matrices Test (RCPM) was administered to 894 normal healthy adults who were randomly selected in six Italian cities and in the Republic of San Marino. Gender, age, and education significantly influenced overall test performance, and performance on different RCPM subsets. Findings from this large random sample provide demographic corrections to test scores for use in clinical practice. C1 BAYLOR COLL,DEPT NEUROL,HOUSTON,TX. NIMH,ROCKVILLE,MD 20857. EXPHARMA SR,PADUA,ITALY. MEMORY ASSESSMENT CLIN,BETHESDA,MD. UNIV PADUA,INST HYG,I-35100 PADUA,ITALY. UNIV FLORENCE,DEPT NEUROL & PSYCHIAT,I-50121 FLORENCE,ITALY. FIDIA RES LABS,DEPT BIOSTAT EPIDEMIOL,ABANO TERME,ITALY. FIDIA RES LABS,CTR RES MEMORY,ABANO TERME,ITALY. NR 16 TC 26 Z9 26 U1 2 U2 4 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PD JUL PY 1993 VL 88 IS 1 BP 70 EP 74 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA LN566 UT WOS:A1993LN56600015 PM 8372633 ER PT J AU GAWIN, AZ BARANIUK, JN KALINER, MA AF GAWIN, AZ BARANIUK, JN KALINER, MA TI EFFECTS OF SUBSTANCE-P AND CALCITONIN-GENE-RELATED PEPTIDE (CGRP) ON GUINEA-PIG NASAL MUCOSAL SECRETION IN-VIVO SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE NASAL MUCOSA; NEUROPEPTIDES; THIORPHAN; ALBUMIN; VASCULAR PERMEABILITY; EXUDATION; GLANDULAR SECRETION; AXON RESPONSE ID RESPIRATORY-TRACT; NEUROPEPTIDES; CAPSAICIN; EXUDATION; RHINITIS; DEFENSE AB Trigeminal sensory nerves contain and release the neurotransmitters substance P (SP) and calcitonin gene related peptide (CGRP) in nasal mucosa. The effects of SP and CGRP on nasal secretion were tested in an in vivo model of guinea pig nasal mucosal secretion by topically applying the peptides directly to turbinates, and then lavaging the nostrils 10 min later. Concentrations of total protein, albumin, and I-125-bovine serum albumin (25I-BSA, injected intravenously at time 0 of the studies) were measured in lavage fluid. SP (beginning at 10(-8) M) and CGRP (beginning at 10(-6) M) stimulated the secretion of I-125-BSA indicating stimulation of plasma protein exudation. SP and CGRP increased total protein concentration at 10(-6) M indicating stimulation of glandular secretion. Topically applied thiorphan (I mug), an inhibitor of neutral endopeptidase, did not potentiate the maximal response to SP. However, thiorphan significantly prolonged the duration of I-125-BSA, total protein, and albumin secretion in response to SP indicating that the vascular and glandular responses were enhanced. This implies the presence of neutral endopeptidase, and demonstrates a regulatory role for this enzyme in vivo. These findings are consistent with the concept that SP and CGRP released by nociceptive sensory nerve axon responses in guinea pig nasal mucosa lead to plasma extravasation, albumin exudation, and glandular secretion, and that these mechanisms contribute to nasal responses to injury in this species. C1 GEORGETOWN UNIV,DIV RHEUMATOL IMMUNOL & ALLERGY,WASHINGTON,DC 20007. RP GAWIN, AZ (reprint author), NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 28 TC 23 Z9 24 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD JUL PY 1993 VL 113 IS 4 BP 533 EP 539 DI 10.3109/00016489309135859 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA LQ682 UT WOS:A1993LQ68200014 PM 7691022 ER PT J AU REGIER, DA FARMER, ME RAE, DS MYERS, JK KRAMER, M ROBINS, LN GEORGE, LK KARNO, M LOCKE, BZ AF REGIER, DA FARMER, ME RAE, DS MYERS, JK KRAMER, M ROBINS, LN GEORGE, LK KARNO, M LOCKE, BZ TI ONE-MONTH PREVALENCE OF MENTAL-DISORDERS IN THE UNITED-STATES AND SOCIODEMOGRAPHIC CHARACTERISTICS - THE EPIDEMIOLOGIC CATCHMENT-AREA STUDY SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE EPIDEMIOLOGY; MENTAL DISORDER; PREVALENCE; SOCIOECONOMIC STATUS ID DIAGNOSTIC INTERVIEW SCHEDULE; WHITE COMMUNITY RESIDENTS; PSYCHIATRIC-DISORDERS; SOMATIZATION DISORDER; COGNITIVE IMPAIRMENT; GENERAL-POPULATION; SENILE DEMENTIA; SOCIAL-CLASS; EDUCATION; MORBIDITY AB The associations between the one-month prevalence rates of mental disorders and sociodemographic characteristics were investigated for 18 571 people interviewed in the first-wave community samples of all 5 sites in the US National Institute of Mental Health (NIMH) Epidemiologic Catchment Area program. Men were found to have a significantly higher rate of cognitive impairment than women after controlling for the effects of age, race or ethnicity, marital status and socioeconomic status. Marital status was one of the most powerful correlates of mental disorder risk: the odds of separated or divorced people having any NIMH Diagnostic Interview Schedule disorder were twice that of married people after controlling for age, gender, race or ethnicity and socioeconomic status. The odds of those in the lowest socioeconomic status group having any Diagnostic Interview Schedule disorder was about 2.5 times that of those in the highest socioeconomic status group, controlling for age, gender, race or ethnicity and marital status. For all disorders except cognitive impairment, race or ethnicity did not remain statistically significant after controlling for age, gender, marital status and socioeconomic status. C1 JOHNS HOPKINS SCH HYG & PUBL HLTH, DEPT MENT HYG, BALTIMORE, MD USA. DUKE UNIV, DIV SOCIAL & COMMUNITY PSYCHIAT, DURHAM, NC 27706 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT PSYCHIAT & BIOBEHAV SCI, LOS ANGELES, CA USA. YALE UNIV, DEPT SOCIOL, NEW HAVEN, CT 06520 USA. WASHINGTON UNIV, DEPT PSYCHIAT, ST LOUIS, MO 63130 USA. RP REGIER, DA (reprint author), NIMH, DIV EPIDEMIOL & SERV RES, RM 10-105, PARKLAWN BLDG, 5600 FISHERS LANE, ROCKVILLE, MD 20857 USA. NR 77 TC 270 Z9 273 U1 5 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JUL PY 1993 VL 88 IS 1 BP 35 EP 47 DI 10.1111/j.1600-0447.1993.tb03411.x PG 13 WC Psychiatry SC Psychiatry GA LM822 UT WOS:A1993LM82200007 PM 8372694 ER PT J AU HARFORD, TC AF HARFORD, TC TI THE MEASUREMENT OF ALCOHOL-RELATED ACCIDENTS SO ADDICTION LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON ALCOHOL-RELATED ACCIDENTS AND INJURIES CY DEC 02-05, 1991 CL YVERDON, SWITZERLAND ID CONSUMPTION AB This paper examines some of the major ethical and research issues associated with the measurement and recording of alcohol-related problems. Because self-reports of the history of the amount of alcohol ingested are sometimes unreliable, the assessment of the role of alcohol in casualties often relies on a variety of methods which are both diverse and interrelated. The unique measurement problems posed by the diversity of alcohol measures are reviewed and issues in selection and recording bias of alcohol's involvement in injury are discussed A number of fundamental ethical and moral issues related to measurement are identified. RP HARFORD, TC (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,5600 FISHERS LANE,ROOM 14C-26,ROCKVILLE,MD 20857, USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD JUL PY 1993 VL 88 IS 7 BP 907 EP 912 DI 10.1111/j.1360-0443.1993.tb02108.x PG 6 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA LL661 UT WOS:A1993LL66100006 PM 8358262 ER PT J AU SEIDEL, EA KOENIG, S POLIS, MA AF SEIDEL, EA KOENIG, S POLIS, MA TI A DOSE-ESCALATION STUDY TO DETERMINE THE TOXICITY AND MAXIMALLY TOLERATED DOSE OF FOSCARNET SO AIDS LA English DT Note DE FOSCARNET; TRISODIUM PHOSPHONOFORMATE HEXAHYDRATE; AIDS; HIV; DRUG TOXICITY; RENAL FAILURE; SEIZURE ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HERPES-SIMPLEX VIRUS; CYTOMEGALOVIRUS RETINITIS; PHOSPHONOFORMATE FOSCARNET; CONTROLLED TRIAL; AIDS PATIENTS; THERAPY; INFECTION AB Objective: To determine the maximum tolerated dose of intravenous foscarnet (trisodium phosphonoformate hexahydrate); and to examine antiviral activity at plasma levels shown to inhibit HIV-1. Design: Dose escalation study in three male subjects with AIDS who received foscarnet by continuous intravenous infusion at a dose of 200 mg/kg per day, after a 20 mg/kg loading dose. The dose was increased until a plasma level > 150 mug/ml was attained. Results: Foscarnet was discontinued due to progressive renal insufficiency in all three patients (days 11, 19, and 21). Renal function normalized in all three, and no adverse sequelae due to foscarnet were observed at 1 year of follow-up. A seizure was observed in one patient on day 19. Maximum daily doses of foscarnet achieved were 395 mg/kg, 389 mg/kg, and 523 mg/kg. No changes in serum Ca2+, Mg2+, or PO4- were observed. Conclusions: Renal effects and toxicity of foscarnet in evolving renal insufficiency is self-limiting and reversible when the drug is discontinued. Incremental increases in dose can result in rapid rises in the plasma level with renal failure and may be compounded by concomitant medications and underlying illnesses. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B13,BETHESDA,MD 20892. OI Polis, Michael/0000-0002-9151-2268 NR 28 TC 11 Z9 11 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD JUL PY 1993 VL 7 IS 7 BP 941 EP 945 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LL492 UT WOS:A1993LL49200006 PM 8357555 ER PT J AU EARL, PL MOSS, B AF EARL, PL MOSS, B TI MUTATIONAL ANALYSIS OF THE ASSEMBLY DOMAIN OF THE HIV-1 ENVELOPE GLYCOPROTEIN SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUS; DISULFIDE BOND FORMATION; DNA-BINDING DOMAIN; LEUCINE ZIPPER; OLIGOMERIC STRUCTURE; CYSTEINE RESIDUES; HEMAGGLUTININ-NEURAMINIDASE; INTRACELLULAR-TRANSPORT; TRANSMEMBRANE PROTEIN AB The amino-terminal 129 amino acids of gp41 of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein constitute the assembly domain required for efficient oligomer formation and stability. Point mutations in highly conserved structural features including cysteine residues, potential N-linked glycosylation sites, and a leucine zipper motif have been made in a soluble secreted form of Env (Env(sec)). No single point mutation had adverse effects on Env protein oligomerization. However, truncation of the C terminus of gp41 from 129 amino acids to 68 amino acids drastically reduced oligomerization efficiency, indicating that amino acids 68-129 are essential for assembly. RP EARL, PL (reprint author), NIAID,VIRAL DIS LAB,BLDG 4,ROOM 237,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 39 TC 67 Z9 67 U1 0 U2 1 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 JUL PY 1993 VL 9 IS 7 BP 589 EP 594 DI 10.1089/aid.1993.9.589 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LQ607 UT WOS:A1993LQ60700002 PM 8369163 ER PT J AU POTTS, KE KALISH, ML BANDEA, CI ORLOFF, GM STLOUIS, M BROWN, C MALANDA, N KAVUKA, M SCHOCHETMAN, G OU, CY HEYWARD, WL AF POTTS, KE KALISH, ML BANDEA, CI ORLOFF, GM STLOUIS, M BROWN, C MALANDA, N KAVUKA, M SCHOCHETMAN, G OU, CY HEYWARD, WL TI GENETIC DIVERSITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 STRAINS IN KINSHASA, ZAIRE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID NUCLEOTIDE-SEQUENCE ANALYSIS; NEUTRALIZING MONOCLONAL-ANTIBODY; ENVELOPE GENE; MOLECULAR CHARACTERIZATION; SYNTHETIC PEPTIDES; VARIABLE REGIONS; HIV-1; DETERMINANT; EPITOPE; GLYCOPROTEIN AB The envelope (env) gene of human immunodeficiency virus type 1 (HIV-1) was amplified by polymerase chain reaction (PCR) from the peripheral blood mononuclear cells (PBMCs) of 14 HIV-1-infected women from Kinshasa, Zaire. Amplified DNA was directly sequenced with a primer specific for the HIV-1 env C2 region. The predicted amino acid sequences for the C2-V3 region for the 14 specimens are presented. The tetrapeptide sequence, GPGQ, located at the crown of the V3 loop, is conserved in all specimens. The same tetrapeptide sequence is present in the Zairian isolate MAL, but not in other published Zairian isolates (Z6, ELI, Z321, JY1, and NDK). Sequence comparison of the env C2-V3 region among the 14 specimens from Kinshasa revealed a 9-25 % range of nucleotide divergence, with an average of 16 %. Divergence between the 14 specimens and the Zairian isolates MAL, Z6, ELI, Z321, JY1, and NDK ranged from 13 to 31 %. A range of 18-28 % nucleotide sequence divergence was demonstrated between the 14 Kinshasa specimens and the North American isolate MN. These results demonstrate the importance of examining HIV-1 samples from diverse geographic origins in the development of effective HIV-1 vaccines. C1 CTR DIS CONTROL,NATL CTR INFECT DIS,DIV HIV AIDS,MAILSTOP G15,ATLANTA,GA 30333. NIAID,IMMUNOREGULAT LAB,WASHINGTON,DC. PROJET SIDA,KINSHASA,ZAIRE. FU NIAID NIH HHS [N01-AI-8003] NR 43 TC 32 Z9 32 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 JUL PY 1993 VL 9 IS 7 BP 613 EP 618 DI 10.1089/aid.1993.9.613 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LQ607 UT WOS:A1993LQ60700005 PM 8369166 ER PT J AU ROSENBERG, YJ ZACK, PM WHITE, BD PAPERMASTER, SF ELKINS, WR EDDY, GA LEWIS, MG AF ROSENBERG, YJ ZACK, PM WHITE, BD PAPERMASTER, SF ELKINS, WR EDDY, GA LEWIS, MG TI DECLINE IN THE CD4+ LYMPHOCYTE POPULATION IN THE BLOOD OF SIV-INFECTED MACAQUES IS NOT REFLECTED IN LYMPH-NODES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MORPHOLOGIC CHANGES; TYPE-1 INFECTION; SOOTY MANGABEYS; HIV INFECTION; AIDS; LYMPHADENOPATHY; REPLICATION; RESERVOIRS; DISEASE AB Although loss of CD4+ lymphocytes in peripheral blood is a standard criterion for evaluating the course of HIV disease, little is known about changes within lymphoid organs, which contain the bulk (>50%) of the body's lymphocytes. Because such studies are feasible only by using non-human primates, we have examined lymph nodes (LNs), spleen, and blood from monkeys infected with two isolates of simian immunodeficiency virus (SIV). During both the acute and chronic phases of these infections, characteristic reductions in the blood CD4+ cell levels are not reflected in LN, where the CD4+ pool remains within normal levels. However, when circulating CD4/CD8 ratios have consistently fallen to approximately 0.5, striking decreases in the percentage of CD4 cells (CD4%) and CD4/CD8 ratios in LN occur concomitantly with dramatic increases in viral antigen expression on follicular dendritic cells within LN germinal centers (GCs). The data suggest that loss from the total T cell pool in minimal until the final stages of SIV and HIV disease and that the immunological deterioration of LN is the event that precipitates the increased susceptibility to infections and progression to AIDS. C1 WALTER REED ARMY INST RES,ROCKVILLE,MD 20852. NIAID,BETHESDA,MD 20892. RP ROSENBERG, YJ (reprint author), HENRY M JACKSON FDN,1500 E GUDE DR,ROCKVILLE,MD 20850, USA. NR 36 TC 56 Z9 56 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 JUL PY 1993 VL 9 IS 7 BP 639 EP 646 DI 10.1089/aid.1993.9.639 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LQ607 UT WOS:A1993LQ60700009 PM 8103665 ER PT J AU FERRARI, G OTTINGER, J PLACE, C NIGIDA, SM ARTHUR, LO WEINHOLD, KJ AF FERRARI, G OTTINGER, J PLACE, C NIGIDA, SM ARTHUR, LO WEINHOLD, KJ TI THE IMPACT OF HIV-1 INFECTION ON PHENOTYPIC AND FUNCTIONAL PARAMETERS OF CELLULAR-IMMUNITY IN CHIMPANZEES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; SEROPOSITIVE INDIVIDUALS; GLYCOPROTEIN GP120; HTLV-III; ENVELOPE GLYCOPROTEIN-GP120; HOMOSEXUAL MEN; VACCINIA VIRUS; CYTO-TOXICITY; ANTIBODY AB As a means of assessing the immunological impact of HIV infection in the chimpanzee, as well as the participation of the cellular components in the control of HIV infection in these animals, various aspects of cellular immunity were investigated in chronically HIV-infected chimpanzees. Eight HIV-1-infected chimpanzees were included in this study; two of them were infected for more than 5 years and six for nearly 3 years at the time of study. All of the chimpanzees received either 40 or 100 TCID50 of HTLV-IIIB. Circulating peripheral blood lymphocytes were studied by flow cytofluorimetric analysis in order to reveal possible alterations in the CD4:CD8 ratio, as well as in specific CD4+ and CD8+ cell subpopulations. Chronically infected chimpanzees did not present significant alterations in the percentage of CD4+ or CD8+ lymphocyte subsets. Interestingly, the CD8+/CD57+ cell subset was not detectable. The expression of markers for activation on circulating lymphocytes, usually higher in the HIV-infected patients, was not altered in infected animals. The functional aspects of specific anti-HIV-1 non-MHC and MHC-restricted cellular cytotoxic reactivities were also investigated. The results were compared with the findings in normal uninfected chimpanzees and in HIV-infected humans. Only one chimpanzee (881) developed a detectable, specific non-MHC-restricted anti-HIV-1 reactivity. Compared to that seen in humans, the ontogeny of this activity is delayed. Among the other infected chimpanzees, no specific anti-HIV cellular reactivities were detectable in the peripheral blood. In chimpanzees, HIV-1 infection evidently does not elicit the same strong cellular reactivity as that detected in infected patients. The absence of chronic cellular activation, despite continued viral replication, may highlight a key determinant in HIV-1-induced pathogenesis that is likewise absent in infected chimpanzees. C1 DUKE UNIV,MED CTR,DEPT SURG,POB 2926,DURHAM,NC 27710. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNACORP INC,FREDERICK,MD 21702. RI Ferrari, Guido/A-6088-2015 FU NCI NIH HHS [2-P01-CA43447]; NIAID NIH HHS [5-R01-AI29852] NR 49 TC 17 Z9 17 U1 0 U2 1 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 JUL PY 1993 VL 9 IS 7 BP 647 EP 656 DI 10.1089/aid.1993.9.647 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LQ607 UT WOS:A1993LQ60700010 PM 8369169 ER PT J AU MENEZ, JF MACHU, TK SONG, BJ BROWNING, MD DEITRICH, RA AF MENEZ, JF MACHU, TK SONG, BJ BROWNING, MD DEITRICH, RA TI PHOSPHORYLATION OF CYTOCHROME-P4502E1 (CYP2E1) BY CALMODULIN-DEPENDENT PROTEIN-KINASE, PROTEIN-KINASE-C AND CAMP-DEPENDENT PROTEIN-KINASE SO ALCOHOL AND ALCOHOLISM LA English DT Article ID ISOLATED RAT HEPATOCYTES; LIVER CYTOCHROME-P-450; FORMS; DEGRADATION; INDUCTION; CLEAVAGE AB Phosphorylation of pure cytochrome P4502E1 (CYP2E1) was achieved in vitro using Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), protein kinase C (PKC) and cAMP-dependent protein kinase (PKA). The stoichiometry and time-course of phosphorylation were determined. CaM kinase II was the most efficient enzyme capable of catalyzing this phosphorylation reaction: the maximum incorporation of (PO4)-P-32 was 0.8 mol/mol CYP2E1 in 20 min. PKA phosphorylated a maximum of 0.7 mol of (PO4)-P-32/mol of cytochrome within 60 min. The phosphorylation by PKC reached a maximum of 0.19 mol of (PO4)-P-32/mol of cytochrome and this occurred within a few minutes of incubation. Limited digestion by S. aureus V8 protease (SAP) of CYP2E1, which had been phosphorylated by either PKA and PKC, yielded a single major phosphopeptide with an M(r) of approximately 18,000. Limited digestion of CYP2E1, that had been phosphorylated by CaM kinase II, yielded phosphorylated polypeptides with M(r) of approximately 18,000 and 15,000. These results raise the possibility that these three kinases may be involved in the regulation of CYP2E1. C1 UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. NIAAA,METAB & MOLEC BIOL LAB,ROCKVILLE,MD 20852. FU NIAAA NIH HHS [AA00093, AA05868, AA03527] NR 30 TC 22 Z9 23 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD JUL PY 1993 VL 28 IS 4 BP 445 EP 451 PG 7 WC Substance Abuse SC Substance Abuse GA LU225 UT WOS:A1993LU22500010 PM 8397526 ER PT J AU COHEN, SG AF COHEN, SG TI FISH, IN AND OUT OF WATER - FOOD, TOXINS, ALLERGENS SO ALLERGY PROCEEDINGS LA English DT Note RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD JUL-AUG PY 1993 VL 14 IS 4 BP 287 EP 316 DI 10.2500/108854193778812044 PG 30 WC Allergy SC Allergy GA LU334 UT WOS:A1993LU33400009 PM 8224836 ER PT J AU SHIRANI, J ROBERTS, WC AF SHIRANI, J ROBERTS, WC TI CORONARY OSTIAL DIMPLE (IN THE POSTERIOR AORTIC SINUS) IN THE ABSENCE OF OTHER CORONARY ARTERIAL ABNORMALITIES SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note RP SHIRANI, J (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 9 TC 3 Z9 3 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 JUL 1 PY 1993 VL 72 IS 1 BP 118 EP 119 DI 10.1016/0002-9149(93)90235-5 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LK114 UT WOS:A1993LK11400027 PM 8517421 ER PT J AU NAIR, PP JUDD, JT BERLIN, E TAYLOR, PR SHAMI, S SAINZ, E BHAGAVAN, HN AF NAIR, PP JUDD, JT BERLIN, E TAYLOR, PR SHAMI, S SAINZ, E BHAGAVAN, HN TI DIETARY FISH-OIL INDUCED CHANGES IN THE DISTRIBUTION OF ALPHA-TOCOPHEROL, RETINOL, AND BETA-CAROTENE IN PLASMA, RED-BLOOD-CELLS, AND PLATELETS - MODULATION BY VITAMIN-E SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE N-3 POLYUNSATURATED FATTY ACIDS; ALPHA-TOCOPHEROL; BETA-CAROTENE; RETINOL; FISH OIL; RED BLOOD CELLS; PLATELETS; VITAMIN-A; VITAMIN-E; POLYUNSATURATED FATTY ACIDS ID FATTY-ACIDS; SUPPLEMENTATION; METABOLISM; MEN AB Healthy men (ages 24-57 y) were fed a controlled basal diet supplemented with 15 g/d of placebo oil (PO) for 10 wk followed by 15 g/d of fish-oil concentrate (FO) (fortified with 15 mg all-rac-tocopherol) for 10 wk without additional alpha-tocopherol and the last 8 wk with 200 mg alpha-tocopherol/d (FO + E). Compared with PO, FO raised plasma malondialdehyde, lowered alpha-tocopherol in plasma, red blood cells, and platelets; and raised plasma and platelet beta-carotene. Supplementation with additional alpha-tocopherol (FO + E) not only restored tocopherol concentrations but also reversed the rise in beta-carotene. The response in retinol, particularly in platelets, showed an inverse relationship to beta-carotene, alpha-tocopherol exhibiting a modulating effect on these changes. From these observations it is postulated that platelets may be a significant extraintestinal site of retinol formation from beta-carotene. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR HUMAN NUTR,DEPT INT HLTH,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21218. NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DEPT CLIN NUTR,NUTLEY,NJ 07110. RP NAIR, PP (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,LIPID RES LAB,BLDG 308,BELTSVILLE,MD 20705, USA. FU NCI NIH HHS [YO-1-CN-40620] NR 28 TC 70 Z9 71 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1993 VL 58 IS 1 BP 98 EP 102 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LK535 UT WOS:A1993LK53500016 PM 8317397 ER PT J AU DOSEMECI, M CHEN, JQ HEARL, F CHEN, RG MCCAWLEY, M WU, Z MCLAUGHLIN, JK PENG, KL CHEN, AL REXING, SH BLOT, WJ AF DOSEMECI, M CHEN, JQ HEARL, F CHEN, RG MCCAWLEY, M WU, Z MCLAUGHLIN, JK PENG, KL CHEN, AL REXING, SH BLOT, WJ TI ESTIMATING HISTORICAL EXPOSURE TO SILICA AMONG MINE AND POTTERY WORKERS IN THE PEOPLES-REPUBLIC-OF-CHINA SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE EXPOSURE ASSESSMENT METHOD; SILICA; MINES; POTTERY FACTORIES ID LUNG-CANCER; MORTALITY; DUST; INDUSTRY AB A quantitative retrospective exposure assessment method was developed for use in a nested case-control study of lung cancer among mine and pottery workers exposed to silica dust in the People's Republic of China. Exposure assessment was carried out in 20 mines (10 tungsten, 6 iron/copper, and 4 tin) and nine pottery factories. A job title dictionary was developed and used in both the collection of historical exposure information and work histories of 1,668 (316 cases and 1,352 controls) study subjects. Several data abstraction forms were developed to collect historical and current exposure information and employees' work histories, starting in 1950. A retrospective exposure matrix was developed on the basis of facility/job title/calendar year combinations using available historical exposure information and current exposure profiles. Information on the amount of respirable, thoracic, and free silica content in total dust was used in estimating exposure to silica. Starting in 1950, 6,805 historical estimates had been carried out for 14 calendar-year periods. We estimated the average total dust concentration to be 9 mg/M3, with a range from 28 mg/M3 in earlier years to 3 mg/M3 in recent years. Several exposure indices [such as cumulative dust, average dust, cumulative respirable (<5 mu in particle size) and thoracic (<10 mu in particle size) silica dust, average respirable and thoracic silica dust, exposure-weighted duration, and the highest/longest exposure] were calculated for individuals by merging work history and historical exposure matrix for each study subject. We developed these various measures of exposure to allow investigators to compare and contrast different indices of historical exposure to silica. (C) 1993 Wiley-Liss, Inc.* C1 TONGJI MED UNIV,DEPT LABOR HLTH & OCCUPAT DIS,WUHAN,PEOPLES R CHINA. NIOSH,MORGANTOWN,WV 26505. WESTAT CORP,ROCKVILLE,MD. RP DOSEMECI, M (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,ROOM 418,ROCKVILLE,MD 20892, USA. NR 20 TC 29 Z9 33 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1993 VL 24 IS 1 BP 55 EP 66 DI 10.1002/ajim.4700240106 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LJ360 UT WOS:A1993LJ36000005 PM 8394648 ER PT J AU WUWILLIAMS, AH XU, ZY BLOT, WJ DAI, XD LOUIE, R XIAO, HP STONE, BJ SUN, XW YU, SF FENG, YP FRAUMENI, JF HENDERSON, BE AF WUWILLIAMS, AH XU, ZY BLOT, WJ DAI, XD LOUIE, R XIAO, HP STONE, BJ SUN, XW YU, SF FENG, YP FRAUMENI, JF HENDERSON, BE TI OCCUPATION AND LUNG-CANCER RISK AMONG WOMEN IN NORTHERN CHINA SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE LUNG CANCER; FEMALE OCCUPATIONAL EXPOSURES; METAL SMELTING; FOUNDRY WORKERS; TEXTILE INDUSTRIES; COAL DUST AND SMOKE ID AIR-POLLUTION; FOUNDRY WORKERS; UNITED-STATES; COAL-MINERS; XUAN-WEI; EXPOSURE; MORTALITY; PROPORTION; PATTERNS; SHANGHAI AB Lifetime occupational histories were obtained in a case-control study of 965 female lung cancer patients and 959 controls selected from the general population in Shenyang and Harbin, People's Republic of China, where most women have worked outside the home. After adjusting for smoking, we found a significantly increased risk of lung cancer associated with employment involving the manufacture of transportation equipment (OR = 1.6, 95% CI = 1.0, 2.6), in particular the manufacturing of automobiles (OR = 3.0, 95% CI = 1.4, 6.4). Metal smelting and treatment workers were at an increased risk of lung cancer (OR = 1.5, 95% CI = 1.0, 2. 1); the highest risks were observed among metal surfacers (OR = 3.1, 95% CI = 1.1, 9.0) and currently employed foundry workers (OR = 13.0, 95% CI = 1.7, 99.4). On the other hand, about a 50% decreased risk of lung cancer was observed among those employed in textile industries or as leaders of state and party organizations. Based on self-reports, exposures to coal dust and smoke from burning fuel at the workplace were also significant risk factors. The findings were similar when the analyses were confined to nonsmokers and were comparable across the major cell types of lung cancer. (C) 1993 Wiley-Liss, Inc. C1 NCI,BETHESDA,MD 20892. LIAONING PUBL HLTH & ANTI EPIDEM STN,SHENYANG,PEOPLES R CHINA. HARBIN MED SCH,HARBIN,PEOPLES R CHINA. RP WUWILLIAMS, AH (reprint author), UNIV SO CALIF,DEPT PREVENT MED,1420 SAN PABLO ST,LOS ANGELES,CA 90033, USA. NR 46 TC 29 Z9 30 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1993 VL 24 IS 1 BP 67 EP 79 DI 10.1002/ajim.4700240107 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LJ360 UT WOS:A1993LJ36000006 PM 8352293 ER PT J AU CHOW, WH MCLAUGHLIN, JK ZHENG, W BLOT, WJ GAO, YT AF CHOW, WH MCLAUGHLIN, JK ZHENG, W BLOT, WJ GAO, YT TI OCCUPATIONAL RISKS FOR PRIMARY LIVER-CANCER IN SHANGHAI, CHINA SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE OCCUPATIONAL RISKS; PRIMARY LIVER CANCER; CHINA ID CAUSE-SPECIFIC MORTALITY; HEPATOCELLULAR-CARCINOMA; TEXTILE WORKERS; VINYL-CHLORIDE; DEATH; EXPOSURE AB Using occupational data for over 3,400 primary liver cancer cases diagnosed between 1980 and 1984 reported to the Shanghai Cancer Registry, and employment information from the 1982 census for the Shanghai population, standardized incidence ratios were computed to generate leads to occupational risks of liver cancer. Among men, a statistically significant excess number of cases was observed for chemical processors, textile workers, wood workers, blacksmiths and machine-tool operators, and material handlers and dock workers. Increased incidence of liver cancer also was observed among female transport equipment operators. These findings indicate that a number of similar occupations are associated with increased risk of primary liver cancer in western countries and China. Although causal inferences cannot be drawn from these data, our study adds to the limited evidence of the potential role of occupational exposures in liver carcinogenesis. (C) 1993 Wiley-Liss, Inc.* C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 37 TC 7 Z9 7 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1993 VL 24 IS 1 BP 93 EP 100 DI 10.1002/ajim.4700240109 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LJ360 UT WOS:A1993LJ36000008 PM 8352295 ER PT J AU MOWREY, PN CHORNEY, MJ VENDITTI, CP LATIF, F MODI, WS LERMAN, MI ZBAR, B ROBINS, DB ROGAN, PK LADDA, RL AF MOWREY, PN CHORNEY, MJ VENDITTI, CP LATIF, F MODI, WS LERMAN, MI ZBAR, B ROBINS, DB ROGAN, PK LADDA, RL TI CLINICAL AND MOLECULAR ANALYSES OF DELETION 3P25-PTER SYNDROME SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CHROMOSOME-3; 3P DELETION; GROWTH RETARDATION; MENTAL RETARDATION ID SHORT ARM; HUMAN CHROMOSOME-3; DNA FRAGMENTS; LOCALIZATION; KARYOTYPE; SEQUENCES; ONCOGENE; GENE AB Hemizygous deletion of 3p25-pter is associated with a phenotype of profound growth failure, microcephaly, characteristic facial changes, and mental retardation. Since the severity may be quite variable, we have studied 3 cases of del 3p25-pter to define the clinical manifestations and the critical chromosome region for phenotypic expression. The patient we now report died at age 6 months and provided an opportunity for a detailed necropsy analysis for only the second time in a del(3p) patient. He had marked hypoplasia of all organs, hypomyelination of white matter, and multiple renal cortical microcysts. Ordered genomic markers from the distal regions of chromosome 3p aided in determining the parent of origin of each deletion and in defining the boundaries of the deleted chromosomal segments. The deleted markers distal to the RAFI oneogene in 2 of the 3 patients were consistently hemizygous. One patient had an interstitial deletion based on evidence of diploid inheritance of one of the most distal loci (D3S17). Available genetic linkage maps suggest that the deletion spans at least 19 centimorgans (cM). (C) 1993 Wiley-Liss, Inc. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PEDIAT,POB 850,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PATHOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. RI Rogan, Peter/B-9845-2017 OI Rogan, Peter/0000-0003-2070-5254 NR 21 TC 42 Z9 42 U1 0 U2 4 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 JUL 1 PY 1993 VL 46 IS 6 BP 623 EP 629 DI 10.1002/ajmg.1320460604 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA LP905 UT WOS:A1993LP90500003 PM 8103286 ER PT J AU WILSON, GN HALL, JG DELACRUZ, F AF WILSON, GN HALL, JG DELACRUZ, F TI GENOMIC IMPRINTING - SUMMARY OF AN NICHHD CONFERENCE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE GROWTH FACTORS; CHROMOSOMAL TRANSLOCATIONS; MALFORMATION SYNDROMES; CHILDHOOD CANCERS; X-CHROMOSOME ID X-CHROMOSOME INACTIVATION; FRAGILE-X; MENTAL-RETARDATION; UNIPARENTAL DISOMY; PARENTAL ORIGIN; GENE; METHYLATION; EXPRESSION; MECHANISM; COMMON AB Compelling evidence for genomic imprinting as a pathogenetic mechanism in humans mandates re-evaluation of every genetic or multifactorial disease for parent-of-origin effects. In an expanding list of malformation syndromes, cancers, growth abnormalities, and chromosomal disorders, phenotypes may be determined by source rather than content of transmitted DNA. A multidisciplinary conference held on April 13-14, 1992, reviewed the substantial impact of genomic imprinting in mouse development and discussed in role in human pregnancy, childhood cancers, chromosomal translocations, X-inactivation, and several disorders associated with mental retardation. Topics for future research include the mechanism, timing, reversibility, and homology of the imprinting process. (C) 1993 Wiley-Liss, Inc. C1 UNIV BRITISH COLUMBIA,DEPT PEDIAT & MED GENET,VANCOUVER V6T 1W5,BC,CANADA. NICH,MENT RETARDAT & DEV DISABILITIES BRANCH,BETHESDA,MD. RP WILSON, GN (reprint author), UNIV TEXAS,SW MED CTR,DEPT PEDIAT,DIV PEDIAT GENET,5323 HARRY HINES,DALLAS,TX 75235, USA. NR 28 TC 12 Z9 12 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 JUL 1 PY 1993 VL 46 IS 6 BP 675 EP 680 DI 10.1002/ajmg.1320460614 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LP905 UT WOS:A1993LP90500013 PM 8103287 ER PT J AU DELACRUZ, F AF DELACRUZ, F TI REPORT OF NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN-DEVELOPMENT WORKSHOP ON CHORIONIC VILLUS SAMPLING AND LIMB AND OTHER DEFECTS, OCTOBER 20, 1992 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID PRENATAL-DIAGNOSIS; REDUCTION DEFECTS; MINOR ANOMALIES; MALFORMATIONS; ABNORMALITIES; INFANTS; CVS RP DELACRUZ, F (reprint author), NICHHD,6100 EXECUT BLVD,ROOM 4B09,BETHESDA,MD 20892, USA. NR 25 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 1993 VL 169 IS 1 BP 1 EP 6 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LN987 UT WOS:A1993LN98700001 ER PT J AU HAN, JS MAEDA, Y KNEPPER, MA AF HAN, JS MAEDA, Y KNEPPER, MA TI DUAL ACTIONS OF VASOPRESSIN AND OXYTOCIN IN REGULATION OF WATER PERMEABILITY IN TERMINAL COLLECTING DUCT SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE RAT; ISOLATED PERFUSED TUBULE; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE; RECEPTORS; INNER MEDULLARY COLLECTING DUCT ID CYTOSOLIC FREE CALCIUM; ANTIDIURETIC-HORMONE; V1 RECEPTORS; RAT; CELLS; EXCRETION; UREA; STIMULATION; SUBSEGMENTS; ACTIVATION AB We conducted studies in isolated perfused terminal inner medullary collecting ducts (IMCD) from rats to investigate the roles of oxytocin and vasopressin in the regulation of osmotic water permeability. Vasopressin and oxytocin were found to have both stimulatory effects (at 0.1 nM) and inhibitory effects (at 10 nM) on osmotic water permeability. Measurements of adenosine 3',5'-cyclic monophosphate (cAMP) production demonstrated that both vasopressin and oxytocin increase cAMP production. Both the selective oxytocin-receptor agonist [Thr4Gly7]oxytocin (10 nM) and the selective V1b agonist [deamino1,D-3-(pyridyl)Ala2,Arg8]vasopressin (10 nM) inhibited vasopressin-stimulated osmotic water permeability. In contrast, the selective V1a vasopressin-receptor agonist [Phe2,Ile3 Orn8]vasopressin (10 nM) had no effect on vasopressin-stimulated osmotic water permeability. These effects on water permeability correlated with the ability of the agents to transiently increase intracellular free calcium. The oxytocin/vasopressin-receptor antagonist [des-glycinamide9, d(CH2)51,O-Me-Tyr2,Thr4,Orn8]vasotocin, which almost completely blocks vasopressin-induced calcium mobilization, also blocked the ability of 10 nM vasopressin to inhibit osmotic water permeability relative to that found with 0.1 nM vasopressin. We conclude the following. 1) Oxytocin, like vasopressin, has dual effects on osmotic water permeability, increasing it at subnanomolar concentrations and inhibiting it at suprananomolar concentrations. 2) Oxytocin, like vasopressin, can increase cAMP production, perhaps accounting for the increase in water permeability. 3) Inhibition of water permeability by vasopressin, oxytocin, and their analogues is associated with their ability to cause intracellular calcium mobilization (and presumably activation of the phosphoinositide signaling pathway). 4) The inhibitory effect on water permeability is associated with binding of vasopressin or oxytocin to either an oxytocin receptor, a novel vasopressin receptor, or both. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. NR 33 TC 31 Z9 31 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP F26 EP F34 PN 2 PG 9 WC Physiology SC Physiology GA LP432 UT WOS:A1993LP43200100 PM 8393623 ER PT J AU MAEDA, Y HAN, JS GIBSON, CC KNEPPER, MA AF MAEDA, Y HAN, JS GIBSON, CC KNEPPER, MA TI VASOPRESSIN AND OXYTOCIN RECEPTORS COUPLED TO CA2+ MOBILIZATION IN RAT INNER MEDULLARY COLLECTING DUCT SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE FURA-2; KIDNEY; INNER MEDULLA ID CYTOSOLIC FREE CALCIUM; CYCLIC ADENOSINE-MONOPHOSPHATE; ARGININE-VASOPRESSIN; BINDING-SITES; AUTORADIOGRAPHIC LOCALIZATION; INTRACELLULAR CALCIUM; V1 RECEPTORS; CELLS; POTENT; SPECIFICITY AB In renal collecting duct epithelial cells, arginine vasopressin (AVP) at greater than nanomolar concentrations has been reported to transiently increase intracellular free calcium ([Ca2+]i) in a manner consistent with activation of the phosphoinositide pathway. To investigate whether any of the known neurohypophysial hormone subtypes are involved, we measured [Ca2+]i in microdissected rat terminal inner medullary collecting duct (IMCD) using fura-2. To allow quantitative comparisons of the response under different conditions, we determined the areas under the response curves (in nM.min) over 1.5 min using numerical integration. AVP, the V1b-receptor agonist [deamino1,D-3-(pyridyl)Ala2,Arg8]vasopressin, the V2-receptor agonist 1-desamino-8-D-arginine vasopressin, oxytocin, and the selective oxytocin-receptor agonist [Thr4,Gly7]-oxytocin (TG-OXT), each at 10 nM, significantly increased [Ca2+]i (69.52 +/- 10.25, 27.0 +/- 11.7, 24.33 +/- 5.83, 14.75 +/- 2.81, and 14.57 +/- 3.50 nM.min, respectively). In contrast, a V1a-selective agonist ([Phe2,Ile3,Orn8]vasopressin) did not increase [Ca2+]i (0.43 +/- 2.36 nM.min). In desensitization studies, challenge with 10 nM AVP or TG-OXT completely prevented a rise in [Ca2+]i in response to immediate rechallenge with the same agent, but not the other, demonstrating homologous desensitization. The lack of cross-desensitization implies that at least two receptors are present that can trigger a rise in [Ca2+]i in response to neurohypophysial hormones. Antagonists for oxytocin {[des-glycinamide9,d(CH2)51,O-Me-Tyr2,Thr4,Orn8]vasotocin}, V2 {[d(CH2)51,OD-Ile2,Ile4,Arg8]vasopressin), and V1a {[d(CH2)51,O-Me-Tyr2,Arg8]vasopressin) receptors partially inhibited the [Ca2+]i response induced by 10 nM AVP (89.5, 81.6, and 51.4% inhibition, respectively). These data are consistent with the view that both an oxytocin receptor and a vasopressin receptor are coupled to a [Ca2+]i mobilization response in rat terminal IMCD. This vasopressin receptor is distinct from both the V1a receptor and the V2 receptor and may be either the V1b receptor or a novel vasopressin receptor subtype. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N307,BETHESDA,MD 20892. NR 46 TC 47 Z9 48 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP F15 EP F25 PN 2 PG 11 WC Physiology SC Physiology GA LP432 UT WOS:A1993LP43200099 PM 8393622 ER PT J AU YUN, JCH ORIJI, G GILL, JR COLEMAN, BR PETERS, J KEISER, H AF YUN, JCH ORIJI, G GILL, JR COLEMAN, BR PETERS, J KEISER, H TI ROLE OF MUSCARINIC RECEPTORS IN RENAL RESPONSE TO ACETYLCHOLINE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ATROPINE; RENAL PLASMA FLOW; SODIUM EXCRETION; INDOMETHACIN; PROSTAGLANDINS ID SMOOTH-MUSCLE; ENDOTHELIUM; ARTERY; CELLS AB Renal arterial infusion of acetylcholine (ACh) (40 mug/min) in control dogs produced an ipsilateral increase in renal plasma flow (RPF) and in sodium excretion (U(Na)V) without a change in glomerular filtration rate (GFR). The increase in RPF and U(Na)V was maintained during the infusion of ACh. In indomethacin (Indo)-treated dogs (5 mg/kg) ACh produced a transient rise in RPF and U(Na)V, followed by a progressive decline in RPF and U(Na)V. The profound renal vasoconstriction was accompanied by a decline in GFR. To determine the role of the muscarinic receptor in the renal vasodilation and in vasoconstriction produced by ACh in Indo-treated dogs, atropine at 6, 60, and 600 mug/min was infused into the renal artery before and during the infusion of ACh. In Indo-treated dogs, all dosages of atropine prevented renal vasoconstriction by ACh. Renal arterial infusion of atropine at 600 mug/min completely inhibited the renal vasodilation produced by ACh. Atropine infused at 60 mug/min partially inhibited, whereas 6 mug/min atropine failed to inhibit, the renal vasodilation produced by ACh. Our data suggest that the renal vasodilator and vasoconstrictor effects of ACh in Indo-treated dogs are mediated by two separate types of muscarinic receptors. C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20205. RP YUN, JCH (reprint author), HOWARD UNIV,COLL MED,DEPT PHYSIOL & BIOPHYS,520 W ST NW,WASHINGTON,DC 20059, USA. FU NIGMS NIH HHS [SO6GM08016] NR 17 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP F46 EP F52 PN 2 PG 7 WC Physiology SC Physiology GA LP432 UT WOS:A1993LP43200102 PM 8342614 ER PT J AU BOLUYT, MO YOUNES, A CAFFREY, JL ONEILL, L BARRON, BA CROW, MT LAKATTA, EG AF BOLUYT, MO YOUNES, A CAFFREY, JL ONEILL, L BARRON, BA CROW, MT LAKATTA, EG TI AGE-ASSOCIATED INCREASE IN RAT CARDIAC OPIOID PRODUCTION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CARDIAC OPIOID PEPTIDES; METHIONINE ENKEPHALIN; LEUCINE ENKEPHALIN; CARDIAC HYPERTROPHY; PREPROENKEPHALIN MESSENGER RNA; AGING ID PREPROENKEPHALIN MESSENGER-RNA; AORTIC CONSTRICTION; HEART; ENKEPHALIN; PEPTIDES; TISSUES; BRAIN; HYPERTROPHY; STIMULATION; SENESCENCE AB Several lines of evidence suggest that opioid peptide production in the heart may increase during aging from adulthood through senescence. We tested the hypothesis that cardiac opioid peptides and preproenkephalin (PNK) mRNA would increase with advancing age. Ventricles and atria from male Wistar rats, aged 2, 6, 18, and 22-24 mo of age, were acid extracted and assayed for methionine enkephalin (ME) and leucine enkephalin (LE). Total RNA was extracted from hearts of age-matched rats and probed for PNK mRNA by Northern blot analysis using a cDNA probe. ME and LE peptides were significantly elevated with advancing age in both ventricles [P < 0.001; by analysis of variance (ANOVA)]. Ventricular ME concentration exhibited a biphasic increase with approximately twofold higher peaks at 6 and 22-24 mo of age compared with the 2 mo value of 1.04 +/- 0.05 (SE) pmol/g wet wt. In contrast, ventricular LE concentration was largely unchanged until 22-24 mo of age when it increased approximately threefold over the 2-mo value of 2.19 +/- 0.14 pmol/g wet wt. Left ventricular PNK mRNA increased approximately fivefold between 2 and 18 mo of age (P < 0.01; ANOVA). Thus both enkephalins and the mRNA coding for them were increased in hearts of older vs. younger rats. Because opioid receptor stimulation can negatively modulate several characteristics of cardiac myocyte contraction, these results may have important functional implications for the senescent heart. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. TEXAS COLL OSTEOPATH MED,FT WORTH,TX 76107. INST UNIV TECHNOL CLERMONT FERRAND,F-63172 CLERMONT FERRAND,FRANCE. NR 36 TC 33 Z9 34 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP H212 EP H218 PN 2 PG 7 WC Physiology SC Physiology GA LP432 UT WOS:A1993LP43200030 PM 8342635 ER PT J AU GLEASON, CA IIDA, H OBRIEN, TP JONES, MD CONE, EJ TRAYSTMAN, RJ AF GLEASON, CA IIDA, H OBRIEN, TP JONES, MD CONE, EJ TRAYSTMAN, RJ TI FETAL RESPONSES TO ACUTE MATERNAL COCAINE INJECTION IN SHEEP SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PERINATAL; DRUGS; BRAIN ID CEREBRAL BLOOD-FLOW; INTRAVENOUS COCAINE; GLUCOSE-UTILIZATION; AUTO-REGULATION; OXYGENATION; ABUSE; BRAIN; VASOCONSTRICTION; NOREPINEPHRINE; METABOLITES AB Maternal cocaine abuse has been associated with neonatal neurological and neurobehavioral problems of unknown pathogenesis. We administered a single intravenous dose of cocaine (2 mg/kg) to 12 unanesthetized pregnant sheep; their fetuses had been catheterized in utero 2 days before the study. We measured fetal cerebral blood flow (CBF), cerebral metabolic rate of O2 (CMR(O2)), mean arterial blood pressure (MAP), and blood gases before and 2, 5, 15, and 30 min after maternal cocaine injection. Fetal CBF increased by 37 +/- 33% (mean +/- SD) at 5 min and returned to baseline by 15 min. Regional brain blood flow changes paralleled CBF changes with the greatest increases occurring in cerebellum (54 +/- 43%) and brain stem (54 +/- 52%). Cerebral vascular resistance was decreased for cerebellum (22%) and brain stem (19%) but was unchanged for cerebral hemispheres and caudate. Increased CBF at 5 min was associated with a 20 +/- 9% increase in fetal MAP and a 38 +/- 13% decrease in fetal arterial O2 content. Fetal CMR(O2), was unchanged. There was a decrease in fetal intestinal blood flow at 2 min, an increase in myocardial, adrenal, and renal blood flow at 5 min, and no change in placental blood flow. Maternal cocaine injection causes fetal hypoxemia, hypertension, and increased CBF. Possible mechanisms for cerebral vasodilation (in some areas) include hypoxemia, impaired autoregulatory response to increased blood pressure, and/or direct or indirect vascular effects of cocaine or its metabolites. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT GYNECOL & OBSTET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL CRIT CARE MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,EUDOWOOD NEONATAL PULM DIV,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. FU PHS HHS [6658] NR 34 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP H9 EP H14 PN 2 PG 6 WC Physiology SC Physiology GA LP432 UT WOS:A1993LP43200002 PM 8342669 ER PT J AU NECKERS, L WHITESELL, L AF NECKERS, L WHITESELL, L TI ANTISENSE TECHNOLOGY - BIOLOGICAL UTILITY AND PRACTICAL CONSIDERATIONS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Review ID ANTI-SENSE RNA; HUMAN LYMPHOCYTES-T; MURINE ERYTHROLEUKEMIA-CELLS; NORMAL HUMAN HEMATOPOIESIS; ONCOGENE MESSENGER-RNA; EPSTEIN-BARR VIRUS; C-MYC EXPRESSION; GENE-EXPRESSION; INSITU HYBRIDIZATION; F9 CELLS AB Antisense RNA and DNA techniques have been developed as a relatively recent approach to the specific modulation of gene expression in vitro and in vivo. This review discusses general considerations for the application of antisense techniques. We shall examine the relative advantages and disadvantages of DNA versus RNA techniques, as well as the common pitfalls peculiar to each strategy. RP NECKERS, L (reprint author), NCI,CLIN PHARMACOL BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 81 TC 66 Z9 66 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1993 VL 265 IS 1 BP L1 EP L12 PN 1 PG 12 WC Physiology SC Physiology GA LP431 UT WOS:A1993LP43100091 PM 8393300 ER PT J AU CARLSON, EB PUTNAM, FW ROSS, CA TOREM, M COONS, P DILL, DL LOEWENSTEIN, RJ BRAUN, BG AF CARLSON, EB PUTNAM, FW ROSS, CA TOREM, M COONS, P DILL, DL LOEWENSTEIN, RJ BRAUN, BG TI VALIDITY OF THE DISSOCIATIVE EXPERIENCES SCALE IN SCREENING FOR MULTIPLE PERSONALITY-DISORDER - A MULTICENTER STUDY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID INSTRUMENT; INTERVIEW AB Objective: The Dissociative Experiences Scale has proved a reliable and valid instrument to measure dissociation in many groups, but its capacity to distinguish patients with multiple personality disorder from patients with other psychiatric disorders has not yet been conclusively tested. Method: A discriminant analysis was performed to classify 1,051 subjects as having or not having multiple personality disorder. Another discriminant analysis was performed on a subgroup of 883 subjects more closely representing patients in a typical psychiatric facility in terms of base rates of dissociative disorders. A cutoff score of 30 was also used to classify subjects, and Bayes's theorem, which allows for the calculation of the positive predictive value and the negative predictive value of a screening test, was applied. Results: According to discriminant analysis of the total study group, the scale's sensitivity was 76% and its specificity was also 76%; according to discriminant analysis of the more representative subgroup, the scale's sensitivity was 76% and its specificity was 85%. Use of the cutoff score of 30 produced similar results. Results of the application of Bayes's theorem showed that 17% of the subjects scoring 30 or higher would actually have multiple personality disorder and 99% of those scoring less than 30 would not have multiple personality disorder. Conclusions: These results indicate that the Dissociative Experiences Scale performs quite well as a screening instrument to identify subjects with multiple personality disorder. In addition, the consistency of responses to scale items across centers indicates that the symptoms reported by patients with multiple personality disorder are highly similar across diverse geographic centers. This consistency supports the reliability and validity of the diagnosis of multiple personality disorder across centers. C1 NIMH,DEV PSYCHOL LAB,DISSOCIAT DISORDERS UNIT,BETHESDA,MD 20892. ST BONIFACE GEN HOSP,WINNIPEG R2H 2A6,MANITOBA,CANADA. AKRON GEN MED CTR,AKRON,OH. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN 46202. SHEPPARD & ENOCH PRATT HOSP,BALTIMORE,MD 21204. RUSH N SHORE MED CTR,DISSOCIAT DISORDERS PROGRAM,INPATIENT UNIT,CHICAGO,IL. RP CARLSON, EB (reprint author), BELOIT COLL,DEPT PSYCHOL,700 COLL ST,BELOIT,WI 53511, USA. OI Carlson, Eve/0000-0002-4431-2415 NR 24 TC 246 Z9 248 U1 2 U2 22 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 JUL PY 1993 VL 150 IS 7 BP 1030 EP 1036 PG 7 WC Psychiatry SC Psychiatry GA LL398 UT WOS:A1993LL39800007 PM 8317572 ER PT J AU PUTNAM, FW LOEWENSTEIN, RJ AF PUTNAM, FW LOEWENSTEIN, RJ TI TREATMENT OF MULTIPLE PERSONALITY-DISORDER - A SURVEY OF CURRENT PRACTICES SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DISSOCIATIVE DISORDERS; INTERVIEW; CHILDREN; ILLNESS; ABUSE AB Objective: Reported cases of multiple personality disorder have increased dramatically in the last decade. Few data are available on the treatment of multiple personality disorder. Current recommendations are based on the experience of individual clinicians rather than on systematic research. Method: A questionnaire study of 305 clinicians representing a spectrum of mental health professionals was conducted to survey the types and relative efficacy of treatment modalities currently used with cases of multiple personality disorder. Results: Individual psychotherapy facilitated by hypnosis was uniformly endorsed as the primary treatment by all practitioner groups. The average patient was in twice-weekly psychotherapy facilitated by hypnosis for 3.8 years. Antidepressant and anxiolytic medications were reported to be moderately useful adjunctive treatments. Conclusions: These findings support current impressionistic treatment recommendations for multiple personality disorder regarding the primacy of psychotherapy and the moderate benefits of psychopharmacology with antidepressant and antianxiety agents. RP PUTNAM, FW (reprint author), NIMH,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 28 Z9 28 U1 0 U2 3 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 JUL PY 1993 VL 150 IS 7 BP 1048 EP 1052 PG 5 WC Psychiatry SC Psychiatry GA LL398 UT WOS:A1993LL39800010 PM 8100401 ER PT J AU BERGNER, L AF BERGNER, L TI RACE, HEALTH, AND HEALTH-SERVICES SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID CANCER; BLACK RP BERGNER, L (reprint author), NCI,EXECUT PLAZA N,ROOM 233,BETHESDA,MD 20892, USA. NR 13 TC 21 Z9 21 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1993 VL 83 IS 7 BP 939 EP 941 DI 10.2105/AJPH.83.7.939 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LN036 UT WOS:A1993LN03600001 PM 8328610 ER PT J AU BROERS, JLV VIALLET, J JENSEN, SM PASS, H TRAVIS, WD MINNA, JD LINNOILA, RI AF BROERS, JLV VIALLET, J JENSEN, SM PASS, H TRAVIS, WD MINNA, JD LINNOILA, RI TI EXPRESSION OF C-MYC IN PROGENITOR CELLS OF THE BRONCHOPULMONARY EPITHELIUM AND IN A LARGE NUMBER OF NONSMALL CELL LUNG CANCERS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID FAMILY DNA AMPLIFICATION; N-MYC; INSITU HYBRIDIZATION; MONOCLONAL-ANTIBODY; ONCOGENE AMPLIFICATION; GENE FAMILY; LINES; TUMORS; RNA; PROTOONCOGENES AB We performed in situ hybridization for c-myc, N-myc, and L-myc mRNA expression using S-35-labeled cRNA probes on frozen sections of 19 pairs of non-small cell lung cancers (NSCLC) and the surrounding non-neoplastic lung tissue. In non-neoplastic lung, c-myc expression was strongest in bronchial epithelium basal cells and hyperplastic alveolar type II pneumocytes, which are potential progenitor cells for bronchopulmonary epithelium and their tumors. In contrast, N-myc and L-myc mRNAs were not detected in non-neoplastic lung. In studies of freshly resected primary tumors, expression of c-myc was detected in 11 of 19 NSCLC (with the highest levels in squamous cell carcinomas), two of which also expressed L-myc, while N-myc expression was never detected. Levels of c-myc expression in tumors were significantly higher than in non-neoplastic lung samples. We conclude that: (1) c-myc expression in non-neoplastic lung tissues is highest in bronchial basal cells and hyperplastic type II cells, and (2) in NSCLC, overexpression of the myc-proto-oncogene is common. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NCI,NAVY MED ONCOL BRANCH,SURG BRANCH,BETHESDA,MD 20892. NR 47 TC 47 Z9 47 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 JUL PY 1993 VL 9 IS 1 BP 33 EP 43 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA LT038 UT WOS:A1993LT03800008 PM 8393325 ER PT J AU ANDRADE, ZA COX, TM CHEEVER, AM AF ANDRADE, ZA COX, TM CHEEVER, AM TI REGRESSION OF HEPATIC-LESIONS AFTER TREATMENT OF SCHISTOSOMA-MANSONI OR SCHISTOSOMA-JAPONICUM INFECTION IN MICE - A COMPARATIVE-STUDY SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID GRANULOMA SIZE; CELLULAR COMPOSITION; COLLAGEN RESORPTION; FIBROSIS; PRAZIQUANTEL; STRAINS; EGGS AB Experimental infections with Schistosoma mansoni and S. japonicum differ in several aspects and post-treatment resorption of fibrosis might be one of them. To investigate this point, mice infected with each of these schistosome species were treated with praziquantel and the evolution of hepatic lesions was sequentially followed for five months. Parasitologic data showing destruction of worms and eggs and biochemical findings of progressively decreased collagen concentration after cure indicated that the lesions caused by S. mansoni and S. japonicum involuted in a similar fashion following chemotherapy. The time sequence of the histologic changes indicative of decreasing inflammation and progressive matrix degradation and resorption was also similar in both cases. C1 NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892. GONCALO MONIZ RES CTR FIOCRUZ,BR-91945 SALVADOR,BA,BRAZIL. FU NIAID NIH HHS [AI-052590] NR 21 TC 9 Z9 10 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 1993 VL 49 IS 1 BP 1 EP 9 PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA LU313 UT WOS:A1993LU31300001 PM 8352381 ER PT J AU WEIL, JV CASTRO, O MALIK, AB RODGERS, G BONDS, DR JACOBS, TP AF WEIL, JV CASTRO, O MALIK, AB RODGERS, G BONDS, DR JACOBS, TP TI PATHOGENESIS OF LUNG-DISEASE IN SICKLE HEMOGLOBINOPATHIES SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article C1 NHLBI,DIV LUNG DIS,WESTWOOD BLDG,5333 WESTBARD AVE,ROOM 6A09,BETHESDA,MD 20892. NR 0 TC 58 Z9 58 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD JUL PY 1993 VL 148 IS 1 BP 249 EP 256 PG 8 WC Respiratory System SC Respiratory System GA LV447 UT WOS:A1993LV44700044 PM 8317809 ER PT J AU KURPISZ, M DOBRATZ, B ALEXANDER, NJ AF KURPISZ, M DOBRATZ, B ALEXANDER, NJ TI SPERM ANTIGENS AND REACTIVITY OF ANTISPERM MONOCLONAL-ANTIBODIES IN ELISA SO ANDROLOGIA LA English DT Article DE ELISA; SPERM ANTIGENS; ANTISPERM MONOCLONAL ANTIBODIES; HUMAN ID PLASMA AB Several types of sperm antigenic suspensions as well as the whole sperm, either methanol-fixed or air-dried, were checked for intensity of binding to monoclonal antisperm antibodies with known characteristics of reactivity to sperm. The activity of sperm antigen-antibody binding was measured by ELISA (enzyme-linked immunosorbent assay) and compared in several variations (parallely run) of the assay where different types of sperm antigen preparations were applied. The obtained results were then evaluated for statistical significance in Wilcox test. It was shown that antibody reactivity was markedly higher in experiments where the whole sperm was coated in a solid-phase in comparison to results obtained with adhered different sperm antigenic suspensions. However, one exception was noted, where the results from ELISA, run with sperm organic extract, were (statistically) insignificantly lower than those obtained with the whole sperm. Therefore, organic sperm extracts (containing mostly glycolipids) can be a valuable alternative to screening for antisperm antibody activity and or infertility background. C1 EVMS,JONES INST REPROD MED,NORFOLK,VA. NICHHD,CTR POPULAT RES,BETHESDA,MD. RP KURPISZ, M (reprint author), POLISH ACAD SCI,INST HUMAN GENET,UL STRZESZYNSKA 32,PL-60479 POZNAN,POLAND. NR 16 TC 3 Z9 3 U1 1 U2 2 PU BLACKWELL VERLAG GMBH PI BERLIN PA KURFURSTENDAMM 58, D-10707 BERLIN, GERMANY SN 0303-4569 J9 ANDROLOGIA JI Andrologia PD JUL-AUG PY 1993 VL 25 IS 4 BP 175 EP 179 PG 5 WC Andrology SC Endocrinology & Metabolism GA LK743 UT WOS:A1993LK74300001 PM 8352425 ER PT J AU ALLADA, R NASH, HA AF ALLADA, R NASH, HA TI DROSOPHILA-MELANOGASTER AS A MODEL FOR STUDY OF GENERAL-ANESTHESIA - THE QUANTITATIVE RESPONSE TO CLINICAL ANESTHETICS AND ALKANES SO ANESTHESIA AND ANALGESIA LA English DT Article ID CAENORHABDITIS-ELEGANS; SITES AB Using an assay of the geotactic behavior of the fruit fly, we have quantified anesthetic effects in Drosophila melanogaster. We determined dose-responses for nine conventional anesthetics and a series of n-alkanes. For the conventional anesthetics, anesthetic potency and olive oil/gas partition coefficients are well correlated. However, as one ascends the series of alkanes of chain lengths 5-11, the increase in anesthetic potency is considerably less than that predicted by olive oil solubility. These examples of agreement and disagreement with the Meyer-Overton rule provide a basis for comparing the responses of fruit flies with those of higher organisms; such comparisons suggest that the anesthetic target is evolutionarily conserved. For alkanes with chain lengths greater than 11, anesthetic effects are variable and slow to develop. This behavior reflects limited volatility and provides no evidence for a cut-off in the action of alkanes at their target. C1 NIMH,MOLEC BIOL LAB,BLDG 36,RM 1B08,BETHESDA,MD 20892. NR 22 TC 54 Z9 57 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 1993 VL 77 IS 1 BP 19 EP 26 PG 8 WC Anesthesiology SC Anesthesiology GA LL119 UT WOS:A1993LL11900005 PM 8317731 ER PT J AU TAUB, D BLANK, KJ AF TAUB, D BLANK, KJ TI SUPERANTIGENS AND MICROBIAL PATHOGENESIS SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID STAPHYLOCOCCAL ENTEROTOXIN-B; TOXIC SHOCK SYNDROME; MAMMARY-TUMOR VIRUS; T-CELLS; MYCOPLASMA-ARTHRITIDIS; BETA; MICE; STIMULATION; LYMPHOCYTES; ACTIVATION C1 HAHNEMANN UNIV,DEPT PATHOL,MS435,ROOM 5409,BROAD & VINE,PHILADELPHIA,PA 19102. NCI,FREDERICK,MD 21702. NR 24 TC 5 Z9 5 U1 0 U2 0 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 JUL 1 PY 1993 VL 119 IS 1 BP 89 EP 90 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LJ266 UT WOS:A1993LJ26600016 PM 8498771 ER PT J AU PASCUALLEONE, A CAMMAROTA, A WASSERMANN, EM BRASILNETO, JP COHEN, LG HALLETT, M AF PASCUALLEONE, A CAMMAROTA, A WASSERMANN, EM BRASILNETO, JP COHEN, LG HALLETT, M TI MODULATION OF MOTOR CORTICAL OUTPUTS TO THE READING HAND OF BRAILLE READERS SO ANNALS OF NEUROLOGY LA English DT Article ID MAGNETIC STIMULATION; NEURAL MECHANISMS; REORGANIZATION; MAMMALS; CORTEX AB We used focal transcranial magnetic stimulation to map the motor cortical areas targeting the first dorsal interosseous and the abductor digiti minimi muscles bilaterally in 10 proficient braille readers and 10 blind controls who were matched for age (mean, 50.6 yr) and age at time of blindness (mean, 7.5 yr). The proficient braille readers had learned braille at age 8 to 14 years and used it daily for 5 to 10 hours. Controls had not learned braille until age 17 to 21 years and used it daily for <1 hour. In the controls, motor representations of the right and left first dorsal interosseous and abductor digiti minimi muscles were not significantly different. However, in the proficient braille readers, the representation of the first dorsal interosseous muscle in the reading hand was significantly larger than that in the nonreading hand or in either hand of the controls. Conversely, the representation of the abductor digiti minimi muscle in the reading hand was significantly smaller than that in the nonreading hand or in either hand of the controls. These differences were not due to differences in motor thresholds. Our results suggest that the cortical representation of the reading finger in proficient braille readers is enlarged at the expense of the representation of other fingers. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORTICAL PHYSIOL UNIT,BETHESDA,MD 20892. RI Brasil-Neto, Joaquim/A-1171-2009 NR 24 TC 170 Z9 172 U1 0 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 1993 VL 34 IS 1 BP 33 EP 37 DI 10.1002/ana.410340108 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LK404 UT WOS:A1993LK40400006 PM 8517678 ER PT J AU ROSENTHAL, AK MCLAUGHLIN, JK LINET, MS PERSSON, I AF ROSENTHAL, AK MCLAUGHLIN, JK LINET, MS PERSSON, I TI SCLERODERMA AND MALIGNANCY - AN EPIDEMIOLOGIC-STUDY SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID NON-HODGKINS LYMPHOMA; PROGRESSIVE SYSTEMIC-SCLEROSIS; GROWTH FACTOR-BETA; RHEUMATOID-ARTHRITIS; CANCER; ADENOCARCINOMA; ASSOCIATION; DISEASE; RISK AB Objectives-Although case reports and some patient series suggest an increased risk of cancer among patients with scleroderma, there are no population based studies to support this association. A population based follow up study was therefore carried out of 233 patients with scleroderma from the six-county Uppsala health care region of Sweden for the time period 1955-84. Methods-Using the inpatient registry for the Uppsala health care region, all patients with scleroderma were identified. Their unique identification codes were then used to perform a record linkage with the National Cancer Registry. Expected cancer rates were determined using the age and gender specific rates for the Uppsala health care region. Results-The standardised incidence ratio (SIR) for all cancers among these patients was significantly increased (SIR=2.4; 95% CI=1.5 to 3.6). The SIRs for lung cancer (SIR=7.8; 95% CI=2.5 to 18.2) and non-Hodgkin's lymphoma (SIR=9.6; 95% CI=1.1 to 34.5) were also significantly increased. Excluding patients who were diagnosed with cancer within a year of their scleroderma diagnosis resulted in similar findings, though the SIR for non-Hodgkin's lymphoma was no longer statistically significant. Conclusions-Larger population based investigations of cancer risk among patients with scleroderma are needed to confirm these initial findings and to evaluate in greater detail possible cancer risk among these patients. C1 MED COLL WISCONSIN,DEPT RHEUMATOL,MILWAUKEE,WI 53226. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV UPPSALA,CANC EPIDEMIOL UNIT,S-75105 UPPSALA,SWEDEN. NR 34 TC 72 Z9 74 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 1993 VL 52 IS 7 BP 531 EP 533 DI 10.1136/ard.52.7.531 PG 3 WC Rheumatology SC Rheumatology GA LJ620 UT WOS:A1993LJ62000010 PM 8346981 ER PT J AU BUCKHEIT, RW HOLLINGSHEAD, MG GERMANYDECKER, J WHITE, EL MCMAHON, JB ALLEN, LB ROSS, LJ DECKER, WD WESTBROOK, L SHANNON, WM WEISLOW, O BADER, JP BOYD, MR AF BUCKHEIT, RW HOLLINGSHEAD, MG GERMANYDECKER, J WHITE, EL MCMAHON, JB ALLEN, LB ROSS, LJ DECKER, WD WESTBROOK, L SHANNON, WM WEISLOW, O BADER, JP BOYD, MR TI THIAZOLOBENZIMIDAZOLE - BIOLOGICAL AND BIOCHEMICAL ANTIRETROVIRAL ACTIVITY OF A NEW NONNUCLEOSIDE REVERSE-TRANSCRIPTASE INHIBITOR SO ANTIVIRAL RESEARCH LA English DT Article DE THIAZOLOBENZIMIDAZOLE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; MECHANISM OF ACTION; COMBINATION THERAPY ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA POLYMERASE-ALPHA; MOLECULAR CHARACTERIZATION; THYMIDINE 5'-TRIPHOSPHATE; ANTIVIRAL ACTIVITY; HIV-1 REPLICATION; TIBO DERIVATIVES; ZIDOVUDINE AZT; 3'-AZIDO-3'-DEOXYTHYMIDINE; INVITRO AB Thiazolobenzimidazole (NSC 625487) was a highly potent inhibitor of human immunodeficiency virus-induced cell killing and viral replication in a variety of human cell lines, as well as fresh human peripheral blood lymphocytes and macrophages. The compound was active against a panel of biologically diverse laboratory and clinical strains of HIV-1, including the AZT-resistant strain G910-6. However, the agent was inactive against HIV-2 and a pyridinone-resistant strain (A17) of HIV-1, a strain which is cross-resistant to several structurally diverse members of a common pharmacologic class of nonnucleoside reverse transcriptase inhibitors. The compound selectively inhibited HIV-1 reverse transcriptase but not HIV-2 reverse transcriptase. Combinations of thiazolobenzimidazole with either AZT or ddI synergistically inhibited HIV-1 induced cell killing in vitro. Thiazolobenzimidazole also inhibited the replication of the Rauscher murine leukemia retrovirus. Thus, thiazolobenzimidazole is a new active anti-HIV-1 chemotype and may represent a subclass of nonnucleoside reverse transcriptase inhibitors with an enhanced range of anti-retroviral activity. C1 SO RES INST,MICROBIOL RES DEPT,BIRMINGHAM,AL 35255. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,ANTIVIRAL EVALUAT BRANCH,BETHESDA,MD 20892. DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD. PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. FU NCI NIH HHS [N01-CM-87237]; NIAID NIH HHS [P30 AI27767] NR 46 TC 99 Z9 101 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUL PY 1993 VL 21 IS 3 BP 247 EP 265 DI 10.1016/0166-3542(93)90031-D PG 19 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA LM819 UT WOS:A1993LM81900005 PM 7692815 ER PT J AU DAVIS, MD KAUFMAN, S AF DAVIS, MD KAUFMAN, S TI PRODUCTS OF THE TYROSINE-DEPENDENT OXIDATION OF TETRAHYDROBIOPTERIN BY RAT-LIVER PHENYLALANINE-HYDROXYLASE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID BIOLOGICALLY-ACTIVE PTERIDINES; PROLYL 4-HYDROXYLASE; TETRAHYDROPTERIN OXIDATION; ABSOLUTE-CONFIGURATION; LYSYL HYDROXYLASE; ENZYME; IRON; 4A-CARBINOLAMINE; LYSOLECITHIN; PURIFICATION RP DAVIS, MD (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 46 TC 41 Z9 41 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1993 VL 304 IS 1 BP 9 EP 16 DI 10.1006/abbi.1993.1315 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LL838 UT WOS:A1993LL83800002 PM 8323303 ER PT J AU HIRAIWA, M OBRIEN, JS KISHIMOTO, Y GALDZICKA, M FLUHARTY, AL GINNS, EI MARTIN, BM AF HIRAIWA, M OBRIEN, JS KISHIMOTO, Y GALDZICKA, M FLUHARTY, AL GINNS, EI MARTIN, BM TI ISOLATION, CHARACTERIZATION, AND PROTEOLYSIS OF HUMAN PROSAPOSIN, THE PRECURSOR OF SAPOSINS (SPHINGOLIPID ACTIVATOR PROTEINS) SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID LYSOSOMAL STORAGE; CELLS C1 UCLA,MRRC,RES GRP,CTR LANTERMAN DEV,POMONA,CA 91769. NIMH,CLIN NEUROSCI BRANCH,MOLEC NEUROGENET SECT,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. FU NINDS NIH HHS [NS-08682, NS-13559, NS-22655] NR 19 TC 76 Z9 78 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1993 VL 304 IS 1 BP 110 EP 116 DI 10.1006/abbi.1993.1328 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LL838 UT WOS:A1993LL83800015 PM 8323276 ER PT J AU KARLSTROM, AR SHAMES, BD LEVINE, RL AF KARLSTROM, AR SHAMES, BD LEVINE, RL TI REACTIVITY OF CYSTEINE RESIDUES IN THE PROTEASE FROM HUMAN-IMMUNODEFICIENCY-VIRUS - IDENTIFICATION OF A SURFACE-EXPOSED REGION WHICH AFFECTS ENZYME FUNCTION SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID SYNTHETIC HIV-1 PROTEASE; ASPARTIC PROTEASE; ESCHERICHIA-COLI; AIDS; PROTEINASE; TARGET C1 NHLBI, BIOCHEM LAB, BLDG 3, ROOM 106, BETHESDA, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 36 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1993 VL 304 IS 1 BP 163 EP 169 DI 10.1006/abbi.1993.1334 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LL838 UT WOS:A1993LL83800021 PM 8323281 ER PT J AU HAMASAKI, Y KITZLER, J HARDMAN, R NETTESHEIM, P ELING, TE AF HAMASAKI, Y KITZLER, J HARDMAN, R NETTESHEIM, P ELING, TE TI PHORBOL ESTER AND EPIDERMAL GROWTH-FACTOR ENHANCE THE EXPRESSION OF 2 INDUCIBLE PROSTAGLANDIN-H SYNTHASE GENES IN RAT TRACHEAL EPITHELIAL-CELLS SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MESSENGER-RNA; DENOVO SYNTHESIS; CYCLOOXYGENASE; STIMULATION; INDUCTION; BIOSYNTHESIS; ACTIVATION; PROTEIN; ENCODES C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 19 TC 91 Z9 92 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1993 VL 304 IS 1 BP 226 EP 234 DI 10.1006/abbi.1993.1343 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LL838 UT WOS:A1993LL83800030 PM 8323287 ER PT J AU RANDOLPH, C HYDE, TM GOLD, JM GOLDBERG, TE WEINBERGER, DR AF RANDOLPH, C HYDE, TM GOLD, JM GOLDBERG, TE WEINBERGER, DR TI TOURETTES-SYNDROME IN MONOZYGOTIC TWINS - RELATIONSHIP OF TIC SEVERITY TO NEUROPSYCHOLOGICAL FUNCTION SO ARCHIVES OF NEUROLOGY LA English DT Article ID EARLY PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; PERFORMANCE; DISORDER; DYSFUNCTION; CHILDREN AB Objective.-To determine whether there is a relationship between tic severity and neuropsychological function in Tourette's syndrome (TS). Design.-The study employed a case-control series involving monozygotic twin pairs, divided into more severe and less severe groups based on tic severity and tested with a neuropsychological battery of tests. Setting.-Twin pairs were recruited nationwide and evaluated in the National Institute of Mental Health Neuropsychiatric Research Hospital. Patients.-Twelve twin pairs (mean age, 10.5 years; range, 8 to 16 years) in which at least one member met criteria for a diagnosis of TS. Results.-Global neuropsychological performance was significantly worse in the twins with more severe tic symptoms, with significant differences emerging on individual tests of attention, visuospatial perception, and motor function. In each twin pair, the twin with more severe tics had poorer global neuropsychological function. Conclusions.-The results suggest that the nongenetic factors that influence tic severity in TS exert a similar effect on neuropsychological function, and that these two clinical manifestations of TS may share a common pathophysiologic state. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NR 30 TC 41 Z9 41 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 1993 VL 50 IS 7 BP 725 EP 728 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA LL116 UT WOS:A1993LL11600010 PM 8323476 ER PT J AU MARCOVINA, SM ALBERS, JJ JACOBS, DR PERKINS, LL LEWIS, CE HOWARD, BV SAVAGE, P AF MARCOVINA, SM ALBERS, JJ JACOBS, DR PERKINS, LL LEWIS, CE HOWARD, BV SAVAGE, P TI LIPOPROTEIN[A] CONCENTRATIONS AND APOLIPOPROTEIN[A] PHENOTYPES IN CAUCASIANS AND AFRICAN-AMERICANS - THE CARDIA STUDY SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE LIPOPROTEIN[A]; APOLIPOPROTEIN[A] PHENOTYPES; CARDIA STUDY; AFRICAN AMERICANS; CAUCASIANS ID LP(A) GLYCOPROTEIN PHENOTYPES; BLACK-WHITE DIFFERENCES; HUMAN-PLASMA; POLYMORPHISM; INHERITANCE; ASSOCIATION; GENETICS; DISEASE; TRAIT AB Little is known about racial differences in lipoprotein[a] (Lp[a]) concentrations and apolipoprotein[a] (apo[a]) phenotypes. Lp[a] protein concentrations were determined by a double monoclonal antibody enzyme-linked immunosorbent assay method in 4165 Caucasian and African American men and women from four US communities. Apo[a] phenotypes were determined by polyacrylamide gel electrophoresis and immunoblotting on a random subset of these participants (n=690). The distribution of Lp[a] protein levels in Caucasians was highly skewed (mean, 6.9 mg/dL; median, 3.7 mg/dL). In contrast, the distribution in African Americans was less skewed (mean, 13.0 mg/dL; median, 11.6 mg/dL), and Lp[a] protein levels were approximately double those in Caucasians within most apo[a] phenotypes. The previously described inverse relationship between apo[a] size and Lp[a] concentration was generally confirmed in Caucasians, but the B phenotype had lower Lp[a] levels than the S1 or S2 phenotype. In African Americans, both the B and S1 phenotypes had lower Lp[a] levels than the S2 phenotype. The frequencies of the apo[a] phenotypes in African Americans differed from those in Caucasians (P<.001) and also differed from the frequencies reported in a Sudanese population (P<.002). African Americans had a lower frequency of the S2 phenotype than Caucasians (8% vs 18%; P<.01) and a higher frequency of S3 (36% vs 25%; P<.01). As compared with the data reported in Sudanese, African Americans also had a higher frequency of the S3 phenotype (36% vs 14%; P<.001) and a lower frequency of S4 (29% vs 44%; P<.01). The apo[a] polymorphism explained 35% of the variability in Lp[a] concentrations in Caucasians and 27% of the variability in African Americans. Though frequencies of the apo[a] phenotypes differ between Caucasians and African Americans, they do not explain the differences in Lp[a] levels between the two racial groups. C1 UNIV ALABAMA,CARDIA COORDINATING CTR,BIRMINGHAM,AL 35294. UNIV ALABAMA,DIV GEN & PREVENT MED,BIRMINGHAM,AL 35294. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195. UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. MEDLANT RES INST,WASHINGTON,DC. RP MARCOVINA, SM (reprint author), UNIV WASHINGTON,NW LIPID RES LABS,2121 N 35TH ST,SEATTLE,WA 98103, USA. FU NHLBI NIH HHS [HC-48048, HL-30086, HC-48047] NR 33 TC 122 Z9 123 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUL PY 1993 VL 13 IS 7 BP 1037 EP 1045 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LL127 UT WOS:A1993LL12700012 PM 8318505 ER PT J AU PARKER, JC BRADLEY, LA DEVELLIS, RM GERBER, LH HOLMAN, HR KEEFE, FJ LAWRENCE, TS LIANG, MH LORIG, KR NICASSIO, PM REVENSON, TA ROGERS, MP WALLSTON, KA WILSON, MG WOLFE, F AF PARKER, JC BRADLEY, LA DEVELLIS, RM GERBER, LH HOLMAN, HR KEEFE, FJ LAWRENCE, TS LIANG, MH LORIG, KR NICASSIO, PM REVENSON, TA ROGERS, MP WALLSTON, KA WILSON, MG WOLFE, F TI BIOPSYCHOSOCIAL CONTRIBUTIONS TO THE MANAGEMENT OF ARTHRITIS DISABILITY - BLUEPRINTS FROM AN NIDRR-SPONSORED CONFERENCE SO ARTHRITIS AND RHEUMATISM LA English DT Article ID COGNITIVE-BEHAVIORAL TREATMENT; RHEUMATOID-ARTHRITIS; PSYCHOLOGICAL ADJUSTMENT; WORK DISABILITY; CHRONIC DISEASE; PAIN; HELPLESSNESS; WOMEN; IMPACT; EDUCATION C1 UNIV MISSOURI,COLUMBIA,MO 65201. UNIV ALABAMA,BIRMINGHAM,AL 35294. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NIH,BETHESDA,MD 20892. STANFORD UNIV,PALO ALTO,CA 94304. DUKE UNIV,DURHAM,NC 27706. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. CALIF SCH PROFESS PSYCHOL,SAN DIEGO,CA. CUNY,NEW YORK,NY 10021. VANDERBILT UNIV,NASHVILLE,TN 37240. CTR DIS CONTROL,ATLANTA,GA 30333. WICHITA ARTHRITIS CTR,WICHITA,KS. OI Parker, Jerry/0000-0001-7784-1199 NR 40 TC 16 Z9 16 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1993 VL 36 IS 7 BP 885 EP 889 DI 10.1002/art.1780360703 PG 5 WC Rheumatology SC Rheumatology GA LM080 UT WOS:A1993LM08000002 PM 8318036 ER PT J AU BRAATZ, JA YASUDA, Y OLDEN, K YAMADA, KM HEIFETZ, AH AF BRAATZ, JA YASUDA, Y OLDEN, K YAMADA, KM HEIFETZ, AH TI FUNCTIONAL PEPTIDE POLYURETHANE CONJUGATES WITH EXTENDED CIRCULATORY HALF-LIVES SO BIOCONJUGATE CHEMISTRY LA English DT Article ID POLYETHYLENE-GLYCOL INCREASES; MURINE MELANOMA-CELLS; SUPEROXIDE-DISMUTASE; RECOMBINANT INTERLEUKIN-2; EXPERIMENTAL METASTASIS; POLYMERIC INHIBITORS; PLATELET-AGGREGATION; COVALENT ATTACHMENT; FIBRONECTIN; COPOLYMERS AB Peptides containing the RGD sequence were covalently attached to an isocyanate-containing polyurethane prepolymer and the biological properties of the complexes were evaluated. For the pentapeptide H2N-Tyr-Arg-Gly-Asp-Ser-OH (single-letter code, YRGDS), polymer conjugation lead to an increased half-life in the blood circulation of mice to > 10 h. The effect of covalent attachment of polymer on biological activity was examined in a related peptide, H2N-Gly-Arg-Gly-Asp-Ser-Pro-Ala-Cys-OH (GRGDSPAC). Inhibition of B16-F10 melanoma cell attachment and spreading on plates coated with fibronectin by an RGD-containing peptide and polymer-conjugated GRGDSPAC was observed to occur at similar concentrations. We conclude that the conjugation of peptides containing the Arg-Gly-Asp motif to this polymer resolves previous problems of their rapid loss from the circulation, while still allowing retention of full biological inhibitory activity. C1 KUMAMOTO UNIV,SCH MED,DEPT ANAT,KUMAMOTO 880,JAPAN. NIEHS,RES TRIANGLE PK,NC 27709. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP BRAATZ, JA (reprint author), W R GRACE & CO CONN,DEPT MAMMALIAN CELL RES,DIV RES,7379 ROUTE 32,COLUMBIA,MD 21044, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 35 TC 10 Z9 10 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 1993 VL 4 IS 4 BP 262 EP 267 DI 10.1021/bc00022a003 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA LV457 UT WOS:A1993LV45700003 PM 8218482 ER PT J AU ZAHN, TP PICKAR, D AF ZAHN, TP PICKAR, D TI AUTONOMIC EFFECTS OF CLOZAPINE IN SCHIZOPHRENIA - COMPARISON WITH PLACEBO AND FLUPHENAZINE SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SCHIZOPHRENIA; CLOZAPINE; NEUROLEPTICS; ELECTRODERMAL ACTIVITY; HEART RATE ID CONDUCTANCE ORIENTING RESPONSE; NERVOUS-SYSTEM ACTIVITY AB Peripheral indicators of autonomic nervous system activity, including electrodermal activity and heart rate, were studied in 25 chronic schizophrenic patients given clinical trials of clozapine, a standard neuroleptic (fluphenazine), and placebo. The protocol included a rest period, presentation of nonsignal tones, and a reaction time task. Clozapine markedly attenuated electrodermal base levels and both phasic and tonic electrodermal responsivity compared to placebo, and somewhat less consistently compared to fluphenazine. Both electrodermal and vasoconstrictive orienting responses to tones were reduced. Elevated heart rate and reduced heart rate variability were also observed in patients taking clozapine. Many of these effects can be accounted for by clozapine's anticholinergic and antihistaminic properties. There was evidence that a smaller autonomic response to the mild stress of task performance and larger heart rate responses to nonsignal tones on the alternate treatments were predictive of a good clinical response to clozapine. These results suggest that when on alternate treatments good clozapine responders show more psychophysiological signs of pathology than clinical nonresponders. C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP ZAHN, TP (reprint author), NIMH,PSYCHOL & PSYCHOPATHOL LAB,BLDG 10,RM 4C110,BETHESDA,MD 20892, USA. NR 18 TC 58 Z9 58 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 JUL 1 PY 1993 VL 34 IS 1-2 BP 3 EP 12 DI 10.1016/0006-3223(93)90250-H PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LQ802 UT WOS:A1993LQ80200003 PM 8104043 ER PT J AU WELLER, M KORNHUBER, J AF WELLER, M KORNHUBER, J TI SERUM IRON LEVELS IN NEUROLEPTIC MALIGNANT SYNDROME SO BIOLOGICAL PSYCHIATRY LA English DT Letter ID AKATHISIA C1 UNIV WURZBURG,DEPT PSYCHIAT,D-97080 WURZBURG,GERMANY. RP WELLER, M (reprint author), NIMH,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 3N256,BETHESDA,MD 20892, USA. RI Kornhuber, Johannes/B-9613-2014 OI Kornhuber, Johannes/0000-0002-8096-3987 NR 9 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 1993 VL 34 IS 1-2 BP 123 EP 124 DI 10.1016/0006-3223(93)90268-I PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LQ802 UT WOS:A1993LQ80200021 PM 8373934 ER PT J AU KALER, SG GAHL, WA AF KALER, SG GAHL, WA TI APPLICATION OF A COPPER BLOTTING METHOD TO THE STUDY OF MENKES DISEASE SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE MENKES DISEASE; 67CUCL2; COPPER BLOTTING ID PROTEIN; ACID AB Menkes disease is an X-linked recessive disorder of copper metabolism. Deficient quantity or functional activity of a molecule involved in intracellular copper transport is believed to represent the basic defect. We applied an in vitro copper binding assay (copper blotting) to tissue proteins from Menkes patients and controls to evaluate differences in copper-binding. Proteins were separated by SDS-PAGE, electrotransferred to nitrocellulose, and probed with (CuCl2)-Cu-67. Copper-binding polypeptides were visualized by autoradiography. No major differences were observed between a Menkes patient and control subjects in copper blots of post-mortem liver, kidney, or brain-tissues affected clinically by the disturbance of copper metabolism in Menkes disease. We also applied the copper blotting technique to fibroblast proteins from an affected female in whom the gene responsible for Menkes disease is interrupted by a chromosomal translocation, and detected no differences in copper-binding proteins relative to normal controls. These experiments suggest that the gene product defective in Menkes disease is not detectable in copper blots, either because normal tissue levels are below the limits of detection of this method, or because the molecule involved does not bind copper under these conditions. RP KALER, SG (reprint author), NICHHD,HUMAN BIOCHEM GENET SECT,HUMAN GENET BRANCH,BETHESDA,MD 20892, USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD JUL PY 1993 VL 38 IS 1 BP 73 EP 81 DI 10.1007/BF02783984 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA LN258 UT WOS:A1993LN25800008 PM 7691134 ER PT J AU STEVEN, AC AF STEVEN, AC TI CONFORMATIONAL CHANGE - AN ALTERNATIVE ENERGY-SOURCE - EXOTHERMIC PHASE-TRANSITION IN PHAGE CAPSID MATURATION SO BIOPHYSICAL JOURNAL LA English DT Note ID PROTEIN; BACTERIOPHAGE-T4 RP STEVEN, AC (reprint author), NIAMSD,STRUCT BIOL LAB,ROCKVILLE,MD 20892, USA. NR 12 TC 8 Z9 8 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1993 VL 65 IS 1 BP 5 EP 6 PG 2 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700002 PM 8369454 ER PT J AU ZIMMERBERG, J AF ZIMMERBERG, J TI FUSION FLASHES ILLUMINATE KINETICS SO BIOPHYSICAL JOURNAL LA English DT Note ID CELL-FUSION; MICROSCOPY RP ZIMMERBERG, J (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1993 VL 65 IS 1 BP 7 EP 8 PG 2 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700003 PM 8369462 ER PT J AU RALL, W AF RALL, W TI TRANSIENTS IN NEURON WITH ARBITRARY DENDRITIC BRANCHING AND SHUNTED SOMA SO BIOPHYSICAL JOURNAL LA English DT Note RP RALL, W (reprint author), NIDDK,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 3 Z9 3 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1993 VL 65 IS 1 BP 15 EP 16 PG 2 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700007 PM 8369424 ER PT J AU KELLER, SL BEZRUKOV, SM GRUNER, SM TATE, MW VODYANOY, I PARSEGIAN, VA AF KELLER, SL BEZRUKOV, SM GRUNER, SM TATE, MW VODYANOY, I PARSEGIAN, VA TI PROBABILITY OF ALAMETHICIN CONDUCTANCE STATES VARIES WITH NONLAMELLAR TENDENCY OF BILAYER PHOSPHOLIPIDS SO BIOPHYSICAL JOURNAL LA English DT Note ID BLACK LIPID-MEMBRANES; INTRINSIC CURVATURE; PHASE; CHANNELS; TRANSITIONS; BEHAVIOR; PACKING AB With few exceptions, membrane lipids are usually regarded as a kind of filler or passive solvent for membrane proteins. Yet, cells exquisitely control membrane composition. Many phospholipids found in plasma membrane bilayers favor packing into inverted hexagonal bulk phases. It was suggested that the strain of forcing such lipids into a bilayer may affect membrane protein function, such as the operation of transmembrane channels. To investigate this, we have inserted the peptide alamethicin into bilayer membranes composed of lipids of empirically determined inverted hexagonal phase ''spontaneous radii'' Ro, which will have expectably different degrees of strain when forced into bilayer form. We observe a correlation between measured Ro and the relative probabilities of different conductance states. States of higher conductance are more probable in dioleoylphosphatidylethanolamine, the lipid of highest curvature, 1/Ro, than in dioleoylphosphatidylcholine, the lipid of lowest curvature. C1 NIH,BLDG 10,ROOM 9B-07,BETHESDA,MD 20892. PRINCETON UNIV,DEPT PHYS,PRINCETON,NJ 08544. RUSSIAN ACAD SCI,ST PETERSBURG NUCL PHYS INST,MOSCOW 188350,RUSSIA. OFF NAVAL RES,ARLINGTON,VA 22217. RI Gruner, Sol/G-2924-2010 OI Gruner, Sol/0000-0002-1171-4426 FU NIGMS NIH HHS [GM32614] NR 33 TC 214 Z9 217 U1 1 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1993 VL 65 IS 1 BP 23 EP 27 PG 5 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700011 PM 8369434 ER PT J AU CHEN, YD RUBIN, RJ SZABO, A AF CHEN, YD RUBIN, RJ SZABO, A TI FLUORESCENCE DEQUENCHING KINETICS OF SINGLE CELL-CELL FUSION COMPLEXES SO BIOPHYSICAL JOURNAL LA English DT Article ID VESICULAR STOMATITIS-VIRUS; PH-DEPENDENT FUSION; INFLUENZA HEMAGGLUTININ; REDISTRIBUTION; MEMBRANES; DIFFUSION; BARRIER; EVENTS AB In an earlier paper which models the cell-cell (or virus-cell) fusion complex as two partial spherical vesicles joined at a narrow neck (Rubin, R. J., and Yi-der Chen. 1990. Biophys. J. 58:1157-1167), the redistribution by diffusion of lipid-like molecules through the neck between the two fused cell surfaces was studied. In this paper, we extend the study to the calculation of the kinetics of fluorescence increase in a single fusion complex when the lipid-like molecules are fluorescent and self-quenching. The formalism developed in this paper is useful in deducing fusion activation mechanisms from cuvette fluorescence measurements in cell-cell fusion systems. Two different procedures are presented: 1) an exact one which is based on the exact local density functions obtained from diffusion equations in our earlier study, and 2) an approximate one which is based on treating the kinetics of transfer of probes between the two fused cells as a two-state chemical reaction. For typical cell-cell fusion complexes, the fluorescence dequenching curves calculated from the exact and approximate procedures are very similar. Due to its simplicity, the approximate method should be very useful in future applications, 'he formalism is applied to a typical cell-cell fusion complex to study the sensitivity of dequenching curves to changes in various fusion parameters, such as the radii of the cells, the radius of the pore at the fusion junction, and the number of probes initially loaded to the complex. RP CHEN, YD (reprint author), NIDDK,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012 NR 18 TC 15 Z9 15 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1993 VL 65 IS 1 BP 325 EP 333 PG 9 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700042 PM 8369440 ER PT J AU IWASA, KH AF IWASA, KH TI EFFECT OF STRESS ON THE MEMBRANE CAPACITANCE OF THE AUDITORY OUTER HAIR CELL SO BIOPHYSICAL JOURNAL LA English DT Article ID ELECTROKINETIC SHAPE CHANGES; MECHANICAL RESPONSES AB The membrane capacitance of the outer hair cell, which has unique membrane potential-dependent motility, was monitored during application of membrane tension. It was found that the membrane capacitance of the cell decreased when stress was applied to the membrane. This result is the opposite of stretching the lipid bilayer in the plasma membrane. It thus indicates the importance of some other capacitance component that decreases on stretching. It has been known that charge movement across the membrane can appear to be a nonlinear capacitance. If membrane stress at the resting potential restricts the movement of the charge associated with force generation, the nonlinear capacitance will decrease. Furthermore, less capacitance reduction by membrane stretching is expected when the membrane is already extended by the (hyperpolarizing) membrane potential. Indeed, it was found that at hyperpolarized potentials, the reduction of the membrane capacitance due to stretching is less. The capacitance change can be described by a two state model of a force-producing unit in which the free energy difference between the contracted and stretched states has both electrical and mechanical components. From the measured change in capacitance, the estimated difference in the membrane area of the unit between the two states is about 2 nm2. RP IWASA, KH (reprint author), NIDCD,CELLULAR BIOL LAB,BLDG 10,RM 5D46,BETHESDA,MD 20892, USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 20 TC 132 Z9 132 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1993 VL 65 IS 1 BP 492 EP 498 PG 7 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700056 PM 8369452 ER PT J AU HERRMANN, A CLAGUE, MJ BLUMENTHAL, R AF HERRMANN, A CLAGUE, MJ BLUMENTHAL, R TI ENHANCEMENT OF VIRAL FUSION BY NONADSORBING POLYMERS SO BIOPHYSICAL JOURNAL LA English DT Article ID VESICULAR STOMATITIS-VIRUS; PH-DEPENDENT FUSION; RED BLOOD-CELLS; INDUCED MEMBRANE-FUSION; INFLUENZA-VIRUS; POLY(ETHYLENE GLYCOL); OSMOTIC FORCES; HEMAGGLUTININ; FLUORESCENCE; KINETICS AB Nonadsorbing polymers such as dextran and poly(ethylene glycol) enhance binding as well as extents of fusion of influenza virus with erythrocytes. Kinetics and extent of viral membrane fusion were measured using an assay based on lipid mixing of a fluorescent dye. The effects of nonadsorbing polymers were in the concentration range from 0 to 10 wt%, far below the concentration required to overcome hydration repulsion forces. The enhancing effects were dependent on the molecular weight of nonadsorbing polymer, and only occurred at molecular weight > 1500; this links the phenomena we observe to the so-called ''excluded volume effect'' of nonadsorbing polymers. The time delay between triggering and the onset of influenza virus fusion was significantly reduced in the presence of nonadsorbing polymers. High molecular weight poly(ethylene glycol) also induced fusion of vesicular stomatitis virus with intact erythrocytes, which do not serve as target of vesicular stomatitis virus fusion in the absence of the polymer. The forces between membranes which determine rate-limiting processes in viral fusion and how they are affected by nonadsorbing polymers are discussed. C1 EUROPEAN MOLEC BIOL LAB,W-6900 HEIDELBERG,GERMANY. NCI,LTB,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. RP HERRMANN, A (reprint author), HUMBOLDT UNIV BERLIN,FACHBEREICH BIOL,INST BIOPHYS,INVALIDENSTR 42,O-1040 BERLIN,GERMANY. OI Clague, Michael/0000-0003-3355-9479 NR 44 TC 15 Z9 15 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 1993 VL 65 IS 1 BP 528 EP 534 PG 7 WC Biophysics SC Biophysics GA LL137 UT WOS:A1993LL13700060 PM 7690263 ER PT J AU SIDRANSKY, E STUBBLEFIELD, B AF SIDRANSKY, E STUBBLEFIELD, B TI DRIED UMBILICAL CORDS AS A SOURCE OF DNA FOR GENETIC-STUDIES SO BIOTECHNIQUES LA English DT Note RP SIDRANSKY, E (reprint author), NIMH,MOLEC NEUROGENET SECT,BLDG 49,ROOM B1EE16,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 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 JUL PY 1993 VL 15 IS 1 BP 30 EP 30 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL212 UT WOS:A1993LL21200005 PM 8363834 ER PT J AU TEMPLETON, NS URCELAY, E SAFER, B AF TEMPLETON, NS URCELAY, E SAFER, B TI REDUCING ARTIFACT AND INCREASING THE YIELD OF SPECIFIC DNA TARGET FRAGMENTS DURING PCR-RACE OR ANCHOR PCR SO BIOTECHNIQUES LA English DT Note RP TEMPLETON, NS (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,ROOM 7D18,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 U1 1 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 1993 VL 15 IS 1 BP 52 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL212 UT WOS:A1993LL21200011 ER PT J AU JAFFE, JS STROBER, W SNELLER, MC AF JAFFE, JS STROBER, W SNELLER, MC TI FUNCTIONAL ABNORMALITIES OF CD8+ T-CELLS DEFINE A UNIQUE SUBSET OF PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY SO BLOOD LA English DT Article ID NORMAL HUMAN-LYMPHOCYTES; EPSTEIN-BARR VIRUS; INTERFERON-GAMMA; KILLER-CELLS; INTERLEUKIN-2; ACTIVATION; DIFFERENTIATION; SUPPRESSOR; RESPONSES; IMMUNOREGULATION C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 39 TC 48 Z9 48 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 JUL 1 PY 1993 VL 82 IS 1 BP 192 EP 201 PG 10 WC Hematology SC Hematology GA LL366 UT WOS:A1993LL36600026 PM 8100719 ER PT J AU ABRUZZO, LV SCHMIDT, K WEISS, LM JAFFE, ES MEDEIROS, LJ SANDER, CA RAFFELD, M AF ABRUZZO, LV SCHMIDT, K WEISS, LM JAFFE, ES MEDEIROS, LJ SANDER, CA RAFFELD, M TI B-CELL LYMPHOMA AFTER ANGIOIMMUNOBLASTIC LYMPHADENOPATHY - A CASE WITH OLIGOCLONAL GENE REARRANGEMENTS ASSOCIATED WITH EPSTEIN-BARR-VIRUS SO BLOOD LA English DT Article ID ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY; MALIGNANT-LYMPHOMA; CLONAL ANALYSIS; LESIONS; TERMINI; DNA C1 NCI,PATHOL LAB,BLDG 10,RM 2N110,BETHESDA,MD 20892. NR 17 TC 62 Z9 64 U1 0 U2 3 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 JUL 1 PY 1993 VL 82 IS 1 BP 241 EP 246 PG 6 WC Hematology SC Hematology GA LL366 UT WOS:A1993LL36600032 PM 8391875 ER PT J AU ROSENBERG, HF GALLIN, JI AF ROSENBERG, HF GALLIN, JI TI NEUTROPHIL-SPECIFIC GRANULE DEFICIENCY INCLUDES EOSINOPHILS SO BLOOD LA English DT Article ID MAJOR BASIC-PROTEIN; MOLECULAR-CLONING; LACTOFERRIN DEFICIENCY; CATIONIC PROTEIN; GENE; PATIENT; LOCALIZATION; NEUROTOXIN; PEROXIDASE; INFECTIONS RP ROSENBERG, HF (reprint author), NIAID,HOST DEF LAB,BLDG 10,ROOM 11N113,BETHESDA,MD 20892, USA. NR 27 TC 31 Z9 31 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 JUL 1 PY 1993 VL 82 IS 1 BP 268 EP 273 PG 6 WC Hematology SC Hematology GA LL366 UT WOS:A1993LL36600035 PM 8324226 ER PT J AU QUINONES, RR GUTIERREZ, RH DINNDORF, PA GRESS, RE NEY, AB TAYLOR, B KARANDISH, S CARTER, CS LUBAN, NLC REAMAN, GH AF QUINONES, RR GUTIERREZ, RH DINNDORF, PA GRESS, RE NEY, AB TAYLOR, B KARANDISH, S CARTER, CS LUBAN, NLC REAMAN, GH TI EXTENDED-CYCLE ELUTRIATION TO ADJUST T-CELL CONTENT IN HLA-DISPARATE BONE-MARROW TRANSPLANTATION SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; LYMPHOCYTES-T; COUNTERFLOW CENTRIFUGATION; HEMATOLOGIC MALIGNANCIES; MYELOGENOUS LEUKEMIA; CYTOSINE-ARABINOSIDE; GRAFT-REJECTION; DEPLETION; DONORS; RECIPIENTS C1 CHILDRENS NATL MED CTR,CHILDRENS RES INST,DEPT LAB MED,WASHINGTON,DC. CHILDRENS NATL MED CTR,CHILDRENS RES INST,CTR CANC & TRANSPLANTAT BIOL,WASHINGTON,DC. GEORGE WASHINGTON UNIV,SCH MED,DEPT PEDIAT,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED,DEPT RADIAT ONCOL & BIOPHYS,WASHINGTON,DC 20052. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. RP QUINONES, RR (reprint author), CHILDRENS NATL MED CTR,CHILDRENS RES INST,DEPT HEMATOL ONCOL,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 49 TC 29 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 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 1993 VL 82 IS 1 BP 307 EP 317 PG 11 WC Hematology SC Hematology GA LL366 UT WOS:A1993LL36600040 PM 8324231 ER PT J AU AVERY, A PARASKEVA, C HALL, P FLANDERS, KC SPORN, M MOORGHEN, M AF AVERY, A PARASKEVA, C HALL, P FLANDERS, KC SPORN, M MOORGHEN, M TI TGF-BETA EXPRESSION IN THE HUMAN COLON - DIFFERENTIAL IMMUNOSTAINING ALONG CRYPT EPITHELIUM SO BRITISH JOURNAL OF CANCER LA English DT Article ID GROWTH-FACTOR-BETA; COMPLEX AB Samples of colorectal carcinoma, adenoma and normal colorectal mucosa were examined for the expression of TGF-beta by immunohistochemistry. Immunoreactivity for TGF-beta was present in 52 out of a total of 58 samples of normal mucosa examined. In adenomas and carcinomas TGF-beta expression was observed in eight out of ten and 46 out of 48 samples respectively and was largely restricted to epithelial cells. In normal mucosa differential expression of TGF-beta was present within epithelial cells, those in the upper parts of the crypts showing enhanced immunoreactivity compared to cells in the proliferative compartment. This pattern of differential staining is consistent with TGF-beta having an important role in the control of growth and differentiation in colonic mucosa. C1 UNIV BRISTOL,SCH MED SCI,DEPT PATHOL & MICROBIOL,BRISTOL BS8 1TH,AVON,ENGLAND. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 8 TC 114 Z9 114 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1993 VL 68 IS 1 BP 137 EP 139 DI 10.1038/bjc.1993.301 PG 3 WC Oncology SC Oncology GA LH632 UT WOS:A1993LH63200026 PM 8318404 ER PT J AU BEVAN, KA NEWMAN, AH CALDERON, SN TORTELLA, FC BOWERY, NG AF BEVAN, KA NEWMAN, AH CALDERON, SN TORTELLA, FC BOWERY, NG TI CARBETAPENTANE ANALOGS - ANTICONVULSANT AGENTS ACTING VIA DEXTROMETHORPHAN RECEPTORS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Meeting Abstract C1 UNIV LONDON SCH PHARM,DEPT PHARMACOL,LONDON WC1N 1AX,ENGLAND. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. WRAIR,WASHINGTON,DC 20307. NR 3 TC 0 Z9 0 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 JUL PY 1993 VL 109 SU S BP P26 EP P26 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LK194 UT WOS:A1993LK19400026 ER PT J AU WOODSMALL, RM BENSON, DA AF WOODSMALL, RM BENSON, DA TI INFORMATION RESOURCES AT THE NATIONAL-CENTER-FOR-BIOTECHNOLOGY-INFORMATION SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB The National Center for Biotechnology Information (NCBI), part of the National Library of Medicine, was established in 1988 to perform basic research in the field of computational molecular biology as well as build and distribute molecular biology databases. The basic research has led to new algorithms and analysis tools for interpreting genomic data and has been instrumental in the discovery of human disease genes for neurofibromatosis and Kallmann syndrome. The principal database responsibility is the National Institutes of Health (NIH) genetic sequence database, GenBank(R). NCBI, in collaboration with international partners, builds, distributes, and provides online and CD-ROM access to over 112,000 DNA sequences. Another major program is the integration of multiple sequences databases and related bibliographic information and the development of network-based retrieval systems for Internet access. RP WOODSMALL, RM (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,INFORMAT RESOURCES BRANCH,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 13 Z9 14 U1 0 U2 2 PU MED LIBRARY ASSN PI CHICAGO PA SUITE 300 6 N MICHIGAN AVE, CHICAGO, IL 60602 SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD JUL PY 1993 VL 81 IS 3 BP 282 EP 284 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA LL859 UT WOS:A1993LL85900007 PM 8374583 ER PT J AU SCHINDLER, CW THORNDIKE, EB GOLDBERG, SR AF SCHINDLER, CW THORNDIKE, EB GOLDBERG, SR TI ACQUISITION OF A NOSE-POKE RESPONSE IN RATS AS AN OPERANT SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Article ID INDEPENDENT FOOD; EXPERIENCE; TRACKING AB Acquisition of a nose-poke operant response was investigated in rats. The baseline level of this response was high and acquisition with food reinforcement occurred rapidly, particularly when compared with a leverpress operant response. A variety of control procedures clearly indicated that this response was acquired due to the contingency between nose pokes and food reinforcement. The response was also sensitive to manipulations of delay of reinforcement and food-deprivation level. Acquisition was slowed with longer delays of reinforcement and with decreases in deprivation level. Therefore, the nose-poke response appears to be particularly useful for the study of the acquisition of operant responses. RP SCHINDLER, CW (reprint author), NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 21 TC 9 Z9 9 U1 1 U2 3 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD JUL PY 1993 VL 31 IS 4 BP 291 EP 294 PG 4 WC Psychology, Mathematical SC Psychology GA LM855 UT WOS:A1993LM85500015 ER PT J AU HEIDEMAN, RL PACKER, RJ REAMAN, GH ALLEN, JC LANGE, B HOROWITZ, ME STEINBERG, SM GILLESPIE, A KOVNAR, EH BALIS, FM POPLACK, DG AF HEIDEMAN, RL PACKER, RJ REAMAN, GH ALLEN, JC LANGE, B HOROWITZ, ME STEINBERG, SM GILLESPIE, A KOVNAR, EH BALIS, FM POPLACK, DG TI A PHASE-II EVALUATION OF THIOTEPA IN PEDIATRIC CENTRAL-NERVOUS-SYSTEM MALIGNANCIES SO CANCER LA English DT Article DE THIOTEPA; PHASE-II TRIAL; BRAIN TUMORS; MEDULLOBLASTOMA ID BONE-MARROW TRANSPLANTATION; CHILDHOOD BRAIN-TUMORS; CANCER-STUDY-GROUP; HUMAN MEDULLOBLASTOMA; EXPERIMENTAL CHEMOTHERAPY; THERAPY; CYCLOPHOSPHAMIDE; CISPLATIN AB Background. Both thiotepa and its active metabolite, tepa, efficiently cross the blood-brain barrier. After intravenous administration, the cerebrospinal fluid concentrations achieved are nearly identical to those in plasma. This provides a strong rationale for testing this agent against brain tumors. Methods. Sixty pediatric patients with recurrent primary brain tumors were treated on a multiinstitutional Phase II study of intravenous thiotepa at a dose of 65 mg/m2 administered every 3 weeks. This dose is the result of a prior pediatric Phase I trial and is significantly higher than those previously recommended. Results. Three of 13 assessable patients with medulloblastoma had partial responses lasting 22, 25, and 54 weeks. Although no objective responses were observed in 16 assessable patients with malignant gliomas and 14 with brain stem gliomas, 5 of 16 and 4 of 14 patients in these respective strata had prolonged periods of stable disease (SD) lasting from 12 to more than 33 weeks. Nine assessable patients with ependymoma had no objective response, but two had SD, both for more than 33 weeks. Myelosuppression was the principle toxic effect encountered and appeared to be more severe in patients who had received prior craniospinal radiation therapy or nitrosourea therapy. Conclusions. By conventional Phase II criteria, thiotepa appears to have activity in medulloblastoma. Based on several patients with prolonged SD, it also may possess some limited activity in brain stem and malignant gliomas. The steep in vitro dose-response curve of thiotepa and the long durations of response or SD observed with the dose reported here suggest that moderate-dose to high-dose thiotepa with cytokine support or autologous bone marrow rescue may be associated with an improved response rate to this agent. C1 NCI, PEDIAT BRANCH, BLDG 10, ROOM 13N240, BETHESDA, MD 20892 USA. NCI, DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. CHILDRENS HOSP, NATL MED CTR, NATL MED CTR, DEPT HEMATOL ONCOL, WASHINGTON, DC 20010 USA. NYU MED CTR, DEPT NEUROL, NEW YORK, NY 10016 USA. CHILDRENS HOSP PHILADELPHIA, DEPT HEMATOL ONCOL, PHILADELPHIA, PA USA. ST JUDE CHILDRENS RES HOSP, DIV NEUROL, MEMPHIS, TN 38101 USA. ST JUDE CHILDRENS RES HOSP, DEPT HEMATOL ONCOL, MEMPHIS, TN 38101 USA. NR 25 TC 47 Z9 47 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 1993 VL 72 IS 1 BP 271 EP 275 DI 10.1002/1097-0142(19930701)72:1<271::AID-CNCR2820720147>3.0.CO;2-K PG 5 WC Oncology SC Oncology GA LH257 UT WOS:A1993LH25700046 PM 8508417 ER PT J AU DOSEMECI, M HAYES, RB VETTER, R HOOVER, RN TUCKER, M ENGIN, K UNSAL, M BLAIR, A AF DOSEMECI, M HAYES, RB VETTER, R HOOVER, RN TUCKER, M ENGIN, K UNSAL, M BLAIR, A TI OCCUPATIONAL PHYSICAL-ACTIVITY, SOCIOECONOMIC-STATUS, AND RISKS OF 15 CANCER SITES IN TURKEY SO CANCER CAUSES & CONTROL LA English DT Article DE CANCER; CASE-CONTROL; COLON; LARYNX; MELANOMA; OCCUPATION; PHYSICAL ACTIVITY; PROSTATE; RECTUM; SOCIOECONOMIC STATUS; TURKEY AB A multiple-site case-control study of 15 cancers (stomach; colon; rectum; larynx; lung; melanoma; skin; female breast; male breast; cervix; ovary; uterus; prostate; testis; and bladder) was conducted to evaluate their association with occupational physical activity and socioeconomic status (SES). A hospital-based study population (3,486 male cases and 379 female cases, and 2,127 male and 244 female controls) was established in an oncological treatment center in Istanbul, Turkey, from 1979-84. Assessment of physical activity and SES was based on job titles held by the study subjects. Two measures of physical activity were developed based on energy expenditure and 'sitting time' during working hours. Observed risks were adjusted for age, smoking, and SES. Elevated risks were observed among workers who held sedentary jobs for cancers of the colon (odds ratio [OR] = 1.6), rectum (OR = 1.3), melanoma (OR = 1.9), male breast (OR = 1.4), prostate (OR = 5.0), and ovary (OR = 2.0). Cancers of the cervix and uterus showed significantly decreasing risks with decreased activity. Risks of cancers of the colon, rectum, larynx, ovary, and melanoma were enhanced after risks for physical activity indices were adjusted for SES, while the associations between physical activity and cancers of the prostate, cervix, and uterus were weakened after SES adjustment. Risks of melanoma rose significantly with both activity indices after SES adjustment. The results of this study support previously reported associations between physical activity and cancers of the colon and rectum observed in developed countries, and provide additional evidence for cancers of the larynx, prostate, cervix, uterus, and melanoma, and point out the importance of SES in evaluation of physical activity and cancers of the colon, rectum, larynx, prostate, breast, cervix, and melanoma in developing countries. RP DOSEMECI, M (reprint author), NCI,OCCUPAT STUDIES SECT,ENVIRONM EPIDEMIOL BRANCH,EBP,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. NR 0 TC 191 Z9 193 U1 2 U2 8 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1993 VL 4 IS 4 BP 313 EP 321 DI 10.1007/BF00051333 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LN100 UT WOS:A1993LN10000003 PM 8347780 ER PT J AU HARTGE, P SILVERMAN, DT SCHAIRER, C HOOVER, RN AF HARTGE, P SILVERMAN, DT SCHAIRER, C HOOVER, RN TI SMOKING AND BLADDER-CANCER RISK IN BLACKS AND WHITES IN THE UNITED-STATES SO CANCER CAUSES & CONTROL LA English DT Note DE BLACKS; BLADDER CANCER; CASE-CONTROL STUDY; EPIDEMIOLOGY; RACE; SMOKING; UNITED-STATES; WHITES AB A population-based case-control study of bladder cancer (2,982 cases and 5,782 controls) conducted in 10 areas of the United States examined the effect of smoking as a risk factor among Blacks and Whites, after adjustment for occupation and other potential confounders. Although the overall risk for smoking was slightly higher in Blacks than Whites (relative risk = 2.7 and 2.2, respectively), this difference was not statistically significant. Estimation of risk by dose and currency of exposure revealed no consistent racial disparities in smoking-related risks. Race-specific, attributable risk estimates indicated that nearly half of bladder cancers among both Blacks and Whites could have been prevented by elimination of smoking. RP HARTGE, P (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,6130 EXECUT BLVD,ROOM 443,ROCKVILLE,MD 20892, USA. NR 0 TC 20 Z9 20 U1 1 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JUL PY 1993 VL 4 IS 4 BP 391 EP 394 DI 10.1007/BF00051343 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LN100 UT WOS:A1993LN10000013 PM 8347788 ER PT J AU BERG, SL BALIS, FM MCCULLY, CL GODWIN, KS POPLACK, DG AF BERG, SL BALIS, FM MCCULLY, CL GODWIN, KS POPLACK, DG TI PHARMACOKINETICS OF PEG-L-ASPARAGINASE AND PLASMA AND CEREBROSPINAL-FLUID L-ASPARAGINE CONCENTRATIONS IN THE RHESUS-MONKEY SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE L-ASPARAGINASE; PHARMACOKINETICS; CEREBROSPINAL FLUID; RHESUS MONKEY ID GLYCOL-L-ASPARAGINASE; PHARMACOLOGY; METABOLISM AB The pharmacokinetics of the polyethylene glycol-conjugated form of the enzyme L-asparaginase and the depletion Of L-asparagine from the plasma and cerebrospinal fluid (CSF) following an i. m. dose of 2500 IU/m2 PEG-L-asparaginase was studied in rhesus monkeys. PEG-L-asparaginase activity in plasma was detectable by 1 h after injection and maintained a plateau of approximately 4 IU/ml for more than 5 days. Subsequent elimination from plasma was monoexponential with a half-life of 6 +/- 1 days. Plasma L-asparagine concentrations fell from pretreatment levels of 14-47 muM to <2 muM by 24 h after injection in all animals and remained undetectable for the duration of the 25-day observation period in four of six animals. In two animals, plasma L-asparagine became detectable when the PEG-L-asparaginase plasma concentration dropped below 0.1 IU/ml. Pretreatment CSF L-asparagine levels ranged from 4.7 to 13.6 muM and fell to <0.25 muM by 48 h in five of six animals. CSF L-asparagine concentrations remained below 0.25 muM for 10- 14 days in four animals. One animal had detectable CSF L-asparagine concentrations within 24 h and another had detectable concentrations within 1 week of drug administration despite a plasma PEG-L-asparaginase activity profile that did not differ from that of the other animals. These observations may be useful in the design of clinical trials with PEG-L-asparaginase in which correlations among PEG-L-asparaginase pharmacokinetics, depletion of L-asparagine, and clinical outcome should be sought. RP BERG, SL (reprint author), NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 29 Z9 29 U1 0 U2 0 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 JUL PY 1993 VL 32 IS 4 BP 310 EP 314 DI 10.1007/BF00686177 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA LJ927 UT WOS:A1993LJ92700010 PM 8324873 ER PT J AU ROTHMAN, N STEWART, WF CAPORASO, NE HAYES, RB AF ROTHMAN, N STEWART, WF CAPORASO, NE HAYES, RB TI MISCLASSIFICATION OF GENETIC SUSCEPTIBILITY BIOMARKERS - IMPLICATIONS FOR CASE-CONTROL STUDIES AND CROSS-POPULATION COMPARISONS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID AROMATIC AMINE ACETYLTRANSFERASE; LUNG-CANCER; ACETYLATION PHENOTYPE; POOR METABOLIZERS; COLORECTAL-CANCER; RELATIVE RISK; DEBRISOQUINE; POLYMORPHISM; ASSOCIATION; IDENTIFICATION AB Phenotype and genotype markers of genetic susceptibility are of increasing interest in case-control studies of cancer. It is well established that bias to the odds ratio is caused by less-than-perfect assay sensitivity and specificity and varies with risk factor prevalence. As such, the observed variation in odds ratio between studies of genetic markers and cancer risk may be real, or may be attributed, in part, to variation in assay accuracy or in risk factor prevalence (e.g., prevalence differences between racial groups). The latter can be a particular concern when the prevalence of the ''at risk'' polymorphism in one or more populations is either very high (e.g., >85%) or very low (e.g., <15%). For example, even very high sensitivity (e.g., 98%) can produce substantial bias to the odds ratio when the risk factor prevalence is high. Under some prevalence conditions, however, assays with only moderate accuracy are sufficient and result in minimal bias to the odds ratio. Understanding misclassification in the context of marker prevalence may help to explain disparate findings in the literature and should assist investigators in selecting markers that are appropriate for future studies. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. RP ROTHMAN, N (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,EXECUT PLAZA N AM 418,BETHESDA,MD 20892, USA. NR 41 TC 60 Z9 60 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL-AUG PY 1993 VL 2 IS 4 BP 299 EP 303 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LM268 UT WOS:A1993LM26800001 PM 8348052 ER PT J AU SWANSON, CA POTISCHMAN, N WILBANKS, GD TWIGGS, LB MORTEL, R BERMAN, ML BARRETT, RJ BAUMGARTNER, RN BRINTON, LA AF SWANSON, CA POTISCHMAN, N WILBANKS, GD TWIGGS, LB MORTEL, R BERMAN, ML BARRETT, RJ BAUMGARTNER, RN BRINTON, LA TI RELATION OF ENDOMETRIAL CANCER RISK TO PAST AND CONTEMPORARY BODY-SIZE AND BODY-FAT DISTRIBUTION SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; WOMEN; OBESITY; WEIGHT; ASSOCIATION; CARCINOMA; ESTROGENS; ESTRADIOL; HEIGHT AB In a multicenter case-control study that included 403 cases and 297 controls, we examined the relation of past and contemporary body size, including body fat distribution, to the risk of endometrial cancer. The relative contributions of past and contemporary body size were assessed by examining weight and height histories provided by the subjects. Anthropometric indicators thought to reflect early environmental influences (e.g., height and sitting height), current weight, and fat distribution patterns were measured directly. Height was not a risk factor for endometrial cancer, but inexplicably, sitting height was inversely associated with risk. Weight during early adulthood appeared to be directly related to disease risk, but the association was explained by contemporary weight and thus weight gain during adulthood. While contemporary weight was associated with risk of endometrial cancer, the effect was restricted to those in the top quartile. Women whose measured weight at interview exceeded 78 kg had 2.3 times the risk of those weighing less than 58 kg (95% confidence interval, 1.4 to 3.7). Upper-body obesity (waist-to-thigh circumference ratio) was a risk factor independent of body weight. After adjustment for weight, the relative risks of endometrial cancer across increasing quartiles of upper-body obesity were 1.0, 1.5, 1.8, and 2.6 (P for trend < 0.001). These data indicate that both obesity and the distribution of adipose tissue accumulated during adult life increase endometrial cancer risk substantially. C1 RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. UNIV MINNESOTA,SCH MED,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA 17033. UNIV CALIF IRVINE,COLL MED,DEPT OBSTET & GYNECOL,IRVINE,CA 92717. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. UNIV NEW MEXICO,SCH MED,CLIN NUTR RES LAB,ALBUQUERQUE,NM 87131. RP SWANSON, CA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 34 TC 107 Z9 110 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 JUL-AUG PY 1993 VL 2 IS 4 BP 321 EP 327 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LM268 UT WOS:A1993LM26800004 PM 8348055 ER PT J AU ROTHMAN, N CORREAVILLASENOR, A FORD, DP POIRIER, MC HAAS, R HANSEN, JA OTOOLE, T STRICKLAND, PT AF ROTHMAN, N CORREAVILLASENOR, A FORD, DP POIRIER, MC HAAS, R HANSEN, JA OTOOLE, T STRICKLAND, PT TI CONTRIBUTION OF OCCUPATION AND DIET TO WHITE BLOOD-CELL POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCTS IN WILDLAND FIREFIGHTERS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COKE-OVEN WORKERS; SISTER CHROMATID EXCHANGE; FOUNDRY WORKERS; IMMUNOASSAYS; CARCINOGENS; ANTIBODIES; EXPOSURE; HUMANS AB Wildland (forest) firefighters are exposed to a wide range of carcinogenic polycyclic aromatic hydrocarbons (PAH) in forest fire smoke. PAH undergo metabolic activation and can subsequently bind to DNA. In this study, we investigated the association between occupational and dietary PAH exposures and the formation of WBC PAH-DNA adducts in a population of wildland firefighters. An enzyme-linked immunosorbent assay using an antiserum elicited against benzo(a)pyrene-modified DNA was used to measure PAH-DNA adducts in WBC obtained from 47 California firefighters at two time points, early and late in the 1988 forest fire season. PAH-DNA adduct levels were not associated with cumulative hours of recent firefighting activity. However, firefighters who consumed charbroiled food within the previous week had elevated PAH-DNA adduct levels, which were related to frequency of charbroiled food intake. These findings suggest that dietary sources of PAH contribute to PAH-DNA adduct levels in peripheral WBC and should be evaluated when using this assay to assess occupational and environmental PAH exposure. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. CALIF DEPT HLTH SERV,BERKELEY,CA 94704. RP ROTHMAN, N (reprint author), NCI,DIV CANC ETIOL,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [ES03819] NR 38 TC 70 Z9 71 U1 2 U2 11 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 JUL-AUG PY 1993 VL 2 IS 4 BP 341 EP 347 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LM268 UT WOS:A1993LM26800007 PM 8348057 ER PT J AU SCHOKET, B DOTY, WA VINCZE, I STRICKLAND, PT FERRI, GM ASSENNATO, G POIRIER, MC AF SCHOKET, B DOTY, WA VINCZE, I STRICKLAND, PT FERRI, GM ASSENNATO, G POIRIER, MC TI INCREASED SENSITIVITY FOR DETERMINATION OF POLYCYCLIC AROMATIC HYDROCARBON-DNA ADDUCTS IN HUMAN DNA SAMPLES BY DISSOCIATION-ENHANCED LANTHANIDE FLUOROIMMUNOASSAY (DELFIA) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MONOCLONAL-ANTIBODIES; DIOL EPOXIDE; FLUORESCENCE; IMMUNOASSAYS; RADIOIMMUNOASSAY; CARCINOGENESIS; QUANTITATION; BINDING; INVIVO; ASSAY AB A competitive enzyme-linked immunosorbent assay (ELISA), the most frequently used immunoassay for the determination of polycyclic aromatic hydrocarbon-DNA adducts in human tissues, has been modified to achieve approximately a 6-fold increase in sensitivity. The new assay, a competitive dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA) has utilized the same rabbit antiserum as the ELISA, antiserum elicited against DNA modified with benzo[a]pyrene. However, the alkaline phosphatase conjugate has been replaced with a biotin-europium-labeled streptavidin signal amplification system, and the release of europium into the solution forms a highly fluorescent chelate complex that is measured by time-resolved fluorometry. The DELFIA has achieved a 5- to 6-fold increase in sensitivity for measurement of DNA samples modified in vitro with benzo[a]pyrene, for cultured cells exposed to radiolabeled benzo[a]pyrene, and for human samples from occupationally exposed workers. The assay has been validated by comparison of adduct levels determined by DELFIA, ELISA, and radioactivity in DNA from mouse keratinocytes exposed to radiolabeled benzo[a]pyrene. Human lymphocyte DNA samples from 104 Hungarian aluminum plant workers were assayed by ELISA and compared to blood cell DNA samples from 69 Italian coke oven workers assayed by DELFIA. The standard curves demonstrated that the limit of detection of 4.0 adducts in 10(8) nucleotides for polycyclic aromatic hydrocarbon-DNA adducts by ELISA, using 35 mug of DNA/microtiter plate well, has been decreased to 1.3 adducts in 10(8) nucleotides by DELFIA, using 20 mug of DNA/microtiter well. If 35 mug of DNA were used in the DELFIA, the calculated detection limit would be 0.7 adducts in 10(8) nucleotides. For the occupationally exposed groups presented here, the biologically effective dose, as evidenced by blood cell polycyclic aromatic hydrocarbon-DNA adduct levels, was clearly higher in the Hungarian aluminum plant workers; without the added sensitivity of the DELFIA many of the positive samples among the Italian coke oven workers would have been undetectable. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,RM 3B25,BETHESDA,MD 20892. WALLAC INC,GAITHERSBURG,MD 20877. JOHAN BELA NATL INST PUBL HLTH,DEPT BIOCHEM,H-1097 BUDAPEST,HUNGARY. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205. UNIV BARI POLICLIN,IST MED LAVORO,I-70124 BARI,ITALY. NR 27 TC 37 Z9 39 U1 1 U2 2 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 JUL-AUG PY 1993 VL 2 IS 4 BP 349 EP 353 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LM268 UT WOS:A1993LM26800008 PM 8348058 ER PT J AU TANGREA, JA ADRIANZA, ME HELSEL, WE TAYLOR, PR HARTMAN, AM PECK, GL EDWARDS, BK AF TANGREA, JA ADRIANZA, ME HELSEL, WE TAYLOR, PR HARTMAN, AM PECK, GL EDWARDS, BK TI CLINICAL AND LABORATORY ADVERSE-EFFECTS ASSOCIATED WITH LONG-TERM, LOW-DOSE ISOTRETINOIN - INCIDENCE AND RISK-FACTORS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID 13-CIS-RETINOIC ACID; TRIGLYCERIDE LEVELS; ORAL ISOTRETINOIN; SERUM-LIPIDS; ACNE; THERAPY; RETINOIDS AB Adverse effects associated with the long-term, low-dose regimens of retinoids used in cancer chemoprevention studies are not well described. In order to examine the clinical and laboratory adverse effects of 3 years of intervention with isotretinoin (10 mg/day) and to assess potential risk factors for developing these, we collected adverse effect data on patients participating in a randomized, placebo-controlled trial designed to evaluate the effectiveness of isotretinoin in preventing the subsequent occurrence of new basal cell carcinoma. Our results showed a significantly higher incidence of adverse mucocutaneous effects and serum triglyceride elevations in the isotretinoin group (P < 0.001). Associated risk factors included male gender, very fair skin, and elevated pretreatment triglyceride levels. The toxicity observed, although less severe and less frequent, was similar to that seen with higher doses and should be weighed with adverse skeletal effects when considering long-term treatment of patients with moderate cancer risk. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. UNIV MARYLAND,SCH MED,DEPT DERMATOL,BALTIMORE,MD 21201. NR 27 TC 23 Z9 23 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL-AUG PY 1993 VL 2 IS 4 BP 375 EP 380 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LM268 UT WOS:A1993LM26800012 PM 8348061 ER PT J AU HUKKU, B RHIM, JS AF HUKKU, B RHIM, JS TI ROLE OF CHROMOSOME-5 IN IMMORTALIZATION AND TUMORIGENESIS OF HUMAN KERATINOCYTES SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; EPITHELIAL-CELL LINES; SIMIAN VIRUS-40; NEOPLASTIC CONVERSION; TRANSFORMATION; ABNORMALITIES; INSTABILITY; PROGRESSION; CANCER; REARRANGEMENTS AB Rhim et al. were first to show that superinfection of Ad12-SV40-infected immortalized human epidermal cell with an RNA tumor virus containing a ras oncogene, such as Ki-MSV, or their treatment with chemical carcinogens, leads to the ability of cells to both grow in anchorage-independent fashion and to form tumors in athymic nude mice. We describe details of the chromosome changes observed during the transformation. The culture was monitored through 40 passages after Ad12-SV40 infection. Chromosomes 9 and 11 showed random monosomy during the initial stages, but by passage 10 clonal evolution of the cell line was well established. Observed chromosome monosomy/trisomy coupled with chromosome rearrangements (identified as chromosomes A through F) were monosomy 13, loss of p arms of 8 and 10, partial loss of 5 (del(5)(q13) and of the q arm of 18(del(18)(q12)), and extra copies of 11q, 20 and 21. During its progression to tumorigenicity, a derived chromosome E containing a segment of 5q, also appeared to play a major role. The cells remained immortalized as long as the 5q segment was present in some of the cell population as derived chromosomes E or F Derivative chromosome E showed noteworthy changes during the progression to tumorigenicity, in both viral and chemical transformations. There was loss of heterozygosity of 5q due to an exchange of 5q with chromosomes E or F. In Ki-MSV- and 4NQO-transformed cells, presence of an altered chromosome E (identified as E1) was observed. In MNNG-treated cells, there was a selection of population of cells with further alteration in chromosome E (identified as E3). Besides alterations in chromosome E, additional chromosome changes leading to gene activation and amplification indicating a multistep progression to tumorigenicity were observed. The cytogenetic data reiterate the ever-increasing need for molecular analysis of nonrandom karyotype changes. C1 WAYNE STATE UNIV,SCH MED,DETROIT,MI 48201. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP HUKKU, B (reprint author), CHILDRENS HOSP MICHIGAN,DEPT PEDIAT,CELL CULTURE LAB,3901 BEAUBIEN BLVD,DETROIT,MI 48201, USA. NR 41 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUL 1 PY 1993 VL 68 IS 1 BP 22 EP 31 DI 10.1016/0165-4608(93)90069-X PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA LQ035 UT WOS:A1993LQ03500002 PM 8330279 ER PT J AU VANBENEDEN, RJ GARDNER, GR BLAKE, NJ BLAIR, DG AF VANBENEDEN, RJ GARDNER, GR BLAKE, NJ BLAIR, DG TI IMPLICATIONS FOR THE PRESENCE OF TRANSFORMING GENES IN GONADAL TUMORS IN 2 BIVALVE MOLLUSK SPECIES SO CANCER RESEARCH LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CHEMICAL CARCINOGENESIS; OVARIAN-CANCER; MYA-ARENARIA; HERBICIDES; OYSTER; CLAMS AB Studies were initiated on oncogene activation in two bivalve species with high frequencies of histologically identifiable gonadal neoplasms. Pathological assessments identified epizootic seminomas and dysgerminomas in softshell clams (Mya arenaria) from three Maine estuarine sites contaminated by herbicides and in hardshell clams (Mercenaria) from the Indian River in Florida, an area of potential citrus agrochemical exposure. NIH3T3 transfection assays were used to examine DNA isolated from these molluscan tumors for the presence of activated oncogenes. DNAs isolated from advanced tumors in both species were able to transform NIH3T3 cells in a standard focus assay. These same cells were also able to form colonies in low concentrations of serum and induce tumors in athymic mice. Cells expanded from isolated foci demonstrated anchorage-independent growth in soft agar. The results of these studies indicate that DNA from the clam tumors is able to transform mouse fibroblasts, which suggests that a transforming gene is present in these tumor cells. Studies are under way to identify the gene(s) detected by these assays. C1 DUKE UNIV, MED CTR, DEPT CELL BIOL, DURHAM, NC 27710 USA. FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. US EPA, NARRAGANSETT, RI 02882 USA. UNIV S FLORIDA, ST PETERSBURG, FL 33701 USA. RP VANBENEDEN, RJ (reprint author), DUKE UNIV, SCH ENVIRONM, MARINE LAB, BEAUFORT, NC 28516 USA. NR 27 TC 25 Z9 25 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1993 VL 53 IS 13 BP 2976 EP 2979 PG 4 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100011 PM 8319204 ER PT J AU SUPKO, JG MALSPEIS, L AF SUPKO, JG MALSPEIS, L TI PHARMACOKINETICS OF THE 9-AMINO AND 10,11-METHYLENEDIOXY DERIVATIVES OF CAMPTOTHECIN IN MICE SO CANCER RESEARCH LA English DT Article ID PLANT ANTITUMOR AGENTS; MAMMALIAN TOPOISOMERASE-I; BIOLOGICAL-ACTIVITY; ANTILEUKEMIC ACTIVITY; F 104864-A; NUDE-MICE; ANALOGS; INHIBITION; XENOGRAFTS; CANCER AB Although, 20(S)-camptothecin (CA) exhibited potent cytotoxicity against a broad spectrum of tumor models, clinical trials with the sodium salt of its opened lactone ring form were discontinued due to highly variable and severe toxicity. Recently, the 9-amino (AC) and 10,11-methylenedioxy (MC) derivatives of CA were selected for preclinical evaluation by the National Cancer Institute. In the present investigation, the pharmacokinetic behavior of CA, its sodium salt CA, AC, and MC in mice was characterized using specific liquid chromatographic assays which permitted determination of the intact lactone and opened ring carboxylate forms of these compounds. CA disposition was triexponential with a prolonged terminal phase that had a 24.6-h half-life (t1/2,z) that comprised only 14.6% of the area under the concentration-time profile. The relative magnitudes of the total body apparent volume of distribution (V(z)) and terminal phase rate constant suggest that the high observed total plasma clearance (CL, 104 ml/min/kg) may be associated with extensive accumulation in peripheral tissue regions from which the drug is slowly released. In comparison. the terminal disposition phase of MC accounted for 49.7% of the area under the curve profile. It also had a shorter t1/2,z (15.2 h) and appreciably greater CL (526 ml/min/kg) and V(z) (694 liters/kg). This suggested that the degree of binding to tissues relative to plasma proteins was enhanced by the methylenedioxy moiety. In contrast, the 9-amino substituent profoundly diminished the apparent extent of tissue distribution, as indicated by the magnitude of V(z) (7.7 liters/kg), effecting an enhanced rate of elimination (t1/2,z), 1.4 h). Comparison of the Cl, of CA and its two derivatives provided an inaccurate indication of drug elimination due to the influence of their unusually large V(z) values. For these compounds. the relative ease of elimination from the body was best represented by mean residence times. which were 0.55, 7.24, and 11.2 h for AC, CA. and MC, respectively. Intact lactone plasma levels achieved after dosing with the lactone form of CA and its 9-amino and 10.11-methylenedioxy derivatives exceeded the far less active carboxylate at all times. In summary, these studies indicate that considerable alterations in pharmacokinetic behavior result from structural modification the A ring of CA. The large differences in pharmacokinetic parameters of the potential candidates for clinical development, AC and MC, will play an important role in the selection of a therapeutically effective dosing regimen. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,PHARMACEUT CHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM-97619] NR 48 TC 44 Z9 44 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1993 VL 53 IS 13 BP 3062 EP 3069 PG 8 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100025 PM 8319213 ER PT J AU REITER, RE ANGLARD, P LIU, S GNARRA, JR LINEHAN, WM AF REITER, RE ANGLARD, P LIU, S GNARRA, JR LINEHAN, WM TI CHROMOSOME-17P DELETIONS AND P53 MUTATIONS IN RENAL-CELL CARCINOMA SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; GENE-MUTATIONS; BREAST-CANCER; ORIGIN AB Studies of the role of tumor suppressor genes in human renal cell carcinoma from our laboratory have suggested the presence of a disease gene(s) on the short arm of chromosome 3. Little is known about the role other tumor suppressor genes may play in this malignancy. Abnormalities of chromosome 17p and, in particular of p53, are common in many human malignancies. In order to evaluate the role of this region in renal cell carcinoma, we performed restriction fragment length polymorphism analyses of chromosome 17 with probes localized to the p53 region. Fourteen of 29 (48%) evaluable cell lines showed loss of heterozygosity at this locus. Northern blot analysis did not detect a p53 transcript in 4 of 27 cell lines tested. In addition, we screened cell lines for p53 mutations using a polymerase chain reaction-single strand conformation polymorphism technique. Cell lines positive for mutations by this technique were then sequenced. Mutations were detected in 11 of 33 (33%) cell lines, including 8 derived from primary tumors and 3 derived from metastatic foci. Six of 9 (67%) patients with loss of heterozygosity demonstrated a mutation in the remaining allele, while only 1 of 8 (13%) without loss of heterozygosity had a mutation. Three of 3 (100%) cell lines derived from metastases had the same mutation as their matched primary cell line. Loss or mutation of p53 did not correlate either with loss of chromosome 3p or with histological subtype. These results suggest that, while the primary disease gene for kidney cancer appears to be on chromosome 3, abnormalities of p53 are common and may be involved in the progression of this malignancy. C1 NCI,SURG BRANCH,UROL ONCOL SECT,BLDG 10,ROOM 2B47,BETHESDA,MD 20892. NR 29 TC 91 Z9 92 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 JUL 1 PY 1993 VL 53 IS 13 BP 3092 EP 3097 PG 6 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100030 PM 8319216 ER PT J AU JONCZYK, P WHITE, A LUM, K BARRETT, JC TLSTY, TD AF JONCZYK, P WHITE, A LUM, K BARRETT, JC TLSTY, TD TI AMPLIFICATION POTENTIAL IN PRENEOPLASTIC AND NEOPLASTIC SYRIAN-HAMSTER EMBRYO FIBROBLASTS TRANSFORMED BY VARIOUS CARCINOGENS SO CANCER RESEARCH LA English DT Article ID CAD GENE AMPLIFICATION; MULTISTEP CARCINOGENESIS; SOMATIC MUTATION; UMP SYNTHESIS; CELL-LINES; ONCOGENE; PROGRESSION; ASBESTOS; PROTEIN; CULTURE AB Using a well-defined in vitro model system for neoplastic progression, we have examined two basic characteristics in the acquisition of amplification potential. Since Syrian hamster embryo fibroblasts can be transformed by a variety of methods (spontaneously, chemically, virally, or by transfection with oncogenes), we determined whether the method of transformation affects the capability of a cell to amplify. In addition, since variants can be isolated from cell populations as they progress toward tumorigenicity, we can monitor changes in amplification potential during this multistep process. We rind that the capability to amplify is independent of the method of transformation and that the acquisition of this ability occurs in a defined step in the transformation process. In this model system, acquisition of amplification ability occurred concomitantly with the loss of tumor suppression function. C1 UNIV N CAROLINA,SCH MED,DEPT PATHOL,CB 7295,ROOM 309,LINEBERGER COMPREHENS CANC CTR,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH MED,CURRICULUM GENET,CHAPEL HILL,NC 27599. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. FU NCI NIH HHS [CA51912] NR 37 TC 15 Z9 15 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 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1993 VL 53 IS 13 BP 3098 EP 3102 PG 5 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100031 PM 8319217 ER PT J AU TENERIELLO, MG EBINA, M LINNOILA, RI HENRY, M NASH, JD PARK, RC BIRRER, MJ AF TENERIELLO, MG EBINA, M LINNOILA, RI HENRY, M NASH, JD PARK, RC BIRRER, MJ TI P53 AND KI-RAS GENE-MUTATIONS IN EPITHELIAL OVARIAN NEOPLASMS SO CANCER RESEARCH LA English DT Article ID ONCOGENE; ADENOCARCINOMAS; AMPLIFICATION; ACTIVATION; CANCER; TUMORS AB In an effort to define the pathogenic relationship between ovarian neoplasms spanning the clinicopathological spectrum from benign to malignant, the incidence of Ki-ras and p53 mutations was determined in 20 ovarian cystadenomas, 20 low malignant potential (LMP) tumors of the ovary, and 23 ovarian carcinomas. Using DNA extracted from paraffin embedded tissue, polymerase chain reaction amplification, designed restriction fragment length polymorphism analysis, and DNA sequencing, 1 cystadenoma (5%), 6 LMP tumors (30%), and 1 ovarian carcinoma (4%) demonstrated an activated Ki-ras gene. All of the Ki-ras mutations identified except one were GGT to GAT transversions at codon 12. One LMP tumor demonstrated a CAA to CAC transversion at codon 61. Using polymerase chain reaction/single strand conformational polymorphism, DNA sequencing, and immunohistochemistry, 11 ovarian carcinomas (48%) demonstrated a p53 mutation. These mutations included 5 mis-sense. 2 nonsense, and 1 frameshift mutation located within exons 6-8 and 3 mutations that were identified only by immunohistochemical staining. No p53 mutations could be identified in cystadenomas or LMP tumors. Clinically, the presence of either a Ki-ras or p53 mutation was associated with advanced stage disease. The pattern of Ki-ras and p53 mutations appears to distinguish LMP tumors from invasive carcinomas and suggests that they may be separate biological entities. C1 NAT NAVAL MED CTR, DEPT OBSTET & GYNECOL GYNECOL ONCOL, BETHESDA, MD 20889 USA. WALTER REED ARMY MED CTR, DEPT OBSTET & GYNECOL GYNECOL ONCOL, WASHINGTON, DC 20307 USA. NATL NAVAL MED CTR, DEPT PATHOL, BETHESDA, MD 20889 USA. NCI, DIV CANC PREVENT & CONTROL, BIOMARKERS & PREVENT RES BRANCH, ROCKVILLE, MD 20850 USA. NR 28 TC 220 Z9 223 U1 0 U2 2 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 JUL 1 PY 1993 VL 53 IS 13 BP 3103 EP 3108 PG 6 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100032 PM 8319218 ER PT J AU LAFORGIA, S LASOTA, J LATIF, F BOGHOSIANSELL, L KASTURY, K OHTA, M DRUCK, T ATCHISON, L CANNIZZARO, LA BARNEA, G SCHLESSINGER, J MODI, W KUZMIN, I TORY, K ZBAR, B CROCE, CM LERMAN, M HUEBNER, K AF LAFORGIA, S LASOTA, J LATIF, F BOGHOSIANSELL, L KASTURY, K OHTA, M DRUCK, T ATCHISON, L CANNIZZARO, LA BARNEA, G SCHLESSINGER, J MODI, W KUZMIN, I TORY, K ZBAR, B CROCE, CM LERMAN, M HUEBNER, K TI DETAILED GENETIC AND PHYSICAL MAP OF THE 3P-CHROMOSOME REGION SURROUNDING THE FAMILIAL RENAL-CELL CARCINOMA CHROMOSOME-TRANSLOCATION, T(3,8)(P14.2,Q24.1) SO CANCER RESEARCH LA English DT Article ID TUMOR SUPPRESSOR GENES; UNIQUE DNA-SEQUENCES; SHORT ARM; MOLECULAR ANALYSIS; LUNG-CANCER; INSITU HYBRIDIZATION; MAPPING PANEL; SINGLE-COPY; DELETION; HETEROZYGOSITY AB Extensive studies of loss of heterozygosity of 3p markers in renal cell carcinomas (RCCs) have established that there are at least three regions critical in kidney tumorigenesis, one most likely coincident with the von Hippel-Lindau gene at 3p25.3, one in 3p21 which may also be critical in small cell lung carcinomas, and one in 3p13-p14.2, a region which includes the 3p chromosome translocation break of familial RCC with the t(3;8)-(p14.2;q24.1) translocation. A panel of rodent-human hybrids carrying portions of 3p, including a hybrid carrying the derivative 8 (der(8)(8pter-->8q24.1=3p14.2-->3pter)) from the RCC family, have been characterized using 3p anchor probes and cytogenetic methods. This 3p panel was then used to map a large number of genetically mapped probes into seven physical intervals between 3p12 and 3pter defined by the hybrid panel. Markers have been physically, and some genetically, placed relative to the t(3;8) break, such that positional cloning of the break is feasible. C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON CANC INST,BLSB,RM 1008A,233 S 10TH ST,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYN CORP,FREDERICK,MD 21701. CHESTNUT HILL COLL,PHILADELPHIA,PA 19118. NYU,DEPT PHARMACOL,NEW YORK,NY 10012. FU NCI NIH HHS [N01-CO-74102, CA21124] NR 64 TC 45 Z9 45 U1 0 U2 3 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 JUL 1 PY 1993 VL 53 IS 13 BP 3118 EP 3124 PG 7 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100034 PM 8319219 ER PT J AU MONSKY, WL KELLY, T LIN, CY YEH, YY STETLERSTEVENSON, WG MUELLER, SC CHEN, WT AF MONSKY, WL KELLY, T LIN, CY YEH, YY STETLERSTEVENSON, WG MUELLER, SC CHEN, WT TI BINDING AND LOCALIZATION OF M(R)-72,000 MATRIX METALLOPROTEINASE AT CELL-SURFACE INVADOPODIA SO CANCER RESEARCH LA English DT Article ID TISSUE INHIBITOR; IV COLLAGENASE; TRANSFORMED-CELLS; CONTACT SITES; EXPRESSION; FIBRONECTIN; MEMBRANE; GELATINASE; 72-KDA; PROGELATINASE AB Degradation (turnover) of collagenous matrix occurs on the surface of specialized membrane extensions termed ''invadopodia,'' which are sites of cell invasion into the extracellular matrix. Here we show the localization of the M(r) 72,000 type IV collagenase of the matrix metalloproteinase family at invadopodia. When added exogenously, latent M(r) 72,000 collagenase binds to invadopodia of chicken embryo fibroblasts transformed by Rous sarcoma virus, whereupon the bound collagenase loses its propeptide. The collagenase binds to a component contained within the detergent extract of transformed cells, and increased levels of the active M(r) 62,000 form of the collagenase are seen here. Such an association is not detected in the detergent extract derived from normal cells. Using a recently developed cell fractionation procedure to collect cell surfaces enriched in invadopodia, we show that the M(r) 72,000 collagenase associates with the invadopodial fraction and active forms of the enzyme become immobilized on the collagenous surface. Thus, invadopodia direct intense localized degradation of the extracellular matrix by concentrating active membrane-associated collagenases at sites of cellular invasion. C1 GEORGETOWN UNIV,SCH MED,DEPT ANAT & CELL BIOL,WASHINGTON,DC 20007. GEORGETOWN UNIV,SCH MED,LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NCI NIH HHS [F32 CA-08780, R01 CA-39077] NR 35 TC 166 Z9 167 U1 0 U2 2 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 JUL 1 PY 1993 VL 53 IS 13 BP 3159 EP 3164 PG 6 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100041 PM 8391388 ER PT J AU OHSAKI, Y YANG, HK LE, PT JENSEN, RT JOHNSON, BE AF OHSAKI, Y YANG, HK LE, PT JENSEN, RT JOHNSON, BE TI HUMAN SMALL-CELL LUNG-CANCER CELL-LINES EXPRESS FUNCTIONAL ATRIAL-NATRIURETIC-PEPTIDE RECEPTORS SO CANCER RESEARCH LA English DT Article ID BOMBESIN-LIKE PEPTIDES; SMOOTH-MUSCLE CELLS; SWISS 3T3 CELLS; GROWTH FACTOR-I; GUANYLATE-CYCLASE; CLEARANCE RECEPTOR; DNA-SYNTHESIS; TUMOR-CELLS; HELA-CELLS; STIMULATION AB Small cell lung cancer cell (SCLC) lines, NCI-H82, NCI-H660, and NCI-H1284, and HeLa cells were analyzed for the presence of atrial natriuretic peptide (ANP) receptors. In these SCLC cell lines and HeLa cells, ANP A receptor mRNA was identified by Southern blot analyses or polymerase chain reaction products and RNase protection assays using poly(A)+-selected RNA. Saturable binding assays revealed that HeLa cells had 2000 to 5000 high affinity atrial natriuretic peptide receptors per cell with a dissociation constant of 140 pM. In the SCLC cell lines, the binding was saturable but too low to accurately estimate the number of binding sites. After addition of human ANP, radioimmunoassays revealed accumulation of cyclic GMP in SCLC cells as well as HeLa cells in a dose-dependent fashion. The half-maximal stimulation concentration of cyclic GMP accumulation in HeLa and these SCLC cell lines was approximately 2 nM. Tetrazolyl blue assays and tritiated thymidine incorporation did not show any remarkable growth inhibition or growth stimulation of SCLC cell lines after addition of human ANP up to 3.3 muM, more than 1000-fold greater than the half-maximal stimulation concentration of cyclic GMP accumulation. Our results indicate that human SCLC cells express functional ANP receptors but ANP addition produced no detectable change in their growth pattern. C1 NCI,NATL NAVAL MED CTR,NCI USN,MED ONCOL BRANCH,BETHESDA,MD 20889. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20889. RI Yang, Han-Kwang/J-2767-2012 NR 53 TC 13 Z9 13 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 JUL 1 PY 1993 VL 53 IS 13 BP 3165 EP 3171 PG 7 WC Oncology SC Oncology GA LL131 UT WOS:A1993LL13100042 PM 8391389 ER PT J AU ROUTLEDGE, MN WINK, DA KEEFER, LK DIPPLE, A AF ROUTLEDGE, MN WINK, DA KEEFER, LK DIPPLE, A TI MUTATIONS INDUCED BY SATURATED AQUEOUS NITRIC-OXIDE IN THE PSP189 SUPF GENE IN HUMAN AD293 AND ESCHERICHIA-COLI MBM7070 CELLS SO CARCINOGENESIS LA English DT Article ID SHUTTLE VECTOR PLASMID; CYTOSINE RESIDUES; P53 MUTATIONS; DNA; 5-METHYLCYTOSINE; DEOXYINOSINE; HYPOXANTHINE; DEAMINATION; INHIBITION; LEUKEMIA AB Nitric oxide is an important bioregulatory agent that may also be an endogenous and exogenous human mutagen. In order to study mutations generated following exposure of a shuttle vector-borne target gene to nitric oxide, mutations were induced in the supF gene of the pSP189 shuttle vector by treatment with nitric oxide in aerobic buffered solution followed by replication of the plasmid in either human Ad293 or Escherichia coli MBM7070 cells. The induced mutation frequency, which increased with nitric oxide dose, was 44-fold greater than the spontaneous background in human cells and > 15-fold greater than background in the bacterial cells when a total of 100 mmol of nitric oxide was oxidatively absorbed/l of pH 7.4 buffer containing the plasmid. The majority of point mutations analysed (61 and 75% for human and E. coli cells respectively) were AT-->6GC transitions with GC-->AT transitions (29 and 23%) being the next most prevalent. The overall frequencies of the various point mutations seen in the supF gene were similar in the two cell types, although the distribution of hotspots showed differences. The results are consistent with a mutational mechanism initiated by deamination of DNA bases. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RP ROUTLEDGE, MN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-74101] NR 30 TC 92 Z9 93 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1993 VL 14 IS 7 BP 1251 EP 1254 DI 10.1093/carcin/14.7.1251 PG 4 WC Oncology SC Oncology GA LM978 UT WOS:A1993LM97800001 PM 8330336 ER PT J AU SPALDING, JW MOMMA, J ELWELL, MR TENNANT, RW AF SPALDING, JW MOMMA, J ELWELL, MR TENNANT, RW TI CHEMICALLY-INDUCED SKIN CARCINOGENESIS IN A TRANSGENIC MOUSE LINE (TG.AC) CARRYING A V-HA-RAS GENE SO CARCINOGENESIS LA English DT Article ID PROMOTING ACTIVITY; VINYL CARBAMATE; ETHYL CARBAMATE; HARVEY; TUMORS; INITIATORS; ONCOGENE; PEROXIDE; ACID AB A transgenic mouse line (TG-AC) created in the FVB/N strain, carries a v-Ha-ras gene fused to a zeta-globin promoter gene. These trangenic mice have the properties of genetically initiated skin and have been shown to be sensitive to 12-O-tetradecanoylphorbol-13-acetate (TPA), a well-described promoter of skin papillomas in the two-stage mouse skin tumorigenesis model. It was of interest to determine whether the TG . AC mouse strain was also responsive to other known promoters. Groups of heterozygous or homozygous TG . AC mice were treated topically, 2 X/week, for up to 20 weeks with benzoyl peroxide (BPO), 2-butanol peroxide (2-BUP), phenol (PH), acetic acid (AA), TPA and acetone (ACN), the vehicle control. Skin papillomas were induced in all groups treated with TPA, BPO and 2-BUP. Papillomas were observed in some treatment groups as early as 3 weeks. The relative activity of the promoters was TPA > 2-BUP > BPO > PH = AA=ACN. No papillomas were observed in any of the uninitiated FVB/N mice treated in a similar manner and which served as treatment control groups. Studies to determine the sensitivity of TG . AC mice to TPA, indicated that a total dose of 25-30 mug of TPA administered in 3 or 10 applications, was sufficient to induce an average incidence of 11-15 papillomas per mouse. The papilloma incidence continued to increase and was maintained up to 15 weeks after TPA treatment was terminated. The short latency period and high incidence of papilloma induction indicate that TG . AC mice have a high sensitivity to known skin promoters. The TG . AC line should prove to be a sensitive model for identifying putative tumor promoters or complete carcinogens. C1 NIEHS,EXPTL TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP SPALDING, JW (reprint author), NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 20 TC 108 Z9 109 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1993 VL 14 IS 7 BP 1335 EP 1341 DI 10.1093/carcin/14.7.1335 PG 7 WC Oncology SC Oncology GA LM978 UT WOS:A1993LM97800014 PM 8330346 ER PT J AU SNYDERWINE, EG DAVIS, CD NOUSO, K ROLLER, PP SCHUT, HAJ AF SNYDERWINE, EG DAVIS, CD NOUSO, K ROLLER, PP SCHUT, HAJ TI P-32 POSTLABELING ANALYSIS OF IQ, MEIQX AND PHIP ADDUCTS FORMED IN-VITRO IN DNA AND POLYNUCLEOTIDES AND FOUND IN-VIVO IN HEPATIC DNA FROM IQ-TREATED, MEIQX-TREATED AND PHIP-TREATED MONKEYS SO CARCINOGENESIS LA English DT Article ID FOOD-BORNE CARCINOGEN; HETEROCYCLIC AMINES; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; COOKED FOOD; METABOLIC-ACTIVATION; URINARY MUTAGENS; BLACK TOBACCO; CDF1 MICE; IDENTIFICATION; BINDING AB The P-32-postlabeling method was used to examine the adducts in DNA, polynucleotides, and mononucleotides reacted in vitro with the N-hydroxy and N-acetoxy derivatives of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Adduct profiles were compared to those found in vivo in liver of cynomolgus monkeys fed IQ, MeIQx or PhIP. The N-acetoxy derivatives of IQ, MeIQx and PhIP (generated in situ from the corresponding N-hydroxylamine in the presence of acetic anhydride) each formed three principal adducts in DNA. Adduct 1 of IQ, MeIQx and PhIP was chromatographically identical to the P-32-labeled bis(phosphate) derivative of N-(deoxyguanosin-8-yl)-IQ, N-(deoxyguanosin-8-yl)-MeIQx, and N-(deoxyguanosin-8-yl)-PhIP respectively, and this adduct comprised approximately 65% of total adduct levels found in DNA in vitro. The C8-guanine adduct and the two minor adducts were also found in poly(dG-dC).poly(dG-dC), suggesting that the two minor adducts of IQ, MeIQx and PhIP are also formed on the guanine base. The N-acetoxy derivatives of IQ, MeIQx, and to a much lesser extent PhIP, also formed adducts with adenine-containing polynucleotides including poly(dA), poly(dA).poly(dT) and poly(dA-dT).poly(dA-dT), but these adenine adducts were chromatographically different from those found in DNA. The three guanine adducts of N-acetoxy-IQ, -MeIQx and -PhIP found in vitro in DNA and in guanine-containing polynucleotides were also found in the liver of monkeys fed IQ, MeIQx or PhIP respectively, indicating that metabolic activation via N-hydroxylation and esterification occurred in vivo in monkeys. With each compound, the C8-guanine adduct was the predominant adduct found in vivo. The results indicate similarities among IQ, MeIQx and PhIP in the DNA adducts formed in vitro and in vivo and substantiate the use of the P-32-postlabeling method for comparative adduct studies. C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. RP SNYDERWINE, EG (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 41 TC 93 Z9 93 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1993 VL 14 IS 7 BP 1389 EP 1395 DI 10.1093/carcin/14.7.1389 PG 7 WC Oncology SC Oncology GA LM978 UT WOS:A1993LM97800023 PM 8330355 ER PT J AU TIANO, HF HOSOKAWA, M CHULADA, PC SMITH, PB WANG, RL GONZALEZ, FJ CRESPI, CL LANGENBACH, R AF TIANO, HF HOSOKAWA, M CHULADA, PC SMITH, PB WANG, RL GONZALEZ, FJ CRESPI, CL LANGENBACH, R TI RETROVIRAL-MEDIATED EXPRESSION OF HUMAN CYTOCHROME-P450-2A6 IN C3H/10T1/2 CELLS CONFERS TRANSFORMABILITY BY 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK) SO CARCINOGENESIS LA English DT Article ID TOBACCO-SPECIFIC NITROSAMINES; HUMAN LIVER-MICROSOMES; METABOLIC-ACTIVATION; CHEMICAL CARCINOGENS; MUTAGEN ACTIVATION; STABLE EXPRESSION; EPITHELIAL-CELLS; GENE-TRANSFER; F344 RATS; CDNA AB In order to develop more efficient in vitro systems for the study of pro-mutagenic or pro-carcinogenic chemicals, we have produced transgenic C3H/10T1/2 cell lines expressing human cytochrome P450 (CYP) 2A6. A retroviral vector containing the cDNA was packaged in PSI-2 cells, and used to infect C3H/10T1/2 cells. From 100 G418-resistant clones initially isolated, three cell lines were chosen for further study based upon their morphologies, growth rates and CYP2A6-dependent coumarin 7-hydroxylase activities. Infected clone 10T1/2-04, like the 10T1/2 cells, had no detectable CYP2A6 enzyme activity, while clones 10T1/2 - 10 and 10T1/2 -29 had microsomal CYP2A6 enzyme activities within the range found in human liver microsomes. CYP2A6 protein levels were in agreement with the observed enzyme activities. Southern blots revealed that cells from clone 10T1/2 - 04 contained a vector lacking the CYP2A6 cDNA, while cells from clones 10T1/2-10 and 10T1/2-29 contained multiple full-length inserts. Southern analysis also indicated the presence of an endogenous CYP2A6 ortholog in the four cell lines. All cell lines exhibited about equal sensitivity to induction of cytotoxicity and conversion to ouabain resistance by the direct acting mutagen N-methyl-N'-nitro-N-nitrosoguanidine. The four lines were also about equally sensitive to transformation by benzo[a]pyrene, a chemical requiring metabolic activation. However, only clones 10T1/2-10 and 10T1/2-29, which express CYP2A6 activity, were mutated and morphologically transformed by the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. C1 NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. GENTEST CORP,WOBURN,MA 01801. NR 57 TC 30 Z9 30 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1993 VL 14 IS 7 BP 1421 EP 1427 DI 10.1093/carcin/14.7.1421 PG 7 WC Oncology SC Oncology GA LM978 UT WOS:A1993LM97800028 PM 8330360 ER PT J AU MOON, RC KELLOFF, GJ DETRISAC, CJ STEELE, VE THOMAS, CF SIGMAN, CC AF MOON, RC KELLOFF, GJ DETRISAC, CJ STEELE, VE THOMAS, CF SIGMAN, CC TI CHEMOPREVENTION OF OH-BBN-INDUCED BLADDER-CANCER IN MICE BY PIROXICAM SO CARCINOGENESIS LA English DT Note ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; ORNITHINE DECARBOXYLASE ACTIVITY; ALPHA-DIFLUOROMETHYLORNITHINE; COLON CARCINOGENESIS; PROSTAGLANDIN SYNTHESIS; INTESTINAL TUMORS; INHIBITION; PROMOTION; ASPIRIN; RATS AB Piroxicam inhibited induction of transitional cell carcinoma in mouse urinary bladder by N-butyl-N-(4-hydroxybutyl)nitrosamine. At 15 mg piroxicam/kg diet, tumor incidence was reduced 82% (P < 0.0001) compared with carcinogen controls. At 30 mg piroxicam/kg diet, tumor incidence was reduced 70% (P < 0.001). Results at the higher dose level suggested that piroxicam also may have inhibited invasion slightly. Combination treatment with 2-difluoromethylornithine (DFMO) or all-trans-N-(4-hydroxyphenyl)retinamide (4-HPR) or both agents did not improve the chemopreventive potential of piroxicam. However, the three-agent combination of 30 mg piroxicam/kg, 1200 mg DFMO/kg and 313 mg 4-HPR/kg diet was highly effective. Tumor incidence was reduced 91% (P < 0.0001) compared with carcinogen controls. Unfortunately, the high efficacy was somewhat compromised by a significant decrease in survival and body weight gain in mice receiving the combination of agents compared with the carcinogen control. C1 IIT,RES INST,CHICAGO,IL 60616. NCI,CHEMOPREVENT BRANCH,BETHESDA,MD 20892. CCS ASSOCIATES,PALO ALTO,CA 94301. FU NCI NIH HHS [N01-CN-85097-02] NR 22 TC 51 Z9 51 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1993 VL 14 IS 7 BP 1487 EP 1489 DI 10.1093/carcin/14.7.1487 PG 3 WC Oncology SC Oncology GA LM978 UT WOS:A1993LM97800040 PM 8330371 ER PT J AU DIDISHEIM, P AF DIDISHEIM, P TI AN APPROACH TO BIOCOMPATIBILITY SO CARDIOVASCULAR PATHOLOGY LA English DT Article RP DIDISHEIM, P (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 7 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JUL-SEP PY 1993 VL 2 IS 3 SU S BP S1 EP S2 PG 2 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA MA485 UT WOS:A1993MA48500001 ER PT J AU SCHOEN, FJ LIBBY, P DIDISHEIM, P AF SCHOEN, FJ LIBBY, P DIDISHEIM, P TI FUTURE-DIRECTIONS AND THERAPEUTIC APPROACHES SO CARDIOVASCULAR PATHOLOGY LA English DT Article ID MUSCLE CELL-PROLIFERATION; ENDOTHELIAL-CELLS; GROWTH-FACTOR; THROMBOSIS; INHIBITION; INVIVO; IMMOBILIZATION; INTERRUPTION; HYPERPLASIA; ADSORPTION AB Clinically important problems encountered with cardiovascular biomaterials and medical devices are predominantly mediated by cellular and molecular interactions between forein surfaces and the blood and tissue they contact. The most frequest cardiovascular device complications are thromboembolism, hemorrhage due to therepeutic anticoagulation, infection, abnormal healing such as intimal hyperplasia, and structural dysfunction due to biomaterials failure. This chapter summarizes recent progress toward alleviating some of these complications, particularly in preventing thrombosis and thromboembolism, intimal thickening and biomaterials calcification. C1 NHLBI,DIV HEART & VASC DIS,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DEPT VASC MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,ARTHERIOSCLEROSIS UNIT,BOSTON,MA 02115. RP SCHOEN, FJ (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,BOSTON,MA 02115, USA. NR 51 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD JUL-SEP PY 1993 VL 2 IS 3 SU S BP S209 EP S216 PG 8 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA MA485 UT WOS:A1993MA48500021 ER PT J AU KINGMAN, A AF KINGMAN, A TI METHODS OF PROJECTING LONG-TERM RELATIVE EFFICACY OF PRODUCTS EXHIBITING SMALL SHORT-TERM EFFICACY SO CARIES RESEARCH LA English DT Article DE CARIES; DENTIFRICES; FLUORIDE; PREVENTION; PROPAGATION ID SCHOOL-CHILDREN; DENTAL-CARIES; PREVALENCE AB There is ample evidence that caries can develop well into the middle-aged years, and for many subjects, for most of their adult lives. The kinds of benefits to expect for adults in the longer term for improved fluoride products, especially dentifrices, based upon small observed relative improvements in short-term efficacy is a topic currently of considerable interest. For example, what longer-term benefits can be expected by the continued use of an improved fluoride dentifrice, corresponding to an observed 5% or 10% short-term improved efficacy relative to a positive control product? In this study, three models are presented and discussed for projecting longer-term relative benefits of fluoride products for which valid short-term efficacy estimates are available: the compound growth model (CGM), which is a derivative of the compound interest model; the demineralization square root model (DSR), used in demineralization-remineralization studies, and the stabilization model (STA), which is based on the assumption of constant caries attack rates. Published results from long-term studies of fluoride dentifrices and other topical fluoride products (rinses and tablets) suggest that anticaries benefits for topical fluorides do propagate over time, providing increased relative benefits to patients in the longer-term, as compared with the benefit estimates from short-term clinical experiences. In general, these results suggest that some combination of the CGM and the DSR models most adequately describes the expected propagation benefits of topical fluorides, provided the anticaries effects of the product are not 'saturated'. Expected 10- and 20-year estimated cumulative relative efficacy figures are derived for improved dentifrice products having small short-term efficacy values separately for the CGM, DSR and STA models. A dentifrice having an observed improved efficacy of 5% relative to a positive control product would be expected to produce a cumulative 10-year relative benefit between 9% (DSR) and 15% (CGM); over a 20-year period a cumulative benefit between 13% (DSR) and 28% (CGM). The actual values may depend upon the dose of the fluoride administered and other factors. RP KINGMAN, A (reprint author), NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,WESTWOOD BLDG,ROOM 522,BETHESDA,MD 20892, USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PD JUL-AUG PY 1993 VL 27 IS 4 BP 322 EP 327 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LW135 UT WOS:A1993LW13500016 PM 8402810 ER PT J AU LAROCHELLE, WJ JENSEN, RA HEIDARAN, MA MAYSIROFF, M WANG, LM AARONSON, SA PIERCE, JH AF LAROCHELLE, WJ JENSEN, RA HEIDARAN, MA MAYSIROFF, M WANG, LM AARONSON, SA PIERCE, JH TI INHIBITION OF PLATELET-DERIVED GROWTH-FACTOR AUTOCRINE GROWTH-STIMULATION BY A MONOCLONAL-ANTIBODY TO THE HUMAN ALPHA PLATELET-DERIVED GROWTH-FACTOR RECEPTOR SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID SIMIAN SARCOMA-VIRUS; HUMAN CSF-1 RECEPTOR; PDGF RECEPTOR; SIGNALING PATHWAYS; EXPRESSION; LOCALIZATION; ESTABLISHES; GENES; SIS AB A potent neutralizing monoclonal antibody to the human alpha platelet-derived growth factor (PDGF) receptor (alpha PDGFR) was raised by immunizing BALB/c mice with 32D cells expressing the human alpha PDGFR. This monoclonal antibody, designated alphaR1, immunoprecipitated human, monkey, rabbit, pig, dog, and cat, but not hamster, rat, or mouse alpha PDGFRs. Comparison with PR292, a monoclonal antibody previously generated against the alpha PDGFR, showed that both recognized alpha PDGFR extracellular domains, but neither demonstrated reactivity against the beta PDGFR. In vitro binding studies revealed that alphaR1, but not PR292, detection of the a PDGFR was blocked by either PDGF AA or PDGF BB. These results strongly suggest that the receptor ligand-binding domain spatially overlapped with the alphaR1 epitope. Monoclonal antibody alphaR1 also inhibited PDGF stimulation of [H-3]thymidine uptake by 32D cells expressing the alpha PDGFR (32D alphaR) as well as autocrine growth stimulation of 32D alphaR cells transfected with and expressing PDGF AA or PDGF BB. Therefore, monoclonal antibody alphaR1 may be useful in the detection and growth inhibition of malignancies in which PDGF autocrine stimulation and/or alpha PDGFR overexpression plays an important role(s). RP LAROCHELLE, WJ (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,ROOM 1E24,BETHESDA,MD 20892, USA. NR 25 TC 21 Z9 21 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1993 VL 4 IS 7 BP 547 EP 553 PG 7 WC Cell Biology SC Cell Biology GA LM110 UT WOS:A1993LM11000003 PM 7691151 ER PT J AU EVARTS, RP HU, ZY FUJIO, K MARSDEN, ER THORGEIRSSON, SS AF EVARTS, RP HU, ZY FUJIO, K MARSDEN, ER THORGEIRSSON, SS TI ACTIVATION OF HEPATIC STEM-CELL COMPARTMENT IN THE RAT - ROLE OF TRANSFORMING GROWTH-FACTOR-ALPHA, HEPATOCYTE GROWTH-FACTOR, AND ACIDIC FIBROBLAST GROWTH-FACTOR IN EARLY PROLIFERATION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID CHOLINE-DEFICIENT DIET; DNA-SYNTHESIS; LIVER CARCINOGENESIS; PARTIAL-HEPATECTOMY; SCATTER FACTOR; OVAL CELLS; REGENERATION; FETOPROTEIN; EXPRESSION; GALACTOSAMINE AB We have demonstrated previously a pronounced increase in the expression of hepatocyte growth factor (HGF) (Z. Hu, R. P. Evarts, K. Fujio, E. R. Marsden, and S. S. Thorgeirsson, Am. J. Pathol., 142: 1823-1830, 1993), transforming growth factor alpha (TGF-alpha) (R. P. Evarts, H. Nakatsukasa, E. R. Marsden, Z. Hu, and S. S. Thorgeirsson, Mol. Carcinog., 5. 25-31, 1992), and acidic fibroblast growth factor (aFGF) (E. R. Marsden, Z. Hu, K. Fujio, H. Nakatsukasa, S. S. Thorgeirsson, and R. P. Evarts, Lab. Invest., 67. 427-433, 1992) that coincided with the proliferation and differentiation of putative hepatic stem cells and perisinusoidal stellate (Ito) cells. Here, we examine the earliest stages of stem cell activation in rat liver using an experimental model involving treatment with acetylaminofluorene and partial hepatectomy (R. P. Evarts, P. Nagy, E. Marsden, and S. S. Thorgeirsson, Carcinogenesis (Lond.), 8: 1737-1740, 1987). Histochemical identification of stem cell progeny and Ito cells was accomplished by OV6 and desmin antibodies, respectively. Expression of the 2.1-kilobase a-fetoprotein transcripts and the concomitant DNA synthesis ([H-3]thymidine label) were used as indicators for the activation of the stem cell compartment. Expression of HGF, TGF-alpha, and aFGF was analyzed at the time of partial hepatectomy and 4, 12, 24, 48, 72, and 92 h after the operation. [H-3]-Thymidine-labeled OV6- and desmin-positive cells were present in the portal space and in the Glisson capsule 4 h after partial hepatectomy. The appearance of these [H-3]thymidine-labeled cells coincided with the increase in the expression of AFP, HGF, and TGF-alpha, whereas the increase in the expression of aFGF was first observed 24 h after the operation. By 72 h, a large number of the cells in the periportal space were in DNA synthesis, and about one-half of them were OV6 positive. The desmin-positive cells infiltrated the liver parenchyma and seemed to move ahead of the OV6-positive oval cells. The early expression of TGF-alpha and HGF suggests an immediate involvement of these growth factors in proliferation and the characteristic 'infiltration' of liver stem cells into the liver acinus. Since HGF has a powerful motogenic effect upon numerous cell types including hepatocyte, we suggest that TGF-alpha may be the primary mitogen, whereas the primary action of HGF may be as a motogen in hepatic stem cell activation. The delayed expression of aFGF may indicate a function for this cytokine in the expanding progeny of the hepatic stem cells that is different from those of TGF-alpha and HGF. RP EVARTS, RP (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 108 Z9 111 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1993 VL 4 IS 7 BP 555 EP 561 PG 7 WC Cell Biology SC Cell Biology GA LM110 UT WOS:A1993LM11000004 PM 7691152 ER PT J AU RONG, S OSKARSSON, M FALETTO, D TSARFATY, I RESAU, JH NAKAMURA, T ROSEN, E HOPKINS, RF VANDEWOUDE, GF AF RONG, S OSKARSSON, M FALETTO, D TSARFATY, I RESAU, JH NAKAMURA, T ROSEN, E HOPKINS, RF VANDEWOUDE, GF TI TUMORIGENESIS INDUCED BY COEXPRESSION OF HUMAN HEPATOCYTE GROWTH-FACTOR AND THE HUMAN MET PROTOONCOGENE LEADS TO HIGH-LEVELS OF EXPRESSION OF THE LIGAND AND RECEPTOR SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID SCATTER FACTOR; EPITHELIAL-CELLS; KINASE-ACTIVITY; PROTO-ONCOGENE; RAT PLATELETS; C-MET; PURIFICATION; FIBROBLASTS; ACTIVATION; MOBILITY AB We have previously shown that, in mouse NIH/3T3 cells, it is necessary to coexpress the gene for human hepatocyte growth factor/scatter factor (HGF/SF(hu)) with its receptor, the human met protooncogene (met(hu)), to activate the transforming activity of the receptor (S. Rong, M. Bodescot, D. Blair, T. Nakamura, K. Mizuno, M. Park, A. Chan, S. Aaronson, and G. F. Vande Woude, Mol. Cell. Biol., 12: 5152-5158, 1992). In this study, we report that exceptionally high levels of the ligand and its receptor are expressed in tumor cell explants after several tumor passages through nude mice. Confluent tumor cells explanted after the second passage in nude mice can express 1700 units/ml/10(6) cells/72 h of scatter activity as determined in Madin-Darby canine kidney cell scatter assays. The motogenic factor produced by these cells is easily purified by heparin-Sepharose chromatography, and the purified factor efficiently induces tyrosine phosphorylation of Met(hu) in YaOvBix2NMA human ovarian carcinoma cells. To account for the unusually high level of HGF/SF(hu) and Met(hu) expression, we propose that normal levels of Met(hu) receptor are inefficient at transducing the signal(s) required for transformation of mouse cells. Therefore, high levels of Met(hu) receptor are required for tumorigenesis, and correspondingly high levels of the ligand are required to induce the signal. Consistent with this model, endogenous mouse scatter factor is not detected in conditioned medium from cells transformed by overexpression of the Met(hu) receptor. C1 NCI,FREDERICK CANC RES & DEV CTR,PRI DYN CORP INC,FERMENTAT PROD FACIL,FREDERICK,MD 21702. KYUSHU UNIV,FAC SCI,DEPT BIOL,FUKUOKA 812,JAPAN. YALE UNIV,SCH MED,DEPT THERAPEUT RADIOL,NEW HAVEN,CT 06510. NCI,FREDERICK CANC RES,PRI,DYNCORP INC,FERMENTAT PROD FACIL,FREDERICK,MD 21702. RP RONG, S (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ABL,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 42 TC 96 Z9 96 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1993 VL 4 IS 7 BP 563 EP 569 PG 7 WC Cell Biology SC Cell Biology GA LM110 UT WOS:A1993LM11000005 PM 8398896 ER PT J AU HARGROVE, ME WANG, J TING, CC AF HARGROVE, ME WANG, J TING, CC TI REGULATION BY GLUTATHIONE OF THE ACTIVATION AND DIFFERENTIATION OF IL-4-DEPENDENT ACTIVATED KILLER-CELLS SO CELLULAR IMMUNOLOGY LA English DT Article ID STIMULATORY FACTOR-I; TOXIC T-CELLS; MONOCLONAL-ANTIBODY; LYMPHOCYTES-T; TARGET-CELLS; LYMPHOKINE; INTERLEUKIN-2; DEGRADATION; UBIQUITIN RP HARGROVE, ME (reprint author), NCI,DIV CELL BIOL DIAGNOSIS & CTR,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 33 TC 14 Z9 14 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL PY 1993 VL 149 IS 2 BP 433 EP 443 DI 10.1006/cimm.1993.1168 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA LM261 UT WOS:A1993LM26100019 PM 8330319 ER PT J AU MOSS, J VAUGHAN, M AF MOSS, J VAUGHAN, M TI ADP-RIBOSYLATION FACTORS, 20,000 M(R) GUANINE-NUCLEOTIDE-BINDING PROTEIN ACTIVATORS OF CHOLERA-TOXIN AND COMPONENTS OF INTRACELLULAR VESICULAR TRANSPORT-SYSTEMS SO CELLULAR SIGNALLING LA English DT Review DE ADENYLYL CYCLASE; GOLGI; ESCHERICHIA-COLI HEAT-LABILE ENTEROTOXINS; VESICULAR TRANSPORT; G-PROTEINS ID LABILE ENTERO-TOXIN; PANCREATIC MICROSOMAL VESICLES; ADENYLATE-CYCLASE; ESCHERICHIA-COLI; RIBOSYLTRANSFERASE ACTIVITY; MESSENGER-RNA; FACTOR ARF; REGULATORY COMPONENT; GOLGI MEMBRANES; SACCHAROMYCES-CEREVISIAE RP MOSS, J (reprint author), NHLBI,CELLULAR METAB LAB,ROOM 5N-307,BLDG 10,BETHESDA,MD 20892, USA. NR 93 TC 24 Z9 24 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JUL PY 1993 VL 5 IS 4 BP 367 EP & DI 10.1016/0898-6568(93)90076-X PG 0 WC Cell Biology SC Cell Biology GA LQ046 UT WOS:A1993LQ04600002 PM 8373721 ER PT J AU PATTEN, CJ THOMAS, PE GUY, RL LEE, MJ GONZALEZ, FJ GUENGERICH, FP YANG, CS AF PATTEN, CJ THOMAS, PE GUY, RL LEE, MJ GONZALEZ, FJ GUENGERICH, FP YANG, CS TI CYTOCHROME-P450 ENZYMES INVOLVED IN ACETAMINOPHEN ACTIVATION BY RAT AND HUMAN LIVER-MICROSOMES AND THEIR KINETICS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID N-NITROSODIMETHYLAMINE DEMETHYLASE; REACTIVE METABOLITE FORMATION; INDUCED HEPATIC NECROSIS; INDUCED HEPATOTOXICITY; PARA-BENZOQUINONE; OXIDATION; INHIBITION; ISOZYMES; INDUCTION; AFLATOXIN-B1 AB Acetaminophen (APAP), a commonly used analgesic, is catalyzed by cytochrome P450 (P450) enzymes to a toxic intermediate which can be trapped by glutathione. Using this approach, involvement of enzymes in the activation of APAP and their kinetics were studied. With human liver microsomes, there were three apparent K(m) values (approximately 10, 474, and 13 000 AM) for the oxidation of APAP to its glutathione conjugate. With rat liver microsomes (control and ethanol induced) the kinetic data were best fit to a two-Km model (approximately 30 and 1100 muM). Liver microsomes from dexamethasone (DEX)-treated female rats showed a single K(m) of 56 muM and a V(max) of 7500 pmol of product formed/ (min-mg of protein). Antibodies specific for rat P450s 2E1 and 1A2 each inhibited approximately 40% of the APAP metabolism in control male rat microsomes. Only slight inhibition was observed with the P450 3A1/2 antibodies in control male or female rat liver microsomes. Antibodies against rat P450s 3A1/2 inhibited the activity in DEX microsomes by 80 %. Antibodies inhibitory to human P450 3A4 inhibited 38% of the activity in human liver microsome sample HL107 and 76% in human microsome sample HL110. Human P450s (2A6, 2E1, 1A2, 3A4, 3A5, 3A3, 2D6, 2F1, 2C8, 2B6, and 2C9) expressed in Hep G2 cells using a vaccinia virus expression system were each tested for APAP metabolism. Of these, P450 2E1, 1A2, and 3A4 showed substantial activity, with respective K(m) and V(max) values of 680 muM and 330 pmol/(min-mg) for P450 2E1 (with added cytochrome b5), 3430 muM and 74 pmol/(min.mg) for P450 1A2, and 280 muM and 130 pmol/(min.mg) for P450 3A4. In the presence of alpha-naphthoflavone (alpha-NF), expressed P450 3A4 activity was increased 11-fold, expressed P450 2E1 activity was unaffected, and expressed 1A2 activity was inhibited 83%. With expressed P450 3A4, both the K(m) and V(max) for APAP oxidation were increased by alpha-NF. Alpha-NF stimulated APAP oxidation 2- to 5-fold in human and control male rat liver microsomes. In the presence of alpha-NF, the P450 3A1/2 antibody became strongly inhibitory in control male rat liver microsomes, suggesting 3A2 activation by this flavone compound. C1 RUTGERS UNIV,COLL PHARM,CANC RES LAB,PISCATAWAY,NJ 08855. RUTGERS UNIV,COLL PHARM,DEPT TOXICOL & PHARMACOL,PISCATAWAY,NJ 08855. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA44353]; NIEHS NIH HHS [ES05022, ES03938] NR 47 TC 273 Z9 279 U1 2 U2 25 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1993 VL 6 IS 4 BP 511 EP 518 DI 10.1021/tx00034a019 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA LM738 UT WOS:A1993LM73800019 PM 8374050 ER PT J AU LANDI, MT BERTAZZI, PA CLARK, G LUCIER, GW GARTE, SJ COSMA, G SHIELDS, PG CAPORASO, NE AF LANDI, MT BERTAZZI, PA CLARK, G LUCIER, GW GARTE, SJ COSMA, G SHIELDS, PG CAPORASO, NE TI SUSCEPTIBILITY MARKERS IN NORMAL SUBJECTS - A PILOT-STUDY FOR THE INVESTIGATION OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN RELATED DISEASES SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 12TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS ( DIOXINS-92 ) CY AUG 24-28, 1992 CL TAMPERE, FINLAND SP INST OCCUPAT HLTH, UNIV TAMPERE DE DIOXINS; SUSCEPTIBILITY MARKERS; ETHOXYRESORUFIN-O-DEETHYLASE; CYPLAL; GENETIC POLYMORPHISMS; INDUCIBILITY ID CYTOCHROME-P450IA1 GENE; LUNG-CANCER; POLYMORPHISMS; RECEPTOR; DIOXIN AB Studies on dioxin (TCDD) carcinogenicity in humans have yielded conflicting results. One possible explanation of these mixed findings rests on the role of susceptibility factors. We are currently addressing this hypothesis in a case-control study in the Seveso population. In a pilot investigation, a set of susecptibility markers have been measured in 20 healthy volunteers. Ethoxyresorufin-O-Deethylase (EROD) activity was significantly greater in subjects with mutant CYP1a1 genotypes than in homozygous wild type subjects. No difference in mRNA expression was noted. Meat consumption possibly influences this result. Suggestions of an interaction between ''mutation'' and ''TCDD induction'' were obtained. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV MILAN,EPIDEMIOL RES CTR,I-20122 MILAN,ITALY. NIEHS,RES TRIANGLE PK,NC 27709. NYU,MED CTR,ANTHONY J LANZA RES LAB,TUXEDO PK,NY 10987. RP LANDI, MT (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. RI bertazzi, pietro alberto/D-5039-2017 OI bertazzi, pietro alberto/0000-0003-3475-2449 NR 20 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL-AUG PY 1993 VL 27 IS 1-3 BP 375 EP 381 DI 10.1016/0045-6535(93)90315-V PG 7 WC Environmental Sciences SC Environmental Sciences & Ecology GA LJ946 UT WOS:A1993LJ94600048 ER PT J AU YANG, JH RIM, JS AF YANG, JH RIM, JS TI CHARACTERIZATION OF TCDD-TRANSFORMED HUMAN KERATINOCYTE CELL-LINE SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 12TH INTERNATIONAL SYMP ON CHLORINATED DIOXINS AND RELATED COMPOUNDS ( DIOXINS-92 ) CY AUG 24-28, 1992 CL TAMPERE, FINLAND SP INST OCCUPAT HLTH, UNIV TAMPERE DE HUMAN; KERATINOCYTE; TCDD; TRANSFORMATION; TRANSGLUTAMINASE ID TRANSGLUTAMINASE AB Exposure of Ad12-SV40 immortalized human keratinocyte cell line to TCDD led to morphological transformation and the subsequent injection of these transformed cells into nude mice induced carcinoma. Induction of EROD activity was dose-dependent, as was transformation. Thus, the carcinogenicity of TCDD in this human cell system appears to be an Ah receptor-mediated process. Analysis of transformed cells revealed significant increase of total transglutaminase, as compared to parent cells. Subsequent treatment of transformed cells with retinoic acid (3 mumol/L) induced 3-fold increase of transglutaminase activity. C1 NCI,BETHESDA,MD 20892. RP YANG, JH (reprint author), TAEGU CATHOLIC UNIV,DEPT PREVENT MED,TAEGU,SOUTH KOREA. NR 8 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 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD JUL-AUG PY 1993 VL 27 IS 1-3 BP 407 EP 411 DI 10.1016/0045-6535(93)90320-5 PG 5 WC Environmental Sciences SC Environmental Sciences & Ecology GA LJ946 UT WOS:A1993LJ94600053 ER PT J AU PASSERI, DR SPIEGEL, J AF PASSERI, DR SPIEGEL, J TI KILLING CANCER WITHOUT SURGERY SO CHEMTECH LA English DT Article ID PSEUDOMONAS EXOTOXIN; TRANSFERRIN RECEPTOR; DIPHTHERIA-TOXIN; IMMUNOTOXINS; ANTIBODY; BINDING; MICE; MUTATIONS; DOMAINS; CELLS RP PASSERI, DR (reprint author), NIH,OFF TECHNOL TRANSFER,BETHESDA,MD 20892, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0009-2703 J9 CHEMTECH JI Chemtech PD JUL PY 1993 VL 23 IS 7 BP 24 EP 28 PG 5 WC Chemistry, Applied SC Chemistry GA LQ650 UT WOS:A1993LQ65000010 ER PT J AU GAY, PC DELLINGER, RP SHELHAMER, JH OFFORD, K AF GAY, PC DELLINGER, RP SHELHAMER, JH OFFORD, K TI THE PRACTICE OF CRITICAL CARE MEDICINE - A NATIONAL SURVEY REPORT SO CHEST LA English DT Article ID PULMONARY-ARTERY CATHETER; PRACTICE GUIDELINES; PHYSICIANS AB Aggressive reimbursement reform has been an imposing directive for care providers of ICU medicine. Timely knowledge of actual care routines obtained from a large sample of actively practicing physicians should be mandatory when developing any guidelines or practice standards. A questionnaire was therefore designed by the steering committee of the ACCP Council on Critical Care and sent to its members. The 1,294 responses were analyzed for demographics of the individual practitioner, local aspects of ICU staffing and policies, reimbursement, and a specific practice issue, nutrition. The typical respondent was aged 41 to 50 (41 percent), was a pulmonary subspecialist (68 percent), was not critical care certified (55 percent), worked 25 to 50 percent of his or her total time in the ICU (40 percent), and would continue ICU practice despite poor reimbursement (82 percent). Physicians practiced within a group (53 percent), in a 100- to 500-bed hospital (69 percent), with house staff available (60 percent), and predominantly cared for Medicare patients (55 percent). The following data may allow better judgments to be made pertaining to the implementation of care policies in the current ICU environment. C1 MAYO CLIN & MAYO FDN,BIOSTAT SECT,ROCHESTER,MN 55905. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. NIH,BETHESDA,MD 20892. RP GAY, PC (reprint author), MAYO CLIN & MAYO FDN,DIV THORAC DIS & INTERNAL MED,ROCHESTER,MN 55905, USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD JUL PY 1993 VL 104 IS 1 BP 271 EP 278 DI 10.1378/chest.104.1.271 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA LL901 UT WOS:A1993LL90100054 PM 8325083 ER PT J AU MODI, WS AF MODI, WS TI RAPID, LOCALIZED AMPLIFICATION OF A UNIQUE SATELLITE DNA FAMILY IN THE RODENT MICROTUS-CHROTORRHINUS SO CHROMOSOMA LA English DT Article ID GIANT SEX-CHROMOSOMES; NUCLEOTIDE-SEQUENCES; HETEROCHROMATIN; METHYLATION; ASSOCIATION; SENSITIVITY; EVOLUTION; CLONING AB A novel satellite DNA family (called MSAT-2570) was isolated and characterized from the rodent Microtus chrotorrhinus. With a length of 2,570 bp the repeat unit is among the largest yet reported in mammals and comprises a series of short direct and inverted repeats. These repeat motifs may prevent nucleosome formation or represent an endless source of genetic variation. Restriction enzyme digestion using the two pairs of isoschizomers HpaII/MspI and MboI/Sau3AI demonstrated tissue specific differences in satellite DNA methylation that may reflect variable chromatin conformation or differences in patterns of gene expression. The sex chromosomes of M. chrotorrhinus are unusually large in size among mammals, comprising 15%-20% of the karyotype and containing large blocks of heterochromatin. In situ hybridization of the satellite DNA revealed chromosomal localization predominantly to sex chromosome heterochromatin. A survey of related rodents including three congeneric species also with giant sized sex chromosomes demonstrated that MSAT-2570 is present only in the genome of M. chrotorrhinus. However, another previously reported satellite DNA also isolated from M. chrotorrhinus has been shown to reside on sex chromosome heterochromatin in one of the other three species, indicating that these giant blocks of heterochromatin are complex in structure and comprise multiple, unrelatined satellite DNA families. RP MODI, WS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 37 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD JUL PY 1993 VL 102 IS 7 BP 484 EP 490 DI 10.1007/BF00357104 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LR518 UT WOS:A1993LR51800007 PM 8375217 ER PT J AU LENFANT, C AF LENFANT, C TI THE NHLBI CENTERS PROGRAM - THE SUN ALSO RISES SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1993 VL 88 IS 1 BP 3 EP 3 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LM127 UT WOS:A1993LM12700001 PM 8319344 ER PT J AU HO, KKL ANDERSON, KM KANNEL, WB GROSSMAN, W LEVY, D AF HO, KKL ANDERSON, KM KANNEL, WB GROSSMAN, W LEVY, D TI SURVIVAL AFTER THE ONSET OF CONGESTIVE-HEART-FAILURE IN FRAMINGHAM HEART-STUDY SUBJECTS SO CIRCULATION LA English DT Article DE SURVIVAL; CONGESTIVE HEART FAILURE; EPIDEMIOLOGY; MORTALITY; PROGNOSIS ID IDIOPATHIC DILATED CARDIOMYOPATHY; LEFT-VENTRICULAR FUNCTION; VASODILATOR THERAPY; HEMODYNAMIC MEASUREMENTS; DIASTOLIC DYSFUNCTION; ISOSORBIDE DINITRATE; SYSTOLIC FUNCTION; NATURAL-HISTORY; MORTALITY; PROGNOSIS AB Background. Relatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting. Methods and Results. Proportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0+/-10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3+/-7.6 years in the 1950s, 65.9+/-7.9 years in the 1960s, 71.6+/-9.4 years in the 1970s, and 76.4+/-10.0 years in the 1980s; p <0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26). Conclusions. CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population. C1 NHLBI, FRAMINGHAM HEART STUDY, 5 THURBER ST, FRAMINGHAM, MA 01701 USA. BETH ISRAEL HOSP, CHARLES A DANA RES INST, DIV CARDIOVASC, BOSTON, MA 02215 USA. CENTOCOR INC, DEPT STAT, MALVERN, PA USA. HARVARD UNIV, SCH MED, BOSTON, MA 02115 USA. BETH ISRAEL HOSP, DEPT MED, HARVARD THORNDIKE LAB, BOSTON, MA 02215 USA. BOSTON UNIV, SCH MED, BOSTON, MA 02215 USA. BOSTON UNIV HOSP, DEPT EPIDEMIOL & PREVENT MED, BOSTON, MA 02218 USA. FU NHLBI NIH HHS [5T32-HL-07374-13, N01-HC-38038] NR 48 TC 1066 Z9 1101 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL PY 1993 VL 88 IS 1 BP 107 EP 115 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LM127 UT WOS:A1993LM12700016 PM 8319323 ER PT J AU GOLDSPIEL, BR GREEN, L CALIS, KA AF GOLDSPIEL, BR GREEN, L CALIS, KA TI HUMAN GENE-THERAPY SO CLINICAL PHARMACY LA English DT Review DE GENE THERAPY; GENETIC ENGINEERING; NEOPLASMS; RESEARCH; TRANSFECTION AB Current concepts in gene transfer and its application to the treatment of human genetic disorders, cancer, and other diseases are discussed. Gene therapy is a technique in which a functioning gene is inserted into a human cell to correct a genetic error or to introduce a new function to the cell. Many methods, including retroviral vectors, have been developed for ex vivo and in vivo gene insertion into cells. Some pharmacists have likened gene therapy to a sophisticated form of drug delivery and have envisioned an active role for the pharmacy profession. There are several safety and ethical issues related to manipulating the human genome that need to be understood. Current gene therapy efforts focus on gene insertion into somatic (non-germinal) cells only. Gene therapy has the potential to revolutionize the treatment of genetic disorders, diseases associated with a genetic component (e.g., cystic fibrosis), cancer, AIDS, and many other diseases. Gene transfer may also be used to better understand the biology of disease processes, such as the source of relapse in bone marrow transplant patients. The human genome project will undoubtedly lead to the identification, characterization, and understanding of genes that are responsible for many human diseases, and gene therapy trials are sure to expand accordingly. To date, over 40 clinical trials have been approved and more than 110 patients have been entered in gene therapy studies. There are still many technical obstacles to overcome before gene therapy can have widespread application. Injectable vectors need to be developed to simplify foreign gene administration. Perhaps the biggest problem to overcome will be engineering the target cells to be able to regulate gene expression according to physiologic needs. Pharmacists should become knowledgeable about gene transfer techniques and possible clinical applications of gene therapy to keep abreast of the newest trends in medicine. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,CTR CLIN,BLDG 10,ROOM 1N-257,BETHESDA,MD 20892. NR 0 TC 14 Z9 15 U1 2 U2 25 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0278-2677 J9 CLIN PHARMACY PD JUL PY 1993 VL 12 IS 7 BP 488 EP 505 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LJ457 UT WOS:A1993LJ45700005 PM 8354036 ER PT J AU WILLIAMS, DY SELEPAK, ST GILL, VJ AF WILLIAMS, DY SELEPAK, ST GILL, VJ TI IDENTIFICATION OF CLINICAL ISOLATES OF NONDIPHTHERIAL CORYNEBACTERIUM SPECIES AND THEIR ANTIBIOTIC SUSCEPTIBILITY PATTERNS SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID GROUP-JK; BACTERIA AB Starting in 1982, our laboratory has performed species identification of coryneform bacteria isolated from blood cultures, in travenous (i.v.) catheter tips and sites, urines with high colony counts, and other potentially significant cultures, using predefined criteria. Of 283 isolates identified, Corynebacterium jeikeium was the most common (47%), followed by CDC group G2 (12%) and C. minutissimum (8%). Blood cultures and i.v. catheter-related sources were the most frequent sources (58% of total). Certain species or groups, like CDC group G2, were most frequently isolated from blood or i.v. catheter sites. CDC group G2 showed a progression to greater multiple antibiotic resistance during this 9-year period. Occasional multiresistant strains of other species were also encountered. By in vitro testing, we note vancomycin remains the most active agent against corynebacterialike organisms, and is the most reliable antibiotic to use while awaiting susceptibility testing results. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BETHESDA,MD 20892. NR 11 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JUL PY 1993 VL 17 IS 1 BP 23 EP 28 DI 10.1016/0732-8893(93)90065-F PG 6 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA LK269 UT WOS:A1993LK26900005 PM 8359002 ER PT J AU PISEGNA, JR DOPPMAN, JL NORTON, JA METZ, DC JENSEN, RT AF PISEGNA, JR DOPPMAN, JL NORTON, JA METZ, DC JENSEN, RT TI PROSPECTIVE COMPARATIVE-STUDY OF ABILITY OF MR-IMAGING AND OTHER IMAGING MODALITIES TO LOCALIZE TUMORS IN PATIENTS WITH ZOLLINGER-ELLISON SYNDROME SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE GASTRINOMA; ISLET CELL TUMOR; TUMOR LOCALIZATION ID ISLET CELL TUMORS; MALIGNANT GASTRINOMA; COMPUTED-TOMOGRAPHY; HEPATIC HEMANGIOMA; LIVER; ANGIOGRAPHY; MANAGEMENT; CONTRAST; CT; METASTASES AB The role of magnetic resonance (MR) imaging in patients with pancreatic endocrine tumors such as Zollinger-Ellison syndrome (ZES) is controversial. In the present study we have examined the ability of current MR imaging compared with other imaging modalities, to localize gastrinomas in 43 patients with ZES. All results were subsequently assessed at exploratory laparotomy (N = 34) or by liver biopsy (N = 9). For the 18 patients with metastatic gastrinoma in the liver, MR imaging had a sensitivity of 83%, ultrasound 50%, CT 56%, and angiography 61%. The combination of MR imaging, ultrasound, and CT were the same as MR imaging alone. For MR imaging, both Tl and STIR sequences had equal sensitivity, although tumors were more easily seen with STIR sequences Specificity of MR imaging was slightly lower (88%) than the other modalities (96-100%) because MR imaging incorrectly identified small hemangiomas as possible tumors in four patients. MR imaging was better than CT in identifying metastatic lesions in the liver. For the localization of primary gastrinoma, assessed in 32 patients, MR imaging had a sensitivity of 25%, ultrasound 19%, CT 28%, all three together 38%, and angiography 59%. Localization of metastatic gastrinoma in the liver or primary gastrinomas in 16 patients was assessed before and after gadolinium-DTPA (0.1 mmol/kg). The sensitivity and specificity of MR imaging was unchanged but bolus injection and rapid MR acquisition techniques were not used. These results indicate that recent advances in MR imaging have greatly improved its sensitivity for the detection and assessment of the extent of metastatic gastrinoma. MR imaging is now the imaging study of choice to assess metastatic pancreatic endocrine tumors in the liver. In contrast, the detection of primary tumors by MR imaging has not improved; therefore, angiography remains the study of choice. C1 NIH,BLDG 10,ROOM 9C-103,BETHESDA,MD 20892. CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. NCI,SURG METAB SECT,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 45 TC 52 Z9 53 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 JUL PY 1993 VL 38 IS 7 BP 1318 EP 1328 DI 10.1007/BF01296084 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LN129 UT WOS:A1993LN12900022 PM 8325191 ER PT J AU XU, C AF XU, C TI CDNA CLONING OF A MOUSE FACTOR THAT ACTIVATES TRANSCRIPTION FROM A METAL RESPONSE ELEMENT OF THE MOUSE METALLOTHIONEIN-I GENE IN YEAST SO DNA AND CELL BIOLOGY LA English DT Article ID REGULATORY ELEMENTS; NUCLEAR FACTOR; DNA-BINDING; MOLECULAR-CLONING; CONTROL SEQUENCES; PROMOTER; INTERACTS; RECEPTOR; IDENTIFICATION; ASSOCIATION AB A cDNA that encodes a mouse factor that activates expression from a metal response element of the mouse metallothionein-I gene has been isolated by complementation cloning in yeast cells. The cDNA encodes a peptide with a maximum length of 99 amino acids that includes a single zinc finger sequence. In yeast cells, the cloned factor induces transcription from the metal response element in a sequence-specific but metal-independent fashion. The cDNA hybridizes to a 550-base mRNA that is constitutively expressed in mouse tissue culture cells. The ability of the mouse factor to activate transcription in yeast cells is dependent upon the carbon source. C1 NCI, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 46 TC 14 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 EI 1557-7430 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUL-AUG PY 1993 VL 12 IS 6 BP 517 EP 525 DI 10.1089/dna.1993.12.517 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA LN776 UT WOS:A1993LN77600007 PM 8329119 ER PT J AU MANI, C GELBOIN, HV PARK, SS PEARCE, R PARKINSON, A KUPFER, D AF MANI, C GELBOIN, HV PARK, SS PEARCE, R PARKINSON, A KUPFER, D TI METABOLISM OF THE ANTIMAMMARY CANCER ANTIESTROGENIC AGENT TAMOXIFEN .1. CYTOCHROME P-450-CATALYZED N-DEMETHYLATION AND 4-HYDROXYLATION SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID RAT-LIVER MICROSOMES; MONOCLONAL-ANTIBODIES; HEPATIC CYTOCHROME-P-450; BREAST-CANCER; ENDOMETRIAL ADENOCARCINOMA; AFFINITY CHROMATOGRAPHY; CHLOROTRIANISENE TACE; PURIFICATION; HYDROXYLATION; IDENTIFICATION AB Previous studies suggested that the therapeutic effect of the antimammary cancer agent tamoxifen might be related to its metabolism. This study examined the cytochrome P-450 enzymes in rat and human liver catalyzing the metabolism of tamoxifen. Incubations of tamoxifen with rat liver microsomes yielded three major polar metabolites identified as the N-oxide, N-desmethyl, and 4-hydroxy derivatives. N-Oxide formation was catalyzed by the flavin-containing monooxygenase (see part II). Carbon monoxide, SKF-525A, metyrapone, and benzylimidazole strongly inhibited N-demethylation and 4-hydroxylation, indicating the participation of P-450 monooxygenase in these reactions. Antibodies to NADPH-P450 reductase inhibited N-demethylation and 4-hydroxylation. Comparison of the metabolism of tamoxifen in untreated male and female rats demonstrated some sexual dimorphism. N-Demethylation was higher in the male rat and 4-hydroxylation was higher in the female. Treatment of rats with phenobarbital (PB), pregnenolone-16alpha-carbonitrile (PCN), and methylcholanthrene ( MC) enhanced N-demethylation, demonstrating the potential participation of multiple P-450s in N-demethylation. Evidence strongly indicates that CYP3A enzyme(s) catalyzes N-demethylation in liver microsomes of PB- and PCN-treated rats (PB and PCN microsomes, respectively): i) N-demethylation was inhibited by cortisol and erythromycin (alternate substrates) and a time-dependent inhibition was observed with troleandomycin (TAO) in vitro; ii) treatment of female rats with TAO, followed by dissociation of the microsomal TAO-P-450 complex, elevated N-demethylation; iii) treatment of PCN-induced female rats with chloramphenicol inhibited N-demethylation; and iv) polyclonal antibodies (PAbs) to CYP3A1 inhibited N-demethylation in PCN- and PB-treated female rats. Although we were unable to reconstitute the N-demethylation activity with purified CYP3A1, which is difficult to reconstitute, collectively the evidence demonstrated that CYP3A enzymes catalyze N-demethylation in PB and PCN microsomes. By contrast, antibodies against CYP2B1/B2 did not inhibit N-demethylation and reconstituted 2B1 did not catalyze N-demethylation of tamoxifen, indicating that 2B1 was not involved. The increase in N-demethylation by MC treatment appears to be due to elevation of CYP1A1/1A2 (P-450c/d). Alternate substrates of CYP1A1/1A2 inhibited N-demethylation and reconstituted rat CYP 1A1-catalyzed N-demethylation. Surprisingly, monoclonal antibodies (MAbs) against CYP1A1/1A2 only partially inhibited, and PAbs against CYP1A1 did not inhibit N-demethylation in MC microsomes, indicating that in MC microsomes, 1A1 does not contribute significantly to that reaction. MAb anti-CYP2C11/2C6 (P-450h/k) inhibited N-demethylation in PB, PCN, and control male rat liver microsomes, suggesting that CYP2C11 and/or CYP2C6 catalyze this reaction to some extent. Human liver microsomes formed tamoxifen metabolites at a much lower rate than rats. Inhibitors of P-450 diminished the formation of N-desmethyl and 4-hydroxy metabolites in human liver microsomes. Cortisol and erythromycin inhibited N-demethylation, but not 4-hydroxylation in human microsomes. Based on these findings, we concluded that tamoxifen N-demethylation is catalyzed in the rat by CYP1A, CYP2C, and CYP3A enzymes and in the human by CYP3A enzyme(s). By contrast, 4-hydroxylation appears to be catalyzed by constitutive P-450s: i) inducers of P-450 did not enhance that reaction; ii) neither alternate substrates of induced P-450s nor antibodies to these P-450s inhibited that reaction; and iii) neither reconstituted CYP2B1 nor CYP1A1 catalyzed 4-hydroxylation. C1 WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,BETHESDA,MD 20892. UNIV KANSAS,MED CTR,DEPT PHARMACOL TOXICOL & THERAPEUT,KANSAS CITY,KS 66103. FU NIEHS NIH HHS [ES00834, ES07079]; NIGMS NIH HHS [GM37044] NR 61 TC 130 Z9 131 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL-AUG PY 1993 VL 21 IS 4 BP 645 EP 656 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LP256 UT WOS:A1993LP25600014 PM 8104124 ER PT J AU ZHANG, H STOWE, EE AHLUWALIA, G BAKER, DC HEBBLER, AK CHISENA, C MUSSER, SM KELLEY, JA PERNO, CF JOHNS, DG COONEY, DA AF ZHANG, H STOWE, EE AHLUWALIA, G BAKER, DC HEBBLER, AK CHISENA, C MUSSER, SM KELLEY, JA PERNO, CF JOHNS, DG COONEY, DA TI CHARACTERIZATION OF 2',3'-DIDEOXYCYTIDINE DIPHOSPHOCHOLINE AND 2',3'-DIDEOXYCYTIDINE DIPHOSPHOETHANOLAMINE - PROMINENT PHOSPHODIESTER METABOLITES OF THE ANTI-HIV NUCLEOSIDE 2',3'-DIDEOXYCYTIDINE SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID IMMUNODEFICIENCY VIRUS INVITRO; 2',3'-DIDEOXYNUCLEOSIDES; INFECTIVITY; COMPOUND AB 2',3'-Dideoxycytidine (ddCyd) is among the most potent of the antihuman immunodeficiency virus (HIV) agents of the dideoxynucleoside class. Its pharmacologically active metabolite 2',3'-dideoxycytidine 5'-triphosphate (ddCTP) is an effective inhibitor of HIV reverse transcriptase and thus of HIV replication. ddCyd differs, however, from other dideoxynucleoside agents such as 3'-azido-3'-deoxythymidine and 2',3'-dideoxyinosine in its capacity to generate phosphodiester metabolites (i.e. ddCDP choline and ddCDP ethanolamine). We have synthesized and characterized these two diesters, and established their identity with the metabolites formed in ddCyd-treated Molt-4 cells. Toward this end, the biologically generated metabolites have been isolated on a preparative scale and compared with the synthetic compounds mass spectroscopically, chromatographically, and enzymatically (i.e. their relative susceptibility to the catabolic enzymes alkaline phosphatase and venom phosphodiesterase). The concentration reached by each of these two phosphodiesters within cells can, under certain conditions, equal or exceed that of ddCTP, and their half-times of disappearance are long, indicating that they may serve as depot forms of ddCyd. The possible role of these phosphodiesters in contributing to the unusual toxicity of ddCyd is discussed. C1 NCI,MED CHEM LAB,375B22,BETHESDA,MD 20892. UNIV TENNESSEE,DEPT CHEM,KNOXVILLE,TN 37996. UNIV ROMA TOR VERGATA,DIPARTIMENTO MED SPERIMENTALE,ROME,ITALY. RI perno, carlo federico/O-1544-2016 NR 16 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL-AUG PY 1993 VL 21 IS 4 BP 738 EP 744 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LP256 UT WOS:A1993LP25600027 ER PT J AU CLIVER, SP GOLDENBERG, RL NEEL, NR TAMURA, T JOHNSTON, KE HOFFMAN, HJ AF CLIVER, SP GOLDENBERG, RL NEEL, NR TAMURA, T JOHNSTON, KE HOFFMAN, HJ TI NEONATAL CORD SERUM ALPHA-2-MACROGLOBULIN AND FETAL SIZE AT BIRTH SO EARLY HUMAN DEVELOPMENT LA English DT Article DE ALPHA-2-MACROGLOBULIN; FETAL GROWTH RESTRICTION; BIRTH WEIGHT ID INFANTS; GROWTH AB Serum concentrations of alpha-2-macroglobulin (alpha2M) were measured in cord blood from neonates born in Alabama, USA and in Guatemala. Results indicate an inverse relationship between cord serum alpha2M concentrations and birth weight of newborns in both locations. Infants with lower birth weight had higher cord serum alpha2M concentrations as compared to those with higher birth weight. The results of the present study using cord serum are similar to those in our previous reports indicating an inverse relationship between maternal serum alpha2M concentrations and birth weight. This distinctive and reproducible association between alpha2M concentrations and fetal size in maternal as well as cord blood samples warrants further investigations to determine the mechanism of this relationship. C1 UNIV ALABAMA,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,PERINATAL EPIDEMIOL UNIT,620 S 20TH ST,BIRMINGHAM,AL 35233. UNIV ALABAMA,SCH PUBL HLTH,DEPT PUBL HLTH SCI,DIV MATERNAL & CHILD HLTH,BIRMINGHAM,AL 35233. UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35233. NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. FU NICHD NIH HHS [N01-HD-4-2811] NR 15 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD JUL PY 1993 VL 33 IS 3 BP 201 EP 206 DI 10.1016/0378-3782(93)90146-L PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA LW949 UT WOS:A1993LW94900005 PM 7693436 ER PT J AU LAW, SK ROHRBAUGH, JW ADAMS, CM ECKARDT, MJ AF LAW, SK ROHRBAUGH, JW ADAMS, CM ECKARDT, MJ TI IMPROVING SPATIAL AND TEMPORAL RESOLUTION IN EVOKED EEG RESPONSES USING SURFACE LAPLACIANS SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EVOKED POTENTIALS; LAPLACIAN DERIVATION; SOURCE LOCALIZATION; TOPOGRAPHIC MAPPING; AUDITORY EVOKED RESPONSE ID EVENT-RELATED POTENTIALS; SCALP CURRENT-DENSITY; INTERPOLATION; ATTENTION; COMPONENT; MODEL; CORTEX; AREAS; WAVE AB Spline generated surface Laplacian temporal wave forms are presented as a method to improve both spatial and temporal resolution of evoked EEG responses. Middle latency and the N1 components of the auditory evoked response were used to compare potential-based methods with surface Laplacian methods in the time domain. Results indicate that surface Laplacians provide better estimates of underlying cortical activity than do potential wave forms. Spatial discrimination among electrode sites was markedly better with surface Laplacian than with potential wave forms. Differences in the number and latencies of peaks, and their topographic distributions, were observed for surface Laplacian, particularly during the time period encompassing the middle latency responses. Focal activities were observed in surface Laplacian wave forms and topographic maps which were in agreement with previous findings from auditory evoked response studies. Methodological issues surrounding the application of spline methods to the time domain are also discussed. Surface Laplacian methods in the time domain appear to provide an improved way for studying evoked EEG responses by increasing temporal and spatial resolution of component characteristics. C1 WASHINGTON UNIV, DEPT PSYCHIAT, ST LOUIS, MO 63130 USA. RP LAW, SK (reprint author), NIAAA, LCS, BRAIN ELECTROPHYSIOL & IMAGING SECT, 10-3C102, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 38 TC 61 Z9 61 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD JUL-AUG PY 1993 VL 88 IS 4 BP 309 EP 322 DI 10.1016/0168-5597(93)90055-T PG 14 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA LR330 UT WOS:A1993LR33000008 PM 7688286 ER PT J AU WHITE, SR REESE, K SATO, S KALER, SG AF WHITE, SR REESE, K SATO, S KALER, SG TI SPECTRUM OF EEG FINDINGS IN MENKES DISEASE SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Note DE MENKES DISEASE; ELECTROENCEPHALOGRAM; PLASMA COPPER ID HAIR SYNDROME; COPPER; TRICHOPOLIODYSTROPHY; THERAPY AB We evaluated electroencephalograms (EEGs) in 10 boys with Menkes disease, ranging in age from 9 days to 27 months. Three of 10 tracings were normal (the newborn, his 27-month-old half-brother with the classic phenotype, and a 27-month-old mildly affected patient). Plasma copper levels were low in all patients except the newborn and tended to be lowest in patients whose EEGs were moderately or severely abnormal. EEG differences in Menkes patients could reflect biochemical and molecular heterogeneity with respect to copper availability and utilization in the brain. C1 NINCDS,OFF CLIN DIRECTOR,EEG SECT,BLDG 10,ROOM 9S242,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 23 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD JUL PY 1993 VL 87 IS 1 BP 57 EP 61 DI 10.1016/0013-4694(93)90175-U PG 5 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA LQ661 UT WOS:A1993LQ66100007 PM 7687955 ER PT J AU WHEELER, D CHRAMBACH, A AF WHEELER, D CHRAMBACH, A TI A 3-DIMENSIONAL PLOT FOR THE DISPLAY OF TRANSVERSE PORE GRADIENT GEL-ELECTROPHORESIS DATA - APPLICATION TO A KINETOPLAST DNA FRAGMENT OF PLANAR CIRCULAR CONFORMATION SO ELECTROPHORESIS LA English DT Article AB A 219 bp fragment of kinetoplast DNA from Crithidia fasciculata has previously been shown to exhibit a gel concentration dependent, anomalously low migration rate in 3-10% polyacrylamide transverse pore gradient gels relative to that of straight standards. The anomaly was interpreted in accordance with previous results of Marini et al. [1] as being due to the planar circular conformation of the fragment. The transverse pore gradient gel pattern is displayed here as a three-dimensional plot of migration distance vs. gel concentration and DNA length for the kinetoplast fragment and straight DNA standards. The plot yields a smooth surface for the standards clearly separated from the curve of the kinetoplast DNA fragment. Thus, transverse gradient gel electrophoresis in conjunction with the three-dimensional plot provides a unique method for the recognition of abnormal conformational features of DNA on the basis of electrophoretic mobility in a pore-size gradient. RP WHEELER, D (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,RM 6C101,BETHESDA,MD 20892, USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUL PY 1993 VL 14 IS 7 BP 570 EP 572 DI 10.1002/elps.1150140190 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LP469 UT WOS:A1993LP46900003 PM 8375346 ER PT J AU WERNER, S WEINBERG, W LIAO, X PETERS, KG BLESSING, M YUSPA, SH WEINER, RL WILLIAMS, LT AF WERNER, S WEINBERG, W LIAO, X PETERS, KG BLESSING, M YUSPA, SH WEINER, RL WILLIAMS, LT TI TARGETED EXPRESSION OF A DOMINANT-NEGATIVE FGF RECEPTOR MUTANT IN THE EPIDERMIS OF TRANSGENIC MICE REVEALS A ROLE OF FGF IN KERATINOCYTE ORGANIZATION AND DIFFERENTIATION SO EMBO JOURNAL LA English DT Article DE DERMIS; EPIDERMIS; FGF; FGF RECEPTOR; KERATIN ID FIBROBLAST GROWTH-FACTOR; GENE-EXPRESSION; MONOSPECIFIC ANTIBODIES; MOLECULAR MARKERS; MOUSE EPIDERMIS; CELLS; CLONING; EPITHELIA; PEPTIDES; FAMILY AB In this study we used a dominant-negative FGF receptor mutant to block FGF function in a specific tissue of transgenic mice. The mutant receptor, which is known to block signal transduction in celts when co-expressed with wild-type receptors, was targeted to suprabasal keratinocytes using a keratin 10 promoter. The transgene was expressed specifically in the skin and highest expression levels were found in the tail. Expression of the mutant receptor disrupted the organization of epidermal keratinocytes, induced epidermal hyperthickening and resulted in an aberrant expression of keratin 6. This suggests that FGF is essential for the morphogenesis of suprabasal keratinocytes and for the establishment of the normal program of keratinocyte differentiation. Our study demonstrates that dominant-negative growth factor receptors can be used to block selectively the action of a growth factor in specific tissues of transgenic mice. C1 UNIV CALIF SAN FRANCISCO,HOWARD HUGHES MED INST,CARDIOVASC RES INST,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT GYNECOL & OBSTET,SAN FRANCISCO,CA 94143. NCI,BETHESDA,MD 20892. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37232. FU NHLBI NIH HHS [HL-43821, R01 HL-32898] NR 46 TC 219 Z9 220 U1 0 U2 2 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 JUL PY 1993 VL 12 IS 7 BP 2635 EP 2643 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LK364 UT WOS:A1993LK36400007 PM 7687538 ER PT J AU REINHARDT, RR CHIN, E ZHANG, B ROTH, RA BONDY, CA AF REINHARDT, RR CHIN, E ZHANG, B ROTH, RA BONDY, CA TI INSULIN RECEPTOR-RELATED RECEPTOR MESSENGER-RIBONUCLEIC-ACID IS FOCALLY EXPRESSED IN SYMPATHETIC AND SENSORY NEURONS AND RENAL DISTAL TUBULE CELLS SO ENDOCRINOLOGY LA English DT Article ID GROWTH FACTOR-I; HYBRID RECEPTORS; IGF-I; GENE; HETEROGENEITY; LIGAND AB The insulin receptor-related receptor (IRR) demonstrates striking structural homology to the insulin receptor (IR) and insulin-like growth factor-I receptor (IGFR), suggesting that IRR is a member of the IR family. However, the endogenous ligand and biological role for this ''orphan'' receptor are unknown. To identify potential sites of action for the IRR, in situ hybridization was employed to reveal cellular patterns of IRR gene expression in the developing and adult rat and in the adult human kidney. From embryonic days 15-20, IRR mRNA is most abundant in sensory neurons of the trigeminal and dorsal root ganglia and, to a lesser extent, neurons of the autonomic system. IRR gene expression diminishes in the majority of sensory neurons postnatally, but remains abundant in a subpopulation of adult rat trigeminal and dorsal root ganglion neurons. IRR mRNA is localized in peripheral autonomic ganglia localized in the adrenal medulla and renal hilum in the adult. From birth to maturity, IRR mRNA is abundant in renal epithelial cells focally localized in the distal tubule in both rat and human kidney. The specificity of this pattern of IRR gene expression was demonstrated by hybridization of serial tissue sections with two different nonoverlapping cRNA probes. Nonspecific signal, as measured by IRR sense probe hybridization, was negligible. This highly restricted pattern of IRR gene expression is in marked contrast to the very widespread pattern of gene expression demonstrated by the IR and IGFR. This study showed that IRR, IR, and IGFR mRNAs were colocalized in some sensory neurons, suggesting the possibility for hybrid receptor formation in these cells. In summary, IRR gene expression is focally localized in sensory and autonomic neurons and renal distal tubule cells. These observations suggest that the IRR, in contrast to the related IR and IGFR, serves a narrow cell-specific role. C1 STANFORD UNIV, DEPT PHARMACOL, STANFORD, CA 94305 USA. RP REINHARDT, RR (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [DK-45652] NR 31 TC 41 Z9 42 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1993 VL 133 IS 1 BP 3 EP 10 DI 10.1210/en.133.1.3 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LK836 UT WOS:A1993LK83600002 PM 8319578 ER PT J AU TINAJERO, JC FABBRI, A DUFAU, ML AF TINAJERO, JC FABBRI, A DUFAU, ML TI SEROTONERGIC INHIBITION OF RAT LEYDIG-CELL FUNCTION BY PROPRANOLOL SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; TESTIS; RECEPTORS; AGENTS AB The beta-adrenergic antagonist propranolol binds to serotonin (5HT) receptors (5HT1B > 5HT1A > 5HT2) in brain membranes. We have recently demonstrated that 5HT acts through 5HT2 receptors in rat Leydig cells to release CRF, which, in turn, inhibits hCG-stimulated cAMP production and steroidogenesis. These observations prompted us to study the effects of propranolol on CRF secretion and cAMP and testosterone production in cultured rat Leydig cells. Treatment with (-)propranolol increased CRF release and inhibited basal and hCG-stimulated cAMP and steroidogenesis, with effects evident at 0.1 muM, an IC50 of 6 muM, and reduction of stimulated levels to near basal at 100 muM. These effects of the drug were prevented by pretreatment of cultures with the 5HT2 receptor antagonist ketanserin or a CRF antagonist or antiserum. Furthermore, propranolol increased the level of 5HT in the incubation medium of cultured Leydig cells. The (+) isomer of propranolol had minor effects on these parameters. Increasing concentrations of (-)propranolol displaced the binding of [I-125]+/-1-[2,5-dimethoxy-4-iodophyryl]-2-amino propane hydrochloride (DOI), a selective 5HT2 ligand, to Leydig cell membranes (IC50, 0.2 muM), and (+)propanolol showed weaker potency. The inhibitory actions of propranolol were exerted through its blockade of the Leydig cell 5HT2 low affinity receptor, which has functional properties of an autoreceptor, with consequent increases in 5HT and stimulation of CRF release through 5HT action at the high affinity site. The serotonergic actions of propranolol were prevented by DOI, an inhibitor of 5HT actions at the high affinity site. In addition, the propranolol-induced blockade of the low affinity site further increased the cAMP and steroidogenic responses to gonadotropin over those observed with DOI treatment alone. These studies demonstrate that propranolol acts as an antagonist at the Leydig cell low affinity 5HT2 receptor and stimulates CRF release via a serotonergic mechanism, with consequent inhibition of cAMP generation and steroidogenesis. This serotonergic action of the drug could contribute to the impairment of sexual function reported during propranolol treatment in man. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,MOLEC ENDOCRINOL SECT,BLDG 49,6A-36,BETHESDA,MD 20892. NR 34 TC 29 Z9 29 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1993 VL 133 IS 1 BP 257 EP 264 DI 10.1210/en.133.1.257 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LK836 UT WOS:A1993LK83600036 PM 8391422 ER PT J AU BARTALENA, L HAMMOND, GL FARSETTI, A FLINK, IL ROBBINS, J AF BARTALENA, L HAMMOND, GL FARSETTI, A FLINK, IL ROBBINS, J TI INTERLEUKIN-6 INHIBITS CORTICOSTEROID-BINDING GLOBULIN SYNTHESIS BY HUMAN HEPATOBLASTOMA-DERIVED (HEP G2) CELLS SO ENDOCRINOLOGY LA English DT Article ID ACUTE-PHASE RESPONSE; CENTRAL NERVOUS-SYSTEM; GENE-EXPRESSION; PROTEIN-SYNTHESIS; SERUM; HORMONE; LIVER; SECRETION; INFECTION; INDUCTION AB Corticosteroid-binding globulin (CBG) belongs to the superfamily of serine proteinase inhibitors which include alpha1-antitrypsin, alpha1-anti-chymotrypsin, and T4-binding globulin. Interleukin-6 (IL-6), the main mediator of the acute phase phenomenon, increases alpha1-antitrypsin and alpha1-antichymotrypsin synthesis and decreases T4-binding globulin synthesis by human hepatoblastoma-derived (Hep G2) cells. This effect is predominantly at a transcriptional level. When Hep G2 cells were exposed to different concentrations of IL-6 for variable time intervals, IL-6 caused a dose- and time-dependent decrease in the amount of [S-35]methionine-labeled CBG immunoprecipitated in the culture medium. This effect could be greatly reduced by preincubation of IL-6 with its neutralizing antibody and reversed by removing the cytokine from the culture medium. The secretion rate of CBG was not affected by cell exposure to IL-6. CBG mRNA steady state levels were reduced; changes in mRNA were quantitatively similar to changes in secreted protein. Nuclear run-off assays failed to show a change in the rate of transcription of the CBG gene. These data indicate that IL-6 diminishes CBG synthesis by Hep G2 cells acting at a posttranscriptional level, presumably through a reduced stability of mRNA. In view of the role of IL-6 in the inflammatory process and other acute phase phenomena, these data suggest that its effects on CBG synthesis might influence the bioavailability of cortisol indirectly and play a role in regulating the homeostatic process during these conditions. C1 NIDDKD, GENET & BIOCHEM BRANCH, ENDOCRINOL SECT, BETHESDA, MD 20892 USA. CNR, IST MED SPERIMENTALE, ROME, ITALY. UNIV WESTERN ONTARIO, MRC, FETAL & NEONATAL HLTH & DEV GRP, LONDON N6A 4L6, ONTARIO, CANADA. UNIV ARIZONA, HLTH SCI CTR, TUCSON, AZ 85724 USA. RP BARTALENA, L (reprint author), UNIV PISA, IST ENDOCRINOL, VIALE TIRRENO 64, I-56018 TIRRENIA, ITALY. NR 43 TC 50 Z9 50 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1993 VL 133 IS 1 BP 291 EP 296 DI 10.1210/en.133.1.291 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LK836 UT WOS:A1993LK83600041 PM 8391424 ER PT J AU YANG, YWH PIOLI, P FIORELLI, G BRANDI, ML RECHLER, MM AF YANG, YWH PIOLI, P FIORELLI, G BRANDI, ML RECHLER, MM TI CYCLIC ADENOSINE-MONOPHOSPHATE STIMULATES INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-4 AND ITS MESSENGER-RIBONUCLEIC-ACID IN A CLONAL ENDOTHELIAL-CELL LINE SO ENDOCRINOLOGY LA English DT Article ID ADULT-RAT SERUM; IGF-I; MOLECULAR-CLONING; CAPILLARY ENDOTHELIUM; CONDITIONED MEDIUM; CARDIAC-MUSCLE; DNA-SYNTHESIS; EXPRESSION; IDENTIFICATION; FIBROBLASTS AB Endothelial cells regulate the passage of insulin-like growth factors (IGFs) or IGFs complexed to IGF-binding proteins (IGFBPs) from plasma to the extravascular space, and in addition respond to plasma and tissue IGFs. The IGFBPs are thought to determine the availability and localization of IGFs to tissues, and to inhibit or potentiate their biological activity. Because of the potential importance of the IGF system in endothelial cell pathophysiology, and because IGFBPs modulate IGF action, we have characterized the IGFBPs synthesized by a clonal endothelial cell line (BPE-1) established from bovine parathyroid microvessels. The only IGFBPs identified by ligand blotting in media conditioned by BPE-1 cells were N-glycosylated 28 kilodalton and non-N-glycosylated 24 kilodalton IGFBP-4 species. Both forms were immunoprecipitated by antibodies to human IGFBP-4. Northern blot hybridization of BPE-1 RNA identified messenger RNAs for IGFBP-4 and IGFBP-6, but not for IGFBP-1, 2, 3, or 5. Agents that increase cAMP including forskolin, (Bu)2cAMP, isobutyl-methylxanthine, and histamine increased IGFBP-4 and IGFBP-4 messenger RNA in BPE-1 cells 2- to 5-fold and 2- to 3-fold, respectively, similar to results previously reported in human osteosarcoma cells and fibroblasts. Increased IGFBP-4 was detected in BPE-1 media 6 h after forskolin addition and was maximal after 24 h. Maximal stimulation (6- to 9-fold) was observed with 1-30 muM forskolin. IGFBP-4 also was the predominant IGFBP synthesized by two other endothelial cell lines, a clonal cell line established from bovine bone microvessels, and a polyclonal cell line established from calf pulmonary artery. Further study is required to determine the role of endothelial cell IGFBP-4 on endothelium and adjacent cells, and on the transport of IGFs from plasma to specific subendothelial sites. C1 UNIV FLORENCE,SCH MED,DEPT CLIN PHYSIOPATHOL,I-50139 FLORENCE,ITALY. RP YANG, YWH (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,ROOM 8D14,BETHESDA,MD 20892, USA. NR 60 TC 26 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1993 VL 133 IS 1 BP 343 EP 351 DI 10.1210/en.133.1.343 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LK836 UT WOS:A1993LK83600049 PM 7686482 ER PT J AU VANECEK, J KLEIN, DC AF VANECEK, J KLEIN, DC TI A SUBPOPULATION OF NEONATAL GONADOTROPIN-RELEASING HORMONE-SENSITIVE PITUITARY-CELLS IS RESPONSIVE TO MELATONIN SO ENDOCRINOLOGY LA English DT Article ID PARS TUBERALIS; BINDING-SITES; K+ CHANNELS; CALCIUM; INHIBITION; CA-2+; RAT; INCREASE AB Melatonin partially inhibits the GnRH-induced elevation of intracellular free Ca2+ ([Ca2+]i) and depolarization of the plasma membrane of neonatal rat GnRH-responsive pituitary cells. This effect is lost during development. In the present study, this line of investigation was extended using single cell analysis. This revealed that melatonin does not alter basal [Ca2+]i in GnRH-responsive cells, but it does inhibit the effect of GnRH on [Ca2+]i in approximately 40% of these cells. Complete inhibition is seen in only approximately 11% of the GnRH-sensitive cells. Analysis of membrane potential also indicated that melatonin hyperpolarizes only a subpopulation of neonatal GnRH-sensitive cells and reverses GnRH-induced depolarization. In the absence of extracellular Ca2+, this effect was greater and more frequently observed. Simultaneous analysis of membrane potential and [Ca2+]i in individual GnRH-treated cells indicated that melatonin altered both parameters in the same cell. This is consistent with the hypothesis that melatonin decreases [Ca2+]i by hyperpolarizing the cell, thereby inhibiting Ca2+ influx through voltage-sensitive channels. The finding that melatonin only acts on a subpopulation of GnRH-responsive cells probably explains why melatonin partially reverse the effects of GnRH in mixed population studies. The existence of a specific melatonin-sensitive population of cells raises the possibilities that the developmental loss of melatonin sensitivity might reflect their selective death or the decreased expression of melatonin receptors in these cells. In addition, it is possible that melatonin-sensitive GnRH-responsive cells might have other remarkable features, such as secretion of a biologically active substance not produced by melatonin-insensitive GnRH-responsive cells. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BLDG 49,ROOM 5A38,BETHESDA,MD 20892. CZECHOSLOVAK ACAD SCI,INST PHYSIOL,PRAGUE 4,CZECHOSLOVAKIA. NR 27 TC 30 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1993 VL 133 IS 1 BP 360 EP 367 DI 10.1210/en.133.1.360 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LK836 UT WOS:A1993LK83600051 PM 8319582 ER PT J AU VONDERHAAR, BK AF VONDERHAAR, BK TI LOCAL-EFFECTS OF CHOLESTEROL CARRIER SYSTEM ON BINDING OF LACTOGENS AND EPIDERMAL GROWTH-FACTOR TO THE DEVELOPING MAMMARY-GLAND SO ENDOCRINOLOGY LA English DT Note ID ATHYMIC MICE; NUDE-MICE; MOUSE; MEMBRANES; RECEPTOR; ESTROGEN AB Cholesterol pellets inserted directly into mammary glands of 4- and 10-week-old mice resulted in lactogens, such as human growth hormone and prolactin, and epidermal growth factor. The effects of choleste the binding of lactogens and epidermal growth factor to the livers of these same animals was unaffected. Pelle the interscapular region had no effect on binding of either ligand to mammary glands or livers. RP VONDERHAAR, BK (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 5B56,BETHESDA,MD 20892, USA. NR 18 TC 1 Z9 1 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1993 VL 133 IS 1 BP 427 EP 429 DI 10.1210/en.133.1.427 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LK836 UT WOS:A1993LK83600060 PM 8319590 ER PT J AU NEGROVILAR, A AF NEGROVILAR, A TI STRESS AND OTHER ENVIRONMENTAL-FACTORS AFFECTING FERTILITY IN MEN AND WOMEN - OVERVIEW SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON THE IMPACT OF THE ENVIRONMENT ON REPRODUCTIVE HEALTH CY SEP 30-OCT 04, 1991 CL COPENHAGEN, DENMARK SP WHO, DANISH MINIST ENVIRONM, DANISH MINIST HLTH, COMMISS EUROPEAN COMMUNITIES, DANISH MED RES COUNCIL, INT PROGRAMME CHEM SAFETY, NIEHS ID CORTICOTROPIN-RELEASING FACTOR; LUTEINIZING-HORMONE; HYPOTHALAMIC AMENORRHEA; GONADOTROPIN-SECRETION; CORTISOL SECRETION; BETA-ENDORPHIN; MACACA-MULATTA; RHESUS-MONKEY; PEPTIDES; TESTOSTERONE AB To understand how environmental factors contribute to fertility or infertility in humans, it is first necessary to define environment. A view that will guide this review is that environment represents the ''external milieu,'' analogous to the well-defined concept of ''internal milieu'' first introduced by Claude Bernard. Within this context, the environment provides both positive and adverse influences on reproductive health and development. Environmental factors can then be classified into categories such as physical, chemical, biological, behavioral, and socioeconomic. In many circumstances, multiple environmental factors may contribute to adversely modify human health. It has been suspected and in some cases demonstrated that stress can adversely affect reproductive function. Both animal and human data support this contention; however, the human data are clear in extreme situations (e.g, inmates of concentration camps) but less so under less drastic conditions. In recent years many advances have been made concerning the neurochemical mechanisms that mediate the effects of stress on reproductive functions and on the identification of ''stress hormones'' that may not only be involved in the stress response but also serve as biochemical markers to identify and correlate stress with different fertility parameters. Nutrition also plays an important role in infertility, and undernutrition or nutrition disorders are associated with stress in infertility. Environmental factors are often invoked as contributing to many cases of unexplained infertility. However, the direct causal relationship between those factors and the ensuing infertility of the couple are seldom well established and remain largely anecdotal. Several problems contribute to this state of affairs: a) the multifactorial nature of the contributing factors; b) the poor design of many of the studies; c) the diversity of parameters evaluated and whether they measure outcome (i.e, pregnancy rates) or intermediate events (semen values, ovulation, etc.); and d) the difficulty in monitoring exposure in terms of time and degree of intensity. Until unified criteria are applied consistently and systematically to evaluate environmental influences on human reproductive health, many cases of infertility will remain unexplained. RP NEGROVILAR, A (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 37 TC 51 Z9 53 U1 1 U2 8 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 59 EP 64 DI 10.2307/3431377 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400010 PM 8243408 ER PT J AU MICHAL, F GRIGOR, KM NEGROVILAR, A SKAKKEBAEK, NE AF MICHAL, F GRIGOR, KM NEGROVILAR, A SKAKKEBAEK, NE TI IMPACT OF THE ENVIRONMENT ON REPRODUCTIVE HEALTH - EXECUTIVE SUMMARY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON THE IMPACT OF THE ENVIRONMENT ON REPRODUCTIVE HEALTH CY SEP 30-OCT 04, 1991 CL COPENHAGEN, DENMARK SP WHO, DANISH MINIST ENVIRONM, DANISH MINIST HLTH, COMMISS EUROPEAN COMMUNITIES, DANISH MED RES COUNCIL, INT PROGRAMME CHEM SAFETY, NIEHS AB The papers presented at the workshop on the ''Impact of the Environment on Reproductive Health'' are published in this issue of the EHP Supplements. After the formal presentation of the papers, the authors and scientists met to discuss the important aspects of environmental issues affecting human reproductive health. This Executive Summary was compiled by the organizers and editors of the workshop and the proceedings. C1 UNIV EDINBURGH,DEPT PATHOL,EDINBURGH EH8 9YL,MIDLOTHIAN,SCOTLAND. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. UNIV COPENHAGEN,RIGSHOSP,DEPT GROWTH & REPROD,DK-2100 COPENHAGEN,DENMARK. RP MICHAL, F (reprint author), WHO,SPECIAL PROGRAMME RES DEV & RES TRAINING HUMAN REPROD,CH-1211 GENEVA 27,SWITZERLAND. NR 0 TC 13 Z9 14 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 159 EP 167 DI 10.2307/3431390 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400023 PM 8243387 ER PT J AU MARCUS, M SILBERGELD, E MATTISON, D BELLVE, A CHAPIN, R DAVIS, DL ESKENAZI, B FRIEDLER, G KAVLOCK, R LEMASTERS, G LEVINE, R MCDIARMID, M SASSAMAN, A SCHNATTER, AR SCHNORR, T SCHRADER, S SULLIVAN, P AF MARCUS, M SILBERGELD, E MATTISON, D BELLVE, A CHAPIN, R DAVIS, DL ESKENAZI, B FRIEDLER, G KAVLOCK, R LEMASTERS, G LEVINE, R MCDIARMID, M SASSAMAN, A SCHNATTER, AR SCHNORR, T SCHRADER, S SULLIVAN, P TI A REPRODUCTIVE HAZARDS RESEARCH AGENDA FOR THE 1990S SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT INTERNATIONAL WORKSHOP ON THE IMPACT OF THE ENVIRONMENT ON REPRODUCTIVE HEALTH CY SEP 30-OCT 04, 1991 CL COPENHAGEN, DENMARK SP WHO, DANISH MINIST ENVIRONM, DANISH MINIST HLTH, COMMISS EUROPEAN COMMUNITIES, DANISH MED RES COUNCIL, INT PROGRAMME CHEM SAFETY, NIEHS ID CRITERIA; TOXICITY AB There is substantial scientific and public concern about the potential effects of occupational and environmental toxicants on reproductive health. These effects include impaired functioning of the reproductive systems of men and women as well as a broad spectrum of developmental problems expressed in offspring. Research on reproduction and development is among the most complex undertakings in biomedical research. This complexity is due in part to the intricate biology of reproduction, the multiple targets involved (male, female, and offspring), the uncertainties in extrapolating from animal models to humans, and the problems involved in accurately characterizing exposures and outcomes in epidemiologic investigations. However, given the relatively brief history of research into toxicant-induced reproductive health effects, we have made enormous strides in our knowledge over the past decade. In particular, recent advances in reproductive biology and biotechnology and in the development of biological markers of exposure, effect, and susceptibility are greatly enhancing our ability to study cause-effect relationships. In this paper, the Research Needs Working Group proposes ways to apply existing knowledge to better protect reproductive health and suggests directions for future research. Fulfilling this challenging agenda will require responsible cooperation by labor, industry, government, individual citizens, and the scientific community. Further research and collaboration are essential to both prevent adverse reproductive and developmental outcomes and to formulate a sound scientific basis for policy making. C1 CUNY MT SINAI SCH MED,DEPT COMMUNITY MED,DIV ENVIRONM & OCCUPAT MED,NEW YORK,NY 10029. UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. UNIV PITTSBURGH,GRAD SCH PUBL HLTH,PITTSBURGH,PA 15261. COLUMBIA UNIV,NEW YORK,NY 10027. NIEHS,RES TRIANGLE PK,NC 27709. NATL ACAD SCI,WASHINGTON,DC 20418. UNIV CALIF BERKELEY,BERKELEY,CA 94720. RADCLIFFE COLL,CAMBRIDGE,MA. US EPA,RES TRIANGLE PK,NC 27711. UNIV CINCINNATI,CINCINNATI,OH 45221. NICHHD,BETHESDA,MD 20892. OCCUPAT SAFETY & HLTH ADM,WASHINGTON,DC. NIES,RES TRIANGLE PK,NC. EXXON BIOMED SCI INC,E MILLSTONE,NJ. NIOSH,CINCINNATI,OH 45226. UNIV MASSACHUSETTS LOWELL,LOWELL,MA. RI Mattison, Donald/C-2015-2009; Schrader, Steven/E-8120-2011; OI Mattison, Donald/0000-0001-5623-0874; Chapin, Robert/0000-0002-5997-1261 NR 16 TC 7 Z9 7 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 175 EP 180 DI 10.2307/3431392 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400025 PM 8243388 ER PT J AU TENNANT, RW AF TENNANT, RW TI TRANSFORMATION OF BALB/C-3T3 CELLS - INTRODUCTION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article RP TENNANT, RW (reprint author), NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 275 EP 276 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400033 ER PT J AU MATTHEWS, EJ SPALDING, JW TENNANT, RW AF MATTHEWS, EJ SPALDING, JW TENNANT, RW TI TRANSFORMATION OF BALB/C-3T3 CELLS .4. RANK-ORDERED POTENCY OF 24 CHEMICAL RESPONSES DETECTED IN A SENSITIVE NEW ASSAY PROCEDURE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID EMBRYO CELLS; CARCINOGENICITY; MUTAGENICITY; SALMONELLA; BALB/3T3; RODENTS; PROGRAM AB This report introduces an improved method of detecting chemical-induced morphological transformation of A-31-1-13 BALB/c-3T3 cells. The new procedure uses an increased target cell population to assess chemical-induced damage by increasing the initial seeding density and by delaying the initiation time of chemical treatment. Furthermore, a newly developed co-culture clonal survival assay was used to select chemical doses for the transformation assay. This assay measured the relative cloning efficiency (RCE) of chemical treatments in high-density cell cultures. In addition, transformation assay sensitivity was enhanced through the use of improved methods to solubilize many chemicals. From a group of 24 chemicals tested in at least two trials, clear evidence of chemical-induced transformation was detected for 12 chemicals (aphidicolin, barium chloride-2H2O, 5-bromo-2'-deoxyuridine, C.I. direct blue 15, trans-cinnamaldehyde, cytosine arabinoside, diphenylnitrosamine, manganese sulfate-H2O, 2-mereaptobenzimidazole, mezerein, riddelliine, and 2,6-xylidine); 2 chemicals had equivocal activity [C.I. direct blue 218 and mono(2-ethylhexyl)phthalatel, 9 chemicals were inactive [carisoprodol, chloramphenicol sodium succinate, 4-chloro-2-nitroaniline, C.I. acid red 114, isobutyraldehyde, mono(2-ethylhexyl)adipate, sodium fluoride, and 12-O-tetradecanoylphorbol-13-acetate), and 1 chemical had an indeterminate response (2,6-dinitrotoluene). All positive responses were detected in the absence of an exogenous activation system and exhibited significant activity at two or more consecutive doses. This report also presents a mathematical method that uses t-statistics for rank-ordering the potency of chemical-induced transformation responses. This model detects sensitivity differences in experiments used to evaluate chemical-induced transformation. Furthermore, it provides a method to estimate a chemical's transformation response in terms of the historical behavior of the assay, as well as its future activity. The most active of the 24 chemicals was mezerein, and the least active chemical was diphenylnitrosamine. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NIEHS NIH HHS [N01-ES-65150] NR 29 TC 22 Z9 22 U1 1 U2 4 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 319 EP 345 DI 10.2307/3431404 PG 27 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400037 PM 8243401 ER PT J AU MATTHEWS, EJ SPALDING, JW TENNANT, RW AF MATTHEWS, EJ SPALDING, JW TENNANT, RW TI TRANSFORMATION OF BALB/C-3T3 CELLS .5. TRANSFORMATION RESPONSES OF 168 CHEMICALS COMPARED WITH MUTAGENICITY IN SALMONELLA AND CARCINOGENICITY IN RODENT BIOASSAYS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID EMBRYO CELLS; TOXICITY; BALB/3T3; PROGRAM; SYSTEM; ASSAY AB This report describes the activities of 168 chemicals tested in a standard transformation assay using A-31-1-13 BALB/c-3T3 cells. The data set includes 84 carcinogens, 77 noncarcinogens, and 7 research chemicals. Carcinogens included 49 mutagens and 35 nonmutagens; noncarcinogens included 24 mutagens and 53 nonmutagens. The transformation assay did not use an exogenous activation system, thus, all chemical responses depended on the inherent target cell metabolic capacity where metabolic activation was required. The upper dose limit was 100 milli-osmolar because the assay could not discriminate active and inactive chemicals tested above this concentration. Certain physicochemical properties resulted in technical problems that affected chemical biological activity. For example, chemicals that reacted with plastic were usually nonmutagenic carcinogens. Similarly, chemicals that were insoluble in medium, or bound metals, were usually nonmutagenic and nontransforming. Multifactorial data analyses revealed that the transformation assay discriminated between nonmutagenic carcinogens and noncarcinogens; it detected 64% of the carcinogens and only 26% of the noncarcinogens. In contrast, the transformation assay detected most mutagenic chemicals, including 94% of the mutagenic carcinogens and 70% of the mutagenic noncarcinogens. Thus, transformation or Salmonella typuimurium mutagenicity assays could not discriminate mutagenic carcinogens from mutagenic noncarcinogens. Data analyses also revealed that mutagenic chemicals were more cytotoxic than nonmutagenic chemicals; 88% of the mutagens had an LD50 < 5 mM, whereas half of the nonmutagens had an LD50 > 5 mM. Binary data analyses of the same data set revealed that the transformation assay and rodent bioassay had a concordance of 71%, a sensitivity for carcinogens of 80.0%, and a specificity for detecting noncarcinogens of 60%. In contrast, Salmonella mutagenicity assays and rodent bioassays had a concordance of 63%, a sensitivity of 58%, and a specificity of 69%. The transformation assay complemented the Salmonella mutagenesis assay in the identification of nonmutagenic carcinogens; thus, the two assays had a combined 83% sensitivity for all carcinogens and a 75% specificity for nonmutagenic noncarcinogens. C1 NIEHS,POB 12233,RES TRIANGLE PK,NC 27709. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. FU NIEHS NIH HHS [N01-ES-65150] NR 26 TC 75 Z9 77 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 1993 VL 101 SU 2 BP 347 EP 482 DI 10.2307/3431405 PG 136 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA LY574 UT WOS:A1993LY57400038 PM 8243403 ER PT J AU WEINBERG, C AF WEINBERG, C TI MEASURES OF EFFECT BASED ON THE SUFFICIENT CAUSES MODEL SO EPIDEMIOLOGY LA English DT Letter RP WEINBERG, C (reprint author), NIEHS,DEPT HLTH & HUMAN SERV,MD A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 1993 VL 4 IS 4 BP 386 EP 386 DI 10.1097/00001648-199307000-00018 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LK829 UT WOS:A1993LK82900018 PM 8347753 ER PT J AU RAPAPORT, MH TORREY, EF MCALLISTER, CG NELSON, DL PICKAR, D PAUL, SM AF RAPAPORT, MH TORREY, EF MCALLISTER, CG NELSON, DL PICKAR, D PAUL, SM TI INCREASED SERUM-SOLUBLE INTERLEUKIN-2 RECEPTORS IN SCHIZOPHRENIC MONOZYGOTIC TWINS SO EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE LA English DT Article DE IMMUNOLOGY; SCHIZOPHRENIA; TWINS; SOLUBLE INTERLEUKIN-2 RECEPTORS ID LYMPHOCYTE SUBSETS; DISCORDANT AB There is a confusing history of immune findings associated with schizophrenia. At least some of these discrepant results may be artifacts caused by heterogeneity. In an attempt to decrease heterogeneity, we studied three groups of monozygotic twins who were either discordant for schizophrenia, concordant and ill, or concordant and well. This comparison minimizes environmental and genetic variance, and heightens differences that are actually due to the disorder. Overall, schizophrenic subjects had higher levels of serum soluble interleukin-2 receptors (SIL-2Rs) than unaffected individuals (480.8, SD 238.6 U/ml vs 380.9, SD 170.6 U/ml; F = 5.256, df = 1.61, P = 0.02). When data from discordant and concordant twin groups were analysed separately, both the discordant ill twins (P = 0.06) and concordant ill twin pairs (P = 0.08) showed trends towards higher serum SIL-2R levels than their respective control groups. These data contribute to the growing body of evidence that immune activation is associated with some forms of schizophrenia. C1 SAN DIEGO VET AFFAIRS MED CTR,PSYCHIAT SERV,SAN DIEGO,CA. ST ELIZABETH HOSP,NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA 15260. NCI,METAB BRANCH,BETHESDA,MD 20892. NIMH,DIV INTRAMURAL RES,BETHESDA,MD 20892. NIMH,CLIN THERAPEUT BRANCH,BETHESDA,MD 20892. RP RAPAPORT, MH (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT,9500 GILMAN DR,LA JOLLA,CA 92093, USA. NR 28 TC 52 Z9 53 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-1334 J9 EUR ARCH PSY CLIN N JI Eur. Arch. Psych. Clin. Neurosci. PD JUL PY 1993 VL 243 IS 1 BP 7 EP 10 DI 10.1007/BF02191517 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LP916 UT WOS:A1993LP91600002 PM 8399412 ER PT J AU BLAGOSKLONNY, MV NECKERS, LM AF BLAGOSKLONNY, MV NECKERS, LM TI SENSITIVE AND SIMPLE BIOASSAY FOR HUMAN TUMOR-NECROSIS-FACTOR-ALPHA SO EUROPEAN CYTOKINE NETWORK LA English DT Article DE TNF-ALPHA; BIOASSAY; U937 CELLS ID INVITRO BIOASSAY; CELLS; EXPRESSION; ASSAYS; ELISA; TNF AB A simple, sensitive, and specific in vitro bioassay is described for human tumour necrosis factor alpha (TNF-alpha). The system employs the U937 cell line incubated with 10 ng/ml actinomycin D for maximum sensitivity. This method allows the detection of less than 0.6 pg/ml of TNF-alpha and the log dose-response curve is linear at concentrations 0.6-250 pg/ml TNF-alpha. Highly sensitive subclones of U937 were obtained which were capable of detecting as little as 0.1 pg/ml TNF-alpha. Finally, this bioassay demonstrates specificity by discriminating between TNF-alpha and TNF-beta. RP BLAGOSKLONNY, MV (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 19 TC 1 Z9 1 U1 1 U2 1 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 1148-5493 J9 EUR CYTOKINE NETW JI Eur. Cytokine Netw. PD JUL-AUG PY 1993 VL 4 IS 4 BP 279 EP 283 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA MB455 UT WOS:A1993MB45500005 PM 8268418 ER PT J AU YAKOVLEV, GI MOISEYEV, GP STRUMINSKAYA, NK ROMAKHINA, ER LESHCHINSKAYA, IB HARTLEY, RW AF YAKOVLEV, GI MOISEYEV, GP STRUMINSKAYA, NK ROMAKHINA, ER LESHCHINSKAYA, IB HARTLEY, RW TI INCREASE OF SPECIFICITY OF RNASE FROM BACILLUS-AMYLOLIQUEFACIENS (BARNASE) BY SUBSTITUTION OF GLU FOR SER57 USING SITE-DIRECTED MUTAGENESIS SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID AMINO-ACID SEQUENCE; MICROBIAL RIBONUCLEASES; INTERMEDIUS 7P AB Bacterial ribonucleases from Bacillus amyloliquefaciens and Bacillus intermedius show the specificity towards the nature of a nucleoside at the 03' end of the phoshodiester bond to be split in the preference order G > A much greater than U > C in the cleavage reactions of polynucleotides. It follows from the X-ray data that the substrate guanosine base is bound at the active site of these RNases in the same manner as for high-specificity guanylic RNases. We supposed that the difference in specificity for the two types of RNases is due to the additional hydrogen bond between the protein and a purine base in the case of bacterial guanyl-preferring RNases in contrast to the high-specificity guanylic RNases. To examine this hypothesis we prepared the Ser57 --> 4Glu mutant of B. amyloliquefaciens, in which this hydrogen bond is eliminated. Kinetic studies demonstrate that the specificity of this mutant towards guanylic substrates is 35-times greater than that of the wild-type RNases from B. amyloliquefaciens and close to that of RNases T1. C1 KAZAN VI LENIN STATE UNIV,DEPT BIOL,KAZAN,RUSSIA. NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD. RP YAKOVLEV, GI (reprint author), VA ENGELHARDT MOLEC BIOL INST,MOSCOW,RUSSIA. NR 24 TC 6 Z9 6 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUL 1 PY 1993 VL 215 IS 1 BP 167 EP 170 DI 10.1111/j.1432-1033.1993.tb18019.x PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LM144 UT WOS:A1993LM14400020 PM 8344276 ER PT J AU BOEHME, SA LENARDO, MJ AF BOEHME, SA LENARDO, MJ TI PROPRIOCIDAL APOPTOSIS OF MATURE T-LYMPHOCYTES OCCURS AT S-PHASE OF THE CELL-CYCLE SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE APOPTOSIS; CELL CYCLE; MATURE T-LYMPHOCYTES; PROPRIOCIDAL REGULATION ID CD3/T-CELL RECEPTOR COMPLEX; DNA FRAGMENTATION; MONOCLONAL-ANTIBODY; IMMATURE THYMOCYTES; CLONAL ELIMINATION; ENTEROTOXIN-B; GENE-PRODUCT; DEATH; ACTIVATION; PROGRESSION AB We found that mature nontransformed CD4+ and CD8+ T lymphocytes could be made susceptible to T cell receptor(TcR)-mediated apoptosis by pretreatment with interleukin-4 (IL-4) or interleukin-2 (IL-2). The degree of susceptibility to death could be correlated with the level of cell cycling as measured by thymidine incorporation, cell doubling times, or the number of cells incorporating bromodeoxyuridine during S phase. However, using pharmacologic cell cycle blocking agents,we found that progression through the cell cycle was not required for cell death. Rather, we found that cells must be in a certain phase of the cell cycle to be susceptible to TcR-mediated death. Cells blocked in G1 phase were resistant to T cell receptor-induced apoptosis, whereas cells blocked in S phase were susceptible. These observations suggest that an important feature of growth lymphokines is their ability to drive T cells into portions of the cell cycle where they are sensitive to antigen receptor-induced apoptosis. Furthermore, these results provide additional evidence that the T cell growth lymphokines IL-2 and IL-4 may participate in the down-regulation of T cell responses by apoptosis - a pathway we have termed ''propriocidal regulation''. C1 NIAID,IMMUNOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 11N311,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. NR 59 TC 244 Z9 246 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1993 VL 23 IS 7 BP 1552 EP 1560 DI 10.1002/eji.1830230724 PG 9 WC Immunology SC Immunology GA LM708 UT WOS:A1993LM70800023 PM 8325332 ER PT J AU ZIEGLER, SF RAMSDELL, F HJERRILD, KA ARMITAGE, RJ GRABSTEIN, KH HENNEN, KB FARRAH, T FANSLOW, WC SHEVACH, EM ALDERSON, MR AF ZIEGLER, SF RAMSDELL, F HJERRILD, KA ARMITAGE, RJ GRABSTEIN, KH HENNEN, KB FARRAH, T FANSLOW, WC SHEVACH, EM ALDERSON, MR TI MOLECULAR CHARACTERIZATION OF THE EARLY ACTIVATION ANTIGEN CD69 - A TYPE-II MEMBRANE GLYCOPROTEIN RELATED TO A FAMILY OF NATURAL-KILLER-CELL ACTIVATION ANTIGENS SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE NATURAL KILLER CELLS; ACTIVATION ANTIGEN ID LYMPHOCYTES-T; B-CELL; PLATELET ACTIVATION; EXPRESSION; RECEPTOR; PROTEIN; LEU-23; SURFACE; LIGAND; EA-1 AB CD69 is a disulfide-linked homo-dimer expressed on the surface of activated T cells, B cells, natural killer cells, neutrophils and platelets. Antibody cross-linking of CD69 in the presence of phorbol ester results in cellular activation events including proliferation and the induction of specific genes. Using an expression cloning strategy we have isolated cDNA encoding human CD69 from a CD4+ T cell clone. Transfection of the cDNA clone in CV-1/EBNA cells results in the expression of a covalently linked homodimer. The cDNA insert hybridizes to a 1.7-kb mRNA in phorbol 12-myristate 13-acetate- or phytohemoagglutinin-stimulated human T cells. Using the human clone we have isolated cDNA encoding mouse CD69, which, when expressed in human T cells allowed those cells to respond to anti-mouse CD69 antibodies by secreting interleukin-2 and interferon-gamma. Sequence analysis showed that both mouse and human CD69 are type II membrane glycoproteins related to the NKR-P1 and Ly-49 families of natural killer cell activation molecules. C1 IMMUNEX CORP,DEPT PROT CHEM & IMMUNOL,SEATTLE,WA 98101. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP ZIEGLER, SF (reprint author), IMMUNEX CORP,DEPT MOLEC GENET,51 UNIV ST,SEATTLE,WA 98101, USA. NR 35 TC 109 Z9 111 U1 0 U2 5 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1993 VL 23 IS 7 BP 1643 EP 1648 DI 10.1002/eji.1830230737 PG 6 WC Immunology SC Immunology GA LM708 UT WOS:A1993LM70800036 PM 8100776 ER PT J AU GAFFAN, D MURRAY, EA FABRETHORPE, M AF GAFFAN, D MURRAY, EA FABRETHORPE, M TI INTERACTION OF THE AMYGDALA WITH THE FRONTAL-LOBE IN REWARD MEMORY SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE CYNOMOLGUS; MACAQUE; VISUAL LEARNING; VENTRAL STRIATUM; VENTROMEDIAL PREFRONTAL CORTEX; MEDIODORSAL NUCLEUS OF THE THALAMUS ID MONKEYS; CORTEX; DISCONNECTION; ORGANIZATION; PROJECTIONS; NUCLEUS AB Five cynomolgus monkeys (Macaca fascicularis) were assessed for their ability to associate visual stimuli with food reward. They learned a series of new two-choice visual discriminations between coloured patterns displayed on a touch-sensitive monitor screen; the feedback for correct choice was delivery of food. Normal learning in this task is known to be dependent on the amygdala. The monkeys received brain lesions which were designed to disconnect the amygdala from interaction with other brain structures thought to be involved in this memory task. All the monkeys received an amygdalectomy in one hemisphere and lesions in the other hemisphere of some of the projection targets of the amygdala, namely the ventral striatum, the mediodorsal thalamus and the ventromedial prefrontal cortex. The rate of learning new problems was assessed before and after each operation. Disconnection of the amygdala from the ventral striatum was without effect on learning rate. An earlier study had shown that disconnection of the amygdala from either the mediodorsal thalamus or the ventromedial prefrontal cortex produced only a mild impairment, significantly less severe than that produced by bilateral lesions of any of these three structures. The present results show, however, that disconnection of the amygdala from both the mediodorsal thalamus and the ventromedial prefrontal cortex in the same animal, by crossed unilateral lesions of the amygdala in one hemisphere and of both the mediodorsal thalamus and the ventromedial prefrontal cortex in the other hemisphere, produces an impairment as severe as that which follows bilateral lesions of any of these three structures. These results show that, in stimulus - reward associative memory, the role of the amygdala is entirely dependent on its interaction with the frontal lobe, either by direct projections or by indirect subcortical pathways including the mediodorsal nucleus of the thalamus; and that there are at least two partially independent pathways by which the amygdala can influence the frontal lobe. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. UPMC,CNRS,DEPT NEUROSCI VISION ACT,F-75005 PARIS,FRANCE. RP GAFFAN, D (reprint author), UNIV OXFORD,DEPT EXPTL PSYCHOL,S PARKS RD,OXFORD OX1 3UD,ENGLAND. RI Fabre-Thorpe, Michele/B-2698-2008; OI Murray, Elisabeth/0000-0003-1450-1642 NR 17 TC 100 Z9 100 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUL 1 PY 1993 VL 5 IS 7 BP 968 EP 975 DI 10.1111/j.1460-9568.1993.tb00948.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA LM143 UT WOS:A1993LM14300020 PM 8281307 ER PT J AU ZONDERMAN, AB SIEGLER, IC BAREFOOT, JC WILLIAMS, RB COSTA, PT AF ZONDERMAN, AB SIEGLER, IC BAREFOOT, JC WILLIAMS, RB COSTA, PT TI AGE AND GENDER DIFFERENCES IN THE CONTENT SCALES OF THE MINNESOTA MULTIPHASIC PERSONALITY-INVENTORY SO EXPERIMENTAL AGING RESEARCH LA English DT Article ID 5-FACTOR MODEL; MMPI; ADULTHOOD; STABILITY; RATINGS AB We examined time of measurement, gender, and age differences on the nine content scales of the Minnesota Multiphasic Personality Inventory using data collected by three separate studies during the 1950s, 1960s and 1980s. No evidence was found for differences in the content scales due to time of measurement that also could not have been explained by demographic differences. Differences due to gender were found on only one of the nine scales, Masculinity-Femininity, and age differences were found on the Neuroticism, Extraversion, and Agreeableness scales. Younger men and women had significantly higher scores on the Neuroticism and Extraversion scales, and these differences were consistent in both magnitude and direction across sample and gender. Our results suggest that it is likely that openness reaches its lifetime stable level by the time typical adolescents enter college, because we found no significant age differences in intellectual interests. Neuroticism, extraversion, and agreeableness on the other hand, are likely to show instability throughout, and probably after, adolescence and early adulthood, because we found significant age differences in the content dimensions associated with these factors in separate analyses of three samples. C1 DUKE UNIV,BEHAV MED RES CTR,DURHAM,NC 27706. RP ZONDERMAN, AB (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712; Zonderman, Alan B/0000-0002-6523-4778 FU NIA NIH HHS [AG-09276] NR 24 TC 6 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD JUL-SEP PY 1993 VL 19 IS 3 BP 241 EP 257 DI 10.1080/03610739308253936 PG 17 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA LX513 UT WOS:A1993LX51300005 PM 8223825 ER PT J AU BOUSSAOUD, D WISE, SP AF BOUSSAOUD, D WISE, SP TI PRIMATE FRONTAL-CORTEX - NEURONAL-ACTIVITY FOLLOWING ATTENTIONAL VERSUS INTENTIONAL CUES SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE PREMOTOR CORTEX; ATTENTION; VISUALLY GUIDED MOVEMENT; PREFRONTAL CORTEX; MONKEY ID PREFRONTAL UNIT-ACTIVITY; DELAYED-RESPONSE PERFORMANCE; GO/NO-GO DISCRIMINATION; VISUALLY GUIDED ARM; PREMOTOR CORTEX; RHESUS-MONKEY; MACAQUE MONKEY; INFERIOR AREA-6; HAND MOVEMENTS; EYE-MOVEMENTS AB We examined neuronal activity in three parts of the primate frontal cortex: the dorsal (PMd) and ventral (PMv) premotor cortex and a ventrolateral part of the dorsolateral prefrontal (PF) cortex. Two monkeys fixated a 0.2-degrees white square in the center of a video display while depressing a switch located between two touch pads. On each trial, a spatial-attentional/mnemonic (SAM) cue was presented first. The SAM cue consisted of one 2-degrees x 2-degrees square, usually red or green, and its location indicated where a conditional motor instruction would appear after a delay period. The stimulus event containing the motor instruction, termed the motor instructional/conditional (MIC) cue, could be of two general types. It might consist of a single 2-degrees x 2-degrees square stimulus identical to one of the SAM cues presented at the same location as the SAM cue on that trial. When the MIC cue was a single square, it instructed the monkey to move its forelimb to one of the two touch pads according to the following conditional rule: a green MIC cue meant that contact with the right touch pad would be rewarded on that trial and a red MIC cue instructed a movement to the left touch pad. Alternatively, the MIC cue might consist of two 2-degrees x 2-degrees squares, only one of which was at the SAM-cue location: in those cases, one square was red and the other was green. The colored square at the SAM cue location for that trial was the instructing stimulus, and the other part of the MIC cue was irrelevant. When, after a variable delay period, the MIC cue disappeared, the monkey had to touch the appropriate target within 1 s to receive a reward and could break visual fixation. The experimental design allowed comparison of frontal cortical activity when one stimulus, identical in retinocentric, craniocentric, and allocentric spatial location as well as all other stimulus parameters, had two different meanings for the animal's behavior. When a stimulus was the SAM cue, it led to either a reorientation of spatial attention to its location, or the storage of its location in spatial memory. By contrast, when it was the MIC cue, the same stimulus instructed a motor act to be executed after a delay period. For the majority of PMd neurons (55%), post-MIC cue activity exceeded post-SAM cue activity. In many instances, no activity followed the SAM cue, although the identical stimulus caused profound modulation when it served as the MIC cue. In PF, by contrast, significantly fewer cells (30%) showed such a property, and PMv was intermediate in this respect (36%). The results support the hypothesis that many PMd cells reflect the motor significance of stimuli, and that a significantly smaller proportion of cells in PF do so. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. RI Boussaoud, Driss/B-6932-2008 NR 52 TC 140 Z9 141 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 1993 VL 95 IS 1 BP 15 EP 27 PG 13 WC Neurosciences SC Neurosciences & Neurology GA LP915 UT WOS:A1993LP91500003 PM 8405247 ER PT J AU BOUSSAOUD, D WISE, SP AF BOUSSAOUD, D WISE, SP TI PRIMATE FRONTAL-CORTEX - EFFECTS OF STIMULUS AND MOVEMENT SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE INTENTION; PREMOTOR CORTEX; VISUALLY GUIDED MOVEMENT; PREFRONTAL CORTEX; MONKEY ID PREFRONTAL UNIT-ACTIVITY; GO/NO-GO DISCRIMINATION; CORTICAL MOTOR AREAS; PREMOTOR CORTEX; NEURONAL-ACTIVITY; RHESUS-MONKEYS; ARM MOVEMENTS; FUNCTIONAL-ORGANIZATION; INFERIOR AREA-6; MACAQUE MONKEY AB We compared neuronal activity in the dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and prefrontal (PF) cortex of two rhesus monkeys. The behavioral design was a variant of the instructed delay task which established that: (1) a given visual stimulus could, on different trials, instruct different limb movements and (2) several different visual stimuli could instruct the same movement. Neurons in all frontal areas displayed the often replicated activity patterns that occur during instructed delay tasks, including phasic increases after instruction stimuli (signal-related activity), tonic discharge during an instructed delay period (set-related activity), and phasic premovement discharge (movement-related activity). For signal-, set-, and movement-related activity, the majority of neurons in PMd (51-64%), but only a minority in PF (16-18%) and PMv (32-40%), showed activity levels that significantly depended on the action instructed by that stimulus rather than simply the characteristics of the stimulus per se. Thus, most PMd activity, including the aspects that most resembled a sensory response, reflected factors in addition to the signal. Taken together with the results of related studies, it seems most likely that these other factors are dominated by the motor instructional significance of the stimulus. In addition, many neurons (17-37%) in all examined areas showed activity that significantly depended on which of various stimuli guided the same movement. This finding shows that, in those frontal areas, neuronal activity can be affected by both the action to be taken and the events guiding that action. C1 NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. RI Boussaoud, Driss/B-6932-2008 NR 47 TC 137 Z9 138 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 1993 VL 95 IS 1 BP 28 EP 40 PG 13 WC Neurosciences SC Neurosciences & Neurology GA LP915 UT WOS:A1993LP91500004 PM 8405252 ER PT J AU SONG, LJ KIM, YH CHOPRA, RK PROUST, JJ NAGEL, JE NORDIN, AA ADLER, WH AF SONG, LJ KIM, YH CHOPRA, RK PROUST, JJ NAGEL, JE NORDIN, AA ADLER, WH TI AGE-RELATED EFFECTS IN T-CELL ACTIVATION AND PROLIFERATION SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE T-LYMPHOCYTES; INTERLEUKIN-2; MESSENGER RNA; LYMPHOCYTE TRANSFORMATION; GENE EXPRESSION; AGING ID PERIPHERAL-BLOOD LYMPHOCYTES; MESSENGER-RNA EXPRESSION; INTERLEUKIN-2 RECEPTOR; OLD MICE; PROTEIN; CD2; INTERFERON; MOLECULES; PATHWAY; HUMANS AB Age-associated thymic involution manifests its effects in a variety of ways that are related to a loss of T cell function. These include the appearance of a non-functional subset of T cells that increase in representation with age. Moreover there is a loss of T cell proliferative ability, a decline in the synthesis and release of interleukin-2 (IL-2), a decline in the ability of the T cell to express the IL-2 receptor, and a loss of control activity. This loss of control is demonstrated by the age-related appearance of autoantibodies and an increase in the elaboration of inflammatory cytokines such as TNF, IFN, IL-6, and TGF. A major part of the basis for the loss of T cell function is an inability of the T cell to respond to activation signals that are transmitted through the membrane binding of specific stimulatory signals. Transduction events, differentiation signals, and a loss of control mechanisms are all parts of a complicated picture of age-related immune deficiencies. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,CLIN IMMUNOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 30 TC 98 Z9 99 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 313 EP 321 DI 10.1016/0531-5565(93)90058-L PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700003 PM 8224030 ER PT J AU MIYAMOTO, A KOWATCH, MA ROTH, GS AF MIYAMOTO, A KOWATCH, MA ROTH, GS TI SIMILAR EFFECTS OF SAPONIN TREATMENT AND AGING ON COUPLING OF ALPHA(1)-ADRENERGIC RECEPTOR G-PROTEIN SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE SAPONIN; PAROTID; ALPHA-ADRENERGIC ACTION ID BETA-ADRENERGIC RECEPTORS; ADENYLATE-CYCLASE; ALPHA-1-ADRENERGIC RECEPTOR; BINDING; MODULATION; MEMBRANES; RESPONSIVENESS; AFFINITY; CALCIUM; AGE AB The effects of the nonionic detergent saponin on alpha1-adrenergic signal transduction were investigated using rat parotid cells and membrane preparations. Fifty muM epinephrine-stimulated Ca-45(2+) efflux and inositol 1,4,5-triphosphate (Ins[1,4,5]P3) production in adult parotid cells were significantly decreased after saponin treatment. Saponin did not alter the concentration of alpha1-adrenergic receptors labeled by [H-3]prazosin, but significantly reduced the guanosine imido diphosphate (GppNHp)-induced shift from high to low affinity sites. Fifty muM epinephrine-stimulated high affinity GTPase activity was also reduced by saponin treatment. These data suggest that reduced alpha1-adrenergic receptor-stimulated functional responsiveness following saponin treatment may be due to impaired uncoupling of receptor-G-protein complexes. C1 NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,MOLEC PHYSIOL & GENET SECT,4940 EASTERN AVE,BALTIMORE,MD 21224. SAPPORO MED COLL,DEPT PHARMACOL,CHUO KU,SAPPORO,HOKKAIDO 060,JAPAN. NR 24 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 349 EP 359 DI 10.1016/0531-5565(93)90062-I PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700007 PM 8224034 ER PT J AU PRATLEY, RE COON, PJ MULLER, DC ROGUS, EM GOLDBERG, AP AF PRATLEY, RE COON, PJ MULLER, DC ROGUS, EM GOLDBERG, AP TI THE EFFECTS OF SINGLE AND SEQUENTIAL INSULIN INFUSIONS ON GLUCOSE DISPOSAL IN OLDER MEN SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE GLUCOSE CLAMP TECHNIQUE; INSULIN SENSITIVITY; AGING ID RESISTANCE; SENSITIVITY; MECHANISMS; TOLERANCE; OBESITY; INVIVO AB The hyperinsulinemic euglycemic glucose clamp is widely used to quantitate in vivo insulin action. Modification of this technique by sequentially infusing multiple doses of insulin allows determination of insulin sensitivity and maximal responsiveness; however, the validity of this approach has not been determined in older individuals. In this study, glucose disposal rates during a sequential three-dose clamp at insulin infusion rates of 20, 100, and 500 mU/m2 . min were compared to those obtained during a single-dose 100 MU/M2 . min clamp in eight healthy older men. There were no differences in plasma insulin levels (256 +/- 46 vs. 261 +/- 32 muU/ml) or glucose disposal rates (11.0 +/- 3.6 vs. 10.8 +/- 3.0 mg/kg(fat-free mass) . min) during the 100 mU/m2 . min infusion of the three-dose clamp and the one-dose clamp.1 In four subjects with impaired glucose tolerance, the EC50 (insulin concentration producing a half-maximal response) was higher and M(max) (maximal glucose disposal) lower than in subjects with normal glucose tolerance, suggesting impairments in both insulin sensitivity and responsiveness in older subjects with impaired glucose tolerance. Future studies using this modification of the hyperinsulinemic euglycemic glucose clamp to determine insulin sensitivity and responsiveness may lead to an improved understanding of the insulin resistance of aging and the pathogenesis of diseases such as diabetes and hypertension. C1 NIA,CLIN PHYSIOL LAB,METAB SECT,BALTIMORE,MD 21224. RP PRATLEY, RE (reprint author), UNIV MARYLAND,BALTIMORE VET ADM MED CTR,DEPT MED,DIV GERONTOL,GERIATR 18,3900 LOCH RAVEN BLVD,BALTIMORE,MD 21218, USA. FU NCRR NIH HHS [MO1 RR02719]; NIA NIH HHS [NIA KO8 AG00347, P01 AG04402-06] NR 22 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 381 EP 391 DI 10.1016/0531-5565(93)90065-L PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700010 PM 8224036 ER PT J AU ELAHI, D MULLER, DC MCALOONDYKE, M TOBIN, JD ANDRES, R AF ELAHI, D MULLER, DC MCALOONDYKE, M TOBIN, JD ANDRES, R TI THE EFFECT OF AGE ON INSULIN-RESPONSE AND GLUCOSE-UTILIZATION DURING 4 HYPERGLYCEMIC PLATEAUS SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE HYPERGLYCEMIA; AGE; GLUCOSE UTILIZATION; INSULIN RESPONSE ID UNITED-STATES POPULATION; DIABETES-MELLITUS; SKELETAL-MUSCLE; SECRETION; METABOLISM; TOLERANCE; KINETICS; MEN; SENSITIVITY; INTOLERANCE AB In order to evaluate the potential role of insulin insensitivity as a cause of the glucose (G) intolerance of aging, we performed 230 hyperglycemic clamps, 85 on young (Y, 24 to 39 years), 47 on middle age (M, 40 to 59 years), and 98 on old (0, 60 to 90 years) carefully screened subjects of the Baltimore Longitudinal Study of Aging. The 2-h plasma G levels on an oral glucose tolerance test (OGTT) were < 7.8 mmol/l in Y and M and < 10 mmol/l in old; the latter group was further dichotomized at 7.8 mmol/l into a ''normal'' group, ON, and an impaired group, OI. Four hyperglycemic plateaus were created: 3.0, 5.4, 7.9, and 12.8 mmol/l above basal. Three measures of glucose tolerance-1) G at 2 h after glucose ingestion, 2) glucose utilization, M, at each hyperglycemic plateau, and 3) glucose decay constant, K, obtained at the conclusion of each clamp-showed the best performance in the young group (Y > M = ON > OI). Despite these differences in glucose tolerance, plasma insulin responses (I) during the clamp were not significantly different except that ON < Y at the basal + 12.8 plateau (300 t 42 vs. 456 +/- 48 pmol/l, p < 0.01). Insulin-dependent glucose uptake, a measure of tissue sensitivity to insulin, was decreased in the old-impaired group at every plateau except the highest. We conclude that healthy, active older subjects showed moderate intolerance to oral and IV glucose and that the mechanism of this physiological aging process is most likely decreased insulin sensitivity. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. RP ELAHI, D (reprint author), HARVARD UNIV,BETH ISRAEL HOSP,SCH MED,CHARLES A DANA RES INST,HARVARD THORNDIKE LAB,DIV GERONTOL,BOSTON,MA 02215, USA. FU NIA NIH HHS [AG-00294, AG-00599] NR 37 TC 48 Z9 49 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 393 EP 409 DI 10.1016/0531-5565(93)90066-M PG 17 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700011 PM 8224037 ER PT J AU HALLFRISCH, J MULLER, DC AF HALLFRISCH, J MULLER, DC TI DOES DIET PROVIDE ADEQUATE AMOUNTS OF CALCIUM, IRON, MAGNESIUM, AND ZINC IN A WELL-EDUCATED ADULT-POPULATION SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE CALCIUM; IRON; MAGNESIUM; ZINC; AGING; MINERAL REQUIREMENTS ID NUTRIENT INTAKE; SUPPLEMENT USE; UNITED-STATES; NHANES-II; WOMEN; PEOPLE; ANEMIA; AGE; MEN AB Standard advice from dietitians, nutritionists, and physicians is that if one eats a well-balanced diet containing a variety of foods, supplements are not necessary. Little information is available, especially in those over 75, to determine whether actual diets do provide adequate amounts of these minerals. The participants of the Baltimore Longitudinal Study of Aging provide seven-day records which include vitamin and mineral supplement intakes. Median daily dietary intakes from diet in all 564 subjects and from diet plus supplements in those who use them were analyzed by age group and gender. More women than men took supplements. Median intakes of calcium from diet were below the recommended dietary allowance (RDA) for unsupplemented women and for supplemented women over 60. Approximately 25% of women under 50 and 10% of women over 50 consumed less than two thirds of the RDA for iron from diet. For both men and women, all groups had median diet intakes below the RDA for magnesium. Forty percent of men and about half of women consumed less than two thirds of the RDA. These results indicate that many people in this well-educated, presumably well-nourished population did not consume adequate amounts of calcium, iron, magnesium, and zinc from diet. More women than men are at risk. Even those taking supplements did not consume adequate levels of some minerals. C1 NIA,GERONTOL RES CTR,METAB SECT,BALTIMORE,MD 21224. NR 36 TC 16 Z9 16 U1 6 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 473 EP 483 DI 10.1016/0531-5565(93)90072-L PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700017 PM 8224043 ER PT J AU GIAMBRA, LM AF GIAMBRA, LM TI THE INFLUENCE OF AGING ON SPONTANEOUS SHIFTS OF ATTENTION FROM EXTERNAL STIMULI TO THE CONTENTS OF CONSCIOUSNESS SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE AGING; SPONTANEOUS ATTENTIONAL SHIFTS; DAYDREAMING; CONCENTRATION; LONGITUDINAL CHANGE AB In a series of studies using laboratory procedures and retrospective reports it has been established that with increasing age adults less frequently have unbidden task-unrelated image and thought intrusions (TUITs). TUITs - also referred to as daydreams - have been linked to the ''current concerns'' and ''unfinished business'' of the individual, and old adults have been shown to express fewer current concerns than young adults. It has also been hypothesized that selective loss of neurons in old age might interfere with thought production, resulting in fewer unbidden thoughts and spontaneous shifts of attention to them. In this article we examine the extent to which intraindividual change in the frequency of TUITs over 6 to 8 years is consistent with the decrease expected from the prior cross-sectional studies. In particular, we examine the frequency of daydreams based upon retrospective self reports using the Daydreaming Frequency scale of the Imaginal Processes Inventory. The longitudinal sample consisted of 93 women and 169 men. Significant and equivalent decreases in Daydreaming Frequency scale values occurred at all ages. Longitudinal decreases were consistent with cross-sectional age differences. Thus, spontaneous shifts of attention to the contents of consciousness were seen to decrease over a 6 to 8 year interval within individuals - a result consistent with a within-individual change in conditions leading to spontaneous shifts. RP GIAMBRA, LM (reprint author), NIA,FRANCIS SCOTT KEY MED CTR,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 12 TC 30 Z9 32 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 485 EP 492 DI 10.1016/0531-5565(93)90073-M PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700018 PM 8224044 ER PT J AU EICHHORN, GL AF EICHHORN, GL TI IS THERE ANY RELATIONSHIP BETWEEN ALUMINUM AND ALZHEIMERS-DISEASE SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE ALZHEIMERS DISEASE; ALUMINUM; BRAIN; METALS ID BRAIN ALUMINUM; ADENYLATE-CYCLASE; PATHOGENESIS; DEMENTIA; ALUMINOSILICATES; ENCEPHALOPATHY; HYPOTHESIS; MECHANISM; COMPLEX; SENILE AB The controversial role of aluminum in Alzheimer's disease (AD) is reviewed. While current data would suggest the lack of a causative role, alterations in the brain and other organ systems caused by AD might increase the penetration of aluminum as well as other metals into the brain and lead to their contribution to such pathological features as neurofibrillar tangles (NFTs). RP NIA, CELLULAR & MOLEC BIOL LAB, BALTIMORE, MD 21224 USA. NR 42 TC 11 Z9 11 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 EI 1873-6815 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 493 EP 498 DI 10.1016/0531-5565(93)90074-N PG 6 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700019 PM 8224045 ER PT J AU ENGEL, BT AF ENGEL, BT TI AUTONOMIC BEHAVIOR SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE AUTONOMIC; LEARNING; BEHAVIOR; OPERANT CONDITIONING; CLASSICAL CONDITIONING ID HEART-RATE; LEARNED CONTROL; EXERCISE; HYPERTENSION; ATTENUATION AB This article summarizes a body of work which collectively shows that autonomic responses meet the criteria for behavior. They can be modified reliably through the systematic use of antecedent (cues) and consequent (contingencies) stimuli. This means that autonomic responses, which are usually characterized as elicited reflexes, can be learned responses (viz., behaviors). This review cites a number of experimental and clinical studies in which autonomic learning has been shown to occur and to have clinical importance. Of special interest to gerontologists are the clinical studies which show that incontinent and hypertensive elderly patients can be trained to normalize their pathognomic responses. RP ENGEL, BT (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JUL-OCT PY 1993 VL 28 IS 4-5 BP 499 EP 502 DI 10.1016/0531-5565(93)90075-O PG 4 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA LQ417 UT WOS:A1993LQ41700020 PM 8224046 ER PT J AU QUAY, J ROSENTHAL, G BECKER, S AF QUAY, J ROSENTHAL, G BECKER, S TI EFFECT OF PENTAMIDINE ON CYTOKINE (IL-1-BETA, TNF-ALPHA, IL-6) PRODUCTION BY HUMAN ALVEOLAR MACROPHAGES IN-VITRO SO EXPERIMENTAL LUNG RESEARCH LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; TUMOR NECROSIS FACTOR; MESSENGER-RNA; INTERLEUKIN-1; EXPRESSION; SEQUENCE; CLONING; LUNG; BLOOD; GENE AB Pentamidine (Pe) is an aromatic diamidine drug used clinically to treat Pneumocystis carinii pneumonia by aerosol inhalation. Nothing has been reported about the effects of this drug on human alveolar macrophage (AM) properties. In this study AM were exposed in vitro to various concentrations of Pe (10(-4)-10(-6) M) alone or in combination with bacterial endotoxin (LPS). Supernatants were collected at 3, 6, and 24 b and assayed for secreted IL-1beta, IL-6, and TNFalpha. While the drug did not induce release of these cytokines, LPS-induced secretion of all three cytokines was inhibited by Pe in a dose-dependent manner. At the most effective Pe dose, 10(-5) M, AM viability (as determined by trypan blue dye exclusion) was reduced by 14% at 24 h, while no effect on viability was seen at lower concentrations. mRNA expression of all three cytokines was examined by PCR and Northern analysis to establish if the decrease in cytokine secretion was determined on a pre- or post-translational level. Reduced steady-state mRNA levels were found as early as 3 b after LPS stimulation, with Pe concentrations corresponding to those that decreased cytokine secretion. At the later time points, Pe also inhibited beta-actin, ornithine decarboxylase, and GAPDH mRNA expression, indicating that pentamidine bad a general toxic effect on mRNA transcription in the macrophages. It is concluded that Pe, at pharmaceutically relevant concentrations and with apparent low cytotoxicity as determined by dye uptake, nonspecifically inhibits cytokine production by a toxic effect on transcriptional events. C1 NIEHS,DIV TOXICOL RES & TESTING,RES TRIANGLE PK,NC 27709. RP QUAY, J (reprint author), TRC ENVIRONM CORP,6320 QUADRANGLE DR,CHAPEL HILL,NC 27514, USA. NR 35 TC 4 Z9 4 U1 0 U2 1 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 JUL-AUG PY 1993 VL 19 IS 4 BP 429 EP 443 DI 10.3109/01902149309064356 PG 15 WC Respiratory System SC Respiratory System GA LM704 UT WOS:A1993LM70400002 PM 8370344 ER PT J AU FREED, WJ AF FREED, WJ TI NEURAL TRANSPLANTATION - A SPECIAL ISSUE SO EXPERIMENTAL NEUROLOGY LA English DT Editorial Material ID BRAIN GRAFTS RP FREED, WJ (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,PRECLIN NEUROSCI SECT,WASHINGTON,DC 20032, USA. NR 27 TC 4 Z9 4 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 1993 VL 122 IS 1 BP 1 EP 4 DI 10.1006/exnr.1993.1101 PG 4 WC Neurosciences SC Neurosciences & Neurology GA LR102 UT WOS:A1993LR10200001 PM 8339780 ER PT J AU HEIM, RC WILLINGHAM, G FREED, WJ AF HEIM, RC WILLINGHAM, G FREED, WJ TI A COMPARISON OF SOLID INTRAVENTRICULAR AND DISSOCIATED INTRAPARENCHYMAL FETAL SUBSTANTIA-NIGRA GRAFTS IN A RAT MODEL OF PARKINSONS-DISEASE - IMPAIRED GRAFT-SURVIVAL IS ASSOCIATED WITH HIGH BASE-LINE ROTATIONAL BEHAVIOR SO EXPERIMENTAL NEUROLOGY LA English DT Article ID NIGROSTRIATAL DOPAMINE PATHWAY; DENERVATED STRIATUM; 6-OHDA LESIONS; ADULT-RAT; 6-HYDROXYDOPAMINE LESIONS; MESENCEPHALIC XENOGRAFTS; INTRACEREBRAL DIALYSIS; SYNAPTIC CONNECTIONS; ADRENAL-MEDULLA; CAUDATE-NUCLEUS C1 USN HOSP,DEPT NEUROSURG,BETHESDA,MD 20814. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,PRECLIN NEUROSCI SECT,WASHINGTON,DC 20032. NR 58 TC 14 Z9 15 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 1993 VL 122 IS 1 BP 5 EP 15 DI 10.1006/exnr.1993.1102 PG 11 WC Neurosciences SC Neurosciences & Neurology GA LR102 UT WOS:A1993LR10200002 PM 8101821 ER PT J AU ISONO, M POLTORAK, M KULAGA, H ADAMS, AJ FREED, WJ AF ISONO, M POLTORAK, M KULAGA, H ADAMS, AJ FREED, WJ TI CERTAIN HOST-DONOR RAT STRAIN COMBINATIONS DO NOT REJECT BRAIN ALLOGRAFTS AFTER SYSTEMIC SENSITIZATION SO EXPERIMENTAL NEUROLOGY LA English DT Article ID IMMUNE-RESPONSE GENES; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I ANTIGENS; ANTERIOR-CHAMBER; NEURAL GRAFTS; IMMUNOLOGICAL PRIVILEGE; MONOCLONAL-ANTIBODY; CONGENIC PANEL; MICE; TRANSPLANTATION C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 39 TC 23 Z9 23 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 1993 VL 122 IS 1 BP 48 EP 56 DI 10.1006/exnr.1993.1106 PG 9 WC Neurosciences SC Neurosciences & Neurology GA LR102 UT WOS:A1993LR10200006 PM 8339789 ER PT J AU SUN, Y DONG, ZG NAKAMURA, K COLBURN, NH AF SUN, Y DONG, ZG NAKAMURA, K COLBURN, NH TI DOSAGE-DEPENDENT DOMINANCE OVER WILD-TYPE P53 OF A MUTANT P53 ISOLATED FROM NASOPHARYNGEAL CARCINOMA SO FASEB JOURNAL LA English DT Note DE P53; TUMOR SUPPRESSOR GENE; NASOPHARYNGEAL CARCINOMA; HETEROZYGOUS MUTATION; DOMINANT NEGATIVE ID TUMOR SUPPRESSOR GENE; TATA-BINDING PROTEIN; CANCER CELLS; SV40-TRANSFORMED CELLS; LUNG-CANCER; MUTATIONS; ANTIGEN; TRANSFORMATION; GROWTH; EXPRESSION AB Mutational inactivation of p53, a tumor suppressor gene, is the most common genetic alteration found in human cancer. Most mutated p53s either lose tumor suppressor function or gain oncogenic activity. We recently reported the detection of a heterozygous point mutation of p53 at codon 280 in nasopharyngeal carcinoma (NPC) (1), a high-incidence malignancy in southern China and southeast Asia. Given its heterozygous state, in which both wild-type and mutated p53 gene were expressed, p53-thr280 should function dominantly in the presence of the wild-type form if it is to play a role in nasopharynx carcinogenesis. We tested this dominance hypothesis in the cells of two model systems: 1) human Saos-2 cells lacking endogenous p53, and 2) mouse JB6 tumor promotion-resistant cells (P-) expressing endogenous wild-type p53. The results showed dosage-dependent dominance of p53-thr280 in controlling WT p53-driven transcriptional activity; in governing cell growth; and in progressing P- phenotype to tumor promotion-sensitive (P+) phenotype. This dominant negative effect was seen at a 1:1 (WT:MU) ratio and was more striking at a ratio of 1:3. A model is proposed to explain the dominant negative effect of mutant p53. We conclude from this study that p53-thr280 is likely to be dominant in the heterozygous state found in NPC and that this dominant-negative mutated p53 may contribute to the genesis of NPC or of other carcinomas in which both mutant and wild-type p53 are expressed. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BCDP,FREDERICK,MD 21702. RP SUN, Y (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702, USA. NR 54 TC 54 Z9 57 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 JUL PY 1993 VL 7 IS 10 BP 944 EP 950 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA LQ337 UT WOS:A1993LQ33700019 PM 8344492 ER PT J AU BHATIA, K GOLDSCHMIDTS, W GUTIERREZ, M GAIDANO, G DALLAFAVERA, R MAGRATH, I AF BHATIA, K GOLDSCHMIDTS, W GUTIERREZ, M GAIDANO, G DALLAFAVERA, R MAGRATH, I TI HEMIZYGOSITY OR HOMOZYGOSITY - A REQUIREMENT FOR SOME BUT NOT OTHER P53 MUTANT PROTEINS TO ACCUMULATE AND EXERT A PATHOGENETIC EFFECT SO FASEB JOURNAL LA English DT Note DE BURKITT LYMPHOMA; P53; HETEROZYGOSITY ID WILD-TYPE; BURKITTS-LYMPHOMA; MUTATIONS; CANCER; MALIGNANCIES; ASSOCIATION; EXPRESSION; RELEVANCE; CELLS; GENE AB Activating mutations within the p53 gene cause stabilization and therefore increased steady-state levels of the p53 protein; some, but not all, also result in the generation of an epitope recognized by the antibody pAB240. We have shown here that in 70% of Burkitt lymphoma cell lines, but not in normal EBV transformed B cell lines, p53 protein is readily detectable by Western blot analysis using either an antibody directed against the 240 epitope or an antibody against wild-type p53. Genomic analysis of these BL cell lines demonstrated the presence of mutations within the p53 gene in all cell lines with detectable p53 protein. We have also shown that in the cell lines ST486, Raji, and TE 110, which are heterozygous for a neutral sequence codon polymorphism (Arg/Pro) that causes altered migration of an otherwise normal protein and also contain a heterozygous mutation, only the protein derived from the mutated allele is stabilized. Thus the dominant effect of the mutations present in these cell lines apparently does not result from sequestering of the normal protein by the abnormal protein, and therefore presumably is a consequence of a gain-of-function resulting from the mutation. Although all cell lines with stabilized p53 also contained p53 mutations, three lymphoid tumors (two cell lines and one fresh B-CLL) with a heterozygous mutation at codon 248 did not express elevated levels of p53. In contrast, p53 was readily detectable in Western blot analysis from cell lines KK124, Namalwa, and CA46, which had homo- or hemizygous mutations at codon 248, and from PP1084, a cell line with a codon 273 mutation and a carboxyl-terminal truncation in the other allele. These results suggest that mutations at codon 248, unlike those in cell lines ST486 and TE110, are stabilizing only in the absence of the wild-type p53. Heterozygous mutations at codons 248 have been described in the germline of individuals belonging to cancer-prone families described by Li and Fraumeni (see ref 18), but tumors detected in such individuals are homozygous, i.e., contain only mutated p53. This is consistent with the possibility that such mutations exert a pathogenetic effect only in the absence of the wild-type protein, and are coupled to our findings that stabilization of p53 is a necessary component of the oncogenic pathways relevant to p53. However, whereas some mutations are stabilizing in the presence of the normal p53 protein, others are stabilizing only in the homozygous state. C1 COLUMBIA UNIV,DEPT PATHOL,NEW YORK,NY 10032. RP BHATIA, K (reprint author), NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BLDG 10,ROOM 13C206,BETHESDA,MD 20892, USA. NR 20 TC 38 Z9 39 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 JUL PY 1993 VL 7 IS 10 BP 951 EP 956 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA LQ337 UT WOS:A1993LQ33700020 PM 8344493 ER PT J AU WILCOX, LS PETERSON, HB HASELTINE, FP MARTIN, MC AF WILCOX, LS PETERSON, HB HASELTINE, FP MARTIN, MC TI DEFINING AND INTERPRETING PREGNANCY SUCCESS RATES FOR IN-VITRO FERTILIZATION SO FERTILITY AND STERILITY LA English DT Article DE IN-VITRO FERTILIZATION; PREGNANCY; STATISTICS ID INFERTILITY THERAPY; EMBRYO-TRANSFER; ENDOMETRIOSIS; PROGRAMS; WOMEN AB Objectives: To review current practice in describing pregnancy success rates after IVF-ET, to identify issues associated with interpreting these rates, and to suggest useful methods of describing these rates in the future. Design: Review of literature concerning medical, epidemiologic, and statistical aspects of reporting IVF-ET pregnancy success rates. Setting: The United States. Patients: Infertile couples participating in IVF-ET. Main Outcome Measures: Usefulness and accuracy of IVF-ET pregnancy reporting. Results: Several groups have collected information on the pregnancy success rates of IVF-ET clinics and have discussed appropriate definitions of pregnancy success. The largest of these groups in the United States is The American Fertility Society and its affiliate, the Society for Assisted Reproductive Technology. The number of live deliveries per 100 ET procedures and the number of live deliveries per 100 egg retrieval procedures are among the most commonly used definitions. Conclusion: The most commonly used definitions are particularly useful for describing the probability that a live infant will be delivered after IVF-ET is completed. To measure the effectiveness of the IVF-ET procedures and the costs of undergoing IVF-ET, other definitions are also important. Success rates need to be stratified by patient characteristics, such as age, that affect the probability of success. C1 NIH,CTR POPULAT RES,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT OBSTET & GYNECOL,SAN FRANCISCO,CA 94143. AMER FERTIL SOC,SOC ASSISTED REPROD TECHNOL,BIRMINGHAM,AL. RP WILCOX, LS (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,DIV REPROD HLTH,ATLANTA,GA 30333, USA. NR 38 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1993 VL 60 IS 1 BP 18 EP 25 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA LK480 UT WOS:A1993LK48000003 PM 8513941 ER PT J AU SUELDO, CE OEHNINGER, S SUBIAS, E MAHONY, M ALEXANDER, NJ BURKMAN, LJ ACOSTA, AA AF SUELDO, CE OEHNINGER, S SUBIAS, E MAHONY, M ALEXANDER, NJ BURKMAN, LJ ACOSTA, AA TI EFFECT OF PROGESTERONE ON HUMAN ZONA-PELLUCIDA SPERM BINDING AND OOCYTE PENETRATING CAPACITY SO FERTILITY AND STERILITY LA English DT Article DE PROGESTERONE; ACROSOME REACTION; HUMAN ZONA SPERM BINDING; HAMSTER OVA PENETRATION; SPERM HYPERACTIVE MOTILITY ID HUMAN FOLLICULAR-FLUID; ACROSOME REACTION; HUMAN-SPERMATOZOA; HYPERACTIVATED MOTILITY; HEMIZONA ASSAY; POPULATIONS; FRACTION; CALCIUM; INVITRO; INFLUX AB Objective: To determine if sperm exposure to P produces an enhancement in its fertilizing capacity. Design: Sperm from fertile donors were exposed to P at 0.1 and 1.0 mug/mL for 1 or 24 hours. The effects on hyperactivated (HA) motility at 1 and 4 hours, acrosome reaction (as determined by Pisum sativum agglutinin or T6/antibody techniques), on human zona pellucida binding (by using the hemizona assay), and on the penetrating ability (by using the zona-free hamster ova assay) were evaluated. Results: Exposure to P at 1.0 mug/mL enhanced HA motility after 1 and 4 hours of P exposure, the acrosome reaction after 24 hours' incubation, the number of sperm bound/hemizona after 1-hour incubation, and the penetration rates in the hamster ova assay at both incubation intervals. Conclusion: Sperm exposure to P enhances its fertilizing capacity in fertile men, and further investigation is warranted as a possible treatment for male factor patients. C1 EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,NORFOLK,VA 23501. NIH,CONTRACEPT DEV BRANCH,BETHESDA,MD 20892. GRAND ISL BIOL CO LABS,GRAND ISL,NY. RP SUELDO, CE (reprint author), UNIV CALIF SAN FRANCISCO,DEPT OBSTET & GYNECOL,FRESNO,CA 93703, USA. NR 19 TC 66 Z9 70 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1993 VL 60 IS 1 BP 137 EP 140 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA LK480 UT WOS:A1993LK48000024 PM 8513930 ER PT J AU SPIRTAS, R KAUFMAN, SC ALEXANDER, NJ AF SPIRTAS, R KAUFMAN, SC ALEXANDER, NJ TI FERTILITY DRUGS AND OVARIAN-CANCER - RED ALERT OR RED HERRING - NEW INFORMATION - REPLY SO FERTILITY AND STERILITY LA English DT Letter RP SPIRTAS, R (reprint author), NICHHD,CTR POPULAT RES,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 1993 VL 60 IS 1 BP 200 EP 200 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA LK480 UT WOS:A1993LK48000055 ER PT J AU DIETER, MP GOEHL, TJ JAMESON, CW ELWELL, MR HILDEBRANDT, PK YUAN, JH AF DIETER, MP GOEHL, TJ JAMESON, CW ELWELL, MR HILDEBRANDT, PK YUAN, JH TI COMPARISON OF THE TOXICITY OF CITRAL IN F344 RATS AND B6C3F(1) MICE WHEN ADMINISTERED BY MICROENCAPSULATION IN FEED OR BY CORN-OIL GAVAGE SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL AB A study of the potential effects of microencapsulation on the toxicity of citral was conducted in 14-day continuous feeding studies with both sexes of F344 rats and B6C3F1 mice. Toxicity by the feeding route was compared with that from bolus doses of the neat chemical in com oil administered by gavage. Both sexes of rats and mice were given diet containing 0, 0.63, 1.25, 2.5, 5 and 10% citral microcapsules. These feed formulations were equivalent to daily doses of 0, 142, 285, 570, 1140 and 2280 mg citral/kg body weight for rats and 0, 534, 1068, 2137, 4275 and 8550 mg citral/kg body weight for mice. The daily gavage doses were 0, 570, 1140 and 2280 mg citral/kg body weight for both sexes of rats, and 0, 534, 1068 and 2137 mg citral/kg body weight for both sexes of mice. Citral microcapsules administered in the diet did not cause mortality in mice or rats. Toxicity was confined to decreases in body weight at the 10% concentration in mice, at the 5 and 10% concentrations in rats, and decreases in absolute weights of the liver, kidney and spleen at the 10% concentration in rats. The only histopathological change observed was minimal to mild hyperplasia and/or squamous metaplasia of the respiratory epithelium in the anterior portion of the nasal passages of rats fed 5 or 10% citral microcapsules. By contrast, citral gavage caused mortality in five out of five male and female mice at 2137 mg/kg body weight, and in two out of five male mice at 1068 mg/kg body weight. There were dose-related increases in absolute liver weights of male and female mice. Cytoplasmic vacuolization of hepatocytes occurred in all female mice gavaged with 1068 and 2137 mg citral/kg body weight, and in male mice from the 2137 mg/kg dose group. Necrosis, ulceration and/or acute inflammation of the forestomach occurred in the high-dose mice of both sexes. Inflammation and/or hyperplasia of the forestomach occurred in about half of the male and female mice dosed with 1068 mg citral/kg. Citral gavage at doses that were equivalent to up to 10% in the diet (2280 mg/kg body weight) did not cause toxicity in rats, except for minimal hyperplasia of the squamous epithelium of the forestomach in high-dose males. Microencapsulated citral given in the diet has distinct advantages as an alternative route of administration for long-term studies: the microencapsulation process prevents the normally rapid degradation of the chemical; continual ingestion from the diet mimics the human route of exposure; and higher doses of the chemical can be attained in the animal model to maximize the detection of potential toxic or carcinogenic responses. C1 PATHCO INC,IJAMSVILLE,MD 21754. RP DIETER, MP (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 30 TC 11 Z9 11 U1 4 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JUL PY 1993 VL 31 IS 7 BP 463 EP 474 DI 10.1016/0278-6915(93)90105-8 PG 12 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA LN695 UT WOS:A1993LN69500001 PM 8340024 ER PT J AU CHAPIN, RE MORRISSEY, RE GULATI, DK HOPE, E BARNES, LH RUSSELL, SA KENNEDY, SR AF CHAPIN, RE MORRISSEY, RE GULATI, DK HOPE, E BARNES, LH RUSSELL, SA KENNEDY, SR TI ARE MOUSE STRAINS DIFFERENTIALLY SUSCEPTIBLE TO THE REPRODUCTIVE TOXICITY OF ETHYLENE-GLYCOL MONOMETHYL ETHER - A STUDY OF 3 STRAINS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID TESTICULAR TOXICITY; RATS; TOXICOLOGY; METABOLISM; FERTILITY; MICE C1 ENVIRONM HLTH RES & TESTING INC,LEXINGTON,KY 40503. ANALYT SCI INC,DURHAM,NC 27713. RP CHAPIN, RE (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES-45061, N01-ES-65142, N01-ES-95615] NR 26 TC 11 Z9 14 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1993 VL 21 IS 1 BP 8 EP 14 DI 10.1006/faat.1993.1065 PG 7 WC Toxicology SC Toxicology GA LM171 UT WOS:A1993LM17100002 PM 8365589 ER PT J AU LUSTER, MI PORTIER, C PAIT, DG ROSENTHAL, GJ GERMOLEC, DR CORSINI, E BLAYLOCK, BL POLLOCK, P KOUCHI, Y CRAIG, W WHITE, KL MUNSON, AE COMMENT, CE AF LUSTER, MI PORTIER, C PAIT, DG ROSENTHAL, GJ GERMOLEC, DR CORSINI, E BLAYLOCK, BL POLLOCK, P KOUCHI, Y CRAIG, W WHITE, KL MUNSON, AE COMMENT, CE TI RISK ASSESSMENT IN IMMUNOTOXICOLOGY .2. RELATIONSHIPS BETWEEN IMMUNE AND HOST-RESISTANCE TESTS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID TOXICITY C1 NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. UNIV MILAN,DEPT TOXICOL,I-20122 MILAN,ITALY. TAIHO PHARMACEUT,KOKUSHIMA 77101,JAPAN. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOSTAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,RICHMOND,VA 23298. RP LUSTER, MI (reprint author), NIEHS,INTEGRAT BIOL LAB,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709, USA. RI Corsini, Emanuela/B-5602-2011; Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 17 TC 217 Z9 220 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 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1993 VL 21 IS 1 BP 71 EP 82 DI 10.1006/faat.1993.1074 PG 12 WC Toxicology SC Toxicology GA LM171 UT WOS:A1993LM17100011 PM 8365588 ER PT J AU EKBOM, A YUEN, J ADAMI, HO MCLAUGHLIN, JK CHOW, WH PERSSON, I FRAUMENI, JF AF EKBOM, A YUEN, J ADAMI, HO MCLAUGHLIN, JK CHOW, WH PERSSON, I FRAUMENI, JF TI CHOLECYSTECTOMY AND COLORECTAL-CANCER SO GASTROENTEROLOGY LA English DT Article ID LARGE BOWEL-CANCER; RISK JAPANESE POPULATION; COLONIC-CANCER; INCIDENCE RATES; CARCINOMA; CHOLELITHIASIS; GALLSTONES; INCREASE; DISEASE; ABSENCE C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP EKBOM, A (reprint author), UNIV HOSP UPPSALA,CANC EPIDEMIOL UNIT,S-75185 UPPSALA,SWEDEN. NR 44 TC 44 Z9 47 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 1993 VL 105 IS 1 BP 142 EP 147 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LJ984 UT WOS:A1993LJ98400017 PM 8514031 ER PT J AU PETTIT, GR GAO, F DOUBEK, DL BOYD, MR HAMEL, E BAI, RL SCHMIDT, JM TACKETT, LP RUTZLER, K AF PETTIT, GR GAO, F DOUBEK, DL BOYD, MR HAMEL, E BAI, RL SCHMIDT, JM TACKETT, LP RUTZLER, K TI ANTINEOPLASTIC AGENTS .252. ISOLATION AND STRUCTURE OF HALISTATIN-2 FROM THE COMOROS MARINE SPONGE AXINELLA-CARTERI SO GAZZETTA CHIMICA ITALIANA LA English DT Article ID TUMOR-CELL-LINES; ABSOLUTE-CONFIGURATION; PETROSIA-WEINBERGI AB An intensive long-term investigation of marine organisms as sources of new anticancer drugs has led to the isolation and structural elucidation (primarily by high-field NMR and mass spectrometry) of halistatin 2, 7b, a new polyether macrolide of the halipyran-type, from the Western Indian Ocean sponge Axinella cf. carteri (Dendy). Halistatin 2 (1.4 x 10(-6)% yield) was accompanied by the closely related, and also strongly antineoplastic, halistatin 1 (6b, 1.3 x 10(-6)% yield), halichondrin B (6a, 6.1 x 10(-6)% yield) and homohalichondrin B (7a, 4.3 x 10(-6)% yield). Halistatin 2, like halichondrin B and homohalichondrin B, caused the accumulation of cells arrested in mitosis, inhibited tubulin polymerization, and inhibited the binding of radiolabelled vinblastine and GTP to tubulin. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,FREDERICK CANC RES & DEV CTR,DCT,DTP,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NATL MUSEUM NAT HIST,WASHINGTON,DC 20560. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. NR 29 TC 35 Z9 35 U1 1 U2 3 PU SOC CHIMICA ITALIANA PI ROME PA VIALE LIEGI 48, I-00198 ROME, ITALY SN 0016-5603 J9 GAZZ CHIM ITAL JI Gazz. Chim. Ital. PD JUL PY 1993 VL 123 IS 7 BP 371 EP 377 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA LP772 UT WOS:A1993LP77200002 ER PT J AU GERRARD, B STEWART, C DEAN, M AF GERRARD, B STEWART, C DEAN, M TI ANALYSIS OF MDR50 - A DROSOPHILA P-GLYCOPROTEIN MULTIDRUG-RESISTANCE GENE HOMOLOG SO GENOMICS LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS GENE; PLASMODIUM-FALCIPARUM; BACTERIAL TRANSPORT; COMPLEMENTARY-DNA; IDENTIFICATION; CLONING; AMPLIFICATION; SEQUENCE; PROTEINS C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 41 TC 37 Z9 37 U1 0 U2 2 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 JUL PY 1993 VL 17 IS 1 BP 83 EP 88 DI 10.1006/geno.1993.1286 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LN156 UT WOS:A1993LN15600012 PM 7691715 ER PT J AU MASSA, PT OZATO, K MCFARLIN, DE AF MASSA, PT OZATO, K MCFARLIN, DE TI CELL-TYPE-SPECIFIC REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) CLASS-I GENE-EXPRESSION IN ASTROCYTES, OLIGODENDROCYTES, AND NEURONS SO GLIA LA English DT Article DE GLIAL CELLS; CENTRAL NERVOUS SYSTEM; INTERFERON; TRANSCRIPTIONAL REGULATION ID NF-KAPPA-B; INTERFERON-INDUCED TRANSCRIPTION; EMBRYONAL CARCINOMA-CELLS; GEL-ELECTROPHORESIS; NEGATIVE REGULATION; CONSENSUS SEQUENCE; MULTIPLE-SCLEROSIS; RESPONSE SEQUENCE; NUCLEAR FACTORS; GLIAL-CELLS AB Mechanisms of major histocompatibility complex (MHC) class I gene regulation in cells of the CNS have been studied in vitro. Astrocytes in primary cultures, but neither oligodendrocytes nor neurons, constitutively expressed cell surface MHC class I molecules. Interferon-gamma (IFN-gamma) treatment led to induction of MHC class I expression in astrocytes and oligodendrocytes but not in neurons. The conserved upstream sequence containing the juxtaposed nuclear factor (NF)-kappaB-like region I and IFN-response consensus sequence (ICS) constitutively enhanced MHC class I gene promoter activity in astrocytes, but not in oligodendrocytes or in neurons. Nuclear extracts from astrocytes, but not from oligodendrocytes and neurons, had a binding activity specific for the NF-kappaB-like region I sequence, indicating that constitutive expression of MHC class I genes is governed by the upstream region I enhancer and its binding factor. IFN-gamma treatment led to induction of MHC class I promoter activity in astrocytes and oligodendrocytes, but not in neurons. In accordance with this observation, a nuclear factor that binds to the ICS was induced in astrocytes and oligodendrocytes but not in neurons following IFN-gamma treatment. This study illustrates cell type-specific regulation of MHC class I genes in the CNS that correlates with the expression of DNA binding factors relevant to MHC class I gene transcription. C1 NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. RP MASSA, PT (reprint author), SUNY HLTH SCI CTR,DEPT NEUROL,750 E ADAMS ST,SYRACUSE,NY 13210, USA. NR 54 TC 80 Z9 81 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 0894-1491 J9 GLIA JI Glia PD JUL PY 1993 VL 8 IS 3 BP 201 EP 207 DI 10.1002/glia.440080307 PG 7 WC Neurosciences SC Neurosciences & Neurology GA LH142 UT WOS:A1993LH14200006 PM 8225560 ER PT J AU VINORES, SA ORMAN, W HOOKS, JJ DETRICK, B CAMPOCHIARO, PA AF VINORES, SA ORMAN, W HOOKS, JJ DETRICK, B CAMPOCHIARO, PA TI ULTRASTRUCTURAL-LOCALIZATION OF RPE-ASSOCIATED EPITOPES RECOGNIZED BY MONOCLONAL-ANTIBODIES IN HUMAN RPE AND THEIR INDUCTION IN HUMAN FIBROBLASTS BY VITREOUS SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID PERI-RETINAL PROLIFERATION; PIGMENT EPITHELIAL-CELLS; EPIRETINAL MEMBRANES; DETACHMENT; EXPRESSION; GLIA; VIMENTIN; PATTERNS; CULTURE; INVITRO AB Electron microscopic immunocytochemistry was performed to localize the epitopes recognized by monoclonal antibodies RPE15 and RPE9, reported to specifically stain retinal pigment epithelial (RPE) cells by light microscopy, and to evaluate the usefulness of these antibodies for recognizing phenotypically altered, pathological RPE cells. The labeling patterns of the two antibodies were indistinguishable, and in human eyes positivity was limited to RPE cells. In in situ and vitreous-cultured human RPE cells the epitopes were localized to the surface and intracellular membranes and to the cytoplasm. In vitreous culture many RPE cells developed processes containing filaments which reacted with either antibody. Human retinal glial cells were negative. Some human fibroblasts in vitreous culture showed labeling of the same structures as RPE cells with either antibody, limiting the usefulness of these antibodies for distinguishing RPE cells from fibroblasts, which can assume similar morphologies when in contact with vitreous; however, they may be useful adjuncts to anti-cytokeratin antibodies for RPE cell identification in various pathological conditions. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21287. NEI,IMMUNOL LAB,IMMUNOL & VIROL SECT,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. RP VINORES, SA (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,825 MAUMENEE BLDG,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NEI NIH HHS [EY 05951, EY 10017] NR 25 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JUL PY 1993 VL 231 IS 7 BP 395 EP 401 DI 10.1007/BF00919647 PG 7 WC Ophthalmology SC Ophthalmology GA LM329 UT WOS:A1993LM32900006 PM 7691691 ER PT J AU SIGMON, HD AF SIGMON, HD TI ANSWERING CRITICAL CARE NURSING QUESTIONS BY INTERFACING NURSING RESEARCH TRAINING, CAREER-DEVELOPMENT, AND RESEARCH WITH BIOLOGIC AND MOLECULAR SCIENCE SO HEART & LUNG LA English DT Editorial Material AB Critical care nursing practice encompasses physiologic as well as psychosocial responses of individuals to acute and chronic health care problems. Before solving integrative nursing problems, pathophysiologic information based on state-of-the-science biotechnology is needed. More critical care nurse researchers need to answer clinical questions with biologic and molecular science information, measurements, and techniques. The purpose of this article is to describe research training, career development, and research opportunities to facilitate the interface of critical care nursing research with the biologic and molecular sciences. RP SIGMON, HD (reprint author), NIH,NATL CTR NURSING RES,WESTWOOD BLDG,ROOM 754,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL-AUG PY 1993 VL 22 IS 4 BP 285 EP 288 PG 4 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA LN687 UT WOS:A1993LN68700001 PM 8360061 ER PT J AU BUCK, S WELLS, RA DUDAS, SP BAKER, GT ARKING, R AF BUCK, S WELLS, RA DUDAS, SP BAKER, GT ARKING, R TI CHROMOSOMAL LOCALIZATION AND REGULATION OF THE LONGEVITY DETERMINANT GENES IN A SELECTED STRAIN OF DROSOPHILA-MELANOGASTER SO HEREDITY LA English DT Article DE ADDITIVE INHERITANCE; DROSOPHILA; GENETICS OF AGING; LIFE SPAN; LONGEVITY; NONADDITIVE INHERITANCE ID LIFE-SPAN; QUANTITATIVE GENETICS; AGING PROCESSES; SENESCENCE; RESISTANCE; EVOLUTION AB A controlled chromosome substitution experiment was performed on a strain (NDC-L) selected for long life to determine if the genes responsible for the extended-longevity phenotype could be localized to any particular chromosome(s). All 27 different possible combinations of the three major chromosomes of Drosophila melanogaster were constructed and longevities were determined on 3875 individual animals of both sexes and analysed. The results are statistically significant and demonstrate that mean longevity is specified primarily by recessive genes on the third chromosome (c3). The extended longevity phenotype (ELP) is only expressed in those lines which are homozygous for the NDC-L type c3. Loci on the first (c1) and second (c2) chromosomes interact, both positively (cl) and negatively (c2), respectively, such that c1 represses c2 which in turn represses c3. The ELP is fully expressed in the mutual presence and mutual absence of cl and c2. The significance of these results is discussed in the context of broader categories of molecular genetic mechanisms suggested previously to be involved in the modulation of longevity in Drosophila. C1 WAYNE STATE UNIV,DEPT BIOL SCI,DETROIT,MI 48202. WAYNE STATE UNIV,INST GERONTOL,DETROIT,MI 48202. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 44 TC 35 Z9 35 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0018-067X J9 HEREDITY JI Heredity PD JUL PY 1993 VL 71 BP 11 EP 22 DI 10.1038/hdy.1993.102 PN 1 PG 12 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA LN679 UT WOS:A1993LN67900002 PM 8360075 ER PT J AU BUCK, S NICHOLSON, M DUDAS, S WELLS, R FORCE, A BAKER, GT ARKING, R AF BUCK, S NICHOLSON, M DUDAS, S WELLS, R FORCE, A BAKER, GT ARKING, R TI LARVAL REGULATION OF ADULT LONGEVITY IN A GENETICALLY-SELECTED LONG-LIVED STRAIN OF DROSOPHILA SO HEREDITY LA English DT Article DE GENETICS OF AGING; LARVAL ENVIRONMENT; LONGEVITY ID LIFE-SPAN; GROWTH-RATE; DEVELOPMENTAL TEMPERATURE; BIPHASIC RELATIONSHIP; HEAT-SHOCK; BODY SIZE; MELANOGASTER; RESISTANCE; FECUNDITY; STRESS AB Our previous work has shown that the major genes involved in the expression of the extended-longevity phenotype are located on the third chromosome. Furthermore, their expression is negatively and positively influenced by chromosomes 2 and 1, respectively. In this report we show that the expression of the extended-longevity phenotype is dependent on the larval environment. A controlled chromosome substitution experiment was carried out using a strain selected for long life (L) and its parent (R) strain. Twenty different combinations of the three major chromosomes were conducted and their longevities were determined under both high (HD) and low (LD) larval density conditions. The extended-longevity phenotype was only expressed under HD conditions. The chromosome interactions were not apparent under LD conditions. Density-shift experiments delineate a critical period for expression of the extended-longevity phenotype, extending from 60 h after egg laying (AEL) to 96 h AEL, during which the developing animal must be exposed to HD conditions if the extended-longevity phenotype is to be expressed. The change from HD to LD conditions is accompanied by statistically significant increases in body weight. The possible role of a dietary restriction phenomenon is examined and the implications of these findings discussed. It is now apparent, however, that the extended-longevity phenotype in Drosophila is a developmental genetic process. C1 WAYNE STATE UNIV,DEPT BIOL SCI,DETROIT,MI 48202. WAYNE STATE UNIV,INST GERONTOL,DETROIT,MI 48202. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 41 TC 32 Z9 32 U1 1 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0018-067X J9 HEREDITY JI Heredity PD JUL PY 1993 VL 71 BP 23 EP 32 DI 10.1038/hdy.1993.103 PN 1 PG 10 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA LN679 UT WOS:A1993LN67900003 PM 8360076 ER PT J AU GHANAYEM, BI SULLIVAN, CA AF GHANAYEM, BI SULLIVAN, CA TI ASSESSMENT OF THE HEMOLYTIC-ACTIVITY OF 2-BUTOXYETHANOL AND ITS MAJOR METABOLITE, BUTOXYACETIC ACID, IN VARIOUS MAMMALS INCLUDING HUMANS SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Article ID MONOBUTYL ETHER 2-BUTOXYETHANOL; TOXICITY; RATS AB 2-Butoxyethanol (BE) is a glycol ether produced in volumes exceeding 335 million pounds/year for industrial and domestic uses. BE causes acute haemolytic anaemia in rats and some other mammals. While BE is inactive in vitro, 2-butoxyacetic acid (BAA) is a potent haemolytic agent in vivo and in vitro. This finding suggests that metabolic activation of BE to BAA is required for haemolysis of erythrocytes to occur in vivo. Haemolysis Of red blood cells (RBC) by BAA is preceded by swelling (increased mean cell volume [MCV] and haematocrit [HCT]). In an attempt to assess the potential risk to humans exposed to BE, studies were designed to determine the in vitro effect of BAA on RBCs from 1 0 mammalian species including humans. Blood SamPles from each mammalian species (n=3-5) were incubated with BAA at a final concentration of 0 (vehicle), 1 or 2 mm and kept at 37-degrees-C in a.gently shaking water bath. Complete blood counts (CBCs) were measured at 0, 1, 2 and 4 h. BAA caused a time- and concentration-dependent increase in MCV and HCT of blood from rats, mice and hamsters (rodents), rabbits (lagomorphs), and baboons (primates). In contrast, blood from pigs (artiodactyls), dogs and cats (carnivores), guinea pigs (rodents/marsupials), and humans (primates), minimally affected by BAA. These results were confirmed in guinea pigs and rats in vivo. Gavage administration of BE (250 mg kg-1) to rats resulted in increased MCV and HCT followed by haemolysis (decreased RBCs). Identical treatment with BE resulted in no significant change in these parameters in guinea pigs. These data clearly demonstrated that BE-induced haemolytic anaemia is species-dependent. This information may prove important for selecting appropriate animal models for use in the assessment of the health risk to humans exposed to BE. Future studies will focus on the cellular basis of the differential sensitivity of RBCs from various mammals to BAA. RP GHANAYEM, BI (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 20 TC 61 Z9 63 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0144-5952 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD JUL PY 1993 VL 12 IS 4 BP 305 EP 311 PG 7 WC Toxicology SC Toxicology GA LK726 UT WOS:A1993LK72600009 PM 8104009 ER PT J AU AKSENTIJEVICH, I GRUBERG, L PRAS, E BALOW, JE KOVO, M GAZIT, E DEAN, M PRAS, M KASTNER, DL AF AKSENTIJEVICH, I GRUBERG, L PRAS, E BALOW, JE KOVO, M GAZIT, E DEAN, M PRAS, M KASTNER, DL TI EVIDENCE FOR LINKAGE OF THE GENE CAUSING FAMILIAL MEDITERRANEAN FEVER TO CHROMOSOME 17Q IN NON-ASHKENAZI JEWISH FAMILIES - 2ND LOCUS OR TYPE-I ERROR SO HUMAN GENETICS LA English DT Article ID MAPPED GENES; DNA POLYMORPHISMS; COMMITTEE; ARMENIANS; POLYSEROSITIS; EXCLUSION; CATALOGS; MARKER; TRAITS; RFLP AB Familial Mediterranean fever (FMF) is an autosomal recessive disorder of unknown pathogenesis, characterized by recurrent, selflimited attacks of fever with synovitis, peritonitis, or pleurisy. Using DNAs from affected Israeli families, we have recently mapped the gene causing FMF (designated MEF) to the short arm of chromosome 16, with two-point lod scores in excess of 20. In this report we consider the possibility of a second FMF susceptibility locus. Before discovering linkage to markers on chromosome 16, we had found suggestive evidence for linkage to chromosome 17q, with the following maximal two-point lod scores: D17S74 (pCMM86), Z = 2.47, (theta = 0.20); D17S40 (pLEW101), Z = 2.15 (theta = 0.15); D17S35 (CRI-pP3-1), Z = 1.78 (theta = 0.15); D17S46 (pLEW108), Z = 1.69 (theta = 0.18), D17S254, Z = 2.30 (theta = 0.20). Moreover, multipoint linkage analysis using D17S74 and D17S40 as fixed loci gave Z = 3.27 approximately 10 centimorgans (cM) telomeric to D17S40. Data with the chromosome 17 markers alone in our families suggested locus heterogeneity. Nevertheless, our families were not separable into complementary subsets showing linkage either to chromosome 16 or to chromosome 17. We also examined the possibility that the positive lod scores for chromosome 17 might reflect a secondary, modifying locus. By several measures of disease severity, families with positive lod scores for chromosome 17 loci had no worse disease than those with negative lod scores for these loci. We conclude that chromosome 17 does not encode a major FMF susceptibility gene for some of the families, nor does it encode a disease-modifying gene. Rather, it would appear that linkage to chromosome 17 is a ''false positive'' (type I) error. These results reemphasize the fact that a lod score of 3.0 corresponds to a posterior probability of linkage of 95%, with an attendant 1 in 20 chance of observing a false positive. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BLDG 6,ROOM 112,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,DEPT MED F,IL-52621 TEL HASHOMER,ISRAEL. TEL AVIV UNIV,WOLFSON HOSP,IL-69978 TEL AVIV,ISRAEL. CHAIM SHEBA MED CTR,DEPT PEDIAT,IL-52621 TEL HASHOMER,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 32 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 1993 VL 91 IS 6 BP 527 EP 534 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA LQ228 UT WOS:A1993LQ22800002 PM 8340105 ER PT J AU OHARA, BF SMITH, SS BIRD, G PERSICO, AM SUAREZ, BK CUTTING, GR UHL, GR AF OHARA, BF SMITH, SS BIRD, G PERSICO, AM SUAREZ, BK CUTTING, GR UHL, GR TI DOPAMINE-D(2)RECEPTOR RFLPS, HAPLOTYPES AND THEIR ASSOCIATION WITH SUBSTANCE USE IN BLACK AND CAUCASIAN RESEARCH VOLUNTEERS SO HUMAN HEREDITY LA English DT Article DE LINKAGE DISEQUILIBRIUM; FOUNDER EFFECTS; HUMAN GENETICS; ALCOHOLISM; SUBSTANCE ABUSE ID DOPAMINE-D2 RECEPTOR GENE; DNA POLYMORPHISMS; ALLELIC ASSOCIATION; CONTINGENCY-TABLES; ALCOHOLISM; LINKAGE; LOCUS AB Alleles of the dopamine D2 receptor gene are distinguished by polymorphic A and B TaqI sites approximately 10 kb 3' to the final exon and bordering the second exon, respectively. These alleles have been reported to be more prevalent in heavy substance users than in control populations in several, although not all studies. Meta-analyses of combined data from available work support significant association. Two competing hypotheses could explain this association: (1) the A1 and B1 RFLPs are in linkage disequilibrium with a functional allelic determinant that in some way influences behavior; (2) the affected subjects are drawn disproportionately from populations stratified on the basis of, for example, ethnicity that happen to have higher A1 and B1 RFLP frequencies. We report here data collected from 616 substance-abusing and control individuals that document substantial differences in A1 RFLP frequencies between white and black Americans, the almost exclusive presence of the A3 RFLP in blacks, and low frequencies of rare A4 and B3 RFLPs. In blacks, neither the A1 nor B1 RFLPs display association with substance use, while white individuals display significant association with polysubstance use. When expressed as a percent of the maximum possible disequilibrium, both white and black individuals display strong linkage disequilibrium between these loci, although blacks display many more A1/B2 chromosomes. These racial differences in TaqI RFLP haplotypes underscore the need for caution in interpreting allelic associations when careful matching for ethnicity has not been performed. C1 NIDA, MOLEC NEUROBIOL ADDICT RES CTR, BALTIMORE, MD USA. WASHINGTON UNIV, SCH MED, DEPT PSYCHIAT, ST LOUIS, MO 63110 USA. WASHINGTON UNIV, SCH MED, DEPT GENET, ST LOUIS, MO 63110 USA. JOHNS HOPKINS UNIV, DEPT PEDIAT & MED, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, DEPT NEUROSCI & NEUROL, BALTIMORE, MD 21218 USA. RP OHARA, BF (reprint author), STANFORD UNIV, DEPT BIOL SCI, STANFORD, CA 94305 USA. FU NHLBI NIH HHS [HL41035]; NIAAA NIH HHS [AA08401]; NIMH NIH HHS [MH31302] NR 35 TC 96 Z9 96 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 EI 1423-0062 J9 HUM HERED JI Hum. Hered. PD JUL-AUG PY 1993 VL 43 IS 4 BP 209 EP 218 DI 10.1159/000154133 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA LK065 UT WOS:A1993LK06500002 PM 8102114 ER PT J AU RICHARDS, FM PHIPPS, ME LATIF, F YAO, M CROSSEY, PA FOSTER, K LINEHAN, WM AFFARA, NA LERMAN, MI ZBAR, B FERGUSONSMITH, MA MAHER, ER AF RICHARDS, FM PHIPPS, ME LATIF, F YAO, M CROSSEY, PA FOSTER, K LINEHAN, WM AFFARA, NA LERMAN, MI ZBAR, B FERGUSONSMITH, MA MAHER, ER TI MAPPING THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE - IDENTIFICATION OF GERMLINE DELETIONS BY PULSED-FIELD GEL-ELECTROPHORESIS SO HUMAN MOLECULAR GENETICS LA English DT Article ID LINKAGE ANALYSIS; SMALL REGION; CHROMOSOME-3P AB Von Hippel - Lindau (VHL) disease is a dominantly inherited familial cancer syndrome in which affected individuals have a greatly increased predisposition to the development of haemangioblastomas of the central nervous system and retina, renal cell carcinoma and phaeochromocytoma. The VHL gene has been mapped to chromosome 3p25 - p26 by genetic linkage studies and we have previously demonstrated that the VHL gene is tightly linked to the D3S601 locus (Zmax = 18.86 at theta = 0.0) suggesting that D3S601 maps close to the VHL disease gene. We have constructed a long range physical map around D3S601 and screened 91 VHL patients from 80 kindreds for germline rearrangements using pulsed field gel electrophoresis. Two patients showed abnormal fragments in Mlul digested DNA probed with D3S601. Further analysis was consistent with both patients having germline deletions (approximately 120 kb and 50 kb) telomeric to D3S601. These results have (i) established the position of the VHL disease gene with respect to D3S601, (ii) refined the localisation of the VHL disease gene to a small region (approximately 50 kb) of chromosome 3p25-p26 and (iii) excluded the plasma membrane Ca++-transporting ATPase isoform 2 (PMCA-2) gene as a candidate gene for VHL disease. C1 UNIV CAMBRIDGE,ADDENBROOKES HOSP,DEPT PATHOL,BOX 134,HILLS RD,CAMBRIDGE CB2 2QQ,ENGLAND. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. NCI,SURG BRANCH,BETHESDA,MD 20892. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 16 TC 39 Z9 39 U1 1 U2 8 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1993 VL 2 IS 7 BP 879 EP 882 DI 10.1093/hmg/2.7.879 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LM668 UT WOS:A1993LM66800008 PM 8364570 ER PT J AU LAUBACH, VE RYAN, WJ BRANTLY, M AF LAUBACH, VE RYAN, WJ BRANTLY, M TI CHARACTERIZATION OF A HUMAN ALPHA-1-ANTITRYPSIN NULL ALLELE INVOLVING ABERRANT MESSENGER-RNA SPLICING SO HUMAN MOLECULAR GENETICS LA English DT Article ID DEFICIENCY; GENE; MUTATION; SITE; DNA; EXPRESSION; DISEASE; VARIANT; DEFECT; ACID AB Alpha1-Antitrypsin (alpha1AT) is a major protease inhibitor present in high concentrations in the plasma. Inheritance of alpha1AT deficiency or null alleles (alleles associated with no detectable serum alpha1AT) is associated with an increased risk for emphysema. In contrast to beta-degrees-thalassemia variants in which RNA splicing and promoter mutations constitute more than 40% of beta-degrees-thalassemia variants, all nine alpha1AT null variants identified are the result of mutations involving the protein coding region of the alpha1AT gene. During routine screening of individuals applying for enrollment in the USA alpha1AT Deficiency Registry we identified an individual with emphysema and a Protease Inhibitor (PI*) type heterozygous for a novel alpha1AT null allele. Direct DNA sequencing of this individual's alpha1AT alleles demonstrated one normal and one novel allele, designated PI*QOwest, characterized by a single G --> T base substitution at position 1 of intron II, a highly conserved nucleotide position in vertebrate splice donor sites. Metabolic labeling of NIH-3T3 cells transfected with a plasmid vector containing an alpha1AT minigene with the QOwest mutation demonstrated an absence of detectable immunoprecipitable alpha1AT confirming that the G --> T mutation is responsible for the observed null phenotype. QOwest al AT minigene transfected cells expressed 25 - 1 00 fold less alpha1AT mRNA than a normal control. DNA sequencing of polymerase chain reaction amplified mRNA obtained from transfected cells demonstrated the use of a cryptic splice site 84 bases upstream from the normal splice site. Translation of this sequence would result in an in-frame deletion of amino acids Gly164 to Lys191, corresponding structurally to alpha-helix F and beta-sheet 3A of the alpha1AT protein. Identification of alpha1AT QOwest represents the first splicing mutation observed in the human alpha1AT gene and add errors of RNA processing to the growing list of mechanisms responsible for the alpha1AT null phenotype. C1 NICHHD,HUMAN GENET BRANCH,GENET DISORDERS SECRETED PROT UNIT,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892. RI Laubach, Victor/E-8818-2015 OI Laubach, Victor/0000-0001-9673-5383 NR 27 TC 13 Z9 13 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1993 VL 2 IS 7 BP 1001 EP 1005 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LM668 UT WOS:A1993LM66800026 PM 8364536 ER PT J AU YOKOTANI, N DOI, K WENTHOLD, RJ WADA, K AF YOKOTANI, N DOI, K WENTHOLD, RJ WADA, K TI NONCONSERVATION OF A CATALYTIC RESIDUE IN A DIPEPTIDYL AMINOPEPTIDASE IV-RELATED PROTEIN ENCODED BY A GENE ON HUMAN CHROMOSOME-7 SO HUMAN MOLECULAR GENETICS LA English DT Note ID PEPTIDASE-IV; PROTEOLYTIC-ENZYMES; CDNA; SEQUENCE; CLONING; DNA; IDENTIFICATION; INHIBITORS C1 NIDOCD,NEUROCHEM LAB,BETHESDA,MD 20892. NR 25 TC 36 Z9 38 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1993 VL 2 IS 7 BP 1037 EP 1039 DI 10.1093/hmg/2.7.1037 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LM668 UT WOS:A1993LM66800032 PM 8103397 ER PT J AU XIAO, H IDE, SE MERRIL, CR POLYMEROPOULOS, MH AF XIAO, H IDE, SE MERRIL, CR POLYMEROPOULOS, MH TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE D11S982E LOCUS SO HUMAN MOLECULAR GENETICS LA English DT Note C1 ST ELIZABETH HOSP,NATL INST MENTAL HLTH NEUROSCI CTR,ROOM 131,WASHINGTON,DC 20032. NR 2 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL PY 1993 VL 2 IS 7 BP 1081 EP 1081 DI 10.1093/hmg/2.7.1081-a PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LM668 UT WOS:A1993LM66800054 PM 8364557 ER PT J AU SANTINI, F BEAVEN, MA AF SANTINI, F BEAVEN, MA TI NONSELECTIVE ACTIONS OF HERBIMYCIN-A SO IMMUNOLOGY TODAY LA English DT Letter ID CELLS RP SANTINI, F (reprint author), NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD JUL PY 1993 VL 14 IS 7 BP 369 EP 370 DI 10.1016/0167-5699(93)90239-H PG 2 WC Immunology SC Immunology GA LN043 UT WOS:A1993LN04300011 PM 8363729 ER PT J AU FAHEY, BJ BEEKMANN, SE SCHMITT, JM FEDIO, JM HENDERSON, DK AF FAHEY, BJ BEEKMANN, SE SCHMITT, JM FEDIO, JM HENDERSON, DK TI MANAGING OCCUPATIONAL EXPOSURES TO HIV-1 IN THE HEALTH-CARE WORKPLACE SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS C1 NIH, CTR CLIN, HOSP EPIDEMIOL SERV, BETHESDA, MD 20892 USA. NIH, CTR CLIN, DIV SAFETY, OCCUPAT MED SERV, BETHESDA, MD 20892 USA. NIH, CTR CLIN, OFF DIRECTOR, BETHESDA, MD 20892 USA. NR 10 TC 9 Z9 9 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X EI 1559-6834 J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUL PY 1993 VL 14 IS 7 BP 405 EP 412 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA LL108 UT WOS:A1993LL10800010 PM 8354872 ER PT J AU MILLER, RH BUKH, J PURCELL, RH AF MILLER, RH BUKH, J PURCELL, RH TI IMPORTANCE OF THE POLYMERASE CHAIN-REACTION IN THE STUDY OF HEPATITIS-VIRUS INFECTION SO INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH LA English DT Review DE HEPATOCELLULAR CARCINOMA; HEMOPHILIA; FULMINANT HEPATITIS; CHRONIC HEPATITIS ID NON-B-HEPATITIS; C VIRAL-RNA; POSTTRANSFUSION NON-A; RECOMBINANT IMMUNOBLOT ASSAY; FULMINANT NON-A; BLOOD-DONORS; HEPATOCELLULAR-CARCINOMA; LIVER-TISSUES; HCV-RNA; VERTICAL TRANSMISSION AB Recently, the principal etiological agent of parenterally transmitted non-A, non-B hepatitis was molecularly cloned from the plasma of an experimentally infected chimpanzee and has been named hepatitis C virus. Determination of the complete nucleotide sequence of the hepatitis C virus genome was a crucial step in preparing the way for future study of this medically important human pathogen. Due to the very low concentration of virus in serum, amplification of viral RNA sequences by reverse transcription and polymerase chain reaction is the only practical method currently available for demonstrating viremia in patients with hepatitis C virus infection. This review examines the pivotal role of the polymerase chain reaction in understanding the biology of hepatitis C virus. RP MILLER, RH (reprint author), NIAID,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 96 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-5437 J9 INT J CLIN LAB RES JI Int. J. Clin. Lab. Res. PD JUL PY 1993 VL 23 IS 3 BP 139 EP 145 DI 10.1007/BF02592298 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LP124 UT WOS:A1993LP12400004 PM 8400334 ER PT J AU BREWERTON, TD GEORGE, MS AF BREWERTON, TD GEORGE, MS TI IS MIGRAINE RELATED TO THE EATING DISORDERS SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID BULIMIA-NERVOSA; ANOREXIA-NERVOSA; YOUNG-ADULTS; EPIDEMIOLOGY; HEADACHES; WOMEN AB Migraine and the eating disorders, particularly bulimia nervosa, share some common demographics, phenomenology, psychopathology, and treatments. Bulimics also appear to be more sensitive to the induction of severe migrainous headaches than controls following challenge with the 5-HT agonist, m-chlorophenylpiperazine (m-CPP), but not placebo or L-tryptophan. This supports a common pathophysiological relationship involving postsynaptic 5-HT dysfunction between these disorders. In order to further explore the possible relationship between eating disorders and migraine, we administered a modified version of the Diagnostic Survey of the Eating Disorders (DSED) and the Eating Disorders Inventory (EDI) to a group of female migraine patients attending the Medical University of South Carolina (MUSC) Neurology Clinic (n = 34). Of the 34 migraine patients surveyed, 88% reported dieting behavior, 59% reported binge eating, and 26% reported self-induced vomiting during their lifetimes. Compared to the responses of a group of normal female controls (n = 577), patients with migraine had elevated scores on four of the eight subscales of the EDI: Body Dissatisfaction (p less-than-or-equal-to .02), Perfectionism (p less-than-or-equal-to .01), Interpersonal Distrust (p less-than-or-equal-to .02), and Ineffectiveness (p less-than-or-equal-to .06). These findings support the hypothesis that common pathophysiological mechanisms, perhaps involving 5-HT dysregulation, may be involved in these two disorders. (c) 1993 by John Wiley & Sons, Inc. C1 NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. RP BREWERTON, TD (reprint author), MED UNIV S CAROLINA, INST PSYCHIAT, EATING DISORDERS PROGRAM, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. NR 34 TC 23 Z9 23 U1 2 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 1993 VL 14 IS 1 BP 75 EP 79 DI 10.1002/1098-108X(199307)14:1<75::AID-EAT2260140110>3.0.CO;2-D PG 5 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA LJ738 UT WOS:A1993LJ73800009 PM 8339102 ER PT J AU GARRISON, RJ KANNEL, WB AF GARRISON, RJ KANNEL, WB TI A NEW APPROACH FOR ESTIMATING HEALTHY BODY WEIGHTS SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE BODY WEIGHT; ADIPOSE TISSUE; SKINFOLD THICKNESS; CARDIOVASCULAR DISEASES ID LEFT-VENTRICULAR MASS; BLOOD-PRESSURE; FRAMINGHAM; ASSOCIATION; CHOLESTEROL AB Optimal body weight standards have most often been based on the relationship of relative weight to all cause mortality. This report proposes a strategy based on a more direct measure of adiposity, subscapular skinfolds and cardiovascular disease risk factors, rather than mortality. This approach provides a means for determining standards that are consistent with optimum cardiovascular health without the lengthy follow-up required for mortality studies. The report utilizes data on 2447 non-smoking men and women aged 20-59 years. Seven cardiovascular disease risk factors were significantly related to subscapular skinfold thickness in both sexes in an unfavourable direction. The optimal subscapular skinfolds based on these risk factors for 20-39 year olds were determined to be below 12 mm for men and 15 mm for women. Men and women who had subscapular skinfolds at or below the optimal level had a mean body mass index of 22.6 kg/m2 and 21.1 kg/m2 for men and women, respectively. The probability of being above the optimum adiposity rises rapidly across body mass index levels above 20 kg/m2 and plateaus at above 0.90 in both men and women with body mass index above 24 kg/m2. Thus, screening for above optimal adiposity is necessary only in individuals with body mass index at or below 24 kg/m2. C1 BOSTON UNIV, SCH MED, EVANS MEM DEPT CLIN RES, PREVENT MED & EPIDEMIOL SECT, BOSTON, MA 02118 USA. RP GARRISON, RJ (reprint author), NHLBI, DIV EPIDEMIOL & CLIN APPLICAT, EPIDEMIOL & BIOMETRY PROGRAM, BETHESDA, MD 20892 USA. NR 24 TC 51 Z9 51 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 EI 1476-5497 J9 INT J OBESITY JI Int. J. Obes. PD JUL PY 1993 VL 17 IS 7 BP 417 EP 423 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA LK185 UT WOS:A1993LK18500007 PM 8395477 ER PT J AU WHITCOMB, RF CHASTEL, C ABALAINCOLLOC, M STEVENS, C TULLY, JG ROSE, DL CARLE, P BOVE, JM HENEGAR, RB HACKETT, KJ CLARK, TB KONAI, M WILLIAMSON, DL AF WHITCOMB, RF CHASTEL, C ABALAINCOLLOC, M STEVENS, C TULLY, JG ROSE, DL CARLE, P BOVE, JM HENEGAR, RB HACKETT, KJ CLARK, TB KONAI, M WILLIAMSON, DL TI SPIROPLASMA-CANTHARICOLA SP-NOV, FROM CANTHARID BEETLES (COLEOPTERA, CANTHARIDAE) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID MOSQUITOS; FRANCE; MOLLICUTES; GENUS AB Spiroplasma strain CC-1T, isolated from the gut of the soldier beetle Cantharis carolinus, was serologically distinct from other spiroplasma species, groups, and subgroups. Cells of strain CC-1T were shown by light microscopy to be helical, motile filaments. Electron microscopy showed that the cells were bounded by a single cytoplasmic membrane, with no evidence of a cell wall. The organism was insensitive to penicillin. Strain CC-1T grew well in SM-1, M1D, and SP-4 liquid media under aerobic or anaerobic conditions. The strain also grew in 1% serum fraction medium. Optimal growth occurred at 32-degrees-C, with a doubling time of 2.6 h, but the strain muitiplied at temperatures of 10 to 37-degrees-C. Strain CC-1T produced acid from glucose but hydrolyzed neither arginine nor urea. The guanine-plus-cytosine (G+C) content of the DNA was 26 +/- 1 mol%. Other uncloned isolates from C. carolinus exhibited similar or identical serological patterns. On the basis of the data presented here, strain CC-1T (= ATCC 43207), previously proposed as the representative strain of subgroup XVI-1, is designated the type strain of a new species, Spiroplasma cantharicola. C1 INRA,BIOL CELLULAIRE & MOLEC LAB,F-33883 VILLENAVE DORNON,FRANCE. TUSKEGEE UNIV,DEPT BIOL,TUSKEGEE,AL 36088. NIAID,FREDERICK CANC RES FACIL,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21702. SUNY,DEPT ANAT SCI,STONY BROOK,NY 11794. FAC MED BREST,F-29285 BREST,FRANCE. RP WHITCOMB, RF (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705, USA. NR 38 TC 4 Z9 4 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 421 EP 424 PG 4 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200004 ER PT J AU BEATI, L PETER, O BURGDORFER, W AESCHLIMANN, A RAOULT, D AF BEATI, L PETER, O BURGDORFER, W AESCHLIMANN, A RAOULT, D TI CONFIRMATION THAT RICKETTSIA-HELVETICA SP-NOV - IS A DISTINCT SPECIES OF THE SPOTTED-FEVER GROUP OF RICKETTSIAE SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID CENTRIFUGATION; STRAINS; IMMUNOFLUORESCENCE; IDENTIFICATION; PROTEINS AB We propose the name Rickettsia helvetica sp. nov. for a rickettsial serotype of unknown pathogenicity isolated in 1979 in Switzerland from Ixodes ricinus ticks and designated the Swiss agent. The growth characteristics and the results of microimmunofluorescence serologic typing, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blotting (immunoblotting) with specific mice sera, and a polymerase chain reaction followed by restriction fragment length polymorphism analysis confirmed previously reported preliminary findings which suggested that this rickettsia, to which a name was given provisionally, does represent a new member of the spotted fever group of rickettsiae. The type strain is C3 (Reference Center for Rickettsioses, Marseille, France). C1 FAC MED MARSEILLE,UNITE RICKETTSIES,27 BLVD JEAN MOULIN,F-13385 MARSEILLE,FRANCE. HOP VALAISANS,INST CENT,CH-1950 SION,SWITZERLAND. UNIV NEUCHATEL,INST ZOOL,CH-2000 NEUCHATEL,SWITZERLAND. NIH,ROCK MT LABS,HAMILTON,MT 59840. NR 23 TC 69 Z9 73 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 521 EP 526 PG 6 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200018 PM 8102245 ER PT J AU ROSE, DL TULLY, JG BOVE, JM WHITCOMB, RF AF ROSE, DL TULLY, JG BOVE, JM WHITCOMB, RF TI A TEST FOR MEASURING GROWTH-RESPONSES OF MOLLICUTES TO SERUM AND POLYOXYETHYLENE SORBITAN SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID SP-NOV; FIELD ELECTROPHORESIS; ACHOLEPLASMA; CLASSIFICATION; REQUIREMENT; MYCOPLASMAS; SURFACES; FLOWERS AB A test is described that is useful for characterizing mollicutes in terms of the ability to maintain growth in medium containing 15 to 20% fetal bovine serum or in serum-free media with or without 0.04% Tween 80 (polyoxyethylene sorbitan). Representative Acholeplasma species maintained growth in serum-free medium, and about half of the strains tested grew well in Tween 80-supplemented medium. Representative Mycoplasma and Entomoplasma species did not maintain growth in either serum-free medium alone or when Tween 80 was added. Spiroplasma species and group representatives generally failed to sustain growth in serum-free medium with or without Tween 80, but at least four of the spiroplasmas tested maintained growth in serum-free medium. The representative Mesoplasma species grew in serum-free media only when Tween 80 was added, as did Mycoplasma lactucae. Although the test has obvious determinative uses for members of the class Mollicutes, it does not supplant the conventional methodology for assaying the cholesterol requirements of these organisms. C1 NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,FREDERICK,MD 21702. INRA,BIOL CELLULAIRE & MOLEC LAB,F-33883 VILLENAVE DORNON,FRANCE. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. USDA,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. NR 30 TC 35 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 527 EP 532 PG 6 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200019 PM 8347511 ER PT J AU PANANGALA, VS STRINGFELLOW, JS DYBVIG, K WOODARD, A SUN, F ROSE, DL GRESHAM, MM AF PANANGALA, VS STRINGFELLOW, JS DYBVIG, K WOODARD, A SUN, F ROSE, DL GRESHAM, MM TI MYCOPLASMA-COROGYPSI SP-NOV, A NEW SPECIES FROM THE FOOTPAD ABSCESS OF A BLACK VULTURE, CORAGYPS-ATRATUS SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID SEQUENCE; PULMONIS AB Strain BV1 was isolated from the exudate of the footpad abscess of a black vulture (Coragyps atratus). The colonies had a ''fried-egg'' appearance consistent with that of mycoplasmal species. Electron microscopic examination of the cells revealed irregular elongated or elliptical forms and smaller circular budding processes. Profuse growth was observed in Frey medium supplemented with 20% swine serum at 37-degrees-C in a humidified atmosphere of 10% CO2 and air. Typical of mycoplasma, strain BV1 required sterol for growth and catabolized glucose but did not hydrolyze arginine or urea. The guanine-plus-cytosine content of the DNA was 28 mol%. The organism demonstrated the ability to hemolyze, absorb onto, and agglutinate the erythrocytes from several animal species. Strain BV1 was serologically unrelated bv the growth inhibition test to previously established Mycoplasma, Acholeplasma, Entomoplasma, and Mesoplasma species, as well as to strains belonging to these genera but not identified to species level. Moreover, BV1 had a 16S rRNA gene with a nucleotide sequence distinct from reported sequences of other mycoplasmas. This organism represents a new species for which the name Mycoplasma corogypsi is proposed. Strain BV1 (ATCC 51148T) is the type strain of Mycoplasma corogypsi sp. nov. C1 UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT COMPARAT MED,BIRMINGHAM,AL 35294. NIAID,FREDERICK CANC RES & DEV CTR,MOLEC MICROBIOL LAB,MYCOPLASMA SECT,FREDERICK,MD 21712. RP PANANGALA, VS (reprint author), AUBURN UNIV,COLL VET MED,DEPT PATHOBIOL,AUBURN,AL 36849, USA. FU NCI NIH HHS [CA13148]; NIAID NIH HHS [AI27767, AI25640] NR 38 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 585 EP 590 PG 6 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200026 PM 8347515 ER PT J AU BONNET, F SAILLARD, C BOVE, JM LEACH, RH ROSE, DL COTTEW, GS TULLY, JG AF BONNET, F SAILLARD, C BOVE, JM LEACH, RH ROSE, DL COTTEW, GS TULLY, JG TI DNA RELATEDNESS BETWEEN FIELD ISOLATES OF MYCOPLASMA F38-GROUP, THE AGENT OF CONTAGIOUS CAPRINE PLEUROPNEUMONIA, AND STRAINS OF MYCOPLASMA-CAPRICOLUM SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; PAGE PROTEIN-PATTERNS; MYCOIDES CLUSTER; ELECTROPHORETIC ANALYSIS; NUMERICAL-ANALYSIS; F38; ANTIBODY; GOATS; SHEEP; TESTS AB DNA-DNA hybridization experiments were carried out in order to clarify the taxonomic relationships between the F38 group of caprine mycoplasmas, the established etiologic agents of classical contagious caprine pleuropneumonia, and Mycoplasma capricolum, an organism associated with septicemia, arthritis, and mastitis in goats and sheep. The taxonomic status of the F38 group has been uncertain, principally because of the serological, genomic, and other properties which it shares with M. capricolum. Tritium-labeled DNAs from the M. capricolum type strain (California kid) and from prototype strain F38 were hybridized with unlabeled DNAs from these two strains and from four other isolates belonging to each group. The results showed consistent DNA relatedness values of about 70% between the F38 and M. capricolum groups, compared with levels of relatedness of about 90 and 85%, respectively, for the strains within each group. In addition, the results of comparisons of these 10 strains in which growth inhibition and immunofluorescence tests were used confirmed the previously reported serological relationships between the two groups and reinforced other observations concerning their shared genomic and cell membrane characteristics, indicating that there is a close taxonomic relationship. However, as the 70% DNA relatedness values between the M. capricolum and F38 groups also indicate a degree of genomic difference inconsistent with a relationship at the species level, we conclude that our findings support previous proposals for classification of the F38 group as a subspecies of M. capricolum. In view of the prospective diagnostic problems, particularly those arising from the serological similarities of two putative subspecies, we believe that further studies should be performed to define additional phenotypic and genotypic properties that would allow more rapid and specific differentiation of the F38 group mycoplasmas. C1 INRA,BIOL CELLULAIRE & MOLEC LAB,DOMAINE GRANDE FERRADE,F-33883 VILLENAVE DORNON,FRANCE. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. PUBL HLTH LAB SERV,NATL COLLECT TYPE CULTURES,MYCOPLASMA LAB,LONDON NW9 5HT,ENGLAND. NIAID,MYCOPLASMA SECT,FREDERICK,MD 21702. CSIRO,DIV ANIM HLTH,PARKVILLE,VIC 3052,AUSTRALIA. NR 57 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 597 EP 602 PG 6 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200028 PM 8347516 ER PT J AU GAYDOS, CA PALMER, L QUINN, TC FALKOW, S EIDEN, JJ AF GAYDOS, CA PALMER, L QUINN, TC FALKOW, S EIDEN, JJ TI PHYLOGENETIC RELATIONSHIP OF CHLAMYDIA-PNEUMONIAE TO CHLAMYDIA-PSITTACI AND CHLAMYDIA-TRACHOMATIS AS DETERMINED BY ANALYSIS OF 16S-RIBOSOMAL DNA-SEQUENCES SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Note ID STRAIN TWAR; IDENTIFICATION; AGENT AB The 16S ribosomal DNA sequence of Chlamydia pneumoniae was determined and compared with the corresponding gene sequences of Chlamydia psittaci and Chlamydia trachomatis. C. pneumoniae has been reported to exhibit little chromosomal DNA homology with the other chlamydial species, and its phylogenetic relationships within the genus Chlamydia have not been described. A polymerase chain reaction was employed to determine the 16S rRNA gene sequence of C pneumoniae. Ten primers from the C. psittaci sequences were used to amplify a C. pneumoniae template in overlapping segments of the gene. Sequence data for 1,554 bases indicated that the levels of homology of C. pneumoniae with C. psittaci and C. trachomatis were 96.19 and 94.07%, respectively. These data support the results of previous biochemical and developmental studies indicating that C. pneumoniae is more closely related to C. psittaci than to C. trachomatis. C1 JOHNS HOPKINS UNIV,DEPT PEDIAT,DIV PEDIAT INFECT DIS,BALTIMORE,MD 21205. STANFORD UNIV,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV CALIF DAVIS,SCH VET MED,DEPT MED,DAVIS,CA 95616. NIAID,BETHESDA,MD 20892. RP GAYDOS, CA (reprint author), JOHNS HOPKINS UNIV,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205, USA. RI Gaydos, Charlotte/E-9937-2010 NR 21 TC 25 Z9 28 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 610 EP 612 PG 3 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200031 PM 8347519 ER PT J AU TULLY, JG BOVE, JM LAIGRET, F WHITCOMB, RF AF TULLY, JG BOVE, JM LAIGRET, F WHITCOMB, RF TI REVISED TAXONOMY OF THE CLASS MOLLICUTES - PROPOSED ELEVATION OF A MONOPHYLETIC CLUSTER OF ARTHROPOD-ASSOCIATED MOLLICUTES TO ORDINAL RANK (ENTOMOPLASMATALES ORD-NOV), WITH PROVISION FOR FAMILIAL RANK TO SEPARATE SPECIES WITH NONHELICAL MORPHOLOGY (ENTOMOPLASMATACEAE FAM-NOV) FROM HELICAL SPECIES (SPIROPLASMATACEAE), AND EMENDED DESCRIPTIONS OF THE ORDER MYCOPLASMATALES, FAMILY MYCOPLASMATACEAE (VOL 43, PG 383, 1993) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Correction, Addition C1 INRA,BIOL CELLULAIRE & MOLEC LAB,F-33883 VILLENAVE DORNON,FRANCE. UNIV BORDEAUX 2,F-33883 VILLENAVE DORNON,FRANCE. USDA,INSECT BIOCONTROL LAB,BELTSVILLE,MD 20705. RP TULLY, JG (reprint author), NIAID,FREDERICK CANC RES & DEV CTR,MYCOPLASMA SECT,FREDERICK,MD 21702, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD JUL PY 1993 VL 43 IS 3 BP 630 EP 630 PG 1 WC Microbiology SC Microbiology GA LM382 UT WOS:A1993LM38200036 ER PT J AU PODELL, M OGLESBEE, M MATHES, L KRAKOWKA, S OLMSTEAD, R LAFRADO, L AF PODELL, M OGLESBEE, M MATHES, L KRAKOWKA, S OLMSTEAD, R LAFRADO, L TI AIDS-ASSOCIATED ENCEPHALOPATHY WITH EXPERIMENTAL FELINE IMMUNODEFICIENCY VIRUS-INFECTION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE FELINE IMMUNODEFICIENCY VIRUS; CENTRAL NERVOUS SYSTEM; ENCEPHALOPATHY; ELECTROENCEPHALOGRAPHY; EVOKED POTENTIALS; CEREBROSPINAL FLUID; NEUROPATHOLOGY; PEDIATRICS ID AUDITORY-EVOKED-RESPONSE; T-LYMPHOTROPIC VIRUS; MULTIPLE-SCLEROSIS; DEMENTIA COMPLEX; NERVOUS-SYSTEM; HIV-INFECTION; CATS; BRAIN; LEUKOENCEPHALOPATHY; NEUROPATHOLOGY AB Experimental intravenous challenge of 8-week-old kittens with the feline immunodeficiency virus Maryland isolate (FIV-MD) was investigated for its ability to infect the central nervous system (CNS) and induce neurologic abnormalities. Six cats were inoculated with 1,000 TCID50 units of FIV-MD isolate, with six age-matched cats serving as uninfected controls. Clinical and immunological evaluation documented that challenged cats developed immunodeficiency and growth delay. Neurologic examination revealed an abnormal stereotypic motor behavior consisting of repetitive, compulsive roaming that developed as early as 4 weeks postinfection (PI) and persisted throughout the 16-month study in three cats. Serial neuroelectrodiagnostic evaluation revealed persistent abnormal electroencephalographic recordings in three infected cats. Serial evoked potential (EP) recordings at 3, 8, and 12 months PI demonstrated significantly prolonged interpeak latencies III-V at 3 months PI and I-III at 12 months PI for brainstem EP recordings. Alterations of visual EPs were detected only at the 3-month time period. Retinocortical time, however, was significantly different from that in control cats at 3 and 12 months PI. Magnetic resonance imaging evaluation of FIV-MD-infected cats at 12 months PI revealed cortical atrophy, mild ventricular enlargement, and discrete white matter lesions. At 16 months PI, however, histopathological examination of brain tissue indicated only mild lesions limited to satellitosis and perivascular lymphocytic infiltrates. Virus was detected in the CNS by reverse transcriptase, immunofluorescence, and antigen capture. Evaluation of the cerebrospinal fluid revealed intrathecal anti-FIV-MD antibody despite lack of detectable viremia in five challenged cats. Collectively, these findings demonstrate the induction of virus-associated neurologic disease following parenteral FIV challenge in conjunction with an immunodeficiency state. The nature of the nervous system infection is analogous to HIV-1 pediatric encephalopathy. C1 NIH,ROCKVILLE,MD. OHIO STATE UNIV,CTR RETROVIRUS RES,COLUMBUS,OH 43210. OHIO STATE UNIV,DEPT VET PATHOBIOL,COLUMBUS,OH 43210. RP PODELL, M (reprint author), OHIO STATE UNIV,DEPT VET CLIN SCI,601 VERNON THARP ST,COLUMBUS,OH 43210, USA. FU NCI NIH HHS [CA-56295] NR 81 TC 79 Z9 80 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 JUL PY 1993 VL 6 IS 7 BP 758 EP 771 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LH852 UT WOS:A1993LH85200002 PM 8389849 ER PT J AU DEZUBE, BJ PARDEE, AB CHAPMAN, B BECKETT, LA KORVICK, JA NOVICK, WJ CHIURCO, J KASDAN, P AHLERS, CM ECTO, LT CRUMPACKER, CS AF DEZUBE, BJ PARDEE, AB CHAPMAN, B BECKETT, LA KORVICK, JA NOVICK, WJ CHIURCO, J KASDAN, P AHLERS, CM ECTO, LT CRUMPACKER, CS TI PENTOXIFYLLINE DECREASES TUMOR-NECROSIS-FACTOR EXPRESSION AND SERUM TRIGLYCERIDES IN PEOPLE WITH AIDS SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; TUMOR NECROSIS FACTOR; PENTOXIFYLLINE; CYTOKINES; TRIGLYCERIDES ID IMMUNODEFICIENCY-VIRUS TYPE-1; BONE-MARROW TRANSPLANTATION; BLOOD MONONUCLEAR-CELLS; FACTOR-ALPHA; CANCER-PATIENTS; T-CELLS; CACHECTIN; INDUCTION; HYPERTRIGLYCERIDEMIA; REPLICATION AB Tumor necrosis factor-alpha (TNF)-cachectin increases the expression of the human immunodeficiency virus (HIV), reverses the therapeutic efficacy of zidovudine (ZDV), and may contribute to the wasting syndrome. Pentoxifylline (Trental) decreases TNF activity; in cell culture, it decreases HIV replication and down-regulates expression of the HIV long terminal repeat (LTR). Therefore, pentoxifylline was administered to 25 patients with advanced AIDS in this AIDS Clinical Trial Group study (ACTG # 160), the goal of which was to investigate the ability of the drug to decrease TNF expression and HIV replication in this patient population. One patient discontinued drug treatment because of toxicity. Data were analyzed on the 17 patients who completed the 8-week study treatment with pentoxifylline, 400 mg, thrice daily. The median pretreatment CD4+ lymphocyte count was 32 cells/mm3. Fasting serum triglycerides, which have previously been shown to correlate with levels of interferon-alpha and/or TNF, fell on average by 66 mg/dl (p = 0.06). TNF mRNA levels in peripheral blood mononuclear cells fell in 10 of 16 patients (p = 0.02). HIV load decreased and increased significantly in four and one patients, respectively, but did not change in the group as a whole. This study demonstrates the safety of pentoxifylline in AIDS patients and its ability to decrease triglycerides and TNF mRNA levels. C1 BETH ISRAEL HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02215. BETH ISRAEL HOSP,DEPT MED,DIV INFECT DIS,BOSTON,MA 02215. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL 60612. NIAID,DIV AIDS,BETHESDA,MD 20892. ACTG OPERAT OFF,ROCKVILLE,MD. HOECHST ROUSSEL PHARMACEUT PROPRIETARY LTD,SOMERVILLE,NJ 08876. RP DEZUBE, BJ (reprint author), HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CELL GROWTH & REGULAT,D810A,BOSTON,MA 02115, USA. FU NIAID NIH HHS [N0-AI-62534, N0-AI-95030] NR 39 TC 101 Z9 101 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 JUL PY 1993 VL 6 IS 7 BP 787 EP 794 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA LH852 UT WOS:A1993LH85200005 PM 8099612 ER PT J AU MOSIMANN, BL WHITE, MV HOHMAN, RJ GOLDRICH, MS KAULBACH, HC KALINER, MA AF MOSIMANN, BL WHITE, MV HOHMAN, RJ GOLDRICH, MS KAULBACH, HC KALINER, MA TI SUBSTANCE-P, CALCITONIN-GENE-RELATED PEPTIDE, AND VASOACTIVE-INTESTINAL-PEPTIDE INCREASE IN NASAL SECRETIONS AFTER ALLERGEN CHALLENGE IN ATOPIC PATIENTS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE NEUROPEPTIDES; SUBSTANCE-P; CALCITONIN GENE RELATED PEPTIDE; VASOACTIVE INTESTINAL PEPTIDE; ALLERGIC RHINITIS; NASAL SECRETION ID ANGIOTENSIN-CONVERTING ENZYME; VASCULAR-PERMEABILITY; RESPIRATORY-TRACT; MAST-CELLS; NEUROPEPTIDES; CAPSAICIN; RHINITIS; RELEASE; MUCOSA; LUNG AB Background: There is suggestive evidence that neuropeptides participate in allergic reactions. Substance P (SP) and calcitonin gene-related peptide (CGRP) are released by sensory nerves, whereas vasoactive intestinal peptide (VIP) is released mainly by parasympathetic nerves. Both sets of nerves are thought to be stimulated by allergic inflammation. The aim of this study was to assess nasal secretions to determine whether SP CGRP, and VIP were increased after allergen challenge. Methods: Eight patients with allergic rhinitis were challenged nasally with 1 mg histamine or increasing doses of allergen. Nasal lavages were collected into a cocktail of protease inhibitors in order to restrict neuropeptide degradation. Radioimmunoassay for SP CGRP, and VIP were performed on each sample. Results: All patients had immediate clinical reactions to both histamine and allergen challenges, and seven patients experienced a later allergic reaction. After histamine challenge, SP and CGRP did not increase significantly above baseline in the nasal lavages, whereas VIP did (p < 0.02). In contrast, SP, CGRP, and VIP all significantly increased immediately after allergen challenge and returned to baseline within 2 hours. At the clinical peak of the late allergic reaction, SP, but not CGRP or VIP was increased slightly but significantly (p < 0.01). Conclusions: Thus SP CGRP, and VIP are found in nasal secretions after allergen challenge, which confirms that neuropeptides are released in human beings during allergic reactions. The selective stimulation of VIP secretion by histamine challenge suggests that histamine-induced cholinergic reflexes induce the release of VIP. These data support the suggestion that neuropeptides may be partly responsible for some of the nasal symptoms of allergy. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,ROOM 11-C-205,BETHESDA,MD 20892. NR 38 TC 110 Z9 112 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 1993 VL 92 IS 1 BP 95 EP 104 DI 10.1016/0091-6749(93)90043-F PN 1 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA LQ353 UT WOS:A1993LQ35300015 PM 7687608 ER PT J AU KALINER, MA AF KALINER, MA TI HOW THE CURRENT UNDERSTANDING OF THE PATHOPHYSIOLOGY OF ASTHMA INFLUENCES OUR APPROACH TO THERAPY SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID BRONCHIAL HYPERRESPONSIVENESS; BECLOMETHASONE DIPROPIONATE; IMMUNOTHERAPY; SODIUM; RESPONSIVENESS; PATHOGENESIS; RESPONSES; RHINITIS; ADHESION; TRIAL AB Asthma can no longer be equated with bronchospasm; instead, we know now that this disease is due to combinations of mucosal edema and inflammation, increased secretions, and muscle contraction. The appreciation of the contribution of these various causes of airflow obstruction and the role that inflammation plays in asthma dictates that we approach treatment using two parallel modalities: (1) symptomatic drugs that act to relieve the airflow obstruction but have no effects on the underlying causes of the disease (e.g., bronchodilators such as beta-adrenergic agonists, theophylline, and anticholinergic compounds) and (2) specific treatment aimed at preventing or reversing the underlying causes responsible for the disease. Four specific treatments are available today. allergen avoidance, immunotherapy, cromolyn sodium, and inhaled corticosteroids. Management of asthma in the 1990s requires that all patients receive specific treatments intended to reduce the disease processes and that symptomatic treatment be used only as necessary. RP KALINER, MA (reprint author), NIAID,ALLERG DIS SECT,BETHESDA,MD 20892, USA. NR 23 TC 7 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 1993 VL 92 IS 1 BP 144 EP 147 DI 10.1016/0091-6749(93)90096-X PN 2 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA LQ354 UT WOS:A1993LQ35400002 PM 8335861 ER PT J AU BRICKMAN, TJ BARRY, CE HACKSTADT, T AF BRICKMAN, TJ BARRY, CE HACKSTADT, T TI MOLECULAR-CLONING AND EXPRESSION OF HCTB ENCODING A STRAIN-VARIANT CHLAMYDIAL HISTONE-LIKE PROTEIN WITH DNA-BINDING ACTIVITY SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; TRACHOMATIS; POLYMERASE; SEQUENCE; GENE; IDENTIFICATION; PURIFICATION; RECOGNITION AB Two DNA-binding proteins with similarity to eukaryotic histone H1 have been described in Chlamydia trachomatis. In addition to the 18-kDa histone H1 homolog Hc1, elementary bodies of C. trachomatis possess an antigenically related histone H1 homolog, which we have termed Hc2, that varies in apparent molecular mass among strains. We report the molecular cloning, expression, and nucleotide sequence of the hctB gene encoding Hc2 and present evidence for in vivo DNA-binding activity of the expressed product. Expression of Hc2 in Escherichia coli induces a compaction of bacterial chromatin that is distinct from that observed upon Hcl expression. Moreover, isolated nucleoids from Hc2-expressing E. coli exhibit markedly reduced sensitivity to DNase 1. These properties of Hc2 are consistent with a postulated role in establishing the nucleoid structure of elementary bodies. RP NIAID, ROCKY MT LABS, INTRACELLULAR PARASITES LAB, HAMILTON, MT 59840 USA. RI Barry, III, Clifton/H-3839-2012 NR 39 TC 45 Z9 47 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1993 VL 175 IS 14 BP 4274 EP 4281 PG 8 WC Microbiology SC Microbiology GA LM260 UT WOS:A1993LM26000002 PM 7687246 ER PT J AU KARPATI, S AMAGAI, M PRUSSICK, R CEHRS, K STANLEY, JR AF KARPATI, S AMAGAI, M PRUSSICK, R CEHRS, K STANLEY, JR TI PEMPHIGUS-VULGARIS ANTIGEN, A DESMOGLEIN TYPE OF CADHERIN, IS LOCALIZED WITHIN KERATINOCYTE DESMOSOMES SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CELL-ADHESION MOLECULES; CONSTITUTIVE TRANSMEMBRANE GLYCOPROTEIN; NON-EPIDERMAL DESMOSOMES; ULTRASTRUCTURAL-LOCALIZATION; MR-165000 DESMOGLEIN; FOLIACEUS ANTIGENS; AUTOANTIBODIES; IDENTIFICATION; COMPONENT; PROTEIN AB Pemphigus vulgaris antigen (PVA) is a member of the desmoglein subfamily of cadherin cell adhesion molecules. Because autoantibodies in this disease cause blisters due to loss of epidermal cell adhesion, and because desmoglein is found in the desmosome cell adhesion junction, we wanted to determine if PVA is also found in desmosomes. By immunofluorescence, PV IgG bound, in a dotted pattern, to the cell surface of cultured human keratinocytes induced to differentiate with calcium, suggesting junctional staining. However, by preembedding, immunogold electron microscopic studies only slight labeling could be detected in desmosomes, presumably because of difficulty in gold penetration of intact desmosomes. We therefore treated the keratinocytes with 0.01% trypsin in 1 mM calcium, conditions known to preserve cadherin antigenicity but that caused slight separation of desmosomes, before immunogold staining. In this case there was extensive labeling of the extracellular part of desmosomes but not of the interdesmosomal cell membrane which was stained with anti-beta2-microglobulin antibodies. To confirm the specificity of this binding we showed that antibodies raised in rabbits against the extracellular portions of PVA also bound desmosomes in these cultures. In intact mouse epidermis we could also show slight, but specific, immunogold desmosomal labeling with PV IgG. Furthermore, neonatal mice injected with PV IgG affinity purified on PVA showed desmosomal separation with the IgG localized to desmosomal cores. These results indicate that PVA is organized and concentrated within the desmosome where it presumably functions to maintain the integrity of stratifying epithelia. RP KARPATI, S (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,BETHESDA,MD 20892, USA. RI Amagai, Masayuki/K-5325-2013 OI Amagai, Masayuki/0000-0003-3314-7052 NR 40 TC 92 Z9 94 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1993 VL 122 IS 2 BP 409 EP 415 DI 10.1083/jcb.122.2.409 PG 7 WC Cell Biology SC Cell Biology GA LM584 UT WOS:A1993LM58400011 PM 8320263 ER PT J AU LINDHOLM, D CASTREN, E TSOULFAS, P KOLBECK, R BERZAGHI, MD LEINGARTNER, A HEISENBERG, CP TESAROLLO, L PARADA, LF THOENEN, H AF LINDHOLM, D CASTREN, E TSOULFAS, P KOLBECK, R BERZAGHI, MD LEINGARTNER, A HEISENBERG, CP TESAROLLO, L PARADA, LF THOENEN, H TI NEUROTROPHIN-3 INDUCED BY TRIIODOTHYRONINE IN CEREBELLAR GRANULE CELLS PROMOTES PURKINJE-CELL DIFFERENTIATION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; THYROID-HORMONE RECEPTOR; FACTOR MESSENGER-RNA; TYROSINE KINASE RECEPTOR; DEVELOPING RAT-BRAIN; MOLECULAR-CLONING; GENE-EXPRESSION; FACTOR FAMILY; HIPPOCAMPAL-NEURONS; PROTEIN AB Thyroid hormones play an important role in brain development, but the mechanism(s) by which triiodothyronine (T3) mediates neuronal differentiation is poorly understood. Here we demonstrate that T3 regulates the neurotrophic factor, neurotrophin-3 (NT-3), in developing rat cerebellar granule cells both in cell culture and in vivo. In situ hybridization experiments showed that developing Purkinje cells do not express NT-3 mRNA but do express trkC, the putative neuronal receptor for NT-3. Addition of recombinant NT-3 to cerebellar cultures from embryonic rat brain induces hypertrophy and neurite sprouting of Purkinje cells, and upregulates the mRNA encoding the calcium-binding protein, calbindin-28 kD. The present study demonstrates a novel interaction between cerebellar granule neurons and developing Purkinje cells in which NT-3 induced by T3 in the granule cells promotes Purkinje cell differentiation. C1 MAX PLANCK INST PSYCHIAT,DEPT NEUROBIOCHEM,W-8033 MARTINSRIED,GERMANY. NCI,FREDERICK CANC RES FACIL,MOLEC EMBRYOL SECT,FREDERICK,MD 21702. RP LINDHOLM, D (reprint author), MAX PLANCK INST PSYCHIAT,DEPT NEUROCHEM,AM KLOPFERSPITZ 18A,W-8033 MARTINSRIED,GERMANY. RI Castren, Eero/A-4618-2010; Lindholm, Dan/B-3777-2014; Parada, luis/B-9400-2014; OI Tsoulfas, Pantelis/0000-0003-1974-6366 NR 59 TC 157 Z9 157 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1993 VL 122 IS 2 BP 443 EP 450 DI 10.1083/jcb.122.2.443 PG 8 WC Cell Biology SC Cell Biology GA LM584 UT WOS:A1993LM58400014 PM 8320266 ER PT J AU KATO, H FARIA, TN STANNARD, B LEVYTOLEDANO, R TAYLOR, SI ROBERTS, CT LEROITH, D AF KATO, H FARIA, TN STANNARD, B LEVYTOLEDANO, R TAYLOR, SI ROBERTS, CT LEROITH, D TI PARADOXICAL BIOLOGICAL EFFECTS OF OVEREXPRESSED INSULIN-LIKE GROWTH FACTOR-I RECEPTORS IN CHINESE-HAMSTER OVARY CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID FACTOR-I RECEPTOR; TYROSINE KINASE; MUTANT AB One major approach to the study of growth factor receptor action has been to overexpress wild-type or mutant receptors in cultured cells and to evaluate biological responses to exogenous ligand. Studies of this type with insulin and insulin-like growth factor-I (IGF-I) receptors often use Chinese hamster ovary (CHO) cells. We have compared the effect of receptor overexpression in CHO cells and in NIH-3T3 fibroblasts in order to assess the suitability of CHO cells for studies of this nature and the contribution of cell type-specific factors to those responses generally assayed. Overexpression of IGF-I receptors in NIH-3T3 cells resulted in increased sensitivity and maximal responsiveness of thymidine incorporation, 2-deoxyglucose uptake, and phosphatidylinositol-3 (PI3) kinase activation to IGF-I stimulation. In CHO cells, on the other hand, overexpression of either IGF-I or insulin receptors increased the sensitivity of thymidine incorporation to ligand, but maximal responsiveness was unchanged or decreased. Overexpression of the insulin receptor increased sensitivity of glucose uptake and the maximal response of PI3 kinase activation to insulin. Overexpression of the IGF-I receptor did not affect sensitivity or maximal responsiveness of glucose uptake or PI3 kinase activation to IGF-I. These data suggest that IGF-I and insulin signal pathways may differ in CHO cells, and that there may even be divergent IGF-I signaling pathways for short vs. long-term effects. Whether this is a result of differences in the number of endogenous receptors, hybrid receptor formation, or defects in post-receptor signaling, the use of CHO cells to assess receptor function must be approached with caution. (C) 1993 Wiley-Liss, Inc. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 35 TC 18 Z9 18 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1993 VL 156 IS 1 BP 145 EP 152 DI 10.1002/jcp.1041560120 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA LK268 UT WOS:A1993LK26800019 PM 7686165 ER PT J AU MILNE, GWA AF MILNE, GWA TI 1992 ACS SYMPOSIUM ON MODERN METHODS OF SUBSTRUCTURE SEARCHING WASHINGTON, DC, AUGUST 1992 SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Editorial Material RP MILNE, GWA (reprint author), NIH,MED CHEM LAB,BLDG 37,ROOM 5C28,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 8 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JUL-AUG PY 1993 VL 33 IS 4 BP 531 EP 531 DI 10.1021/ci00014a600 PG 1 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA LT185 UT WOS:A1993LT18500001 ER PT J AU NICKLAUS, MC MILNE, GWA ZAHAREVITZ, D AF NICKLAUS, MC MILNE, GWA ZAHAREVITZ, D TI CHEM-X AND CAMBRIDGE - COMPARISON OF COMPUTER-GENERATED CHEMICAL STRUCTURES WITH X-RAY CRYSTALLOGRAPHIC DATA SO JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES LA English DT Article; Proceedings Paper CT SYMP ON STRUCTURE SEARCHING, AT THE 204TH NATIONAL MEETING OF THE AMERICAN CHEMICAL SOC CY AUG 24, 1992 CL WASHINGTON, DC SP AMER CHEM SOC ID INFORMATION AB The structures of a number of molecules as determined by X-ray crystallography have been compared with the structures for the same molecules as calculated by the 3D structure generation program, Chem-X. In the group of molecules examined, ChemModel produced structures that were essentially identical to those based upon X-ray data in 57% of the cases. The corresponding figure for the widely used alternative model builder, CONCORD, was 38%. The superior performance of ChemModel was due entirely to that program's ability to generate multiple structures covering the entire conformational space. C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP INC,FREDERICK,MD 21702. RI Nicklaus, Marc/N-4183-2014 NR 14 TC 13 Z9 13 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0095-2338 J9 J CHEM INF COMP SCI JI J. Chem. Inf. Comput. Sci. PD JUL-AUG PY 1993 VL 33 IS 4 BP 639 EP 646 DI 10.1021/ci00014a019 PG 8 WC Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Chemistry; Computer Science GA LT185 UT WOS:A1993LT18500020 PM 8366147 ER PT J AU ELIA, J WELSH, PA GULLOTTA, CS RAPOPORT, JL AF ELIA, J WELSH, PA GULLOTTA, CS RAPOPORT, JL TI CLASSROOM ACADEMIC-PERFORMANCE - IMPROVEMENT WITH BOTH METHYLPHENIDATE AND DEXTROAMPHETAMINE IN ADHD BOYS SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE HYPERACTIVITY; ACADEMIC PERFORMANCE; STIMULANTS; DEXTROAMPHETAMINE; METHYLPHENIDATE ID ATTENTION-DEFICIT DISORDER; MINIMAL BRAIN DYSFUNCTION; STIMULANT DRUG-TREATMENT; HYPERACTIVE-CHILDREN; UNDERACHIEVING CHILDREN; LEARNING-DISABILITIES; AMPHETAMINE; LEVEL AB Daily academic classroom performance was recorded in a day hospital school using a commonly employed reading and math series as part of an 11-week double-blind, placebo controlled, crossover comparison of dextroamphetamine (d-AMPH) and methylphenidate (MPH) in 33 hyperactive boys. Students attempted more math and reading tasks while on either active drug. The percent correct and the number of attempted problems of the reading series improved with both drugs while the percent correct for the math series occurred with d-AMPH only. No dose-response relationship was found for either stimulant. Moderate, transient adverse effects were common for both drugs. C1 NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. MONTGOMERY CTY PUBL SCH,ROCKVILLE,MD. NR 58 TC 33 Z9 34 U1 3 U2 10 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD JUL PY 1993 VL 34 IS 5 BP 785 EP 804 DI 10.1111/j.1469-7610.1993.tb01071.x PG 20 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA LL001 UT WOS:A1993LL00100011 PM 8340445 ER PT J AU KOSUGI, S BAN, T AKAMIZU, T VALENTE, W KOHN, LD AF KOSUGI, S BAN, T AKAMIZU, T VALENTE, W KOHN, LD TI USE OF THYROTROPIN RECEPTOR (TSHR) MUTANTS TO DETECT STIMULATING TSHR ANTIBODIES IN HYPOTHYROID PATIENTS WITH IDIOPATHIC MYXEDEMA, WHO HAVE BLOCKING TSHR ANTIBODIES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GRAVES-DISEASE; GONADOTROPIN RECEPTORS; IMMUNOGLOBULIN-G; AUTOANTIBODIES; DOMAINS; ASSAY; SITE AB Deletions of residues 295-306, 299-301, and 387-395 of the TSH receptor, as well as point mutations of cysteine 301 or 390 to serine, and tyrosine 385 to phenylalanine or alanine, markedly diminish the ability of a transfected receptor to measure the activity of blocking TSH receptor autoantibodies (TSHRAbs) in patients with idiopathic myxedema and hypothyroidism, but not stimulating TSHRAbs in Graves' patients. This has allowed us to use these mutants to detect stimulating TSHRAb activity in the sera of hypothyroid patients with idiopathic myxedema who have blocking TSHRAbs. In 7 such patients, we show that 50% or more have significant stimulatory activity in cells transfected with mutant receptors, as evidenced by the ability of the immunoglobulin G to directly increase cAMP levels or to enhance the ability of TSH or a Graves' stimulating TSHRAb to increase cAMP levels. Three of the TSH receptor mutants, deletions of residues 295-306 and 387-395 and the point mutation of cysteine 301 to serine, are shown to be particularly useful in these assays and may be useful to clarify the pathogenetic role and clinical significance of stimulating TSHRAbs in patients with autoimmune thyroid disease who also have blocking TSHRAbs. C1 NIDDKD, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. NR 22 TC 45 Z9 45 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1993 VL 77 IS 1 BP 19 EP 24 DI 10.1210/jc.77.1.19 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LL828 UT WOS:A1993LL82800006 PM 8100829 ER PT J AU GOMEZ, MT MAGIAKOU, MA MASTORAKOS, G CHROUSOS, GP AF GOMEZ, MT MAGIAKOU, MA MASTORAKOS, G CHROUSOS, GP TI THE PITUITARY CORTICOTROPH IS NOT THE RATE-LIMITING STEP IN THE POSTOPERATIVE RECOVERY OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS IN PATIENTS WITH CUSHING SYNDROME SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATION TEST; HORMONE; ADRENOCORTICOTROPIN; VASOPRESSIN; SECRETION; CORTISOL; DISEASE; RELEASE AB Patients cured from endogenous Cushing syndrome usually develop postoperative adrenal suppression in the year ensuing surgery. To define whether the pituitary corticotroph is the rate limiting step in the postoperative recovery of this secondary/tertiary form of adrenal insufficiency, we examined surgically cured patients with Cushing syndrome 10 days, 3 months, and 6-12 months after surgery, by administering ovine CRH (oCRH) iv at the dose of 1 mug/kg.h over 24 h. The pituitary corticotroph of these patients responded vigorously to oCRH, with ACTH concentrations reaching above the normal range at all three times of testing. Parallel measurements of cortisol in nonadrenalectomized patients demonstrated subnormal adrenal responsiveness at 10 days and 3 months and normalization at 6-12 months after surgery. The circadian rhythm of ACTH was maintained postoperatively at 10 days and 6-12 months, and the circadian rhythm of cortisol was also present at 6-12 months after surgery, in spite of the constant infusions of pharmacological doses of oCRH, suggesting that factors other than CRH secretion regulate this rhythm. We conclude that the corticotroph is not the rate limiting step in the recovery of the hypothalamic-pituitary-adrenal axis from glucocorticoid-induced adrenal suppression, and that the locus of the defect resides in the hypothalamic CRH neuron and/or its higher regulatory inputs. C1 NICHHD, DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N 262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 23 TC 48 Z9 48 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1993 VL 77 IS 1 BP 173 EP 177 DI 10.1210/jc.77.1.173 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LL828 UT WOS:A1993LL82800035 PM 8392083 ER PT J AU EISENSTEIN, EM JAFFE, JS STROBER, W AF EISENSTEIN, EM JAFFE, JS STROBER, W TI REDUCED INTERLEUKIN-2 (IL-2) PRODUCTION IN COMMON VARIABLE IMMUNODEFICIENCY IS DUE TO A PRIMARY ABNORMALITY OF CD4+ T-CELL DIFFERENTIATION SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE HYPOGAMMAGLOBULINEMIA; T-LYMPHOCYTE; INTERLEUKIN-2 ID HUMAN LYMPHOCYTES-T; GENE-EXPRESSION; ACTIVATION; RECEPTOR AB Common variable immunodeficiency (CVI) is a condition characterized by hypogammaglobulinemia and impaired antibody responses, resulting in recurrent bacterial infections in untreated patients. In addition, affected individuals exhibit an increased incidence of autoimmunity, malignancy, and certain viral infections, suggesting the presence of an underlying generalized immune dysregulation. We have previously described a subgroup of CVI patients in whom T cells within PBMC populations exhibit a selective defect in lymphokine production. IL-2, IL-4, and IL-5 mRNA production was impaired in these patients, while proliferation, IL-2R expression, and c-myc mRNA production were normal. In the present series of experiments, using highly purified CD4+ T cells prepared by negative selection, we show that this lymphokine production defect is a primary abnormality of CVI CD4+ T cells: whereas CD4+ T cells from CVI patients proliferate normally in response to stimulation by PHA, staphylococcal enterotoxin B (SEB), or anti-CD2 antibodies, these stimuli induce significantly less IL-2 production than observed with CD4+ T cells from normal individuals. Furthermore, we show that this IL-2 production defect is not due to an accessory cell abnormality, since it was seen in the presence of normal (allogeneic) accessory cells, and patient accessory cells supported normal amounts of IL-2 production by PHA-stimulated CD4+ T cells obtained from normal individuals. Of interest, we also found that while IL-2 production by CD4+ T cells from CVI patients induced by stimulation with immobilized anti-CD3 antibody was reduced compared to CD4+ T cells from normal control individuals, this reduction was not statistically significant. Furthermore, stimulation of both CVI patient and normal CD4+ T cells with either ionomycin + phorbol myristate acetate or a combination of immobilized anti-CD3 antibody plus anti-CD28 antibody resulted in a 50-fold increase in IL-2 production compared to stimulation with immobilized anti-CD3 antibody alone, and, under these conditions, CVI and normal CD4+ T cells produced equivalent amounts of IL-2. Finally, minor defects in interferon-gamma production by CD4+ T cells from CVI donors were observed, but these were less severe than the IL-2 production defects and were not statistically significant. We conclude that a primary abnormality of lymphokine production exists in the CD4+ T cells of a subset of patients with CVI. The fact that the IL-2 production defect is more severe upon stimulation with superantigen as opposed to anti-CD3 antibody, and could be overcome by stimulation with ionomycin + phorbol myristate acetate or by costimulation with immobilized anti-CD3+ anti-CD28 antibodies, implies that this defect is due to impairment of a specific signaling pathway. C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 32 TC 43 Z9 45 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD JUL PY 1993 VL 13 IS 4 BP 247 EP 258 DI 10.1007/BF00919383 PG 12 WC Immunology SC Immunology GA LQ348 UT WOS:A1993LQ34800002 PM 7901231 ER PT J AU MOHTAI, M SMITH, RL SCHURMAN, DJ TSUJI, Y TORTI, FM HUTCHINSON, NI STETLERSTEVENSON, WG GOLDBERG, GI AF MOHTAI, M SMITH, RL SCHURMAN, DJ TSUJI, Y TORTI, FM HUTCHINSON, NI STETLERSTEVENSON, WG GOLDBERG, GI TI EXPRESSION OF 92-KD TYPE-IV COLLAGENASE GELATINASE (GELATINASE-B) IN OSTEOARTHRITIC CARTILAGE AND ITS INDUCTION IN NORMAL HUMAN ARTICULAR-CARTILAGE BY INTERLEUKIN-1 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE GELATINASE; HUMAN ARTICULAR CARTILAGE; INTERLEUKIN-1; METALLOPROTEINASE; OSTEOARTHRITIS ID EPIDERMAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; MATRIX METALLOPROTEINASES; POLYMORPHONUCLEAR LEUKOCYTES; SYNOVIAL FIBROBLASTS; RAT FIBROBLASTS; TUMOR-CELLS; GENE; CHONDROCYTES; PROTEOGLYCAN AB We report here that a 92-kD gelatinolytic metalloproteinase is expressed as protein and mRNA in human osteoarthritic cartilage, but not in normal adult articular cartilage. Western immunoblotting demonstrated that the 92-kD gelatinolytic activity corresponded to 92-kD type IV collagenase/gelatinase (gelatinase B); mRNA for gelatinase B was identified by Northern blotting. Chondrocytes from normal cartilage also exhibited mRNA for 72-kD type IV collagenase/gelatinase (gelatinase A), tissue collagenase, and stromelysin-1. and these mRNAs were increased in osteoarthritic cartilage. Regional analysis of osteoarthritic cartilage samples from four individuals revealed that gelatinase B mRNA was expressed in grossly fibrillated areas; two of four nonfibrillated cartilage samples failed to exhibit the mRNA, but did have increased levels of mRNA for other neutral metalloproteinases. IL-1alpha treatment of normal human cartilage explants or isolated chondrocytes induced increased levels of gelatinase B and increased mRNA for tissue collagenase and stromelysin-1. Under identical conditions, mRNA levels for gelatinase A were not increased indicating that regulation of this enzyme in human articular chondrocytes is distinct from that of other metalloproteinases. Our data showing expression of gelatinase B in fibrillated cartilage suggest that it is a marker of progressive articular cartilage degradation in osteoarthritis. C1 STANFORD UNIV,MED CTR,SCH MED,DEPT FUNCT RESTORAT,DIV ORTHOPAED,ORTHOPAED RES LAB,300 PASTEUR DR,STANFORD,CA 94305. STANFORD UNIV,MED CTR,SCH MED,DEPT MED,STANFORD,CA 94305. VET AFFAIRS MED CTR,PALO ALTO,CA 94304. MERCK SHARP & DOHME LTD,DEPT MOLEC IMMUNOL,RAHWAY,NJ 07065. NCI,TUMOR INVAS & METASTASIS SECT,PATHOL LAB,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DIV DERMATOL,ST LOUIS,MO 63110. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NIAMS NIH HHS [AR-30796-06, AR-26833-10] NR 54 TC 131 Z9 132 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 179 EP 185 DI 10.1172/JCI116547 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300024 PM 8325982 ER PT J AU FLANDERS, KC WINOKUR, TS HOLDER, MG SPORN, MB AF FLANDERS, KC WINOKUR, TS HOLDER, MG SPORN, MB TI HYPERTHERMIA INDUCES EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-S IN RAT CARDIAC-CELLS IN-VITRO AND IN-VIVO SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CARDIOPROTECTION; HEAT SHOCK; STRESS RESPONSE; GROWTH FACTORS; IMMUNOHISTOCHEMISTRY ID HEAT-SHOCK PROTEIN; ENDOTHELIAL-CELLS; MESSENGER-RNA; ADULT TISSUES; PRECURSOR; INDUCTION; ISCHEMIA; LOCALIZATION; SYNTHESIZE; EMBRYOS AB Hyperthermia causes changes in expression of TGF-beta mRNA and protein in cultured cardiac cells, as well as in the heart in vivo. 12 h after hyperthermia, primary cultures of neonatal rat cardiomyocytes show a two- to threefold decreased expression of TGF-beta mRNAs which returns to control levels by 48 h after heat shock. In cultures of cardiac fibroblasts, expression of TGF-beta mRNAs increases 5-25-fold, 12-48 h after heat shock, while fetal bovine heart endothelial cells show little change in TGF-beta expression after hyperthermia. In each case, mRNAs for TGF-betas 1, 2, and 3 are regulated similarly. Hearts isolated from rats exposed to hyperthermia show an initial 20-fold decrease in TGF-beta 1 and 3 mRNA levels which return to control levels by 24 h and subsequently are elevated two- to threefold above normal 48-72 h after heat shock; there is little change in TGF-beta2 mRNA. Expression of immunoreactive TGF-beta1 and 3 protein, localized intracellularly in myocytes, follows the same pattern as the mRNA expression. By 72 h, some myocytes show hyperstaining for TGF-beta1. Staining for extracellular TGF-beta1/3 exhibits the opposite time course, being most intense 3-6 h after heat shock and returning to control levels by 48 h. The increase in TGF-betas after hyperthermia could play a role in mediating the reported cardioprotective effects of heat shock. RP FLANDERS, KC (reprint author), NCI,CHEMOPREVENT LAB,BLDG 41,ROOM C-629,BETHESDA,MD 20892, USA. NR 50 TC 25 Z9 26 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 404 EP 410 DI 10.1172/JCI116581 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300052 PM 8326008 ER PT J AU BONNER, JC GOODELL, AL COIN, PG BRODY, AR AF BONNER, JC GOODELL, AL COIN, PG BRODY, AR TI CHRYSOTILE ASBESTOS UP-REGULATES GENE-EXPRESSION AND PRODUCTION OF ALPHA-RECEPTORS FOR PLATELET-DERIVED GROWTH-FACTOR (PDGF-AA) ON RAT LUNG FIBROBLASTS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE PLATELET-DERIVED GROWTH FACTOR; PLATELET-DERIVED GROWTH FACTOR RECEPTOR; FIBROBLAST; ASBESTOS; FIBROGENESIS ID SMOOTH-MUSCLE CELLS; IDIOPATHIC PULMONARY FIBROSIS; ALVEOLAR MACROPHAGES; CELLULAR PROLIFERATION; UP-REGULATION; ISOFORMS; PATHOGENESIS; ACTIVATION; SUBUNITS; BINDING AB PDGF isoforms have been postulated to serve as mediators of fibroblast proliferation and chemotaxis during lung fibrogenesis induced by asbestos inhalation. We have studied the interaction of chrysotile asbestos fibers with rat lung fibroblasts (RLF) in vitro and the consequent changes in PDGF receptor mRNA expression, PDGF binding, and mitogenic activity of PDGF isoforms. Northern blot analysis revealed that mRNA for the PDGF-receptor alpha subtype (PDGF-Ralpha) on RLF was upregulated after a 24-h exposure to asbestos in culture (0.5-15 mug fibers/cm2). [I-125]pDGF-BB receptor assays showed that normal RLF possess mainly PDGF-Rbeta and a paucity of PDGF-Ralpha. In agreement with the Northern data, saturation binding of [I-125] PDGF-BB to RLF exposed to asbestos demonstrated an approximately 40% increase in binding sites accompanied by a twofold decrease in receptor affinity. Treating asbestos-exposed RLF with PDGF-AA, which binds only PDGF-Ralpha, blocked the PDGF binding sites that were upregulated by fiber exposure. PDGF-AA had increased mitogenic potency for fiber-exposed RLF, but PDGF-BB was a less potent mitogen for these RLF. Nonfibrogenic carbonyl iron spheres induced similar changes in PDGF growth responses. These data show that inorganic particulates alter the PDGF-Ralpha population on RLF without significant change in PDGF-Rbeta. RP BONNER, JC (reprint author), NIEHS,PULM PATHOBIOL LAB,MAILDROP D2-02,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 57 Z9 58 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 425 EP 430 DI 10.1172/JCI116584 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300055 PM 8392089 ER PT J AU FERRARO, RT ECKEL, RH LARSON, DE FONTVIEILLE, AM RISING, R JENSEN, DR RAVUSSIN, E AF FERRARO, RT ECKEL, RH LARSON, DE FONTVIEILLE, AM RISING, R JENSEN, DR RAVUSSIN, E TI RELATIONSHIP BETWEEN SKELETAL-MUSCLE LIPOPROTEIN-LIPASE ACTIVITY AND 24-HOUR MACRONUTRIENT OXIDATION SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE LIPOPROTEIN LIPASE; 24-H RESPIRATORY QUOTIENT; EUGLYCEMIC, HYPERINSULINEMIC CLAMP; SKELETAL MUSCLE; HUMAN ID PIMA-INDIANS; INSULIN RESISTANCE; WEIGHT-GAIN; OBESITY; GLUCOSE; ETIOLOGY; EXERCISE; RATS AB A low ratio of whole-body 24-h fat/carbohydrate (CHO) oxidation has been shown to be a predictor of subsequent body weight gain. We tested the hypothesis that the variability of this ratio may be related to differences in skeletal muscle metabolism. Since lipoprotein lipase (LPL) plays a pivotal role in partitioning lipoprotein-borne triglycerides to adipose (storage) and skeletal muscle (mostly (oxidation), we postulated that a low ratio of fat/CHO oxidation was associated with a low skeletal muscle LPL (SMLPL) activity. As an index of substrate oxidation, 24-h RQ was measured under sedentary and eucaloric conditions in 16 healthy nondiabetic Pima males. During a 6-h euglycemic, hyperinsulinemic clamp, muscle biopsies were obtained at baseline, 3, and 6 h. Heparin-elutable SMLPL activity was 2.92 +/- 0.56 nmol free fatty acids/g . min (mean +/- SD) at baseline, was unchanged (2.91 +/- 0.51) at the third hour, and increased significantly (P < 0.05) to 3.13 +/- 0.57 at the sixth hour of the clamp. The mean (of baseline and 3-h) SMLPL activity correlated inversely with 24-h RQ (r = 0.57, P < 0.03) but not with body size, body composition, or insulin-mediated glucose uptake. Since SMLPL activity is related to the ratio of whole body fat/CHO oxidation rate, a decreased muscle LPL activity may, therefore, predispose to obesity. C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80262. FU NIDDK NIH HHS [DK-26354] NR 36 TC 91 Z9 93 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 441 EP 445 DI 10.1172/JCI116586 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300057 PM 8326010 ER PT J AU KLEIN, HG SANTAMARINAFOJO, S DUVERGER, N CLERC, M DUMON, MF ALBERS, JJ MARCOVINA, S BREWER, HB AF KLEIN, HG SANTAMARINAFOJO, S DUVERGER, N CLERC, M DUMON, MF ALBERS, JJ MARCOVINA, S BREWER, HB TI FISH EYE SYNDROME - A MOLECULAR DEFECT IN THE LECITHIN-CHOLESTEROL ACYLTRANSFERASE (LCAT) GENE ASSOCIATED WITH NORMAL ALPHA-LCAT-SPECIFIC ACTIVITY - IMPLICATIONS FOR CLASSIFICATION AND PROGNOSIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE FISH EYE DISEASE; HYPOALPHALIPOPROTEINEMIA; DNA SEQUENCE ANALYSIS; LCAT; RESTRICTION FRAGMENT LENGTH POLYMORPHISM ID MASSIVE CORNEAL OPACITIES; DENSITY LIPOPROTEIN LECITHIN; FAMILIAL CONDITION; SECONDARY STRUCTURE; GENOMIC SEQUENCES; GLOBULAR-PROTEINS; CHAIN-REACTION; HUMAN-PLASMA; DISEASE; ACID AB We have identified the molecular defect in two siblings presenting with classical clinical and biochemical features of Fish Eye disease (FED), including corneal opacities, HDL cholesterol < 10 mg/dl, normal plasma cholesteryl esters, and elevated triglycerides. In contrast to previously reported patients with FED who are unable to esterify HDL-associated cholesterol, our patients' plasma lecithin-cholesterol acetyltransferase (alpha-LCAT)-specific activities assayed using an HDL-like proteoliposome substrate were 12.7-25.7 nmol/mug ( 19.5+/-1.8 in controls). In addition, significant residual cholesterol esterification was present in VLDL/LDL-depleted plasma, confirming the presence of HDL-associated alpha-LCAT activity. DNA sequence analysis of the proband's LCAT gene identified deletion of the triplet coding for leu300, which resulted in the loss of a restriction site for MlnI. Digestion of PCR-amplified DNA using MlnI established that both siblings are homozygous for this defect. Expression of LCAT300-del. in human embryonic kidney-293 cells revealed normal mRNA and intracellular LCAT concentrations. However, reduced amounts of LCAT300-del., which had a normal specific alpha-LCAT activity, were present in the media. In summary, we report the first case of FED associated with a mutant enzyme that has a normal alpha-LCAT-specific activity. The functional significance of this LCAT gene defect has been established in an in vitro expression system, which demonstrates that very small amounts of this functional LCAT mutant enzyme accumulate in the media. Characterization of LCAT300-del- established that selective alpha-LCAT deficiency is not a prerequisite for the development of FED. On the basis of our combined results, we propose that the residual amounts of total plasma LCAT activity and not its distribution on lipoproteins primarily determines the heterogeneity in phenotypic expression observed in familial LCAT deficiency syndromes. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. UNIV BORDEAUX 2,BIOCHIM MED LAB A,F-33076 BORDEAUX,FRANCE. UNIV WASHINGTON,SCH MED,DEPT MED,NW LIPID RES LABS,SEATTLE,WA 98195. FU NHLBI NIH HHS [HL 3-00H6] NR 41 TC 49 Z9 50 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1993 VL 92 IS 1 BP 479 EP 485 DI 10.1172/JCI116591 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LL773 UT WOS:A1993LL77300062 PM 8326012 ER PT J AU STEELE, AD GARCIA, D SEARS, J GERNA, G NAKAGOMI, O FLORES, J AF STEELE, AD GARCIA, D SEARS, J GERNA, G NAKAGOMI, O FLORES, J TI DISTRIBUTION OF VP4 GENE ALLELES IN HUMAN ROTAVIRUSES BY USING PROBES TO THE HYPERDIVERGENT REGION OF THE VP4 GENE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; SUBGROUP-I; NEUTRALIZATION EPITOPES; MONOCLONAL-ANTIBODIES; VENEZUELAN INFANTS; UNIQUE VP4; 4TH GENE; IDENTIFICATION; GASTROENTERITIS; CONSERVATION AB The rotavirus VP4 protein elicits the production of neutralizing antibodies and is known to play a role in inducing resistance to disease. At least five human rotavirus VP4 gene alleles have been described on the basis of antigenic polymorphism and/or nucleotide sequence differences. In the present study, we developed cDNA probes directed at the hyperdivergent region of the VP4 gene of the five described human rotavirus VP4 alleles (Wa, DS1, M37, AU228, and 69M) and used them in hybridization assays with human rotavirus strains from Latin America and Europe to determine the distribution of the VP4 gene alleles in nature. The Wa-like allele was detected most frequently, occurring in 57% of the 402 rotavirus strains tested, and the DS1-like allele was the next most common, occurring in 14% of the strains tested. The M37- and AU228-like alleles were detected in only 4 and 3% of the rotavirus strains tested, respectively, whereas the 69M-like VP4 gene allele was not detected. Several rotavirus strains from Europe did not react with any of the VP4 gene probes, although they did hybridize to a probe generated from a representative strain from the group. These data indicate the global distribution of various VP4 gene alleles and raise the possibility that other, unrecognized human VP4 alleles exist in nature because almost one-fourth of the strains could not be classified into any of the established VP4 groups. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. INST BIOMED,CARACAS,VENEZUELA. UNIV PAVIA,I-27100 PAVIA,ITALY. AKITA UNIV,SCH MED,AKITA 010,JAPAN. NR 30 TC 48 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1993 VL 31 IS 7 BP 1735 EP 1740 PG 6 WC Microbiology SC Microbiology GA LJ201 UT WOS:A1993LJ20100011 PM 8394374 ER PT J AU RASOOL, NBG GREEN, KY KAPIKIAN, AZ AF RASOOL, NBG GREEN, KY KAPIKIAN, AZ TI SEROTYPE ANALYSIS OF ROTAVIRUSES FROM DIFFERENT LOCATIONS IN MALAYSIA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; MONOCLONAL-ANTIBODIES; CELL-CULTURE; ELECTROPHEROTYPES; CHILDREN; STRAINS; NEUTRALIZATION; IDENTIFICATION; EPIDEMIOLOGY; SUBGROUPS AB The distribution of rotavirus G (VP7) serotypes circulating in four locations in Malaysia, representing three geographical areas, was evaluated in 341 RNA-positive stool specimens obtained discontinuously between 1977 and 1988 from infants and young children under the age of five years who were hospitalized with acute gastroenteritis. A total of 306 specimens (256 stool suspensions and 50 that were adapted to growth in tissue culture) that were rotavirus positive by the confirmatory enzyme-linked immunosorbent assay (ELISA) were examined for serotype by ELISA utilizing monoclonal antibodies to rotavirus G serotype 1, 2, 3, 4, or 9. One hundred eighty (59%) of the 306 specimens could be serotyped; of these 180 specimens, 71% were serotype 4, 15% were serotype 1, 4% were serotype 2, and 4% were serotype 3. Serotype 9 rotavirus was not detected. Most (71%) of the specimens tested were obtained in 1988, when serotype 4 predominated in three locations in West Malaysia; no single serotype was predominant in a limited number of specimens from East Malaysia. C1 NIAID,INFECT DIS LAB,EPIDEMIOL SECT,BETHESDA,MD 20892. RP RASOOL, NBG (reprint author), UNIV MALAYA,DEPT GENET & CELLULAR BIOL,KUALA LUMPUR 2211,MALAYSIA. NR 31 TC 13 Z9 14 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1993 VL 31 IS 7 BP 1815 EP 1819 PG 5 WC Microbiology SC Microbiology GA LJ201 UT WOS:A1993LJ20100026 PM 8394376 ER PT J AU PARK, KH CHANG, WH SCHWAN, TG AF PARK, KH CHANG, WH SCHWAN, TG TI IDENTIFICATION AND CHARACTERIZATION OF LYME-DISEASE SPIROCHETES, BORRELIA-BURGDORFERI SENSU-LATO, ISOLATED IN KOREA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; MAJOR SURFACE-PROTEINS; MONOCLONAL-ANTIBODY; INVITRO CULTIVATION; IXODES-PERSULCATUS; TICK; JAPAN; CALIFORNIA; AGENT; POLYMORPHISMS AB Lyme disease spirochetes, Borrelia burgdorferi sensu lato, were identified and characterized for the first time in Korea. Four isolates, designated Konkuk-1, Konkuk-2, Kangwon-3, and KM-4, were made from midgut suspensions of three Ixodes ticks and heart tissue from one mouse, Apodemus agrarius, collected from Chungbuk and Kangwon provinces. The four Korean isolates and B. burgdorferi sensu lato from other geographic areas and biological sources were compared by using sodium dodecyl sulfate-polyacrylamide gel electrophoresis for protein profiles, Western blot (immunoblot) analysis for reactivities with monoclonal and polyclonal antibodies, and agarose gel electrophoresis for plasmid profiles. Two typing schemes using polymerase chain reaction identified three of the isolates as members of group VS461 and one, Kangwon-3, as Borrelia garinii. These results demonstrate the potential for human Lyme disease to occur in some provinces of Korea. C1 NIAID, ROCKY MT LABS, VECTORS & PATHOGENS LAB, ARTHROPOD BORNE DIS SECT, HAMILTON, MT 59840 USA. KONKUK UNIV, COLL MED, DEPT MICROBIOL, CHOONGJU 380701, SOUTH KOREA. SEOUL NATL UNIV, COLL MED, DEPT MICROBIOL, SEOUL 110799, SOUTH KOREA. NR 58 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 1993 VL 31 IS 7 BP 1831 EP 1837 PG 7 WC Microbiology SC Microbiology GA LJ201 UT WOS:A1993LJ20100029 PM 8349761 ER PT J AU KRAUS, KH GUGINO, LD LEVY, WJ CADWELL, J ROTH, BJ AF KRAUS, KH GUGINO, LD LEVY, WJ CADWELL, J ROTH, BJ TI THE USE OF A CAP-SHAPED COIL FOR TRANSCRANIAL MAGNETIC STIMULATION OF THE MOTOR CORTEX SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MAGNETICS; MOTOR EVOKED POTENTIALS; MOTOR CORTEX; ELECTROMYOGRAPHY; MUSCLES; HUMAN ID SPINAL ARTERY SYNDROME; HUMAN CEREBRAL-CORTEX; EVOKED-POTENTIALS; ELECTRICAL-STIMULATION; NEUROSURGICAL OPERATIONS; THEORETICAL CALCULATION; BRAIN-STIMULATION; NITROUS-OXIDE; CORD; PROJECTIONS AB A cap-shaped coil is introduced as a superior design for inducing transcranial magnetic motor evoked potentials for spinal cord monitoring. Evaluation of the magnetic characteristics of the cap coil showed higher induced electrical fields at and below the depth of the cortical surface. compared to a 9-cm, butterfly-shaped coil. Twenty normal adults were stimulated with the cap coil and a 9-cm round coil in three positions. Compound muscle action potentials were recorded from the left and right abductor digiti minimi and anterior tibialis muscles. The cap coil induced potentials with higher intensities and lower variability between consecutive stimuli. The cap coil was also more able to simultaneously induce motor evoked potentials from the four muscles studied. This coil design should provide superior means of inducing transcranial magnetic motor evoked potentials in multiple muscles. C1 NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. CADWELL LABS INC,KENNEWICK,WA. CLEVELAND CLIN FDN,DEPT NEUROSURG,FT LAUDERDALE,FL. RP KRAUS, KH (reprint author), HARVARD UNIV,SCH MED,DEPT ANESTHESIA,BOSTON,MA 02115, USA. RI Roth, Bradley/A-4920-2008 NR 44 TC 14 Z9 15 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUL PY 1993 VL 10 IS 3 BP 353 EP 362 DI 10.1097/00004691-199307000-00009 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LR783 UT WOS:A1993LR78300009 PM 8408600 ER PT J AU BORNER, MM SARTOR, O AF BORNER, MM SARTOR, O TI RESPONSE TO MORE IS NOT ALWAYS BETTER - A CASE FOR LOW-DOSE LEUCOVORIN - REPLY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID BIOCHEMICAL MODULATION; FLUOROURACIL RP BORNER, MM (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 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 JUL PY 1993 VL 11 IS 7 BP 1435 EP 1435 PG 1 WC Oncology SC Oncology GA LL233 UT WOS:A1993LL23300039 ER PT J AU ASHERY, RS AF ASHERY, RS TI NONTRADITIONAL EMPLOYEES - INDIGENOUS OUTREACH WORKERS EMPLOYED AS AIDS EDUCATORS FOR STREET ADDICTS SO JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article ID COMMUNITY AB This descriptive study examined issues in the employment of indigenous outreach workers (OWs) hired to deliver AIDS risk-reduction messages to street addicts who were not in treatment. Twenty-six projects responded to a mailed questionnaire. These projects were part of the National Institute on Drug Abuse (NIDA) funded National AIDS Demonstration Research (NADR) projects. Fifty-eight percent of the OWs hired were recovering addicts with an average of just over 2 years in recovery. Out of a total of 395 OWs hired, 61% left prior to the conclusion of the 3-year project. Of those who left, 62% left employment within the first year. The study recognizes that OWs are ''nontraditional'' employees, and suggestions are given for further study and to increase retention. C1 NIDA,COMMUNITY RES BRANCH,ROCKVILLE,MD. NR 21 TC 4 Z9 4 U1 1 U2 1 PU CLINICAL PSYCHOLOGY PUBL CO PI BRANDON PA 4 CONANT SQUARE, BRANDON, VT 05733 SN 0090-4392 J9 J COMMUNITY PSYCHOL JI J. Community Psychol. PD JUL PY 1993 VL 21 IS 3 BP 200 EP 209 DI 10.1002/1520-6629(199307)21:3<200::AID-JCOP2290210304>3.0.CO;2-P PG 10 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA LT320 UT WOS:A1993LT32000003 ER PT J AU KULYNYCH, JJ VLADAR, K JONES, DW WEINBERGER, DR AF KULYNYCH, JJ VLADAR, K JONES, DW WEINBERGER, DR TI 3-DIMENSIONAL SURFACE RENDERING IN MRI MORPHOMETRY - A STUDY OF THE PLANUM-TEMPORALE SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE BRAIN, ANATOMY; MAGNETIC RESONANCE IMAGING, 3-DIMENSIONAL; MORPHOMETRY, TECHNIQUES; PLANUM-TEMPORALE ID LEFT-RIGHT ASYMMETRIES; MAGNETIC-RESONANCE; DEVELOPMENTAL DYSLEXIA; CEREBRAL-CORTEX; BRAIN; IMAGES; SCHIZOPHRENIA; LANGUAGE; HUMANS AB Objective: The emergence of methodologies for accurately rendering cortical surfaces suggests possible quantitative applications of surface rendering to morphometry of the cerebral cortex. We examined this novel use of surface renderings in a study of the planum temporale, a neuroanatomical structure exhibiting well-documented normal asymmetry previously visible only in postmortem studies. Materials and Methods: With the aid of three-dimensional rendering of the supratemporal cortex, the area of the planum temporale was analyzed in the volume MRIs of seven normal. strongly right-handed males. Results: In comparison with areas derived from conventional measurements of serial MRI sections. planum temporale areas derived from supratemporal surface renderings offered far greater interrater reliability, and presumably improved validity as reflected by more consistent evidence of the anticipated planum asymmetry. Conclusion: Morphometry of the supratemporal cortes is enhanced by the use of three-dimensional surface renderings. Application of surface-rendering techniques to morphometry of other Cortical regions is discussed. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. NR 33 TC 65 Z9 65 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 1993 VL 17 IS 4 BP 529 EP 535 DI 10.1097/00004728-199307000-00003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LM749 UT WOS:A1993LM74900003 PM 8331221 ER PT J AU PATRONAS, NJ MAKARIOU, EV AF PATRONAS, NJ MAKARIOU, EV TI MRI OF CHOROIDAL PLEXUS INVOLVEMENT IN INTRACRANIAL CRYPTOCOCCOSIS SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CRYPTOCOCCOSIS; CENTRAL NERVOUS SYSTEM, INFECTION; CHOROID PLEXUS; MAGNETIC RESONANCE IMAGING ID LATERAL VENTRICLES; FEATURES; CT; CYSTICERCOSIS; APPEARANCE; DIAGNOSIS; CYSTS; AIDS AB Objective: The sensitivity of medical imaging in the diagnosis of intracranial cryptococcosis is poor. MRI can provide additional information in establishing this diagnosis. Materials and Methods: We present two cases of CNS cryptococcosis (HIV negative) studied by MRI and discuss the involvement of the ventricles and the choroid plexuses. Results: The choroid plexuses are unusually enlarged and they enhance intensely. Intraventricular loculations were also noted including entrapment of CSF in the temporal horns. Conclusion: The constellation of these findings is highly suggestive of cryptococcosis. RP PATRONAS, NJ (reprint author), NIH,DEPT RADIOL,BLDG 10,ROOM 1C660,BETHESDA,MD 20892, USA. NR 20 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JUL-AUG PY 1993 VL 17 IS 4 BP 547 EP 550 DI 10.1097/00004728-199307000-00005 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LM749 UT WOS:A1993LM74900005 PM 8331223 ER PT J AU SATO, S KADOR, PF AF SATO, S KADOR, PF TI HUMAN KIDNEY ALDOSE AND ALDEHYDE REDUCTASES SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article AB Mounting experimental evidence links increased aldose reductase activity with diabetes-related kidney functional changes. To investigate the interrelationship of NADPH-dependent reductases in the human kidney, both aldose reductase and aldehyde reductase were purified from human kidney by a series of chromatographic procedures, including gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A, and chromatofocusing on Mono P. Each purified enzyme appeared as a single band on polyacrylamide gel after electrophoresis or isoelectric focusing. Aldose reductase has a pI of 5.7 and apparent molecular weight of 37 kDa, calculated from SDS-polyacrylamide gel electrophoresis, while aldehyde reductase has a pI of 5.2 and molecular weight of 39 kDa. Similar molecular weights were also obtained by gel filtration, indicating that both aldose and aldehyde reductases are present as monomers in the human kidney. Aldehyde reductase is primarily localized in the cortex, while the medulla contains aldose reductase. Both enzymes displayed properties consistent with the general characteristics of aldose and aldehyde reductases obtained from either rat or dog kidney. Purified aldose reductase utilizes aldose sugars such as D-xylose, D-glucose, and D-galactose as substrates while aldehyde reductase preferentially reduces D-glucuronate and oxidizes L-gulonate to D-glucuronate. Despite the lower apparent affinity of aldehyde reductase for aldose sugars (approximately 20- to 100-fold less) both enzymes reduced D-xylose, D-glucose, and D-galactose to their respective sugar alcohols in in vitro incubation studies where the generated sugar alcohols were identified by gas chromatography. Both enzymes were also inhibited by aldose reductase inhibitors. Of the compounds investigated, the carboxylic acids Ponalrestat and FK 366 displayed greater selectivity for inhibiting aldose reductase, whereas the hydantoins sorbinil and Al 1576 displayed more equal inhibition of both enzymes. RP SATO, S (reprint author), NEI,OCULAR THERAPEUT LAB,BLDG 10,ROOM 10B09,BETHESDA,MD 20892, USA. NR 0 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JUL-SEP PY 1993 VL 7 IS 3 BP 179 EP 187 DI 10.1016/1056-8727(93)90043-X PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LZ308 UT WOS:A1993LZ30800003 PM 8343612 ER PT J AU NAGY, EV BURCH, HB LUKES, YG CARR, FE KOSUGI, S KOHN, LD BURMAN, KD AF NAGY, EV BURCH, HB LUKES, YG CARR, FE KOSUGI, S KOHN, LD BURMAN, KD TI IMMUNOGENICITY OF A UNIQUE REGION OF THE HUMAN THYROTROPIN RECEPTOR SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE TSH RECEPTOR; ANTIBODIES; PEPTIDE ID AUTOIMMUNE THYROID-DISEASE; FAT-CELL MEMBRANES; GRAVES-DISEASE; MOLECULAR-CLONING; RABBIT ANTIBODIES; TSH RECEPTOR; EXPRESSION; BINDING; IDENTIFICATION; PROTEIN AB Clarifying the role of the TSH receptor protein in the autoimmune process may be the key to understanding the development of Graves' disease. In the present study we used a 16 amino acid peptide of the human TSH receptor (hTSHR) to immunize rabbits. A comparable, but theoretically less immunogenic, peptide was injected into other rabbits. The antibody response against these and other peptides, as well as against solubilized human thyroid membrane (TM) and guinea pig fat cell membrane (GPF) proteins, was tested using ELISA and Western blots. The GPF and TM binding pattern of rabbits' sera was compared to that of Graves' patients' sera. We have identified an area of antigenic cross-reactivity between GPF and TM; a 63 kD protein was present in both GPF and TM, and this protein uniformly bound IgG-s of the rabbits' postimmunization sera and one of eight Graves' patient's serum. We have shown that i) a theoretically immunogenic 16 amino acid peptide was indeed highly immunogenic in rabbits, ii) antibodies binding to GPF and TM were detected after immunization, and iii) the peak of thyroid stimulating immunoglobulin activity of sera was followed by a transient elevation of serum triiodothyronine levels. Further studies investigating the immunogenic epitopes of the hTSHR as well as characterizing the 63 kD protein are indicated. C1 WALTER REED ARMY MED CTR,DEPT CLIN INVEST,KYLE METAB UNIT,ENDOCRINE METAB SERV,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. NIDDKD,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD. FU FIC NIH HHS [1 F05 TW04412-01] NR 34 TC 11 Z9 11 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JUL-AUG PY 1993 VL 16 IS 7 BP 485 EP 493 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LQ748 UT WOS:A1993LQ74800003 PM 7901266 ER PT J AU LOSS, GE ELIAS, CG FIELDS, PE RIBAUDO, RK MCKISIC, M SANT, AJ AF LOSS, GE ELIAS, CG FIELDS, PE RIBAUDO, RK MCKISIC, M SANT, AJ TI MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II-RESTRICTED PRESENTATION OF AN INTERNALLY SYNTHESIZED ANTIGEN DISPLAYS CELL-TYPE VARIABILITY AND SEGREGATES FROM THE EXOGENOUS CLASS-II AND ENDOGENOUS CLASS-I PRESENTATION PATHWAYS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HLA-DR MOLECULES; INVARIANT CHAIN; T-CELLS; MONOCLONAL-ANTIBODIES; SURFACE EXPRESSION; PEPTIDE-BINDING; MHC MOLECULES; MOUSE; GENE; LINES AB Although reported examples of endogenous antigen (Ag) presentation by major histocompatibility complex (MHC) class II molecules have increased, the mechanisms governing this process remain poorly defined. In this communication, we describe an experimental system designed to examine the mechanisms governing class II presentation of internal Ag. Our target peptide is processed from a transmembrane protein constitutively expressed by a variety of nucleated cells (MHC class I, H-2L(d)), is naturally displayed by MHC class II molecules in vivo, and is recognized by a class II-restricted, CD4+ T cell hybridoma. Our results indicate that presentation of the L(d) target Ag is independent of its plasma membrane expression, may not involve endosomal proteolysis, and thus may be distinct from the classically defined class II presentation pathway. In addition, the observations that L(d) presentation does not require a functional TAP-1 complex, is not blocked by invariant chain, and cannot utilize cytoplasmic forms of H-2L(d), suggest that a classical class I pathway is not involved in this presentation event. Finally, our data suggest that different cofactors participate in MHC class II presentation of exogenous and endogenous Ag, and that disparate Ag presenting cells, such as B, T, and pancreatic islet cells, may differentially express these two class II pathways of Ag presentation. C1 UNIV CHICAGO,DEPT PATHOL,COMM IMMUNOL,5841 S MARYLAND,MC 1089,CHICAGO,IL 60637. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. UNIV CHICAGO,DEPT SURG,CHICAGO,IL 60637. RI Loss, George/A-6015-2011 FU NCI NIH HHS [P01-CA14599, P01-CA19266]; NHLBI NIH HHS [HL-07665] NR 66 TC 67 Z9 67 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1993 VL 178 IS 1 BP 73 EP 85 DI 10.1084/jem.178.1.73 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LH549 UT WOS:A1993LH54900006 PM 8315396 ER PT J AU WAKATSUKI, Y STROBER, W AF WAKATSUKI, Y STROBER, W TI EFFECT OF DOWN-REGULATION OF GERMLINE TRANSCRIPTS ON IMMUNOGLOBULIN-A ISOTYPE DIFFERENTIATION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HEAVY-CHAIN TRANSCRIPTS; B-CELL DIFFERENTIATION; SWITCH RECOMBINATION; GENE-EXPRESSION; RNA; LINE; INTERLEUKIN-4; IGE; LIPOPOLYSACCHARIDE; REARRANGEMENT AB In this study we determined the role of immunoglobulin (Ig) germline transcripts in the isotype switch differentiation of the cloned lymphoma B cell line CH12.LX. In initial studies, we showed that addition of transforming growth factor beta (TGF-beta) and interleukin 4 (IL-4), either alone or in combination, augment switching from membrane (m)IgM+ to mIgA+ cells, and that increased switching is preceded and paralleled by an increase in the steady-state level of alpha germline transcripts (alphaGLT). Interestingly, TGF-beta and IL-4 affect switching in different ways, as shown by the fact that IL-4 increases and TGF-beta decreases the number of dual-positive (mIgM+/mIgA+) cells; in addition, TGF-beta and IL-4 have different effects on the time course of induction of alphaGLT. In subsequent studies, we established that we could downregulate alphaGLT levels in CH12.LX B cells by transfecting an expression vector that can be induced to produce transcripts antisense to the Ialpha exon. Using this approach we downregulated alphaGLT in CH12.LX B cells undergoing switching in the presence of TGF-beta and IL-4 and showed that such downregulation led to decreased switching, as evidenced by decreased appearance of dual-positive B cells as well as decreased IgA synthesis relative to IgM synthesis. This result was corroborated by the fact that incubation of CH12.LX cells with phosphorothio-oligo antisense DNA to Ia sequence also led to a decrease in the number of dual-positive cells and in the IgA/IgM secretion ratio. In summary, IgA isotype differentiation in CH12.LX B cell, particularly the steps necessary for the elaboration of mIgM+/mIgA+ switch intermediate cells, is inhibited by downregulation of alphaGLT, it is therefore apparent that alphaGLT plays a key role in the initial stage of isotype switch differentiation. RP WAKATSUKI, Y (reprint author), NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BLDG 10,ROOM 11N250,BETHESDA,MD 20892, USA. NR 42 TC 38 Z9 38 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1993 VL 178 IS 1 BP 129 EP 138 DI 10.1084/jem.178.1.129 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LH549 UT WOS:A1993LH54900011 PM 8315375 ER PT J AU MURPHY, WJ DURUM, SK LONGO, DL AF MURPHY, WJ DURUM, SK LONGO, DL TI DIFFERENTIAL-EFFECTS OF GROWTH-HORMONE AND PROLACTIN ON MURINE T-CELL DEVELOPMENT AND FUNCTION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DWARF MOUSE; IMMUNODEFICIENCY; LYMPHOCYTES; DISEASE AB DW/J dwarf mice have a defect in their anterior pituitary and are deficient in growth hormone (GH) and prolactin (PRL). These mice have been demonstrated previously to have a deficiency in CD4/CD8 double-positive thymocytes, which could be corrected by treatment of these mice with recombinant human GH. Since PRL has been implicated in T cell function and human GH can interact with the PRL receptor, DW/J dwarf mice were treated with either ovine GH (ovGH) (20 mug/d) or ovine PRL (ovPRL) (20 mug/d). The ovine hormones can only bind their own specific receptors in the mouse. After several weeks of treatment, it was found that these two hormones produced markedly contrasting effects on T cells. Phenotypic analysis of the lymphoid organs was performed by flow cytometry and the functional capability of the peripheral T cells was assessed by immunizing the mice and determining the extent of antigen-specific proliferation of T cells obtained from the draining lymph nodes or by determining splenic mitogen responses. The results indicated that ovGH administration to dwarf mice resulted in significant increases in thymic cellularity yet had little effect on peripheral T cell responses. In contrast, the administration of ovPRL resulted in a further decrease in thymic cellularity when compared with untreated dwarf mice. No thymic effects of either ovGH or ovPRL administration were detected on the normal +/? counterparts. However, ovPRL administration resulted in a significant increase in the number and function of antigen-specific peripheral T cells in both immunized dwarf and +/? mice. The adjuvant effects of PRL occurred even though the mice also received complete Freund's adjuvant. These results suggest that neuroendocrine hormones may act in concert in T cell development. GH appears to promote thymocyte proliferation, while PRL appears to decrease thymus size and yet augment the number and function of antigen-specific T cells in the periphery. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 15 TC 131 Z9 135 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1993 VL 178 IS 1 BP 231 EP 236 DI 10.1084/jem.178.1.231 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LH549 UT WOS:A1993LH54900020 PM 8315380 ER PT J AU HWU, P SHAFER, GE TREISMAN, J SCHINDLER, DG GROSS, G COWHERD, R ROSENBERG, SA ESHHAR, Z AF HWU, P SHAFER, GE TREISMAN, J SCHINDLER, DG GROSS, G COWHERD, R ROSENBERG, SA ESHHAR, Z TI LYSIS OF OVARIAN-CANCER CELLS BY HUMAN-LYMPHOCYTES REDIRECTED WITH A CHIMERIC GENE COMPOSED OF AN ANTIBODY VARIABLE REGION AND THE FC-RECEPTOR GAMMA-CHAIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID TUMOR-INFILTRATING LYMPHOCYTES; T-CELL; FUNCTIONAL RECEPTORS; TISSUE-CULTURE; ZETA-CHAIN; EXPRESSION; SPECIFICITY; PROTEINS; MELANOMA; FAMILY AB To expand the spectrum of recognition of effector lymphocytes and to redirect them towards predefined targets, we have altered the specificity of human tumor-infiltrating lymphocytes (TIL) through stable modification with chimeric receptor genes consisting of single-chain antibody variable regions linked to the gamma subunit common to the immunoglobulin (Ig)G and IgE Fc receptors. Using either hapten or ovarian carcinoma-specific monoclonal antibodies, we constructed chimeric receptor genes and retrovirally introduced them into CD8+ TIL. Redirected TIL specifically lysed trinitrophenyl-labeled Daudi or a human ovarian carcinoma cell line (IGROV-1), and secreted granulocyte/macrophage colony-stimulating factor upon stimulation with the appropriate antigen. This strategy may allow new approaches towards the adoptive immunotherapy of cancer in humans. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. RP HWU, P (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 35 TC 179 Z9 180 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUL 1 PY 1993 VL 178 IS 1 BP 361 EP 366 DI 10.1084/jem.178.1.361 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LH549 UT WOS:A1993LH54900035 PM 8315392 ER PT J AU WEISS, SJ PANLILIO, LV SCHINDLER, CW AF WEISS, SJ PANLILIO, LV SCHINDLER, CW TI SINGLE-INCENTIVE SELECTIVE ASSOCIATIONS PRODUCED SOLELY AS A FUNCTION OF COMPOUND-STIMULUS CONDITIONING CONTEXT SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-ANIMAL BEHAVIOR PROCESSES LA English DT Article ID BIOLOGICAL CONSTRAINTS; NEGATIVE REINFORCEMENT; ATTENTION; RAT AB Barpressing was maintained in a tone-plus-light (TL) condition in 2 groups of rats by shock-related contingencies and in 2 other groups by food-related contingencies. Responding ceased in TL absence (TLBAR). Contingency arrangements made TL hedonically positive, relative to TLBAR, for 1 shock group and for 1 food group and hedonically negative for 1 shock group and for 1 food group. In a stimulus-element test, the visual modality was dominant when TL was hedonically positive, whereas auditory control increased when TL was negative, irrespective of the reinforcers involved. Within-incentive contingency manipulations produced selective associations hitherto ascribed to stimulus-reinforcer interactions, suggesting that biological constraints on learning may operate at the level of conditioned psychological states. C1 NIDA,BALTIMORE,MD. RP WEISS, SJ (reprint author), AMERICAN UNIV,DEPT PSYCHOL,WASHINGTON,DC 20016, USA. FU NIMH NIH HHS [MH-45545] NR 42 TC 9 Z9 9 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0097-7403 J9 J EXP PSYCHOL ANIM B JI J. Exp. Psychol.-Anim. Behav. Process. PD JUL PY 1993 VL 19 IS 3 BP 284 EP 294 DI 10.1037//0097-7403.19.3.284 PG 11 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental; Zoology SC Psychology; Behavioral Sciences; Zoology GA LJ203 UT WOS:A1993LJ20300007 PM 8340770 ER PT J AU NISHIDA, M FUJII, S KIMOTO, H HAYAKAWA, Y SAWADA, H COHEN, LA AF NISHIDA, M FUJII, S KIMOTO, H HAYAKAWA, Y SAWADA, H COHEN, LA TI FACILE PERFLUOROALKYLATION OF URACILS AND URIDINES AT THE C-5 POSITION SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Article ID BIS(PERFLUOROALKANOYL) PEROXIDES; ANTIVIRAL ACTIVITY AB Perfluoroalkylation at the C-5 position of uracil has been achieved in yields of 38-56% by the reaction of its bis(trimethylsilyl) derivative with bis(perfluoroalkanoyl) peroxides and the hydrolytic deprotection of the silylated products. A substituent or nitrogen replacement at C-6 does not interfere with perfluoroalkylation at C-5, but no significant reaction occurs at C-6 when C-5 is blocked. C1 NIPPON OIL & FATS CO LTD,TSUKUBA RES LAB,TSUKUBA 30026,JAPAN. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP NISHIDA, M (reprint author), GOVT IND RES INST,KITA KU,NAGOYA,AICHI 462,JAPAN. RI Nishida, Masakazu/I-7698-2016 OI Nishida, Masakazu/0000-0001-6588-9566 NR 19 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD JUL PY 1993 VL 63 IS 1-2 BP 43 EP 52 DI 10.1016/S0022-1139(00)80396-6 PG 10 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA LJ372 UT WOS:A1993LJ37200007 ER PT J AU COLLINS, PL MOTTET, G AF COLLINS, PL MOTTET, G TI MEMBRANE ORIENTATION AND OLIGOMERIZATION OF THE SMALL HYDROPHOBIC PROTEIN OF HUMAN RESPIRATORY SYNCYTIAL VIRUS SO JOURNAL OF GENERAL VIROLOGY LA English DT Note ID INFLUENZA-A VIRUS; M2 PROTEIN; SH PROTEIN; SUBGROUP-A; GLYCOPROTEIN; SEQUENCE; TRANSPORT AB Previous work has demonstrated that the small hydrophobic (SH) protein of human respiratory syncytial virus (RSV) A2 strain is a 64 amino acid integral membrane protein that accumulates intracellularly as an unglycosylated major species (SH0), a minor species truncated at the amino terminus and two N-glycosylated species one of which contains a further addition of polylactosamine. In this study, the membrane orientation of SH0 was mapped by trypsinization of intact RSV-infected cells followed by washout, lysis and immunoprecipitation of protected fragments with antisera specific for the protein termini. This showed that the C terminus is extracellular and the SH protein was not detectably palmitylated. Analysis of the SH protein by sedimentation on sucrose gradients showed that it rapidly assembles into a homo-oligomer that cosediments with the F protein tetramer. Interestingly, all forms of the SH protein were found in the oligomeric fraction. Chemical cross-linking generated species which appeared to represent dimers, trimers, tetramers and pentamers as well as a minor species of 180K which might correspond to the oligomeric form detected by sucrose gradient sedimentation. RP COLLINS, PL (reprint author), NIAID,INFECT DIS LAB,BLDG 7,ROOM 100,BETHESDA,MD 20892, USA. NR 18 TC 53 Z9 54 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUL PY 1993 VL 74 BP 1445 EP 1450 DI 10.1099/0022-1317-74-7-1445 PN 7 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA LM946 UT WOS:A1993LM94600030 PM 8336126 ER PT J AU BAKER, CS GILBERT, DA WEINRICH, MT LAMBERTSEN, R CALAMBOKIDIS, J MCARDLE, B CHAMBERS, GK OBRIEN, SJ AF BAKER, CS GILBERT, DA WEINRICH, MT LAMBERTSEN, R CALAMBOKIDIS, J MCARDLE, B CHAMBERS, GK OBRIEN, SJ TI POPULATION CHARACTERISTICS OF DNA FINGERPRINTS IN HUMPBACK WHALES (MEGAPTERA-NOVAEANGLIAE) SO JOURNAL OF HEREDITY LA English DT Article ID HUMAN MITOCHONDRIAL-DNA; GENETIC-VARIATION; NORTH PACIFIC; HYPERVARIABLE MINISATELLITES; LIONS; CONSERVATION; HAPLOTYPES; BOTTLENECK; MIGRATION; EVOLUTION AB Humpback whales exhibit a remarkable social organization that is characterized by seasonal long-distance migration (> 10,000 km/year) between summer feeding grounds in high latitudes and winter calving and breeding grounds in tropical or near-tropical waters. All populations are currently considered endangered as a result of intensive commercial exploitation during the last 200 years. Using three hypervariable minisatellite DNA probes (33.15, 3'HVR, and M13) originally developed for studies of human genetic variation, we examined genetic variation within and among three regional subpopulations of humpback whales from the North Pacific and one from the North Atlantic oceans. Analysis of DNA extracted from skin tissues collected by biopsy darting from free-ranging whales revealed considerable variation in each subpopulation. The extent of this variation argues against a recent history of inbreeding among humpback whales as a result of nineteenth- and twentieth-century hunting. A canonical variate analysis suggested a relationship between scaled genetic distance, based on similarities of DNA fingerprints, and geographic distance (i.e., longitude of regional subpopulation). Significant categorical differences were found between the two oceanic populations using a multivariate analysis of variance (MANOVA) with a modification of the Mantel nonparametric permutation test. The relationship between DNA fingerprint similarities and geographic distance suggests that nuclear gene flow between regional subpopulations within the North Pacific is restricted by relatively low rates of migratory interchange between breeding grounds or assortative mating on common wintering grounds. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. VICTORIA UNIV WELLINGTON,SCH BIOL SCI,WELLINGTON,NEW ZEALAND. UNIV AUCKLAND,SCH BIOL SCI,AUCKLAND,NEW ZEALAND. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. UNIV PENN,CITY SCI CTR,ECOSYST TECHNOL TRANSFER INC,PHILADELPHIA,PA 19104. CETACEAN RES UNIT,GLOUCESTER,MA. CASCADIA RES COLLECT,OLYMPIA,WA. OI Chambers, Geoffrey/0000-0003-1019-6855 NR 73 TC 38 Z9 39 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0022-1503 J9 J HERED JI J. Hered. PD JUL-AUG PY 1993 VL 84 IS 4 BP 281 EP 290 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA LR292 UT WOS:A1993LR29200008 PM 8340617 ER PT J AU LAW, CL TORRES, RM SUNDBERG, HA PARKHOUSE, RME BRANNAN, CI COPELAND, NG JENKINS, NA CLARK, EA AF LAW, CL TORRES, RM SUNDBERG, HA PARKHOUSE, RME BRANNAN, CI COPELAND, NG JENKINS, NA CLARK, EA TI ORGANIZATION OF THE MURINE CD22 LOCUS - MAPPING TO CHROMOSOME-7 AND CHARACTERIZATION OF 2 ALLELES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID B-CELL ANTIGEN; MYELIN-ASSOCIATED GLYCOPROTEIN; MONOCLONAL-ANTIBODY; ADHESION MOLECULE; GENE; IMMUNOGLOBULIN; EXPRESSION; SEQUENCE; ASSIGNMENT; MEMBERS AB Murine CD22 (mCD22) is a B cell-associated adhesion protein with seven extracellular Ig-like domains that has 62% amino acid identity to its human homologue. Southern analysis on genomic DNA isolated from tissues and cell lines from several mouse strains using mCD22 cDNA demonstrated that the Cd22 locus encoding mCD22 is a single copy gene of less-than-or-equal-to 30 kb. Digestion of genomic DNA preparations with four restriction endonucleases revealed the presence of restriction fragment length polymorphisms (RFLP) in BALB/c, C57BL/6, and C3H strains vs DBA/2J, NZB, and NZC strains, suggesting the presence of two or more Cd22 alleles. Using a mCD22 cDNA clone derived from the BALB/c strain, we isolated genomic clones from a DBA/2J genomic library that contained all the exons necessary to encode the full length mCD22 cDNA. Fifteen exons, including exon 3 that encodes the translation start codon, were identified. Each extracellular Ig-like domain of mCD22 is encoded by a single exon. A comparison between the nucleotide sequences of the BALB/c CD22 cDNA and the exons of the DBA/2J CD22 genomic clones revealed an 18-nucleotide deletion in exon 4 (encoding the most distal Ig-like domain 1 of mCD22) of the DBA/2J genomic sequence in addition to a number of substitutions, insertions, and deletions in other exons. These nucleotide differences were also present in a cDNA clone isolated from total RNA of LPS-activated DBA/2J splenocytes by reverse transcription-polymerase chain reaction. The Cd22 locus was mapped to the proximal region of chromosome 7, a region sytenic to human chromosome 19q, close to the previously reported loci, Lyb-8 and Mag (a homologue of Cd22). An antibody (CY34) against the Lyb-8.2 B cell marker reacted with a BHK transfectant expressing the full length mCD22 cDNA, thus demonstrating that Lyb-8 and Cd22 loci are identical. Furthermore, a rat anti-mCD22 mAb, NIM-R6, bound to sIgM+ DBA/2J B cells, confirming the expression of a CD22 protein by the Cd22a/Lyb-8a allele. C1 INST ANIM HLTH,ARBRIGHT,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP LAW, CL (reprint author), UNIV WASHINGTON,DEPT MICROBIOL SC-42,SEATTLE,WA 98195, USA. RI Clark, Edward/K-3462-2012 FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [GM42508] NR 63 TC 50 Z9 51 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 JUL 1 PY 1993 VL 151 IS 1 BP 175 EP 187 PG 13 WC Immunology SC Immunology GA LM579 UT WOS:A1993LM57900019 PM 8100843 ER PT J AU KANG, CY HARIHARAN, K POSNER, MR NARA, P AF KANG, CY HARIHARAN, K POSNER, MR NARA, P TI IDENTIFICATION OF A NEW NEUTRALIZING EPITOPE CONFORMATIONALLY AFFECTED BY THE ATTACHMENT OF CD4 TO GP120 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; RECEPTOR-MEDIATED ACTIVATION; HIV ENVELOPE GLYCOPROTEIN; VIRAL FUSION; BINDING-SITE; INFECTION; CELLS; CHIMPANZEES; RESIDUES AB We have developed a strategy to purify and characterize various anti-gp120 antibody populations in HIV+ sera by using anti-Id mAb. One preparation of human anti-gp120 antibody (ES+Ab) isolated on an anti-Id mAb (ES)-conjugated immunoabsorbent exhibited a novel neutralizing epitope specificity. The ES+Ab bound only to the native form of recombinant gp120SF2 and gp1201IIIB and not to the third hypervariable region (V3) loop peptide. In contradistinction to other CD4-gp120-inhibiting and V3-specific neutralizing antibodies, ES+Ab exhibited a dose-dependent enhancement of binding to recombinant gp120 in the presence of recombinant soluble CD4. In addition, flow cytometric analysis revealed a similar increase in the binding of ES+Ab to the native form of gp120 expressed on the HIV-infected cells. The ES+Ab competed with CD4 binding site- and V3-specific antibodies in binding to gp120, suggesting that the ES+Ab epitope is located near the CD4 binding site epitope and the V3 region. The ES+Ab neutralized six genetically distinct HIV-1 strains. The neutralizing activity of ES+Ab on HIV(IIIB) was significantly increased in the presence of human anti-CD4 binding site mAb. These data suggest that the ES+Ab epitope represents a conserved, conformational, neutralization target on gp120 that may be involved in viral infection in an event after the CD4-gp120 interaction and that is distinct from previously defined neutralizing epitopes of gp120. This finding may be important for the development of an AIDS vaccine and immunotherapy. C1 HARVARD UNIV,NEW ENGLAND DEACONESS HOSP,SCH MED,BOSTON,MA 02215. NCI,FCRDC,TUMOR CELL BIOL LAB,VIRUS BIOL UNIT,FREDERICK,MD 21701. RP KANG, CY (reprint author), IDEC PHARMACEUT CORP,11099 N TORREY PINES RD,160,LA JOLLA,CA 92037, USA. FU NIAID NIH HHS [AI29269, AI31310] NR 46 TC 37 Z9 38 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 JUL 1 PY 1993 VL 151 IS 1 BP 449 EP 457 PG 9 WC Immunology SC Immunology GA LM579 UT WOS:A1993LM57900046 PM 7686944 ER PT J AU KING, CL NUTMAN, TB AF KING, CL NUTMAN, TB TI IGE AND IGG SUBCLASS REGULATION BY IL-4 AND IFN-GAMMA IN HUMAN HELMINTH INFECTIONS - ASSESSMENT BY B-CELL PRECURSOR FREQUENCIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; HUMAN FILARIASIS; INTERLEUKIN-4; ANTIGEN; RESPONSES; QUANTITATION; RECOGNITION; LYMPHOCYTES; SECRETION; CLONES AB Helminth infections, like atopic disorders, show characteristic elevations of serum IgE and IgG4. To examine the mechanisms underlying the regulation of these two isotypes and of the other IgG subclasses, the frequency (Fo) of isotype-specific B lymphocytes (Bc) from 11 patients with helminth infections was compared by filter-spot ELISA using fresh peripheral blood-derived lymphocytes after 14-day Ag stimulation in vitro. The role of IL-4 and IFN-gamma in the generation and regulation of Ag-driven isotype responses was determined. The Fo of freshly obtained lymphocytes (expressed/1O(5) Bc) secreting polyclonal Ig for the following isotypes was: IgE (geometric mean = 0.72; range, 0 to 17.7); IgG4 (geometric mean = 4.9; range, 1.8 to 24.4); IgG1 (geometric mean = 134.3; range, 16.7 to 318). The Fo of IgE correlated with IgG4-secreting Bc among study subjects (r = 0.8, p < 0.01), however there was no association with the other isotypes. Parasite Ag added to cultured lymphocytes induced significant expansion in the number of Ig-secreting Bc for IgE and all IgG subclasses. In contrast, addition of a nonparasite Ag, tetanus toxoid, generated increased Fo of Ig-secreting Bc for IgG1, IgG2, and IgG3, and no expansion of IgG4 or IgE. The essential role of IL-4 in the expansion of IgE- and IgG4-secreting B cells in response to filarial Ag was demonstrated when simultaneous addition of neutralizing anti-IL-4 antibodies completely inhibited this response in all 11 patients studied. Neutralizing anti-IL-4 had no effect on either filarial or tetanus toxoid-driven expansion of IgG1-, IgG2-, or IgG3-secreting Bc. An inhibitory role of endogenously produced IFN-gamma was also shown when addition of neutralizing anti-IFN-gamma to cultures significantly augmented Ag-driven expansion of Bc-secreting IgE and all IgG subclasses; IgE, 0.4- to 9-fold; IgG4, 1.4- to 12-fold; IgG1, 1.6- to 13-fold; IgG2, 1.9- to 5-fold; and IgG3, 2.7- to 6-fold. This study demonstrates that parasite Ag stimulates Bc expansion in helminth-infected patients. Although this response for all five isotypes studied is down-regulated by IFN-gamma, the generation of only the IgE and IgG4 responses appears to be mediated selectively by IL-4. These findings support the concept that IgE and IgG4 production are linked and related to the quantities of IL-4 and IFN-gamma induced by Ag-specific T cells. C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RP KING, CL (reprint author), CASE WESTERN RESERVE UNIV,DIV GEOG MED,2109 ADELBERT RD,CLEVELAND,OH 44106, USA. NR 26 TC 79 Z9 79 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 JUL 1 PY 1993 VL 151 IS 1 BP 458 EP 465 PG 8 WC Immunology SC Immunology GA LM579 UT WOS:A1993LM57900047 PM 8326137 ER PT J AU MANTOVANI, L WILDER, RL CASALI, P AF MANTOVANI, L WILDER, RL CASALI, P TI HUMAN RHEUMATOID-B-1A (CD5+ B) CELLS MAKE SOMATICALLY HYPERMUTATED HIGH-AFFINITY IGM RHEUMATOID FACTORS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; VARIABLE REGION GENES; IMMUNOGLOBULIN-VH GENES; HEAVY-CHAIN DIVERSITY; WA IDIOTYPIC FAMILY; EPSTEIN-BARR VIRUS; IMMUNE-RESPONSE; ANTIBODY-RESPONSE; PREFERENTIAL UTILIZATION; NUCLEOTIDE-SEQUENCES AB To analyze the structure and formally ascertain the B-1a cellular origin of IgM rheumatoid factor (RF) autoantibodies, we generated 4 IgM RF mAb-producing cell lines using sorted (surface CD5+) B-1a cells from a patient with active rheumatoid arthritis. The RF mAb111, mAb112, mAb113, and mAb114 were monoreactive and displayed a relatively high affinity for human IgG Fc fragment (K(d), 3.1 x 10(-7) to 6.8 x 10(-7) M). The B-1a origin of the lymphocytes that gave rise to the IgM RF was confirmed by the expression of surface CD5 and specific CD5 mRNA by all mAb-producing cell lines. Analysis of the genes encoding the RF mAb V(H) and V(L) regions revealed that members of the V(H)I and V(H)III families were utilized in conjunction with VkappaIIIa, VkappaIIIB or VlambdaI genes. J(H)3 and J(H)4 genes were each utilized twice. The H chain CDR3 sequences were divergent and variable in length. The RF mAb V(H) genes were identical or closely related to those expressed in the ''restricted'' fetal B cell repertoire and/or were J(H)-proximal. For instance, mAb111 V(H) gene likely constituted a mutated variant of the expressed fetal 20P3 which is the second most J(H)-proximal gene (125 kb from J(H)). In addition, the expressed V(H) and V(L) genes were among those that have been found to encode other RF, different autoantibodies, high affinity antibodies induced by exogenous Ag, and natural autoantibodies in the adult and neonatal B cell repertoires. When compared with those of known germline genes, the expressed V gene sequences displayed a number of differences. By cloning and sequencing DNA from PMN of the same patient whose B lymphocytes were used for the mAb generation, we showed that such differences resulted from somatic hypermutation in the RF mAb112 V(H) gene. The germline gene (112GL) that presumably gave rise to the RF mAb112 V(H) segment was identical to the expressed fetal 51P1 gene. The distribution and the high replacement to silent mutation ratio of the nucleotide mutations in RF mAb112 V(H) segment were highly consistent with their selection by Ag. RF mAb113 was clonally related to RF mAb112, as shown by the utilization of the same sets Of V(H)I-D-J(H)4 and VkappaIIIb-Jkappa4 genes, displaying identical junctional sequences, and the presence of two identical replacement and one silent mutations. The presence of a high number of unique amino acid changes, a total of 14 and 9 in the two RF mAb V(H) and V(L) segments, respectively, suggested that RF mAb112- and mAb113-producing cells diverged relatively early in their expansion from the common progenitor clone. These studies show that high affinity RF can arise through a hypermutation process from antibodies expressed by B-1a cells. They also suggest that the affinity maturation of a human autoimmune response can apply to IgM and is independent of Ig class switch. C1 NYU,SCH MED,DEPT PATHOL,MSB-599,550 1ST AVE,NEW YORK,NY 10016. NYU,SCH MED,KAPLAN COMPREHENS CANC CTR,NEW YORK,NY 10016. NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. RI Casali, Paolo/F-6579-2010 FU NIAMS NIH HHS [AR-40908, R01 AR040908] NR 85 TC 112 Z9 113 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 JUL 1 PY 1993 VL 151 IS 1 BP 473 EP 488 PG 16 WC Immunology SC Immunology GA LM579 UT WOS:A1993LM57900049 PM 7686945 ER PT J AU ABRAMS, JS EISEMAN, JL MELINK, TJ SRIDHARA, R HIPONIA, DJ BELL, MM BELANI, CP ADLER, WH AISNER, J AF ABRAMS, JS EISEMAN, JL MELINK, TJ SRIDHARA, R HIPONIA, DJ BELL, MM BELANI, CP ADLER, WH AISNER, J TI IMMUNOMODULATION OF INTERLEUKIN-2 BY CYCLOPHOSPHAMIDE - A PHASE-IB TRIAL SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CYCLOPHOSPHAMIDE; INTERLEUKIN-2; LAK CELLS; IMMUNOMODULATION; CANCER ID LOW-DOSE CYCLOPHOSPHAMIDE; ACTIVATED KILLER CELLS; PERIPHERAL-BLOOD LYMPHOCYTES; REPETITIVE WEEKLY CYCLES; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; MALIGNANT-MELANOMA; ADVANCED CANCER; RECEPTOR; CARCINOMA AB The objective of this phase IB trail was to determine if cyclophosphamide (CY) could enhance the immune effects of interleukin-2 (IL-2), and if it could, was there an optimal immunomodulatory dosage. IL-2 alone at 30 million IU/m2 thrice weekly for 6 weeks or in combination with varying dosages of CY (300, 600, and 1,200 mg/m2) administered 3 days before IL-2 and repeated 3 weeks later was given to consecutive cohorts of patients (at least five per group) with advanced malignancies of varying types. To gauge the immune effects of the treatment, the variation in the amount of lymphokine-activated killer (LAK) cells generated in the peripheral blood mononuclear cells of patients and in a control group of normal volunteers was measured weekly over 7 consecutive weeks. Other immune parameters [natural killer cells (NK), peripheral blood eosinophils and lymphocytes, cell surface markers, soluble IL-2 receptor, and IL-2 antibodies] were also closely followed to study if they correlated with the degree of LAK activity. The group of patients that received low-dosage CY (300 mg/m2) and IL-2 produced the highest and most sustained levels of LAK and NK activity (p < 0.05) when compared with the cohorts receiving IL-2 alone or to those receiving the higher dosages of CY. No other immune parameter showed a significant difference between the groups. Although low-dosage CY does increase the LAK activity seen with IL-2, only randomized clinical trials can determine if this enhancement will improve tumor responses. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. UNIV MARYLAND,MED CTR,COLL PK,MD 20742. UNIV MARYLAND,CTR CANC,DIV MED ONCOL,COLL PK,MD 20742. UNIV MARYLAND,CTR CANC,DIV DEV THERAPEUT,COLL PK,MD 20742. FU NCI NIH HHS [N01-CM-57734] NR 34 TC 12 Z9 12 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD JUL PY 1993 VL 14 IS 1 BP 56 EP 64 DI 10.1097/00002371-199307000-00008 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA LT586 UT WOS:A1993LT58600008 PM 8399071 ER PT J AU KLION, AD MASSOUGBODJI, A HORTON, J EKOUE, S LANMASSO, T AHOUISSOU, NL NUTMAN, TB AF KLION, AD MASSOUGBODJI, A HORTON, J EKOUE, S LANMASSO, T AHOUISSOU, NL NUTMAN, TB TI ALBENDAZOLE IN HUMAN LOIASIS - RESULTS OF A DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LOA-LOA; M-PERSTANS; DIETHYLCARBAMAZINE; FILARIASIS; IVERMECTIN; INFECTION; ONCHOCERCIASIS; BENZIMIDAZOLES; EOSINOPHILIA; MEBENDAZOLE AB To assess the filaricidal activity and clinical safety of albendazole in human loiasis, a double-blind, placebo-controlled study was conducted in an endemic area in Benin, Africa. Twenty-three men with microfilaremia (100-30,000/mL) were randomly assigned to receive albendazole (200 mg; n = 11) or placebo (n = 12) twice daily for 21 days; 1 patient from each group withdrew from the study. There were no clinical adverse effects and no observed hepatotoxicity, renal toxicity, or hematologic abnormalities attributable to the drug. In the albendazole group, microfilarial levels began to decrease at day 14 after treatment and by 6 months had fallen to a geometric mean of 20% of pretreatment levels (vs. 84.8% in the placebo group). Blood eosinophil levels and anti-filarial IgG and IgG4 also fell significantly in response to albendazole. Taken together, these data suggest that albendazole has a primary (possibly embryotoxic) effect on the adult parasite, resulting in a slow decrease in microfilaremia. C1 NIH,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV NATL BENIN,FAC SCI SANTE,COTONOU,BENIN. SOC RECH PALMIER HUILE,POBE,BENIN. SMITHKLINE BEECHAM PHARMACEUT,WELWYN GARDEN CIT,ENGLAND. OI Klion, Amy/0000-0002-4986-5326 NR 35 TC 49 Z9 49 U1 0 U2 1 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 JUL PY 1993 VL 168 IS 1 BP 202 EP 206 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA LH880 UT WOS:A1993LH88000030 PM 8515109 ER PT J AU TSUBOI, R SATO, C KURITA, Y RON, D RUBIN, JS OGAWA, H AF TSUBOI, R SATO, C KURITA, Y RON, D RUBIN, JS OGAWA, H TI KERATINOCYTE GROWTH-FACTOR (FGF-7) STIMULATES MIGRATION AND PLASMINOGEN-ACTIVATOR ACTIVITY OF NORMAL HUMAN KERATINOCYTES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SERUM-FREE MEDIUM; UROKINASE-TYPE; ENDOTHELIAL-CELLS; FACTOR RECEPTORS; FIBROBLAST; DIFFERENTIATION; EXPRESSION; KGF; SPECIFICITY; INHIBITOR AB Keratinocyte growth factor (KGF), a member of the fibroblast growth factor (FGF) family (and alternatively designated FGF-7), is a paracrine growth factor produced by mesenchymal cells and mitogenic specifically for epithelial cells. The potential effect of KGF on wound healing was assessed in vitro by measuring randomized migration and plasminogen activator (PA) activity of keratinocytes in response to the growth factor. Incubation of normal human keratinocytes with KGF in modified MCDB 153 medium significantly stimulated cell migration and PA activity compared with control (p < 0.001 and p < 0.01, respectively). When tested in these assays on an equimolar basis, 1 nM KGF was at least as potent as transforming growth factor alpha and more active than basic FGF. None of these effects were observed when KGF was administered to fibroblasts or endothelial cells. Stimulation of keratinocyte migration by KGF was dose dependent, and a neutralizing monoclonal antibody against KGF reduced KGF-stimulated migration and cell growth. Zymographic analyses of cell extracts and conditioned medium from KGF-treated keratinocytes revealed increased PA activity, which was mainly attributable to an elevated level of urokinase-type PA. These in vitro results suggest that KGF may have an important role in stimulating reepithelialization during the process of wound repair. C1 TECHNION ISRAEL INST TECHNOL,FAC BIOL,HAIFA,ISRAEL. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP TSUBOI, R (reprint author), JUNTENDO UNIV,SCH MED,DEPT DERMATOL,2-1-1 HONGO,BUNKYO KU,TOKYO 113,JAPAN. NR 30 TC 114 Z9 117 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1993 VL 101 IS 1 BP 49 EP 53 DI 10.1111/1523-1747.ep12358892 PG 5 WC Dermatology SC Dermatology GA LM653 UT WOS:A1993LM65300009 PM 8331296 ER PT J AU LICHTI, U WEINBERG, WC GOODMAN, L LEDBETTER, S DOOLEY, T MORGAN, D YUSPA, SH AF LICHTI, U WEINBERG, WC GOODMAN, L LEDBETTER, S DOOLEY, T MORGAN, D YUSPA, SH TI IN-VIVO REGULATION OF MURINE HAIR-GROWTH - INSIGHTS FROM GRAFTING DEFINED CELL-POPULATIONS ONTO NUDE-MICE SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 41ST ANNUAL SYMP ON THE BIOLOGY OF THE SKIN : FUNDAMENTALS OF HAIR BIOLOGY CY JUL 25-29, 1992 CL SNOWMASS VILLAGE, CO SP CUTANEOUS BIOL FDN ID DERMAL PAPILLA CELLS; COLLAGEN MATRIX; STEM-CELLS; MOUSE SKIN; FOLLICLE; CULTIVATION; INVITRO; CULTURES; TRANSPLANTATION; MORPHOGENESIS AB The nude mouse graft model for testing the hair-forming ability of selected cell populations has considerable potential for providing insights into factors that are important for hair follicle development and proper hair formation. We have developed a minimal component system consisting of immature hair follicle buds from newborn pigmented C57BL/6 mice and adenovirus E1A-immortalized rat vibrissa dermal papilla cells. Hair follicle buds contribute to formation of hairless skin when grafted alone or with Swiss 3T3 cells, but produce densely haired skin when grafted with a fresh dermal cell preparation. The fresh dermal cell preparation represents the single cell fraction after hair follicles have been removed from a collagenase digest of newborn mouse dermis. It provides dermal papilla cells, fibroblasts, and possibly other important growth factor-producing cell types. Rat vibrissa dermal papilla cells supported dense hair growth at early passage in culture but progressively lost this potential during repeated passage in culture. Of 19 E1A-immortalized, clonally derived rat vibrissa dermal papilla cell lines, the four most positive clones supported hair growth to the extent of approximately 200 to 300 hairs per 1-2 cm2 graft area. The remaining clones were moderately positive (five clones), weakly positive (three clones), or negative (seven clones). Swiss 3T3 cells prevented contraction of the graft area but did not appear to affect the number of hairs in the graft site produced by dermal papilla cells plus hair follicle buds alone. The relatively low hair density (estimated 1-5% of normal) resulting from grafts of hair follicle buds with the most positive of the immortalized dermal papilla cell clones compared to fresh dermal cells suggests that optimal reconstitution of hair growth requires some function of dermal papilla cells partially lost during the immortalization process and possibly the contribution of other cell types present in the fresh dermal cell preparation, which is not supplied by the Swiss 3T3 cells. The current graft system, comprising hair follicle buds and immortalized dermal papilla cell clones, provides an assay for positive or negative influences on hair growth exerted by added selected cell types, growth factors, or other substances. Characterization of the phenotype of the dermal papilla cell lines, which differ in their ability to support hair growth when grafted with hair follicle buds, may provide insight into specific dermal papilla cell properties important for their function in this system. C1 NCI,CELLULAR CARCINOGENES & TUMOR PROMOT LAB,BETHESDA,MD 20892. UPJOHN CO,CANC RES,KALAMAZOO,MI 49001. SW FDN BIOMED RES,SAN ANTONIO,TX 78284. RI Weinberg, Wendy/A-8920-2009 NR 36 TC 69 Z9 75 U1 0 U2 6 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1993 VL 101 IS 1 SU S BP S124 EP S129 DI 10.1111/1523-1747.ep12363165 PG 6 WC Dermatology SC Dermatology GA LN154 UT WOS:A1993LN15400021 PM 8326145 ER PT J AU OKEEFE, EJ HAMILTON, EH LEE, SC STEINERT, P AF OKEEFE, EJ HAMILTON, EH LEE, SC STEINERT, P TI TRICHOHYALIN - A STRUCTURAL PROTEIN OF HAIR, TONGUE, NAIL, AND EPIDERMIS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 41ST ANNUAL SYMP ON THE BIOLOGY OF THE SKIN : FUNDAMENTALS OF HAIR BIOLOGY CY JUL 25-29, 1992 CL SNOWMASS VILLAGE, CO SP CUTANEOUS BIOL FDN ID EPITHELIAL CYTOKERATINS; INTERMEDIATE FILAMENTS; MAMMALIAN-TISSUES; KERATIN; FOLLICLE; EXPRESSION; DIFFERENTIATION; ANTIBODIES; SEQUENCE; PATTERNS AB In the course of studies of desmosomes, we found trichohyalin, a 200-kDa protein of the inner root sheath and medulla, in a citric acid-insoluble fraction (''desmosome preparation'') from tongue epithelium. Pig tongue epithelium yielded milligram quantities of pure trichohyalin from about 100 g of keratomed epithelium. The protein has an extended shape as determined by gel filtration, ultracentrifugation, and electron microscopy, with a rod domain and a globular domain at one end and overall dimensions of about 85 nm. Crosslinking studies suggest that the protein may be dimeric in solution. The protein is a doublet in some animals but apparently is a single polypeptide of 220 kDa in humans. Immunofluorescence studies showed that it is a major protein of the filiform papillae of the tongue of mammals and is present in isolated cells of the stratum granulosum of some regions of epidermis in a subset of cells containing filaggrin and in the nail matrix. Similarly, in filiform papillae some cells contain granules that stain for both trichohyalin and filaggrin. Immunoblotting confirmed that trichohyalin is present in tongue and epidermis. Polymerase chain reaction with human genomic DNA using oligonucleotide primers based on sheep trichohyalin resulted in synthesis of multiple DNAs, from which a 504-bp fragment was subcloned and sequenced and found to resemble closely the carboxyl terminus of sheep trichohyalin. Studies with antibody to the carboxyl-terminal 14 amino acids of the human sequence show that, whereas the carboxyl-terminal epitope is present only in the stratum granulosum, in epidermis epitopes detected by a monoclonal antibody are demonstrated in both the stratum granulosum and stratum corneum, suggesting that the carboxyl terminus is cleaved in the stratum corneum. C1 NIAMSD,SKIN BIOL BRANCH,BETHESDA,MD. RP OKEEFE, EJ (reprint author), UNIV N CAROLINA,DEPT DERMATOL,137 NCMH,CB 7600,CHAPEL HILL,NC 27514, USA. FU NIAMS NIH HHS [AR 25871] NR 24 TC 23 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1993 VL 101 IS 1 SU S BP S65 EP S71 DI 10.1111/1523-1747.ep12362866 PG 7 WC Dermatology SC Dermatology GA LN154 UT WOS:A1993LN15400012 PM 7686953 ER PT J AU YUSPA, SH WANG, QZ WEINBERG, WC GOODMAN, L LEDBETTER, S DOOLEY, T LICHTI, U AF YUSPA, SH WANG, QZ WEINBERG, WC GOODMAN, L LEDBETTER, S DOOLEY, T LICHTI, U TI REGULATION OF HAIR FOLLICLE DEVELOPMENT - AN IN-VITRO MODEL FOR HAIR FOLLICLE INVASION OF DERMIS AND ASSOCIATED CONNECTIVE-TISSUE REMODELING SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 41ST ANNUAL SYMP ON THE BIOLOGY OF THE SKIN : FUNDAMENTALS OF HAIR BIOLOGY CY JUL 25-29, 1992 CL SNOWMASS VILLAGE, CO SP CUTANEOUS BIOL FDN ID GROWTH-FACTORS; CELL-PROLIFERATION; GENE-EXPRESSION; PAPILLA CELLS; INTERSTITIAL COLLAGENASE; COLLAGENOLYTIC ACTIVITY; SKIN DEVELOPMENT; IV COLLAGENASE; MOUSE EMBRYO; MATRIX AB During embryonic development presumptive hair follicle cells of epithelial and mesenchymal origin are determined in defined body locations. This is followed by rapid proliferation of epithelial cells and associated penetration into the dermis in response to as yet undetermined signals. A collagen matrix culture system, which maintains the three-dimensional relationships of hair follicle cells to each other, was developed to study the regulation of the enlargement of immature hair follicles and the accompanying remodeling of the dermis. In studies with a heterogeneous dermis-derived preparation of murine hair follicles, ranging in size from the earliest down-growing budding cell mass to hair-forming follicles, we had previously shown that cell proliferation was stimulated by cholera toxin and epidermal growth factor, but only the epidermal growth factor-stimulated proliferation was accompanied by digestion of the collagen matrix due to release of collagenolytic enzymes. Further studies revealed that transforming growth factor-alpha also stimulated hair follicle cell proliferation and collagenase release. However, although transforming growth factor-beta inhibited the transforming growth factor-alpha-stimulated proliferation, it enhanced the release and activation of collagenases and other gelatin-degrading enzymes detectable by gelatin zymography. Stimulation of collagenolytic activity depended on the three-dimensional hair follicle structure and did not occur in monolayer cultures of hair follicle cells. Comparison of hair follicle buds with more developed dermis-derived hair follicles, plated at the same cell density (based on DNA content), suggested that a greater fraction of cells in the bud-stage follicle responded to the growth factors by release of collagenases. Possibly only the cells in the advancing portion of growing hair follicles that are closest to the dermal papilla cell cluster produce the collagenases in response to growth factors. To examine the participation of dermal papilla cells in collagenase release and activation, several immortalized rat whisker dermal papilla cell lines were co-cultured with mouse hair follicle buds. Co-culture resulted in a marked enlargement of follicles as well as activation of the 92-kDa type IV collagenase, produced by hair follicle buds, that correlated with ability of the dermal papilla cells to stimulate hair formation in grafts of hair follicle buds on nude mice. Dermal papilla cells cultured alone produced the 72-kDa type IV collagenase, which was also activated during co-culture with hair follicle buds. Thus, two activities, both relevant for hair follicle development, namely, cell proliferation and release and activation Of collagenases, have been stimulated in immature hair follicle buds by either growth-factor supplementation or interaction with dermal papilla cells. The collagen matrix culture system allows investigation of the mechanism by which these activities are controlled under defined in vitro conditions. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NCI,BIOL CHEM LAB,BETHESDA,MD 20892. UPJOHN CO,CANC RES,KALAMAZOO,MI 49001. SW FDN RES & EDUC,SAN ANTONIO,TX 78284. RI Weinberg, Wendy/A-8920-2009 NR 35 TC 26 Z9 26 U1 0 U2 4 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 1993 VL 101 IS 1 SU S BP S27 EP S32 DI 10.1111/1523-1747.ep12362567 PG 6 WC Dermatology SC Dermatology GA LN154 UT WOS:A1993LN15400006 PM 8326151 ER PT J AU HE, XS KIESEWETTER, DO LEE, KS MATTSON, MV WEINBERGER, DR DECOSTA, BR AF HE, XS KIESEWETTER, DO LEE, KS MATTSON, MV WEINBERGER, DR DECOSTA, BR TI A COMPARISON OF THE INCORPORATION OF I-123 AND F-18 INTO 1-[1-(3-HYDROXYPHENYL) CYCLOHEXYL]-4-(METHANESULFONYLOXY)PIPERIDINE BY NUCLEOPHILIC DISPLACEMENT WITH I-123 AND F-18 SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE 4-FLUORO-1-[-(3-HYDROXYPHENYL)CYCLOHEXYL] AND 4-IODO-1-[1-(3-HYDROXYPHENYL)CYCLOHEXYL]PIPERIDINES; 1-[1-(3-HYDROXPHENYL)CYCLOHEXYL]-4-(METHANESULFONYLOXY)PIPERIDINE (8); PHENCYCLIDINE; NUCLEOPHILIC DISPLACEMENT; BU4N+I-; BU4N+F-NA123I-; BU4N+18F-; ELIMINATION; KRYPTOFIX ID PHENCYCLIDINE; RECEPTOR; BINDING AB Unlabelled and labelled 4-fluoro- and 4-iodo-1-[1-(3-hydroxyphenyl)cyclohexyl]piperidines (3 and 4, respectively), derivatives of phencyclidine, were synthesized in 3-steps via nucleophilic displacement reaction of 1-[1-(3-hydroxyphenyl) cyclohexyl]-4-(methanesulfonyloxy)piperidine (8). The displacement reaction with 3 molar equivalents of Bu4N+I- gave 58% of 4 with no detectable methanesulfonate elimination. Reaction of a large excess of 8 with (NaI)-I-123- under similar conditions gave up to 40% yield of (I-123]8. In contrast reaction of 8 with 3 molar equivalents of unlabelled Bu4N+F- in refluxing acetonitrile yielded only 3.1% of 3 and 97% of elimination product. Similarly, reaction of a large excess of 8 with (Bu4N+F-)-F-18- at 80-degrees-C in acetonitrile failed to yield detectable quantities of [F-18]3. However, low (0-4%) yields of [F-18]3 were obtained using F-18- in the presence of varying proportions of inorganic base and Krytofix in acetonitrile. C1 NIMH,WARREN GRANT MAGNUSON CLIN CTR,DEPT POSITRON EMISS TOMOG,WASHINGTON,DC 20032. NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP HE, XS (reprint author), NIDDKD,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 14 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUL PY 1993 VL 33 IS 7 BP 573 EP 581 DI 10.1002/jlcr.2580330703 PG 9 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA LK751 UT WOS:A1993LK75100002 ER PT J AU KIESEWETTER, DO DECOSTA, B AF KIESEWETTER, DO DECOSTA, B TI SYNTHESIS OF N1-3-[F-18]FLUOROPROPYL-N4-2-([3,4-DICHLOROPHENYL]ETHYL)PIPERAZINE, A HIGH-AFFINITY LIGAND FOR SIGMA-RECEPTOR SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE SIGMA-RECEPTOR; SIGMA-LIGAND; [F-18]FLUORIDE; N(1)-3-[F-18]FLUOROPROPYL-N(4)-2-([3,4-DICHLOROPHENYL]ETHYL)PIPERAZINE ID ANION-EXCHANGE RESIN; F-18 FLUORIDE; WATER AB The radiochemical synthesis of the high affinity, selective sigma receptor ligand, N1-3-[F-18]Fluoropropyl-N4-2-([3,4-dichlorophenyl]ethyl)piperazine, is reported. The labeled compound is prepared by fluoride displacement on a bis-methanesulfonate salt of the propyl methanesulfonyloxy precursor. The product is isolated by first passage through a BONDELUT-SI and subsequently HPLC in high radiochemical and chemical purity with a decay corrected radiochemical yield of 49 +/- 9 %. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP KIESEWETTER, DO (reprint author), NIDDKD,WARREN GRANT MAGNUSEN CLIN CTR,DEPT POSITRON EMISS TOMOG,BETHESDA,MD 20892, USA. NR 6 TC 14 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUL PY 1993 VL 33 IS 7 BP 639 EP 643 DI 10.1002/jlcr.2580330711 PG 5 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA LK751 UT WOS:A1993LK75100010 ER PT J AU COXEY, RA PENTCHEV, PG CAMPBELL, G BLANCHETTEMACKIE, EJ AF COXEY, RA PENTCHEV, PG CAMPBELL, G BLANCHETTEMACKIE, EJ TI DIFFERENTIAL ACCUMULATION OF CHOLESTEROL IN GOLGI COMPARTMENTS OF NORMAL AND NIEMANN-PICK TYPE-C FIBROBLASTS INCUBATED WITH LDL - A CYTOCHEMICAL FREEZE-FRACTURE STUDY SO JOURNAL OF LIPID RESEARCH LA English DT Article DE UNESTERIFIED CHOLESTEROL TRANSPORT; LOW DENSITY LIPOPROTEIN; FILIPIN ID CELLS; CISTERNAE; MEMBRANES; APPARATUS; TRANSPORT; PROTEINS; PATHWAY; FILIPIN AB Cholesterol accumulation in the Golgi of normal and Niemann-Pick Type C (NP-C) fibroblasts was shown by freeze-fracture electron microscopy using filipin as a probe for unesterified cholesterol. The specific distribution of cholesterol within individual Golgi compartments could be examined because membrane cholesterol forms complexes with filipin that are visible as membrane deformations (pits and protuberances) in freeze-fracture replicas. The density of filipin-cholesterol deformations, quantitated for cis, medial, and trans Golgi cisternae and trans Golgi vacuoles, was shown to increase in a cis to trans direction. After addition of low density lipoproteins (LDL) to cultured fibroblasts for 24 h, the cholesterol content increased within specific compartments of the Golgi. Normal cells showed an increase in filipin-cholesterol deformations in membranes of cis/medial cisternae and trans Golgi vacuoles, whereas NP-C cells showed only an increase in membranes of trans Golgi cisternae. LDL uptake by cells appears to induce a disparate cholesterol enrichment of Golgi compartments of normal and mutant cells. The ability of cells to process endocytosed cholesterol may in part depend on modulation of cholesterol-enriched membrane transport through the Golgi, a function which appears to be defective in NP-C cells. C1 NIDDKD,CELLULAR & DEV BIOL,ENDOCRINOL SECT,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,STAT & MATH METHODOL,BETHESDA,MD 20892. NR 25 TC 102 Z9 103 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 1993 VL 34 IS 7 BP 1165 EP 1176 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL829 UT WOS:A1993LL82900010 PM 8371064 ER PT J AU ROSS, AC KEMPNER, ES AF ROSS, AC KEMPNER, ES TI RADIATION INACTIVATION ANALYSIS OF ACYL-COA RETINOL ACYLTRANSFERASE AND LECITHIN RETINOL ACYLTRANSFERASE IN RAT-LIVER SO JOURNAL OF LIPID RESEARCH LA English DT Article DE VITAMIN-A; MICROSOMES; TARGET SIZE; ACYLTRANSFERASE ID MAMMARY-GLAND MICROSOMES; CHOLESTEROL ACYLTRANSFERASE; COENZYME-A; ESTER HYDROLASES; SMALL-INTESTINE; TARGET ANALYSIS; ESTERIFICATION; SOLUBILIZATION; MEMBRANE; ENZYMES AB Microsomes from liver and several other tissues esterify retinol through both fatty acyl-CoA-dependent and -independent reactions. Two activities, acyl-CoA:retinol acyltransferase (ARAT) and lecithin:retinol acyltransferase (LRAT) activities, have been characterized enzymatically but neither has yet been purified and characterized biochemically. We have used the method of radiation inactivation to determine the target sizes of ARAT and LRAT in intact microsomal membranes from rat liver. After exposure of frozen liver microsomes to ionizing radiation, the activity of ARAT decayed exponentially yielding a target size of 73 +/- 18 kDa (mean +/- SD, n = 6). The activity of LRAT was assayed both by monitoring the esterification of retinol bound to the cellular retinol-binding protein (CRBP) and of solvent-dispersed retinol. With both assays a single exponential was observed with radiation doses of 9 to 150 Mrads. The slopes obtained with both LRAT assays were similar, yielding target sizes of 52 +/- 10 kDa (n = 10) for the LRAT assay with CRBP-retinol and 56 +/- 7 kDa (n = 6) for the LRAT assay with dispersed retinol. These target sizes did not differ from each other but were significantly smaller than that of ARAT. These data provide the first physical evidence of the independent entities which catalyze the ARAT and LRAT reactions of liver microsomes. C1 NIAMSD,BETHESDA,MD 20892. RP ROSS, AC (reprint author), MED COLL PENN,DEPT BIOCHEM,2900 QUEEN LANE,PHILADELPHIA,PA 19129, USA. FU NHLBI NIH HHS [HL-22633] NR 33 TC 10 Z9 10 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUL PY 1993 VL 34 IS 7 BP 1201 EP 1207 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL829 UT WOS:A1993LL82900013 PM 8371067 ER PT J AU TABOR, E CAIRNS, J GERETY, RJ BAYLEY, AC AF TABOR, E CAIRNS, J GERETY, RJ BAYLEY, AC TI 9-YEAR FOLLOW-UP-STUDY OF A PLASMA-DERIVED HEPATITIS-B VACCINE IN A RURAL AFRICAN SETTING SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HEPATOCELLULAR CARCINOMA; HEPATITIS-B VIRUS; NONRESPONDER; ANTI-HBS; ANTI-HBC; HUMAN IMMUNODEFICIENCY VIRUS TYPE-1; ANTI-HIV-1; HUMAN T-LYMPHOTROPIC VIRUS TYPE-1; ANTI-HTLV-1 ID LONG-TERM IMMUNOGENICITY; PERSISTENCE; ADULTS; REVACCINATION; EFFICACY; DURATION; ANTIBODY; CHILDREN; VIRUS; HIV AB One hundred and one of 255 recipients of a plasma-derived hepatitis B vaccine were evaluated in 1990, 9 years after the first vaccine dose in a study in Zambia to evaluate the efficacy of one, two, or three doses. In 1983, 2 years after the first vaccine dose, antibody to the hepatitis B surface antigen (anti-HBs) had been detectable in 90 of these 101 participants (89%). In 1990, anti-HBs was still detectable in 72 of 101 (71%), and was present at a protective level (greater-than-or-equal-to 10 mIU/ml) in 68 of 101 (67%). Although the original vaccine study elicited a protective level of antibody in a greater percentage of children and adolescents than in adults, there were no significant differences among the three groups at 9 years. (In 1990, anti-HBs was still detectable in 52 of 70 [74%] who had had no serologic markers of the hepatitis B virus in 1981, and a protective level was detected in 47 of 70 [67%].) A protective level of anti-HBs was detected in 1990 in 26 of 36 (72%) recipients of three doses and in 23 of 31 (74%) recipients of two doses; the slightly lower prevalence among recipients of one dose (19 of 34 [56%]) was not statistically significant. However, between the years 1983-1990, hepatitis 8 virus infections had occurred in one of 36 (3%) of those who had been vaccinated with three doses, one of 31 (3%) vaccinated with two doses, and eight of 34 (24%) of those vaccinated with one dose (P < .02 for either two or three doses compared with one dose). These data support the long-term immunogenicity and protective efficacy of a two- or three-dose regimen of the hepatitis B vaccine in a rural African setting. (C) 1993 Wiley-Liss, Inc.* C1 ST FRANCIS HOSP,KATETE,ZAMBIA. BIOGEN,CAMBRIDGE,MA. UNIV ZAMBIA,TEACHING HOSP,LUSAKA,ZAMBIA. RP TABOR, E (reprint author), NCI,BETHESDA,MD 20892, USA. NR 20 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUL PY 1993 VL 40 IS 3 BP 204 EP 209 DI 10.1002/jmv.1890400307 PG 6 WC Virology SC Virology GA LK252 UT WOS:A1993LK25200006 PM 8355018 ER PT J AU KERSTING, U NAPATHORN, S SPRING, KR AF KERSTING, U NAPATHORN, S SPRING, KR TI NECTURUS GALLBLADDER EPITHELIAL-CELL VOLUME REGULATION AND INHIBITORS OF ARACHIDONIC-ACID METABOLISM SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE CELL VOLUME; ION PERMEABILITIES; EPOXYGENASE INHIBITORS; KETOCONAZOLE ID ASCITES TUMOR-CELLS; PROSTAGLANDINS; LEUKOTRIENES; MECHANISMS AB Inhibition of the metabolism of arachidonic acid by the epoxygenase (cytochrome P-450) pathway with the inhibitor ketoconazole results in excessive cell swelling upon exposure to hyposmolality instead of the rapid and complete regulatory volume decrease (RVD) normally observed. NaCl entry from bathing solutions to cell interior was shown to cause this swelling, with Na influx occurring across the basolateral membrane and electrically silent Cl influx across the apical membrane. Ion substitution experiments show that the KCl efflux mediating RVD was unimpaired by ketoconazole, but was overwhelmed by the NaCl influx. Measurements of transepithelial fluid flux, Cl concentration, osmolality and pH showed that gallbladders treated with ketoconazole transiently secreted fluid rather than the normal absorption. We conclude that inhibition of arachidonic acid metabolism does not directly affect RVD by Necturus gallbladder, but that blockade of the epoxygenase pathway can have a profound influence on NaCl entry into gallbladder epithelial cells. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892. NR 12 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUL PY 1993 VL 135 IS 1 BP 11 EP 18 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA LN865 UT WOS:A1993LN86500002 PM 8411129 ER PT J AU MODI, WS AF MODI, WS TI HETEROGENEITY IN THE CONCERTED EVOLUTION PROCESS OF A TANDEM SATELLITE ARRAY IN MEADOW MICE (MICROTUS) SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE CONCERTED EVOLUTION; SATELLITE DNA; MICROTUS ID DNA-SEQUENCES; CANIDS CARNIVORA; GENE CONVERSION; HYBRIDIZATION; CHROMOSOMES; RODENTS; MOUSE; MUS; RECOMBINATION; AMPLIFICATION AB The evolutionary history of a 160-bp tandem satellite array, originally described from Microtus chrotorrhinus and called MSAT-160, was examined in related species of arvicolid rodents by sequence analyses, quantitative dot blotting, and Southern blotting. Results indicate that MSAT-160 is present in 12 of the 20 species and subspecies of Microtus assayed, but not in species belonging to any of the eight other genera examined. DNA from each species containing MSAT-160 was digested with 12 restriction endonucleases and restriction patterns were obtained reflecting the variable extent of homogenization of any given variant in different species. For example, with MboI digestion, M. chrotorrhinus produced a type A ladder pattern where most monomers contain the restriction site, M. ochrogaster generated a type B pattern where most monomers lack the site, and M. agrestis yielded a pattern intermediate between the A and B types. Further, dot blotting revealed copy-number differences between species. These findings indicate that changes in the periodic structure and amount of satellite DNA have occurred since these species last shared a common ancestor. In addition, various species-specific patterns were documented, illustrating that mechanisms other than genome-wide homogenization, such as stochastic mutation, out-of-register crossing over, deletion, and random amplification also play a role in structuring tandem arrays. Stochastic mutation and homogenization rates in satellite DNA, levels of species diversity, and magnitudes of chromosomal divergence differ significantly in Microtus, Mus and Ctenomys, the three rodent lineages examined. RP MODI, WS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N0I-CO-74102] NR 37 TC 33 Z9 33 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD JUL PY 1993 VL 37 IS 1 BP 48 EP 56 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA LH163 UT WOS:A1993LH16300007 PM 8360918 ER PT J AU GARRAFFO, HM CACERES, J DALY, JW SPANDE, TF ANDRIAMAHARAVO, NR ANDRIANTSIFERANA, M AF GARRAFFO, HM CACERES, J DALY, JW SPANDE, TF ANDRIAMAHARAVO, NR ANDRIANTSIFERANA, M TI ALKALOIDS IN MADAGASCAN FROGS (MANTELLA) - PUMILIOTOXINS, INDOLIZIDINES, QUINOLIZIDINES, AND PYRROLIZIDINES SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID POISON FROGS; DENDROBATID FROGS; SKELETAL-MUSCLE; SKIN ALKALOIDS; 8-METHYLINDOLIZIDINES; MYOBATRACHIDAE; PHARMACOLOGY; CHANNEL; CALCIUM; SITES AB Brightly colored ranid frogs of the genus Mantella are found only in min forests of Madagascar. Gc-ms and gc-Ft-ir analyses of skin alkaloids of seven different species, including four populations of Mantella madagascariensis, are reported. All contain one or more representatives of the pumiliotoxin A (PTX-A) class with the 13,14-dihydro derivatives 309A and 325A found in major amounts in the four populations of M. madagascariensis, while 307A (PTX-A) is found in two populations of M. madagascariensis and in three additional species, Mantella aurantiaca, Mantella viridis, and Mantella crocea. The latter three species also contain appreciable quantities of 323A (PTX-B). The four populations of M. madagascariensis show major amounts of two 1,4-disubstituted quinolizidines, 217A and 231A, and a 5,8-disubstituted indolizidine, 217B, in addition to many minor or trace quinolizidines and indolizidines. Such disubstituted quinolizidines and indolizidines are present as trace alkaloids in the six other species of Mantella, along with 3,5-disubstituted indolizidines, 3,5-disubstituted pyrrolizidines, the decahydroquinoline cis-195A, tricyclic alkaloids, and homopumiliotoxins. A new alkaloid class, which appears to contain a quinolizidine moiety, is seen in M. aurantiaca and M. crocea and is represented by 235C and several congeners. C1 UNIV ANTANANARIVO,CHIM ORGAN PROD NAT LAB,ANTANANARIVO 1001,MALAGASY REPUBL. RP GARRAFFO, HM (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A17,BETHESDA,MD 20892, USA. NR 30 TC 86 Z9 87 U1 0 U2 6 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUL PY 1993 VL 56 IS 7 BP 1016 EP 1038 DI 10.1021/np50097a005 PG 23 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA LP675 UT WOS:A1993LP67500005 PM 8377013 ER PT J AU CARDELLINA, JH MUNRO, MHG FULLER, RW MANFREDI, KP MCKEE, TC TISCHLER, M BOKESCH, HR GUSTAFSON, KR BEUTLER, JA BOYD, MR AF CARDELLINA, JH MUNRO, MHG FULLER, RW MANFREDI, KP MCKEE, TC TISCHLER, M BOKESCH, HR GUSTAFSON, KR BEUTLER, JA BOYD, MR TI A CHEMICAL-SCREENING STRATEGY FOR THE DEREPLICATION AND PRIORITIZATION OF HIV-INHIBITORY AQUEOUS NATURAL-PRODUCTS EXTRACTS SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID REVERSE-TRANSCRIPTASE; IMMUNODEFICIENCY AB A relatively high percentage (ca. 15 %) of aqueous extracts from terrestrial plants, cyanobacteria, and marine invertebrates and algae has exhibited activity in the National Cancer Institute's primary AIDS-antiviral screen. By removal of anionic polysaccharides in a first stage of dereplication, we have eliminated from further consideration a considerable number of these extracts. However, a still substantial proportion of the active extracts remained, from which we wished to select and prioritize a small percentage for our detailed bioassay-directed fractionation studies. Therefore, a chemical screening protocol, utilizing various solid-phase extraction cartridges, has been developed for a second-stage dereplication and to assist in prioritization of these extracts for our further investigations. C1 NATL CANC INST,DIV CANC,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,ROOM 121,FREDERICK,MD 21702. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 20 TC 72 Z9 74 U1 0 U2 6 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUL PY 1993 VL 56 IS 7 BP 1123 EP 1129 DI 10.1021/np50097a016 PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA LP675 UT WOS:A1993LP67500016 PM 8104236 ER PT J AU MCMILLIAN, MK HUDSON, PM SUH, HH YE, H TUOMINEN, RK HONG, JS AF MCMILLIAN, MK HUDSON, PM SUH, HH YE, H TUOMINEN, RK HONG, JS TI ROLE OF OMEGA-CONOTOXIN GVIA-SENSITIVE CA2+ ENTRY IN ANGIOTENSIN II-STIMULATED [3H]PHORBOL 12,13-DIBUTYRATE BINDING IN BOVINE ADRENAL-MEDULLARY CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CHROMAFFIN; ADRENAL MEDULLA; PROTEIN KINASE-C; ANGIOTENSIN-II; PHORBOL DIBUTYRATE BINDING; K+ CHANNELS; OMEGA-CONOTOXIN GVIA ID PROTEIN-KINASE-C; CHROMAFFIN CELLS; CATECHOLAMINE SECRETION; CALCIUM CHANNELS; CYTOSOLIC CA-2+; RECEPTOR SUBTYPES; PHORBOL ESTERS; SMOOTH-MUSCLE; K+-CHANNELS; RESPONSES AB The relative contributions of Ca2+ influx and intracellular Ca2+ mobilization were examined for angiotensin II-stimulated [H-3]phorbol 12,13-dibutyrate binding, which reflects the level of activated protein kinase C in bovine chromaffin cells. Angiotensin II receptors activate phospholipase C in chromaffin cells, leading to a short-lived mobilization of intracellular Ca2+ . Angiotensin II-stimulated [H-3]phorbol 12,13-dibutyrate binding was largely blocked in Ca2+-free buffer and by pretreatment with the Ca2+-channel blocker omega-conotoxin GVIA. The [H-3]phorbol 12,13-dibutyrate binding response to [Sar1]angiotensin II also appeared to be voltage sensitive, as no additivity was observed with the response to the depolarizing agent 4-aminopyridine (3 mM). Threshold sensitivities of the extra- and intracellular Ca2+ -mobilizing pathways to angiotensin II were similar, and all examined effects of angiotensin II in these cells were apparently mediated by Iosartan-sensitive (AT1-like) receptors. The dependence of angiotensin II-stimulated [H-3]phorbol 12,13-dibutyrate binding on extracellular Ca2+ entry, in contrast to stimulation by other phospholipase C-linked receptor agonists (bradykinin and methacholine), suggests that angiotensin II preferentially stimulates protein kinase C translocation to the plasma membrane, rather than to internal membranes, in bovine adrenal medullary cells. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. NR 43 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1993 VL 61 IS 1 BP 93 EP 99 DI 10.1111/j.1471-4159.1993.tb03541.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LH227 UT WOS:A1993LH22700010 PM 8515289 ER PT J AU SYNDULKO, K TOURTELLOTTE, WW CONRAD, AJ IZQUIERDO, G BELENDUK, G KASPER, B KLATZMAN, D MIETLOWSKI, W SOLCH, S FRANKLIN, G BURKS, J NELSON, L WANGAARD, C MCFARLAND, H GOODMAN, A MCFARLIN, D KREBS, H MALONI, H DEBRONOZO, J SCHEINBERG, L TRAUGOTT, U AISEN, M ROBBINS, K SIBLEY, W LAGUNA, J LAGUNA, J TROTTER, J CLIFORD, D SMITH, L MCINNIS, J ARNASON, B ROOS, R REDER, A ANTEL, J AGUIS, M MARTIA, R HURWITZ, B GREENBURG, S FREDANE, L HERBSTREITH, R HURWITZ, J JOHNSON, K PANITCH, H KOSKI, CL FISHMAN, P HALEY, S PETAJAN, J BRAY, P ROSE, J THURMAN, D GALSTER, W ELLISON, G MYERS, L NEWTON, L WOLINSKY, J SEARS, ES NATH, A WEISBRODT, C KASTRUKOFF, LF OGER, JJ PATY, D BAUMHEFNER, RW AF SYNDULKO, K TOURTELLOTTE, WW CONRAD, AJ IZQUIERDO, G BELENDUK, G KASPER, B KLATZMAN, D MIETLOWSKI, W SOLCH, S FRANKLIN, G BURKS, J NELSON, L WANGAARD, C MCFARLAND, H GOODMAN, A MCFARLIN, D KREBS, H MALONI, H DEBRONOZO, J SCHEINBERG, L TRAUGOTT, U AISEN, M ROBBINS, K SIBLEY, W LAGUNA, J LAGUNA, J TROTTER, J CLIFORD, D SMITH, L MCINNIS, J ARNASON, B ROOS, R REDER, A ANTEL, J AGUIS, M MARTIA, R HURWITZ, B GREENBURG, S FREDANE, L HERBSTREITH, R HURWITZ, J JOHNSON, K PANITCH, H KOSKI, CL FISHMAN, P HALEY, S PETAJAN, J BRAY, P ROSE, J THURMAN, D GALSTER, W ELLISON, G MYERS, L NEWTON, L WOLINSKY, J SEARS, ES NATH, A WEISBRODT, C KASTRUKOFF, LF OGER, JJ PATY, D BAUMHEFNER, RW TI TRANS-BLOOD-BRAIN-BARRIER ALBUMIN LEAKAGE AND COMPARISONS OF INTRATHECAL IGG SYNTHESIS CALCULATIONS IN MULTIPLE-SCLEROSIS PATIENTS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE CEREBROSPINAL FLUID; IMMUNOGLOBULIN-G; ALBUMIN; MULTIPLE SCLEROSIS; INTRATHECAL ID CENTRAL NERVOUS-SYSTEM; HUMORAL IMMUNE-RESPONSE; LYMPHOBLASTOID INTERFERON THERAPY; CEREBROSPINAL-FLUID; IMMUNOGLOBULIN-G; FORMULAS; QUANTITATION; DISEASES AB We compared four equations for estimating intrathecal IgG synthesis (Tibbling and Link IgG index (T/L), Schuller and Sagar (S/S), Reiber and Felgenhauer (R/F), and Tourtellotte (T) equations) using data from chronic progressive MS patients. For normal albumin leakage (AL) (< 75 mg/day - intact BBB), T (r = 0.15) and R/F (r = 0. 10) showed comparable positive correlations with trans-BBB AL, T/L (r = - 0. 10) was negative and S/S was uncorrelated (r = 0.05). For abnormal AL (greater-than-or-equal-to 75 mg/day), the R/F (r = - 0.24), S/S (r = - 0.37) and the T/L (r = - 0.22) equations overcorrected, whereas the T (r = 0.07) equation values did not correlate with AL. The albumin index and trans-BBB albumin leakage rate formulae gave essentially identical estimates of BBB leakage (r = 0.99, P = 0.0001). We conclude that in chronic progressive MS patients the R/F, T/L and S/S formulae overcompensate for large abnormal T-BBB albumin leakage rates. The T formula corrected best for IgG transudate at high AL rate values in MS. C1 VAMC W LOS ANGELES, NEUROL SERV, LOS ANGELES, CA 90073 USA. VAMC W LOS ANGELES, RES SERV, LOS ANGELES, CA 90073 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, LOS ANGELES, CA USA. HOSP UNIV SEVILLA, SERV NEUROL, SEVILLE, SPAIN. SANDOZ PHARMACEUT CORP, SANDOZ RES INST, E HANOVER, NJ USA. UNIV COLORADO, HLTH SCI CTR, ROCKY MT MULTIPLE SCLEROSIS CTR, DENVER, CO 80262 USA. NIH, NEUROIMMUNOL BRANCH, BETHESDA, MD 20892 USA. YESHIVA UNIV ALBERT EINSTEIN COLL MED, BRONX, NY 10461 USA. ARIZONA HLTH SCI CTR, TUCSON, AZ 85724 USA. WASHINGTON UNIV, SCH MED, ST LOUIS, MO 63110 USA. UNIV CHICAGO, CHICAGO, IL 60637 USA. DUKE UNIV, COLL MED, DURHAM, NC 27706 USA. UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. UNIV UTAH, MED CTR, SALT LAKE CITY, UT 84112 USA. UNIV TEXAS, HLTH SCI CTR, HOUSTON, TX 77225 USA. UNIV BRITISH COLUMBIA, HLTH SCI CTR HOSP, DEPT MED, VANCOUVER V6T 1W5, BC, CANADA. NR 28 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 1993 VL 46 IS 1-2 BP 185 EP 192 DI 10.1016/0165-5728(93)90248-W PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA LZ487 UT WOS:A1993LZ48700023 PM 8360328 ER PT J AU LENZ, FA SEIKE, M RICHARDSON, RT LIN, YC BAKER, FH KHOJA, I JAEGER, CJ GRACELY, RH AF LENZ, FA SEIKE, M RICHARDSON, RT LIN, YC BAKER, FH KHOJA, I JAEGER, CJ GRACELY, RH TI THERMAL AND PAIN SENSATIONS EVOKED BY MICROSTIMULATION IN THE AREA OF HUMAN VENTROCAUDAL NUCLEUS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SINGLE-UNIT ANALYSIS; POSTERIOR LATERAL NUCLEUS; CENTRAL NERVOUS-SYSTEM; THALAMIC VPM NUCLEUS; SPINOTHALAMIC TRACT; BODY REPRESENTATION; NEURONS; MONKEY; PRIMATE; TERMINATIONS AB 1. We have studied the sensations evoked by threshold microstimulation (TMS) in the area of the human principal sensory nucleus of the thalamus [ventralis caudalis (Vc)] in patients (n = 11) undergoing stereotactic surgery for the treatment of movement disorders and pain. Preoperatively, patients were trained to describe somatic sensory stimuli using a standard list of descriptors. This same list was used to describe sensations evoked intraoperatively by thalamic microstimulation. Stimulation sites (n = 216) were defined by location within the area where the majority of cells had a reproducible response to innocuous cutaneous stimulation (core region) or in the cellular area posterior and inferior to the core region (posteroinferior region). 2. TMS-evoked sensations were categorized as paresthetic if the descriptors ''tingle,'' ''vibration,'' or ''electric current'' were chosen by the patient to describe the sensation and as thermal/pain if the descriptors ''cool,'' ''warm,'' ''warm and cool,'' or ''pain'' were chosen. Thermal/pain sensations were evoked by stimulation in 82% (9/11) of patients and at 19% of sites studied. These results suggest that thalamic microstimulation can evoke thermal/pain sensations reproducibly across patients. 3. Thermal/pain sensations were evoked more frequently by stimulation at sites in the posteroinferior region (30%) than by stimulation at sites in the core region (5%). Nonpainful thermal sensations composed the majority of thermal/pain sensations evoked by stimulation in both the core (80%) and posteroinferior regions (86%). Sites where stimulation evoked pain and nonpainful cool sensations were found anterior to the area where nonpainful warm sensations were evoked. Thermal/pain sensations were evoked at sites located medially near the border between the core and posteroinferior regions. 4. Radiologic techniques were used to determine the presumed nuclear location of stimulation sites. Thermal/pain sensations were evoked less frequently by stimulation in the part of Vc included in the core region than by stimulation in any of the following: the part of Vc included in the posteroinferior region, ventralis caudalis portae nucleus, ventralis caudalis parvocellularis nucleus, or the white matter underlying the ventral nuclear group. 5. The location of the sensation evoked by stimulation [projected field (PF)] varied widely in size. PFs were categorized as large if they involved more than one part of the body (e.g., face and arm) or if they crossed at least one joint proximal to the metacarpophalangeal joint or to the metatarsophalangeal joint. PFs were more frequently large at sites where thermal/pain sensations were evoked by TMS (33%) than at those where paresthesia were evoked (6%). 6. PFs were referred to subcutaneous structures more frequently for stimulation sites located in the posteroinferior region (50%) than in the core region (28%), where PFs were often referred to cutaneous structures. 7. These results demonstrate that the sensations evoked by stimulation in the posteroinferior region are significantly different from those evoked by stimulation in the cutaneous core of Vc. TMS in the posteroinferior region evokes thermal sensations or pain often referred to large receptive fields and subcutaneous structures. These results suggest that neural elements in the posteroinferior region and in the posterior inferior aspect of the core region are involved in the perception of nonpainful thermal sensations as well as pain. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP LENZ, FA (reprint author), JOHNS HOPKINS UNIV HOSP,DEPT NEUROSURG,MEYER BLDG,7-113,600 N WOLFE ST,BALTIMORE,MD 21287, USA. FU NINDS NIH HHS [K08 NS-01384, NS-28598] NR 59 TC 148 Z9 149 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 1993 VL 70 IS 1 BP 200 EP 212 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LM760 UT WOS:A1993LM76000016 PM 8360716 ER PT J AU BOWMAN, EM BROWN, VJ KERTZMAN, C SCHWARZ, U ROBINSON, DL AF BOWMAN, EM BROWN, VJ KERTZMAN, C SCHWARZ, U ROBINSON, DL TI COVERT ORIENTING OF ATTENTION IN MACAQUES .1. EFFECTS OF BEHAVIORAL CONTEXT SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VISUAL SPATIAL ATTENTION; POSTERIOR PARIETAL CORTEX; DIRECTED ATTENTION; MONKEY; RESPONSES; PULVINAR; NEURONS; ENHANCEMENT; SENSITIVITY; MODULATION AB 1. A task was used by Posner (1980) to measure shifts of attention that occurred covertly, in the absence of an eye movement or other orienting response. This paradigm was used here to assess the nature of covert attentional orienting in monkeys to develop an animal model for neurophysiological studies. Shifts of attention were measurable in monkeys and were consistent across a variety of experimental conditions. 2. The paradigm required that monkeys fixate and release a bar at the appearance of a target, which was preceded by a cue. Reaction times to targets that followed peripheral cues at the same location (validly cued) were significantly faster than those that followed cues in the opposite visual field (invalidly cued). This difference was defined as the validity effect, which as in humans, is used as the measure of a covert attentional shift. 3. When the proportion of validly to invalidly cued targets was decreased, no change was seen in the validity effect of the monkeys. This is in contrast to humans, for whom the ratio of validly to invalidly cued targets affected the magnitude of the validity effect. When 80% of the targets were preceded by cues at the same location, the validity effect was greatest. The effect was reversed when the proportions were reversed. From this result, it is concluded that cognitive processes can affect covert orienting to peripheral cues in humans, whereas in trained monkeys, performance was automatic. 4. To test whether cognitive influences on attention could be demonstrated in the monkey, an animal was taught to use symbolic, foveal signals to covertly direct attention. The magnitude of this validity effect was greater than that obtained with peripheral cues. 5. The effects of motivational and perceptual processes were tested. Although overall reaction times could. be modified, the facilitating effects of the cues persisted. This constancy across motivational and perceptual levels supports the notion that the monkeys were performing the task in an automatic way, under the exogenous control of peripheral cues. 6. Most visual cuing has been tested with visual landmarks at the locations of cues and targets. These monkeys were trained with such landmarks, and when tested without them, the attentional effect of the cues was nearly abolished. These data suggest that local visual features can be important for covert orienting. 7. To determine the spatial extent of the effect of the cue, monkeys and humans were tested with four cue-target distances (0-60-degrees). Reaction times were fastest at a cue-target distance of 0-degrees (validly cued) for the earliest temporal interval for both monkeys and humans. For the monkey, the validity effect peaked at 20-degrees and declined more eccentrically. For humans, the validity effect was qualitatively similar for distances from 20 to 60-degrees. 8. The present studies demonstrate that peripheral visual cues result in attentional shifts in monkeys, similar to those described in humans. This approach provides an animal model for exogenously elicited attentional shifts. The effects of peripheral cues are reliable in trained monkeys and are minimally susceptible to endogenous or experimental influences. However, like humans, monkeys can exert endogenous control over the covert orienting of attention when symbolic cues are used. C1 NEI,SENSORIMOTOR RES LAB,VISUAL BEHAV SECT,BLDG 49,RM 2A50,BETHESDA,MD 20892. RI Bowman, Eric/A-3780-2010; Brown, Verity/A-5235-2011 OI Brown, Verity/0000-0001-5762-1797 NR 53 TC 69 Z9 69 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 1993 VL 70 IS 1 BP 431 EP 443 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LM760 UT WOS:A1993LM76000033 PM 8360720 ER PT J AU GAWNE, TJ RICHMOND, BJ AF GAWNE, TJ RICHMOND, BJ TI HOW INDEPENDENT ARE THE MESSAGES CARRIED BY ADJACENT INFERIOR TEMPORAL CORTICAL-NEURONS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE INFORMATION; TEMPORAL MODULATION; CODING; SIGNAL; NOISE; VISION ID TWO-DIMENSIONAL PATTERNS; SINGLE UNITS; STRIATE CORTEX; VISUAL-CORTEX; INFORMATION; MONKEY; ORGANIZATION; RESPONSES; CAT AB There are at least three possibilities for encoding information in a small area of cortex. First, neurons could have identical characteristics, thus conveying redundant information; second, neurons could give different responses to the same stimuli, thus conveying independent information; or third, neurons could cooperate with each other to encode more information jointly than they do separately, that is, synergistically. We recorded from 28 pairs of neurons in inferior temporal cortex of behaving rhesus monkeys. Each pair was recorded from a single microelectrode. Both the magnitude and the temporal modulation of the responses were quantified. We separated the responses into signal (average response to each stimulus) and noise (deviation of each response from the average). Linear regression showed that an average of only 18.7% of the magnitude of the signal carried by one neuron could be predicted from the magnitude of the other, and only 22.0% could be predicted by including the temporal modulation. For the noise, the figures were 5.5% and 6.3%, respectively, even less than for the signal. Information theoretic analysis shows that the pairs of neurons we studied carried an average of 20% redundant information. However, even this relatively small amount of redundancy places a severe upper limit on the information that can be transmitted by a neuronal pool. A pool of neurons for which each pair is mutually redundant to extent y can only carry a maximum of 1/y, here five times, as much information as one neuron alone. Information theoretic analysis gave no evidence for the presence of information as a function of both neurons considered together, that is, synergistic codes. Cross-correlation showed that at least 61% of the neuronal pairs shared connections in some manner. Given these shared connections, if adjacent neurons had had identical characteristics, then the noise on the outputs of these neurons would have been highly correlated, and it would not be possible to separate the signal and noise. The severe impact of correlated noise and information redundancy leads us to propose that the processing carried out by these neurons evolved both to provide a rich description of many stimulus properties and simultaneously to minimize the redundancy in a local group of neurons. These two principles appear to be a major constraint on the organization of inferior temporal, and possibly all, cortex. C1 NIMH,NEUROPSYCHOL LAB,BLDG 9,ROOM 1E104,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 35 TC 301 Z9 303 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1993 VL 13 IS 7 BP 2758 EP 2771 PG 14 WC Neurosciences SC Neurosciences & Neurology GA LM273 UT WOS:A1993LM27300003 PM 8331371 ER PT J AU SAVAKI, HE KENNEDY, C SOKOLOFF, L MISHKIN, M AF SAVAKI, HE KENNEDY, C SOKOLOFF, L MISHKIN, M TI VISUALLY GUIDED REACHING WITH THE FORELIMB CONTRALATERAL TO A BLIND HEMISPHERE - A METABOLIC MAPPING STUDY IN MONKEYS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ARM REACHING; MOTOR CORTEX; SENSORY CORTEX; VISUAL CORTEX; AREA-7; AREA-5; VISUOMOTOR TASK; SPLIT-BRAIN MONKEYS; C-14-DEOXYGLUCOSE METHOD ID POSTERIOR PARIETAL CORTEX; PRIMATE MOTOR CORTEX; CORTICO-CORTICAL CONNECTIONS; DIMENSIONAL ARM MOVEMENTS; LATERAL THALAMIC REGION; SOMATIC SENSORY CORTEX; RHESUS-MONKEY; 3-DIMENSIONAL SPACE; ASSOCIATION CORTEX; NEURONAL-ACTIVITY AB The 2-C-14-deoxyglucose method was used to map local cerebral metabolic activity in monkeys performing a unimanual task requiring visually guided arm reaching and key pressing. The study was carried out with monkeys that either had intact brains or had one hemisphere deprived of visual input by unilateral optic tract section combined in some cases with forebrain commissurotomy. The metabolic mapping revealed activation of sensorimotor cortex only in the hemisphere contralateral to the moving forelimb, irrespective of whether this hemisphere was intact or visually deafferented. These results suggest that visually guided reaching with the forelimb contralateral to the ''blind'' hemisphere is sub-served by that hemisphere's sensorimotor cortex and not by the cortex of the ipsilateral, ''seeing'' hemisphere. Other areas that were more active metabolically in the ''blind'' than in the ''seeing'' hemisphere included the supplementary motor, the secondary somatosensory, and certain posterior parietal cortical areas, intraparietal lateral 5 (lateral 5-ip), 7a, and intraparietal 7 (7-ip). It is suggested that the ''blind'' hemisphere utilizes at least two distinct pieces of information to guide forelimb movements to visual targets: (1) information about the location of the visual target derived from head and eye movements made to this target and mediated via the inferior parietal cortical areas 7a and 7-ip, and (2) information about the instantaneous upper extremity position derived from forelimb proprioceptive mechanisms and mediated via the somatosensory cortex and thereafter via the superior parietal cortical area, lateral 5-ip. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP SAVAKI, HE (reprint author), UNIV CRETE,SCH HLTH SCI,DEPT BASIC SCI,DIV MED,PHYSIOL LAB,GR-71110 IRAKLION,GREECE. NR 80 TC 52 Z9 52 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1993 VL 13 IS 7 BP 2772 EP 2789 PG 18 WC Neurosciences SC Neurosciences & Neurology GA LM273 UT WOS:A1993LM27300004 PM 8331372 ER PT J AU PORET, JC LINDGREN, E ROSEN, M SUTER, JJ RIFKIND, JM AF PORET, JC LINDGREN, E ROSEN, M SUTER, JJ RIFKIND, JM TI LASER-GENERATED ULTRASONIC CHARACTERIZATION OF IRRADIATED GLASS OPTICAL FIBERS SO JOURNAL OF NON-CRYSTALLINE SOLIDS LA English DT Article ID DEFECT CENTERS AB Glass optical fibers were irradiated from 100 krad (Si) to 1 Mrad (Si) with gamma radiation from a cobalt-60 source. The irradiated fibers were characterized with laser-generated ultrasonics as well as electron spin resonance techniques. Phosphorus- and germanium-based color centers were observed in the exposed fibers, and the intensity of the color centers was found to increase as the fibers were exposed to larger radiation doses. The extensional wave speed was found to decrease with increasing radiation exposure owing to elastic softening of the fiber. A linear relationship was inferred between the electron spin resonance intensity and the extensional wave speed. C1 JOHNS HOPKINS UNIV,DEPT MAT SCI & ENGN,102 MARYLAND HALL,3400 N CHARLES ST,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,APPL PHYS LAB,LAUREL,MD 20723. NIH,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-3093 J9 J NON-CRYST SOLIDS JI J. Non-Cryst. Solids PD JUL PY 1993 VL 160 IS 1-2 BP 82 EP 88 DI 10.1016/0022-3093(93)90287-8 PG 7 WC Materials Science, Ceramics; Materials Science, Multidisciplinary SC Materials Science GA LP629 UT WOS:A1993LP62900010 ER PT J AU GLOWNIAK, JV KILTY, JE AMARA, SG HOFFMAN, BJ TURNER, FE AF GLOWNIAK, JV KILTY, JE AMARA, SG HOFFMAN, BJ TURNER, FE TI EVALUATION OF METAIODOBENZYLGUANIDINE UPTAKE BY THE NOREPINEPHRINE, DOPAMINE AND SEROTONIN TRANSPORTERS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID ADRENERGIC NERVOUS-SYSTEM; NEURONAL UPTAKE; CLONING; EXPRESSION; HEART; CELLS; NORADRENALINE; AGENTS; DNA AB Metaiodobenzylguanidine (MIBG) is taken up by sympathetic neurons, but the precise mechanism of uptake has not been elucidated. Uptake of monoamines by presynaptic neurons is mediated by plasma membrane proteins, the monoamine transporters. The human norepinephrine transporter (hNET), the bovine dopamine transporter (bDAT) and the rat serotonin transporter (r5HTT) have been cloned, sequenced and expressed in various cell lines. This study involves the measurement of MIBG uptake by cell lines that have been transfected with complementary DNAs encoding these monoamine transporters. At 20 nM MIBG, hNET transfected cells demonstrate a ninefold greater uptake of MIBG than nontransfected cells. MIBG uptake in hNET transfected cells is inhibited by 3 x 10(-6) M norepinephrine (87% inhibition) and by hNET transport inhibitors: 10(-7) M desipramine (94% inhibition) and 10(-7) M Mazindol (97% inhibition). hNET transfected cells exhibit a K(m) for MIBG transport of 264 nM. Percent nonspecific uptake rises with increasing concentrations of MIBG while specific uptake is saturable. There is no significant uptake by bDAT or r5HTT. The NET appears to be responsible for the specific uptake of MIBG. C1 OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201. YALE UNIV,SCH MED,PROGRAM NEUROSCI,NEW HAVEN,CT 06510. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP GLOWNIAK, JV (reprint author), VET AFFAIRS MED CTR,NUCL MED SERV,POB 1034,PORTLAND,OR 97207, USA. FU NIDA NIH HHS [DA07595] NR 32 TC 105 Z9 106 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1993 VL 34 IS 7 BP 1140 EP 1146 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LL238 UT WOS:A1993LL23800024 PM 8315492 ER PT J AU MARIANI, G CEI, A COLLECCHI, P BARANOWSKAKORTYLEWICZ, J VANDENABBEELE, AD DILUCA, L DISTEFANO, R VIACAVA, P FERDEGHINI, EM DISACCO, S SALVADORI, PA BEVILACQUA, G ADELSTEIN, SJ MOSCA, F KASSIS, AI AF MARIANI, G CEI, A COLLECCHI, P BARANOWSKAKORTYLEWICZ, J VANDENABBEELE, AD DILUCA, L DISTEFANO, R VIACAVA, P FERDEGHINI, EM DISACCO, S SALVADORI, PA BEVILACQUA, G ADELSTEIN, SJ MOSCA, F KASSIS, AI TI TUMOR TARGETING IN-VIVO AND METABOLIC-FATE OF 5-[IODINE-125]IODO-2'-DEOXYURIDINE FOLLOWING INTRATUMORAL INJECTION IN PATIENTS WITH COLORECTAL-CANCER SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID MAMMALIAN-CELLS; PYRIMIDINE ANALOGS; RADIOTOXICITY; THYMIDINE; I-125; DNA; CARCINOMA; KINETICS; IODODEOXYURIDINE; PROLIFERATION AB Previous studies have demonstrated the tumor-targeting potential of radioiodinated 5-iodo-2'-deoxyuridine (IUdR) in experimental animal models following direct intratumoral or intracavitary administration. The aim of this study was to measure the tumor uptake and metabolic fate of 5-[I-125]iodo-2'-deoxyuridine (I-125]IUdR) in humans after a single intratumoral injection. Ten patients with colorectal cancer were injected intratumorally with [I-125]IUdR (0.24-3.9 MBq) during endoscopy 24 hr before ablative surgery. Blood and urine samples were collected up to 72 hr after [I-125]IUdR injection. Following resection, the radioactivity in the tumor and the surrounding tissues was measured in a gamma counter, and microautoradiography was performed on semi-thin tissue sections to assess localization of the radiopharmaceutical at the cellular level. An average of 0.234% of the injected dose was present per gram of tumor (range 0.009-0.918, median value 0.147), and tumor-to-nontumor radioactivity incorporation ratios were high for colonic mucosa when the nontumor tissue was taken at 1 cm (mean 629, range 27-2391) and 15 cm (mean 2387, range 122-12674) from the injection site. Microautoradiography confirmed these high tumor-to-nontumor ratios and demonstrated localization of [I-125]IUdR in the tumor cell nuclei. These results suggest that radioiodinated IUdR might have potential as a tumor-targeting agent in humans, provided homogeneous intratumoral distribution of the radiopharmaceutical by a suitable route of loco-regional administration can be achieved. C1 UNIV PISA,INST GEN & VASC SURG,CTR NUCL MED,I-56100 PISA,ITALY. UNIV PISA,INST PATHOL ANAT,I-56100 PISA,ITALY. NATL CANC INST,IST,GENOA,ITALY. HARVARD UNIV,SCH MED,DEPT RADIOL NUCL MED,SHIELDS WARREN RADIAT LAB,BOSTON,MA 02115. RP MARIANI, G (reprint author), UNIV PISA,INST CLIN PHYSIOL,CNR,VIA P SAVI 8,I-56126 PISA,ITALY. RI Di Stefano, Rossella/C-3880-2009; Salvadori, Piero/B-2342-2012 OI Salvadori, Piero/0000-0001-6114-1059 NR 55 TC 36 Z9 36 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1993 VL 34 IS 7 BP 1175 EP 1183 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LL238 UT WOS:A1993LL23800031 PM 8315499 ER PT J AU LANDS, WEM AF LANDS, WEM TI A SUMMARY OF THE WORKSHOP ALCOHOL AND CALORIES - A MATTER OF BALANCE SO JOURNAL OF NUTRITION LA English DT Editorial Material ID ENERGY-INTAKE; ETHANOL; HYPERTHERMIA; HYPOTHERMIA; METABOLISM; INVIVO; RATS RP LANDS, WEM (reprint author), NIAAA,DIV BASIC RES,ROCKVILLE,MD 20857, USA. NR 32 TC 8 Z9 9 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUL PY 1993 VL 123 IS 7 BP 1338 EP 1341 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LK562 UT WOS:A1993LK56200018 PM 8320570 ER PT J AU JOHNSON, PF STERNECK, E WILLIAMS, SC AF JOHNSON, PF STERNECK, E WILLIAMS, SC TI ACTIVATION DOMAINS OF TRANSCRIPTIONAL REGULATORY PROTEINS SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Review ID DNA-BINDING PROTEINS; RNA POLYMERASE-II; CELL-SPECIFIC INHIBITOR; C-JUN; FUNCTIONAL DISSECTION; ALLEVIATE REPRESSION; GENE-TRANSCRIPTION; RESPONSE ELEMENT; MAMMALIAN-CELLS; GLUTAMINE-RICH RP JOHNSON, PF (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,BLDG 539,FREDERICK,MD 21702, USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 105 TC 24 Z9 24 U1 0 U2 6 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUL PY 1993 VL 4 IS 7 BP 386 EP 398 DI 10.1016/0955-2863(93)90069-9 PG 13 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA LL112 UT WOS:A1993LL11200001 ER PT J AU HUSSON, RN SHIRASAKA, T BUTLER, KM PIZZO, PA MITSUYA, H AF HUSSON, RN SHIRASAKA, T BUTLER, KM PIZZO, PA MITSUYA, H TI HIGH-LEVEL RESISTANCE TO ZIDOVUDINE BUT NOT TO ZALCITABINE OR DIDANOSINE IN HUMAN-IMMUNODEFICIENCY-VIRUS FROM CHILDREN RECEIVING ANTIRETROVIRAL THERAPY SO JOURNAL OF PEDIATRICS LA English DT Article ID AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; AZIDOTHYMIDINE AZT; DOUBLE-BLIND; MUTATIONS; INFECTION; HIV; DISEASE AB Human immunodeficiency virus type 1 (HIV-1) isolates from children receiving long-term therapy with an alternating regimen of zidovudine and zalcitabine, or with didanosine monotherapy, were evaluated for resistance to zidovudine, zalcitabine, and didanosine, and for mutations known to be associated with zidovudine or didanosine resistance. HIV-1 from four of six patients receiving zidovudine with zalcitabine developed high-level resistance to zidovudine. A mutation in the HIV-1 reverse transcriptase that is highly associated with zidovudine resistance was identified in all four zidovudine-resistant posttherapy isolates. In contrast, none of the HIV-1 isolates from the seven patients receiving didanosine developed high-level resistance to this agent, despite the identification of a didanosine-associated mutation in six of these posttherapy isolates, although small decreases in sensitivity to didanosine were observed. These results indicate that nucleoside analog-associated mutations in HIV-1 occur frequently in children receiving long-term antiretroviral therapy and that alternating combination therapy does not prevent the development of resistance to zidovudine. They also suggest that there may be differences in the degree of resistance conferred by mutations that result from therapy with different nucleoside analogs. These findings underscore the need for studies to define the clinical importance of these mutations, and for treatment strategies to overcome the emergence of viral resistance in vivo. C1 NCI, MED BRANCH, EXPTL RETROVIROL SECT, BETHESDA, MD 20892 USA. NCI, PEDIAT BRANCH, INFECT DIS SECT, BETHESDA, MD 20892 USA. NR 24 TC 30 Z9 30 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 1993 VL 123 IS 1 BP 9 EP 16 DI 10.1016/S0022-3476(05)81530-6 PG 8 WC Pediatrics SC Pediatrics GA LL223 UT WOS:A1993LL22300002 PM 8391570 ER PT J AU WALSH, TJ LEE, JW SEIBEL, N PIZZO, PA AF WALSH, TJ LEE, JW SEIBEL, N PIZZO, PA TI FAILURE OF FLUCONAZOLE TREATMENT IN CANDIDA MENINGITIS - REPLY SO JOURNAL OF PEDIATRICS LA English DT Letter ID CEREBROSPINAL-FLUID; PENETRATION; TRIAZOLES; RABBITS C1 CHILDRENS HOSP, NATL MED CTR, DEPT HEMATOL & ONCOL, WASHINGTON, DC 20010 USA. NIH, UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20892 USA. RP WALSH, TJ (reprint author), NCI, PEDIAT BRANCH, INFECT DIS SECT, BETHESDA, MD 20892 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 1993 VL 123 IS 1 BP 168 EP 169 DI 10.1016/S0022-3476(05)81572-0 PG 2 WC Pediatrics SC Pediatrics GA LL223 UT WOS:A1993LL22300038 ER PT J AU MILLER, RW AF MILLER, RW TI DIGESTIVE-TRACT CANCER IN CYSTIC-FIBROSIS SO JOURNAL OF PEDIATRICS LA English DT Letter RP MILLER, RW (reprint author), NIH, CLIN EPIDEMIOL BRANCH, EPN-400, BETHESDA, MD 20892 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 1993 VL 123 IS 1 BP 172 EP 172 DI 10.1016/S0022-3476(05)81578-1 PG 1 WC Pediatrics SC Pediatrics GA LL223 UT WOS:A1993LL22300044 PM 8320618 ER PT J AU YUAN, JH AF YUAN, JH TI ESTIMATION OF VARIANCE FOR AUC IN ANIMAL STUDIES SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Note RP YUAN, JH (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 9 TC 92 Z9 96 U1 0 U2 3 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JUL PY 1993 VL 82 IS 7 BP 761 EP 763 DI 10.1002/jps.2600820718 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA LK094 UT WOS:A1993LK09400017 PM 8360854 ER PT J AU OGURA, H AIGNER, TG AF OGURA, H AIGNER, TG TI MK-801 IMPAIRS RECOGNITION MEMORY IN RHESUS-MONKEYS - COMPARISON WITH CHOLINERGIC DRUGS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NUCLEUS BASALIS MAGNOCELLULARIS; NMDA RECEPTOR ANTAGONISTS; LONG-TERM POTENTIATION; D-ASPARTATE RECEPTORS; ALZHEIMERS-DISEASE; MAZE PERFORMANCE; SCOPOLAMINE; PHYSOSTIGMINE; RATS; TASKS AB Both N-methyl-D-aspartate (NMDA) and cholinergic receptors are thought to participate in processes of learning and memory. The effects of the noncompetitive NMDA antagonist ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine) MK-801 on recognition memory in rhesus monkeys performing a computer-automated version of delayed nonmatching-to-sample DNMS were compared to those of the cholinergic compounds physostigmine and scopolamine. In the sample phase of the test, 20 symbols were presented sequentially every 30 sec on a color monitor fitted with a touch-sensitive screen. These symbols were then presented again in the same order as before, but each symbol was now paired with a different novel symbol. A monkey was rewarded with a food pellet if it touched the symbol in the sample phase and the previously unseen symbol in the choice phase. Physostigmine (3.2, 1 0 and 32 mug/kg), scopolamine (3.2, 10, 17.8 and 32 mug/kg) or MK-801 (3.2, 10 and 32 mug/kg) was injected i.m. 20, 20 and 30 min before testing, respectively. The highest doses of both MK-801 and scopolamine significantly impaired performance. In addition, scopolamine, but not MK-801, prolonged response latency, whereas MK-801, but not scopolamine, increased response bias. Physostigmine produced a small but significant increase in correct responses at the intermediate dose, but not at the highest dose. These results suggest that both the glutamatergic and the cholinergic systems participate in visual recognition memory in monkeys, though probably by different mechanisms. C1 NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM IB80,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 49 TC 54 Z9 55 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 JUL PY 1993 VL 266 IS 1 BP 60 EP 64 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LN293 UT WOS:A1993LN29300009 PM 8331575 ER PT J AU ACKER, CJ AF ACKER, CJ TI STIGMA OR LEGITIMATION - A HISTORICAL EXAMINATION OF THE SOCIAL POTENTIALS OF ADDICTION DISEASE-MODELS SO JOURNAL OF PSYCHOACTIVE DRUGS LA English DT Article DE OPIATE ADDICTION; DISEASE MODEL AB This article presents a historical discussion of disease models of opiate addiction in the United States in the twentieth century. First, several approaches to defining disease are discussed. Then. the shifts in formulations of opiate addiction as a disease in the twentieth century in the U.S. are analysed in light of the preceding theoretical discussion. The period before 1920 is described as heterodox, as researchers attempted to develop scientific models of opiate addiction, while various medically legitimate and quasi-legitimate treatment approaches flourished in an unregulated marketplace. After 1920, a stigmatizing disease model of opiate addiction was based on a psychiatric formulation that linked chronic addiction with psychorieurotic deficits in certain individuals. After 1940, this model dominated medical and scientific thinking about opiate addiction for several decades. After 1970, enormous changes in the demographics of drug use forced changes to the prevailing model of addiction. A new focus on behavioral aspects of addiction allowed the creation of a nonstigmatizing Parsonian disease model. RP ACKER, CJ (reprint author), NIH,HIST OFF,BLDG 31 ROOM 2B09,BETHESDA,MD 20892, USA. NR 49 TC 22 Z9 23 U1 1 U2 5 PU HAIGHT-ASHBURY PUBL PI SAN FRANCISCO PA 409 CLAYTON ST, SAN FRANCISCO, CA 94117 SN 0279-1072 J9 J PSYCHOACTIVE DRUGS JI J. Psychoact. Drugs PD JUL-SEP PY 1993 VL 25 IS 3 BP 193 EP 205 PG 13 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA MA350 UT WOS:A1993MA35000001 PM 8258758 ER PT J AU ABRAMS, SA LIPNICK, RN VIEIRA, NE STUFF, JE YERGEY, AL AF ABRAMS, SA LIPNICK, RN VIEIRA, NE STUFF, JE YERGEY, AL TI CALCIUM-ABSORPTION AND METABOLISM IN CHILDREN WITH JUVENILE RHEUMATOID-ARTHRITIS ASSESSED USING STABLE ISOTOPES SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE CALCIUM; STABLE ISOTOPES; JRA ID BONE-MINERAL DENSITY; EXCRETION AB Objective. To assess calcium intake, absorption, urinary excretion and the fraction of urinary calcium originating from bone and diet in patients with juvenile rheumatoid arthritis (JRA). Methods. A dual tracer stable isotope technique was used to study 6 girls and 3 boys with JRA. Results. Fractional absorption in the 6 girls, ages 4-9, with JRA was significantly lower than that in 10 similar, healthy girls (22.6 +/- 4.7% vs 30.4 +/- 8.4%, p = 0.033). Urinary calcium excretion tended to be higher in the girls with JRA than in controls, (2.9 +/- 1.5 vs 1.6 +/- 1.7, p = 0.15). The urinary calcium in patients with JRA was derived principally from bone, and there was no increase in diet derived urinary calcium. One of the boys with new onset JRA was markedly hypercalciuric and in negative calcium balance (-222 mg/day). Conclusion. Our data show that hypercalciuria in patients with JRA results from bone resorption, not hyperabsorption of dietary calcium and suggest that increases in calcium intake may benefit children with JRA. C1 CHILDRENS NATL MED CTR,WASHINGTON,DC. NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RP ABRAMS, SA (reprint author), BAYLOR COLL MED,USDA ARS,CHILDRENS NUTR RES CTR,DEPT PEDIAT,1100 BATES ST,HOUSTON,TX 77030, USA. OI Abrams, Steven/0000-0003-4972-9233 NR 20 TC 29 Z9 30 U1 0 U2 0 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 JUL PY 1993 VL 20 IS 7 BP 1196 EP 1200 PG 5 WC Rheumatology SC Rheumatology GA LM769 UT WOS:A1993LM76900021 PM 8371217 ER PT J AU CARUNCHO, HJ DASILVA, PP ANADON, R AF CARUNCHO, HJ DASILVA, PP ANADON, R TI THE MORPHOLOGY OF TELEOST MENINGOCYTES AS REVEALED BY FREEZE-FRACTURE SO JOURNAL OF SUBMICROSCOPIC CYTOLOGY AND PATHOLOGY LA English DT Article DE TELEOST MENINGES; MEMBRANE STRUCTURE; INTERCELLULAR JUNCTIONS; PLASMALEMMAL VESICLES; CARASSIUS-AURATUS; ONCHORRYNCHUS-MYKISS ID BRAIN; ORGANIZATION; MEMBRANE; BARRIER; CELLS AB We describe the morphology of the cells in the three layers of the teleost endomeninx, as viewed by freeze-fracturing. The cells of the outer endomeningeal layer are fusiform and closely packed, with interdigitations that hold the cells together, gap junctions and a few strands of particles resembling tight junctions, but no desmosomes. The intermediate layer is formed by a single layer of flattened and elongated cells with rectangular shape, and well developed junctional complexes (gap junctions, tight junctions and desmosomes). These cells also show numerous plasmalemmal vesicles (6.5 +/- 1.3/mum2) in the upper (in contact with the outer layer) and lower (in contact with the inner layer) membranes. Cross fracture of these cells shows many membrane-bound and free vesicles, The inner layer is formed by spindle shaped cells with wide intercellular spaces filled with a granular matrix and collagen fibers. The density of intramembrane particles is higher than that in the meningocytes of the outer and intermediate layers. The morphology of the teleost endomeninx appears similar to that of the leptomeninges of birds and mammals, but the outer endomeningeal layer of teleosts (which resembles the arachnoid of elasmobranchs and amphibians) appears different from any cell layer in the meninges of amniotic vertebrates. C1 UNIV SANTIAGO DE COMPOSTELA,DEPT FUNDAMENTAL BIOL,SANTIAGO,SPAIN. RP CARUNCHO, HJ (reprint author), NCI,FCRDC,MATH BIOL LAB,STRUCT BIOL SECT,BLDG 538,ROOM 124,FREDERICK,MD 21702, USA. NR 24 TC 5 Z9 5 U1 0 U2 0 PU EDITRICE COMPOSITORI BOLOGNA PI BOLOGNA PA VIA STALINGRADO 97/2, I-40128 BOLOGNA, ITALY SN 1122-9497 J9 J SUBMICR CYTOL PATH JI J. Submicrosc. Cytol. Pathol. PD JUL PY 1993 VL 25 IS 3 BP 397 EP 406 PG 10 WC Pathology SC Pathology GA LL378 UT WOS:A1993LL37800011 PM 8402540 ER PT J AU SHILONI, E SZOLD, A WHITE, DE FREUND, HR AF SHILONI, E SZOLD, A WHITE, DE FREUND, HR TI HIGH-GRADE RETROPERITONEAL SARCOMAS - ROLE OF AN AGGRESSIVE PALLIATIVE APPROACH SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE HIGH-GRADE SOFT TISSUE RETROPERITONEAL SARCOMA; TUMOR RESECTION; AGGRESSIVE SUBTOTAL EXCISION ID SOFT-TISSUE SARCOMAS; MANAGEMENT; TUMORS; SURVIVAL; THERAPY AB Between 1968 and 1988 we treated 41 patients with high-grade soft tissue retroperitoneal sarcomas. Clinical, pathological, and treatment variables were analyzed retrospectively with regard to their influence on recurrence rate and mortality. The actuarial 5-year median survival for the whole group was 48 months, with 33% of the patients surviving 10 years. Gender, clinical presentation, tumor size, and histological types did not predict outcome by multivariate analysis. Complete tumor resection was performed in 56% of the patients, but at 10 years after surgery only 10% of those patients remained disease free. Patients were classified into four groups according to the most aggressive surgical procedure employed: (1) total gross tumor resection; (2) subtotal resection, in which the major tumor bulk was excised (often with adjacent organs), but in which obvious residual disease remained; (3) palliative resection, in which minimal tumor resection was performed in order to alleviate symptoms; and (4) exploration only. Patients who were either explored and had no tumor removed or who underwent a palliative resection had a similarly poor prognosis, with a median survival of 12 and 20 months, respectively. To our surprise, patients after total resection had no survival benefit over patients who had undergone subtotal resection. However, both groups together had a significantly longer median survival of 241 months compared to the median survival of the patients with either no resection or only palliative resection (P < 0.02). The addition of chemotherapy or radiation therapy failed to show any advantage in this series. We claim from our experience that the impossibility of performing a complete resection should not prevent attempts at aggressive subtotal tumor excision, including the removal of adjacent organs, since this aggressive surgical approach may prolong survival significantly. (C) 1993 Wiley-Liss, Inc. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT SURG,IL-91010 JERUSALEM,ISRAEL. RP SHILONI, E (reprint author), HADASSAH UNIV HOSP,DEPT SURG,POB 12000,IL-91120 JERUSALEM,ISRAEL. NR 23 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUL PY 1993 VL 53 IS 3 BP 197 EP 203 DI 10.1002/jso.2930530315 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA LM736 UT WOS:A1993LM73600011 PM 7687315 ER PT J AU JENSEN, PS SHAW, J AF JENSEN, PS SHAW, J TI CHILDREN AS VICTIMS OF WAR - CURRENT KNOWLEDGE AND FUTURE-RESEARCH NEEDS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE WAR; MILITARY; TRAUMA; POSTTRAUMATIC STRESS DISORDER ID POSTTRAUMATIC-STRESS-DISORDER; BEREAVEMENT REACTIONS; PSYCHIC TRAUMA; BUFFALO CREEK; SCHOOL; ADJUSTMENT; DISASTER AB Recent international events have drawn attention to the effects of war-related events and processes on children and their families. This review of the literature concerning the existence, frequency, and type of social, emotional, and behavioral problems in children exposed to war indicates significant methodological problems in previous research. Available evidence suggests that massive exposure to wartime trauma seems likely to overwhelm most children's defenses; however, children's cognitive immaturity, plasticity, and innate adaptive capacities may mitigate war's effects in low-to-moderately intense wartime settings, resulting in self-protective, adaptive, cognitive styles that allow effective functioning after acclimatization. Promising recent research has shifted from the focus on psychopathology to social awareness, values, and attitudes. More research will be needed to determine how age, developmental, family, and community factors may mediate the strength and nature of wartime effects, and to determine which interventions are most effective in a variety of settings and cultural contexts. C1 UNIV MIAMI,SCH MED,DEPT PSYCHIAT,DIV CHILD & ADOLESCENT PSYCHIAT,MIAMI,FL 33152. RP JENSEN, PS (reprint author), NIMH,DIV CLIN RES,CHILD & ADOLESCENT DISORDERS RES BRANCH,ROOM 10-104,PARKLAWN BLDG,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 80 TC 117 Z9 119 U1 5 U2 8 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 JUL PY 1993 VL 32 IS 4 BP 697 EP 708 DI 10.1097/00004583-199307000-00001 PG 12 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA LH947 UT WOS:A1993LH94700001 PM 8340288 ER PT J AU MESAROS, JD AF MESAROS, JD TI FLUOXETINE FOR PRIMARY ENURESIS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter RP MESAROS, JD (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 5 TC 13 Z9 14 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 JUL PY 1993 VL 32 IS 4 BP 877 EP 878 DI 10.1097/00004583-199307000-00029 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA LH947 UT WOS:A1993LH94700029 PM 8340316 ER PT J AU GOLDSTEIN, AM BALE, SJ PECK, GL DIGIOVANNA, JJ AF GOLDSTEIN, AM BALE, SJ PECK, GL DIGIOVANNA, JJ TI SUN EXPOSURE AND BASAL-CELL CARCINOMAS IN THE NEVOID BASAL-CELL CARCINOMA SYNDROME SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Background: Nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder. Persons with the NBCC gene have varied susceptibility to basal cell carcinoma (BCC) development. Objective: We examined the anatomic site-specific distribution of BCCs and the relation between sun exposure and numbers of BCCs in NBCC cases. Methods. A questionnaire asking about lifetime sun exposure, sun behavior habits, and number of BCCs was sent to 16 families with NBCC evaluated between 1985 and 1991. The results were compared with previously published data for the general population. Results: In the general population, 88% of all BCCs in women and 86% in men occurred on the face, head, neck, and arms versus 59% in women with NBCC and 65% in men with NBCC. Of BCCs in the general population 9% and 12% occurred on the trunk versus 38% and 32% of BCCs in NBCC cases, in women and men, respectively. We did not observe a strong relation between numbers of BCCs and history of lifetime sun exposure. Conclusion: The anatomic-site distribution of BCCs suggests that frequent sun exposure may not be essential for the development of BCCs in patients with NBCC. However, the observation that there are more tumors on sun-exposed areas suggests that exposure to the sun promotes the development of BCCs in patients with NBCC. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. RP GOLDSTEIN, AM (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,FAMILY STUDIES SECT,EXECUT PLAZA N,ROOM 439,BETHESDA,MD 20892, USA. NR 16 TC 39 Z9 39 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 JUL PY 1993 VL 29 IS 1 BP 34 EP 41 PG 8 WC Dermatology SC Dermatology GA LJ844 UT WOS:A1993LJ84400003 PM 8315076 ER PT J AU SHIRANI, J ROBERTS, WC AF SHIRANI, J ROBERTS, WC TI CLINICAL, ELECTROCARDIOGRAPHIC AND MORPHOLOGIC FEATURES OF MASSIVE FATTY DEPOSITS (LIPOMATOUS HYPERTROPHY) IN THE ATRIAL SEPTUM SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID DIAGNOSIS; HEART AB Objectives. This study examined the morphologic features and the clinical significance of massive fatty deposits in the atrial septum of the heart. Background. Large deposits of adipose tissue in the atrial septum were first described in 1964 and have been referred to as ''lipomatous hypertrophy'' of the atrial septum. A relation between these fatty deposits and atrial arrhythmias has been suggested. Methods. The thickness of the atrial septum cephalad to the fossa ovalis ranged from 1.5 to 6 cm in 91 patients and was greater-than-or-equal-to 2 cm in 80 patients. This report focuses primarily on the latter 80 patients. Results. The thickness of the atrial septum in the 80 patients correlated with body weight and the thickness of the adipose tissue in the atrioventricular groove and that covering the right ventricle. In 53 patients (67%), one or more of the four major epicardial coronary arteries were narrowed > 75% in cross-sectional area by atherosclerotic plaque. Atrial arrhythmias were present in 31 patients (40%). Patients with larger deposits of fat (atrial septal thickness greater-than-or-equal-to 3 cm) had a higher frequency of atrial arrhythmias (60% vs. 34%, p < 0.01). The atrial septum was significantly thicker in patients with atrial arrhythmia compared with those without atrial arrhythmias (2.9 vs. 2.3 cm, p < 0.01). Of the 28 patients with available electrocardiograms, 20 (71%) showed atrial arrhythmias (nine atrial premature complexes, seven atrial fibrillation, three atrial tachycardia, one ectopic atrial rhythm and one junctional rhythm). Conclusions. Massive fatty deposits in the atrial septum are associated with large deposits of fat elsewhere in the body and other parts of the heart. They are frequently associated with atrial arrhythmias and atherosclerotic coronary artery disease. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 22 TC 85 Z9 88 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL PY 1993 VL 22 IS 1 BP 226 EP 238 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LK566 UT WOS:A1993LK56600031 PM 8509546 ER PT J AU WILBUR, WJ AF WILBUR, WJ TI RETRIEVAL TESTING WITH HYPERGEOMETRIC DOCUMENT MODELS SO JOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE LA English DT Article ID INFORMATION-RETRIEVAL; SYSTEM; TERMS AB If one could identify the source subject areas of documents and could compute the probability that any given document came from a given source, one could apply Baye's theorem to compute the probability that a query document and any other document came from the same subject area (i.e., were related). Even correct prior probabilities could be assigned under this hypothesis by examining the whole database to obtain the probabilities with which different sources occur. While we do not know how to carry out this scheme in such a way as to account for all the information contained in documents, we show here how it may be realized in a limited way. A method of modeling the sources of documents is described which accounts for the information in global term weights. The methodology is based on the hypergeometric probability distribution. Such a source model may be fit closely to a real database and may be used to convert the real database to an abstract database in which document sources are known and model retrieval is the best retrieval possible based on model document content. We have constructed such an abstract model corresponding to a database of MEDLINE records. Tests of vector retrieval methods on the abstract model indicate they are near optimal but suggest minor improvement with correct parameter choices. Preliminary results based on a test set (human judged) from the real database support these results. RP NIH, NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT, BLDG 38A,ROOM 8S806, 8600 ROCKVILLE PIKE, BETHESDA, MD 20894 USA. NR 28 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-8231 J9 J AM SOC INFORM SCI JI J. Am. Soc. Inf. Sci. PD JUL PY 1993 VL 44 IS 6 BP 340 EP 351 DI 10.1002/(SICI)1097-4571(199307)44:6<340::AID-ASI4>3.0.CO;2-Z PG 12 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA LJ307 UT WOS:A1993LJ30700004 ER PT J AU PINN, VW AF PINN, VW TI THE NIH AGENDA FOR WOMENS HEALTH SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Editorial Material RP PINN, VW (reprint author), NIH,OFF RES WOMENS HLTH,BLDG 1,RM 201,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUL PY 1993 VL 85 IS 7 BP 511 EP 515 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LM310 UT WOS:A1993LM31000006 PM 8350371 ER PT J AU LONG, JP CHOYKE, PL SHAWKER, TA ROBERTSON, CA PASS, HI WALTHER, MM LINEHAN, WM AF LONG, JP CHOYKE, PL SHAWKER, TA ROBERTSON, CA PASS, HI WALTHER, MM LINEHAN, WM TI INTRAOPERATIVE ULTRASOUND IN THE EVALUATION OF TUMOR INVOLVEMENT OF THE INFERIOR VENA-CAVA SO JOURNAL OF UROLOGY LA English DT Article DE VENA CAVA, INFERIOR; ULTRASONOGRAPHY; NEOPLASM INVASIVENESS ID RENAL-CELL-CARCINOMA; COMPUTERIZED-TOMOGRAPHY; SURGICAL-MANAGEMENT; EXTENSION; THROMBUS; ULTRASONOGRAPHY; VENACAVOGRAPHY; ANGIOGRAPHY; SONOGRAPHY; RESECTION AB The successful excision of genitourinary malignancies extending to the inferior vena cava relies heavily on accurate preoperative imaging. For the majority of these patients magnetic resonance imaging, inferior venacavography, abdominal ultrasound or abdominal computerized tomography will reliably predict the extent of inferior vena caval involvement by tumor. However, occasionally the results of these studies will conflict or be called into question intraoperatively. We report on 8 patients considered to be at risk for inferior vena caval involvement by tumor and for whom intraoperative ultrasound was obtained to clarify the presence or extent of thrombus. Five patients had renal cell carcinoma and 3 had adrenal carcinoma. In all patients concern as to the extent or presence of tumor was based on either inconclusive preoperative studies or unexpected intraoperative findings. In each case intraoperative ultrasound clearly visualized the inferior vena cava and established the presence or extent of tumor invasion. In 4 patients venacavotomy was avoided as a consequence of these findings. Intraoperative ultrasound is a useful tool that can accurately assess the inferior vena cava for possible tumor invasion, especially when the presence or extent of tumor involvement is not definitively established preoperatively. RP LONG, JP (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,SURG BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 12 Z9 12 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1993 VL 150 IS 1 BP 13 EP 17 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA LH013 UT WOS:A1993LH01300003 PM 8510233 ER PT J AU PARTIN, AW YOO, J CARTER, HB PEARSON, JD CHAN, DW EPSTEIN, JI WALSH, PC AF PARTIN, AW YOO, J CARTER, HB PEARSON, JD CHAN, DW EPSTEIN, JI WALSH, PC TI THE USE OF PROSTATE-SPECIFIC ANTIGEN, CLINICAL STAGE AND GLEASON SCORE TO PREDICT PATHOLOGICAL STAGE IN MEN WITH LOCALIZED PROSTATE-CANCER SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 1992 ANNUAL MEETING OF THE AMERICAN UROLOGICAL ASSOC CY MAY 10-14, 1992 CL WASHINGTON, DC SP AMER UROL ASSOC DE PROSTATE NEOPLASMS; ANTIGENS; PATHOLOGY; TUMOR MARKERS, BIOLOGICAL ID ADENOCARCINOMA AB Clinical stage, Gleason score and serum prostate specific antigen (PSA) levels are used separately to predict pathological stage in patients with localized prostate cancer. Because the degree of tumor differentiation has a profound influence on the expression of serum PSA, serum PSA levels alone do not reflect tumor burden accurately. To overcome this obstacle we tested these 3 variables alone and in combinations as predictors of final pathological stage in 703 men with clinically localized prostate cancer at our institution. All patients were assigned a clinical stage by 1 urologist. The Gleason score was determined from preoperative needle biopsy and serum PSA levels were measured on an ambulatory basis. Final pathological stage was determined to be either organ confined, established capsular penetration, seminal vesicle involvement or lymph node involvement. Logistic regression analysis with the likelihood ratio chi-square test determined that serum PSA, Gleason score and clinical stage all predicted final pathological stage well. The results were improved with combinations of the 3 variables (serum PSA, Gleason score and clinical stage) and the combination provided the best separation. From these analyses probability plots and nomograms have been constructed to assist urologists in the preoperative prediction of final pathological stage for patients with clinically localized prostate cancer. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT UROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL & LAB MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,BALTIMORE,MD 21224. RP PARTIN, AW (reprint author), JOHNS HOPKINS UNIV HOSP,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,600 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 8 TC 839 Z9 871 U1 2 U2 12 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1993 VL 150 IS 1 BP 110 EP 114 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA LH013 UT WOS:A1993LH01300029 PM 7685418 ER PT J AU LONG, JP WALTHER, MM ALEXANDER, RB LINEHAN, WM ROSENBERG, SA AF LONG, JP WALTHER, MM ALEXANDER, RB LINEHAN, WM ROSENBERG, SA TI THE MANAGEMENT OF ISOLATED RENAL RECURRENCE OF RENAL-CELL CARCINOMA FOLLOWING COMPLETE RESPONSE TO INTERLEUKIN-2 BASED IMMUNOTHERAPY SO JOURNAL OF UROLOGY LA English DT Note DE CARCINOMA, RENAL CELL; KIDNEY NEOPLASMS; NEOPLASM METASTASIS; INTERLEUKIN-2; IMMUNOTHERAPY ID HIGH-DOSE INTERLEUKIN-2; CONSERVATIVE SURGERY; ADVANCED CANCER; INTERFERON; EXPERIENCE; THERAPY AB The role of interleukin-2 based immunotherapy in advanced renal cell carcinoma is gradually expanding. Among patients who achieve significant responses to these regimens the subsequent development of isolated recurrences raises difficult management questions. We report 2 unusual cases of isolated recurrence in the remaining kidney following a sustained, complete response to interleukin-2 based adoptive immunotherapy. Both patients were treated with interleukin-2 based therapy following surgical resection of the primary renal tumor. The disease course of each patient is described and the literature is reviewed. Both patients were free of disease after relatively short-term followup. Surgery for patients with limited recurrence of renal cell carcinoma following an objective response to immunotherapy may, in select cases, be a reasonable treatment alternative. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NR 20 TC 12 Z9 12 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 1993 VL 150 IS 1 BP 176 EP 178 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA LH013 UT WOS:A1993LH01300051 PM 8510245 ER PT J AU CHEN, MY MALDARELLI, F KARCZEWSKI, MK WILLEY, RL STREBEL, K AF CHEN, MY MALDARELLI, F KARCZEWSKI, MK WILLEY, RL STREBEL, K TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPU PROTEIN INDUCES DEGRADATION OF CD4 INVITRO - THE CYTOPLASMIC DOMAIN OF CD4 CONTRIBUTES TO VPU SENSITIVITY SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; MATURATION; CELLS; GENE; MEMBRANE; GP160; HIV-1 AB CD4 is an integral membrane glycoprotein which functions as the human immunodeficiency virus (HIV) receptor for infection of human host cells. We have recently demonstrated that Vpu, an HIV type 1 (HIV-1) encoded integral membrane phosphoprotein, induces rapid degradation of CD4 in the endoplasmic reticulum. In this report, we describe an in vitro model system that allowed us to define important parameters for Vpu-dependent CD4 degradation. The rate of CD4 decay in rabbit reticulocyte lysate was approximately one-third of that observed previously in tissue culture experiments in the presence of Vpu (40 versus 12 min) and required no other HIV-1 encoded proteins. Degradation was contingent on the presence of microsomal membranes in the assay and the coexpression of Vpu and CD4 in the same membrane compartment. By using the in vitro degradation assay, the effects of specific mutations in CD4, including C-terminal truncations and glycosylation mutants, were analyzed. The results of these experiments indicate that Vpu has the capacity to induce degradation of glycosylated as well as nonglycosylated membrane-associated CD4. Truncation of 13 C-terminal amino acids of CD4 did not affect the ability of Vpu to induce its degradation. However, the removal of 32 amino acids from the C-terminus of CD4 completely abolished sensitivity to Vpu. This suggests that Vpu targets specific sequences in the cytoplasmic domain of CD4 to induce its degradation. We also analyzed the effects of mutations in Vpu on its biological activity in the in vitro CD4 degradation assay. The results of these experiments suggest that sequences critical for this function of Vpu are located in its hydrophilic C-terminal domain. C1 NIAID,MOLEC MICROBIOL LAB,BLDG 4,ROOM 312,BETHESDA,MD 20892. NR 31 TC 117 Z9 118 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 JUL PY 1993 VL 67 IS 7 BP 3877 EP 3884 PG 8 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400021 PM 8510209 ER PT J AU CARVALHO, M DERSE, D AF CARVALHO, M DERSE, D TI THE PU.1/SPI-1 PROTOONCOGENE IS A TRANSCRIPTIONAL REGULATOR OF A LENTIVIRUS PROMOTER SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS-ANEMIA VIRUS; PEA3; ACTIVATION; EXPRESSION; INDUCTION; ELEMENT; SPI-1; TAT AB The enhancer unit present in the retrovirus equine infectious anemia virus (EIAV) was previously shown to contain binding sites for proteins belonging to MDBP, PEA2, AP-1, and ets families. The EIAV ets motif matches the consensus sequence for both PEA3- and PU.1-binding sites. Here, we show by gel shift analysis that PU.1, present in nuclear extracts from monocyte and B-lymphocyte cell lines, binds to oligonucleotides containing the EIAV ets element. HeLa cells transiently transfected with a PU. 1 expression plasmid expressed nuclear factors that formed complexes indistinguishable from those seen with monocyte extracts. Antibodies to PU.1 protein either supershifted or abolished formation of these complexes, depending on the PU.1 epitopes recognized. The binding of PU.1 to the EIAV ets motif in vitro correlated with transcriptional activity of the EIAV promoter in transfected monocyte cell lines. In HeLa cells, the product of PU.1 cDNA bound to the EIAV ets motif and activated transcription from the EIAV promoter. The PU.1-binding site was the primary determinant of EIAV promoter activity in cell lines that express PU.1. Nucleotide determinants of PU.1 binding and a consensus PU.1 binding sequence were defined in gel shift assays using a panel of mutated oligonucleotides. To our knowledge, this is the first report of a retroviral promoter controlled by PU.1. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 24 TC 35 Z9 35 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 JUL PY 1993 VL 67 IS 7 BP 3885 EP 3890 PG 6 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400022 PM 8389910 ER PT J AU GORELICK, RJ CHABOT, DJ REIN, A HENDERSON, LE ARTHUR, LO AF GORELICK, RJ CHABOT, DJ REIN, A HENDERSON, LE ARTHUR, LO TI THE 2 ZINC FINGERS IN THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NUCLEOCAPSID PROTEIN ARE NOT FUNCTIONALLY EQUIVALENT SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; CYS-HIS BOX; RETROVIRUSES; MUTATIONS; RNA; SEQUENCE; MUTANTS; CELLS AB The highly conserved zinc fingers in retroviral nucleocapsid (NC) proteins have the general structure CyS-(X)2-CYS-(X)4-HiS-(X)4-CYS. Human immunodeficiency virus type 1 (HIV-1) contains two Zn2+ fingers, and mutants were constructed in which the native sequence of each Zn2+ finger was maintained but their positions in the NC protein were changed. Mutants had either two first-finger sequences (pNC1/1), two second-finger sequences (pNC2/2), or reversed first- and second-finger sequences (pNC2/1). Cells transfected with mutant or wild-type clones produced similar levels of Tat, Gag, Pol, and Env proteins, formed syncytia, and shed viruslike particles that were indistinguishable by electron microscopy. However, the pNC2/1 and pNC2/2 mutants were inefficient in packaging genomic RNA (less than 15% of wild-type levels), whereas the pNC1/1 mutant packaged approximately 70% of wild-type levels of RNA. No infectious virus could be detected with either the pNC2/1 or pNC2/2 mutants, whereas the pNC1/I mutant appeared to sustain a low level of replication and reverted to a competent wild-type-like viral species after a 2- to 4-week lag period. The data strongly suggest that the two Zn2+ fingers of HIV-1 are not functionally equivalent and that the first Zn2+ finger in the Gag precursor plays a more prominent role in RNA selection and packaging. The data also indicate that both Zn2+ fingers in the mature NC protein play as yet unknown roles in viral assembly or the early stages of the viral infection process. C1 NCI,FREDERICK CANC RES & DEV CTR,INC BASIC RES PROGRAM,ADV BIOSCI LABS,FREDERICK,MD 21702. RP GORELICK, RJ (reprint author), DYNCORP,PROGRAM RESOURCES INC,AIDS VACCINE DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 34 TC 206 Z9 207 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 JUL PY 1993 VL 67 IS 7 BP 4027 EP 4036 PG 10 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400038 PM 8510214 ER PT J AU EIDEN, MV FARRELL, K WARSOWE, J MAHAN, LC WILSON, CA AF EIDEN, MV FARRELL, K WARSOWE, J MAHAN, LC WILSON, CA TI CHARACTERIZATION OF A NATURALLY-OCCURRING ECOTROPIC RECEPTOR THAT DOES NOT FACILITATE ENTRY OF ALL ECOTROPIC MURINE RETROVIRUSES SO JOURNAL OF VIROLOGY LA English DT Article ID APE LEUKEMIA-VIRUS; MAMMALIAN-CELLS; PLASMID DNA; CONSTRUCTION; INFECTION; SEQUENCES; CLONING AB A fibroblast cell line (MDTF) derived from the feral mouse Mus dunni is resistant to infection by MoloneY murine leukemia virus (Mo-MuLV), an ecotropic murine leukemia virus (E-MuLV) (M. R. Lander and S. K. Chattopadadhyay, J. Virol. 52:695-698, 1984). MDTF cells can be infected by other E-MuLVs such as Friend MuLV and Rauscher MuLV, which have been demonstrated to use the same receptor as Mo-MuLV in NIH 3T3 cells (A. Rein and A. Schultz, Virology 136:144-152, 1984). We have now shown that the block to Mo-MuLV infection of MDTF cells occurs at the level of the envelope-receptor interaction. We have cloned the ecotropic receptor cDNA from MDTF cells (dRec) and compared its sequence with that of the NIH 3T3 cell receptor (mRec). Although the deduced dRec and mRec proteins differ at only four amino acid residues, we demonstrate that these changes account for the resistance of MDTF cells to Mo-MuLV infection. Our findings suggest that retroviruses in the same receptor class can exhibit different host ranges due to single amino acid differences in their cellular receptor. RP EIDEN, MV (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D10,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CO74102] NR 21 TC 59 Z9 59 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 JUL PY 1993 VL 67 IS 7 BP 4056 EP 4061 PG 6 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400041 PM 8510216 ER PT J AU KULKARNI, AB MORSE, HC BENNINK, JR YEWDELL, JW MURPHY, BR AF KULKARNI, AB MORSE, HC BENNINK, JR YEWDELL, JW MURPHY, BR TI IMMUNIZATION OF MICE WITH VACCINIA VIRUS-M2 RECOMBINANT INDUCES EPITOPE-SPECIFIC AND CROSS-REACTIVE KD-RESTRICTED CD8+ CYTOTOXIC-T CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; F-GLYCOPROTEIN; HOST IMMUNITY; EXPRESSION; ANTIGEN; PEPTIDE; RECOGNITION; INFECTION; PROTEINS; 22K AB The M2 protein of respiratory syncytial virus (RSV) is a protective antigen in H-2d, but not H-2b or H-2k mice. None of the other RSV proteins, excluding the surface glycoproteins that induce neutralizing antibodies, is protective in mice beating these haplotypes. Thus, the M2 protein stands alone as a nonglycoprotein-protective antigen of RSV. The M2 protein is a target for murine K(d)-restricted cytotoxic T lymphocytes (CTLs), and the resistance induced by infection with a vaccinia virus-RSV M2 (vac-M2) recombinant is mediated by CD8+ CTLs. Since the nonameric consensus sequence for H-2 K(d)-restricted T-cell epitopes and the amino acid sequence of the M2 protein of subgroup A and B strains of RSV are known, the present study sought to identify the specific epitope(s) on the M2 protein recognized by CD8+ CTLs. This was done by examining the ability of four predicted K(d)-specific motif peptides present in the M2 amino acid sequence of an RSV subgroup A strain to sensitize target cells for lysis by pulmonary or splenic CTLs obtained from mice infected with RSV or vac-M2. The following observations were made. First, two of the four peptides sensitized target cells for lysis by pulmonary or splenic CTLs induced by infection with either vac-M2 or RSV. Second, one of the two peptides, namely the 82-90 (M2) peptide, sensitized targets at a very low peptide concentration (10(-10) to 10(-12) M). Third, cold-target competition experiments revealed that the predominant CTL population induced by infection with vac-M2 or RSV recognized the 82-90 (M2) peptide, and this CTL population appeared to recognize the 71-79 (M2) peptide in a cross-reactive manner. Fourth, CTL recognition of targets sensitized with either the 71-79 (M2) or the 82-90 (M2) peptide was K(d) restricted. Fifth, CTLs induced by infection with RSV subgroup A or B strains recognized the two M2 peptides. The findings suggest that the M2 protein of RSV contains an immunodominant K(d)-restricted CTL epitope consisting of amino acid residues 82 to 90 (SYIGSINNI), which are shared by subgroup A and B RSVs. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP KULKARNI, AB (reprint author), NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; OI Morse, Herbert/0000-0002-9331-3705 NR 24 TC 71 Z9 72 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 JUL PY 1993 VL 67 IS 7 BP 4086 EP 4092 PG 7 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400045 PM 7685408 ER PT J AU LIMJOCO, TI DICKIE, P IKEDA, H SILVER, J AF LIMJOCO, TI DICKIE, P IKEDA, H SILVER, J TI TRANSGENIC FV-4 MICE RESISTANT TO FRIEND-VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ECOTROPIC RETROVIRUS RECEPTOR; COAT PROTEIN GENE; CELL-SURFACE; INFECTION; GLYCOPROTEIN; INTERFERENCE; EXPRESSION; RECOVERY; SUSCEPTIBILITY AB Fv-4 is a mouse gene that confers resistance to infection with ecotropic retroviruses. A candidate Fv-4 gene was cloned previously and found to resemble the 3' half of a murine leukemia virus (MuLV). To study the effect of this gene in vivo, we generated two transgenic mouse strains carrying the Fv-4 env gene under control of its presumed natural promoter, a cellular sequence unrelated to retroviruses. Transgenic progeny expressed a 3-kb Fv-4 env RNA in all of the organs and tissues examined, as well as an Fv-4 envelope antigen on the surface of thymocytes and spleen cells, similar to mice carrying the natural Fv-4 gene. One of the two transgenic strains (designated Fv4-2) expressed three to nine times as much transgene RNA and protein as the other strain (Fv4-11). When challenged with a Friend virus complex containing up to 10(4) XC PFU of Friend MuLV, Fv4-2 mice were completely resistant to development of splenomegaly and had no detectable ecotropic virus in the spleen or blood, confirming that the cloned Fv-4 gene is responsible for resistance to ecotropic MuLV in vivo. In contrast, Fv4-11 mice were only partially resistant, developing viremia and splenomegaly at the highest inoculum dose but recovering from viremia several weeks after inoculation with 10-fold less virus. The phenotype of recovery from viremia in Fv4-11 mice was unexpected and suggests that low levels of expression of the Fv-4 gene enhance the effectiveness of the immune response. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. AICHI CANC CTR,RES INST,NAGOYA,AICHI 464,JAPAN. NR 39 TC 48 Z9 50 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 JUL PY 1993 VL 67 IS 7 BP 4163 EP 4168 PG 6 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400053 PM 8510219 ER PT J AU LI, CCH RUSCETTI, FW RICE, NR CHEN, EY YANG, NS MIKOVITS, J LONGO, DL AF LI, CCH RUSCETTI, FW RICE, NR CHEN, EY YANG, NS MIKOVITS, J LONGO, DL TI DIFFERENTIAL EXPRESSION OF REL FAMILY MEMBERS IN HUMAN T-CELL LEUKEMIA-VIRUS TYPE I-INFECTED CELLS - TRANSCRIPTIONAL ACTIVATION OF C-REL BY TAX PROTEIN SO JOURNAL OF VIROLOGY LA English DT Article ID NF-KAPPA-B; TROPICAL SPASTIC PARAPARESIS; ENHANCER-BINDING-PROTEIN; MULTIPLE NUCLEAR FACTORS; LONG TERMINAL REPEAT; DNA-BINDING; TRANS-ACTIVATION; LYMPHOID-CELLS; GENE; RECEPTOR AB The Tax protein of the human T-cell leukemia virus type I (HTLV-I) has been shown to induce nuclear expression of Rel family NF-kappaB-binding proteins. However, under different experimental conditions, different members of the Rel family were induced (N. Arima, J. A. Molitor, M. R. Smith, J. H. Kim, Y. Daitoku, and W. G. Greene, J. Virol. 65:6892-6899, 1991). In this study, using specific immunological reagents capable of distinguishing individual members of the Rel family proteins, we show that only c-Rel, not NF-kappaB p50 or p65, is induced in HTLV-I-infected cells. Preferential c-rel induction by HTLV-1 infection was detected at the protein and RNA levels as well as in the nuclear NF-kappaB-binding form. Induced c-rel expression was also detected in cells stably transfected with tax cDNA, further correlating the c-rel induction with viral Tax expression. An increase in c-rel mRNA was detected within 3 h after induction of Tax expression, suggesting that this effect is at least partially regulated at the level of transcription. Furthermore, using a particle bombardment method for gene cotransfection, we show that Tax can transcriptionally activate the c-rel promoter in a T-cell line, Jurkat. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. AGRACETUS,MIDDLETON,WI 53562. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. RP LI, CCH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,PROGRAM RESOURCES,FREDERICK,MD 21702, USA. NR 64 TC 43 Z9 44 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 JUL PY 1993 VL 67 IS 7 BP 4205 EP 4213 PG 9 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400058 PM 8510222 ER PT J AU KARUPIAH, G FREDRICKSON, TN HOLMES, KL KHAIRALLAH, LH BULLER, RML AF KARUPIAH, G FREDRICKSON, TN HOLMES, KL KHAIRALLAH, LH BULLER, RML TI IMPORTANCE OF INTERFERONS IN RECOVERY FROM MOUSEPOX SO JOURNAL OF VIROLOGY LA English DT Article ID ECTROMELIA VIRUS-INFECTION; VACCINIA VIRUS; T-CELLS; MONOCLONAL-ANTIBODY; ANTIVIRAL ACTIVITY; MICE; GAMMA; RESISTANCE; INHIBITION; RECEPTOR AB Gamma interferon is shown to be critical in recovery of C57BL/6 mice from mousepox. Anti-gamma interferon treatment of mice infected in the footpad with ectromelia virus resulted in enhanced spread to and efficient virus replication in the spleen, lungs, ovaries, and, especially, liver. All treated, infected mice died within a mean of 7 days, 2.5 days earlier than mice with severe combined immunodeficiency that were given a comparable infection. On the other hand, alpha interferon appeared not to have a major role in controlling virus replication in tissues examined, and beta interferon was important for virus clearance in the liver and ovaries but not the spleen. Either anti-alpha, beta interferon or anti-beta interferon antibody therapy resulted in only 25% mortality. Infected control mice survived but showed persistence of ectromelia virus at the site of infection (the footpad) and transient presence of the virus in the spleen, liver, lungs, and ovaries and in the fibroreticular but not lymphoid cells of the draining popliteal lymph node. Depletion of gamma interferon but not alpha and/or beta interferon resulted in a significant reduction in the numbers of splenic T (especially gammdelta-TCR+), B, and Mac-1+ cells, although the proportion of Mac-l+ cells in the spleen increased compared with control values. Depletion of alpha, beta, or gamma interferons did not severely affect the generation of virus-specific cytotoxic T-lymphocyte responses or natural killer cell cytolytic activity. This study, in which a natural virus disease model was used, underscores the crucial importance of gamma interferon in virus clearance at all stages of infection and in all tissues tested except the primary site of infection, where virus clearance appears to be delayed. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NCI,REGISTRY EXPTL CANC,BETHESDA,MD 20892. UNIV CONNECTICUT,DEPT PHYSIOL & NEUROBIOL,STORRS,CT 06292. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. RI Karupiah, Gunasegaran/J-4707-2013 NR 49 TC 128 Z9 129 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 JUL PY 1993 VL 67 IS 7 BP 4214 EP 4226 PG 13 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400059 PM 7685412 ER PT J AU COHEN, JI HEFFEL, D SEIDEL, K AF COHEN, JI HEFFEL, D SEIDEL, K TI THE TRANSCRIPTIONAL ACTIVATION DOMAIN OF VARICELLA-ZOSTER VIRUS OPEN READING FRAME-62 PROTEIN IS NOT CONSERVED WITH ITS HERPES-SIMPLEX VIRUS HOMOLOG SO JOURNAL OF VIROLOGY LA English DT Article ID IMMEDIATE-EARLY PROTEIN; COMPLETE DNA-SEQUENCE; PSEUDORABIES VIRUS; REGULATORY PROTEIN; TYPE-1; BINDING; GENES; ICP4; TRANSACTIVATION; SEPARATION AB Varicella-zoster virus (VZV) open reading frame 62 (ORF62) encodes an immediate-early protein that transactivates expression of VZV, herpes simplex virus (HSV), and cellular genes in transient expression assays. VZV ORF62 is homologous to HSV ICP4 and pseudorabies virus immediate-early (IE180) proteins. All three viral proteins have conserved DNA binding domains that recognize similar sites in their corresponding promoters. Here, we show that the transcriptional activation domain of ORF62 is located near the amino terminus of the protein and is not conserved with the activation domain of ICP4. A 161-amino-acid activation domain of ORF62 activates transcription to a level comparable to that of the potent HSV VP16 activation domain; much of the activity is contained in the first 90 amino acids of ORF62. Deletion of the activation domain from full-length ORF62 markedly reduced transactivating activity. These experiments indicate that while VZV ORF62 and HSV ICP4 have conserved amino acid sequences, including their DNA binding domains, the transcriptional activation domains are poorly conserved. RP COHEN, JI (reprint author), NIAID,MED VIROL SECT,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 32 TC 23 Z9 23 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 JUL PY 1993 VL 67 IS 7 BP 4246 EP 4251 PG 6 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400062 PM 8389926 ER PT J AU MORIUCHI, H MORIUCHI, M STRAUS, SE COHEN, JI AF MORIUCHI, H MORIUCHI, M STRAUS, SE COHEN, JI TI VARICELLA-ZOSTER VIRUS (VZV) OPEN READING FRAME-61 PROTEIN TRANSACTIVATES VZV GENE PROMOTERS AND ENHANCES THE INFECTIVITY OF VZV-DNA SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; FACTOR VMW65 AB The varicella-zoster virus (VZV) open reading frame 61 (ORF61) protein is the homolog of herpes simplex virus type 1 (HSV-1) ICP0. Both genes are located in similar parts of the genome, their predicted products share a cysteine-rich motif, and cell lines expressing VZV ORF61 are able to complement an HSV-1 ICP0 deletion mutant (H. Moriuchi, M. Moriuchi, H. A. Smith, S. E. Straus, and J. 1. Cohen, J. Virol. 66:7303-7308, 1992). In transient expression assays, HSV-1 ICP0 is a transactivator alone and transactivates in synergy with another viral transactivator, ICP4. However, VZV ORF61 represses the activation by VZV-encoded proteins ORF62 (the homolog of ICP4) and ORF4. To further characterize the function of VZV ORF61 and its role(s) in regulation of viral gene expression, we performed transient expression assays using target promoters from VZV, HSV-1, and unrelated viruses. In the absence of other viral activators, VZV ORF61 transactivated most promoters tested. In addition, a cell line stably expressing VZV ORF61 complemented the HSV-1 mutant in 1814, which lacks the transactivating function of VP16. The cell line expressing VZV ORF61 enhanced the infectivity of HSV-1 virion DNA. Moreover, transient expression of VZV ORF61 also enhanced the infectivity of VZV DNA. These results indicate that VZV ORF61 can stimulate expression of HSV-1 and VZV genes at an early stage in the viral replicative cycle and that ORF61 has an important role in VZV gene regulation. C1 NIAID,MED VIROL SECT,CLIN INVEST LAB,BETHESDA,MD 20892. NR 25 TC 59 Z9 59 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 JUL PY 1993 VL 67 IS 7 BP 4290 EP 4295 PG 6 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400067 PM 8389928 ER PT J AU BALOTTA, C LUSSO, P CROWLEY, R GALLO, RC FRANCHINI, G AF BALOTTA, C LUSSO, P CROWLEY, R GALLO, RC FRANCHINI, G TI ANTISENSE PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES TARGETED TO THE VPR GENE INHIBIT HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN PRIMARY HUMAN MACROPHAGES SO JOURNAL OF VIROLOGY LA English DT Note ID HTLV-III/LAV; SOR GENE; MONONUCLEAR PHAGOCYTES; PRODUCTIVE INFECTION; VIRAL REPLICATION; BRAIN-TISSUE; VIF-GENE; HIV-1; AIDS; CELLS AB The replication of human immunodeficiency viruses (HIV) in human macrophages is influenced by genetic determinants which have been mapped predominantly to the viral envelope. However, in HIV-2, the vpr gene has also been suggested as an important modulator of viral expression in human macrophages. We synthesized five antisense phosphorothioate oligodeoxynucleotides complementary to the vpr mRNA of HIV-1(Ba-L,) a highly macrophage-tropic viral strain, and measured their effect on HIV-1(Ba-L) replication in primary human macrophages. All of the oligodeoxynucleotides displayed some level of non-sequence-specific inhibition of viral replication; however, only the antisense one had an additional effect on viral production in primary macrophages. Of the five antisense oligodeoxynucleotides tested, only one did not show any additional effect on viral production, whereas all the others inhibited viral replication to a similar degree (70 to 100%). Variation in the degree of inhibition was observed by using five different donors of human primary macrophages. The phosphorothioate oligonucleotides, targeted to the initiating methionine of the Vpr protein, had an inhibitory effect at both 20 and 10 muM only when the size was increased from 24 to 27 bases. Thus, HIV-1 replication in human macrophages is modulated by the expression of the vpr gene, and it is conceivable that vpr antisense oligodeoxynucleotides could be used in combination with antisense oligodeoxynucleotides against other HIV-1 regulatory genes to better control viral expression in human macrophages. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 47 TC 91 Z9 91 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 JUL PY 1993 VL 67 IS 7 BP 4409 EP 4414 PG 6 WC Virology SC Virology GA LH124 UT WOS:A1993LH12400084 PM 8510229 ER PT J AU BURNS, PA PRANIKOFF, K NOCHAJSKI, TH HADLEY, EC LEVY, KJ ORY, MG AF BURNS, PA PRANIKOFF, K NOCHAJSKI, TH HADLEY, EC LEVY, KJ ORY, MG TI A COMPARISON OF EFFECTIVENESS OF BIOFEEDBACK AND PELVIC MUSCLE EXERCISE TREATMENT OF STRESS-INCONTINENCE IN OLDER COMMUNITY-DWELLING WOMEN SO JOURNALS OF GERONTOLOGY LA English DT Article ID URINARY-INCONTINENCE; SURGERY AB Background. Research using biofeedback as a treatment for sphincteric incontinence began with Kegel's early studies using a perineometer and pelvic muscle exercises demonstrating a 90% improvement in urine loss symptoms. More recent studies using varying combinations of biofeedback and pelvic muscle exercises found symptom reduction rates of 78% to 90%, but these studies lacked the rigor of a ''phase three,'' or randomized controlled clinical trial. Methods. A randomized controlled trial assessed the efficacy of biofeedback for older women for treatment of sphincteric incompetence. One hundred thirty-five community-dwelling women were randomized in a single-blind trial to three groups: biofeedback, pelvic muscle exercise, or control. Incontinent episodes were monitored over 8 weeks of treatment and at 3 and 6 months thereafter. Results. The number of incontinent episodes decreased significantly in the biofeedback and pelvic muscle exercise subjects but not in the control subjects for all severity of incontinence frequency subgroups. Improvement was maintained within the moderate and severe symptom subgroups for both treatments for at least 6 months but declined in subjects with mild incontinence frequency. Pelvic muscle activity (EMG) was significantly correlated with decreases in incontinent episodes, and only the biofeedback subjects showed significant improvement in EMGs. Conclusions. Biofeedback and pelvic muscle exercises are efficacious for sphincteric incompetence in older women. Benefits are maintained and improvement continues for at least 6 months postintervention. These therapies may be useful before considering invasive treatment. C1 INST ADDICT, BUFFALO, NY USA. SUNY Buffalo, SCH NURSING, BUFFALO, NY 14260 USA. SUNY Buffalo, DEPT UROL, BUFFALO, NY 14260 USA. SUNY Buffalo, DEPT PSYCHOL, BUFFALO, NY 14260 USA. NIA, BETHESDA, MD 20892 USA. RP SUNY Buffalo, KIMBALL TOWER SCH NURSING 806, FAAN, BUFFALO, NY 14214 USA. FU NIA NIH HHS [UO1 AG05260] NR 33 TC 70 Z9 73 U1 2 U2 6 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1993 VL 48 IS 4 BP M167 EP M174 PG 8 WC Gerontology SC Geriatrics & Gerontology GA LL261 UT WOS:A1993LL26100033 PM 8315230 ER PT J AU CORPAS, E BLACKMAN, MR ROBERSON, R SCHOLFIELD, D HARMAN, SM AF CORPAS, E BLACKMAN, MR ROBERSON, R SCHOLFIELD, D HARMAN, SM TI ORAL ARGININE-LYSINE DOES NOT INCREASE GROWTH-HORMONE OR INSULIN-LIKE GROWTH FACTOR-I IN OLD MEN SO JOURNALS OF GERONTOLOGY LA English DT Article ID GH-RELEASING HORMONE; SOMATOMEDIN-C LEVELS; AMINO-ACIDS; BODY-COMPOSITION; AGED MEN; SECRETION; METABOLISM; PROTEIN; YOUNG; SERUM AB Background. Older adults tend to have reduced growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) levels as well as changes in body composition which are partially reversed by GH injections. Arginine stimulates GH release, and lysine may amplify this response. We investigated whether oral arginine/lysine could be used to increase basal IGF-I and GH levels in non-obese old men (age 69 +/- 5 years; mean +/- SD) to values similar to those of untreated young men (age 26 +/- 4 years). Methods. Two groups of 8 healthy old men were treated with 3 g of arginine plus 3 g of lysine or with placebo capsules twice daily for 14 days. Before and on day 14 of each treatment GH levels were determined in blood samples taken at 20-minute intervals from 2000-0800 h, IGF-I was measured at 0800 h, and a 1 mug/kg GHRH stimulation test was done. Results. At baseline, mean GH peak amplitude (p < .02) and serum IGF-I (p < .0001) were lower, whereas GHRH responses were similar, in old vs young men. Arginine/lysine did not significantly alter spontaneous or GHRH-stimulated GH levels, or serum IGF-I. Arginine absorption was age-independent. The correlation (p < .005) between measured increments in serum arginine and increases in serum GH after a single dose of arginine/lysine was similar in old and young groups. Conclusions. Our data suggest that oral arginine/lysine is not a practical means of chronically enhancing GH secretion in old men. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,ENDOCRINOL SECT,ROOM 2BI9,4940 EASTERN AVE,BALTIMORE,MD 21224. FRANCIS SCOTT KEY MED CTR,DEPT MED,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. CARBOHYDRATE NUTR LAB,BELTSVILLE,MD. USDA,HUMAN NUTR RES CTR,WASHINGTON,DC 20250. FU NCRR NIH HHS [MO1-RR02719] NR 39 TC 14 Z9 15 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1993 VL 48 IS 4 BP M128 EP M133 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LL261 UT WOS:A1993LL26100027 PM 8315224 ER PT J AU CAMPBELL, MK BUSH, TL HALE, WE AF CAMPBELL, MK BUSH, TL HALE, WE TI MEDICAL CONDITIONS ASSOCIATED WITH DRIVING CESSATION IN COMMUNITY-DWELLING, AMBULATORY ELDERS SO JOURNALS OF GERONTOLOGY LA English DT Article AB The decision to stop driving leads to severe contraction of independence, and most localities do not curtail driving privileges in impaired elders. In a population of community-based, ambulatory individuals 70-96 years old, annual medical screening showed that 276 of 1,656 (16.7 +/- 1.8%) who reported driving regularly in the past do not currently drive. The cessation of driving behavior was examined in terms of specific medical conditions occurring within the past 5 years. Retired drivers were disproportionately female, and driving cessation risk rose with age. Age-sex-adjusted logistic regression found that six conditions explained about 50 percent of the decisions to stop driving: macular degeneration; retinal hemorrhage; any deficit in Activities of Daily Living; Parkinson's disease; stroke-related residual paralysis or weakness; and syncope. Strikingly, only 1. 8 percent of those who stopped driving had ever had a license revoked; 58.7 percent reported voluntarily stopping; 31.9 percent gave health or medical reasons. Clearly, the decision to cede driving privileges is complex and not dependent solely on medical problems. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. MORTON PLANT HLTH SYST,FLORIDA GERIATR RES PROGRAM,CLEARWATER,FL. RP CAMPBELL, MK (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA S,SUITE T-41,BETHESDA,MD 20892, USA. NR 17 TC 92 Z9 93 U1 0 U2 5 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1993 VL 48 IS 4 BP S230 EP S234 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA LL261 UT WOS:A1993LL26100016 PM 8315247 ER PT J AU GEIGER, H BAHNER, U KRAUS, I HOFFMANN, M PALKOVITS, M HEIDLAND, A LUFT, FC AF GEIGER, H BAHNER, U KRAUS, I HOFFMANN, M PALKOVITS, M HEIDLAND, A LUFT, FC TI EFFECT OF ACE-INHIBITORS ON ATRIAL-NATRIURETIC-FACTOR IN THE BRAINS OF RATS WITH REDUCED RENAL MASS SO KIDNEY INTERNATIONAL LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME; SPONTANEOUSLY HYPERTENSIVE RATS; CENTRAL NERVOUS-SYSTEM; BLOOD-PRESSURE; INVITRO AUTORADIOGRAPHY; IMMUNOREACTIVE NEURONS; POLYPEPTIDE; EXCRETION; PEPTIDE; NUCLEI AB We tested the effect of renal insufficiency, with and without angiotensin (Ang) converting enzyme (ACE) inhibition, on blood and brain atrial natriuretic factor (ANF) in rats. Two ACEs, one which penetrates into the CNS and one which does not, were used to distinguish between peripheral and central ACE effects. Rats underwent 5/6 nephrectomy (5/6-NPX) by ligation of renal arterial branches. After seven days, 28 5/6-NPX rats received lisinopril 20 mg/kg/day and 28 5/6-NPX rats received quinapril 30 mg/kg/day orally for five days, while 28 5/6-NPX control rats and 28 sham rats did not. Body weight, blood pressure, drinking and urine volume were monitored. At sacrifice, urine, plasma, and brain tissue was collected. ANF in 16 brain areas was measured by radioimmunoassay. 5/6-NPX resulted in increased blood pressure, increased urine volume, proteinuria, and increased drinking. Both ACEs lowered blood pressure to sham values and decreased proteinuria. Both ACEs increased plasma renin activity and decreased plasma ANF. However, only lisinopril decreased drinking and urine volume. 5/6-NPX increased ANF values in six brain areas, namely the periventricular preoptic nucleus, the arcuate nucleus, the perifornical nucleus, the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus compared to sham rats. These same increases in brain ANF were also observed in 5/6-NPX rats given quinapril, compared to shams. However, lisinopril lowered ANF to sham levels in the periventricular preoptic nucleus, the arcuate nucleus, and the perifornical nucleus. In the three additional brain areas, namely the periventricular hypothalamic nucleus, the paraventricular nucleus, and the dorsal raphe nucleus, lisinopril did not effect the elevated ANF concentrations. The data suggest that 5/6-NPX increases ANF in six brain areas, independent of blood pressure. The increased urine volume and increased drinking associated with 5/6-NPX are at least in part mediated centrally. ANF may play a role in drinking behavior and volume homeostasis in certain brain areas. Furthermore, ANF in three of these areas may be influenced by Ang II-related mechanisms. C1 UNIV ERLANGEN NURNBERG,DEPT MED NEPHROL,W-8520 ERLANGEN,GERMANY. UNIV WURZBURG,DEPT MED NEPHROL,W-8700 WURZBURG,GERMANY. SEMMELWEIS UNIV MED,SCH MED,DEPT ANAT 1,H-1085 BUDAPEST 8,HUNGARY. NIMH,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Luft, Friedrich/0000-0002-8635-1199; Palkovits, Miklos/0000-0003-0578-0387 NR 43 TC 6 Z9 6 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 JUL PY 1993 VL 44 IS 1 BP 24 EP 29 DI 10.1038/ki.1993.208 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA LG816 UT WOS:A1993LG81600004 PM 8394952 ER PT J AU GEIGER, H BAHNER, U KRAUS, I HOFMANN, M PALKOVITS, M HEIDLAND, A LUFT, FC AF GEIGER, H BAHNER, U KRAUS, I HOFMANN, M PALKOVITS, M HEIDLAND, A LUFT, FC TI ACE-INHIBITION AND ANF IN THE BRAINS OF 5/6 NPX RATS SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 UNIV ERLANGEN NURNBERG,W-8520 ERLANGEN,GERMANY. UNIV WURZBURG,W-8700 WURZBURG,GERMANY. NIMH,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 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 JUL PY 1993 VL 44 IS 1 BP 246 EP 246 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA LG816 UT WOS:A1993LG81600074 ER PT J AU REHM, S PALMER, AE HARBAUGH, SW RICE, JM AF REHM, S PALMER, AE HARBAUGH, SW RICE, JM TI INFILTRATING ANGIOLIPOMA OF SKELETAL-MUSCLE - TRANSPLACENTAL INDUCTION IN NONHUMAN-PRIMATES BY N-NITROSOETHYLUREA SO LABORATORY INVESTIGATION LA English DT Article DE IMMUNOELECTRON MICROSCOPY; VON-WILLEBRAND FACTOR; IMMUNOHISTOCHEMISTRY; VASCULAR NEOPLASM; MALFORMATION; CARCINOGEN; TRANSPLACENTAL CARCINOGENESIS ID MONKEY ERYTHROCEBUS-PATAS; CAPILLARY HEMANGIOMA; MASSETER MUSCLE; CELL; LIPOMA AB BACKGROUND: In humans, relatively little is known on the association of prenatal exposure to cancer-causing agents and the development of specific tumors later in life as a consequence. Therefore, the effects on the offspring of carcinogen exposure during gestation and the development of tumors later in life were studied in nonhuman primates. EXPERIMENTAL DESIGN: Pregnancy was confirmed in Erythrocebus patas (patas) and Macaca mulatta (rhesus) by palpation at 27 to 40 days of gestation. Pregnant animals were treated once weekly intravenously from that time with N-nitrosoethylurea according to different dosing regimens for 6 to 19 weeks with 0.05 to 0.2 mmol/kg/injection. RESULTS: A common lesion developing in only the offspring of mothers treated early in pregnancy was identical with the human condition referred to as intramuscular angioma, hemangioma, or infiltrating angiolipoma of skeletal muscle. In the rhesus, one of 7 animals, and in the patas, 18 of 78 monkeys developed these processes (10 to 40% per group). The lesions typically arose within, infiltrated and displaced skeletal muscle. They occurred most commonly in the lower extremities, followed by the upper extremities and the head; they recurred in three cases of incomplete resection but did not metastasize. The tumors were seen mainly in young adults of both sexes (latency range: 4 to 76 months) and consisted of vessels of variable caliber, and to varying degrees, mature adipose and connective tissue, undifferentiated mesenchymal cells, and lymphoid cell aggregates. Ultrastructurally, the endothelium possessed numerous Weibel-Palade bodies and showed strong immunoreactivity for von Willebrand factor by immunohistochemistry and immunoelectron microscopy. CONCLUSIONS: The present investigation suggests a classification of these lesions as infiltrating angiolipoma of skeletal muscle originating from a pluripotent mesenchymal stem cell, caused by exposure to carcinogens during early pregnancy. The great clinical and morphologic similarity of this condition with that observed in humans suggests that it may likewise be caused by exposure to an agent during pregnancy. C1 BIOQUAL INC,ROCKVILLE,MD. RP REHM, S (reprint author), NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,PRIMATE RES WORKING GRP,FCRDC,BLDG 538,RM 220,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CP-15657, N01-CO-74101] NR 41 TC 2 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 1993 VL 69 IS 1 BP 111 EP 120 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA LN308 UT WOS:A1993LN30800013 PM 8331894 ER PT J AU LENFANT, C QUESENBERRY, PJ AF LENFANT, C QUESENBERRY, PJ TI THE STATUS OF BONE-MARROW TRANSPLANTATION FOR HEMATOLOGIC DISEASES - INTRODUCTION SO LEUKEMIA LA English DT Editorial Material C1 UNIV MASSACHUSETTS,MED CTR,CTR CANC,AMHERST,MA 01003. RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 1993 VL 7 IS 7 BP 1076 EP 1076 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA LP127 UT WOS:A1993LP12700025 ER PT J AU PHILLIPS, GL LONGO, DL AF PHILLIPS, GL LONGO, DL TI INDICATIONS FOR HIGH-DOSE THERAPY WITH HEMATOPOIETIC SUPPORT IN PATIENTS WITH HODGKINS-DISEASE SO LEUKEMIA LA English DT Article; Proceedings Paper CT CONF ON THE STATUS OF BONE MARROW TRANSPLANTATION FOR HEMATOLOGIC DISEASES CY SEP 22-23, 1992 CL ARLINGTON, VA SP LEUKEMIA SOC AMER, NHLBI ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; 1ST COMPLETE REMISSION; COMBINATION CHEMOTHERAPY; SALVAGE CHEMOTHERAPY; CHLVPP CHEMOTHERAPY; PROGNOSTIC FACTORS; RADIATION-THERAPY; MOPP; RELAPSE C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701. RP PHILLIPS, GL (reprint author), VANCOUVER GEN HOSP,LEUKEMIA BONE MARROW TRANSPLANTAT PROGRAM BRITISH COLUMBIA,VANCOUVER V5Z 1M9,BC,CANADA. NR 36 TC 3 Z9 3 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 1993 VL 7 IS 7 BP 1087 EP 1089 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA LP127 UT WOS:A1993LP12700031 PM 8321031 ER PT J AU GADIAN, DG SHAW, D MOONEN, CTW VANZIJL, P AF GADIAN, DG SHAW, D MOONEN, CTW VANZIJL, P TI ADVANCES IN PROTON MAGNETIC-RESONANCE SPECTROSCOPY OF THE BRAIN - A REPORT ON A WORKSHOP HELD IN OXFORD, ENGLAND DECEMBER 16-18, 1992 SO MAGNETIC RESONANCE IN MEDICINE LA English DT Editorial Material C1 GE MED SYST LTD,SLOUGH SL1 4ER,BERKS,ENGLAND. NIH,IN VIVO NMR RES CTR,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,DEPT RADIOL,BALTIMORE,MD 21205. RP GADIAN, DG (reprint author), ROYAL COLL SURGEONS ENGLAND,INST CHILD HLTH,BIOPHYS UNIT,30 GUILFORD ST,LONDON WC1N 1EH,ENGLAND. RI van Zijl, Peter/B-8680-2008; Gadian, David/C-4961-2008 NR 0 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUL PY 1993 VL 30 IS 1 BP 1 EP 3 DI 10.1002/mrm.1910300102 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LK916 UT WOS:A1993LK91600001 PM 8396708 ER PT J AU LIU, GY SOBERING, G OLSON, AW VANGELDEREN, P MOONEN, CTW AF LIU, GY SOBERING, G OLSON, AW VANGELDEREN, P MOONEN, CTW TI FAST ECHO-SHIFTED GRADIENT-RECALLED MRI - COMBINING A SHORT REPETITION TIME WITH VARIABLE T(2)ASTERISK WEIGHTING SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE FAST MRI; T(2)ASTERISK-IMAGING; FUNCTIONAL MRI; BLOOD VOLUME IMAGING ID CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE; CONTRAST; BRAIN; SUPPRESSION; SEQUENCES; SELECTION; IMAGE AB The principles of a fast T2*-sensitized MR imaging method (Moonen et al., Magn. Reson. Med. 26, 184 (1992)) are extended to further increase T2* sensitivity. It is shown that the period of T2*-weighting can be lengthened by n TR-periods by appropriate gradient schemes without RF refocusing resulting in progressively delayed gradient-recalled echoes. This extension of the echo-shifting concept thus introduces large flexibility in the choice of T2*-weighting without changing total imaging time. The coherence pathway formalism is used to evaluate and describe the selection of the desired echo and the attenuation of unwanted coherences. The new techniques are demonstrated for tracking a bolus of susceptibility contrast agent in cat brain. Relative blood-volume maps are derived with expected contrast between white and gray matter. C1 NIH,NCRR,BEIP,IN VIVO NMR RES CTR,BLDG 10,ROOM B1D-123,BETHESDA,MD 20892. DELFT UNIV TECHNOL,DEPT APPL PHYS,DELFT,NETHERLANDS. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 27 TC 47 Z9 47 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUL PY 1993 VL 30 IS 1 BP 68 EP 75 DI 10.1002/mrm.1910300111 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LK916 UT WOS:A1993LK91600010 PM 8371677 ER PT J AU BASSER, PJ AF BASSER, PJ TI CABLE EQUATION FOR A MYELINATED AXON DERIVED FROM ITS MICROSTRUCTURE SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE CABLE EQUATION; COMPOSITE MODEL; HOMOGENIZATION; MICROCONTINUUM; MYELINATED AXON; SUBTHRESHOLD RESPONSE ID ELECTROMAGNETIC INDUCTION; STIMULATION; NERVE; MODEL AB A simplified cable equation that describes the subthreshold behaviour of a myelinated axon is derived from its microstructure. Specifically, a microcontinuum cable model of a composite axon is homogenised, yielding a familiar macrocontinuum cable equation of electrotonus, for which the space and time constants depend on microstructural electrical parameters. Activating functions for magnetic and electrical stimulation can be incorporated into this homogenised cable equation as sources or sinks of transmembrane potential. An integral solution to the forced cable equation is also presented for the subthreshold regime. Errors are introduced when myelin membrane resistance is assumed to be infinite. RP BASSER, PJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Basser, Peter/H-5477-2011 NR 30 TC 15 Z9 15 U1 1 U2 4 PU PETER PEREGRINUS LTD PI HERTS PA SOUTHGATE HOUSE STEVENAGE PO BOX 8, HERTS, ENGLAND SG1 1HQ SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD JUL PY 1993 VL 31 SU S BP S87 EP S92 DI 10.1007/BF02446655 PG 6 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA LR748 UT WOS:A1993LR74800014 PM 8231331 ER PT J AU CLIFFORD, C KRAMER, B AF CLIFFORD, C KRAMER, B TI DIET AS RISK AND THERAPY FOR CANCER SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID TOTAL PARENTERAL-NUTRITION; BONE-MARROW TRANSPLANTATION; TERMINAL HUMAN CANCER; WOMENS HEALTH TRIAL; COLO-RECTAL CANCER; LARGE BOWEL-CANCER; DOSE VITAMIN-C; BREAST-CANCER; COLORECTAL-CANCER; ASCORBIC-ACID RP CLIFFORD, C (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 111 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 1993 VL 77 IS 4 BP 725 EP 744 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA LM797 UT WOS:A1993LM79700003 PM 8391617 ER PT J AU STGEORGIEV, V AF STGEORGIEV, V TI OPPORTUNISTIC NOSOCOMIAL INFECTIONS - TREATMENT AND DEVELOPMENTAL THERAPEUTICS .1. CRYPTOCOCCOSIS SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LIPOSOMAL AMPHOTERICIN-B; CELL-MEDIATED-IMMUNITY; COMBINATION THERAPY; NEOFORMANS INFECTION; PULMONARY CRYPTOCOCCOSIS; CUTANEOUS CRYPTOCOCCOSIS; EXPERIMENTAL CANDIDIASIS; MURINE CRYPTOCOCCOSIS; METHYL-ESTER RP STGEORGIEV, V (reprint author), NIAID,SOLAR BLDG,ROOM 4C-39,BETHESDA,MD 20892, USA. NR 148 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD JUL PY 1993 VL 13 IS 4 BP 493 EP 506 PG 14 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LJ092 UT WOS:A1993LJ09200004 PM 8361256 ER PT J AU REX, JH LARSEN, RA DISMUKES, WE CLOUD, GA BENNETT, JE AF REX, JH LARSEN, RA DISMUKES, WE CLOUD, GA BENNETT, JE TI CATASTROPHIC VISUAL-LOSS DUE TO CRYPTOCOCCUS-NEOFORMANS MENINGITIS SO MEDICINE LA English DT Article ID AMPHOTERICIN-B; AIDS PATIENTS; DECOMPRESSION; FLUCYTOSINE; INFECTION C1 UNIV SO CALIF,LOS ANGELES CTY HOSP,MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90033. UNIV ALABAMA,SCH MED,DIV INFECT DIS,BIRMINGHAM,AL 35233. UNIV ALABAMA,SCH MED,BIOSTAT UNIT,BIRMINGHAM,AL 35233. NIAID,CLIN MYCOL SECT,CLIN INVEST LAB,BETHESDA,MD 20892. RP REX, JH (reprint author), UNIV TEXAS,HLTH SCI CTR,CTR INFECT DIS,6431 FANNIN,1728 JFB,HOUSTON,TX 77030, USA. FU NIAID NIH HHS [N01-AI-15082] NR 46 TC 73 Z9 77 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JUL PY 1993 VL 72 IS 4 BP 207 EP 224 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA LP477 UT WOS:A1993LP47700001 PM 8341139 ER PT J AU LEFF, RL MILLER, FW HICKS, J FRASER, DD PLOTZ, PH AF LEFF, RL MILLER, FW HICKS, J FRASER, DD PLOTZ, PH TI THE TREATMENT OF INCLUSION-BODY MYOSITIS - A RETROSPECTIVE REVIEW AND A RANDOMIZED, PROSPECTIVE TRIAL OF IMMUNOSUPPRESSIVE THERAPY SO MEDICINE LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHY; SIGNAL RECOGNITION PARTICLE; ENZYMATIC AMINOACYLATION; MONONUCLEAR-CELLS; POLYMYOSITIS; DERMATOMYOSITIS; AUTOANTIBODIES; DISEASE; RNA C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. NIH,CTR CLIN,DEPT REHABIL MED,BETHESDA,MD 20892. NR 43 TC 70 Z9 70 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JUL PY 1993 VL 72 IS 4 BP 225 EP 235 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA LP477 UT WOS:A1993LP47700002 PM 8393509 ER PT J AU LOCKWICH, T AMBUDKAR, IS SHAMOO, AE AF LOCKWICH, T AMBUDKAR, IS SHAMOO, AE TI CA2+ PERMEABILITY OF RAT PAROTID-GLAND BASOLATERAL PLASMA-MEMBRANE VESICLES IS MODULATED BY MEMBRANE-POTENTIAL AND EXTRAVESICULAR [CA2+] SO MEMBRANE BIOCHEMISTRY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; RECONSTITUTED LIPID VESICLES; CYTOSOLIC FREE CALCIUM; DIVALENT-CATION ENTRY; ACINAR-CELLS; SARCOPLASMIC-RETICULUM; CA-2+ RELEASE; ADENINE-NUCLEOTIDES; SALIVARY SECRETION; MAST-CELLS AB This study examines the Ca2+ permeability of basolateral plasma membrane vesicles (BLMVs) isolated from the rat parotid gland by monitoring the rate of Ca-45(2+) efflux from actively-loaded (via the Ca2+-ATPase) inside-out BLMVs. Ca2+ efflux from BLMVs into a K+-gluconate medium which hyperpolarizes the cytoplasmic side (i. e. outside) of the inside-out BLMVs resulted in a faster rate of Ca2+ efflux compared with a control medium containing N-methyl-D-glucamine (NMDG)-gluconate. Conversely, Ca2+ efflux into a medium which depolarizes the cytoplasmic side of the BLMVs (NMDG-chloride) resulted in slower rates of efflux compared with those observed with the control medium. This increased rate of Ca-45(2+) efflux from the hyperpolarized BLMV was inhibited by 1 mM Ni2+, yielding a rate of efflux similar to the rate observed in depolarized BLMVs. The rate of Ca2+ efflux from BLMVs was affected by [Ca2+]o ([Ca2+] on the extravesicular, cytoplasmic side of the vesicle). When [Ca2+]o was kept > 200 nM during efflux, the rate of Ca2+ efflux from both hyper- and depolarized BLMVs was slow and relatively unresponsive to changes in [Ca2+]o, despite sizeable changes in the Ca2+ gradient across the BLMV. However, when [Ca2+]o was lowered < 200 nM, there was an abrupt increase in the rate of Ca2+ efflux from both hyper- and depolarized BLMVs. Additionally, when [Ca2+] was < 200 nM, the rate of Ca2+ efflux appeared to be more sensitive to driving force changes. These data suggest that Ca2+ permeability across the rat parotid gland basolateral plasma membrane is modulated by membrane potential and [Ca2+] on the cytoplasmic side. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,ROOM IN-113,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21201. NR 35 TC 4 Z9 4 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0149-046X J9 MEMBRANE BIOCHEM PD JUL-SEP PY 1993 VL 10 IS 3 BP 171 EP 179 DI 10.3109/09687689309150264 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LZ603 UT WOS:A1993LZ60300005 PM 8231900 ER PT J AU MURPHY, E AF MURPHY, E TI MEASUREMENT OF INTRACELLULAR IONIZED MAGNESIUM SO MINERAL AND ELECTROLYTE METABOLISM LA English DT Article DE FLUORESCENCE; FURAPTRA; MAG-FURA-2 ID CYTOSOLIC FREE MAGNESIUM; FLUORESCENT INDICATOR FURAPTRA; SQUID GIANT-AXONS; FREE MG-2+; MAGNETIC-RESONANCE; RAT-HEART; CARDIAC MYOCYTES; INFLUX PATHWAY; SMOOTH-MUSCLE; FREE MG2+ AB Recent advances in methods for measuring Mg(i) have advanced our understanding of Mg(i) homeostasis. Several methods exist for measuring Mg(i); all have strengths and weaknesses and one needs to match the experimental needs with the limitations of the method. For example, if one needs rapid (ms) time resolution, or only relative directional changes in a cell that is not easily impaled with an electrode, the fluorescent indicators may best suit ones needs. If on the other hand one wants to measure Mg(i) in a perfused organ, then the NMR methods may best address one's needs. If one needs to accurately know Mg(i) in a papillary muscle or some other tissue which is readily impaled then ion-selective microelectrodes may be the method of choice. RP MURPHY, E (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. NR 73 TC 23 Z9 23 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-0392 J9 MINER ELECTROL METAB JI Miner. Electrolyte Metab. PD JUL-OCT PY 1993 VL 19 IS 4-5 BP 250 EP 258 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA MG487 UT WOS:A1993MG48700007 PM 8264511 ER PT J AU WARE, LA KAIN, KC SIM, BKL HAYNES, JD BAIRD, JK LANAR, DE AF WARE, LA KAIN, KC SIM, BKL HAYNES, JD BAIRD, JK LANAR, DE TI 2 ALLELES OF THE 175-KILODALTON PLASMODIUM-FALCIPARUM ERYTHROCYTE BINDING ANTIGEN SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE PLASMODIUM-FALCIPARUM; ERYTHROCYTE BINDING ANTIGEN; ALLELE ID MEROZOITE INVASION; MALARIA; PARASITE; GLYCOPHORIN; PROTEINS; RECEPTOR AB EBA-175, erythrocyte binding antigen 175, is a 175-kDa antigen of Plasmodium falciparum which has been shown to be involved in the recognition of erythrocytes by merozoites and may be involved in the process of erythrocyte invasion. Invasion of erythrocytes by Camp strain merozoites is inhibited by pre-treatment of red blood cells by EBA-175 from the heterologous strain, FCR-3. The sequence of the Camp strain has been published and we report here the sequence of the FCR-3 strain. The sequences are nearly identical except for a 423-bp segment in the FCR-3 strain, F-segment, that is not found in the Camp strain and a 342-bp segment, C-segment, present in the Camp strain but not in the FCR-3 strain. The locations of these two segments are different in Camp and FCR-3 EBA-175 genes and there is little DNA or amino acid sequence homology between them. The essentially dimorphic alleles, F-segment and C-segment, are conserved in all isolates examined to date. Evidence of genetic cross-over between the FCR-3 and the Camp EBA-175 genes was not observed in the analysis of a limited number of wild isolates. The continued study of the biological relevance of these sequence divergences in EBA-175 may further elucidate the sequence of events resulting in merozoite invasion of erythrocytes. C1 WALTER REED ARMY INST RES,DEPT IMMUNOL,WASHINGTON,DC 20307. NAMRU,JAKARTA,INDONESIA. TORONTO GEN HOSP,TROP DIS UNIT,TORONTO M5G 1L7,ONTARIO,CANADA. NIH,PARASIT DIS LAB,BETHESDA,MD 20892. RI Lanar, David/B-3560-2011 NR 18 TC 41 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 1993 VL 60 IS 1 BP 105 EP 110 DI 10.1016/0166-6851(93)90033-T PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA LL861 UT WOS:A1993LL86100012 PM 8366884 ER PT J AU KANNO, Y KOZAK, CA SCHINDLER, C DRIGGERS, PH ENNIST, DL GLEASON, SL DARNELL, JE OZATO, K AF KANNO, Y KOZAK, CA SCHINDLER, C DRIGGERS, PH ENNIST, DL GLEASON, SL DARNELL, JE OZATO, K TI THE GENOMIC STRUCTURE OF THE MURINE ICSBP GENE REVEALS THE PRESENCE OF THE GAMMA INTERFERON-RESPONSIVE ELEMENT, TO WHICH AN ISGF3-ALPHA SUBUNIT (OR SIMILAR) MOLECULE BINDS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CLASS-I GENE; MEDIATE VIRUS INDUCIBILITY; TRANSCRIPTIONAL ACTIVATOR; NUCLEAR FACTORS; CYTOPLASMIC ACTIVATION; REGULATED EXPRESSION; CONSENSUS SEQUENCE; ALPHA-INTERFERON; PROMOTER ELEMENT; STIMULATED GENES AB ICSBP, a member of the interferon regulatory factor family, is expressed predominantly in lymphoid tissues and is induced by gamma interferon (IFN-gamma). We have studied the genomic organization of the murine ICSBP gene and its 5' upstream region. The murine ICSBP gene (Icsbp) is present as a single copy on chromosome 8 and consists of nine exons. Transcription initiates at two juxtaposed sites downstream from the TATA and CAAT boxes and produces two species of ICSBP mRNA (3.0 and 1.7 kb), presumably by differential usage of poly(A)+ signals. A sequence from -175 to -155 was identified to be an IFN response region that conferred IFN-gamma induction upon a heterologous promoter in lymphoid cell line ELA. This region includes a motif, TTCNNGGAA, designated the palindromic IFN response element (pIRE), to which an IFN-gamma-inducible, cycloheximide-sensitive factor(s) binds. A similar palindromic motif was found in the upstream region of the murine IRF-1 gene, the IFN-gamma activation site of the guanylate-binding protein gene and the IFN-gamma-responsive region of the Fc receptor type I gene, all of which competed with the pIRE for factor binding in gel mobility shift assays. We show that the pIRE binding factor reacts with the antibody against the 91-kDa subunit of ISGF3alpha recently shown to bind to the IFN-gamma activation site. These results suggest that this factor is related to the IFN-gamma activation factor and contains the 91-kDa subunit of ISGF3alpha. Taken together, pIRE represents an IRE that is distinct from the classical IFN-stimulated response element and that is capable of conferring IFN-gamma induction through the binding of the 91-kDa ISGF3alpha subunit (or an antigenically similar molecule). C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. ROCKEFELLER UNIV,MOLEC CELL BIOL LAB,NEW YORK,NY 10021. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. COLUMBIA UNIV,MED CTR,DEPT MED,NEW YORK,NY 10032. RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319 NR 75 TC 176 Z9 176 U1 0 U2 1 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 JUL PY 1993 VL 13 IS 7 BP 3951 EP 3963 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200012 PM 8321202 ER PT J AU REITMAN, M LEE, E WESTPHAL, H FELSENFELD, G AF REITMAN, M LEE, E WESTPHAL, H FELSENFELD, G TI AN ENHANCER LOCUS-CONTROL REGION IS NOT SUFFICIENT TO OPEN CHROMATIN SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BETA-GLOBIN GENE; I-HYPERSENSITIVE SITES; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; ACTIVATION REGION; SACCHAROMYCES-CEREVISIAE; INDEPENDENT EXPRESSION; TRANSCRIPTION; DOMAINS; BINDING AB To study the way in which an enhancer/locus control region (LCR) activates chromatin, we examined transgenic mice carrying various combinations of the chicken beta(A)-globin gene coding region, promoter, and 3' enhancer/LCR. We compared lines carrying only the coding region and enhancer/LCR (E) and only the coding region and promoter (P) with those containing all three elements (PE). We have shown previously that all PE mice transcribe the transgene in a copy number-dependent manner while the P mice do not express their transgene. In the current study, we examined chromatin activation by monitoring formation of erythroid-specific hypersensitive sites at the promoter and enhancer. We found that all of the PE lines but none of the P lines show hypersensitivity. In contrast, only three of six E lines are hypersensitive (two strongly and one weakly), demonstrating position dependence of this transgene. The two E lines with strong hypersensitive sites were found also to have RNA complementary to the transgene, presumably starting from an adjacent adventitious mouse promoter. In all of these lines, we found a correlation between erythroid-specific hypersensitivity and erythroid-specific general DNase I sensitivity, an indicator of regional chromatin activation. The results support a mutual interaction model for the mechanism of chromatin opening by LCRs in which the enhancer/LCR and promoter must cooperate in order to generate open chromatin. The data are not consistent with a dominant enhancer model in which the enhancer/LCR can open chromatin autonomously. C1 NIADDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RP REITMAN, M (reprint author), NIADDKD,DIABET BRANCH,BETHESDA,MD 20892, USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 54 TC 89 Z9 89 U1 0 U2 1 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 JUL PY 1993 VL 13 IS 7 BP 3990 EP 3998 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200016 PM 8321206 ER PT J AU CHEN, Y WEEKS, J MORTIN, MA GREENLEAF, AL AF CHEN, Y WEEKS, J MORTIN, MA GREENLEAF, AL TI MAPPING MUTATIONS IN GENES ENCODING THE 2 LARGE SUBUNITS OF DROSOPHILA RNA POLYMERASE-II DEFINES DOMAINS ESSENTIAL FOR BASIC TRANSCRIPTION FUNCTIONS AND FOR PROPER EXPRESSION OF DEVELOPMENTAL GENES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ALPHA-AMANITIN RESISTANCE; 2ND-LARGEST SUBUNIT; NUCLEOTIDE-SEQUENCE; ACTIVE-SITE; DNA; MELANOGASTER; YEAST; LOCUS; POLYMORPHISMS; CONTACTS AB We have mapped a number of mutations at the DNA sequence level in genes encoding the largest (RpII215) and second-largest (RpII140) subunits of Drosophila melanogaster RNA polymerase II. Using polymerase chain reaction (PCR) amplification and single-strand conformation polymorphism (SSCP) analysis, we detected 12 mutations from 14 mutant alleles (86%) as mobility shifts in nondenaturing gel electrophoresis, thus localizing the mutations to the corresponding PCR fragments of about 350 bp. We then determined the mutations at the DNA sequence level by directly subcloning the PCR fragments and sequencing them. The five mapped RpII140 mutations clustered in a C-terminal portion of the second-largest subunit, indicating the functional importance of this region of the subunit. The RpII215 mutations were distributed more broadly, although six of eight clustered in a central region of the subunit. One notable mutation that we localized to this region was the alpha-amanitin-resistant mutation RpII2]5C4, which also affects RNA chain elongation in vitro. RpII215C4 mapped to a position near the sites of corresponding mutations in mouse and in Caenorhabditis elegans genes, reinforcing the idea that this region is involved in amatoxin binding and transcript elongation. We also mapped mutations in both RpII215 and RpII140 that cause a developmental defect known as the Ubx effect. The clustering of these mutations in each gene suggests that they define functional domains in each subunit whose alteration induces the mutant phenotype. C1 DUKE UNIV,MED CTR,DEPT BIOCHEM,DURHAM,NC 27710. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Mortin, Mark/B-4251-2008 FU NIGMS NIH HHS [GM 28078] NR 58 TC 39 Z9 40 U1 0 U2 1 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 JUL PY 1993 VL 13 IS 7 BP 4214 EP 4222 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200039 PM 8321225 ER PT J AU MARAIA, RJ DRISCOLL, CT BILYEU, T HSU, K DARLINGTON, GJ AF MARAIA, RJ DRISCOLL, CT BILYEU, T HSU, K DARLINGTON, GJ TI MULTIPLE DISPERSED LOCI PRODUCE SMALL CYTOPLASMIC ALU RNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ALPHA-FETOPROTEIN GENE; POLYMERASE-III; REPETITIVE SEQUENCES; SECONDARY STRUCTURE; SUCCESSIVE WAVES; LINEAGE HISTORY; SRP-RNA; FAMILY; EVOLUTION; TRANSCRIPTION AB Alu repeats are short interspersed elements (SINEs) of dimeric structure whose transposition sometimes leads to heritable disorders in humans. Human cells contain a poly(A)- small cytoplasmic transcript of approximately 120 nucleotides (nt) homologous to the left Alu monomer. Although its monomeric size indicates that small cytoplasmic Alu (scAlu) RNA is not an intermediary of human Alu transpositions, a less abundant poly(A)-containing Alu transcript of dimeric size and specificity expected of a transposition intermediary is also detectable in HeLa cells (A. G. Matera, U. Hellmann, M. F. Hintz, and C. W. Schmid, Mol. Cell. Biol. 10:5424-5432, 1990). Although its function is unknown, the accumulation of Alu RNA and its ability to interact with a conserved protein suggest a role in cell biology (D.-Y. Chang and R. J. Maraia, J. Biol. Chem. 268:6423-28, 1993). The relationship between the approximately 120- and approximately 300-nt Alu transcripts had not been determined. However, a B1 SINE produces scB1 RNA by posttranscriptional processing, suggesting a similar pathway for scAlu. An Alu SINE which recently transposed into the neurofibromatosis 1 locus was expressed in microinjected frog oocytes. This neurofibromatosis 1 Alu produced a primary transcript followed by the appearance of the scAlu species. 3' processing of a synthetic approximately 300-nt Alu RNA by HeLa nuclear extract in vitro also produced scAlu RNA. Primer extension of sCAlu RNA indicates synthesis by RNA polymerase III. HeLa-derived scAlu cDNAs were cloned so as to preserve their 5'-terminal sequences and were found to correspond to polymerase Ill transcripts of the left monomeric components of three previously identified Alu SINE subfamilies. Rodent x human somatic cell hybrids express Alu RNAs whose size, heterogeneous length, and chromosomal distribution indicate their derivation from SINEs. The coexpression of dimeric and monomeric Alu RNA in several hybrids suggests a precursor-product relationship. C1 TEXAS CHILDRENS HOSP,DEPT PATHOL,HOUSTON,TX 77030. RP MARAIA, RJ (reprint author), NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892, USA. NR 62 TC 60 Z9 60 U1 0 U2 1 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 JUL PY 1993 VL 13 IS 7 BP 4233 EP 4241 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200041 PM 7686619 ER PT J AU ZHAN, QM CARRIER, F FORNACE, AJ AF ZHAN, QM CARRIER, F FORNACE, AJ TI INDUCTION OF CELLULAR P53 ACTIVITY BY DNA-DAMAGING AGENTS AND GROWTH ARREST SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID IONIZING-RADIATION; MAMMALIAN-CELLS; GENE; RNA; EXPOSURE; PROTEIN AB The tumor suppressor p53 can function as a sequence-specific transcription factor and is required for activation by ionizing radiation (IR) of one or more downstream effector genes, such as the human GADD45 gene. One important consequence of IR that is probably mediated by these downstream effector genes is activation of the p53-mediated G1 cell cycle checkpoint. While the induction of reporter constructs containing p53-binding sites has already been demonstrated with p53 expression vectors, we have now demonstrated the direct activation of such a construct after treatment of the human RKO line, which has a normal p53 phenotype, with various types of DNA-damaging agents and also after growth arrest produced by medium depletion (starvation). IR, UV radiation, and methylmethane sulfonate were found to induce p53 activity when a stably integrated reporter construct containing functional p53-binding sites was used and also in mobility shift assays with a p53-binding site from the GADD45 gene, and IR-inducible gene previously associated with growth arrest. The same cell treatments that induced this p53 activity also caused an increase in cellular p53 protein levels. The response in cells lacking normal p53 or in RKO cells expressing a dominant negative mutant p53 was markedly reduced. Interestingly, the spectrum of effective inducing agents for the above-described experiments was similar to that which induces GADD45 either in cells with a normal p53 status or, with the exception of IR, in cells lacking normal p53. These results indicate a role for p53 in the IR pathway, which is completely p53 dependent, and in other genotoxic stress responses, in which p53 has a cooperative effect but is not required. C1 NCI,DCT,DTP,MOLEC PHARMACOL LAB,ROOM 5C09,BLDG 37,BETHESDA,MD 20892. RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 35 TC 454 Z9 462 U1 0 U2 5 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 JUL PY 1993 VL 13 IS 7 BP 4242 EP 4250 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200042 PM 8321226 ER PT J AU ROMAN, DG DANCIS, A ANDERSON, GJ KLAUSNER, RD AF ROMAN, DG DANCIS, A ANDERSON, GJ KLAUSNER, RD TI THE FISSION YEAST FERRIC REDUCTASE GENE FRP1+ IS REQUIRED FOR FERRIC IRON UPTAKE AND ENCODES A PROTEIN THAT IS HOMOLOGOUS TO THE GP91-PHOX SUBUNIT OF THE HUMAN NADPH PHAGOCYTE OXIDOREDUCTASE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; CELLS AB We have identified a cell surface ferric reductase activity in the fission yeast Schizosaccharomyces pombe. A mutant strain deficient in this activity was also deficient in ferric iron uptake, while ferrous iron uptake was not impaired. Therefore, reduction is a required step in cellular ferric iron acquisition. We have cloned frp1+, the wild-type allele of the mutant gene. frp1+ mRNA levels were repressed by iron addition to the growth medium. Fusion of 138 nucleotides of frp1+ promoter sequences to a reporter gene, the bacterial chloramphenicol acetyltransferase gene, conferred iron-dependent regulation upon the latter when introduced into S. pombe. The predicted amino acid sequence of the frp1+ gene exhibits hydrophobic regions compatible with transmembrane domains. It shows similarity to the Saccharomyces cerevisiae FRE1 gene product and the gp91-phox protein, a component of the human NADPH phagocyte oxidoreductase that is deficient in X-linked chronic granulomatous disease. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RI Anderson, Gregory/G-4148-2013 OI Anderson, Gregory/0000-0002-8814-5866 NR 39 TC 99 Z9 102 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 JUL PY 1993 VL 13 IS 7 BP 4342 EP 4350 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200052 PM 8321236 ER PT J AU KIKUCHI, T RAJU, K BREITMAN, ML SHINOHARA, T AF KIKUCHI, T RAJU, K BREITMAN, ML SHINOHARA, T TI THE PROXIMAL PROMOTER OF THE MOUSE ARRESTIN GENE DIRECTS GENE-EXPRESSION IN PHOTORECEPTOR CELLS AND CONTAINS AN EVOLUTIONARILY CONSERVED RETINAL FACTOR-BINDING SITE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID COUP TRANSCRIPTION FACTOR; S-ANTIGEN GENE; INVITRO TRANSCRIPTION; RECEPTOR SUPERFAMILY; RHODOPSIN-KINASE; 48-KDA PROTEIN; PINEAL-GLAND; DROSOPHILA; DNA; ENCODES AB Regulatory sequences and nuclear factors governing tissue-restricted expression of the mouse arrestin gene were investigated. The results showed that while proximal promoter sequence positions -38 to +304 are sufficient to direct low levels of retina-specific gene expression, sequences extending upstream to position -209 support higher levels of expression in the retina, as well as detectable expression in the lens, pineal gland, and brain. Within the interval between positions -209 and -38, a broadly expressed nuclear factor, Bd, binds to sequences centered between positions -205 and -185, a region which contains two direct repeats of the hexamer, TGACCT. The proximal promoter binds three apparently retina-specific nuclear factors, Bp1, Bp2, and Bp3, through overlapping sequences centered between positions -25 and -15. Bp1 and Bp3 also recognize a closely related sequence found in the promoter regions of several other vertebrate photoreceptor-specific genes. Moreover, the consensus binding site for Bp1, designated PCE I, is identical to RCS I, an element known to play a critical role in eliciting photoreceptor-specific gene expression in Drosophila melanogaster. The results suggest that PCE I and RCS I are functionally as well as structurally similar and that, despite marked differences in the fly and vertebrate visual systems, the transcriptional machinery involved in photoreceptor-specific gene expression has been strongly evolutionarily conserved. C1 NAT EYE INST,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. MT SINAI HOSP,SAMUEL LUNENFELD RES INST,DIV MOLEC & DEV BIOL,TORONTO M5G 1X5,ONTARIO,CANADA. UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO M5S 1A8,ONTARIO,CANADA. OI Shinohara, Toshimichi/0000-0002-7197-9039 NR 50 TC 106 Z9 107 U1 0 U2 0 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 JUL PY 1993 VL 13 IS 7 BP 4400 EP 4408 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200058 PM 8321239 ER PT J AU MILLER, AC GAFNER, J CLARK, EP SAMID, D AF MILLER, AC GAFNER, J CLARK, EP SAMID, D TI POSTTRANSCRIPTIONAL DOWN-REGULATION OF RAS ONCOGENE EXPRESSION BY INHIBITORS OF CELLULAR GLUTATHIONE SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INTERFERON-INDUCED REVERTANTS; MESSENGER-RNA; MOUSE FIBROBLASTS; BINDING-FACTOR; CELLS; RADIATION; PROTEIN; RESISTANCE; INVITRO; GROWTH AB Alterations in intracellular glutathione (GSH) content are known to affect intrinsic responses to ionizing radiation. More recently, it became apparent that radiation responses may depend also on the expression of specific oncogenes, including ras. These findings, suggesting a possible link between GSH and ras, led us to examine the effect of various GSH modulators on ras expression. Treatment of c-Ha-ras-transformed NIH 3T3 cells with L-buthionine S'R'-sulfoximine, dimethylfumarate, or N',N'-1,3-bis(trans-4-hydroxycyclohexyl)-N'-nitrosourea resulted in dose- and time-dependent reduction in ras mRNA steady-state levels followed by a decrease in ras-encoded p21 protein production. The effect on ras correlated with the extent of GSH decline, was common to different members of the ras family, and was independent of the mode of oncogene activation or cell phenotype. Indeed, similar drug effects were observed with murine cells in which overexpression of the c-Ha-ras proto-oncogene was due to transcriptional activation (PR4, nontumorigenic) or gene amplification (NIH 136, tumorigenic) and with malignant cells expressing a mutated Ha-ras (RS504). Moreover, N-ras, EJras, and Ki-ras in human tumor cells were similarly affected. Molecular analysis revealed a significant decrease in ras mRNA half-life in cells subjected to GSH inhibition, an effect that required de novo protein synthesis, but there was no change in the rate of gene transcription. These results indicate that pharmacological manipulation of cellular GSH content can down-regulate ras expression at the posttranscriptional level by destabilizing ras transcripts. The potential clinical implications are discussed. C1 ARMED FORCES RADIOBIOL RES INST,DEPT RADIAT BIOCHEM,BETHESDA,MD 20889. NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NR 34 TC 33 Z9 33 U1 0 U2 0 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 JUL PY 1993 VL 13 IS 7 BP 4416 EP 4422 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200060 PM 8321241 ER PT J AU KITADA, K JOHNSON, AL JOHNSTON, LH SUGINO, A AF KITADA, K JOHNSON, AL JOHNSTON, LH SUGINO, A TI A MULTICOPY SUPPRESSOR GENE OF THE SACCHAROMYCES-CEREVISIAE G1 CELL-CYCLE MUTANT-GENE DBF4 ENCODES A PROTEIN-KINASE AND IS IDENTIFIED AS CDC5 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BUDDING YEAST; DNA-SEQUENCE; S-PHASE; MITOSIS; THREONINE; HOMOLOG; SERINE; ACTIVATION; INITIATION; TYROSINE AB We have isolated a multicopy suppressor of the temperature-sensitive growth phenotype of organisms carrying mutations of DBF4, a gene that is required for the initiation of chromosomal DNA replication in Saccharomyces cerevisiae and that interacts with the CDC7 protein kinase. Nucleotide sequence analysis of the suppressor gene, provisionally named MSD2, revealed an open reading frame encoding a protein with a calculated M(r) of 81,024, with amino acid sequence similarity to the catalytic domains of protein kinases. Both genetic linkage and complementation analyses indicated that MSD2 is identical to the cell division cycle gene CDC5. An activity that phosphorylated exogenously added casein was immunoprecipitated by antiserum against a TrpE-Cdc5 fusion protein from lysates of wild-type cells containing CDC5 on a multicopy plasmid but not of cells bearing a small deletion in the predicted protein kinase domain of CDC5 on the plasmid. Deletion of CDCS was lethal and resulted in a dumbbell-shaped terminal morphology, with the nuclei almost divided but still connected. Consistent with the function at the G2/M boundary, the CDC5 transcript accumulated periodically during the cell cycle, peaking at the G2/M boundary. CDC5 on a multicopy plasmid also suppresses temperature-sensitive cdc15, cdc20, and dbf2 mutations which affect mitosis during the cell cycle. C1 NIEHS, MOLEC GENET LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. NATL INST MED RES, YEAST GENET LAB, LONDON NW7 1AA, ENGLAND. OSAKA UNIV, MICROBIAL DIS RES INST, DEPT MOLEC IMMUNOL, SUITA, OSAKA 565, JAPAN. NR 50 TC 228 Z9 232 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 1993 VL 13 IS 7 BP 4445 EP 4457 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LJ362 UT WOS:A1993LJ36200063 PM 8321244 ER PT J AU VAMVAKOPOULOS, NC CHROUSOS, GP AF VAMVAKOPOULOS, NC CHROUSOS, GP TI REGULATED ACTIVITY OF THE DISTAL PROMOTER-LIKE ELEMENT OF THE HUMAN CORTICOTROPIN-RELEASING HORMONE GENE AND SECONDARY STRUCTURAL FEATURES OF ITS CORRESPONDING TRANSCRIPTS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE (CRH); CORTICOTROPIN-RELEASING HORMONE GENE (CRH GENE); MESSENGER RNA (CRH); GENE REGULATION; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR ID HUMAN GLUCOCORTICOID RECEPTOR; HUMAN-PLACENTA; MESSENGER-RNA; CHRONIC STRESS; CELL-LINE; EXPRESSION; SEQUENCE; MOUSE; MONOPHOSPHATE; INITIATOR AB Corticotropin-releasing hormone (CRH) plays a major role in the coordination of the stress response. Its gene is expressed in multiple brain regions, the peripheral sympathetic system and the placenta, as well as in peripheral inflammatory sites where CRH acts as a pro-inflammatory cytokine. The human (h) CRH gene, in addition to its primary promoter (TATA box I), has a second distal promoter-like structure (TATA box II) and a functional cyclic adenosine monophosphate-responsive element, all of which are preserved in the rat and ovine genes. To examine the functionality of TATA II, we positioned a 881-bp-long segment of the 5' flanking region of the hCRH gene containing TATA II, but lacking TATA I, upstream from a chloramphenicol acetyltransferase (CAT) reporter gene cloned in a pUC vector. We transfected COS-7 cells with this construct and examined responsiveness of CAT activity to potential stimulants and inhibitors. Phorbol ester (TPA) and forskolin had mild but clear stimulatory effects on CAT expression (approximately 1.5- and approximately 1.3-fold, respectively), with a combined effect of approximately 1.9-fold. Dexamethasone (DEX) inhibited TPA-stimulated CAT activity by approximately 2.6-fold. In contrast, in the presence of a co-transfected glucocorticoid receptor cDNA expression plasmid, DEX augmented TPA-stimulated CAT expression by approximately 3.1-fold. The predicted secondary structures of the primary transcripts employing the distal and proximal promoters had significant differences, which could affect their stability and translatability. These observations suggest that TATA II functions weakly in the heterologous system examined, independently of TATA I, and directs the synthesis of the second largest pool of CRH transcripts with a longer 5' non-coding region than the transcripts driven by TATA I. The former possess structural features that may differentiate them from the latter in terms of stability and translatability. RP VAMVAKOPOULOS, NC (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N-240,BETHESDA,MD 20892, USA. NR 42 TC 22 Z9 22 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUL PY 1993 VL 94 IS 1 BP 73 EP 78 DI 10.1016/0303-7207(93)90053-M PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA LL157 UT WOS:A1993LL15700009 PM 8397123 ER PT J AU WATERS, AP HIGGINS, DG MCCUTCHAN, TF AF WATERS, AP HIGGINS, DG MCCUTCHAN, TF TI EVOLUTIONARY RELATEDNESS OF SOME PRIMATE MODELS OF PLASMODIUM SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE 18S RIBOSOMAL-RNA; MALARIA; PLASMODIUM; PHYLOGENY ID RIBOSOMAL-RNA GENE; SEQUENCE; DNA; FALCIPARUM; TREES AB Primate-and, specifically, monkey-malaria infections are commonly used for understanding the pathology of and immune response to the human disease because they are thought to resemble most closely the host-parasite relationship found in humans. Plasmodium cynomolgi is used extensively as a model for the human parasite, P. vivax, and P. knowlesi is used primarily as a model for the development of erythrocytic-stage vaccines. Both of these simian parasites can naturally infect man, resulting in mildly symptomatic episodes of the disease. The phylogenetic relationship between these two simian parasites and previously characterized Plasmodium species, including P. vivax, was examined by comparison of the asexually expressed small-subunit ribosomal RNA genes. Our analysis confirmed that P. vivax is most closely related to P. cynomolgi and that it remains an appropriate model of the human pathogen. Furthermore, with P. knowlesi and P. fragile, these two species form a group of closely related species, distant from other Plasmodium species. What is considered to be the most ancient of the human malaria pathogens, P. malariae, was also included in the analysis and does not group at all with other simian or human parasites. C1 EUROPEAN MOLEC BIOL LAB, W-6900 HEIDELBERG, GERMANY. NIAID, MALARIA RES LAB, BETHESDA, MD 20892 USA. RP WATERS, AP (reprint author), LEIDEN UNIV, PARASITOL LAB, POSTBUS 9605, 2300 RC LEIDEN, NETHERLANDS. RI Waters, Andy/C-9377-2009; Higgins, des/J-6314-2012 OI Waters, Andy/0000-0001-8900-2982; NR 30 TC 83 Z9 83 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUL PY 1993 VL 10 IS 4 BP 914 EP 923 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA LL868 UT WOS:A1993LL86800012 PM 7689135 ER PT J AU JOHNSON, G REFOLO, LM MERRIL, CR WALLACE, W AF JOHNSON, G REFOLO, LM MERRIL, CR WALLACE, W TI ALTERED EXPRESSION AND PHOSPHORYLATION OF AMYLOID PRECURSOR PROTEIN IN HEAT-SHOCKED NEURONAL PC12 CELLS SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; AMYLOID PRECURSOR PROTEIN; PHOSPHORYLATION; PC12 CELL; HEAT SHOCK ID NERVE GROWTH-FACTOR; ALZHEIMERS-DISEASE; MESSENGER-RNA; INDUCTION; UBIQUITIN; STRESS; BRAIN; TAU AB The pathology of the Alzheimer's disease (AD) brain, including amyloid plaques, neurofibrillary tangles and neuronal degeneration, indicates that neurons affected by AD exist under conditions of stress. In fact, the brains of AD patients undergo many changes classically associated with the heat shock response, which is one form of a stress response. These changes include reduced protein synthesis, disrupted cytoskeleton, increased number of proteins associated with ubiquitin, and the induction of heat shock proteins. To investigate the response of neurons to stress, we examined neuronal PC12 cells incubated at either 37-degrees-C (control cells) or 45-degrees-C (heat-shocked cells). After a 30 min exposure at 45-degrees-C, the heat-shocked cells exhibited several features characteristic of the classical heat shock response including a 45% reduction in total protein synthesis, the induction of heat shock protein 72, and an increased phosphorylation of the protein synthesis initiation factor eIF-2alpha. We used this cellular model system to study the neuronal response to stress specifically focusing on protein synthesis elongation factor 2 (EF-2) and the Alzheimer's amyloid precursor protein (APP), the precursor form of beta-amyloid peptide. Hyperphosphorylation of EF-2 has been observed in the neocortex and hippocampus of AD brain18. However, in our system, we find no hyperphosphorylation of EF-2 in response to heat shock. Heat-shocked neuronal PC12 cells exhibited two additional APP-like polypeptides not present in controls. We also found a significant decrease in the phosphorylation state of APP in response to heat shock. Protein kinase C phosphorylated APP in the neuronal PC12 cells, as evidenced by the response to PMA, a phorbol ester which stimulated the phosphorylation of APP and staurosporine which reduced its phosphorylation. Therefore, heat-shocked neuronal PC12 cells undergo several biochemical alterations which are also associated with the AD brain. We have used heat-shocked neuronal PC12 cells as a cell culture model system to investigate changes in several proteins (EF-2, APP, and tau) known to be altered in the AD brain. C1 NIMH,BIOCHEM GENET LAB,WASHINGTON,DC 20032. CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,ARTHUR FISHBERG CTR NEUROBIOL,NEW YORK,NY 10029. NR 42 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1993 VL 19 IS 1-2 BP 140 EP 148 DI 10.1016/0169-328X(93)90159-M PG 9 WC Neurosciences SC Neurosciences & Neurology GA LL297 UT WOS:A1993LL29700018 ER PT J AU WALLACE, W JOHNSON, G SUGAR, J MERRIL, CR REFOLO, LM AF WALLACE, W JOHNSON, G SUGAR, J MERRIL, CR REFOLO, LM TI REVERSIBLE PHOSPHORYLATION OF TAU TO FORM A68 IN HEAT-SHOCKED NEURONAL PC12 CELLS SO MOLECULAR BRAIN RESEARCH LA English DT Article DE ALZHEIMERS DISEASE; HEAT SHOCK PROTEIN; PROTEIN KINASE; CYTOSKELETON ID PAIRED HELICAL FILAMENTS; ALZHEIMERS-DISEASE; DEPENDENT KINASE; PROTEIN-TAU; BRAINS; PATHOLOGY; UBIQUITIN; TANGLES AB A68, the primary protein constituent of Alzheimer's disease-associated neurofibrillary tangles, is an abnormally phosphorylated form of the microtubule-associated protein tau. We find that A68 is formed in neuronal PC12 cells when the cells are subjected to a heat shock (45-degrees-C for 30 min). A68 was identified by immunopreciptation with two different anti-tau antibodies (tau-2 and Alz50). Upon separation by SDS-polyacrylamide gel electrophoresis, the tau immunoprecipitates from heat-shocked cells exhibited an additional polypeptide of reduced electrophoretic mobility (approximately 68 kDa) when compared to control cells. A68 was formed with heat shock in the presence of cycloheximide, suggesting that its production occurred by post-translational modification of existing polypeptides. The tau/A68 polypeptides were identified as phosphoproteins by incorporation of P-32 into the immunoprecipitates. The phosphorylation of tau to form A68 was reversed with recovery of the intact cells from the heat shock. Finally, immunoprecipitation of lysates from heat-shocked cells with antibodies to heat shock protein (hsp) 72/73 resulted in co-precipitation of tau with hsp 72, which indicates a stable complex formation between these two proteins. On the other hand, A68 remained unassociated with hsp during the heat shock. These results suggest that tau is reversibly phosphorylated to form A68 in neuronal PC12 cells under conditions of stress. C1 CUNY MT SINAI SCH MED,ARTHUR M FISHBERG CTR NEUROBIOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. RP WALLACE, W (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,2700 MARTIN LUTHER KING AVE SE,WASHINGTON,DC 20032, USA. NR 23 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1993 VL 19 IS 1-2 BP 149 EP 155 DI 10.1016/0169-328X(93)90160-Q PG 7 WC Neurosciences SC Neurosciences & Neurology GA LL297 UT WOS:A1993LL29700019 ER PT J AU JIAN, M STAINES, WA IADAROLA, MJ ROBERTSON, GS AF JIAN, M STAINES, WA IADAROLA, MJ ROBERTSON, GS TI DESTRUCTION OF THE NIGROSTRIATAL PATHWAY INCREASES FOS-LIKE IMMUNOREACTIVITY PREDOMINANTLY IN STRIATOPALLIDAL NEURONS SO MOLECULAR BRAIN RESEARCH LA English DT Note DE DOPAMINE; IMMEDIATE-EARLY GENE; FOS-LIKE IMMUNOREACTIVITY; NIGROSTRIATAL PATHWAY; STRIATOPALLIDAL NEURON ID C-FOS; 6-HYDROXYDOPAMINE LESIONS; STRIATAL NEURONS; GENE-EXPRESSION; RAT FOREBRAIN; PROTEINS; INDUCTION; RECEPTORS; JUN; D1 AB Unilateral destruction of the nigrostriatal pathway by injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) produces a long-lasting ( > 3 months) increase in the expression of Fos-like immunoreactivity (FLI) in medium-sized neurons (12-18 mum) of the ipsilateral striatum. In order to determine the nature of neurons which contain FLI in the 6-OHDA-denervated striatum, striatonigral and striatopallidal neurons were retrogradely labelled with the fluorescent tracer Fluoro-Gold. Nuclei displaying FLI were frequently found in striatopallidal neurons (72% overlap) but seldom in striatonigral neurons (11% overlap). These results are consistent with studies suggesting that dopamine tonically inhibits striatopallidal neurons which become more active in its absence. Moreover, the preferential localization of FLI in striatopallidal neurons supports the proposal that the AP-1 transcriptional regulating factor may contribute to neuropeptide and/or D2 dopamine receptor increases which occur in these neurons after 6-OHDA lesions. C1 UNIV OTTAWA,FAC MED,DEPT ANAT & NEUROBIOL,OTTAWA K1H 8M5,ONTARIO,CANADA. NIDR,DEPT NEUROBIOL & ANESTHESIOL,BETHESDA,MD 20492. OI Staines, Willim/0000-0002-7288-5026 NR 29 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1993 VL 19 IS 1-2 BP 156 EP 160 DI 10.1016/0169-328X(93)90161-H PG 5 WC Neurosciences SC Neurosciences & Neurology GA LL297 UT WOS:A1993LL29700020 ER PT J AU BARRY, CE BRICKMAN, TJ HACKSTADT, T AF BARRY, CE BRICKMAN, TJ HACKSTADT, T TI HC1-MEDIATED EFFECTS ON DNA-STRUCTURE - A POTENTIAL REGULATOR OF CHLAMYDIAL DEVELOPMENT SO MOLECULAR MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; EUKARYOTIC HISTONE H1; ESCHERICHIA-COLI; GENE-EXPRESSION; PSEUDOMONAS-AERUGINOSA; SALMONELLA-TYPHIMURIUM; OSMOTIC REGULATION; ENVIRONMENTAL-REGULATION; BACTERIAL VIRULENCE; CHROMATIN STRUCTURE AB Chlamydiae are obligate intracellular bacteria which undergo a unique developmental cycle, alternating between non-replicative elementary bodies (EBs) and replicative reticulate bodies (RBs). The transition from RB to EB is characterized by condensation of the chromosome into a dense nucleoid structure. The chlamydial histone homologue Hc1 is sufficient to induce formation of a similar structure in Escherichia coli. High-level Hc1 expression in E. coli is self-limiting and down-regulates transcription, translation, and replication at concentrations similar to those observed in chlamydial elementary bodies. Expression of Hc1 at sub-structural levels may have specific regulatory functions through its interaction with chromosomal DNA. In E. coli this is reflected in a dramatic shift in the pattern of gene expression. The differential expression of the outer membrane porin proteins OmpC and OmpF and analysis of IacZ fusions with promoter regions sensitive to supercoiling suggests that low-level Hc1 expression results in a net relaxation of chromosomal DNA. Topological analysis of plasmid DNA from both E. coli and Chlamydia trachomatis supports a decrease in superhelicity preceding nucleoid formation. In vitro analysis of purified Hc1-DNA interactions supports preferential binding based upon DNA conformation. These results suggest a dual role in which Hc1-mediated changes in gene expression may precede metabolic inactivity. RP BARRY, CE (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. RI Barry, III, Clifton/H-3839-2012 NR 61 TC 48 Z9 48 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 1993 VL 9 IS 2 BP 273 EP 283 DI 10.1111/j.1365-2958.1993.tb01689.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA LN832 UT WOS:A1993LN83200005 PM 8412680 ER PT J AU RUSSO, TA GUENTHER, JE WENDEROTH, S FRANK, MM AF RUSSO, TA GUENTHER, JE WENDEROTH, S FRANK, MM TI GENERATION OF ISOGENIC K54 CAPSULE-DEFICIENT ESCHERICHIA-COLI STRAINS THROUGH TNPHOA-MEDIATED GENE DISRUPTION SO MOLECULAR MICROBIOLOGY LA English DT Article ID GRAM-NEGATIVE BACTERIA; MOLECULAR-CLONING; GEL-ELECTROPHORESIS; POLYSACCHARIDE; RESISTANCE; DNA; SERUM; LIPOPOLYSACCHARIDE; DETERMINANTS; MUTAGENESIS AB Transposon mutagenesis, using IS50L=phoA(TnphoA), was performed in a K54/O4/H5 blood isolate of Escherichia coli (CP9), to generate a library of random mutants. Five hundred and twenty-six independent CP9 TnphoA mutants were isolated with active gene fusions to alkaline phosphatase. From this mutant library, eight capsule-deficient strains were detected and were found to have a single copy of TnphoA. Sixteen additional capsule deficient mutants with TnphoA inserts were subsequently obtained that did not possess active PhoA fusions. In conjunction with the initial eight capsule-deficient isolates we have defined genes on three different Xbal fragments as being involved in capsule production. Generalized transduction with the bacteriophage T4 established that these insertions were responsible for the loss of capsule and that they are linked. These capsule-deficient strains can be used to assess the pathogenic role of the K54 capsular polysaccharide. RP RUSSO, TA (reprint author), NIAID,CLIN INVEST LAB,BACTERIAL PATHOGENESIS UNIT,BETHESDA,MD 20892, USA. NR 32 TC 55 Z9 55 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 1993 VL 9 IS 2 BP 357 EP 364 DI 10.1111/j.1365-2958.1993.tb01696.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA LN832 UT WOS:A1993LN83200012 PM 8412686 ER PT J AU PLOPPER, CG WEIR, AJ MORIN, D CHANG, A PHILPOT, RM BUCKPITT, AR AF PLOPPER, CG WEIR, AJ MORIN, D CHANG, A PHILPOT, RM BUCKPITT, AR TI POSTNATAL CHANGES IN THE EXPRESSION AND DISTRIBUTION OF PULMONARY CYTOCHROME-P450 MONOOXYGENASES DURING CLARA CELL-DIFFERENTIATION IN RABBITS SO MOLECULAR PHARMACOLOGY LA English DT Article ID RHESUS-MONKEY; RAT-LIVER; LUNG; QUANTITATION; METABOLISM; MOUSE; FETAL; 3-METHYLCHOLANTHRENE; CYTODIFFERENTIATION; CYTOTOXICITY AB Previous studies have indicated that both cytodifferentiation of Clara cells and the onset of pulmonary cytochrome P450 activity are postnatal events. However, the relationship between these two events during lung development remains poorly understood. To determine how these events interrelate, we examined rabbit Clara cells during postnatal differentiation, with the following goals in mind: 1) to identify the patterns of intracellular expression of cytochrome P450 monooxygenase isozymes 2B and 4B and cytochrome P450 reductase, 2) to describe the biogenesis of the organelles with which these isozymes are associated, namely smooth and rough endoplasmic reticulum, and 3) to compare the patterns of expression with cytochrome P450 activity in the whole lung over the same period. Lungs of rabbits ranging in age from 24 days gestational age (DGA) to 25 weeks postnatally were studied. Ultrastructural morphometry showed that smooth endoplasmic reticulum averaged <5% of the Clara cell volume in late gestational (24-30 DGA) and neonatal rabbits [0-7 days postnatally (DPN)], grew to 20-30% of the cell volume in 14-21-DPN animals, and approximated adult levels (>40%) in 28-DPN rabbits. In contrast, rough endoplasmic reticulum decreased from >10% of the cell volume at 27 DGA to <5% in adults. All postnatal animals showed considerable heterogeneity in the abundance of smooth endoplasmic reticulum among individual cells. Immunohistochemistry revealed that cytochrome P450 reductase appeared in Clara cells earlier (28 DGA) than did either isozyme 2B or 4B (1 DPN). Each antigen was detected first in the apical borders of the cells, then throughout the cytoplasm in a few cells by 7 DPN, and finally in adult abundance by 28 DPN. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting showed that cytochrome P450 protein concentrations increased postnatally. Cytochrome P450 heme protein was not detected spectrophotometrically in the lungs of animals younger than 3 DPN but increased to approximately 70% of adult levels by 28 DPN. Likewise, cytochrome P450 activity (measured as ethoxy- and pentoxyresorufin O-dealkylation) was not detected in animals younger than 2 DPN but increased to approximately 75% of adult levels by 28 DPN. We conclude that, in rabbits, 1) pulmonary cytochrome P450 monooxygenase activity begins in the perinatal period and attains adult levels after 28 DPN, 2) cytochrome P450 protein expression appears and differentiates postnatally in Clara cells, 3) the appearance of smooth endoplasmic reticulum and the expression of cytochrome P450 protein do not occur uniformly in differentiating Clara cells even in the same bronchiole, and 4) the biogenesis of endoplasmic reticulum precedes the expression of cytochrome P450 protein in differentiating Clara cells. C1 UNIV CALIF DAVIS,SCH VET MED,DEPT VET PHARMACOL & TOXICOL,DAVIS,CA 95616. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP PLOPPER, CG (reprint author), UNIV CALIF DAVIS,SCH VET MED,DEPT VET ANAT & CELL BIOL,DAVIS,CA 95616, USA. FU NHLBI NIH HHS [HL43032]; NIEHS NIH HHS [P30 ES05707] NR 32 TC 35 Z9 35 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 JUL PY 1993 VL 44 IS 1 BP 51 EP 61 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LN992 UT WOS:A1993LN99200008 PM 8341279 ER PT J AU LIN, WW CHUANG, DM AF LIN, WW CHUANG, DM TI ENDOTHELIN-INDUCED AND ATP-INDUCED INHIBITION OF ADENYLYL-CYCLASE ACTIVITY IN C(6)-GLIOMA CELLS - ROLE OF G(I) AND CALCIUM SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-KINASE-C; CYCLIC-AMP ACCUMULATION; SIGNAL TRANSDUCTION SYSTEMS; ADENOSINE-MONOPHOSPHATE ACCUMULATION; THYROID-CELLS; GLIOMA-CELLS; HUMAN-PLATELETS; PHORBOL ESTER; NCB-20 CELLS; RAT AB Endothelin-1 (ET) and ATP mobilize Ca2+ in rat C6 glioma cells by stimulating phosphoinositide turnover. Both agents also inhibit adenylyl cyclase (AC) activity in C6 glioma cells. The goal of this study was to characterize the molecular mechanisms responsible for the inhibition of AC activity. The administration of either ET, ATP, A23187, or thapsigargin to cells simultaneously with isoproterenol for 5 min inhibited isoproterenol-stimulated cAMP synthesis by a maximum of 60%, 91%, 65%, and 68%, respectively. Pretreatment of cells with pertussis toxin (PTX) did not alter the inhibitory effects of A23187 or thapsigargin, whereas the inhibitory effects of ET or ATP were completely eliminated. Removal of extracellular Ca2+ and 1,2-bis(2-aminophen-oxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester treatment failed to affect the inhibition caused by ET or ATP, whereas the inhibition caused by A23187 or thapsigargin was completely eliminated in Ca2+-free medium and was attenuated by 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester treatment. The inhibition by both receptor agonists in the earlier phase (30 sec) of the AC reaction was, however, reduced by using either Ca2+-free medium or PTX pretreatment. The administration of 3-isobutyl-1-methylxanthine or Ro 20-1724 suggested that the inhibitory effects of A23187 and thapsigargin were partially due to Ca2+-dependent stimulation of PDE activity. Short term treatment with phorbol-12-myristate-13-acetate (PMA) had no effect on isoproterenol-stimulated AC activity. However, the inhibition of cAMP induced by ET or ATP, but not by A23187 or thapsigargin, was diminished by PMA, suggesting that the receptor signal via G(i) was blocked by PMA treatment. The antagonistic effect of PMA was blocked by staurosporine. All four agents still inhibited AC activity in cells that had been treated with PMA for 24 hr to deplete protein kinase C. ET produced an additional decrease in AC activity in cells that had been treated with a maximally effective concentration of A23187 or thapsigargin. The ET- or ATP-induced decrease in cAMP levels showed homologous desensitization. These results demonstrate that ET(A) receptors and ATP receptors in C6 glioma cells inhibit AC activity primarily by interaction with a PTX-sensitive G(i) and partially by elevation of [Ca2+]i. Protein kinase C activation is not responsible for agonist-induced inhibition of AC but appears to uncouple the G(i)/AC system activated by ET or ATP. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. RP LIN, WW (reprint author), NATL TAIWAN UNIV,COLL MED,DEPT PHARMACOL,TAIPEI,TAIWAN. OI Lin, Wan Wan/0000-0002-3207-734X NR 42 TC 33 Z9 33 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 JUL PY 1993 VL 44 IS 1 BP 158 EP 165 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LN992 UT WOS:A1993LN99200021 PM 8341270 ER PT J AU KADIISKA, MB HANNA, PM JORDAN, SJ MASON, RP AF KADIISKA, MB HANNA, PM JORDAN, SJ MASON, RP TI ELECTRON-SPIN-RESONANCE EVIDENCE FOR FREE-RADICAL GENERATION IN COPPER-TREATED VITAMIN-E-DEFICIENT AND SELENIUM-DEFICIENT RATS - IN-VIVO SPIN-TRAPPING INVESTIGATION SO MOLECULAR PHARMACOLOGY LA English DT Article ID LIPID-PEROXIDATION; GLUTATHIONE-PEROXIDASE; BIOCHEMICAL-MECHANISMS; OXIDATIVE DAMAGE; MEMBRANES; TOXICITY; SYSTEMS; METALS; LIVER; SELENOENZYME AB The ESR spin-trapping technique has been used to investigate free radical generation in copper-challenged rats deficient in vitamin E and/or selenium. Radical adduct excreted in the bile was detected only from copper-challenged rats deficient in both vitamin E and selenium. The phenyl-N-t-butylnitrone radical adduct has hyperfine coupling constants of a(N) = 15.36 G and a(beta)H = 2.50 G and arises from the trapping of a radical formed from an endogenous molecular species. The induction of this radical species in vivo may be important in the increased toxicity of copper in rats deficient in both vitamin E and selenium. These findings support the proposal that dietary selenium and vitamin E can protect against lipid peroxidation and copper toxicity. The results obtained suggest that the presence of only one of these nutrients in the diet is enough to prevent the formation of this radical adduct at ESR-detectable levels, and they provide the most direct ESR evidence yet obtained for the involvement of in vivo lipid peroxidation in the toxicity of copper. C1 BULGARIAN ACAD SCI,INST PHYSIOL,BU-1113 SOFIA,BULGARIA. RP KADIISKA, MB (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 51 TC 31 Z9 35 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1993 VL 44 IS 1 BP 222 EP 227 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LN992 UT WOS:A1993LN99200030 PM 8393522 ER PT J AU RAABE, F JANZ, S WOLFF, G MERTEN, H LANDROCK, A BIRKENFELD, T HERZSCHUH, R AF RAABE, F JANZ, S WOLFF, G MERTEN, H LANDROCK, A BIRKENFELD, T HERZSCHUH, R TI GENOTOXICITY ASSESSMENT OF WASTE PRODUCTS OF ALUMINUM PLASMA-ETCHING WITH THE SOS CHROMOTEST SO MUTATION RESEARCH LA English DT Article DE SOS CHROMOTEST; ALUMINUM PLASMA ETCHING; COMPLEX MIXTURE ID COLORIMETRIC BACTERIAL ASSAY; ESCHERICHIA-COLI; SALMONELLA MUTAGENICITY; CHEMICAL-STRUCTURE; CARCINOGENICITY; SAFETY; 4-NITROQUINOLINE-1-OXIDE; MIXTURES; POTENCY; TESTS AB We evaluated 36 characteristic waste products from the plasma etching of aluminum for genotoxicity with the SOS chromotest. The majority of the samples showed genotoxic activity in tester strain Escherichia coli PQ37 without metabolic activation using S9 mix. In the presence of S9, a deactivation of the samples was regularly observed. Comparable studies with the Salmonella/microsome (Ames) test using tester strains Salmonella typhimurium TA98 and TA100 indicated actual mutagenicity of waste products. Gas chromatograms of the organic constituents of all waste products were performed in parallel with the genotoxicity assays. In contrast to the similarity of the peak patterns of all chromatograms, the biological effects of individual waste samples showed large differences. Information on chemical composition and the SOS chromotest results of a representative sample recovered over a period of 2 years is given. For this sample, the influences of sample preparation and cytotoxic matrix effects on the test parameters are also shown. C1 UNIV LEIPZIG,FAC CHEM,DEPT ANAL,W-7010 LEIPZIG,GERMANY. INST FRESENIUS,DRESDEN,GERMANY. NIH,GENET LAB,BETHESDA,MD 20892. RP RAABE, F (reprint author), UNIV LEIPZIG,FAC MED,INST CLIN IMMUNOL,LINNESTR 3,W-7010 LEIPZIG,GERMANY. NR 28 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1993 VL 300 IS 2 BP 99 EP 109 DI 10.1016/0165-1218(93)90127-Y PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LJ660 UT WOS:A1993LJ66000005 PM 7685499 ER PT J AU KLIGERMAN, AD CHAPIN, RE EREXSON, GL GERMOLEC, DR KWANYUEN, P YANG, RSH AF KLIGERMAN, AD CHAPIN, RE EREXSON, GL GERMOLEC, DR KWANYUEN, P YANG, RSH TI ANALYSES OF CYTOGENETIC DAMAGE IN RODENTS FOLLOWING EXPOSURE TO SIMULATED GROUNDWATER CONTAMINATED WITH PESTICIDES AND A FERTILIZER SO MUTATION RESEARCH LA English DT Article DE SISTER-CHROMATID EXCHANGE; CHROMOSOME ABERRATIONS; PESTICIDES; HERBICIDES; RODENTS; GROUNDWATER ID SISTER-CHROMATID EXCHANGES; CULTURED HUMAN-LYMPHOCYTES; ETHYLENE DIBROMIDE; 1,2-DIBROMO-3-CHLOROPROPANE DBCP; CHROMOSOMAL-ABERRATIONS; CARBAMATE PESTICIDE; DOMINANT LETHAL; INDUCTION; CELLS; GENOTOXICITY AB Male Fischer 344 rats and female B6C3F1 mice were each exposed through their drinking water to a mixture of pesticides and ammonium nitrate that simulated contaminated groundwater in California (California Chemical Mixture [CCM]). Exposures were for 71 or 91 days, respectively. In addition, B6C3F1 female mice were exposed for 91 days to another pesticide and ammonium nitrate mixture (Iowa Chemical Mixture [ICM]) through their drinking water. The spleens were removed from the animals, and the splenocytes were cultured for analyses of sister-chromatid exchange (SCE), chromosome aberrations (CA), and micronuclei (MN) in cytochalasin B-induced binucleate cells. A concentration-related increase in SCEs was found in the splenocytes of the rat at the 1 x , 10 x and 100 x levels of the CCM and at the 100 x concentration of the CCM in the mouse. There were no other consistent cytogenetic effects observed with the CCM, and no statistically significant cytogenetic damage was observed in mice exposed to the ICM. Evidence from the literature is discussed in order to infer which chemical or chemicals in the CCM might be responsible for the observed SCE response. C1 NIEHS, DEV & REPROD TOXICOL GRP, RES TRIANGLE PK, NC 27709 USA. ENVIRONM HLTH RES & TESTING INC, RES TRIANGLE PK, NC USA. NIEHS, IMMUNOTOXICOL GRP, RES TRIANGLE PK, NC 27709 USA. COLORADO STATE UNIV, DEPT ENVIRONM HLTH, FT COLLINS, CO 80523 USA. RP KLIGERMAN, AD (reprint author), US EPA, DIV GENET TOXICOL, HLTH EFFECTS RES LAB, MAIL DROP 68, RES TRIANGLE PK, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 56 TC 24 Z9 24 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES JI Mutat. Res. PD JUL PY 1993 VL 300 IS 2 BP 125 EP 134 DI 10.1016/0165-1218(93)90130-6 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LJ660 UT WOS:A1993LJ66000008 PM 7685493 ER PT J AU WESTON, A AF WESTON, A TI PHYSICAL METHODS FOR THE DETECTION OF CARCINOGEN-DNA ADDUCTS IN HUMANS SO MUTATION RESEARCH LA English DT Article DE MOLECULAR DOSIMETRY; FLUORESCENCE SPECTROSCOPY; GAS CHROMATOGRAPHY MASS SPECTROMETRY; ELECTROCHEMICAL CONDUCTANCE; ATOMIC ABSORBENCY SPECTROSCOPY ID BENZOPYRENE DIOL EPOXIDE; CHROMATOGRAPHY MASS-SPECTROMETRY; FAST-ATOM-BOMBARDMENT; HEMOGLOBIN ADDUCTS; ELECTROCHEMICAL DETECTION; HUMAN-PLACENTA; FLUORESCENCE; DAMAGE; EXPOSURE; TOBACCO AB This report has attempted to summarize the principles, advantages, limitations and the source of data derived in the use of physical detection techniques for DNA-adduct measurement in human biomonitoring. Each method, although inherently chemically-specific, has advantages and limitations depending on the adduct type under study. These methods have a niche that is at least consistent with corroborative technology, and are being applied to dosimetry problems in the field. C1 NCI,HUMAN CARCINOGENESIS LAB,MOLEC EPIDEMIOL SECT,BETHESDA,MD 20892. NR 70 TC 40 Z9 41 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1993 VL 288 IS 1 BP 19 EP 29 DI 10.1016/0027-5107(93)90204-S PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LL295 UT WOS:A1993LL29500003 PM 7686262 ER PT J AU POIRIER, MC AF POIRIER, MC TI ANTISERA SPECIFIC FOR CARCINOGEN-DNA ADDUCTS AND CARCINOGEN-MODIFIED DNA - APPLICATIONS FOR DETECTION OF XENOBIOTICS IN BIOLOGICAL SAMPLES SO MUTATION RESEARCH LA English DT Article DE DNA DAMAGE; RADIOIMMUNOASSAY; ENZYME-LINKED IMMUNOSORBENT ASSAY; IMMUNOAFFINITY CHROMATOGRAPHY ID DIOL-EPOXIDE-DNA; ASSAYS SATURATION ANALYSES; COKE-OVEN WORKERS; MONOCLONAL-ANTIBODIES; POLYCLONAL ANTIBODIES; HUMAN-POPULATION; HUMAN-PLACENTA; NUCLEIC-ACIDS; BLOOD-CELLS; BENZOPYRENE AB The development of immunoassays and immunoaffinity chromatography methods for determination of carcinogen-DNA adducts and carcinogen-modified DNA samples rests upon eliciting and characterizing polyclonal and monoclonal antisera against these haptens. The use of such antisera has widespread application in investigating chronic carcinogen administration in animal models and in monitoring human tissues for evidence of carcinogen exposure. Radioimmunoassays and enzyme-linked immunosorbent assays developed with carcinogen-DNA adduct antisera are exceedingly sensitive, measuring 1 adduct in 108 nucleotides. Not only can DNA damage be quantified directly by immunoassay, but the antisera have also been used to isolate DNA adducts of a particular chemical class by immunoaffinity chromatography before application of more chemically-specific end-points. Both of these methodological approaches have made seminal contributions to the newly-emerging field of molecular epidemiology. This chapter will focus on methods for preparing immunogens, the establishment of immunoassays, characterization of antisera and specific problems encountered with biological samples in addition, the use of immunoaffinity chromatography for preparative concentration of DNA adducts of a particular class will be included. RP POIRIER, MC (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B25,BETHESDA,MD 20892, USA. NR 62 TC 46 Z9 47 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1993 VL 288 IS 1 BP 31 EP 38 DI 10.1016/0027-5107(93)90205-T PG 8 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LL295 UT WOS:A1993LL29500004 PM 7686263 ER PT J AU PIENKOWSKA, M GLICKMAN, BW FERREIRA, A ANDERSON, M ZIELENSKA, M AF PIENKOWSKA, M GLICKMAN, BW FERREIRA, A ANDERSON, M ZIELENSKA, M TI LARGE-SCALE MUTATIONAL ANALYSIS OF EMS-INDUCED MUTATION IN THE LACI GENE OF ESCHERICHIA-COLI SO MUTATION RESEARCH LA English DT Article DE MUTATIONAL SPECIFICITY; EMS; LACI; EXCISION REPAIR; COLONY HYBRIDIZATION; DNA SEQUENCING ID AMINO-ACID REPLACEMENTS; ALKYLATING-AGENTS; ETHYL METHANESULFONATE; MUTAGENIC SPECIFICITY; REGULATORY PROTEIN; DNA-BINDING; REPAIR; REPRESSOR; MECHANISMS; SEQUENCE AB Mutational spectra produced by mutagens in various repair backgrounds can provide important information about the roles of different repair systems in the mutagenic process. Until recently, such studies have been restricted to the characterisation of comparatively small numbers of mutants or reversion analysis at relatively few sites. The colony hybridisation method used in this study in conjunction with DNA sequencing allows the characterisation of large numbers of mutants and therefore allows analysis of resultant mutational distributions to be made with confidence. We have determined the DNA alterations recovered after treatment with EMS in the N-terminal region of the lacI gene of E. coli. A total of 1138 and 1102 independent lacI(-d) mutants were characterised in Uvr+ and UvrB-, respectively. Consistent with the known ethylating ability of this compound, the predominant mutation was G: C --> A: T transitions, which accounted for 97% and 93% in Uvr+ and UvrB- strains, respectively. An analysis of the DNA context of mutation induction indicates differential reparability by the Uvr repair pathway. Excision repair appears to more efficiently counter EMS-induced G: C --> A: T transitions at sites flanked by A: T base pairs. However, the influence of excision repair on the ultimate distribution of mutation can not be easily defined with respect to neighbouring sequence, C1 UNIV VICTORIA,DEPT BIOL,VICTORIA V8W 2Y2,BC,CANADA. UNIV VICTORIA,CTR ENVIRONM HLTH,VICTORIA V8W 2Y2,BC,CANADA. NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 35 TC 11 Z9 11 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUL PY 1993 VL 288 IS 1 BP 123 EP 131 DI 10.1016/0027-5107(93)90214-Z PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LL295 UT WOS:A1993LL29500013 PM 7686256 ER PT J AU CLAVERIE, JM AF CLAVERIE, JM TI DATABASE OF ANCIENT SEQUENCES SO NATURE LA English DT Letter RP CLAVERIE, JM (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 5 TC 17 Z9 17 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD JUL 1 PY 1993 VL 364 IS 6432 BP 19 EP 20 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK818 UT WOS:A1993LK81800036 PM 8316293 ER PT J AU GODFREY, P RAHAL, JO BEAMER, WG COPELAND, NG JENKINS, NA MAYO, KE AF GODFREY, P RAHAL, JO BEAMER, WG COPELAND, NG JENKINS, NA MAYO, KE TI GHRH RECEPTOR OF LITTLE MICE CONTAINS A MISSENSE MUTATION IN THE EXTRACELLULAR DOMAIN THAT DISRUPTS RECEPTOR FUNCTION SO NATURE GENETICS LA English DT Article ID HORMONE-RELEASING HORMONE; MESSENGER-RIBONUCLEIC-ACID; PANCREATIC-ISLET TUMOR; MOUSE GENOME; RAT PLACENTA; GROWTH; GENE; EXPRESSION; SEQUENCES; DWARF AB The growth hormone-releasing hormone receptor (GHRHR) is a member of the family of G protein-coupled receptors that is expressed on pituitary somatotrope cells and mediates the actions of GHRH in stimulating growth hormone (GH) synthesis and secretion. We report that the Ghrhr gene is located in the middle of mouse chromosome 6 in the same region as the little mutation. Mice homozygous for this mutation have reduced GH secretion and a dwarf phenotype. A missense mutation was identified in the extracellular domain of the little GHRHR that disrupts receptor function, suggesting that the growth deficit in these mice results from a defect in the GHRHR. Similar alterations in GHRHR might explain some isolated GH deficiencies in humans. C1 NORTHWESTERN UNIV, DEPT BIOCHEM, EVANSTON, IL 60208 USA. NORTHWESTERN UNIV, DEPT MOLEC BIOL, EVANSTON, IL 60208 USA. NORTHWESTERN UNIV, DEPT CELL BIOL, EVANSTON, IL 60208 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. JACKSON LAB, BAR HARBOR, ME 04609 USA. FU NCI NIH HHS [CA-54889, N01-CO-74101] NR 56 TC 305 Z9 308 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JUL PY 1993 VL 4 IS 3 BP 227 EP 232 DI 10.1038/ng0793-227 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA LJ842 UT WOS:A1993LJ84200008 PM 8395283 ER PT J AU LIN, WW CHUANG, DM AF LIN, WW CHUANG, DM TI AGONIST-INDUCED DESENSITIZATION OF ATP RECEPTOR-MEDIATED PHOSPHOINOSITIDE TURNOVER IN C6 GLIOMA-CELLS - COMPARISON WITH THE NEGATIVE-FEEDBACK REGULATION BY PROTEIN-KINASE-C SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID HOMOLOGOUS DESENSITIZATION; ENDOTHELIAL-CELLS; TUMOR PROMOTERS; MECHANISMS; CALCIUM; VASOCONSTRICTION; P2-PURINOCEPTOR; TRISPHOSPHATE; PURINOCEPTOR; TELEOCIDIN AB In C6 glioma cells, ATP increased H-3-inositol phosphate (IP) accumulation in a dose-dependent manner. Preincubation of cells with ATP (100 muM or 1 mM) resulted in a time-dependent loss of the ability of ATP to stimulate phosphoinositide (PI) hydrolysis. The agonist-induced desensitization of ATP-stimulated PI hydrolysis developed rapidly, and appeared to be independent on the activation of protein kinase C (PKC). Thus, PKC inhibitors (staurosporine, H-7 and polymyxin B), depletion of PKC and diacylglycerol (DG) kinase inhibitors (R59002, R59949) had no effect on the homologous desensitization. ATP-induced PI breakdown was inhibited by a 10 min pretreatment with the PKC activator, phorbol 12-myristate 13-acetate (PMA) or octylindolactam V, with a comparable IC50 of 5 nM, but was unaffected by the biologically inactive 4-alpha-phorbol 12,13-didecanoate (4alpha-PDD). The inhibition caused by PMA and octylindolactam V was completely prevented by staurosporine (1 muM) and partially prevented by H-7 (300 muM), H-8 (300 muM) and polymyxin B (300 mug/ml). In addition, PKC activator-induced inhibition was unchanged after ATP pretreatment, but disappeared after PKC depletion. The IP formation elicited by NaF was inhibited by PMA and octylindolactam V with a comparable IC50 value of 7.5 nM while was unchanged after ATP pretreatment. These results indicate that ATP receptors are present in the C6 glioma cells, and that these receptors are coupled to PI turnover and undergo homologous desensitization. The agonist-induced desensitization, unlike the negative-feedback regulation caused by PMA and octylindolactam V, does not seem to involve PKC activation. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. RP LIN, WW (reprint author), NATL TAIWAN UNIV,COLL MED,DEPT PHARMACOL,TAIPEI,TAIWAN. OI Lin, Wan Wan/0000-0002-3207-734X NR 25 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JUL PY 1993 VL 23 IS 1 BP 53 EP 60 DI 10.1016/0197-0186(93)90143-S PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LK654 UT WOS:A1993LK65400005 PM 8396484 ER PT J AU SHIMODA, K SHEN, GH PFEIFFER, RF MCCOMB, RD YANG, HYT AF SHIMODA, K SHEN, GH PFEIFFER, RF MCCOMB, RD YANG, HYT TI ANTISERUM AGAINST NEUROPEPTIDE-Y ENHANCES THE NICOTINE-MEDIATED RELEASE OF CATECHOLAMINES FROM CULTURED RAT ADRENAL CHROMAFFIN CELLS SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID IMMUNOREACTIVE MATERIAL; MESSENGER-RNA; BRAIN PEPTIDE; MEDULLA; GLAND; NPY; DENERVATION; EXPRESSION; ACTIVATION; INVITRO AB A primary culture of chromaffin cells was prepared from adult rats and the stability of cell contents, NPY and catecholamines (CAs), during the culture was studied. The responsiveness of cultured chromaffin cells to NGF or secretagogues and the possible role of NPY on the CA secretion from cultured chromaffin cells were investigated. After plating of isolated cells, there was marked decrease in the cell content of CAs but a significant increase in the cell content of NPY. Though both NPY and CAs in the cultured cells were positively regulated by NGF, the results of this study seemed to suggest a differential regulation for NPY and CAs in the chromaffin cell. The cultured chromaffin cells secreted NPY and CAs in response to stimulation by nicotine. The nicotine stimulated secretion of CA was enhanced by the presence of IgG fraction, prepared from NPY antiserum, in the secretion medium. The results suggested that NPY was co-released with CAs from chromaffin cells and then acted as a modulator on CA secretion. C1 GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. UNIV NEBRASKA,MED CTR,DEPT NEUROL,OMAHA,NE 68105. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68105. ST ELIZABETHS HOSP BOSTON,CTR NEUROSCI,NIMH,BIOCHEM GENET LAB,BRIGHTON,MA 02135. NR 27 TC 12 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JUL PY 1993 VL 23 IS 1 BP 71 EP 77 DI 10.1016/0197-0186(93)90145-U PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LK654 UT WOS:A1993LK65400007 PM 8369734 ER PT J AU WHITNALL, MH KISS, A AGUILERA, G AF WHITNALL, MH KISS, A AGUILERA, G TI CONTRASTING EFFECTS OF CENTRAL ALPHA-1-ADRENOCEPTOR ACTIVATION ON STRESS-RESPONSIVE AND STRESS-NONRESPONSIVE SUBPOPULATIONS OF CORTICOTROPIN-RELEASING HORMONE NEUROSECRETORY-CELLS IN THE RAT SO NEUROENDOCRINOLOGY LA English DT Article DE VASOPRESSIN; CATECHOLAMINES; ALPHA-1-ADRENERGIC RECEPTOR; MEDIAN EMINENCE; CORTICOSTERONE; CORTICOTROPIN-RELEASING HORMONE; ACTH; METHOXAMINE; NEUROSECRETORY VESICLES; ELECTRON-MICROSCOPIC IMMUNOCYTOCHEMISTRY ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; PITUITARY-ADRENOCORTICAL RESPONSES; ENHANCES VASOPRESSIN; MEDIAN-EMINENCE; IMMUNOREACTIVE INNERVATION; SYNTHESIZING NEURONS; TYROSINE-HYDROXYLASE; ARGININE VASOPRESSIN; FACTOR SECRETION; TISSUE ANTIGENS AB Stimulation of the rat hypothalamopituitary-adrenal axis during stress involves activation of central alpha1-adrenergic receptors. The subpopulation of corticotropin-releasing hormone (CRH) neurosecretory cells that contains vasopressin (VP) is selectively activated by several types of stress (immobilization, hypoglycemia, and intracerebroventricular, i.c.v., colchicine), and is located in a catecholamine-rich area of the hypothalamic paraventricular nucleus. Therefore, we tested the hypothesis that the CRH+/VP+ subpopulation is selectively activated by central alpha1-adrenergic receptors. The al-agonist methoxamine or vehicle alone was injected i.c.v. after habituation of rats to daily injections of vehicle through a chronic i.c.v. cannula. Activation of the CRH+/VP+ and CRH+/VP- subpopulations was measured by quantifying depletion of neurosecretory vesicles from immunocytochemically identified axons in the external zone of the median eminence. The habituated, vehicle-injected sham control group had normal levels of plasma ACTH and corticosterone, but possessed a significantly higher proportion of VP-containing CRH axons than naive animals. This change is similar to what was observed previously in rats subjected to repeated daily stress. I.c.v. methoxamine caused elevations of plasma ACTH and corticosterone and significant depletions of vesicles from the CRH+/VP+ axons at 1 and 2 h after injection, compared to the sham control group. The CRH+/VP- axons, however, displayed significant accumulations of neurosecretory vesicles at the same times after 300 mug methoxamine, compared to the sham control group. After 100 mug methoxamine, there was no change in the CRH+/VP- axons, compared to the sham control group. We interpret the accumulation of vesicles in the VP-deficient CRH neurosecretory axons after 300 mug i.c.v. methoxamine to reflect inhibition of this subpopulation after central alpha1-adrenergic receptor activation. The results demonstrate for the first time that central catecholamines induce release of both CRH and VP in the portal capillary plexus. These findings support the hypothesis that stress induces release of catecholamines from axons projecting to the paraventricular nucleus, thus activating alpha1-adrenergic receptors that selectively stimulate the VP-containing subpopulation of CRH neurosecretory cells. C1 NIH,INST CHILD HLTH & HUM DEV,ENDOCRINE PHYSIOL SECT,BETHESDA,MD 20892. RP WHITNALL, MH (reprint author), USA,RADIOBIOL RES INST,DEPT PHYSIOL,BETHESDA,MD 20889, USA. NR 53 TC 34 Z9 34 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUL PY 1993 VL 58 IS 1 BP 42 EP 48 DI 10.1159/000126510 PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA MA162 UT WOS:A1993MA16200006 PM 8264854 ER PT J AU PATCHEV, VK MASTORAKOS, G BRADY, LS REDWINE, J WILDER, RL CHROUSOS, GP AF PATCHEV, VK MASTORAKOS, G BRADY, LS REDWINE, J WILDER, RL CHROUSOS, GP TI INCREASED ARGININE-VASOPRESSIN SECRETION MAY PARTICIPATE IN THE ENHANCED SUSCEPTIBILITY OF LEWIS RATS TO INFLAMMATORY DISEASE SO NEUROENDOCRINOLOGY LA English DT Article DE CORTICOTROPIN-RELEASING FACTOR; ARGININE VASOPRESSIN; INFLAMMATION; GENE EXPRESSION; IMMUNONEUTRALIZATION ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; NERVOUS-SYSTEM; ADRENOCORTICOTROPIN; ARTHRITIS; OXYTOCIN; RECEPTOR; INVIVO AB Lewis (LEW/N) and Fischer (F344/N) rats are histocompatible inbred strains characterized respectively by susceptibility and resistance to inflammatory disease. LEW/N rats have deficient corticotropin-releasing hormone (CRH), ACTH and corticosterone responses to inflammation, and increased circulating and hypothalamic concentrations of arginine vasopressin (AVP). CRH is produced locally at inflammatory sites, where it acts as a proinflammatory agent, while AVP has been reported to exert immunopotentiating effects in vivo and in vitro. In order to further investigate the mechanism of increased AVP secretion in LEW/N rats, we measured AVP and CRH mRNA in several hypothalamic nuclei in LEW/N and F344/N rats, using in situ hybridization histochemistry. LEW/N rats had increased AVP mRNA concentrations in the supraoptic (SON) and paraventricular (PVN), but not in the suprachiasmatic (SCN) nuclei. CRH mRNA, on the other hand, was decreased in the PVN of LEW/N rats. To examine the potential role of AVP and CRH in the exaggerated inflammatory responses of LEW/N rats, we pretreated young female Lewis and Fischer rats with AVP- and/or CRH-neutralizing rabbit antisera and elicited subsequently an inflammatory response by a nuchal subcutaneous injection of carrageenin. We demonstrated that both antisera decreased significantly the leukocyte concentration in the inflammatory exudate in LEW/N rats, but found no synergistic or additive effects between them. We conclude that previously observed differences in hypothalamic AVP and CRH contents between LEW/N and F344/N rats correspond to differences in the steady state mRNA levels of the two neuropeptides and that both AVP and CRH participate in the excessive inflammatory response of Lewis rats as locally active proinflammatory agents. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. NR 24 TC 33 Z9 33 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUL PY 1993 VL 58 IS 1 BP 106 EP 110 DI 10.1159/000126519 PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA MA162 UT WOS:A1993MA16200015 PM 8264843 ER PT J AU YAMAMOTO, M OOYAMA, M OZAWA, Y OKADA, M TADA, S YAMAGUCHI, T ENDO, H AF YAMAMOTO, M OOYAMA, M OZAWA, Y OKADA, M TADA, S YAMAGUCHI, T ENDO, H TI EFFECTS OF INDELOXAZINE HYDROCHLORIDE, A CEREBRAL ACTIVATOR, ON PASSIVE-AVOIDANCE LEARNING IMPAIRED BY DISRUPTION OF CHOLINERGIC TRANSMISSION IN RATS SO NEUROPHARMACOLOGY LA English DT Article DE INDELOXAZINE HYDROCHLORIDE; ACETYLCHOLINE DISRUPTION; PASSIVE AVOIDANCE; ACETYLCHOLINE; RAT ID COGNITIVE DISTURBANCE; MEMORY; YM-14673; BEHAVIOR; ANALOG; ANOXIA; MICE AB The effect of indeloxazine [(+/-)-2-[(inden-7-yloxy)methyl]morpholine hydrochloride, YM-08054], a cerebral activator, on passive avoidance learning by disruption of cholinergic transmission was investigated in rats. Indeloxazine prolonged the latency for stepping out of an illuminated compartment into a dark compartment, in both mature and aged rats. Disruption of cholinergic transmission was induced by injection of scopolamine, ethylcholine, treatment with aridinium ion (AF64A) and by lesioning the nucleus basalis magnocellularis. The shortened latency in these models was prolonged when indeloxazine was administered before training in doses which did not affect spontaneous movement or the response to pain in mature rats and administration of indeloxazine, immediately after training, also had an ameliorating effect on passive avoidance in the lesioned rats. In biochemical studies, indeloxazine increased the extracellular concentration of acetylcholine in the frontal cortex of mature rats. These results suggest that indeloxazine possesses facilitatory effects on cerebral function, in part due to activation of the central cholinergic system. C1 YAMANOUCHI PHARMACEUT CO LTD,CENT RES LABS,IBARAKI 305,JAPAN. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP YAMAMOTO, M (reprint author), INST DEV & PHARMACOL,AZUSAWA 1-1-8,ITABASHI KU,TOKYO 174,JAPAN. NR 24 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1993 VL 32 IS 7 BP 695 EP 701 DI 10.1016/0028-3908(93)90083-F PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA LK305 UT WOS:A1993LK30500010 PM 8395664 ER PT J AU LAW, WA MARTIN, A SALAZAR, AM MAPOU, RL AF LAW, WA MARTIN, A SALAZAR, AM MAPOU, RL TI SYMPTOMS OF DEPRESSION IN HIV-INFECTED INDIVIDUALS - ETIOLOGIC CONSIDERATIONS SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE REACTION TIME; NEUROPSYCHOLOGICAL EVALUATION; INTELLECTUAL ABILITY ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS DEMENTIA COMPLEX; MAJOR DEPRESSION; INVENTORY; MEN; MANIFESTATIONS; COMPLICATIONS; PREVALENCE; DISORDERS; DISEASE AB The relationship between self-reported symptoms of depression and reaction time were evaluated in 51 HIV seropositive (HIV+) individuals, 15 HIV seronegative (HIV-) individuals with a diagnosis of adjustment disorder, and 18 HIV- normal control subjects. The HIV+ and adjustment disorder groups had equivalent scores on the Beck Depression Inventory (BDI) that were significantly higher than the normal control group. Individual items and the group of items with somatic content were endorsed equally by the HIV+ and the psychiatric HIV- groups. A mild but significant correlation between BDI scores and reaction time was obtained only for the HIV+ group. Exploratory factor analysis of the BDI produced specific symptom clusters that correlated with reaction time in the HIV+ but not in the HIV- psychiatric subjects. These findings suggest certain self-reported symptoms of depression may reflect, at least in part, central nervous system involvement in HIV+ individuals. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PSYCHIAT,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20814. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP LAW, WA (reprint author), WALTER REED ARMY MED CTR,HENRY M JACKSON FDN ADV MIL MED,6825 16TH ST NW,WASHINGTON,DC 20307, USA. RI martin, alex/B-6176-2009 NR 44 TC 16 Z9 16 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD JUL PY 1993 VL 6 IS 3 BP 181 EP 186 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA LK298 UT WOS:A1993LK29800008 ER PT J AU LEBIHAN, D TURNER, R DOUEK, P AF LEBIHAN, D TURNER, R DOUEK, P TI IS WATER DIFFUSION RESTRICTED IN HUMAN BRAIN WHITE-MATTER - AN ECHO-PLANAR NMR IMAGING STUDY SO NEUROREPORT LA English DT Article DE MYELIN; MEMBRANE PERMEABILITY; WATER TRANSPORT; MAGNETIC RESONANCE IMAGING; ECHO-PLANAR IMAGING ID NUCLEAR MAGNETIC-RESONANCE; PULSED FIELD GRADIENT; INVIVO; MUSCLE; SYSTEM AB WATER diffusion is extremely anisotropic in brain white matter, depending on myelin fiber orientation. A suggested, but unproven cause of anisotropy is that, in the direction transverse to the myelin fibers, axonal water diffusion is prevented by the presence of the myelin sheath. We found, however, using an ultra-fast nuclear magnetic resonance imaging technique, that the dependence of the diffusion coefficient on the diffusion time does not support the model of water restriction by impenetrable barriers. These results, which were obtained non-invasively in vivo in the human brain, imply that water diffuses with a measurable rate across myelin fibers. C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. RP LEBIHAN, D (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892, USA. RI Turner, Robert/C-1820-2008 NR 25 TC 98 Z9 98 U1 0 U2 7 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL PY 1993 VL 4 IS 7 BP 887 EP 890 PG 4 WC Neurosciences SC Neurosciences & Neurology GA LM114 UT WOS:A1993LM11400012 PM 8369479 ER PT J AU GLOWA, JR AF GLOWA, JR TI BEHAVIORAL AND NEUROENDOCRINE EFFECTS OF DIETHYL-ETHER EXPOSURE IN THE MOUSE SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE ETHER; OPERANT BEHAVIOR; SOLVENTS; NEUROENDOCRINE; ACTH; CORTICOSTERONE; RO-15-4513; MICE ID VOLATILE ORGANIC-SOLVENTS; INDIVIDUAL VULNERABILITY; CHRONIC EXERCISE; STRESS; CORTICOTROPIN; TOXICOLOGY; CORTICOSTERONE; SECRETION; RESPONSES; ETHANOL AB Diethyl ether has diverse behavioral effects and is known for its ability to stimulate stress hormones, yet little is known of the concentrations in which these effects occur. To more fully characterize these effects, adult male NIH mice were exposed to a range of concentrations of ether (1000-30000 ppm) in an inhalation chamber and both behavioral and neuroendocrine responses were assessed. When responding was maintained under FI-60 s schedules of milk presentation, 30-min exposures to 1000 ppm ether resulted in minimal behavioral effects, 3000-10000 ppm increased rates of responding over two-fold and higher concentrations decreased responding almost completely. Five-min exposures to the same range of concentrations resulted in concentration-related effects which were smaller than those produced by 30-min exposures. Exposure to a similar range of concentrations in naive mice increased adrenocorticotrophic hormone (ACTH) and corticosterone levels in a time- and concentration-dependent manner. Five-min exposures to 10000 ppm ether increased levels of ACTH from a baseline of 25.95 pg/ml to 310.5 pg/ml but did not affect corticosterone. Thirty-min exposures to the full range of concentrations of ether, increased corticosterone from control levels of 70 ng/ml to 418 ng/ml at 30000 ppm, and increased ACTH from control levels of 19.13 pg/ml to 80.5 pg/ml at 30000 ppm, in a concentration-dependent manner. The increase in ACTH for 30-min exposures was not as large as that observed for 5-min exposures at 10000 ppm, nor was it as large as that seen for corticosterone. The imidazobenzodiazepine, Ro 15-4513 decreased FI responding at doses greater than 3 mg/kg and attenuated the rate-increasing effects of diethyl ether at 1 mg/kg. Diethyl ether exhibits robust behavioral and neuroendocrine activating effects. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP GLOWA, JR (reprint author), NIDDK,LMC,BEHAV PHARMACOL & TOXICOL UNIT,BLDG 14D,ROOM 311,BETHESDA,MD 20892, USA. NR 39 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 1993 VL 15 IS 4 BP 215 EP 221 DI 10.1016/0892-0362(93)90001-5 PG 7 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA LR738 UT WOS:A1993LR73800001 PM 8413074 ER PT J AU CASTRONOVO, FP MCKUSICK, KA DOPPELT, SH BARTON, NW AF CASTRONOVO, FP MCKUSICK, KA DOPPELT, SH BARTON, NW TI RADIOPHARMACOLOGY OF INHALED XE-133 IN SKELETAL SITES CONTAINING DEPOSITS OF GAUCHER CELLS SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article ID DISEASE; VENTILATION AB Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of inhaled Xe-133 uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a gamma-camera interfaced to a computer system. All patients rebreathed Xe-133 gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered ''dose''). There was essentially no Xe-133 uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Skeletal Gaucher deposits released the Xe-133 at a greater rate relative to soft tissue. C1 MASSACHUSETTS GEN HOSP,BOSTON,MA 02114. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. RP CASTRONOVO, FP (reprint author), BRIGHAM & WOMENS HOSP,DEPT RADIOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JUL PY 1993 VL 20 IS 5 BP 707 EP 714 DI 10.1016/0969-8051(93)90042-S PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LK303 UT WOS:A1993LK30300019 PM 8358357 ER PT J AU BENSON, D LIPMAN, DJ OSTELL, J AF BENSON, D LIPMAN, DJ OSTELL, J TI GENBANK SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The GenBank sequence database has undergone an expansion in data coverage, annotation content and the development of new services for the scientific community. In addition to nucleotide sequences, data from the major protein sequence and structural databases, and from U.S. and European patents is now included in an integrated system. MEDLINE abstracts from published articles describing the sequences provide an important new source of biological annotation for sequence entries. In addition to the continued support of existing services, new CD-ROM and network-based systems have been implemented for literature retrieval and sequence similarity searching. Major releases of GenBank are now more frequent and the data are distributed in several new forms for both end users and software developers. RP BENSON, D (reprint author), NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,NIH,BLDG 38A,RM 85 803,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 6 TC 244 Z9 246 U1 0 U2 1 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 JUL 1 PY 1993 VL 21 IS 13 BP 2963 EP 2965 DI 10.1093/nar/21.13.2963 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL722 UT WOS:A1993LL72200001 PM 8332518 ER PT J AU GHOSH, D AF GHOSH, D TI STATUS OF THE TRANSCRIPTION FACTORS DATABASE (TFD) SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The Transcription Factors Database is a specialized database focusing on transcription factors and their properties. This report describes the present status of this database and developments during the past year. Within this time, the size of this database has increased by a 2799 total records, and has become accessible through a number of new mechanisms. RP NIH, NLM, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 18 TC 118 Z9 119 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 1993 VL 21 IS 13 BP 3117 EP 3118 DI 10.1093/nar/21.13.3117 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LL722 UT WOS:A1993LL72200020 PM 8332533 ER PT J AU DALY, MC XIANG, RH BUCHHAGEN, D HENSEL, CH GARCIA, DK KILLARY, AM MINNA, JD NAYLOR, SL AF DALY, MC XIANG, RH BUCHHAGEN, D HENSEL, CH GARCIA, DK KILLARY, AM MINNA, JD NAYLOR, SL TI A HOMOZYGOUS DELETION ON CHROMOSOME-3 IN A SMALL-CELL LUNG-CANCER CELL-LINE CORRELATES WITH A REGION OF TUMOR-SUPPRESSOR ACTIVITY SO ONCOGENE LA English DT Article ID SHORT ARM; DNA POLYMORPHISMS; CARCINOMA; GENE; RETINOBLASTOMA; SEQUENCE; 3P; IDENTIFICATION; HETEROZYGOSITY; PROTEIN AB Small cell lung cancer (SCLC) tumors frequently display deletions on the short arm of chromosome 3 suggesting the existence of a 'tumor suppressor' gene within that region whose functional inactivation may be involved in tumorigenesis. Recently, a hybrid, HA(3)BB9F, was identified that contains a small fragment of human chromosome 3 of approximately 2 Mb on a mouse (A9) background (Killary et. al., 1992). This hybrid was utilized to define a functional tumor suppressor gene within 3p22-p21 which could suppress the tumorigenic properties of the mouse fibrosarcoma cell line. The existence of a tumor suppressor gene in the region 3p22-p21 is supported by the present report which describes the assessment of 89 SCLC and 32 non-SCLC lung cancer tumors and cell lines for the existence of a homozygous deletion(s) at 43 loci on the short arm of chromosome 3. One of the SCLC cell lines was found to harbor a homozygous deletion involving the loss of five markers on chromosome 3p. All five of the markers map to the region 3p21.3-p21.2 and four of the five markers are located within the chromosome 3 fragment exhibiting properties of tumor suppression in the HA(3)BB9F hybrid. The other tumors analysed all retained at least one copy of each of the markers assessed. C1 UNIV TEXAS,SW MED CTR,SIMMONS CANC INST,DALLAS,TX 75235. UNIV TEXAS,MD ANDERSON HOSP & TUMOR INST,HOUSTON,TX 77030. UNIFORMED SERV UNIV HLTH SCI,DEPT MED,MED ONCOL BRANCH,NCI NAVY MED ONCOL BRANCH,BETHESDA,MD 20814. RP DALY, MC (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. FU NCI NIH HHS [CA44764] NR 40 TC 112 Z9 115 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1993 VL 8 IS 7 BP 1721 EP 1729 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LG682 UT WOS:A1993LG68200002 PM 8390035 ER PT J AU SETH, A ROBINSON, L THOMPSON, DM WATSON, DK PAPAS, TS AF SETH, A ROBINSON, L THOMPSON, DM WATSON, DK PAPAS, TS TI TRANSACTIVATION OF GATA-1 PROMOTER WITH ETS1, ETS2 AND ERGB/HU-FLI-1 PROTEINS - STABILIZATION OF THE ETS1 PROTEIN-BINDING ON GATA-1 PROMOTER SEQUENCES BY MONOCLONAL-ANTIBODY SO ONCOGENE LA English DT Article ID ERYTHROID TRANSCRIPTION FACTOR; LONG TERMINAL REPEAT; C-ETS-1 PROTOONCOGENE; GENE; EXPRESSION; INDUCTION; COOPERATE; ONCOGENE; LINEAGES; VIRUS AB Ets family proteins activate transcription via binding to the GGAA core sequence located in the promoter/ enhancer elements of many cellular and viral genes. GATA-1 is an erythroid-specific transcription factor. The promoter of the chicken GATA-1 gene contains multiple ets binding sites (EBS), two of them are present in palindromic form. The GATA-1 promoter has been shown to be activated by the E26 virus. In this study, we have analysed whether the palidromic EBS of the chicken GATA-1 promoter is a target for binding and activation by members of the cellular ets gene family products. The results herein indicate that both EBS in the palindrome are required for DNA-binding because mutations in either site reduces the activity by at least 95%. Moreover, DNA binding of ETS1 to the EBS palindrome is dramatically stabilized in the presence of a specific monoclonal antibody whose epitope maps between amino acid positions 240-260. Although each of the single sites bind, the efficiency of binding is extremely low. Furthermore, for efficient binding the two sites must be in an inverted configuration because of the fact that the oligonucleotide containing the left and right EBS in the same orientation binds 10-fold less than the oligonucleotide containing the EBS palindrome. Additionally, we show that the transcription of a reporter gene (CAT) either linked to the GATA-1 EBS palindrome or GATA-1 promoter can be activated by cotransfection with ETS1, alternatively-spliced ETS1, ETS2 or ERGB/Hu-FLI-1 expression vectors. C1 PROGRAM RESOURCES INC,DYNCORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP SETH, A (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 38 TC 90 Z9 90 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1993 VL 8 IS 7 BP 1783 EP 1790 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LG682 UT WOS:A1993LG68200009 PM 8510925 ER PT J AU SAKAMOTO, K HOWARD, T OGRYZKO, V XU, NZ CORSICO, CC JONES, DH HOWARD, B AF SAKAMOTO, K HOWARD, T OGRYZKO, V XU, NZ CORSICO, CC JONES, DH HOWARD, B TI RELATIVE MITOGENIC ACTIVITIES OF WILD-TYPE AND RETINOBLASTOMA BINDING-DEFECTIVE SV40 T-ANTIGENS IN SERUM-DEPRIVED AND SENESCENT HUMAN-DIPLOID FIBROBLASTS SO ONCOGENE LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; SUPPRESSOR GENE-PRODUCT; LARGE TUMOR-ANTIGEN; SUSCEPTIBILITY GENE; TRANSCRIPTION FACTOR; SV40-TRANSFORMED CELLS; INTERLEUKIN-2 RECEPTOR; CELLULAR PROTEINS; SODIUM-BUTYRATE; RB PROTEIN AB A novel gene transfer approach was used to investigate whether the retinoblastoma (Rb)-binding domain of simian virus 40 (SV40) T antigen is required for efficient T antigen-mediated stimulation of DNA synthesis is quiescent or senescent human embryo fibroblasts. In senescent cells, comparison between wild-type T antigen and a mutant defective in Rb binding (Glu-107-->Lys) revealed the latter to have almost-equal-to 15-fold lower activity. In contrast, comparison of wild-type and Rb- T antigens in serum-deprived quiescent cells revealed a much smaller (1.8-fold) difference. Surprisingly, an 18-fold differential could be induced by treating quiescent cells with the differentiating agent sodium butyrate. These results suggest that the role of Rb in control of the cell cycle is strongly dependent on the physiological state of the cell and the mechanism of growth arrest. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BLDG 6,ROOM 416,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 55 TC 28 Z9 29 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1993 VL 8 IS 7 BP 1887 EP 1893 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LG682 UT WOS:A1993LG68200021 PM 8390037 ER PT J AU HILBERT, DM PUMPHREY, JG TROPPMAIR, J RAPP, UR RUDIKOFF, S AF HILBERT, DM PUMPHREY, JG TROPPMAIR, J RAPP, UR RUDIKOFF, S TI SUSCEPTIBILITY AND RESISTANCE TO J3V1 RETROVIRUS-INDUCED MURINE PLASMACYTOMAGENESIS IN RECONSTITUTED SEVERE COMBINED IMMUNODEFICIENT MICE SO ONCOGENE LA English DT Article ID MOUSE PLASMACYTOMAS; BALB/C MICE; B-CELLS; V-MYC; INDUCTION; GENETICS; LOCALIZATION; EXPRESSION; MACROPHAGE; MUTATION AB To date much is known about the genetics of susceptibility and resistance to plasmacytoma induction in mice, however little is known about the cellular aspects of these phenotypes. The complexity of plasmacytomagenesis allows for susceptibility and resistance to reflect differences in B cells, T cells, accessory cells and/or stromal elements contributing to the disease process. Alternatively, these phenotypes may result from differential abilities to affect events critical to plasmacytomagenesis, such as myc deregulation. To address these possibilities, the v-myc-raf-containing retrovirus, J3V1, was used to induce plasmacytomas (PCTs) in severe combined immunodeficient (SCID) mice reconstituted with susceptible (Balb/c) and/or resistant (DBA/2) cells. The results demonstrate that Balb/c bone marrow (BM)-reconstituted SCID mice yielded PCTs of donor origin, while DBA/2 BM-reconstituted mice did not. Mice reconstituted with both DBA/2 BM and Balb/c peripheral lymphocytes, as well as those reconstituted with Balb/c peripheral lymphocytes alone, also yielded only Balb/c PCTs. These results indicate that: (1) a microenvironment supportive of plasmacytomagenesis is insufficient to allow PCT development among resistant cells; (2) DBA/ 2 BM-derived cells do not suppress plasmacytomagenesis by target cell elimination or microenvironment destruction; (3) resistance is not solely attributable to the inability of DBA/2 B cells to deregulate myc; and (4) potential PCT targets reside in a number of lymphoid tissues. Taken together, these results demonstrate that a major aspect of resistance/susceptibility to plasmacytomagenesis is dictated by the genotype of the target B cell. C1 NCI,FREDERICK CANC RES CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. RP HILBERT, DM (reprint author), NCI,GENET LAB,BETHESDA,MD 20892, USA. NR 40 TC 12 Z9 12 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1993 VL 8 IS 7 BP 1993 EP 2000 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LG682 UT WOS:A1993LG68200032 PM 7685514 ER PT J AU EVANS, CH FLUGELMAN, AA DIPAOLO, JA AF EVANS, CH FLUGELMAN, AA DIPAOLO, JA TI CYTOKINE MODULATION OF IMMUNE DEFENSES IN CERVICAL-CANCER SO ONCOLOGY LA English DT Article DE CERVICAL CANCER; CISPLATIN; GAMMA-INTERFERON; IMMUNE DEFENSES; LEUKOREGULIN; LYMPHOKINE-ACTIVATED KILLER LYMPHOCYTE; NATURAL KILLER LYMPHOCYTE; PAPILLOMAVIRUS ID NATURAL-KILLER CELLS; HUMAN PAPILLOMAVIRUS INFECTION; LEUKOREGULIN UP-REGULATION; INTRAEPITHELIAL NEOPLASIA; EPITHELIAL-CELLS; UTERINE CERVIX; INTERFERON; LYMPHOCYTES; CARCINOMA; TOXICITY AB Human papilloma viruses (HPV) are major factors in the etiology of cervical cancer. Natural killer (NK) lymphocytes, an important defense against viral diseases, are present in most HPV-associated lesions and cervical intraepithelial neoplasia. HPV positive cervical cancer cells and HPV-immortalized human cervical epithelial cells which possess properties similar to cervical dysplasia, however, are resistant to NK but are sensitive to lymphokine-activated killer (LAK) lymphocyte lysis. Sensitivity can be enhanced by treatment of cervical cells with leukoregulin, a cytokine secreted by lymphocytes. Combination treatment with leukoregulin and a chemotherapeutic drug, e.g. cisplatin, further enhances sensitivity of HPV-infected cells to LAK lymphocyte lysis. In contrast, gamma-interferon treatment of cervical cells can result in decreased sensitivity to LAK lysis illustrating the potential balance cytokines can exert in the immunologic control of cervical cancer. RP EVANS, CH (reprint author), NCI,BIOL LAB,TUMOR BIOL SECT,BLDG 37 RM 2A17,BETHESDA,MD 20892, USA. NR 49 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD JUL-AUG PY 1993 VL 50 IS 4 BP 245 EP 251 PG 7 WC Oncology SC Oncology GA LJ043 UT WOS:A1993LJ04300012 PM 8388555 ER PT J AU SHIP, JA BAUM, BJ AF SHIP, JA BAUM, BJ TI OLD-AGE IN HEALTH AND DISEASE - LESSONS FROM THE ORAL CAVITY SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID FLOW-RATE; MEN; SALIVA AB It is not clear if aging distinctions can be made at the level of an organ or organism. The purpose of this study was to determine if a general definition of systemic aging, primary aging (influence of the passage of time), versus secondary aging (influence of extrinsic factors), can be used to discriminate the functional status of an individual organ system, the oral cavity. Thirty healthy, nonmedicated subjects (that is, those who exhibit primary aging) and 42 persons being treated for medical problems and taking prescription medications (that is, those who exhibit secondary aging), aged 75 to 96 years, from the oral physiology component of the Baltimore Longitudinal Study of Aging were evaluated. A standardized examination assessed gingival, periodontal, dental, and oral mucosal tissues. There were few substantive differences in oral health and function between primary and secondary aging subjects. Thus use of broad definitions of aging in an organism did not lead to meaningful predictions of the health or function of an individual organ system. Furthermore, the similarity in the oral condition between both groups studied here suggests substantial resiliency of the oral cavity during aging. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RP SHIP, JA (reprint author), UNIV MICHIGAN,SCH DENT,DEPT ORAL MED PATHOL & SURG,1011 N UNIV,ANN ARBOR,MI 48109, USA. NR 25 TC 6 Z9 6 U1 1 U2 1 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 JUL PY 1993 VL 76 IS 1 BP 40 EP 44 DI 10.1016/0030-4220(93)90291-B PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LQ421 UT WOS:A1993LQ42100011 PM 8351119 ER PT J AU WATERS, AP HIGGINS, DG MCCUTCHAN, TF AF WATERS, AP HIGGINS, DG MCCUTCHAN, TF TI THE PHYLOGENY OF MALARIA - A USEFUL STUDY SO PARASITOLOGY TODAY LA English DT Review ID CIRCUMSPOROZOITE PROTEIN; PLASMODIUM-FALCIPARUM; REICHENOWI; EVOLUTION; GENE AB Phylogenetic analyses allow an inference of the origins and evolutionary relationships between organisms. Andy Waters, Des Higgins and Tom McCutchan here discuss the benefits of an accurate understanding of these origins and relationships for malaria parasites to the modern fields of vaccine development, pathology and epidemiology. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. EUROPEAN MOLEC BIOL LAB,W-6900 HEIDELBERG,GERMANY. RP WATERS, AP (reprint author), LEIDEN UNIV,DEPT PARASITOL,POSTBUS 9605,2300 RC LEIDEN,NETHERLANDS. RI Waters, Andy/C-9377-2009; Higgins, des/J-6314-2012 OI Waters, Andy/0000-0001-8900-2982; NR 23 TC 24 Z9 24 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD JUL PY 1993 VL 9 IS 7 BP 246 EP 250 DI 10.1016/0169-4758(93)90066-O PG 5 WC Parasitology SC Parasitology GA LJ585 UT WOS:A1993LJ58500004 PM 15463768 ER PT J AU SHAHABUDDIN, M KASLOW, DC AF SHAHABUDDIN, M KASLOW, DC TI CHITINASE - A NOVEL TARGET FOR BLOCKING PARASITE TRANSMISSION SO PARASITOLOGY TODAY LA English DT Editorial Material ID PERITROPHIC MEMBRANE; ALLOSAMIDIN; PENETRATION; GLOSSINA RP SHAHABUDDIN, M (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BETHESDA,MD 20892, USA. NR 19 TC 29 Z9 29 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD JUL PY 1993 VL 9 IS 7 BP 252 EP 255 DI 10.1016/0169-4758(93)90069-R PG 4 WC Parasitology SC Parasitology GA LJ585 UT WOS:A1993LJ58500007 PM 15463771 ER PT J AU MALIN, DH LAKE, JR PAYZA, K CORRIERE, LS BENSON, TM GARBER, TL WALLER, ML LUU, TA KELLEY, RS SMITH, DA HO, KK BURGESS, K AF MALIN, DH LAKE, JR PAYZA, K CORRIERE, LS BENSON, TM GARBER, TL WALLER, ML LUU, TA KELLEY, RS SMITH, DA HO, KK BURGESS, K TI ENHANCED ANTIOPIATE ACTIVITY AND ENZYME RESISTANCE IN PEPTIDOMIMETICS OF FMRFAMIDE CONTAINING (E)-2,3-METHANOMETHIONINE SO PEPTIDES LA English DT Article DE FMRFAMIDE; NPFF; NPFF RECEPTORS; NEUROPEPTIDE-FF; F8FAMIDE; ANTIOPIATE PEPTIDES; CYCLOPROPYLOGS; PEPTIDOMIMETICS; RAT; OPIATE DEPENDENCE; OPIATE ABSTINENCE SYNDROME ID SPINAL-CORD; NEUROPEPTIDE; MORPHINE; RAT; PHE-MET-ARG-PHE-NH2; IMMUNOREACTIVITY; INHIBITION; ABSTINENCE; PEPTIDE AB FMRFamide is a molluscan peptide that has shown antiopiate activity in a number of mammalian test systems. The current study determined the antiopiate potency of FMRFamide and two conformationally constrained peptidomimetics of FMRFamide containing stereoisomers of (E)-2,3-methanomethionine. Morphine abstinence signs were observed after varying doses (0.25-25.0 mug) of these substances were injected into the third ventricle of morphine-dependent rats. Both peptidomimetics were far more potent than FMRFamide itself. In addition, although both peptidomimetics bound with lower affinity than FMRFamide to rat spinal cord receptors for NPFF (the mammalian FMRFamide-like peptide), they were far more resistant than FMRFamide to enzymatic degradation by leucine aminopeptidase. C1 ST ELIZABETH HOSP, NIMH, WASHINGTON, DC 20032 USA. TEXAS A&M UNIV SYST, COLL STN, TX 77843 USA. RP MALIN, DH (reprint author), UNIV HOUSTON CLEAR LAKE, BOX 237, HOUSTON, TX 77058 USA. RI Burgess, Kevin/B-5372-2015 OI Burgess, Kevin/0000-0001-6597-1842 FU NIDA NIH HHS [NIDA DAO6554] NR 21 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL-AUG PY 1993 VL 14 IS 4 BP 731 EP 734 DI 10.1016/0196-9781(93)90105-P PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA LN690 UT WOS:A1993LN69000012 PM 8234017 ER PT J AU BILSKI, P MOTTEN, AG BILSKA, M CHIGNELL, CF AF BILSKI, P MOTTEN, AG BILSKA, M CHIGNELL, CF TI THE PHOTOOXIDATION OF DIETHYLHYDROXYLAMINE BY ROSE-BENGAL IN MICELLAR AND NONMICELLAR AQUEOUS-SOLUTIONS SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SINGLET MOLECULAR-OXYGEN; SUPEROXIDE-DISMUTASE; SOLUBILITY; RESONANCE; RADICALS; AMINES; EOSIN; STATE AB The photooxidation of N,N-diethylhydroxylamine (DEHA) by Rose Bengal (RB) has been investigated in micellar and nonmicellar aqueous solutions. We measured the quantum yield of oxygen consumption forming H2O2 and monitored two intermediates, the superoxide and diethylnitroxide radicals. When the pH was varied, the quantum yield of oxidation remained constant for 6 < pH < 10.5, decreased in acidic pH, and increased considerably in NaOH solution; these changes could be attributed to the protonation and dissociation processes of the > N-OH moiety of DEHA. The formation of diethylnitroxide radical was enhanced by superoxide dismutase or strong alkaline solution. Around neutral pH, the oxidation proceeded mainly via electron transfer from DEHA to the RB triplet (k(q) = 10(7) M-1 s-1) with little O-1(2) participation (k(q) < 10(5) M-1 s-1). However, when RB was incorporated into micelles in alkaline solution, the contribution of the singlet oxygen pathway increased at the expense of electron transfer, which was inhibited by the less polar micellar environment. Dark autoxidation of DEHA was accelerated by heavy metal impurities and increased very strongly in NaOH solution. RP BILSKI, P (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 30 TC 25 Z9 25 U1 1 U2 4 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1993 VL 58 IS 1 BP 11 EP 18 DI 10.1111/j.1751-1097.1993.tb04896.x PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LR037 UT WOS:A1993LR03700002 PM 8378429 ER PT J AU GLYNN, TJ AF GLYNN, TJ TI IMPROVING THE HEALTH OF UNITED-STATES CHILDREN - THE NEED FOR EARLY INTERVENTIONS IN TOBACCO USE SO PREVENTIVE MEDICINE LA English DT Article ID SMOKING; PREVENTION; CANCER RP GLYNN, TJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,6130 EXECUT BLVD,EXECUT PLAZA N,ROOM 243,ROCKVILLE,MD 20852, USA. NR 22 TC 27 Z9 27 U1 2 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1993 VL 22 IS 4 BP 513 EP 519 DI 10.1006/pmed.1993.1044 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA LU399 UT WOS:A1993LU39900008 PM 8415503 ER PT J AU GLYNN, TJ GREENWALD, P MILLS, SM MANLEY, MW AF GLYNN, TJ GREENWALD, P MILLS, SM MANLEY, MW TI YOUTH TOBACCO USE IN THE UNITED-STATES - PROBLEM, PROGRESS, GOALS, AND POTENTIAL SOLUTIONS SO PREVENTIVE MEDICINE LA English DT Article ID SMOKING PREVENTION; CHILDREN; CANCER RP GLYNN, TJ (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 243,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 26 TC 28 Z9 28 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1993 VL 22 IS 4 BP 568 EP 575 DI 10.1006/pmed.1993.1049 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA LU399 UT WOS:A1993LU39900013 PM 8415508 ER PT J AU OLDEN, K AF OLDEN, K TI ENVIRONMENTAL RISKS TO THE HEALTH OF AMERICAN CHILDREN SO PREVENTIVE MEDICINE LA English DT Article RP OLDEN, K (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 6 Z9 6 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 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1993 VL 22 IS 4 BP 576 EP 578 DI 10.1006/pmed.1993.1050 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA LU399 UT WOS:A1993LU39900014 PM 8415509 ER PT J AU TAGGART, VS FULWOOD, R AF TAGGART, VS FULWOOD, R TI YOUTH HEALTH REPORT CARD - ASTHMA SO PREVENTIVE MEDICINE LA English DT Article ID EDUCATION-PROGRAM; INNER-CITY; CHILDREN; PREVALENCE; SEVERITY C1 NHLBI,NATL ASTHMA EDUC PROGRAM,BETHESDA,MD 20892. RP TAGGART, VS (reprint author), NHLBI,DIV LUNG DIS,WESTWOOD BLDG,ROOM 6A09,BETHESDA,MD 20892, USA. NR 13 TC 14 Z9 14 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 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 1993 VL 22 IS 4 BP 579 EP 584 DI 10.1006/pmed.1993.1051 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA LU399 UT WOS:A1993LU39900015 PM 8415510 ER PT J AU WESTERGAARD, GC SUOMI, SJ AF WESTERGAARD, GC SUOMI, SJ TI HAND PREFERENCE IN CAPUCHIN MONKEYS VARIES WITH AGE SO PRIMATES LA English DT Note DE CAPUCHIN; CEBUS-APELLA; MONKEY; HAND PREFERENCE; LATERALITY; TOOL-USE ID CEBUS-APELLA; HANDEDNESS AB The purpose of this research was to examine the influence of age on hand preference in capuchin monkeys (Cebus apella). Twenty-two capuchins, aged 6 months to 30 years, were presented with a task that involved reaching for food and a task that involved using sponging tools to absorb juice. Adults exhibited a greater percentage of right-handed actions in each task than did immature subjects. Adults also exhibited a stronger lateral bias than did immature subjects in the sponging task. These results are consistent with hypotheses: a) adult capuchin monkeys are biased toward use of their right hand for reaching; b) adult capuchins exhibit a greater incidence of right-hand preference than do immature capuchins; and c) primates exhibit age-related differences in the strength and direction of hand preference in tasks that involve the use of tools. RP WESTERGAARD, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,BLDG 112,NIHAC,POB 529,POOLESVILLE,MD 20837, USA. NR 12 TC 49 Z9 49 U1 0 U2 3 PU JAPAN MONKEY CENTRE PI INUYAMA AICHI PA PRIMATES, EDITORIAL OFFICE, INUYAMA AICHI 484, JAPAN SN 0032-8332 J9 PRIMATES JI Primates PD JUL PY 1993 VL 34 IS 3 BP 295 EP 299 DI 10.1007/BF02382624 PG 5 WC Zoology SC Zoology GA LV812 UT WOS:A1993LV81200005 ER PT J AU TANAKA, T HULI, J SEDER, RA FAZEKAS DE ST GROTH, B PAUL, WE AF TANAKA, T HULI, J SEDER, RA FAZEKAS DE ST GROTH, B PAUL, WE TI INTERLEUKIN-4 SUPPRESSES INTERLEUKIN-2 AND INTERFERON-GAMMA PRODUCTION BY NAIVE T-CELLS STIMULATED BY ACCESSORY CELL-DEPENDENT RECEPTOR ENGAGEMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOCLONAL-ANTIBODY; IL-4; EXPRESSION; ANTIGENS AB Interleukin 2 (IL-2) and interferon gamma (IFN-gamma) production by CD4+ T cells and IFN-gamma production by CD8+ T cells from naive mice in response to soluble anti-CD3 and antigen-presenting cells (APCs) were strikingly inhibited by culture in the presence of IL-4. IL-4 decreased IL-2 and IFN-gamma mRNA levels after 15-24 hr but gave relatively little decrease in these mRNAs at 6-12 hr after stimulation with soluble anti-CD3. A 16-hr preculture of T cells with anti-CD3, APCs, and IL-4 was sufficient to inhibit subsequent production of IL-2 and IFN-gamma in response to restimulation in the absence of IL-4. Furthermore, IL-4 treatment of T cells purified 24 hr after stimulation inhibited their capacity to subsequently produce IL-2 in response to anti-CD3 and APCs, indicating that T cells were targets of IL-4-mediated inhibition. IL-4 blocked acute IL-2 production in response to a cytochrome c peptide of T cells derived from transgenic mice expressing T-cell receptors specific for cytochrome c but it did not block IL-2 production by such cells after they had been primed in vitro. Nor did IL-4 inhibit production of IFN-gamma by cloned T cells in response to antigen and APCs or production of IL-2 and IFN-gamma by naive T cells in response to phorbol ester and calcium ionophore. These results indicate that IL-4 strikingly inhibits IL-2 and IFN-gamma production by naive T cells in response to accessory cell-dependent, receptor-mediated stimulation (i.e., soluble anti-CD3 and APCs or antigen and APCs) but does not inhibit accessory cell-independent stimulation of naive T cells or accessory cell-dependent receptor-mediated stimulation of recently primed T cells or cloned T-cell lines. C1 NIAID, IMMUNOL LAB, BETHESDA, MD 20892 USA. UNIV SYDNEY, CENTENARY INST CANC MED & CELL BIOL, SYDNEY, NSW 2006, AUSTRALIA. NR 29 TC 154 Z9 157 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 JUL 1 PY 1993 VL 90 IS 13 BP 5914 EP 5918 DI 10.1073/pnas.90.13.5914 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500009 PM 8100998 ER PT J AU ULLRICH, SJ SAKAGUCHI, K LEESMILLER, SP FISCELLA, M MERCER, WE ANDERSON, CW APPELLA, E AF ULLRICH, SJ SAKAGUCHI, K LEESMILLER, SP FISCELLA, M MERCER, WE ANDERSON, CW APPELLA, E TI PHOSPHORYLATION AT SER-15 AND SER-392 IN MUTANT P53-MOLECULES FROM HUMAN TUMORS IS ALTERED COMPARED TO WILD-TYPE P53 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CASEIN KINASE-II; LARGE-T-ANTIGEN; PROTEIN-KINASE; CELL-LINES; RAT-CELLS; ASSOCIATION; MUTATIONS; SEQUENCE; GROWTH; SUPPRESSION AB The product of the p53 gene suppresses cell growth and plays a critical role in suppressing development of human tumors. p53 protein binds DNA, activates transcription, and can be phosphorylated at N- and C-terminal sites. Previously, wild-type p53 was shown to be hyperphosphorylated compared to mutant p53 during p53-mediated growth arrest in vivo. Here we show that Ser-15 and Ser-9 in the N-terminal transactivation domain of wild-type human p53 are phosphorylated in vivo in cells derived from the human glioblastoma line T98G. In [Ile237]p53 and [Ala143]p53, two natural p53 mutants from human tumors that are defective for activation of transcription, phosphorylation at Ser-15 was reduced and phosphorylation at Ser-392 was increased compared to wild-type p53. No change was observed at Ser-9. [His273]p53, a third mutant, had a phosphorylation state similar to that of wild-type p53. We suggest that phosphorylation of Ser-15 may depend on the ability of p53 to adopt a wild-type conformation and may contribute to p53's ability to block cell growth. C1 AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RP ULLRICH, SJ (reprint author), NCI,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 56 TC 85 Z9 85 U1 0 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 JUL 1 PY 1993 VL 90 IS 13 BP 5954 EP 5958 DI 10.1073/pnas.90.13.5954 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500017 PM 8327466 ER PT J AU LOUIS, JM SAXE, CL KIMMEL, AR AF LOUIS, JM SAXE, CL KIMMEL, AR TI 2 TRANSMEMBRANE SIGNALING MECHANISMS CONTROL EXPRESSION OF THE CAMP RECEPTOR GENE CAR1 DURING DICTYOSTELIUM DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GENE EXPRESSION; PROMOTERS; GUANINE NUCLEOTIDE BINDING PROTEINS ID CYCLIC-AMP RECEPTOR; CELL-SURFACE RECEPTOR; ADENYLATE-CYCLASE; MESSENGER-RNA; DISCOIDEUM; INDUCTION; DIFFERENTIATION; IDENTIFICATION; PRESPORE AB Dictyostelium discoideum is among the best characterized organisms for the study of receptor/guanine nucleotide binding protein-mediated control of differentiation. Dictyostelium grow unicellularly but form fully differentiated multicellular organisms through a developmental program regulated by secreted cAMP activating specific cell-surface receptors. Dictyostelium respond differentially to cAMP at different developmental stages. During early development, expression of certain genes is induced by low-level oscillations of extracellular cAMP. Later, continuous, high cAMP concentrations will promote expression of specific genes in multicellular structures. Here, we show that the cAMP receptor gene CAR1, which is essential for development, utilizes two promoters that are activated at distinct stages of development and respond to different extracellular cAMP conditions. One promoter is active with low-level oscillations of cAMP; exposure to high cAMP concentrations will repress this promoter and induce a second promoter. The CAR1 mRNAs are alternatively spliced but encode identical proteins. Thus, through differential sensitivity to its own ligand, cAMP, two promoters and alternative splicing regulate CAR1 expression during Dictyostelium development. RP LOUIS, JM (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,BLDG 6-B1-22,BETHESDA,MD 20892, USA. NR 35 TC 42 Z9 43 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 JUL 1 PY 1993 VL 90 IS 13 BP 5969 EP 5973 DI 10.1073/pnas.90.13.5969 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500020 PM 8392183 ER PT J AU SHIMIZU, YK PURCELL, RH YOSHIKURA, H AF SHIMIZU, YK PURCELL, RH YOSHIKURA, H TI CORRELATION BETWEEN THE INFECTIVITY OF HEPATITIS-C VIRUS IN-VIVO AND ITS INFECTIVITY IN-VITRO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NON-B-HEPATITIS; NON-A; RNA; GENOME; CYCLOHEXIMIDE; EXPRESSION; HIV-1 AB A murine retrovirus-infected human T-cell line, HPB-Ma, supported replication of hepatitis C virus (HCV) at least as well as the previously reported Molt4-Ma cells. Cloning of HPB-Ma cells revealed a clonal variation of cellular susceptibility to HCV infection. Using one of the sensitive clones, we tested HCV inocula from different sources for their infectivity titer in cell culture. The in vitro titers obtained correlated with the reported infectivity titers of the inocula in chimpanzees. Thus, the system appears to be useful for estimating the in vivo infectivity of HCV. C1 NATL INST HLTH,DEPT VIRAL DIS & VACCINE CONTROL,MUSASHIMURAYAMA,TOKYO 208,JAPAN. NIH,INFECT DIS LAB,BETHESDA,MD 20892. RP SHIMIZU, YK (reprint author), UNIV TOKYO,FAC MED,DEPT BACTERIOL,7-3-1 HONGO,BUNKYO KU,TOKYO 113,JAPAN. NR 18 TC 147 Z9 151 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 JUL 1 PY 1993 VL 90 IS 13 BP 6037 EP 6041 DI 10.1073/pnas.90.13.6037 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500034 PM 8392185 ER PT J AU GLICK, AB KULKARNI, AB TENNENBAUM, T HENNINGS, H FLANDERS, KC OREILLY, M SPORN, MB KARLSSON, S YUSPA, SH AF GLICK, AB KULKARNI, AB TENNENBAUM, T HENNINGS, H FLANDERS, KC OREILLY, M SPORN, MB KARLSSON, S YUSPA, SH TI LOSS OF EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA IN SKIN AND SKIN TUMORS IS ASSOCIATED WITH HYPERPROLIFERATION AND A HIGH-RISK FOR MALIGNANT CONVERSION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE SKIN; TERMINAL DIFFERENTIATION; ALTERED REGULATION; RAS GENE; PAPILLOMAS; KERATINOCYTES; CARCINOGENESIS; CHROMOSOME-7; PROGRESSION; INDUCTION AB Mouse skin carcinomas arise from a small subpopulation of benign papillomas with an increased risk of malignant conversion. These papillomas arise with limited stimulation by tumor promoters, appear rapidly, and do not regress, suggesting that they differ in growth properties from the majority of benign tumors. The transforming growth factor beta (TGF-beta) proteins are expressed in the epidermis and are growth inhibitors for mouse keratinocytes in vitro; altered TGF-beta expression could influence the growth properties of high-risk papillomas. Normal epidermis, tumor promoter-treated epidermis, and skin papillomas at low risk for malignant conversion express TGF-beta1 in the basal cell compartment and TGF-beta2 in the suprabasal strata. In low-risk tumors, 90% of the proliferating cells are confined to the basal compartment. In contrast, the majority of high-risk papillomas are devoid of both TGF-beta1 and TGF-beta2 as soon as they arise; these tumors have up to 40% of the proliferating cells in the suprabasal layers. Squamous cell carcinomas are also devoid of TGF-beta, suggesting that they arise from the TGF-beta-deficient high-risk papillomas. In some high-risk papillomas, TGF-beta1 loss can occur first and correlates with basal cell hyperproliferation, while TGF-beta2 loss correlates with suprabasal hyperproliferation. Similarly, TGF-beta1-null transgenic mice, which express wild-type levels of TGF-beta2 in epidermis but no TGF-beta1 in the basal layer, have a hyperproliferative basal cell layer without suprabasal proliferation. In tumors, loss of TGF-beta is controlled at the posttranscriptional level and is associated with expression of keratin 13, a documented marker of malignant progression. These results show that TGF-beta expression and function are compartmentalized in epidermis and epidermal tumors and that loss of TGF-beta is an early, biologically relevant risk factor for malignant progression. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NINCDS,MOLEC MED GENET SECT,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. RP GLICK, AB (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892, USA. NR 35 TC 181 Z9 184 U1 1 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 JUL 1 PY 1993 VL 90 IS 13 BP 6076 EP 6080 DI 10.1073/pnas.90.13.6076 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500042 PM 7687059 ER PT J AU GAZZINELLI, RT HIENY, S WYNN, TA WOLF, S SHER, A AF GAZZINELLI, RT HIENY, S WYNN, TA WOLF, S SHER, A TI INTERLEUKIN-12 IS REQUIRED FOR THE T-LYMPHOCYTE-INDEPENDENT INDUCTION OF INTERFERON-GAMMA BY AN INTRACELLULAR PARASITE AND INDUCES RESISTANCE IN T-CELL-DEFICIENT HOSTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE TOXOPLASMA-GONDII; NATURAL KILLER CELLS ID TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; STIMULATORY FACTOR; TOXOPLASMA-GONDII; SCID MICE; CYTOKINE; ANTIBODY AB Immunity against the intracellular protozoan Toxoplasma gondii is highly dependent on interferon gamma(IFN-gamma). We have previously shown that, in addition to T lymphocytes, natural killer (NK) cells can be stimulated by the parasite to produce this cytokine by a reaction requiring adherent accessory cells and tumor necrosis factor alpha. We now demonstrate that a recently characterized cytokine, interleukin 12 (IL-12), is also necessary for parasite-induced IFN-gamma synthesis by NK cells. Anti-IL-12 antibodies completely inhibited T. gondii or bacterial endotoxin-stimulated IFN-gamma production by NK-enriched spleen cells from severe combined immunodeficient mice. Moreover, potent NK cytokine responses were induced by the combination of IL-12 and tumor necrosis factor alpha. In addition, adherent spleen cells from scid/scid mice or thyoglycollate-elicited macrophages from BALB/c animals produced high levels of both IL-12 (p40) and tumor necrosis factor alpha mRNAs when exposed to either live tachyzoites, parasite extracts, or endotoxin, confirming that these cytokines are produced by accessory cells. Finally, in vivo studies showed that treatment with recombinant IL-12 results in prolonged survival of scid mice after infection with T. gondii by means of a response dependent on both IFN-gamma and NK cells. Together the data argue that IL-12 is required for the T-cell-independent triggering of NK cells by intracellular parasites and that the cytokine may be useful for inducing this protective pathway in immunodeficient hosts. C1 GENET INST INC, CAMBRIDGE, MA 02140 USA. RP GAZZINELLI, RT (reprint author), NIAID, IMMUNOL & CELL BIOL SECT, PARASIT DIS LAB, BETHESDA, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 29 TC 703 Z9 710 U1 1 U2 8 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 JUL 1 PY 1993 VL 90 IS 13 BP 6115 EP 6119 DI 10.1073/pnas.90.13.6115 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500050 PM 8100999 ER PT J AU YANG, YL VACCHIO, MS ASHWELL, JD AF YANG, YL VACCHIO, MS ASHWELL, JD TI 9-CIS-RETINOIC ACID INHIBITS ACTIVATION-DRIVEN T-CELL APOPTOSIS - IMPLICATIONS FOR RETINOID-X RECEPTOR INVOLVEMENT IN THYMOCYTE DEVELOPMENT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CD4+8+ THYMOCYTES; CYCLE BLOCK; ANTIGEN; DEATH; DIFFERENTIATION; FRAGMENTATION; REQUIREMENTS; ANTIBODIES; HYBRIDOMAS; PATHWAYS AB Retinoic acid is a morphogenetic signaling molecule derived from vitamin A and involved in vertebrate development. Two groups of receptors, retinoic add receptors and retinoid X receptors (RXRs), have been identified. All-trans-retinoic acid is the high-affinity ligand for retinoic acid receptors, and 9-cis-retinoic acid additionally binds RXRs with high affinity. Here we report that although retinoic acid has little inhibitory effect on activation-induced T-cell proliferation, it specifically prevents activation-induced apoptosis of T-cell hybridomas and antigen-specific deletion of immature CD4+CD8+ thymocytes from alphabeta T-cell receptor transgenic mice. 9-cis-Retinoic acid was almost-equal-to 10-fold more potent than all-trans-retinoic acid, suggesting that RXRs participate in this process. Thus, although 9-cis-retinoic acid has little immunosuppressive activity, it is a potent negative regulator of activation-induced T-cell apoptosis, raising the possibility that RXRs may take part in regulating T-cell development. C1 NCI,IMMUNE CELL BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,ROOM 1B-40,BETHESDA,MD 20892. NR 39 TC 118 Z9 120 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 JUL 1 PY 1993 VL 90 IS 13 BP 6170 EP 6174 DI 10.1073/pnas.90.13.6170 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500061 PM 8392190 ER PT J AU MCDONALD, LJ MOSS, J AF MCDONALD, LJ MOSS, J TI STIMULATION BY NITRIC-OXIDE OF AN NAD LINKAGE TO GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ADP-RIBOSYLATION; SODIUM NITROPRUSSIDE; MERCURY ID AMINO-ACID SEQUENCE; ADP-RIBOSYLATION; ALPHA-SUBUNIT; PROTEINS; RIBOSYLTRANSFERASE; TRANSDUCIN AB Nitric oxide-stimulated modification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by [adenylate-P-32] NAD has been interpreted in recent reports as ADP-ribosylation. Incubations of GAPDH with the NO-releasing agent sodium nitroprusside (SNP) and NAD resulted, however, in essentially equal incorporation of radiolabel from the adenine, phosphate, and nicotinamide moieties to the extent of almost-equal-to 0.02 mol of NAD.mol of GAPDH-1. Modification of GAPDH by free adenosine 5'-diphosphoribose (ADP-ribose) was only 10% of that by NAD. Exposure of GAPDH modified by NAD in the presence of SNP to HgCl2, Which acts at thiol linkages, released two products. Both contained nicotinamide and adenylate but did not cochromatograph with NAD. GAPDH activity was inhibited by SNP in a dose-dependent manner in the presence of NAD. When inhibition was 80%, with 1 mM SNP and 1 mM dithiothreitol, covalent modification with NAD was <2%. This result is consistent with the conclusion that inhibition of GAPDH activity by SNP in the presence of NAD is due primarily to active-site nitrosylation, as reported by other workers, and is not due to the minor modification with NAD. These results demonstrate that NO-stimulated modification of GAPDH with NAD is not ADP-ribosylation as previously reported but rather is covalent binding of NAD through a NO-dependent thiol intermediate, possibly providing an example of an unexpected, altered reactivity of a nitrosylated protein. RP MCDONALD, LJ (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10,ROOM 5N-307,BETHESDA,MD 20892, USA. NR 28 TC 183 Z9 183 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 JUL 1 PY 1993 VL 90 IS 13 BP 6238 EP 6241 DI 10.1073/pnas.90.13.6238 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500075 PM 8327504 ER PT J AU JACOBOMOLINA, A DING, JP NANNI, RG CLARK, AD LU, XD TANTILLO, C WILLIAMS, RL KAMER, G FERRIS, AL CLARK, P HIZI, A HUGHES, SH ARNOLD, E AF JACOBOMOLINA, A DING, JP NANNI, RG CLARK, AD LU, XD TANTILLO, C WILLIAMS, RL KAMER, G FERRIS, AL CLARK, P HIZI, A HUGHES, SH ARNOLD, E TI CRYSTAL-STRUCTURE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE COMPLEXED WITH DOUBLE-STRANDED DNA AT 3.0 ANGSTROM RESOLUTION SHOWS BENT DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RIBONUCLEASE-H; HIV-1 REPLICATION; RESISTANCE; INHIBITION; ERRORS; MODELS; AZT AB The crystal structure of a ternary complex of human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) heterodimer (p66/p51), a 19-base/18-base double-stranded DNA template-primer, and a monoclonal antibody Fab fragment has been determined at 3.0 angstrom resolution. The four individual subdomains of RT that make up the polymerase domains of p66 and p51 are named fingers, palm, thumb, and connection [Kohlstaedt, L. A., Wang, J., Friedman, J. M., Rice, P. A. & Steitz, T. A. (1992) Science 256, 1783-1790]. The overall folding of the subdomains is similar in p66 and p51 but the spatial arrangements of the subdomains are dramatically different. The template-primer has A-form and B-form regions separated by a significant bend (40-45-degrees). The most numerous nucleic acid interactions with protein occur primarily along the sugar-phosphate backbone of the DNA and involve amino acid residues of the palm, thumb, and fingers of p66. Highly conserved regions are located in the p66 palm near the polymerase active site. These structural elements, together with two alpha-helices of the thumb of p66, act as a clamp to position the template-primer relative to the polymerase active site. The 3'-hydroxyl of the primer terminus is close to the catalytically essential Asp-110, Asp-185, and Asp-186 residues at the active site and is in a position for nucleophilic attack on the alpha-phosphate of an incoming nucleoside triphosphate. The structure of the HIV-1 RT/DNA/Fab complex should aid our understanding of general mechanisms of nucleic acid polymerization. AIDS therapies may be enhanced by a fuller understanding of drug inhibition and resistance emerging from these studies. C1 RUTGERS UNIV,CTR ADV BIOTECHNOL & MED,DEPT CHEM,679 HOES LANE,PISCATAWAY,NJ 08854. RUTGERS UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. KAMER CRYSTALLOG SOFTWARE,W LAFAYETTE,IN 47906. PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK,MD 21702. TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. FU NIAID NIH HHS [AI 27690] NR 29 TC 1046 Z9 1063 U1 3 U2 38 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 JUL 1 PY 1993 VL 90 IS 13 BP 6320 EP 6324 DI 10.1073/pnas.90.13.6320 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500092 PM 7687065 ER PT J AU PISEGNA, JR WANK, SA AF PISEGNA, JR WANK, SA TI MOLECULAR-CLONING AND FUNCTIONAL EXPRESSION OF THE PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE TYPE-I RECEPTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEUROPEPTIDE RECEPTOR; GASTROINTESTINAL PEPTIDE RECEPTOR; G-PROTEIN-COUPLED RECEPTOR ID BINDING-SITES; HYPOTHALAMIC POLYPEPTIDE; STRUCTURAL FEATURES; BOVINE RHODOPSIN; RAT-BRAIN; PACAP; PEPTIDE; IDENTIFICATION; CDNA; MEMBRANES AB Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide belonging to the vasoactive intestinal peptide (VIP)/secretin/glucagon family of peptides, interacts with a distinct high-affinity receptor (type I receptor) on a number of tissues. These PACAP type I receptors have a high affinity for PACAP and a low affinity for VIP and are present in the hypothalamus and anterior pituitary, where they regulate the release of adrenocorticotropin, luteinizing hormone, growth hormone, and prolactin, and in the adrenal medulla, where they regulate the release of epinephrine. Type I PACAP receptors are also present in high concentrations in testicular germ cells, where they may regulate spermatogenesis, and some transformed cell lines, such as the rat pancreatic acinar carcinoma cell AR4-2J. Here we report the molecular cloning and functional expression of the PACAP type I receptor isolated from an AR4-2J cell cDNA library by cross-hybridization screening with a rat VIP receptor cDNA. The cDNA sequence encodes a unique 495-amino acid protein with seven transmembrane domains characteristic of guanine nucleotide-binding regulatory protein-coupled receptors. A high degree of sequence homology with the VIP, secretin, glucagon-like peptide 1, parathyroid, and calcitonin receptors suggests its membership in this subfamily of G(s)-coupled receptors. Results of binding studies and stimulation of cellular cAMP accumulation in COS-7 cells transfected with this cDNA are characteristic of a PACAP type I receptor. Cloning of the PACAP type I receptor will enhance our understanding of its distribution, structure, and functional properties and ultimately increase our understanding of its physiological role. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. NR 46 TC 348 Z9 351 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 JUL 1 PY 1993 VL 90 IS 13 BP 6345 EP 6349 DI 10.1073/pnas.90.13.6345 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LM035 UT WOS:A1993LM03500097 PM 8392197 ER PT J AU FISCHER, D NOREL, R WOLFSON, H NUSSINOV, R AF FISCHER, D NOREL, R WOLFSON, H NUSSINOV, R TI SURFACE MOTIFS BY A COMPUTER VISION TECHNIQUE - SEARCHES, DETECTION, AND IMPLICATIONS FOR PROTEIN LIGAND RECOGNITION SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE PROTEIN STRUCTURAL COMPARISON; 3-D PROTEIN MOTIFS; SURFACE MOTIFS; DOCKING; COMPUTER VISION; GEOMETRIC HASHING ID COMPLEMENTARITY AB We describe the application of a method geared toward structural and surface comparison of proteins. The method is based on the Geometric Hashing Paradigm adapted from Computer Vision. It allows for comparison of any two sets of 3-D coordinates, such as protein backbones, protein core or protein surface motifs, and small molecules such as drugs. Here we apply our method to 4 types of comparisons between pairs of molecules: (1) comparison of the backbones of two protein domains; (2) search for a predefined 3-D C. motif within the full backbone of a domain; and in particular, (3) comparison of the surfaces of two receptor proteins; and (4) comparison of the surface of a receptor to the surface of a ligand. These aspects complement each other and can contribute toward a better understanding of protein structure and biomolecular recognition. Searches for 3-D surface motifs can be carried out on either receptors or on ligands. The latter may result in the detection of pharmacophoric patterns. If the surfaces of the binding sites of either the receptors or of the ligands are relatively similar, surface superpositioning may aid significantly in the docking problem. Currently, only distance invariants are used in the matching, although additional geometric surface invariants are considered. The speed of our Geometric Hashing algorithm is encouraging, with a typical surface comparison taking only seconds or minutes of CPU time on a SUN 4 SPARC workstation. The direct application of this method to the docking problem is also discussed. We demonstrate the success of this method in its application to two members of the globin family and to two dehydrogenases. C1 NCI,FCRF,PRI DYNCORP,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702. TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011; OI Norel, Raquel/0000-0001-7737-4172 FU NCI NIH HHS [1-CO-74102] NR 29 TC 43 Z9 45 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-3585 J9 PROTEINS JI Proteins PD JUL PY 1993 VL 16 IS 3 BP 278 EP 292 DI 10.1002/prot.340160306 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LG165 UT WOS:A1993LG16500005 PM 8394000 ER PT J AU SWEDO, SE AF SWEDO, SE TI TRICHOTILLOMANIA SO PSYCHIATRIC ANNALS LA English DT Article ID CLOMIPRAMINE; FLUOXETINE; DESIPRAMINE RP SWEDO, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT UNIT,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 16 Z9 17 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD JUL PY 1993 VL 23 IS 7 BP 402 EP 407 PG 6 WC Psychiatry SC Psychiatry GA LM338 UT WOS:A1993LM33800009 ER PT J AU POLYMEROPOULOS, MH XIAO, H TORREY, EF DELISI, LE CROW, T MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H TORREY, EF DELISI, LE CROW, T MERRIL, CR TI SEARCH FOR A GENETIC EVENT IN MONOZYGOTIC TWINS DISCORDANT FOR SCHIZOPHRENIA SO PSYCHIATRY RESEARCH LA English DT Article DE MOLECULAR GENETIC METHODS; MITOTIC CROSSOVER; POLYMORPHIC MARKERS ID DINUCLEOTIDE REPEAT POLYMORPHISM; MITOTIC CROSSING-OVER; UNIPARENTAL DISOMY; DNA POLYMORPHISMS; LOCUS; COMMON AB When monozygotic twins are discordant for the diagnosis of schizophrenia, this discordance has been traditionally attributed to environmental factors acting upon a genome susceptible for the schizophrenia phenotype. The study presented here was designed to examine the occurrence of a genetic event, such as a postzygotic mitotic crossover, that could account for the discordance. Such a postzygotic event could affect cis-acting sequences and result in a phenotype of variable severity. We used molecular genetic methods to evaluate such an event with 94 microsatellite repeat polymorphic markers distributed on all autosomes and the X chromosome in five pairs of monozygotic twins discordant for schizophrenia. In this search, no genetic marker discordancies were identified between the co-twins. The lack of a genetic difference may implicate nongenetic factors that are responsible in eliciting or suppressing the phenotype. However, the experiments performed in this study cannot eliminate the possibility that a tissue-specific mitotic crossover might have occurred in one of the discordant twins, which could not have been detected in our current study. C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,TWIN STUDY UNIT,WASHINGTON,DC 20032. SUNY,HLTH SCI CTR,SCH MED,DEPT PSYCHIAT & BEHAV SCI,STONY BROOK,NY 11794. CLIN RES CTR,DIV PSYCHIAT,HARROW HA1 3UJ,MIDDX,ENGLAND. RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,WASHINGTON,DC 20032, USA. NR 63 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUL PY 1993 VL 48 IS 1 BP 27 EP 36 DI 10.1016/0165-1781(93)90110-3 PG 10 WC Psychiatry SC Psychiatry GA LU608 UT WOS:A1993LU60800004 PM 8416016 ER PT J AU COTE, TR SIVERTSON, D HORAN, JM LINDEGREN, ML DWYER, DM AF COTE, TR SIVERTSON, D HORAN, JM LINDEGREN, ML DWYER, DM TI EVALUATION OF A 2-DOSE MEASLES, MUMPS, AND RUBELLA VACCINATION SCHEDULE IN A COHORT OF COLLEGE ATHLETES SO PUBLIC HEALTH REPORTS LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; EPIDEMIC MEASLES; POPULATION; IMMUNITY AB Despite high vaccination levels, measles out-breaks continue to occur among vaccinated adults. In response, new guidelines call for two doses of measles vaccine. To determine seroprevalance and response to vaccination in seronegative persons, we tested serums from 256 college athletes at a Maryland State college by enzyme-linked immunosorbant assay, vaccinated seronegatives, then re-tested vaccinees. High school records were obtained for persons seronegative to measles. Of 256 students, 53 (21 percent) were seronegative to measles alone, 13 (5 percent) were seronegative to rubella alone, and 5 (2 percent) were seronegative to both. Among those seronegative to measles, 86 percent had previously received a dose of measles vaccine. After vaccination, 37 persons initially seronegative to measles and 9 seronegative to rubella were 97 percent and 100 percent seropositive, respectively. The high measles seroconversion rate suggests that the two-dose vaccine schedule should effectively control campus measles outbreaks and, if given as measles-mumps-rubella vaccine, will also improve immunity to rubella and mumps. C1 CTR DIS CONTROL & PREVENT,DIV FIELD EPIDEMIOL,EPIDEM INTELLIGENCE SERV,ATLANTA,GA. MARYLAND DEPT HLTH & MENTAL HYG,EPIDEMIOL & DIS CONTROL PROGRAM,CTR CLIN EPIDEMIOL,BALTIMORE,MD 21201. UNIV MARYLAND,STUDENT HLTH SERV,BALTIMORE,MD 21201. RP COTE, TR (reprint author), NCI,VIRAL EPIDEMIOL BRANCH,6130 EXECUT BLVD,EPN 434,BETHESDA,MD 20892, USA. NR 22 TC 7 Z9 7 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1993 VL 108 IS 4 BP 431 EP 435 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LR603 UT WOS:A1993LR60300004 PM 8341775 ER PT J AU SALIVE, ME WALLACE, RB OSTFELD, AM SATTERFIELD, S HAVLIK, RJ AF SALIVE, ME WALLACE, RB OSTFELD, AM SATTERFIELD, S HAVLIK, RJ TI RISK-FACTORS FOR SEPTICEMIA-ASSOCIATED MORTALITY IN OLDER ADULTS SO PUBLIC HEALTH REPORTS LA English DT Article ID BLOOD-STREAM INFECTIONS; PNEUMOCOCCAL BACTEREMIA; CHARLESTON COUNTY; SOUTH-CAROLINA; PREDICTORS; DEATH; MEN AB Septicemia is the 10th leading cause of death among older adults in the United States; its mortality rate has steadily increased over the past decades. Little is known about factors which predispose to septicemia mortality in the elderly. The authors investigated risk factors for septicemia-associated mortality in 10,269 older adults as part of a longitudinal study of three communities (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA). During 6 years of followup, 177 persons (3.2 per 1,000 person-years) had septicemia ICD9 038 (International Classification of Diseases, ninth revision) reported on their death certificate. In a multivariate proportional-hazards model, septicemia mortality was significantly (P<0.05) and independently associated with age, male sex, history of diabetes, history of cancer requiring hospitalization, smoking one pack of cigarettes per day or more, not drinking alcohol in the year prior to baseline, disability in activities of daily living, cognitive impairment, and missing cognitive testing score. These factors might be useful in developing an at-risk population for testing septicemia treatment or prevention strategies in a community setting. Further investigation is needed to explain underlying mechanisms of increased risk of subsequent septicemia. C1 E BOSTON NEIGHBORHOOD HLTH CTR,BOSTON,MA. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06510. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. HARVARD UNIV,SCH MED,DEPT MED,CHANNING LAB,BOSTON,MA 02115. FU NIA NIH HHS [N01-AG-02107, N01-AG-02106, N01-AG-02105] NR 34 TC 6 Z9 7 U1 3 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD JUL-AUG PY 1993 VL 108 IS 4 BP 447 EP 453 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LR603 UT WOS:A1993LR60300007 PM 8341778 ER PT J AU INSKIP, PD KLEINERMAN, RA STOVALL, M COOKFAIR, DL HADJIMICHAEL, O MOLONEY, WC MONSON, RR THOMPSON, WD WACTAWSKIWENDE, J WAGONER, JK BOICE, JD AF INSKIP, PD KLEINERMAN, RA STOVALL, M COOKFAIR, DL HADJIMICHAEL, O MOLONEY, WC MONSON, RR THOMPSON, WD WACTAWSKIWENDE, J WAGONER, JK BOICE, JD TI LEUKEMIA, LYMPHOMA, AND MULTIPLE-MYELOMA AFTER PELVIC RADIOTHERAPY FOR BENIGN DISEASE SO RADIATION RESEARCH LA English DT Article ID SINGLE TREATMENT COURSE; BONE-MARROW; ANKYLOSING-SPONDYLITIS; IONIZING-RADIATION; STEM-CELLS; X-RAYS; MORTALITY; CANCER; EXPOSURE; WORKERS C1 UNIV TEXAS, MD ANDERSON CANC CTR, DEPT RADIAT PHYS, HOUSTON, TX 77030 USA. SUNY BUFFALO, SCH MED, DEPT SOCIAL & PREVENT MED, BUFFALO, NY 14214 USA. YALE UNIV, SCH MED & PUBL HLTH, DEPT EPIDEMIOL & PUBL HLTH, NEW HAVEN, CT 06510 USA. HARVARD UNIV, SCH PUBL HLTH, DEPT EPIDEMIOL, BOSTON, MA 02115 USA. BRIGHAM & WOMENS HOSP, DIV HEMATOL, BOSTON, MA 02115 USA. SUNY BUFFALO, SCH MED, DEPT GYNECOL & OBSTET, BUFFALO, NY 14222 USA. RP NCI, EPIDEMIOL & BIOSTAT PROGRAM, RADIAT EPIDEMIOL BRANCH, EXECUT PLAZA N, ROOM 408, BETHESDA, MD 20892 USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 59 TC 63 Z9 64 U1 0 U2 1 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 JUL PY 1993 VL 135 IS 1 BP 108 EP 124 DI 10.2307/3578404 PG 17 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA LM856 UT WOS:A1993LM85600015 PM 8327655 ER PT J AU ACKERMAN, MJ AF ACKERMAN, MJ TI INFORAD - COMPUTERS FOR CLINICAL-PRACTICE AND EDUCATION IN RADIOLOGY - SEARCHING ONLINE DATA-BASES SO RADIOGRAPHICS LA English DT Article DE RADIOLOGY AND RADIOLOGISTS, RESEARCH AB Medical Literature Analysis and Retrieval System (MEDLARS) is the National Library of Medicine's family of on-line health-oriented data bases. The MEDLINE (Index Medicus on-line) data base is probably the most well known. GRATEFUL MEI) is an inexpensive, user-friendly program for searching the MEDLARS data bases. With this program, a user can sort through a data base on author name, title, journal name, and subject words. A search can be further restricted to only articles written in English and to review articles. For a subject word search, the program helps the user select index terms used in the data base: The user types in a subject, and the program suggests appropriate terms available in the data base. Subject terms can also be linked to further restrict the search. When the search has been completed, the user can ask the program to print selected citations, copy them to a specified disk file, or cite them as relevant. For relevant citations, the program analyzes the associated index terms and suggests terms that might better retrieve the desired subject matter. The new terms can be used to revise the previously conducted search. RP ACKERMAN, MJ (reprint author), NATL LIB MED,DIV SPECIALIZED INFORMAT SERV,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD JUL PY 1993 VL 13 IS 4 BP 939 EP 941 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LM860 UT WOS:A1993LM86000020 PM 8356280 ER PT J AU MILLER, DL LOTZE, MT AF MILLER, DL LOTZE, MT TI A PLEA FOR A STANDARD STANDARD SO RADIOLOGY LA English DT Editorial Material DE EDITORIALS; LIVER NEOPLASMS, THERAPY; NEOPLASMS, THERAPY; RADIOLOGY AND RADIOLOGISTS, RESEARCH ID TRANSCATHETER ARTERIAL EMBOLIZATION; UNRESECTABLE HEPATOCELLULAR-CARCINOMA; CLINICAL-TRIALS; DRUG; CHEMOEMBOLIZATION; GUIDELINES; INFUSION; CANCER C1 HENRY M JACKSON FDN, ROCKVILLE, MD USA. UNIV PITTSBURGH, DEPT SURG, PITTSBURGH, PA 15260 USA. NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT DIAGNOSE RADIOL, BETHESDA, MD 20892 USA. RP MILLER, DL (reprint author), SUNY HLTH SCI CTR, DEPT RADIOL, 750 E ADAMS ST, SYRACUSE, NY 13210 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1993 VL 188 IS 1 BP 19 EP 20 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH284 UT WOS:A1993LH28400004 PM 8390068 ER PT J AU AVILA, NA SHAWKER, TH CHOYKE, PL OLDFIELD, EH AF AVILA, NA SHAWKER, TH CHOYKE, PL OLDFIELD, EH TI CEREBELLAR AND SPINAL HEMANGIOBLASTOMAS - EVALUATION WITH INTRAOPERATIVE GRAY-SCALE AND COLOR DOPPLER FLOW ULTRASOUND SO RADIOLOGY LA English DT Article DE ANGIOMA; BRAIN, NEOPLASMS; BRAIN, ULTRASOUND; SPINE, PRIMARY NEOPLASMS; SPINE, ULTRASOUND; ULTRASOUND (US), DOPPLER STUDIES ID CORD AB Intraoperative gray-scale and color Doppler flow ultrasound (US) studies were performed in 12 patients with von Hippel-Lindau disease during surgical excision of hemangioblastomas. There were a total of 21 lesions: two were in the cerebellum and 19 were in the spinal cord. Twelve of the 19 spinal hemangioblastomas were hyperechoic to the spinal cord and thus were easily detected with gray-scale US. Color Doppler flow images provided improved delineation of all lesions compared with the images produced with standard gray-scale US. Seven of the 19 spinal lesions were detected only with color Doppler flow imaging because they were isoechoic to the normal spinal cord at gray-scale US. Color Doppler flow imaging enabled differentiation of the cysts and syrinx cavities associated with hemangioblastomas from dilated intraspinal vascular structures. In all cases, intraoperative color Doppler flow imaging facilitated the localization of hemangioblastomas during the neurosurgical procedure. C1 GEORGETOWN UNIV, SCH MED, DEPT RADIOL, WASHINGTON, DC 20007 USA. NINCDS, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. RP AVILA, NA (reprint author), NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT RADIOL, BLDG 10, RM 1C660, BETHESDA, MD 20892 USA. NR 11 TC 12 Z9 12 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1993 VL 188 IS 1 BP 143 EP 147 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH284 UT WOS:A1993LH28400028 PM 8511288 ER PT J AU DUYN, JH GILLEN, J SOBERING, G VANZIJL, PCM MOONEN, CTW AF DUYN, JH GILLEN, J SOBERING, G VANZIJL, PCM MOONEN, CTW TI MULTISECTION PROTON MR SPECTROSCOPIC IMAGING OF THE BRAIN SO RADIOLOGY LA English DT Note DE BRAIN, MR; MAGNETIC RESONANCE (MR), SPECTROSCOPY ID STIMULATED ECHOES; INTRACRANIAL TUMORS; INVIVO; SUPPRESSION; EXCITATION AB The authors developed a hydrogen-1 proton magnetic resonance (MR) imaging method in which metabolic information is acquired by obtaining multiple sections through the brain. A spin-echo sequence is used for section selection, an octangular outer volume saturation pulse for lipid suppression, and a chemical-shift-selective saturation pulse for water suppression. High-quality maps of choline, creatine, and N-acetylaspartate were obtained in six studies performed in four volunteers. Water and lipid signal from the skull area was well suppressed by the pulse sequence used. C1 NIH, BIOMED ENGN & INSTRUMENTAT BRANCH, INVIVO NMR RES CTR,BLDG 10,ROOM B1D-125, BETHESDA, MD 20892 USA. PITTSBURGH NMR INST, PITTSBURGH, PA USA. JOHNS HOPKINS MED INST, RUSSELL H MORGAN DEPT RADIOL & RADIOL SCI, BALTIMORE, MD 21205 USA. NIH, BIOMED ENGN & INSTRUMENTAT BRANCH, DIAGNOST RADIOL RES LAB, BETHESDA, MD 20892 USA. RI van Zijl, Peter/B-8680-2008; Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 34 TC 280 Z9 282 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 1993 VL 188 IS 1 BP 277 EP 282 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA LH284 UT WOS:A1993LH28400054 PM 8511313 ER PT J AU MAGE, RG AF MAGE, RG TI RABBIT FACTS AND DIVERSIFICATION OF V(H) SEQUENCES BY GENE CONVERSION - A THEORY OF THE ONTOGENY OF THE CHICKEN HUMORAL IMMUNE-SYSTEM - THE CONSEQUENCES OF DIVERSIFICATION BY GENE HYPERCONVERSION AND ITS EXTENSION TO RABBIT - COMMENTS SO RESEARCH IN IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN HEAVY-CHAINS; ANTIBODY DIVERSITY; REGION GENES; VDJ GENES; B-CELLS; VH; EXPRESSION; REARRANGEMENT; GENERATION; ALICIA RP MAGE, RG (reprint author), NIAID,IMMUNOL LAB,MOLEC IMMUNOGENET SECT,BLDG 10,RM 11 N 311,BETHESDA,MD 20892, USA. NR 53 TC 7 Z9 7 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2494 J9 RES IMMUNOL JI Res. Immunol. PD JUL-SEP PY 1993 VL 144 IS 6-7 BP 476 EP 486 DI 10.1016/0923-2494(93)80143-M PG 11 WC Immunology SC Immunology GA MF881 UT WOS:A1993MF88100012 PM 8303069 ER PT J AU VANDERVEEN, T AF VANDERVEEN, T TI ANTHROPOLOGY IN A MULTIDISCIPLINARY FIELD - SUBSTANCE-ABUSE - EPILOGUE SO SOCIAL SCIENCE & MEDICINE LA English DT Article RP VANDERVEEN, T (reprint author), NIAAA,ROCKVILLE,MD 20852, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUL PY 1993 VL 37 IS 1 BP 31 EP 31 DI 10.1016/0277-9536(93)90314-T PG 1 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA LG701 UT WOS:A1993LG70100005 ER PT J AU BURTON, B DESPOSITO, F FROSTER, U HOLMES, LB HOLZGREVE, W JACKSON, L LAGE, J MAHONEY, MJ MENNUTI, M MILNER, R OLNEY, R WILSON, RD ZACHARY, JM DELACRUZ, F KAMINETZKY, H AF BURTON, B DESPOSITO, F FROSTER, U HOLMES, LB HOLZGREVE, W JACKSON, L LAGE, J MAHONEY, MJ MENNUTI, M MILNER, R OLNEY, R WILSON, RD ZACHARY, JM DELACRUZ, F KAMINETZKY, H TI REPORT OF NATIONAL-INSTITUTE-OF-CHILD-HEALTH AND HUMAN-DEVELOPMENT-WORKSHOP-ON-CHORIONIC-VILLUS-SAMPLING AND LIMB AND OTHER DEFECTS, OCTOBER 20, 1992 SO TERATOLOGY LA English DT Editorial Material ID PRENATAL-DIAGNOSIS; MINOR ANOMALIES; MALFORMATIONS; ABNORMALITIES; REDUCTION; CVS AB A Workshop on Chorionic Villus Sampling (CVS) was convened by the National Institute of Child Health and Human Development (NICHD) and the American College of Obstetricians and Gynecologists at the National Institutes of Health on April 17, 1992, to discuss recent reports of an increased occurrence of malformations of the upper and lower limbs and oral structures among CVS-exposed infants. We summarize here the defects described in the CVS-exposed infants, the retrospective reassessments of published studies of the safety of CVS, the prevalence of limb deficiencies in infants not exposed to CVS, the status of the 7-9 week (conception or fertilization age) embryo, and the relevant human and animal experimental models of how CVS might be harmful to the embryo or fetus. C1 UNIV HOSP BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. GEORGETOWN UNIV,CTR BIOSTAT,WASHINGTON,DC 20057. HUMANA HOSP MICHAEL REESE,CTR MED GENET,CHICAGO,IL. AMER ACAD PEDIAT,COMM GENET,EVANSTON,IL 60204. LUBECK MED UNIV,DEPT OBSTET & GYNECOL,LUBECK,GERMANY. MASSACHUSETTS GEN HOSP,EMBRYOL TERATOL UNIT,BOSTON,MA 02114. UNIV MUNSTER,ZENTRUM FRAUENHEILKUNDE,W-4400 MUNSTER,GERMANY. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DIV MED GENET,PHILADELPHIA,PA 19107. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20057. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. UNIV PENN,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. UNIV BRITISH COLUMBIA,DEPT AIME COTTON,VANCOUVER V6T 1W5,BC,CANADA. CTR ENVIRONM HLTH,DIV BIRTH DEFECTS & DEV DISABIL,ATLANTA,GA. NICHHD,MENTAL RETARDAT & DEV DISABIL BRANCH,BETHESDA,MD 20892. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. NR 29 TC 13 Z9 13 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 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 1993 VL 48 IS 1 BP 7 EP 13 PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA LH937 UT WOS:A1993LH93700003 ER PT J AU FIELD, EA PRICE, CJ SLEET, RB GEORGE, JD MARR, MC MYERS, CB SCHWETZ, BA MORRISSEY, RE AF FIELD, EA PRICE, CJ SLEET, RB GEORGE, JD MARR, MC MYERS, CB SCHWETZ, BA MORRISSEY, RE TI DEVELOPMENTAL TOXICITY EVALUATION OF DIETHYL AND DIMETHYL PHTHALATE IN RATS SO TERATOLOGY LA English DT Article ID ZERO DOSE CONTROL; ACID ESTERS; TERATOGENICITY; MOUSE; MICE AB Diethyl phthalate (DEP) and dimethyl phthalate (DMP), phthalic acid ester (PAE) plasticizers, were evaluated for developmental toxicity because of reports in the literature that some PAE were embryotoxic and teratogenic. A previous study (Singh et al., '72) suggested that an increased incidence of skeletal defects in rats might result from gestational exposure to DEP (0.6-1.9 g/kg) or DMP (0.4-1.3 g/kg), ip, on gestational days (gd) 5, 10, and 15. In the current study DEP (0, 0.25, 2.5, and 5%) or DMP (0, 0.25, 1, and 5%) in feed (approximately 0.2-4.0 g/kg/day) were supplied to timed-mated rats from gd 6 to 15. Treatment with 5% DMP resulted in increased relative maternal liver weight. Also, animals exhibited reduced body weight gain during treatment (5% DEP or DMP) and during gestation (5% DEP). Weight gain corrected for gravid uterine weight was also reduced in animals fed 5% DEP. However, high-dose treatment with either DEP or DMP resulted in changes in food and water consumption paralleling the body weight reductions, suggesting that apparent toxic effects on maternal body weight may reflect PAE/feed unpalatability. Treatment with 2.5% DEP resulted in only transient changes in body weight during early treatment. The only maternal effects at 0.25 or 1% DMP were minor changes in food and/or water consumption, and there were no effects at 0.25% DEP. Thus, the NOAELs for maternal toxicity were 1% DMP and 0.25% DEP. In contrast to the observed maternal toxicity, there was no effect of DEP or DMP treatment on any parameter of embryo/fetal development, except an increased incidence of supernumerary ribs (a variation) in the 5% DEP group. These results do not support the conclusion of other investigators that DEP and DMP are potent developmental toxicants. Rather, they suggest that the shortchain PAE are less developmentally toxic than PAE with more complex substitution groups, e.g., di(2-ethylhexyl) phthalate, mono(2-ethylhexyl) phthalate, and butyl benzyl phthalate. C1 RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [NTP NIEHS N01-ES-55080] NR 47 TC 19 Z9 19 U1 0 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD JUL PY 1993 VL 48 IS 1 BP 33 EP 44 DI 10.1002/tera.1420480107 PG 12 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA LH937 UT WOS:A1993LH93700006 PM 8351646 ER PT J AU DICHEK, DA AF DICHEK, DA TI GENE-TRANSFER IN THE TREATMENT OF THROMBOSIS SO THROMBOSIS AND HAEMOSTASIS LA English DT Article ID TISSUE PLASMINOGEN-ACTIVATOR; HUMAN-ENDOTHELIAL CELLS; EXPRESSION INVIVO; ARTERIAL-WALL; BALLOON CATHETER; MESSENGER-RNA; PROTEIN-S; INHIBITOR; UROKINASE; INDUCTION RP DICHEK, DA (reprint author), NHLBI,MOLEC HEMATOL BRANCH,BLDG 10,ROOM 7D-18,BETHESDA,MD 20892, USA. NR 47 TC 11 Z9 11 U1 0 U2 0 PU F K SCHATTAUER VERLAG GMBH PI STUTTGART PA P O BOX 10 45 45, LENZHALDE 3, D-70040 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL 1 PY 1993 VL 70 IS 1 BP 198 EP 201 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA LT064 UT WOS:A1993LT06400039 PM 8236103 ER PT J AU HOLLADAY, SD BLAYLOCK, BL COMMENT, CE HEINDEL, JJ LUSTER, MI AF HOLLADAY, SD BLAYLOCK, BL COMMENT, CE HEINDEL, JJ LUSTER, MI TI FETAL THYMIC ATROPHY AFTER EXPOSURE TO T-2 TOXIN - SELECTIVITY FOR LYMPHOID PROGENITOR CELLS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; MURINE THYMOCYTES; DIOXIN TCDD; MICE; INFECTION; MOUSE; SUBPOPULATIONS; RESISTANCE; MYCOTOXIN; TOXICITY C1 NIEHS,IMMUNOTOXICOL GRP,RES TRIANGLE PK,NC 27709. NIEHS,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. NE LOUISIANA UNIV,DEPT BIOL,MONROE,LA 71209. RP HOLLADAY, SD (reprint author), VIRGINIA POLYTECH INST & STATE UNIV,VIRGINIA MARYLAND REG COLL VET MED,DEPT BIOMED SCI,BLACKSBURG,VA 24061, USA. NR 48 TC 41 Z9 43 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL PY 1993 VL 121 IS 1 BP 8 EP 14 DI 10.1006/taap.1993.1122 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LM692 UT WOS:A1993LM69200002 PM 8337703 ER PT J AU ZAWIA, NH HARRY, GJ AF ZAWIA, NH HARRY, GJ TI TRIMETHYLTIN-INDUCED C-FOS EXPRESSION - ADOLESCENT VS NEONATAL RAT HIPPOCAMPUS SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; TRANSCRIPTION FACTORS; MESSENGER-RNA; SYNAPSIN-I; ADULT-RAT; BRAIN; NEUROPATHOLOGY; INDUCTION; INJURY; PROTEIN RP ZAWIA, NH (reprint author), NIEHS,SYST TOX BRANCH,DEV & REPROD TOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 29 TC 16 Z9 16 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL PY 1993 VL 121 IS 1 BP 99 EP 102 DI 10.1006/taap.1993.1133 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LM692 UT WOS:A1993LM69200013 PM 8337705 ER PT J AU LUCIER, G CLARK, G HIERMATH, C TRITSCHER, A SEWALL, C HUFF, J AF LUCIER, G CLARK, G HIERMATH, C TRITSCHER, A SEWALL, C HUFF, J TI CARCINOGENICITY OF TCDD IN LABORATORY-ANIMALS - IMPLICATIONS FOR RISK ASSESSMENT SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Review ID EPIDERMAL GROWTH-FACTOR; POLYCYCLIC AROMATIC-HYDROCARBONS; BREAST-CANCER-CELLS; DOSE-RESPONSE RELATIONSHIPS; NUCLEAR ESTROGEN-RECEPTOR; HEPATIC PLASMA-MEMBRANE; RAT-LIVER MICROSOMES; SPRAGUE-DAWLEY RATS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; AH-RECEPTOR C1 US EPA,WASHINGTON,DC 20460. RP LUCIER, G (reprint author), NIEHS,NATL TOXICOL PROGRAM,BIOCHEM RISK ANAL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 179 TC 23 Z9 23 U1 0 U2 0 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUL-AUG PY 1993 VL 9 IS 4 BP 631 EP 668 PG 38 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA MD216 UT WOS:A1993MD21600006 PM 8296316 ER PT J AU IWATA, H KITAGAWA, S SATO, S KOSUGI, A HIROSE, H HAMAOKA, T SHEARER, GM FUJIWARA, H AF IWATA, H KITAGAWA, S SATO, S KOSUGI, A HIROSE, H HAMAOKA, T SHEARER, GM FUJIWARA, H TI SUPPRESSION OF ALLOGRAFT RESPONSES BY COMBINING DONOR ALLOANTIGEN-SPECIFIC INTRAVENOUS PRESENSITIZATION WITH SUBOPTIMAL DOSES OF FK506 SO TRANSPLANTATION LA English DT Article ID HELPER T-CELLS; H-2-DISPARATE SKIN-GRAFT; CLASS-I; BLOOD-TRANSFUSIONS; TOLERANCE INDUCTION; KIDNEY TRANSPLANTS; PROLONGED SURVIVAL; STRAIN BLOOD; REJECTION; CYCLOSPORINE AB C57BL/6 (B6) mice were injected i.v. with class I H-2-disparate B10.QBR spleen cells (10(7)/mouse). This regimen, termed ''donor alloantigen-specific i.v. presensitization'' (DSP), induced almost complete elimination of anti-B10.QBR mixed lymphocyte reaction/IL-2 production but did not affect the generation of CTL responses. Repeated (5 or 11 times) administration in vivo (over 7 or 18 days) of FK506 at suboptimal doses (0.75-1.0 mg/kg/day) failed to eliminate the capacities to exhibit MLR/IL-2 production and to generate CTL responses. Prolongation of skin graft survival was not induced by either of a single DSP or FK treatment (0.75-1.0 mg/kg/day, 11 times during 18 days) alone, but by the combination of these. Such combined treatment also resulted in almost complete reduction of CTL responses before (5 rounds of FK injection) or after (11 rounds of FK injection) recipients were engrafted with B10.QBR skin grafts. Under conditions in which lymphoid cells from mice receiving both treatments failed to generate CTL responses, the addition of recombinant IL-2 to cultures restored the CTL generation, suggesting that CTL precursors themselves are not attenuated by the combined treatment. Both prolongation of graft survival and suppression of CTL responses were obtained when the administration of FK506 was started before but not after DSP. Prolongation of graft survival could also be obtained in class I and II MHC-disparate combinations when the combined treatment was performed in a particular protocol. These results indicate that (1) DSP alone fails to prolong graft survival in class I and class I and II MHC-disparate combinations; (2) such failure is ascribed to the induction of CTL responses by CTL precursors and CTL helpers, both of which are DSP-resistant; (3) the administration of suboptimal doses of FK506 is not sufficient for the suppression of CTL responses, but is effective selectively for suppressing DSP-resistant CTL helpers; and (4) the combination of DSP with FK506 treatment in an appropriate protocol can thus prolong graft survival through the suppression of CTL-involved as well as CTL-independent graft rejection pathways. C1 OSAKA UNIV,SCH MED,BIOMED RES CTR,2-2 YAMADA OKA,SUITA,OSAKA 565,JAPAN. GIFU UNIV,SCH MED,DEPT SURG 1,GIFU 500,JAPAN. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 40 TC 18 Z9 18 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUL PY 1993 VL 56 IS 1 BP 173 EP 180 DI 10.1097/00007890-199307000-00032 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA LP580 UT WOS:A1993LP58000034 PM 7687396 ER PT J AU KEMPNER, ES AF KEMPNER, ES TI NOVEL PREDICTIONS FROM RADIATION TARGET ANALYSIS SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID LIVER 3-HYDROXY-3-METHYLGLUTARYL COENZYME; ACID BETA-GLUCOSIDASE; SIZE DETERMINATION; ADENYLATE-CYCLASE; FUNCTIONAL SIZE; BINDING-SITES; A REDUCTASE; INACTIVATION; RECEPTOR; MEMBRANES AB The unusual technique of radiation inactivation has been used to determine the mass of many different macromolecules. Most of the radiation target sizes obtained agree with the known protein structures. However, in several cases the sizes obtained were not easily interpreted since they did not agree with values determined by more conventional methods. Subsequent studies have shown that many of these perplexing radiation target sizes were indeed correct, often revealing unanticipated details about the nature of the systems being studied. RP KEMPNER, ES (reprint author), NIAMSD,PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 31 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 1993 VL 18 IS 7 BP 236 EP 239 DI 10.1016/0968-0004(93)90169-N PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LM679 UT WOS:A1993LM67900002 PM 8212129 ER EF