FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Suttles, J Evans, M Miller, RW Poe, JC Stout, RD Wahl, LM AF Suttles, J Evans, M Miller, RW Poe, JC Stout, RD Wahl, LM TI T cell rescue of monocytes from apoptosis: Role of the CD40-CD40L interaction and requirement for CD40-mediated induction of protein tyrosine kinase activity SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE inflammation; autoimmunity; signal transduction; flow cytometry ID MACROPHAGE EFFECTOR FUNCTION; NECROSIS-FACTOR-ALPHA; B-CELLS; PERIPHERAL-BLOOD; PLASMA-MEMBRANES; DEATH APOPTOSIS; DENDRITIC CELLS; LYMPHOCYTES-T; CROSS-LINKING; ACTIVATION AB Circulating monocytes have a limited life span and will undergo apoptosis in the absence of specific stimuli, Recent studies have demonstrated that monocytes can be rescued from apoptosis via lipopolysaccharide (LPS) activation or stimulation with interleukin-l or tumor necrosis factor-alpha. Based on previous studies from our laboratory, we hypothesized that, in nonseptic (e.g., autoimmune) inflammation, the presence of activated T cells may enhance monocyte longevity through T cell contact-dependent signaling. Plasma membranes prepared from 6 h activated (Tm-A) and resting (Tm-R) purified CD4(+) T cells were added to resting elutriation-purified monocytes cultured in serum-free medium, Cells were assayed for degree of apoptosis occurring over a 72-h incubation using both agarose gel electrophoresis and flow cytometry, The addition of Tm-A (but not Tm-R) was capable of blocking monocyte apoptosis and the ability of Tm-A to rescue monocytes was abrogated by the addition of anti-CD40L antibodies, Rescue of monocytes from apoptosis could also be mediated by direct cross-linking of monocyte CD40. Inhibitors of tyrosine kinase activity blocked both Tm-A and anti-CD40-mediated rescue of monocytes from apoptosis, suggesting a primary role of a tyrosine kinase signaling pathway in the events controlling monocyte longevity. C1 E TENNESSEE STATE UNIV,JAMES H QUILLEN COLL MED,DEPT MICROBIOL,JOHNSON CITY,TN 37614. NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,NIH,BETHESDA,MD 20892. RP Suttles, J (reprint author), E TENNESSEE STATE UNIV,JAMES H QUILLEN COLL MED,DEPT BIOCHEM,PROGRAM IMMUNOL,BOX 70581,JOHNSON CITY,TN 37614, USA. FU NIAID NIH HHS [R01-AI34875] NR 41 TC 30 Z9 33 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 1996 VL 60 IS 5 BP 651 EP 657 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VT474 UT WOS:A1996VT47400013 PM 8929557 ER PT J AU Biesecker, LG Kang, S Schaffer, AA Abbott, M Kelley, RI Allen, JC Clericuzio, C Grebe, T Olney, A Graham, JM AF Biesecker, LG Kang, S Schaffer, AA Abbott, M Kelley, RI Allen, JC Clericuzio, C Grebe, T Olney, A Graham, JM TI Exclusion of candidate loci and cholesterol biosynthetic abnormalities in familial Pallister-Hall syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE hypothalamic hamartoma; polydactyly; autosomal dominant inheritance; linkage analysis ID LEMLI-OPITZ SYNDROME; CONGENITAL HYPOTHALAMIC HAMARTOBLASTOMA; LINKAGE ANALYSIS; IMPERFORATE ANUS; HYPOPITUITARISM; TRANSLOCATION; DELINEATION AB Pallister-Hall syndrome (PHS) was originally described in 1980 in six sporadic cases of children with structural anomalies including hypothalamic hamartoma, polydactyly, imperforate anus, and renal and pulmonary anomalies. In 1993, the first familial cases were reported, including affected sibs and vertical transmission. Three of these families are sufficiently large to allow initial evaluation by linkage studies to candidate genes or loci. We have evaluated candidate loci for PHS based on three clinical observations. The first is a patient with PHS-like malformations, including a hypothalamic hamartoma, and an unbalanced translocation involving 7q and 3p. The second is a family with familial PHS where the founder's father had an autosomal dominant hand malformation previously mapped to 17q. The third is the phenotypic overlap of PHS and Smith-Lemli-Opitz syndrome. In this report, we exclude these loci as candidates for linkage to the PHS phenotype on the basis of lod scores of less than -2.0. We conclude that hypothalamic hamartoma is not specific to PHS and that the dominant hand mal- formation in one of the families was a coincidence. To evaluate the relationship of PHS to Smith-Lemli-Opitz syndrome, we analysed levels of cholesterol and intermediate metabolites of the later stages of cholesterol biosynthesis. There is no evidence of a generalised disorder of cholesterol biosynthesis in patients with familial PHS. On genetic and biochemical grounds, we conclude that PHS and Smith-Lemli-Opitz syndrome are not allelic variants of a single locus. C1 RICE UNIV,DEPT COMP SCI,HOUSTON,TX 77251. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NYU,MED CTR,NEW YORK,NY 10016. UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. UNIV ARIZONA,COLL MED,PHOENIX,AZ. UNIV NEBRASKA,SCH MED,OMAHA,NE 68198. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP Biesecker, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,49 CONVENT DR,ROOM 4A80,BETHESDA,MD 20892, USA. RI Schaffer, Alejandro/F-2902-2012 FU NICHD NIH HHS [HD24061]; NIDDK NIH HHS [DK44933] NR 24 TC 6 Z9 7 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 1996 VL 33 IS 11 BP 947 EP 951 DI 10.1136/jmg.33.11.947 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VU423 UT WOS:A1996VU42300010 PM 8950676 ER PT J AU Newcomb, WW Homa, FL Thomsen, DR Booy, FP Trus, BL Steven, AC Spencer, JV Brown, JC AF Newcomb, WW Homa, FL Thomsen, DR Booy, FP Trus, BL Steven, AC Spencer, JV Brown, JC TI Assembly of the herpes simplex virus capsid: Characterization of intermediates observed during cell-free capsid formation SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE herpes simplex virus; capsid assembly; electron microscopy; scaffolding protein; procapsid ID RECOMBINANT BACULOVIRUSES; BACTERIOPHAGE-LAMBDA; TYPE-1 PROTEASE; MOLECULAR-ORGANIZATION; SUBSTRATE ICP35; VIRAL GROWTH; AMINO-ACIDS; DNA; PROTEINS; MATURATION AB The herpes simplex virus-1 (HSV-1) capsid is an icosahedral shell approximately 15 nm thick and 125 nm in diameter. Three of its primary structural components are a major capsid protein (VP5; coded by the UL19 gene) and two minor proteins, VP19C (UL38 gene) and VP23 (UL18 gene). Assembly of the capsid involves the participation of two additional. proteins, the scaffolding protein (UL26.5 gene) and the maturational protease (UL26 gene). With the goal of identifying morphological intermediates in the assembly process, we have examined capsid formation in a cell-free system containing the five HSV-1 proteins mentioned above. Capsids and capsid-related structures formed during progressively longer periods of incubation were examined by electron microscopy of thin-sectioned specimens. After one minute, 90 minutes and eight hours of incubation the structures observed, respectively, were partial capsids, dosed spherical capsids and polyhedral capsids. Partial capsids were two-layered structures consisting of a segment of external shell partially surrounding a region of scaffold. They appeared as wedges or angular segments of closed spherical capsids, the angle ranging from less than 30 degrees to greater than 270 degrees. Partial capsids are suggested to be precursors of closed spherical capsids because, whereas partial capsids were the predominant assembly product observed after one minute of incubation, they were rare in reactions incubated for 45 minutes or longer. Closed spherical capsids were highly uniform in morphology, consisting of a closed external shell surrounding a thick scaffold similar in morphology to the same layers seen in partial capsids. In negatively stained specimens, closed spherical capsids appeared round in profile, suggesting that they are spherical rather than polyhedral in shape. A three-dimensional reconstruction computed from cryoelectron micrographs confirmed that closed spherical capsids are spherical with T=16 icosahedral symmetry. The reconstruction showed further that, compared to mature HSV-1 capsids, closed spherical capsids are more open structures in which the capsid floor layer is less pronounced. In contrast to closed spherical capsids, polyhedral capsids exhibited distinct facets and vertices, indicating that they are icosahedral like the capsids in mature virions. Upon incubation in vitro, purified closed spherical capsids matured into polyhedral capsids, indicating that the latter arise by angularization of the former. Partial capsids, closed spherical capsids and polyhedral capsids were all found to contain VP5, VP19C, VP23, VP21 and the scaffolding protein; the scaffolding protein being predominantly in the immature, uncleaved form in all cases. Polyhedral capsids and closed spherical capsids were found to differ in their sensitivity to disruption at 2 degrees C. Closed spherical capsids were disassembled while polyhedral capsids were unaffected. Our results suggest that HSV-1 capsid assembly begins with the partial capsid and proceeds through a closed, spherical, unstable capsid intermediate to a closed, stable, icosahedral form similar to that found in the mature virion. Structures resembling HSV-1 partial capsids have been described as capsid assembly intermediates in Salmonella typhimurium bacteriophage P22. HSV-1 capsid maturation from a fragile, spherical state to a robust polyhedral form resembles the prohead maturation events undergone by dsDNA bacteriophages including lambda, T4 and P22. Because of this similarity, we propose the name procapsid for the closed spherical capsid intermediate in HSV-1 capsid assembly. (C) 1996 Academic Press Limited C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. PHARMACIA & UPJOHN INC,MOL BIOL RES,KALAMAZOO,MI 49001. NIAMSD,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,NIH,BETHESDA,MD 20892. NIH,COMPUTAT BIOSCI & ENGN LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-137549] NR 62 TC 159 Z9 161 U1 3 U2 8 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 NOV 1 PY 1996 VL 263 IS 3 BP 432 EP 446 DI 10.1006/jmbi.1996.0587 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ148 UT WOS:A1996VQ14800006 PM 8918599 ER PT J AU Trus, BL Booy, FP Newcomb, WW Brown, JC Homa, FL Thomsen, DR Steven, AC AF Trus, BL Booy, FP Newcomb, WW Brown, JC Homa, FL Thomsen, DR Steven, AC TI The herpes simplex virus procapsid: Structure, conformational changes upon maturation, and roles of the triplex proteins VP19c and VP23 in assembly SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE herpes simplex virus; capsid assembly; cryo-electron microscopy; conformational changes; assembly scaffold ID CRYO-ELECTRON-MICROSCOPY; RECOMBINANT BACULOVIRUSES; 3-DIMENSIONAL STRUCTURE; CAPSID FORMATION; SIMIAN VIRUS-40; CLEAVAGE SITES; AMINO-ACIDS; GENE UL26; TYPE-1; DNA AB The proteins coded by the five major capsid genes of herpes simplex virus 1, VP5 (gene UL19), VP19c (UL38), VP23 (UL18), pre-VP22a (UL26.5), and pre-VP21 (UL26), assemble into fragile roundish ''procapsids'', which mature into robust polyhedral capsids in a transition similar to that undergone by bacteriophage proheads. Here we describe the HSV-1 procapsid structure to a resolution of similar to 2.7 nm from three-dimensional reconstructions of cryo-electron micrographs. Comparison with the mature capsid provides insight into the large-scale conformational changes that take place upon maturation. In the procapsid, the elongated protomers (VP5 subunits) make little contact with each other except around the bases of the herons and pentons, whereas they are tightly clustered into capsomers in the mature state; the axial channels, which are constricted or blocked in the mature capsid, are fully open; and unlike the well observed 6-fold symmetry of mature herons, procapsid herons are distorted into oval and triangular shapes. These deformations reveal a VP5 domain in the inner part of the protrusion wall which participates in inter-protomer bonding in the procapsid and is close to the site where the channel closes upon maturation. Remarkably, there are no direct contacts between neighboring capsomers; instead, interactions between them are mediated by the ''triplexes'' at the sites of local 3-fold symmetry. This observation discloses the mechanism whereby the tripler proteins, VP19c and VP23, play their essential roles in capsid morphogenesis. In the mature capsid, density extends continuously between neighboring capsomers in the inner ''floor'' layer. In contrast, there are large gaps in the corresponding region of the procapsid, implying that formation of the floor involves extensive remodeling. Inside the procapsid shell is the hollow spherical scaffold, whose radial density profile indicates that the major scaffold protein, pre-VP22a, is a long molecule (>24 nm) composed of three domains. Since no evidence of icosahedral symmetry is detected in the scaffold, we infer that (unless higher resolution is required) the scaffold may not be an icosahedral shell but may instead be a protein micelle with a preferred radius of curvature. (C) 1996 Academic Press Limited C1 NIAMS,STRUCT BIOL LAB,NIH,BETHESDA,MD 20892. NIH,COMPUTAT BIOSCI & ENGN LAB,DCRT,BETHESDA,MD 20892. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,CTR CANC,CHARLOTTESVILLE,VA 22908. PHARMACIA & UPJOHN INC,MOL BIOL RES,KALAMAZOO,MI 49001. FU NIAID NIH HHS [AI-1375549] NR 59 TC 174 Z9 178 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 NOV 1 PY 1996 VL 263 IS 3 BP 447 EP 462 DI 10.1016/S0022-2836(96)80018-0 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VQ148 UT WOS:A1996VQ14800007 PM 8918600 ER PT J AU McCormick, JL McKee, TC Cardellina, JH Leid, M Boyd, MR AF McCormick, JL McKee, TC Cardellina, JH Leid, M Boyd, MR TI Cytotoxic triterpenes from a marine sponge, Stelletta sp SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID JASPIS-STELLIFERA; MALABARICANE TRITERPENES; COLLECTION; PIGMENT AB Bioassay-guided fractionation of an extract of a marine sponge, Stelletta sp., has led to the isolation and characterization of four new cytotoxic isomalabaricane triterpenes, named stellettins C (1), D (2), E (3), and F (4). Three known triterpenes (5-7) were also isolated from the same extract. The most sensitive of the tested cell Lines (e.g., leukemia, central nervous system, renal) generally responded with GI(50) concentrations in the low-to-mid nanomolar range. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21702. OREGON STATE UNIV,COLL PHARM,CORVALLIS,OR 97331. NR 15 TC 39 Z9 43 U1 0 U2 1 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 NOV PY 1996 VL 59 IS 11 BP 1047 EP 1050 DI 10.1021/np960541v PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VV628 UT WOS:A1996VV62800010 PM 8946745 ER PT J AU Putnam, FW Carlson, EB Ross, CA Anderson, G Clark, P Torem, M Bowman, ES Coons, P Chu, JA Dill, DL Loewenstein, RJ Braun, BG AF Putnam, FW Carlson, EB Ross, CA Anderson, G Clark, P Torem, M Bowman, ES Coons, P Chu, JA Dill, DL Loewenstein, RJ Braun, BG TI Patterns of dissociation in clinical and nonclinical samples SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID MULTIPLE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ABUSE; EATING DISORDERS; VIETNAM VETERANS; COMBAT VETERANS; EXPERIENCES; BORDERLINE; CHILDHOOD; TRAUMA AB Research has consistently found elevated mean dissociation scores in particular diagnostic groups. In this study, we explored whether mean dissociation scores for different diagnostic groups resulted from uniform distributions of scores within the group or were a function of the proportion of highly dissociative patients that the diagnostic group contained. A total of 1566 subjects who were psychiatric patients, neurological patients, normal adolescents, or normal adult subjects completed the Dissociative Experience Scale (DES). An analysis of the percentage of subjects with high DES scores in each diagnostic group indicated that the diagnostic group's mean DES scores were a function of the proportion of subjects within the group who were high dissociators. The results contradict a continuum model of dissociation but are consistent with the existence of distinct dissociative types. C1 BELOIT COLL,BELOIT,WI 53511. CHARTER HOSP DALLAS,PLANO,TX. ST BONIFACE GEN HOSP,WINNIPEG,MB R2H 2A6,CANADA. AKRON GEN MED CTR,AKRON,OH. INDIANA UNIV,SCH MED,INDIANAPOLIS,IN. MCLEAN HOSP,BELMONT,MA 02178. SHEPPARD & ENOCH PRATT HOSP,TOWSON,MD. RUSH N SHORE MED CTR,CHICAGO,IL. RP Putnam, FW (reprint author), NIMH,UNIT DEV TRAUMATOL,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Carlson, Eve/E-3520-2010 OI Carlson, Eve/0000-0002-4431-2415 NR 48 TC 151 Z9 153 U1 4 U2 14 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 1996 VL 184 IS 11 BP 673 EP 679 DI 10.1097/00005053-199611000-00004 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VW027 UT WOS:A1996VW02700004 PM 8955680 ER PT J AU Goldstein, DS Lenders, JWM Kaler, SG Eisenhofer, G AF Goldstein, DS Lenders, JWM Kaler, SG Eisenhofer, G TI Catecholamine phenotyping: Clues to the diagnosis, treatment, and pathophysiology of neurogenetic disorders SO JOURNAL OF NEUROCHEMISTRY LA English DT Review DE neurochemistry; catecholamines; norepinephrine; dopamine; DOPA; phenotype; neurogenetics ID DOPA-RESPONSIVE DYSTONIA; DIHYDROPTERIDINE REDUCTASE DEFICIENCY; HEREDITARY PROGRESSIVE DYSTONIA; SULFOTRANSFERASE GENE STM; VONHIPPEL-LINDAU DISEASE; MOUSE FETAL DEVELOPMENT; CARDIO-FACIAL SYNDROME; TUMOR-SUPPRESSOR GENE; CYCLOHYDROLASE-I GENE; MENKES DISEASE AB One purpose of clinical neurochemistry has been to indicate ''activities'' of catecholamine systems, by assaying levels of the effector compounds or their metabolites in body fluids such as plasma, cerebrospinal fluid, urine, or microdialysate. This review discusses a new purpose: relating specific catecholaminergic phenotypes to neurogenetic disorders. Distinctive catecholamine patterns in several neurogenetic conditions reflect enzyme deficiencies as direct or indirect effects of gene mutations. These neurochemical patterns can provide potentially important clues to the diagnosis, treatment, and pathophysiology of neurogenetic disorders. Linking genetic abnormalities with molecular mechanisms and clinical manifestations of disease represents a useful new direction in clinical neurochemistry. C1 UNIV NIJMEGEN, NIJMEGEN, NETHERLANDS. RP Goldstein, DS (reprint author), NINCDS, NIH,CLIN NEUROSCI BRANCH,10-6N252,10 CTR DR, MSC 1424, BETHESDA, MD 20892 USA. RI Lenders, J.W.M./L-4487-2015 NR 87 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1996 VL 67 IS 5 BP 1781 EP 1790 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VM684 UT WOS:A1996VM68400001 PM 8863481 ER PT J AU Hahm, SH Eiden, LE AF Hahm, SH Eiden, LE TI Tissue-specific expression of the vasoactive intestinal peptide gene requires both an upstream tissue specifier element and the 5' proximal cyclic AMP-responsive element SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE vasoactive intestinal peptide; gene expression; signal transduction; cyclic AMP-responsive element; protein kinase C; neuroblastoma cells ID NEUROBLASTOMA CELL-LINE; NEURO-BLASTOMA CELLS; ALPHA-SUBUNIT GENE; BINDING PROTEINS; TRANSCRIPTION; POLYPEPTIDE; ENHANCER; ACID; FAMILY; GROWTH AB An upstream enhancer element [tissue specifier element (TSE)] located between 4.66 and 4.02 kb from the transcription start site is important for cell type-specific expression and phorbol ester induction of the vasoactive intestinal peptide (VIP) gene. An element located within 100 bases of the VIP promoter [the VIP cyclic AMP-responsive element (VIP-CRE)] confers cyclic AMP and phorbol ester responsiveness to heterologous promoters. The possibility that these two regions of the VIP gene function cooperatively to determine tissue-specific and second messenger-dependent expression of the VIP gene was addressed by assaying transcription from a VIP-luciferase reporter gene with progressive deletions from the 5' flanking sequence of the gene, with or without inactivation of the proximal VIP-CRE. Basal expression of the reporter gene in both SH-EP and SK-N-SH human neuroblastoma cells, which express endogenous VIP mRNA, was absolutely dependent on the presence of the upstream TSE. Full constitutive expression was also dependent on the intact VIP-CRE. Forskolin-mediated induction of the reporter gene in SH-EP and SK-N-SH cells was completely abolished by mutations in the VIP-CRE but not by deletion of the upstream sequence, indicating that the VIP-CRE alone determines cyclic AMP responsiveness. In contrast to reports that the VIP-CRE imparts 12-O-teaatradecanoylphorbol 13-acetate (phorbol 12-myristate 13-acetate; PMA) responsiveness to heterologous promoters, PMA stimulation in SK-N-SH cells was independent of an intact VIP-CRE but dependent on a region between -2.5 kb and the VIP-CRE. Sequencing of the entire 5.2-kb VIP 5' flank revealed a consensus PMA-responsive element (TGACTCA) 2.25 kb upstream of the transcription start site that may represent the site imparting PMA responsiveness to the VIP gene. RP Hahm, SH (reprint author), NIMH,CELL BIOL LAB,NIH,MOL NEUROSCI SECT,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892, USA. OI Eiden, Lee/0000-0001-7524-944X NR 35 TC 19 Z9 20 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 NOV PY 1996 VL 67 IS 5 BP 1872 EP 1881 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VM684 UT WOS:A1996VM68400012 PM 8863492 ER PT J AU Chen, G Pan, BS Hawver, DB Wright, CB Potter, WZ Manji, HK AF Chen, G Pan, BS Hawver, DB Wright, CB Potter, WZ Manji, HK TI Attenuation of cyclic AMP production by carbamazepine SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE carbamazepine; adenylyl cyclase; seizure; mania; anticonvulsant; cyclic AMP response element binding protein ID BIPOLAR AFFECTIVE-DISORDER; DEPENDENT PROTEIN-KINASE; RAT-BRAIN SLICES; ADENOSINE-MONOPHOSPHATE; SIGNAL-TRANSDUCTION; CEREBRAL-CORTEX; IN-VITRO; LITHIUM; CAMP; RECEPTORS AB The anticonvulsant carbamazepine is an effective treatment both for epilepsy and for bipolar affective disorder, but the molecular mechanism(s) underlying its therapeutic effects have not been identified. We have found that carbamazepine exerts significant inhibitory effects on the cyclic AMP (cAMP) generating system. Within the clinical therapeutic range (similar to 50 mu M), carbamazepine inhibited both basal and forskolin-stimulated cAMP production, without having any significant effects on phosphodiesterase activity. Carbamazepine also exerted its inhibitory effects on the cAMP generating system in pertussis toxin-treated cells, suggesting that the action of carbamazepine was likely mediated through an inhibitory guanine nucleotide binding protein-independent mechanism. A forskolin affinity purification column was used to purify adenylyl cyclases from rat cerebral cortex, and we found that carbamazepine inhibited both basal and forskolin-stimulated activity of purified adenylyl cyclase. We also investigated the effects of carbamazepine on the levels of the transcription factor, cAMP response element binding protein in the phosphorylated (active) state, and found that carbamazepine significantly inhibited forskolin-induced phosphorylation of the cAMP response element binding protein. The data indicate that carbamazepine inhibits adenylyl cyclase activity as well as the downstream effects of activation of adenylyl cyclase. C1 WAYNE STATE UNIV, SCH MED, DEPT PSYCHIAT & BEHAV NEUROSCI, DETROIT, MI 48201 USA. DETROIT RECEIVING HOSP & UNIV HLTH CTR, NEUROPSYCHIAT RES UNIT, DETROIT, MI USA. NIMH, CLIN PHARMACOL SECT, BETHESDA, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 52 TC 57 Z9 59 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1996 VL 67 IS 5 BP 2079 EP 2086 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VM684 UT WOS:A1996VM68400037 PM 8863517 ER PT J AU Young, WS Shepard, E Amico, J Hennighausen, L Wagner, KU LaMarca, ME McKinney, C Ginns, EI AF Young, WS Shepard, E Amico, J Hennighausen, L Wagner, KU LaMarca, ME McKinney, C Ginns, EI TI Deficiency in mouse oxytocin prevents milk ejection, but not fertility or parturition SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE homologous recombination; lactation; mammary gland; reproduction paraventricular; supraoptic ID CORTICOTROPIN-RELEASING FACTOR; FACTOR MESSENGER-RNA; PARAVENTRICULAR NUCLEUS; IMMUNOREACTIVE NEURONS; RAT NEUROHYPOPHYSIS; STIMULATED RELEASE; MATERNAL-BEHAVIOR; GENE-EXPRESSION; HUMAN-PLASMA; VASOPRESSIN AB Oxytocin is a nonapeptide hormone that participates in the regulation of parturition and lactation. It has also been implicated in Various behaviors, such as mating and maternal, and memory, To investigate whether or not oxytocin (OT) is essential for any of these functions, we eliminated, by homologous recombination, most of the first intron and the last two exons of the OT gene in mice. Those exons encode the neurophysin portion of the oxytocin preprohormone which is hypothesized to help in the packaging and transport of OT, The homozygous mutant mice have no detectable neurophysin or processed oxytocin in the paraventricular nucleus, supraoptic nucleus or posterior pituitary, Interestingly, homozygous mutant males and females are fertile and the homozygous mutant females are able to deliver their litters. However, the pups do not successfully suckle and die within 24 h without milk in their stomachs. OT injection into the dams restores the milk ejection in response to suckling. These results indicate an absolute requirement for oxytocin for successful milk ejection, but not for mating, parturition and milk production, in mice. C1 NIMH, CELL BIOL LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROSCI BRANCH, NATL INST HLTH, BETHESDA, MD 20892 USA. NIDDK, BIOCHEM & METAB LAB, PITTSBURGH, PA 15261 USA. UNIV PITTSBURGH, SCH MED, DIV ENDOCRINOL & METAB, PITTSBURGH, PA 15261 USA. VET ADM MED CTR, PITTSBURGH, PA 15261 USA. RI Young, W Scott/A-9333-2009; Wagner, Kay-Uwe/B-6044-2009 OI Young, W Scott/0000-0001-6614-5112; NR 63 TC 192 Z9 192 U1 1 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD NOV PY 1996 VL 8 IS 11 BP 847 EP 853 DI 10.1046/j.1365-2826.1996.05266.x PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA VQ835 UT WOS:A1996VQ83500006 PM 8933362 ER PT J AU Voskuhl, RR Farris, RW Nagasato, K McFarland, HF Dalcq, MD AF Voskuhl, RR Farris, RW Nagasato, K McFarland, HF Dalcq, MD TI Epitope spreading occurs in active but not passive EAE induced by myelin basic protein SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE epitope spreading; myelin basic protein; proteolipid protein; T lymphocyte; experimental allergic encephalomyelitis ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GLUTAMIC-ACID DECARBOXYLASE; PROTEOLIPID PROTEIN; SJL MICE; ENCEPHALITOGENIC DETERMINANT; ADOPTIVE TRANSFER; IMMUNE-RESPONSE; SPINAL-CORD; EXPRESSION AB Using experimental allergic encephalomyelitis, EAE, as a model for the study of autoimmune demyelinating disease in the CNS, previous studies have indicated that spread may occur with respect to the specificity of T cell responses during disease. This phenomenon, known as epitope spreading, is central to therapeutic strategies in multiple sclerosis (MS). However, in EAE, the clinical course, neuropathology and immunopathogenesis vary depending upon host factors and the method of disease induction. Since passive EAE in SJL/J mice resembles MS clinically and neuropathologically, this model was chosen to study the immune phenomenon of epitope spreading. T cells specific for whole 18.5 kDa MBP were used to initiate disease since MBP or one of its naturally occurring cleavage fragments may initiate a more physiological immune response than one generated to an artificially designed synthetic peptide. While a progressive increase in T cell responsiveness specific for the immunodominant MBP 87-106 region was observed during disease, there was no evidence of either intermolecular epitope spreading to the immunodominant region of proteolipid protein (PLP) 139-151 or of intramolecular epitope spreading to the exon 2 encoded region of MBP, which is spliced out of 18.5 kDa MBP. In addition there was no shift in immunodominance toward the subdominant MBP 16-35 region during disease. In contrast, during active EAE induced by MBP, epitope spreading to the immunodominant epitope of PLP, 139-151, was observed. These data demonstrate that immune responses generated during passive versus active EAE may differ, and suggest that significant epitope spreading does nor occur in chronic relapsing demyelinating disease initiated with T cells specific for whole MBP in the absence of exogenous antigen, complete Freund's adjuvant and pertussis. Implications of these findings with regard to epitope spreading in MS are discussed. C1 NINCDS,VIRAL & MOL PATHOGENESIS LAB,NIH,BETHESDA,MD 20892. NINCDS,NEUROIMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NR 34 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV PY 1996 VL 70 IS 2 BP 103 EP 111 DI 10.1016/S0165-5728(96)00054-9 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA VN223 UT WOS:A1996VN22300002 PM 8898718 ER PT J AU Krauzlis, RJ Miles, FA AF Krauzlis, RJ Miles, FA TI Release of fixation for pursuit and saccades in humans: Evidence for shared inputs acting on different neural substrates SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MONKEY SUPERIOR COLLICULUS; HUMAN EXPRESS SACCADES; SHORT REACTION-TIMES; EYE-MOVEMENTS; SMOOTH-PURSUIT; VISUAL-ATTENTION; RHESUS-MONKEY; RESPONSES; LATENCY; MOTION AB 1. In three human subjects, we measured the latency of pursuit and saccadic eye movements made to an eccentric target after a fixated central target was extinguished. In one set of experiments, we varied the time interval between the extinction of the central target and the appearance of the eccentric target (''gap duration''). In a second set of experiments, we varied the eccentricity at which the second target appeared. 2. Varying the gap duration produced similar changes in the latencies of pursuit and saccades. Gaps as short as 30 ms caused significant decreases in latency; progressively longer gaps produced shorter latencies, reaching a minimum for gaps of 150-200 ms. Over the range of gap durations used, the latencies of pursuit and saccades displayed the same dependence on gap duration. 3. Varying the eccentricity of the second target produced different effects on the latencies of pursuit and saccades. Saccade latencies increased when the eccentricity of the second target was decreased from 4 degrees to 0.5 degrees, whereas pursuit latencies were not consistently altered. Despite these differences in the dependence on retinal eccentricity between pursuit and saccades, imposing a 200-ms gap between the extinction of the fixation point and appearance of the second target still reduced the latency of both. 4. Our results are consistent with the idea that the mechanisms underlying the release of fixation fur pursuit and saccades have shared inputs but a different neural substrate. The common dependence on gap duration may indicate that a single preparatory input coordinates bath types of movements. The different dependence on retinal eccentricity indicates that there are differences in the spatial organization of the premotor circuits that trigger the onset of the two types of movements. RP Krauzlis, RJ (reprint author), NEI, SENSORIMOTOR RES LAB, NIH, BLDG 49, RM 2A-50, BETHESDA, MD 20892 USA. NR 50 TC 101 Z9 101 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1996 VL 76 IS 5 BP 2822 EP 2833 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT082 UT WOS:A1996VT08200002 PM 8930235 ER PT J AU Colby, CL Duhamel, JR Goldberg, ME AF Colby, CL Duhamel, JR Goldberg, ME TI Visual, presaccadic, and cognitive activation of single neurons in monkey lateral intraparietal area SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSTERIOR PARIETAL CORTEX; SACCADE-RELATED ACTIVITY; LIGHT-SENSITIVE NEURONS; SUPERIOR COLLICULUS; EYE-MOVEMENTS; SELECTIVE ATTENTION; ASSOCIATION CORTEX; SPACE; RESPONSES; MACAQUE AB 1. Posterior parietal cortex contains neurons that are visually responsive and active in relation to saccadic eye movements. We recorded from single neurons in a subregion of parietal cortex, the lateral intraparietal area (LIP), in alert rhesus monkeys. To characterize more completely the circumstances under which LTP neurons are responsive, we used five tasks designed to test the impact of sensory, motor, and cognitive factors. We obtained quantitative data in multiple tasks in 91 neurons. We measured neural activity during central fixation and in relation to stimulus onset and saccade onset. 2. LIP neurons have visual responses to the onset of a stationary stimulus in the receptive field. These visual responses occurred both in tasks that require a subsequent eye movement toward the stimulus and in tasks in which eye movements are not permitted, indicating that this activity is sensory rather than presaccadic. 3. Visual responses were enhanced when the monkey had to use information provided by the stimulus to guide its behavior. The amplitude of the sensory response to a given stimulus was increased in a task in which the monkey would subsequently make a saccade to the location signaled by the stimulus, as compared with the amplitude of the visual response in a simple fixation task. 4. The visual response was also enhanced when the monkey attended to the stimulus without looking at it. This result shows that enhancement does not reflect saccade preparation because the response is enhanced even when the monkey is not permitted to make a saccade. Instead, enhancement reflects the allocation of attention to the spatial locus of the receptive field. 5. Many LIP neurons had saccade-related activity in addition to their visual responses. The visual response for most neurons was stronger than the saccade-related activation. 6. Saccade-related activity was independent of visual activity. Similar presaccadic activity was observed in trials that included a recent visual stimulus (memory-guided saccade task) and in trials with no visual stimulus (learned saccade task). 7. We observed increases in activity during fixation in tasks in which the monkey could anticipate the onset of a behaviorally significant stimulus. LIP neurons usually showed low levels of background firing in the fixation task during the period before stimulus onset. This background activity was increased in the peripheral attention and memory-guided saccade tasks during the period when the monkey was waiting for a behaviorally relevant stimulus to appear. 8. The results from these several tasks indicate that LIP neurons are activated in a variety of circumstances and are not involved exclusively in sensory processing or motor planning. The modulation of sensory responses by attention and anticipation suggests that cognitive factors play a major role in parietal function. C1 UNIV PITTSBURGH,DEPT NEUROSCI,PITTSBURGH,PA 15260. UNIV PITTSBURGH,CTR NEURAL BASIS COGNIT,PITTSBURGH,PA 15260. GEORGETOWN UNIV,SCH MED,DEPT NEUROL,WASHINGTON,DC 20007. RP Colby, CL (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 49,RM 2A50,BETHESDA,MD 20892, USA. RI Martin Arevalo, Elisa/L-4472-2014 OI Martin Arevalo, Elisa/0000-0002-4546-6440 NR 40 TC 425 Z9 427 U1 2 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1996 VL 76 IS 5 BP 2841 EP 2852 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT082 UT WOS:A1996VT08200004 PM 8930237 ER PT J AU Degtyarenko, MA Simon, ES Burke, RE AF Degtyarenko, MA Simon, ES Burke, RE TI Differential modulation of disynaptic cutaneous inhibition and excitation in ankle flexor motoneurons during fictive locomotion SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DISTAL HINDLIMB MUSCULATURE; PHASIC GAIN CONTROL; PRIMARY AFFERENTS; CAT; REFLEXES; INTERNEURONS; STIMULATION; RESPONSES; PATHWAYS; WALKING AB 1. Intracellular recording from extensor digitorum longus (EDL) and tibialis anterior (TA) alpha-motoneurons during fictive locomotion was used to examine patterns of modulation of oligo synaptic postsynaptic potentials (PSPs) produced by electrical stimulation of the cutaneous superficial peroneal (SP) and medial plantar (MPL) nerves in unanesthetized, decerebrate adult cats. 2. In all 20 EDL motoneurons studied, electrical stimulation of the SP nerve with single pulses at about twice threshold for the most excitable fibers in the nerve (2xT) produced either no synaptic potentials or relatively small oligosynaptic excitatory or Inhibitory PSPs (EPSPs or IPSPs), both at rest and during the extension phase of Fictive stepping. However, at the onset of the flexion phase large, presumably disynaptic IPSPs (central latencies 1.7-2.0 ms) appeared in the SP responses. These IPSPs usually decreased in amplitude later in the flexion phase despite maintained membrane depolarization. 3. In most (7/8) TA motoneurons, SP stimulation produced oligosynaptic EPSPs at rest and during the extension phase of fictive stepping. These EPSPs were suppressed during flexion in a majority of TA cells studied (5/8) but no clearly disynaptic IPSPs were found in any TA motoneuron. 4. In most EDL and TA motoneurons, stimulation of the MPL nerve produced oligosynaptic EPSPs at rest and during the extension phase, most with latencies in the presumably disynaptic range (less than or equal to 2.0 ms). When present, these MPL EPSPs were suppressed throughout the flexion phase of stepping in almost all EDL (18/20) and TA (6/5) motoneurons examined. 5. The available evidence suggests that these modulation effects during fictive stepping are due primarily to convergence of control information from the spinal central pattern generator (CPG) for locomotion onto segmental interneurons in the oligosynaptic cutaneous pathways. 6. These observations extend the evidence for precise differential control of transmission through cutaneous reflex pathways in the cat hindlimb by the locomotor CPG. Taken together with earlier evidence about locomotor modulation of cutaneous PSPs in flexor digitorum longus (FDL) motoneurons, the data suggest that cutaneous information from the dorsal surface of the foot, carried in part by the SP nerve, projects to digit motoneurons (FDL and EDL) through discrete sets of last-order interneurons that also receive powerful excitation from the locomotor CPG during flexion. In contrast, the last-order interneurons that convey excitatory information from the SP nerve to at least some TA motoneurons are inhibited by the CPG during flexion. 7. Another contrast resides in the fact that oligosynaptic cutaneous excitation from the plantar surface of the foot, via the MPL nerve, is suppressed in FDL, EDL, and TA motoneurons during the flexion phase of locomotion. The available Information is consistent with the possibility that MPL effects may be delivered to these motor nuclei by common interneurons. 8. We suggest an interneuronal circuitry that could account for these observations and discuss possible functional implications of modulation of these sensory pathways during locomotion. RP Degtyarenko, MA (reprint author), NINCDS,NEURAL CONTROL LAB,NIH,BLDG 49,RM 3A50,BETHESDA,MD 20892, USA. NR 33 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1996 VL 76 IS 5 BP 2972 EP 2985 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT082 UT WOS:A1996VT08200015 ER PT J AU Ren, K Dubner, R AF Ren, K Dubner, R TI Enhanced descending modulation of nociception in rats with persistent hindpaw inflammation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DORSAL HORN NEURONS; NUCLEUS RAPHE MAGNUS; RECEPTIVE-FIELD PROPERTIES; I PROJECTION NEURONS; MEDULLARY RETICULAR-FORMATION; SPINAL-CORD LESIONS; C-FOS EXPRESSION; BRAIN-STEM; PERIAQUEDUCTAL GRAY; SPINOMESENCEPHALIC TRACT AB 1. The role of descending brain stem modulatory systems in the development of persistent behavioral hyperalgesia and dorsal horn hyperexcitability was studied in rats with unilateral hindpaw inflammation. Inflammation was induced by intraplantar injection of complete Freund's adjuvant (CFA, 0.05 ml of an 1:1 oil/saline emulsion, 25 mu g Mycobacterium), or lambda carrageenan (1 mg/0.1 ml saline). Thermal hyperalgesia was assessed by testing paw withdrawal latency (PWL) to a noxious heat stimulus. Superficial dorsal horn nociceptive (nociceptive specific, NS, and wide dynamic range, WDR) neuronal activity in the lumbar spinal cord was recorded extracellularly in chloralose-anesthetized rats. 2. Bilateral lesions of the dorsolateral funiculus (DLFX) at the T10 level were made in 13 rats, and the development of thermal hyperalgesia in these rats was compared with sham-operated or nonoperated control rats. Ln rats receiving a 0.05-ml CFA injection, a similar magnitude of hyperalgesia developed in the inflamed paw in DLFX (n = 7) and control (n = 8) rats. In addition, there appeared to be a contralateral hyperalgesia that was most apparent between 2 and 24 h after injection of CFA in DLFX rats. The CFA-induced contralateral effects were significantly different (P < 0.05) from the control rats at 2 and 6 h. 3. The intensity of the thermal stimulus was reduced and a low dose of carrageenan (1 mg) was injected into one hindpaw to further reveal the potentiation of hyperalgesia in DLFX rats. Throughout the 0.5- to 4-h time period after the injection of carrageenan, the PWL of the inflamed paws in DLFX rats (n = 6) was significantly shorter than that of control rats (n = 10; 2-way analysis of variance, F-1.14, = 14.04, P < 0.01), suggesting the enhancement of hyperalgesia in DLFX rats. A hyperalgesia on the noninflamed paws was also more apparent in this experiment in DLFX rats, when compared with control rats. DLFX did not affect the baseline PWL of the rats. 4. A reversible spinalization was produced by application of a local anesthetic, lidocaine (2%, 0.1 ml), onto the dorsal surface of the thoracic cord (T10-12). This procedure produced thoracic spinal block that lasted for 90 min. The effects of thoracic lidocaine block on nociceptive neuronal activity were studied in 11 neurons (NS = 7, WDR = 4) in CFA-inflamed rats and 10 neurons (NS = 6, WDR = 4) in noninflamed naive rats. After the thoracic lidocaine block, rats showed increases in background activity, expansion of the receptive fields, and increased responses to noxious thermal, mechanical, and electrical stimuli. 5. Quantitative comparison revealed that the mean change in background firing rate of dorsal horn neurons was greater in inflamed [NS: 18.3 +/- 0.4 Hz, (mean +/- SE) n = 7; WDR: 10.9 +/- 0.7 Hz, n = 4] than that in noninflamed (NS: 2.3 +/- 0.3 Hz, n = 6; WDR: 3.3 +/- 0.4 Hz, n = 4) rats (P < 0.01, t-test) after thoracic lidocaine block. Thoracic saline application produced a 2.8 +/- 0.4 Hz decrease in background activity (2 NS and 2 WDR units). The expansion of the receptive fields after thoracic lidocaine block was also greater in inflamed (NS: 141 +/- 9% control, n = 6; WDR: 240 +/- 36% control, n = 4) than in noninflamed (NS: 114 +/- 9% control, n = 6; WDR: 167 +/- 21% control, n = 4) rats (P < 0.05, t-test). Thoracic saline did not produce a significant change in the receptive field size (105 +/- 9%, n = 4). The increases in responses to noxious thermal and mechanical stimuli after thoracic lidocaine block were also significantly greater in inflamed than in noninflamed rats (P < 0.01). There was no significant difference in the increase in responses to electrical stimulation of the sciatic nerve after Lidocaine between inflamed and noninflamed rats. 6. A local anesthetic block was produced by microinjection of lidocaine (2%, 0.5 mu l) into the medial rostroventral medulla, primarily the nucleus raphe magnus (NRM), and the changes in nociceptive neuronal activity (NS = 8, WDR = 5) were studied in CFA-inflamed rats. After the NRM lidocaine block, increased neuronal activity was observed in the majority of neurons, although reduced responsiveness also was seen. The effects of NRM lidocaine appeared 10 min after the injection and lasted for greater than or equal to 90 min. There were increases in background activity from 4.3 +/- 0.9 to 6.9 +/- 1.3 Hz (n = 13, P < 0.05), receptive field size from 248 +/- 50 to 308 +/- 52 mm(2) (n = 13, P < 0.05), noxious thermal responses from 279 +/- 46 to 721 +/- 153 impulses (n = 12, P < 0.01), and noxious pinch-evoked responses from 311 +/- 73 to 494 +/- 88 impulses (n = 13, P < 0.05). The increase in electrical stimulus-evoked responses after lidocaine did not reach statistical significance. The injection of saline (0.5 ml) into the NRM (n = 3) or lidocaine into the areas of the predorsal bundle (n = 1) or perifacial zone (n = 2) did not produce significant changes in neuronal activity. 7. The present study provides convergent behavioral and electrophysiological evidence that the blockade of the brain stem spinal descending pathways results in potentiation of behavioral hyperalgesia and dorsal horn hyperexcitability in rats with hindpaw inflammation. Quantitative comparison between inflamed and noninflamed rats revealed an enhanced net descending inhibition as a result of inflammation. The results of local anesthesia of the NRM suggest that this site of descending modulation is a source of enhanced net tonic inhibitory modulation in inflamed animals. The brain stem descending input to the spinal cord will dampen or counteract the cascade of events that ultimately lead to the development of inflammatory hyperalgesia. C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Ren, K (reprint author), UNIV MARYLAND, SCH DENT, DEPT ORAL & CRANIOFACIAL BIOL SCI, RM 5A-12, 666 W BALTIMORE ST, BALTIMORE, MD 21201 USA. FU NIDA NIH HHS [DA-10275] NR 77 TC 144 Z9 147 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1996 VL 76 IS 5 BP 3025 EP 3037 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT082 UT WOS:A1996VT08200019 PM 8930252 ER PT J AU Li, CY Peoples, RW Weight, FF AF Li, CY Peoples, RW Weight, FF TI Proton potentiation of ATP-gated ion channel responses to ATP and Zn2+ in rat nodose ganglion neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SYNAPTIC TRANSMISSION; HIPPOCAMPAL SLICES; SENSORY NEURONS; ACTIVATED CHANNELS; MAMMALIAN NEURONS; PHEOCHROMOCYTOMA CELLS; EXTRACELLULAR ATP; INTRACELLULAR PH; NERVOUS-SYSTEM; NMDA RECEPTORS AB 1. The modulation by protons of ATP-gated ion channel responses to ATP and Zn2+ was studied in freshly isolated rat nodose ganglion neurons using the whole cell parch-clamp technique. 2. Reduced external pH enhanced, whereas elevated external pH suppressed, current activated by 10 mu M ATP. The pH producing the half-maximal effect (EC(50)) at this ATP concentration was 7.1. 3. Acidification shifted the ATP concentration-response curve to the left, decreasing the EC(50) for ATP, and alkalinization shifted the ATP concentration-response curve to the right, increasing the EC(50) for ATP. Fitting the data to a single-site pH model yielded an apparent pk(a) of the site on the ATP-gated ion channel of 7.6. Between PH 6.8 and 7.8, a change of 0.1 DH unit was calculated to change the ATP EC(50) by 4.03 mu M. Changing pH did not alter the maximal response to ATP. 4. The potentiating effect of protons appeared to be due to a direct action on the ATP-gated channel, as it could not be explained by an increase in the concentration of one or more species of ATP. 5. Lowering PH also increased the potency of Zn2+ for enhancement of ATP-activated current without altering its maximal response. Changing the pH from 7.3 to 6.8 changed the Zn2+ EC(50) from 12 to 1.7 mu M. 6. The potentiation of ATP-activated current by protons could not be attributed solely to an increase in the affinity of the receptor for Zn2+, as the Zn2+ chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine did not alter the effect of protons. 7. Protons and Zn2+ do not appear to act at the same site on ATP-gated channels. as responses to maximally effective concentrations of Zn2+ were enhanced further by protons and vice verse. 8. These results suggest that protons regulate the function of P2X purinoceptors in rat nodose ganglion neurons by modulating the affinity of the binding sites for ATP and Zn2+ on these receptor channels. RP Li, CY (reprint author), NIAAA,CELLULAR & MOL NEUROBIOL LAB,NIH,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 62 TC 58 Z9 60 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1996 VL 76 IS 5 BP 3048 EP 3058 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT082 UT WOS:A1996VT08200021 PM 8930254 ER PT J AU Olson, CR Musil, SY Goldberg, ME AF Olson, CR Musil, SY Goldberg, ME TI Single neurons in posterior cingulate cortex of behaving macaque: Eye movement signals SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PARIETAL ASSOCIATION CORTEX; SACCADE-RELATED ACTIVITY; DORSOMEDIAL FRONTAL-CORTEX; HEAD-DIRECTION CELLS; RHESUS-MONKEY; CORTICOCORTICAL CONNECTIONS; SUBCORTICAL PROJECTIONS; CORTICAL AFFERENTS; SPATIAL PROPERTIES; VISUAL RESPONSES AB 1. Posterior cingulate cortex, although widely regarded as a part of the limbic system, is connected most strongly to parietal and frontal areas with sensory, motor, and cognitive functions. To gain insight into the functional nature of posterior cingulate cortex, we have recorded from its tasks known to activate parietal and frontal neurons. We have found that posterior cingulate neurons fire during periods of ocular fixation at a rate determined by the angle of gaze and by the size and direction of the preceding eye movement. 2. The activity of 530 posterior cingulate neurons was monitored while rhesus macaque monkeys made visually guided eye movements to spots projected on a tangent screen. 3. In 150/530 neurons, a statistically significant shift in the rate of discharge occurred around the time of onset of saccadic eye movements. The preponderant form of response was an increase in activity (142/150 neurons). 4. In 142 neurons exhibiting significant excitation after saccades in at least one direction, the level of discharge was analyzed as a function of time relative to onset of the saccade. Across the neuronal population as a whole, activity increased sharply at the moment of onset of the saccade, rising to a maximum after 200 ms and then declining slowly. The net level of discharge remained well above presaccadic baseline even after >1 s of postsaccadic fixation. 5. In 63 neurons, the postsaccadic rate of discharge was analyzed relative to the angle of the eye in the orbit by monitoring neuronal activity while the monkey executed saccades of uniform direction and amplitude to four targets spaced at 16-deg intervals along a line. The postsaccadic firing level was significantly dependent on orbital angle in 44/63 neurons. 6. In 45 neurons, the postsaccadic rate of discharge was analyzed relative to the angle of the eye in the orbit by monitoring neuronal activity while the monkey executed 16-deg saccades to a constant target from diametrically opposed starting points. The postsaccadic level of activity was significantly dependent on saccade direction in 20/5 neurons. 7. In 58 neurons, the postsaccadic rate of discharge was analyzed relative to saccade amplitude by monitoring neuronal activity while the monkey executed saccades, which varied in amplitude (4, 8, 16, and 32 deg) but which were constant in direction and brought the eye to bear on a constant endpoint. The postsaccadic level of activity was significantly dependent on saccade amplitude in 24/58 neurons. In all neurons exhibiting significant amplitude-dependence, stronger firing accompanied larger saccades. 8 The activity of in 10 neurons was monitored during smooth pursuit eye movements (20 deg/s upward, downward, leftward, and rightward). The level of firing varied as a function of both the position of the eye (9 neurons) and the velocity of the eye (6 neurons). 9. We conclude that posterior cingulate neurons monitor eye movements and eye position. It is unlikely that they participate in the generation of eye movements because their shifts of discharge follow the onset of the movements. Eye-movement-related signals in posterior cingulate cortex may reflect the participation of this area in assigning spatial coordinates to retinal images. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT NEUROL,WASHINGTON,DC 20007. RP Olson, CR (reprint author), CARNEGIE MELLON UNIV,MELON INST,CTR NEURAL BASIS COGNIT,ROOM 115,4400 5TH AVE,PITTSBURGH,PA 15213, USA. FU NINDS NIH HHS [R01 NS-27287] NR 70 TC 78 Z9 78 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1996 VL 76 IS 5 BP 3285 EP 3300 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT082 UT WOS:A1996VT08200040 PM 8930273 ER PT J AU Nick, TA Moreira, JE Kaczmarek, LK Carew, TJ Wayne, NL AF Nick, TA Moreira, JE Kaczmarek, LK Carew, TJ Wayne, NL TI Developmental dissociation of excitability and secretory ability in Aplysia bag cell neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EGG-LAYING HORMONE; RAT SUBMANDIBULAR-GLAND; ABDOMINAL-GANGLION; NEUROENDOCRINE CELLS; DIFFERENTIATION; CALIFORNICA; BEHAVIOR; AFTERDISCHARGE; NEUROPEPTIDES; PROTEINS AB 1. Despite the considerable progress made in understanding the role of electrical activity in triggering secretion, the developmental relationships between excitability and secretion are not well understood. The well-characterized bag cell neurons of Aplysia provide an advantageous system in which to investigate developmental interactions of these two key properties of neurons. 2. A prolonged afterdischarge triggers egg laying hormone (ELH) secretion in mature bag cell neurons. To investigate secretion in the developmental framework of excitability, we first examined whether immature neurons, which are incapable of the mature form of excitability (afterdischarge), contain ELH and whether this hormone is packaged in vesicles. We used immunoelectron microscopy to compare vesicular localization of ELH and to compare the size and density of ELH-containing vesicles in neurons from adult and juvenile Aplysia. This comparison revealed that immature neurons contain ELH in vesicles in the size range of secretory vesicles. However, they lack a class of large vesicles (>250 nm in diameter) that is characteristic of mature neurons. 3. To investigate whether the ELH contained in immature bag cell neurons could be secreted in response to electrical activity, we used the potassium channel blocker tetraethylammonium (TEA) combined with nerve stimulation to depolarize neurons from both juvenile animals (ovotestes do not contain eggs) and from adult Aplysia (ovotestes contain eggs). Using radioimmunoassay, we have found that the duration and amount of ELH secreted from bag cell neurons from juvenile Aplysia in response tc, TEA does not depend on whether or not the cells can be induced to afterdischarge, and the amount and duration of ELH secreted from bag cell neurons of juvenile Aplysia (whether or not they afterdischarged) differed from those secreted by adult neurons. However, by normalizing for body size, we found that the final estimated hemolymph concentration of ELH would be similar in juvenile and adult animals. 4. We investigated the potential functional significance of secretion of bag cell hormones in juvenile Aplysia by attempting to bypass the bag cell neurons and directly activate downstream elements with extract from adult bag cell neurons (BCE), known to contain ELH and other peptides. We found that juvenile Aplysia exhibit at least one component of egg-laying behavior, cessation of locomotion, in response to BCE during a developmental period (as measured by weight) in which they normally would possess neurons incapable of afterdischarge. Thus developmental regulation of excitability in the bag cell neurons may prevent inappropriate hormone release and subsequent premature expression of reproductive behaviors. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PHYSIOL,LOS ANGELES,CA 90095. YALE UNIV,DEPT CELLULAR & MOL PHYSIOL,NEW HAVEN,CT 06510. YALE UNIV,DEPT PSYCHOL,NEW HAVEN,CT 06510. YALE UNIV,DEPT BIOL,NEW HAVEN,CT 06510. NINCDS,NIH,BETHESDA,MD 20892. MARINE BIOL LAB,WOODS HOLE,MA 02543. YALE UNIV,DEPT PHARMACOL,INTERDEPARTMENTAL NEUROSCI PROGRAM,NEW HAVEN,CT 06510. FU NICHD NIH HHS [HD-28336]; NINDS NIH HHS [NS-78492] NR 35 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1996 VL 76 IS 5 BP 3351 EP 3359 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT082 UT WOS:A1996VT08200045 PM 8930278 ER PT J AU Partin, KM Fleck, MW Mayer, ML AF Partin, KM Fleck, MW Mayer, ML TI AMPA receptor flip/flop mutants affecting deactivation, desensitization, and modulation by cyclothiazide, aniracetam, and thiocyanate SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate receptors; cyclothiazide; aniracetam; thiocyanate; mutagenesis; AMPA; desensitization; deactivation; alternative splicing; flip and flap ID EXCITATORY SYNAPTIC CURRENTS; RAT HIPPOCAMPAL SLICES; OUTSIDE-OUT PATCHES; GLUTAMATE-OPERATED CHANNELS; ACID-BINDING PROTEINS; KAINATE RECEPTORS; ACETYLCHOLINE-RECEPTOR; BRAIN MEMBRANES; PURKINJE-CELLS; NMDA RECEPTOR AB AMPA receptor GluRA subunits with mutations at position 750, a residue shown previously to control allosteric regulation by cyclothiazide, were analyzed for modulation of deactivation and desensitization by cyclothiazide, aniracetam, and thiocyanate, Point mutations from Ser to Asn, Ala, Asp, Gly, Gin, Met, Cys, Thr, Leu, Val, and Tyr were constructed in GluRA(flip). The last four of these mutants were not functional; S750D was active only in the presence of cyclothiazide, and the remaining mutants exhibited altered rates of deactivation and desensitization for control responses to glutamate, and showed differential modulation by cyclothiazide and aniracetam. Results from kinetic analysis are consistent with aniracetam and cyclothiazide acting via distinct mechanisms. Our experiments demonstrate for the first time the functional importance of residue 750 in regulating intrinsic channel-gating kinetics and emphasize the biological significance of alternative splicing in the M3-M4 extracellular loop. C1 NICHHD,LCMN,NIH,BETHESDA,MD 20892. RI Mayer, Mark/H-5500-2013; Partin, Kathryn/A-8706-2015 OI Partin, Kathryn/0000-0003-3801-3299 NR 63 TC 272 Z9 280 U1 3 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1996 VL 16 IS 21 BP 6634 EP 6647 PG 14 WC Neurosciences SC Neurosciences & Neurology GA VN618 UT WOS:A1996VN61800002 PM 8824304 ER PT J AU Delaney, CL Brenner, M Messing, A AF Delaney, CL Brenner, M Messing, A TI Conditional ablation of cerebellar astrocytes in postnatal transgenic mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE astrocyte; cerebellum; development; glial fibrillary acidic protein; herpes simplex virus thymidine kinase; transgenic ID CENTRAL-NERVOUS-SYSTEM; FIBRILLARY ACIDIC PROTEIN; SIMPLEX VIRUS TYPE-1; THYMIDINE KINASE; PURKINJE-CELLS; GROWTH-FACTOR; OLIGODENDROCYTE DEVELOPMENT; GENETIC ABLATION; MOUSE CEREBELLUM; TOXIN GENE AB Astrocytes have been proposed to have multiple roles in the development and maintenance of the vertebrate CNS. To facilitate documentation of these roles, we designed a transgene to enable their ablation at selectable times. The transgene consists of the coding region for the herpes simplex virus-thymidine kinase (HSV-TK) under the control of the human glial fibrillary acidic protein gene promoter. The HSV-TK is innocuous but converts the antiherpetic agent ganciclovir (GCV) to a toxic product that interferes with DNA replication in proliferating cells. In a developmental study, transgenic mice were treated with GCV during the first postnatal week, with evaluation at P19. Treated mice displayed severe ataxia. Histological examination revealed disrupted astrocyte development, particularly in the cerebellum with marked secondary effects on other cell types. cerebellar defects included a loss in the numbers of astrocytes and an overall reduction in cerebellar size and disruption of the normally well defined cellular layers. Radial glia were disordered, Purkinje cells were ectopically distributed and displayed abnormal dendritic trees, and granule cells were markedly depleted. These effects were more severe in animals treated on postnatal day 1 versus treatment at day 5. A major factor causing granule cell death was excitotoxicity attributable to activation of NMDA receptors. These results suggest a critical role for astrocytes in cerebellar development. C1 UNIV WISCONSIN,SCH VET MED,DEPT PATHOBIOL SCI,MADISON,WI 53706. NINCDS,STROKE BRANCH,NATL INST HLTH,BETHESDA,MD 20892. RP Delaney, CL (reprint author), UNIV WISCONSIN,SCH VET MED,NEUROSCI TRAINING PROGRAM,2015 LINDEN DR W,MADISON,WI 53706, USA. NR 84 TC 86 Z9 88 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1996 VL 16 IS 21 BP 6908 EP 6918 PG 11 WC Neurosciences SC Neurosciences & Neurology GA VN618 UT WOS:A1996VN61800027 PM 8824329 ER PT J AU Smith, TG Lange, GD Marks, WB AF Smith, TG Lange, GD Marks, WB TI Fractal methods and results in cellular morphology - Dimensions, lacunarity and multifractals SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Review DE fractal geometry; fractal dimension; lacunarity; multifractal; self-similarity; cell borders ID OPTIC-NERVE; CELLS; NEURONS; DIFFERENTIATION; COMPLEXITY; GROWTH AB This paper discusses the concepts of fractal geometry in a cellular biological context. It defines the concept of the fractal dimension, D, as a measure of complexity and illustrates the two different general ways of quantitatively measuring D by length-related and mass-related methods. Then, these several Ds are compared and contrasted. A goal of the paper is to find methods other than length-related measures that can distinguish between two objects that have the same D but are structurally different. The mass-related D is shown potentially to be such a measure. The concept of lacunarity, L, is defined and methods of measuring L are illustrated. L is also shown to be a potentially distinguishing measure. Finally, the notion of multifracticality is defined and illustrated to exist in certain individual nerve and glial cells. C1 NINCDS,INSTRUMENTAT & COMP SECT,NIH,BETHESDA,MD 20892. NINCDS,NEURAL CONTROL LAB,NIH,BETHESDA,MD 20892. RP Smith, TG (reprint author), NINCDS,NEUROPHYSIOL LAB,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 31 TC 251 Z9 257 U1 2 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV PY 1996 VL 69 IS 2 BP 123 EP 136 DI 10.1016/S0165-0270(96)00080-5 PG 14 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VV820 UT WOS:A1996VV82000001 PM 8946315 ER PT J AU Matsuzawa, M Liesi, P Knoll, W AF Matsuzawa, M Liesi, P Knoll, W TI Chemically modifying glass surfaces to study substratum-guided neurite outgrowth in culture SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE chemical modification; culture; hippocampal neuron; laminin peptide; neurite outgrowth; substratum guidance ID COPLANAR MOLECULAR ASSEMBLIES; HIPPOCAMPAL-NEURONS; NEUROBLASTOMA-CELLS; LAMININ; GROWTH; ADHESION; GUIDANCE; IDENTIFICATION AB We describe here a modification procedure for chemically fabricating neuron adhesive substrates to study the substratum-guided neurite outgrowth in culture. These substrates were fabricated by chemically attaching a synthetic peptide derived from a neurite-outgrowth-promoting domain of the B2 chain of laminin. The attachment was carried out by coupling the peptide to an amine-derived glass surface using a heterobifunctional crosslinker. Hippocampal neurons were dissociated from embryonic rats and placed on the substrate at low-density in a chemically defined medium to examine the direct effect of the modified surface on their outgrowth. We observed that the neurons developed a morphology typical to that of hippocampal neurons having multiple short and single long processes within 24 h in culture. The chemical modification procedure was then combined with a UV-photo-masking technique to fabricate patterns of peptide surfaces on glass substrates. By culturing the hippocampal neurons on substrates having alternate stripes of peptide surface and non-adhesive surface, we demonstrated substratum-controlled changes in the neuronal morphology. The modification procedure presented here can be easily achieved in the standard culture facility and should be useful in fabricating an in vitro tool for studying substratum-guided neurite outgrowth. C1 NIAAA,MOL & CELLULAR NEUROBIOL LAB,ROCKVILLE,MD 20852. MAX PLANCK INST POLYMER RES,D-55128 MAINZ,GERMANY. RP Matsuzawa, M (reprint author), RIKEN,FRONTIER RES PROGRAM,WAKO,SAITAMA 35101,JAPAN. NR 20 TC 56 Z9 57 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD NOV PY 1996 VL 69 IS 2 BP 189 EP 196 DI 10.1016/S0165-0270(96)00052-0 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VV820 UT WOS:A1996VV82000008 PM 8946322 ER PT J AU Ruggieri, M Pavone, V Tine, A Polizzi, A Magro, G Duray, PH Merino, M Albanese, V AF Ruggieri, M Pavone, V Tine, A Polizzi, A Magro, G Duray, PH Merino, M Albanese, V TI Ossifying fibroma of the skull in a patient with neurofibromatosis type 1 - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE neurofibromatosis; fibrous dysplasia AB Ossifying fibroma is a rare, benign, primary bone tumor that occurs most commonly in the mandible; a cranial vault location is extremely rare. In this report a case of symptomatic frontoparietotemporal ossifying fibroma with intracranial growth and cerebral displacement in a 12-year-old boy with neurofibromatosis type 1 (NF1) is described. Once excised the lesion did not recur. The skeletal system is frequently affected in NF1, and bone abnormalities are present in 50% to 70% of patients with this condition. The etiology of such lesions in NF1 is still controversal. To the authors' knowledge, ossifying fibromas of calvarial bones have not been described in NF1. C1 UNIV CATANIA, INST NEUROSURG, CATANIA, ITALY. OXFORD RADCLIFFE HOSP, DEPT CLIN GENET, OXFORD, ENGLAND. NIH, DEPT HLTH & HUMAN SERV, PATHOL LAB, BETHESDA, MD 20892 USA. RP Ruggieri, M (reprint author), UNIV CATANIA, INST ATOM PATHOL, ORTHOPED CLIN, PEDIAT CLIN, DIV PEDIAT NEUROL, CATANIA, ITALY. OI Magro, Gaetano Giuseppe/0000-0003-3244-6827 NR 21 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 1996 VL 85 IS 5 BP 941 EP 944 DI 10.3171/jns.1996.85.5.0941 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA VP489 UT WOS:A1996VP48900028 PM 8893736 ER PT J AU Bartlett, ML Srinivasan, G Barker, WC Kitsiou, AN Dilsizian, V Bacharach, SL AF Bartlett, ML Srinivasan, G Barker, WC Kitsiou, AN Dilsizian, V Bacharach, SL TI Left ventricular ejection fraction: Comparison of results from planar and SPECT gated blood-pool studies SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE ejection fraction; SPECT gated blood-pool imaging; left ventricular function ID CORONARY-ARTERY DISEASE; EMISSION COMPUTED-TOMOGRAPHY; RADIONUCLIDE VENTRICULOGRAPHY; WALL-MOTION; VOLUME; PET AB Global ejection fraction (EF) from planar gated blood-pool (GBP) imaging is a widely accepted measure of cardiac function. It has been suggested that planar GBP could be replaced by SPECT. In this article, we compare counts-based global EF measured from SPECT and planar images and investigate reasons for discrepancies between the two. Methods: Twenty-three subjects were imaged with both planar and SPECT GBP. SPECT short-axis slices were projected to create reprojected images. Reprojected SPECT (rSPECT) images were created in both the true long-axis view and also in a view typical of planar studies (found to be 60 degrees from the true long-axis). Thus, angle of view effects on global EF could be investigated. In addition, we studied the effects of background and attenuation. Results: Long-axis rSPECT EF correlated well with planar EF (r = 0.89) but EF values were significantly higher for rSPECT than for planar (slope = 1.4, intercept = -8 EF units; p < 0.001). We found that background correction may not be necessary with rSPECT, but neither background nor attenuation explained the observed discrepancy between rSPECT and planar EFs. This discrepancy was found to be caused by atrial overlap in the planar image and disappeared when the SPECT slices were reprojected at the same angle of view as the planar images. Conclusion: Global EF can be easily measured from rSPECT GBP images. Long-axis rSPECT EFs are, however, greater than planar EFs by a factor of 1.4 because atrial overlap causes a significant drop in planar EF in planar images. These results suggest that (long-axis) rSPECT EFs may be more accurate than planar EFs. C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. NR 14 TC 45 Z9 47 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 1996 VL 37 IS 11 BP 1795 EP 1799 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VR846 UT WOS:A1996VR84600019 PM 8917177 ER PT J AU Byrne, C Ursin, G Ziegler, RG AF Byrne, C Ursin, G Ziegler, RG TI A comparison of food habit and food frequency data as predictors of breast cancer in the NHANES I/NHEFS cohort SO JOURNAL OF NUTRITION LA English DT Article DE humans; epidemiology; breast cancer; dietary habits; dietary fat ID DIETARY-FAT; FOLLOW-UP; EPIDEMIOLOGIC ANALYSES; NATIONAL-HEALTH; RISK; REPRODUCIBILITY; QUESTIONNAIRE; PATTERNS; VALIDITY AB We compared two methods of assessing dietary fat and breast cancer incidence in the first complete follow-up of the National Health Epidemiologic Follow-up Study (NHEFS) cohort. Between 1982 and 1984, 6156 women aged 32-86 y completed the NHEFS survey, which included a 93-item food frequency questionnaire (FFQ). In addition, women answered questions regarding food habits, such as choice of salad dressing, trimming fat from meat, and eating. skin on poultry. In the 4 y of follow-up, these women contributed a total of 23,949 person years, during which 53 women reported a breast cancer diagnosis. The rate ratio (RR) and 95% confidence interval (CI) for each quartile of percentage of energy from fat were 1.0, 0.96 (0.5-2.1), 1.0 (0.5-2.2) and 0.98 (0.5-2.1); Thus the breast cancer rates for women in the upper three quartiles, who reported a diet with higher than 30% of energy from fat, were not different from those of women in the lowest quartile of intake (less than or equal to 29.4% energy from fat). in contrast, the ''high-fat'' response to three of the four food habit questions identified women at increased risk of developing breast cancer: women who used salad dressings other than low fat had a RR and 95% CI of 1.3 (0.7-2.3), women who reported eating the skin on poultry had a RR and 95% CI of 1.7 (0.9-2.9), and women who did not use lean or extra lean ground beef had a RR and 95% CI of 2.2 (1.2-4.0). These food habit questions may be less subject to misclassification than dietary information of fat intake derived from the FFQ. Further investigation is needed to evaluate what is measured by the food habit questions. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. UNIV SO CALIF,DEPT PREVENT MED,LOS ANGELES,CA 90033. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. RI Byrne, Celia/K-2964-2015 OI Byrne, Celia/0000-0001-8289-4252 NR 30 TC 17 Z9 17 U1 2 U2 3 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 1996 VL 126 IS 11 BP 2757 EP 2764 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VT726 UT WOS:A1996VT72600008 PM 8914946 ER PT J AU Grether, JK Nelson, KB AF Grether, JK Nelson, KB TI Placental infection and risk of cerebral palsy in very low birth weight infants - Reply SO JOURNAL OF PEDIATRICS LA English DT Letter RP Grether, JK (reprint author), NINCDS, NIH, BETHESDA, MD 20892 USA. NR 9 TC 0 Z9 0 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 NOV PY 1996 VL 129 IS 5 BP 777 EP 778 DI 10.1016/S0022-3476(96)70180-4 PG 2 WC Pediatrics SC Pediatrics GA VR957 UT WOS:A1996VR95700042 ER PT J AU Pickworth, WB Fant, RV Butschky, MF Henningfield, JE AF Pickworth, WB Fant, RV Butschky, MF Henningfield, JE TI Effects of transdermal nicotine delivery on measures of acute nicotine withdrawal SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SMOKING CESSATION; CIGARETTE-SMOKING; TOBACCO WITHDRAWAL; CHEWING GUM; METAANALYSIS; DEPENDENCE; BATTERY; HUMANS; PATCH AB The effects of transdermal nicotine on acute physiologic, performance and subjective measures of tobacco withdrawal were evaluated in a residential, double-blind, placebo-controlled, crossover study. Ten subjects smoked ad libitum for 4 days and underwent monitored tobacco abstinence for 3 days. On no-smoking days, three transdermal nicotine delivery systems (patches) that delivered a total of 0, 10, 20 or 30 mg of nicotine were applied for 16 hr. Experimental measures were collected 6 hr after the application of the patches. Plasma levels of nicotine and cotinine indicated that the 20- and 30-mg treatment condition fully replaced the nicotine ordinarily Obtained from smoking. During nicotine abstinence (0 mg condition) typical signs of tobacco withdrawal were evident including: decreases in pulse rate, increases in electroencephalographic theta power, increases in subjective measures of tobacco abstinence and slowed performance on computer-delivered cognitive tests. Nicotine patch treatment diminished the physiologic and performance changes, but subjective measures of tobacco abstinence (cigarette craving, increases in withdrawal scores) were not significantly reduced. These data indicate that the nicotine patch may be used to diminish aspects of tobacco abstinence that could affect performance even though withdrawal discomfort may persist. RP Pickworth, WB (reprint author), NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,DIV INTRAMURAL RES,POB 5180,BALTIMORE,MD 21224, USA. NR 35 TC 38 Z9 38 U1 0 U2 0 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 NOV PY 1996 VL 279 IS 2 BP 450 EP 456 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT122 UT WOS:A1996VT12200002 PM 8930145 ER PT J AU Currens, MJ Gulakowski, RJ Mariner, JM Moran, RA Buckheit, RW Gustafson, KR McMahon, JB Boyd, MR AF Currens, MJ Gulakowski, RJ Mariner, JM Moran, RA Buckheit, RW Gustafson, KR McMahon, JB Boyd, MR TI Antiviral activity and mechanism of action of calanolide A against the human immunodeficiency virus type-1 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; RAIN-FOREST TREE; NONNUCLEOSIDE INHIBITORS; ESCHERICHIA-COLI; ZIDOVUDINE AZT; RESISTANCE; DNA; AIDS; RESOLUTION; EXPRESSION AB Calanolide A, recently discovered in extracts from the tropical rainforest tree, Calophyllum lanigerum, is a novel inhibitor of the human immunodeficiency virus (HIV) type 1. The compound is essentially inactive against strains of the less common HIV type 2. The present study focused on the further characterization of the selective,antiviral activity and mechanism of action of calanolide A. The compound inhibited a wide variety of laboratory strains of HIV type 1, with EC(50) values ranging from 0.10 to 0.17 mu M. The compound similarly inhibited promonocytotropic and lymphocytotropic isolates from patients in various stages of HIV disease, as well as drug-resistant strains. Viral life-cycle studies indicated that calanolide A acted early in the infection process, similar to the known HIV reverse transcriptase (RT) inhibitor 2', 3'-dideoxycytidine. In enzyme inhibition assays, calanolide A potently and selectively inhibited recombinant HIV type 1 RT but not cellular DNA polymerases or HIV type 2 RT within the concentration range tested. Serial passage of the virus in host cells exposed to increasing concentrations of calanolide A yielded a calanolide A resistant virus strain. RT from the resistant virus was not inhibited by calanolide A but retained sensitivity to other nonnucleoside as well as nucleoside RT inhibitors, including 3'-azido-2',3'-dideoxythymidine triphosphate and nevirapine. The study substantially supports the conclusion that calanolide A represents a novel subclass of nonnucleoside RT inhibitor which merits consideration for anti-HIV drug development. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT DIAG & CTR,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 37 TC 56 Z9 60 U1 0 U2 3 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 NOV PY 1996 VL 279 IS 2 BP 645 EP 651 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT122 UT WOS:A1996VT12200024 PM 8930167 ER PT J AU Currens, MJ Mariner, JM McMahon, JB Boyd, MR AF Currens, MJ Mariner, JM McMahon, JB Boyd, MR TI Kinetic analysis of inhibition of human immunodeficiency virus type-1 reverse transcriptase by calanolide A SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NONNUCLEOSIDE INHIBITORS; 1-<(2-HYDROXYETHOXY)METHYL>-6-(PHENYLTHIO)THYMINE DERIVATIVES; SELECTIVE-INHIBITION; RESISTANCE; HIV; ANALOGS; TRIPHOSPHATE; BINDING; POTENT AB Calanolide A, first isolated from the tropical rain forest tree Calophyllum lanigerum, is a potent human immunodeficiency virus type-1 (HIV-1) specific reverse transcriptase (RT) inhibitor, broadly active against diverse HIV-1 strains, including nucleoside and nonnucleoside-resistant variants. We examined the biochemical mechanism of inhibition of HIV-1 RT by calanolide A. Two template/primer systems were examined: ribosomal RNA and homopolymeric rA-dT(12-18). Galanolide A inhibited HIV-1 RT by a complex mechanism involving two calanolide A binding sites. With respect to either deoxynucleotide triphosphate (dNTP) or template/primer binding, one site was competitive and the other was uncompetitive. The data indicated that calanolide A bound near the active site of the enzyme and interfered with dNTP binding. Calanolide A inhibited HIV-1 RT in a synergistic fashion with nevirapine, further distinguishing it from the general class of nonnucleoside RT inhibitors. At certain concentrations, calanolide A bound HIV-1 RT in a mutually exclusive fashion with respect to both the pyrophosphate analog, phosphonoformic acid and the acyclic nucleoside analog 1-ethoxymethyl-5-ethyl-6-phenylthio-2-thiouracil. This indicates that calanolide A shares some binding domains with both phosphonoformic acid and 1-ethoxymethyl-5-ethyl-6-phenylthio-2-thiouracil, presumably reflecting that it interacts with RT near both the pyrophosphate binding site and the active site of the enzyme. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT DIAG & CTR,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 30 TC 44 Z9 47 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 NOV PY 1996 VL 279 IS 2 BP 652 EP 661 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT122 UT WOS:A1996VT12200025 PM 8930168 ER PT J AU MazzolaPomietto, P Aulakh, CS Huang, SJ Murphy, DL AF MazzolaPomietto, P Aulakh, CS Huang, SJ Murphy, DL TI Repeated administration of meta-chlorophenylpiperazine or 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane produces tolerance to its stimulatory effect on adrenocorticotropin hormone but not prolactin or corticosterone secretion in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SEROTONIN AGONISTS; PHARMACOLOGICAL CHARACTERIZATION; LOCOMOTOR-ACTIVITY; CROSS-TOLERANCE; RECEPTOR; PLASMA; 5-HT2; BRAIN; RESPONSES AB In an attempt to clarify whether m-chlorophenylpiperazine- (mCPP) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-(DOI) induced increases in plasma adrenocorticotropin hormone, corticosterone and prolactin secretion are mediated by the same or different mechanisms, we studied the time course of development of tolerance to the neuroendocrine effects of m-CPP (2.5 mg/kg/day) and DOI (2.5 mg/kg/day) in rats and, furthermore, also evaluated possible cross-tolerance in responses to m-CPP and DOI. We observed the development of tolerance in adrenocorticotropin hormone responses after a single i.p. injection of m-CPP. However, there was no cross-tolerance to DOI when chronic (13 days) m-CPP-treated animals were challenged with DOI (2.5 mg/kg). injections of DOI (2.5 mg/kg) for six days were required before tolerance developed to the effect of DOI on adrenocorticotropin hormone. Furthermore, cross-tolerance was observed when DOI-treated animals (2.5 mg/kg/day x 6) were challenged with m-CPP (2.5 mg/kg) on day 7. In contrast, daily administration of m-CPP and DOI for 13 days did not produce tolerance to their stimulating effects on corticosterone and prolactin secretion. Hypothalamic levels of 5-hydroxyindoleacetic acid but not 5-HT were significantly reduced after acute or subchronic administration of both m-CPP and DOI. Furthermore, no change in the approximate 50% reduction in 5-hydroxyindoleacetic acid after m-CPP was observed after subchronic administration of this drug. These findings suggest that separate mechanisms mediate m-CPP and DOI-induced adrenocorticotropin hormone secretion in rats. RP MazzolaPomietto, P (reprint author), NIMH,CLIN SCI LAB,BLDG 10,RM 3D41,10 CTR DR MSC 1264,BETHESDA,MD 20892, USA. NR 44 TC 6 Z9 6 U1 0 U2 0 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 NOV PY 1996 VL 279 IS 2 BP 782 EP 789 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT122 UT WOS:A1996VT12200041 PM 8930184 ER PT J AU Vistica, DT Kenney, S Hursey, M Boyd, MR AF Vistica, DT Kenney, S Hursey, M Boyd, MR TI Role of membrane potential in the accumulation of quaternized ellipticines by human tumor cell lines SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HUMAN BRAIN; STREPTOCOCCUS-PNEUMONIAE; CYTOTOXICITY AB 9-Methoxy-N-2-methylellipticinium acetate (MMEA) is representative of a series of quaternized ellipticines that exhibited selective cytotoxicity for human brain tumor cell lines of glial origin in the in vitro primary screen of the U.S. National Cancer Institute. The present investigation was initiated to determine whether membrane potential contributes to the cellular accumulation of this lipophilic cation by selected brain tumor and non-brain tumor cell lines. The results indicate that accumulation of MMEA by drug-sensitive cell lines, but not drug-resistant cell lines, is reduced by experimental conditions that depolarize the plasma membrane, e.g., stepped increases in the extracellular potassium concentration. These experimental conditions result in increased cellular fluorescence of cells stained with the voltage-sensitive anionic dye bis(1,3-dibutylbarbituric acid) trimethine oxonol, suggesting that decreased accumulation of MMEA is the result of decreased membrane potential. Membrane potential measurements using the null point method indicated that the mean membrane potential of selected MMEA-sensitive cell lines (-39.4 +/- 6.8 mV) was significantly lower (P < .005) than MMEA-resistant cell lines (-17 +/- 3.8 mV). Ultrastructural studies with the MMEA-sensitive U-251 glioblastoma indicated that the first morphological effects of MMEA occurred in mitochondria, where dissolution of cristae was observed, followed by engulfment of mitochondria in multilameller phagocytic vesicles. Electron microscopic autoradiographic studies with tritium-labeled MMEA revealed that the drug was localized in mitochondria and nuclei. RP Vistica, DT (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIAG & CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702, USA. NR 22 TC 6 Z9 6 U1 0 U2 0 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 NOV PY 1996 VL 279 IS 2 BP 1018 EP 1025 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT122 UT WOS:A1996VT12200069 PM 8930212 ER PT J AU Sparago, M Wlos, J Yuan, J Hatzidimitriou, G Tolliver, J DalCason, TA Katz, J Ricaurte, G AF Sparago, M Wlos, J Yuan, J Hatzidimitriou, G Tolliver, J DalCason, TA Katz, J Ricaurte, G TI Neurotoxic and pharmacologic studies on enantiomers of the N-methylated analog of cathinone (methcathinone): A new drug of abuse SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID IPRINDOLE-TREATED RATS; SEROTONIN NEUROTOXICITY; D-AMPHETAMINE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; DOPAMINE DEPLETION; CAUDATE-NUCLEUS; METHAMPHETAMINE; BRAIN; NEURONS; METHYLENEDIOXYMETHAMPHETAMINE AB These studies evaluated neurotoxic and pharmacologic properties of the R(+) and S(-) enantiomers of methcathinone, a psychostimulant drug that has surfaced in the illicit drug market, primarily in the S(-) form. Neurotoxic potential toward brain dopamine (DA) and serotonin (5-HT) neurons was assessed by measuring DA and 5-HT axonal markers and by means of silver degeneration studies; pharmacologic effects were evaluated by measuring locomotor stimulation. Methcathinone produced dose-related neurotoxic and locomotor stimulant effects which were species- and enantiomer-dependent, In mice, although both enantiomers produced toxic effects on DA neurons, the R(+) enantiomer was more potent, and neither enantiomer produced long-term effects on 5-HT neurons, By contrast, in behavioral studies, both enantiomers increased mouse locomotor activity, but the S(-) enantiomer was more potent, which suggests that methcathinone's neurotoxic and locomotor stimulant effects may be separable. Additional studies were done with rats, because mice are often refractory to 5-HT neurotoxicity induced by amphetamines. In the rat, both enantiomers produced toxic effects on DA neurons, only S(-)-methcathinone produced toxic effects on 5-HT neurons, and both enantiomers produced comparable locomotor stimulant effects. Together, these results indicate that: 1) Methcathinone has the potential to damage DA and 5-HT neurons; 2) Methcathinone neurotoxicity is enantiomer and species dependent; 3) Methcathinone's neurotoxic and locomotor stimulant effects are dissociable in mice but not rats; and 4) N-methylation confers 5-HT toxic activity onto cathinone, the N-desmethyl derivative of methcathinone, which is known to lack 5-HT neurotoxic activity. C1 JOHNS HOPKINS MED INST,DEPT NEUROL,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. DRUG ENFORCEMENT ADM,ARLINGTON,VA. DRUG ENFORCEMENT ADM,CHICAGO,IL. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA05707, DA06275] NR 67 TC 36 Z9 36 U1 0 U2 6 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 NOV PY 1996 VL 279 IS 2 BP 1043 EP 1052 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VT122 UT WOS:A1996VT12200072 PM 8930215 ER PT J AU Marples, D Rasch, R Knepper, MA Nielsen, S AF Marples, D Rasch, R Knepper, MA Nielsen, S TI Decreased aquaporin-2 expression of rat kidney collecting duct in acquired diabetes insipidus is not a consequence of polyuria or medullary osmotic washout SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract ID WATER CHANNEL EXPRESSION C1 AARHUS UNIV,DEPT CELL BIOL,AARHUS,DENMARK. NHLBI,NIH,BETHESDA,MD 20892. RP Marples, D (reprint author), UNIV LEEDS,DEPT PHYSIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. NR 4 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV PY 1996 VL 497P BP P91 EP P92 PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VT751 UT WOS:A1996VT75100110 ER PT J AU LethbridgeCejku, M Tobin, JD Scott, WW Reichle, R Roy, TA Plato, CC Hochberg, MC AF LethbridgeCejku, M Tobin, JD Scott, WW Reichle, R Roy, TA Plato, CC Hochberg, MC TI Axial and hip bone mineral density and radiographic changes of osteoarthritis of the knee: Data from the Baltimore longitudinal study of aging SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE epidemiology; osteoarthritis; osteoporosis ID WOMEN; MASS; OSTEOPOROSIS; MEN AB Objective, To examine the relationship between axial and hip bone mineral density (BMD) and radiographic changes of knee osteoarthritis (OA). Methods. BMD of the lumbar spine and/or right hip was measured, using dual photon absorptiometry, in 402 men and 247 women in the Baltimore Longitudinal Study of Aging who had bilateral standing knee radiographs taken between 1984 and 1991. Radiographs were read for features of OA using Kellgren-Lawrence and reliable individual feature scales. The relationship between BMD and radiographic changes of OA was examined using multiple linear regression adjusting for age, body mass index, and smoking. Additional analyses with adjustment for menopausal status and estrogen replacement therapy were performed in a subset of women. Results. Adjusted mean lumbar spine BMD was higher in subjects with knee osteophytes in both sexes: 1.23 +/- 0.02 vs 1.18 +/- 0.01 g/cm(2) (p = 0.02) in men, and 1.12 +/- 0.02 vs 1.08 +/- 0.01 g/cm(2) (p = 0.07) in women. There were no differences in levels of adjusted hip BMD by presence of any radiographic features of OA in either men or women. Conclusion, These results show that both men and women with radiographic changes of knee OA, specifically osteophytosis, have higher levels of adjusted spine but not hip BMD. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT RADIOL,DIV SKELETAL RADIOL,BALTIMORE,MD 21205. VET AFFAIRS MED CTR,CTR GERIATR RES EDUC & CLIN,BALTIMORE,MD. UNIV MARYLAND,SCH MED,DEPT MED,DIV CLIN IMMUNOL & RHEUMATOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT EPIDEMIOL & PREVENT MED,BALTIMORE,MD 21201. RP LethbridgeCejku, M (reprint author), NIA,GERONTOL RES CTR,APPL PHYSIOL SECT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 20 TC 35 Z9 37 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 NOV PY 1996 VL 23 IS 11 BP 1943 EP 1947 PG 5 WC Rheumatology SC Rheumatology GA VR075 UT WOS:A1996VR07500023 PM 8923372 ER PT J AU Didolkar, MS Jackson, AJ Lesko, LJ Fitzpatrick, JL Buda, BS Johnston, GS Zech, LA AF Didolkar, MS Jackson, AJ Lesko, LJ Fitzpatrick, JL Buda, BS Johnston, GS Zech, LA TI Pharmacokinetics of dacarbazine in the regional perfusion of extremities with melanoma SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article ID IMIDAZOLE CARBOXAMIDE; NSC-45388; MELPHALAN; THERAPY AB Background: The pharmacokinetics of dacarbazine (DTIC), which has been shown to be an effective therapeutic agent against metastatic melanoma, has not been extensively studied. However, to improve the clinical use of the drug, more information on the kinetics is required. Methods: A pharmacokinetic study was undertaken in six patients with melanoma of an extremity who were undergoing hyperthermic isolation perfusion with DTIC in order to understand better its clinical pharmacokinetics. Plasma was sampled from the arterial and venous lines of an extracorporeal pump during the perfusion with the systemic vein and urine sampled postperfusion. Samples were analyzed for DTIC, 2-azahypoxanthine (2-AZA), and aminoimidazole carboxamide (AIC). Tc-99m (Technetium) human serum albumin (HSA) was used in the perfusion circuit to monitor the crossover of the perfusate into the systemic circulation during the procedure. The data were analyzed using a compartmental model of sampled body compartments incorporating the isolated extremity. Results: High tissue DTIC levels were maintained throughout the perfusion, whereas in the systemic circulation, plasma DTIC concentrations, when observed, were 40-100-fold less than those in the perfusate. Almost 70% of the DTIC administered was not recovered in the perfusate after the washout of the extremity. Conclusions: High levels of DTIC can be maintained in an extremity (i.e., arm or leg) during perfusion. (C) 1996 Wiley-Liss, Inc. C1 UNIV MARYLAND,BALTIMORE,MD 21201. US FDA,ROCKVILLE,MD 20857. NIH,BETHESDA,MD 20892. RP Didolkar, MS (reprint author), SINAI HOSP,DEPT SURG,2435 W BELVEDERE AVE,BALTIMORE,MD 21215, USA. NR 19 TC 0 Z9 0 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV PY 1996 VL 63 IS 3 BP 148 EP 158 DI 10.1002/(SICI)1096-9098(199611)63:3<148::AID-JSO4>3.0.CO;2-D PG 11 WC Oncology; Surgery SC Oncology; Surgery GA VW032 UT WOS:A1996VW03200004 PM 8944058 ER PT J AU Prussick, R Horn, TD Wilson, WH Turner, MC AF Prussick, R Horn, TD Wilson, WH Turner, MC TI A characteristic eruption associated with ifosfamide, carboplatin, and etoposide chemotherapy after pretreatment with recombinant interleukin-1 alpha SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CUTANEOUS TOXICITY; TUMORS AB Background: Patients who received recombinant interleukin-1 alpha (IL-1 alpha) before chemotherapy followed by autologous bone marrow transplantation had a characteristic intertriginous cutaneous eruption that has not previously been described. Objective: Our aim was to document these skin changes and to determine whether IL-1 alpha as a sole agent caused recognizable changes in the skin. Methods: A prospective study of the skin changes in eight patients was performed. We characterized the clinical, histologic, and immunohistochemical features of the patients' skin after IL-1 alpha infusions and after chemotherapy. Results: No specific clinical or histologic changes were seen immediately after IL-1 alpha infusions. Immunohistochemical studies showed significant upregulation of endothelial leukocyte adhesion molecule-1 (ELAM-1) expression. Within 1 day of the Initiation of chemotherapy (ifosfamide, carboplatin, and etoposide), a cutaneous eruption consisting of mucositis and varying degrees of erythema progressing to painful erosions in body folds and under adhesive tape developed in all patients. Histologic features were consistent with a chemotherapeutic effect on the epidermis as well as eccrine and apocrine glands. Expression of keratinocyte intercellular adhesion molecule-1 and HLA-DR as well as of ELAM-1 on dermal endothelial cells was increased. The perivascular lymphocytic infiltrate consisted mainly of CD4(+) T cells. Conclusion: High-dose chemotherapy with ifosfamide, carboplatin, and etoposide resulted in a characteristic cutaneous eruption that is consistent with a toxic reaction to chemotherapeutic agents. Its accentuation in skin folds and under taped areas suggests that eccrine excretion of the drugs or a toxic metabolite is an important contributing factor. IL-1 alpha may induce the expression of ELAM-1 but does not cause a cutaneous eruption. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NCI,MED BRANCH,NIH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT DERMATOL,BALTIMORE,MD 21205. NR 8 TC 12 Z9 12 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 NOV PY 1996 VL 35 IS 5 BP 705 EP 709 DI 10.1016/S0190-9622(96)90725-2 PN 1 PG 5 WC Dermatology SC Dermatology GA VY375 UT WOS:A1996VY37500009 PM 8912565 ER PT J AU Slavkin, HC AF Slavkin, HC TI The A, B, C, D and E of viral hepatitis SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD NOV PY 1996 VL 127 IS 11 BP 1667 EP 1670 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VR077 UT WOS:A1996VR07700029 PM 8952247 ER PT J AU Ferrucci, L Cecchi, F Guralnik, JM Giampaoli, S LoNoce, C Salani, B Bandinelli, S Baroni, A AF Ferrucci, L Cecchi, F Guralnik, JM Giampaoli, S LoNoce, C Salani, B Bandinelli, S Baroni, A TI Does the clock drawing test predict cognitive decline in older persons independent of the mini-mental state examination? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID ALZHEIMERS-DISEASE; ELDERLY PATIENTS; SENILE DEMENTIA; SCREENING-TEST; IMPAIRMENT; EDUCATION; DELIRIUM; CRITERIA AB OBJECTIVE: To evaluate the value of the Clock Drawing Test (CDT) in predicting cognitive deterioration over a 4-year period, independent of baseline cognitive status evaluated by the Mini-Mental State Examination (MMSE). DESIGN: A preplanned analysis of data collected during the second (1991) and the third (1995) follow-up of the Italian rural cohorts of the FINE Study (Finland, Italy, the Netherlands Elderly). SUBJECTS: Of the 427 men (mean age 77.6 +/- 4.1 years; range 72-90 years) interviewed in 1991, 264 survived and were reinterviewed in 1995. The study population included 247 persons who were interviewed and received a complete cognitive evaluation in both 1991 and in 1995. MEASUREMENTS: Cognitive assessment in 1991 included the MMSE, the Dementia Rating Scale (DRS), and the CDT. The CDT was classified as normal or pathological, based on previously established criteria. The MMSE and the DRS were repeated in 1995. RESULTS: Independent of age and baseline MMSE score, subjects with pathological CDT compared with normal CDT had lower MMSE scores at follow-up (P < .01). These results were also confirmed by evaluating cognitive decline through its impact on change over time in daily life autonomy, as measured by the DRS (P < .01). Among persons scoring more than 21 on the MMSE, compared with persons with a normal CDT, those with pathological CDT performance were 5.4 (95% CI: 2.1-14.2) and 5.5 (95% CI: 1.6-19.6) times more likely to have a MMSE score below 21 and 18, respectively, 4 years later, independent of age and baseline MMSE score. CONCLUSIONS: Findings suggest that the CDT identifies older persons at high risk of cognitive decline and adds prognostic information that supplements the standard MMSE test. C1 NIA,EPIDEMIOL BIOMETRY & DERMATOG PROGRAM,NIH,BETHESDA,MD 20892. NIH,EPIDEMIOL & BIOSTAT LAB,ROME,ITALY. RP Ferrucci, L (reprint author), INRCA FLORENCE,GERIATR DEPT I FRATICINI,VIA MASSONI 21,I-50139 FLORENCE,ITALY. NR 33 TC 70 Z9 73 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 1996 VL 44 IS 11 BP 1326 EP 1331 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VR271 UT WOS:A1996VR27100007 PM 8909348 ER PT J AU Hughson, MD Schmidt, L Zbar, B Daugherty, S Meloni, AM Silva, FG Sandberg, AA AF Hughson, MD Schmidt, L Zbar, B Daugherty, S Meloni, AM Silva, FG Sandberg, AA TI Renal cell carcinoma of end-stage renal disease: A histopathologic and molecular genetic study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE renal cell carcinoma; cancer genetics; ESRD ID TUMOR-SUPPRESSOR GENE; ACQUIRED CYSTIC-DISEASE; LONG-TERM DIALYSIS; VON HIPPEL-LINDAU; KIDNEY-DISEASE; CHROMOSOME-ABNORMALITIES; HEMODIALYSIS; CYTOGENETICS; NEOPLASMS; MUTATIONS AB Renal cell carcinomas (RCC) are responsible for the deaths of 3% to 4% of patients with ESRD. The clear cell carcinoma of the kidney, which comprises 80% of sporadic RCC within the general population, shows a deletion of gene sequences in the short arm of chromosome 3 (3p) in as many as 100% of cases. The von Hippel-Lindau tumor suppressor gene at 3p25-26 is found to be mutated in the nondeleted allele in 57% of these sporadic clear cell carcinomas. This study was undertaken to determine the histopathologic types of RCC occurring in ESRD patients in the United States and to investigate the frequency with which 3p genetic changes can be found in these ESRD tumors. Seventeen end-stage kidneys containing RCC were collected from 15 ESRD patients at ten US medical centers. The tumors were classified by Thoenes' histopathologic typing. DNA extracted from paraffin blocks of tumor and nontumorous tissue was analyzed by single-stranded conformational polymorphism analysis for von Hippel-Lindau mutations and by microsatellite amplification for deletion of 3p gene sequences. Twenty-one RCC were identified in the 18 kidneys, The 21 RCC were classified histopathologically as follows: clear cell, compact, three cases; chromophilic, tubulopapillary, 15 cases; chromophilic, compact, three cases. Among the three clear cell carcinomas, one showed 3p genetic loss, None of the chromophilic RCC showed a 3p deletion and none of 19 tumors studied by single-stranded conformational polymorphism analysis disclosed von Hippel-Lindau mutations. In contrast to the general population, clear cell RCC with 3p abnormalities represent only a small proportion of the renal carcinomas in this collection of ESRD tumors. The findings indicate that the genetic changes underlying the development of most ESRD tumors are different from those occurring in sporadic clear cell RCC and do not characteristically involve the inactivation of a 3p tumor suppressor gene. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21701. SW BIOMED RES INST,SCOTTSDALE,AZ. UNIV OKLAHOMA,HLTH SCI CTR,DEPT PATHOL,OKLAHOMA CITY,OK. RP Hughson, MD (reprint author), DEPT VET AFFAIRS MED CTR,NORTHPORT,NY 11768, USA. OI hughson, michael/0000-0003-1310-707X NR 42 TC 37 Z9 37 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 1996 VL 7 IS 11 BP 2461 EP 2468 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA VV359 UT WOS:A1996VV35900026 PM 8959640 ER PT J AU Zbar, B Linehan, M AF Zbar, B Linehan, M TI Hereditary papillary renal cell carcinoma and Hereditary papillary renal cell carcinoma: Clinical studies in 10 families SO JOURNAL OF UROLOGY LA English DT Letter C1 NCI,SURG BRANCH,BETHESDA,MD 20892. RP Zbar, B (reprint author), NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,BLDG 560,ROOM 12-71,FREDERICK,MD 21702, USA. NR 7 TC 1 Z9 1 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 NOV PY 1996 VL 156 IS 5 BP 1781 EP 1781 DI 10.1016/S0022-5347(01)65520-4 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VM117 UT WOS:A1996VM11700076 PM 8863608 ER PT J AU Chang, R Horne, MK Mayo, DJ Doppman, JL AF Chang, R Horne, MK Mayo, DJ Doppman, JL TI Pulse-spray treatment of subclavian and jugular venous thrombi with recombinant tissue plasminogen activator SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE thrombolysis; thrombosis, venous; tissue-type plasminogen activator; veins, jugular; veins, subclavian ID VEIN-THROMBOSIS; FIBRINOLYTIC THERAPY; UPPER EXTREMITY; THROMBOLYSIS; HEPARIN; INHIBITION; INFUSION; HISTORY AB PURPOSE: To evaluate the efficacy of recombinant tissue plasminogen activator (rtPA) injected by pulse-spray in lysing subclavian and jugular venous thrombi, MATERIALS AND METHODS: Twelve patients with symptomatic, venogram-confirmed, occlusive thrombi of the subclavian-axillary or jugular veins were treated with one or two daily 15-minute injections of rtPA delivered directly into the clots with pulse-spray catheters, Twenty-four hours after each treatment, repeated venograms were obtained to assess venous patency, Successful thrombolysis was defined as antegrade flow through the previously occluded segments with minimal collateral venous flow, Continued patency was assessed with repeated venograms obtained after 1 and 2 months of oral anticoagulation, RESULTS: The 15-minute rtPA injections successfully lysed thrombi in eight of the 12 patients, Hypofibrinogenemia developed in only one patient. The technique had a high success rate with thrombi less than 2 weeks old (seven of eight) regardless of the length of the clot, but had limited success with thrombi more than 2 weeks old (one of four). Continued patency over a 2-month interval was documented in four of the eight patients whose thrombi were successfully lysed, However, patency could be maintained in only one of the four patients who retained a venous access device in the treated vein, CONCLUSION: Pulse spray rtPA is an effective, safe, and practical alternative to continuous infusions of thrombolytic agents to treat upper extremity venous thrombi. C1 NIH,WARREN G MAGNUSON CLIN CTR,HEMATOL SECT,DEPT CLIN PATHOL,BETHESDA,MD. RP Chang, R (reprint author), HENRY M JACKSON FDN,SPECIAL PROCEDURES SECT,DEPT RADIOL,RM 1C660,BLDG 10,BETHESDA,MD 20892, USA. NR 21 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV-DEC PY 1996 VL 7 IS 6 BP 845 EP 851 DI 10.1016/S1051-0443(96)70858-8 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA WJ727 UT WOS:A1996WJ72700008 PM 8951751 ER PT J AU Nakatsuji, Y Shih, JWK Tanaka, E Kiyosawa, K Wages, J Kim, JP Alter, HJ AF Nakatsuji, Y Shih, JWK Tanaka, E Kiyosawa, K Wages, J Kim, JP Alter, HJ TI Prevalence and disease association of hepatitis G virus infection in Japan SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE dual viral infection; hepatitis G virus; non A-E hepatitis; parenteral transmission; quantification HGV RNA; RT-PCR ID NON-B-HEPATITIS; NON-A-HEPATITIS; C VIRUS; POSTTRANSFUSION HEPATITIS; FAILURE; 1ST-GENERATION; FLAVIVIRUS; ETIOLOGY; TESTS; ASSAY AB A reverse transcriptase-polymerase chain reaction procedure (RT-PCR) for the detection of hepatitis G virus (HGV) RNA was used to examine the prevalence of HGV infection and HGV-related disease in Japan. Among 48 patients with acute non-A, B, C, D, E (non-A-E) hepatitis (five transfusion-associated cases and 43 sporadic cases), only one patient (2%), a transfusion recipient, was HGV RNA positive. Similarly, among 50 patients with established chronic non-A-E hepatitis, only two (4%) were positive for HGV RNA. These frequencies were not significantly different from those in 129 voluntary blood donors (0.8%). By contrast, HGV infection was relatively common among patients who were also infected with other hepatitis viruses. HGV co-infection or superinfection was found in seven of 53 (13%) patients with acute hepatitis C, in 15 of 126 (12%) patients with chronic hepatitis C, in three of 21 (14%) patients with acute hepatitis B and in four of 81 (5%) patients with chronic hepatitis B. Among the 29 dually infected patients, 15 (52%) had a history of blood transfusion. HGV was also detected in seven (10%) of 69 haemodialysis patients, of whom only one had a dual infection with hepatitis C virus (HCV) and an elevated aminotransferase level. In conclusion: HGV RNA was found in only a low percentage of patients with either acute or chronic non-A-E hepatitis; HGV appears toco-infect or superinfect in 10-15% of HCV infections and in 5-15% of HBV infections; the prevalence of HGV infection (0.8%) among voluntary blood donors in Japan is similar to that for HCV infection; a history of blood transfusion was obtained in 22 (55%) of the total 40 HGV-positive subjects; and isolated HGV infection appears to have a low disease burden. C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD 20852. SHINSHU UNIV,SCH MED,DEPT INTERNAL MED 2,MATSUMOTO,NAGANO 390,JAPAN. GENELABS TECHNOL INC,REDWOOD CITY,CA. NR 31 TC 84 Z9 86 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD NOV PY 1996 VL 3 IS 6 BP 307 EP 316 DI 10.1111/j.1365-2893.1996.tb00103.x PG 10 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA VT741 UT WOS:A1996VT74100005 PM 8947882 ER PT J AU Hu, XL Carroll, LJ Wolffe, EJ Moss, B AF Hu, XL Carroll, LJ Wolffe, EJ Moss, B TI De novo synthesis of the early transcription factor 70-kilodalton subunit is required for morphogenesis of vaccinia virions SO JOURNAL OF VIROLOGY LA English DT Article ID POLYMERASE-ASSOCIATED PROTEIN; DEPENDENT ATPASE ACTIVITY; EARLY GENE-TRANSCRIPTION; VIRUS LATE GENES; RNA-POLYMERASE; EARLY PROMOTER; POLY(A) POLYMERASE; ESCHERICHIA-COLI; LAC REPRESSOR; STAGE GENES AB Vaccinia virus early transcription factor (VETF) is a heterodimeric protein that is packaged in virus particles for expression of early genes during the next round of infection. To investigate additional roles of VETF, we constructed a conditionally lethal recombinant vaccinia virus in which the D6R gene, encoding the 70-kDa subunit of VETF, is under stringent Escherichia coli lac operator control. When cells were infected with the recombinant virus in the absence of an inducer, synthesis of the 70-kDa protein was undetectable and the yield of infectious virus was severely reduced. Under these nonpermissive conditions, DNA replication and synthesis of viral proteins other than the one encoded by D6R occurred, suggesting that de novo synthesis of VETF is not required for expression of early or late genes during the virus growth cycle. Electron microscopy, however, revealed that immature virus particles and masses of electron-dense material accumulated in the absence of an inducer. We concluded that VETF has a direct role in virion morphogenesis or is required for expression of a novel subset of genes that have such a role. C1 NIAID,VIRAL DIS LAB,NIH,BETHESDA,MD 20892. NR 49 TC 28 Z9 28 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 NOV PY 1996 VL 70 IS 11 BP 7669 EP 7677 PG 9 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200035 PM 8892887 ER PT J AU Ott, DE Coren, LV Kane, BP Busch, LK Johnson, DG Sowder, RC Chertova, EN Arthur, LO Henderson, LE AF Ott, DE Coren, LV Kane, BP Busch, LK Johnson, DG Sowder, RC Chertova, EN Arthur, LO Henderson, LE TI Cytoskeletal proteins inside human immunodeficiency virus type 1 virions SO JOURNAL OF VIROLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; CYCLOPHILIN-A; GAMMA-ACTIN; BETA-ACTIN; MICROVASCULAR PERICYTES; NUCLEOTIDE-SEQUENCE; APICAL MICROVILLI; INFECTED-CELLS; HIV-1 VIRIONS; GAG PROTEINS AB We have identified three types of cytoskeletal proteins inside human immunodeficiency virus type 1 (HTV-1) virions by analyzing subtilisin-digested particles. HIV-1 virions were digested with protease, and the treated particles mere isolated by sucrose density centrifugation. This method removes both exterior viral proteins and proteins associated with microvesicles that contaminate virion preparations. Since the proteins inside the virion are protected from digestion by the viral lipid envelope, they can be isolated and analyzed after treatment. Experiments presented here demonstrated that this procedure removed more than 95% of the protein associated with microvesicles. Proteins in digested HIV-1(MN) particles from infected H9 and CEM(ss) cell lines were analyzed by high-pressure liquid chromatography, protein sequencing, and immunoblotting. The data revealed that three types of cytoskeletal proteins are present in virions at different concentrations relative to the molar level of Gag: actin (approximately 10 to 15%), ezrin and moesin (approximately 2%), and cofilin (approximately 2 to 10%). Our analysis of proteins within virus particles detected proteolytic fragments of cw-smooth muscle actin and moesin that were cleaved at sites which might be recognized by HIV-1 protease. These cleavage products are not present in microvesicles from uninfected cells. Therefore, these processed proteins are most probably produced by HIV-1 protease digestion. The presence of these fragments, as well as the incorporation of a few specific cytoskeletal proteins into virions, suggests an active interaction between cytoskeletal and, viral proteins. RP Ott, DE (reprint author), NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. NR 52 TC 169 Z9 175 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 NOV PY 1996 VL 70 IS 11 BP 7734 EP 7743 PG 10 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200042 PM 8892894 ER PT J AU Chen, W Qin, HL Chesebro, B Cheever, MA AF Chen, W Qin, HL Chesebro, B Cheever, MA TI Identification of a gag-encoded cytotoxic T-lymphocyte epitope from FBL-3 leukemia shared by Friend, Moloney, and Rauscher murine leukemia virus-induced tumors SO JOURNAL OF VIROLOGY LA English DT Article ID ENV GENE; RECOMBINANT VACCINIA; VIRAL PEPTIDES; CELL EPITOPE; IMMUNOTHERAPY; SPECIFICITY; ANTIGENS; IMMUNE; IMMUNODOMINANT; PROTECTION AB FBL-3 is a highly immunogenic murine leukemia of C57BL/6 origin induced by Friend murine leukemia virus (MuLV). Immunization of C57BL/6 mice with FBL-3 readily elicits CD8(+) cytotoxic T lymphocytes (CTL) capable of lysing FBL-3 as well as syngeneic leukemias induced by Moloney and Rauscher MuLV. The aim of this current study was to identify the immunogenic epitope(s) recognized by the FBL-3-specific CD8(+) CTL. A series of FBL-3-specific CD8(+) CTL clones were generated from C57BL/6 mice immunized to FBL-3. The majority of CTL clones (32 of 38) were specific for F-MuLV gag-encoded antigen. By using a series of recombinant vaccinia viruses expressing full-length and truncated F-MuLV gag genes, the antigenic epitope recognized by the FBL-3 gag-specific CTL clones, as well as by bulk-cultured Cm from spleens of mice immune to FBL-3, aas localized to the leader sequence of gPr80(gag) protein. The precise amino acid sequence of the CTL epitope in the leader sequence was identified as CCLCLTVFL (positions 85-93) by examining lysis of targets incubated with a series of synthetic leader sequence peptides. No evidence of other CTL epitopes in the gPr80(gag) or Pr65(gag) core virion structural polyproteins was found. The identity of CCLCLTVFL as the target peptide was validated by showing that immunization with the peptide elicited CTL that Lysed FBL-3. The CTL elicited by the Gag peptide also specifically lysed syngeneic leukemia cells induced by Moloney and Rauscher MuLV (MBL-2 and RBL-5). The transmembrane peptide was shown to be the major gag-encoded antigenic epitope recognized by bulk-cultured CTL derived from C57BL/6 mice immunized to MBL-2 or RBL-5. Thus, the CTL epitope of FBL-3 is localized to the transmembrane anchor domain of the nonstructural Gag polyprotein and is shared by leukemia/lymphoma cell lines induced by Friend, Moloney, and Rauscher MuLV. C1 UNIV WASHINGTON,DEPT MED,DIV ONCOL,SEATTLE,WA 98195. NIAID,PERSISTENT VIRAL DIS LAB,ROCKY MT LABS,HAMILTON,MT 59840. FU NCI NIH HHS [CA54561, CA57851, CA30558] NR 40 TC 80 Z9 80 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 NOV PY 1996 VL 70 IS 11 BP 7773 EP 7782 PG 10 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200046 PM 8892898 ER PT J AU Weber, J Fenyo, EM Beddows, S Kaleebu, P Bjorndal, A Osmanov, S Heyward, W Esparza, J GalvaoCastro, B vandePerre, P Karita, E Wasi, C Sempala, S Tugume, B Biryahwaho, B RubsamenWaigmann, H vonBriesen, H Esser, R Grez, M Holmes, H Newberry, A Ranjbar, S Tomlinson, P Bradac, J McCutchan, F Louwagie, J Hegerich, P LopezGalindez, C Olivares, I Dopazo, J Mullins, JI Delwart, EL Bachmann, HM Goudsmit, J deWolf, F Hahn, BH Gao, F Yue, L Saragosti, S Schochetman, G Kalish, M Luo, CC George, R Pau, CP CheingsongPopov, R Nara, P Albert, J Myers, G Korber, B AF Weber, J Fenyo, EM Beddows, S Kaleebu, P Bjorndal, A Osmanov, S Heyward, W Esparza, J GalvaoCastro, B vandePerre, P Karita, E Wasi, C Sempala, S Tugume, B Biryahwaho, B RubsamenWaigmann, H vonBriesen, H Esser, R Grez, M Holmes, H Newberry, A Ranjbar, S Tomlinson, P Bradac, J McCutchan, F Louwagie, J Hegerich, P LopezGalindez, C Olivares, I Dopazo, J Mullins, JI Delwart, EL Bachmann, HM Goudsmit, J deWolf, F Hahn, BH Gao, F Yue, L Saragosti, S Schochetman, G Kalish, M Luo, CC George, R Pau, CP CheingsongPopov, R Nara, P Albert, J Myers, G Korber, B TI Neutralization serotypes of human immunodeficiency virus type 1 field isolates are not predicted by genetic subtype SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL GENOTYPE; HIV TYPE-1; ANTIBODIES; CELL AB Human immunodeficiency virus type 1 (HIV-1) primary isolates from four geographical locations in Thailand, Brazil, Rwanda, and Uganda, representing genetic subtypes A, B, C, D, and E, were examined for autologous and heterologous neutralization by panels of human HIV+ polyclonal plasma. In independent linked experiments in three laboratories using diverse methodologies and common reagents, no defined pattern of genetic subtype-specific neutralization was observed. Most plasma tested were broadly cross-neutralizing across two or more genetic subtypes, although the titer of neutralization varied across a wide range. We conclude that the genetic subtypes of HIV-1 are not classical neutralization serotypes. C1 KAROLINSKA INST,MICROBIOL & TUMOUR BIOL CTR,S-10401 STOCKHOLM,SWEDEN. WHO,GLOBAL PROGRAMME AIDS,CH-1211 GENEVA,SWITZERLAND. OSWALDO CRUZ FDN,SALVADOR,BA,BRAZIL. NATL HIV AIDS REFERENCE LAB,KIGALI,RWANDA. MAHIDOL UNIV,DEPT MICROBIOL,BANGKOK 10700,THAILAND. UGANDA VIRUS RES INST,ENTEBBE,UGANDA. GEORG SPEYER HAUS CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. NIAID,DIV AIDS,BETHESDA,MD 20892. WALTER REED ARMY INST RES,HENRY M JACKSON FDN LAB,ROCKVILLE,MD. INST SALUD CARLOS III,CTR NACL BIOL CELULAR & RETROVIRUS,MADRID,SPAIN. STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. UNIV AMSTERDAM,ACAD MED CTR,HUMAN RETROVIRUS LAB,NL-1105 AZ AMSTERDAM,NETHERLANDS. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. INST COCHIN,PARIS,FRANCE. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. ST MARYS HOSP,SCH MED,LONDON,ENGLAND. NCI,VIRUS BIOL UNIT,FREDERICK,MD 21701. SWEDISH INST INFECT DIS CONTROL,STOCKHOLM,SWEDEN. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. RP Weber, J (reprint author), ST MARYS HOSP,UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT COMMUNICABLE DIS,LONDON W2,ENGLAND. RI Dopazo, Joaquin/A-9270-2014; Lopez-Galindez, Cecilio/A-3603-2008; Van de Perre, Philippe/B-9692-2008 OI Dopazo, Joaquin/0000-0003-3318-120X; Lopez-Galindez, Cecilio/0000-0002-2324-9584; Van de Perre, Philippe/0000-0002-3912-0427 NR 27 TC 113 Z9 113 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 1996 VL 70 IS 11 BP 7827 EP 7832 PG 6 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200052 PM 8892904 ER PT J AU Wentz, MJ Patton, JT Ramig, RF AF Wentz, MJ Patton, JT Ramig, RF TI The 3'-terminal consensus sequence of rotavirus mRNA is the minimal promoter of negative-strand RNA synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID SINGLE-SHELLED PARTICLES; INFECTED-CELLS; PROTEIN NSP3; VIRUS-RNA; REPLICATION; SEGMENTS; BACTERIOPHAGE-PHI-6; SIGNAL; TRANSCRIPTION; ENCAPSIDATION AB We used an in vitro template-dependent replicase assay (D. Chen, C. Zeng, M. Wentz, M. Gorziglia, M. Estes, and R. Ramig. J. Virol. 68:7030-7039, 1994) to identify the cis-acting signals required for replication of a genome segment 9 template from the group A rotavirus strain OSU. The replicase phenotypes for a panel of templates with internal deletions or 3'-terminal truncations indicated that no essential replication signals were present within the open reading frame and that key elements were present in the 5' and 3' noncoding regions. Chimeric constructs containing portions of viral sequence ligated to a nonviral backbone were generated to further map the regions required for in vitro replication of segment 9. The data from these constructs showed that the 3'-terminal seven nucleotides of the segment 9 mRNA provided the minimum requirement for replication (minimal promoter). Analysis of additional chimeric templates demonstrated that sequences capable of enhancing replication from the minimal promoter were located immediately upstream of the minimal promoter and at the extreme 5' terminus of the template. Mutational analysis of the minimal promoter revealed that the 3'-terminal -CC residues are required for efficient replication. Comparison of the replication levels for templates with guanosines and uridines at nucleotides -4 to -6 from the 3' terminus compared with levels for templates containing neither of these residues at these positions indicated that either or both residues must be present in this region for efficient replication in vitro. C1 BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. NIH,INFECT DIS LAB,BETHESDA,MD 20892. RI Patton, John/P-1390-2014 FU NIAID NIH HHS [AI 21478, AI 16687, AI 36385] NR 32 TC 47 Z9 49 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 NOV PY 1996 VL 70 IS 11 BP 7833 EP 7841 PG 9 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200053 PM 8892905 ER PT J AU Patton, JT AF Patton, JT TI Rotavirus VP1 alone specifically binds to the 3' end of viral mRNA, but the interaction is not sufficient to initiate minus-strand synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID SINGLE-SHELLED PARTICLES; BOVINE ROTAVIRUS; GUANYLYLTRANSFERASE ACTIVITY; 3-DIMENSIONAL STRUCTURE; NUCLEOTIDE-SEQUENCE; PROTEIN NSP3; RNA; REPLICATION; IDENTIFICATION; EXPRESSION AB Recent studies have shown that disrupted (open) rotavirus cores have an associated replicase activity which supports the synthesis of dsRNA from viral mRNA in a cell-free system (D. Chen, C. Q.-Y. Zeng, M. J. Wentz, M. Gorziglia, M. K. Estes, and R. F. Ramig, J. Virol. 68:7030-7039, 1994). To determine which of the core proteins, VP1, VP2, or VP3, recognized the template mRNA during RNA replication, SA11 open cores were incubated with P-32-labeled RNA probes of viral and nonviral origin and the reaction mixtures were analyzed for the formation of RNA-protein complexes by gel mobility shift assay. In mixtures containing a probe representing the 3' end of SA11 gene 8 mRNA, two closely migrating RNA-protein complexes, designated s and f, were detected. The interaction between the RNA and protein of the s and f complexes was shown to be specific by competitive binding assay with tRNA and brome mosaic virus RNA. By electrophoretic analysis of RNA-protein complexes recovered from gels, VP1 was shown to be the only viral protein component of the complexes, thereby indicating that VP1 specifically recognized the 3' end of gene 8 mRNA. Analysis of VP1 purified from open cores by glycerol gradient centrifugation verified that VP1 lacks replicase activity. When reconstituted with VP2-rich portions of the gradient, VP1 stimulated levels of replicase activity severalfold. These data indicate the VP1 can bind to viral mRNA in the absence of any other viral proteins and suggest that VP2 must interact with the RNA-protein complex before VP1 gains replicase activity. RP Patton, JT (reprint author), NIAID,INFECT DIS LAB,NIH,7 CTR DR,MSC 0720,ROOM 117,BETHESDA,MD 20892, USA. RI Patton, John/P-1390-2014 FU NIAID NIH HHS [AI-21478] NR 31 TC 61 Z9 64 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 NOV PY 1996 VL 70 IS 11 BP 7940 EP 7947 PG 8 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200065 PM 8892917 ER PT J AU Funkhouser, AW Raychaudhuri, G Purcell, RH Govindarajan, S Elkins, R Emerson, SU AF Funkhouser, AW Raychaudhuri, G Purcell, RH Govindarajan, S Elkins, R Emerson, SU TI Progress toward the development of a genetically engineered attenuated hepatitis a virus vaccine SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; 5' NONTRANSLATED REGION; WILD-TYPE VIRUS; A VIRUS; CELL-CULTURE; ENCEPHALOMYOCARDITIS VIRUS; VIRAL-RNA; MUTATIONS; LIVE; IMMUNOGENICITY AB Mutations which positively affect growth of hepatitis A virus in cell culture may negatively affect growth in vivo. Therefore, development of an attenuated vaccine for hepatitis A may require a careful balancing of mutations to produce a virus that will grow efficiently in cell suitable for vaccine production and still maintain a satisfactory level of attenuation in vivo. Since such a balance could be achieved most directly by genetic engineering, we are analyzing mutations that accumulated during serial passage of the HM-175 strain of hepatitis A virus in MRC-5 cell cultures in order to determine the relative importance of the mutations for growth in MRC-5 cells and for attenuation in susceptible primates. Chimeric viral genomes of the HM-175 strain were constructed from cDNA clones derived from a virulent virus and from two attenuated viruses adapted to growth in African green monkey kidney (AGMK) and MRC-5 cells, respectively. Viruses encoded by these chimeric genomes were recovered by in vitro or in vivo transfection and assessed for their ability to grow in cultured MRC-5 cells or to cause hepatitis in primates (tamarins). The only MRC-5-specific mutations that substantially increased the efficiency of growth in MRC-5 cells were a group of four mutations in the 5' NC mutations that accumulated during earlier passages of the HM-175 virus in primary AGMK cells appeared, independently and additively, to result in decreased biochemical evidence of hepatitis in tamarins. However, neither group of 5' NC mutations had a demonstrable effect on the extent of virus excretion or liver pathology in these animals. C1 UNIV SO CALIF,RANCHO LOS AMIGOS MED CTR,PATHOL & CLIN LABS,DOWNEY,CA 90242. BIOQUAL INC,ROCKVILLE,MD 20853. RP Funkhouser, AW (reprint author), NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [N01-AO-52706, N01-AO-45180] NR 39 TC 10 Z9 10 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 NOV PY 1996 VL 70 IS 11 BP 7948 EP 7957 PG 10 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200066 PM 8892918 ER PT J AU McCarty, TC Chattopadhyay, SK Scherer, MT Fredrickson, TN Hartley, JW Morse, HC AF McCarty, TC Chattopadhyay, SK Scherer, MT Fredrickson, TN Hartley, JW Morse, HC TI Endogenous Mtv-encoded superantigens are not required for development of murine AIDS SO JOURNAL OF VIROLOGY LA English DT Article ID INDUCED IMMUNODEFICIENCY SYNDROME; MAMMARY-TUMOR VIRUS; CD4+ T-CELLS; SYNDROME MAIDS; MICE; GENES; INDUCTION; DISEASE; EXPRESSION; ACTIVATION AB Immune activation in murine AIDS (MAIDS) has been suggested to involve a superantigen (SAG). The possibility that SAGs encoded by mammary tumor virus (MTV) might he the source of stimulation was studied by using Mtv mice, Mtv(-) mice developed typical MAIDS, excluding a requirement for Mtv-encodcd SAGs in the pathogenesis of this disorder. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NCI,REGISTRY EXPT CANC,BETHESDA,MD 20892. NATL JEWISH CTR IMMUNOL & RESP MED,DEPT MED,DIV BASIC IMMUNOL,HOWARD HUGHES MED INST,DENVER,CO 80206. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 32 TC 3 Z9 4 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 NOV PY 1996 VL 70 IS 11 BP 8148 EP 8150 PG 3 WC Virology SC Virology GA VL792 UT WOS:A1996VL79200091 PM 8892943 ER PT J AU Capogrossi, MC AF Capogrossi, MC TI Invited lecture 4 - VEGF(165) expressed by a replication-deficient recombinant adenovirus vector induces angiogenesis in vivo. SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 NIA,CARDIOVASC SCI LAB,GENE THERAPY UNIT,NIH,BALTIMORE,MD. 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 NOV PY 1996 VL 50 IS 5 BP 1804 EP 1804 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VN326 UT WOS:A1996VN32600197 ER PT J AU Rozemuller, H Rombouts, WJC Touw, IP FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM AF Rozemuller, H Rombouts, WJC Touw, IP FitzGerald, DJP Kreitman, RJ Pastan, I Hagenbeek, A Martens, ACM TI Treatment of acute myelocytic leukemia with interleukin-6 Pseudomonas exotoxin fusion protein in a rat leukemia model SO LEUKEMIA LA English DT Article DE IL-6 Pseudomonas exotoxin; IL-6PE- IL-6 receptor; AML; BNML; growth factor toxin fusion proteins; leukemia treatment ID RECOMBINANT HUMAN INTERLEUKIN-6; MINIMAL RESIDUAL DISEASE; SERUM-FREE CULTURE; BONE-MARROW; GROWTH-FACTORS; IL-6 RECEPTOR; CELLS; EXPRESSION; CARCINOMA; CANCER AB We studied the applicability of interleukin-6 Pseudomonas exotoxin fusion protein (IL-6PE4E) for treatment of acute myelocytic leukemia (AML). Leukemic cells from five out of 10 AML patients studied expressed IL-6 receptor (IL-6R) and proliferation in vitro was Inhibited in four of these cases, The potential of this approach in vivo was tested in a pre-clinical model for AML; the Brown Norway acute myelocytic leukemia (BNML). To obtain IL-6R expression levels on BNML cells comparable to the numbers expressed on human AML, human IL-6R gene transfectants of the BNML sub-line LT12 (LT12/IL-6R) were generated. IL-6PE4E is cytotoxic in vitro to LT12/IL-6R expressing 1400 high affinity IL-6R per cell with 50% inhibition of DNA synthesis at 1 ng/ml, In vivo treatment of leukemic rats carrying LT12/IL-6R leukemia indicated that the maximal tolerated dose of IL-6PE4E was 275+/-25 mu g/kg/day, when continuously administered for 7 days and resulted in a 90% reduction in leukemic cell load. AT this dose level of IL-6PE4E no reduction of normal hemopoietic progenitors was seen in non-leukemic rats. At higher dose levels (350-1050 mu g/kg/day) severe systemic toxicity was encountered. On the basis of these pre-clinical studies the feasibility of growth factor-toxins for selective in vivo targeting to AML cells is evaluated. C1 ERASMUS UNIV ROTTERDAM,INST HEMATOL,NL-3000 DR ROTTERDAM,NETHERLANDS. DR DANIEL DEN HOED CANC CTR,NL-3008 AE ROTTERDAM,NETHERLANDS. NCI,MOL BIOL LAB,DCBDC,BETHESDA,MD 20892. NR 48 TC 15 Z9 15 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1996 VL 10 IS 11 BP 1796 EP 1803 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA VQ581 UT WOS:A1996VQ58100019 PM 8892684 ER PT J AU Garcia, JI Zalba, G DeteraWadleigh, SD deMiguel, C AF Garcia, JI Zalba, G DeteraWadleigh, SD deMiguel, C TI Isolation of a cDNA encoding the rat MAP-kinase homolog of human p63(mapk) SO MAMMALIAN GENOME LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; XENOPUS OOCYTES; GROWTH-FACTOR; ACTIVATION; CELLS; CASCADE; SEQUENCE; INSULIN AB Using a combination of screening, RACE, and RT-PCR, we have isolated a new rat brain cDNA, we refer to as rMNK2, that showed strong homology to known MAP-kinases. The deduced amino acid sequence of rMNK2 indicated that it is the rat homolog of human p63(mapk), showing 94.5% identity, rMNK2 showed 77% homology with rat ERK3 and its human homolog p97(mapk), and 43% homology with both rat genes rMNK1(ERK1) and ERK2, within the kinase domain. This suggest that rMNK2 and ERK3 belong to a separate subfamily within the rat MAP-kinase multigene family. The most interesting difference lies in subdomain VIII, where this new subfamily contain a SEG/SPR motif instead of the TEY/APE found in the ERK subfamily, the TPY/APE found in the JNK/SAPK subfamily or the TGY/APE found in the p38/RK subfamily. The human homologs of ERK3 and rMNK2 (p97(mapk) and p63(mapk)) also show this significant change. Expression of rMNK2 has been detected in brain and to a lesser extent in lung by reverse transcription/PCR (RT-PCR). In situ hybridization of rat brain slices demonstrated a restricted expression of rMNK2 in the choroid plexus and hippocampus. This is interesting because the human homolog p63(mapk) maps to 18q12-21, a region that might be implicated in manic-depressive illness. C1 UNIV NAVARRA,DEPT BIOQUIM,E-31080 PAMPLONA,SPAIN. NIMH,NIH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RI de Miguel, Carlos/H-2153-2011 NR 38 TC 7 Z9 8 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1996 VL 7 IS 11 BP 810 EP 814 DI 10.1007/s003359900242 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VW045 UT WOS:A1996VW04500004 PM 8875888 ER PT J AU Ge, L Remmers, EF Du, Y Wilder, RL AF Ge, L Remmers, EF Du, Y Wilder, RL TI Genomic cloning and genetic mapping of the rat Nramp1 (Bcg) gene on chromosome 9 SO MAMMALIAN GENOME LA English DT Article ID NATURAL-RESISTANCE; INTRACELLULAR PARASITES; LINKAGE MAP; INFECTION; MOUSE; SUSCEPTIBILITY; HOST RP Ge, L (reprint author), NIAMSD,NIH,ARTHRIT & RHEUMATISM BRANCH,BLDG 10,RM 9N228,10 CENTER DR,MSC1820,BETHESDA,MD 20892, USA. NR 16 TC 4 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD NOV PY 1996 VL 7 IS 11 BP 856 EP 857 DI 10.1007/s003359900251 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VW045 UT WOS:A1996VW04500013 PM 8875897 ER PT J AU Spouge, JL Shrager, RI Dimitrov, DS AF Spouge, JL Shrager, RI Dimitrov, DS TI HIV-1 infection kinetics in tissue cultures SO MATHEMATICAL BIOSCIENCES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLS; LYMPHOCYTES; INHIBITION; SCD4 AB Despite intensive experimental work on HIV-1, very little theoretical work has focused on HIV-1 spread in tissue culture. This article uses two systems of ordinary differential equations to model two modes of viral spread, cell-free virus and cell-to-cell contact. The two models produce remarkably similar qualitative results. Simulations using realistic parameter regimes showed that starting with a small fraction of cells infected, both cell-free viral spread and direct cell-to-cell transmission give an initial exponential phase of viral growth, followed by either a crash or a gradual decline, extinguishing the culture. Under some conditions, an oscillatory phase may precede the extinction. Some previous models of in vivo HIV-1 infection oscillate, but only in unrealistic parameter regimes. Experimental tissue infections sometimes display several sequential cycles of oscillation, however, so our models can at least mimic them qualitatively. Significantly, the models show that infective oscillations can be explained by infection dynamics; biological heterogeneity is not required. The models also display proportionality between infected cells and cell-free virus, which is reassuringly consistent with assumptions about the equivalence of several measures of viral load, except that the proportionality requires a relatively constant total cell concentration. Tissue culture parameter values can be determined from accurate, controlled experiments. Therefore, if verified, our models should make interpreting experimental data and extrapolating it to in vivo conditions sharper and more reliable. (C) Elsevier Science Inc., 1996 C1 NIH,DIV COMP RES & TECHNOL,LAB PHYS SCI,BETHESDA,MD 20892. NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RP Spouge, JL (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 33 TC 31 Z9 32 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD NOV PY 1996 VL 138 IS 1 BP 1 EP 22 DI 10.1016/S0025-5564(96)00064-8 PG 22 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA VT563 UT WOS:A1996VT56300001 PM 8942173 ER PT J AU DeBaun, MR Brown, M Kessler, L AF DeBaun, MR Brown, M Kessler, L TI Screening for Wilms' tumor in children with high-risk congenital syndromes: Considerations for an intervention trial SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT 2nd International Conference on Molecular and Clinical Genetics of Childhood Renal Tumors CY MAY, 1995 CL PHILADELPHIA, PA DE cancer screening; Wilms' tumor; intervention trial ID BECKWITH-WIEDEMANN SYNDROME; COST-EFFECTIVENESS; BREAST-CANCER; HEMIHYPERTROPHY; MANAGEMENT; ANIRIDIA; PATIENT; DESIGN AB Screening for cancer in children is uncommon. However, in children with congenital syndromes associated with Wilms' tumor, conditions exist that potentially make screening effective. This select population of children 1) are relatively easily identified; 2) have a high incidence of Wilms' tumor; 3) if identified before development of Wilms' tumor, may have a decrement in morbidity/mortality; and 4) are amenable to a simple and acceptable screening technology, renal sonography exams. Many clinicians have recommended screening for cancer in children with congenital syndromes associated with Wilms' tumor. However, neither costs nor effectiveness of such recommendations have been evaluated systematically. The strongest evidence for or against Wilms' tumor screening in this select population would be provided by a randomized screening trial. Prior to undertaking such a trial, the key parameters that dominate the cost and effectiveness of screening should be identified. Simulation models, such as cost-effectiveness analysis, offer a starting point for deciding whether cancer screening is appropriate, and ii so, under what set of conditions. We review basic conditions required for a successful screening trial in children with syndromes that are at increased risk of Wilms' tumor. We also discuss the use of cost-effectiveness analysis as a preliminary step in determining the feasibility of an intervention trial. (C) 1996 Wiley-Liss, Inc. C1 NCI,APPL RES BRANCH,NIH,ROCKVILLE,MD 20892. RP DeBaun, MR (reprint author), NCI,GENET EPIDEMIOL BRANCH,NIH,EPN 439,6130 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 38 TC 17 Z9 17 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 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD NOV PY 1996 VL 27 IS 5 BP 415 EP 421 PG 7 WC Oncology; Pediatrics SC Oncology; Pediatrics GA VJ705 UT WOS:A1996VJ70500006 PM 8827068 ER PT J AU Chernomordik, V Nossal, R Gandjbakhche, AH AF Chernomordik, V Nossal, R Gandjbakhche, AH TI Point spread functions of photons in time-resolved transillumination experiments using simple scaling arguments SO MEDICAL PHYSICS LA English DT Article ID OPTICAL TRANSILLUMINATION; RESOLUTION LIMITS; MEDIA; SCATTERING; TISSUES; BREAST; LIGHT AB Simple scaling arguments are used to determine spatial resolution achievable in time-resolved transillumination experiments involving highly diffuse media. These arguments allow us to obtain relationships linking target resolution at different planes inside an optically turbid slab to the gating times of the imaging system. We show that this approach yields the same results as those obtained previously from an approximate and rather complicated analytical derivation. In addition, we are now able to assess the effects of scattering anisotropy on spatial resolution attainable when gating times are so short that a constant scaling of photon transport scattering length is not appropriate. These results should enable one to devise more accurate and simpler image reconstruction algorithms. RP Chernomordik, V (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. NR 17 TC 28 Z9 28 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 1996 VL 23 IS 11 BP 1857 EP 1861 DI 10.1118/1.597748 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VU691 UT WOS:A1996VU69100003 PM 8947897 ER PT J AU Singh, SP Miller, S Williams, YU Rudd, KE Nikaido, H AF Singh, SP Miller, S Williams, YU Rudd, KE Nikaido, H TI Immunochemical structure of the OmpD porin from Salmonella typhimurium SO MICROBIOLOGY-UK LA English DT Article DE Salmonella typhimurium; OmpD; porins; amino acid sequence; monoclonal antibodies ID OUTER-MEMBRANE PROTEIN; ESCHERICHIA-COLI K-12; MONOCLONAL-ANTIBODIES; ANTIGENIC DETERMINANTS; RHODOBACTER-CAPSULATUS; PSEUDOMONAS-AERUGINOSA; MURINE SALMONELLOSIS; CELL SURFACE; LIPOPOLYSACCHARIDE; GENE AB The OmpD porin was isolated and purified from Salmonella typhimurium strain SH 7454 (ompC::Tn10), digested with cyanogen bromide (CNBr) and the peptide fragments were separated by SDS-PAGE. N-terminal sequencing identified a total of 96 residues from four distinct peptides. The sequence showed that OmpD is homologous to NmpC (75% identity), Lc (75%) and OmpC (70%) from Escherichia coli, and OmpC (68%) from S. typhimurium. The sequence was essentially identical to the translated sequence of an nmpC-like gene of S. typhimurium, currently placed at 38.6 centisomes of the chromosome. Our results and other data suggest, however, that this gene is actually the ompD gene, which is more correctly placed in the 34 centisome region of the chromosome. The CNBr-generated peptides were also screened with 16 anti-S. typhimurium OmpD monoclonal antibodies by Western blotting. These results, in conjunction with the prediction of the OmpD folding pattern based on the known three-dimensional structure of E. coli OmpF, showed a close immunological relationship among S. typhimurium OmpD and E. coli NmpC and Lc, and a strong conservation of sequences within the transmembrane beta strands of these porins and E. coli OmpC, PhoE and OmpF, and Salmonella typhi OmpC. C1 ALABAMA STATE UNIV,TRAINING PROGRAMS,MONTGOMERY,AL 36101. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,BERKELEY,CA 94720. RP Singh, SP (reprint author), ALABAMA STATE UNIV,BIOMED RES PROGRAM,MONTGOMERY,AL 36101, USA. FU NIGMS NIH HHS [GM08219] NR 54 TC 17 Z9 21 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD NOV PY 1996 VL 142 BP 3201 EP 3210 PN 11 PG 10 WC Microbiology SC Microbiology GA VX246 UT WOS:A1996VX24600029 PM 8969517 ER PT J AU Gong, QH McDowell, JC Dean, A AF Gong, QH McDowell, JC Dean, A TI Essential role of NF-E2 in remodeling of chromatin structure and transcriptional activation of the epsilon-globin gene in vivo by 5' hypersensitive site 2 of the beta-globin locus control region SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOMINANT CONTROL REGION; LEUCINE ZIPPER PROTEIN; HUMAN ERYTHROID-CELLS; EPSTEIN-BARR-VIRUS; TRANSGENIC MICE; ENHANCER ACTIVITY; SACCHAROMYCES-CEREVISIAE; DEVELOPMENTAL REGULATION; POSITIONED NUCLEOSOMES; LEUKEMIA-CELLS AB Much of our understanding of the process by which enhancers activate transcription has been gained from transient-transfection studies in which the DNA is not assembled with histones and other chromatin proteins as it is in the cell nucleus, To study the activation of a mammalian gene in a natural chromatin context in vivo, we constructed a minichromosome containing the human e-globin gene and portions of the P-globin locus control region (LCR), The minichromosomes replicate and are maintained at stable copy number in human erythroid cells, Expression of the minichromosomal epsilon-globin gene requires the presence of beta-globin LCR elements in cis, as is the case for the chromosomal gene, We determined the chromatin structure of the epsilon-globin gene in both the active and inactive states. The transcriptionally inactive locus is covered by an array of positioned nucleosomes extending over 1,400 bp. In minichromosomes with a mu LCR or DNase I-hypersensitive site 2 (HS2) which actively transcribe the epsilon-globin gene, the nucleosome at the promoter is altered or disrupted while positioning of nucleosomes in the rest of the locus is retained, All or virtually all minichromosomes are simultaneously hypersensitive to DNase I both at the promoter and at HS2. Transcriptional activation and promoter remodeling, as well as formation of the HS2 structure itself, depended on the presence of the NF-E2 binding motif in HS2. The nucleosome at the promoter which is altered upon activation is positioned over the transcriptional elements of the epsilon-globin gene, i.e., the TATA, CCAAT, and CACCC elements, and the GATA-1 site at -165. The simple availability of erythroid transcription factors that recognize these motifs is insufficient to allow expression, As in the chromosomal globin locus, regulation also occurs at the level of chromatin structure, These observations are consistent,vith the idea that one role of the beta-globin LCR is to maintain promoters free of nucleosomes, The restricted structural change observed upon transcriptional activation may indicate that the LCR need only make a specific contact with the proximal gene promoter to activate transcription. C1 NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. NR 82 TC 82 Z9 83 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 NOV PY 1996 VL 16 IS 11 BP 6055 EP 6064 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN820 UT WOS:A1996VN82000012 PM 8887635 ER PT J AU Taylor, DR Lee, SB Romano, PR Marshak, DR Hinnebusch, AG Esteban, M Mathews, MB AF Taylor, DR Lee, SB Romano, PR Marshak, DR Hinnebusch, AG Esteban, M Mathews, MB TI Autophosphorylation sites participate in the activation of the double-stranded-RNA-activated protein kinase PKR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DSRNA BINDING DOMAIN; INTERFERON ACTION; INITIATION FACTOR-2-ALPHA; TRANSLATIONAL CONTROL; HUMAN-CELLS; INTERMOLECULAR AUTOPHOSPHORYLATION; TYROSINE PHOSPHORYLATION; EIF-2-ALPHA KINASE; MOUSE FIBROBLASTS; VACCINIA VIRUS AB The interferon-induced RNA-dependent protein kinase PKR is found in cells in a latent state. In response to the binding of double-stranded RNA, the enzyme becomes activated and autophosphorylated on several serine and threonine residues. Consequently, it has been postulated that autophosphorylation is a prerequisite for activation of the kinase. We report the identification of PKR sites that are autophosphorylated in vitro concomitantly with activation and examine their roles in the activation of PKR, Mutation of one site, threonine 258, results in a kinase that is less efficient in autophosphorylation and in phosphorylating its substrate, the initiation factor eIF2, in vitro. The mutant kinase is also impaired in vivo, displaying reduced ability to inhibit protein synthesis in yeast and mammalian cells and to induce a slow-growth phenotype in Saccharomyces cerevisiae. Mutations at two neighboring sites, serine 242 and threonine 255, exacerbated the effect. Taken together with earlier results (S. B. Lee, S. R. Green, M. B. Mathews, and M. Esteban, Proc. Natl. Acad. Sci. USA 91:10551-10555, 1994), these data suggest that the central part of the PKR molecule, lying between its RNA-binding and catalytic domains, regulates kinase activity via autophosphorylation. C1 COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. SUNY STONY BROOK,GENET PROGRAM,STONY BROOK,NY 11794. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. NICHHD,LAB EUKARYOT GENE REGULAT,BETHESDA,MD 20892. FU NCI NIH HHS [CA 13106]; NIAID NIH HHS [AI32361, AI34552] NR 71 TC 95 Z9 96 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 NOV PY 1996 VL 16 IS 11 BP 6295 EP 6302 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN820 UT WOS:A1996VN82000036 PM 8887659 ER PT J AU Wang, IM Blanco, JCG Tsai, SY Tsai, MJ Ozato, K AF Wang, IM Blanco, JCG Tsai, SY Tsai, MJ Ozato, K TI Interferon regulatory factors and TFIIB cooperatively regulate interferon-responsive promoter activity in vivo and in vitro SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR-TFIIB; TATA-BINDING PROTEIN; RNA-POLYMERASE-II; NF-KAPPA-B; LIGAND-DEPENDENT TRANSCRIPTION; THYROID-HORMONE RECEPTOR; RETINOIC ACID RECEPTOR; INITIATION FACTOR-IIB; IFN-INDUCIBLE GENES; ACTIVATION DOMAIN AB Interferon regulatory factors (IRFs) bind to the interferon-stimulated response element (ISRE) and regulate interferon- and virus-mediated gene expression. IRF-1 acts as a transcriptional activator, while IRF-2 acts as a repressor. Here we show that IRF-1 and IRF-2 bind to both cellular TFIIB, a component of the basal transcription machinery, and recombinant TFIIB (rTFIIB) and that this protein-protein interaction facilitates binding of IRFs to the ISRE. A functional interaction between TFIIB and IRF was assessed by a newly established in vitro transcription assay in which recombinant IRF-1 (rIRF-1) stimulated transcription specifically from an ISRE-containing template. With this assay we show that rIRF-1 and rTFIIB cooperatively enhance the ISRE promoter in vitro. We found that the activity of an ISRE-containing promoter was cooperatively enhanced upon cotransfection of TFIIB and IRF-1 cDNAs into P19 embryonal carcinoma cells, further demonstrating functional interactions in vivo. The cooperative enhancement by TFIIB and IRF-1 was independent of the TATA sequence in the ISRE promoter but dependent on the initiator sequence (Inr) and was abolished when P19 cells were induced to differentiate by retinoic acid treatment. In contrast, cotransfection of TFIIB and IRF-1 into NIH 3T3 cells resulted in a dose-dependent repression of promoter activation which occurred in a TATA-dependent manner. Our results indicate the presence of a cell type-specific factor that mediates the functional interaction between IRFs and TFIIB and that acts in conjunction with the requirement of TATA and Inr for promoter activation. C1 NICHHD,LAB MOL GROWTH REGULAT,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NR 70 TC 59 Z9 59 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 NOV PY 1996 VL 16 IS 11 BP 6313 EP 6324 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN820 UT WOS:A1996VN82000038 PM 8887661 ER PT J AU Yang, WM Hinnebusch, AG AF Yang, WM Hinnebusch, AG TI Identification of a regulatory subcomplex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INITIATION FACTOR-II; NEGATIVE TRANSLATIONAL REGULATORS; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; SHUTTLE VECTORS; YEAST; GCN4; EXPRESSION; SUBUNIT; GCD7 AB Eukaryotic translation initiation factor 2B (eIF2B) is a five-subunit complex that catalyzes guanine nucleotide exchange on eIF2. Phosphorylation of the alpha subunit of eIF2 [creating eIF2(alpha P]) converts eIF2 GDP from a substrate to an inhibitor of eIF2B. We showed previously that the inhibitory effect of eIF2(alpha P) can be decreased by deletion of the eIF2B a subunit (encoded by GCN3) and by point mutations in the beta and delta subunits of eIF2B (encoded by GCD7 and GCD2, respectively). These findings, plus sequence similarities among GCD2, GCD7, and GCN3, led us to propose that these proteins comprise a regulatory domain that interacts with eIF2(alpha P) and mediates the inhibition of eIF2B activity. Supporting this hypothesis, we report here that overexpression of GCD2, GCD7, and GCN3 specifically reduced the inhibitory effect of eIF2(alpha P) on translation initiation in vivo. The excess GCD2, GCD7, and GCN3 were coimmunoprecipitated from cell extracts, providing physical evidence that these three proteins can form a stable subcomplex. Formation of this subcomplex did not compensate for a loss of eIF2B function by mutation and in fact lowered eIF2B activity in strains lacking eIF2(alpha P). These findings indicate that the trimeric subcomplex does not possess guanine nucleotide exchange activity; we propose, instead, that it interacts with eIF2(alpha P) and prevents the latter from inhibiting native eIF2B. Overexpressing only GCD2 and GCD7 also reduced eIF2(alpha P) toxicity, presumably by titrating GCN3 from eIF2B and producing the four-subunit form of eIF2B that is less sensitive to eIF2(alpha P). This interpretation is supported by the fact that overexpressing GCD2 and GCD7 did not reduce eIF2(alpha P) toxicity in a strain lacking GCN3; however, it did suppress the impairment of eIF2B caused by the gcn3(c)-R104K mutation. An N-terminally truncated GCD2 protein interacted with other eIF2B subunits only when GCD7 and GCN3 were overexpressed, in accordance with the idea that the portion of GCD2 homologous to GCD7 and GCN3 is sufficient for complex formation by these three proteins. Together, our results provide strong evidence that GCN3, GCD7, and the C-terminal half of GCD2 comprise the regulatory domain in eIF2B. C1 NICHHD, LAB EUKARYOT GENE REGULAT, BETHESDA, MD 20892 USA. NR 36 TC 51 Z9 53 U1 0 U2 3 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 NOV PY 1996 VL 16 IS 11 BP 6603 EP 6616 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN820 UT WOS:A1996VN82000066 PM 8887689 ER PT J AU Hershkovitz, MA Lewis, LA AF Hershkovitz, MA Lewis, LA TI Deep-level diagnostic value of the rDNA-ITS region SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE ITS; 5.8S; rDNA evolution; eukaryotes; maximum-likelihood; among-site rate variation ID RIBOSOMAL-RNA SEQUENCE; INTERNAL TRANSCRIBED SPACER-2; PHYLOGENETIC ANALYSIS; NUCLEOTIDE-SEQUENCES; STRUCTURAL ELEMENTS; GREEN-ALGAE; DNA; ORIGIN; GENE; 5.8S AB The similarity of certain reported angiosperm rDNA internal transcribed spacer (ITS) region sequences to those of green algae prompted our analysis of the deep-level phylogenetic signal in the highly conserved but short 5.8S and hypervariable ITS2 sequences. We found that 5.8S sequences yield phylogenetic trees similar to but less well supported than those generated by a ca. 10-fold longer alignment from rDNA-18S sequences, as well as independent evidence. We attribute this result to our finding that, compared to 18S, the 5.8S has a higher proportion of sites subject to vary and greater among-site substitution rate homogeneity. We also determined that our phylogenetic results are not likely affected by intramolecular compensatory mutation to maintain RNA secondary structure nor by evident systematic biases in base composition. Despite historical homology, there appears to be no ITS2 primary sequence similarity shared between fungi, green algae, and angiosperms. ITS2 sequences within each of these groups, however, share sufficient similarity to cluster correctly on the basis of alignability. Our results indicate that ITS region sequences can diagnose organismal origins and phylogenetic relationships at many phylogenetic levels and provide a useful paradigm for molecular evolutionary study. C1 SMITHSONIAN INST,LAB MOL SYSTEMAT,WASHINGTON,DC 20560. UNIV NEW MEXICO,DEPT BIOL,ALBUQUERQUE,NM 87131. RP Hershkovitz, MA (reprint author), NIH,NATL LIB MED,NCBI GENBANK,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20984, USA. NR 55 TC 134 Z9 143 U1 0 U2 14 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD NOV PY 1996 VL 13 IS 9 BP 1276 EP 1295 PG 20 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA VR299 UT WOS:A1996VR29900014 PM 8896380 ER PT J AU Sheng, P Ladenheim, B Moran, TH Wang, XB Cadet, JL AF Sheng, P Ladenheim, B Moran, TH Wang, XB Cadet, JL TI Methamphetamine-induced neurotoxicity is associated with increased striatal AP-1 DNA-binding activity in mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE AP-1 transcription factor; methamphetamine; neurotoxicity ID TRANSCRIPTION FACTORS; ACTIVATOR PROTEIN-1; EXPRESSION; BRAIN; GENES; CELLS AB Multiple injections of methamphetamine (METH) produce long-lasting neurotoxic effects on the nigrostriatal dopamine (DA) system. The drug also causes increases in AP-1 DNA-binding activity in mice. In the present study, we tested the idea that toxic doses of METH might cause long-term increases in AP-1 DNA-binding. Mice were given 10 mg/kg of METH 2, 3 or 4 times at a 2 h interval in 1 day. Striatal DA levels were markedly decreased at 3 h and 24 h in all injection groups. After 1 week, striatal DA level recovered to near control in the METH X2 group, but were still significantly decreased in the METH X3 and X4 groups. Similar drug administration schedules caused increases in AP-1 DNA-binding activity at the 3 h time point in all groups. The AP-l-binding activity almost returned back to control level in the X2 and X3 injection groups at the 24 h and 1 week time point, but there were still increased levels of AP-1-binding activity in the METH X4 group. These findings raise the possibility that METH-induced neurotoxicity might involve prolonged activation of AP-1 transcription factor. This might be related to the report that c-fos or c-jun activation may be important in some models of neurodegeneration. C1 NIDA,MOL NEUROPSYCHIAT SECT,NIH,IRP,BALTIMORE,MD 21224. NIDA,MOL NEUROBIOL SECT,NIH,IRP,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NR 18 TC 18 Z9 18 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 NOV PY 1996 VL 42 IS 1 BP 171 EP 174 DI 10.1016/S0169-328X(96)00192-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VP334 UT WOS:A1996VP33400025 ER PT J AU Shields, PG Ambrosone, CB Graham, S Bowman, ED Harrington, AM Gillenwater, KA Marshall, JR Vena, JE Laughlin, R Nemoto, T Freudenheim, JL AF Shields, PG Ambrosone, CB Graham, S Bowman, ED Harrington, AM Gillenwater, KA Marshall, JR Vena, JE Laughlin, R Nemoto, T Freudenheim, JL TI A cytochrome P4502E1 genetic polymorphism and tobacco smoking in breast cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE tobacco; cytochrome P4502E1; genetic polymorphisms; metabolizing enzymes; N-nitrosamines ID MAMMARY EPITHELIAL-CELLS; NITROSO-N-METHYLUREA; FRAGMENT-LENGTH-POLYMORPHISM; LUNG-CANCER; NEOPLASTIC TRANSFORMATION; CIGARETTE-SMOKING; NEW-YORK; RISK; DNA; RAT AB Known breast-cancer risk factors account for only part of the variability in breast-cancer incidence. Tobacco smoke is not commonly considered a breast carcinogen, but many of its constituents, such as N-nitrosamines, are carcinogenic in laboratory animal studies. Herein, we assessed a cytochrome P4502E1 (CYP2E1) genetic polymorphism (a Dral restriction enzyme site in intron 6) as a risk factor for breast cancer in both premenopausal and postmenopausal women. Because N-nitrosamines are metabolically activated by CYP2E1, the risk among women smokers was investigated. Caucasian women were enrolled in a case-control study of breast cancer between 1986 and 1991. A subset of the women (219 premenopausal and 387 postmenopausal women) consented to phlebotomy. The allelic frequencies for the premenopausal women (D allele = 0.91 and C allele = 0.09) and postmenopausal women (D allele = 0.93 and C allele = 0.07) were similar to those previously reported. There was no statistically significant association between the CYP2E1 polymorphism and breast-cancer risk for premenopausal or postmenopausal women (adjusted odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.48, 2.24, and OR = 1.01, 95% CI = 0.55, 1.84, respectively). When the women were categorized as nonsmokers versus smokers (those who smoked more than one cigarette per week for more than 1 yr), premenopausal women with one or two C alleles who had a history of smoking were found to be at increased risk (unadjusted OR = 7.00, 95% CI = 0.75, 14.53, and adjusted OR = 11.09, 95% Cl = 1.51, 81.41), although the number of study subjects with those genotypes was small. The small number of study subjects with a C allele precluded meaningful classification by level of smoking, but categorizing the smokers into two groups (above and below the median) also suggested an increased risk. Premenopausal women with the DD genotype and postmenopausal women with any genotype were not at increased risk. Breast-cancer risk was not related to the CYP2E1 genotype in either premenopausal nonsmokers or smokers (adjusted OR = 0.66, 95% CI = 0.20, 2.17, and OR = 2.13, 95% CI = 0.60, 7.59, respectively) or postmenopausal nonsmokers or smokers (OR = 0.90, 95% CI = 0.34, 2.35, and OR = 1.02, 95% CI = 0.46, 2.23, respectively), although the difference in the ORs for premenopausal nonsmokers and smokers suggests an increased risk for smokers. While there are limitations to this study, particularly related to the small number of subjects with the DC and CC genotypes, the study suggests that some women may be susceptible to tobacco smoke because of a CYP2E1 polymorphism. However, these results are preliminary and must be replicated. (C) 1996 Wiley-Liss, Inc.* C1 SUNY BUFFALO,DEPT PREVENT & SOCIAL MED,BUFFALO,NY 14260. SUNY BUFFALO,DEPT SURG,BUFFALO,NY 14260. RP Shields, PG (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C16,BETHESDA,MD 20892, USA. RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA 62995, CA 01633, CA 11535] NR 38 TC 35 Z9 36 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1996 VL 17 IS 3 BP 144 EP 150 DI 10.1002/(SICI)1098-2744(199611)17:3<144::AID-MC6>3.0.CO;2-F PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA VV437 UT WOS:A1996VV43700007 PM 8944074 ER PT J AU Lancaster, JM Brownlee, HA Bell, DA Futreal, PA Marks, JR Berchuck, A Wiseman, RW Taylor, JA AF Lancaster, JM Brownlee, HA Bell, DA Futreal, PA Marks, JR Berchuck, A Wiseman, RW Taylor, JA TI Microsomal epoxide hydrolase polymorphism as a risk factor for ovarian cancer SO MOLECULAR CARCINOGENESIS LA English DT Article DE ovarian cancer; epoxide hydrolase; expression; metabolism; enzymes; polymorphism ID SMOKING; TRANQUILIZERS; EXPRESSION AB Microsomal epoxide hydrolase (EPHX) is one of many enzymes involved in the metabolism of endogenous and exogenous toxicants. Polymorphic forms of the human EPHX gene have been described that vary in enzymatic activity, and one, Tyr113His, has been associated with hepatocellular carcinoma susceptibility. We demonstrated that EPHX was highly expressed in the human ovary, and investigated whether specific EPHX genotypes are associated with ovarian cancer susceptibility. Seventy-three Caucasian patients with ovarian cancer and 75 Caucasian-female controls without cancer were genotyped for the Tyr113His polymorphism by a polymerase chain reaction-restriction fragment length polymorphism assay. The frequency of the homozygous high-activity genotype was 41% in the control population and 64% in the ovarian cancer patients. The odds ratio for ovarian cancer with this genotype was 2.6 (95% confidence interval 1.3, 5.0; P < 0.01). The increased ovarian cancer risk associated with the high-activity genotype could reflect differences in metabolic activation of endogenous or exogenous carcinogens. (C) 1996 Wiley-Liss, Inc. C1 DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. RP Lancaster, JM (reprint author), NIEHS,NIH,MD C-4-06,111 ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. OI taylor, jack/0000-0001-5303-6398 NR 19 TC 102 Z9 106 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1996 VL 17 IS 3 BP 160 EP 162 DI 10.1002/(SICI)1098-2744(199611)17:3<160::AID-MC8>3.0.CO;2-J PG 3 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA VV437 UT WOS:A1996VV43700009 PM 8944076 ER PT J AU Gray, K Bullock, B Dickson, R Raszmann, K Walmer, D McLachlan, J Merlino, G AF Gray, K Bullock, B Dickson, R Raszmann, K Walmer, D McLachlan, J Merlino, G TI Potentiation of diethylstilbestrol-induced alterations in the female mouse reproductive tract by transforming growth factor-alpha transgene expression SO MOLECULAR CARCINOGENESIS LA English DT Article DE TGF alpha; DES; reproductive tract carcinogenesis ID ESTROGEN-REGULATED GENES; TGF-ALPHA; SKIN TUMORIGENESIS; MESSENGER-RNA; MAMMARY-GLAND; MICE; RECEPTOR; UTERUS; OVEREXPRESSION; DIFFERENTIATION AB Neonatal estrogen exposure causes numerous abnormalities in the female reproductive tract, including carcinogenesis. One mechanism by which neonatal estrogen elicits teratogenic and carcinogenic effects is epigenetic and involves the modulation of a number of estrogen-regulated genes including epidermal growth factor (EGF). Because of the evidence that there is an integral relationship between the EGF family, estrogen action, and the regulation of the growth and differentiation of the reproductive tract, we used transforming growth factor-alpha (TGF alpha) transgenic mice to investigate the interaction of constitutive TGF alpha expression with the potent estrogen diethylstilbestrol (DES) in the induction of reproductive-tract alterations. Our study was designed to determine whether TGF alpha expression could modulate DES-induced carcinogenesis of the female mouse reproductive tract. The animals were homozygous TGF alpha transgenic female mice from the MT42 line and the parental CD-1 outbred mice. The presence of the TGF alpha transgene significantly increased the incidence of DES-induced vaginal adenosis, uterine endometrial hyperplasia, uterine polyps, hypospadia, benign ovarian cysts, and pituitary adenomas. However, constitutive TGF alpha expression did not promote reproductive-tract neoplasia. This study demonstrates that TGF alpha participates in the regulation of developmental and morphogenic events in the Mullerian duct and urogenital sinus, suggesting a role for TGF alpha in the pathogenesis of reproductive-tract diseases. Furthermore, we showed that although constitutive expression of the TGF alpha transgene did have an effect on the reproductive tract, TGF alpha overexpression alone could not substitute for DES as a reproductive-tract carcinogen or as a promoter of uterine neoplasia, indicating that DES-induced carcinogenesis requires events in addition to the overexpression of this single peptide growth factor. (C) 1996 Wiley-Liss, Inc.* C1 NCI,MOL BIOL LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT OBSTET & GYNECOL,BETHESDA,MD 20814. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT ANAT & CELL BIOL,WASHINGTON,DC 20057. DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 33 TC 8 Z9 9 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1996 VL 17 IS 3 BP 163 EP 173 DI 10.1002/(SICI)1098-2744(199611)17:3<163::AID-MC9>3.0.CO;2-G PG 11 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA VV437 UT WOS:A1996VV43700010 PM 8944077 ER PT J AU Ohmori, M Ohta, M Shimura, H Shimura, Y Suzuki, K Kohn, LD AF Ohmori, M Ohta, M Shimura, H Shimura, Y Suzuki, K Kohn, LD TI Cloning of the single strand DNA-binding protein important for maximal expression and thyrotropin (TSH)-induced negative regulation of the TSH receptor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TRANSCRIPTION FACTOR-I; C-MYC GENE; HISTOCOMPATIBILITY COMPLEX GENES; SYSTEMIC LUPUS-ERYTHEMATOSUS; RNA-RECOGNITION MOTIF; PRE-MESSENGER-RNA; KI-RAS PROMOTER; FOAMY VIRUS; THYROID AUTOANTIBODIES; CONSENSUS SEQUENCE AB Contiguous with the 5'-end of the thyroid transcription factor-1 (TTF-1) element upstream of the minimal TSH receptor (TSHR) promoter and within it, there is an element on the noncoding strand with single strand- binding activity. Mutation analyses indicate that it is functionally distinct from the TTF-1 element and is important for the constitutive expression and TSH/cAMP-induced negative autoregulation of the TSHR in thyroid cells but only constitutive expression in nonthyroid cells. In this report we identify a cDNA encoding a single strand-binding protein (SSBP) that forms a specific complex with the noncoding strand of the TSHR, contiguous with the 5'-end of both TTF-1 elements; we term it SSBP-1. SSBP-1 increases promoter activity when cotransfected with heterologous SV40 promoter-chloramphenicol acetyltransferase (CAT) chimeras containing the upstream SSBP-binding element from the TSHR promoter or with TSHR promoter-CAT chimeras containing both or only the downstream SSBP element. Mutational analyses reveal that a GXXXXG motif is important for the binding and enhancer function of SSBP-1. TSH/cAMP decreases SSBP-1 RNA levels, as well as SSBP-1/TSHR DNA complex formation, in functioning rat FRTL-5 thyroid cells but not nonfunctioning FRT thyroid or Buffalo rat liver cells that have no TTF-1. SSBP-1 RNA is present ubiquitously; however, its levels are higher in FRTL-5 cells and are increased by overexpression of TTF- in cells treated with TSH. This reverses TSH-induced negative regulation of the TSHR. SSBP-1 is, therefore, a positive regulator of TSHR gene expression that contributes to TSHR maximal expression by binding to the SSBP elements. It is a ubiquitous, single-strand transcription factor whose expression in FRTL-5 thyroid cells is, however, regulated by a thyroid-specific gene, TTF-1. TSH/cAMP induces negative autoregulation of the TSHR, in part, by decreasing maximal expression resultant from SSBP-1 binding to the SSBP elements. Like Y-box proteins, which are involved in negative regulation of the TSHR, SSBP-1 also interacts with the major histocompatibility class II promoter S-box; the interaction is single strand-specific. This supports the hypothesis that common transcription factors regulate TSHR and major histocompatibility gene expression. Of additional interest and again like Y-box proteins, SSBP-1 is a member of a family of SSBPs that interact with RNA and are important in RNA processing, can interact with the promoter of retroviruses, and can interact with a gene linked to growth and DNA replication, c-myc. C1 NIDDKD, METAB DIS BRANCH, CELL REGULAT SECT, NIH, BETHESDA, MD 20892 USA. NR 81 TC 25 Z9 25 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 1996 VL 10 IS 11 BP 1407 EP 1424 DI 10.1210/me.10.11.1407 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VR430 UT WOS:A1996VR43000012 PM 8923467 ER PT J AU Miller, CE Karpas, A Schneerson, R Huppi, K Kovac, P Pozsgay, V Glaudemans, CPJ AF Miller, CE Karpas, A Schneerson, R Huppi, K Kovac, P Pozsgay, V Glaudemans, CPJ TI Of four murine, anti-Shigella dysenteriae type 1 O-polysaccharide antibodies, three employ V-genes that differ extensively from those of the fourth SO MOLECULAR IMMUNOLOGY LA English DT Article DE Shigella; antibodies; carbohydrates; sequences ID MONOCLONAL-ANTIBODIES; BINDING; OLIGOSACCHARIDES; SPECIFICITY; CHAIN; FRAGMENT; DEXTRAN AB Three murine, monoclonal antibodies, IgM 5286 F2, IgM 5297 C1, and IgG 5338 H4 were generated against Shigella dysenteriae type 1 O-specific polysaccharide (O-SP)-conjugate. They are specific for the O-SP, which is a poly-[alpha-L-rhamnopyranosyl-(1 --> 3)-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha(D-galactopyranosyl-(1 --> 3)-2-deoxy-2-amino-N-acetyl-alpha-D-glucopyranosyl]. The VH and VL genes of these antibodies were cloned and their sequences determined. They showed 93% homology, but were quite different to the primary sequence of IgM 3707 E9, of the same O-SP-specificity, previously reported. The fine-specificities of both IgG 5338 H4 and IgM 3707 E9 were for the same disaccharide moiety in the O-SP, while IgMs 5286 F2 and 5297 C1 showed fine-specificity for the entire repeating unit of the O-SP. Therefore, divergent sequences can confer upon antibodies similar-, or even identical-carbohydrate-epitope fine-specificity. In addition, close primary sequence-homology does not preclude differences in antibody fine-specificity. Published by Elsevier Science Ltd. C1 NCI,GENET LAB,NATL INST HLTH,BETHESDA,MD 20892. NICHHD,DEV & MOL IMMUN LAB,NATL INST HLTH,BETHESDA,MD 20892. RP Miller, CE (reprint author), NIDDK,MED CHEM LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 28 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD NOV PY 1996 VL 33 IS 16 BP 1217 EP 1222 DI 10.1016/S0161-5890(96)00105-8 PG 6 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA WT675 UT WOS:A1996WT67500001 PM 9129157 ER PT J AU Lobos, E Zahn, R Weiss, N Nutman, TB AF Lobos, E Zahn, R Weiss, N Nutman, TB TI Major allergen of lymphatic filarial nematodes is a parasite homolog of the gamma-glutamyl transpeptidase SO MOLECULAR MEDICINE LA English DT Article ID TROPICAL PULMONARY EOSINOPHILIA; RESPIRATORY-TRACT INFLAMMATION; TRANSFERASE TRANSPEPTIDASE; NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; LIGHT SUBUNIT; PROTEINS; IDENTIFICATION; ANTIGEN; BINDING AB Background: Bm2325, a major IgE-inducing antigen of the filarial parasite Brugia malayi has been implicated in the pathology of tropical pulmonary eosinophilia (TPE), a pulmonary syndrome thought to result from hypersensitivity to microfilariae. Materials and Methods: Affinity-purified IgE to Bm2325 from patients with TPE was used to identify a complementary DNA (cDNA) from a B. malayi expression library. Sequence analysis of the cDNA revealed a hitherto unknown parasite protein. Immunoblotting of the recombinant filarial protein using sera of patients with TPE determined its IgE-binding capacity. Reactivity to human lung epithelial cell proteins was analysed using murine anti-Bm2325 antibodies and serum from patients with TPE. Results: The predicted protein is a homolog of the entire precursor of the gamma-glutamyl transpeptidase (gamma-GT), a key enzyme in the synthesis and degradation of glutathione. The filarial precursor encodes both the heavy (H) and the light (Lj chain subunits and shares structural similarities with the mammalian enzymes. The Bm2325 allergen was identified as the homolog of the enzyme light chain subunit. Murine antibodies against the recombinant parasite gamma-GT cross-reacted with the human enzyme present in human airway epithelial cells, and human gamma-GT is a target of antibodies present in the serum of patients with TPE. Conclusion: Molecular mimicry between the parasite gamma-GT homolog and the host membrane-bound gamma-GT present in lung epithelial cells likely contributes to the pathogenesis observed in tropical pulmonary eosinophilia. C1 NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RP Lobos, E (reprint author), SWISS TROP INST,DEPT MED PARASITOL,SOCINSTR 57,CH-4002 BASEL,SWITZERLAND. NR 48 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1076-1551 J9 MOL MED JI Mol. Med. PD NOV PY 1996 VL 2 IS 6 BP 712 EP 724 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VX836 UT WOS:A1996VX83600008 PM 8972486 ER PT J AU Chiron, MF Ogata, M FitzGerald, DJ AF Chiron, MF Ogata, M FitzGerald, DJ TI Pseudomonas exotoxin exhibits increased sensitivity to furin when sequences at the cleavage site are mutated to resemble the arginine-rich loop of diphtheria toxin SO MOLECULAR MICROBIOLOGY LA English DT Article ID RECEPTOR-RELATED PROTEIN; LOW PH; PROTEOLYTIC ACTIVATION; PROTECTIVE ANTIGEN; MEDIATED CLEAVAGE; REFINED STRUCTURE; BACTERIAL TOXINS; ACTIVE FRAGMENT; MOUSE FURIN; CELLS AB To be toxic for mammalian cells, Pseudomonas exotoxin (PE) requires proteolytic cleavage between Arg-279 and Gly-280, Cleavage, which is mediated by the cellular protease furin, generates an active C-terminal fragment which translocates to the cytosol and inhibits protein synthesis, In vitro, furin-mediated cleavage is optimal at pH 5.5 with a relatively slow turnover rate. Within cells, only 5-10% of cell-associated PE is cleaved, To investigate the reasons for this inefficient cleavage, the amino acid composition near the cleavage site was altered to resemble more closely the arginine-rich sequence from the functionally similar region of diphtheria toxin (DT). Four PE-DT mutants were generated, whereby 1, 5, 6 or 8 amino acids at the PE-cleavage site were changed to amino acids found at the DT-cleavage site, Mutant proteins were expressed in Escherichia coli, purified and then analysed for their susceptibility to cleavage by furin and trypsin, susceptibility to cell-mediated cleavage, and cytotoxic activity relative to wild-type PE. At pH 5.5, the rate of both furin-mediated cleavage and trypsin-mediated cleavage increased dramatically when amino acids in PE were altered to resemble the DT sequence. This increase did not alter the pH optimum for furin-mediated cleavage of PE toxins, which remained at pH 5.0-5.5, When radioactive versions of selected PE-DT proteins were added to intact cells, an increase in the percentage of molecules that were cleaved relative to wild-type PE was also seen, However, changes that favoured increased proteolysis apparently interfered with other important toxin functions because none of the PE-DT proteins exhibited enhanced toxicity for cells when compared with the activity of wildtype PE. C1 NCI, MOL BIOL LAB,BIOTHERAPY SECT,DIV BASIC SCI, NATL HLTH INST, BETHESDA, MD 20892 USA. NR 43 TC 15 Z9 15 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1996 VL 22 IS 4 BP 769 EP 778 DI 10.1046/j.1365-2958.1996.d01-1721.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VU689 UT WOS:A1996VU68900016 PM 8951823 ER PT J AU Zeldin, DC Foley, J Ma, JX Boyle, JE Pascual, JMS Moomaw, CR Tomer, KB Steenbergen, C Wu, S AF Zeldin, DC Foley, J Ma, JX Boyle, JE Pascual, JMS Moomaw, CR Tomer, KB Steenbergen, C Wu, S TI CYP2J subfamily P450s in the lung: Expression, localization, and potential functional significance SO MOLECULAR PHARMACOLOGY LA English DT Article ID ARACHIDONIC-ACID EPOXYGENASE; ENDOGENOUS EPOXYEICOSATRIENOIC ACIDS; HYPOXIC PULMONARY VASOCONSTRICTION; CDNA-DIRECTED EXPRESSION; CYTOCHROME-P-450 MONOOXYGENASE; RABBIT LUNG; CLARA CELL; EICOSANOID METABOLISM; EXTRAHEPATIC TISSUES; ENZYME COMPONENTS AB Cytochrome P450 (P450) monooxygenases catalyze the epoxidation of arachidonic acid to form epoxyeicosatrienoic acids, which modulate bronchial smooth muscle tone and airway transepithelial ion transport. We recently described a new human P450 arachidonic acid epoxygenase (CYP2J2) and the corresponding rat homologue (CYP2J3). Northern analysis of lung RNA using CYP2J cDNA probes demonstrated that CYP2J2 and CYP2J3 mRNAs were expressed in the lung. Immunoblotting of microsomal fractions prepared from human and rat lungs using a polyclonal antibody raised against recombinant human CYP2J2 revealed a single 56-kDa band confirming abundant pulmonary CYP2J2 and CYP2J3 protein expres sion. Immunohistochemical analysis of formalin-fixed paraffin-embedded human and rat lung sections using the anti-human CYP2J2 IgG and avidin/biotin/peroxidase detection showed that CYP2J proteins were primarily expressed in ciliated epithelial cells lining the airway. Prominent staining was also noted in nonciliated airway epithelial cells, bronchial and pulmonary vascular smooth muscle cells, pulmonary vascular endothelium, and alveolar macrophages, whereas less intense staining was noted in alveolar epithelial cells. Endogenous epoxyeicosatrienoic acids were detected in both human and rat lung using gas chromatography/mass spectrometry, thus providing direct evidence for the in vivo human and rat pulmonary P450 metabolism of arachidonic acid. Based on these data, we conclude that CYP2J2 and CYP2J3 are abundant pulmonary arachidonic acid epoxygenases and that CYP2J products, the epoxyeicosatrienoic acids, are endogenous constituents of human and rat lung. In addition to known effects on airway smooth muscle tone and transepithelial electrolyte transport, the localization of CYP2J proteins to vascular smooth muscle and endothelium suggests that epoxyeicosatrienoic acids may also be involved in the modulation of pulmonary vascular tone. C1 NIEHS, LAB EXPT PATHOL, NIH, RES TRIANGLE PK, NC 27709 USA. NIEHS, LAB MOL BIOPHYS, NIH, RES TRIANGLE PK, NC 27709 USA. UNIV N CAROLINA, DEPT MED, CHAPEL HILL, NC 27599 USA. DUKE UNIV, MED CTR, DEPT MED, DURHAM, NC 27719 USA. DUKE UNIV, MED CTR, DEPT PATHOL, DURHAM, NC 27719 USA. RP NIEHS, PULM PATHOBIOL LAB, NIH, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 FU NHLBI NIH HHS [R01 HL039752]; NIA NIH HHS [P50-AG05128]; NIEHS NIH HHS [N01-ES35356] NR 58 TC 109 Z9 112 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1996 VL 50 IS 5 BP 1111 EP 1117 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VU893 UT WOS:A1996VU89300008 PM 8913342 ER PT J AU Corton, JC Bocos, C Moreno, ES Merritt, A Marsman, DS Sausen, PJ Cattley, RC Gustafsson, JA AF Corton, JC Bocos, C Moreno, ES Merritt, A Marsman, DS Sausen, PJ Cattley, RC Gustafsson, JA TI Rat 17 beta-hydroxysteroid dehydrogenase type IV is a novel peroxisome proliferator-inducible gene SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACYL-COA OXIDASE; STEROL CARRIER PROTEIN-2; RETINOID-X-RECEPTOR; AMINO-ACID-SEQUENCE; PHTHALATE SUPPRESSES ESTRADIOL; POLYMERASE CHAIN-REACTION; LIPID-TRANSFER PROTEIN; ACTIVATED RECEPTOR; BETA-OXIDATION; MOLECULAR-CLONING AB To better understand the molecular mechanisms of the pleiotropic responses induced by exposure to peroxisome proliferator chemicals (PPCs), we conducted a systematic search for genes whose mRNA levels are modulated by the PPC WY-14,643 (WY) in rat liver. The sequence of one up-regulated cDNA (2480 bp) was predicted to encode a protein of 735 aa with 82% identity to the porcine 17 beta-hydroxysteroid dehydrogenase type IV (HSD IV). Like the porcine enzyme, the rat HSD IV contains a region homologous to yeast hydratase-dehydrogenase-epimerases and to sterol carrier proteins, indicating that the rat HSD IV has broad substrate specificity and contributes to cholesterol metabolism. The rat HSD IV was regulated by diverse PPCs via two distinct mechanisms. Induction of HSD IV and acyl-CoA oxidase (AGO) proteins in rat liver at different treatment times and concentrations of gemfibrozil and di-n-butyl phthalate were almost identical, indicating that HSD IV mRNA induction involves the peroxisome proliferator-activated receptor alpha, a regulator of AGO. In contrast, HSD IV protein levels were only weakly induced by WY, a strong inducer of ACO protein, even though the levels of HSD IV and ACO mRNA were strongly stimulated by WY and gemfibrozil. Thus, HSD IV protein levels were uniquely regulated pretranslationally by WY via a novel mechanism. Increased conversion of estradiol to the less-active estrone by HSD IV induction may explain how phthalate exposure leads to decreases in serum estradiol levels and suppression of ovulation. C1 HUDDINGE UNIV HOSP,NOVUM,DEPT MED NUTR,S-14186 HUDDINGE,SWEDEN. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP Corton, JC (reprint author), CHEM IND INST TOXICOL,6 DAVIS DR,POB 12137,RES TRIANGLE PK,NC 27709, USA. RI Bocos, Carlos/B-8460-2015 OI Bocos, Carlos/0000-0003-0364-5958 NR 59 TC 54 Z9 56 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 NOV PY 1996 VL 50 IS 5 BP 1157 EP 1166 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VU893 UT WOS:A1996VU89300013 PM 8913347 ER PT J AU Rogowski, RS Collins, JH ONeill, TJ Gustafson, TA Werkman, TR Rogawski, MA Tenenholz, TC Weber, DJ Blaustein, MP AF Rogowski, RS Collins, JH ONeill, TJ Gustafson, TA Werkman, TR Rogawski, MA Tenenholz, TC Weber, DJ Blaustein, MP TI Three new toxins from the scorpion Pandinus imperator selectively block certain voltage-gated K+ channels SO MOLECULAR PHARMACOLOGY LA English DT Article ID PRESYNAPTIC NERVE-TERMINALS; MAGNETIC-RESONANCE SPECTROSCOPY; RAT-BRAIN SYNAPTOSOMES; POTASSIUM CHANNELS; 3-DIMENSIONAL STRUCTURE; ALPHA-DENDROTOXIN; CHARYBDOTOXIN; PEPTIDE; VENOM; RECEPTOR AB Three 35-amino acid peptide K+ channel toxins (pandinotoxins) were purified from the venom of the scorpion Pandinus imperator: the toxins are designated pandinotoxin (PiTX)-K alpha, PiTX-K beta, and PiTX-K gamma. In an Rb-86 tracer flux assay on rat brain synaptosomes, all three toxins selectively blocked the component of the K+-stimulated Rb-86 efflux that corresponds to a voltage-gated, rapidly inactivating (A-type) K+ current (IC50 = 6, 42, and 100 nM, respectively). These toxins blocked neither the noninactivating component of the K+-stimulated Rb-86 efflux (corresponding to a delayed rectifier) nor the Ca2+-dependent component of the Rb-86 efflux (i.e., a Ca2+-activated K+ current) in these terminals. PiTX-K alpha, which was expressed by recombinant methods, also blocked the Kv1.2 channel expressed in fibroblasts (IC50 = 32 pM). PiTX-K alpha and PiTX-K beta have identical amino acid sequences except for the seventh amino acid: a proline in PiTX-K alpha, and a glutamic acid in PiTX-K beta. They have substantial sequence homology, especially at the carboxyl termini, with another scorpion toxin, charybdotoxin (ChTX), which blocks both the Ca2+-activated and the rapidly inactivating, K+-stimulated Rb-86 efflux components in synaptosomes and the Kv1.2 channel. PiTX-K gamma, however, has much less sequence homology. Conserved in all four toxins are three identically positioned disulfide bridges; an asparagine at position 30; and positive charges al positions 27, 31, and 34 (based on ChTX numbering). PiTX-K gamma is novel in that it has a fourth pair of cysteines. The PiTX structures were computer simulated, using ChTX as a model. We speculate that the three-dimensional structures of all three PiTXs resemble that of ChTX: a beta-sheet al the carboxyl terminus, containing three cysteines, is linked to the central alpha-helix by two disulfide bridges (C17-35 and C13-33) and to an extended amino-terminal fragment by the third disulfide bridge (C7-C28). Further analysis of the three-dimensional structures reveals differences that may help to explain the selectivity and affinity differences of these toxins. C1 UNIV MARYLAND,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT BIOCHEM & MOL BIOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT MED,BALTIMORE,MD 21201. UNIV MARYLAND,INST BIOTECHNOL,CTR MED BIOTECHNOL,BALTIMORE,MD 21201. NINCDS,EPILEPSY RES BRANCH,NEURONAL EXCITABIL SECT,NIH,BETHESDA,MD 20892. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NIGMS NIH HHS [GM52071]; NIMH NIH HHS [P50-MH44211]; NINDS NIH HHS [NS16106] NR 40 TC 32 Z9 36 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 1996 VL 50 IS 5 BP 1167 EP 1177 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VU893 UT WOS:A1996VU89300014 PM 8913348 ER PT J AU Masserano, JM Gong, L Kulaga, H Baker, I Wyatt, RJ AF Masserano, JM Gong, L Kulaga, H Baker, I Wyatt, RJ TI Dopamine induces apoptotic cell death of a catecholaminergic cell line derived from the central nervous system SO MOLECULAR PHARMACOLOGY LA English DT Article ID PARKINSONS-DISEASE; TRANSGENIC MICE; PROTOONCOGENE BCL-2; DNA FRAGMENTATION; HYDROGEN-PEROXIDE; GLOBAL-ISCHEMIA; FREE-RADICALS; GROWTH-FACTOR; RAT-BRAIN; NEURONS AB Dopamine produces a time- and dose-dependent increase in cell death in a clonal catecholaminergic cell line (CATH.a) derived from the central nervous system. Cell death also occurred after treatment with the catecholamines L-dihydroxyphenylalanine, norepinephrine, epinephrine, and isoproterenol, as well as the neurotoxic compound 6-hydroxydopamine. Cell death is not receptor mediated because selective noradrenergic and dopaminergic receptor agonists had no effect on CATH.a cell viability. Dopamine induces apoptotic cell death as indicated by DNA fragmentation measured by gel electrophoresis and by flow cytometric analysis. Apoptosis seems to be produced by dopamine autoxidation, because intracellular peroxides increase after dopamine treatment and cell death can be inhibited by catalase and N-acetylcysteine. N-acetylcysteine produced a dose-dependent decrease in dopamine-induced cell death; this correlated with a decrease in peroxide formation. In addition, antisense to the antioxidant protein bcl-2 increases the sensitivity of CATH.a cells to dopamine-induced cell death. These findings indicate that the oxidative products of dopamine cause neurotoxicity through apoptosis. RP Masserano, JM (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE,WASHINGTON,DC 20032, USA. NR 39 TC 90 Z9 95 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 NOV PY 1996 VL 50 IS 5 BP 1309 EP 1315 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VU893 UT WOS:A1996VU89300028 PM 8913362 ER PT J AU Licinio, J AF Licinio, J TI Molecular psychiatry joins Biomedicine SO MOLECULAR PSYCHIATRY LA English DT Editorial Material RP Licinio, J (reprint author), NIMH,UNIT CLIN RES,CLIN NEUROENDOCRINOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BLDG 10,RM 3S231,BETHESDA,MD 20892, USA. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 3 TC 1 Z9 1 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1996 VL 1 IS 5 BP 345 EP 346 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VV911 UT WOS:A1996VV91100001 PM 9154221 ER PT J AU Wolozin, B AF Wolozin, B TI Reductionist science and Alzheimer's disease: Redoubling our effort in redox chemistry SO MOLECULAR PSYCHIATRY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; BETA-AMYLOID PEPTIDES; CELL-DEATH; SUPEROXIDE-DISMUTASE; APOPTOSIS; PROTEIN; CALCIUM; NEURONS; PHOSPHORYLATION; INHIBITION RP Wolozin, B (reprint author), NIMH,SECT GERIATR PSYCHIAT,BETHESDA,MD 20892, USA. NR 29 TC 0 Z9 0 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1996 VL 1 IS 5 BP 352 EP 355 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VV911 UT WOS:A1996VV91100003 PM 9154224 ER PT J AU Malhotra, AK Virkkunen, M Rooney, W Eggert, M Linnoila, M Goldman, D AF Malhotra, AK Virkkunen, M Rooney, W Eggert, M Linnoila, M Goldman, D TI The association between the dopamine D-4 receptor (D4DR) 16 amino acid repeat polymorphism and Novelty Seeking SO MOLECULAR PSYCHIATRY LA English DT Article DE dopamine D-4 receptor; polymorphism; personality; allele; genotype; association study ID CLOZAPINE; VARIANTS; GENE AB Ebstein and colleagues have recently reported a significant association between the 7-repeat allele of the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and the personality trait of Novelty Seeking (NS) in 124 Israeli subjects. This study, and another study conducted in the US (although with a different personality measure) that observed a similar association, have generated wide interest in the identification of the genes involved in personality variation. We have determined D4DR genotypes in two groups of Finnish subjects; 193 psychiatrically screened normal controls and 138 alcoholic offenders and assessed NS with the Tridimensional Personality Questionnaire (TPQ). In normals, we find no significant association between NS and the 7-repeat allele despite similar allele frequencies and the use of the same personality measure as Ebstein et al. The group of alcoholic offenders have significantly higher NS than normals, however we fail to replicate the previous association in this group and, in fact, find a significant association in the opposite direction as previously observed. These data suggest that D4DR may require re-evaluation as a candidate gene for personality variation. C1 UNIV HELSINKI,DEPT PSYCHIAT,FIN-00014 HELSINKI,FINLAND. NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. NIAAA,DIV INTRAMURAL CLIN & BIOL RES,NEUROGENET LAB,BETHESDA,MD 20892. RP Malhotra, AK (reprint author), NIMH,EXPT THERAPEUT BRANCH,DIV INTRAMURAL RES,10 CTR DR,BLDG 10,ROOM 4N212,BETHESDA,MD 20892, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 15 TC 163 Z9 165 U1 2 U2 9 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1996 VL 1 IS 5 BP 388 EP 391 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VV911 UT WOS:A1996VV91100012 PM 9154232 ER PT J AU Polymeropoulos, MH Schaffer, AA AF Polymeropoulos, MH Schaffer, AA TI Scanning the genome with 1772 microsatellite markers in search of a bipolar disorder susceptibility gene SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar disorder; linkage ID LINKAGE AB Bipolar disorder affects approximately 1% of the population and there is evidence that genetic factors play an important role in the production of symptoms. We undertook a genetic linkage study for the discovery of a major locus conferring susceptibility for bipolar illness in an Old Order Amish pedigree. Our study took advantage of publicly available phenotypic and genotypic information, the latter as a byproduct of the human genome project effort. We present a genomic scan using 1772 polymorphic genetic markers and we suggest candidate genetic regions for harboring a bipolar disorder susceptibility gene. RP Polymeropoulos, MH (reprint author), NIH,GENE MAPPING UNIT,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BLDG 49 RM 4A66,BETHESDA,MD 20892, USA. RI Schaffer, Alejandro/F-2902-2012 NR 9 TC 19 Z9 19 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1996 VL 1 IS 5 BP 404 EP 407 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VV911 UT WOS:A1996VV91100015 PM 9154235 ER PT J AU Gatev, P Thomas, S Lou, JS Lim, M Hallett, M AF Gatev, P Thomas, S Lou, JS Lim, M Hallett, M TI Effects of diminished and conflicting sensory information on balance in patients with cerebellar deficits SO MOVEMENT DISORDERS LA English DT Article DE posture; cerebellar deficits; sensory organization test; sensory conflict ID POSTURAL SWAY; STANCE; ATAXIA; VISION; MOTION; RESPONSES; NORMALS; ATROPHY; MODEL AB We studied the effects of altered sensory information on standing balance in 25 patients with cortical cerebellar atrophy (CCA), nine patients with olivopontocerebellar atrophy (OPCA), and 10 normal subjects. The total sway path and its components, the anteroposterior (AP) sway path and the lateral sway path, were measured under six conditions: (1) standing on a fixed platform with the eyes open and visual surroundings fixed, (2) standing on a fu;ed platform with the eyes closed, (3) standing on a fixed platform with the eyes open and visual surroundings AP sway referenced, (4) standing on an AP sway-referenced platform with the eyes open and visual surroundings fixed, (5) standing on an AP sway-referenced platform with the eyes closed, and (6) standing on an AP sway-referenced platform with the eyes open and visual surroundings AP sway referenced. Patients swayed more than normal subjects during normal stance (condition 1), when the visual information was absent (condition 2) or distorted (condition 3), and when the proprioceptive information from the ankles was distorted (condition 4). Patients swayed much more than normal, and most fell, when two sensory modalities were affected under condition 5 (proprioceptive information distorted and visual information absent) and condition 6 (both proprioceptive information and visual information distorted). When the patients' sway was normalized to that of the first condition, however, only their lateral sway was greater than the sway in normal subjects. Unlike in normal subjects, the patients' lateral sway varied with the AP sway to approximately the same degree in each condition for conditions 1-5. Clinical ratings of gait and balance were highly correlated with the sway measures. Quantitative testing of standing balance with altered sensory information has better sensitivity than normal stance testing. C1 NINCDS, HUMAN MOTOR CONTROL SECT, MED NEUROL BRANCH, NIH, BETHESDA, MD 20892 USA. FU PHS HHS [5F05 W04643] NR 31 TC 15 Z9 15 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 1996 VL 11 IS 6 BP 654 EP 664 DI 10.1002/mds.870110610 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA VP958 UT WOS:A1996VP95800009 PM 8914091 ER PT J AU Luciano, CA Sivakumar, K Spector, SA Dalakas, MC AF Luciano, CA Sivakumar, K Spector, SA Dalakas, MC TI Electrophysiologic and histologic studies in clinically unaffected muscles of patients with prior paralytic poliomyelitis SO MUSCLE & NERVE LA English DT Article DE macro-EMG; poliomyelitis; reinnervation; morphometry; postpolio syndrome ID MUSCULAR-ATROPHY; MOTOR UNITS; PRIOR POLIO; MACRO EMG; DENERVATION; SIMULATION; FIBERS AB Macro-electromyography (macro-EMG) studies have provided important information about the size of the motor units and the degree of reinnvervation in clinically affected muscles of patients with a history of poliomyelitis and postpolio syndrome. The study of clinically unaffected muscles and correlation of their electrophysiologic characteristics with the muscle architecture could provide meaningful information about the ongoing subclinical denervation. We performed macro-EMG and concomitantly measured fiber density in the clinically unaffected gastrocnemius muscle of 10 patients with postpolio syndrome and 10 normal subjects of similar age. We also performed biopsies on the gastrocnemius muscle of 8 of the patients. The median amplitude and area of the macro-motor unit potentials (macro-MUPs) were increased in 8 of the 10 patients, and occasionally were five times as large as the mean median value for the normal subjects. Seven biopsy specimens showed moderate to very large fiber-type grouping. In 5 patients, there was correlation between the electrophysiologic and histologic indices of reinnervation. Amplitude and area of the macro-MUPs were associated with the muscle fiber cross-sectional area. We conclude that clinically unaffected muscles of patients with postpolio syndrome often have large motor units as the result of effective reinnervation after the original motor neuron loss. In spite of possible differences in the cytoarchitecture of muscles affected to different degrees, macro-EMG and fiber density measurements are reliable noninvasive techniques for studying the extent and effectiveness of reinnervation in patients with postpolio syndrome. (C) 1996 John Wiley & Sons, Inc. C1 NINCDS,NEUROMUSCULAR DIS SECT,NATL INST HLTH,BETHESDA,MD 20892. RP Luciano, CA (reprint author), NINCDS,EMG SECT,NATL INST HLTH,BLDG 10,ROOM 5C101,10 CTR DR MSC 1404,BETHESDA,MD 20892, USA. NR 26 TC 22 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD NOV PY 1996 VL 19 IS 11 BP 1413 EP 1420 DI 10.1002/(SICI)1097-4598(199611)19:11<1413::AID-MUS5>3.3.CO;2-3 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VN041 UT WOS:A1996VN04100005 PM 8874398 ER PT J AU Cremer, C Munkel, C Granzow, M Jauch, A Dietzel, S Eils, R Guan, XY Meltzer, PS Trent, JM Langowski, J Cremer, T AF Cremer, C Munkel, C Granzow, M Jauch, A Dietzel, S Eils, R Guan, XY Meltzer, PS Trent, JM Langowski, J Cremer, T TI Nuclear architecture and the induction of chromosomal aberrations SO MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; DIFFRACTION RESOLUTION LIMIT; CHINESE-HAMSTER CHROMOSOMES; DIGITAL IMAGE-ANALYSIS; INTERPHASE NUCLEUS; HUMAN-LYMPHOCYTES; CELL-NUCLEI; BIOLOGICAL DOSIMETRY; AXIAL RESOLUTION; RADIATION AB Progress in fluorescence in situ hybridization, three dimensional microscopy and image analysis has provided the means to study the three-dimensional structure and distribution of chromosome territories within the cell nucleus. In this contribution, we summarize the present state of knowledge of the territorial organization of interphase chromosomes and their topological relationships with other macromolecular domains in the human cell nucleus, and present data from computer simulations of chromosome territory distributions. On this basis, we discuss models of chromosome territory and nuclear architecture and topological consequences for the formation of chromosome exchanges. C1 UNIV HEIDELBERG,INTERDISZIPLINARES ZENTRUM WISSENSCH RECHEN,D-69120 HEIDELBERG,GERMANY. DEUTSCH KREBSFORSCHUNGSZENTRUM,D-69120 HEIDELBERG,GERMANY. UNIV HEIDELBERG,INST HUMAN GENET,D-69120 HEIDELBERG,GERMANY. NIH,NATL CTR HUMAN GENOME RES,CANC GENET LAB,BETHESDA,MD 20892. RP Cremer, C (reprint author), UNIV HEIDELBERG,INST ANGEW PHYS,ALBERT UEBERLE STR 3-5,D-69120 HEIDELBERG,GERMANY. RI Guan, Xin-Yuan/A-3639-2009; Eils, Roland/B-6121-2009; Langowski, Jorg/A-1843-2011 OI Guan, Xin-Yuan/0000-0002-4485-6017; Eils, Roland/0000-0002-0034-4036; Langowski, Jorg/0000-0001-8600-0666 NR 79 TC 104 Z9 108 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1110 J9 MUTAT RES-REV GENET JI Mutat. Res.-Rev. Genet. Toxicol. PD NOV PY 1996 VL 366 IS 2 BP 97 EP 116 DI 10.1016/S0165-1110(96)90031-7 PG 20 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA VZ224 UT WOS:A1996VZ22400004 PM 9001577 ER PT J AU Dean, M AF Dean, M TI Polarity, proliferation and the hedgehog pathway SO NATURE GENETICS LA English DT Editorial Material ID SONIC-HEDGEHOG; DROSOPHILA; GENE; PROTEIN; FAMILY; ENCODES RP Dean, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,HUMAN GENET SECT,LAB GENOM DIVERS,BLDG 560,RM 21-18,FREDERICK,MD 21702, USA. OI Dean, Michael/0000-0003-2234-0631 NR 39 TC 19 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1996 VL 14 IS 3 BP 245 EP 247 DI 10.1038/ng1196-245 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VQ146 UT WOS:A1996VQ14600006 PM 8896548 ER PT J AU Liyanage, M Coleman, A duManoir, S Veldman, T McCormack, S Dickson, RB Barlow, C WynshawBoris, A Janz, S Wienberg, J FergusonSmith, MA Schrock, E Ried, T AF Liyanage, M Coleman, A duManoir, S Veldman, T McCormack, S Dickson, RB Barlow, C WynshawBoris, A Janz, S Wienberg, J FergusonSmith, MA Schrock, E Ried, T TI Multicolour spectral karyotyping of mouse chromosomes SO NATURE GENETICS LA English DT Article ID TUMORIGENESIS; MODELS; MICE C1 NIH,DIAGNOST DEV BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NIH,LAB GENET DIS RES,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NCI,GENET LAB,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,LOMBARDI CANC CTR,WASHINGTON,DC 20057. UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1TN,ENGLAND. FU NCI NIH HHS [1P50CA58185] NR 15 TC 218 Z9 224 U1 0 U2 6 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1996 VL 14 IS 3 BP 312 EP 315 DI 10.1038/ng1196-312 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VQ146 UT WOS:A1996VQ14600026 PM 8896561 ER PT J AU Sango, K McDonald, MP Crawley, JN Mack, ML Tifft, CJ Skop, E Starr, CM Hoffmann, A Sandhoff, K Suzuki, K Proia, RL AF Sango, K McDonald, MP Crawley, JN Mack, ML Tifft, CJ Skop, E Starr, CM Hoffmann, A Sandhoff, K Suzuki, K Proia, RL TI Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis SO NATURE GENETICS LA English DT Article ID TAY-SACHS-DISEASE; TARGETED DISRUPTION; HEXA GENE; MODEL C1 NIDDKD,SECT BIOCHEM GENET,GENET & BIOCHEM BRANCH,NIH,BETHESDA,MD 20892. NIMH,SECT BEHAV NEUROPHARMACOL,EXPT THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT MED GENET,WASHINGTON,DC 20010. GLYKO INC,NOVATO,CA 94949. UNIV BONN,INST ORGAN CHEM & BIOCHEM,D-53121 BONN,GERMANY. UNIV N CAROLINA,DEPT PATHOL & LAB MED,CHAPEL HILL,NC 27599. UNIV N CAROLINA,UNC NEUOSCI CTR,CHAPEL HILL,NC 27599. RI Proia, Richard/A-7908-2012 FU NICHD NIH HHS [HD-03110]; NINDS NIH HHS [NS-24453] NR 12 TC 140 Z9 142 U1 0 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1996 VL 14 IS 3 BP 348 EP 352 DI 10.1038/ng1196-348 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VQ146 UT WOS:A1996VQ14600035 PM 8896570 ER PT J AU Shi, ZZ Habib, GM Rhead, WJ Gahl, WA He, XW Sazer, S Lieberman, MW AF Shi, ZZ Habib, GM Rhead, WJ Gahl, WA He, XW Sazer, S Lieberman, MW TI Mutations in the glutathione synthetase gene cause 5-oxoprolinuria SO NATURE GENETICS LA English DT Article ID SCHIZOSACCHAROMYCES-POMBE; INBORN ERROR; FIBROBLASTS; DEFICIENCY; EXPRESSION; PATIENT C1 BAYLOR COLL MED,DEPT PATHOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT BIOCHEM,HOUSTON,TX 77030. UNIV IOWA,COLL MED,DEPT PEDIAT,IOWA CITY,IA 52242. NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. FU NIEHS NIH HHS [ES07827]; NIGMS NIH HHS [GM49119] NR 22 TC 49 Z9 50 U1 1 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1996 VL 14 IS 3 BP 361 EP 365 DI 10.1038/ng1196-361 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VQ146 UT WOS:A1996VQ14600038 PM 8896573 ER PT J AU Tonin, P Weber, B Offit, K Couch, F Rebbeck, TR Neuhausen, S Godwin, AK Daly, M WagnerCostalos, J Berman, D Grana, G Fox, E Kane, MF Kolodner, RD Krainer, M Haber, DA Struewing, JP Warner, E Rosen, B Lerman, C Peshkin, B Norton, L Serova, O Foulkes, WD Lynch, HT Lenoir, GM Narod, SA Garber, JE AF Tonin, P Weber, B Offit, K Couch, F Rebbeck, TR Neuhausen, S Godwin, AK Daly, M WagnerCostalos, J Berman, D Grana, G Fox, E Kane, MF Kolodner, RD Krainer, M Haber, DA Struewing, JP Warner, E Rosen, B Lerman, C Peshkin, B Norton, L Serova, O Foulkes, WD Lynch, HT Lenoir, GM Narod, SA Garber, JE TI Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families SO NATURE MEDICINE LA English DT Editorial Material ID GENE C1 MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ H3G 1A4,CANADA. MONTREAL GEN HOSP,RES INST,MONTREAL,PQ H3G 1A4,CANADA. UNIV PENN,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. MEM SLOAN KETTERING CANC CTR,DEPT HUMAN GENET,CLIN GENET SERV,NEW YORK,NY 10021. UNIV PENN,DEPT BIOSTAT & EPIDEMIOL,PHILADELPHIA,PA 19104. UNIV UTAH,DEPT MED INFORMAT,GENET EPIDEMIOL GRP,SALT LAKE CITY,UT 84108. FOX CHASE CANC CTR,DIV BASIC SCI,PHILADELPHIA,PA 19111. FOX CHASE CANC CTR,DIV POPULAT SCI,PHILADELPHIA,PA 19111. COOPER HOSP UNIV MED CTR,DEPT MED,DIV HEMATOL ONCOL,CAMDEN,NJ 08103. DANA FARBER CANC INST,DIV HUMAN CANC GENET,BOSTON,MA 02115. DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,CTR CANC,CTR CANC RISK ANAL,CHARLESTOWN,MA 02129. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIH,LAB GENE TRANSFER,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. TORONTO SUNNYBROOK REG CANC CTR,DIV MED ONCOL,TORONTO,ON M4N 3M5,CANADA. TORONTO GEN HOSP,DEPT OBSTET & GYNECOL,TORONTO,ON M5G 2C4,CANADA. GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,WASHINGTON,DC 20007. MEM SLOAN KETTERING CANC CTR,DEPT MED,BREAST CANC MED SERV,NEW YORK,NY 10021. INT AGCY RES CANC,F-69372 LYON,FRANCE. SIR MORTIMER B DAVIS JEWISH HOSP,CANC PREVENT RES UNIT,MONTREAL,PQ H3T 1E2,CANADA. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED & PUBL HLTH,OMAHA,NE 68178. UNIV TORONTO,WOMENS COLL HOSP,DEPT MED,TORONTO,ON M5G 1N8,CANADA. MCGILL UNIV,DEPT MED,DIV MED GENET,MONTREAL,PQ H3G 1A4,CANADA. RP Tonin, P (reprint author), UNIV TORONTO,WOMENS COLL HOSP,DEPT MED,790 BAY ST,ROOM 750,TORONTO,ON M5G 1N8,CANADA. RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU NCI NIH HHS [CA 55914, CA 06516]; NIAID NIH HHS [AI 28691] NR 25 TC 211 Z9 212 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1996 VL 2 IS 11 BP 1179 EP 1183 DI 10.1038/nm1196-1179 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VQ101 UT WOS:A1996VQ10100023 PM 8898735 ER PT J AU Zubieta, JK Gorelick, DA Stauffer, R Ravert, HT Dannals, RF Frost, JJ AF Zubieta, JK Gorelick, DA Stauffer, R Ravert, HT Dannals, RF Frost, JJ TI Increased mu opioid receptor binding detected by PET in cocaine-dependent men is associated with cocaine craving SO NATURE MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; MESSENGER-RNA; EXPOSURE INCREASES; OPIATE RECEPTORS; BRAIN; BUPRENORPHINE; EXPRESSION; METABOLISM; STRIATUM; HUMANS AB The endogenous opioid system has been recently implicated in the reinforcing actions of cocaine and other addictive drugs. In this study we examined mu opioid receptor binding in ten cocaine-dependent men and seven nonaddicted controls using positron emission tomography and [C-11]carfentanil. Mu opioid binding was increased in several brain regions of the cocaine addicts studied 1-4 days after their last use of cocaine. Binding was positively correlated with the severity of cocaine craving experienced at the time. The upregulation of mu opioid receptor binding persisted after 4 weeks of monitored cocaine abstinence. These findings demonstrate for the first time the involvement of the endogenous opioid system in cocaine dependence and cocaine craving in living human subjects. C1 JOHNS HOPKINS MED INST,DEPT RADIOL,DIV NUCL MED,BALTIMORE,MD 21287. NIDA,INTRAMURAL RES PROGRAM,TREATMENT BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT NEUROSCI,DIV NUCL MED,BALTIMORE,MD 21287. FU NIDA NIH HHS [IR01-DA 09479] NR 32 TC 181 Z9 188 U1 2 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1996 VL 2 IS 11 BP 1225 EP 1229 DI 10.1038/nm1196-1225 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VQ101 UT WOS:A1996VQ10100037 PM 8898749 ER PT J AU Cocchi, F DeVico, AL GarzinoDemo, A Cara, A Gallo, RC Lusso, P AF Cocchi, F DeVico, AL GarzinoDemo, A Cara, A Gallo, RC Lusso, P TI The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SOLUBLE CD4 NEUTRALIZATION; T-CELLS; HTLV-III; TYPE-1; REPLICATION; IDENTIFICATION; MACROPHAGE; TROPISM; LYMPHOCYTES AB The ability of CD8(+) T cells derived from human immunodeficiency virus (HIV)-infected patients to produce soluble HIV-suppressive factor(s) (HIV-SF)(1-3) has been suggested as an important mechanism of control of HIV infection in vivo(4,5). The C-C chemokines RANTES, MIP-1 alpha and MIP-1 beta were recently identified as the major components of the HIV-SF produced by both immortalized and primary patient CD8(+) T cells. Whereas they potently inhibit infection by primary and macrophage-tropic HIV-1 isolates, T-cell line-adapted viral strains tend to be insensitive to their suppressive effects(6). Consistent with this discrepancy, two distinct chemokine receptors, namely, CXCR4 (ref. 7) and CCR5 (ref. 8), were recently identified as potential co-receptors for T-cell line-adapted and macrophage-tropic HIV-1 isolates, respectively(9-12). Here, we demonstrate that the third hypervariable domain of the gp120 envelope glycoprotein is a critical determinant of the susceptibility of HIV-1 to chemokines. Moreover, we show that RANTES, MIP-1 alpha. and MIP-1 beta block the entry of HIV-1 into cells and that their antiviral activity is independent of pertussis toxin-sensitive signal transduction pathways mediated by chemokine receptors. The ability of the chemokines to block the early steps of HIV infection could be exploited to develop novel therapeutic approaches for AIDS. C1 UNIV MARYLAND,BIOTECNOL INST & SCH MED,CTR MED BIOTECHNOL,INST HUMAN VIROL,BALTIMORE,MD 21201. SAN RAFFAELE SCI INST,DIPARTIMENTO RIC BIOL & TECNOL,I-20132 MILAN,ITALY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 34 TC 429 Z9 438 U1 1 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1996 VL 2 IS 11 BP 1244 EP 1247 DI 10.1038/nm1196-1244 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VQ101 UT WOS:A1996VQ10100041 PM 8898753 ER PT J AU Smith, MA Cizza, G AF Smith, MA Cizza, G TI Stress-induced changes in brain-derived neurotrophic factor expression are attenuated in aged Fischer 344/N rats SO NEUROBIOLOGY OF AGING LA English DT Article DE nerve growth factor; neurotrophin 3; hippocampus; paraventricular; nucleus; locus coeruleus ID NERVE GROWTH-FACTOR; MESSENGER-RNA EXPRESSION; CA3 PYRAMIDAL NEURONS; SPATIAL MEMORY; CORTICOSTEROID RECEPTORS; ALZHEIMERS-DISEASE; MOLECULAR-CLONING; LOCUS-COERULEUS; HIPPOCAMPUS; PITUITARY AB Aging and stress can sometimes result in a decline in brain function. We addressed the question whether changes in the expression of neurotrophic factors, which are necessary for the survival and maintenance of neurons, might occur during aging and stress. Therefore, we used in situ hybridization to investigate the effects of aging and stress on neurotrophic factor expression in young (3-4 month) and old (24 month) male Fischer 344/N rats. The ability of acute immobilization stress (2 h) to modulate BDNF mRNA levels in old rats was significantly reduced both in the hippocampus (a smaller decrease in BDNF) and the PVN (a smaller increase in BDNF) compared to young rats. In contrast, the induction of nerve growth factor and neurotrophin 3 (NT-3) by stress was not influenced by age. The diminished BDNF responses to stress in aged rats may be relevant to difficulties in adaptation to stress encountered during old age. Copyright (C) 1996 Elsevier Science Inc. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP Smith, MA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 41 Z9 41 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1996 VL 17 IS 6 BP 859 EP 864 DI 10.1016/S0197-4580(96)00066-8 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA VY127 UT WOS:A1996VY12700006 PM 9363796 ER PT J AU Moriwaki, A Wang, JB Svingos, A vanBockstaele, E Cheng, P Pickel, V Uhl, GR AF Moriwaki, A Wang, JB Svingos, A vanBockstaele, E Cheng, P Pickel, V Uhl, GR TI mu Opiate receptor immunoreactivity in rat central nervous system SO NEUROCHEMICAL RESEARCH LA English DT Article DE mu opiate receptor; immunoreactivity; distribution ID KAPPA-OPIOID RECEPTORS; MESSENGER-RNA EXPRESSION; IN-SITU HYBRIDIZATION; SPINAL-CORD; IMMUNOHISTOCHEMICAL LOCALIZATION; PHARMACOLOGICAL CHARACTERIZATION; MOLECULAR-CLONING; DORSAL HORN; DELTA; BRAIN AB Immunoreactivity corresponding to the C-terminus of the rat mu opiate receptor can be detected by light microscopy in fiber- and terminal-like patterns in a number of rat brain and spinal cord regions, and in immunoreactive perikarya in several of these regions. Especially abundant fiber- and terminal-like patterns were localized to superficial layers of the spinal cord dorsal horn and nucleus caudalis of the spinal tract of the trigeminal, the nucleus of the solitary tract, nucleus ambiguous, locus coeruleus, interpeduncular nucleus, medial aspect of the lateral habenular nucleus, presumed ''striasomes'' of the caudate-putamen and nucleus accumbens. Moderate fiber and terminal densities were found in the ventral tegmental area, more medial aspects of the thalamus and hypothalamus, and several amygdaloid nuclei. Immunostained perikarya were prominent in the nucleus accumbens and also observed in the middle layers of the cerebral cortex, septum and diagonal band, preoptic area, medial thalamic and habenular nuclei, locus coeruleus, nucleus ambiguous, nucleus of the solitary tract, trigeminal nucleus caudalis, and spinal cord substantia gelatinosa zones. Many of these localizations correspond well with the previously-determined autoradiographic distributions of mu opiate receptor ligand binding, and with reports of mu opiate receptor immunoreactivity determined using other antisera. Electron microscopic immunohistochemical studies reveal details of the membrane distribution of the mu receptor in nucleus accumbens, caudate/putamen, locus coeruleus, and spinal cord. These results suggest largely neuronal and largely extrasynaptic distributions of mu receptors that show differential patterns of perikaryal, dendritic, and/or axonal immunostaining in different central nervous system zones. Identification of these distributions adds substantially to data identifying the cellular localization of the principal opiate receptor involved in both analgesic and addictive processes. C1 NIDA,MOL NEUROBIOL BRANCH,INTRAMURAL RES PROGRAM,NIH,BETHESDA,MD. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,DIV NEUROBIOL,NEW YORK,NY 10021. NR 28 TC 54 Z9 55 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 1996 VL 21 IS 11 BP 1315 EP 1331 DI 10.1007/BF02532373 PG 17 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VU944 UT WOS:A1996VU94400007 PM 8947922 ER PT J AU Litvan, I Mega, MS Cummings, JL Fairbanks, L AF Litvan, I Mega, MS Cummings, JL Fairbanks, L TI Neuropsychiatric aspects of progressive supranuclear palsy SO NEUROLOGY LA English DT Article ID RICHARDSON-OLSZEWSKI SYNDROME; ADVANCED PARKINSONS-DISEASE; NURSING-HOME PLACEMENT; ALZHEIMERS-DISEASE; PSYCHIATRIC-SYMPTOMS; BASAL GANGLIA; DEMENTIA; DEPRESSION; IMPAIRMENT; COGNITION AB Administering the Neuropsychiatric Inventory (NPI), we examined the behavioral symptoms of 22 patients with progressive supranuclear palsy (PSP), 50 patients with Alzheimer's disease, and 40 controls. PSP patients exhibited apathy (91%), disinhibition (36%), dysphoria (18%) and anxiety (18%), but rarely (<9%) irritability, abnormal motor behaviors, or agitation. Apathy in PSP was significantly associated with executive dysfunction. The presence of high apathy and low agitation and anxiety scale scores correctly identified the PSP patients 85% of the time. Evaluating the behavioral abnormalities of patients with neurodegenerative disorders will aid diagnosis and facilitate management. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT NEUROL,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,BEHAV NEUROSCI SECT,PSYCHIAT SERV,LOS ANGELES,CA 90073. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20892, USA. OI Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [AG10123] NR 60 TC 134 Z9 137 U1 0 U2 5 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1996 VL 47 IS 5 BP 1184 EP 1189 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA VR425 UT WOS:A1996VR42500012 PM 8909427 ER PT J AU Litvan, I FitzGibbon, EJ AF Litvan, I FitzGibbon, EJ TI Can tropicamide eye drop response differentiate patients with progressive supranuclear palsy and Alzheimer's disease from healthy control subjects? SO NEUROLOGY LA English DT Article AB Pupillary dilation in response to dilute tropicamide eye drops has been proposed as a noninvasive diagnostic test to identify patients with Alzheimer's disease (AD). We examined 14 patients with progressive supranuclear palsy (PSP), another related neurodegenerative disorder characterized by severe widespread cholinergic deficits and known central hypersensitivity to cholinergic blockade, to determine whether they also showed a marked pupil dilation after administration of dilute tropicamide eye drops. Both PSP patients and healthy age-matched control subjects had a similar pupillary response comparable with that previously reported in AD patients. Given its lack of specificity, physicians should be very cautious in using this test for identification of patients with AD. C1 NIH,NEI,BETHESDA,MD 20814. RP Litvan, I (reprint author), NIH,NINDS,FED BLDG ROOM 714,BETHESDA,MD 20814, USA. OI Litvan, Irene/0000-0002-3485-3445 NR 12 TC 25 Z9 25 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1996 VL 47 IS 5 BP 1324 EP 1326 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA VR425 UT WOS:A1996VR42500036 PM 8909451 ER PT J AU Silburn, P Cervenakova, L Varghese, P Tannenberg, A Brown, P Boyle, R AF Silburn, P Cervenakova, L Varghese, P Tannenberg, A Brown, P Boyle, R TI Fatal familial insomnia: A seventh family SO NEUROLOGY LA English DT Article ID PRION PROTEIN GENE; CREUTZFELDT-JAKOB DISEASE; CODON-178; MUTATION AB A 60-year-old woman with a typical history of fatal familial insomnia (FFI) had FFI proven by histologic examination and molecular testing. Her son, who died at the age of 20 in 1978, had a rapidly progressive dementing illness without reported insomnia. He carried the characteristic mutation for FFI and is the youngest patient reported with this condition. C1 PRINCESS ALEXANDRA HOSP,DEPT NEUROL,BRISBANE,QLD 4102,AUSTRALIA. NIH,BETHESDA,MD. PRINCE CHARLES HOSP,BRISBANE,QLD 4032,AUSTRALIA. RI Silburn, Peter/A-3614-2011; Varghese, Paulose/B-3480-2011 NR 10 TC 16 Z9 16 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1996 VL 47 IS 5 BP 1326 EP 1328 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA VR425 UT WOS:A1996VR42500037 PM 8909452 ER PT J AU Borchelt, DR Thinakaran, G Eckman, CB Lee, MK Davenport, F Ratovitsky, T Prada, CM Kim, G Seekins, S Yager, D Slunt, HH Wang, R Seeger, M Levey, AI Gandy, SE Copeland, NG Jenkins, NA Price, DL Younkin, SG AF Borchelt, DR Thinakaran, G Eckman, CB Lee, MK Davenport, F Ratovitsky, T Prada, CM Kim, G Seekins, S Yager, D Slunt, HH Wang, R Seeger, M Levey, AI Gandy, SE Copeland, NG Jenkins, NA Price, DL Younkin, SG TI Familial Alzheimer's disease-linked presenilin 1 variants elevate A beta 1-42/1-40 ratio in vitro and in vivo SO NEURON LA English DT Article ID AMYLOID PRECURSOR PROTEIN; BETA-PROTEIN; A-BETA; MISSENSE MUTATIONS; SENILE PLAQUES; DOWN-SYNDROME; GENE; A-BETA-42(43); CHROMOSOME-1; PEPTIDE AB Mutations in the presenilin 1 (PS1) and presenilin 2 genes cosegregate with the majority of early-onset familial Alzheimer's disease (FAD) pedigrees. We now document that the A beta 1-42(43)/A beta 1-40 ratio in the conditioned media of independent N2a cell lines expressing three FAD-linked PS1 variants is uniformly elevated relative to cells expressing similar levels of wild-type PS1. Similarly, the A beta 1-42(43)/A beta 1-40 ratio is elevated in the brains of young transgenic animals coexpressing a chimeric amyloid precursor protein (APP) and an FAD-linked PS1 variant compared with brains of transgenic mice expressing APP alone or transgenic mice coexpressing wild-type human PS1 and APP. These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of A beta peptides terminating at 42(43), species that foster A beta deposition. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. CASE WESTERN RESERVE UNIV,DEPT NEUROSCI,CLEVELAND,OH 44106. MAYO CLIN JACKSONVILLE,JACKSONVILLE,FL 32224. ROCKEFELLER UNIV,MASS SPECTROMETRY LAB,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI,NEW YORK,NY 10021. EMORY UNIV,SCH MED,DEPT NEUROL,ATLANTA,GA 30322. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RP Borchelt, DR (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205, USA. RI Lee, Michael/D-9491-2013; Wang, Rong/A-8721-2009; Levey, Allan/F-2104-2011 OI Lee, Michael/0000-0001-5865-9682; Levey, Allan/0000-0002-3153-502X FU NIA NIH HHS [AG05146, AG05689]; NINDS NIH HHS [NS 20471] NR 41 TC 1079 Z9 1101 U1 3 U2 47 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1996 VL 17 IS 5 BP 1005 EP 1013 DI 10.1016/S0896-6273(00)80230-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VV151 UT WOS:A1996VV15100021 PM 8938131 ER PT J AU Alexander, RC Wright, R Freed, W AF Alexander, RC Wright, R Freed, W TI Quantitative trait loci contributing to phencyclidine-induced and amphetamine-induced locomotor behavior in inbred mice SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE amphetamine; inbred mice; locomotor activity; model psychosis; phencyclidine ID GENETIC DISSECTION; COMPLEX TRAITS; STRAINS; SCHIZOPHRENIA; LOCALIZATION; PSYCHOSIS; MODEL AB Phencyclidine (PCP) and amphetamine (AMP) can induce psychotic syndromes in humans, whereas administration of these drugs to mice results in behavioral activation that is influenced by genetic factors. Quantitative trait loci (QTL) underlying genetic differences in responses to PCP and AMP in mice were provisionally identified by correlating allelic variation at known marker loci in the BXD series of recombinant inbred (RI) mice and its progenitors (C57BL/6J and DBA/2J inbred strains) with the locomotor response of each strain to PCP and AMP. Total distance traveled for individual mice from each of the 26 BXD RI and two progenitor strains was measured after injections of normal saline and 7.5 mg/kg IP injection of PCP. This procedure was repeated after 1 week, using 5.0 mg/kg of AMP, instead of PCP. Markers significantly (p < .01) correlated with response to PCP map to murine chromosomes 1, 14, and 15. Response to amphetamine was correlated with markers mapping to chromosomes 4, 5, 6, 8, 14, and 18. Identification of the QTL underlying PCP-induced and AMP-induced behavior in mice may provide clues into the complicated genetics of psychosis in humans. (C) 1996 American College of Neuropsychopharmacology C1 UNIV PENN,CTR STUDIES ADDICT,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. NIMH,PRECLIN NEUROSCI SECT,WASHINGTON,DC. NIMH,NEUROPSYCHIAT BRANCH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC. NR 35 TC 32 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 1996 VL 15 IS 5 BP 484 EP 490 DI 10.1016/S0893-133X(96)00058-9 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VP993 UT WOS:A1996VP99300007 PM 8914121 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 in the monkey: Contribution of the cerebellum SO NEUROSCIENCE LA English DT Article DE sensorimotor transformation; [C-14]deoxyglucose; metabolic mapping ID C-14 2-DEOXYGLUCOSE UPTAKE; NEURONAL-ACTIVITY; EYE-MOVEMENTS; SUPERIOR COLLICULUS; CORTEX STIMULATION; CORTICAL FIELDS; ARM MOVEMENTS; METRIC TENSOR; MOTOR CORTEX; PROJECTIONS AB Metabolic activity was mapped in the cerebellar cortex and its major inputs and projection targets in monkeys performing visually guided reaching with the left forelimb. Normal monkeys and monkeys deprived of visual input to the right cerebral hemisphere by right optic tract section, combined in some cases with forebrain commissurotomy, were studied. We reported previously that visually guided reaching with the left forelimb activated the motor cortex of the right hemisphere equally in all these monkeys, indicating that reaching was controlled by the right hemisphere whether it was visually intact or ''blind'' [Savaki H. E. et al. (1993) J. Neurosci. 13, 2772-2789]. In the present study, metabolic activations were observed in the left cerebellar hemispheric extensions of vermian lobules V, VI and VIII, again regardless of whether the right hemisphere was visually intact or ''blind''. In intact monkeys, however, the activations were significantly smaller in the lateral than in the paravermal zone of these hemispheric extensions, whereas in tractotomized/commissurotomized monkeys the activations were equal in the two zones. The greater activations in the left lateral zone in tractotomized/commissurotomized monkeys may represent compensation in part for the visual deafferentation of the right cerebral hemisphere. Also observed were metabolic activation in the left dorsolateral pontine nucleus in tractotomized/commissurotomized monkeys and metabolic depression in the left dentate nucleus in visually intact monkeys. This pattern of results suggests the following conclusions. The activated loci in the left cerebellar cortex combine (i) visual information about the target relayed by seeing cerebral hemispheres, and (ii) sensorimotor information concerning intended and actual movements of the left forelimb relayed by the right cerebral hemisphere and the limb, respectively, and then (iii) send this integrated information back to the motor cortex of the right cerebral hemisphere, thus enabling it to guide the left forelimb to the target whether the hemisphere is visually intact or ''blind''. Copyright (C) 1996 IBRO. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RP Savaki, HE (reprint author), UNIV CRETE,DIV MED,LAB FUNCT BRAIN IMAGING,POB 1393,GR-71110 IRAKLION,CRETE,GREECE. NR 70 TC 41 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV PY 1996 VL 75 IS 1 BP 143 EP 159 DI 10.1016/0306-4522(96)00258-8 PG 17 WC Neurosciences SC Neurosciences & Neurology GA VR131 UT WOS:A1996VR13100015 PM 8923530 ER PT J AU Xiao, Q Castillo, SO Nikodem, VM AF Xiao, Q Castillo, SO Nikodem, VM TI Distribution of messenger RNAs for the orphan nuclear receptors Nurr1 and Nur77 (NGFI-B) in adult rat brain using in situ hybridization SO NEUROSCIENCE LA English DT Article DE immediate early genes; expression; brain ID IMMEDIATE-EARLY GENES; LONG-TERM POTENTIATION; C-FOS; DENTATE GYRUS; TRANSCRIPTION FACTORS; INDUCIBLE MEMBER; GROWTH-FACTORS; DNA-BINDING; EXPRESSION; INDUCTION AB Nurr1 and Nur77 (NGFI-B) are orphan nuclear receptors, belonging to the steroid/thyroid hormone receptor gene superfamily. They have conserved amino acid sequence in the zinc-finger DNA binding domains and similar COOH-terminal regions, but have no known ligands. However, different expression patterns during brain development and tissue distributions of these messenger RNAs imply that they might reflect a different transcriptional role in the brain. In this study, the regional and cellular expression of messenger RNAs encoding these two proteins in rat brain has been determined by in situ hybridization. Nurr1 messenger RNA is highly expressed in the piriform and entorhinal cortices, hippocampus, medial habenular and paraventricular thalamic nuclei. Moderate labeling was detected in layers II-V of most of the cerebral cortex, and in the dorsal lateral geniculate nucleus, substantia nigra (pars compacta and reticularis) and interpeduncular nucleus. No Nurr1 hybridization signal was seen in the rhombencephalon. In the cerebellum, Nurr1 messenger RNA is present in the internal granular cell layer and Purkinje cell layer. In contrast, Nur77 has a widespread distribution, with the highest level of expression in the cerebral cortex. Moderate hybridization signals were detected in the hippocampus, the lateral dorsal and posterior nuclei, reuniens thalamic nuclei, and paraventricular and supraoptic hypothalamic nuclei. In the rhombencephalon, higher signals were present in the medial and lateral vestibular, dorsal cochlear and Facial, and raphe magnus nuclei. Nur77 signal was also detected in the nucleus of the spinal tract of the trigeminal nerve. In the cerebellum, Nur77 messenger RNA is highly expressed in the Purkinje cell layer and lateral deep nucleus of the cerebellum. Our results show that Nurr1 and Nur77 messenger RNAs have both overlapping and different distribution patterns within the brain, suggesting that they might regulate different sets of responsive genes. C1 NIDDKD,NIH,GENET & BIOCHEM BRANCH,MECHANISMS GENE REGULAT SECT,BETHESDA,MD 20892. NR 43 TC 93 Z9 98 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV PY 1996 VL 75 IS 1 BP 221 EP 230 DI 10.1016/0306-4522(96)00159-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VR131 UT WOS:A1996VR13100021 PM 8923536 ER PT J AU Fields, RD AF Fields, RD TI Signaling from neural impulses to genes SO NEUROSCIENTIST LA English DT Review DE gene expression; protein kinase; cfos; calcium signaling; activity-dependent plasticity; CREB; signal transduction; development ID IMMEDIATE-EARLY GENES; NERVOUS-SYSTEM; CALCIUM; EXPRESSION; NEURONS AB Nerve impulses regulate expression of genes that control receptors, channels, enzymes, and structural proteins. This activity-dependent feedback allows adaptation to changing requirements and environmental conditions. The signal transduction mechanisms carrying information from the cell membrane to the nucleus are becoming well characterized, but a more dynamic view of intracellular signaling is emerging to explain cellular responses to specific patterns of neural impulses. This review analyzes this interface between electrophysiology and molecular cell biology to examine the signals, substrates, and processes that enable the nervous system to regulate its structure and function as a consequence of its own operation. C1 NICHHD,DEV NEUROBIOL LAB,HEAD NEUROCYTOL & PHYSIOL UNIT,BETHESDA,MD 20892. NR 25 TC 24 Z9 24 U1 0 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1073-8584 J9 NEUROSCIENTIST JI Neuroscientist PD NOV PY 1996 VL 2 IS 6 BP 315 EP 325 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VX116 UT WOS:A1996VX11600009 ER PT J AU Chang, DY Hsu, K Maraia, RJ AF Chang, DY Hsu, K Maraia, RJ TI Monomeric scAlu and nascent dimeric Alu RNAs induced by adenovirus are assembled into SRP9/14-containing RNPs in HeLa cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SIGNAL-RECOGNITION PARTICLE; POLYMERASE-III TRANSCRIPTION; HERPES-SIMPLEX VIRUS; PROTEIN TRANSLOCATION; PRECURSOR MOLECULES; BINDING PROTEIN; INFLUENZA-VIRUS; 7S RNA; SEQUENCES; ELEMENTS AB Nearly 1 000 000 copies of Alu interspersed elements comprise similar to 5% of human DNA. Alu elements cause gene disruptions by a process known as retrotransposition, in which dimeric Alu RNA is a presumed intermediate, Dimeric Alu transcripts are labile, giving rise to stable left monomeric scAlu RNAs whose levels are tightly regulated, Induction of Alu RNA by viral infection or cell stress leads to a dramatic increase in dimeric Alu transcripts, while scAlu RNA increases modestly. Each monomer of the dimeric Alu element shares sequence homology with the 7SL RNA component of the signal recognition particle (SRP). The SRP protein known as SRP9/14 is also found in a discrete complex with scAlu RNA, although whether dimeric Alu RNA is associated with SRP9/14 had been unknown. Here we show that antiserum to human SRPS immunoprecipitates both scAlu RNA and dimeric Alu RNAs and that these RNPs accumulate after adenovirus infection, while levels of SRP9, SRP14, SRP54 and 7SL SRP RNA are unaffected. Dimeric Alu RNAs are also associated with the La protein, indicating that these are indeed nascent RNA polymerase III transcripts. This report documents that induced Alu transcripts are assembled into SRP9/14-containing RNPs in vivo while SRP levels are unchanged. Implications for Alu RNA metabolism and evolution are discussed. C1 NICHHD,NIH,LAB MOL GROWTH REGULAT,BETHESDA,MD 20892. NR 42 TC 39 Z9 39 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 NOV 1 PY 1996 VL 24 IS 21 BP 4165 EP 4170 DI 10.1093/nar/24.21.4165 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VT249 UT WOS:A1996VT24900010 PM 8932367 ER PT J AU Ross, SA De Luca, LM AF Ross, SA De Luca, LM TI A new metabolite of retinol: All-trans-4-oxo-retinol as a receptor activator and differentiation agent SO NUTRITION REVIEWS LA English DT Review ID NUCLEAR RECEPTOR; ACID; CELLS AB All-trans-4-oxo-retinol, a metabolite of retinol synthesized in mouse embryonal carcinoma F9 cells, is active in inducing differentiation of these cells. It also functions as a ligand of retinoic acid receptors and a transcriptional activator of reporter genes. These findings may dispel the notion that retinoic acids are the only transactivators of retinoid receptor-dependent pathways. However, there are weaknesses that need to be addressed in order to confirm the relevance of this retinol-mediated signaling pathway. RP Ross, SA (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, DIFFERENTIAT CONTROL SECT,NIH, BLDG 37, ROOM 3A17, BETHESDA, MD 20892 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD NOV PY 1996 VL 54 IS 11 BP 355 EP 356 PN 1 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WT558 UT WOS:A1996WT55800003 PM 9110564 ER PT J AU Ellwein, LB Friedlin, V McBean, AM Lee, PP AF Ellwein, LB Friedlin, V McBean, AM Lee, PP TI Use of eye care services among the 1991 Medicare population SO OPHTHALMOLOGY LA English DT Article ID QUALITY-OF-LIFE; CATARACT-SURGERY; BENEFICIARIES; PREVALENCE; BLINDNESS; BALTIMORE AB Purpose: TO determine the use of eye care services by type of provider (ophthalmologist, optometrist, and non-ophthalmologist physician) in the Medicare population. Methods: As a basis for characterizing eye conditions and ophthalmic services among a population 65 years of age and older, 1991 claims from a representative 5% sample of Medicare beneficiaries were analyzed using a previously described classification scheme. Analysis was specifically conducted by type of provider as well as by the service provided. Results: Almost one half of the approximately 30 million Medicare beneficiaries 65 years of age or older received eye care services in 1991, resulting in more than 35,000,000 visits (caims). Ophthalmologists provided services to 71% of this eye care population, and optometrists to 22%; 36% of this population received ophthalmic-related services from other providers, and 14% from only other providers (commonly for eye lid dermatitis and tumors). Cataract was the most common condition, accounting for 41% of visits to ophthalmologists (and 1.2 million cases of surgery), glaucoma accounted for 19% of visits, and retinal diseases for 14%. The visit percentages for optometrists are 58%, 8%, and 11%, respectively. Ophthalmic examination and evaluation accounted for 63% of the 28,000,000 paid ophthalmologists' procedures, and 58% of the 5,500,000 optometrists' procedures. Conclusion: Optometrists and physicians other than ophthalmologists were the sole providers of ophthalmic-related services to a large percentage of beneficiaries who received eye care in 1991. Within the universe of service provided by ophthalmologists, the majority of all care consisted of evaluation and management services as opposed to surgical procedure-based care. C1 HLTH CARE FINANCING ADM,BALTIMORE,MD. RAND CORP,SANTA MONICA,CA 90406. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90089. RP Ellwein, LB (reprint author), NEI,BLDG 31,RM 6A04,31 CTR DR,MSC 2510,BETHESDA,MD 20892, USA. OI Lee, Paul/0000-0002-3338-136X NR 16 TC 24 Z9 24 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1996 VL 103 IS 11 BP 1732 EP 1743 PG 12 WC Ophthalmology SC Ophthalmology GA VU097 UT WOS:A1996VU09700015 PM 8942864 ER PT J AU Lee, CH Lee, SK Chi, JG Park, SC Chung, SI Saitoh, M Shrestha, P Mori, M AF Lee, CH Lee, SK Chi, JG Park, SC Chung, SI Saitoh, M Shrestha, P Mori, M TI Immunohistochemical evaluation of transglutaminase C in tumours of salivary glands SO ORAL ONCOLOGY LA English DT Article DE immunohistochemistry; salivary gland tumours; transglutaminase ID MICROTUBULE PROTEINS INVITRO; PIG LIVER TRANSGLUTAMINASE; S-100 PROTEIN; TISSUE TRANSGLUTAMINASE; MYOEPITHELIAL CELLS; PLEOMORPHIC ADENOMA; EXPRESSION; KERATIN; IDENTIFICATION; INVOLVEMENT AB Transglutaminase C (TGase C), a family of Ca2+-dependent enzymes and an essential component in the cross-linking of peptide bonds, has been found to be a marker of epithelial differentiation with a possible role in cellular apoptosis, extracellular matrix stabilisation and Ca2+ binding, thereby having a potential role in tumour growth, differentiation and invasive behaviour. The expression of TGase C was evaluated in normal human salivary glands and their neoplastic lesions which included pleomorphic adenoma (n = 30), Warthin's tumour (n = 5), adenoid cystic carcinoma (n = 10), acinic cell carcinoma (n = 5), mucoepidermoid carcinoma (n = 5) and control tissue specimens of normal oral mucosa and squamous cell carcinoma, using polyclonal antibody, the specificity of which was determined by Western blotting, generated by immunising rabbits with purified transglutaminase. The TGase C was observed in the epithelial cells in the control tissue specimens examined. Pleiomorphic adenoma revealed reaction products in luminal tumour cells, the non-luminal or modified myoepithelial cells and their plasmacytoid variants, squamous metaplastic cells and chondroid cells. Adenoid cystic carcinomas had tumour cells in the luminal cells of tubular and cribriform structures and the acinic cell carcinoma had from low to moderate immunoreactivity in the tumour cell component and a diffuse immunoreactivity in the stroma for TGase C. Mucoepidermoid carcinoma showed no reaction products in the mucous-producing cells, while intermediate and epidermoid cells had immunoreactivity in the cell cytoplasm. As the presence of TGase C in salivary gland tumours was confined to those tumour cells which form the predominant histomorphology in each tumour subtype, it may be suggested that these enzymes may have a potential role in the regulation of cellular function in neoplastic salivary tissues affecting tumour growth, differentiation and neoplastic behaviour. Copyright (C) 1996 Elsevier Science Ltd C1 ASAHI UNIV,SCH DENT,DEPT ORAL & MAXILLOFACIAL SURG,MOZUMI,GIFU 50102,JAPAN. NIDR,NIH,BETHESDA,MD 20892. SEOUL NATL UNIV,COLL MED,DEPT BIOCHEM,SEOUL,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,DEPT PATHOL,SEOUL,SOUTH KOREA. DANGKOK UNIV,SCH DENT,DEPT ORAL PATHOL,SEOUL,SOUTH KOREA. RI Chi, Je Geun/G-4989-2011; Seoul National University, Pathology/B-6702-2012; OI Chi, Je-Geun/0000-0002-9950-2072 NR 36 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol. PD NOV PY 1996 VL 32B IS 6 BP 401 EP 406 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA WD719 UT WOS:A1996WD71900007 ER PT J AU Lockhart, PB Fox, PC Gentry, AC Acharya, R Norton, HJ AF Lockhart, PB Fox, PC Gentry, AC Acharya, R Norton, HJ TI Pilot study of controlled-release pilocarpine in normal subjects SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID SALIVARY-GLAND HYPOFUNCTION; ORAL PILOCARPINE; NECK-CANCER; XEROSTOMIA; HEAD; DYSFUNCTION; FLOW AB Objectives. Current systemic treatments with sialogogues for patients with xerostomia are limited because of minimal efficacy, short duration of activity, or problems with side effects. The purpose of this pilot study wag an initial assessment of safety, efficacy, duration of action, multiple dose tolerance, and side effects of a controlled-release formulation of pilocarpine hydrochloride. Study design. Eight healthy hospitalized subjects were given 15 mg of a controlled-release pilocarpine formulation every 12 hours for three doses. Saliva and blood samples were collected at assigned intervals. Repeated measures analysis and paired tests were used for statistical analyses. Results. A significant (p < 0.05) increase in both parotid and whole saliva output followed all three doses beginning within 1 hour of dosing and lasting over 10 hours. Mean plasma pilocarpine concentration reached a maximum of 8.2 ng/ml at approximately 1 hour after the first dose, 11.5 ng/ml after the third dose, and declined to near baseline (0.06 ng/ml) 24 hours after the final dose. None of the participants showed evidence of adverse effects including complaints of sweating or gastrointestinal discomfort Conclusions. A controlled-release formulation of pilocarpine may overcome the therapeutic weaknesses of current pilocarpine preparations by prolonging salivary secretion and reducing undesirable side effects. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,CLIN INVEST SECT,NIH,BETHESDA,MD 20892. CAROLINAS MED CTR,DEPT BIOSTAT,CHARLOTTE,NC 28232. ORAMED INC,CHICAGO,IL. RP Lockhart, PB (reprint author), CAROLINAS MED CTR,DEPT DENT,POB 32861,CHARLOTTE,NC 28232, USA. NR 23 TC 8 Z9 8 U1 0 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 NOV PY 1996 VL 82 IS 5 BP 517 EP 524 DI 10.1016/S1079-2104(96)80196-X PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VU289 UT WOS:A1996VU28900013 PM 8936515 ER PT J AU Reid, KI Carlson, CR Sherman, JJ Curran, SL Gracely, RH AF Reid, KI Carlson, CR Sherman, JJ Curran, SL Gracely, RH TI Influence of a sympathomimetic amine On masticatory and trapezius pain/pressure thresholds and electromyographic levels SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Article ID SYMPATHETIC ACTIVATION; PRIMARY FIBROMYALGIA; PAIN; STRESS; STIMULATION; RESPONSES; MUSCLE AB Objectives. This study examined the influence of terbutaline, a beta-adrenergic sympathomimetic amine on pain/pressure thresholds in the index fingers and masseter and trapezius muscles and electromyographic activity in trapezii. Study design. In a randomized and double-blind controlled trial, 20 asymptomatic female subjects were assigned tb receive either an injection of terbutaline or sterile water before collection of pain/pressure thresholds and electromyographic levels. Repeated analysis of variance and paired t tests were calculated to test for baseline and postinjection differences between groups. Results. No significant baseline or postinjection group differences in pain/pressure thresholds or electromyographic were detected. Conclusions. beta-adrenergic sympathomimetic stimulation does not influence pain/pressure thresholds or electromyographic activity in the masselet and trapezius muscles or pain/pressure thresholds in the index fingers. These results suggest that development of painful muscle conditions is not caused by elevations of sympathetic activity. C1 UNIV KENTUCKY, COLL DENT, OROFACIAL PAIN CTR, LEXINGTON, KY USA. UNIV KENTUCKY, DEPT PSYCHOL, LEXINGTON, KY 40506 USA. NIDR, NEUROBIOL & ANESTHESIOL BRANCH, BETHESDA, MD 20892 USA. NR 36 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD NOV PY 1996 VL 82 IS 5 BP 525 EP 531 DI 10.1016/S1079-2104(96)80197-1 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VU289 UT WOS:A1996VU28900014 PM 8936516 ER PT J AU Ron, E Saftlas, AF AF Ron, E Saftlas, AF TI Head and neck radiation carcinogenesis: Epidemiologic evidence SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Workshop on the Public Health Response to Nasopharyngeal Radium Irradiation CY SEP 27-28, 1995 CL NEW HAVEN, CT ID ATOMIC-BOMB SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; DOSE-RESPONSE RELATIONSHIPS; INDUCED THYROID-CANCER; DENTAL X-RAYS; THERAPEUTIC RADIATION; RADIUM IRRADIATION; SKIN HEMANGIOMA; CHILDHOOD; TUMORS AB This article provides an overview of the long-term carcinogenic effects of medical radiation exposure to the head and neck and focuses on studies that allow risk quantification. The thyroid gland in children is extremely sensitive to the tumorigenic effects of external radiation for many years after exposure. Risk of thyroid cancer decreases with increasing age at exposure, with little risk, if any, apparent among persons exposed as adults. Large risks of neural tumors have been reported after moderate- and high-dose radiotherapy in childhood; however, the magnitude of the risk at low doses and for adult exposures is unclear. Data on salivary gland tumors are limited but fend to support an association with radiation exposure. In contrast, the pituitary gland appears to be relatively resistant to the tumorigenic effects of radiation. Several cohort studies have reported an increased risk of hyperparathyroidism among irradiated populations. In summary, radiation exposure to the head and neck can result in tumors of the thyroid, salivary, and parathyroid glands, as well as the brain and central nervous system. C1 YALE UNIV,SCH MED,DEPT EPIDEMIOL & PUBL HLTH,NEW HAVEN,CT 06520. NCI,DIV EPIDEMIOL & GENET,NIH,BETHESDA,MD 20892. NR 38 TC 29 Z9 29 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1996 VL 115 IS 5 BP 403 EP 408 DI 10.1016/S0194-5998(96)70073-6 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VU694 UT WOS:A1996VU69400007 PM 8903437 ER PT J AU Sandler, DP AF Sandler, DP TI Nasopharyngeal radium irradiation: The Washington County, Maryland, study SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Workshop on the Public Health Response to Nasopharyngeal Radium Irradiation CY SEP 27-28, 1995 CL NEW HAVEN, CT ID NEOPLASMS; CHILDHOOD; TUMORS; HEAD AB Although there have been many studies of cancer risk associated with a variety of x-ray treatments for benign conditions of the head and neck, little is known about the possible long-term health consequences of nasopharyngeal radium irradiation. This treatment results in minimal radiation exposure to the thyroid gland, which is the focus of much of the research regarding other head and neck irradiation. With nasopharyngeal radiation, on the other hand, exposure to the pituitary gland and the nasopharynx in the area immediately adjacent to the application site may have been substantial. In 1975 a follow-up study was undertaken in Washington County, Maryland, of 2925 persons who were treated at the Health Department's Clinic for the Prevention of Deafness in Children between 1943 and 1960. Of these, 904 persons had been treated with nasopharyngeal radium, After an average of 24 years of follow-up, an excess risk from brain cancer was suggested on the basis of three cases of cancer occurring in the treated group and none occurring in those who were not treated. This finding could have resulted by chance, Other results were consistent with a potential pituitary effect of radiation, but interpretation is limited by the absence of clinical and laboratory data. The history of the study is reported along with an overview of study methods and results. C1 NIEHS,RES TRIANGLE PK,NC 27709. OI Sandler, Dale/0000-0002-6776-0018 NR 23 TC 3 Z9 3 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1996 VL 115 IS 5 BP 409 EP 414 DI 10.1016/S0194-5998(96)70074-8 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VU694 UT WOS:A1996VU69400008 PM 8903438 ER PT J AU Shy, C Anderson, H Ducatman, A Fleissner, ML Fox, M Jackson, R Kenneally, F Mather, S Mirza, N Ron, E Ross, D Royal, H Sandler, D Schneider, A Shore, R AF Shy, C Anderson, H Ducatman, A Fleissner, ML Fox, M Jackson, R Kenneally, F Mather, S Mirza, N Ron, E Ross, D Royal, H Sandler, D Schneider, A Shore, R TI Summary report of the panel SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material C1 UNIV N CAROLINA,CHAPEL HILL,NC. WISCONSIN DEPT PUBL HLTH,MADISON,WI. W VIRGINIA UNIV,SCH MED,MORGANTOWN,WV 26506. CONNECTICUT DEPT PUBL HLTH & ADDICT SERV,HARTFORD,CT 06106. VET FOREIGN WARS,WASHINGTON,DC. SUBMARINE SURVIVORS HOTLINE,CIVILIAN DIV,WATERFORD,CT. DEPT VET AFFAIRS,WASHINGTON,DC. VET AFFAIRS MED CTR,PHILADELPHIA,PA. NCI,BETHESDA,MD 20892. W HAVEN VET AFFAIRS MED CTR,W HAVEN,CT. WASHINGTON UNIV,MED CTR,MALLINCKRODT INST RADIOL,ST LOUIS,MO 63110. NIEHS,RES TRIANGLE PK,NC 27709. UNIV ILLINOIS,CHICAGO,IL. NYU,NEW YORK,NY. NR 1 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1996 VL 115 IS 5 BP 442 EP 446 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA VU694 UT WOS:A1996VU69400015 PM 8903445 ER PT J AU Yang, CF Collins, WE Xiao, LH Patterson, PS Reed, RC Hunter, RL Kaslow, DC Lal, AA AF Yang, CF Collins, WE Xiao, LH Patterson, PS Reed, RC Hunter, RL Kaslow, DC Lal, AA TI Influence of adjuvants on murine immune responses against the C-terminal 19 kDa fragment of Plasmodium vivax merozoite surface protein-1 (MSP-1) SO PARASITE IMMUNOLOGY LA English DT Article DE malaria; vaccine; recombinant protein; MSP-1; Plasmodium vivax ID COPOLYMER ADJUVANTS; SACCHAROMYCES-CEREVISIAE; MONOCLONAL-ANTIBODIES; RODENT MALARIA; 19KDA FRAGMENT; T-CELL; FALCIPARUM; ISOTYPE; BLOOD; ANTIGEN AB The immunogenicity of a yeast-expressed 19 kDa fragment of P vivax MSP-1 in the presence of different adjuvant formulations was evaluated. ICR mice were immunized with the 19 kDa antigen, using Freund's, alum, and block copolymer P1005 in water-in-oil (W/O) or oil-in-water (O/W) emulsions with or without detoxified lipopolysaccharide (RaLPS) as adjuvants. Five weeks following immunization with the antigen, mice were boosted with asexual blood-stage antigens. Three weeks after the last immunization with the 19 kDa antigen, mice from the Freund's group and most groups that received P1005 as adjuvant had higher total IgG titres than those that received alum as adjuvant or antigen alone. Antibody responses after the antigen immunization were predominantly of the IgG1 isotype, but mice in the Freund's and P1005 (W/O or O/W emulsion with or without RaLPS) groups also had high titres of IgG2a and IgG2b. Antibody titres against merozoites increased in all groups after the parasite antigen boost. IgG2a levels in the group that received antigen in P1005 plus RaLPS in the W/O emulsion were higher than those receiving Freund's, alum or the other copolymer adjuvants. The high IgG2a titres in this group were associated with reduced IL-10 production. C1 CTR DIS CONTROL & PREVENT,DIV PARASIT DIS,NATL CTR INFECT DIS,PUBL HLTH SERV,ATLANTA,GA 30341. EMORY UNIV,DEPT PATHOL & LAB MED,ATLANTA,GA 30322. NIAID,MALARIA RES LAB,NIH,BETHESDA,MD 20892. RI Xiao, Lihua/B-1704-2013; Yang, Chunfu/G-6890-2013 OI Xiao, Lihua/0000-0001-8532-2727; NR 40 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD NOV PY 1996 VL 18 IS 11 BP 547 EP 558 DI 10.1046/j.1365-3024.1996.d01-32.x PG 12 WC Immunology; Parasitology SC Immunology; Parasitology GA VT821 UT WOS:A1996VT82100002 PM 9226693 ER PT J AU Olliaro, PL Gottlieb, M Wirth, DF AF Olliaro, PL Gottlieb, M Wirth, DF TI Plasmodium falciparum proteinases: Targeted drug development SO PARASITOLOGY TODAY LA English DT Editorial Material C1 NIAID,DIV MICROBIOL & INFECT DIS,PARASITOL & INT PROGRAMS BRANCH,BETHESDA,MD 20892. HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. RP Olliaro, PL (reprint author), UN,DP,WORLD BANK,WHO,SPECIAL PROGRAMME RES & TRAINING TROP DIS,GENEVA,SWITZERLAND. NR 0 TC 6 Z9 6 U1 0 U2 0 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 NOV PY 1996 VL 12 IS 11 BP 413 EP 414 DI 10.1016/0169-4758(96)30028-8 PG 2 WC Parasitology SC Parasitology GA VP707 UT WOS:A1996VP70700001 ER PT J AU Zeichner, SL Mueller, BU Pizzo, PA Dimitrov, DS AF Zeichner, SL Mueller, BU Pizzo, PA Dimitrov, DS TI Kinetics of HIV-1 RNA concentration changes in pediatric patients SO PATHOBIOLOGY LA English DT Article DE HIV-1; AIDS; pediatric patients; diurnal variations ID DRUG-USERS; INFECTION; COUNT; LYMPHOCYTES; DYNAMICS; PLASMA AB Recent studies have used potent antiviral agents to investigate the kinetics of HIV infection in vivo [1-3]. They provided estimates for important kinetic parameters, including the decay constants for circulating virus and infected CD4+ cells. However, since all of these studies fundamentally rely on the use of antiviral agents, it would be useful to develop other approaches capable of independently verifying the values of the kinetic parameters through other means. Since CD4+ cells are known to exhibit diurnal variations and since there have been suggestions that circulating virus concentrations also vary in a diurnal fashion, as well as nonperiodically, we developed a mathematical model to describe those natural variations. The model predicted variations in viral RNA concentrations and produced estimates of the values of viral kinetic parameters without the use of antiviral agents. To compare the model with experimental data we measured the temporal dependence of the concentration of plasma viral RNA obtained from pediatric HIV-1 patients. The data analysis led to finding diurnal variation in the viral RNA and an estimate of the circulating virus half-life in the order of few hours, in reasonable agreement with the estimates obtained using antiviral agents. These results are the first demonstration of diurnal variations in AIDS patients and confirm the order of magnitude of the virus half-life found by using antiviral drugs [3]. These findings may have implications for understanding HIV-1 pathogenesis and the development of therapeutic protocols. C1 NCI,LAB EXPT & COMPUTAT BIOL,NIH,BETHESDA,MD 20892. HARVARD UNIV,CHILDRENS HOSP,SCH MED,BOSTON,MA 02115. RP Zeichner, SL (reprint author), NCI,HIV AIDS MALIGNANCIES BRANCH,NIH,10 CTR DR,BETHESDA,MD 20892, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-2008 J9 PATHOBIOLOGY JI Pathobiology PD NOV-DEC PY 1996 VL 64 IS 6 BP 289 EP 294 DI 10.1159/000164063 PG 6 WC Cell Biology; Pathology SC Cell Biology; Pathology GA WY186 UT WOS:A1996WY18600001 PM 9159022 ER PT J AU Englund, JA Baker, CJ Raskino, C McKinney, RE Lifschitz, MH Petrie, B Fowler, MG Connor, JD Mendez, H ODonnell, K Wara, DW Shliozberg, J Shearer, WT Stechenberg, B Borkowsky, W Bonaforte, RJ Cooper, ER Wiznia, A Toltzis, P Israele, V VanDyke, RB Yogev, R Starr, S Oleske, F Frenkel, L McIntosh, K Montgomery, M Petru, A Squires, JE Wade, N Moore, EC Rakusan, TA Baker, RC Brady, MT Pildes, RS Cervia, JS Wilfert, C Nesheim, S Bellanti, JA Keller, M Abrams, EJ Dossett, JH Rana, SR Tishler, DM Nicholas, SW Lambert, JS Wong, V Gupta, A Deveikis, A Kovacs, A Johnson, G Bamji, M Sacks, HS Pahwa, S GarciaRias, D Flynn, C Philipp, CS Jimenez, E Bonagura, VR Shenap, JL Grieco, MH Lischner, H Minnefor, AB Maldonado, Y Nachman, SA Fikrig, S Weiner, LB Levin, M Gershon, AA Bryson, Y Spector, S Diaz, C Reichman, RR Robinson, J Luzuriaga, K Crain, MJ Lim, W Rich, K Vink, PE Doyle, MG Scott, GB Munoz, J Andiman, WA Behrman, R Hetherington, S McLaren, C Millison, K Moye, J Nozyce, M Pearson, DA Purdue, L Schoenfeld, D Scott, G Spector, SA AF Englund, JA Baker, CJ Raskino, C McKinney, RE Lifschitz, MH Petrie, B Fowler, MG Connor, JD Mendez, H ODonnell, K Wara, DW Shliozberg, J Shearer, WT Stechenberg, B Borkowsky, W Bonaforte, RJ Cooper, ER Wiznia, A Toltzis, P Israele, V VanDyke, RB Yogev, R Starr, S Oleske, F Frenkel, L McIntosh, K Montgomery, M Petru, A Squires, JE Wade, N Moore, EC Rakusan, TA Baker, RC Brady, MT Pildes, RS Cervia, JS Wilfert, C Nesheim, S Bellanti, JA Keller, M Abrams, EJ Dossett, JH Rana, SR Tishler, DM Nicholas, SW Lambert, JS Wong, V Gupta, A Deveikis, A Kovacs, A Johnson, G Bamji, M Sacks, HS Pahwa, S GarciaRias, D Flynn, C Philipp, CS Jimenez, E Bonagura, VR Shenap, JL Grieco, MH Lischner, H Minnefor, AB Maldonado, Y Nachman, SA Fikrig, S Weiner, LB Levin, M Gershon, AA Bryson, Y Spector, S Diaz, C Reichman, RR Robinson, J Luzuriaga, K Crain, MJ Lim, W Rich, K Vink, PE Doyle, MG Scott, GB Munoz, J Andiman, WA Behrman, R Hetherington, S McLaren, C Millison, K Moye, J Nozyce, M Pearson, DA Purdue, L Schoenfeld, D Scott, G Spector, SA TI Clinical and laboratory characteristics of a large cohort of symptomatic, human immunodeficiency virus-infected infants and children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE acquired immunodeficiency syndrome; human immunodeficiency virus; children; infection; antiretroviral therapy; zidovudine; didanosine; development; cortical atrophy; growth failure ID ZIDOVUDINE; TYPE-1; GROWTH AB Background. A large cohort of antiretroviral therapy-naive, symptomatic, HIV-infected children were enrolled into a controlled therapeutic trial (AIDS Clinical Trials Group Protocol 152), providing an opportunity to describe their clinical and laboratory characteristics and determine age-related distinctions. Methods. Study entry evaluations for 838 of 839 enrolled children were analyzed. Weight, head circumference (if <30 months of age), neuroradiologic imaging of the head, developmental or cognitive status and neurologic examination were assessed. Laboratory studies included hemoglobin, absolute neutrophil count, CD4 cell count, serum amylase, alanine aminotransaminase, p24 antigen and HIV blood culture. Data were categorized by age (3 to <12 months, 12 to <30 months, 30 months to 6 years and greater than or equal to 6 years). Results. Younger children had significantly higher rates of abnormalities before antiretroviral therapy, especially factors relating to growth and neurologic or cognitive function. Lower CD4+ cell counts and percentages as well as a positive serum p24 antigen correlated with lower weight-for-age Z scores and developmental indices. Conclusions. These data provide a description of the clinical characteristics of HIV-infected US children at the time antiretroviral therapy is initiated for HIV-related symptoms. The high rate of abnormalities of growth, development and cognitive ability that were observed in children <30 months of age demonstrates that treatment strategies should be developed for earlier intervention. C1 BAYLOR COLL MED,DEPT PEDIAT,HOUSTON,TX 77030. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. DUKE UNIV,SCH MED,DEPT PEDIAT,DURHAM,NC. NIAID,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,DEPT PEDIAT & PHARMACOL,SAN DIEGO,CA 92103. SUNY HLTH SCI CTR,DEPT PEDIAT,BROOKLYN,NY 11203. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. US FDA,KENSINGTON,MD. GLAXO WELLCOME INC,RES TRIANGLE PK,NC 27709. BRISTOL MYERS SQUIBB CO,WALLINGFORD,CT 06492. ACTG OPERAT OFF,BETHESDA,MD. NICHHD,PEDIAT & ADOLESCENT BRANCH,BETHESDA,MD. BRONX LEBANON HOSP CTR,NEW YORK,NY. UNIV TEXAS,SCH MED,HOUSTON,TX. UNIV MIAMI,SCH MED,MIAMI,FL. RP Englund, JA (reprint author), BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030, USA. OI moye, john/0000-0001-9976-8586 NR 27 TC 52 Z9 55 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 1996 VL 15 IS 11 BP 1025 EP 1036 DI 10.1097/00006454-199611000-00018 PG 12 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA VT450 UT WOS:A1996VT45000010 PM 8933553 ER PT J AU Woods, J Ward, G Salem, N AF Woods, J Ward, G Salem, N TI Is docosahexaenoic acid necessary in infant formula? Evaluation of high linolenate diets in the neonatal rat SO PEDIATRIC RESEARCH LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; HUMAN-MILK; PREMATURE-INFANTS; PRETERM INFANTS; BREAST-MILK; WEIGHT-GAIN; FISH OIL; BRAIN; GROWTH; RETINA AB Neural accretion of docosahexaenoic acid (DHA) is thought to play an important role in the neural development of human infants. The lack of DHA in infant formulas contributes to the lowered neural accretion of DHA observed in formula-fed infants relative to those breast-fed. We hypothesized that lowering the dietary linoleic acid (LA) to oc-linolenic acid (LNA) ratio may lead to increases in the level of DHA in the developing brain and retina. Lowering the LA to LNA ratio from 10:1 to 1:1 and to 1:12 in the artificially reared (AR) neonatal rat pup resulted in a significant increase in the percentage of brain DI-IA between AR dietary groups. The brain level of DHA in the AR group fed a 1:12 ratio was similar to that of a dam-reared reference group. However, levels of DHA in the retina of all AR groups were significantly lower than that of the (chow fed) dam-reared group. It appears that LNA may serve as an adequate substrate for the accretion of DHA in the brain, but not the retina of the developing rat. In both the brain and the retina, levels of arachidonic acid in the AR pups fed the 1:1 ratio were similar to that of the dam-reared group. However, levels in the 1:12 group were significantly reduced. The addition of long chain n-3 polyunsaturates such as DHA to infant formula may therefore be necessary for adequate neural DHA accretion and optimal neural development. C1 NIAAA, LAB MEMBRANE BIOCHEM & BIOPHYS, DICBR, ROCKVILLE, MD 20852 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PEDIAT, BETHESDA, MD 20814 USA. NR 69 TC 41 Z9 45 U1 0 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 1996 VL 40 IS 5 BP 687 EP 694 DI 10.1203/00006450-199611000-00007 PG 8 WC Pediatrics SC Pediatrics GA VP173 UT WOS:A1996VP17300007 PM 8910933 ER PT J AU Desposito, F Cho, S Frias, JL Sherman, J Wappner, RS Wilson, MG delaCruz, F Hanson, JW LinFu, J McDonough, PG Pletcher, BA Pyeritz, RE Seashore, MR AF Desposito, F Cho, S Frias, JL Sherman, J Wappner, RS Wilson, MG delaCruz, F Hanson, JW LinFu, J McDonough, PG Pletcher, BA Pyeritz, RE Seashore, MR TI Health supervision for children with Marfan syndrome SO PEDIATRICS LA English DT Article ID SURGICAL-TREATMENT; FIBRILLIN; GENE; DISORDERS; MUTATIONS; REPAIR AB This set of guidelines is designed to assist the pediatrician in caring for children with Marfan syndrome confirmed by clinical criteria. Although pediatricians usually first see children with Marfan syndrome during infancy, occasionally they will be called on to advise the pregnant woman who has been informed of the prenatal diagnosis of Marfan syndrome. Therefore, these guidelines offer advice for this situation as well. C1 US DEPT HHS,HLTH RESOURCES & SERV,WASHINGTON,DC 20201. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC 20024. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. RP Desposito, F (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 17 TC 20 Z9 22 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1996 VL 98 IS 5 BP 978 EP 982 PG 5 WC Pediatrics SC Pediatrics GA VR466 UT WOS:A1996VR46600023 ER PT J AU Katcher, ML Bull, MJ Laraque, D Palmer, SD Pollack, SH Smith, BL Spivak, HR Tully, SB Agran, P Brenner, R Bryn, S Maples, DL Neverman, C Schieber, RA Stanwick, R Tinsworth, D Griffith, J Russell, J Sleet, D Brownlee, M Waller, PF Felice, ME Boulter, S Kaplan, DW Olmedo, LF RomeAsbeck, ES Shenker, IR Staggers, BC Hillard, P Sacks, D AF Katcher, ML Bull, MJ Laraque, D Palmer, SD Pollack, SH Smith, BL Spivak, HR Tully, SB Agran, P Brenner, R Bryn, S Maples, DL Neverman, C Schieber, RA Stanwick, R Tinsworth, D Griffith, J Russell, J Sleet, D Brownlee, M Waller, PF Felice, ME Boulter, S Kaplan, DW Olmedo, LF RomeAsbeck, ES Shenker, IR Staggers, BC Hillard, P Sacks, D TI The teenage driver SO PEDIATRICS LA English DT Article ID CRASH INVOLVEMENT AB Motor vehicle-related injuries continue to be of paramount importance to adolescents. This statement describes why teenagers are at particularly great risk, suggests topics suitable for office-based counseling, describes innovative programs, and proposes steps for prevention for pediatricians, legislators, educators, and other child advocates. C1 NICHHD,BETHESDA,MD 20892. US DEPT TRANSPORTAT,WASHINGTON,DC 20590. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. US CONSUMER PROD SAFETY COMMISS,BETHESDA,MD. CTR DIS CONTROL & PREVENT,NATL CTR INJURY PREVENT & CONTROL,ATLANTA,GA 30333. NATL HIGHWAY TRAFF SAFETY ADM US,WASHINGTON,DC 20590. UNIV MICHIGAN,TRANSPORTAT RES INST,ANN ARBOR,MI 48109. AMER COLL OBSTETRICIANS & GYNECOLOGISTS,WASHINGTON,DC. NR 23 TC 18 Z9 18 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 1996 VL 98 IS 5 BP 987 EP 990 PG 4 WC Pediatrics SC Pediatrics GA VR466 UT WOS:A1996VR46600026 ER PT J AU Ivanov, BB Robey, FA AF Ivanov, BB Robey, FA TI Effective use of free thiols as scavengers for HF cocktails to deprotect bromo- and chloroacetylated synthetic peptides SO PEPTIDE RESEARCH LA English DT Article ID CHEMICAL SYNTHESIS; PROTEIN; DOMAIN AB A variety of thiol-containing compounds, in combination with m-cresol, were tested as scavengers in hydrogen fluoride (HF) cocktails that are used to deprotect haloacetylated peptidyl resins. Our results indicate that bromo- and chloroacetyl moieties on a synthetic peptide remain intact following HF treatment when the HF cocktail contains m-cresol along with either thiophenol, m-thiocresol or 1,2-ethanedithiol. The free thiols prevent the formation of a number of impurities in the preparation of bromo- and chloroacetylated peptides that contain amino acids that could be oxidized in a nonreducing HF environment. Ethylmethylsulfide, however, could not be used with bromoacetylated peptides, but it could be used with chloroacetylated peptides. C1 NIDR,NIH,BETHESDA,MD 20892. NR 13 TC 13 Z9 13 U1 1 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 1040-5704 J9 PEPTIDE RES JI Peptide Res. PD NOV-DEC PY 1996 VL 9 IS 6 BP 305 EP 307 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WJ930 UT WOS:A1996WJ93000008 PM 9048424 ER PT J AU Long, RM AF Long, RM TI What research training opportunities are sponsored by NIGMS at the NIH? How can I get information about this and other postdoctoral programs at the NIH? SO PHARMACEUTICAL RESEARCH LA English DT News Item RP Long, RM (reprint author), NIGMS,PHARMACOL & PHYSIOL SCI BRANCH,DIV PHARMACOL PHYSIOL & BIOL CHEM,NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD NOV PY 1996 VL 13 IS 11 BP 1589 EP 1589 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA VW974 UT WOS:A1996VW97400001 ER PT J AU Pickworth, WB Baumann, MH Fant, RV Rothman, RB Henningfield, JE AF Pickworth, WB Baumann, MH Fant, RV Rothman, RB Henningfield, JE TI Endocrine responses during acute nicotine withdrawal SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE nicotine; transdermal nicotine; ACTh; cortisol; prolactin; nicotine abstinence ID CIGARETTE-SMOKING; COCAINE WITHDRAWAL; PROLACTIN; CORTISOL; SMOKERS; SYSTEM AB Acute administration of nicotine increases cortisol and prolactin but the endocrine effects of tobacco withdrawal are unknown. In a residential, double-blind, placebo-controlled, crossover study, volunteers smoked ad lib for 4 days and underwent monitored tobacco abstinence for 3 days. On no-smoking days, patches delivering 0, 10, 20, or 30 mg nicotine were applied for 16 h. Daily plasma samples were analyzed for ACTH, cortisol, and prolactin. During nicotine abstinence (0 mg patch), circulating levels of ACTH, cortisol, and prolactin did not significantly change from ad lib smoking levels. Over all the patch conditions there was a significant effect of day, with modest but significant elevations of cortisol and ACTH levels on the second no-smoking day (Wed, 37 h abstinent). Prolactin levels increased during nicotine abstinence, but this effect was not significant. The observed endocrine changes did not correlate with physiologic, performance, or subjective measures of tobacco withdrawal. Our data indicate endocrine changes during acute tobacco withdrawal are transient and small. Thus, the present results do not support the use of ACTH as a treatment for tobacco cessation. Copyright (C) 1996 Elsevier Science Inc. RP Pickworth, WB (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,POB 5180,BALTIMORE,MD 21224, USA. NR 30 TC 23 Z9 23 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 1996 VL 55 IS 3 BP 433 EP 437 DI 10.1016/S0091-3057(96)00114-1 PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA VV756 UT WOS:A1996VV75600015 PM 8951985 ER PT J AU Ain, KB Pucino, F Csako, G Wesley, RA Drass, JA Clark, C Ketteridge, P Crawford, K Banks, SM Dorworth, TE AF Ain, KB Pucino, F Csako, G Wesley, RA Drass, JA Clark, C Ketteridge, P Crawford, K Banks, SM Dorworth, TE TI Effects of restricting levothyroxine dosage strength availability SO PHARMACOTHERAPY LA English DT Article ID FORMULARY RESTRICTIONS; COST SAVINGS; CEPHALOSPORINS AB We conducted a prospective, randomized, controlled trial to assess whether hospital formulary restrictions involving limiting dosage strengths of levothyroxine affect physicians' ability to manage patients effectively and provide pharmacy cost savings in a tertiary care federal government research hospital. Thirty-three endocrinologists were randomly assigned to prescribe levothyroxine from a restrictive (dosage strengths of 25, 50, 100, 125, and 150 mu g) or a nonrestrictive (dosage strengths of 25, 50, 75, 100, 112, 125, 150, 175, 200, and 300 mu g) formulary through a central computer system. Their 241 respective outpatients' laboratory results and drug compliance were outcome measures. Achievement of treatment objectives was measured by thyroid function tests (free and total thyroxine, total triiodothyronine, thyrotropin), number of clinic visits, and compliance (survey method). Additional measures were drug distribution patterns, drug costs, and pharmacy inventory costs. Restriction of levothyroxine's dosage strength did not significantly alter therapeutic outcomes. However, the restricted formulary was associated with more complex dosing regimens, and resulted in no significant cost savings. It is not known whether such restriction would adversely affect the care of patients of nonspecialists. Prospective studies are required to verify presumed cost-containment measures before such measures are adopted for widespread application. C1 NIAID,DEPT PHARM,NIH,BETHESDA,MD 20892. VET AFFAIRS MED CTR,MED SERV,LEXINGTON,KY. UNIV KENTUCKY,MED CTR,DEPT MED,LEXINGTON,KY 40536. WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BETHESDA,MD. WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD. WARREN G MAGNUSON CLIN CTR,DEPT INFORMAT SYST,BETHESDA,MD. WARREN G MAGNUSON CLIN CTR,DEPT NURSING,BETHESDA,MD. NIAID,DIV INTRAMURAL RES,NIH,BETHESDA,MD 20892. NIDDKD,CLIN ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. PROCYTE CORP,KIRKLAND,WA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 24 TC 3 Z9 3 U1 1 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV-DEC PY 1996 VL 16 IS 6 BP 1103 EP 1110 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VU957 UT WOS:A1996VU95700018 PM 8947984 ER PT J AU Lanczycki, CJ Jejjala, V DasSarma, S AF Lanczycki, CJ Jejjala, V DasSarma, S TI Far from equilibrium nonconserved growth under a surface diffusion bias SO PHYSICAL REVIEW E LA English DT Article ID KURAMOTO-SIVASHINSKY EQUATION; MOLECULAR-BEAM EPITAXY; STOCHASTIC-MODEL; KINETIC GROWTH; INTERFACES; CONTINUUM; DYNAMICS; EROSION AB We study a generic one-dimensional atomistic model of interface growth under random ballistic deposition in the presence of a surface diffusion bias allowing for surface overhangs and bulk vacancies. We find that various diffusion bias induced surface instabilities recently found in the solid-on-solid approximation of kinetic growth are absent in the generic model with the usual statistically self-affine Kardar-Parisi-Zhang scaling dominating the surface morphology. For strong biases and high temperatures, the growing surface resembles the zero temperature ballistic growth without a diffusion bias. The growth front morphologies show intricate flamelike nonlocal structures not typically present in self-affine surfaces. This indicates that the standard coarse-grained single-variable description of the growing film by its local surface height coordinate misses an important qualitative feature, namely, a novel flamelike roughening behavior along vertical faces of the growth front. C1 NIH,COMPUTAT BIOSCI & ENGN LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP Lanczycki, CJ (reprint author), UNIV MARYLAND,DEPT PHYS,COLLEGE PK,MD 20742, USA. RI Das Sarma, Sankar/B-2400-2009 OI Das Sarma, Sankar/0000-0002-0439-986X NR 31 TC 3 Z9 3 U1 0 U2 1 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD NOV PY 1996 VL 54 IS 5 BP 4755 EP 4759 DI 10.1103/PhysRevE.54.4755 PG 5 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA VU537 UT WOS:A1996VU53700044 ER PT J AU Podgornik, R AF Podgornik, R TI Isotropic-nematic transition of surface embedded polymers and the associated tubulization transition of the embedding surface SO PHYSICAL REVIEW E LA English DT Article ID FLUID MEMBRANES AB A self-interacting polymer can undergo an orientational ordering transition, depending an the magnitude of the nematic interaction. The effect of embedding such a polymer into a flexible surface on this transition is studied on the mean-field level. Renormalized values of the elastic constants of the ''dressed'' surface are derived as functions of the orientational order parameter of the polymer chain. In the disordered stale the surface tension and curvature modulus remain scalars, but depend on the surface coverage of the embedded polymer. In the nematic state there is a symmetry-breaking transition leading to anisotropic elastic constants. At a sufficiently large nematic order parameter the effective surface tension in the direction perpendicular to the nematic axis can become negative, leading to tubulization of the tubulization of the embedding surface. C1 JOZEF STEFAN INST,DEPT THEORET PHYS,LJUBLJANA 1000,SLOVENIA. RP Podgornik, R (reprint author), NIH,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,BETHESDA,MD 20892, USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 12 TC 7 Z9 7 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD NOV PY 1996 VL 54 IS 5 BP 5268 EP 5277 DI 10.1103/PhysRevE.54.5268 PG 10 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA VU537 UT WOS:A1996VU53700101 ER PT J AU McCarthy, MM McDonald, CH Brooks, PJ Goldman, D AF McCarthy, MM McDonald, CH Brooks, PJ Goldman, D TI An anxiolytic action of oxytocin is enhanced by estrogen in the mouse SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE septum; hypothalamus; vasopressin; stress ID VENTROMEDIAL HYPOTHALAMIC NUCLEUS; GONADAL-STEROIDS; RECEPTOR-BINDING; MALE-RATS; VASOPRESSIN; BEHAVIOR; STRESS; DIAZEPAM; NEURONS; BRAIN AB The established role of oxytocin (OT) in facilitation of steroid-modulated reproductive and affiliative behaviors led to the speculation that it may have anxiolytic actions under certain hormonal conditions. NM-Swiss mice were tested for responsiveness to OT in two behavioral tests of anxiety, the holeboard apparatus and elevated plus-maze. Dose-response assessment indicated that 3 mg/kg was the optimal dose for peripherally administered (IF) OT on the elevated plus-maze. There were no consistent effects at any dose on the holeboard apparatus. In ovariectomized mice pretreated with estradiol (E(2)), peripherally administered OT increased the number of entrances onto the open arms, as well as the amount of time on the open arms compared to other groups (ANOVA; p < 0.05). There was little to no effect of OT in ovariectomized animals not pretreated with E(2). When OT was administered intracerebroventricularly (ICV), there was an increase in entrances and time on the open arms compared to that of females infused with arginine vasopressin (AVP). This increase was apparent in ovariectomized females, but was further enhanced in those pretreated with E(2) (ANOVA; p < 0.05). In contrast, the combination of E(2) pretreatment and ICV AVP decreased the number of entrances and time spent on the open arms of the elevated plus-maze compared to those receiving OT, suggesting an estrogen-modulated anxiogenic action of AVP. Analyses of I-[125]-OVTA binding density indicated a significant increase in binding density in the lateral septum of E(2)-treated females compared to OIL-treated controls (ANOVA; p < 0.05). There was no effect of E(2) treatment on I-[125]-OVTA binding density in the amygdala or ventromedial nucleus of the hypothalamus. Taken together, these data indicate that OT exerts an anxiolytic action that is enhanced in the presence of circulating estrogen. This behavioral effect may be mediated by estrogen-induced increases in OT binding density in the lateral septum and may be important to the facilitation of social interactions. Copyright (C) 1996 Elsevier Science Inc. C1 NIAAA,NIH,NEUROGENET LAB,ROCKVILLE,MD 20852. RP McCarthy, MM (reprint author), UNIV MARYLAND,SCH MED,DEPT PHYSIOL,655 W BALTIMORE ST,BALTIMORE,MD 21201, USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 30 TC 214 Z9 218 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD NOV PY 1996 VL 60 IS 5 BP 1209 EP 1215 PG 7 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA VR322 UT WOS:A1996VR32200004 PM 8916173 ER PT J AU Talan, MI Kirov, SA Clow, LA Kosheleva, NA AF Talan, MI Kirov, SA Clow, LA Kosheleva, NA TI Cold acclimation-associated changes in brown adipose tissue do not necessarily indicate an increase of nonshivering thermogenesis in C57BL/6J mice SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE adaptation; body temperature; cold tolerance; temperature regulation; heat production; brown adipose tissue; thermogenin; uncoupling protein; mitochondria; rodents ID METABOLIC HEAT-PRODUCTION; UNCOUPLING PROTEIN; ADRENERGIC-RECEPTORS; STRESS; UCP; MITOCHONDRIA; EXPRESSION; TOLERANCE; AGONIST; ADULT AB We have reported previously that a cold acclimation procedure (3-hr partial restraint at 6 degrees C, repeated 3 times at 2-week intervals) usually improves the cold tolerance of adult C57BL/6J mice. Those mice that did not improve their cold tolerance had lower cold-induced sympathetic nervous outflow to the interscapular brown adipose tissue (IBAT), suggesting a failure in the mechanisms of nonshivering thermogenesis. To understand the origin of this failure, this study was intended to measure nonshivering thermogenesis in mice that did not improve their cold tolerance after the cold acclimation procedure. After being subjected 3 times to a partial restraint al 6 degrees C, mice were anesthetized with urethane, immobilized with vecuronium bromide, and placed on artificial ventilation. The VO2 and VCO2 in expired air were measured and metabolic heat production (MHP) was calculated while body temperature was artificially lowered to 7.5 degrees C below control level. In a separate group of mice, the total amount and concentration of mitochondrial uncoupling protein, thermogenin (UCP), in IBAT was measured immediately after completion of the cold-acclimation procedure. The concentration and the amount of UCP in the mitochondria of IBAT was significantly higher in all mice that had been presented to the cold acclimation procedure, regardless of its outcome, than in mice that had never been exposed to an environment below room temperature (NAIVE). MHP increased significantly during body cooling in all mice. However, MHP before and during cold stimulation in mice that did not improve their cold tolerance as a result of the cold-acclimation procedure was significantly lower than the MHP of animals in which cold tolerance was improved, and was not different from MHP of the NAIVE group. Therefore, in mice in which cold tolerance did not improve after repeated cold exposure, the anatomical and biochemical changes in brown adipose tissue typical of cold acclimation were not associated with a cold-induced increase in MHP. We infer that the expression of UCP in brown adipose tissue is a necessary, but not sufficient, attribute of cord acclimation. Cold acclimation, measured as increased cold tolerance, occurs only if synthesis of UCP in BAT is associated with an increased cold-induced response of the sympathetic nervous system. Copyright (C) 1996 Elsevier Science Inc. C1 CARDIOL RES CTR,MOSCOW 121552,RUSSIA. RP Talan, MI (reprint author), NIA,BEHAV SCI LAB,CTR GERONTOL RES,NIH,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 32 TC 3 Z9 3 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD NOV PY 1996 VL 60 IS 5 BP 1285 EP 1289 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA VR322 UT WOS:A1996VR32200014 PM 8916183 ER PT J AU Paulyson, KJ Sherer, DM Christian, SL Lewis, KM Ledbetter, DH Salafia, CM Meck, JM AF Paulyson, KJ Sherer, DM Christian, SL Lewis, KM Ledbetter, DH Salafia, CM Meck, JM TI Prenatal diagnosis of an infant with mosaic trisomy 16 of paternal origin SO PRENATAL DIAGNOSIS LA English DT Article DE mosaic trisomy 16; paternal non-disjunction; prenatal diagnosis; prenatal ultrasound; amniocentesis ID FLUID CELL-CULTURES; NEWBORN-INFANT; HUMAN SPERM; PSEUDOMOSAICISM; NONDISJUNCTION AB We present the first case of an infant with paternally-derived mosaic trisomy 16. Amniocentesis following an elevated maternal serum alpha-fetoprotein level and early fetal growth restriction at 19 weeks detected a high level of mosaicism with 25/33 colonies demonstrating trisomy 16 and 8/33 colonies with a normal 46,XX karyotype. Molecular studies revealed a paternal origin of the trisomy which was present in amniotic fluid cells, representing either a post-zygotic error or a meiosis II non-disjunction without crossing-over. In addition, there was normal biparental inheritance in the normal cell fine. The symmetrically growth-restricted fetus was closely monitored for the remainder of the gestation. Decreased fetal movements at 36 weeks in conjunction with electronic fetal monitoring showing evidence of fetal distress necessitated abdominal delivery. Severe growth restriction, mild facial dysmorphism, and cardiac anomalies were identified. Microsatellite analysis demonstrated biparental inheritance in skin fibroblasts with a paternal origin for the trisomy in the placenta. Follow-up cytogenetic studies of additional tissues revealed 85 per cent trisomy 16 mosaicism in the placenta, yet only cytogenetically normal cells in lymphocytes and fibroblasts. C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV GENET,WASHINGTON,DC 20007. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,WASHINGTON,DC 20007. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 22 TC 13 Z9 13 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD NOV PY 1996 VL 16 IS 11 BP 1021 EP 1026 PG 6 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA VW576 UT WOS:A1996VW57600005 PM 8953635 ER PT J AU Malloy, MH Hoffman, HJ AF Malloy, MH Hoffman, HJ TI Home apnea monitoring and sudden infant death syndrome SO PREVENTIVE MEDICINE LA English DT Article DE Sudden Infant Death Syndrome; apnea monitor; race ID MORTALITY AB Objective. To estimate the U.S. national prevalence of apnea monitor use by birth weight classification and to examine the relationship between the use of apnea monitors and the occurrence of Sudden Infant Death Syndrome (SIDS). Design and setting. Data obtained from the 1988 National Maternal and Infant Health Survey (NMIHS) were used. Prevalence estimates of apnea monitor use were obtained by weighting survey data, and the relationship between monitor use and SIDS was accomplished by a case-control analysis using SIDS deaths and live controls obtained from the NMIHS. Outcome measure. Weighted estimates of the prevalence of apnea monitor use and odds ratios for the odds of use of an apnea monitor among SIDS victims compared with the odds of use of an apnea monitor among living controls. Results. The national prevalence estimates for home apnea monitor use among birth weight strata of 500 to 1,499 g, 1,500 to 2,499 g, and 2,500 g or more for blacks were 19.9, 2.6, and 1.1% compared with 44.0, 8.8, and 1.2% for non-blacks. The only significant association between the use of apnea monitors and SIDS was for black 500- to 1,499-g infants. The adjusted odds ratio for SIDS among monitored black 500- to 1,499-g infants vs unmonitored infants was 3.93 (1.09, 14.17). Conclusions. This analysis suggests a marked difference in reported monitor use between U.S. black and non-black infants. In addition, black very low birth weight infants at highest risk for SIDS appear to be preferentially selected for monitoring. The protective effect of home apnea monitoring in this survey population is unclear. C1 NATL INST DEAF & OTHER COMMUN DISORDERS,EPIDEMIOL STAT & DATA SYST BRANCH,BETHESDA,MD. RP Malloy, MH (reprint author), UNIV TEXAS,DEPT PEDIAT,MED BRANCH,GALVESTON,TX 77555, USA. FU NHLBI NIH HHS [R03-HL48932] NR 13 TC 10 Z9 10 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 NOV-DEC PY 1996 VL 25 IS 6 BP 645 EP 649 DI 10.1006/pmed.1996.9998 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VT803 UT WOS:A1996VT80300001 PM 8936564 ER PT J AU Liu, C Yu, K Shen, K Liu, ZY Noguchi, CT AF Liu, C Yu, K Shen, K Liu, ZY Noguchi, CT TI Transgenic mice containing the human erythropoietin receptor gene exhibit correct hematopoietic and neural expression SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE brain; development; erythropoiesis ID TRANSCRIPTION; BINDING; CELLS AB The erythropoietin receptor (EpoR), known for its role in the proliferation and differentiation of erythroid cells, has been detected in nonhematopoietic tissues. We have reported previously that in addition to hematopoietic expression, EpoR is expressed at high levels in embryonic mouse brain and decreased to nondetectable levels by birth. While using transgenic mice to characterize human EpoR expression, we observed that a 15-kb human EpoR transgene (expressed in hematopoietic tissues but at a reduced level) also exhibited in the embryonic brain low levels of expression that persisted through adulthood. To examine further the basis of tissue and developmental specificity of the human EpoR gene, we produced additional transgenic mice using an 80-kb human EpoR genomic fragment isolated from a P1 phagemid human library. We found that this transgene is expressed appropriately in hematopoietic tissues (including yolk sac, fetal liver, adult spleen, and bone marrow) at levels comparable to the endogenous murine EpoR. The 80-kb transgene also provided high-level expression in the embryonic brain that paralleled the levels of the endogenous murine EpoR and was no longer detectable after birth. These data suggest that the high level of embryonic brain expression may be relevant to the human EpoR gene and that the transgenic mouse with an 80-kb fragment is a suitable model for studying the regulation and possible functional importance of human EpoR expression in the developing embryo. C1 NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. NR 16 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD NOV PY 1996 VL 108 IS 6 BP 449 EP 454 PG 6 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VW867 UT WOS:A1996VW86700005 PM 8956368 ER PT J AU Ravussin, E Tataranni, PA AF Ravussin, E Tataranni, PA TI The role of altered sympathetic nervous system activity in the pathogenesis of obesity SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Article; Proceedings Paper CT Symposium on Predisposition to Obesity - Metabolic and/or Behavioural Factors, at Winter Meeting of Nutrition-Society / Association-for-the-Study-of-Obesity CY FEB 07, 1996 CL ROYAL COLL PHYSICIANS, LONDON, ENGLAND SP Nutr Soc, Assoc Study Obes HO ROYAL COLL PHYSICIANS ID 24-HOUR ENERGY-EXPENDITURE; BROWN ADIPOSE-TISSUE; BODY-WEIGHT GAIN; NOREPINEPHRINE TURNOVER; PIMA-INDIANS; METABOLIC-RATE; FOOD-INTAKE; FAT; GLUCOSE; HUMANS RP Ravussin, E (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,RM 541,PHOENIX,AZ 85016, USA. NR 61 TC 24 Z9 25 U1 1 U2 1 PU C A B INTERNATIONAL PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD, OXON, ENGLAND OX10 8DE SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PD NOV PY 1996 VL 55 IS 3 BP 793 EP 802 DI 10.1079/PNS19960079 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA WB119 UT WOS:A1996WB11900003 PM 9004324 ER PT J AU Oriji, GK Tate, JE Keiser, HR AF Oriji, GK Tate, JE Keiser, HR TI Endothelin-induced prostacyclin production in rat aortic rings is mediated by protein kinase C SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID PIGLET PARIETAL CORTEX; PROSTAGLANDIN-E2 PRODUCTION; SIGNAL TRANSDUCTION; PLATELET ACTIVATION; MESANGIAL CELLS; PROSTANOIDS; PHORBOL; RELEASE; PHOSPHORYLATION; ACCUMULATION AB Endothelin (ET) is a vasoconstrictor peptide released from endothelial cells that is known to cause prostaglandin release. The mechanism remains unclear. To determine whether the protein kinase C (PKC) signaling pathway is stimulated by endothelin, we pretreated rat aortic rings with either PKC activator or inhibitors and measured the release of prostacyclin (PGI(2)) by radioimmunoassay. ET (10(-9) M) produced a 10-fold increase in PGI(2) release. Pretreatment with 10(-9) M of three different PKC inhibitors, 1-(5-isoquinolinesulfonyl)piperazine(CL), staurosporine, and 1-(5-isoquinolinesulfonyltmethyl)piperazine (H7), blocked ET-induced PGI(2) release. ET-induced PGI(2) release was also blocked by pretreatment with inhibitors of either phospholipase A(2)7,7-dimethyleicosadienoic acid or trifluoromethyl ketone analogue) (10(-9) M) or cyclooxygenase (indomethacin) (10(-9) M). We conclude that ET activates PKC, which activates phospholipase A(2), which liberates arachidonic acid, which increases PGI(2) production and release. RP Oriji, GK (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,10 CTR DR,MSC 1754,BETHESDA,MD 20892, USA. NR 33 TC 8 Z9 8 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD NOV PY 1996 VL 55 IS 5 BP 309 EP 313 DI 10.1016/S0952-3278(96)90036-8 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA VY195 UT WOS:A1996VY19500003 PM 8981627 ER PT J AU Bagossi, P Cheng, YSE Oroszlan, S Tozser, J AF Bagossi, P Cheng, YSE Oroszlan, S Tozser, J TI Activity of linked HIV-1 proteinase dimers containing mutations in the active site region SO PROTEIN ENGINEERING LA English DT Article DE active site; enzyme kinetics; linked HIV proteinase dimer; oligopeptide substrates ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOLECULAR-DYNAMICS SIMULATIONS; ASPARTIC PROTEINASES; CHEMICAL SYNTHESIS; INHIBITOR BINDING; POL POLYPROTEINS; FORCE-FIELD; PROTEASE; SUBSTRATE; GAG AB Mutations were introduced into the active site triplet (Asp-Thr-Gly) of one or both subunits of a linked dimer of human immunodeficiency virus type 1 proteinase. Mutation of Thr to Ser in one or both subunits did not alter the activity of the enzyme substantially, whereas its mutation to Asn in one subunit caused a dramatic decrease in catalytic efficiency. Mutation of Gly to Val one subunit also yielded an enzyme with very low activity. The enzymes containing Thr --> Asn and Gly --> Val mutations in both subunits resulted in inactive enzymes, based on their inability to self-process and on assay with an oligopeptide substrate. The dramatic decrease in enzyme efficiency of the mutants was interpreted using molecular models of the enzymes. C1 DEBRECEN UNIV MED, SCH MED, DEPT BIOCHEM, H-4012 DEBRECEN, HUNGARY. DUPONT MERCK PHARMACEUT CO, EXPT STN, WILMINGTON, DE 19803 USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOL VIROL & CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 48 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD NOV PY 1996 VL 9 IS 11 BP 997 EP 1003 DI 10.1093/protein/9.11.997 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA VX257 UT WOS:A1996VX25700007 PM 8961352 ER PT J AU McCrae, RR AF McCrae, RR TI Social consequences of experiential openness SO PSYCHOLOGICAL BULLETIN LA English DT Article; Proceedings Paper CT Nags Head Conference on Personality and Social Behavior CY JUN 19-24, 1995 CL HIGHLAND BEACH, FL ID NEO PERSONALITY-INVENTORY; 5-FACTOR MODEL; INDIVIDUAL-DIFFERENCES; BIG 5; UNCERTAINTY ORIENTATION; SPOUSE SIMILARITY; COGNITIVE STYLES; SELF-REPORTS; ATTITUDES; SCALES AB Openness to Experience is one of the 5 broad factors that subsume most personality traits. Openness is usually considered an intrapsychic dimension, defined in terms of characteristics of consciousness. However, different ways of approaching and processing experience lead to different value systems that exercise a profound effect on social interactions. In this article, the author reviews the effects of Openness versus Closedness in cultural innovation, political ideology, social attitudes, marital choice, and interpersonal relations. The construct of Openness and its measures could profitably be incorporated into research conducted by social psychologists, sociologists, political scientists, anthropologists, and historians. C1 NIA,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 143 TC 353 Z9 354 U1 9 U2 51 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0033-2909 J9 PSYCHOL BULL JI Psychol. Bull. PD NOV PY 1996 VL 120 IS 3 BP 323 EP 337 DI 10.1037//0033-2909.120.3.323 PG 15 WC Psychology; Psychology, Multidisciplinary SC Psychology GA VQ277 UT WOS:A1996VQ27700001 PM 8900080 ER PT J AU Post, RM Ketter, TA Denicoff, K Pazzaglia, PJ Leverich, GS Marangell, LB Callahan, AM George, MS Frye, MA AF Post, RM Ketter, TA Denicoff, K Pazzaglia, PJ Leverich, GS Marangell, LB Callahan, AM George, MS Frye, MA TI The place of anticonvulsant therapy in bipolar illness SO PSYCHOPHARMACOLOGY LA English DT Review DE carbamazepine; valproate; lithium; nimodipine; benzodiazepines; limbic seizures; regional glucose utilization ID MANIC-DEPRESSIVE ILLNESS; REFRACTORY AFFECTIVE-DISORDERS; THYROTROPIN-RELEASING-HORMONE; AMYGDALA-KINDLED SEIZURES; RANDOMIZED CLINICAL-TRIAL; DOUBLE-BLIND TRIAL; LITHIUM PROPHYLAXIS; SODIUM VALPROATE; MIXED MANIA; ELECTROCONVULSIVE-THERAPY AB With the increasing recognition of lithium's inadequacy as an acute and prophylactic treatment for many patients and subtypes of bipolar illness, the search for alternative agents has centered around the mood stabilizing anticonvulsants carbamazepine and valproate. In many instances, these drugs are effective alone or in combination with lithium in those patients less responsive to lithium monotherapy, including those with greater numbers of prior episodes, rapid-cycling, dysphoric mania, co-morbid substance abuse or other associated medical problems, and patients without a family history of bipolar illness in first-degree relatives. Nineteen double-blind studies utilizing a variety of designs suggest that carbamazepine, or its keto-congener oxcarbazepine, is effective in acute mania; six controlled studies report evidence of the efficacy of valproate in the treatment of acute mania as well. Fourteen controlled or partially controlled studies of prophylaxis suggest carbamazepine is also effective in preventing both manic and depressive episodes. Valproate prophylaxis data, although based entirely on uncontrolled studies, appear equally promising. Thus, both drugs are widely used and are now recognized as major therapeutic tools for lithium-nonresponsive bipolar illness. The high-potency anticonvulsant benzodiazepines, clonazepam and lorazepam, are used adjunctively with lithium or the anticonvulsant mood stabilizers as substitutes or alternatives for neuroleptics in the treatment of manic breakthroughs. Preliminary controlled clinical trials suggest that the calcium channel blockers may have antimanic or mood-stabilizing effects in a subgroup of patients. A new series of anticonvulsants has just been FDA-approved and warrant clinical trials to determine their efficacy in acute and long-term treatment of mania and depression. Systematic exploration of the optimal use of lithium and the mood-stabilizing anticonvulsants alone and in combination, as well as with adjunctive antidepressants, is now required so that more definitive treatment recommendations for different types and stages of bipolar illness can be more strongly evidence based. C1 UNIV MISSISSIPPI,MED CTR,DEPT PSYCHIAT & HUMAN BEHAV,JACKSON,MS 39216. BAYLOR COLL MED,HOUSTON,TX 77030. RP Post, RM (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,10 CTR DR,MSC 1272,BETHESDA,MD 20892, USA. NR 167 TC 130 Z9 132 U1 2 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1996 VL 128 IS 2 BP 115 EP 129 DI 10.1007/s002130050117 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VU304 UT WOS:A1996VU30400001 PM 8956373 ER PT J AU Bradley, MM Cuthbert, BN Lang, PJ AF Bradley, MM Cuthbert, BN Lang, PJ TI Picture media and emotion: Effects of a sustained affective context SO PSYCHOPHYSIOLOGY LA English DT Article DE emotion; pictures; habituation; sensitization; attention; media ID STARTLE REFLEX; VISUAL-STIMULI; MOOD STATES; ATTENTION; MEMORY AB Pleasant, neutral, or unpleasant pictures were presented in a continuous series, and the effects of repetitive exposure to pictures of the same affective valence were assessed in somatic (corrugator electromyographic [EMG] activity) and visceral (heart rate and skin conductance) systems. Probe stimuli (startle or reaction time probes) were presented to index emotional and attentional concomitants of processing. affective discrimination was maintained across time in all response systems, and sensitization was found for the corrugator EMG response. Responses to reaction time probes indexed differences in attentional allocation as a function of cognitive and affective variables in this paradigm. Taken together, the data suggest that presentation of a series of affective pictures of similar valence produces emotional reactions that are either maintained or sensitized across the temporal intervals used here but that do not habituate. RP Bradley, MM (reprint author), UNIV FLORIDA,NIMH,CTR STUDY EMOT & ATTENT,BOX 100165 HSC,GAINESVILLE,FL 32610, USA. FU NIMH NIH HHS [MH37757, MH43975, MH52384] NR 35 TC 174 Z9 178 U1 3 U2 35 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 1996 VL 33 IS 6 BP 662 EP 670 DI 10.1111/j.1469-8986.1996.tb02362.x PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA VT616 UT WOS:A1996VT61600007 PM 8961788 ER PT J AU Zahn, TP Kruesi, MJP Swedo, SE Leonard, HL Rapoport, JL AF Zahn, TP Kruesi, MJP Swedo, SE Leonard, HL Rapoport, JL TI Autonomic activity in relation to cerebrospinal fluid neurochemistry in obsessive and disruptive children and adolescents SO PSYCHOPHYSIOLOGY LA English DT Article DE electrodermal activity; heart rate; cerebrospinal fluid; monoamines; adrenocorticotropic hormone; obsessive compulsive disorder ID SKIN-CONDUCTANCE ACTIVITY; SCHIZOPHRENIC-PATIENTS; BEHAVIOR DISORDERS; ORIENTING RESPONSE; HEART-RATE; YOHIMBINE; SYSTEM; CSF; INTERVIEW; SYMPTOMS AB Electrodermal activity and heart rate were recorded during rest, simple tones, and a reaction time task in 43 male and female adolescents and children with obsessive compulsive disorder and 30 male adolescents and children with disruptive behavior disorders who had lumbar cerebrospinal fluid drawn during the same week. Partial correlations controlling for age and sex showed that in the obsessive group metabolites of serotonin and dopamine, but not of norepinephrine, were positively correlated with electrodermal responsivity, most consistently in the reaction time task. This result was not replicated in disruptive boys. Adrenocorticotropic hormone was positively related to electrodermal activity and heart rate throughout the session. The results for the obsessive adolescents suggest that nigrostriatal dopamine turnover and central serotonin turnover affect electrodermal activity, generally confirming and extending conclusions from pharmacological studies. Diagnosis may affect these relationships. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NIMH,CHILD PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 46 TC 8 Z9 8 U1 0 U2 0 PU SOC PSYCHOPHYSIOL RES PI WASHINGTON PA 1010 VERMONT AVE NW SUITE 1100, WASHINGTON, DC 20005 SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 1996 VL 33 IS 6 BP 731 EP 739 DI 10.1111/j.1469-8986.1996.tb02369.x PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA VT616 UT WOS:A1996VT61600014 PM 8961795 ER PT J AU Lindberg, DAB AF Lindberg, DAB TI The NLM and grateful med: Promise, public health, and policy SO PUBLIC HEALTH REPORTS LA English DT Editorial Material RP Lindberg, DAB (reprint author), NATL LIB MED,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 0 TC 1 Z9 1 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 NOV-DEC PY 1996 VL 111 IS 6 BP 552 EP 555 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VT972 UT WOS:A1996VT97200037 PM 8955707 ER PT J AU Kempner, ES Salovey, R Bernstein, SL AF Kempner, ES Salovey, R Bernstein, SL TI Radiation energy transfer in RNA polymers SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article; Proceedings Paper CT Radiation Chemistry of Polymers Symposium CY DEC, 1995 CL HONOLULU, HI ID INACTIVATION AB Ribozymes are a special class of polyribonucleotide (RNA) molecules which possess intrinsic catalytic activity, capable of cleaving nucleic acid substrates. RNA molecules were synthesized containing a hammerhead ribozyme moiety of 52 nucleotides linked to an inactive leader sequence, for total lengths of either 262 or 1226 nucleotides. These RNAs were frozen and irradiated with high energy electrons. Surviving ribozyme activity was determined, using the ability of the irradiated ribozymes to cleave a labeled substrate. From the same irradiated samples, the amount of intact RNA remaining was determined following denaturing gel electrophoresis. Radiation target analyses of these data revealed a structural target size of 80 kDa and a ribozyme activity target size of 15 kDa for the smaller ribozyme, and 319 and 16 kDa, respectively, for the larger ribozyme. The disparity in target size for activity vs structure indicates that, in contrast to proteins, there is no spread of radiation damage far from the primary site of ionization in RNA molecules. The smaller target size for activity indicates that only primary ionizations occurring in the specific active region are effective. This is similar to the case for oligosaccharides. it is concluded that the presence of the ribose sugar in the polymer chain restricts radiation damage to a small region and prevents major energy transfer throughout the molecule. C1 UNIV SO CALIF,DEPT CHEM ENGN,LOS ANGELES,CA 90089. NEI,NIH,BETHESDA,MD 20892. RP Kempner, ES (reprint author), NIAMSD,NIH,BETHESDA,MD 20892, USA. NR 25 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 J9 RADIAT PHYS CHEM JI Radiat. Phys. Chem. PD NOV PY 1996 VL 48 IS 5 BP 577 EP 581 DI 10.1016/0969-806X(96)00079-5 PG 5 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA VR111 UT WOS:A1996VR11100009 ER PT J AU Mattay, VS Frank, JA Santha, AKS Pekar, JJ Duyn, JH McLaughlin, AC Weinberger, DR AF Mattay, VS Frank, JA Santha, AKS Pekar, JJ Duyn, JH McLaughlin, AC Weinberger, DR TI Whole-brain functional mapping with isotropic MR imaging SO RADIOLOGY LA English DT Article DE brain, function; brain, MR; magnetic resonance (MR), brain mapping; magnetic resonance (MR), technology ID POSITRON EMISSION TOMOGRAPHY; MOTOR CORTICAL AREAS; CEREBRAL BLOOD-FLOW; SENSORY STIMULATION; HAND MOVEMENTS; 1.5 T; CORTEX; MONKEYS AB PURPOSE: To assess the reliability and sensitivity of gradient-echo, isotropic multisection echo-planar magnetic resonance (MR) imaging for within-subject whole-brain mapping. MATERIALS AND METHODS: Eight right-handed healthy volunteers underwent gradient-echo, echo-planar MR imaging while they performed a motor task on three occasions over 23 months. Ninety-six whole-brain volumes were acquired in 8 minutes 48 seconds. A rigorous statistical threshold for determining activation was set at P < .05 and was Bonferroni corrected for approximately 15,000 cortical voxels. RESULTS: In all subjects, reproducible activation was demonstrated in multiple cortical areas and in the cerebellum specific to the motor system. Of the activated voxels, 75%-78% were confined to the motor areas during all sessions. No statistically significant difference was found in the proportion of activated voxels in any motor region (relative to the total number of activated voxels in the whole brain) across the three sessions. The centers of mass of the activated areas were within 2.5 resolution elements of the image across the three sessions. CONCLUSION: Isotropic multisection echo-planar MR imaging has the potential for noninvasive, reliable within-subject mapping of whole-brain functional anatomy. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NIH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. NIH,LAB DIAGNOST RADIOL RES,OFF INTRAMURAL RES,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,INST COGNIT & COMPUTAT SCI,WASHINGTON,DC 20007. RI Duyn, Jozef/F-2483-2010 NR 35 TC 58 Z9 59 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1996 VL 201 IS 2 BP 399 EP 404 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VP389 UT WOS:A1996VP38900019 PM 8888231 ER PT J AU Doppman, JL Skarulis, MC Chen, CC Chang, R Pass, HI Fraker, DL Alexander, HR Niederle, B Marx, SJ Norton, JA Wells, SA Spiegel, AM AF Doppman, JL Skarulis, MC Chen, CC Chang, R Pass, HI Fraker, DL Alexander, HR Niederle, B Marx, SJ Norton, JA Wells, SA Spiegel, AM TI Parathyroid adenomas in the aortopulmonary window SO RADIOLOGY LA English DT Article DE mediastinum, neoplasms; parathyroid, CT; parathyroid, hyperparathyroidism; parathyroid, MR; parathyroid, neoplasms; parathyroid radionuclide studies; parathyroid, vascular studies ID PRIMARY HYPERPARATHYROIDISM; PREOPERATIVE LOCALIZATION; TC-99M SESTAMIBI; THYMIC TISSUE; DOUBLE-PHASE; TECHNETIUM-99M-SESTAMIBI; EXPLORATION; EXPERIENCE; SURGERY; GLANDS AB PURPOSE: To describe localization studies in nine patients with ectopic parathyroid adenomas in the aortopulmonary window, MATERIALS ANC, METHODS: Nine patients with ectopic parathyroid tissue (eight adenomas, one hyperplastic gland) in the aortopulmonary window-M ere examined with ultrasound (US), computed tomography (CT), magnetic resonance (MR) imaging, and scintigraphy. Diagnostic arteriography (n = 4) and venous sampling (n = 3) were performed in the first purpose of staining was four patients; arteriography for purpose of staining was attempted in the last five patients. RESULTS: The results of CT and MR imaging studies were positive in eight of nine patients (89%) and five of eight patients (63%), respectively. The results of thallium/technetium scintigraphy were negative in three patients scanned (0%), but the results of a repeat study in one patient were positive (33%). Sestamibi scans were positive in six of six patients (100%). Single photon emission CT was performed in all six patients and enabled distinction between adenomas in the aortopulmonary window and those in the thymus. CONCLUSION: Ectopic parathyroid glands in the aortopulmonary window are usually detected at sestamibi scintigraphy, and SPECT is helpful in distinguishing these adenomas from more common adenomas in the anterior mediastinum. CT and MR imaging studies can also enable this distinction, but imaging must extend below the aortic arch. C1 NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT NUCL MED, BETHESDA, MD 20892 USA. NCI, SURG BRANCH, DIV CANC TREATMENT, NIH, BETHESDA, MD 20892 USA. UNIV VIENNA, SCH MED, DEPT SURG, VIENNA, AUSTRIA. WASHINGTON UNIV, SCH MED, DEPT SURG, ST LOUIS, MO 63110 USA. NIDDK, DIV INTRAMURAL RES, NIH, BETHESDA, MD USA. NIDDK, GENET & ENDOCRINOL SECT, METAB DIS BRANCH, NIH, BETHESDA, MD USA. RP Doppman, JL (reprint author), NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT DIAGNOST RADIOL,BLDG 10, ROOM 1C660, MSC 1182, BETHESDA, MD 20892 USA. NR 43 TC 28 Z9 29 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1996 VL 201 IS 2 BP 456 EP 462 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VP389 UT WOS:A1996VP38900028 PM 8888240 ER PT J AU Nicholson, BT Center, SA Randolph, JF Rowland, PJ Thompson, MB Yeager, AE Erb, HN Corbett, J Watrous, D AF Nicholson, BT Center, SA Randolph, JF Rowland, PJ Thompson, MB Yeager, AE Erb, HN Corbett, J Watrous, D TI Effects of oral ursodeoxycholic acid in healthy cats on clinicopathological parameters, serum bile acids and light microscopic and ultrastructural features of the liver SO RESEARCH IN VETERINARY SCIENCE LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; CLASS-I; CHOLESTASIS; THERAPY; DISEASE; SALTS; HEPATOCYTES; EXPRESSION; ABSORPTION; RABBIT AB A blind, placebo-controlled study evaluated the effects of ursodeoxycholic acid (UDCA) given orally, at a dose of 15 mg kg(-1) per day for eight weeks, on the physical condition, haematological and serum biochemical profiles, urinalysis, total serum bile acids (TSBA) and hepatic histology of four healthy cats. There were no clinically important significant differences between the groups or within thr treatment groups in clinicopathological parameters, TSBA concentrations or histology. A significant lower concentration/proportion of taurochenodeoxycholic acid was observed in the treated cats (P=0 . 05). Only one treated cat accumulated measurable quantities of UDCA, and the compound appeared to be non-toxic. It did not increase the concentration of TSBA, and accumulated minimally in the serum. It should be investigated for therapeutic use in cats with hepatobiliary disease. C1 CORNELL UNIV,SECT PATHOL,ITHACA,NY 14853. NATL INST ENVIRONM HLTH SCI,DEPT HLTH & HUMAN SERV,RES TRIANGLE PK,NC 27709. CORNELL UNIV,SECT RADIOL,ITHACA,NY 14853. CORNELL UNIV,EPIDEMIOL SECT,ITHACA,NY 14853. RP Nicholson, BT (reprint author), CORNELL UNIV,SECT SMALL ANIM MED,ITHACA,NY 14853, USA. NR 33 TC 8 Z9 8 U1 0 U2 6 PU BRITISH VETERINARY ASSOC PI LONDON PA 7 MANSFIELD ST, LONDON, ENGLAND W1M 0AT SN 0034-5288 J9 RES VET SCI JI Res. Vet. Sci. PD NOV PY 1996 VL 61 IS 3 BP 258 EP 262 DI 10.1016/S0034-5288(96)90074-0 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA VU441 UT WOS:A1996VU44100015 PM 8938858 ER PT J AU Morozov, VA Lagaye, S Lyakh, L terMeulen, J AF Morozov, VA Lagaye, S Lyakh, L terMeulen, J TI Type D retrovirus markers in healthy Africans from Guinea SO RESEARCH IN VIROLOGY LA English DT Article DE retrovirus; AIDS; SRV; screening; Africans; Mason-Pfizer monkey virus; antibodies; nucleotide sequences ID PFIZER MONKEY VIRUS; CELL-LINE; NUCLEOTIDE-SEQUENCE; IMMUNODEFICIENCY SYNDROME; MOLECULAR-CLONING; HUMAN INFECTION; GENE-PRODUCTS; ANTIBODIES; POLYPEPTIDES; AIDS AB Sixteen matching sera and DNA samples from healthy African blood donors living in rural areas of Guinea were analysed for the presence of type D retrovirus markers. Screening for the antibodies against structural proteins of Mason-Pfizer monkey virus (M-PMV) was carried out by Western blot with a purified M-PMV as an antigen. Eight out of 16 sera samples were found to contain antibodies against at least two gag gene-coded proteins, and three of these were weakly positive against env gene-coded protein. Using PCR amplification and Southern hybridization, we detected M-PMV-like gag sequences in 11 out of 16 samples and env-related sequences in 8 out of 16 samples. Six DNAs were found to contain both M-PMV gag and env-related sequences. Restriction endonuclease analysis of the PCR-amplified gag sequences from two individuals and direct DNA sequencing analysis of the amplimers confirmed their M-PMV-like origin. Detection of antibodies and M-PMV-related sequences in blood donors from Guinea, but not in French or Algerian blood donors, indicated exogenous SRV infection in humans from certain geographic areas of Western Africa. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,LAB MOL VIROL & CARCINOGENESIS,FREDERICK,MD 21702. INST PASTEUR,F-75724 PARIS,FRANCE. BERNHARD NOCHT INST TROP MED,DEPT BIOL,D-20359 HAMBURG,GERMANY. NR 29 TC 8 Z9 10 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0923-2516 J9 RES VIROLOGY JI Res. Virol. PD NOV-DEC PY 1996 VL 147 IS 6 BP 341 EP 351 DI 10.1016/S0923-2516(97)85126-6 PG 11 WC Virology SC Virology GA VU341 UT WOS:A1996VU34100003 PM 8958587 ER PT J AU Austin, HA Boumpas, DT AF Austin, HA Boumpas, DT TI Treatment of lupus nephritis SO SEMINARS IN NEPHROLOGY LA English DT Article ID ACUTE NONLYMPHOCYTIC LEUKEMIA; ANTI-DNA ANTIBODIES; GROWTH-FACTOR-BETA; PULSE CYCLOPHOSPHAMIDE; RENAL BIOPSY; LONG-TERM; INTRAVENOUS CYCLOPHOSPHAMIDE; CONTROLLED TRIAL; IMMUNOSUPPRESSIVE AGENTS; MEMBRANOUS NEPHROPATHY RP Austin, HA (reprint author), NIDDKD,KIDNEY DIS SECT,NIAMSD,NIH,BLDG 10,RM 3N112,BETHESDA,MD 20892, USA. NR 87 TC 15 Z9 18 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 1996 VL 16 IS 6 BP 527 EP 535 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA VR465 UT WOS:A1996VR46500005 PM 9125797 ER PT J AU Alexander, HR Fraker, DL Bartlett, DL AF Alexander, HR Fraker, DL Bartlett, DL TI Isolated limb perfusion for malignant melanoma SO SEMINARS IN SURGICAL ONCOLOGY LA English DT Article DE in-transit melanoma; regional perfusion; hyperthermia; melphalan; tumor necrosis Factor ID TUMOR-NECROSIS-FACTOR; REGIONAL ISOLATED PERFUSION; STAGE-I MELANOMA; HYPERTHERMIC ANTIBLASTIC PERFUSION; RECURRENCE-FREE INTERVAL; EXTREMITY MELANOMA; INTERFERON-GAMMA; FACTOR-ALPHA; TRANSIT METASTASES; CLARK-V AB The technique of isolated limb perfusion (ILP) for the treatment of extremity melanoma has been used in the United States for almost 40 years. The treatment is based upon the ability to isolate the circulation of the afflicted extremity from the systemic circulation, thereby allowing dose-intensive delivery of anti-cancer agents to the limb while eliminating systemic exposure and toxicity. A number of agents have been used in ILP, however, the bulk of clinical experience has been with the allylating agent melphalan, typically used under conditions of mild hyperthermia. Despite considerable clinical experience, there has been a lack of agreement about the role of ILP in the prophylaxis against or the treatment of recurrent extremity melanoma. Recently there has been renewed interest in the use of ILP based upon the very promising results using a combination of tumor necrosis factor, melphalan, and interferon-gamma which have produced complete response (CR) rates of almost 90%. The utility of this regimen in extremity melanoma is actively being evaluated by clinical trials in the United States and Europe. (C) 1996 Wiley-Liss, Inc. RP Alexander, HR (reprint author), NCI,SURG METAB SECT,SURG BRANCH,NIH,BLDG 10,ROOM 2B17,BETHESDA,MD 20892, USA. NR 84 TC 42 Z9 44 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 8756-0437 J9 SEMIN SURG ONCOL JI Semin. Surg. Oncol. PD NOV-DEC PY 1996 VL 12 IS 6 BP 416 EP 428 DI 10.1002/(SICI)1098-2388(199611/12)12:6<416::AID-SSU7>3.0.CO;2-D PG 13 WC Oncology; Surgery SC Oncology; Surgery GA VQ780 UT WOS:A1996VQ78000007 PM 8914206 ER PT J AU Polak, JF Kronmal, RA Tell, GS OLeary, DH Savage, PJ Gardin, JM Rutan, GH Borhani, NO AF Polak, JF Kronmal, RA Tell, GS OLeary, DH Savage, PJ Gardin, JM Rutan, GH Borhani, NO TI Compensatory increase in common carotid artery diameter - Relation to blood pressure and artery intima-media thickness in older adults SO STROKE LA English DT Article DE carotid arteries; risk factors; ultrasonics ID LEFT-VENTRICULAR MASS; ESSENTIAL-HYPERTENSION; CARDIOVASCULAR HEALTH; ATHEROSCLEROSIS RISK; CORONARY-ARTERIES; ELASTIC-MODULUS; WALL; ENLARGEMENT AB Background and Purpose Common carotid artery (CCA) diameter is thought to increase as a consequence of hypertension and may increase as the thickness of the arterial wall increases. The purpose of this study was to determine CCA dimensions and correlate them with clinical features. Methods We performed a cross-sectional community-based study of adults 65 years of age and older, measuring inner and outer diameter of the CCA in vivo with carotid sonography. Findings were correlated against risk factors for atherosclerosis, CCA intima-media thickness (IMT), and echocardiographically determined left ventricular (LV) mass. Results Independent variables showing strong positive associations with outer and inner CCA diameter included age, male sex, height. weight, and systolic blood pressure. As an independent variable, LV mass (r = .40 and r = .37, respectively; P < .00001) had a strong positive relation to inner and outer CCA diameters. The relationship between diameter and IMT was different. In a model that controlled for age, sex, and estimated LV mass, an increase of 1 mm in CCA IMT corresponded to a 1.9-mm increase in the outer diameter of the artery (P < .00001) but was not significantly related to the inner diameter (slope = +0.07 mm; P = .26. Conclusions Increase in the outer diameter of the CCA is associated with subject size, sex, age, echocardiographically estimated LV mass, and CCA IMT. Increases in internal diameter of the CCA have similar relationships but are not related to IMT. This supports the hypothesis that the human CCA dilates as the thickness of the artery wall increases. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT RADIOL,BOSTON,MA 02115. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. UNIV BERGEN,DEPT PUBL HLTH & PRIMARY HLTH CARE,BERGEN,NORWAY. TUFTS UNIV NEW ENGLAND MED CTR,DEPT RADIOL,BOSTON,MA 02111. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,EPIDEMIOL & BIOMETRY PROGRAM,BETHESDA,MD 20892. MEMPHIS VET ADM MED CTR,MEMPHIS,TN. RP Polak, JF (reprint author), UNIV WASHINGTON,CARDIOVASC HLTH STUDY COORDINATING CTR,1501 4TH ST,SUITE 2105,SEATTLE,WA 98101, USA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU PHS HHS [N01-85079, N01-85086] NR 31 TC 83 Z9 84 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1996 VL 27 IS 11 BP 2012 EP 2015 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VQ163 UT WOS:A1996VQ16300014 PM 8898807 ER PT J AU Takahashi, H Kirsch, JR Hashimoto, K London, ED Koehler, RC Traystman, RJ AF Takahashi, H Kirsch, JR Hashimoto, K London, ED Koehler, RC Traystman, RJ TI PPBP [4-phenyl-1-(4-phenylbutyl) piperidine] decreases brain injury after transient focal ischemia in rats SO STROKE LA English DT Article DE cerebral ischemia, focal; neuronal damage; receptors, sigma; rats ID CEREBRAL-ARTERY OCCLUSION; D-ASPARTATE RECEPTOR; SIGMA-RECEPTORS; IFENPRODIL; LIGANDS; NEURONS; GERBIL; NEUROTOXICITY; ANTAGONISTS; SKF-10,047 AB Background and Purpose We tested the hypothesis that intravenous administration of the potent sigma-receptor ligand 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP) during transient focal ischemia would decrease postischemic brain infarction volume in rats. Methods Rats underwent intravascular focal ischemia for 2 hours followed by 22 hours of reperfusion. Halothane anesthesia was used only during initiation and cessation of ischemia. Rats received saline (n=10) or 1 mu mol/kg per hour PPBP (n=10) by continuous intravenous infusion starting 1 hour after the initiation of ischemia and continuing through 22 hours of reperfusion. Results There was no difference between groups in blood pressure, arterial blood gas values, and body temperature. Triphenyltetrazolium-determined infarction volume of ipsilateral cerebral cortex (saline, 39 +/- 6%; PPBP, 21 +/- 7% of ipsilateral hemisphere; mean +/- SEM) and striatum (saline, 68 +/- 6%; PPBP, 33 +/- 8% of ipsilateral striatum) was smaller in mts treated with PPBP than in rats treated with saline. Conclusions These data indicate that sigma-receptors may play an important role in the mechanism of injury both in cortex and striatum after 2 hours of transient focal ischemia in rats. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, sigma-receptors may influence the progression of injury in ischemic border regions. C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. NIDA,DIV INTRAMURAL RES,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD. FU NINDS NIH HHS [NS20020] NR 22 TC 43 Z9 44 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1996 VL 27 IS 11 BP 2120 EP 2123 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VQ163 UT WOS:A1996VQ16300037 PM 8898825 ER PT J AU Tilley, BC Marler, J Geller, NL Lu, M Legler, J Brott, T Lyden, P Grotta, J AF Tilley, BC Marler, J Geller, NL Lu, M Legler, J Brott, T Lyden, P Grotta, J TI Use of a global test for multiple outcomes in stroke trials with application to the national institute of neurological disorders and stroke t-PA stroke trial SO STROKE LA English DT Article DE cerebral ischemia; cerebrovascular disorders; clinical trials; data analysis, statistical ID BINARY OUTCOMES; URGENT THERAPY; ENDPOINTS; MINUTES; SCALE AB Background The National Institute of Neurological Disorders and Stroke (NINDS) held a workshop on statistical approaches to analysis of acute stroke trials that have multiple prespecified outcomes, An objective was to plan for statistical analysis of the NINDS t-PA Stroke Trial, a randomized, double-blind, placebo-controlled trial of recombinant tissue plasminogen activator (rt-PA) for patients with acute ischemic stroke. Treatment success was defined as a ''consistent and persuasive difference'' in the proportion of patients achieving favorable outcomes on the Barthel Index, Modified Rankin Scale, Glasgow Outcome Scale. and National Institutes of Health Stroke Scale. The Data and Safety Monitoring Committee for the trial recommended this outcome because the committee did not believe that a positive result for a single outcome would provide sufficient evidence of efficacy. Summary of Comment Workshop participants accepted the global test as a viable approach to testing the primary trial hypothesis. Clinician participants advocated categorizing outcomes as favorable/unfavsrable, outcomes more clinically meaningful than continuous outcomes for evaluating a drug with potentially serious side effects. They agreed that a global test was appropriate for ischemic stroke when no single outcome is accepted. Hypothetical, special-case examples illustrate that highly correlated outcomes diminish the power of the global test. NINDS t-PA Stroke Trial data demonstrate the clinical interpretability of the global test. Conclusions Workshop participants concluded that a global statistic should be used to test the trial's primary hypothesis accompanied by secondary tests of individual outcomes. Workshop participants recommended familiarizing the clinical/scientific community with the global approach. C1 NINCDS,DIV STROKE & TRAUMA,BETHESDA,MD 20892. NHLBI,OFF BIOSTAT RES,BETHESDA,MD 20892. UNIV CINCINNATI,MED CTR,DEPT NEUROL,CINCINNATI,OH 45267. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV CALIF SAN DIEGO,STROKE CTR,SAN DIEGO,CA 92103. UNIV TEXAS,SCH MED,DEPT NEUROL,HOUSTON,TX. RP Tilley, BC (reprint author), HENRY FORD HLTH SCI CTR,DIV BIOSTAT & RES EPIDEMIOL,1 FORD PL,DETROIT,MI 48202, USA. FU NINDS NIH HHS [N01-NS-02377, N01-NS-02382, N01-NS-02374] NR 23 TC 144 Z9 148 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1996 VL 27 IS 11 BP 2136 EP 2142 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA VQ163 UT WOS:A1996VQ16300042 PM 8898828 ER PT J AU Sheng, PL Wang, XB Ladenheim, B Epstein, C Cadet, JL AF Sheng, PL Wang, XB Ladenheim, B Epstein, C Cadet, JL TI AP-1 DNA-binding activation by methamphetamine involves oxidative stress SO SYNAPSE LA English DT Article DE METH; AP-1; DNA binding; free radicals ID DISMUTASE TRANSGENIC MICE; METHYLENEDIOXYMETHAMPHETAMINE MDMA; SUPEROXIDE RADICALS; STRIATAL DOPAMINE; HYDROGEN-PEROXIDE; RAT STRIATUM; C-FOS; NEUROTOXICITY; BRAIN; EXPRESSION AB Methamphetamine (METH) caused dose-dependent increases in AP-1 DNA-binding activity in both nontransgenic (Non-Tg) and CuZn-SOD transgenic (SOD-Tg) mice. However, the increases in SOD-Tg mice were less prominent than those observed in Non-Tg animals. The time-course of METH-induced AP-1 changes was similar in both strains of mice. AP-1 binding activity showed an initial increase at 1 h, peaked at 3 h, and then gradually declined. AP-1 binding activity was back to normal by the 72-h time point. Regional analyses of METH effects revealed increases in the caudate putamen and cerebellum, with the striatum showing relatively higher METH-induced AP-1 DNA-binding activation. These regional effects were also attenuated in the SOD-Tg mice. These data indicate that METH-induced stimulation of AP-1 DNA-binding depends on cellular redox status. These results are consistent with in vitro studies that have reported that several transcription factors are regulated through redox mechanisms. (C) 1996 Wiley-Liss, Inc.* C1 NIDA,MOL NEUROPSYCHIAT SECT,NIH,DIR,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. NIDA,MOL NEUROBIOL SECT,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD 21224. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. NR 22 TC 20 Z9 20 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 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1996 VL 24 IS 3 BP 213 EP 217 PG 5 WC Neurosciences SC Neurosciences & Neurology GA VQ912 UT WOS:A1996VQ91200002 PM 8923660 ER PT J AU Hyde, TM Knable, MB Murray, AM AF Hyde, TM Knable, MB Murray, AM TI Distribution of dopamine D1-D4 receptor subtypes in human dorsal vagal complex SO SYNAPSE LA English DT Article DE area postrema; nucleus of the solitary tract; dorsal motor nucleus of the vagus ID NUCLEUS TRACTUS SOLITARIUS; RAT-BRAIN; INDUCED EMESIS; AREA POSTREMA; VAGUS NERVE; MEDULLA-OBLONGATA; BLOOD-PRESSURE; MESSENGER-RNA; MOTOR-NEURONS; ORGANIZATION AB The distribution of D1/D5, D2/D3, D2/D3/D4, and individually, putative D2-D4 receptors across the dorsal vagal complex of the human medulla was assessed with quantitative receptor autoradiography. D1/D5 receptors were found in very low levels. D2 receptors were concentrated in the intermediate and medial subnuclei of the nucleus of the solitary tract (NTS), and in the dorsal motor nucleus of the vagus (DMN), while D3 receptors were more homogenous across the entire NTS, area postrema (AP), and DMN. In contrast, D4 receptors were found almost exclusively in the intermediate and medial subnuclei of the NTS, and in the DMN. These findings suggest that the ''D2 family'' of receptors is an important component of brain stem mechanisms regulating visceral function, including gastrointestinal systems, such as emesis, along with cardiovascular and pulmonary systems. Compounds with individual selectivity for D2, D3, or D4 receptors may be useful in the manipulation of neural networks regulating these visceral systems. (C) 1996 Wiley-Liss, Inc.* RP Hyde, TM (reprint author), ST ELIZABETH HOSP,NIMH,CLIN BRAIN DISORDERS BRANCH,INTRAMURAL RES PROGRAM,NEUROSCI RES CTR,WASHINGTON,DC 20032, USA. NR 49 TC 41 Z9 42 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1996 VL 24 IS 3 BP 224 EP 232 DI 10.1002/(SICI)1098-2396(199611)24:3<224::AID-SYN4>3.0.CO;2-G PG 9 WC Neurosciences SC Neurosciences & Neurology GA VQ912 UT WOS:A1996VQ91200004 PM 8923662 ER PT J AU Mahler, JF Stokes, W Mann, PC Takaoka, M Maronpot, RR AF Mahler, JF Stokes, W Mann, PC Takaoka, M Maronpot, RR TI Spontaneous lesions in aging FVB/N mice SO TOXICOLOGIC PATHOLOGY LA English DT Article DE tumors; mouse; spontaneous; transgenic ID TRANSGENIC MICE; HA-RAS; MOUSE; NEOPLASMS; INDUCTION; GENES; SKIN; STEP AB The FVB/N mouse strain was created in the early 1970s and has since been used extensively in transgenic research because of its well-defined inbred background, superior reproductive performance, and prominent pronuclei of fertilized zygotes, which facilitate microinjection of DNA. Little is known, however, about the survivability and spontaneous disease of nontransgenic FVB/N mice. Therefore, the purpose of this study was to determine survival to 24 mo of age and the incidence of neoplastic and nonneoplastic disease at 14 and 24 mo of age. At 14 mo of age, the incidence of tumor-bearing mice was 13% in males (n = 45) and 26% in females (n = 98). All tumors in males and most in females at this time were alveolar-bronchiolar (AB) neoplasms of the lung. Survival to 24 mo of age was approximately 60% in both sexes (29/50 males, 71/116 females), and the incidence of mice with tumors at this time was 55% in males and 66% in females. In decreasing order of frequency, the following neoplasms were observed in >5% of subjects: in males, lung AB tumors, liver hepatocellular tumors, subcutis neural crest tumors, and Harderian gland adenomas; in females, lung AB tumors, pituitary gland adenomas, ovarian tumors (combined types), lymphomas, histiocytic sarcomas, Harderian gland adenomas, and pheochromocytomas. Compared with other mouse strains, the observed incidences of tumors in FVB/N mice suggest a higher than usual rate of lung tumors and a lower than usual incidence of liver tumors and lymphomas. This tumor profile should be considered in the interpretation of neoplastic phenotypes in FVB/N-derived transgenic lines. RP Mahler, JF (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,LAB EXPT PATHOL,MD B3-06,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 20 TC 129 Z9 130 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1996 VL 24 IS 6 BP 710 EP 716 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA WB824 UT WOS:A1996WB82400006 PM 8994298 ER PT J AU Mahler, JF Davis, BJ Morham, SG Langenbach, R AF Mahler, JF Davis, BJ Morham, SG Langenbach, R TI Disruption of cyclooxygenase genes in mice SO TOXICOLOGIC PATHOLOGY LA English DT Article ID MOUSE RP Mahler, JF (reprint author), NIEHS,LAB EXPT PATHOL,MD B3-06,111 ALEXANDER DR,RES TRIANGLE PK,NC 27709, USA. NR 6 TC 11 Z9 11 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1996 VL 24 IS 6 BP 717 EP 719 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA WB824 UT WOS:A1996WB82400007 PM 8994299 ER PT J AU Maronpot, RR Boorman, GA AF Maronpot, RR Boorman, GA TI The contribution of the mouse in hazard identification studies SO TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT XV International Symposium of the Society-of-Toxicologic-Pathologists CY JUN 09-13, 1996 CL ST LOUIS, MO SP Soc Toxicol Pathologists DE National Toxicology Program; cancer bioassays; mouse liver tumors; animal models; species-specific responses; mechanisms of carcinogenicity; chronic toxicity; pharmaceuticals ID B6C3F1 MICE; CARCINOGENICITY; CHEMICALS; OZONE AB Because there is usually more extensive toxicity, metabolism, and pharmacokinetic information for pharmaceuticals as opposed to environmental agents, including pesticides, the argument has been made that carcinogenicity testing in two rodent species may not have been necessary for carcinogenicity testing of pharmaceuticals. On the basis of numerical data only, it may be argued that carcinogenicity testing of pharmaceuticals in one species, typically the rat, is sufficient to identify potential human carcinogens. The argument that testing in a second species, typically the mouse, is redundant overlooks the value added by the second species carcinogenicity study. Bioassay data from the second species allows balance and perspective in evaluating the observed effects, and this is especially critical when there is a marginal, questionable, or inconclusive response in one species. Utilization of two species for carcinogen identification is the principal means for identifying trans-species carcinogens-those mostly likely to be carcinogenic in humans. Given that neither rat nor mouse are ideal surrogates for humans, concordant data from both species strengthens the ability to extrapolate findings to humans. We believe that testing in two species should continue to be the default approach used for carcinogen hazard identification whenever scientifically indicated until such time that acceptable and suitable alternatives are available. To utilize only one species for this important means of protecting human health is premature at this time. RP Maronpot, RR (reprint author), NIEHS,LAB EXPT PATHOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1996 VL 24 IS 6 BP 726 EP 731 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA WB824 UT WOS:A1996WB82400011 PM 8994301 ER PT J AU Ward, JM AF Ward, JM TI Rat or mouse cancer bioassay - Or none of the above? SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material ID CARCINOGENS RP Ward, JM (reprint author), NCI,FREDERICK,MD 21702, USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1996 VL 24 IS 6 BP 734 EP 735 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA WB824 UT WOS:A1996WB82400013 PM 8994302 ER PT J AU Maronpot, RR AF Maronpot, RR TI A symposium summary and perspective on comparative molecular biology of cancer SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material RP Maronpot, RR (reprint author), NIEHS,LAB EXPT PATHOL,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SOC TOXICOLOGIC PATHOLOGISTS PI LAWRENCE PA 1041 NEW HAMPSHIRE ST PO BOX 368, LAWRENCE, KS 66044 SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD NOV-DEC PY 1996 VL 24 IS 6 BP 801 EP 804 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA WB824 UT WOS:A1996WB82400027 PM 8994312 ER PT J AU ElMasri, HA Constan, AA Ramsdell, HS Yang, RSH AF ElMasri, HA Constan, AA Ramsdell, HS Yang, RSH TI Physiologically based pharmacodynamic modeling of an interaction threshold between trichloroethylene and 1,1-dichloroethylene in fischer 344 rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID MICE; METABOLITE; LIVER; BIOTRANSFORMATION; MOUSE; DNA AB Physiologically based pharmacokinetic modeling (PBPK) and gas uptake experiments have been used by researchers to demonstrate the competitive inhibition mechanism between trichloroethylene (TCE) and 1,1-dichloroethylene (DCE), Expanding on their work, we showed that this pharmacokinetic interaction was absent at levels of 100 ppm or less of either chemical in gas uptake systems, In this study, we further illustrate the presence of such an interaction threshold at the pharmacodynamic level by examining the interaction effect of either chemical on the other's ability to bind and deplete hepatic glutathione (GSH) in Fischer 344 rats. However, at this end point, the pharmacodynamic interaction is complicated by the ability of the liver to resynthesize GSH in response to its depletion. To quantitatively resolve the interaction effects on GSH content from the resynthesis effects, physiologically based pharmacodynamic (PBPD) modeling is applied, Initially, the PBPD model description of hepatic GSH kinetics was calibrated against previously published data and by gas uptake experiments conducted in our laboratory. Then, the model was used to determine the duration of the gas uptake exposure experiments by identifying the critical time point at which hepatic GSH is at a minimum in response to both chemicals. Subsequently, gas uptake experiments were designed following the PBPK/PD model predictions, In these model-directed experiments, DCE was the only chemical capable of significantly depleting hepatic GSH. The application of TCE to the rats at concentrations higher than 100 ppm obstructed the ability of DCE to deplete hepatic GSH, Since the metabolites of DCE bind to hepatic GSH, this obstruction signaled the presence of metabolic inhibition by TCE. However, TCE, at concentrations less than 100 ppm, was not effective in inhibiting DCE from significantly depleting hepatic GSH. The same observations were made when the ability of DCE to cause hepatic injury, as measured by aspartate aminotransferase serum activity, was assessed, Both conclusions validated the previous findings of the presence of the interaction threshold at the pharmacokinetic level. (C) 1996 Academic Press, Inc. C1 CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. COLORADO STATE UNIV,DEPT ENVIRONM HLTH,CTR ENVIRONM TOXICOL & TECHNOL,FT COLLINS,CO 80523. RP ElMasri, HA (reprint author), NIEHS,LAB COMPUTAT BIOL & RISK ANAL,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [P42ES05949] NR 19 TC 26 Z9 26 U1 2 U2 5 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 NOV PY 1996 VL 141 IS 1 BP 124 EP 132 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VV016 UT WOS:A1996VV01600016 PM 8917684 ER PT J AU Valentine, JL Lee, SST Seaton, MJ Asgharian, B Farris, G Corton, JC Gonzalez, FJ Medinsky, MA AF Valentine, JL Lee, SST Seaton, MJ Asgharian, B Farris, G Corton, JC Gonzalez, FJ Medinsky, MA TI Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID MOUSE BONE-MARROW; LIVER-MICROSOMES; B6C3F1 MICE; IN-VIVO; EXPOSURE; PHENOL; RATS; INHALATION; TOLUENE; ETHANOL AB Transgenic CYP2E1 knockout mice (cyp2e1(-/-)) were used to investigate the involvement of CYP2E1 in the in vivo metabolism of benzene and in the development of benzene-induced toxicity. After benzene exposure, absence of CYP2E1 protein was confirmed by Western blot analysis of mouse liver samples. For the metabolism studies, male cyp2e1(-/-) and wild-type control mice were exposed to 200 ppm benzene, along with a radiolabeled tracer dose of [C-14]benzene (1.0 Ci/mol) by nose-only inhalation for 6 hr. Total urinary radioactivity and all radiolabeled individual metabolites were reduced in urine of cyp2e1(-/-) mice compared to wildtype controls during the 48-hr period after benzene exposure. In addition, a significantly greater percentage of total urinary radioactivity could be accounted for as phenylsulfate conjugates in cyp2e1(-/-) mice compared to wild-type mice, indicating the importance of CYP2E1 in oxidation of phenol following benzene exposure in normal mice. For the toxicity studies, male cyp2e1(-/-), wildtype, and B6C3F1 mice were exposed by whole-body inhalation to 0 ppm (control) or 200 ppm benzene, 6 hr/day for 5 days. On Day 5, blood, bone marrow, thymus, and spleen were removed for evaluation of micronuclei frequencies and tissue cellularities. No benzene-induced cytotoxicity or genotoxicity was observed in cyp2e1(-/-) mice. In contrast, benzene exposure resulted in severe genotoxicity and cytotoxicity in both wild-type and B6C3F1 mice. These studies conclusively demonstrate that CYP2E1 is the major determinant of in vivo benzene metabolism and benzene-induced myelotoxicity in mice. (C) 1996 Academic Press, Inc. C1 NCI,NIH,BETHESDA,MD 20892. RP Valentine, JL (reprint author), CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709, USA. NR 42 TC 149 Z9 159 U1 2 U2 6 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 NOV PY 1996 VL 141 IS 1 BP 205 EP 213 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VV016 UT WOS:A1996VV01600025 PM 8917693 ER PT J AU Germolec, DR Yoshida, T Gaido, K Wilmer, JL Simeonova, PP Kayama, F Burleson, F Dong, WM Lange, RW Luster, MI AF Germolec, DR Yoshida, T Gaido, K Wilmer, JL Simeonova, PP Kayama, F Burleson, F Dong, WM Lange, RW Luster, MI TI Arsenic induces overexpression of growth factors in human keratinocytes SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; COLONY-STIMULATING FACTOR; FACTOR RECEPTOR LIGANDS; ALPHA TRANSGENIC MICE; TGF-ALPHA; EPIDERMAL GROWTH; MOUSE SKIN; GM-CSF; INDUCTION; AUTOCRINE AB Although epidemiological studies have shown that inorganic arsenicals are human skin carcinogens and induce hyperproliferation and hyperkeratosis, there is currently no known mechanism for their action or an established animal model for its study. We observed increased mRNA transcripts and secretion of keratinocyte growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-alpha (TGF alpha) and the proinflammatory cytokine tumor necrosis factor-alpha in primary human epidermal keratinocytes cultured in the presence of low micromolar concentrations of sodium arsenite. Treatment with sodium arsenite resulted in a significant increase in cell proliferation, as indicated by increases in cell numbers, c-myc gene expression, and incorporation of [H-3]thymidine into cellular DNA. Studies of transcriptional regulation indicate that the rate of GMCSF mRNA transcription is increased, while the elevated TGF alpha is likely the result of message stabilization, While a number of cytokine regulatory networks exist in the skin, studies utilizing neutralizing antibodies against the growth factors of interest indicate that inhibition of the arsenic-induced increase in TGF alpha results in a corresponding decrease in the gene expression and secretion of CM-CSF. The present studies demonstrate that growth-promoting cytokines and growth factors are induced in keratinocytes following treatment with arsenic and could play a significant role in arsenic-induced skin cancer. (C) 1996 Academic Press, Inc. C1 TOKAI UNIV,DEPT ENVIRONM MED,KANAGAWA,JAPAN. UNIV OCCUPAT & ENVIRONM HLTH MED,KITAKYUSHU,FUKUOKA,JAPAN. CHEM IND INST TOXICOL,RES TRIANGLE PK,NC 27709. NIOSH,TOXICOL & MOL BIOL BRANCH,MORGANTOWN,WV 26502. RP Germolec, DR (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 59 TC 115 Z9 119 U1 1 U2 2 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 NOV PY 1996 VL 141 IS 1 BP 308 EP 318 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VV016 UT WOS:A1996VV01600036 PM 8917704 ER PT J AU DiPaolo, JA Popescu, NC Woodworth, CD Zimonjic, DB AF DiPaolo, JA Popescu, NC Woodworth, CD Zimonjic, DB TI Papillomaviruses and potential copathogens SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 5th European Meeting of Environmental Hygiene CY JUN 27-29, 1995 CL PRAGUE, CZECH REPUBLIC SP Univ Dusseldorf, Med Inst Environm Hygiene, Alfried Krupp von Bohlen & Halbach Fdn Essen DE papillomaviruses; cervical epithelium; cocarcinogens; oncogenes; suppressor genes ID HUMAN HERPESVIRUS-6; EPITHELIAL-CELLS; CERVICAL-CANCER; INFECTION; DNA; CARCINOMA; GENE; RAS AB An in vitro multistage genital epithelial cell model for cervical cancer that parallels the in vivo neoplastic process has been developed using recombinant human papillomavirus (HPV) DNA and genital cells. HPV-16-immortalized genital cells are responsive to the genotoxic action of known chemical carcinogens (polycyclic hydrocarbons, alkylating agents or cigarette smoke condensate), but are not converted to malignancy. Ras oncogene and human herpes virus-2 did convert HPV immortalized cells to malignancy, whereas human herpes virus-6 infection only increased HPV expression. Human immunodeficiency virus did not infect genital cells. RP DiPaolo, JA (reprint author), NCI,BIOL LAB,BETHESDA,MD 20892, USA. NR 25 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 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV PY 1996 VL 88 IS 1-3 BP 1 EP 7 DI 10.1016/0378-4274(96)03710-1 PG 7 WC Toxicology SC Toxicology GA VR059 UT WOS:A1996VR05900002 PM 8920709 ER PT J AU Nettesheim, P Bader, T AF Nettesheim, P Bader, T TI Tumor necrosis factor alpha stimulates arachidonic acid metabolisms and mucus production in rat tracheal epithelial cell cultures SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 5th European Meeting of Environmental Hygiene CY JUN 27-29, 1995 CL PRAGUE, CZECH REPUBLIC SP Univ Dusseldorf, Med Inst Environm Hygiene, Alfried Krupp von Bohlen & Halbach Fdn Essen DE airway epithelium; TNF alpha; eicosanoids; mucus secretion AB Air-liquid interface (ALI) cultures of rat tracheal epithelial (RTE) cells were used to study the response of differentiated airway epithelial cells to the inflammatory cytokine, tumor necrosis factor alpha(TNF alpha). We found that the cultures expressed low levels of TNF alpha receptors. TNF alpha stimulated the AA-cascade: cytoplasmic phospholipase A2 (cPLA2) and prostaglandin H synthase 2 (PGHS2) were upregulated; as a result prostaglandin E (PGE2) secretion was increased. Subsequent to the increase in PGE2 mucus secretion increased, suggesting that PGE2 may act as an autocrine regulator of mucus secretion. RP Nettesheim, P (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 3 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD NOV PY 1996 VL 88 IS 1-3 BP 35 EP 37 DI 10.1016/0378-4274(96)03715-0 PG 3 WC Toxicology SC Toxicology GA VR059 UT WOS:A1996VR05900007 PM 8920714 ER PT J AU Martinez, F Becerril, B Gurrola, GB Martin, BM Possani, LD AF Martinez, F Becerril, B Gurrola, GB Martin, BM Possani, LD TI Synthesis and expression of the gene coding for noxiustoxin, a K+ channel-blocking peptide from the venom of the scorpion Centruroides noxius SO TOXICON LA English DT Article; Proceedings Paper CT Proceedings of the Fifth Pan American Symposium on Animal Plant and Microbial Toxins CY JUL 30-AUG 04, 1995 CL FREDERICK, MD ID CHARYBDOTOXIN; BINDING AB A set of six synthetic overlapping oligonucleotides coding for noxiustoxin were coupled into a continuous DNA fragment by means of recursive polymerase chain reaction. The polymerase chain reaction product was digested with SalI and HindIII, ligated into the E. coli vector pCSP105 and expressed as a fusion protein. The fusion protein was purified and digested with trypsin and the hydrolysis products were separated by high-performance liquid chromatography. Approximately 1.3mg of recombinant noxiustoxin per liter of culture was obtained. Amino acid analysis and N-terminal amino acid sequence of the recombinant noxiustoxin confirmed the nucleotide sequence of the cloned DNA. Binding experiments using rat brain synaptosomal membranes revealed that recombinant noxiustoxin displaced bound radioactive native NTX with a similar efficiency to cold native noxiustoxin. Copyright (C) 1996 Elsevier Science Ltd C1 NATL AUTONOMOUS UNIV MEXICO,INST BIOTECHNOL,DEPT MOL RECOGNIT & STRUCT BIOL,CUERNAVACA 62271,MORELOS,MEXICO. NIMH,CLIN NEUROSCI BRANCH,UNITE MOL STRUCTURES,BETHESDA,MD 20892. RI Possani, Lourival/J-2397-2013 NR 14 TC 7 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD NOV-DEC PY 1996 VL 34 IS 11-12 BP 1413 EP 1419 DI 10.1016/S0041-0101(96)00092-X PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA WE725 UT WOS:A1996WE72500022 PM 9027998 ER PT J AU Sloand, EM Yu, M Klein, HG AF Sloand, EM Yu, M Klein, HG TI Comparison of random-donor platelet concentrates prepared from whole blood units and platelets prepared from single-donor apheresis collections SO TRANSFUSION LA English DT Article ID GLYCOPROTEIN-IIB-IIIA; ACTIVATED PLATELETS; MONOCLONAL-ANTIBODY; MEMBRANE; STORAGE; TRANSFUSIONS; EXPRESSION; VIABILITY; COMPLEX; SURFACE AB Background: The use of fresh platelets results in better posttransfusion recovery and survival than does the use of platelets that have been stored before transfusion. Activation of platelets during preparation and storage may be one of the factors responsible for a number of storage-related changes in platelet membrane proteins, Blood centers commonly prepare platelet concentrates from both multiple units of whole blood and single-donor plateletpheresis collections. Study Design and Methods: Seventeen plateletpheresis concentrates, anticoagulated with ACD, were compared to platelets prepared from whole blood from the same donor that was anticoagulated with CPDA-1 (random-donor platelets). After preparation, plateletpheresis and random-donor platelets were stored in plastic storage bags at 22 degrees C for 5 days, Platelet surface glycoproteins were examined by flow cytometry after platelets were fixed in dilute plasma with 1-percent formaldehyde and stained with fluorescein isothiocyanate-labeled monoclonal antibodies CD42b (anti-glycoprotein [GP]lb), CD41a (anti-GPIIb/IIIa), and CD62 (anti-P-selectin). Results: The binding of anti-CD42b was greater in plateletpheresis concentrates than in random-donor platelets on Days 3 and 5 (p<0.01) of storage; binding of anti-CD62 was greater in the random-donor concentrates (p<0.01) on Days 3 and 5. Plateletpheresis concentrate aggregation responses were greater on Day 5 (p<0.01). To determine ii the type of anticoagulant and the method of mixture with blood contributed to these changes, 10 samples were split into aliquots and prepared in two separate ways: One group of samples was prepared by allowing anticoagulant (ACD) and blood to flow into the tube at a rate of 3 mu L per second, and the other group of samples was prepared by allowing blood to flow into tubes containing a measured amount of CPDA-1, The first samples bound more anti-CD42b than the second samples (p<0.01), The second group of samples contained significantly more microvesicles that bound anti-CD41a than did the first group (p<0.01). Samples prepared by the first method but anticoagulated with CPDA-1 contained more microvesicles but had the same amount of anti-CD42b binding as did similarly prepared samples anticoagulated with ACD (p<0.05). Conclusion: Platelet concentrates prepared from single units of whole blood and anticoagulated with CPDA-1 bind less anti-CD42b and more anti-CD62 than do platelets obtained by apheresis. These differences may be attributed to platelet sedimentation and the transient exposure of some of the platelets in the blood that is first collected during whole-blood donation to high concentrations of anticoagulant. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP Sloand, EM (reprint author), NHLBI,31 CTR DR,MSC 2490,BLDG 31,ROOM 4A11,BETHESDA,MD 20892, USA. NR 25 TC 33 Z9 33 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV-DEC PY 1996 VL 36 IS 11-12 BP 955 EP 959 DI 10.1046/j.1537-2995.1996.36111297091737.x PG 5 WC Hematology SC Hematology GA VU726 UT WOS:A1996VU72600004 PM 8937403 ER PT J AU Bowman, CA Yu, M CottlerFox, M AF Bowman, CA Yu, M CottlerFox, M TI Evaluation of methods for preparing and thawing cryopreserved CD34+ and CD34- cell lines for use as reagents in flow cytometry of hematopoietic progenitor cells SO TRANSFUSION LA English DT Article AB Background: Flow cytometry is used to quantitate CD34+ hematopoietic progenitor cells for transplantation. The present study evaluates methods for preparing and thawing cryopreserved CD34+ and CD34- cell lines for use as flow cytometry reagents. Study Design and Methods: The human myeloid leukemic cell lines KG1a(CD34+) and K562 (CD34-) were grown in culture under standard conditions and then prepared on ficoll gradients of different densities to determine which gave the component that was most reproducible. After ficoll preparation, the cells were frozen in standard cryopreservation media and four methods of thawing were examined. Determination of the method that gave the cell component that was most reproducible was based on viability, percentage of cell recovery, and maintenance of CD34 antigenicity status. Results: Ficoll gradient preparation improved the ease of flow cytometry analysis when original viability was low, and it produced a more uniform cell population. However, it resulted in significant cell loss for both cell lines. While the cell recovery for K562 cells was not significantly different with any of the densities of ficoll, recovery was significantly better for KG1 a cells with ficoll at a specific gravity of 1.077. Of the thawing methods examined, all three that involved a rapid thaw at 37 degrees C were statistically equivalent to each other and were better than thawing at 4 degrees C. Conclusion: With a standardized method of preparing cell lines as reagents for quality control purposes, data comparison among cell processing laboratories may more readily be initiated. Such cell lines could also be useful as a teaching tool for flow cytometry and in proficiency testing. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,SPECIAL SERV LAB,BETHESDA,MD 20892. NR 8 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV-DEC PY 1996 VL 36 IS 11-12 BP 985 EP 988 DI 10.1046/j.1537-2995.1996.36111297091743.x PG 4 WC Hematology SC Hematology GA VU726 UT WOS:A1996VU72600010 PM 8937409 ER PT J AU Stroncek, DF Leonard, K Eiber, G Malech, HL Gallin, JI Leitman, SF AF Stroncek, DF Leonard, K Eiber, G Malech, HL Gallin, JI Leitman, SF TI Alloimmunization after granulocyte transfusions SO TRANSFUSION LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; QUININE-DEPENDENT ANTIBODIES; COLONY-STIMULATING FACTOR; NADPH OXIDASE; MARROW TRANSPLANTATION; RECEPTOR-III; ANTIGEN NB1; NEUTROPENIA; DEFICIENCY; LEUKEMIA AB Background: Although granulocyte transfusions are recommended for neutropenic patients with bacterial infections that are unresponsive to antibiotic therapy, the presence of white cell (WBC) antibodies in the recipient can render these transfusions ineffective. Study Design and Methods: A 25-year-old man with chronic granulomatous disease experienced a pulmonary transfusion reaction while receiving granulocyte transfusions, and he was found to be immunized to neutrophil antigen NA2. A retrospective study of alloimmunization to HLA and neutrophil antigens in 18 patients with chronic granulomatous disease who had also received repeated granulocyte transfusions was then performed. Sera were tested in lymphocytotoxicity, granulocyte agglutination, granulocyte immunofluorescence, monoclonal antibody immobilization of granulocyte antigen, and immunoprecipitation assays. Results: After the granulocyte transfusions, sera from 14 of the 18 patients contained WBC antibodies. Seven sera samples reacted in the lymphocytotoxicity, granulocyte immunofluorescence, and granulocyte agglutination assays; seven reacted in the lymphocytotoxicity and granulocyte immunofluorescence assays but not the granulocyte agglutination assay, and four did not react. When the monoclonal antibody immobilization of granulocyte antigen assay was used, three sera samples reacted with Fc gamma receptor III, three with the 58- to 64-kDa protein carrying the neutrophil antigen NBI, one with CD11a, and one with CD18, Antibodies from three patients immunoprecipitated a neutrophil protein of 60 kDa, Overall, antibodies to neutrophil antigens other than HLA could be detected in sera from eight patients, Transfusion reactions occurred in 11 of the 14 individuals with WBC antibodies and in none of the 4 without antibodies, Seven pulmonary reactions occurred in patients with WBC antibodies, The patients with WBC antibodies were given significantly more granulocyte concentrates (78 +/- 65 vs. 29 +/- 15 units, p<0.05). Conclusion: Recipients of granulocyte transfusions often become alloimmunized. Screening for WBC antibodies periodically during transfusions, after adverse reactions, or before subsequent transfusions is indicated, if WBC antibodies are present, no further granulocyte transfusions should be given unless the granulocytes are collected from HLA- and/or neutrophil antigen-compatible donors. C1 UNIV MINNESOTA,DEPT PATHOL & LAB MED,MINNEAPOLIS,MN 55455. NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. AMER RED CROSS,N CENT BLOOD SERV,ST PAUL,MN. NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. RP Stroncek, DF (reprint author), UNIV MINNESOTA,BLOOD BANK,BOX 198 UMHC-D211 MAYO,420 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. NR 32 TC 58 Z9 59 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV-DEC PY 1996 VL 36 IS 11-12 BP 1009 EP 1015 DI 10.1046/j.1537-2995.1996.36111297091747.x PG 7 WC Hematology SC Hematology GA VU726 UT WOS:A1996VU72600014 PM 8937413 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Eliminating ghost bands from plasmid preps SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID PURIFICATION; DNA AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column updates the discussion of a ghost DNA band that continues to haunt netters. For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 6 TC 1 Z9 1 U1 4 U2 18 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 NOV PY 1996 VL 21 IS 11 BP 441 EP 442 DI 10.1016/S0968-0004(96)30041-8 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VV786 UT WOS:A1996VV78600009 PM 8987401 ER PT J AU Gibson, TJ Koonin, EV Musco, G Pastore, A Bork, P AF Gibson, TJ Koonin, EV Musco, G Pastore, A Bork, P TI Friedreich's ataxia protein: Phylogenetic evidence for mitochondrial dysfunction SO TRENDS IN NEUROSCIENCES LA English DT Article ID SEQUENCE DATABASES; ALPHA-TOCOPHEROL; DNA DAMAGE; MUTATION; GENE; ALIGNMENT; LOCUS AB Friedreich's ataxia is the most common inherited spinocerebellar ataxia. A decade of linkage and physical mapping studies have culminated in the identification of the Friedreich's ataxia gene. The presence of homologues in purple bacterial genomes, but not in other bacteria, allows us to infer a mitochondrial location for frataxin (Friedreich's ataxia protein) on the basis of bacterial phylogeny. Frataxin possesses a non-globular N-terminus domain providing a candidate mitochondrial targeting peptide. Clues to the function of frataxin are provided by the mitochondrial location, a clinically similar ataxia with vitamin E deficiency, and certain neuropathies with mitochondrial DNA instability caused by mutations in nuclear genes. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. MAX DELBRUCK CTR MOL MED,D-13122 BERLIN,GERMANY. RP Gibson, TJ (reprint author), EUROPEAN MOL BIOL LAB,POSTFACH 102209,MEYERHOFSTR 1,D-69012 HEIDELBERG,GERMANY. RI musco, giovanna/I-7122-2012; Bork, Peer/F-1813-2013 OI musco, giovanna/0000-0002-0469-2994; Bork, Peer/0000-0002-2627-833X NR 32 TC 110 Z9 110 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1996 VL 19 IS 11 BP 465 EP 468 DI 10.1016/S0166-2236(96)20054-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VR301 UT WOS:A1996VR30100005 PM 8931268 ER PT J AU Zimmer, A AF Zimmer, A TI Gene targeting and behaviour: A genetic problem requires a genetic solution SO TRENDS IN NEUROSCIENCES LA English DT Letter RP Zimmer, A (reprint author), NIH,DEPT HLTH & HUMAN SERV,BLDG 36-3A17,BETHESDA,MD 20892, USA. RI Zimmer, Andreas/B-8357-2009 NR 1 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1996 VL 19 IS 11 BP 470 EP 470 DI 10.1016/S0166-2236(96)20053-0 PG 1 WC Neurosciences SC Neurosciences & Neurology GA VR301 UT WOS:A1996VR30100009 PM 8931271 ER PT J AU Fields, RD Itoh, K AF Fields, RD Itoh, K TI Neural cell adhesion molecules in activity-dependent development and synaptic plasticity SO TRENDS IN NEUROSCIENCES LA English DT Review ID LONG-TERM POTENTIATION; ADULT SKELETAL-MUSCLE; 2ND MESSENGER SYSTEMS; N-CAM; NEURITE OUTGROWTH; POLYSIALIC ACID; MEMORY FORMATION; NERVOUS-SYSTEM; CYTOPLASMIC DOMAIN; ARACHIDONIC-ACID AB Cell adhesion molecules (CAMs) have a vital role in forming connections between neurons during embryonic development. Increasing evidence suggests that CAMs also participate in activity-dependent plasticity during development and synaptic plasticity in adults. Neural impulses of appropriate patterns can regulate expression of specific CAMs in mouse neurons from dorsal-root ganglia, alter cell-cell adhesion and produce structural reorganization of axon terminals in culture. Synaptic plasticity in Aplysia, learning in chick and long-term potentiation in rat hippocampus are accompanied by changes in CAM expression. Long-term potentiation can be blocked by disrupting CAM function in rat hippocampus, and learning deficits result from antibody blockade of CAMs in chicks and in transgenic mice lacking specific CAMs. Cell adhesion molecules might produce these effects by controlling several cellular processes, including cell adhesion, cytoskeletal structure and intracellular signalling. C1 TOKYO METROPOLITAN INST MED SCI,BUNKYOU KU,TOKYO 113,JAPAN. RP Fields, RD (reprint author), NICHHD,NIH,DEV NEUROBIOL LAB,UNIT NEUROCYTOL & PHYSIOL,BETHESDA,MD 20892, USA. NR 94 TC 223 Z9 229 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD NOV PY 1996 VL 19 IS 11 BP 473 EP 480 DI 10.1016/S0166-2236(96)30013-1 PG 8 WC Neurosciences SC Neurosciences & Neurology GA VR301 UT WOS:A1996VR30100012 PM 8931273 ER PT J AU Kondo, T Misik, V Riesz, P AF Kondo, T Misik, V Riesz, P TI Sonochemistry of cytochrome c. Evidence for superoxide formation by ultrasound in argon-saturated aqueous solution SO ULTRASONICS SONOCHEMISTRY LA English DT Article DE cytochrome c reduction; superoxide; superoxide dismutase ID FREE-RADICAL FORMATION; HYDROXYL RADICALS; DISSOLVED-GASES; WATER AB Formation of superoxide anion radicals (O-2(.-)) induced by 50 kHz ultrasound in argon (Ar)-saturated aqueous solution was studied. Although EPR-spin trapping study with 5,5-dimethyl-1-pyrroline N-oxide (DMP0;100 mM) revealed the formation of DMPO-adducts of hydroxyl radicals ((OH)-O-.) and hydroperoxy radicals (HO2; acid form of O2(.-)) in O-2-saturated solution after sonication, no evidence of HO2.- was found in Ar-saturated solution. When ferricytochrome c (cytochrome c) in Ar-saturated aqueous solution was sonicated, the reduced form of cytochrome c was observed and 80% of its formation was inhibited by the addition of superoxide dismutase (SOD). Sodium formate enhanced the production of the reduced form of cytochrome c. The % inhibition by SOD for the reduction increased in the order of Xe > Ar > He in accord with the higher temperatures of the cavitation bubbles. These results indicate that the O-2(.-) is formed by directly by the sonolysis of water in the absence of O-2 when the temperature of cavitation bubble collapse is sufficiently high. C1 NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892. RP Kondo, T (reprint author), KOBE UNIV,SCH MED,DEPT RADIAT BIOPHYS,KOBE,HYOGO 650,JAPAN. NR 25 TC 13 Z9 13 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1350-4177 J9 ULTRASON SONOCHEM JI Ultrason. Sonochem. PD NOV PY 1996 VL 3 IS 3 BP S193 EP S199 DI 10.1016/S1350-4177(96)00025-9 PG 7 WC Acoustics; Chemistry, Multidisciplinary SC Acoustics; Chemistry GA WA724 UT WOS:A1996WA72400008 ER PT J AU Misik, V Riesz, P AF Misik, V Riesz, P TI Recent applications of EPR and spin trapping to sonochemical studies of organic liquids and aqueous solutions SO ULTRASONICS SONOCHEMISTRY LA English DT Article DE ultrasound; spin trapping; EPR; sonochemistry; sonodynamic therapy ID ISOTOPE-EXCHANGE-REACTIONS; THERMAL-DECOMPOSITION; WATER MIXTURES; ULTRASOUND; SONOLUMINESCENCE; CAVITATION; SONOLYSIS; MECHANISM; BUBBLES; ATX-70 AB In this paper we review some of our recent applications of the EPR spin trapping technique to sonochemical studies which include identification of radicals formed in organic liquids and aqueous mixtures of organic liquids, estimation of temperatures of sonochemical regions in mixtures of deuterated and non-deuterated solvents, and the identification of reactive radical intermediates which may play a role in synergistic cell killing by ultrasound and drugs (sonodynamic interactions). C1 NCI, RADIAT BIOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 45 TC 19 Z9 19 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1350-4177 J9 ULTRASON SONOCHEM JI Ultrason. Sonochem. PD NOV PY 1996 VL 3 IS 3 BP S173 EP S186 DI 10.1016/S1350-4177(96)00023-5 PG 14 WC Acoustics; Chemistry, Multidisciplinary SC Acoustics; Chemistry GA WA724 UT WOS:A1996WA72400006 ER PT J AU Boursnell, MEG Rutherford, E Hickling, JK Rollinson, EA Munro, AJ Rolley, N McLean, CS Borysiewicz, LK Vousden, K Inglis, SC AF Boursnell, MEG Rutherford, E Hickling, JK Rollinson, EA Munro, AJ Rolley, N McLean, CS Borysiewicz, LK Vousden, K Inglis, SC TI Construction and characterisation of a recombinant vaccinia was expressing human papillomavirus proteins for immunotherapy of cervical cancer SO VACCINE LA English DT Article DE HPV; vaccinia virus; cervical carcinoma ID TUMOR-INFILTRATING LYMPHOCYTES; NUCLEOTIDE-SEQUENCE; CARCINOMA CELLS; VIRUS-VACCINE; GENE-PRODUCT; TYPE-16; E7; ANTIGEN; E6; VECTORS AB The presence and consistent expression of the genes encoding the human papillomavirus (HPV) E6 and E7 proteins in the great majority of cervical tumours presents the opportunity for an immunotherapeutic approach for control of the disease. This report describes the construction and characterisation of a recombinant vaccinia virus designed to express modified forms of the E6 and E7 proteins from HPV16 and HPV18, the viruses most commonly associated with cervical cancer. The recombinant virus (designated TA-HPV) was based on the Wyeth vaccine strain of vaccinia, and was shown to express the desired gene products, Studies in mice indicated that the recombinant virus was less neurovirulent than the parental virus and was capable of inducing an HPV-specific CTL response. This pre-clinical evaluation has provided a basis for the initiation of human trials in cervical cancer patients. Copyright (C) 1996 Elsevier Science Ltd. C1 CANTAB PHARMACEUT RES LTD,CAMBRIDGE CB4 4GN,ENGLAND. UNIV WALES COLL MED,DEPT MED,CARDIFF CF4 4XN,S GLAM,WALES. NCI,FREDERICK,MD 21702. NR 40 TC 87 Z9 94 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD NOV PY 1996 VL 14 IS 16 BP 1485 EP 1494 DI 10.1016/S0264-410X(96)00117-X PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA WC534 UT WOS:A1996WC53400001 PM 9014288 ER PT J AU Ono, S Hatanaka, T Miyazawa, S Tsutsui, M Aoyama, T Gonzalez, FJ Satoh, T AF Ono, S Hatanaka, T Miyazawa, S Tsutsui, M Aoyama, T Gonzalez, FJ Satoh, T TI Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: Role of CYP2B6, 2C19 and the 3A subfamily SO XENOBIOTICA LA English DT Article ID S-MEPHENYTOIN HYDROXYLATION; ADULT HUMAN-LIVER; GENETIC-POLYMORPHISM; VACCINIA VIRUS; MESSENGER-RNAS; JAPANESE; IDENTIFICATION; DEBRISOQUIN; TOLBUTAMIDE; OXIDATION AB 1. We have examined the metabolism of diazepam by ten human cytochrome P450 forms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5) expressed in HepG(2) cells using a recombinant vaccinia virus system. 2. Among the P450 forms tested, diazepam was significantly demethylated by CYP2B6, 2C9, 2C19, 3A4 and 3A5, with 2C19 exhibiting the highest rate at concentrations < 0.1 mM, and hydroxylated only by the latter three enzymes, with 3A5 being the most active. The N-demethylation activity of diazepam by 2C19 at a concentration of 20 mu M was six times of that by 3A4. However, that by 2C9 was detected at only a trace level. 3. CYP2C19, 3A4 and 3A5 of the ten human P450s catalysed the 3-hydroxylation of nordiazepam, and 2B6, the 2C subfamily and the 3A subfamily catalysed the N-demethylation of temazepam. CYP3A4 exhibited the highest activity of nordiazepam 3-hydroxylation and temazepam N-demethylation. 4. Diazepam N-demethylation by human liver microsomes correlated with diazepam 3-hydroxylation, but not S-mephenytoin 4'-hydroxylation. 5. Our results suggest that in the human liver, the metabolism of diazepam to nordiazepam is mediated by CYP3A4, which has been reported as the most abundant P450 form in human liver as well as 2C19, which has been reported as a polymorphic enzyme. C1 SHINSHU UNIV,SCH MED,DEPT BIOCHEM,MATSUMOTO,NAGANO 390,JAPAN. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. CHIBA UNIV,FAC PHARMACEUT SCI,BIOCHEM PHARMACOL & BIOTOXICOL LAB,CHIBA 260,JAPAN. RP Ono, S (reprint author), AMERSHAM KK,CENT LAB RES & DEV,2802-1 HIRATSUKA,SHIROI,CHIBA 27014,JAPAN. NR 38 TC 95 Z9 98 U1 0 U2 6 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD NOV PY 1996 VL 26 IS 11 BP 1155 EP 1166 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VU396 UT WOS:A1996VU39600005 PM 8948091 ER PT J AU Meldahl, AC Nithipatikom, K Lech, JJ AF Meldahl, AC Nithipatikom, K Lech, JJ TI Metabolism of several C-14-nonylphenol isomers by rainbow trout (Oncorhynchus mykiss): In vivo and in vitro microsomal metabolites SO XENOBIOTICA LA English DT Article ID ALKYLPHENOLS AB 1. Gas chromatographic/mass spectroscopic analysis of a mixture of C-14-nonylphenols produced by alkylation of C-14-RUL-phenol with n-1-nonene indicated that the radiosynthesis produced three major isomers, 2-(4-hydroxyphenyl)-nonane, 3-(4-hydroxyphenyl)-nonane and 4-(4-hydroxyphenyl)-nonane. 2. Bile from rainbow trout exposed to a mixture of these isomers of C-14-nonylphenol was found to contain the glucuronic acid conjugates of three radiolabelled metabolites, which were more polar than their parent compounds. 3. Incubation of trout hepatic microsomes with NADPH and the C-14-nonylphenol isomers resulted in the production of three radiolabelled metabolites whose mobility on silica thin layer chromatography were similar to the deglucuronidated metabolites recovered from trout bile. 4. Metabolism of the C-14-nonylphenol isomers by trout hepatic microsomes was inhibited by omission of NADPH from the incubations as well as by addition of a P450 inhibitor, piperonyl butoxide to the incubations. 5. Analysis of the metabolites extracted from the microsomal incubations by gas chromatography/mass spectroscopy indicated that the parent isomers had been hydroxylated in the C-8 position on the nonane chain to give 2-(4-hydroxyphenyl)-8-hydroxynonane, 3-(4-hydroxyphenyl)-8-hydroxynonane and 4-(4-hydroxyphenyl)-8-hydroxynonane. C1 MED COLL WISCONSIN,DEPT PHARMACOL & TOXICOL,MILWAUKEE,WI 53226. NIEHS,FRESHWATER & MARINE BIOMED CORE CTR,MILWAUKEE,WI 53204. NR 24 TC 36 Z9 37 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD NOV PY 1996 VL 26 IS 11 BP 1167 EP 1180 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VU396 UT WOS:A1996VU39600006 PM 8948092 ER PT J AU Ogawa, Y Lei, PS Kovac, P AF Ogawa, Y Lei, PS Kovac, P TI Synthesis of eight glycosides of hexasaccharide fragments representing the terminus of the O-polysaccharide of Vibrio cholerae O:1, serotype Inaba and Ogawa, bearing aglycons suitable for linking to proteins SO CARBOHYDRATE RESEARCH LA English DT Article DE Vibrio cholerae O-antigen; hexasaccharide; neoglycoconjugate; 4-O-benzyl-3-deoxy-L-glycerotetronic acid ID METHYL ALPHA-GLYCOSIDE; MONOSACCHARIDE REPEATING UNIT; BRUCELLA-A-ANTIGEN; 2-(TRIMETHYLSILYL)ETHYL GLYCOSIDES; CRYSTAL-STRUCTURE; BLOCK SYNTHESIS; O/1; DETERMINANTS; LIPOPOLYSACCHARIDE; PENTASACCHARIDE AB The title substances were prepared from intermediate, fully acetylated alpha-trimethylsilylethyl (SE) glycosides. The latter were assembled in a blockwise manner, using as the glycosyl donor the alpha-glycosyl chloride of a disaccharide bearing two 4-azido-4-deoxy functions. Next, the azido groups in the assembled hexasaccharides were converted to the corresponding amines, and these were acylated with 4-O-benzyl-3-deoxy-L-glycero-tetronic acid in the presence of a water-soluble carbodiimide. The SE glycosides were then transformed to glycosyl imidates, and these were coupled with methyl 6-hydroxyhexanoate or methyl 2-(2-hydroxyethylthio)propionate. The aglycons in the glycosides thus obtained were then converted to the corresponding carboxylic acids or acyl hydrazides. Such compounds are suitable for linking to proteins to obtain neoglycoproteins. C1 NIDDK,NATL INST HLTH,BETHESDA,MD 20892. NR 24 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD OCT 31 PY 1996 VL 293 IS 2 BP 173 EP 194 DI 10.1016/0008-6215(96)00202-9 PG 22 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA VR359 UT WOS:A1996VR35900002 PM 8938375 ER PT J AU Kostenis, E Cid, HMB Holzgrabe, U Mohr, K AF Kostenis, E Cid, HMB Holzgrabe, U Mohr, K TI Evidence for a multiple binding mode of bispyridinium-type allosteric modulators of muscarinic receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE muscarinic receptor; allosteric modulation; structure-activity relationship; heart porcine ID AMMONIUM COMPOUND W84; ACETYLCHOLINE-RECEPTOR; DOPAMINE-RECEPTOR; ANTAGONISTS; SITE AB The ligand binding properties of muscarinic receptors can be modulated by allosterically acting compounds. Here, a set of novel bispyridinium-type compounds was investigated which were designed to study structure-activity relationships and to provide more insight into the molecular events underlying the allosteric delay of the dissociation of [H-3]N-methylscopolamine from muscarinic M(2) receptors in porcine cardiac membranes. The parent compound, a non-substituted bispyridinium oxime, displayed a weak allosteric potency and was unable to prevent radioligand dissociation at maximum concentrations. Introduction of either a phthalimidomethyl-moiety or a dichlorobenzyl-moiety at one end of the parent compound led to a considerable increase of the allosteric activity with regard to both the potency and the maximum effect. In these unilaterally ring-substituted bispyridiniums, homologous contralateral non-aromatic modifications were accompanied by divergent potency shifts depending on whether the unilateral ring was phthalimidomethyl or dichlorobenzyl. The findings point to a multiple binding mode of bispyridinium compounds at M(2) receptors in the [H-3]N-methylscopolamine-occupied state, i.e., different orientations of the compounds at the allosteric binding area or even an interaction with distinct allosteric recognition sites. C1 UNIV BONN,INST PHARM,D-53121 BONN,GERMANY. NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV BONN,INST PHARM,D-53115 BONN,GERMANY. OI Holzgrabe, Ulrike/0000-0002-0364-7278 NR 31 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 31 PY 1996 VL 314 IS 3 BP 385 EP 392 DI 10.1016/S0014-2999(96)00568-7 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VV169 UT WOS:A1996VV16900020 PM 8957263 ER PT J AU Taouis, M Taylor, SI Reitman, M AF Taouis, M Taylor, SI Reitman, M TI Cloning of the chicken insulin receptor substrate 1 gene SO GENE LA English DT Article DE signal transduction; tyrosine kinase substrate; SH2 binding; phosphotyrosine; pleckstrin homology ID TYROSINE KINASE-ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; STRUCTURAL BASIS; ALPHA-SUBUNIT; IRS-1 GENE; PROTEIN; DOMAIN; CDNA; EXPRESSION; SEQUENCE AB The action of insulin, IGF-1, and IGF-2 is mediated via two receptor tyrosine kinases, the insulin and IGF-1 receptors. Upon ligand binding, these receptors become active kinases, undergoing autophosphorylation and phosphorylating cellular substrates, including insulin receptor substrate-1 (IRS-1). IRS-1 acts as a docking protein and mediates multiple interactions among other proteins, resulting in transduction of the metabolic and mitogenic signals. The IRS-1 gene has been cloned from four species (human, rat, mouse, and frog). In the present study, the chicken IRS-1 gene was cloned. Chickens, as is true of birds in general, have a higher fasting and fed blood glucose than do mammals. Chicken IRS-1 DNA sequence encodes a 1240 amino acid protein. The most conserved regions were the IRS homology-2 (IH-2), the pleckstrin homology, and the she and IRS-1 NPXY-binding (SAIN) domains. Twelve of the cIRS-1 tyrosine residues are in sequence motifs that, when phosphorylated, could interact with proteins containing SH2 domains. All twelve of these motifs were conserved. IRS-1 mRNA is expressed during embryogenesis in chicken and persists after hatching. In LMH cells, derived from a chicken hepatoma, two bands were tyrosine phosphorylated in an insulin-dependent manner: IRS-1 (similar to 180 kDa) and the insulin receptor beta subunit (similar to 95 kDa). Chicken IRS-1 is structurally and functionally similar to its human homolog, despite the difference in blood glucose levels and the evolutionary distance between birds and mammals. C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD. RP Taouis, M (reprint author), INRA,RECH AVICOLES STN,F-37380 NOUZILLY,FRANCE. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 27 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 31 PY 1996 VL 178 IS 1-2 BP 51 EP 55 DI 10.1016/0378-1119(96)00333-2 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VT126 UT WOS:A1996VT12600009 PM 8921891 ER PT J AU Lee, BJ Park, SI Park, JM Chittum, HS Hatfield, DL AF Lee, BJ Park, SI Park, JM Chittum, HS Hatfield, DL TI Molecular biology of selenium and its role in human health SO MOLECULES AND CELLS LA English DT Review ID SELENOCYSTEYL-TRANSFER RNA; SERINE TRANSFER-RNA; TRANSFER RNA(SER)SEC GENE; PHOSPHOSERYL-TRANSFER RNA; GLUTATHIONE-PEROXIDASE; ESCHERICHIA-COLI; POLYMERASE-III; TRANSFER RNASEC; FUNCTIONAL-CHARACTERIZATION; SELENOPHOSPHATE SYNTHETASE C1 NCI,LAB DIRECTOR,DIV BASIC SCI,NIH,BETHESDA,MD 20892. SEOUL NATL UNIV,INST MOL BIOL & GENET,GENET MOL LAB,SEOUL 151742,SOUTH KOREA. NR 134 TC 32 Z9 34 U1 2 U2 3 PU KOREAN SOC MOLECULAR BIOLOGY PI SEOUL PA KOREA SCI TECHNOLOGY CENTER, ROOM 815, 635-4 YEOGSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD OCT 31 PY 1996 VL 6 IS 5 BP 509 EP 520 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VQ070 UT WOS:A1996VQ07000001 ER PT J AU Abbas, AK Murphy, KM Sher, A AF Abbas, AK Murphy, KM Sher, A TI Functional diversity of helper T lymphocytes SO NATURE LA English DT Review ID CELL-MEDIATED-IMMUNITY; STIMULATORY FACTOR-I; INTERFERON-GAMMA; PHENOTYPE DEVELOPMENT; AUTOIMMUNE-DISEASES; CYTOKINE PROFILES; LEISHMANIA-MAJOR; INTERLEUKIN-12; ANTIGEN; MICE AB The existence of subsets of CD4(+) helper T lymphocytes that differ in their cytokine secretion patterns and effector functions provides a framework for understanding the heterogeneity of normal and pathological immune responses. Defining the cellular and molecular mechanisms of helper-T-cell differentiation should lead to rational strategies for manipulating immune responses for prophylaxis and therapy. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. NIAID,NIH,PARASIT DIS LAB,IMMUNOBIOL SECT,BETHESDA,MD 20892. RP Abbas, AK (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,IMMUNOL RES DIV,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 94 TC 3304 Z9 3430 U1 23 U2 160 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 31 PY 1996 VL 383 IS 6603 BP 787 EP 793 DI 10.1038/383787a0 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VQ144 UT WOS:A1996VQ14400053 PM 8893001 ER PT J AU Kovacs, JA Vogel, S Albert, JM Falloon, J Davey, RT Walker, RE Polis, MA Spooner, K Metcalf, JA Baseler, M Fyfe, G Lane, HC AF Kovacs, JA Vogel, S Albert, JM Falloon, J Davey, RT Walker, RE Polis, MA Spooner, K Metcalf, JA Baseler, M Fyfe, G Lane, HC TI Controlled trial of interleukin-2 infusions in patients infected with the human immunodeficiency virus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TYPE-1 INFECTION; HIV-1 PROTEASE; RITONAVIR; INHIBITOR; EFFICACY; PLASMA AB Background Interleukin-2 is a cytokine that regulates the proliferation and differentiation of lymphocytes. In preliminary studies, intermittent infusions of interleukin-2 led to increases in CD4 counts in patients with human immunodeficiency virus (HIV) infection and more than 200 CD4 cells per cubic millimeter. We conducted a controlled study to evaluate the long-term effects of such therapy on both CD4 counts and the viral burden. Methods Sixty HIV-infected patients with base-line CD4 counts above 200 cells per cubic millimeter were randomly assigned to receive either interleukin-2 plus antiretroviral therapy (31 patients, 1 of whom was lost to follow-up) or antiretroviral therapy alone (29 patients). Interleukin-2 was administered every two months for six cycles of five days each, starting at a dosage of 18 million IU per day. Safety and immunologic and virologic measures were monitored monthly until four months after the last treatment cycle. Results In patients treated with interleukin-2, the mean (+/-SE) CD4 count increased from 428+/-25 cells per cubic millimeter at base line to 916+/-128 at month 12, whereas in the control group, the mean CD4 count decreased from 406+/-29 cells per cubic millimeter to 349+/-41 (P<0.001). There were no significant differences between the groups in serial measurements of the plasma HIV RNA or p24 antigen concentration during the 12 months of treatment. Constitutional symptoms (fever, malaise, and fatigue) and asymptomatic hyperbilirubinemia were the chief dose-limiting toxic effects of interleukin-2 therapy. Conclusions In patients with HIV infection and base-line CD4 counts above 200 cells per cubic millimeter, intermittent infusions of interleukin-2 produced substantial and sustained increases in CD4 counts with no associated increase in plasma HIV RNA levels. (C) 1996, Massachusetts Medical Society. C1 NIAID,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NIAID,DIV AIDS,BETHESDA,MD 20892. SCI APPLICAT INT CORP,FREDERICK,MD. CHIRON CORP,EMERYVILLE,CA 94608. OI Polis, Michael/0000-0002-9151-2268 NR 24 TC 360 Z9 366 U1 0 U2 2 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 OCT 31 PY 1996 VL 335 IS 18 BP 1350 EP 1356 DI 10.1056/NEJM199610313351803 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VP484 UT WOS:A1996VP48400003 PM 8857018 ER PT J AU Guo, CX Bhandaru, S Fuchs, PL AF Guo, CX Bhandaru, S Fuchs, PL TI Cephalostatin syntheses. 10. An efficient protocol for the synthesis of unsymmetrical pyrazines. Total synthesis of dihydrocephalostatin SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID KONDRATEVA PYRIDINE SYNTHESIS; BIS-STEROIDAL PYRAZINES; TETRAMETHYLGUANIDINIUM AZIDE; CEPHALOSTATIN-1; ALKALOIDS; UNIT C1 PURDUE UNIV, DEPT CHEM, W LAFAYETTE, IN 47907 USA. NCI, LAB DRUG DISCOVERY RES & DEV, FREDERICK, MD 21702 USA. NR 18 TC 41 Z9 42 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 30 PY 1996 VL 118 IS 43 BP 10672 EP 10673 DI 10.1021/ja962646q PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VQ089 UT WOS:A1996VQ08900051 ER PT J AU Martinez, A Treston, AM AF Martinez, A Treston, AM TI Where does amidation take place? SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE amidation; peptide hormones; endocrine regulation ID PEPTIDE ALPHA-AMIDATION; MESSENGER-RNA; ENZYMES PAM; LUNG; EXPRESSION; PITUITARY; LOCALIZATION; TUMORS; GROWTH; AMIDE C1 NCI,BIOMAKERS & PREVENT RES BRANCH,DIV CLIN SCI,NIH,ROCKVILLE,MD 20850. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 33 TC 22 Z9 23 U1 2 U2 6 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 OCT 30 PY 1996 VL 123 IS 2 BP 113 EP 117 DI 10.1016/S0303-7207(96)03903-2 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA VV445 UT WOS:A1996VV44500001 PM 8961247 ER PT J AU Faraggi, D Simon, R AF Faraggi, D Simon, R TI A simulation study of cross-validation for selecting an optimal cutpoint in univariate survival analysis SO STATISTICS IN MEDICINE LA English DT Article ID BREAST-CANCER PATIENTS; REGRESSION-MODELS; PROGNOSTIC FACTORS; STATISTICS; SPLINES AB Continuous measurements are often dichotomized for classification of subjects. This paper evaluates two procedures for determining a best cutpoint for a continuous prognostic factor with right censored outcome data. One procedure selects the cutpoint that minimizes the significance level of a logrank test with comparison of the two groups defined by the cutpoint. This procedure adjusts the significance level for maximal selection. The other procedure uses a cross-validation approach. The latter easily extends to accommodate multiple other prognostic factors. We compare the methods in terms of statistical power and bias in estimation of the true relative risk associated with the prognostic factor. Both procedures produce approximately the comet type I error rate. Use of a maximally selected cutpoint without adjustment of the significance level, however, results in a substantially elevated type I error rate. The cross-validation procedure unbiasedly estimated the relative risk under the null hypothesis while the procedure based on the maximally selected test resulted in an upward bias. When the relative risk for the two groups defined by the covariate and true changepoint was small, the cross-validation procedure provided greater power than the maximally selected test. The cross-validation based estimate of relative risk was unbiased while the procedure based on the maximally selected test produced a biased estimate, As the true relative risk increased, the power of the maximally selected test was about 10 per cent greater than the power obtained using cross-validation. The maximally selected test overestimated the relative risk by about 10 per cent. The cross-validation procedure produced at most 5 per cent underestimation of the true relative risk. Finally, we report the effect of dichotomizing a continuous non-linear relationship between covariate and risk. We compare using a linear proportional hazard model to using models based on optimally selected cutpoints. Our simulation study indicates that we can have a substantial loss of statistical power when we use cutpoint models in cases where there is a continuous relationship between covariate and risk. RP Faraggi, D (reprint author), NCI,BIOMETR RES BRANCH,6130 EXECUT BLVD,ROOM 739,ROCKVILLE,MD 20852, USA. NR 18 TC 58 Z9 59 U1 0 U2 3 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 OCT 30 PY 1996 VL 15 IS 20 BP 2203 EP 2213 DI 10.1002/(SICI)1097-0258(19961030)15:20<2203::AID-SIM357>3.3.CO;2-7 PG 11 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 VL323 UT WOS:A1996VL32300008 PM 8910964 ER PT J AU Mazumder, A Neamati, N Ojwang, JO Sunder, S Rando, RF Pommier, Y AF Mazumder, A Neamati, N Ojwang, JO Sunder, S Rando, RF Pommier, Y TI Inhibition of the human immunodeficiency virus type I integrase by guanosine quartet structures SO BIOCHEMISTRY LA English DT Article ID OXYTRICHA TELOMERIC DNA; HIV-1 INTEGRASE; VIRAL-DNA; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; POTENT INHIBITOR; STABLE COMPLEX; GENOMIC RNA; PROTEIN; BINDING AB An oligonucleotide (T30177) composed entirely of deoxyguanosine and thymidine has previously been shown to fold upon itself in the presence of potassium into a highly stable four-stranded DNA structure containing two stacked deoxyguanosine quarters (G4s). T30177 also protects host cells from the cytopathic effects of human immunodeficiency virus type 1 (HIV-1). We report that this G4 oligonucleotide is the most potent inhibitor of HIV-1 integrase identified to date, with IC50 values in the nanomolar range. Both the number of quarters formed and the sequence of the loops between the quartets are important for optimal activity. T30177 binds to HIV-1 integrase without being processed and blocks the binding of the normal viral DNA substrate to the enzyme. The normal DNA substrate was not able to compete off T30177 binding to HIV-1 integrase, indicating a tight binding of G4s to the enzyme. Experiments with truncated HIV-1 integrases indicate that the N-terminal region containing a putative zinc finger is required for inhibition by T30177 and that T30177 binds better to full-length or deletion mutant integrases containing the zinc finger region than to a deletion mutant consisting of only the central catalytic domain. The N-terminal region of integrase alone is able to bind efficiently to T30177, but not the linear viral DNA substrate, in the presence of zinc. Hence, G4s represent the first class of compounds that inhibit HIV-1 integrase by interacting with the enzyme N-terminal domain, The greater inhibitory potency of T30177 in buffer containing magnesium versus manganese suggests that divalent metal ion coordination along the phosphodiester backbone may play a role in the inhibitory activity. T30177 inhibited HIV-2 integrase with similar potency as HIV-1 but inhibited feline and simian immunodeficiency virus integrases at higher concentrations, suggesting selectivity can be achieved. We propose that novel AIDS therapies could be based upon guanosine quartets as inhibitors of HIV-I integrase. C1 NCI,MOL PHARMACOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. ARONEX PHARMACEUT INC,THE WOODLANDS,TX 77381. NR 58 TC 117 Z9 118 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 29 PY 1996 VL 35 IS 43 BP 13762 EP 13771 DI 10.1021/bi960541u PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP990 UT WOS:A1996VP99000008 PM 8901518 ER PT J AU Weinberger, DR Berman, KF AF Weinberger, DR Berman, KF TI Prefrontal function in schizophrenia: Confounds and controversies SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; MONOZYGOTIC TWINS DISCORDANT; NEUROLEPTIC-NAIVE PATIENTS; CARD SORTING TEST; GLUCOSE-METABOLISM; COMPUTED-TOMOGRAPHY; TECHNETIUM-99M-HMPAO SPECT; PHYSIOLOGICAL DYSFUNCTION; HUNTINGTONS-DISEASE AB A wealth of clinical data indirectly implicate dysfunction of frontal cortex in schizophrenia, including negative symptoms, the pattern of neuropsychological deficits, and abnormal eye movements. Neuroimaging studies have provided direct evidence of frontal, particularly prefrontal, malfunction, but the results have been inconsistent and controversial. The burning question is whether prefrontal hypofunction is a pathophysiological characteristic of schizophrenia per se or an artifact of the imaging protocol. In studies of patients at rest, 'hypofrontality' has been an inconsistent finding, probably because resting is physiologically and psychologically variable. Cognitive activation paradigms, especially during working memory tasks, have been reliable in showing prefrontal hypofunction in patients, but these results have been challenged as artifacts of poor performance. Performance differences have been addressed by studying patients and controls matched either for poor performance or for normal performance. The former approach, which has the potential of elucidating the specificity of physiological mechanisms associated with poor performance, has shown that prefrontal activity in patients with schizophrenia differs quantitatively and qualitatively from that of normals and of other patient populations who perform at a comparable level. The latter approach, which tends not to find prefrontal differences between patients and controls, may be selecting out important aspects of the disease by focusing on unaffected neural functions. While there are pitfalls to each approach and no single study can address all the potential phenomenological confounds, overall, the functional neuroimaging database in patients with schizophrenia suggests that prefrontal cognitive deficits are because of prefrontal pathophysiology and not the inverse. RP Weinberger, DR (reprint author), NIMH, NEUROSCI CTR ST ELIZABETHS, CLIN BRAIN DISORDERS BRANCH, 2700 MARTIN LUTHER KING JR AVE, SE, WASHINGTON, DC 20032 USA. NR 73 TC 275 Z9 280 U1 2 U2 8 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD OCT 29 PY 1996 VL 351 IS 1346 BP 1495 EP 1503 DI 10.1098/rstb.1996.0135 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA VR540 UT WOS:A1996VR54000023 PM 8941961 ER PT J AU Weinberger, D Robbins, TW Taylor, JG Morris, RG AF Weinberger, D Robbins, TW Taylor, JG Morris, RG TI Dissociating executive functions of the prefrontal cortex - Discussion SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Editorial Material C1 UNIV LONDON KINGS COLL,DEPT MATH,LONDON WC2R 2LS,ENGLAND. UNIV LONDON,INST PSYCHIAT,LONDON SE5 8AF,ENGLAND. RP Weinberger, D (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,2700 MARTIN LUTHER KING JR AVE,SE,WASHINGTON,DC 20032, USA. NR 0 TC 8 Z9 8 U1 0 U2 3 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD OCT 29 PY 1996 VL 351 IS 1346 BP 1470 EP 1471 PG 2 WC Biology SC Life Sciences & Biomedicine - Other Topics GA VR540 UT WOS:A1996VR54000017 ER PT J AU Weinberger, D Passingham, RE Petrides, M AF Weinberger, D Passingham, RE Petrides, M TI Attention to action - Discussion SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Editorial Material C1 MCGILL UNIV,MONTREAL NEUROL INST,MONTREAL,PQ H3A 2B4,CANADA. RP Weinberger, D (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,2700 MARTIN LUTHER KING JR AVE,SE,WASHINGTON,DC 20032, USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD OCT 29 PY 1996 VL 351 IS 1346 BP 1479 EP 1479 PG 1 WC Biology SC Life Sciences & Biomedicine - Other Topics GA VR540 UT WOS:A1996VR54000019 ER PT J AU Lawrence, A Frith, C Weinberger, D AF Lawrence, A Frith, C Weinberger, D TI The role of the prefrontal cortex in self-consciousness: The case of auditory hallucinations - Discussion SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Editorial Material C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP Lawrence, A (reprint author), UNIV CAMBRIDGE,DEPT EXPT PSYCHOL,DOWNING ST,CAMBRIDGE CB2 3EB,ENGLAND. RI Frith, Chris/A-2171-2009 OI Frith, Chris/0000-0002-8665-0690 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD OCT 29 PY 1996 VL 351 IS 1346 BP 1512 EP 1512 PG 1 WC Biology SC Life Sciences & Biomedicine - Other Topics GA VR540 UT WOS:A1996VR54000026 ER PT J AU Robbins, TW Weinberger, DR Frith, CD Weiskrantz, L AF Robbins, TW Weinberger, DR Frith, CD Weiskrantz, L TI Prefrontal dysfunction in neuropsychiatric disorders - General discussion SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Editorial Material C1 NIMH,NEUROSCI CTR ST ELIZABETHS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. INST NEUROL,WELLCOME DEPT COGNIT NEUROL,LONDON WC1N 3BG,ENGLAND. UNIV OXFORD,DEPT EXPT PSYCHOL,OXFORD OX1 3UD,ENGLAND. RP Robbins, TW (reprint author), UNIV CAMBRIDGE,DEPT EXPT PSYCHOL,DOWNING ST,CAMBRIDGE CB2 3EB,ENGLAND. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON, ENGLAND SW1Y 5AG SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD OCT 29 PY 1996 VL 351 IS 1346 BP 1513 EP 1514 DI 10.1098/rstb.1996.0137 PG 2 WC Biology SC Life Sciences & Biomedicine - Other Topics GA VR540 UT WOS:A1996VR54000027 ER PT J AU Sidorova, NY Rau, DC AF Sidorova, NY Rau, DC TI Differences in water release for the binding of EcoRI to specific and nonspecific DNA sequences SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CRYSTAL-STRUCTURE; LAC REPRESSOR; PROTEIN; RESOLUTION; COMPLEX; COMPETITION; HYDRATION; CHANNEL AB The free energy difference between complexes of the restriction nuclease EcoRI with nonspecific DNA and with the enzyme's recognition sequence is linearly dependent on the water chemical potential of the solution, set using several very different solutes, ranging from glycine and glycerol to triethylene glycol and sucrose. This osmotic dependence indicates that the nonspecific complex sequesters some 110 eaters more than the specific complex with the recognition sequence. The insensitivity of the difference in number of waters released to the solute identity further indicates that this water is sequestered in a space that is sterically inaccessible to solutes, most likely at the protein-DNA interface of the nonspecific complex. Calculations based on the structure of the specific complex suggest that the apposing DNA and protein surfaces in the nonspecific complex retain approximately a full hydration layer of water. C1 NIDDKD,OFF DIRECTOR,NIH,BETHESDA,MD 20892. RP Sidorova, NY (reprint author), NIDDKD,STRUCT BIOL LAB,DIV COMP RES & TECHNOL,NIH,BLDG 5,ROOM 405,BETHESDA,MD 20892, USA. NR 31 TC 89 Z9 93 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 OCT 29 PY 1996 VL 93 IS 22 BP 12272 EP 12277 DI 10.1073/pnas.93.22.12272 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VP937 UT WOS:A1996VP93700041 PM 8901570 ER PT J AU Ozcan, S Dover, J Rosenwald, AG Wolfl, S Johnston, M AF Ozcan, S Dover, J Rosenwald, AG Wolfl, S Johnston, M TI Two glucose transporters in Saccharomyces cerevisiae are glucose sensors that generate a signal for induction of gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE yeast; glucose induction; glucose signaling; HXT; SNF3 ID REGULATORY ELEMENTS; HXT GENES; SNF3 GENE; SEQUENCE; PROTEIN; PHOSPHORYLATION; TRANSFORMATION AB Glucose is the preferred carbon source for most eukaryotic cells and has profound effects on many cellular functions, How cells sense glucose and transduce a signal into the cell is a fundamental, unanswered question, Here we describe evidence that two unusual glucose transporters in the yeast Saccharomyces cerevisiae serve as glucose sensors that generate an intracellular glucose signal. The Snf3p high-affinity glucose transporter appears to function as a low glucose sensor, since it is required for induction of expression of several hexose transporter (HXT) genes, encoding glucose transporters, by low levels of glucose, We have identified another apparent glucose transporter, Rgt2p, that is strikingly similar to Snf3p and is required for maximal induction of gene expression in response to high levels of glucose. This suggests that Rgt2p is a high glucose-sensing counterpart to Snf3p, We identified a dominant mutation in RGT2 that causes constitutive expression of several HXT genes, even in the absence of the inducer glucose, This same mutation introduced into SNF3 also causes glucose-independent expression of HXT genes. Thus, the Rgt2p and Snf3p glucose transporters appear to act as glucose receptors that generate an intracellular glucose signal, suggesting that glucose signaling in yeast is a receptor-mediated process. C1 WASHINGTON UNIV,SCH MED,DEPT GENET,ST LOUIS,MO 63110. NCI,NIH,US DEPT HHS,BETHESDA,MD 20892. HANS KNOLL INST,D-07745 JENA,GERMANY. OI Johnston, Mark/0000-0002-4932-7229 FU NIGMS NIH HHS [GM32546, R01 GM032540] NR 29 TC 277 Z9 282 U1 0 U2 13 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 OCT 29 PY 1996 VL 93 IS 22 BP 12428 EP 12432 DI 10.1073/pnas.93.22.12428 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VP937 UT WOS:A1996VP93700069 PM 8901598 ER PT J AU Mingari, MC Schiavetti, F Ponte, M Vitale, C Maggi, E Romagnani, S Demarest, J Pantaleo, G Fauci, AS Moretta, L AF Mingari, MC Schiavetti, F Ponte, M Vitale, C Maggi, E Romagnani, S Demarest, J Pantaleo, G Fauci, AS Moretta, L TI Human CD8(+) T lymphocyte subsets that express HLA class I-specific inhibitory receptors represent oligoclonally or monoclonally expanded cell populations SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE natural killer cell receptors; class I major histocompatibility complex; cytolytic T lymphocytes; monoclonal T cell expansions ID VARIABLE REGION GENES; NATURAL-KILLER-CELLS; LYMPHOKINE PRODUCTION; NK CELLS; MOLECULES; P58; LYSIS; RECOGNITION; ANTIBODIES; ACTIVATION AB A small percentage of human T lymphocytes, predominantly CD8(+) T cells, express receptors for HLA class I molecules of natural killer type (NK-R) that are inhibitory for T-cell antigen receptor (TCR)-mediated functions, In the present study, it is demonstrated that the various NK-R molecules typically expressed by NK cells are also expressed on periheral blood T lymphocytes. These CD3(+) NK-R(+) cells have a cell surface phenotype typical of memory cells as indicated by the expression of CD45RO and CD29 and by the lack of CD28 and CD45RA, Furthermore, by the combined use of anti-TCR V beta-specific antibodies and a semiquantitative polymerase chain reaction assay, the TCR repertoire in this CD3(+) NK-R(+) cell subset was found to be skewed; in fact, one or two Vp families were largely represented, and most of the other Vps were barely detected, In addition, analysis of recombinant clones of the Largely represented V beta families demonstrated that these V beta s were oligoclonally or monoclonally expanded. C1 UNIV GENOA,IST PATOL GEN,GENOA,ITALY. IST SCI STUDIO & CURA TUMORI,GENOA,ITALY. CTR BIOTECNOL AVANZATE,GENOA,ITALY. UNIV FLORENCE,IST CLIN MED 3,FLORENCE,ITALY. NIH,BETHESDA,MD 20892. RP Mingari, MC (reprint author), UNIV GENOA,DIPARTIMENTO ONCOL CLIN & SPERIMENTALE,GENOA,ITALY. RI Vitale, Chiara/J-7226-2016; Pantaleo, Giuseppe/K-6163-2016 OI Vitale, Chiara/0000-0002-0525-0055; NR 31 TC 218 Z9 221 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 OCT 29 PY 1996 VL 93 IS 22 BP 12433 EP 12438 DI 10.1073/pnas.93.22.12433 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VP937 UT WOS:A1996VP93700070 PM 8901599 ER PT J AU Curtis, SW Washburn, T Sewall, C DiAugustine, R Lindzey, J Couse, JF Korach, KS AF Curtis, SW Washburn, T Sewall, C DiAugustine, R Lindzey, J Couse, JF Korach, KS TI Physicological coupling of growth factor and steroid receptor signaling pathways: Estrogen receptor knockout mice lack estrogen-like response to epidermal growth factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cross-talk; ligand independent; transgenic; uterotropic ID TRANSCRIPTIONAL ACTIVATION FUNCTIONS; LIGAND-DEPENDENT PHOSPHORYLATION; MESSENGER RIBONUCLEIC-ACID; PROGESTERONE-RECEPTOR; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE; TRANSACTIVATION DOMAINS; INDEPENDENT ACTIVATION; PROTEIN-KINASE; UTERINE CELLS; FACTOR-I AB Past studies have shown that epidermal growth factor (EGF) is able to mimic the uterotropic effects of estrogen in the rodent, These studies have suggested a ''cross-talk'' model in which EGF receptor (EGF-R) signaling results in activation of nuclear estrogen receptor (ER) and its target genes in an estrogen-independent manner. Furthermore, in vitro studies have indicated the requirement for ER in this mechanism. To verify the requirement for ER in an in who system, EGF effects were studied in the uteri of ER knockout (ERKO) mice, which lack functional ER The EGF-R levels, autophosphorylation, and c-fos induction were observed at equivalent levels in both genotypes indicating that removal of ER did not disrupt the EGF responses. Induction of DNA synthesis and the progesterone receptor gene in the uterus were measured after EGF treatment of both ERKO and wild-type animals, Wild-type mice showed increases of 4.3-fold in DNA synthesis, as well as an increase in PR mRNA after EGF treatment, However, these responses were absent in ERKO mice, confirming that the estrogen-like effects of EGF in the mouse uterus do indeed require the ER These data conclusively demonstrate the coupling of EGF and ER signaling pathways in the rodent reproductive tract. C1 NIEHS,BIOCHEM RISK ANAL LAB,NIH,RES TRIANGLE PK,NC 27709. NIEHS,ENVIRONM TOXICOL PROGRAM,NIH,RES TRIANGLE PK,NC 27709. RP Curtis, SW (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 212 Z9 215 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 OCT 29 PY 1996 VL 93 IS 22 BP 12626 EP 12630 DI 10.1073/pnas.93.22.12626 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VP937 UT WOS:A1996VP93700104 PM 8901633 ER PT J AU Green, CB Besharse, JC Zatz, M AF Green, CB Besharse, JC Zatz, M TI Tryptophan hydroxylase mRNA levels are regulated by the circadian clock, temperature, and cAMP in chick pineal cells SO BRAIN RESEARCH LA English DT Article DE melatonin; forskolin; circadian rhythm ID SEROTONIN N-ACETYLTRANSFERASE; XENOPUS-LAEVIS RETINA; MELATONIN RHYTHM; PHOTOENDOCRINE TRANSDUCTION; CYCLIC-AMP; LIGHT; EXPRESSION; GLAND; PHOTORECEPTORS; OSCILLATOR AB Chick pineal cells contain a circadian oscillator that drives rhythmic synthesis and secretion of melatonin even in dispersed cell culture. Here, we demonstrate that the mRNA encoding tryptophan hydroxylase (TPH), the first enzyme in the melatonin synthetic pathway, is expressed rhythmically under the control of the circadian clock. TPH message levels doubled between early day and early night, under both cyclic lighting and constant lighting conditions. The amplitude of the TPH mRNA rhythm was increased to 4-fold by culturing the cells at 43.3 degrees C for 48 h instead of 36.7 degrees C. Addition of forskolin to the cultures in early day produced a modest increase (50%) in TPH message levels but had no effect at other times. Because TPH mRNA levels are regulated by the endogenous pineal circadian clock, this provides a valuable system in which to study the molecular mechanism of clock control of gene expression. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP Green, CB (reprint author), UNIV KANSAS,MED CTR,DEPT ANAT & CELL BIOL,3901 RAINBOW BLVD,KANSAS CITY,KS 66160, USA. FU NEI NIH HHS [EY02414, R01 EY002414, EY06489] NR 30 TC 21 Z9 23 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 OCT 28 PY 1996 VL 738 IS 1 BP 1 EP 7 DI 10.1016/0006-8993(96)00743-3 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VT492 UT WOS:A1996VT49200001 PM 8949920 ER PT J AU Nomizu, M Song, SY Kuratomi, Y Tanaka, M Kim, WH Kleinman, HK Yamada, Y AF Nomizu, M Song, SY Kuratomi, Y Tanaka, M Kim, WH Kleinman, HK Yamada, Y TI Active peptides from the carboxyl-terminal globular domain of laminin alpha 2 and Drosophila alpha chains SO FEBS LETTERS LA English DT Article DE laminin; synthetic peptide; cell attachment; basement membrane; integrin ID CELL-ADHESION; A-CHAIN; SYNTHETIC PEPTIDE; HEPARIN-BINDING; BASEMENT-MEMBRANES; IKVAV SEQUENCE; IDENTIFICATION; RECEPTOR; GLYCOPROTEIN; FIBRONECTIN AB The laminin alpha 1 chain carboxyl-terminal globular domain (G domain) contains multiple biological activities. Recently, we identified five cell binding sequences from the G domain by screening with overlapping 12-mer peptides encompassing the entire domain. The structures of these five sequences in the alpha 1 chain are conserved in the corresponding regions of the different laminin alpha chains, Here we characterize the adhesion activities of the corresponding peptide segments from both the mouse laminin alpha 2 chain and Drosophila laminin alpha chain using peptide-coated plastic plates and peptide-conjugated Sepharose beads, Using several cell lines, the laminin alpha 2 chain peptides showed cell attachment and/or spreading activities with cell type specificities, Cell spreading on MG-10 was inhibited by integrin antibodies, Four of the Drosophila laminin peptides showed cell attachment activities. These results suggest that biologically active regions in the G domain are conserved in the laminin alpha 1 and alpha 2 chains, and that these regions in laminin play an important role in cell surface receptor interactions. RP Nomizu, M (reprint author), NIDR,DEV BIOL LAB,BLDG 30,RM 410,BETHESDA,MD 20892, USA. NR 34 TC 30 Z9 30 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 OCT 28 PY 1996 VL 396 IS 1 BP 37 EP 42 DI 10.1016/0014-5793(96)01060-5 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VQ576 UT WOS:A1996VQ57600007 PM 8906862 ER PT J AU Russell, LB Hunsicker, PR Shelby, MD AF Russell, LB Hunsicker, PR Shelby, MD TI Chlorambucil and bleomycin induce mutations in the specific-locus test in female mice SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE oocyte; mutation; germ cell; mouse; specific-locus test; chlorambucil; bleomycin ID MOUSE; RADIATION; OOCYTES; LINE; DNA AB Specific-locus studies have shown chlorambucil (CHL) and bleomycin (BLE) to be mutagenic in mouse oocytes, almost doubling the number of chemicals previously known to induce mutations in females. The overall CHL-induced mutation rate in oocytes is, however, one order of magnitude below that for male meiotic and postmeiotic stages, and only 1/50 that for early spermatids. For BLE, no specific-locus data for males are available for comparison, but the chemical had earlier been found negative for dominant-lethal induction in males. Both BLE and CHL were significantly mutagenic only in mature and maturing oocytes. In keeping with an earlier report, BLE produced a high incidence of dominant lethals in these stages. CHL failed to induce dominant lethals, indicating that for mature and maturing oocytes, in contrast with results for males, sensitivity to dominant-lethal mutations is not a prerequisite for induction of specific-locus mutations. Exposure of immature oocytes to either BLE or CHL produced neither dominant lethals nor significant induction of specific-locus mutations; however, CHL gave evidence of killing immature oocytes. By contrast, BLE, which has been considered a radiomimetic chemical, does not appear to kill immature oocytes and thus differs markedly from radiation exposures equivalent for dominant-lethal induction. Therefore, the failure to recover specific-locus mutations cannot be ascribed to cell selection resulting from oocyte killing, as has sometimes been done for radiation. Adding results on the nature of the CHL- and BLE-induced mutations to prior information, the estimated minimum proportion of large DNA lesions induced in oocytes by chemicals becomes 35.3%, significantly different from the corresponding figure (similar to 70%) for radiations. For chemical treatments, the oocyte proportion is highly significantly above the 3.6% induced in spermatogonia, but only on the borderline of statistically significant difference from that induced in postspermatogonial stages. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Russell, LB (reprint author), OAK RIDGE NATL LAB,DIV BIOL,POB 2009,OAK RIDGE,TN 37831, USA. FU NIEHS NIH HHS [1-Y01-ES-50318-00] NR 24 TC 7 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 28 PY 1996 VL 358 IS 1 BP 25 EP 35 DI 10.1016/0027-5107(96)00104-2 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VT118 UT WOS:A1996VT11800004 PM 8921974 ER PT J AU Kohn, MC Melnick, RL AF Kohn, MC Melnick, RL TI Effects of the structure of a toxicokinetic model of butadiene inhalation exposure on computed production of carcinogenic intermediates SO TOXICOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Evaluation of Butadiene and Isoprene Health Risks CY JUN 27-29, 1995 CL BLAINE, WA SP Amer Ind Hygiene Assoc, Amer Petr Inst, Chem Ind Inst Toxicol, Chem Manufacturers Assoc, EPA, European Chem Ind Council, European Ctr Ecotoxicol & Toxicol Chem, Hlth Effects Inst, Int Agcy Res Canc, Int Inst Synthet Rubber Producers, Int Programme Chem Safety, NIEHS, Soc Toxicol, Univ Washington, Sch Public Hlth & Community Med, Int Congress Toxicol DE 1,3-butadiene; toxicokinetic modeling; parameter sensitivity ID SPECIES-DIFFERENCES; GAS UPTAKE; RATS; 1,3-BUTADIENE; MICE; GLUTATHIONE; PHARMACOKINETICS; METABOLISM; PREDICTIONS; EXCRETION AB A flow-limited physiologically based toxicokinetic model was constructed for uptake, metabolism, and clearance of butadiene (ED) and its principal metabolite 1,2-epoxy-3-butene (EB), using physiological and biochemical parameters from the literature where available. The model includes compartments for blood, liver, lung, fat, GI tract, other rapidly perfused tissues, and slowly perfused tissues. The blood was distributed among compartments for arterial plus venous blood and subcompartments for vascular spaces associated with each of the tissue compartments. The lung contained a subcompartment for the alveolar space. Metabolic activation of ED by cytochrome P450-catalyzed epoxidation was modeled as occurring in liver, lung, and the rapidly perfused tissue compartments. The detoxication of EB catalyzed by epoxide hydrolase and glutathione S-transferase (GST) was modeled as occurring in liver, lung, and the rapidly perfused tissues compartments and by blood GST activity. The model also includes depletion of glutathione (GSH) by GST-catalyzed conjugation of EB and 3-butene-1,2-diol and resynthesis of GSH from cysteine. Values of biochemical parameters that were unavailable in the literature were estimated by iteratively reweighted least squares optimization to reproduce data for uptake of ED and EB by rats and mice in closed chambers. The resulting model also reproduced the depletion of GSH in liver and lung in flow-through systems. It reproduced the concentrations of expired EB produced from ED in closed chambers but overpredicted separately measured blood EB concentrations in flow-through systems, indicating an inconsistency between these two experiments that cannot be resolved by this model or an inadequacy in the model. Equilibration of chamber gases with the alveolar space and alveolar gas with lung capillary blood results in much less dilution of the inhaled gas in the blood compared with the predictions of models in which chamber gas equilibrates directly with the total circulation. The production of EB predicted by the present model was found to be sensitive to a number of physiological and biochemical parameters. A valid and useful toxicokinetic model must have reliable physiological and enzymological data for ED biotransformation before it can be credibly used for human risk assessment. RP Kohn, MC (reprint author), NIEHS,LAB QUANTITAT & COMPUTAT BIOL,MAIL DROP A3-06,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD OCT 28 PY 1996 VL 113 IS 1-3 BP 31 EP 39 DI 10.1016/0300-483X(96)03424-5 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VQ391 UT WOS:A1996VQ39100007 PM 8901880 ER PT J AU Hayes, RB Xi, LQ Bechtold, WE Rothman, N Yao, M Henderson, R Zhang, LP Smith, MT Zhang, DP Wiemels, J Dosemeci, M Yin, SN ONeill, JP AF Hayes, RB Xi, LQ Bechtold, WE Rothman, N Yao, M Henderson, R Zhang, LP Smith, MT Zhang, DP Wiemels, J Dosemeci, M Yin, SN ONeill, JP TI hprt mutation frequency among workers exposed to 1,3-butadiene in China SO TOXICOLOGY LA English DT Article DE hprt mutation; 1,3-butadiene; occupation AB Hypoxanthine-guanine phosphoribosyl transferase (hprt) mutation frequency (M(f)) was studied in workers at a polybutadiene rubber production facility in Yanshan, China. Exposed workers included for study were active either as process analysts, who sampled butadiene production process lines and analyzed product by gas chromatography, or as process operators, who did routine process control, minor maintenance and, as needed, major repair operations. For process analysts at the polymer and dimethyl formamide (DMF) facilities, the median air levels of ED were 1.0 and 3.5 ppm, respectively. Among process operators, air levels of 1.1 ppm were found during routine activities, while the median air level during pump repair and related operations was 45 ppm (6-h time-weighted average). Overall, M(f) was similar in unexposed (mean M(f) = 20.2 x 10(-6)) and butadiene-exposed (mean M(f) = 21.6 x 10(-6)) workers (P = 0.68). M(f) decreased with cloning efficiency, increased with age, and was moderately greater in women than in men. After adjustment by multiple regression analysis for mean age, sex, and cloning efficiency, the adjusted mean M(f) (X(adj)) was 13.6 x 10(-6) in unexposed and 18.0 x 10(-6) in butadiene-exposed. This 32% difference was, however, not statistically significant (P = 0.13). Butadiene exposure was associated with a modest, if any, increase in hprt M(f) in this population of Chinese workers. C1 CHINESE ACAD PREVENT MED, INST OCCUPAT MED, BEIJING, PEOPLES R CHINA. INHALAT TOXICOL RES INST, ALBUQUERQUE, NM 87185 USA. UNIV CALIF BERKELEY, SCH PUBL HLTH, BERKELEY, CA 94720 USA. YANSHAN PETROCHEM PROD CORP, INST OCCUPAT MED, YANSHAN, PEOPLES R CHINA. UNIV VERMONT, GENET LAB, BURLINGTON, VT USA. RP Hayes, RB (reprint author), NCI, NIH, DIV CANC EPIDEMIOL & GENET, EPN 418, BETHESDA, MD 20892 USA. NR 11 TC 31 Z9 32 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD OCT 28 PY 1996 VL 113 IS 1-3 BP 100 EP 105 DI 10.1016/0300-483X(96)03433-6 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VQ391 UT WOS:A1996VQ39100016 PM 8901888 ER PT J AU Melnick, RL Sills, RC Roycroft, JH Chou, BJ Ragan, HA Miller, RA AF Melnick, RL Sills, RC Roycroft, JH Chou, BJ Ragan, HA Miller, RA TI Inhalation toxicity and carcinogenicity of isoprene in rats and mice: Comparisons with 1,3-butadiene SO TOXICOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Evaluation of Butadiene and Isoprene Health Risks CY JUN 27-29, 1995 CL BLAINE, WA SP Amer Ind Hygiene Assoc, Amer Petr Inst, Chem Ind Inst Toxicol, Chem Manufacturers Assoc, EPA, European Chem Ind Council, European Ctr Ecotoxicol & Toxicol Chem, Hlth Effects Inst, Int Agcy Res Canc, Int Inst Synthet Rubber Producers, Int Programme Chem Safety, NIEHS, Soc Toxicol, Univ Washington, Sch Public Hlth & Community Med, Int Congress Toxicol DE Isoprene; Lung neoplasia; Liver neoplasia; Forestomach neoplasia; Macrocytic anemia ID B6C3F1 MICE; METABOLISM; EXPOSURE; MUTAGENICITY; HYDROCARBON AB As with 1,3-butadiene(BD), inhalation exposure of B6C3F(1) mice to isoprene (2-methyl-1,3-butadiene) caused a macrocytic anemia; induced increases in sister chromatid exchanges in bone marrow cells and in levels of micronucleated erythrocytes in peripheral blood; and produced degeneration of the olfactory epithelium, forestomach epithelial hyperplasia, and testicular atrophy. Most notable was the finding that like BD, isoprene induced neoplasms in the liver, lung, Harderian gland, and forestomach of mice. The carcinogenic effects of isoprene were observed after a 26-week exposure (6 h/day, 5 days/week) of male mice to 700 ppm or higher concentrations of isoprene followed by a 26-week recovery period. Unlike BD, isoprene did not induce lymphomas or hemangiosarcomas of the heart in mice under these conditions nor did it induce chromosomal aberrations in mouse bone marrow cells. No toxicological effects were evident in rats exposed for 13 weeks to either isoprene or BD at concentrations up to 7000 ppm or 8000 ppm, respectively. Interstitial cell hyperplasia of the testis was observed in male F344 rats exposed to 7000 ppm isoprene for 26 weeks, and following a 26-week recovery period, there was a marginal increase in benign testicular interstitial cell tumors C1 PACIFIC NW LAB, RICHLAND, WA 99352 USA. RP Melnick, RL (reprint author), NIEHS, LAB QUANTITAT & COMPUTAT BIOL, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 20 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD OCT 28 PY 1996 VL 113 IS 1-3 BP 247 EP 252 DI 10.1016/0300-483X(96)03453-1 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA VQ391 UT WOS:A1996VQ39100036 PM 8901905 ER PT J AU Fessler, BJ Paliogianni, F Hama, N Balow, JE Boumpas, DT AF Fessler, BJ Paliogianni, F Hama, N Balow, JE Boumpas, DT TI Glucocorticoids modulate CD28 mediated pathways for interleukin 2 production in human T cells - Evidence for posttranscriptional regulation SO TRANSPLANTATION LA English DT Article ID LYMPHOKINE MESSENGER-RNA; 3' UNTRANSLATED REGION; GENE-EXPRESSION; NUCLEAR TRANSCRIPTION; NEGATIVE REGULATION; LYMPHOCYTES-T; MOLECULE CD28; IL-2 GENE; C-JUN; RECEPTOR AB In T cells stimulated through the T cell receptor (TCR), both cyclosporine (CsA) and glucocorticoids (GC) inhibit the transcription of the IL-2 gene. In these cells costimulation via the CD28 cell surface molecule further increases the transcription of IL-2 and stabilizes its mRNA, resulting in a 20-30 fold induction in IL-2 production. This pathway is relatively resistant to the inhibitory effect of CsA. In this study, we asked whether GC interfere with CD28-mediated costimulatory signals for T cell activation. Primary human T cells or Jurkat T cells were stimulated with anti-CD28 and phorbol myristate acetate (PMA) in the presence of dexamethasone (Dex, 10(-10)-10(-5) M). Dex inhibited both the mRNA for IL-2 and IL-2 production in a dose-dependent fashion (minimum effective dose 10(-9) M). In similar experiments employing anti-CD3 mAb and PMA, a 7-20 fold higher concentration of Dex was required to obtain comparable inhibition. To determine if transcriptional modulation is occurring, Jurkat T cells were transfected with a plasmid containing the IL-2 promoter linked to the chloramphenicol acetyl transferase reporter gene. Following stimulation with ionomycin and PMA, high doses (10(-6) M) of Dex inhibited the activity of the IL-2 promoter (similar to 50% inhibition). However, in the presence of anti-CD28 mAb, this promoter became resistant to Dex (less than or equal to 10% inhibition). These results suggest that GC inhibit accessory pathways for IL-2 production via CD28 by predominantly posttranscriptional mechanisms. Inhibition of the CD28 pathway may be an important mechanism for the T cell directed immunosuppressive effects of low-to-moderate doses of GC. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. RP Fessler, BJ (reprint author), NIDDKD,KIDNEY DIS SECT,NIH,BLDG 10,ROOM 3N112,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 15 Z9 16 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 1996 VL 62 IS 8 BP 1113 EP 1118 DI 10.1097/00007890-199610270-00016 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA VQ590 UT WOS:A1996VQ59000016 PM 8900312 ER PT J AU Pahor, M Ferrucci, L Corti, MC Salive, ME Cerhan, JR AF Pahor, M Ferrucci, L Corti, MC Salive, ME Cerhan, JR TI Calcium-channel blockers and cancer - Reply SO LANCET LA English DT Letter C1 IST NAZL RIEEREA & CURA ANZIANI,DEPT GERIATR,I FRATICINI,FLORENCE,ITALY. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20857. UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. RP Pahor, M (reprint author), UNIV TENNESSEE,DEPT PREVENT MED,MEMPHIS,TN 38105, USA. NR 5 TC 0 Z9 0 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 OCT 26 PY 1996 VL 348 IS 9035 BP 1167 EP 1167 DI 10.1016/S0140-6736(05)65298-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VP106 UT WOS:A1996VP10600042 ER PT J AU Hudgins, WR Fibach, E Safaya, S Rieder, RF Miller, AC Samid, D AF Hudgins, WR Fibach, E Safaya, S Rieder, RF Miller, AC Samid, D TI Transcriptional upregulation of gamma-globin by phenylbutyrate and analogous aromatic fatty acids SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE erythroid precursor; hemoglobin F; beta-hemoglobinopathies; aromatic fatty acids; phenylbutyrate; butyrate responsive promoter ID FETAL HEMOGLOBIN PRODUCTION; SICKLE-CELL-ANEMIA; ORAL SODIUM PHENYLBUTYRATE; BETA-THALASSEMIA; ERYTHROID PRECURSORS; GENE-EXPRESSION; LIQUID CULTURE; GROWTH ARREST; PHENYLACETATE; BUTYRATE AB Phenylbutyrate has been shown recently to induce fetal hemoglobin (HbF) production in patients with sickle cell anemia and beta thalassemia. We have now examined related aromatic fatty acids in order to define the range of active structures and identify plausible mechanisms of action. Structure-function analysis revealed that for effective stimulation of HbF in erythroid precursors: (1) the ideal length for the aliphatic side chain is four carbons; (2) oxygen or sulfur substitutions in the carboxylic chain are allowed, as evidenced by the equal or increased activity of phenoxypropionate, benzylthioglycolate, and benzyloxyacetate compared with phenylbutyrate; and (3) blocking the carboxylate group by conversion to the amide form greatly reduces potency. Molecular analysis indicated that the prototype agent, phenylbutyrate, increases HbF production through transcriptional activation of the gamma-globin gene. The latter contains a butyrate responsive promoter known to up-regulate transcription in the presence of short-chain fatty acids of three to five carbons. To determine whether stimulation of an element in this promoter by phenylbutyrate and its analogues might contribute to their mechanism of action, we used a transient expression system involving K562 erythroleukemia cells transfected with a luciferase reporter gene driven by the minimum gamma-globin promoter. Transcriptional activation in this experimental system correlated well with the capacity of an aromatic fatty acid to increase HbF production in erythroid precursors (r = 0.94). Our studies identify potent analogues of phenylbutyrate for the treatment of P-chain hemoglobinopathies, and suggest that stimulation of a butyrate responsive promoter may be responsible for their activity. C1 UNIV VIRGINIA,CTR CANC,CHARLOTTESVILLE,VA 22908. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NIDDKD,BIOL CHEM LAB,NIH,BETHESDA,MD 20892. HADASSAH UNIV HOSP,DEPT HEMATOL,IL-91120 JERUSALEM,ISRAEL. SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY. USA,ARMED FORCES RADIAT RES INST,RADIAT BIOCHEM DEPT,BETHESDA,MD. NR 31 TC 21 Z9 21 U1 0 U2 0 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 OCT 25 PY 1996 VL 52 IS 8 BP 1227 EP 1233 DI 10.1016/0006-2952(96)00476-5 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VN484 UT WOS:A1996VN48400012 PM 8937430 ER PT J AU Tracy, TS Marra, C Wrighton, SA Gonzalez, FJ Korzekwa, KR AF Tracy, TS Marra, C Wrighton, SA Gonzalez, FJ Korzekwa, KR TI Studies of flurbiprofen 4'-hydroxylation - Additional evidence suggesting the sole involvement of cytochrome P450 2C9 SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE flurbiprofen; cytochrome P450; human liver microsomes; vaccinia virus; cDNA expression ID CYP2C SUBFAMILY; CHLORZOXAZONE; PHARMACOKINETICS; HYDROXYLATION; DISPOSITION; TOLBUTAMIDE; HUMANS AB Flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), is metabolized by both oxidation via the cytochrome P450 system and by glucuronidation. The major oxidative pathway in flurbiprofen metabolism is to a 4'-hydroxy metabolite, and recently we demonstrated that cytochrome P450 2C9 and its R144C variant were involved in this process (Tracy et al., Biochem Pharmacol 49: 1269-1275, 1995). Using complementary DNA (cDNA)-expressed cell systems, it has been demonstrated that at physiological concentrations of flurbiprofen there is a lack of involvement of P450s 1A2, 2C8, 2E1, and 3A4. In evaluating flurbiprofen as a potential probe for cytochrome P450 2C9, it is important to assess the involvement of additional P450s in this process. To this end, further studies were undertaken using specific inhibitors of P450 2C9 and P450 cDNA-expressed microsomes for P450 1A1, 2A6, 2B6, 2C19, and 2D6 to assess their potential involvement. We observed the inhibition of (R)- and (S)-flurbiprofen 4'-hydroxylation by an inhibitor of P450 2C9, sulfaphenazole (K-i = 0.07 and 0.06 mu M, respectively), and the NSAID piroxicam (K-i = 10 and 7 mu M, respectively). Furthermore, using microsomes from a lymphoblastoid cell line, we found chat P450s 1Al, 2A6, 2B6, 2C19, and 2D6 were not involved in flurbiprofen hydroxylation at physiological concentrations of flurbiprofen. This finding is particularly important due to the sequence homology and potential substrate overlap of P450 2C9 and 2C19. These studies then provide additional evidence to suggest that P450 2C9 may be the only isoform involved to any substantial degree in flurbiprofen 4'-hydroxylation, and thus this reaction is useful as an in vitro probe for this particularly cytochrome P450 isoform and may be useful as an in vivo probe. C1 ELI LILLY & CO,DEPT DRUG DISPOSIT,INDIANAPOLIS,IN 46285. NCI,NIH,BETHESDA,MD 20892. UNIV PITTSBURGH,CTR CLIN PHARMACOL,PITTSBURGH,PA. RP Tracy, TS (reprint author), W VIRGINIA UNIV,SCH PHARM,DEPT BASIC PHARMACEUT SCI,HSN POB 9530,MORGANTOWN,WV 26506, USA. NR 19 TC 64 Z9 64 U1 0 U2 6 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 OCT 25 PY 1996 VL 52 IS 8 BP 1305 EP 1309 DI 10.1016/0006-2952(96)00501-1 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VN484 UT WOS:A1996VN48400021 PM 8937439 ER PT J AU Cippitelli, M Ye, JP Viggiano, V Sica, A Ghosh, P Gulino, A Santoni, A Young, HA AF Cippitelli, M Ye, JP Viggiano, V Sica, A Ghosh, P Gulino, A Santoni, A Young, HA TI Retinoic acid-induced transcriptional modulation of the human interferon-gamma promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VITAMIN-A-DEFICIENCY; IMMUNODEFICIENCY-VIRUS TYPE-1; NEGATIVE REGULATORY ELEMENT; LOOP-HELIX PROTEIN; NF-KAPPA-B; GLUCOCORTICOID RECEPTOR; DNA-BINDING; THYROID-HORMONE; FACTOR USF; MAMMALIAN-CELLS AB Disregulation of vitamin A metabolism is able to generate different immunological effects, including altered response to infection, reduced IgG production, and differential regulation of cytokine gene expression (including interleukin-2 and -4 and interferon-gamma (IFN-gamma)). In particular, IFN-gamma gene expression is significantly affected by vitamin A and/or its derivatives (e.g. retinoic acid (RA)), Here, we analyze the effect of retinoic acid on IFN-gamma transcription. Transient transfection assays in the human T lymphoblastoid cell line Jurkat demonstrated that the activation of the IFN-gamma promoter was significantly down-regulated in the presence of RA, Surprisingly, two different AP-1/CREB-ATF-binding elements situated in the initial 108 base pairs of the IFN-gamma promoter and previously shown to be critical for tran scriptional activity were unaffected by Rk Utilizing promoter deletions and electrophoretic mobility shift analysis, we identified a USF/EGR-1-binding element cooperating in the modulation of IFN-gamma promoter activity by RA, This element was found to be situated in a position of the IFN-gamma promoter close to a silencer element previously identified in our laboratory, These results suggest that direct modulation of IFN-gamma promoter activity is one of the possible mechanisms involved in the inhibitory effect of retinoids on IFN-gamma gene expression. C1 NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,EXPT IMMUNOL LAB,FREDERICK,MD 21702. UNIV AQUILA,DEPT EXPT MED,I-67100 LAQUILA,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPT MED & PATHOL,I-00158 ROME,ITALY. REGINA ELENA INST CANC RES,LAB PATHOPHYSIOL,I-00158 ROME,ITALY. NR 93 TC 35 Z9 35 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 OCT 25 PY 1996 VL 271 IS 43 BP 26783 EP 26793 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300053 PM 8900159 ER PT J AU Erickson, JW Zhang, CJ Kahn, RA Evans, T Cerione, RA AF Erickson, JW Zhang, CJ Kahn, RA Evans, T Cerione, RA TI Mammalian Cdc42 is a brefeldin A-sensitive component of the Golgi apparatus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEIN; GUANINE-NUCLEOTIDE EXCHANGE; SACCHAROMYCES-CEREVISIAE GENE; ADP-RIBOSYLATION FACTOR; DBL ONCOGENE PRODUCT; ACTIN STRESS FIBERS; CELL POLARITY; MONOCLONAL-ANTIBODY; MEMBRANE-PROTEIN; PHOSPHOLIPASE-D AB In this study, we have used immunocytochemical and fractionation approaches to provide a description oft he localization of the mammalian Cdc42 protein (designated Cdc42Hs) in vivo. A specific anti-peptide antibody was generated against the C-terminal region of Cdc42Hs. Using affinity-purified preparations of this antibody in indirect immunofluorescence experiments, Cdc42Hs was found to be localized to the Golgi apparatus, Similar to the well-characterized non-clathrin coat proteins ADP-ribosylation factor (ARF) and beta-COP, the perinuclear clustering of Cdc42Hs is rapidly dispersed upon exposure of the cells to the drug brefeldin A, suggesting that it too may play a role in the processes of intracellular lipid and protein transport, Employing cell lines possessing inducible forms of ARF, we demonstrate here a tight coupling of the nucleotide bound state of ARF and the subcellular localization of Cdc42Hs. Specifically, the expression of wild-type ARF had no effect on the brefeldin A sensitivity of Cdc42Hs while, as is the case for ARF and P-COP, expression of a GTPase-deficient form of ARF (ArF(Q71L)) renders these Golgi-localized proteins resistant to brefeldin A treatment (Teal et al., 1994; Zhang et al,, 1994). Moreover, the induced expression of a mutant form of ARF with a low affinity for nucleotide resulted in constitutive redistribution of Cdc42Hs in the absence of brefeldin A treatment. These results suggest that Cdc42Hs may play a role in cell morphogenesis by acting on targets in the Golgi that direct polarized growth at the plasma membrane. C1 NCI,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,NIH,BETHESDA,MD 20892. ONYX PHARMACEUT,RICHMOND,CA 94806. RP Erickson, JW (reprint author), CORNELL UNIV,COLL VET MED,DEPT PHARMACOL,ITHACA,NY 14853, USA. FU NIGMS NIH HHS [GM47458] NR 41 TC 149 Z9 151 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1996 VL 271 IS 43 BP 26850 EP 26854 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300061 PM 8900167 ER PT J AU Crawford, LE Milliken, EE Irani, K Zweier, JL Becker, LC Johnson, TM Eissa, NT Crystal, RG Finkel, T GoldschmidtClermont, PJ AF Crawford, LE Milliken, EE Irani, K Zweier, JL Becker, LC Johnson, TM Eissa, NT Crystal, RG Finkel, T GoldschmidtClermont, PJ TI Superoxide mediated actin response in post-hypoxic endothelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR; TYROSINE KINASE; STRESS FIBERS; PROTEIN; RECEPTOR; REOXYGENATION; ANGIOGENESIS; STIMULATION; GENERATION; MECHANISM AB The mechanism leading to changes in the superstructure of endothelial cells exposed to ischemia and reperfusion remains uncharacterized, We show that in posthypoxic endothelial cells, the simple re-addition of oxygen induces a profound reorganization of the actin cytoskeleton. The total filamentous actin pool increases by 41% and translocation of actin filaments to the submembranous network is observed, Concurrent with the actin polymerization, increased tyrosine phosphorylation of endothelial cell substrates is detected on Western blots. Overexpression of superoxide dismutase using replication incompetent adenovirus inhibits the actin and tyrosine phosphorylation responses to reoxygenation. Inhibition of tyrosine kinases with the isoflavone genistein also suppressed the actin polymerization response to reoxygenation, but unlike superoxide dis mutase, genistein also induced the collapse of the superstructure of endothelial cells upon reoxygenation. These experiments support the concept that reoxygenation following a period of hypoxia can induce the remodeling of the actin cytoskeleton in endothelial cells, Such a response requires the intact coupling of superoxide producing pathway(s) with tyrosine kinase pathway(s). C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,PULM & CRIT CARE BRANCH,NIH,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,PULM & CRIT CARE BRANCH,NEW YORK,NY 10021. FU NHLBI NIH HHS [HL52315] NR 29 TC 75 Z9 75 U1 0 U2 6 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 OCT 25 PY 1996 VL 271 IS 43 BP 26863 EP 26867 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300063 PM 8900169 ER PT J AU Song, JS Gomez, J Stancato, LF Rivera, J AF Song, JS Gomez, J Stancato, LF Rivera, J TI Association of a p95 Vav-containing signaling complex with the Fc epsilon RI gamma chain in the RBL-2H3 mast cell line - Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; AFFINITY IGE RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; T-CELL; IMMUNOGLOBULIN-E; HISTAMINE-RELEASE; EXCHANGE ACTIVITY; CROSS-LINKING; SH2 DOMAIN; B-CELLS AB Aggregation of the high affinity receptor for IgE (Fc epsilon RI) on the mucosal mast cell line, RBL-2H3, results in the rapid and persistent tyrosine phosphorylation of Vav. Immunoprecipitation of Vav from activated cells revealed co-immunoprecipitated phosphoproteins of molecular weights identical to the Fc epsilon RI beta and gamma chains, and the former was reactive with antibody to the Fc epsilon RI beta chain. Conversely, Western blots revealed the presence of p95 Vav in Fc epsilon RI immunoprecipitates. The association of Vav and of Grb2 with the receptor was found to be regulated by aggregation of the receptor, and the interaction of Vav with the Fc epsilon RI was localized to the gamma chain. To gain insight on the signaling pathway in which Vav participates, we investigated the in vivo associations of Vav with other molecules. A reducible chemical cross-linking agent was used to covalently maintain protein interactions under nonreducing conditions. A fraction of Vav increased in mass to form a complex of > 300 kDa in molecular mass. Under reducing conditions the cross-linked Vav immunoprecipitates showed the presence of Grb2, Raf-1, and p42(mapk) (ERK2). In vitro kinase assays of Raf-1 activity associated with Vav revealed that this complex had an activity greater than that of Raf-1 derived from nonactivated cells, and aggregation of the Fc epsilon RI did not modulate this activity. In contrast, aggregation of the Fc epsilon RI increased the total Raf-1 activity by 2-5-fold. These results demonstrate that Vav associates constitutively with components of the mitogen-activated protein kinase pathway to form an active multimeric signaling complex whose in vitro activity and associations may be directed by aggregation of the Fc epsilon RI. The findings of this study may also be relevant to other members of the immune recognition receptor family that share the T-cell antigen receptor zeta/gamma chains. C1 NIAMSD,SECT CHEM IMMUNOL,NIH,BETHESDA,MD 20892. NIAMSD,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. NR 45 TC 42 Z9 42 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 OCT 25 PY 1996 VL 271 IS 43 BP 26962 EP 26970 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300076 PM 8900182 ER PT J AU Brzeska, H Martin, BM Korn, ED AF Brzeska, H Martin, BM Korn, ED TI The catalytic domain of Acanthamoeba myosin I heavy chain kinase .1. Identification and characterization following tryptic cleavage of the native enzyme SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; PHOSPHORYLATION SITES; ACTIN-FILAMENTS; AUTOPHOSPHORYLATION; ACTIVATION; PURIFICATION; FAMILY; LOCALIZATION; CASTELLANII; SUBSTRATE AB The actin-activated Mg2+-ATPase activities of the myosin I isoenzymes from Acanthamoeba castellanii are greatly increased by phosphorylation catalyzed by myosin I heavy chain kinase (MIHC kinase), a monomeric 97-kDa protein whose activity is greatly enhanced by acidic phospholipids and by autophosphorylation of multiple sites, In this paper, we show that the 35-kDa COOH-terminal fragment obtained by trypsin cleavage of maximally activated, autophosphorylated kinase retains the full activity and two to three of the autophosphorylation sites of the native enzyme, Other autophosphorylation sites occur in the middle third of the native enzyme, A trypsin cleavage site within the 35-kDa region is protected in phosphorylated kinase but is readily cleaved in unphosphorylated kinase producing catalytically inactive 25 and 11-kDa fragments from the NH2- and COOH-terminal ends, respectively, of the 35-kDa peptide, This implies that the conformation around the ''25/11'' cleavage site changes upon phosphorylation of the native enzyme, The position of this site corresponds to the activation loop of protein kinase A (see the accompanying paper: Brzeska, H., Szczepanowska, J., Hoey, J., and Korn, E. D. (1996) J. Biol. Chem. 271, 27056-27062), Exogenously added MIHC kinase phosphorylates the 11-kDa fragment, but not the 25-kDa fragment, indicating that the phosphorylation sites of the 35-kDa catalytic fragment are located within the COOH-terminal 11 kDa, The accompanying paper describes the cloning, sequencing, and expression of a fully active 35-kDa catalytic domain. C1 NIMH,NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 38 TC 14 Z9 15 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 OCT 25 PY 1996 VL 271 IS 43 BP 27049 EP 27055 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300089 PM 8900195 ER PT J AU Brzeska, H Szczepanowska, J Hoey, J Korn, ED AF Brzeska, H Szczepanowska, J Hoey, J Korn, ED TI The catalytic domain of Acanthamoeba myosin I heavy chain kinase .2. Expression of active catalytic domain and sequence homology to p21-activated kinase (PAK) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; PHOSPHORYLATION SITES; CRYSTAL-STRUCTURE; AMINO-ACID; MAP KINASE; ACTIVATION; AUTOPHOSPHORYLATION; SUBUNIT; CDC42; LOCALIZATION AB Acanthamoeba myosin I heavy chain (MIHC) kinase is a monomeric 97-kDa protein that is activated by binding to acidic phospholipids or by autophosphorylation. Activation by phospholipids is inhibited by Ca2+-calmodulin. In the accompanying paper (Brzeska, H., Martin, B., and Korn, E. D. (1996) J. Biol. Chem. 271, 27049-27055), we identified the catalytic domain as the COOH-terminal 35 kDa produced by trypsin digestion of phosphorylated MIHC kinase, In this paper, we report the cloning and sequencing of the corresponding cDNA and expression of fully active catalytic domain. The expressed catalytic domain has substrate specificity similar to that of native kinase and resistance to trypsin similar to that of fully phosphorylated MIHC kinase, MIHC kinase catalytic domain has only 25% sequence identity to the catalytic domain of protein kinase A and similarly low sequence identity to the catalytic domains of protein kinase C- and calmodulin-dependent kinases, but 50% sequence identity and 70% similarity to the p21-activated kinase (PAK) and STE20 family of kinases. This suggests that MIHC kinase is (at least) evolutionarily related to the PAK family, whose activities are regulated by small GTP-binding proteins, The homology includes the presence of a potential MIHC kinase autophosphorylation site as well as conserved Tyr and Ser/Thr residues in the region corresponding to the P+1 loop of protein kinase A. A synthetic peptide corresponding to this region of MIHC kinase is phosphorylated by both the expressed catalytic domain and native MIHC kinase. C1 NHLBI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012 NR 43 TC 50 Z9 50 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 OCT 25 PY 1996 VL 271 IS 43 BP 27056 EP 27062 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300090 PM 8900196 ER PT J AU Eissa, NT Strauss, AJ Haggerty, CM Choo, EK Chu, SC Moss, J AF Eissa, NT Strauss, AJ Haggerty, CM Choo, EK Chu, SC Moss, J TI Alternative splicing of human inducible nitric-oxide synthase mRNA - Tissue-specific regulation and induction by cytokines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRUCTURAL DIVERSITY; MOLECULAR-CLONING; MESSENGER-RNA; GENE; EXPRESSION; CALMODULIN; BINDING; TETRAHYDROBIOPTERIN; MACROPHAGES; EPITHELIUM AB Human inducible nitric-oxide synthase (iNOS) is responsible for nitric oxide synthesis in response to inflammatory mediators. The human iNOS gene, containing 26 exons, encodes a protein of 131 kDa. This study was aimed at investigating the presence of alternative splicing of human iNOS mRNA. Total RNA from human alveolar macrophages, nasal and bronchial epithelial cells, and several human tissues was transcribed to cDNA and analyzed using polymerase chain reaction with specific primers for segmental analysis of the iNOS gene, Four sites of alternative splicing were identified by sequence analysis; these included deletion of: (i) exon 5; (ii) exons 8 and 9; (iii) exons 9, 10, and 11; and (iv) exons 15 and 16. The deduced amino acid sequences of the novel iNOS cDNAs predict one truncated protein (resulting from exon 5 deletion) and three iNOS proteins with in-frame deletions, Southern analyses of polymerase chain reaction products were consistent with tissue-specific regulation of alternative splicing, In cultured cells, iNOS induction by cytokines and lipopolysaccharide was associated with an increase in alternatively spliced mRNA transcripts, Because iNOS is active as a dimer, the novel forms of alternatively spliced iNOS may be involved in regulation of nitric oxide synthesis. RP Eissa, NT (reprint author), NHLBI,NIH,PULM CRIT CARE MED BRANCH,10 CTR DR,MSC 1590,RM 6D03,BLDG 10,BETHESDA,MD 20892, USA. OI Choo, Esther/0000-0001-8847-5745 NR 23 TC 78 Z9 78 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 25 PY 1996 VL 271 IS 43 BP 27184 EP 27187 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP233 UT WOS:A1996VP23300106 PM 8900212 ER PT J AU Saavedra, JE Southan, GJ Davies, KM Lundell, A Markou, C Hanson, SR Adrie, C Hurford, WE Zapol, WM Keefer, LK AF Saavedra, JE Southan, GJ Davies, KM Lundell, A Markou, C Hanson, SR Adrie, C Hurford, WE Zapol, WM Keefer, LK TI Localizing antithrombotic and vasodilatory activity with a novel, ultrafast nitric oxide donor SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SODIUM-NITRITE; THROMBOSIS; DELIVERY; ACIDS; MICE; RATS AB Reaction of nitric oxide (NO) with L-proline in methanolic sodium methoxide yields a diazeniumdiolate product, C5H7N3O4Na2 . CH3OH (PROLI/NO), that can be stabilized in basic solution but that dissociates to proline (1 mol) and NO (2 mol) with a half-life of only 1.8 s at pH 7.4 and 37 degrees C. This kinetic behavior has allowed the generation of highly localized antiplatelet and vasodilatory effects. By infusing solutions containing 4 mu M PROLI/NO in 0.1 M sodium hydroxide at the rate of 1 nmol . min(-1) immediately upstream from a polyester vascular graft in the unheparinized baboon circulatory system, for example, platelet deposition at the normally thrombogenic graft surface was substantially reduced relative to controls receiving only 0.1 M sodium hydroxide. In a second study, infusion of PROLI/NO into the right atrium of sheep with induced pulmonary hypertension selectively dilated the lung vasculature, dose-dependently reducing the pulmonary arterial pressure by as much as 9 mmHg with no observable effect on the systemic arterial pressure at an infusion rate of up to 24 nmol . kg(-1). min(-1). PROLI/NO could also be formulated as an insoluble polymer blend that released NO smoothly for prolonged periods. The results suggest that localized delivery of diazeniumdiolates such as PROLI/NO which generate NO with extreme rapidity on entering the blood stream may hold considerable promise for inhibition of thrombus formation, selective dilation of the vasculature, and other research and clinical applications. C1 NCI,FREDERICK CANC RES & DEV CTR,INTRAMURAL RES SUPPORT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,CHEM SECT,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. GEORGE MASON UNIV,DEPT CHEM,FAIRFAX,VA 22030. EMORY UNIV,DIV HEMATOL,ATLANTA,GA 30322. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. MASSACHUSETTS GEN HOSP,DEPT ANAESTHESIA,BOSTON,MA 02114. RI Hurford, William/G-6386-2013; Keefer, Larry/N-3247-2014 OI Hurford, William/0000-0003-1201-0313; Keefer, Larry/0000-0001-7489-9555 FU NHLBI NIH HHS [HL-31469, HL-42397, HL-48667] NR 23 TC 109 Z9 110 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 25 PY 1996 VL 39 IS 22 BP 4361 EP 4365 DI 10.1021/jm960616s PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VP247 UT WOS:A1996VP24700004 PM 8893830 ER PT J AU Galinis, DL Fuller, RW McKee, TC Cardellina, JH Gulakowski, RJ McMahon, JB Boyd, MR AF Galinis, DL Fuller, RW McKee, TC Cardellina, JH Gulakowski, RJ McMahon, JB Boyd, MR TI HIV-inhibitory natural products .30. Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RAIN-FOREST TREE; REVERSE-TRANSCRIPTASE; CALANOLIDE-A; CALOPHYLLUM COUMARINS AB The Delta(7,8) olefinic linkages within (+)-calanolide A (1) and (-)-calanolide B (2) were catalytically reduced to determine impact on the anti-HIV activity of the parent compounds. In addition, a series of structure modifications of the C-12 hydroxyl group in (-)-calanolide B was made to investigate the importance of that substituent to the HIV-1 inhibitory activity of these coumarins. A total of 14 analogs were isolated or prepared and compared to (+)-calanolide A and (-)-calanolide B in the NCI primary anti-HIV assay. While none of the compounds showed activity superior to the two unmodified leads, some structure-activity requirements were apparent from the relative anti-HIV potencies of the various analogs. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT DIAG & CTR,FREDERICK,MD 21702. NR 16 TC 54 Z9 57 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 25 PY 1996 VL 39 IS 22 BP 4507 EP 4510 DI 10.1021/jm9602827 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VP247 UT WOS:A1996VP24700020 PM 8893846 ER PT J AU Brady, GP Szabo, A Sharp, KA AF Brady, GP Szabo, A Sharp, KA TI On the decomposition of free energies SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE free energy components; entropy decomposition; enthalpy decomposition; free energy separability ID COMPONENT ANALYSIS; BORN MODEL; SOLVATION; PROTEINS; COMPLEX; TERMS AB The decomposition of free energies and entropies into components has recently been discussed within the framework of the free energy perturbation (FEP) and thermodynamic integration (TI) methods. In FEP, the cumulant expansion of the excess free energy contains coupling terms in second and higher orders. It is shown here that this expansion can be expressed in terms of temperature derivatives of the mean energy, suggesting a natural decomposition of the free energy into components corresponding to each term in the Hamiltonian. This result is derived in such a way that it establishes the equivalence to a particular form of component analysis based on TI in which all terms in the interaction energy are turned on simultaneously using 1/kT as the coupling parameter. (C) 1996 Academic Press Limited C1 UNIV PENN, DEPT BIOCHEM & BIOPHYS, PHILADELPHIA, PA 19104 USA. NIDDKD, CHEM PHYS LAB, NIH, BETHESDA, MD 20892 USA. RI Szabo, Attila/H-3867-2012 FU NIGMS NIH HHS [GM54105] NR 14 TC 29 Z9 29 U1 0 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 25 PY 1996 VL 263 IS 2 BP 123 EP 125 DI 10.1006/jmbi.1996.0563 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP739 UT WOS:A1996VP73900004 PM 8913295 ER PT J AU Acs, G Palkovits, M Blumberg, PM AF Acs, G Palkovits, M Blumberg, PM TI Specific binding of [H-3]resiniferatoxin by human and rat preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus membrane preparations SO LIFE SCIENCES LA English DT Article DE [H-3]RTX bidding; vanilloid receptors; capsaicin; preoptic area; locus ceruleus; medial hypothalamus; reticular formation and ventral thalamus ID H-3 RESINIFERATOXIN BINDING; VANILLOID CAPSAICIN RECEPTOR; INDUCED NEURONAL DEGENERATION; SUPERFICIAL DORSAL HORN; PROTEIN-KINASE-C; COERULEUS NEURONS; SENSORY NEURONS; SPINAL-CORD; POSITIVE COOPERATIVITY; HORSERADISH-PEROXIDASE AB Specific [H-3]resiniferatoxin (RTX) binding detects the vanilloid (capsaicin) receptors and provides a biochemical means for exploring their pharmacology. In the present study we demonstrate specific vanilloid (RTX) binding sites in various brain areas not known to be innervated by primary afferent neurons. Specific high-affinity binding of [H-3]RTX could be detected in membrane preparations of the posterior (''hypothalamic'') and anterior (''septal'') parts of the preoptic area, locus ceruleus, medial hypothalamus, brainstem reticular formation and ventral thalamic nuclei from naive rats. The determined levels of binding at 4 nM [H-3]RTX were 23.0 +/- 4.5, 7.1 +/- 1.6, 29.9 +/- 2.3, 23.5 +/- 2.4, 9.9 +/- 2.2 and 8.1 +/- 1.9 fmol/mg, respectively; unfortunately, the high levels of non-specific binding (higher than 80 %) in the present experiments made it impossible for us to characterize fully the binding properties of the receptors. However, no detectable specific [H-3]RTX binding was present in membranes of brain nuclei from rats pretreated with 300 mg/kg capsaicin, a treatment which causes loss of response to capsaicin. Significant specific [H-3]RTX binding was also absent in membrane preparations of the midbrain central gray matter, somatosensory cortex and cerebellum either from naive or capsaicin treated rats. In human brain specific [H-3]RTX binding measured at 4 nM [H-3]RTX showed a pattern of distribution similar to that in the rat brain. The corresponding levels of specific [H-3]RTX binding in the preoptic area, locus ceruleus, medial hypothalamus, reticular formation and ventral thalamus were 44.9 +/- 2.4, 50.6 +/- 3.0, 36.1 +/- 2.9, 9.4 +/- 2.8 and 8.4 +/- 2.4 fmol/mg, respectively. Our findings corroborate previous biological evidence that vanilloid receptors are present in brain as well as in sensory afferent neurons. C1 NCI, MOL MECH TUMOR PROMOT SECT, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 55 TC 53 Z9 56 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD OCT 25 PY 1996 VL 59 IS 22 BP 1899 EP 1908 DI 10.1016/S0024-3205(96)00537-1 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VQ105 UT WOS:A1996VQ10500009 PM 8950287 ER PT J AU Pavlov, YI Suslov, VV Shcherbakova, PV Kunkel, TA Ono, A Matsuda, A Schaaper, RM AF Pavlov, YI Suslov, VV Shcherbakova, PV Kunkel, TA Ono, A Matsuda, A Schaaper, RM TI Base analog N-6-hydroxylaminopurine mutagenesis in Escherichia coli: Genetic control and molecular specificity SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE base analog N-6-hydroxylaminopurine; Escherichia coli; mutagenic specificity; antimutator DNA polymerase; Delta(uvrB-bio) deletion ID DNAE-ANTIMUTATOR ALLELES; MISMATCH REPAIR SYSTEM; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; REPLICATION FIDELITY; SPONTANEOUS MUTATION; LACI GENE; POLYMERASE; 6-N-HYDROXYLAMINOPURINE; TRANSVERSIONS AB We have studied the molecular specificity of the base analog N-6-hydroxylaminopurine (HAP) in the E. coli lad gene, as well as the effects of mutations in DNA repair and replication genes on HAP mutagenesis. HAP induced base substitutions of the two transition types (A . T-->G . C and G . C-->A . T) at equal frequency. This bi-directional transition specificity is consistent with in vitro primer extension experiments with the Klenow fragment of DNA polymerase I in which we observed that either dTTP or dCTP were incorporated opposite HAP in an oligonucleotide template. The spectrum of HAP-induced transitions was different from the spontaneous transitions in either a wild-type or a mismatch-repair-defective (mutL) strain. Mutations in genes controlling excision repair, exonucleolytic proofreading, mismatch correction, error-prone (SOS) repair and 8-oxo-guanine repair did not affect HAP-induced mutagenesis substantially, However, an extensive deletion of several genes in the uvrB-bio region conferred supersensitivity to the lethal and mutagenic effects of HAP, perhaps due to an effect on HAP metabolism. dnaE antimutator alleles reduced HAP-forward mutagenicity in allele-specific manner: dnaE911 reduced it several fold, while dnaE915 abolished it almost completely. The results obtained are consistent with the idea that HAP is mutagenic in E. coli via a pathway generating replication errors. C1 NIEHS,RES TRIANGLE PK,NC 27709. HOKKAIDO UNIV,FAC PHARMACEUT SCI,SAPPORO,HOKKAIDO 060,JAPAN. RP Pavlov, YI (reprint author), ST PETERSBURG STATE UNIV,DEPT GENET,UNIV SKAYA EMB 7-9,ST PETERSBURG 199034,RUSSIA. NR 58 TC 26 Z9 26 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 25 PY 1996 VL 357 IS 1-2 BP 1 EP 15 DI 10.1016/0027-5107(96)00060-7 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VM364 UT WOS:A1996VM36400002 PM 8876675 ER PT J AU Kulaeva, OI Koonin, EV McDonald, JP Randall, SK Rabinovich, N Connaughton, JF Levine, AS Woodgate, R AF Kulaeva, OI Koonin, EV McDonald, JP Randall, SK Rabinovich, N Connaughton, JF Levine, AS Woodgate, R TI Identification of a DinB//UmuC homolog in the archeon Sulfolobus solfataricus SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE SOS mutagenesis; UmuDC ID PROTEIN SECONDARY STRUCTURE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; SEQUENCE DATABASES; SOS MUTAGENESIS; RECA PROTEIN; UMU OPERON; GENE; PLASMID; CLEAVAGE AB To date, eight closely related homologs of the Escherichia coli UmuC protein have been identified. All of these homologs appear to play critical roles in damage-inducible mutagenesis in enterobacteriaceae. Recently, a distantly related UmuC-homolog, DinB, has also been identified in E. coli. Using the polymerase chain reaction together with degenerate primers designed against conserved regions found in UmuC like proteins, we have identified a new member of the UmuC-superfamily in the archeon Sulfolobus solfataricus. This new homolog shows high sequence similarity to DinB and a lower level of similarity to UmuC. As a consequence, we have called this new gene dbh (dinB homolog). Analysis of approximately 2.7 kb DNA encompassing the dbh region revealed several open reading frames (orfs). One, encoding a putative ribokinase, was located immediately upstream of dbh. This olf overlaps the dbh gene by 4 bp suggesting that both proteins might be coordinately expressed. Further upstream of the ribokinase-dbh locus was another orf encoding a potential ATPase homologous to two uncharacterized S. cerevisiae proteins (YD9346.02c and SC38KCXVI_20) and another E. coli DNA repair protein, RuvB. While this is the first report of a UmuC-like homolog in an archeon, we detected additional homologs using protein sequence comparisons in Gram-positive bacteria, cyanobacteria, and among potential human EST products, indicating that UmuC-related proteins comprise a ubiquitous superfamily of proteins probably involved in DNA repair and mutagenesis. C1 NICHHD,NIH,SECT DNA REPLICAT REPAIR & MUTAGENESIS,BETHESDA,MD 20892. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. ONCOR INC,GAITHERSBURG,MD 20877. RI Studitskaia, Olga/D-8551-2014 OI Studitskaia, Olga/0000-0001-5417-9964 NR 40 TC 81 Z9 83 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 25 PY 1996 VL 357 IS 1-2 BP 245 EP 253 DI 10.1016/0027-5107(96)00164-9 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VM364 UT WOS:A1996VM36400028 PM 8876701 ER PT J AU Dawson, DA Martin, D Hallenbeck, JM AF Dawson, DA Martin, D Hallenbeck, JM TI Inhibition of tumor necrosis factor-alpha reduces focal cerebral ischemic injury in the spontaneously hypertensive rat SO NEUROSCIENCE LETTERS LA English DT Article DE tumor necrosis factor-alpha; type I soluble tumor necrosis factor receptor; focal cerebral ischemia; microcirculation; neuroprotection; fluorescence microscopy ID BRAIN-DAMAGE; RELEASE AB Tumor necrosis factor-alpha (TNF-alpha) is acutely expressed following focal cerebral ischemia, but its pathophysiological role remains to be extensively characterized. In this study we determined the effect of inhibiting TNF-alpha on the microvascular perfusion impairment and ischemic injury induced by permanent middle cerebral artery occlusion (MCAO). TNF-alpha activity was inhibited with recombinant type I soluble TNF receptor (TNFbp; 1 mg/kg i.v., 0.5 h pre- or post-MCAO). TNFbp significantly attenuated the microvessel perfusion impairment observed in vehicle treated rats, particularly in perifocal/penumbral regions of cortex, and significantly reduced (by 34-38%) the total volume of ischemic injury. These results demonstrate that TNF-alpha contributes to focal ischemic injury and that inhibition of TNF-alpha can confer dramatic neuroprotection. The association of the neuroprotective effect of TNFbp with improved microvascular perfusion suggests that inflammatory and vascular responses to TNF-alpha contribute to its pathological action. C1 AMGEN BOULDER INC,DEPT PHARMACOL,BOULDER,CO 80301. RP Dawson, DA (reprint author), NINCDS,STROKE BRANCH,NIH,BETHESDA,MD 20892, USA. NR 20 TC 139 Z9 142 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 OCT 25 PY 1996 VL 218 IS 1 BP 41 EP 44 DI 10.1016/0304-3940(96)13116-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VT808 UT WOS:A1996VT80800011 PM 8939476 ER PT J AU Roche, PA AF Roche, PA TI Out, damned CLIP! Out, I say! SO SCIENCE LA English DT Editorial Material ID ANTIGEN-PROCESSING MUTANT; INVARIANT CHAIN PEPTIDES; HLA-DR MOLECULES; MHC; DM; DISSOCIATION RP Roche, PA (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 10 TC 9 Z9 9 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 OCT 25 PY 1996 VL 274 IS 5287 BP 526 EP 527 DI 10.1126/science.274.5287.526 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900032 PM 8928005 ER PT J AU Schuler, GD Boguski, MS Stewart, EA Stein, LD Gyapay, G Rice, K White, RE RodriguezTome, P Aggarwal, A Bajorek, E Bentolila, S Birren, BB Butler, A Castle, AB Chiannilkulchai, N Chu, A Clee, C Cowles, S Day, PJR Dibling, T Drouot, N Dunham, I Duprat, S East, C Edwards, C Fan, JB Fang, N Fizames, C Garrett, C Green, L Hadley, D Harris, M Harrison, P Brady, S Hicks, A Holloway, E Hui, L Hussain, S LouisDitSully, C Ma, J MacGilvery, A Mader, C Maratukulam, A Matise, TC McKusick, KB Morissette, J Mungall, A Muselet, D Nusbaum, HC Page, DC Peck, A Perkins, S Piercy, M Qin, F Quackenbush, J Ranby, S Reif, T Rozen, S Sanders, C She, X Silva, J Slonim, DK Soderlund, C Sun, WL Tabar, P Thangarajah, T VegaCzamy, N Vollrath, D Voyticky, S Wilmer, T Wu, X Adams, MD Auffray, C Walter, NAR Brandon, R Dehejia, A Goodfellow, PN Houlgatte, R Hudson, JR Ide, SE Iorio, KR Lee, WY Seki, N Nagase, T Ishikawa, K Nomura, N Phillips, C Polymeropoulos, MH Sandusky, M Schmitt, K Berry, R Swanson, K Torres, R Venter, JC Sikela, JM Beckmann, JS Weissenbach, J Myers, RM Cox, DR James, MR Bentley, D Deloukas, P Lander, ES Hudson, TJ AF Schuler, GD Boguski, MS Stewart, EA Stein, LD Gyapay, G Rice, K White, RE RodriguezTome, P Aggarwal, A Bajorek, E Bentolila, S Birren, BB Butler, A Castle, AB Chiannilkulchai, N Chu, A Clee, C Cowles, S Day, PJR Dibling, T Drouot, N Dunham, I Duprat, S East, C Edwards, C Fan, JB Fang, N Fizames, C Garrett, C Green, L Hadley, D Harris, M Harrison, P Brady, S Hicks, A Holloway, E Hui, L Hussain, S LouisDitSully, C Ma, J MacGilvery, A Mader, C Maratukulam, A Matise, TC McKusick, KB Morissette, J Mungall, A Muselet, D Nusbaum, HC Page, DC Peck, A Perkins, S Piercy, M Qin, F Quackenbush, J Ranby, S Reif, T Rozen, S Sanders, C She, X Silva, J Slonim, DK Soderlund, C Sun, WL Tabar, P Thangarajah, T VegaCzamy, N Vollrath, D Voyticky, S Wilmer, T Wu, X Adams, MD Auffray, C Walter, NAR Brandon, R Dehejia, A Goodfellow, PN Houlgatte, R Hudson, JR Ide, SE Iorio, KR Lee, WY Seki, N Nagase, T Ishikawa, K Nomura, N Phillips, C Polymeropoulos, MH Sandusky, M Schmitt, K Berry, R Swanson, K Torres, R Venter, JC Sikela, JM Beckmann, JS Weissenbach, J Myers, RM Cox, DR James, MR Bentley, D Deloukas, P Lander, ES Hudson, TJ TI A gene map of the human genome SO SCIENCE LA English DT Article ID FAMILIAL ALZHEIMER-DISEASE; RET PROTOONCOGENE; COLON-CANCER; MUTATIONS; EXPRESSION; SEQUENCE; INHIBITOR; CLONING; LINKAGE; BINDING AB The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web al http://www.ncbi.nlm.nih.gov/SCIENCE96/. C1 STANFORD UNIV,SCH MED,CTR HUMAN GENOME,DEPT GENET,STANFORD,CA 94305. MIT,WHITEHEAD INST BIOMED RES,CTR GENOME RES,CAMBRIDGE,MA 02142. GENETHON,CNRS,URA 1922,F-91000 EVRY,FRANCE. SANGER CTR,HINXTON CB10 1SA,CAMBRIDGE,ENGLAND. UNIV OXFORD,WELLCOME TRUST CTR HUMAN GENET,NUFFIELD DEPT CLIN MED,OXFORD OX3 7BN,ENGLAND. ROCKEFELLER UNIV,LAB STAT GENET,NEW YORK,NY 10021. CHU LAVAL,CTR RECH,ST FOY,PQ G1V 4G2,CANADA. INST GENOM RES,ROCKVILLE,MD 20850. EUROPEAN MOL BIOL LAB OUTSTN,EUROPEAN BIOINFORMAT INST,CAMBRIDGE CB10 1SD,ENGLAND. CNRS,UPR 420,F-94801 VILLEJUIF,FRANCE. UNIV COLORADO,HLTH SCI CTR,DEPT PHARMACOL,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,PROGRAM MOL BIOL,DENVER,CO 80262. NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892. UNIV CAMBRIDGE,DEPT GENET,CAMBRIDGE CB2 3EH,ENGLAND. RES GENET INC,HUNTSVILLE,AL 35801. KAZUSA DNA RES INST,CHIBA 292,JAPAN. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. MCGILL UNIV,DEPT MED,MONTREAL,PQ H3G 1A4,CANADA. MCGILL UNIV,DEPT HUMAN GENET,MONTREAL,PQ H3G 1A4,CANADA. MCGILL UNIV,MONTREAL GEN HOSP,RES INST,MONTREAL,PQ H3G 1A4,CANADA. RP Schuler, GD (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. RI Beckmann, Jacques S /A-9772-2008; Deloukas, Panos/B-2922-2013; Hicks, Andrew/E-9518-2017; OI Beckmann, Jacques S /0000-0002-9741-1900; Deloukas, Panos/0000-0001-9251-070X; Hicks, Andrew/0000-0001-6320-0411; Hudson, Thomas/0000-0002-1376-4849; Rozen, Steven G./0000-0002-4288-0056 FU NHGRI NIH HHS [HG00206, HG00098, HG00835]; Wellcome Trust NR 62 TC 854 Z9 892 U1 2 U2 40 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 25 PY 1996 VL 274 IS 5287 BP 540 EP 546 DI 10.1126/science.274.5287.540 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900037 PM 8849440 ER PT J AU Schuler, GD Boguski, MS Hudson, TJ Hui, L Ma, J Castle, AB Wu, X Silva, J Nusbaum, HC Birren, BB Slonim, DK Rozen, S Stein, LD Page, D Lander, ES Stewart, EA Aggarwal, A Bajorek, E Brady, S Chu, A Fang, N Hadley, D Harris, M Hussain, S Maratukulam, A Perkins, S Piercy, M Qin, F Reif, T Sanders, C She, X Sun, WL Tabar, P Voyticky, S Mader, C McKusick, KB Fan, JB Cowles, S Quackenbush, J Vollrath, D Myers, RM Cox, DR Butler, A Clee, C Dibling, T East, C Edwards, C Garrett, C Green, L Harrison, P Hicks, A Holloway, E Ranby, S MacGilvery, A Mungall, A Peck, A Wilmer, T Soderlund, C Rice, K Dunham, I Bentley, D Deloukas, P Gyapay, G Chiannilkulchai, N Fizames, C Bentolila, S Duprat, S VegaCzarny, N Muselet, D Drouot, N Morissette, J Weissenbach, J Morissette, J James, MR White, RE Thangarajah, T LouisDitSully, C Day, PJR Goodfellow, PN Schmitt, K Walter, NAR Berry, R Iorio, KR Sikela, JM Polymeropoulos, MH Torres, R Ide, SE Dehejia, A Houlgatte, R Auffray, C Adams, MD Phillips, C Brandon, R Sandusky, M Venter, JC Seki, N Nagase, T Ishikawa, K Nomura, N RodriguezTome, P Matise, TC Lee, WY Swanson, KA Hudson, JR AF Schuler, GD Boguski, MS Hudson, TJ Hui, L Ma, J Castle, AB Wu, X Silva, J Nusbaum, HC Birren, BB Slonim, DK Rozen, S Stein, LD Page, D Lander, ES Stewart, EA Aggarwal, A Bajorek, E Brady, S Chu, A Fang, N Hadley, D Harris, M Hussain, S Maratukulam, A Perkins, S Piercy, M Qin, F Reif, T Sanders, C She, X Sun, WL Tabar, P Voyticky, S Mader, C McKusick, KB Fan, JB Cowles, S Quackenbush, J Vollrath, D Myers, RM Cox, DR Butler, A Clee, C Dibling, T East, C Edwards, C Garrett, C Green, L Harrison, P Hicks, A Holloway, E Ranby, S MacGilvery, A Mungall, A Peck, A Wilmer, T Soderlund, C Rice, K Dunham, I Bentley, D Deloukas, P Gyapay, G Chiannilkulchai, N Fizames, C Bentolila, S Duprat, S VegaCzarny, N Muselet, D Drouot, N Morissette, J Weissenbach, J Morissette, J James, MR White, RE Thangarajah, T LouisDitSully, C Day, PJR Goodfellow, PN Schmitt, K Walter, NAR Berry, R Iorio, KR Sikela, JM Polymeropoulos, MH Torres, R Ide, SE Dehejia, A Houlgatte, R Auffray, C Adams, MD Phillips, C Brandon, R Sandusky, M Venter, JC Seki, N Nagase, T Ishikawa, K Nomura, N RodriguezTome, P Matise, TC Lee, WY Swanson, KA Hudson, JR TI Genome maps .7. The human transcript map SO SCIENCE LA English DT Article C1 WHITEHEAD INST,CTR GENOME RES,CAMBRIDGE,MA 02142. STANFORD HUMAN GENOME CTR,STANFORD,CA. SANGER CTR,CAMBRIDGE,ENGLAND. CNRS,GENETHON,EVRY,FRANCE. CHU LAVAL,CTR RECH,LAVAL,PQ,CANADA. WELLCOME TRUST CTR HUMAN GENET,OXFORD,ENGLAND. UNIV CAMBRIDGE,CAMBRIDGE CB2 1TN,ENGLAND. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. CNRS,GENEXPRESS,VILLEJUIF,FRANCE. INST GENOM RES,ROCKVILLE,MD. KAZUSA DNA RES INST,KISARAZU,JAPAN. EUROPEAN MOL BIOL LAB OUTSTN,EUROPEAN BIOINFORMAT INST,CAMBRIDGE,ENGLAND. ROCKEFELLER UNIV,NEW YORK,NY. RES GENET,HUNTSVILLE,AL. RP Schuler, GD (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. RI Deloukas, Panos/B-2922-2013 OI Deloukas, Panos/0000-0001-9251-070X NR 1 TC 29 Z9 29 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 OCT 25 PY 1996 VL 274 IS 5287 BP 547 EP 558 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900039 PM 8928009 ER PT J AU Lapham, CK Ouyang, J Chandrasekhar, B Nguyen, NY Dimitrov, DS Golding, H AF Lapham, CK Ouyang, J Chandrasekhar, B Nguyen, NY Dimitrov, DS Golding, H TI Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; T-CELL; CD4; COMPONENT(S); MACROPHAGES; MODULATION; TROPISM AB Accessory cell-surface molecules involved in the entry of human immunodeficiency virus-type 1 into cells have recently been identified and shown to belong to the family of chemokine receptors, Treatment of human cell lines with soluble monomeric gp120 at 37 degrees C induced an association between the surface CD4-gp120 complex and a 45-kilodalton protein, which can be down-modulated by the phorbol ester phorbol 12-myristate 13-acetate. The three proteins were coprecipitated from the cell membranes with antibodies to CD4 or to gp120, The 45-kilodalton protein comigrated with fusin on sodium dodecyl sulfate gels and reacted with rabbit antisera to fusin in protein immunoblots, No 45-kilodalton protein could be coprecipitated from similarly treated nonhuman cells, However, infection of 3T3.CD4.401 cells with vaccinia-fusin recombinant virus (vCBYF1), followed by gp120 treatment, resulted in coprecipitation of fusin and CD4.401 molecules from their membranes. Together these data provide evidence for physical association between fusin and the CD4-gp120 complex on cell membranes. C1 NCI, MEMBRANE STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. US FDA, CTR BIOL EVALUAT & RES, FACIL BIOTECHNOL RESOURCES, BETHESDA, MD 20892 USA. RP Lapham, CK (reprint author), US FDA, CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BLDG 29B, ROOM 3G21,HFM 454, 8800 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 17 TC 331 Z9 336 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 25 PY 1996 VL 274 IS 5287 BP 602 EP 605 DI 10.1126/science.274.5287.602 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900048 PM 8849450 ER PT J AU Pruss, D Bartholomew, B Persinger, J Hayes, J Arents, G Moudrianakis, EN Wolffe, AP AF Pruss, D Bartholomew, B Persinger, J Hayes, J Arents, G Moudrianakis, EN Wolffe, AP TI An asymmetric model for the nucleosome: A binding site for linker histones inside the DNA gyres SO SCIENCE LA English DT Article ID POSITIONED NUCLEOSOMES; CHROMATIN STRUCTURE; CRYSTAL-STRUCTURE; GLOBULAR DOMAIN; MMTV PROMOTER; RNA GENE; TRANSCRIPTION; OCTAMER; CORE; H5 AB Histone-DNA contacts within a nucleosome influence the function of trans-acting factors and the molecular machines required to activate the transcription process, The internal architecture of a positioned nucleosome has now been probed with the use of photoactivatable cross-linking reagents to determine the placement of histones along the DNA molecule. A model for the nucleosome is proposed in which the winged-helix domain of the linker histone is asymmetrically located inside the gyres of DNA that also wrap around the core histones. This domain extends the path of the protein superhelix to one side of the core particle. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. SO ILLINOIS UNIV,SCH MED,DEPT MED BIOCHEM,CARBONDALE,IL 62901. UNIV ROCHESTER,SCH MED & DENT,DEPT BIOCHEM,ROCHESTER,NY 14642. JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. NR 41 TC 142 Z9 142 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD OCT 25 PY 1996 VL 274 IS 5287 BP 614 EP 617 DI 10.1126/science.274.5287.614 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900051 PM 8849453 ER PT J AU Chan, CK Hofrichter, J Eaton, WA AF Chan, CK Hofrichter, J Eaton, WA TI Optical triggers of protein folding SO SCIENCE LA English DT Article ID MODELS; EVENTS RP Chan, CK (reprint author), NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20882, USA. NR 14 TC 38 Z9 38 U1 1 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 OCT 25 PY 1996 VL 274 IS 5287 BP 628 EP 629 DI 10.1126/science.274.5287.628 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900055 PM 8928010 ER PT J AU Zietkiewicz, E Makalowski, W Mitchell, G Labuda, D AF Zietkiewicz, E Makalowski, W Mitchell, G Labuda, D TI Complementary DNA for 15-kilodalton B cell growth factor: Misassigned SO SCIENCE LA English DT Article ID PHYLOGENETIC ANALYSIS; SEQUENCE C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20892. RP Zietkiewicz, E (reprint author), UNIV MONTREAL,HOP ST JUSTINE,CTR RECH,MONTREAL,PQ H3T 1C5,CANADA. RI Makalowski, Wojciech/I-2843-2016 NR 8 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 OCT 25 PY 1996 VL 274 IS 5287 BP 631 EP 631 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VN919 UT WOS:A1996VN91900059 PM 8928012 ER PT J AU Tevzadze, GG Mushegian, AR Esposito, RE AF Tevzadze, GG Mushegian, AR Esposito, RE TI The SPO1 gene product required for meiosis in yeast has a high similarity to phospholipase B enzymes SO GENE LA English DT Article DE Saccharomyces cervisiae; meiosis; spindle pole body; gene expression; phospholipase B ID SACCHAROMYCES-CEREVISIAE AB The SPO1 gene of Saccharomyces cerevisiae has been cloned and sequenced. The Spo1 protein reveals significant similarity with fungal phospholipase B (PLB) enzymes. Features of the SPO1 gene sequence are presented. C1 UNIV CHICAGO, DEPT MOL GENET & CELL BIOL, CHICAGO, IL 60637 USA. NIH, NATL CTR BIOTECHNOL INFORMAT, NATL LIB MED, BETHESDA, MD 20894 USA. OI Mushegian, Arcady/0000-0002-6809-9225 NR 8 TC 12 Z9 13 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD OCT 24 PY 1996 VL 177 IS 1-2 BP 253 EP 255 DI 10.1016/0378-1119(96)00261-2 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA VR644 UT WOS:A1996VR64400040 PM 8921875 ER PT J AU Ali, SF Newport, GD Slikker, W Rothman, RB Baumann, MH AF Ali, SF Newport, GD Slikker, W Rothman, RB Baumann, MH TI Neuroendocrine and neurochemical effects of acute ibogaine administration: A time course evaluation SO BRAIN RESEARCH LA English DT Article DE ibogaine; prolactin; corticosterone; dopamine; serotonin ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; PARASAGITTAL ZONES; GROWTH-HORMONE; MK-801 BINDING; RATS; MORPHINE; DOPAMINE; PHENCYCLIDINE; PROLACTIN AB Ibogaine (IBO) is an indole alkaloid that is reported to facilitate drug abstinence in substance abusers. Despite considerable investigation, the mechanism of IBO action in vivo and its suitability as a treatment for drug addiction remains unclear. The present study was designed to evaluate the time-course effects of acute IBO on neuroendocrine and neurochemical indices. Adult male rats were treated with i.p. saline or 50 mg/kg IBO and sacrificed 15: 30, 60, 120 min and 24 h later. Trunk blood was collected for hormone measures and brains were dissected for neurochemical analyses. IBO produced a rapid elevation in plasma prolactin that declined to control levels by 60 min. Corticosterone levels increased 15 min after drug administration, continued to increase for 120 min, but returned to control levels 24 h after dosing. IBO decreased dopamine (DA) concentrations in the striatum and frontal cortex at 30, 60 and 120 min after injection while DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were elevated over the same time period. 24 h after IBO, DOPAC concentrations in striatum and HVA levels in the frontal cortex were below control values. Serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were decreased at 60 min after IBO administration only in the striatum. These data indicate that a single injection of IBO produces a spectrum of effects that includes: (I) elevation of plasma prolactin and corticosterone, (2) short- and long-term effects on DA neurotransmission, and (3) modest, transient effects of 5-HT neurotransmission. The effects of IBO reported herein may have relevance to the anti-addictive properties of this drug, and this proposal warrants further investigation. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,NIH,IRP,BALTIMORE,MD 21224. US FDA,NATL CTR TOXICOL RES,NEUROCHEM LAB,DIV NEUROTOXICOL,JEFFERSON,AR 72079. NR 36 TC 17 Z9 18 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 OCT 21 PY 1996 VL 737 IS 1-2 BP 215 EP 220 DI 10.1016/0006-8993(96)00734-2 PG 6 WC Neurosciences SC Neurosciences & Neurology GA VR614 UT WOS:A1996VR61400025 PM 8930368 ER PT J AU Ishida, H Matsumura, T Salgaller, ML Ohmizono, Y Kadono, Y Sawada, T AF Ishida, H Matsumura, T Salgaller, ML Ohmizono, Y Kadono, Y Sawada, T TI MAGE-1 and MAGE-3 or -6 expression in neuroblastoma-related pediatric solid tumors SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA; GENE MAGE-1; ANTIGEN; IMMUNOTHERAPY; PERSPECTIVES; CARCINOMAS; CODES AB MAGE-1 and MAGE-3 or -6 are genes encoding melanoma-rejection antigens recognized by cytotoxic T lymphocytes in an HLA-A1 restriction manner. MAGE-1 and MAGE-3 or -6 were expressed in 5/14 (36%) and 6/14 (43%) neuroblastoma (NB) cell lines, and in 20/41 (49%) and 24/41 (59%) clinical NB-related tumors, respectively. Additionally, they were also expressed in pediatric tumors of other types such as rhabdomyosarcoma and Wilms' tumor. MAGE-1 expression at a functional level in tumor cells was confirmed by the cytotoxicity assay using MAGE-1-specific tumor-infiltrating lymphocytes (TIL). In clinical NB-related tumors, MAGE-3 or -6 expression demonstrated an inverse correlation to clinical stage. Furthermore, although the sample number was small, the incidence of MAGE-1 and/or MAGE-3 or -6 expression was significantly correlated to the absence of metastasis and a move favorable clinical outcome (p < 0.05). These results may suggest that NB cells silent far the expression of MAGE genes escape from the host anti-tumor immune response and consequently retain a growth advantage. Finally, NB-related tumors could be reliable candidates for immunotherapy targeted towards MAGE gene products. (C) 1996 Wiley-Liss, Inc. C1 KYOTO PREFECTURAL UNIV MED,DEPT PEDIAT,KYOTO 602,JAPAN. NCI,SURG BRANCH,BETHESDA,MD 20892. NR 18 TC 31 Z9 32 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 21 PY 1996 VL 69 IS 5 BP 375 EP 380 DI 10.1002/(SICI)1097-0215(19961021)69:5<375::AID-IJC4>3.0.CO;2-2 PG 6 WC Oncology SC Oncology GA VR182 UT WOS:A1996VR18200004 PM 8900370 ER PT J AU Myers, RB Brown, D Oelschlager, DK Waterbor, JW Marshall, ME Srivastava, S Stockard, CR Urban, DA Grizzle, WE AF Myers, RB Brown, D Oelschlager, DK Waterbor, JW Marshall, ME Srivastava, S Stockard, CR Urban, DA Grizzle, WE TI Elevated serum levels of p105(erbB-2) in patients with advanced-stage prostatic adenocarcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID BREAST-CANCER PATIENTS; GROWTH-FACTOR RECEPTOR; C-ERBB-2 ONCOPROTEIN; EXTRACELLULAR DOMAIN; OVARIAN-CANCER; POOR SURVIVAL; NEU ONCOGENE; HER-2/NEU; EXPRESSION; CELLS AB Expression of a truncated or extracellular form (p105(erbB-2)) of p185(erbB-2) has been demonstrated in the sera of breast cancer patients. We examined the levels of p105(erbB-2) in, the sera of patients with various stages of prostatic adenocarcinoma, in patients with benign prostatic hyperplasia (BPH) and in a series of control male patients hospitalized for illnesses unrelated to the prostate. p105(erbB-2) levels did not differ between the controls and BPH patients or between these groups and patients with stage A, B or C adenocarcinomas. In contrast, serum p105(erbB-2) levels of patients with stage D adenocarcinomas were significantly elevated when compared with either control or BPH patients. There was no correlation between PSA and p105(erbB-2) levels among controls, patients with BPH or patients with prostate cancer. Patients with poorly differentiated tumors (combined Gleason score >7) or moderately differentiated tumors (combined Gleason scare 5-7) had higher p105(erbB-2) levels as compared to patients with well-differentiated tumors (combined Gleason score <5), though this difference was not statistically significant. There was no correlation between serum p105(erbB-2) levels and p185(erbB-2) expression in malignant tissue, as determined by immunohistochemistry. However, patients with moderate to strong expression of p185(erbB-2) within the adenocarcinomas were approximately 4 times more likely to demonstrate elevated serum p105(erbB-2) levels as compared with patients with low expression of p185(erbB-2). (C) 1996 Wiley-Liss, Inc. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT EPIDEMIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT SURG,BIRMINGHAM,AL 35294. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [N01CN-15340-02] NR 29 TC 24 Z9 24 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 21 PY 1996 VL 69 IS 5 BP 398 EP 402 DI 10.1002/(SICI)1097-0215(19961021)69:5<398::AID-IJC8>3.0.CO;2-0 PG 5 WC Oncology SC Oncology GA VR182 UT WOS:A1996VR18200008 PM 8900374 ER PT J AU Derynck, R Gelbart, WM Harland, RM Heldin, CH Kern, SE Massague, J Melton, DA Mlodzik, MB Padgett, RW Roberts, AB Smith, J Thomsen, GH Vogelstein, B Wang, XF AF Derynck, R Gelbart, WM Harland, RM Heldin, CH Kern, SE Massague, J Melton, DA Mlodzik, MB Padgett, RW Roberts, AB Smith, J Thomsen, GH Vogelstein, B Wang, XF TI Nomenclature: Vertebrate mediators of TGF beta family signals SO CELL LA English DT Letter C1 UNIV CALIF SAN FRANCISCO,DEPT ANAT,PROGRAM CELL & DEV BIOL,SAN FRANCISCO,CA 94143. HARVARD UNIV,DEPT CELLULAR & DEV BIOL,CAMBRIDGE,MA 02138. UNIV CALIF BERKELEY,DEPT MOL & CELL BIOL,DIV BIOCHEM & MOL BIOL,BERKELEY,CA 94720. LUDWIG INST CANC RES,S-75124 UPPSALA,SWEDEN. JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. MEM SLOAN KETTERING CANC CTR,DEPT CELL BIOL,NEW YORK,NY 10021. HOWARD HUGHES MED INST,SEATTLE,WA. EUROPEAN MOL BIOL LAB,DEV BIOL PROGRAMME,D-69117 HEIDELBERG,GERMANY. RUTGERS STATE UNIV,WAKSMAN INST,DEPT MOL BIOL & BIOCHEM,PISCATAWAY,NJ 08855. RUTGERS STATE UNIV,WAKSMAN INST,CANC INST NEW JERSEY,PISCATAWAY,NJ 08855. NCI,NATL INST HLTH,BETHESDA,MD 20892. NATL INST MED RES,LONDON NW7 1AA,ENGLAND. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. SUNY STONY BROOK,DEPT BIOCHEM & CELL BIOL,INST CELL & DEV BIOL,STONY BROOK,NY 11794. RP Derynck, R (reprint author), UNIV CALIF SAN FRANCISCO,DEPT GROWTH & DEV,PROGRAM CELL & DEV BIOL,SAN FRANCISCO,CA 94143, USA. NR 2 TC 138 Z9 145 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 18 PY 1996 VL 87 IS 2 BP 173 EP 173 DI 10.1016/S0092-8674(00)81335-5 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN403 UT WOS:A1996VN40300005 PM 8861901 ER PT J AU Holtschke, T Lohler, J Kanno, Y Fehr, T Giese, N Rosenbauer, F Lou, J Knobeloch, KP Gabriele, L Waring, JF Bachmann, MF Zinkernagel, RM Morse, HC Ozato, K Horak, I AF Holtschke, T Lohler, J Kanno, Y Fehr, T Giese, N Rosenbauer, F Lou, J Knobeloch, KP Gabriele, L Waring, JF Bachmann, MF Zinkernagel, RM Morse, HC Ozato, K Horak, I TI Immunodeficiency and chronic myelogenous leukemia-like syndrome in mice with a targeted mutation of the ICSBP gene SO CELL LA English DT Article ID INTERFERON REGULATORY FACTOR; SEQUENCE-BINDING-PROTEIN; FACTOR FAMILY; T-CELLS; HEMATOPOIETIC-CELLS; FACTOR-II; GAMMA; ALPHA; IFN; TRANSCRIPTION AB Interferon consensus sequence binding protein (ICSBP) is a transcription factor of the interferon (IFN) regulatory factor (IRF) family. Mice with a null mutation of ICSBP exhibit two prominent phenotypes related to previously described activities of the IRF family. The fi rst is enhanced susceptibility to virus infections associated with impaired production of IFN gamma. The second is deregulated hematopoiesis in both ICSBP-/- and ICSBP+/- mice that manifests as a syndrome similar to human chronic myelogenous leukemia. The chronic period of the disease progresses to a fatal beast crisis characterized by a clonal expansion of undifferentiated cells. Normal mice injected with cells from mice in blast crisis developed acute leukemia within 6 weeks of transfer. These results suggest a novel role for ICSBP in regulating the proliferation and differentiation of hematopoietic progenitor cells. C1 UNIV WURZBURG,INST VIROL & IMMUNBIOL,D-8700 WURZBURG,GERMANY. UNIV HAMBURG,HEINRICH PETTE INST,HAMBURG,GERMANY. NICHHD,NATL INST HLTH,LAB MOL GROWTH REGULAT,BETHESDA,MD 20205. UNIV ZURICH,INST EXPT IMMUNOL,CH-8091 ZURICH,SWITZERLAND. NIAID,NATL INST HLTH,IMMUNOPATHOL LAB,BETHESDA,MD 20205. RES INST MOL PHARM,DEPT MOL GENET,D-12207 BERLIN,GERMANY. RI Kanno, Yuka/B-5802-2013; OI Kanno, Yuka/0000-0001-5668-9319; Morse, Herbert/0000-0002-9331-3705 NR 41 TC 434 Z9 439 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 18 PY 1996 VL 87 IS 2 BP 307 EP 317 DI 10.1016/S0092-8674(00)81348-3 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN403 UT WOS:A1996VN40300018 PM 8861914 ER PT J AU Werner, MH Clore, GM Fisher, CL Fisher, RJ Trinh, L Shiloach, J Gronenborn, AM AF Werner, MH Clore, GM Fisher, CL Fisher, RJ Trinh, L Shiloach, J Gronenborn, AM TI The solution structure of the human ETS1-DNA complex reveals a novel mode of binding and true side chain intercalation. (vol 83, pg 761, 1995) SO CELL LA English DT Correction, Addition C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21707. NIDDK,NATL INST HLTH,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20895. RP Werner, MH (reprint author), NIDDK,NATL INST HLTH,PHYS CHEM LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008; Fisher, Robert/B-1431-2009 OI Clore, G. Marius/0000-0003-3809-1027; NR 2 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 18 PY 1996 VL 87 IS 2 BP U23 EP U23 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN403 UT WOS:A1996VN40300022 ER PT J AU Teramoto, H Crespo, P Coso, OA Igishi, T Xu, NZ Gutkind, JS AF Teramoto, H Crespo, P Coso, OA Igishi, T Xu, NZ Gutkind, JS TI The small GTP-binding protein Rho activates c-Jun N-terminal kinases stress-activated protein kinases in human kidney 293T cells - Evidence for a Pak-independent signaling pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERINE THREONINE KINASE; MAP KINASE; SACCHAROMYCES-CEREVISIAE; GTPASES; RAS; HOMOLOG; CDC42; RAC1 AB Work from a number of laboratories has established a role for certain small GTP-binding proteins in controlling the enzymatic activity of a family of serine-threonine kinases known as mitogen-activated protein kinases (MAPKs). MAPKs have been classified into three subfamilies: extracellular signal-regulated kinases (ERKs), also known as MAPKs; c-Jun N-terminal kinases (JNKs); and p38 kinase. Whereas Ras controls the activation of MAPKs, we and others have recently observed that in certain cells, the small GTP-binding proteins Rad and Cdc42 but not Rho regulate the activity of JNKs. Furthermore, because Rad and Cdc42 but not Rho bind and activate a kinase known as Pak1, it has been suggested that Pak1 is the most upstream component of the pathway linking these GTPases to JNK. However, in both yeast and mammalian cells, Rho1p, a Rho homologue, and RhoA, respectively, directly interact with a number of proteins, including kinases related to protein kinase C. In addition, in yeast, Rho1p controls the activity of a MAPK cascade involved in bud formation. Considering this diversity of target molecules for small GTP-binding proteins, their likely tissue specific distribution, and the potential role for Rho in signaling to a kinase cascade, we decided to extend our initial analysis, exploring the ability of Ras and Rho-related GTP-binding proteins to activate MAPK or JNK in a variety of cell lines. We found that in the human kidney epithelial cell line, 293T, Cdc42 and all Rho proteins, RhoA, RhoB, and RhoC, but not Rac or Ras can induce activation of JNK. Furthermore, we provide evidence that signaling from Rho proteins to JNK in 293T cells does not involve Pak1. Taken together these findings demonstrate that Rho signals to JNK in a cell type-specific manner and suggest the existence of a novel, Pak1-independent signaling route communicating the Rho family of small GTP-binding proteins to the JNK pathway. C1 NIDR,MOL SIGNALING UNIT,CELLULAR DEV & ONCOL LAB,NIH,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009; Crespo, Piero/M-3273-2014 OI Crespo, Piero/0000-0003-2825-7783 NR 28 TC 157 Z9 157 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 OCT 18 PY 1996 VL 271 IS 42 BP 25731 EP 25734 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000003 PM 8824197 ER PT J AU Hayes, JJ Kaplan, R Ura, K Pruss, D Wolffe, A AF Hayes, JJ Kaplan, R Ura, K Pruss, D Wolffe, A TI A putative DNA binding surface in the globular domain of a linker histone is not essential for specific binding to the nucleosome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIBOSOMAL-RNA GENE; COOPERATIVE BINDING; CHROMATIN; H5; TRANSCRIPTION; CORE; EXPRESSION; H1; TEMPLATES; CONTACTS AB A fundamental step in the assembly of native chromatin is the specific recognition and binding of linker histones to the nucleoprotein subunit known as the nucleosome. A first step in defining this important interaction is the determination of residues within Linker histones that are important for the structure-specific recognition of the nucleosome core. By combining in vitro assays for the native binding activity of linker histones and site-directed mutagenesis, we have examined a cluster of basic residues within the globular domain of H1(0), a somatic Linker histone variant from Xenopus laevis. We show that these residues, which comprise a putative DNA binding surface within the globular domain, do not play an essential role in the structure-specific binding of a linker histone to the nucleosome. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. RP Hayes, JJ (reprint author), UNIV ROCHESTER,MED CTR,DEPT BIOCHEM,ROCHESTER,NY 14642, USA. FU NIGMS NIH HHS [R01GM52426] NR 38 TC 28 Z9 28 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 OCT 18 PY 1996 VL 271 IS 42 BP 25817 EP 25822 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000017 PM 8824211 ER PT J AU Cravchik, A Sibley, DR Gejman, PV AF Cravchik, A Sibley, DR Gejman, PV TI Functional analysis of the human D-2 dopamine receptor missense variants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID D2 RECEPTOR; STRUCTURAL POLYMORPHISM; MOLECULAR VARIANT; GENE; SCHIZOPHRENIA; ASSOCIATION; ALCOHOLISM; IDENTIFICATION; MUTATIONS; DISEASE AB The human dopamine D-2 receptor gene (DRD2) has three poly-morphic variants that predict the amino acid substitutions Val(96) --> Ala, Pro(310) --> Ser, and Ser(311) --> Cys in the receptor protein. We have investigated the ligand binding and signal transduction properties of these human D-2 receptor variants by stably expressing them in cultured mammalian cells. The Cys(311) and Ser(310) variants of the human D-2 receptor, which involve substitutions located in the third cytoplasmic loop, were markedly less effective in inhibiting cAMP synthesis than the most prevalent form (Pro(310), Ser(311)). Despite this difference, the Cys(311) and Ser(310) variants couple to G proteins in CHO-K1 (Chinese hamster ovary) cells. The impairment of the Cys(311) and Ser(310) variants to inhibit cAMP levels thus appears to result from a reduced ability of those variant receptors to activate the appropriate G(i)-like protein. The demonstration of substantial functional differences between DRD2 gene variants found in the human population might have important pharmacological implications given the widespread use of D-2 receptor blocking drugs in the treatment of schizophrenia and other psychiatric disorders. C1 NIMH,UNIT MOL CLIN INVEST,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NINCDS,MOL NEUROPHARMACOL SECT,NIH,BETHESDA,MD 20892. NR 36 TC 106 Z9 108 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 OCT 18 PY 1996 VL 271 IS 42 BP 26013 EP 26017 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000046 PM 8824240 ER PT J AU Krishna, MC Samuni, A Taira, J Goldstein, S Mitchell, JB Russo, A AF Krishna, MC Samuni, A Taira, J Goldstein, S Mitchell, JB Russo, A TI Stimulation by nitroxides of catalase-like activity of hemeproteins - Kinetics and mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPERM WHALE MYOGLOBIN; HYDROGEN-PEROXIDE; FREE-RADICALS; SUPEROXIDE; OXIDATION; FERRYLMYOGLOBIN; EPOXIDATION; HEMOGLOBIN; REDUCTION; STYRENE AB The ability of stable nitroxide radicals to detoxify hypervalent heme proteins such as ferrylmyoglobin (MbFe(IV)) produced in the reaction of metmyoglobin (MbFe(III)) and H2O2 was evaluated by monitoring O-2 evolution, H2O2 depletion, and redox changes of the heme prosthetic group, The rate of H2O2 depletion and O-2 evolution catalyzed by MbFe(III) was enhanced by stable nitroxides such as 4-OH-2,2,6,6-tetramethyl-piperidinoxyl (TPL) in a catalytic fashion, The reduction of MbFe(IV) to MbFe(III) was the rate-limiting step, Excess TPL over MbFe(III) enhanced catalase-like activity more than 4-fold. During dismutation of H2O2, [TPL] and [MbFe(IV)] remained constant, NADH caused: (a) inhibition of H2O2 decay; (b) progressive reduction of TPL to its respective hydroxylamine TPL-H; and (c) arrest/inhibition of oxygen evolution or elicit consumption of O-2. Following depletion of NADH the evolution of O-2 resumed, and the initial concentration of TPL was re stored, Kinetic analysis showed that two distinct forms of MbFe(IV) might be involved in the process, In summary, by shuttling between two oxidation states, namely nitroxide and oxoammonium cation, stable nitroxides enhance the catalase mimic activity of MbFe(III), thus facilitating H2O2 dismutation accompanied by O-2 evolution and providing protection against hypervalent heme proteins. C1 HEBREW UNIV JERUSALEM,SCH MED,DEPT BIOL MOL,IL-91120 JERUSALEM,ISRAEL. RP Krishna, MC (reprint author), NCI,RADIAT BIOL BRANCH,NIH,BLDG 10,RM B3-B69,BETHESDA,MD 20892, USA. NR 42 TC 134 Z9 135 U1 1 U2 8 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 OCT 18 PY 1996 VL 271 IS 42 BP 26018 EP 26025 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000047 PM 8824241 ER PT J AU Hoang, B Moos, M Vukicevic, S Luyten, FP AF Hoang, B Moos, M Vukicevic, S Luyten, FP TI Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID SEQUENCE; POLARITY GENE; EXPRESSION; OSTEOGENIN; CLEAVAGE; SITES AB Articular cartilage extracts were prepared to characterize protein fractions with in vivo chondrogenic activity (Chang, S., Hoang, B., Thomas, J. T., Vukicevic, S., Luyten, F. P., Ryba, N. J. P., Kozak, C. A., Reddi, A. H., and Woos, M. (1994) J. Biol. Chem. 269, 28227-28234). Trypsin digestion of highly purified chondrogenic protein fractions allowed the identification of several unique peptides by amino acid sequencing. We discovered a novel cDNA encoding a deduced 36-kDa protein by using degenerate oligonucleotide primers derived from a 30-residue peptide in reverse transcription polymerase chain reactions. Its N-terminal domain showed similar to 50%, amino acid identity to the corresponding region of the Drosophila gene frizzled, which has been implicated in the specification of hair polarity during development. Hydropathy and structural analyses of the open reading frame revealed the presence of a signal peptide and a hydrophobic domain followed by multiple potential serine/threonine phosphorylation sites and a serine-rich C terminus. Cell fractionation studies of primary bovine articular chondrocytes and transfected COS cells suggested that the protein is membrane-associated. In situ hybridization and immunostaining of human embryonic sections demonstrated predominant expression surrounding the chondrifying bone primordia and subsequently in the chondrocytes of the epiphyses in a graded distribution that decreased toward the primary ossification center. Transcripts were present in the craniofacial structures but not in the vertebral bodies. Because it is expressed primarily in the cartilaginous cores of developing long bones during embryonic and fetal development (6-13 weeks) and is homologous to the polarity-determining gene frizzled, we believe that this gene, which we named frzb, is involved in morphogenesis of the mammalian skeleton. C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892. MED SCH ZAGREB,DEPT ANAT,ZAGREB 41000,CROATIA. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 29 TC 181 Z9 188 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 OCT 18 PY 1996 VL 271 IS 42 BP 26131 EP 26137 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000063 PM 8824257 ER PT J AU Steinert, PM Kim, SY Chung, SI Marekov, LN AF Steinert, PM Kim, SY Chung, SI Marekov, LN TI The transglutaminase 1 enzyme is variably acylated by myristate and palmitate during differentiation in epidermal keratinocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECESSIVE LAMELLAR ICHTHYOSIS; CORNIFIED CELL-ENVELOPE; CROSS-LINKING ENZYMES; MEMBRANE ANCHORAGE; ALPHA-SUBUNIT; PROTEIN; EXPRESSION; PALMITOYLATION; SUBSTRATE; BINDING AB The transglutaminase 1 (TGase 1) enzyme is involved in the formation of a cornified cell envelope in terminally differentiating epidermal keratinocytes. The enzyme is present in proliferating cells but is more abundantly expressed in differentiating cells and exists in several intact or proteolytically processed cytosolic or membrane-anchored forms, We show here that the equilibrium partitioning of TGase 1 between the cytosol and membranes is controlled by variable modification by myristate and palmitate, During synthesis, it is constitutively N-myristoylated. Later, it is modified by an average of two S-myristoyl adducts in proliferating cells or one S-palmitoyl adduct in differentiating cells. The three myristoyl adducts of the former provide more robust anchorage to membranes than the one myristoyl and one palmitoyl adduct of the latter, The half-lives of the S-myristoyl and especially the S-palmitoyl adducts are less than that of the TGase 1 protein, suggesting a mechanism for cycling off membranes. In in vitro overlay assays, the S-acylated 10-kDa anchorage fragment facilitates binding of TGase 1 forms, supporting a mechanism of cycling back onto membranes in vivo. We conclude that differential acylation increases the repertoire of functional TGase 1 forms, depending on the differentiation state of epidermal keratinocytes. C1 PACIFIC RES & DEV CORP,KIHEUNG EUP 449900,SOUTH KOREA. GREEN CROSS CO,KYOUNGGI DO 449900,SOUTH KOREA. RP Steinert, PM (reprint author), NIAMSD,SKIN BIOL LAB,NIH,BLDG 6,ROOM 425,BETHESDA,MD 20892, USA. NR 40 TC 69 Z9 71 U1 2 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 OCT 18 PY 1996 VL 271 IS 42 BP 26242 EP 26250 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000080 PM 8824274 ER PT J AU Finan, PM Soames, CJ Wilson, L Nelson, DL Stewart, DM Truong, O Hsuan, JJ Kellie, S AF Finan, PM Soames, CJ Wilson, L Nelson, DL Stewart, DM Truong, O Hsuan, JJ Kellie, S TI Identification of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROLINE-RICH PEPTIDES; PHAGOCYTE NADPH OXIDASE; SH3 DOMAIN; TYROSINE KINASES; CRYSTAL-STRUCTURES; FOCAL ADHESION; BINDING MOTIF; HIGH-AFFINITY; GENE; SPECIFICITY AB Src homology 3 (SH3) domains have been shown to mediate selected interactions between signaling molecules and are essential for the activation of a number of receptor-driven pathways. The Wiskott-Aldrich syndrome protein was identified as a protein that associated selectively with the SH3 domains derived from c-Src, p85 alpha, phospholipase C gamma 1, and c-Fgr. Significantly reduced association was detected to the N-terminal SH3 domain and the tandem SH3 domains of p47(phox), and no binding was detected to the SH3 domain of n-Src, the C-terminal SH3 domain of p47(phox), or either of the SH3 domains of p67(phox). Three peptides corresponding to potential Wiskott-Aldrich syndrome protein SH3 domain binding moths were found to inhibit its association with c-Src, Fgr, and phospholipase C gamma 1 SH3 domains, but not the p85 alpha SH3 domain. These peptides have the sequences MRRQEPLPPPPPPSRG, TGRSGPLPPPPPGA, and KGRSGPLPPVPLGI and show homology with other SH3 domain binding motifs. It is possible that the intracellular association of Wiskott-Aldrich syndrome protein with other signaling proteins is mediated by its SH3 domain-binding regions, and this may play a role in its putative function as a regulatory molecule in immune cells. C1 LITTLEMORE HOSP, YAMANOUCHI RES INST, OXFORD OX4 4XN, ENGLAND. NCI, METAB BRANCH, NIH, BETHESDA, MD 20892 USA. UCL, LUDWIG INST CANC RES, LONDON W1P 8BT, ENGLAND. UCL, DEPT BIOCHEM & MOL BIOL, LONDON W1E 6BT, ENGLAND. RI Kellie, Stuart /A-6036-2010; Hsuan, Justin/C-8825-2009 OI Hsuan, Justin/0000-0001-6083-7564 NR 54 TC 54 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 18 PY 1996 VL 271 IS 42 BP 26291 EP 26295 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000086 PM 8824280 ER PT J AU Kobayashi, J ApplebaumBowden, D Dugi, KA Brown, DR Kashyap, VS Parrott, C Duarte, C Maeda, N SantamarinaFojo, S AF Kobayashi, J ApplebaumBowden, D Dugi, KA Brown, DR Kashyap, VS Parrott, C Duarte, C Maeda, N SantamarinaFojo, S TI Analysis of protein structure-function in vivo - Adenovirus-mediated transfer of lipase lid mutants in hepatic lipase-deficient mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LIPOPROTEIN-LIPASE; HIGH-DENSITY-LIPOPROTEIN; SITE-DIRECTED MUTAGENESIS; PANCREATIC LIPASE; HUMAN-PLASMA; INTERFACIAL ACTIVATION; TRIGLYCERIDE LIPASE; CATALYTIC SITE; GENE; SEQUENCE AB Hepatic lipase (HL) and lipoprotein lipase (LPL) are key enzymes involved in the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins. Despite their similarities, the role that each of these two lipases play in the metabolism of triglyceride-rich lipoproteins and high density lipoproteins is distinct. In order to identify structural domains that may confer the different substrate specificities between HL and LPL, we have utilized a novel approach for performing structure-function analysis of a protein, in vivo, by using recombinant adenovirus vectors to express native and mutant enzymes in an animal model for a human genetic deficiency, HL-deficient mice (n = 19) characterized by increased plasma cholesterol and phospholipid concentrations were injected with adenovirus expressing luciferase (rLucif-AdV), native hepatic (rHL-AdV), and lipoprotein lipase (rLPL-AdV) or lipase mutants in which the lid covering the catalytic site of either enzyme was exchanged (rHL+LPL lid-AdV and rLPL+HL lid-AdV). Mice injected with rLucif-AdV had no changes in post-heparin HL and LPL activities (217 +/- 29 and 7 +/- 2 nmol/min/ml, respectively) as well as plasma lipids. Despite expression of similar levels of post-heparin plasma lipase activity on day 5 post-adenovirus infusion (9806 +/- 915 and 9677 +/- 2033 nmol/min/ml, respectively) mice injected with rHL-AdV or rHL+LPL lid-AdV demonstrated marked differences in the reduction of plasma phospholipids (70% and 32%, respectively, p < 0.005), Similarly, despite post-heparin plasma lipolytic activities of 4495 +/- 534 and 4844 +/- 1336 nmol/min/ml, injection of rLPL-AdV or rLPL+HL lid-AdV resulted in phospholipid reductions of 31% and 81% (p < 0.005). Exchange of the lipase lid did not significantly alter plasma triglyceride concentrations. Thus, preferential in vivo hydrolysis of phospholipids was demonstrated in animals expressing lipases containing the HL lid but not the LPL lid. These studies identify the lipase lid as a major structural motif responsible for conferring the different in vivo phospholipase activities between HL and LPL, a function which may modulate the distinct physiological roles of these two similar lipolytic enzymes in lipoprotein metabolism. The use of recombinant adenovirus to express mutant proteins in animal models for human genetic deficiencies represents a powerful, new approach for performing structure-function analysis of proteins in vivo. C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27599. NR 44 TC 30 Z9 30 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 OCT 18 PY 1996 VL 271 IS 42 BP 26296 EP 26301 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000087 PM 8824281 ER PT J AU Donovan, JA Ota, Y Langdon, WY Samelson, LE AF Donovan, JA Ota, Y Langdon, WY Samelson, LE TI Regulation of the association of p120(cbl) with Grb2 in Jurkat T cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; C-CBL PROTOONCOGENE; RECEPTOR SIGNAL TRANSDUCTION; ANTIGEN RECEPTOR; SH3 DOMAIN; ZETA-CHAIN; PHOSPHORYLATED PROTEIN; HEMATOPOIETIC-CELLS; EXCHANGE PROTEIN; V-CBL AB The c-cbl protooncogene product (p120(cbl)) is a known substrate of multiple tyrosine kinases. It is found in complexes with critical signal transduction molecules, including the linker protein Grb2. Here, we demonstrate using an immobilized Grb2-binding peptide that the Grb2-p120(cbl) complex dissociates in vivo following engagement of the T-cell antigen receptor in Jurkat T-cells. The early kinetics of this dissociation correlate with the known time course of tyrosine phosphorylation of p120(cbl) and other substrates. This dissociation persists In vivo even when p120(cbl) becomes dephosphorylated to basal levels. However, this decreased association is not observed in protein overlay assays on nitrocellulose membranes in which a Grb2 fusion protein is used to detect p120(cbl) from stimulated or unstimulated cells. These data suggest that the tyrosine phosphorylation of p120(cbl) does not completely account for the regulation of its association with Grb2. Additionally, we used truncation mutations of p120(cbl) to map the p120(cbl)-Grb2 interaction to amino acids 481-528 of p120(cbl); this interaction is stronger in longer constructs that include additional proline-rich motifs. The in vivo regulation of the Grb2-p120(cbl) complex further supports the idea of a significant role for p120(cbl) in receptor-mediated signaling pathways. C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. UNIV WESTERN AUSTRALIA,NEDLANDS,WA 6009,AUSTRALIA. NR 59 TC 51 Z9 51 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 OCT 18 PY 1996 VL 271 IS 42 BP 26369 EP 26374 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000098 PM 8824292 ER PT J AU Li, WQ Li, W Chen, XH Kelley, CA Alimandi, M Zhang, JC Chen, Q Bottaro, DP Pierce, JH AF Li, WQ Li, W Chen, XH Kelley, CA Alimandi, M Zhang, JC Chen, Q Bottaro, DP Pierce, JH TI Identification of tyrosine 187 as a protein kinase C-delta phosphorylation site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATION; ACTIVATION; PKC AB Protein kinase C-delta (PKC-delta) has been demonstrated to be phosphorylated on tyrosine residue(s) in many different biological systems (Li, W., Yu, J.-C., Michieli, P., Beeler, J. F., Ellmore, N., Heidaran, M. A., and Pierce, J. H. (1994) Mol. Cell. Biol. 14, 6727-6735; Li, W., Mischak, H., Yu, J.-C., Wang, L.-M., Mushinski, J. F., Heidaran, M. A., and Pierce, J. H. (1994) J. Biol. Chem. 269, 2349-2352; Denning, M. F., Dlugosz, A. A., Howett, M. A., and Yuspa, S. H. (1993) J. Biol. Chem. 268, 26079-26081). Tyrosine phosphorylation of PKC-delta has also been shown to occur in vitro when purified PKC-delta is coincubated with different tyrosine kinase sources. However, the tyrosine phosphorylation site(s) is currently unknown and the exact effect of this phosphorylation on its serine/threonine kinase activity and biological functions is still controversial. To directly investigate the potential role of PKC-delta tyrosine phosphorylation, tyrosine 187 was converted to phenylalanine (PKC-delta Y187F) by site-directed mutagenesis, and expression vectors containing PKC-delta Y187F cDNAs were transfected into both 32D myeloid progenitor cells and NIH 3T3 fibroblasts. The results showed that tyrosine 187 of PKC-delta became phosphorylated in vivo in response to 12-O-tetradecanoylphorbol-13-acetate stimulation or platelet-derived growth factor receptor activation. In vivo labeling and subsequent two-dimensional phosphopeptide analysis demonstrated that one phosphopeptide was absent in PKC-delta Y187F when compared to wild type PKC-delta, further substantiating that tyrosine 187 of PKC-delta is phosphorylated in vivo. Although the phosphotyrosine content of PKC-delta Y187F was reduced compared with PKC-delta WT, the kinase activity of PKC-delta Y187F toward a PKC-delta substrate was not altered. Moreover, 12-O-tetradecanoylphorbol-13-acetate-mediated monocytic differentiation of 32D cells was not affected by expression of the PKC-delta Y187F mutant. Taken together, these results suggest that tyrosine phosphorylation of PKC-delta on 187 may not influence PKC-delta activation and known functions. C1 UNIV CHICAGO,BEN MAY INST CANC RES,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PHARMACOL & PHYSIOL SCI,CHICAGO,IL 60637. NHLBI,NATL INST HLTH,BETHESDA,MD 20892. RP Li, WQ (reprint author), NCI,CELLULAR & MOL BIOL LAB,BLDG 37,RM 1E24,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 15 TC 63 Z9 63 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 OCT 18 PY 1996 VL 271 IS 42 BP 26404 EP 26409 DI 10.1074/jbc.271.42.26404 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VN180 UT WOS:A1996VN18000103 PM 8824297 ER PT J AU Pogue, GP Joshi, M Lee, NS Dwyer, DM Kenney, RT Gam, AA Nakhasi, HL AF Pogue, GP Joshi, M Lee, NS Dwyer, DM Kenney, RT Gam, AA Nakhasi, HL TI Conservation of low-copy gene loci in Old World leishmanias identifies mechanisms of parasite evolution and diagnostic markers SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE restriction-fragment length polymorphism(s); pulsed-field gel electrophoresis; chromosome structure; differential gene expression; evolution ID POLYMERASE CHAIN-REACTIONS; MOLECULAR KARYOTYPE; NUCLEAR-DNA; DONOVANI; STRAINS; CLASSIFICATION; POLYMORPHISMS; SEQUENCE; TUBULIN; COMPLEX AB Genome plasticity. has been hypothesized to be a driving force behind parasite speciation. We have evaluated divergence in single and low-copy genes in terms of locus organization, chromosomal localization and gene expression in Leishmania infantum, L. major, L. tropica and three widely divergent geographic isolates of L. donovani. Seventeen genes of low to moderate copy number (1-4 copies/haploid genome) were analyzed to identify restriction fragment length polymorphisms (RFLPs) providing heritable markers distinguishing Old World (OW) leishmanias. These RFLP markers were conserved in parasite isolates from primary infections demonstrating their utility as diagnostic tools. The species designations established by RFLP analysis of field isolates was confirmed by use of monoclonal antibodies. All 17 genes were present in each OW leishmania analyzed except LSIP (A45), which was absent from L. infantum. The 17 genes were found to be distributed among 9 distinct chromosomes. However, in spite of variations in chromosome karyotypes among the various OW leishmanias, individual gene probes localized to a similar sized chromosome from each isolate. These observations coupled with a molecular tree derived from RFLP data suggest that the OW leishmanias comprise a monophyletic lineage, with species associated with cutaneous disease exhibiting the greatest level of divergence. Data from this study supports previous observations that species causing cutaneous and visceral disease have diverged primarily by nucleotide substitutions. Such nucleotide divergence may not only lead to changes in protein function and antigenicity, but may also alter gene regulation programs as exemplified by the finding that the LdI-9-5 and LdE-6-1 genes were expressed only in visceralizing leishmanias. C1 US FDA,VPAR,DVP,OVRR,CBER,LAB MOL PHARMACOL,DIV HEMATOL PROD,OTRR,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. US FDA,LAB PARASIT BIOL & BIOCHEM,DIV ALLERGEN & PARASIT PROD,OVRR,CBER,BETHESDA,MD 20892. NR 39 TC 16 Z9 16 U1 0 U2 3 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 OCT 18 PY 1996 VL 81 IS 1 BP 27 EP 40 DI 10.1016/0166-6851(96)02697-7 PG 14 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VL193 UT WOS:A1996VL19300003 PM 8892303 ER PT J AU Joshi, M Pogue, GP Duncan, RC Lee, NS Singh, NK Atreya, CD Dwyer, DM Nakhasi, HL AF Joshi, M Pogue, GP Duncan, RC Lee, NS Singh, NK Atreya, CD Dwyer, DM Nakhasi, HL TI Isolation and characterization of Leishmania donovani calreticulin gene and its conservation of the RNA binding activity SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE calreticulin; RNA binding protein; phosphorylation; glycosylation; trypanosomatid; functional conservation ID SARCOPLASMIC-RETICULUM; ENDOPLASMIC-RETICULUM; MOLECULAR-CLONING; PROTEIN; IDENTIFICATION; GLYCOPROTEINS; EXPRESSION; MEMBRANE; INVITRO AB Calreticulin has been implicated in multiple cell functions. Recently, we have shown that both human and simian calreticulin are RNA binding proteins and that their binding activity is due to phosphorylation. To demonstrate that the RNA binding property of calreticulin is an intrinsic part of this multi-functional molecule and is evolutionarily conserved, we isolated and characterized the calreticulin gene from the unicellular parasite, Leishmania donovani. Amino acid sequence homology between human and Leishmania calreticulin (L. d. cal) is limited, but like the human homologue, L. d. cal binds Ca++, can be phosphorylated in vitro and binds certain RNA sequences in a phosphorylation-dependent manner. Unlike human calreticulin, L. d. cal is glycosylated and its binding to endogenous Leishmania RNA is phosphorylation-independent. The binding of L. d. cal to Leishmania RNA suggests that the RNA binding activity of calreticulin has remained evolutionarily conserved. C1 US FDA,MOL PHARMACOL LAB,DHP,OTRR,CBER,BETHESDA,MD 20892. NIAID,CELL BIOL SECT,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 39 TC 35 Z9 35 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 OCT 18 PY 1996 VL 81 IS 1 BP 53 EP 64 DI 10.1016/0166-6851(96)02676-X PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VL193 UT WOS:A1996VL19300005 PM 8892305 ER PT J AU Moriwaki, SI Ray, S Tarone, RE Kraemer, KH Grossman, L AF Moriwaki, SI Ray, S Tarone, RE Kraemer, KH Grossman, L TI The effect of donor age on the processing of UV-damaged DNA by cultured human cells: Reduced DNA repair capacity and increased DNA mutability SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE plasmid host cell reactivation; skin cancer; aging; skin fibroblast; EB transformed lymphocyte ID SHUTTLE VECTOR PLASMID; XERODERMA-PIGMENTOSUM PATIENTS; CIRCULATING LYMPHOCYTES-T; HPRT MUTANT FREQUENCY; SKIN-CANCER; ULTRAVIOLET HYPERMUTABILITY; MUTATIONS; SUNLIGHT; GENE; CARCINOMA AB Aging in humans carries an increased risk of skin cancer, a disorder linked to somatic mutations in sun damaged skin. DNA repair plays a major role in protection against sun damage. We found an age-related decline in post-UV DNA repair capacity (measured by the ability to repair a W-treated plasmid (pCMVcat)) of -0.6% per year (p = 0.0001) in cultured primary skin fibroblasts from normal donors from the first to the tenth decade of life. There was a corresponding age-related increase in post-UV mutability (measured as mutations introduced into a transfected, UV-treated plasmid (pSP189)) of + 0.6% per year (p = 0.001) in lymphoblastoid cell lines from normal donors of the same age range. This study indicates that aging in humans is associated with decreasing ability to process new UV-induced DNA damage and this age-related reduction in DNA repair capacity and increase in DNA mutability is reflected in cultured skin and blood cells. C1 NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NCI,BIOSTAT BRANCH,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOCHEM,BALTIMORE,MD 21205. FU Intramural NIH HHS [Z01 BC004517-31]; NCI NIH HHS [CA-62924]; NIEHS NIH HHS [P30 ES-02819]; NIGMS NIH HHS [R01 GM-22846] NR 33 TC 108 Z9 111 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD OCT 18 PY 1996 VL 364 IS 2 BP 117 EP 123 DI 10.1016/0921-8777(96)00029-8 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA VM879 UT WOS:A1996VM87900006 PM 8879277 ER PT J AU Masserano, JM Baker, I Natsukari, N Wyatt, RJ AF Masserano, JM Baker, I Natsukari, N Wyatt, RJ TI Chronic cocaine administration increases tyrosine hydroxylase activity in the ventral tegmental area through glutaminergic- and dopaminergic D-2-receptor mechanisms SO NEUROSCIENCE LETTERS LA English DT Article DE clozapine; cocaine; haloperidol; MK-801; tyrosine hydroxylase; ventral tegmental area ID METHYL-D-ASPARTATE; RAT-BRAIN; MESSENGER-RNA; NUCLEUS-ACCUMBENS; CHRONIC MORPHINE; FRONTAL-CORTEX; ADRENAL-GLAND; NEURONS; SYSTEM; SENSITIZATION AB Tyrosine hydroxylase activity was measured in the brain of rats treated chronically with saline or cocaine (10 mg/kg, 2 x day, for 7 days). Tyrosine hydroxylase activity was significantly increased in the ventral tegmental area 1, 6 and 12 weeks after the last treatment with cocaine. The increase in tyrosine hydroxylase activity at 6 weeks after the last cocaine injection was prevented by the prior administration of MK-801, haloperidol or clozapine but not by the D-1 receptor antagonist, SCH-23390. SCH-23390 produced a significant increase in tyrosine hydroxylase activity when administered with saline. These data indicate that glutaminergic and dopaminergic D-2-receptor mediated mechanisms are important in regulating the effect of cocaine on the ventral tegmental area. RP Masserano, JM (reprint author), NIMH,NEUROPSYCHIAT BRANCH,NEUROSCI CTR ST ELIZABETHS,2700 MARTIN LUTHER KING JR AVE,WASHINGTON,DC 20032, USA. NR 30 TC 39 Z9 43 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 18 PY 1996 VL 217 IS 2-3 BP 73 EP 76 DI 10.1016/0304-3940(96)13047-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VQ398 UT WOS:A1996VQ39800001 PM 8916075 ER PT J AU Luo, Y Sunderland, T Roth, GS Wolozin, B AF Luo, Y Sunderland, T Roth, GS Wolozin, B TI Physiological levels of beta-amyloid peptide promote PC12 cell proliferation SO NEUROSCIENCE LETTERS LA English DT Article DE beta-amyloid; cell growth; physiological function; growth factors; Alzheimer's disease; protein phosphorylation ID ENZYME COMPLEX RECEPTOR; PROTEIN-KINASE-C; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; SUBSTANCE-P; PHOSPHORYLATION; ADHESION; NEURONS AB Alzheimer's beta-amyloid peptide (A beta) is normally present at a subnanomolar (225-625 pM) concentration in body fluids and in the medium of cultured cells. The potential actions of physiologic levels of A beta are being investigated. We have recently shown that nanomolar doses of A beta can stimulate tyrosine phosphorylation and activate phosphatidylinositol-3-kinase in neuronal cells. Here we show evidence that A beta at nanomolar levels promotes cell growth determined by [H-3]thymidine incorporation, protein content and cell counts. Physiological levels of A beta peptides, including 1-40, 1-42, 25-35, all promote growth of PC12 cells in low serum medium with doubling times of 71 h to around 30 h. Although the promotion of cell proliferation can be detected at nanomolar levels of A beta, its potency is less than that of serum. This suggests that A beta may normally play a neurotrophic/mitogenic role in neuronal biology. C1 NIMH,SECT GERIATR PSYCHIAT,BETHESDA,MD 20892. RP Luo, Y (reprint author), NIA,MOL PHYSIOL & GENET SECT,CTR GERONTOL RES,4E02,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 20 TC 37 Z9 38 U1 1 U2 2 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 OCT 18 PY 1996 VL 217 IS 2-3 BP 125 EP 128 DI 10.1016/0304-3940(96)13087-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VQ398 UT WOS:A1996VQ39800014 PM 8916088 ER PT J AU Noga, JT Bartley, AJ Jones, DW Torrey, EF Weinberger, DR AF Noga, JT Bartley, AJ Jones, DW Torrey, EF Weinberger, DR TI Cortical gyral anatomy and gross brain dimensions in monozygotic twins discordant for schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cortex; gyral anatomy; monozygotic twins; discordance; schizophrenia ID TEMPORAL-LOBE; ABNORMALITIES; VOLUME; DISTURBANCES; DISORDER; CORTEX AB Background: This study combines recent advances in three-dimensional neuroimaging technology and the genetic constraints inherent in monozygotic (MZ) twins to examine surface gyral anatomy and gross brain dimensions in monozygotic twin pairs discordant for schizophrenia. Results are presented and evaluated with respect to prior observations of cortical anomalies in schizophrenia and the hypothesis that schizophrenia involves cortical maldevelopment. Design: Three-dimensional renderings from volumetric magnetic resonance imaging (MRI) data of 13 MZ twin pairs discordant for schizophrenia and nine normal MZ pairs were studied. Qualitative assessments of left and right hemisphere surfaces were made by raters blind to diagnosis in an effort to identify developmental gyral abnormalities such as vertical temporal gyri or microgyria. Measurements of brain hemisphere length, area, and volume were also determined. These data were compared within discordant MZ schizophrenia pairs, within normal MZ pairs, and between matched unaffected discordant and normal MZ groups. Results: Raters did not identify qualitatively abnormal gyri in the schizophrenia subjects to enable distinction from their unaffected co-twins or from normal controls. Brain hemisphere volumes in the affected DS were significantly smaller bilaterally by about 3% compared with their unaffected DS co-twins, who did not differ from normals on this measure. Conclusions: We were unable to confirm previous reports of vertical gyri or localized gyral thinning as being characteristic of the cortical anatomy of schizophrenia. If cortical maldevelopment is associated with schizophrenia, it does not appear to disrupt gross gyral pattern formation in these ways. The quantitative results of diminished hemisphere volume and length in the twins with schizophrenia are consistent with previous reports of smaller brain size in schizophrenia. Our results suggest that this is a bilateral phenomenon that may be dependent, at least in part, on environmental factors. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,DIRP,NIH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 41 TC 33 Z9 35 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT 18 PY 1996 VL 22 IS 1 BP 27 EP 40 PG 14 WC Psychiatry SC Psychiatry GA VP044 UT WOS:A1996VP04400004 PM 8908688 ER PT J AU Chen, MS Fornace, A Laszlo, A AF Chen, MS Fornace, A Laszlo, A TI Characterization of an hsp70 related clone encoding a 33 kDa protein with homology to a protein which associates with polysomes SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE ribosomal protein; laminin receptor; heat shock protein; (Chinese hamster) ID LAMININ RECEPTOR; BINDING; DOMAINS; GENE AB Characterization of an bsp70 related Chinese hamster cDNA clone revealed that it encodes a 33 kDa protein with homology to a mouse ribosomal component p40 which associates with polysomes (Auth and Brawerman (1992) Proc. Natl. Acad. Sci, USA 89, 4368). The predicted amino acid sequence of this cDNA which differs by only two residues from p40, shares significant similarity with various members of the hsp70 family, Sequence analysis revealed a 29% identity between the N-terminal region (residues 1 to 120) of the 33 kDa protein and the ATP binding domain of the Chinese hamster hsc70, but no significant Sequence similarity was found between the remaining C-terminal regions of the 33 kDa polypeptide and the hsc70 protein. The N-terminal region of the 33 kDa protein lacks the typical consensus motif for ATP binding, suggesting that the N-terminal domain of the 33 kDa protein may not be involved in ATP binding. In the light of the fact that this 33 kDa protein is a ribosomal component, we speculate that the N-terminal domain may interact with structures containing nucleotides such as RNA. C1 NIH,MOL PHARMACOL LAB,BETHESDA,MD 20892. RP Chen, MS (reprint author), WASHINGTON UNIV,SCH MED,MALLINCKRODT INST RADIOL,RADIAT ONCOL CTR,SECT CANC BIOL,ST LOUIS,MO 63108, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [CA-49018] NR 18 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD OCT 17 PY 1996 VL 1297 IS 2 BP 124 EP 126 DI 10.1016/S0167-4838(96)00140-9 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VQ512 UT WOS:A1996VQ51200004 PM 8917612 ER PT J AU Gao, CY Chauthaiwale, VM Rampalli, AM Zelenka, PS AF Gao, CY Chauthaiwale, VM Rampalli, AM Zelenka, PS TI Expression of alternatively spliced PCTAIRE-1 mRNA in PC12 cells and neonatal rat brain SO GENE LA English DT Article DE PCTAIRE; cell cycle; differentiation; cyclin-dependent kinases; alternative splicing ID NERVE GROWTH-FACTOR; PROTEIN-KINASE ACTIVITY; PHEOCHROMOCYTOMA CELLS; DEATH; CLONING; FAMILY; GENE; DNA AB A rat PCTAIRE-1 cDNA clone was isolated by immunoscreening of a PC12 cDNA library, followed by 5' RACE (rapid amplification of cDNA ends) to determine the 5' end. The rat PCTAIRE-1 cDNA sequence is 96% identical to mouse PCTAIRE-1 and contains an alternatively spliced exon of 131 bp near the 5' end. Although a mouse cDNA containing this exon has been reported, examination of several mouse cell lines provided no evidence for expression of the corresponding mRNA (Okuda et al., 1992). In contrast, reverse transcription and polymerase chain reaction (RT/PCR) across this region using RNA from proliferating, differentiated, and apoptotic PC12 cells demonstrated that alternatively spliced forms of PCTAIRE-1 mRNA with and without this exon are expressed. Both forms of PCTAIRE-1 mRNA are also expressed in vivo in neonatal rat brain, although other tissues examined contained only the form lacking the alternatively spliced exon. In the absence of the alternatively spliced exon PCTAIRE-1 mRNA contains an open reading frame of 1488 bp, corresponding to a 55-kDa protein that is 97% identical to mouse PCTAIRE-1 protein. When the alternatively spliced exon is present, this open reading frame is terminated by a stop codon and a second open reading frame is initiated, predicting a second PCTAIRE-1 protein of 52 kDa. The two predicted PCTAIRE-1 proteins are identical downstream of the splice site, but share no homology at their N-terminal ends. C1 NEI,NIH,MOL & DEV BIOL LAB,BETHESDA,MD 20932. NR 23 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 17 PY 1996 VL 176 IS 1-2 BP 243 EP 247 DI 10.1016/0378-1119(96)83274-4 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VR399 UT WOS:A1996VR39900038 PM 8918260 ER PT J AU Feller, SE Pastor, RW Rojnuckarin, A Bogusz, S Brooks, BR AF Feller, SE Pastor, RW Rojnuckarin, A Bogusz, S Brooks, BR TI Effect of electrostatic force truncation on interfacial and transport properties of water SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; LONG-RANGE INTERACTIONS; PARTICLE MESH EWALD; COMPUTER-SIMULATION; BOUNDARY-CONDITIONS; LIQUID/LIQUID INTERFACES; PHOSPHOLIPID-BILAYERS; SURFACE-TENSION; LIPID BILAYERS; MONTE-CARLO AB The importance of accurately accounting for all Coulombic forces in molecular dynamics simulations of water at interfaces is demonstrated by comparing the Ewald summation technique with various spherical truncation methods, The increased structure induced by truncation methods at 12 Angstrom leads to water/vapor surface tensions and surface potentials that are respectively 50% and 100% greater than obtained with Ewald. The orientational polarization of water at the lipid/water interface is analyzed within the Marcelja-Radic theory of the hydration force, yielding decay parameters of 2.6 and 1.8 Angstrom for spherical truncation and Ewald, respectively, as compared with 1.7-2.1 Angstrom obtained from experiment. Bulk water transport properties such as the viscosity and diffusion constants differ by as much as 100% between simulations carried out with and without truncation; this may be related to ordering in the neighborhood of the cutoff radius. The diffusion constant calculated from the Ewald simulation is significantly further from experiment than the cutoff result, pointing out the need to reparametrize the TIP3P water model for use with Ewald summation. Appendices describe a method for carrying out the Ewald summation on a distributed memory parallel computer and other computational details relevant when simulating large systems. C1 US FDA,CTR BIOL EVALUAT & RES,BIOL LAB,ROCKVILLE,MD 20852. UNIV WISCONSIN,DEPT CHEM ENGN,MADISON,WI 53706. WALTER REED ARMY INST RES,DEPT GASTROENTEROL,WASHINGTON,DC 20307. NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. NR 52 TC 265 Z9 268 U1 1 U2 29 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD OCT 17 PY 1996 VL 100 IS 42 BP 17011 EP 17020 DI 10.1021/jp9614658 PG 10 WC Chemistry, Physical SC Chemistry GA VN802 UT WOS:A1996VN80200034 ER PT J AU Michelson, D Stratakis, C Hill, L Reynolds, J Galliven, E Chrousos, G Gold, P AF Michelson, D Stratakis, C Hill, L Reynolds, J Galliven, E Chrousos, G Gold, P TI Bone mineral density in women with depression SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; BIOCHEMICAL MANIFESTATIONS; THERAPEUTIC IMPLICATIONS; TYROSINE-HYDROXYLASE; CUSHINGS-SYNDROME; RAT-BRAIN; NEUROBIOLOGY; OSTEOPOROSIS; POLYMORPHISM; DISORDERS AB Background Depression is associated with alterations in behavior and neuroendocrine systems that are risk factors for decreased bone mineral density. This study was undertaken to determine whether women with past or current major depression have demonstrable decreases in bone density. Methods We measured bone mineral density at the hip, spine, and radius in 24 women with past or current major depression and 24 normal women matched for age, body-mass index, menopausal status, and race, using dual-energy x-ray absorptiometry. We also evaluated cortisol and growth hormone secretion, bone metabolism, and vitamin D-receptor alleles. Results AS compared with the normal women, the mean (+/- SD) bone density in the women with past or current depression was 6.5 percent lower at the spine (1.00 +/- 0.15 vs. 1.07 +/- 0.09 g per square centimeter, P=0.02), 13.6 percent lower at the femoral neck (0.76 +/- 0.11 vs, 0.88 +/- 0.11 g per square centimeter, P<0.001), 13.6 percent lower at Ward's triangle (0.70 +/- 0.14 vs. 0.81 +/- 0.13 g per square centimeter, P<0.001), and 10.8 percent lower at the trochanter (0.66+/-0.11 vs. 0.74+/-0.08 g per square centimeter, P<0.001), In addition, women with past or current depression had higher urinary cortisol excretion (71 +/- 29 vs. 51 +/- 19 mu g per day [196 +/- 80 vs. 141 +/- 52 nmol per day], P=0.006), lower serum osteocalcin concentrations (P=0.04), and lower urinary excretion of deoxypyridinoline (P=0.02). Conclusions Past or current depression in women is associated with decreased bone mineral density (C) 1996, Massachusetts Medical Society. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,CHILDRENS MED CTR,DIV GENET,WASHINGTON,DC 20007. RP Michelson, D (reprint author), NIH,DEPT NUCL MED,WARREN G MAGNUSON CLIN CTR,ROOM 2D 46,MSC 1284,BETHESDA,MD 20892, USA. NR 30 TC 309 Z9 315 U1 2 U2 9 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 OCT 17 PY 1996 VL 335 IS 16 BP 1176 EP 1181 DI 10.1056/NEJM199610173351602 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VN401 UT WOS:A1996VN40100002 PM 8815939 ER PT J AU Mitchell, J Schinzel, A Langlois, S GillessenKaesbach, G Schuffenhauer, S Michaelis, R Abeliovich, D Lerer, I Christian, S Guitart, M McFadden, DE Robinson, WP AF Mitchell, J Schinzel, A Langlois, S GillessenKaesbach, G Schuffenhauer, S Michaelis, R Abeliovich, D Lerer, I Christian, S Guitart, M McFadden, DE Robinson, WP TI Comparison of phenotype in uniparental disomy and deletion Prader-Willi syndrome: Sex specific differences SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Prader-Willi syndrome; uniparental disomy; sex-ratio; trisomy 15 ID WIEDEMANN-BECKWITH SYNDROME; MOLECULAR DIAGNOSIS; ANGELMAN SYNDROME; MILDER PHENOTYPE; PARENTAL ORIGIN; CHROMOSOME-15; NONDISJUNCTION; INACTIVATION; TRISOMY-15 AB Prader-Willi syndrome (PWS) results primarily from either a paternal deletion of 15q11-q13 or maternal uniparental disomy (UPD) 15. Birth parameters and clinical presentation of 79 confirmed UPD cases and 43 deletion patients were compared in order to test whether any manifestations differ between the two groups. There were no major clinical differences between the two classes analyzed as a whole, other than the presence of hypopigmentation predominantly in the deletion group. However, there was a significant bias in sex-ratio (P<.001) limited to the UPD group with a predominance (68%) of males. An equal number of males and females was observed in the deletion group. When analyzed by sex, several significant differences between the UPD and deletion groups were observed. Female UPD patients were found to be less severely affected than female deletion patients in terms of length of gavage feeding and a later onset of hyperphagia. Although these traits are likely to be influenced by external factors, they may reflect a milder presentation of female UPD patients which could explain the observed sex bias by causing under-ascertainment of female UPD. Alternatively there may be an effect of sex on either early trisomy 15 survival or the probability of somatic loss of a chromosome from a trisomic conceptus. (C) 1996 Wiley-Liss, Inc. C1 UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. UNIV BRITISH COLUMBIA,DEPT PATHOL,VANCOUVER,BC,CANADA. UNIV ZURICH,INST MED GENET,ZURICH,SWITZERLAND. UNIV ESSEN GESAMTHSCH KLINIKUM,INST HUMAN GENET,D-4300 ESSEN,GERMANY. UNIV MUNICH,KINDERPOLIKLIN,ABT PEDIAT GENET,MUNICH,GERMANY. GREENWOOD GENET CTR,GREENWOOD,SC 29646. HEBREW UNIV JERUSALEM,HADASSAH UNIV HOSP,JERUSALEM,ISRAEL. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. HOSP SABADELL,SABADELL,SPAIN. RI Robinson, Wendy/I-9590-2014 OI Robinson, Wendy/0000-0002-2010-6174 NR 26 TC 46 Z9 48 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 16 PY 1996 VL 65 IS 2 BP 133 EP 136 DI 10.1002/(SICI)1096-8628(19961016)65:2<133::AID-AJMG10>3.0.CO;2-R PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VP248 UT WOS:A1996VP24800010 PM 8911605 ER PT J AU Butler, MG Christian, SL Kubota, T Ledbetter, DH AF Butler, MG Christian, SL Kubota, T Ledbetter, DH TI Brief clinical report - A 5-year-old white girl with Prader-Willi syndrome and a submicroscopic deletion of chromosome 15q11q13 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Prader-Willi syndrome; submicroscopic deletion; FISH; genotype phenotype correlations ID DINUCLEOTIDE REPEAT POLYMORPHISM; MOLECULAR DIAGNOSIS; UNIPARENTAL DISOMY; REGION 15Q11-Q13; SNRPN GENE; ANGELMAN; DEFINE; LOCUS AB We report on a 5-year-old white girl with Prader-Willi syndrome (PWS) and a submicroscopic deletion of 15q11q13 of approximately 100-200 kb in size. High resolution chromosome analysis was normal but fluorescence in situ hybridization (FISH), Southern hybridization, and microsatellite data from the 15q11q13 region demonstrated that the deletion was paternal in origin and included the SNRPN, PAR-5, and PAR-7 genes from the proximal to distal boundaries of the deletion segment. SNRPN and PW71B methylation studies showed an abnormal pattern consistent with the diagnosis of PWS and supported the presence of a paternal deletion of 15q11q13 or an imprinting mutation. Biparental (normal) inheritance of PW71B (D15S63 locus) and a deletion of the SNRPN gene were observed by microsatellite, quantitative Southern hybridization, and/or FISH analyses. Our patient met the diagnostic criteria for PWS, but has no reported behavior problems, hyperphagia, or hypopigmentation. Our patient further supports SNRPN and possibly other genomic sequences which are deleted as the cause of the phenotype recognized in PWS patients. (C) 1996 Wiley-Liss, Inc. C1 VANDERBILT UNIV,MED CTR,DEPT PATHOL,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,DEPT ORTHOPED,NASHVILLE,TN 37232. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Butler, MG (reprint author), VANDERBILT UNIV,SCH MED,DIV GENET,DEPT PEDIAT,MED CTR,DD-2205 MED CTR N,NASHVILLE,TN 37232, USA. FU NICHD NIH HHS [P0L HD 30329-01A2, P30 HD15052] NR 21 TC 18 Z9 18 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 16 PY 1996 VL 65 IS 2 BP 137 EP 141 DI 10.1002/(SICI)1096-8628(19961016)65:2<137::AID-AJMG11>3.0.CO;2-R PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VP248 UT WOS:A1996VP24800011 PM 8911606 ER PT J AU Harris, MI Eastman, RC AF Harris, MI Eastman, RC TI Early detection of undiagnosed non-insulin-dependent diabetes mellitus SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID NON-HISPANIC WHITES; NIDDM; TESTS RP Harris, MI (reprint author), NIDDKD,NIH,BLDG 45,ROOM 5AN24,BETHESDA,MD 20892, USA. NR 17 TC 29 Z9 29 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 OCT 16 PY 1996 VL 276 IS 15 BP 1261 EP 1262 DI 10.1001/jama.276.15.1261 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VL691 UT WOS:A1996VL69100037 PM 8849756 ER PT J AU Kannel, WB Wolf, PA Verter, J McNamara, PM AF Kannel, WB Wolf, PA Verter, J McNamara, PM TI Epidemiologic assessment of the role of blood pressure in stroke - The Framingham study (Reprinted from JAMA, vol 214, pg 301-310, 1970) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint AB Control of hypertension, labile or fixed, systolic or diastolic, at any age, in either sex appears to be central to prevention of atherothrombotic brain infarction (ABI), Prospectively, hypertension proved the most common and potent precursor of ABI's, Its contribution was direct and could not be attributed to factors related both to stroke and hypertension, Asymptomatic causal ''hypertension'' was associated with a risk of ABI about four times that of normotensives. The probability of occurrence of an ABI was predicted no better with both blood pressure measurements or the mean arterial pressure than with systolic alone, Since there was no diminishing impact of systolic pressure with advancing age, the concept that systolic elevations are, even in the aged, innocuous is premature. Comparing normotensives and hypertensives in each sex, women did not tolerate hypertension better than men. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. NATL HEART INST,WASHINGTON,DC. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. NATL HEART INST,BIOMETR RES SECT,BETHESDA,MD. NR 19 TC 35 Z9 37 U1 0 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 OCT 16 PY 1996 VL 276 IS 15 BP 1269 EP 1278 DI 10.1001/jama.276.15.1269 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA VL691 UT WOS:A1996VL69100039 PM 8849757 ER PT J AU Largaespada, DA Jackson, MW Thompson, NE Kaehler, DA Byrd, LG Mushinski, JF AF Largaespada, DA Jackson, MW Thompson, NE Kaehler, DA Byrd, LG Mushinski, JF TI The ABL-MYC retrovirus generates antigen-specific plasmacytomas by in vitro infection of activated B lymphocytes from spleen and other murine lymphoid organs SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE retrovirus; plasmacytoma; monoclonal antibody; in vitro ID RESPONSIVE MONOCLONAL-ANTIBODY; RNA POLYMERASE-II; EXPRESSING V-ABL; C-MYC; PURIFICATION; CHROMATOGRAPHY; INDUCTION; GENE; DNA; RECOMBINATION AB ABL-MYC is a recombinant retrovirus that constitutively expresses the v-abl and c-myc oncogenes. When used to infect immunized mice this virus rapidly and efficiently induces plasmacytomas of which an unusually high percentage secrete antigen (Ag)-specific monoclonal antibodies. These findings suggested that ABL-MYC targets Ag-stimulated B cells for transformation and that infection of lymphoid cells in vitro might be a useful, alternative method for generating monoclonal, Ag-specific plasmacytomas (ASPCTs). Therefore, we used helper virus-free ABL-MYC to infect suspensions of cells from spleens and other lymphoid organs from mice that had been immunized with a variety of Ags and transplanted them into naive mice. The results show that ABL-MYC preferentially transforms splenocytes that are AE-reactive. They also demonstrate that ASPCTs can be produced by in vitro infection of cell suspensions from the spleen, lymph nodes and Peyer's patches of mice that had been immunized intraperitoneally with sheep red blood cells, Escherichia coli core RNA polymerase or Epstein-Barr virus gp340 protein or immunized orally with live Giardia lamblia parasites. The ASPCTs usually consisted of one to three clones, secreted antibodies that were quantitatively and qualitatively similar to those obtained from hybridomas, and could continue to secrete Ag-reactive antibody over eight transplant generations. C1 NCI,GENET LAB,NIH,BETHESDA,MD 20892. UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. RI Largaespada, David/C-9832-2014 FU NCI NIH HHS [CA 413022, CA 07175, CA 23076] NR 21 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD OCT 16 PY 1996 VL 197 IS 1-2 BP 85 EP 95 DI 10.1016/0022-1759(96)00130-5 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA VM826 UT WOS:A1996VM82600008 PM 8890896 ER PT J AU Spring, SB Hascall, G Gruber, J AF Spring, SB Hascall, G Gruber, J TI Issues related to development of Epstein-Barr virus vaccines SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LYMPHOPROLIFERATIVE DISORDERS; NASOPHARYNGEAL CARCINOMA; HODGKINS-DISEASE; INFECTIOUS-MONONUCLEOSIS; HEMOPHAGOCYTIC SYNDROME; B-CELLS; A-TYPE; PATHOGENESIS; LYMPHOCYTES; MICE C1 NIAID, VIROL BRANCH, DIV MICROBIOL & INFECT DIS, BETHESDA, MD 20892 USA. NCI, BIOL CARCINOGENISIS BRANCH, DIV CANC BIOL, BETHESDA, MD 20892 USA. NR 66 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 16 PY 1996 VL 88 IS 20 BP 1436 EP 1441 DI 10.1093/jnci/88.20.1436 PG 6 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600010 PM 8841018 ER PT J AU Harris, CC AF Harris, CC TI Structure and function of the p53 tumor suppressor gene: Clues for rational cancer therapeutic strategies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID HEPATITIS-B-VIRUS; WILD-TYPE P53; PROGRAMMED CELL-DEATH; PROTEIN-KINASE-C; DNA-BINDING FUNCTION; HUMAN HEPATOCELLULAR-CARCINOMA; BASAL TRANSCRIPTION FACTOR; CYCLIN-DEPENDENT KINASES; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE CELLS AB The p53 tumor suppressor protein is involved in multiple central cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control, and apoptosis. p53 is functionally inactivated by structural mutations, interaction with viral products, and endogenous cellular mechanisms in the majority of human cancers. This functional inactivation can, in some circumstances, produce resistance to DNA-damaging agents commonly used in cancer chemotherapy and radiotherapeutic approaches. Current research is defining the biochemical pathways through which p53 induces cell cycle arrest and apoptosis, Knowledge of these fundamental processes is leading to the identification of molecular targets toward which multimodality cancer therapies, using chemotherapeutic, immunotherapeutic, and gene-therapeutic strategies, can be based. C1 NCI,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 289 TC 544 Z9 563 U1 2 U2 26 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 OCT 16 PY 1996 VL 88 IS 20 BP 1442 EP 1455 DI 10.1093/jnci/88.20.1442 PG 14 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600011 PM 8841019 ER PT J AU Hayes, DF Bast, RC Desch, CE Fritsche, H Kemeny, NE Jessup, JM Locker, GY MacDonald, JS Mennel, RG Norton, L Ravdin, P Taube, S Winn, RJ AF Hayes, DF Bast, RC Desch, CE Fritsche, H Kemeny, NE Jessup, JM Locker, GY MacDonald, JS Mennel, RG Norton, L Ravdin, P Taube, S Winn, RJ TI Tumor marker utility grading system: A framework to evaluate clinical utility of tumor markers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NEGATIVE BREAST-CANCER; C-ERBB-2 ANTIGEN LEVELS; DNA FLOW-CYTOMETRY; CELL LUNG-CANCER; ESTROGEN-RECEPTOR; PRACTICE GUIDELINES; OVARIAN-CANCER; SUSCEPTIBILITY GENE; PROGNOSTIC FACTORS; SUPPRESSOR GENE AB Introduction of tumor markers into routine clinical practice has been poorly controlled, with few criteria or guidelines as to how such markers should be used. We propose a Tumor Marker Utility Grading System (TMUGS) to evaluate the clinical utility of tumor markers and to establish an investigational agenda for evaluation of new tumor markers, A Tumor Marker Utility Grading Worksheet has been designed. The initial portion of this worksheet is used to clarify the precise characteristics of the marker in question. These characteristics include the marker designation, the molecule and/or substance and the relevant alteration from normalcy, the assay format and reagents, the specimen type, and the neoplastic disease for which the marker is being evaluated, To determine the clinical utility of each marker, one of several potential uses must be designated, including risk assessment, screening, differential diagnosis, prognosis, and monitoring clinical course, For each of these uses, associations between marker assay results and expected biologic process and end paints must be determined, However, knowledge of tumor marker data should contribute to a decision in practice that results in a more favorable clinical outcome for the patient, including increased overall survival, increased disease-free survival, improvement in quality of life, or reduction in cost of care. Semiquantitative utility scales have been developed for each end point, The only markers recommended for use in routine clinical practice are those that are assigned utility scores of ''++'' or ''+++'' on a 6-point scale (ranging from 0 to +++) in the categories relative to more favorable clinical outcomes, Each utility score assignment should be supported by documentation of the level of evidence used to evaluate the marker, TMUGS sill establish a standardized analytic technique to evaluate clinical utility of known and future tumor markers. It should result in improved patient outcomes and more cost-efficient investigation and application of tumor markers. C1 DANA FARBER CANC INST,BREAST EVALUAT CTR,BOSTON,MA 02115. UNIV TEXAS,MD ANDERSON CANC CTR,HOUSTON,TX. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,MASSEY CANC CTR,RICHMOND,VA 23298. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NEW ENGLAND DEACONESS HOSP,BOSTON,MA 02215. NORTHWESTERN UNIV,EVANSTON HOSP,EVANSTON,IL 60201. TEMPLE UNIV,CTR CANC,PHILADELPHIA,PA 19122. TEXAS ONCOL,DALLAS,TX. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. NCI,CANC DIAG BRANCH,DIV CANC BIOL DIAG & CTR,BETHESDA,MD. RI Bast, Robert/E-6585-2011; Ain, Kenneth/A-5179-2012 OI Bast, Robert/0000-0003-4621-8462; Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [CA64057] NR 66 TC 465 Z9 483 U1 0 U2 23 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 OCT 16 PY 1996 VL 88 IS 20 BP 1456 EP 1466 DI 10.1093/jnci/88.20.1456 PG 11 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600012 PM 8841020 ER PT J AU Han, CL Qiao, GB Hubbert, NL Li, LS Sun, CS Wang, Y Yan, MX Xu, DZ Li, YG Lowy, DR Schiller, JT AF Han, CL Qiao, GB Hubbert, NL Li, LS Sun, CS Wang, Y Yan, MX Xu, DZ Li, YG Lowy, DR Schiller, JT TI Serologic association between human papillomavirus type 16 infection and esophageal cancer in Shaanxi Province, China SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; IN-SITU HYBRIDIZATION; VIRUS-LIKE PARTICLES; CERVICAL-CANCER; DNA; NEOPLASIA AB Background: The existence of large geographic variations in the prevalence of esophageal cancer in some countries, such as China, indicates that environmental risk factors may be important in the development of this disease, Some studies have implicated genital-mucosal strains of human papillomaviruses (HPVs) in the etiology of this cancer, Purpose: We conducted a case-control study in Shaanxi Province, China, an area with a population at high risk for esophageal cancer, to assess the association of this disease with infection by HPV type 16 (HPV16), the most common cancer-associated genital-mucosal HPV type, Methods: Ninety individuals with esophageal cancer and 121 cancer-free control subjects were identified among the patients in two hospitals in Xi'an, Shaanxi Province, The control subjects were matched to the case patients on the basis of age and sex, Blood specimens were drawn from all study subjects, and serum was isolated by routine methods, The presence of HPV16 antibodies in serum samples was determined by use of an enzyme-linked immunosorbent assay (ELISA) that used baculovirus-derived HPV16 virus-like particles as the antigen, A similar ELISA that used bovine papillomavirus type 1 (BPV1) virus-like particles as the antigen controlled for the specificity of HPV16 seroreactivity, Data from the HPV16 and the BPV1 assays were normalized with respect to results obtained in each assay with a control serum of known HPV16 seroreactivity, Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine the association between HPV16 seroreactivity and esophageal cancer, Reported P values are two-sided. Results: The mean seroreactivity to HPV16 virus-like particles was significantly higher for the cancer patients than for the control subjects (mean value +/- standard deviation = 0.85 +/- 0.22 versus 0.74 +/- 0.18; P<.0001). When the cancer patients and control subjects were compared by sex and age groups, the differences in mean seroreactivity remained statistically significant, The difference in mean seroreactivity to BPV1 virus-like particles between cancer patients and control subjects was not statistically significant (0.81 +/- 0.28 versus 0.88 +/- 0.32; P = .12); this result was not altered when sex and age groups were compared, By use of a cutoff point for HPV16 seropositivity that was established in studies of cervical neoplasia, 24% of the cancer patients were seropositive compared with 7% of the control subjects, yielding a sex- and age-adjusted OR of 4.5 (95% CI = 1.8-11.9). In general, the OR for esophageal cancer increased with increasing HPV16 seroreactivity, Conclusions and Implications: HPV16 infection may be a risk factor for esophageal cancer, Further studies of the association between HPV16 infection and the incidence of esophageal cancer are needed. C1 NCI,CELLULAR ONCOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. FOURTH MIL MED UNIV,DEPT EPIDEMIOL,XIAN 710032,PEOPLES R CHINA. NR 25 TC 42 Z9 44 U1 0 U2 1 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 OCT 16 PY 1996 VL 88 IS 20 BP 1467 EP 1471 DI 10.1093/jnci/88.20.1467 PG 5 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600013 PM 8841021 ER PT J AU Adami, HO Chow, WH Nyren, O Berne, C Linet, MS Ekbom, A Wolk, A McLaughlin, JK Fraumeni, JF AF Adami, HO Chow, WH Nyren, O Berne, C Linet, MS Ekbom, A Wolk, A McLaughlin, JK Fraumeni, JF TI Excess risk of primary liver cancer in patients with diabetes mellitus SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID PRIMARY HEPATOCELLULAR-CARCINOMA; HEPATITIS-B; GLUCOSE-TOLERANCE; SEX-DIFFERENCES; POPULATION; CIRRHOSIS; SWEDEN; MEN AB Background: Chronic infection with hepatitis B virus, alcohol consumption, and cirrhosis of the liver are recognized risk factors for primary liver cancer, A few, but not all, studies have suggested that diabetes mellitus also increases risk for this cancer, Purpose: We conducted a population-based cohort study to analyze the risk of developing primary liver cancer and biliary tract (gallbladder, extrahepatic bile ducts, and ampulla of Vater) cancers among patients with diabetes, Methods: A cohort of 153 852 patients with a hospital discharge diagnosis of diabetes in the period from 1965 through 1983 was identified by use of the Swedish In-patient Register, Follow-up for these patients extended from the date of cohort entry through December 31, 1989. Incident cases of cancer during follow-lip were identified through the Swedish Cancer Registry, To minimize the impact of selection bias, we excluded from the analysis patients who were diagnosed with liver and biliary tract cancers during the first year of follow-up, Standardized incidence ratios (SIRs) and their 95% confidence intervals (Cfs) were computed by use of nationwide rates of liver and biliary tract cancers, adjusted for age, sex, and calendar year, for comparison, Results: During 1-24 years of follow-up, 819 incident cancers in the combined category of primary liver (n = 533) and biliary tract (n = 286) were identified in the cohort, yielding an overall SIR of 2.5 (95% CI = 2.3-2.6). The risk was higher in men (SIR = 3.2; 95% CI = 2.9-3.6) than in women (SIR = 2.0; 95% CI = 1.8-2.2), The incidence of primary liver cancer alone was increased fourfold (SIR = 4.1; 95% CI = 3.8-4.5); again, the risk was higher in men (SIR = 4.7; 95% CI = 4.2-5.2) than in women (SIR = 3.4; 95% CI = 2.9-3.9). Smaller increases in risk were seen for cancers of the gallbladder, the extrahepatic bile ducts, and the ampulla of Vater. After exclusion of diabetic patients with concomitant diseases that predispose to primary liver cancer, such as alcoholism, cirrhosis, and hepatitis, the persistence of an approximately threefold excess risk was observed, Conclusions: Our findings suggest that patients with diabetes are at increased risk of developing primary liver cancer and perhaps cancers of the biliary tract, The mechanisms involved in the association of diabetes and liver cancer remain to be clarified, Additional studies are needed to determine whether patients with insulin-dependent diabetes mellitus and those with non-insulin-dependent diabetes mellitus differ in their risk for primacy liver cancer or whether the risk is affected by the type of diabetes treatment. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. INT EPIDEMIOL INST,ROCKVILLE,MD. NCI,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. UNIV UPPSALA HOSP,DEPT INTERNAL MED,S-75185 UPPSALA,SWEDEN. RP Adami, HO (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. FU NCI NIH HHS [N01CP85636-05] NR 42 TC 229 Z9 242 U1 1 U2 4 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 OCT 16 PY 1996 VL 88 IS 20 BP 1472 EP 1477 DI 10.1093/jnci/88.20.1472 PG 6 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600014 PM 8841022 ER PT J AU Novakovic, B Goldstein, AM Tucker, MG AF Novakovic, B Goldstein, AM Tucker, MG TI Validation of family history of cancer in deceased family members SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DEATH CERTIFICATES; ACCURACY; MORTALITY; RELATIVES; SARCOMA C1 NCI,GENET EPIDEMIOL BRANCH,DIV CANC ETIOL,BETHESDA,MD 20892. RI Tucker, Margaret/B-4297-2015 NR 8 TC 32 Z9 32 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 OCT 16 PY 1996 VL 88 IS 20 BP 1492 EP 1493 DI 10.1093/jnci/88.20.1492 PG 2 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600018 PM 8841026 ER PT J AU Curtis, RE Boice, JD Shriner, DA Hankey, BF Fraumeni, JF AF Curtis, RE Boice, JD Shriner, DA Hankey, BF Fraumeni, JF TI Second cancers after adjuvant tamoxifen therapy for breast cancer - Reply SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID ENDOMETRIAL CANCER C1 NCI,CANC STAT BRANCH,BETHESDA,MD 20892. RP Curtis, RE (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 10 TC 0 Z9 0 U1 0 U2 1 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 OCT 16 PY 1996 VL 88 IS 20 BP 1497 EP 1499 DI 10.1093/jnci/88.20.1497-a PG 3 WC Oncology SC Oncology GA VM256 UT WOS:A1996VM25600023 ER PT J AU Konstam, V Salem, D Pouleur, H Kostis, J Gorkin, L Shumaker, S Mottard, I Woods, P Konstam, MA Yusuf, S AF Konstam, V Salem, D Pouleur, H Kostis, J Gorkin, L Shumaker, S Mottard, I Woods, P Konstam, MA Yusuf, S TI Baseline quality of life as a predictor of mortality and hospitalization in 5,025 patients with congestive heart failure SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HEALTH SURVEY; OF-LIFE; RELIABILITY; POPULATION; VALIDITY AB This study examined the independent relation of health-related quality of life (HRQL) to mortality and congestive heart failure (CHF)-related hospitalizations in patients with an ejection fraction of <0.35 followed for a mean of 36.5 months. A brief HRQL questionnaire was administered at baseline to patients randomized to placebo or enalapril in the Studies of left Ventricular Dysfunction (SOLVD) trial. participants had an ejection fraction of <0.35 and either symptomatic CHF (treatment trial, n = 2,465) or asymptomatic CHF (prevention trial, n 2,560). Baseline assessment of HRQL predicted mortality and CHF-related hospitalizations in symptomatic and asymptomatic patients randomized to enalapril and placebo treatment. Domains that were the stronger univariate predictors of mortality and CHF-related hospitalizations were activities of daily living (relative risk [RR] for mortality: 1.163, p < 0.000; for hospitalization: 1.215, p < 0.000), general health (RR for mortality: 1.205, p < 0.000; for hospitalization: 1.188, p < 0.000), and social functioning (RR for mortality 1.098, p < 0.000; for hospitalization: RR 1.156, p < 0.000). In the multivariate model, activities of daily living (RR for mortality 1.41, p < 0.000; for hospitalization: RR 1.43, p < 0.002), general health (RR for mortality 1.21, p < 0.000; for hospitalization RR 1.16, p < 0.013) and heart failure symptoms (88 for mortality 1.02, p < 0.025; for hospitalization RR 1.03, p < 0.004) were found to be independent risk factors. HRQL independently predicted mortality and CHF-related hospitalizations after adjustment for ejection fraction, age, treatment, and New York Heart Association classification in patients with an ejection fraction of < 0.35, randomized to enalapril and placebo treatment. HRQL provides additional clinical information regarding disease course and outcome that is not captured by traditional indexes of clinical status. C1 UNIV MASSACHUSETTS,AMHERST,MA 01003. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. UNIV LOUVAIN,SCH MED,BRUSSELS,BELGIUM. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,NEW BRUNSWICK,NJ. CLIN TRIALS APPLICAT INST BEHAV MED,PROVIDENCE,RI. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. HARVARD UNIV,VET AFFAIRS MED CTR,BROCKTON,MA 02401. TUFTS UNIV,NEW ENGLAND MED CTR,DEPT MED,BOSTON,MA 02111. NIH,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP Konstam, V (reprint author), TUFTS UNIV NEW ENGLAND MED CTR,DIV CARDIOL,BOX 108,750 WASHINGTON ST,BOSTON,MA 02111, USA. NR 22 TC 220 Z9 222 U1 1 U2 5 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 OCT 15 PY 1996 VL 78 IS 8 BP 890 EP 895 DI 10.1016/S0002-9149(96)00463-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VN757 UT WOS:A1996VN75700007 PM 8888661 ER PT J AU Domanski, M Solomon, A Gersh, B AF Domanski, M Solomon, A Gersh, B TI Developing a paradigm for training cardiovascular clinical investigators SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material AB A need exists for developing an optimal approach to training clinical investigators who will pursue careers in cardiovascular research, A paradigm for doing this that has been implemented is discussed. C1 GEORGETOWN UNIV HOSP,DIV CARDIOL,WASHINGTON,DC 20007. RP Domanski, M (reprint author), NHLBI,CLIN TRIALS GRP,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 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 OCT 15 PY 1996 VL 78 IS 8 BP 943 EP & PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VN757 UT WOS:A1996VN75700017 PM 8888671 ER PT J AU Wong, FL Ron, E Gierlowski, T Schneider, AB AF Wong, FL Ron, E Gierlowski, T Schneider, AB TI Benign thyroid tumors: General risk factors and their effects on radiation risk estimation SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE dose-response relationship; radiation; family health; radiation; reproductive history; socioeconomic factors; thyroid neoplasms ID CANCER; INFANCY; HISTORY; WOMEN; IRRADIATION; CHILDHOOD; NEOPLASIA; DISEASE; GLAND; HEAD AB The authors examined risk factors for benign thyroid nodules and their influence on radiation effects among 544 subjects who were exposed to childhood radiation treatment for benign head and neck conditions at a Chicago, Illinois hospital during 1939-1962. In follow-up through 1991, benign thyroid nodules were diagnosed in 131 patients. The risk of benign nodules was elevated in women (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.6-3.2), Jews (RR = 1.7, 95% CI 1.1-2.5), college graduates (RR = 1.8, 95% CI 1.2-2.8), and subjects whose mother had cancer (RR = 1.7, 95% CI 1.2-2.5). There were increasing trends for risk with increasing body mass index in women and decreasing height in men. Risk was increased for women who never married (RR - 3.7, 95% CI 1.6-7.3) or who never had a full-term pregnancy (RR = 2.0, 95% CI 1.1-3.3), A significant radiation dose-response relationship was observed that was not modified by sex, education, Jewish religion, or reproductive factors. The data suggest that there are genetic, life-style (including ascertainment), and hormonal factors associated with the development of benign thyroid nodules. C1 UNIV ILLINOIS,COLL MED,SECT ENDOCRINOL & METAB MC 640,CHICAGO,IL 60612. MICHAEL REESE HOSP,DIV ENDOCRINOL,CHICAGO,IL. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-21518, N01-CP-05609, N01-CP-85604] NR 21 TC 15 Z9 15 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 1996 VL 144 IS 8 BP 728 EP 733 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VM097 UT WOS:A1996VM09700003 PM 8857821 ER PT J AU Storer, BE Newcomb, PA Longnecker, MP AF Storer, BE Newcomb, PA Longnecker, MP TI Long-term hormone replacement therapy and risk of breast cancer in postmenopausal women - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP Storer, BE (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,MADISON,WI 53706, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 1996 VL 144 IS 8 BP 798 EP 799 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VM097 UT WOS:A1996VM09700012 ER PT J AU Weinberg, CR Baird, DD Wilcox, AJ AF Weinberg, CR Baird, DD Wilcox, AJ TI Effects of caffeine consumption on delayed conception SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID PREGNANCY; TIME RP Weinberg, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 7 TC 2 Z9 2 U1 1 U2 1 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 1996 VL 144 IS 8 BP 799 EP 799 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VM097 UT WOS:A1996VM09700013 PM 8857830 ER PT J AU DiBisceglie, AM Hoofnagle, JH AF DiBisceglie, AM Hoofnagle, JH TI Ribavirin for chronic hepatitis C - Response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NATL INST HLTH,BETHESDA,MD 20892. RP DiBisceglie, AM (reprint author), ST LOUIS UNIV,CTR HLTH SCI,ST LOUIS,MO 63104, USA. NR 0 TC 0 Z9 0 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 OCT 15 PY 1996 VL 125 IS 8 BP 699 EP 699 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VM889 UT WOS:A1996VM88900027 ER PT J AU Stitt, BL Kempner, ES AF Stitt, BL Kempner, ES TI Structure-function relationships in Escherichia coli transcription termination protein Rho revealed by radiation target analysis SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Rho; transcription termination; radiation inactivation; Escherichia coli ID PHYSICAL-PROPERTIES; RNA; INACTIVATION; BINDING; ATP; SIZE; COFACTORS; HELICASE; HEXAMER; ENERGY AB High-energy electrons were used to measure the target sizes for inactivation of the RNA-dependent ATPase activity of Escherichia coli transcription termination factor Rho, for its ATP binding ability, and for its physical destruction. SDS-PAGE analysis of irradiated samples indicated that the target size for polypeptide destruction in the homohexameric enzyme is the dimer, indicating that energy transfer must occur from a hit subunit to one other subunit, although the subunits are not known to be linked by any covalent bonds. The ATP binding ability of Rho also inactivates as a dimer, a result that is consistent with the physical destruction target size. However, a single subunit as the ATP binding entity is not excluded. The RNA-dependent ATPase activity of Rho inactivates with the apparent target size of trimer to tetramer, indicating that interactions among the subunits of Rho are required for ATP hydrolysis. Rho hexamers are known to exchange subunits, although the identity of the exchanging unit is not known. Models in which this property of Rho is taken into account indicate that the closest fit to the experimental data is for an ATPase target size of a hexamer with dimers as the exchanging units, consistent with earlier chemical inactivation studies. (C) 1996 Academic Press, Inc. C1 NIAMSD, PHYS BIOL LAB, NIH, BETHESDA, MD 20892 USA. RP Stitt, BL (reprint author), TEMPLE UNIV, SCH MED, DEPT BIOCHEM, 3420 N BROAD ST, PHILADELPHIA, PA 19140 USA. NR 40 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 15 PY 1996 VL 334 IS 2 BP 268 EP 276 DI 10.1006/abbi.1996.0455 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VP268 UT WOS:A1996VP26800011 PM 8900401 ER PT J AU London, RE Gabel, SA AF London, RE Gabel, SA TI Mg2+ and other polyvalent cations catalyze nucleotide fluorolysis SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE fluoride; fluorolysis; nucleotide fluorolysis; fluorophosphate; adenosine 5'-O-fluorophosphate; adenosine 5'-O-(2-fluorodiphosphate); F-19 NMR ID NUCLEAR MAGNETIC-RESONANCE; MULTIPLE QUANTUM COHERENCE; ADENOSINE 5'-(2-FLUORODIPHOSPHATE); PHOSPHATE ANALOGS; GAMMA-PHOSPHATE; PYRUVATE-KINASE; ATP HYDROLYSIS; METAL-ION; FLUORIDE; ACTIVATION AB The reaction of fluoride with adenosine triphosphate has been studied as a nonenzymatic analog of the pyruvate kinase-catalyzed fluorokinase reaction. The production of fluorophosphate, as well as adenosine 5'-O-fluorophosphate (FAMP) and adenosine 5'-O-(2-fluorodiphosphate) (beta FADP) was found to be dependent on the presence of polyvalent metal ions. All ions tested showed significant activity. Two catalytic regimes for the cations could be distinguished: a less specific enhancement of product formation at lower fluoride/cation ratios, and a considerably more active and specific (for fluorophosphate production) enhancement at high fluoride/cation ratios. A comparison of the results with studies of cation-catalyzed nucleotide hydrolysis indicates that the fluorolysis mechanisms are analogous to the hydrolysis by hydroxyl ions observed at high pH. In addition to these nonenzymatic studies, experiments performed using several commercially available kinases indicated significant fluorokinase activity for two: glycerokinase and acetate kinase, although the activities were much below that of pyruvate kinase. With the exception of the concentrations used in these studies, these reactions proceed under physiological conditions, yielding products at sufficient concentrations to be readily detected by F-19 NMR spectroscopy. RP London, RE (reprint author), NIEHS,MOL BIOPHYS LAB,BOX 12233,RES TRIANGLE PK,NC 27709, USA. NR 65 TC 5 Z9 5 U1 0 U2 3 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 OCT 15 PY 1996 VL 334 IS 2 BP 332 EP 340 DI 10.1006/abbi.1996.0462 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VP268 UT WOS:A1996VP26800018 PM 8900408 ER PT J AU Tazawa, R Green, ED Ohashi, K Wu, KK Wang, LH AF Tazawa, R Green, ED Ohashi, K Wu, KK Wang, LH TI Characterization of the complete genomic structure of human thromboxane synthase gene and functional analysis of its promoter SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE human thromboxane synthase; genomic structure; promoter ID LEUKEMIA-CELL LINE; MOLECULAR-CLONING; MESSENGER-RNA; EXPRESSION; CHROMOSOME; PROSTAGLANDIN; SEQUENCE; CDNA; INITIATOR; TBXAS1 AB Thromboxane A(2) (TXA) is a potent vasoconstrictor and mediator of platelet aggregation. Thromboxane synthase (TXAS), which catalyzes the biosynthesis of TXA, is a member of the cytochrome P450 superfamily. We report here the complete genomic structure of the human TXAS gene. The gene contains 1.3 exons and is 193 kb long, the largest P450 gene ever isolated. The physical localization of the TXAS gene on the genetic map of human chromosome 7 was established. A major transcription start site is located at a motif similar to the initiator element where the transcription factor TFII-I binds. We have sequenced up to 1.6 kb of the 5'-flanking region of the TXAS gene and characterized the promoter activity in a human megakaryocyte cell line and endothelial cells. Our results demonstrated that the nucleotides -248/+137 relative to the major transcription start site conferred a full promoter activity of the TXAS gene. This region was regulated negatively by cia-elements located between -1562 and -248. Moreover, the regions outside -1562/+137 might control tissue-specific TXAS expression. (C) 1996 Academic Press, Inc. C1 UNIV TEXAS, SCH MED, DEPT INTERNAL MED, VASC BIOL RES CTR, HOUSTON, TX 77030 USA. UNIV TEXAS, SCH MED, DEPT INTERNAL MED, DIV HEMATOL, HOUSTON, TX 77030 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RI Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [R01 HL50675] NR 39 TC 18 Z9 19 U1 1 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 OCT 15 PY 1996 VL 334 IS 2 BP 349 EP 356 DI 10.1006/abbi.1996.0464 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VP268 UT WOS:A1996VP26800020 PM 8900410 ER PT J AU Pommier, Y Kohlhagen, G Bailly, C Waring, M Mazumder, A Kohn, KW AF Pommier, Y Kohlhagen, G Bailly, C Waring, M Mazumder, A Kohn, KW TI DNA sequence- and structure-selective alkylation of guanine N2 in the DNA minor groove by ecteinascidin 743, a potent antitumor compound from the Caribbean tunicate Ecteinascidin turbinata SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURES; TOPOISOMERASE-I; 2-AMINO GROUP; ANTHRAMYCIN; AGENTS; CAMPTOTHECIN; RECOGNITION; CLEAVAGE; BINDING AB Ecteinascidin 743 is one of several related marine alkaloids isolated from the Caribbean tunicate Ecteinascidia turbinata. It is remarkably active and potent in a variety of in vitro and in vivo systems and has been selected for development as an anticancer agent. The present study investigates the interactions of ecteinascidin 743 with DNA. Ecteinascidin 743 retarded the electrophoretic migration of both supercoiled and relaxed simian virus 40 DNA even in the presence of sodium dodecyl sulfate and after ethanol precipitation, consistent with covalent DNA modifications. Similar results were obtained in a DNA oligonucleotide derived from ribosomal DNA, However, DNA denaturation reversed the DNA modifications. The homopolymeric oligonucleotide dG/dC was modified while neither the dI/dC nor the dA/dT oligonucleotides were, consistent with covalent attachment of ecteinascidin 743 to the exocyclic amino group at position 2 of guanine. Ecteinascidin 743 was then compared to another known DNA minor groove alkylating agent, anthramycin, which has also been shown to alkylate guanine N2. Footprinting analyses with DNase I and 1,10-phenanthroline-copper and exonuclease III digestions showed that ecteinascidin 743 covers three to five bases of DNA and exhibits a different sequence specificity than anthramycin in the Escherichia coli tyrosine tRNA promoter (tyrT DNA). The binding of ecteinascidin to DNA was abolished when guanines were substituted with inosines in this promoter. A band shift assay was designed to evaluate the influence of the bases flanking a centrally located guanine in an oligonucleotide containing inosines in place of guanines elsewhere. Ecteinascidin 743 and anthramycin showed similarities as well as differences in sequence selectivity. Ecteinascidin 743-guanine adducts appeared to require at least one flanking guanine and were strongest when the flanking guanine was 3' to the targeted guanine. These data indicate that ecteinascidin 743 is a novel DNA minor groove, guanine-specific alkylating agent. C1 UNIV CAMBRIDGE,DEPT PHARMACOL,CAMBRIDGE CB2 1TN,ENGLAND. RP Pommier, Y (reprint author), NCI,MOL PHARMACOL LAB,DIV BASIC SCI,NIH,BLDG 37,RM 5C25,BETHESDA,MD 20892, USA. NR 19 TC 249 Z9 252 U1 0 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 15 PY 1996 VL 35 IS 41 BP 13303 EP 13309 DI 10.1021/bi960306b PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM555 UT WOS:A1996VM55500007 PM 8873596 ER PT J AU Kocisko, DA Lansbury, PT Caughey, B AF Kocisko, DA Lansbury, PT Caughey, B TI Partial unfolding and refolding of scrapie-associated prion protein: Evidence for a critical 16-kDa C-terminal domain SO BIOCHEMISTRY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; NORMAL BRAIN; PRP 27-30; CONVERSION; CELLS; INFECTIVITY; GENOTYPE; ANTIBODY; FIBRILS; AGENT AB The conversion of the normal form of prion protein (PrPC) to a disease-specific form (PrPSc) is a central event in scrapie and other transmissible spongiform encephalopathies, PrPSc is distinguished from PrPC by its insolubility and its resistance to proteolysis. PrPSc is also capable of converting S-35-PrPC, ii? vitro, into a form which is indistinguishable from PrPSc with respect to its protease-sensitivity. Both the "converting activity" and the protease-resistance of isolated hamster PrPSc can be at least partially eliminated by denaturation and recovered by renaturation, provided that the concentration of denaturant does not exceed a threshold. This study was undertaken in order to localize the regions of native PrPSc structure that must remain intact to allow refolding. Proteinase K was used to digest exposed, denatured PrPSc sequences, and the residual fragments were characterized using anti-PrP antibodies directed toward four PrP epitopes. A 16-kDa fragment marked by an epitope within residues 143-156 remained protease-resistant under conditions which at least partially unfolded epitopes within residues 90-115 and 217-232, However, dilution of denaturant restored protease-resistance to these epitopes. This reversible unfolding was observed with both purified PrPSc and PrPSc in crude brain homogenates. Size fractionation of partially GdnHCl-solubilized PrPSc revealed that only the insoluble aggregates retained the ability to refold, consistent with the hypothesis that native PrPSc is an ordered aggregate, When the threshold denaturant concentration was exceeded, both protease-resistance of the 16-kDa C-terminal domain and converting activity were irreversibly destroyed. These results suggest that the in vitro converting activity requires ordered, protease-resistant PrPSc aggregates and that a critical aspect of the PrPSc structure is the folding of a particularly stable similar to 16-kDa C-terminal domain. C1 NIAID, PERSISTENT VIRAL DIS LAB, ROCKY MT LAB, NIH, HAMILTON, MT 59840 USA. MIT, DEPT CHEM, CAMBRIDGE, MA 02139 USA. NR 35 TC 81 Z9 81 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 15 PY 1996 VL 35 IS 41 BP 13434 EP 13442 DI 10.1021/bi9610562 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM555 UT WOS:A1996VM55500023 PM 8873612 ER PT J AU Leibenluft, E FeldmanNaim, S Turner, EH Schwartz, PJ Wehr, TA AF Leibenluft, E FeldmanNaim, S Turner, EH Schwartz, PJ Wehr, TA TI Salivary and plasma measures of dim light melatonin onset (DLMO) in patients with rapid cycling bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE melatonin; bipolar disorder; circadian rhythms ID RHYTHM; DEPRESSION AB A number of researchers have suggested that the phase (timing) of circadian rhythms in depressed patients is abnormal. Longitudinal studies could help to elucidate the relationship between circadian phase and mood, Such studies would be facilitated by the development of a noninvasive method for measuring circadian phase. In normal volunteers, the concentration of salivary melatonin measurements has been shown to be significantly correlated with those obtained in plasma; however, it is unknown whether salivary melatonin measurements can reliably detect the unmasked time of onset of nocturnal melatonin secretion (a measure of circadian phase), In addition, the relationship between salivary and plasma melatonin measurements in medicated psychiatric patients is unknown. We measured plasma and salivary melatonin simultaneously in a sample of 12 medicated patients with rapid cycling bipolar disorder, The intraclass correlation coefficient between plasma and salivary measures of the dim light melatonin onset (DLMO) was 0.93. We therefore conclude that salivary melatonin can be used to determine the time of the DLMO in this population. RP Leibenluft, E (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 17 TC 22 Z9 23 U1 0 U2 1 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 OCT 15 PY 1996 VL 40 IS 8 BP 731 EP 735 DI 10.1016/0006-3223(95)00488-2 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VL694 UT WOS:A1996VL69400006 PM 8894065 ER PT J AU Persico, AM Bird, G Gabbay, FH Uhl, GR AF Persico, AM Bird, G Gabbay, FH Uhl, GR TI D-2 dopamine receptor gene TaqI A1 and B1 restriction fragment length polymorphisms: Enhanced frequencies in psychostimulant-preferring polysubstance abusers SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dopamine D-2 receptor; genetic association; cocaine; amphetamine; substance abuse; alcoholism ID TRANSPORTER GENE; SUBSTANCE-ABUSE; ALLELIC ASSOCIATION; DRUG-ABUSE; ALCOHOLISM; COCAINE; VULNERABILITY; LOCUS; DRD2; RFLPS AB Several of evidence that presence of a D-2 dopamine receptor (DRD2) gene variant marked by TaqI restriction fragment length polymorphisms (RFLPs) might contribute to vulnerable to substance abuse. Psychostimulants display the most robust enhancement of dopamine activity in mesolimbic/mesocortical circuits important for behavioral reward. The present study tests the hypothesis that a DRD2 gene variant might be more prominent in polysubstance users who preferentially use psychostimulants than in addict with preferential opiate use or in those with no drug preference. Polysubstance users with histories of heavy daily preferential psychostimulant use more often displayed one of two copies of the TaqI A1 (27/62 = 43.5% vs 33/119 = 27.7% for controls), and B1 (20/62 = 32.3% vs 23/119 = 19.8% for controls) markers at the DED2 locus. DRD2 gene marker distributions in abusers with more prominent opiate use, or those with no history of drug preference, were similar to control genotypes. Psychostimulant-preferring drug users also reported earlier onset of psychostimulant use. Our data are consistent with the hypothesis that DRD2 gene variants marked by these polymorphisms may work, probably in concert with other genetic and environmental factors, to enhance vulnerability to psychostimulant abuse. C1 NIDA, ADDICT RES CTR,NIH,DIV INTRAMURAL RES, INTRAMURAL RES PROGRAM, BALTIMORE, MD 21224 USA. NIDA, MOL NEUROBIOL BRANCH, NIH, BALTIMORE, MD 21224 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT MED & CLIN PSYCHOL, BETHESDA, MD 20814 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, BALTIMORE, MD 21205 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROSCI, BALTIMORE, MD 21205 USA. FU NIDA NIH HHS [DA07110] NR 45 TC 100 Z9 101 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 1996 VL 40 IS 8 BP 776 EP 784 DI 10.1016/0006-3223(95)00483-1 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VL694 UT WOS:A1996VL69400012 PM 8894071 ER PT J AU Drize, NJ Keller, JR Chertkov, JL AF Drize, NJ Keller, JR Chertkov, JL TI Local clonal analysis of the hematopoietic system shows that multiple small short-living clones maintain life-long hematopoiesis in reconstituted mice SO BLOOD LA English DT Article ID MEDIATED GENE-TRANSFER; PRIMITIVE STEM-CELLS; BONE-MARROW; PROLIFERATIVE CAPACITY; REPOPULATING CELLS; TERM HEMATOPOIESIS; W/WV MICE; CFU-S; INTEGRATION; NUMBERS AB We describe here a technique to study the clonal contribution of primitive stem cells that account for long-term hematopoiesis in the same mouse over a 14-month period. Specifically, irradiated recipient female mice were transplanted with retrovirally marked male hematopoietic progenitors. Bone marrow was then collected repeatedly from local sites from the same mice throughout a 14-month period and injected into secondary irradiated recipients for analysis of donor retrovirally marked day-ii colony-forming unit-spleen (CFU-S-11). We have tracked the temporal in vivo fate of 194 individual CFU-S-derived cell clones in 38 mice reconstituted with such retrovirally marked bone marrow cells. Our data show that long-term hematopoiesis is maintained by a large number of simultaneously functioning small, short-lived (1 to 3 months) clones that usually grow locally with little or no dispersion between different regions of the hematopoietic system, Furthermore, the clones that disappeared were never detected again. The data suggest that normal hematopoiesis is supported by the sequential recruitment of marrow repopulating cells into a differentiation mode. (C) 1996 by The American Society of Hematology. C1 HEMATOL SCI CTR,LAB PHYSIOL HEMATOPOIESIS,MOSCOW 125167,RUSSIA. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RI Drize, Nina/M-7261-2014 OI Drize, Nina/0000-0002-7150-0403 NR 52 TC 48 Z9 50 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 OCT 15 PY 1996 VL 88 IS 8 BP 2927 EP 2938 PG 12 WC Hematology SC Hematology GA VN595 UT WOS:A1996VN59500013 PM 8874189 ER PT J AU Domachowske, JB Rafferty, SP Singhania, N Mardiney, M Malech, HL AF Domachowske, JB Rafferty, SP Singhania, N Mardiney, M Malech, HL TI Nitric oxide alters the expression of gamma-globin, H-ferritin, and transferrin receptor in human K562 cells at the posttranscriptional level SO BLOOD LA English DT Article ID IRON-RESPONSIVE ELEMENTS; MESSENGER-RNA; TRANSLATIONAL REGULATION; CHRONIC DISEASE; ANEMIA; SEQUENCES; STABILITY; SYNTHASE AB Cellular iron metabolism is altered during chronic inflammatory states, leading to reticuloendothelial iron sequestration and an associated anemia. To study the effects of nitric oxide (NO) on the expression of three genes involved in erythroid cell iron metabolism (gamma-globin, H-ferritin, and transferrin receptor [TfR]), we developed a series of human K562 erythroleukemic cell clones retrovirally transduced with inducible nitric oxide synthase (NOS-2) and producing different steady-state levels of NO. gamma-Globin and H-ferritin protein expression was reduced in NO-producing cells in relation to the amount of NO produced. Conversely, cell surface TfR expression increased in NO-producing clones. Both the inhibitory effects of NO on gamma-globin and H-ferritin expression and the stimulatory effect on TfR were reversed by the NOS inhibitor N-G-methyl-L-arginine (N(G)MMA). gamma-Globin and H-ferritin mRNA levels were unaffected by NO production. In the case of TfR, NO appeared to stabilize mRNA in that the half life of TfR mRNA decreased from approximately 15 hours to less than 3 hours when NO production by NOS-transduced clones was inhibited. Thus, NO can regulate expression of these genes at the posttranscriptional level, an effect that is likely mediated by the known effect of NO on the RNA binding activity of iron regulatory protein-1 (Pantopoulos and Hentze, Proc Natl Acad Sci USA 92:1267, 1995). Furthermore, our findings suggest a mechanism for the observed relationship between NO production and the pathophysiology of the anemia of chronic disease. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 23 TC 30 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 OCT 15 PY 1996 VL 88 IS 8 BP 2980 EP 2988 PG 9 WC Hematology SC Hematology GA VN595 UT WOS:A1996VN59500019 PM 8874195 ER PT J AU Robertson, KD Manns, A Swinnen, LJ Zong, JC Gulley, ML Ambinder, RF AF Robertson, KD Manns, A Swinnen, LJ Zong, JC Gulley, ML Ambinder, RF TI CpG methylation of the major Epstein-Barr virus latency promoter in Burkitt's lymphoma and Hodgkin's disease SO BLOOD LA English DT Article ID SIGNAL BINDING-PROTEIN; REED-STERNBERG CELLS; DNA METHYLATION; J-KAPPA; LYMPHOCYTES; EXPRESSION; GENE; 5-AZACYTIDINE; MALIGNANCIES; ACTIVATION AB The Epstein-Barr virus (EBV) latency C promoter drives expression of a family of viral proteins commonly targeted by CD8 cytotoxic T cells. These proteins are not generally expressed in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. The failure to express these proteins is almost certainly an important factor in the evasion of immunosurveillance by EBV-associated tumors. In a previous study, we have shown that transcriptional activation of the C promoter is inhibited by methylation of a particular CpG site upstream of the promoter that prevents binding of a cellular protein (CBF2), and we have shown that this and adjacent CpG sites are methylated in a Burkitt's lymphoma cell line. In the present study, we show that CpG sites in the CBF2 binding region are predominantly methylated in African Burkitt's lymphoma and in EBV-associated Hodgkin's disease. In addition, we present the first direct evidence that the C promoter is transcriptionally silent in Burkitt's lymphoma. In contrast, we show a complete absence of methylation in the CBF2 binding region in a case of reversible EBV-associated B-cell lymphoma arising in an immunocompromised patient whose tumor shows C promoter transcriptional activity. By inhibiting expression of highly antigenic viral proteins, methylation of transcriptional control sequences may veil the presence of virus in tumor tissue from CD8(+) cytotoxic T-cell immune surveillance and thus facilitate viral tumorigenesis. (C) 1996 by The American Society of Hematology. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOL SCI,BALTIMORE,MD 21205. NCI,VIRAL EPIDEMIOL BRANCH,ROCKVILLE,MD. LOYOLA UNIV,DEPT MED,MAYWOOD,IL 60153. UNIV TEXAS,HLTH SCI CTR,DEPT PATHOL,SAN ANTONIO,TX 78284. FU NCI NIH HHS [5 PO1 CA15396-21] NR 33 TC 53 Z9 55 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 OCT 15 PY 1996 VL 88 IS 8 BP 3129 EP 3136 PG 8 WC Hematology SC Hematology GA VN595 UT WOS:A1996VN59500037 PM 8874213 ER PT J AU Lin, AY Kingma, DW Lennette, ET Fears, TR Whitehouse, JM Ambinder, RF Jaffe, ES Levine, PH Tucker, MA AF Lin, AY Kingma, DW Lennette, ET Fears, TR Whitehouse, JM Ambinder, RF Jaffe, ES Levine, PH Tucker, MA TI Epstein-Barr virus and familial Hodgkin's disease SO BLOOD LA English DT Article ID MALIGNANT-LYMPHOMA; ANTIBODY PATTERNS; SUSCEPTIBILITY; CONCORDANCE; SIBLINGS AB Several studies suggest that the Epstein-Barr virus (EBV) is etiologically linked to Hodgkin's disease (HD). This study was undertaken to examine the role of EBV in familial HD (FHD). Among 60 FHD patients from 27 families with two or more cases per family, we tested available paraffinized tumor tissues from 46 cases by in situ hybridization for EBV-encoded RNA (EBER1) expression. Thirteen of 46 FHD patients (28%) had EBER1 expressed in the Reed-Sternberg cells. Concordance rate of EBV positivity was evaluated among 34 first-degree related pairs from 17 families for which both cases had available paraffinized tumor tissues. Only two of 17 pairs were concordant for EBER1 positivity, There was no excess of positive concordance (P=.18). Serologically, FHD patients had higher geometric mean antibody titers (GMTs) to the viral capsid antigen (VCA) and early antigen D (EA-D). There was no difference in seroprevalence between patients and control groups, nor was there concordance in elevated serology among 15 pairs of first-degree related FHD cases, Young adult unaffected family members (UFM) may not react to EBV in the same way as the general population as evidenced by the lower titer of VCA, although not statistically significant, and significantly lower titers of EA-D, compared with age-matched controls, While EBV might have some role in a subset of HD, lack of concordance of EBER1 expression and EBV serology among the FHD cases in the same family suggest that EBV does not play an important role in FHD. (C) 1996 by The American Society of Hematology. C1 NCI, VIRAL EPIDEMIOL BRANCH, HEMATOPATHOL SECT, PATHOL LAB, BETHESDA, MD 20892 USA. NCI, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD 20892 USA. JOHNS HOPKINS ONCOL CTR, BALTIMORE, MD USA. VIROLAB, BERKELEY, CA USA. WESTAT CORP, ROCKVILLE, MD USA. RP Lin, AY (reprint author), NCI, GENET EPIDEMIOL BRANCH, EPN 400, BETHESDA, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 26 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 1996 VL 88 IS 8 BP 3160 EP 3165 PG 6 WC Hematology SC Hematology GA VN595 UT WOS:A1996VN59500040 PM 8874216 ER PT J AU Mavroudis, D Read, E CottlerFox, M Couriel, D Molldrem, J Carter, C Yu, M Dunbar, C Barrett, J AF Mavroudis, D Read, E CottlerFox, M Couriel, D Molldrem, J Carter, C Yu, M Dunbar, C Barrett, J TI CD34(+) cell dose predicts survival, posttransplant morbidity, and rate of hematologic recovery after allogeneic marrow transplants for hematologic malignancies SO BLOOD LA English DT Article ID BLOOD STEM-CELLS; BONE-MARROW; PERIPHERAL-BLOOD; CFU-GM; ENGRAFTMENT; RECONSTITUTION; DISEASE; NUMBER; CSF AB After autologous or allogeneic transplants of peripheral blood stem cells (PBSC), an adequate dose of CD34(+) cells is necessary to ensure early and sustained hematopoietic engraftment and favorable clinical outcome. There are no comparable data on the relationship between CD34(+) cell dose and recovery after allogeneic bone marrow transplants (BMT). Twenty-eight patients with hematologic malignancies received a BMT from an HLA-identical sibling, using T-cell depletion and cyclosporin for graft-versus-host disease prophylaxis and delayed donor lymphocyte transfusions in an attempt to prevent leukemia relapse, The treatment-related mortality (TRM), primarily due to infections and cytopenias, was significantly higher for 13 patients receiving less than 1 x 10(6) CD34(+) cells/kg (64.9% +/- 12.8% v 6.9% +/- 6.4%, P =.003). Survival at a median follow-up of 1 year was also lower in the group receiving less than 1 x 10(6) CD34(+) cells/kg (30.8% +/- 12.8 v 74.3% +/- 13.7%, P =.005). The CD34(+) cell dose was the only variable significantly associated with TRM. The dose of CD34(+) cells also correlated with speed of hematopoietic recovery. Patients receiving more than 2 x 10(6) CD34(+) cells/kg showed significantly earlier recovery of monocytes and a trend for earlier recovery of lymphocytes. They achieved platelet and red blood cell transfusion independence earlier, required less granulocyte colony-stimulating factor support during ganciclovir treatment, and spent fewer days in the hospital after transplantation. These results suggest that, for allogeneic T-cell-depleted BMT, the higher CD34(+) cell doses may improve outcome in engrafting patients. C1 NIH,DEPT TRANSFUS MED,BETHESDA,MD. RP Mavroudis, D (reprint author), NHLBI,BONE MARROW TRANSPLANTAT UNIT,HEMATOL BRANCH,BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 24 TC 186 Z9 190 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 OCT 15 PY 1996 VL 88 IS 8 BP 3223 EP 3229 PG 7 WC Hematology SC Hematology GA VN595 UT WOS:A1996VN59500048 PM 8874224 ER PT J AU Chidambaram, A Goldstein, AM Gailani, MR Gerrard, B Bale, SJ DiGiovanna, JJ Bale, AE Dean, M AF Chidambaram, A Goldstein, AM Gailani, MR Gerrard, B Bale, SJ DiGiovanna, JJ Bale, AE Dean, M TI Mutations in the human homologue of the Drosophila patched gene in Caucasian and African-American nevoid basal cell carcinoma syndrome patients SO CANCER RESEARCH LA English DT Article ID POINT MUTATIONS; GORLIN SYNDROME; POLYMORPHISMS AB The nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome, is a multisystem autosomal dominant disorder. The salient features of this syndrome include multiple basal cell carcinomas, palmar and/or plantar pits, odontogenic keratocysts, skeletal and developmental anomalies, and ectopic calcification. Other features include such tumors as ovarian fibromas and medulloblastomas. There is extensive interfamilial as well as intrafamilial variability with respect to the manifestation and severity of the phenotype. Alterations in the human homologue (PTCH) of the Drosophila segment polarity gene patched have been identified in NBCCS patients as well as tumors associated with this syndrome. We report several mutations in this gene in NBCCS patients and present the clinical phenotypes of the individuals in whom these mutations were identified. C1 NCI,HUMAN GENET SECT,LAB GENOM DIVERS,FREDERICK CANC RES & DEV CTR,NIH,FREDERICK,MD 21702. SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. NCI,GENET EPIDEMIOL BRANCH,NIH,BETHESDA,MD 20852. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. NIAMSD,INTRAMURAL RES PROGRAM,NIH,BETHESDA,MD 20892. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [P30CA16359, K11CA60199, R01CA57605] NR 18 TC 103 Z9 104 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 OCT 15 PY 1996 VL 56 IS 20 BP 4599 EP 4601 PG 3 WC Oncology SC Oncology GA VL756 UT WOS:A1996VL75600013 PM 8840969 ER PT J AU Yang, K Fan, KH Newmark, H Leung, D Lipkin, M Steele, VE Kelloff, GJ AF Yang, K Fan, KH Newmark, H Leung, D Lipkin, M Steele, VE Kelloff, GJ TI Cytokeratin, lectin, and acidic mucin modulation in differentiating colonic epithelial cells of mice after feeding western-style diets SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; NORMAL MUCOSA; VITAMIN-D; CALCIUM; RISK; CARCINOGENESIS; PROLIFERATION; AZOXYMETHANE; AGGLUTININ; CARCINOMA AB Several studies have recently reported the development of colonic epithelial cell hyperproliferation in rodents following the ingestion of Western-style diets. In this study, additional measurements related to differentiation and maturation of the colonic epithelial cells were made after feeding this type of diet. Two Western-style diets high in fat and phosphate content and low in calcium and vitamin D were fed to C57BL/6J mice for 12, 24, and 52 weeks. Diet A contained American Blend fat as a source of lipids, diet B contained corn oil, and control diet C was a standard AIN-76A semisynthetic diet which is lower in fat content and higher in calcium and vitamin D. Colonic epithelial cells were studied for three biomarkers: cytokeratin catalogue no. 18 (clone LE64) expression, soybean agglutinin carbohydrate lectin binding, and acidic mucins including sialo- and sulfomucins. Feeding of diets A and B revealed that colonic epithelial cells had increased expression of cytokeratin catalogue 18 and SBA carbohydrate lectin binding compared to controls (P = 0.0001 for diet A versus C and diet B versus C). Significant differences were found between diets B and C (P = 0.0001) and diets A and C (P = 0.0001) in total acidic mucins and in the ratio of sialomucin:sulfomucin (P = 0.0001), These findings demonstrate that both functional and structural modifications occurred in colonic epithelial cells under these dietary conditions, and further defined this rodent model for preclinical evaluation of nutritional and chemopreventive interventions. C1 MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. STRANG CANC PREVENT CTR,NEW YORK,NY 10021. NCI,CHEMOPREVENT BRANCH,CANC RES PROGRAM,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CA-25498] NR 30 TC 24 Z9 24 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 OCT 15 PY 1996 VL 56 IS 20 BP 4644 EP 4648 PG 5 WC Oncology SC Oncology GA VL756 UT WOS:A1996VL75600022 PM 8840978 ER PT J AU Rao, GN Collins, BJ Giles, HD Heath, JE Foley, JF May, RD Buckley, LA AF Rao, GN Collins, BJ Giles, HD Heath, JE Foley, JF May, RD Buckley, LA TI Carcinogenicity of 2',3'-dideoxycytidine in mice SO CANCER RESEARCH LA English DT Article ID HEAT-STABLE ANTIGEN; LEUKEMIA-VIRUS DNA; NUCLEOSIDE ANALOGS; III INFECTIVITY; MOUSE; TOXICITY; INVITRO; CELLS; AIDS; PHARMACOKINETICS AB 2',3'-dideoxycytidine (ddC) is a synthetic pyrimidine nucleoside analogue approved for treatment of HIV-positive patients. Previous studies indicated that ddC has the potential to cause thymic lymphoma in C57BL/6 X C3H F-1 (hereafter called B6C3F(1)) mice. In this study, we evaluated the carcinogenic potential of ddC in two different mouse models. B6C3F(1) hybrid mice carry ecotropic endogenous proviral sequences that mau be activated to cause lymphoma, whereas NIH Swiss mice lack proviral sequences that can be expressed. The mice were treated with ddC by gavage at 500 and 1000 mg/kg/day for up to 6 months (human dose, 2.25 mg/day) and evaluated for toxicity, plasma levels of ddC, and pathological changes. Lymphocyte cell markers from the thymic lymphomas were assessed by immunophenotyping. Expression of p53 protein was evaluated using immunohistochemical staining. Treatment-related thymic lymphomas were present in both mouse models with a higher incidence in NIH Swiss than in B6C3F(1) mice. The lymphomas were more prevalent in females than in males of both mouse models. Most mice with thymic lymphoma died during the course of the study. In addition to the thymus, lymphoma was often present in lymph nodes, spleen, and other organs. Lymphomas arose more frequently in mice that lack endogenous ecotropic retroviral sequences and thus were not due to activation of endogenous provirus. During the third month of the study, a few NIH Swiss mice that died had granulosa cell tumors of the ovary. Treatment-related but reversible thymic atrophy was observed in both mouse models. There was a very high correlation between the internal dose of ddC and the incidence of thymic lymphoma in both mouse models. Most of the lymphocytes from control thymuses and ddC-induced lymphomas were positive for Thy-1.2 (pan-T), heat stable antigen, and CD4 and CD8 markers, with no marked differences in the lymphocyte markets of the tumors between sexes or dose groups. p53 protein was detected in only 20% (23/115) of the ddC-induced lymphomas with mostly minimal expression in scattered tells. Because ddC induced lymphomas in two different mouse models, the potential carcinogenic risk should be considered in long-term treatment of HIV-positive patients, especially children and adolescent patients treated with ddC. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. SO RES INST,BIRMINGHAM,AL 35205. RP Rao, GN (reprint author), NIEHS,MD B3-08,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 16 Z9 16 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 OCT 15 PY 1996 VL 56 IS 20 BP 4666 EP 4672 PG 7 WC Oncology SC Oncology GA VL756 UT WOS:A1996VL75600026 PM 8840982 ER PT J AU Salgaller, ML Marincola, FM Cormier, JN Rosenberg, SA AF Salgaller, ML Marincola, FM Cormier, JN Rosenberg, SA TI Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; T-CELL TOLERANCE; MULTIPLE EPITOPES; PERIPHERAL-BLOOD; IN-VITRO; IDENTIFICATION; RECOGNITION; INTERLEUKIN-2; VACCINATION; INDUCTION AB gp100 is a melanocytic lineage-specific antigen recognized by tumor-infiltrating lymphocytes, the adoptive transfer of which is associated with tumor regression in melanoma patients. In this study, peripheral blood mononuclear cells (PBMCs) were harvested from HLA-A2(+) melanoma patients before and after immunization with G9-209 (ITDQVPFSY), G9-280 (YLEPGPVTA), or G9-154 (KTWGQYWQV) peptides in Incomplete Freund's Adjuvant and were tested for the ability to be sensitized in vitro using PBMCs pulsed with the native peptides. In addition, PBMCs from patients receiving the G9-209 or G9-280 peptide were stimulated in vitro with peptides modified at anchor residues to enhance binding to HLA-AZ: G9-209/2M (IMDQVPFSY) or G9-280-9V (YLEPGPVTV). In patients immunized with G9-209, a single in vitro restimulation with G9-209/2M resulted in the generation of specific antipeptide lymphocytes from seven of seven postimmune PBMCs and only three of seven preimmune PBMCs. In patients immunized with G9-280, a single in vitro restimulation with G9-280/9V resulted in the generation of specific antipeptide lymphocytes from five of six postimmune PBMCs and four of six preimmune PBMCs. In almost all cases, CTLs raised against modified epitopes were capable of recognizing targets displaying the native nonamers. Several anti-G9-209 and anti-G9-209/2M CTLs also demonstrated specific lysis of, and specific IFN-gamma release in response to, gp100(+)-established cell lines. Thus, using peptides modified to enhance immunogenicity for in vitro stimulation improved the sensitivity of immune monitoring of patients immunized with synthetic peptides. These results demonstrate that immunization with a peptide derived from a tumor-associated protein such as gp100 can provoke a measurable antitumor immune response in cancer patients. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. NR 29 TC 178 Z9 180 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 OCT 15 PY 1996 VL 56 IS 20 BP 4749 EP 4757 PG 9 WC Oncology SC Oncology GA VL756 UT WOS:A1996VL75600038 PM 8840994 ER PT J AU Lothe, RA Karhu, R Mandahl, N Mertens, F Saeter, G Heim, S BorresenDale, AL Kallioniemi, OP AF Lothe, RA Karhu, R Mandahl, N Mertens, F Saeter, G Heim, S BorresenDale, AL Kallioniemi, OP TI Gain of 17q24-qter detected by comparative genomic hybridization in malignant tumors from patients with von Recklinghausen's neurofibromatosis SO CANCER RESEARCH LA English DT Article ID NERVE SHEATH TUMORS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; CYTOGENETIC ANALYSIS; TYPE-1 GENE; DERMATOFIBROSARCOMA PROTUBERANS; SOLID TUMORS; MUTATIONS; CHROMOSOME-17; SEQUENCE; IDENTIFICATION AB The genetic changes leading to the development of malignant peripheral nerve sheath tumors (MPNSTs) are largely unknown. The few tumors that have been investigated cytogenetically had highly complex karyotypes and no consistent rearrangements, and the attempts to pinpoint consistent DNA-level changes have met with only limited success. We used comparative genomic hybridization to analyze seven MPNSTs and one dermatofibrosarcoma protuberans from eight patients with von Recklinghausen's disease (neurofibromatosis type 1), as well as three sporadic MPNSTs. Gains and losses of DNA sequences were found in all tumors, with an average of four losses (range, 0-14) and two gains (range, 0-5) per tumor. Two striking observations were made: (a) an increase in copy number of the distal part of the long arm of chromosome 17, with the smallest region of overlap 17q24-qter, was seen in five of seven MPNSTs and in the only dermatofibrosarcoma protuberans, all of which were from patients with neurofibromatosis, whereas none of the three sporadic MPNSTs had this alteration; and (b) loss of 13q, with the smallest region of overlap 13q14-q21, was found in 6 of 10 MPNSTs. The consistent involvement of these two chromosomal regions probably reflects two different pathogenetic mechanisms for MPNSTs. C1 NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT ONCOL,N-0310 OSLO,NORWAY. TAMPERE UNIV HOSP,DEPT LAB MED,CANC GENET LAB,FIN-33521 TAMPERE,FINLAND. NIH,CANC GENET LAB,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV HOSP,DEPT CLIN GENET,LUND,SWEDEN. RP Lothe, RA (reprint author), NORWEGIAN RADIUM HOSP,INST CANC RES,DEPT GENET,N-0310 OSLO,NORWAY. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Mertens, Fredrik/0000-0002-6278-5232 NR 27 TC 63 Z9 64 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 OCT 15 PY 1996 VL 56 IS 20 BP 4778 EP 4781 PG 4 WC Oncology SC Oncology GA VL756 UT WOS:A1996VL75600042 PM 8840998 ER PT J AU Keane, MM Ettenberg, SA Lowrey, GA Russell, EK Lipkowitz, S AF Keane, MM Ettenberg, SA Lowrey, GA Russell, EK Lipkowitz, S TI Fas expression and function in normal and malignant breast cell lines SO CANCER RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1-BETA CONVERTING-ENZYME; FACTOR RECEPTOR SUPERFAMILY; MAMMARY EPITHELIAL-CELLS; RESTING HUMAN-BREAST; MEDIATED APOPTOSIS; MONOCLONAL-ANTIBODY; SURFACE ANTIGEN; CARCINOMA CELLS; ICE/CED-3 PROTEASE AB Expression and function of the Fas apoptotic pathway was investigated in normal and malignant human breast epithelial cells. Nontransformed mammary epithelial cell lines all expressed high levels of Fas mRNA and protein, but only one of seven breast cancer cell lines (T47D) expressed high levels of Fas. Apoptosis was induced in the nontransformed lines when they were incubated with the anti-Fas antibody. However, all of the breast cancer cell lines tested, except T47D, were resistant to Fas-mediated apoptosis. Four of five Fas-resistant breast cancer cell lines became sensitive to Fas-mediated apoptosis upon treatment with IFN-gamma. Fas mRNA increased slightly in both cell lines that became sensitive and in the cell line that remained resistant to Fas-mediated apoptosis upon IFN-gamma treatment. However, the cell surface expression of Fas showed little or no increase in any of the cell lines tested upon IFN-gamma treatment. In contrast to Fas expression, interleukin-1 beta-converting enzyme (ICE) expression increased only in the cell lines that became Fas sensitive after IFN-gamma treatment. The importance of ICE and/or ICE-like proteases in Fas-mediated apoptosis in these cells was confirmed by inhibition of Fas-mediated apoptosis by a specific ICE inhibitor, YVAD-cmk. Fas sensitivity was reconstituted in the IFN-gamma-resistant cell line by transfection of ICE into that cell line. Together, these data suggest that down-regulation of Fas and its pathway may be a step in tumor progression and that modulation of Fas expression may provide an approach to inducing apoptosis in breast cancer cells. C1 NCI,NAVY MED ONCOL BRANCH,NATL NAVAL MED CTR,BETHESDA,MD 20889. NR 71 TC 212 Z9 216 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 OCT 15 PY 1996 VL 56 IS 20 BP 4791 EP 4798 PG 8 WC Oncology SC Oncology GA VL756 UT WOS:A1996VL75600044 PM 8841000 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Stimulatory effect of beta-adrenergic agonists on endothelium-derived nitric oxide activity in humans. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 35 EP 35 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900034 ER PT J AU Yusuf, S Garg, R Smith, T Dagenais, G Montague, T Arnold, M Davies, R Teo, KK Bourassa, M Collins, J Williford, W Gorlin, R AF Yusuf, S Garg, R Smith, T Dagenais, G Montague, T Arnold, M Davies, R Teo, KK Bourassa, M Collins, J Williford, W Gorlin, R TI Which heart failure patients benefit the most from long term digoxin therapy? SO CIRCULATION LA English DT Meeting Abstract C1 MCMASTER UNIV,HAMILTON,ON,CANADA. NHLBI,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BOSTON,MA. UNIV MONTREAL,MONTREAL,PQ,CANADA. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 131 EP 131 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900130 ER PT J AU Svetkey, LP Wilson, AF McKeown, SP Chen, YT AF Svetkey, LP Wilson, AF McKeown, SP Chen, YT TI Linkage of diastolic salt sensitivity in African Americans to the beta(2)-adrenergic receptor region of chromosome 5 SO CIRCULATION LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 186 EP 186 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900185 ER PT J AU Anderson, RA Hoeg, JM AF Anderson, RA Hoeg, JM TI Source of acid cholesterol esterase function in cholesterol ester storage disease patients SO CIRCULATION LA English DT Meeting Abstract C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 198 EP 198 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900197 ER PT J AU Bader, G Edelstein, C Shamburek, RD Nishiwaki, M Nazih, H Schwartz, C Scanu, AM Brewer, HB AF Bader, G Edelstein, C Shamburek, RD Nishiwaki, M Nazih, H Schwartz, C Scanu, AM Brewer, HB TI Lp(a): Comparison of the in vivo metabolism of apo(a) and Lp(a) in man SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV CHICAGO,CHICAGO,IL 60637. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 215 EP 215 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900214 ER PT J AU Prasad, A Husain, S Mincemoyer, R Hathaway, L Panza, JA Cannon, RO Quyyumi, AA AF Prasad, A Husain, S Mincemoyer, R Hathaway, L Panza, JA Cannon, RO Quyyumi, AA TI Coronary flow mediated vasodilation improves with angiotensin converting enzyme inhibition SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 222 EP 222 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900221 ER PT J AU Cheng, HP Valdivia, HH Bogdanov, K Valdivia, C Spurgeon, H Xiao, RP Lakatta, EG AF Cheng, HP Valdivia, HH Bogdanov, K Valdivia, C Spurgeon, H Xiao, RP Lakatta, EG TI FK506-binding protein (FKBP) modulates Ca2+ release channel closure and adaptation in heart SO CIRCULATION LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 255 EP 255 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900254 ER PT J AU Xiao, RP Ji, XW Hohl, C Altschuld, R Lakatta, EG AF Xiao, RP Ji, XW Hohl, C Altschuld, R Lakatta, EG TI Coupling of pertussis toxin-sensitive G protein to beta(2)-adrenoceptor dissociates cAMP and contractile responses SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 260 EP 260 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900259 ER PT J AU Morley, JF Jacobson, KA Liang, BT AF Morley, JF Jacobson, KA Liang, BT TI Differential coupling of adenosine A1 and A3 receptors to stimulation of diacylglycerol in chick ventricular myocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD. UNIV PENN,MED CTR,PHILADELPHIA,PA 19104. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 268 EP 268 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900267 ER PT J AU Prasad, A Husain, S Mincemoyer, R Panza, JA Cannon, RO Quyyumi, AA AF Prasad, A Husain, S Mincemoyer, R Panza, JA Cannon, RO Quyyumi, AA TI Coronary endothelial dysfunction in humans improves with angiotensin converting enzyme inhibition SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 348 EP 348 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900347 ER PT J AU Sheps, DS McMahon, R Light, KC Maixner, W Pepine, CJ Cohen, JD Goldberg, AD Coghlin, C Kaufmann, PG AF Sheps, DS McMahon, R Light, KC Maixner, W Pepine, CJ Cohen, JD Goldberg, AD Coghlin, C Kaufmann, PG TI Low hot pain threshold predicts shorter lime to exercise-induced angina: The psychophysiological investigations of myocardial ischemia (PIMI) study SO CIRCULATION LA English DT Meeting Abstract C1 UNIV N CAROLINA,CHAPEL HILL,NC. MARYLAND MED RES INST,BALTIMORE,MD. UNIV FLORIDA,VA MED CTR,GAINESVILLE,FL. ST LOUIS UNIV,MED CTR,ST LOUIS,MO. HENRY FORD HOSP,DETROIT,MI 48202. UNIV ALABAMA,BIRMINGHAM,AL. NHLBI,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 437 EP 437 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900436 ER PT J AU Stone, PH McMahon, RP Andrews, TC MacCallum, G Pepine, CJ Goldberg, AD Cohen, JD Kaufmann, PG Sheps, DS AF Stone, PH McMahon, RP Andrews, TC MacCallum, G Pepine, CJ Goldberg, AD Cohen, JD Kaufmann, PG Sheps, DS TI Heart rate during daily activities and reproducibility of ischemia using ambulatory ECG monitoring: The psychophysiologic investigations of myocardial ischemia (PIMI) study. SO CIRCULATION LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. MARYLAND MED RES INST,BALTIMORE,MD. WILFORD HALL USAF MED CTR,LACKLAND AFB,TX. NHLBI,BETHESDA,MD 20892. UNIV FLORIDA,GAINESVILLE,FL. UNIV N CAROLINA,HENRY FORD HEART & VASC INST,CHAPEL HILL,NC. ST LOUIS UNIV,ST LOUIS,MO 63103. RI McMahon, Robert/C-5462-2009 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 446 EP 446 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900445 ER PT J AU Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Ferrans, VJ AF Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Ferrans, VJ TI Cardiac troponin T: Elevated serum levels and loss from cardiac myocytes in doxorubicin toxicity. SO CIRCULATION LA English DT Meeting Abstract C1 US FDA,LAUREL,MD. BOSTON UNIV,CHILDRENS HOSP,BOSTON,MA. NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 486 EP 486 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900485 ER PT J AU Kronmal, RA Manolio, TA Ettinger, WH Borhani, NO Orchard, TJ AF Kronmal, RA Manolio, TA Ettinger, WH Borhani, NO Orchard, TJ TI The relationship of lipid levels to five year mortality in a healthy elderly cohort: The Cardiovascular Health Study (CHS) SO CIRCULATION LA English DT Meeting Abstract C1 WASHINGTON UNIV,SEATTLE,WA. NHLBI,BETHESDA,MD 20892. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CALIF DAVIS,SACRAMENTO,CA 95817. UNIV PITTSBURGH,PITTSBURGH,PA 15260. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 540 EP 540 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900539 ER PT J AU Alvarez, RJ Irani, K Milliken, EE Finkel, T GoldschmidtClermont, PJ AF Alvarez, RJ Irani, K Milliken, EE Finkel, T GoldschmidtClermont, PJ TI Induction of Fas in pertussis toxin treated endothelial cells: Implications for endothelial cell apoptosis SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 590 EP 590 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900589 ER PT J AU Riccioni, T Cirielli, C Passaniti, A Capogrossi, MC AF Riccioni, T Cirielli, C Passaniti, A Capogrossi, MC TI Wild type p53 inhibits endothelial cell function SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 611 EP 611 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900610 ER PT J AU Fananapazir, L Masters, S Winkler, J Curiel, R Porcelli, J Tripodi, D McAreavey, D AF Fananapazir, L Masters, S Winkler, J Curiel, R Porcelli, J Tripodi, D McAreavey, D TI ACE gene polymorphism and ACE levels as determinants of left ventricular hypertrophy in hypertrophic cardiomyopathy caused by beta-myosin heavy chain mutations. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 636 EP 636 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900634 ER PT J AU Correia, LCL Atalar, E Kelemen, MD Hutchins, GM Fleg, JL Gerstenblith, G Zerhouni, E Lima, JAC AF Correia, LCL Atalar, E Kelemen, MD Hutchins, GM Fleg, JL Gerstenblith, G Zerhouni, E Lima, JAC TI Intraplaque lipid accumulation determined by intravascular magnetic resonance imaging SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. NIA,BALTIMORE,MD 21224. RI Atalar, Ergin/D-3184-2012 OI Atalar, Ergin/0000-0002-6874-6103 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 714 EP 714 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900712 ER PT J AU Rodriguez, BL Kodama, K Abbott, R Kasagi, F Sharp, DS Burchfeil, C Curb, JD AF Rodriguez, BL Kodama, K Abbott, R Kasagi, F Sharp, DS Burchfeil, C Curb, JD TI Diabetes, impaired glucose tolerance and 20 year total and non-cancer mortality in Japanese men in Japan and Hawaii SO CIRCULATION LA English DT Meeting Abstract C1 UNIV HAWAII,SCH MED,HONOLULU,HI 96822. RADIAT EFFECTS RES FDN,HIROSHIMA,JAPAN. UNIV VIRGINIA,CHARLOTTESVILLE,VA. NHLBI,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 828 EP 828 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900826 ER PT J AU Newman, AB Shemanski, L Manolio, TA Cushman, M Mittlemark, M Polak, JF Powe, N Laslett, L Siscovick, D AF Newman, AB Shemanski, L Manolio, TA Cushman, M Mittlemark, M Polak, JF Powe, N Laslett, L Siscovick, D TI Ankle arm index as a predictor of cardiovascular disease in the Cardiovascular Health Study SO CIRCULATION LA English DT Meeting Abstract C1 UNIV VERMONT,COLCHESTER,VT. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. HARVARD UNIV,CAMBRIDGE,MA 02138. JOHNS HOPKINS UNIV,BALTIMORE,MD. UNIV CALIF DAVIS,SACRAMENTO,CA 95817. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 837 EP 837 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900835 ER PT J AU Kai, T Kino, H Takenaka, T Sugimura, K Kamoi, K Shimada, S Kurooka, A Hama, J Katori, R AF Kai, T Kino, H Takenaka, T Sugimura, K Kamoi, K Shimada, S Kurooka, A Hama, J Katori, R TI The role of renin-angiotensin system in transgenic hypertensive mice carrying both human renin and angiotensinogen genes SO CIRCULATION LA English DT Meeting Abstract C1 KINKI UNIV,SCH MED,OSAKA,JAPAN. MAX DELBRUCK CTR MOL MED,BERLIN,GERMANY. NHLBI,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 846 EP 846 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900844 ER PT J AU Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Schumaker, VN Kempner, ES Wong, H AF Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Schumaker, VN Kempner, ES Wong, H TI Human hepatic lipase subunit structure determination SO CIRCULATION LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. W LOS ANGELES VET AFFAIRS MED CTR,LOS ANGELES,CA 90073. NIAMS,BETHESDA,MD. AMGEN INC,THOUSAND OAKS,CA 91320. NR 0 TC 0 Z9 0 U1 4 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 884 EP 884 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900882 ER PT J AU Johnson, TM Epstein, SE Finkel, T AF Johnson, TM Epstein, SE Finkel, T TI Species specific induction of apoptosis in normal vascular smooth muscle cells using an adenovirus expressing human p53 SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 901 EP 901 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11900899 ER PT J AU Hirsch, AT Garg, R Elam, JT Shindler, DM Pettinger, MB Wilt, TJ AF Hirsch, AT Garg, R Elam, JT Shindler, DM Pettinger, MB Wilt, TJ TI Quality-of-life and walking impairment in peripheral arterial disease in the arterial diseases multiple intervention trial SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NHLBI,BETHESDA,MD 20892. UNIV TENNESSEE,MEMPHIS,TN 38163. UMDNJ ROBERT WOOD JOHNSON,NEW BRUNSWICK,NJ. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1013 EP 1013 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901011 ER PT J AU SuttonTyrrell, K Rihal, C Burek, K Sellers, MA Jandova, R Hollak, B Trudel, J Lazzam, L Brooks, MM Sopko, G AF SuttonTyrrell, K Rihal, C Burek, K Sellers, MA Jandova, R Hollak, B Trudel, J Lazzam, L Brooks, MM Sopko, G TI Long-term prognostic value of cerebral and lower extremity atherosclerosis in patients undergoing coronary revascularization in the bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA. MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV MICHIGAN,COLL MED,ANN ARBOR,MI 48109. DUKE UNIV,MED CTR,DURHAM,NC. INST CLIN & EXPT MED,PRAGUE,CZECH REPUBLIC. STANFORD UNIV,MED CTR,STANFORD,CA 94305. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. TORONTO HOSP,TORONTO,ON M5T 2S8,CANADA. NHLBI,NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1014 EP 1014 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901012 ER PT J AU Arai, AE Abouassali, M McAreavey, D Fananapazir, L Balaban, RS Wolff, SD AF Arai, AE Abouassali, M McAreavey, D Fananapazir, L Balaban, RS Wolff, SD TI Imaging early diastolic dysfunction with MRI in one breathhold: Application to the evaluation of hypertrophic cardiomyopathy. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1052 EP 1052 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901050 ER PT J AU Dries, DL Rosenberg, YD Waclwiw, MA Domanski, MJ AF Dries, DL Rosenberg, YD Waclwiw, MA Domanski, MJ TI Gender differences in the relationship of ejection fraction and the risk of thromboembolic events for heart failure patients in sinus rhythm SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,CLIN TRIALS GRP,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007. OFF BIOSTAT RES,BETHESDA,MD. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1126 EP 1126 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901123 ER PT J AU Srinivasan, G Nour, KA Davis, CM Kitsiou, A Bacharach, SL Dilsizian, V AF Srinivasan, G Nour, KA Davis, CM Kitsiou, A Bacharach, SL Dilsizian, V TI Gated thallium imaging with multiheaded SPECT differentiates attenuation from myocardial injury in routine clinical studies. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1402 EP 1402 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901399 ER PT J AU Sakai, N Vaisman, BL Koch, CA Hoyt, RF Meyn, SM Paiz, JA Brewer, HB SantamarinaFojo, S AF Sakai, N Vaisman, BL Koch, CA Hoyt, RF Meyn, SM Paiz, JA Brewer, HB SantamarinaFojo, S TI Lecithin:holesterol acyltransferase (LCAT) knockout mice: A new animal model for human LCAT-deficiency SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. NHLBI,LAMS,NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1594 EP 1594 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901590 ER PT J AU Brousseau, ME Phair, RD Zech, LA SantamarinaFojo, S Brewer, HB Hoeg, JM AF Brousseau, ME Phair, RD Zech, LA SantamarinaFojo, S Brewer, HB Hoeg, JM TI LCAT overexpression modulates the metabolism of apolipoprotein B-containing lipoproteins in transgenic rabbits SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,BALTIMORE,MD. NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1595 EP 1595 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901591 ER PT J AU Nishiwaki, M Bader, G Nazih, H Shamburek, RD Schwartz, C Talley, GD Brewer, HB AF Nishiwaki, M Bader, G Nazih, H Shamburek, RD Schwartz, C Talley, GD Brewer, HB TI Lecithin cholesterol acyltransferase deficiency: Human in vivo kinetics of LDL and LpX-like lipoproteins SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,RICHMOND,VA 23298. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1597 EP 1597 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901593 ER PT J AU Bothe, J Sakai, N Marcovina, S SantamarinaFojo, S Hoeg, JM AF Bothe, J Sakai, N Marcovina, S SantamarinaFojo, S Hoeg, JM TI Lecithin:cholesterol acyl transferase and cholesteryl ester transfer protein contribute to low HDL cholesterol concentrations in familial hypercholesterolemia SO CIRCULATION LA English DT Meeting Abstract C1 UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1598 EP 1598 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901594 ER PT J AU Foeger, B SantamarinaFojo, S Shamburek, RD Parrott, CL Talley, GD Brewer, HB AF Foeger, B SantamarinaFojo, S Shamburek, RD Parrott, CL Talley, GD Brewer, HB TI Phospholipid transfer protein: Adenovirus mediated overexpression in mice leads to decreased plasma HDL, increased VLDL-LDL and accelerated hepatic uptake of HDL phospholipids SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1602 EP 1602 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901598 ER PT J AU Pierzchalski, P Reiss, K Kajstura, J Cheng, W Nitahara, JA Rizk, M Cirielli, C Capogrossi, M Anversa, P AF Pierzchalski, P Reiss, K Kajstura, J Cheng, W Nitahara, JA Rizk, M Cirielli, C Capogrossi, M Anversa, P TI p53 Activates apoptosis in adult ventricular myocytes via the up-regulation of the cellular renin-angiotensin system. SO CIRCULATION LA English DT Meeting Abstract C1 NEW YORK MED COLL,VALHALLA,NY 10595. NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1636 EP 1636 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901632 ER PT J AU Irani, K Milliken, EE Finkel, T GoldschmidtClermont, PJ AF Irani, K Milliken, EE Finkel, T GoldschmidtClermont, PJ TI Modulation of the actin cytoskeleton in endothelial cells by Rac1 is mediated by superoxide. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1660 EP 1660 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901656 ER PT J AU Moore, KA Johnson, TM Irani, K GoldschmidtClermont, PJ Finkel, T AF Moore, KA Johnson, TM Irani, K GoldschmidtClermont, PJ Finkel, T TI Requirement of rac1 for smooth muscle cell viability and cell cycle progression SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1661 EP 1661 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901657 ER PT J AU Korzick, DH Xiao, RP Ziman, BD Koch, MJ Lefkowitz, RJ Lakatta, EG AF Korzick, DH Xiao, RP Ziman, BD Koch, MJ Lefkowitz, RJ Lakatta, EG TI Genetic manipulation of the beta-adrenergic receptor kinase (beta ARK1) modifies contractile response to beta(1)-adrenergic stimulation in single cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1676 EP 1676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901672 ER PT J AU Donovan, M Hahn, RT Tessarollo, L Hempstead, BL AF Donovan, M Hahn, RT Tessarollo, L Hempstead, BL TI Neurotrophin-3 is required for mammalian cardiac development: Identification of an essential nonneuronal neurotrophin function SO CIRCULATION LA English DT Meeting Abstract C1 HARVARD UNIV,CHILDRENS HOSP,BOSTON,MA 02115. CORNELL UNIV MED COLL,NEW YORK,NY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1736 EP 1736 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901731 ER PT J AU Dilsizian, V Panza, JA Kitsiou, AN Laurienzo, JM Bacharach, SL AF Dilsizian, V Panza, JA Kitsiou, AN Laurienzo, JM Bacharach, SL TI Thallium and F-18 deoxyglucose provide incremental viability information to transesophageal dobutamine echocardiography for identifying hibernating myocardium SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1765 EP 1765 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901760 ER PT J AU Whitlow, PL Bashore, TM Bourassa, MG Chaitman, BR Andrews, KH Rosen, AD Stadius, ML Sopko, G Alderman, EL AF Whitlow, PL Bashore, TM Bourassa, MG Chaitman, BR Andrews, KH Rosen, AD Stadius, ML Sopko, G Alderman, EL TI Relationship of extent of revascularization with angina at one year in patients randomized to PTCA or CABG in bypass angioplasty revascularization investigation (BARI) SO CIRCULATION LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. MONTREAL HEART INST,MONTREAL,PQ H1T 1C8,CANADA. ST LOUIS UNIV,MED CTR,ST LOUIS,MO. SEATTLE VA HOSP,SEATTLE,WA. STANFORD UNIV,STANFORD,CA 94305. UNIV PITTSBURGH,NHLBI,NIH,DHVD,PITTSBURGH,PA. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1853 EP 1853 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901848 ER PT J AU Nabulsi, AA Folsom, AR Szklo, M White, A Higgins, M Heiss, G AF Nabulsi, AA Folsom, AR Szklo, M White, A Higgins, M Heiss, G TI No association of menopause and hormone replacement therapy with carotid artery intima-media thickness SO CIRCULATION LA English DT Article DE menopause; hormones; atherosclerosis ID CORONARY HEART-DISEASE; POSTMENOPAUSAL ESTROGEN USE; CARDIOVASCULAR-DISEASE; RISK-FACTORS; MYOCARDIAL-INFARCTION; FOLLOW-UP; PROGESTOGEN REPLACEMENT; WOMEN; ATHEROSCLEROSIS; STROKE AB Background Cardiovascular disease is the major cause of death in older women. Information on the relation of menopause and hormone replacement therapy with carotid atherosclerosis is limited. Methods and Results We examined cross-sectionally the association of menopausal status, years since last menstruation, and hormone replacement therapy status with carotid artery intima-media thickness as determined by B-mode ultrasound. Female participants (n=5436) in the Atherosclerosis Risk in Communities Study without a history of symptomatic cardiovascular disease were included in the analyses. Menopause status in 45- to 54-year-old women who had never used hormone replacement therapy was not strongly associated with carotid intima-media thickness (mean=0.65 mm and 0.67 mm in premenopausal and postmenopausal women, respectively, adjusted for age, race, cigarette years of smoking, body mass index, sport index, systolic blood pressure, use of blood pressure medications, drinking status, diabetes, and education level). In postmenopausal women aged 55 to 64 years, women with less than or equal to 5 years since last menstruation had an adjusted average intima-media thickness (0.74 mm) comparable to those with >5 years since last menstruation (0.75 mm) (P>.05). Although hormone replacement therapy use was associated with a more favorable lipid and hemostasis profile than nonuse, its use was not associated with intima-media thickness in postmenopausal women aged 55 to 64 years (adjusted average=0.74 mm for current users of estrogen alone and approximate to 0.75 mm each for current users of estrogen plus progestin, former users, and never users). Conclusions The data suggest that the well-known associations of hormone replacement therapy with reductions in atherosclerotic cardiovascular disease may be attributable more to acute physiological effects, such as hemodynamic changes or reduced thrombosis, than to atherosclerosis itself. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV N CAROLINA,DEPT EPIDEMIOL,SCH PUBL HLTH,CHAPEL HILL,NC. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. BURROUGHS WELLCOME CO,EPIDEMIOL SURVEILLANCE & PHARMACOECON DIV,RES TRIANGLE PK,NC. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55016, N01-HC-55015] NR 47 TC 46 Z9 47 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 OCT 15 PY 1996 VL 94 IS 8 BP 1857 EP 1863 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VM393 UT WOS:A1996VM39300014 PM 8873660 ER PT J AU Correia, LCL Lakatta, EG OConnor, FC Becker, LC Gerstenblith, G Clulow, J Townsend, S Fleg, JL AF Correia, LCL Lakatta, EG OConnor, FC Becker, LC Gerstenblith, G Clulow, J Townsend, S Fleg, JL TI Cardiovascular response to prolonged submaximal exercise in healthy subjects SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 1896 EP 1896 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901891 ER PT J AU Liu, K Gidding, SS Howard, BV Jacobs, DR Bild, D AF Liu, K Gidding, SS Howard, BV Jacobs, DR Bild, D TI Relationships between changes in dietary fat intake and changes in LDL-C for young adults with different ApoE phenotypes: The CARDIA study SO CIRCULATION LA English DT Meeting Abstract C1 MEDLANT RES INST,WASHINGTON,DC. NORTHWESTERN UNIV,CHICAGO,IL 60611. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 1977 EP 1977 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11901972 ER PT J AU Mantile, G Crow, MT Bilato, C Pauly, R Cheng, L StetlerStevenson, WG Capogrossi, MC AF Mantile, G Crow, MT Bilato, C Pauly, R Cheng, L StetlerStevenson, WG Capogrossi, MC TI Adenovirus mediated gene transfer of human tissue inhibitor of metalloproteinase-2 inhibits vascular smooth muscle cell migration SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,LCS,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD. NCI,PATHOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2036 EP 2036 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902031 ER PT J AU Rozanski, DJ Lakatta, EG Sollott, SJ AF Rozanski, DJ Lakatta, EG Sollott, SJ TI Chemoattractant-gradient-specific Ca2+-signalling regulates vascular myocyte chemotaxis SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2066 EP 2066 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902061 ER PT J AU Chen, CH Ting, CT Lin, SJ Hsu, TL Chou, P Chang, MS OConnor, F Spurgeon, H Lakatta, E Yin, FCP AF Chen, CH Ting, CT Lin, SJ Hsu, TL Chou, P Chang, MS OConnor, F Spurgeon, H Lakatta, E Yin, FCP TI Gender differences in the determinants of left ventricular mass SO CIRCULATION LA English DT Meeting Abstract C1 VET GEN HOSP,TAICHUNG,TAIWAN. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2109 EP 2109 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902104 ER PT J AU Maldonado, C Bagri, H Qiu, YM Tang, XL Auchampach, J Jadoon, A Jacobson, K Teschner, S Bolli, R AF Maldonado, C Bagri, H Qiu, YM Tang, XL Auchampach, J Jadoon, A Jacobson, K Teschner, S Bolli, R TI Late preconditioning against myocardial stunning mediated by adenosine A(1) and A(3) receptors? SO CIRCULATION LA English DT Meeting Abstract C1 UNIV LOUISVILLE,LOUISVILLE,KY 40292. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2112 EP 2112 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902107 ER PT J AU Chen, W Murphy, E Steenbergen, C AF Chen, W Murphy, E Steenbergen, C TI Role of 12-lipoxygenase metabolism of arachidonic acid in cardioprotection SO CIRCULATION LA English DT Meeting Abstract C1 DUKE UNIV,MED CTR,DURHAM,NC. NIEHS,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2113 EP 2113 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902108 ER PT J AU Gottdiener, JS Yanez, D Rautaharju, P Gardin, JM Bild, D Lima, J Newman, A AF Gottdiener, JS Yanez, D Rautaharju, P Gardin, JM Bild, D Lima, J Newman, A TI Orthostatic hypotension in the elderly: Contributions of altered sympathovagal balance and impaired LV filling SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PITTSBURGH,PITTSBURGH,PA. GEORGETOWN UNIV HOSP,WASHINGTON,DC 20007. BOWMAN GRAY MED CTR,WINSTON SALEM,NC. UNIV CALIF IRVINE,IRVINE,CA 92717. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,MED CTR,BALTIMORE,MD 21218. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2272 EP 2272 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902267 ER PT J AU Dichek, DA Dong, G Schulick, AH DeYoung, MB AF Dichek, DA Dong, G Schulick, AH DeYoung, MB TI Identification of a sequence in the human plasminogen activator inhibitor gene that mediates responsiveness to transforming growth factor B1 in endothelium in vivo SO CIRCULATION LA English DT Meeting Abstract C1 UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA. NHLBI,MOL HEMATOL BRANCH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2310 EP 2310 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902305 ER PT J AU ApplebaumBowden, D Brousseau, ME Hoeg, JM Vaisman, BL Parrott, CL Duarte, CJ Brewer, HB SantamarinaFojo, S AF ApplebaumBowden, D Brousseau, ME Hoeg, JM Vaisman, BL Parrott, CL Duarte, CJ Brewer, HB SantamarinaFojo, S TI Adenovirus-mediated transfer of hepatic lipase (HL) in transgenic rabbits overexpressing human lecithin-cholesterol acyltransferase (LCAT) SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,NIH,MDB,BETHESDA,MD. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2315 EP 2315 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902310 ER PT J AU Dugi, KA Knapper, CL ApplebaumBowden, D Bensadoun, A Meyn, SM Le, TT Maeda, N Brewer, HB SantamarinaFojo, S AF Dugi, KA Knapper, CL ApplebaumBowden, D Bensadoun, A Meyn, SM Le, TT Maeda, N Brewer, HB SantamarinaFojo, S TI In vivo evidence for a nonlipolytic hole of hepatic lipase in the metabolism of high density lipoproteins SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC. CORNELL UNIV,ITHACA,NY. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2316 EP 2316 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902311 ER PT J AU Amar, MJA Shamburek, RD Maeda, N Kindt, MR SantamarinaFojo, S Brewer, HB AF Amar, MJA Shamburek, RD Maeda, N Kindt, MR SantamarinaFojo, S Brewer, HB TI Adenovirus mediated expression of hepatic lipase in apoE deficient mice: Evidence for hepatic lipase-mediated clearance of remnant lipoprotein SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 2317 EP 2317 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902312 ER PT J AU Shiota, T Jones, M Aida, S Thigpen, T Chikada, M Yamada, I Sahn, DJ AF Shiota, T Jones, M Aida, S Thigpen, T Chikada, M Yamada, I Sahn, DJ TI Calculation of shunt flow volume through atrial septal defects by a newly developed digital color Doppler flow quantitation method: In vitro and experimental animal study in sheep SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. NHLBI,LAMS,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2422 EP 2422 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902417 ER PT J AU Senzaki, H Richard, T Peter, P Michael, C Zeke, G David, KA AF Senzaki, H Richard, T Peter, P Michael, C Zeke, G David, KA TI Angiotensin-II exacerbates diastolic failure in experimental cardiomyopathy: Role of matrix metalloprotease activation SO CIRCULATION LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NIA,NIH,BALTIMORE,MD 21224. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2530 EP 2530 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902523 ER PT J AU Tracy, RP Arnold, A Ettinger, WH Fried, LP Meilahn, E Savage, PJ AF Tracy, RP Arnold, A Ettinger, WH Fried, LP Meilahn, E Savage, PJ TI Coagulation factor VIII is associated with incident cardiovascular disease and death in the elderly: The cardiovascular health study. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV VERMONT,BURLINGTON,VT. NHLBI,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. JOHNS HOPKINS UNIV,BALTIMORE,MD. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV LONDON LONDON SCH HYG & TROP MED,LONDON WC1E 7HT,ENGLAND. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2668 EP 2668 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902660 ER PT J AU Cushman, M Kuller, LH Psaty, BM Lemaitre, RN Macy, E Sharrett, AR Tracy, RP AF Cushman, M Kuller, LH Psaty, BM Lemaitre, RN Macy, E Sharrett, AR Tracy, RP TI D-dimer level in prediction of incident cardiovascular disease events in the elderly. SO CIRCULATION LA English DT Meeting Abstract C1 UNIV VERMONT,BURLINGTON,VT. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV WASHINGTON,SEATTLE,WA 98195. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2670 EP 2670 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902662 ER PT J AU Garg, R Malinow, R Pettinger, M Hunninghake, D AF Garg, R Malinow, R Pettinger, M Hunninghake, D TI Treatment with niacin increases plasma homocyst(e)ine levels SO CIRCULATION LA English DT Meeting Abstract C1 OREGON REG PRIMATE RES CTR,PORTLAND,OR. NIH,BETHESDA,MD 20892. OSTEX INT INC,SEATTLE,WA. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2672 EP 2672 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902664 ER PT J AU Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA AF Cardillo, C Kilcoyne, CM Quyyumi, AA Cannon, RO Panza, JA TI Abnormal nitric oxide-dependent forearm vasodilation to mental stress in patients with essential hypertension. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2681 EP 2681 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902673 ER PT J AU Remaley, AT Farsi, BD Hoeg, JM AF Remaley, AT Farsi, BD Hoeg, JM TI Polarized cholesterol efflux from basolateral membranes of MDCK cells SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2711 EP 2711 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902703 ER PT J AU Ludomirsky, A Nesser, HJ Ebner, C Tkalec, W Jones, M Chikada, M Yamada, I Aida, S Sahn, DJ AF Ludomirsky, A Nesser, HJ Ebner, C Tkalec, W Jones, M Chikada, M Yamada, I Aida, S Sahn, DJ TI Semi-automated color Doppler (ACM) estimation of shunt volume flow through atrial septal defects: Comparisons of accuracy using great arteries or direct ASD flow computation: Experimental animal studies and clinical validation SO CIRCULATION LA English DT Meeting Abstract C1 OREGON HLTH SCI UNIV,PORTLAND,OR 97201. UNIV MICHIGAN,CS MOTT CHILDRENS HOSP,ANN ARBOR,MI 48109. NHLBI,LAMS,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2879 EP 2879 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902871 ER PT J AU McAreavey, D Tripodi, D Parks, D Fananapazir, L AF McAreavey, D Tripodi, D Parks, D Fananapazir, L TI The natural history of obstructive hypertrophic cardiomyopathy in pediatric patients: Effect of dual chamber pacing on left and right ventricular outflow obstruction. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 2945 EP 2945 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11902937 ER PT J AU Nazih, H Remaley, AT Alaupovic, P Brewer, HB AF Nazih, H Remaley, AT Alaupovic, P Brewer, HB TI Apolipoprotein E: The differential effect of ApoE and LpE particles in cholesterol efflux SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MBD,NIH,BETHESDA,MD 20892. LIPOPROT LAB,OKLAHOMA CITY,OK. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3039 EP 3039 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903031 ER PT J AU Boluyt, MO Zheng, JS Younes, A ONeill, L Lakatta, EG Crow, MT AF Boluyt, MO Zheng, JS Younes, A ONeill, L Lakatta, EG Crow, MT TI Rapamycin selectively inhibits protein and RNA accumulation, but not induction of hypertrophy associated genes during alpha-1-adrenergic stimulated cardiac myocyte hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. UNIV CLERMONT FERRAND,CLERMONT FERRAN,FRANCE. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3103 EP 3103 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903095 ER PT J AU Mootha, VK Balaban, RS AF Mootha, VK Balaban, RS TI Stimulation of mitochondrial oxidative phosphorylation by calcium SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,LCE,NIH,BETHESDA,MD 20892. NIH,HHMI,BETHESDA,MD. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3194 EP 3194 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903184 ER PT J AU Balaban, RS French, S Mootha, V AF Balaban, RS French, S Mootha, V TI Relation between heart mitochondria NADH/NAD and membrane potential: Evidence for near equilibrium of site I. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,LCE,NIH,BETHESDA,MD. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3198 EP 3198 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903188 ER PT J AU Rywik, TM Khan, AA Zirk, RC Gittings, NS Wright, JG OConnor, FC Fleg, JL AF Rywik, TM Khan, AA Zirk, RC Gittings, NS Wright, JG OConnor, FC Fleg, JL TI Do recovery ST segment changes after treadmill exercise predict coronary events in asymptomatic individuals? SO CIRCULATION LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3310 EP 3310 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903300 ER PT J AU Lauer, MS Pashkow, FJ Larson, MG Levy, D AF Lauer, MS Pashkow, FJ Larson, MG Levy, D TI Association of cigarette smoking with chronotropic incompetence and prognosis in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 CLEVELAND CLIN FDN,CLEVELAND,OH 44195. FARMINGHAM HEART STUDY,FRAMINGHAM,MA. NHLBI,FRAMINGHAM HEART STUDY,BETHESDA,MD 20892. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3313 EP 3313 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903303 ER PT J AU Abascal, VM Larson, MG Evans, JC Poll, KA Levy, D AF Abascal, VM Larson, MG Evans, JC Poll, KA Levy, D TI Calcium channel blocker use is net associated with increased mortality SO CIRCULATION LA English DT Meeting Abstract C1 BOSTON UNIV,FRAMINGHAM STUDY,FRAMINGHAM,MA. NHLBI,FRAMINGHAM STUDY,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3383 EP 3383 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903373 ER PT J AU Pahor, M Guralnik, JM Ferrucci, L Corti, MC Salive, ME Cerhan, JR Wallace, RB Havlik, RJ AF Pahor, M Guralnik, JM Ferrucci, L Corti, MC Salive, ME Cerhan, JR Wallace, RB Havlik, RJ TI Calcium channel blocker use and risk of cancer in older persons SO CIRCULATION LA English DT Meeting Abstract C1 CATHOLIC UNIV ROME,ROME,ITALY. NIA,BETHESDA,MD 20892. INRCA FLORENCE,FLORENCE,ITALY. UNIV IOWA,IOWA CITY,IA 52242. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3384 EP 3384 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903374 ER PT J AU Gordon, DJ AF Gordon, DJ TI Cholesterol lowering reduces mortality: Results of updated meta-analysis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3387 EP 3387 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903377 ER PT J AU Shamburek, RD Ikewaki, K Zech, LA Brewer, B AF Shamburek, RD Ikewaki, K Zech, LA Brewer, B TI Apolipoprotein J: Human in vivo metabolism of LpJ and LpJ:A-I SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3415 EP 3415 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903405 ER PT J AU Chesney, CM Herd, JA Elam, MB Garg, R Davis, KB Kennedy, JW Hunninghake, DB Applegate, WB AF Chesney, CM Herd, JA Elam, MB Garg, R Davis, KB Kennedy, JW Hunninghake, DB Applegate, WB TI Niacin lowers fibrinogen in patients with peripheral artery disease (PAD) SO CIRCULATION LA English DT Meeting Abstract C1 UNIV TENNESSEE,MEMPHIS,TN. BAYLOR COLL MED,HOUSTON,TX 77030. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3419 EP 3419 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903409 ER PT J AU Sali, J Gloe, TR DiPaula, AF Becker, LC Capogrossi, MC AF Sali, J Gloe, TR DiPaula, AF Becker, LC Capogrossi, MC TI Adenovirus-mediated gene transfer of acidic fibroblast growth factor reduces the risk region in a rabbit model of myocardial infarction. SO CIRCULATION LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3457 EP 3457 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903447 ER PT J AU Shibutani, T Yu, ZX Ferrans, VJ Moss, J Epstein, SE AF Shibutani, T Yu, ZX Ferrans, VJ Moss, J Epstein, SE TI Pertussis toxin sensitive G-proteins as possible mediators of the SMC signal transduction pathways of cytomegalovirus SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3485 EP 3485 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903475 ER PT J AU Horiba, K Tamura, K Fukuda, Y Usuki, J StetlerStevenson, WG Liotta, LA Yamanaka, N Ferrans, VJ AF Horiba, K Tamura, K Fukuda, Y Usuki, J StetlerStevenson, WG Liotta, LA Yamanaka, N Ferrans, VJ TI Expression of matrix metalloproteinases and their tissue inhibitors in floppy mitral valves. SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NIPPON MED COLL,TOKYO 113,JAPAN. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3547 EP 3547 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903537 ER PT J AU Bennett, SK Gottlieb, SG Fisher, ML Bacharach, SL Dilsizian, V AF Bennett, SK Gottlieb, SG Fisher, ML Bacharach, SL Dilsizian, V TI Beta-blockers improve myocardial glucose uptake in patients with heart failure SO CIRCULATION LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21201. NHLBI,NIH,BETHESDA,MD 20892. NIH,NMD,BETHESDA,MD 20892. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3644 EP 3644 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903635 ER PT J AU Vaisman, BL Berard, AM Paigen, B Marcovina, S Eckhaus, M Maeda, N Brewer, HB SantamarinaFojo, S AF Vaisman, BL Berard, AM Paigen, B Marcovina, S Eckhaus, M Maeda, N Brewer, HB SantamarinaFojo, S TI Overexpression of human lecithin cholesterol acyltransferase (LCAT) in LCAT transgenic and apo E deficient mice leads to enhanced atherosclerosis SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. JACKSON LAB,BAR HARBOR,ME 04609. UNIV N CAROLINA,CHAPEL HILL,NC. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3697 EP 3697 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903688 ER PT J AU London, B Newton, KP Jenkins, NA Copeland, NG Vesely, MR Satler, CA AF London, B Newton, KP Jenkins, NA Copeland, NG Vesely, MR Satler, CA TI Cloning a new murine isoform of the long QT gene HERG SO CIRCULATION LA English DT Meeting Abstract C1 UNIV PITTSBURGH,MED CTR,PITTSBURGH,PA. CHILDRENS HOSP,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3745 EP 3745 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903736 ER PT J AU Rajanayagam, S Harren, RL Feldman, S Thirumurti, V Shou, MT Doanes, M Lazarous, DF Capogrossi, MC Crystal, RG Unger, EF Epstein, SE Finkel, T AF Rajanayagam, S Harren, RL Feldman, S Thirumurti, V Shou, MT Doanes, M Lazarous, DF Capogrossi, MC Crystal, RG Unger, EF Epstein, SE Finkel, T TI Delivery of VEGF to ischemic tissue using adenoviral-modified autologous endothelial cells SO CIRCULATION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. CORNELL MED CTR,NEW YORK,NY. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 3773 EP 3773 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903764 ER PT J AU Hees, PS Stewart, KJ Blackman, MR Harman, SM Shapiro, EP AF Hees, PS Stewart, KJ Blackman, MR Harman, SM Shapiro, EP TI Are growth hormone levels related to cardiac structure and function in the elderly? SO CIRCULATION LA English DT Meeting Abstract C1 NIA,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,BALTIMORE,MD. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 3977 EP 3977 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11903968 ER PT J AU Levy, D Larson, MG Vasan, RS Ho, KKL AF Levy, D Larson, MG Vasan, RS Ho, KKL TI No evidence of an increase in incidence of heart failure from 1950-1990 SO CIRCULATION LA English DT Meeting Abstract C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NHLBI,FRAMINGHAM,MA. BETH ISRAEL HOSP,BOSTON,MA 02215. 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 OCT 15 PY 1996 VL 94 IS 8 SU S BP 4039 EP 4039 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904030 ER PT J AU Sulciner, DJ Irani, K Yu, ZX Ferrans, VJ GoldschmidtClermont, P Finkel, T AF Sulciner, DJ Irani, K Yu, ZX Ferrans, VJ GoldschmidtClermont, P Finkel, T TI Rac1 regulates a cytokine-stimulated, redox-dependent pathway necessary for Nf-kappa B activation and VCAM-1 expression SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI,NIH,ROCKVILLE,MD. JOHNS HOPKINS UNIV HOSP,BALTIMORE,MD 21287. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 15 PY 1996 VL 94 IS 8 SU S BP 4141 EP 4141 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VN119 UT WOS:A1996VN11904132 ER PT J AU John, S Robbins, CM Leonard, WJ AF John, S Robbins, CM Leonard, WJ TI An IL-2 response element in the human IL-2 receptor alpha chain promoter is a composite element that binds Stat5, Elf-1, HMG-I(Y) and a GATA family protein SO EMBO JOURNAL LA English DT Article DE Elf-1; GATA; HMG-I(Y); IL-2 receptors; STAT ID CELL LEUKEMIA-VIRUS; COMMON GAMMA-CHAIN; GENE-EXPRESSION; BETA-CHAIN; TRANSCRIPTION FACTOR; ENHANCER ELEMENTS; T-LYMPHOCYTES; INTERLEUKIN-2; ACTIVATION; KAPPA AB Expression of the human interleukin-2 (IL-2) receptor alpha chain gene is potently upregulated by its own ligand, IL-2, In this study, we characterize an essential upstream IL-2 response element that contains both consensus and non-consensus GAS motifs, two putative Ets binding sites (EBS), one of which overlaps the consensus GAS moth, and a GATA motif, which overlaps the non-consensus GAS motif, We demonstrate that although the individual components of this element do not respond to IL-2, together they form a composite element capable of conferring IL-2 responsiveness to a heterologous promoter. Multiple factors including Stat5, Elf-1, HMG-I(Y) and GATA family proteins bind to the IL-2 response element and mutation of any one of these binding sites diminishes the activity of this element, An unidentified Ets family protein binds to the EBS overlapping the consensus GAS motif and appears to negatively regulate the human IL-2R alpha promoter, Thus, TL-2-induced IL-2R alpha promoter activity requires a complex upstream element, which appears to contain binding sites for both positive and negative regulatory factors. C1 NHLBI,LAB MOL IMMUNOL,BETHESDA,MD 20892. NATL CTR GENOME RES,GENOME TECHNOL BRANCH,BETHESDA,MD 20892. NR 43 TC 117 Z9 120 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 1996 VL 15 IS 20 BP 5627 EP 5635 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VQ071 UT WOS:A1996VQ07100015 PM 8896456 ER PT J AU Powell, DJ Bur, D Wlodawer, A Gustchina, A Payne, SL Dunn, BM Kay, J AF Powell, DJ Bur, D Wlodawer, A Gustchina, A Payne, SL Dunn, BM Kay, J TI Expression, characterisation and mutagenesis of the aspartic proteinase from equine infections anaemia virus SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE equine infectious anaemia virus proteinase; substrate specificity; inhibitor susceptibility ID ANEMIA VIRUS; IMMUNODEFICIENCY-VIRUS; HIV-1 PROTEASE; INHIBITORS; CLEAVAGE; SUBSTRATE; TYPE-1; SPECIFICITY; PREFERENCES; HYDROLYSIS AB The gene encoding the proteinase from equine infectious anaemia virus (EIAV) was cloned and expressed in Escherichia coli. The recombinant EIAV proteinase was purified to homogeneity and shown to have the ability to process polyprotein and synthetic peptide substrates of human immunodeficiency virus (HIV) origin with an efficiency that cad approach that exhibited by HSV proteinase, EIAV proteinase, however, was not susceptible to inhibition by a wide variety of inhibitors of HIV-1 proteinase, including those which have been licenced as anti-AIDS drugs. In this respect, EIAV proteinase behaves like an extreme case of a drug-resistant mutant of HIV-1 proteinase that has arisen under selective drug pressure. Only one potent inhibitor (HBY-793) of HIV-1 proteinase showed comparable efficiency against the EIAV enzyme; the compounds A-77003 and A-76889), which differ only in their stereochemistry and which are otherwise structurally identical to HBY-793 from residues P2 to P2' [nomenclature of Schechter, I. & Berger, A. (1967) Biochem. Biophys. Res. Commun. 27, 157-162], were not effective inhibitors of EIAV proteinase. Mutant forms of EIAV proteinase (Thr30-->Asp and Ile54-->Gly) were generated and their ability to interact with substrates and inhibitors was characterised. HBY-793 inhibited [Gly54]proteinase as effectively as the wild-type proteinase but was tenfold less potent against [Asp30]proteinase. Data interpretations an presented, based on the structure solved for the complex between HBY-793 and EIAV [Gly54]proteinase [Gustchina A., Kervinen, J., Powell, D.J., Zdanov, A., Kay, J. & Wlodawer, A. (1996) Protein Sci. 5, 1453-1465]. C1 UNIV WALES COLL CARDIFF,SCH MOL & MED BIOSCI,CARDIFF CF1 3US,S GLAM,WALES. F HOFFMANN LA ROCHE & CIE AG,PHARMA RES,NEW TECHNOL,BASEL,SWITZERLAND. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MACROMOL STRUCT LAB,FREDERICK,MD. CASE WESTERN RESERVE UNIV,SCH MED,DEPT MOL BIOL & MICROBIOL,CLEVELAND,OH 44106. UNIV FLORIDA,DEPT BIOCHEM & MOL BIOL,GAINESVILLE,FL 32610. RI Payne, Susan/C-8236-2013 FU NIAID NIH HHS [AI 18571] NR 29 TC 14 Z9 14 U1 0 U2 4 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 OCT 15 PY 1996 VL 241 IS 2 BP 664 EP 674 DI 10.1111/j.1432-1033.1996.00664.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP651 UT WOS:A1996VP65100047 PM 8917470 ER PT J AU Abel, KJ Brody, LC Valdes, JM Erdos, MR McKinley, DR Castilla, LH Merajver, SD Couch, FJ Friedman, LS Ostermeyer, EA Lynch, ED King, MC Welcsh, PL OsborneLawrence, S Spillman, M Bowcock, AM Collins, FS Weber, BL AF Abel, KJ Brody, LC Valdes, JM Erdos, MR McKinley, DR Castilla, LH Merajver, SD Couch, FJ Friedman, LS Ostermeyer, EA Lynch, ED King, MC Welcsh, PL OsborneLawrence, S Spillman, M Bowcock, AM Collins, FS Weber, BL TI Characterization of EZH1, a human homolog of Drosophila enhancer of zeste near BRCA1 SO GENOMICS LA English DT Article ID GENE-EXPRESSION; NUCLEOTIDE-SEQUENCE; TRANSCRIPTION MAP; ACUTE LEUKEMIAS; PHYSICAL MAP; ALL-1 GENE; PROTEIN; REGION; BREAST; TRITHORAX AB Recent transcription mapping efforts within chromosome 17q21 have led to the identification of a human homolog of the Drosophila gene Enhancer of zeste, E(z), A member of the Polycomb group (Pc-Gr) of proteins, Drosophila E(z) acts as a negative regulator of the segment identity genes of the Antennapedia and Bithorax complexes. Here we report the full-length protein coding sequence of human EZR1 (Enhancer of zeste homolog 1) and compare the respective protein sequences in both species. EZH1 encodes a protein of 747 amino acids that displays 55% amino acid identity overall (70% similarity) with Drosophila E(z). The strongest homology was noted (79% identity, 89% similarity) within the carboxy-terminal 245 amino acids, including the SET domain, a region of E(z) also conserved in other Drosophila proteins with roles in development and/or chromatin structure. A large Cysrich region with a novel spatial pattern of cysteine residues was also conserved in both EZH1 and E(z). The strong sequence conservation suggests potential roles for EZH1 in human development as a transcriptional regulator and as a component of protein complexes that stably maintain heterochromatin. EZR1 is expressed as two major transcripts in all adult and fetal human tissues surveyed; comparison of cloned cDNAs suggests that alternative splicing may account for at least part of the transcript size difference. Analysis of one cDNA revealed an unusual splicing event involving EZH1 and a tandemly linked gene GPR2 and suggests a potential mechanism for modifying the EZH1 protein in the conserved C-terminal domain. The sequence and isolated cDNAs will provide useful reagents for determining the function of EZH1 and the importance of the evolutionarily conserved domains. (C) 1996 Academic Press, Inc. C1 UNIV MICHIGAN, SCH MED, DEPT HUMAN GENET, ANN ARBOR, MI 48109 USA. UNIV MICHIGAN, SCH MED, DEPT INTERNAL MED, ANN ARBOR, MI 48109 USA. NIH, NATL CTR HUMAN GENOME RES, LAB GENE TRANSFER, BETHESDA, MD 20892 USA. UNIV IOWA HOSP & CLIN, DEPT PSYCHIAT, IOWA CITY, IA 52242 USA. ADDENBROOKES HOSP, CRC, HUMAN CANC GENET GRP, CAMBRIDGE CB2 2QQ, ENGLAND. UNIV WASHINGTON, DEPT MED GENET, SEATTLE, WA 98195 USA. UNIV TEXAS, SW MED CTR, EUGENE MCDERMOTT CTR, DALLAS, TX 75235 USA. UNIV TEXAS, SW MED CTR, DEPT PEDIAT, DALLAS, TX 75235 USA. UNIV PENN, SCH MED, DEPT INTERNAL MED, PHILADELPHIA, PA 19104 USA. UNIV PENN, SCH MED, DEPT GENET, PHILADELPHIA, PA 19104 USA. FU NCI NIH HHS [R01 CA61231]; NHGRI NIH HHS [HG00081, P30 HG00209] NR 51 TC 32 Z9 33 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 EI 1089-8646 J9 GENOMICS JI Genomics PD OCT 15 PY 1996 VL 37 IS 2 BP 161 EP 171 DI 10.1006/geno.1996.0537 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VN667 UT WOS:A1996VN66700002 PM 8921387 ER PT J AU Owman, C Nilsson, C Lolait, SJ AF Owman, C Nilsson, C Lolait, SJ TI Cloning of cDNA encoding a putative chemoattractant receptor SO GENOMICS LA English DT Article ID PROTEIN-COUPLED RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; HUMAN INTERLEUKIN-8 RECEPTOR; FORMYL PEPTIDE RECEPTOR; EPSTEIN-BARR VIRUS; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; MAMMALIAN-CELLS; GENES; DNA AB Based on polymerase chain reaction (PCR) utilizing degenerate primers directed to the second and sixth transmembrane domains of several G-protein-coupled neurotransmitter receptors and screening of a human B-lymphoblast cDNA library, we isolated a cDNA whose predicted amino acid sequence shows considerable homology with human chemoattractant receptors, e.g., 30% overall identity with the C5a anaphylatoxin receptors. The coding region consists of 1056 bp corresponding to 352 amino acid residues and giving an approximate molecular weight of 43 kDa, Northern blot analysis showed hybridizing transcripts in spleen, thymus, and lymph nodes, as well as in bone marrow and peripheral blood leukocytes. Message was also found in lymphoid tumor cell lines, Chromosome mapping with FISH/DAPI technique showed the corresponding gene to reside on human chromosome 14q11.2-q12. In accordance with the Genome Database Nomenclature the receptor was designated CMKRL1 (''chemoattractant receptor-like 1''), Stably transfected mammalian cells (CHO cells and LVTP2.0Zc reporter cells) expressing high levels of corresponding receptor RNA were analyzed for changes in cAMP concentration and cellular calcium fluxes, Chemokines tested to date (GRO-a, MCP-1, MCP-3, MIP-1a, MIP-1b, C5a, RANTES, and LTB(4)) have failed to elicit any reproducible response, Although the ligand for CMKRL1 could thus not be identified among chemotactic peptides, the high expression in lymphoid cells and tissues suggests that the receptor may function in the regulation of the inflammatory system. (C) 1996 Academic Press, Inc. C1 NIMH,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RP Owman, C (reprint author), LUND UNIV,WALLENBERG NEUROSCI CTR,DEPT PHYSIOL & NEUROSCI,MOL NEUROBIOL SECT,SOLVEGATAN 17,S-22362 LUND,SWEDEN. NR 39 TC 47 Z9 51 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 OCT 15 PY 1996 VL 37 IS 2 BP 187 EP 194 DI 10.1006/geno.1996.0541 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VN667 UT WOS:A1996VN66700006 PM 8921391 ER PT J AU Takumi, T Tsuji, L Kondo, C Takahashi, N Morishige, K Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y AF Takumi, T Tsuji, L Kondo, C Takahashi, N Morishige, K Copeland, NG Gilbert, DJ Jenkins, NA Kurachi, Y TI Assignment of the murine inward rectifier potassium channel Irk2 (Kir2.2) gene to the central region of mouse chromosome 11 SO GENOMICS LA English DT Article ID FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; BRAIN; LOCALIZATION; MAP C1 OSAKA UNIV,FAC MED,DEPT PHARMACOL 2,SUITA,OSAKA 565,JAPAN. OSAKA UNIV,FAC MED,DEPT OBSTET & GYNECOL,SUITA,OSAKA 565,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 14 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD OCT 15 PY 1996 VL 37 IS 2 BP 270 EP 272 DI 10.1006/geno.1996.0559 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VN667 UT WOS:A1996VN66700024 PM 8921409 ER PT J AU Leshner, AI AF Leshner, AI TI Understanding drug addiction: Implications for treatment SO HOSPITAL PRACTICE LA English DT Article AB The addicted brain is qualitatively different hcm the nonaddicted brain, in ways that include glucose use, gene expression, and responsiveness to environmental cues. Such discoveries place researchers in the early but hopeful stages of translating fundamental findings into new treatments that address the neurobiologic basis of drug craving-even for cocaine, against which there are currently no pharmacologic interventions. RP Leshner, AI (reprint author), NIDA,NIH,ROCKVILLE,MD, USA. NR 8 TC 22 Z9 23 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD OCT 15 PY 1996 VL 31 IS 10 BP 47 EP & PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA WA491 UT WOS:A1996WA49100009 PM 8859207 ER PT J AU Strickler, J Jacobson, KA Liang, BT AF Strickler, J Jacobson, KA Liang, BT TI Direct preconditioning of cultured chick ventricular myocytes novel functions of cardiac adenosine A(2a) and A(3) receptors SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE myocardium; adenosine; receptor; purinergic; ischemia ID INTRACORONARY ADENOSINE; CORONARY ANGIOPLASTY; MYOCARDIAL-ISCHEMIA; SIMULATED ISCHEMIA; ADENYLATE-CYCLASE; HEART-CELLS; INJURY; PROTECTION; N-6-BENZYLADENOSINE-5'-URONAMIDES; CARDIOPROTECTION AB Preconditioning with brief ischemia before a sustained period of ischemia reduces infarct size in the perfused heart. A cultured chick ventricular myocyte model was developed to investigate the role of adenosine receptor subtypes in cardiac preconditioning. Brief hypoxic exposure, termed preconditioning hypoxia, prior to prolonged hypoxia, protected myocytes against injury induced by the prolonged hypoxia. Activation of the adenosine A(1) receptor with CCPA or the A(3) receptor with CI-IB-MECA can replace preconditioning hypoxia and simulate preconditioning, with a maximal effect at 100 nM. While activation of the A(2a) receptor by 1 mu M CGS21680 could not mimic preconditioning, its stimulation during preconditioning hypoxia, however, attenuated the protection against hypoxia-induced injury. Blockade of A, receptors with the selective antagonist CSC (1 mu M) during preconditioning hypoxia enhanced the protective effect of preconditioning. Nifedipine, which blocked the A(2a) receptor-mediated calcium entry, abolished the Az, agonist-induced attenuation of preconditioning. Isoproterenol, forskolin, and BayK 8644, which stimulated calcium entry, also attenuated preconditioning. Nifedipine blocked the increase in calcium uptake by these agents as well as their attenuating effect on preconditioning. The present study provides the first evidence that the adenosine A(3) receptor is present on ventricular myocytes and can mediate simulation of preconditioning. The data demonstrate, for the first time, that activation of the A(2a) receptor antagonizes the preconditioning effect of adenosine, with increased calcium entry during the preconditioning stimuli as a novel mechanism. C1 UNIV PENN,MED CTR,DEPT MED,DIV CARDIOVASC,PHILADELPHIA,PA 19104. UNIV PENN,MED CTR,DEPT PHARMACOL,PHILADELPHIA,PA 19104. NIDDKD,MOL RECOGNIT SECT,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999]; NHLBI NIH HHS [R01-HL-48225] NR 38 TC 119 Z9 119 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 15 PY 1996 VL 98 IS 8 BP 1773 EP 1779 DI 10.1172/JCI118976 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VN973 UT WOS:A1996VN97300012 PM 8878427 ER PT J AU Ramachandra, S Metcalf, RA Fredrickson, T Marti, GE Raveche, E AF Ramachandra, S Metcalf, RA Fredrickson, T Marti, GE Raveche, E TI Requirement for increased IL-10 in the development of B-1 lymphoproliferative disease in a murine model of CLL SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE IL-10; B-1 cell; CD5+B cell; B-CLL; lymphoproliferation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ANTISENSE IL-10; B-LYMPHOCYTES; CELL LYMPHOMA; SERUM LEVELS; NZB MICE; INTERLEUKIN-10; EXPRESSION; GROWTH AB Malignant B-l cells derived from NZB mice, a murine model of spontaneous autoimmunity and B cell lymphoproliferative disease, produce significantly higher levels of IL-10 mRNA than normal B-l or B cells, IL-10 may act as an autocrine growth factor for the expansion of malignant B-l cells. In order to determine if elevated endogenous production of IL-10 was a required element for the malignant transformation of B-l cells in NZB mice, backcross animals were studied for the linkage between elevated IL-10 expression and the presence of lymphoid malignancy. The phenotypes of aged (NZB x DBA/2)F-1 x NZB animals were determined and a strong correlation was found between the elevated levels of IL-10 mRNA and the development of B-l malignant clones, In contrast, an increased level of IL-10 message was not associated with elevated serum IgM or the presence of anemia or reticulocytosis which is mainly seen in response to autoantibody production. These results indicate that, at least in NZB, the autoimmunity and lymphoproliferation phenotypes are not linked genetically, IL-10 may enhance proliferation and the development of B-l cell malignancy rather than antibody production by the B-l cell subpopulation, Thus, IL-10 plays an important role in B-l malignancies, and downregulation of IL-10 could be a likely site for intervention in B cell malignancies. C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PATHOL,NEWARK,NJ 07103. US FDA,CTR BIOL EVALUAT & RES,NIH,BETHESDA,MD 20812. FU NCI NIH HHS [CA-71478] NR 34 TC 35 Z9 36 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 15 PY 1996 VL 98 IS 8 BP 1788 EP 1793 DI 10.1172/JCI118978 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VN973 UT WOS:A1996VN97300014 PM 8878429 ER PT J AU Fineschi, B Sakaguchi, K Appella, E Miller, J AF Fineschi, B Sakaguchi, K Appella, E Miller, J TI The proteolytic environment involved in MHC class II-restricted antigen presentation can be modulated by the p41 form of invariant chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HLA-DR MOLECULES; PEPTIDE BINDING; CATHEPSIN-B; CYSTEINE PROTEASES; ENDOCYTIC PATHWAY; GENE-PRODUCT; COMPLEX; TRANSPORT; CELLS; COMPARTMENTS AB During biosynthesis, MHC class II associates with invariant chain which exists in two forms, p31 and p41. Both forms of invariant chain prevent peptide binding to class II, facilitate transport, and enhance class II localization to Ag-processing compartments, In spite of these shared functions, presentation of some Ags can be selectively enhanced by expression of p41, Here we show that p41 can function as a protease inhibitor: 1) the functional and biochemical consequences of p41 expression can be mimicked by inhibiting cysteine proteases in vivo; 2) the amount of intracellular active cysteine proteases is dramatically decreased in p41-positive cells; and 3) a polypeptide corresponding to the p41-unique region is a potent inhibitor of cathepsin L in vitro, These data suggest that p41 can enhance Ag presentation by reducing the proteolytic activity of the Ag-processing compartment, thus protecting a subset of antigenic epitopes from excessive degradation. C1 UNIV CHICAGO,DEPT MOL GENET & CELL BIOL,CHICAGO,IL 60637. UNIV CHICAGO,DEPT PHYSIOL & PHARMACOL,CHICAGO,IL 60637. NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NR 33 TC 44 Z9 44 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 OCT 15 PY 1996 VL 157 IS 8 BP 3211 EP 3215 PG 5 WC Immunology SC Immunology GA VP226 UT WOS:A1996VP22600001 PM 8871612 ER PT J AU Gratton, S Yao, XJ Venkatesan, S Cohen, EA Sekaly, RP AF Gratton, S Yao, XJ Venkatesan, S Cohen, EA Sekaly, RP TI Molecular analysis of the cytoplasmic domain of CD4 - Overlapping but noncompetitive requirement for lck association and down-regulation by Nef SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RECEPTOR; TYROSINE-PROTEIN-KINASE; TYPE-1 NEF; MUTATIONAL ANALYSIS; HUMAN-LYMPHOCYTES; TRANSGENIC MICE; COATED PITS; SURFACE CD4; HIV-1 AB Expression of the HIV Nef protein results in the down-regulation of cell surface expression of CD4, with a di-leucine motif in the cytoplasmic domain of CD4 being required for this effect, However, our results indicate that this motif is not sufficient to confer sensitivity to down-regulation by Nef, Using site-directed mutagenesis and a transient expression system, we demonstrate that an alpha-helical stretch of amino acids of the cytoplasmic tail of CD4 is also required for the down-regulation of CD4 induced by Nef, Some CD4 mutations allowed the discrimination between PMA- and Nef-induced down-regulation, suggesting the existence of multiple pathways, In addition, our results demonstrate that this motif is involved in the association of CD4 with the tyrosine kinase p56(lck): thus defining a multifunctional domain of CD4, Although there is overlap between the sequence requirement for lck association and susceptibility to Nef, we fail to detect any preferential decrease in lck association with CD4 when Nef is expressed during acute HIV infection, Altogether, these results demonstrate that there is an overlapping, but noncompetitive, sequence requirement in the cytoplasmic domain of CD4 for lck association and down-regulation by Nef. C1 CLIN RES INST MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. MCGILL UNIV,DEPT MED,DIV EXPT MED,MONTREAL,PQ H3A 2T5,CANADA. UNIV MONTREAL,FAC MED,LAB HUMAN RETROVIROL,MONTREAL,PQ,CANADA. UNIV MONTREAL,FAC MED,DEPT MICROBIOL & IMMUNOL,MONTREAL,PQ,CANADA. NIAID,NIH,MOL MICROBIOL LAB,BETHESDA,MD 20892. NR 61 TC 23 Z9 24 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 OCT 15 PY 1996 VL 157 IS 8 BP 3305 EP 3311 PG 7 WC Immunology SC Immunology GA VP226 UT WOS:A1996VP22600014 PM 8871625 ER PT J AU Peruzzi, M Parker, KC Long, EO Malnati, MS AF Peruzzi, M Parker, KC Long, EO Malnati, MS TI Peptide sequence requirements for the recognition of HLA-B*2705 by specific natural killer cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I MOLECULES; MHC CLASS-I; HLA-B MOLECULES; NK CELLS; CARBOHYDRATE-RECOGNITION; ALLOANTIGEN RECOGNITION; TARGET-CELLS; T-CELLS; RECEPTOR; CLONES AB NK clones that were inhibited by target cell expression of HLA-B*2705 displayed peptide-specific recognition of HLA-B*2705, To evaluate the specificity of this recognition, synthetic versions of 14 endogenous ligands of HLA-B*2705 were tested for their ability to provide protection from NK-mediated lysis by binding to surface HLA-B*2705 molecules on RMA-S cells deficient in the transporter for Ag presentation, Several unrelated peptides inhibited lysis by the same NK clones, Despite similar capacities to stabilize HLA-B*2705 molecules on RMA-S cells, the 14 peptides differed widely in their abilities to provide protection, Single amino acid substitutions in both a protective and a nonprotective peptide revealed the importance of residues 7 and 8 in the peptide for recognition by NK clones, thus localizing the peptide influence to a polymorphic region of the cu-helix of HLA class I molecules known to control discrimination among allelic variants of HLA-B and HLA-C by NK cells. C1 NIAID,NIH,IMMUNOGENET LAB,ROCKVILLE,MD 20852. NIAID,NIH,MOL STRUCT LAB,ROCKVILLE,MD 20852. SAN RAFFAELE SCI INST,DIBIT,UNIT HUMAN VIROL,I-20132 MILAN,ITALY. RI Long, Eric/G-5475-2011; OI Long, Eric/0000-0002-7793-3728; Parker, Kenneth/0000-0002-6282-2478 NR 49 TC 103 Z9 104 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 OCT 15 PY 1996 VL 157 IS 8 BP 3350 EP 3356 PG 7 WC Immunology SC Immunology GA VP226 UT WOS:A1996VP22600020 PM 8871631 ER PT J AU Wu, DK Oh, SH AF Wu, DK Oh, SH TI Sensory organ generation in the chick inner ear SO JOURNAL OF NEUROSCIENCE LA English DT Article DE inner ear development; Msx-1; p75NGFR; BMP4; placode-derived; sensory organ ID BONE-MORPHOGENETIC PROTEIN-4; DEVELOPMENTAL EXPRESSION; TOOTH DEVELOPMENT; XENOPUS EMBRYO; SONIC-HEDGEHOG; NEURAL CREST; MOUSE; BMP-4; RECEPTORS; INDUCTION AB There are a total of eight sensory organs in the chick inner ear. Each sensory organ has a distinct structure tailored for its function, and its morphology is well characterized. However, the origin of these sensory organs and the lineage relationships among them are largely unknown. In this report, we show that BMP4 (bone morphogenetic protein), a secreted protein of the TGF-beta gene family, is the earliest sensory marker identified to date for the chick inner ear. In addition to BMP4, we show that Msx-1 is a sensory marker for the three cristae, the lagena, and macula neglecta. P75NGFR (nerve growth factor receptor) is a marker for the three cristae only. Based pattern of these th ree genes-BMP4, Msx-1, and p75NGFR-it is estimated that the first sensory organs to be generated were; the superior and posterior cristae at stage 19, followed by the macula sacculi at stage 20, the lateral crista at stage 22, the basilar papilla and lagena at stage 23, the macula utriculi at stage 24, and the macula neglecta at stage 29. The age of generation of each sensory organ as defined by the first appearance of these molecular markers is well in advance of the histological differentiation. In addition, the differential gene expressions in each presumptive sensory organ may contribute to the distinct structure of the mature organ. RP Wu, DK (reprint author), NIDCD,5 RES COURT,ROOM 2B34,ROCKVILLE,MD 20850, USA. NR 30 TC 141 Z9 144 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1996 VL 16 IS 20 BP 6454 EP 6462 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VP758 UT WOS:A1996VP75800013 PM 8815924 ER PT J AU Oh, SH Johnson, R Wu, DK AF Oh, SH Johnson, R Wu, DK TI Differential expression of bone morphogenetic proteins in the developing vestibular and auditory sensory organs SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BMP4; BMP5; BMP7; crista ampullaris; basilar papilla; macula ID TGF-BETA SUPERFAMILY; INNER-EAR; BASILAR PAPILLA; MESSENGER-RNAS; SONIC-HEDGEHOG; CHICK-EMBRYOS; HAIR-CELLS; HOX GENES; MOUSE; INDUCTION AB The genes responsible for the formation of various sensory organs in the inner ear are not known. There are eight sensory organs in the chick inner ear, and our previous study showed that all presumptive sensory organs initially express bone morphogenetic protein 4 (BMP4), a member of the transforming growth factor (TGF)-beta gene family. To address the potential role of BMPs in the patterning of different sensory organ structures, we investigated the expression of BMP4, BMP5, and BMP7 during sensory organ differentiation in the chick inner ear. The gene expression pattern of BMP5, although similar to that of BMP4, was transient and disappeared by embryonic day 3.5 (E3.5). In contrast, BMP7 gene expression was quite extensive, starting in the otic placode. By E5, gene expression patterns of BMP4 and BMP7 differed among vestibular and auditory sensory organs. In the vestibular sensory organs, BMP7 gene expression segregated from the main sensory tissue areas at the onset of differentiation, whereas BMP4 expression concentrated in supporting cells. In the cochlea, however, BMP7 gene expression became restricted to sensory tissue over time and eventually concentrated in supporting cells, whereas BMP4 gene expression was localized to hair cells. The different BMP expression patterns in developing auditory and vestibular sensory organs may help to shape each respective sensory structure. Furthermore, the expression of BMP4 in the cochlea also revealed an interesting pattern of sensory cell differentiation: the distal portion of the cochlea differentiates first, and the tall hair cells develop before the short hair cells. C1 NIDOCD,ROCKVILLE,MD 20850. MD ANDERSON CANC CTR,DEPT BIOCHEM & MOL BIOL,HOUSTON,TX 77030. NR 51 TC 121 Z9 123 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 1996 VL 16 IS 20 BP 6463 EP 6475 PG 13 WC Neurosciences SC Neurosciences & Neurology GA VP758 UT WOS:A1996VP75800014 PM 8815925 ER PT J AU Sander, M Benhaim, D AF Sander, M Benhaim, D TI Drosophila Rrp1 3'-exonuclease: Demonstration of DNA sequence dependence and DNA strand specificity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID APURINIC APYRIMIDINIC ENDONUCLEASE; COLI EXONUCLEASE-III; ENZYME APEX NUCLEASE; ESCHERICHIA-COLI; REPAIR ENZYMES; CDNA; EXPRESSION; DAMAGE; RECOGNITION; DEFICIENT AB Drosophila Rrp1 (recombination repair protein 1) is a DNA repair enzyme whose nuclease activities include AP-endonuclease, 3'-exonuclease, 3'-phosphodiesterase and 3'-phosphatase. This study investigates the sequence specificity of the dsDNA 3'-exonuclease activity of Rrp1, We demonstrate that the activity is more efficient in purine-rich regions of dsDNA than in pyrimidine-rich regions, Rrp1 exonuclease activity is examined at 3'-terminal homopurine or homopyrimidine tracts, at junctions between purine- and pyrimidine-rich sequences and upon encountering repeated dinucleotide runs. The data show that purine-purine and 3'-pyrimidine-5'-purine dinucleotide bonds are cleaved faster than 3'-purine-5'-pyrimidine or pyrimidine-pyrimidine bonds, Thus, the base occupying the penultimate position in the 3'-terminal dinucleotide may be important in determining the relative efficiency of bond cleavage by Rrp1. These findings may reflect upon specific DNA-protein interactions in the enzyme active site. RP Sander, M (reprint author), NIEHS,MOL GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 13 Z9 14 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 OCT 15 PY 1996 VL 24 IS 20 BP 3926 EP 3933 DI 10.1093/nar/24.20.3926 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VP702 UT WOS:A1996VP70200007 PM 8918793 ER PT J AU Moss, B AF Moss, B TI Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Genetic Engineering of Viruses and of Virus Vectors CY JUN 09-11, 1996 CL NATL ACAD SCI, IRVINE, CA HO NATL ACAD SCI ID VACCINIA VIRUS RECOMBINANTS; NEWCASTLE-DISEASE VIRUS; BACTERIOPHAGE-T7 RNA-POLYMERASE; RESPIRATORY SYNCYTIAL VIRUS; TOXIC LYMPHOCYTES-T; HEMAGGLUTININ-NEURAMINIDASE GENE; TEMPERATURE-SENSITIVE MUTATIONS; DOMINANT SELECTABLE MARKER; THYMIDINE KINASE GENE; CELL-FREE TRANSLATION AB Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure-function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific;infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients. RP Moss, B (reprint author), NIAID,VIRAL DIS LAB,NIH,BLDG 4,ROOM 229,4 CTR DR,MSC 0445,BETHESDA,MD 20892, USA. NR 180 TC 386 Z9 406 U1 2 U2 15 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 OCT 15 PY 1996 VL 93 IS 21 BP 11341 EP 11348 DI 10.1073/pnas.93.21.11341 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100011 PM 8876137 ER PT J AU Hoeg, JM SantamarinaFojo, S Berard, AM Cornhill, JF Herderick, EE Feldman, SH Haudenschild, CC Vaisman, BL Hoyt, RF Demosky, SJ Kauffman, RD Hazel, CM Marcovina, SM Brewer, HB AF Hoeg, JM SantamarinaFojo, S Berard, AM Cornhill, JF Herderick, EE Feldman, SH Haudenschild, CC Vaisman, BL Hoyt, RF Demosky, SJ Kauffman, RD Hazel, CM Marcovina, SM Brewer, HB TI Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE high density lipoprotein cholesterol; low density lipoprotein cholesterol; atherogenic diet; cholesteryl esters ID HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; APOLIPOPROTEIN-A-I; ESTER TRANSFER PROTEIN; HUMAN-SERUM; GENE; EXPRESSION; LCAT; MICE; HYPERALPHALIPOPROTEINEMIA AB Lecithin:cholesterol acyltransferase (LCAT) is a key plasma enzyme in cholesterol and high density lipoprotein (HDL) metabolism. Transgenic rabbits overexpressing human LCAT had 15-fold greater plasma LCAT activity than nontransgenic control rabbits. This degree of overexpression was associated with a 6.7-fold increase in the plasma HDL cholesterol concentration in LCAT transgenic rabbits. On a 0.3% cholesterol diet, the HDL cholesterol concentrations increased from 24 +/- 1 to 39 +/- 3 mg/dl in nontransgenic control rabbits (n = 10; P < 0.05) and increased from 161 +/- 5 to 200 +/- 21 mg/dl (P < 0.001) in the LCAT transgenic rabbits (n = 9). Although the baseline non-HDL concentrations of control (4 +/- 3 mg/dl) and transgenic rabbits (18 +/- 4 mg/dl) were similar, the cholesterol-rich diet raised the non-HDL cholesterol concentrations, reflecting the atherogenic very low density, intermediate density, and low density lipoprotein particles observed by gel filtration chromatography. The non-HDL cholesterol rose to 509 +/- 57 mg/dl in controls compared with only 196 +/- 14 mg/dl in the LCAT transgenic rabbits (P < 0.005). The differences in the plasma lipoprotein response to a cholesterol-rich diet observed in the transgenic rabbits paralleled the susceptibility to developing aortic atherosclerosis. Compared with nontransgenic controls, LCAT transgenic rabbits were protected from diet-induced atherosclerosis with significant reductions determined by both quantitative planimetry (-86%; P < 0.003) and quantitative immunohistochemistry (-93%; P < 0.009). Our results establish the importance of LCAT in the metabolism of both HDL and apolipoprotein B-containing lipoprotein particles with cholesterol feeding and the response to diet-induced atherosclerosis. In addition, these findings identify LCAT as a new target for therapy to prevent atherosclerosis. C1 NHLBI,LAB ANIM MED,NIH,BETHESDA,MD 20892. OHIO STATE UNIV,CTR BIOMED ENGN,COLUMBUS,OH 43210. AMER RED CROSS,JEROME H HOLLAND LAB,ROCKVILLE,MD 20855. UNIV WASHINGTON,NW LIPID RES LABS,SEATTLE,WA 98103. RP Hoeg, JM (reprint author), NHLBI,MOL DIS BRANCH,NIH,BLDG 10,ROOM 7N115,10 CTR DR,MSC 1666,BETHESDA,MD 20892, USA. FU NHLBI NIH HHS [HL45694, HL5424-01]; PHS HHS [JL30086] NR 53 TC 176 Z9 180 U1 1 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 OCT 15 PY 1996 VL 93 IS 21 BP 11448 EP 11453 DI 10.1073/pnas.93.21.11448 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100029 PM 8876155 ER PT J AU Yang, SW Burgin, AB Huizenga, BN Robertson, CA Yao, KC Nash, HA AF Yang, SW Burgin, AB Huizenga, BN Robertson, CA Yao, KC Nash, HA TI A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA repair; phosphodiesterase; Saccharomyces cerevisiae; camptothecin ID SITE-SPECIFIC RECOMBINASES; YEAST; SENSITIVITY; MECHANISM; CLEAVAGE; CELLS AB The covalent joining of topoisomerases to DNA is normally a transient step in the reaction cycle of these important enzymes. However, under a variety of circumstances, the covalent complex is converted to a long-lived or dead-end product that can result in chromosome breakage and cell death. We have discovered and partially purified an enzyme that specifically cleaves the chemical bond that joins the active site tyrosine of topoisomerases to the 3' end of DNA. The reaction products made by the purified enzyme on a variety of model substrates indicate that the enzyme cleanly hydrolyzes the tyrosine-DNA phosphodiester linkage, thereby liberating a DNA terminated with a 3' phosphate. The wide distribution of this phosphodiesterase in eukaryotes and its specificity for tyrosine linked to the 3' end but not the 5' end of DNA suggest that it plays a role in the repair of DNA trapped in complexes involving eukaryotic topoisomerase I. RP NIMH, MOL BIOL LAB, BETHESDA, MD 20892 USA. NR 31 TC 219 Z9 226 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 1996 VL 93 IS 21 BP 11534 EP 11539 DI 10.1073/pnas.93.21.11534 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100044 PM 8876170 ER PT J AU Hagen, SJ Hofrichter, J Szabo, A Eaton, WA AF Hagen, SJ Hofrichter, J Szabo, A Eaton, WA TI Diffusion-limited contact formation in unfolded cytochrome c: Estimating the maximum rate of protein folding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE laser photolysis; polymer dynamics ID PANCREATIC TRYPSIN-INHIBITOR; COLLISION MODEL; BINDING DOMAIN; LIGAND-BINDING; KINETICS; COLLAPSE; MACROMOLECULES; MECHANISM; DYNAMICS; PATHWAYS AB How fast can a protein fold? The rate of polypeptide collapse to a compact state sets an upper limit to the rate of folding. Collapse may in turn be limited by the rate of intrachain diffusion. To address this question, we have determined the rate at which two regions of an unfolded protein are brought into contact by diffusion. Our nanosecond-resolved spectroscopy shows that under strongly denaturing conditions, regions of unfolded cytochrome c separated by similar to 50 residues diffuse together in 35-40 mu s. This result leads to an estimate of similar to (1 mu s)(-1) as the upper limit for the rate of protein folding. C1 NIDDKD,PHYS CHEM LAB,NIH,BETHESDA,MD 20892. RI Szabo, Attila/H-3867-2012; Hagen, Stephen/E-9737-2015 OI Hagen, Stephen/0000-0002-3373-5033 NR 43 TC 354 Z9 356 U1 0 U2 14 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 OCT 15 PY 1996 VL 93 IS 21 BP 11615 EP 11617 DI 10.1073/pnas.93.21.11615 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100058 PM 8876184 ER PT J AU Orihuela, M Margulies, DH Yokoyama, WM AF Orihuela, M Margulies, DH Yokoyama, WM TI The natural killer cell receptor Ly-49A recognizes a peptide-induced conformational determinant on its major histocompatibility complex class I ligand SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LYMPHOCYTE-T; MHC; MOLECULES; EXPRESSION; BINDING; ANTIGEN; SENSITIVITY; MOUSE; ASSOCIATION; SPECIFICITY AB Natural killer (NK) cells are inhibited from killing cellular targets by major histocompatibility complex (MHC) class I molecules. In the mouse, this can be mediated by the Ly-49A NK cell receptor that specifically binds the H-2D(d) MHC class I molecule, then inhibits NK cell activity. Previous experiments have indicated that Ly-49A recognizes the alpha 1/alpha 2 domains of MHC class I and that no specific MHC-bound peptide appeared to be involved. We demonstrate here that alanine-substituted peptides, having only the minimal anchor motifs, stabilized H-2D(d) expression and provided resistance to H-2Dd-transfected, transporter associated with processing (TAP)-deficient cells from lysis by Ly-49A(+) NK cells. Peptide-induced resistance was blocked only by an mAb that binds a conformational determinant on H-2D(d). Moreover, stabilization of ''empty'' H-2D(d) heavy chains by exogenous beta(2)-microglobulin did not confer resistance. In contrast to data for MHC class I-restricted T cells that are specific for peptides displayed by MHC molecules, these data indicate that NK cells are specific for a peptide-induced conformational determinant, independent of specific peptide. This fundamental distinction between NK cells and T cells further implies that NK cells are sensitive only to global changes in MBC class I conformation or expression, rather than to specific pathogen-encoded peptides. This is consistent with the ''missing self'' hypothesis, which postulates that NK cells survey tissues for normal expression of MHC class I. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL & MED,DIV RHEUMATOL,ST LOUIS,MO 63110. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 45 TC 82 Z9 82 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 15 PY 1996 VL 93 IS 21 BP 11792 EP 11797 DI 10.1073/pnas.93.21.11792 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100090 PM 8876216 ER PT J AU Johnson, TM Yu, ZX Ferrans, VJ Lowenstein, RA Finkel, T AF Johnson, TM Yu, ZX Ferrans, VJ Lowenstein, RA Finkel, T TI Reactive oxygen species are downstream mediators of p53-dependent apoptosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adenovirus; antioxidants; atherosclerosis; restenosis; smooth muscle cell ID MUSCLE CELL-PROLIFERATION; THYMIDINE KINASE GENE; RAT CAROTID-ARTERY; IN-VIVO; BALLOON ANGIOPLASTY; NEOINTIMA FORMATION; GENERATION; THERAPY; INJURY; DEATH AB Reactive oxygen species (ROS) have been implicated as potential modulators of apoptosis. Conversely, experiments under hypoxic conditions have suggested that apoptosis could occur in the absence of ROS. We sought to determine whether a central modulator of apoptosis, p53, regulates the levels of intracellular ROS and whether a rise in ROS levels is required for the induction of p53-dependent apoptosis. We transiently overexpressed wild-type p,53, using adenoviral gene transfer, and identified cell types that were sensitive or resistant to p53-mediated apoptosis. Cells sensitive to p53-mediated apoptosis produced ROS concomitantly with p53 overexpression, whereas cells resistant to p53 failed to produce ROS. In sensitive cells, both ROS production and apoptosis were inhibited by antioxidant treatment. These results suggest that p53 acts to regulate the intracellular redox state and induces apoptosis by a pathway that is dependent on ROS production. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. NR 32 TC 421 Z9 434 U1 1 U2 16 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 OCT 15 PY 1996 VL 93 IS 21 BP 11848 EP 11852 DI 10.1073/pnas.93.21.11848 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100100 PM 8876226 ER PT J AU Dunbar, CE Seidel, NE Doren, S Sellers, S Cline, AP Metzger, ME Agricola, BA Donahue, RE Bodine, DM AF Dunbar, CE Seidel, NE Doren, S Sellers, S Cline, AP Metzger, ME Agricola, BA Donahue, RE Bodine, DM TI Improved retroviral gene transfer into murine and rhesus peripheral blood or bone marrow repopulating cells primed in vivo with stem cell factor and granulocyte colony-stimulating factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEMATOPOIETIC PROGENITOR; VECTOR TRANSDUCTION; C-KIT; TRANSPLANTATION; COMBINATION; EXPRESSION; BABOONS; MOBILIZATION; ENGRAFTMENT; CIRCULATION AB In previous studies we showed that 5 days of treatment with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) mobilized murine repopulating cells into the peripheral blood (PB) and that these cells could be efficiently transduced with retroviral vectors. We also found that, 7-14 days after cytokine treatment, the repopulating ability of murine bone marrow (BM) increased 10-fold. In this study we examined the efficiency of gene transfer into cytokine-primed murine BR4 cells and extended our observations to a nonhuman primate autologous transplantation model. G-CSF/SCF-primed murine BM cells collected 7-14 days after cytokine treatment were equivalent to post-5-fluorouracil BM or G-CSF/SCF-mobilized PB cells as targets for retroviral gene transfer. In nonhuman primates, CD34-enriched PB cells collected after 5 days of G-CSF/SCF treatment and CD34-enriched BM cells collected 14 days later were superior targets for retroviral gene transfer. When a clinically approved supernatant infection protocol with low-titer vector preparations was used, monkeys had up to 5% of circulating cells containing the vector for up to a year after transplantation. This relatively high level of gene transfer was confirmed by Southern blot analysis. Engraftment after transplantation using primed BM cells was more rapid than that using steady-state bone marrow, and the fraction of BM cells having the most primitive CD34(+)/CD38(-) or CD34(+)/CD38(dim) phenotype increased 3-fold. We conclude that cytokine priming with G-CSF/SCF may allow collection of increased numbers of primitive cells from both the PB and BM that have improved susceptibility to retroviral transduction, with many potential applications in hematopoietic stem cell-directed gene therapy. C1 NIH,NATL CTR HUMAN GENOME RES,HEMATOPOIESIS SECT,BETHESDA,MD 20892. RP Dunbar, CE (reprint author), NHLBI,HEMATOL BRANCH,NIH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 38 TC 131 Z9 134 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 OCT 15 PY 1996 VL 93 IS 21 BP 11871 EP 11876 DI 10.1073/pnas.93.21.11871 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100104 PM 8876230 ER PT J AU McCutchan, TF Kissinger, JC Touray, MG Rogers, MJ Li, J Sullivan, M Braga, EM Krettli, AU Miller, LH AF McCutchan, TF Kissinger, JC Touray, MG Rogers, MJ Li, J Sullivan, M Braga, EM Krettli, AU Miller, LH TI Comparison of circumsporozoite proteins from avian and mammalian malarias: Biological and phylogenetic implications SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE plasmodium; apicomplexa; evolution; sporozoite invasion; cell adhesion motif ID PLASMODIUM-FALCIPARUM; EVOLUTIONARY ORIGIN; RIBOSOMAL-RNA; GENE; SEQUENCE; SPOROZOITES; PARASITE; THROMBOSPONDIN; POLYMORPHISM; GALLINACEUM AB The circumsporozoite (CS) protein of malaria parasites (Plasmodium) covers the surface of sporozoites that invade hepatocytes in mammalian hosts and macrophages in avian hosts. CS genes have been characterized from many Plasmodium that infect mammals; two domains of the corresponding proteins, identified initially by their conservation (region I and region II), have been implicated in binding to hepatocytes. The CS gene from the avian parasite Plasmodium gallinaceum was characterized to compare these functional domains to those of mammalian Plasmodium and for the study of Plasmodium evolution. The P. gallinaceum protein has the characteristics of CS proteins, including a secretory signal sequence, central repeat region, regions of charged amino acids, and an anchor sequence. Comparison with CS signal sequences reveals four distinct groupings, with P. gallinaceum most closely related to the human malaria Plasmodium falciparum. The 5-amino acid sequence designated region I, which is identical in all mammalian CS and implicated in hepatocyte invasion, is different in the avian protein. The P. gallinaceum repeat region consists of 9-amino acid repeats with the consensus sequence QP(A/V)GGNGG(A/V). The conserved motif designated region II-plus, which is associated with targeting the invasion of liver cells, is also conserved in the avian protein. Phylogenetic analysis of the aligned Plasmodium CS sequences yields a tree with a topology similar to the one obtained using sequence data from the small subunit rRNA gene. The phylogeny using the CS gene supports the proposal that the human malaria P. falciparum is significantly more related to avian parasites than to other parasites infecting mammals, although the biology of sporozoite invasion is different between the avian and mammalian species. C1 UNIV FED MINAS GERAIS,BR-190002 MINAS GERAIS,BRAZIL. FIOCRUZ MS,CTR PESQUISAS RENE RACHOU,BR-190002 MINAS GERAIS,BRAZIL. RP McCutchan, TF (reprint author), NIAID,NIH,PARASIT DIS LAB,GROWTH & DEV SECT,BLDG 4,ROOM B1-28,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Kissinger, Jessica/E-9610-2010; Braga, Erika/A-6776-2008 OI Kissinger, Jessica/0000-0002-6413-1101; Braga, Erika/0000-0001-5550-7157 NR 38 TC 104 Z9 105 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 OCT 15 PY 1996 VL 93 IS 21 BP 11889 EP 11894 DI 10.1073/pnas.93.21.11889 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100107 PM 8876233 ER PT J AU Okazawa, H Imafuku, I Minowa, MT Kanazawa, I Hamada, H Mouradian, MM AF Okazawa, H Imafuku, I Minowa, MT Kanazawa, I Hamada, H Mouradian, MM TI Regulation of striatal D-1A dopamine receptor gene transcription by Brn-4 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POU-DOMAIN PROTEIN; FACTOR SCIP; HORMONE DEFICIENCY; RETINOIC ACID; MESSENGER-RNA; DNA-BINDING; MUTANT MICE; STEM-CELLS; EXPRESSION; PIT-1 AB Brn-4 is a member of the POU transcription factor family and is expressed in the central nervous system. In this study, we addressed whether Brn-4 regulates expression of the D-1A dopamine receptor gene. We found a functional Brn-4 responsive element in the intron of this gene by means of cotransfection chloramphenical acetyltransferase assays. This region contains two consensus sequences for binding of POU factors. Gel mobility-shift assays using glutathione S-transferase-Brn-4 fusion protein indicated that Brn-4 binds to these sequences. Both these sites are essential for transactivation by Brn-4 because deletion of either significantly reduced this enhancer activity. In situ hybridization revealed colocalization of Brn-4 and D-1A mRNAs at the level of a single neuron in the rat striatum where this dopamine receptor is most abundantly expressed. Gel mobility-supershift assay using rat striatal nuclear extract and Brn-4 antibody confirmed the presence of Brn-4 in this brain region and its ability to bind to its consensus sequences in the D-1A gene. These data suggest a functional role for Brn-4 in the expression of the D-1A dopamine receptor gene both in vitro and in vivo. C1 NINCDS, NIH, EXPT THERAPEUT BRANCH, BETHESDA, MD 20892 USA. TOKYO METROPOLITAN INST MED SCI, DEPT DEV BIOL & CANC PREVENT, TOKYO 113, JAPAN. RP Okazawa, H (reprint author), UNIV TOKYO, FAC MED, DEPT NEUROL, TOKYO 113, JAPAN. OI Mouradian, M. Maral/0000-0002-9937-412X NR 48 TC 25 Z9 25 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 OCT 15 PY 1996 VL 93 IS 21 BP 11933 EP 11938 DI 10.1073/pnas.93.21.11933 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100114 PM 8876240 ER PT J AU Richards, RG DiAugustine, RP Petrusz, P Clark, GC Sebastian, J AF Richards, RG DiAugustine, RP Petrusz, P Clark, GC Sebastian, J TI Estradiol stimulates tyrosine phosphorylation of the insulin-like growth factor-1 receptor and insulin receptor substrate-1 in the uterus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE epithelium; signal transduction; proliferation ID I IGF-I; MESSENGER-RIBONUCLEIC-ACID; UTERINE EPITHELIAL-CELLS; MOUSE UTERUS; FACTOR PRECURSOR; GENE-EXPRESSION; ESTROGEN ACTION; RAT UTERUS; MICE; PROLIFERATION AB The signaling pathways associated with estrogen-induced proliferation of epithelial cells in the reproductive tract have not been defined. To identify receptor tyrosine kinases that are activated in vivo by 17 beta-estradiol (E2), uteri from ovariectomized mice were examined for enhanced tyrosine phosphorylation of various receptors and a receptor substrate following treatment with this hormone. Within 4 hr after hormone exposure, extracts showed increased phosphotyrosine (P-Tyr) immunoreactivity at several bands, including 170- and 180-kDa; these bands were still apparent at 24 hr after E2. Analysis of immunoprecipitates from uterine extracts revealed that E2 enhanced tyrosine phosphorylation of the insulin-like growth factor-1 receptor (IGF-1R) and insulin receptor substrate-1 (IRS-1) by 6 hr. Comparison of supernatants from IRS-1 and control rabbit IgG immunoprecipitates indicated that the 170-kDa P-Tyr band in extracts was equivalent to IRS-1. The receptors for epidermal growth factor, platelet-derived growth factor, and basic fibroblast growth factor did not exhibit an E2-induced increase in P-Tyr content. The nonestrogenic steroid hormones examined did not stimulate the P-Tyr content of IGF-1R or IRS-1. Immunolocalization of P-Tyr and IRS-1 revealed strong reactivity in the epithelial layer of the uterus from E2-treated mice, suggesting that the, majority of P-Tyr bands observed in immunoblots originate in the epithelium. Since hormonal activation of IRS-1 is epithelial, estrogen-specific, and initiated before maximal DNA synthesis occurs following treatment with hormone, this protein, as part of the IGF-1R pathway, may be important in mediating estrogen-stimulated proliferation in the uterus. C1 NIEHS,NIH,BIOCHEM RISK ANAL LAB,HORMONES & CANC SECT,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH MED,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27514. NR 47 TC 93 Z9 94 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 OCT 15 PY 1996 VL 93 IS 21 BP 12002 EP 12007 DI 10.1073/pnas.93.21.12002 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100126 PM 8876252 ER PT J AU Grant, S London, ED Newlin, DB Villemagne, VL Liu, X Contoreggi, C Phillips, RL Kimes, AS Margolin, A AF Grant, S London, ED Newlin, DB Villemagne, VL Liu, X Contoreggi, C Phillips, RL Kimes, AS Margolin, A TI Activation of memory circuits during cue-elicited cocaine craving SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; EXCITOTOXIC LESIONS; GLUCOSE-UTILIZATION; PREFRONTAL CORTEX; EMOTIONAL MEMORY; HUMAN BRAIN; AMYGDALA; ADDICTION; DEPENDENCE; PREFERENCE AB Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic regions implicated in several forms of memory when human volunteers who abuse cocaine are exposed to drug-related stimuli. Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial temporal lobe (amygdala), and cerebellum with self-reports of craving suggest that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving. C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. YALE UNIV,SCH MED,SUBS ABUSE CTR,NEW HAVEN,CT 06510. NR 53 TC 642 Z9 662 U1 3 U2 32 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 OCT 15 PY 1996 VL 93 IS 21 BP 12040 EP 12045 DI 10.1073/pnas.93.21.12040 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM681 UT WOS:A1996VM68100133 PM 8876259 ER PT J AU Weinberg, CR Skjaerven, R Wilcox, AJ AF Weinberg, CR Skjaerven, R Wilcox, AJ TI Statistical evidence for shared transient causes of anatomically distinct birth defects SO STATISTICS IN MEDICINE LA English DT Article ID MULTIPLE AB Certain pairs of anatomically distinct birth defects co-occur in the same baby more often than predicted under independence. Such an excess might reflects either the fact that some subpopulations of parents have inherently increased risk for both, or that certain pregnancies are at increased risk for both, even within the same couple, perhaps, due to transient exposures specific to the pregnancy. We focus on the latter possibility in the context of a large birth registry and two relatively common types of defects, by testing the null hypothesis that within sibships the two defects occur independently, Focusing on sibships where both defects occurred, we propose a test based on the total number of 'co-incidences', sibships where both occurred in the same baby. Such a test can be carried out either with or without allowance for possible dependence of risk on birth order. Applying this to club foot and sex organ defects among sibships from the Medical Birth Registry of Norway, we find strong evidence for excess within-family co-incidence, suggesting that there are shared, time-varying (hence perhaps modifiable) causal components in their aetiology. C1 UNIV BERGEN,MED INFORMAT & STAT SECT,HAUKELAND SYKEHUS,N-5021 BERGEN,NORWAY. RP Weinberg, CR (reprint author), NIEHS,MD A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 5 TC 2 Z9 2 U1 0 U2 0 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 OCT 15 PY 1996 VL 15 IS 19 BP 2029 EP 2036 DI 10.1002/(SICI)1097-0258(19961015)15:19<2029::AID-SIM350>3.0.CO;2-I PG 8 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 VK325 UT WOS:A1996VK32500004 PM 8896137 ER PT J AU Podgor, MJ Gastwirth, JL Mehta, CR AF Podgor, MJ Gastwirth, JL Mehta, CR TI Efficiency robust tests of independence in contingency tables with ordered classifications SO STATISTICS IN MEDICINE LA English DT Article AB Ordered categorical data occur frequently in biomedical research. The linear by linear association test for ordered R x C tables permits the investigator to specify row and column scores for analysis. When an investigator believes that there may be more than one set of reasonable scores or when more than one investigator proposes scores, we need a method to decide upon a single procedure to use, We show how to use efficiency robustness principles to combine tests from two or more sets of scores into one robust test for analysis, This test minimizes the worst possible efficiency loss over all the sets of scores, We illustrate the methodology for the R x C case and, in detail, for the important special 2 x C case. C1 GEORGE WASHINGTON UNIV,DEPT STAT,WASHINGTON,DC 20052. CYTEL SOFTWARE CORP,CAMBRIDGE,MA 02139. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. RP Podgor, MJ (reprint author), NEI,NIH,DIV BIOMETRY & EPIDEMIOL,BLDG 31 ROOM 6A52,31 CTR DR MSC 2510,BETHESDA,MD 20892, USA. NR 25 TC 15 Z9 16 U1 0 U2 4 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 OCT 15 PY 1996 VL 15 IS 19 BP 2095 EP 2105 DI 10.1002/(SICI)1097-0258(19961015)15:19<2095::AID-SIM349>3.0.CO;2-Y PG 11 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 VK325 UT WOS:A1996VK32500009 PM 8896142 ER PT J AU Eaton, WA Thompson, PA Chan, CK Hagen, SJ Hofrichter, J AF Eaton, WA Thompson, PA Chan, CK Hagen, SJ Hofrichter, J TI Fast events in protein folding SO STRUCTURE LA English DT Article ID CHYMOTRYPSIN INHIBITOR-2; TRANSITION; MECHANISM; MODEL; PRINCIPLES; KINETICS; PATHWAYS; FIELD; STATE; HELIX AB Understanding how proteins fold is one of the central problems in biochemistry. A new generation of kinetic experiments has emerged to investigate the mechanisms of protein folding on the previously inaccessible submillisecond time scale. these experiments provide the first glimpse of processes such as secondary structure formation, local hydrophobic collapse, global collapse to compact denatured states, and fast barrier crossings to the native state. Key results are summarized and discussed in terms of the statistical energy landscape theory of protein folding. RP Eaton, WA (reprint author), NIDDKD,NIH,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [R01 GM053640-17] NR 53 TC 81 Z9 81 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0969-2126 J9 STRUCTURE JI Structure PD OCT 15 PY 1996 VL 4 IS 10 BP 1133 EP 1139 DI 10.1016/S0969-2126(96)00121-9 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VP148 UT WOS:A1996VP14800003 PM 8939749 ER PT J AU Hiramatsu, K Tadano, M Men, R Lai, CJ AF Hiramatsu, K Tadano, M Men, R Lai, CJ TI Mutational analysis of a neutralization epitope on the dengue type 2 virus (DEN2) envelope protein: Monoclonal antibody resistant DEN2/DEN4 chimeras exhibit reduced mouse neurovirulence SO VIROLOGY LA English DT Article ID BORNE ENCEPHALITIS-VIRUS; STRUCTURAL PROTEINS; ANTIGENIC DETERMINANTS; NUCLEOTIDE-SEQUENCE; ILL VIRUS; MICE; GLYCOPROTEIN; FLAVIVIRUS; IDENTIFICATION; CONSTRUCTION AB The antigenic site of dengue type 2 virus (DEN2)-neutralizing monoclonal antibody (mab) 3H5 was investigated by mutational analysis. Sequence comparisons indicated that much of the 12-amino-acid sequence extending from position 386 to 397 of the DEN2 envelope glycoprotein (E) previously thought to represent the DEN2-specific mab 3H5 binding site was also present in some dengue type 1, 3, or 4 virus strains. However, the region occupied by the Glu-Pro-Gly sequence at upstream positions 383 to 385 was completely conserved among DEN2 strains, but divergent in other serotype viruses, suggesting that this sequence might be part of the antigenic site of malc 3H5. We investigated this possibility by employing the previously constructed chimeric DEN2(PreM-E)/DEN4 cDNA clone to produce viable mutants bearing DEN2 PreM and E sequences that could be analyzed for binding to and neutralization by mab 3H5. We constructed 13 such DEN2 mutants that contained a single amino acid substitution in the region between positions 383 and 393 of DEN2 E. Each single substitution in the region spanning positions 386 through 393 of DEN2 yielded a virus that was as reactive with mab 3H5 as the parental chimeric virus. These results are consistent with the extent of sequence conservation in the region. In contrast, 5 of 6 mutants that sustained an amino acid substitution at position 383, 384, or 385 failed to react with mab 3H5 as detected by immunofluorescence assay and failed to be neutralized by the mab. Interestingly, each of the 5 mab-resistant DEN2 mutants also exhibited reduced mouse neurovirulence compared to parental chimeric DEN2 when inoculated intracerebrally. These observations suggest that the Glu-Pro-Gly sequence at positions 383-385 of the DEN2 E is a component of the site against which mab 3H5 is directed. In the recently determined three-dimensional structure of the related tick-borne encephalitis virus E, the Glu-Pro-Gly sequence would be located on the lateral surface of the immunoglobulin-likedomain that is proposed to bind to the host cell receptor. (C) 1996 Academic Press, Inc. C1 NIAID,INFECT DIS LAB,MOL VIRAL BIOL SECT,NIH,BETHESDA,MD 20892. NR 45 TC 76 Z9 84 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 15 PY 1996 VL 224 IS 2 BP 437 EP 445 DI 10.1006/viro.1996.0550 PG 9 WC Virology SC Virology GA VV009 UT WOS:A1996VV00900008 PM 8874504 ER PT J AU Soh, Y Rhee, HM Sohn, DH Song, BJ AF Soh, Y Rhee, HM Sohn, DH Song, BJ TI Immunological detection of CYP2E1 in fresh rat lymphocytes and its pretranslational induction by fasting SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID LIPID-PEROXIDATION; ETHANOL; EXPRESSION; PROTEIN; CYTOCHROME-P450IIE1; STABILIZATION; DEHYDROGENASE; CHLORZOXAZONE; GLUTATHIONE; KIDNEY AB The level of ethanol-inducible cytochrome P450 2E1 (CYP2E1) in fresh lymphocytes compared with cultured cells and its induction mechanism by fasting were studied. CYP2E1 in the homogenate and 8-9 fraction of fresh lymphocytes was elevated about 5-fold by fasting, comparable to the induction observed in cultured lymphocytes. This induction was accompanied by increased level of CYP2E1 mRNA, confirmed by nested RT-PCRs, Southern blot, and DNA sequence analysis. Our data thus demonstrated that CYP2E1 in fresh lymphocytes is pretranslationally induced by fasting, in parallel to the hepatic enzyme, and that measurement of CYP2E1 in the lymphocyte homogenate can be useful to estimate the hepatic CYP2E1 level in a relatively noninvasive manner. (C) 1996 Academic Press, Inc. C1 NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. WONKWANG UNIV,COLL PHARM,IKSAN,SOUTH KOREA. US FDA,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. NR 26 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 14 PY 1996 VL 227 IS 2 BP 541 EP 546 DI 10.1006/bbrc.1996.1542 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VP321 UT WOS:A1996VP32100037 PM 8878549 ER PT J AU Marin, C Papa, S Engber, TM Bonastre, M Tolosa, E Chase, TN AF Marin, C Papa, S Engber, TM Bonastre, M Tolosa, E Chase, TN TI MK-801 prevents levodopa-induced motor response alterations in parkinsonian rats SO BRAIN RESEARCH LA English DT Article DE 6-hydroxydopamine; levodopa; motor fluctuation; MK801; rotation ID BASAL GANGLIA; DOPAMINE; DISEASE; ANTAGONIST; THERAPY AB The systemic administration of the N-methyl-D-aspartate (NMDA) receptor antagonist. MK801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), has previously been found to reverse the motor response alterations that develop during long-term levodopa treatment of parkinsonian rats. To determine whether co-administration of MK801 with levodopa might prevent the initial appearance of these response changes, rats, rendered parkinsonian by a 6-hydroxydopamine lesion of the medial forebrain bundle, received either levodopa alone or levodopa with the NMDA receptor antagonist. After four weeks of treatment with levodopa alone, the duration of the turning response declined by 37% (P < 0.05) and the number of ineffectual levodopa injections had more than doubled (P < 0.05). MK801 co-treatment completely blocked the shortening in response duration and prevented the frequency of ineffectual levodopa injection from exceeding baseline levels in animals receiving levodopa alone. The total magnitude of the turning response to levodopa was not affected. These results suggest that NMDA receptor blockade may act prophylactically to prevent the appearance of motor response alterations in levodopa-treated parkinsonian rodents that resemble those occurring in levodopa-treated patients with Parkinson's disease. C1 UNIV BARCELONA,HOSP CLIN,SERV NEUROL,LAB NEUROL EXPT,BARCELONA,SPAIN. CEPHALON INC,W CHESTER,PA. RP Marin, C (reprint author), NINCDS,EXPT THERAPEUT BRANCH,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 15 TC 84 Z9 86 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 14 PY 1996 VL 736 IS 1-2 BP 202 EP 205 DI 10.1016/S0006-8993(96)00693-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA VR613 UT WOS:A1996VR61300024 PM 8930325 ER PT J AU Vonkeman, HE Voorn, P Brady, LS Berendse, HW Richfield, EK AF Vonkeman, HE Voorn, P Brady, LS Berendse, HW Richfield, EK TI Opioid receptor ligand binding in the human striatum .2. Heterogeneous distribution of kappa opioid receptor labeled with [H-3]bremazocine SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE basal ganglia; nucleus accumbens; receptor autoradiography; kappa opioid receptor ID NUCLEUS-ACCUMBENS; OPIATE RECEPTORS; BASAL GANGLIA; RAT-BRAIN; SPECIES-DIFFERENCES; LOCOMOTOR-ACTIVITY; RHESUS-MONKEY; GUINEA-PIG; MU-OPIATE; AUTORADIOGRAPHY AB Selective kappa opioid receptor autoradiography with [H-3]bremazocine (BRM) was used to examine regional and subregional kappa receptor distribution patterns at five rostrocaudal levels through the human striatum. [H-3]BRM binding densities were measured in the individual striatal nuclei and in subregions therein. The distribution of [H-3]BRM binding sites was found to have a strongly heterogeneous character. At the regional level a rostral-to-caudal decrease in [H-3]BRM binding densities was observed. Also, a dorsal-to-ventral differentiation was seen, with higher values in the ventral striatum, especially in the nucleus accumbens, and lower values in the dorsal parts of the caudate nucleus and putamen. These findings suggest an association of kappa receptor function with limbic-related processes in the ventral striatum. Along the ventral edge of the nucleus accumbens and putamen, specific domains with extremely high [H-3]BRM binding values were identified. (C) 1996 Wiley-Liss, Inc. C1 UNIV ROCHESTER,SCH MED & DENT,DIV NEUROPATHOL,ROCHESTER,NY 14642. VRIJE UNIV AMSTERDAM,NEUROSCI RES INST,DEPT ANAT & EMBRYOL,NL-1081 BT AMSTERDAM,NETHERLANDS. VRIJE UNIV AMSTERDAM,ACAD HOSP,DEPT NEUROL,NL-1081 HV AMSTERDAM,NETHERLANDS. NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PHARMACOL,ROCHESTER,NY 14642. FU NIMH NIH HHS [MH 40381] NR 43 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 14 PY 1996 VL 374 IS 2 BP 223 EP 229 DI 10.1002/(SICI)1096-9861(19961014)374:2<223::AID-CNE5>3.0.CO;2-4 PG 7 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VN884 UT WOS:A1996VN88400005 PM 8906495 ER PT J AU Jetten, AM De Luca, LM Nelson, K Schroeder, W Burlingame, S Fujimoto, W AF Jetten, AM De Luca, LM Nelson, K Schroeder, W Burlingame, S Fujimoto, W TI Regulation of cornifin alpha expression in the vaginal and uterine epithelium by estrogen and retinoic acid SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE estrogen; retinoic acid; cornifin; squamous differentiation; uterus; vagina; vitamin A ID HUMAN EPIDERMAL-KERATINOCYTES; CELL-ENVELOPE; TRACHEAL EPITHELIUM; DIFFERENTIATION; METAPLASIA; INVOLUCRIN; PROTEINS; CARCINOMA; RECEPTORS; LORICRIN AB In this study, we analyze the regulation of the squamous-specific gene, cornifin alpha, by estrogen and retinoic acid in vaginal and uterine epithelial cells. In ovariectomized animals, the vaginal epithelium consists of a stratified, nonkeratinizing epithelium which changes into a highly-stratified, keratinizing epithelium upon treatment with estradiol. This transition is accompanied by a dramatic induction of the crosslinked envelope precursor, cornifin alpha. An increase in cornifin mRNA can be detected as early as 3 h after treatment. A similar effect is observed for the synthetic estrogenic agent diethylstilbestrol while other steroid hormones, including testosterone, progesterone or dexamethasone have little effect on cornifin expression. In contrast to the vagina, estradiol induces neither squamous differentiation nor expression of cornifin alpha in the uterine epithelium. Similar to the action of estradiol, vitamin A-deficiency greatly enhances squamous differentiation and keratinization in the vaginal epithelium. But unlike estradiol, it induces squamous metaplasia in the normally columnar, uterine epithelium, which eventually is replaced by a keratinizing epithelium in severe deficiency. This transition is associated with an induction of cornifin sc expression. Immunohistochemical and in situ hybridization analysis localizes cornifin protein and mRNA in the suprabasal layers of the squamous epithelium. Our results demonstrate that estrogen and retinoids play key roles in the regulation of differentiation and cornifin sc expression in the uterine and vaginal epithelium. C1 NCI, DIFFERENTIAT CONTROL SECT, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, NIH, BETHESDA, MD 20892 USA. NIEHS, REPROD & DEV TOXICOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. WESLEYAN COLL, DEPT BIOL, MACON, GA 31297 USA. UNIV TEXAS, HLTH SCI CTR, DEPT PHARMACOL & DERMATOL, HOUSTON, TX 77030 USA. OKAYAMA MED UNIV, DEPT DERMATOL, OKAYAMA, JAPAN. RP Jetten, AM (reprint author), NIEHS, CELL BIOL SECT, PULM PATHOBIOL LAB, NIH, RES TRIANGLE PK, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 44 TC 17 Z9 17 U1 0 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 OCT 14 PY 1996 VL 123 IS 1 BP 7 EP 15 DI 10.1016/0303-7207(96)03871-3 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA VP957 UT WOS:A1996VP95700002 PM 8912806 ER PT J AU Smith, EP Korach, KS AF Smith, EP Korach, KS TI Hot papers - Endocrinology - Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man by E.P. Smith, J. Boyd, T.C. Williams, D.B. Lubahn, K.S. Korach - Comments SO SCIENTIST LA English DT Editorial Material AB Pediatric endocrinologist Eric P. Smith and toxicologist Kenneth S. Korach explain how they found a mutation in the estrogen-receptor gene in a 28-year-old man that caused estrogen resistance; University of Pennsylvania geneticist Barbara L. Weber discusses here study confirming the link between breast and ovarian cancer and mutations in the BRCA1 gene. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Smith, EP (reprint author), UNIV CINCINNATI,COLL MED,CHILDRENS HOSP,CTR MED,CINCINNATI,OH 45229, USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD OCT 14 PY 1996 VL 10 IS 20 BP 14 EP 14 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA VL938 UT WOS:A1996VL93800016 ER PT J AU Fauci, AS AF Fauci, AS TI United States of America - Biomedical research in an era of unlimited aspirations and limited resources SO LANCET LA English DT Article RP Fauci, AS (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 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 OCT 12 PY 1996 VL 348 IS 9033 BP 1002 EP 1003 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VM027 UT WOS:A1996VM02700016 PM 8855860 ER PT J AU Kirke, PN Mills, JL Whitehead, AS Molloy, A Scott, JM AF Kirke, PN Mills, JL Whitehead, AS Molloy, A Scott, JM TI Methylenetetrahydrofolate reductase mutation and neural tube defects SO LANCET LA English DT Letter C1 NICHHD,BETHESDA,MD 20892. TRINITY COLL DUBLIN,DEPT GENET,DUBLIN,IRELAND. TRINITY COLL DUBLIN,INST BIOTECHNOL,DUBLIN,IRELAND. TRINITY COLL DUBLIN,DEPT CLIN MED,DUBLIN,IRELAND. TRINITY COLL DUBLIN,DEPT BIOCHEM,DUBLIN,IRELAND. RP Kirke, PN (reprint author), HLTH RES BOARD,DUBLIN 2,IRELAND. NR 5 TC 67 Z9 68 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 OCT 12 PY 1996 VL 348 IS 9033 BP 1037 EP 1038 DI 10.1016/S0140-6736(05)64971-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VM027 UT WOS:A1996VM02700069 PM 8855891 ER PT J AU Kuznicki, J Isaacs, KR Jacobowitz, DM AF Kuznicki, J Isaacs, KR Jacobowitz, DM TI The expression of calretinin in transfected PC12 cells provides no protection against Ca2+-overload or trophic factor deprivation SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article; Proceedings Paper CT 4th European Symposium on Calcium Binding Proteins in Normal and Transformed Cells CY MAY 02-05, 1996 CL PERUGIA, ITALY DE green fluorescent protein; NGF-induced differentiation; transfection; neuroprotection; calcium overload ID BINDING PROTEIN CALRETININ; CALCIUM-BINDING; RAT-BRAIN; QUANTITATIVE MEASUREMENT; CONFORMATIONAL-CHANGES; HIPPOCAMPAL-NEURONS; ALZHEIMERS-DISEASE; CALBINDIN; LOCALIZATION; PARVALBUMIN AB To address the question whether calretinin (CX) may protect cells against Ca2+ overload or trophic factor deprivation, PC12 cells were transfected with plasmids containing a CR coding region under control of a cytomegalovirus promoter. Nerve growth factor (NGF) treatment induced differentiation, increased transfection efficiency (at least 10-foId) and activated the CR gene (as found by RNase protection method and immunohistochemistry). Exogenous CR expression was identified either in living cells by fluorescence of green fluorescent protein (when the CR coding region was fused to this protein) or in fixed cells by CR immunoreactivity. Undifferentiated and NGF-differentiated populations of transfected cells were incubated in the presence of a Ca2+-ionophore or in media deprived of serum or NGF. Expression of exogenous CR in undifferentiated or NGF-trealed cells (due to transfection) or endogenous CR (due to gene activation by NGF) did not render PC12 cells more resistant to insults such as Ca2+-overload and trophic factor deprivation. C1 NIMH,LCS,BETHESDA,MD 20892. NR 31 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD OCT 11 PY 1996 VL 1313 IS 3 BP 194 EP 200 DI 10.1016/0167-4889(96)00089-4 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN233 UT WOS:A1996VN23300005 PM 8898854 ER PT J AU MacDonald, NJ Freije, JMP Stracke, ML Manrow, RE Steeg, PS AF MacDonald, NJ Freije, JMP Stracke, ML Manrow, RE Steeg, PS TI Site-directed mutagenesis of nm23-H1 - Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOSIDE-DIPHOSPHATE KINASE; X-RAY STRUCTURE; MYXOCOCCUS-XANTHUS; CRYSTAL-STRUCTURE; TUMOR-METASTASIS; HEPATOCELLULAR-CARCINOMA; PROTEIN EXPRESSION; DICTYOSTELIUM-DISCOIDEUM; DROSOPHILA DEVELOPMENT; STIMULATING PROTEIN AB We report the first correlation of Nm23 sequence and its tumor metastasis-suppressive capacity using site-directed mutagenesis and an in vitro tumor cell motility assay. MDA-MB-435 human breast carcinoma cells were transfected with a control expression vector (pCMVB-amneo), the vector containing the wild type nm23-H1, or the nm23-H1 vector encoding mutations at the following amino acids: serine 44, a phosphorylation site; proline 96, the k-pn mutation in the Drosophila nm23 homolog that causes developmental defects; histidine 118, involved in Nm23's nucleoside diphosphate kinase activity; and serine 120, a site of mutation in human neuroblastomas and phosphorylation. The wild type nm23-H1 transfectants were 44-98% less motile to serum and 86-99% less motile to autotaxin than control vector transfectants. The proline 96 k-pn, serine 120 to glycine, and to a lesser extent serine 120 to alanine mutant nm23-H1-transfected cell lines exhibited motility levels at or above the control transfectants, indicating that these mutations can abrogate the motility-suppressive phenotype of nm23-H1. No effect was observed on cellular proliferation, nor were the serine 44 to alanine nm23-H1 mutant transfectants motile, demonstrating the specificity of the data. The data identify the first structural motifs of nm23-H1 that influence its metastasis suppressive effect and suggest complex biochemical associations or activities in the Nm23 suppressive pathway. C1 NCI,WOMENS CANC SECT,PATHOL LAB,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NCI,TUMOR INVAS & METASTASIS SECT,PATHOL LAB,DIV CLIN SCI,NIH,BETHESDA,MD 20892. RI Freije, Jose M.P./A-6535-2008 OI Freije, Jose M.P./0000-0002-4688-8266 NR 75 TC 107 Z9 111 U1 2 U2 8 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 OCT 11 PY 1996 VL 271 IS 41 BP 25107 EP 25116 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300009 PM 8810265 ER PT J AU Lee, SH Minowa, MT Mouradian, MM AF Lee, SH Minowa, MT Mouradian, MM TI Two distinct promoters drive transcription of the human D-1A dopamine receptor gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; MESSENGER-RNA; MOLECULAR-CLONING; GROWTH-HORMONE; ALTERNATIVE PROMOTER; MULTIPLE PROMOTERS; PREFRONTAL CORTEX; RAT-BRAIN; EXPRESSION; D1 AB The human D-1A dopamine receptor gene has a GC-rich, TATA-less promoter located upstream of a small, noncoding exon 1, which is separated from the coding exon 2 by a 116-base pair (bp)-long intron. Serial 3'-deletions of the 5'-noncoding region of this gene, including the intron and 5'-end of exon 2, resulted in 80 and 40% decrease in transcriptional activity of the upstream promoter in two D-1A-expressing neuroblastoma cell lines, SK-N-MC and NS20Y, respectively. To investigate the function of this region, the intron and 245 bp at the 5'-end of exon 2 were investigated, Transient expression analyses using various chloramphenicol acetyltransferase constructs showed that the transcriptional activity of the intron is higher than that of the upstream promoter by 12-fold in SK-N-MC cells and by 5.5-fold in NS20Y cells in an orientation-dependent manner, indicating that the D-1A intron is a strong promoter. Primer extension and ribonuclease protection assays revealed that transcription driven by the intron promoter is initiated at the junction of intron and exon 2 and at a cluster of nucleotides located 50 bp downstream from this junction. The same transcription start sites are utilized by the chloramphenicol acetyltransferase constructs employed in transfections as well as by the D-1A gene expressed within the human caudate. The relative abundance of D-1A transcripts originating from the upstream promoter compared with those transcribed from the intron promoter is 1.5-2.9 times in SK-N-MC cells and 2 times in the human caudate. Transcript stability studies in SK-N-MC cells revealed that longer D-1A mRNA molecules containing exon 1 are degraded 1.8 times faster than shorter transcripts lacking exon 1, Although gel mobility shift assay could not detect DNA-protein interaction at the D-1A intron, competitive co-transfection using the intron as competitor confirmed the presence of trans-acting factors at the intron, These data taken together indicate that the human D-1A gene has two functional TATA-less promoters, both in D-1A expressing cultured neuroblastoma cells and in the human striatum. C1 NINCDS,NIH,EXPT THERAPEUT BRANCH,GENET PHARMACOL UNIT,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X NR 55 TC 33 Z9 35 U1 1 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 OCT 11 PY 1996 VL 271 IS 41 BP 25292 EP 25299 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300036 PM 8810292 ER PT J AU VanLeeuwen, JEM Kearse, KP AF VanLeeuwen, JEM Kearse, KP TI The related molecular chaperones calnexin and calreticulin differentially associate with nascent T cell antigen receptor proteins within the endoplasmic reticulum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMATURE THYMOCYTES; MONOCLONAL-ANTIBODY; INITIAL STEP; DELTA-CHAIN; GLYCOPROTEINS; RECOGNITION; EXPRESSION; MEMBRANE; ALPHA; OLIGOSACCHARIDE AB Assembly of the multisubunit T cell antigen receptor (TCR) complex is an intricate process requiring coordinated regulation of at least six different gene products (alpha, beta, gamma, delta, epsilon and xi) and the ordered pairing of partner chains within the endoplasmic reticulum (ER). To date, two proteins have been implicated as functioning as molecular chaperones in the assembly of nascent TCR proteins: calnexin, a resident ER transmembrane protein, which associates with all TCR components except xi, and T cell receptor-associated protein, which selectively associates with CD3 gamma epsilon pairs, In this study, we examined the association of calreticulin, a soluble protein with significant sequence homology to calnexin, with newly synthesized TCR proteins, Analogous to calnexin, processing of glycan chains by glucosidase enzymes was required for initial association of TCR alpha and -beta proteins with calreticulin; however, several major differences were noted regarding interaction of calnexin and calreticulin chaperones with TCR proteins. First, TCR alpha and -beta proteins showed prolonged association with calnexin molecules compared with calreticulin; interaction of TCR alpha proteins with calreticulin was particularly transient, with most calreticulin-TCR alpha protein complexes dissociating within 15 min of their initial assembly, Second, we found that, unlike calnexin, which associated with clonotypic TCR alpha and -beta proteins and invariant CD3 delta and -epsilon polypeptides, calreticulin associated specifically with clonotypic TCR alpha and -beta proteins. These studies identify calreticulin as a molecular chaperone for nascent clonotypic TCR alpha and -beta proteins and demonstrate that calreticulin and calnexin differentially associate with newly synthesized TCR proteins within the ER. C1 NCI,EXPT IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. RI van Leeuwen, Jeroen/G-3555-2010 NR 35 TC 55 Z9 55 U1 1 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 OCT 11 PY 1996 VL 271 IS 41 BP 25345 EP 25349 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300043 PM 8810299 ER PT J AU Akasawa, A Hsieh, LS Martin, BM Liu, T Lin, Y AF Akasawa, A Hsieh, LS Martin, BM Liu, T Lin, Y TI A novel acidic allergen, Hev b 5, in latex - Purification, cloning and characterization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONTACT URTICARIA; CROSS-REACTIVITY; GLOVES; RUBBER; BRASILIENSIS; PROTEINS AB Latex allergy is recognized as a serious health problem among health care workers and children with spina bifida, A number of IgE-reactive proteins have been identified in natural and processed latex products. One of the most acidic proteins in the cytoplasm of lacticifer cells of rubber trees (Hevea brasiliensis) is demonstrated to be a potent allergen in eliciting allergic reactions in humans, This protein, with pI = 3.5, has a molecular mass of 16 kDa with a blocked N terminus and an unusual amino acid composition, This acidic protein was found in extracts prepared from latex gloves, which were shown to be allergenic, The purified protein elicits histamine release from human basophils passively sensitized with serum from latex-allergic individuals in a dose dependent manner. From a latex cDNA library, the cDNA coding for this protein was isolated and sequenced. The deduced amino acid sequence shows a high degree of homology to another acidic protein identified in kiwifruit (Actinidia deliciosa var. deliciosa). The sequence homology (47% sequence identity) between these two acidic proteins suggests a molecular explanation for the high frequency of fruit hypersensitivity in latex-allergic patients. C1 US FDA,DIV ALLERGEN PROD & PARASITOL,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NIMH,CLIN NEUROSCI BRANCH,UNIT MOL STRUCT,BETHESDA,MD 20892. RI Moussa, Luciana /M-2257-2013 NR 23 TC 73 Z9 76 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 OCT 11 PY 1996 VL 271 IS 41 BP 25389 EP 25393 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300049 PM 8810305 ER PT J AU Mason, MM Grasso, JA Gavrilova, O Reitman, M AF Mason, MM Grasso, JA Gavrilova, O Reitman, M TI Identification of functional elements of the chicken epsilon-globin promoter involved in stage-specific interaction with the beta/epsilon enhancer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOCUS-CONTROL REGION; HUMAN GAMMA-GLOBIN; CORRECT DEVELOPMENTAL EXPRESSION; KRUPPEL-LIKE FACTOR; BETA-GLOBIN; TRANSCRIPTION FACTOR; GENE-EXPRESSION; TRANSGENIC MICE; SELECTOR ELEMENT; ERYTHROID-CELLS AB Expression of the chicken globin genes is regulated in part by competition between the beta(A)-globin and epsilon-globin promoters for the enhancer found between the genes. To understand the determinants of the enhancer-promoter interaction in stage-specific regulation, the functional elements of the embryonic chicken epsilon-globin promoter were characterized. In vitro assays demonstrated that: (a) the TATA motif at -30 bound GATA-1, (b) Sp1 bound to an element centered at -54, and (c) both Sp1 and another factor, designated CACCC (which appears related to erythroid Kruppel-like factor, EKLF) bound in the -120 to -128 region. The functions of these motifs were tested using transient expression in embryonic erythroid cells, In the absence of the enhancer, promoter point mutants showed that the TATA, Sp1, and CCAAT motifs (but not the CACCC motif) contributed to promoter activity. In contrast, in the presence of the enhancer, all four motifs (including the CACCC motif) contributed to transcription. Developmental regulation of the enhancer activity was observed, with enhance ment decreasing sharply from 185-fold at 4 days (cells expressing epsilon-globin) to 16-fold at 10 days (when epsilon-globin is no longer expressed). Taken together, the data suggest that multiple transcription factors contribute to promoter-enhancer interaction and the developmental regulation of epsilon-globin expression, with EKLF-like factors having an especially important role. Regulation of stage specificity occurs at the level of enhancer/epsilon-promoter interaction, even in the absence of competition, and is not simply a property of the enhancer or promoter in isolation. C1 NIDDK,NIH,DIABET BRANCH,BETHESDA,MD 20892. NIDDK,NIH,MOL BIOL LAB,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH,DEPT ANAT,FARMINGTON,CT 06030. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 53 TC 5 Z9 5 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 OCT 11 PY 1996 VL 271 IS 41 BP 25459 EP 25467 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300060 PM 8810316 ER PT J AU Shtrom, SS Hall, ZW AF Shtrom, SS Hall, ZW TI Formation of a ligand-binding site for the acetylcholine receptor in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-DISULFIDE ISOMERASE; TRANSFECTED COS CELLS; ENDOPLASMIC-RETICULUM; ALPHA-SUBUNIT; DELTA-SUBUNIT; LINKED OLIGOSACCHARIDES; MONOCLONAL-ANTIBODIES; TORPEDO-CALIFORNICA; MOLECULAR CHAPERONE; SECRETORY PROTEINS AB Investigation of the mechanisms by which the subunits of ligand-gated ion channels fold and associate to form oligomers has been hampered by the lack of an in vitro system in which these reactions occur. We have established conditions in a rabbit reticulocyte translation system supplemented with canine pancreatic microsomes under which the alpha and delta subunits of the nicotinic acetylcholine receptor (AChR) fold and assemble to form a heterodimer with a cholinergic binding site comparable with that found in the intact AChR. Folding of the alpha subunit was followed by its ability to bind alpha-bungarotoxin. Folding efficiency was highly sensitive to changes in the redox potential of the translation medium and was favored by an oxidizing environment. Acquisition of the toxin binding conformation required N-Linked core glycosylation but not oligosaccharide trimming, suggesting that oligosaccharide-dependent interaction of chaperones with the alpha subunit is not essential for correct subunit folding. The conformationally mature alpha subunit specifically associated with the delta subunit but not the beta subunit to form a heterodimer with a high affinity ligand-binding site. These data demonstrate, for the first time, correct folding and assembly of the AChR subunits in an in vitro system. C1 NIMH,CELL BIOL LAB,SECT SYNAPT MECH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. NR 63 TC 17 Z9 17 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 OCT 11 PY 1996 VL 271 IS 41 BP 25506 EP 25514 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300066 PM 8810322 ER PT J AU Cox, GW Taylor, LS Willis, JD Melillo, G White, RL Anderson, SK Lin, JJ AF Cox, GW Taylor, LS Willis, JD Melillo, G White, RL Anderson, SK Lin, JJ TI Molecular cloning and characterization of a novel mouse macrophage gene that encodes a nuclear protein comprising polyglutamine repeats and interspersing histidines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUKARYOTIC MESSENGER-RNAS; BULBAR MUSCULAR-ATROPHY; 3' UNTRANSLATED REGION; LARGE-T-ANTIGEN; TRANSCRIPTIONAL ACTIVATION; NUCLEOTIDE-SEQUENCE; ANDROGEN RECEPTOR; TRIPLET REPEAT; DNA-BINDING; NEURODEGENERATIVE DISEASES AB Simple tandem repeats of the trinucleotide sequence CAG encode homopolymeric stretches of glutamine. Although polyglutamine has been identified in diverse proteins, it is present predominantly in transcription factors, We observed that oncogene-immortalized mouse macrophages express several genes that contain a CAG repeat motif. Therefore, we attempted to clone a novel gene that contains a CAG repeat and is associated with cytokine activation of macrophages. Screening of a mouse macrophage cDNA library with a probe comprising 12 consecutive CAG triplets identified at least one unique clone. The cDNA encodes a protein (named GRP-1 or glutamine repeat protein-1) with 171 amino acids, a calculated molecular mass of 21.6 kDa, and a predicted pI of 10.67. Greater than two-thirds of GRP-1 are only two amino acids, namely glutamine (50%) and histidine (18%). There are four polyglutamine motifs interspersed with histidine-rich regions. There is also a putative nuclear localization signal flanked by sites for possible serine phosphorylation. GRP-1 mRNA was expressed constitutively in some macrophage cell lines and B and T cell lines. Interferon-gamma or lipopolysaccharide augmented GRP-1 mRNA expression in the mouse macrophage cell line ANA-1. Western blot analyses using an antipeptide serum revealed that GRP-1 was localized in the nucleus of ANA-1 macrophages and transfected 3T3 fibroblasts. Overexpression of GRP-1 decreased Sp1-driven chloramphenicol acetyltransferase gene expression in transient cotransfection experiments. Because polyglutamine motifs can cause protein oligomerization and can function as transcriptional activation domains, we suggest that GRP-1 may be a transcription factor associated with interferon-gamma- or lipopolysaccharide-induced activation of macrophages. C1 SCI APPLICAT INT CORP,EXPT IMMUNOL LAB,FREDERICK,MD. SCI APPLICAT INT CORP,BIOCHEM PHYSIOL LAB,DIV BASIC SCI,FREDERICK,MD. SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,NATL INST HLTH,FREDERICK,MD 21702. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 NR 83 TC 10 Z9 10 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 OCT 11 PY 1996 VL 271 IS 41 BP 25515 EP 25523 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300067 PM 8810323 ER PT J AU Apasov, SG Smith, PT Jelonek, MT Margulies, DH Sitkovsky, MV AF Apasov, SG Smith, PT Jelonek, MT Margulies, DH Sitkovsky, MV TI Phosphorylation of extracellular domains of T-lymphocyte surface proteins - Constitutive serine and threonine phosphorylation of the T cell antigen receptor ectodomains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MHC CLASS-II; CRYSTAL-STRUCTURE; ATP; DEPHOSPHORYLATION; CYTOTOXICITY; SPECIFICITY; ACTIVATION; RESIDUES; SUBUNIT; LYSIS AB The extracellular accumulation of ATP after activation of T-lymphocytes, as well as the presence of ectoprotein kinases in these cells, led us to propose that T cell surface receptors could be regulated through the reversible phosphorylation of their extracellular domains (ectodomains). Here, in a model system, we used T cell transfectants which express T cell antigen receptor chains lacking intracellular and transmembrane protein domains and P-32(i) metabolic labeling of cells to definitively demonstrate phosphorylation of ectodomains of T cell surface proteins, We show that alpha beta TCR ectodomains were phosphorylated intracellularly and constitutively on serine and threonine residues and were then expressed on the T cell surface in phosphorylated form, TCR ectodomains also could be phosphorylated at the cell surface when extracellular [gamma-P-32]ATP or [gamma-P-32]GTP were used as phosphate donors with the same cells, Consensus phosphorylation sites for serine and threonine protein kinases were found to be strongly evolutionary conserved in both a and beta TCR chains constant regions, These results are consistent with the hypothesis, where T cell surface proteins which are phosphorylated intracellularly on their ectodomains, could subsequently be expressed at the cell surface and then be reversibly modified by ectoprotein phosphatase(s) and by ectokinase(s), Such modifications may change T cells cognate interactions by, e.g. affecting TCR-multimolecular complex formation and antigen binding affinity. It is suggested that alpha beta TCR ectodomain phosphorylation could serve as a potential mechanism for regulation of alpha beta TCR-mediated T-lymphocytes response. C1 NIAID,IMMUNOL LAB,NIH,BETHESDA,MD 20892. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 31 TC 30 Z9 30 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 OCT 11 PY 1996 VL 271 IS 41 BP 25677 EP 25683 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VL693 UT WOS:A1996VL69300089 PM 8810345 ER PT J AU Holmquist, CR KeverlineFrantz, KI Abraham, P Boja, JW Kuhar, MJ Carroll, FI AF Holmquist, CR KeverlineFrantz, KI Abraham, P Boja, JW Kuhar, MJ Carroll, FI TI 3 alpha-(4-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters: Novel ligands with high affinity and selectivity at the dopamine transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NOREPINEPHRINE UPTAKE SITES; H-3 NISOXETINE; BINDING; ANALOGS; RADIOLIGAND; SEROTONIN; COCAINE C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. FU NIDA NIH HHS [DA05477] NR 13 TC 36 Z9 36 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 11 PY 1996 VL 39 IS 21 BP 4139 EP 4141 DI 10.1021/jm960515u PG 3 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VM048 UT WOS:A1996VM04800002 PM 8863789 ER PT J AU Kim, YC Ji, XD Jacobson, KA AF Kim, YC Ji, XD Jacobson, KA TI Derivatives of the triazoloquinazoline adenosine antagonist (CGS15943) are selective for the human A(3) receptor subtype SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CENTRAL A(3)-ADENOSINE RECEPTORS; SPECIES-DIFFERENCES; RAT-BRAIN; BINDING; RADIOLIGAND; AFFINITY AB The adenosine antagonist 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943) binds to human A(3) receptors with high affinity (K-i = 14 nM), while it lacks affinity at rat A(3) receptors. Acylated derivatives of the 5-amino group and other modifications were prepared in an effort to provide A(3) subtype selectivity. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA ([H-3]-(R)-N-6-(phenylisopropyl)adenosine) and [H-3]CGS 21680 ([H-3]-2-[[4-(2-carboxy ethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl)adenosine), respectively. Affinity was determined at cloned human A(3) receptors using [I-125]AB-MECA (N-6-(4-amino-3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine). A series of straight chain alkyl amides demonstrated that the optimal chain length occurs with the 5-N-propionyl derivative, 3, which had a K-i value of 7.7 nM at human A(3) receptors, and was 40- and 14-fold selective vs rat A(1) and A(2A) receptors, respectively. The 5-N-benzoyl derivative, 10, displayed K-i values of 680 and 273 nM at rat A(1) and A(2A) receptors, respectively, and 3.0 nM at human A(3) receptors. A 5-N-phenylacetyl derivative, 12, was 470-fold selective for human A(3) VS rat Al receptors with a K-i value of 0.65 nM. A conjugate of Boc-gamma-aminobutyric acid was also prepared but was nonselective. Conversion of the 5-amino group of CGS15943 to an oxo function resulted in lower affinity but 15-fold selectivity for human A(3) receptors. C1 NIDDKD,LBC,MOL RECOGNIT SECT,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 29 TC 132 Z9 134 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 11 PY 1996 VL 39 IS 21 BP 4142 EP 4148 DI 10.1021/jm960482i PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VM048 UT WOS:A1996VM04800003 PM 8863790 ER PT J AU Anzini, M Cappelli, A Vomero, S Giorgi, G Langer, T Bruni, G Romeo, MR Basile, AS AF Anzini, M Cappelli, A Vomero, S Giorgi, G Langer, T Bruni, G Romeo, MR Basile, AS TI Molecular basis of peripheral vs central benzodiazepine receptor selectivity in a new class of peripheral benzodiazepine receptor ligands related to alpidem SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BINDING; RAT; AFFINITY; POTENT; FIELD AB Alpidem (1), the anxiolytic imidazopyridine, has nanomolar binding affinity for both the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor (PER). A novel class of PER ligands related to alpidem has been designed by comparing the interaction models of alpidem with PER and CBR. Several compounds in this class have shown high selectivity for PER vs CBR, and the selectivity has been discussed in terms of interaction models. The binding behavior of the three selected compounds was extensively studied by competition and saturation assays, and the results suggest that they are capable of recognizing two sites labeled by [H-3]PK11195. The molecular structure of one of the most active compounds (4e) has been determined by X-ray diffraction and compared with that of alpidem. Molecular modeling studies suggest that the bioactive conformation of 4e is Likely to be very similar to the conformation found in the crystal. C1 UNIV SIENA, DIPARTIMENTO FARMACOCHIM TECNOL, I-53100 SIENA, ITALY. UNIV SIENA, CTR INTERDIPARTIMENTALE ANAL & DETERMINAZ STRUTTU, I-53100 SIENA, ITALY. UNIV INNSBRUCK, INST PHARMACEUT CHEM, A-6020 INNSBRUCK, AUSTRIA. UNIV SIENA, IST FARMACOL, I-53100 SIENA, ITALY. NIDDKD, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. NR 27 TC 65 Z9 66 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 11 PY 1996 VL 39 IS 21 BP 4275 EP 4284 DI 10.1021/jm960325j PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VM048 UT WOS:A1996VM04800018 PM 8863805 ER PT J AU Shearer, GM Clerici, M AF Shearer, GM Clerici, M TI Rethinking AIDS and cancer SO SCIENCE LA English DT Letter C1 UNIV MILAN,I-20133 MILAN,ITALY. RP Shearer, GM (reprint author), NCI,EXPT IMMUNOL BRANCH,NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 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 OCT 11 PY 1996 VL 274 IS 5285 BP 163 EP 164 DI 10.1126/science.274.5285.163 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VM671 UT WOS:A1996VM67100005 PM 8927973 ER PT J AU Mittleman, BB Shearer, GM AF Mittleman, BB Shearer, GM TI Mother-to-infant transmission of HIV type 1: Role of major histocompatibility antigen differences SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; UMBILICAL-CORD BLOOD; CLASS-I; LEUKOCYTE ANTIGEN; INFECTION; CELLS; HLA; RESPONSES; MACAQUES; TWINS C1 NCI,NIH,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. NR 38 TC 13 Z9 13 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 OCT 10 PY 1996 VL 12 IS 15 BP 1397 EP 1400 DI 10.1089/aid.1996.12.1397 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VM095 UT WOS:A1996VM09500002 PM 8893047 ER PT J AU Saltarelli, MJ Hadziyannis, E Hart, CE Harrison, JV Felber, BK Spira, TJ Pavlakis, GN AF Saltarelli, MJ Hadziyannis, E Hart, CE Harrison, JV Felber, BK Spira, TJ Pavlakis, GN TI Analysis of human immunodeficiency virus type 1 mRNA splicing patterns during disease progression in peripheral blood mononuclear cells from infected individuals SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN T-CELLS; MESSENGER-RNA EXPRESSION; PRIMARY HIV-1 INFECTION; REV PROTEIN; HOMOSEXUAL MEN; GENE-EXPRESSION; NEF GENE; LYMPHADENOPATHY SYNDROME; ACCESSORY PROTEINS; ACTIVATION DOMAIN AB HIV-1 produces more than 20 mRNAs encoding the viral proteins, We have used a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) approach to determine HIV-1 transcriptional patterns during the course of viral infection in unstimulated peripheral blood mononuclear cells (PBMCs) from different patients, Several sets of PCR primers, used in parallel reactions, allowed the amplification and specific detection of almost all individual HIV-1 transcripts, We investigated the transcriptional profile in two individuals during primary acute and early chronic infection, In these individuals, HIV-1 mRNA expression was elevated at the first time points examined and declined over time, In addition, we performed a detailed study of HIV-1 expression in several individuals over a minimum of 7 years following seroconversion, We found that longterm asymptomatic individuals had undetectable or low levels of the three classes of HIV-1 transcripts (unspliced, singly spliced, and multiply spliced), Individuals who demonstrated disease progression showed either a general increase in the amount of expression of ail transcripts or elevated levels of unspliced transcripts in late-stage disease, The splicing pattern in each patient was conserved over the years and differed among the different individuals, No evidence of major changes in the splicing pattern was found during disease progression within the same individual, Thus, HIV-1 transcriptional patterns are viral strain specific rather than disease stage specific, These results indicate that high-level expression of any class of HIV-1 transcripts is associated with clinical progression, Our analysis also demonstrates the importance of using more than one set of primers to evaluate HIV-1 RNA expression, since virus in patient PBMCs showed sequence heterogeneity in conserved regions. C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, HUMAN RETROVIRUS SECT, FREDERICK, MD 21702 USA. CTR DIS CONTROL & PREVENT, RETROVIRUS DIS BRANCH, ATLANTA, GA 30333 USA. NCI, FREDERICK CANC RES & DEV CTR, HUMAN RETROVIRUS PATHOGENESIS GRP, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. CTR DIS CONTROL & PREVENT, IMMUNOL BRANCH, ATLANTA, GA 30333 USA. NR 72 TC 27 Z9 27 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT 10 PY 1996 VL 12 IS 15 BP 1443 EP 1456 DI 10.1089/aid.1996.12.1443 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VM095 UT WOS:A1996VM09500007 PM 8893052 ER PT J AU Brown, NL Paddock, SW Sattler, CA Cronmiller, C Thomas, BJ Carroll, SB AF Brown, NL Paddock, SW Sattler, CA Cronmiller, C Thomas, BJ Carroll, SB TI Daughterless is required for Drosophila photoreceptor cell determination, eye morphogenesis, and cell cycle progression SO DEVELOPMENTAL BIOLOGY LA English DT Article ID LOOP-HELIX PROTEINS; PERIPHERAL NERVOUS-SYSTEM; ACHAETE-SCUTE; PRONEURAL GENE; FURROW PROGRESSION; EARLY NEUROGENESIS; PATTERN-FORMATION; IMAGINAL DISKS; DNA-BINDING; HAIRY GENE AB Initiation of Drosophila peripheral nervous system (PNS) development requires the achaete-scute complex (AS-C) and the atonal (ato) genes. The AS-C and ato encode basic helix-loop-helix (bHLH) transcription factors that dimerize in vitro with another bHLH protein, daughterless (da). da has many functions during Drosophila embryonic development, as it is required for proper sex determination, oogenesis, and neurogenesis. Here, we examine the expression and function of da within the developing Drosophila eye. The use of a monoclonal antibody to the Da protein revealed that Da levels are modulated across the developing eye disc. Within the morphogenetic furrow (ME) and photoreceptor cell R8, there is a cell-by-cell correspondence between high levels of Da protein expression and Ato protein expression. Mosaic analysis of adult tissue demonstrates that da function is cell autonomous and required within R2, R3, R4, R5, and R8. Examination of gene expression in da- imaginal disc clones reveals that da regulates Ato expression in the MF, affects the progression of the MF, and is necessary for the reestablishment of the G(2) and M phases of the synchronized cell cycle posterior to the MF. (C) 1996 Academic Press, Inc. C1 UNIV WISCONSIN,HOWARD HUGHES MED INST,MADISON,WI 53706. UNIV WISCONSIN,MCARDLE LAB,MADISON,WI 53706. UNIV VIRGINIA,DEPT BIOL,CHARLOTTESVILLE,VA 22903. NCI,BIOCHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-07175] NR 50 TC 44 Z9 45 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 10 PY 1996 VL 179 IS 1 BP 65 EP 78 DI 10.1006/dbio.1996.0241 PG 14 WC Developmental Biology SC Developmental Biology GA VP357 UT WOS:A1996VP35700005 PM 8873754 ER PT J AU Richard, BL Nomizu, M Yamada, Y Kleinman, HK AF Richard, BL Nomizu, M Yamada, Y Kleinman, HK TI Identification of synthetic peptides derived from laminin alpha 1 and alpha 2 chains with cell type specificity for neurite outgrowth SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID NERVE GROWTH-FACTOR; CAPILLARY-LIKE STRUCTURES; HUMAN-ENDOTHELIAL CELLS; BASEMENT-MEMBRANE; A-CHAIN; TYROSINE PHOSPHORYLATION; BIOLOGICAL-ACTIVITY; GLOBULAR DOMAIN; NEURONAL CELLS; IKVAV SEQUENCE AB Laminin-1 is a potent promoter of neurite outgrowth. Here we find that the laminin-l cu chain contains peptide sequences that stimulate attachment and neurite outgrowth in some but not all neuronal cells. Testing of a series of overlapping peptides for biologic al activity with three laminin-1-responsive, neuronally derived cell lines resulted in the identification of peptide sequences, RKRLQVQLSIRT and KNRLTIELEVRT, from corresponding regions of the alpha 1 and alpha 2 (merosin) chain globular regions, respectively, that were active for attachment for all three cell lines and for neurite outgrowth with two of the cell lines. These data represent the identification of novel peptide sequences active with certain neuronal cells from the alpha 1 and alpha 2 chains of laminin. The peptides showed different attachment and neurite outgrowth activities depending on the cell type, suggesting cell type specificity in the response of the cells. (C) 1996 Academic Press, Inc. C1 NIDR,CELL BIOL SECT,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NIDR,MOL BIOL SECT,DEV BIOL LAB,NIH,BETHESDA,MD 20892. NR 41 TC 69 Z9 69 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 10 PY 1996 VL 228 IS 1 BP 98 EP 105 DI 10.1006/excr.1996.0304 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA VV058 UT WOS:A1996VV05800014 PM 8892976 ER PT J AU Miller, LH AF Miller, LH TI Malaria - Protective selective pressure SO NATURE LA English DT Editorial Material ID PLASMODIUM-FALCIPARUM; ALPHA-THALASSEMIA; NATURAL-SELECTION; BETA-THALASSEMIA; RESISTANCE; SUSCEPTIBILITY; MORBIDITY; AFRICA RP Miller, LH (reprint author), NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892, USA. NR 15 TC 13 Z9 14 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 10 PY 1996 VL 383 IS 6600 BP 480 EP 481 DI 10.1038/383480a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL755 UT WOS:A1996VL75500025 PM 8849717 ER PT J AU Konig, M Zimmer, AM Steiner, H Holmes, PV Crawley, JN Brownstein, MJ Zimmer, A AF Konig, M Zimmer, AM Steiner, H Holmes, PV Crawley, JN Brownstein, MJ Zimmer, A TI Pain responses, anxiety and aggression in mice deficient in pre-proenkephalin SO NATURE LA English DT Article ID INDUCED ANALGESIA; RATS; MORPHINE; BEHAVIOR; AMYGDALA; BRAIN; FEAR; EXPRESSION; MECHANISMS; SYSTEMS AB ENKEPHALINS are endogenous opioid peptides that are derived from a pre-proenkephalin precursor protein(1,2). They are thought to be vital in regulating many physiological functions, including pain perception and analgesia, responses to stress, aggression and dominance (3-5). Here we have used a genetic approach to study the role of the mammalian opioid system. We disrupted the preproenkephalin gene using homologous recombination in embryonic stem cells to generate enkephalin-deficient mice. Mutant enk(-/-) animals are healthy, fertile, and care for their offspring, but display significant behavioural abnormalities. Mice with the enk(-/-) genotype are more anxious and males display increased offensive aggressiveness. Mutant animals show marked differences from controls in supraspinal, but not in spinal, responses to painful stimuli. Unexpectedly, enk(-/-) mice exhibit normal stress-induced analgesia. Our results show that enkephalins modulate responses to painful stimuli. Thus, genetic factors may contribute significantly to the experience of pain. C1 NIMH,DEV BIOL UNIT,CELL BIOL LAB,BETHESDA,MD 20892. NIMH,NEUROANAT SECT,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NIMH,SECT BEHAV NEUROPHARMACOL,EXPT THERAPEUT BRANCH,BETHESDA,MD 20892. RI Brownstein, Michael/B-8609-2009; Zimmer, Andreas/B-8357-2009 NR 30 TC 306 Z9 306 U1 1 U2 14 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 10 PY 1996 VL 383 IS 6600 BP 535 EP 538 DI 10.1038/383535a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL755 UT WOS:A1996VL75500053 PM 8849726 ER PT J AU Hammer, SM Katzenstein, DA Hughes, MD Gundacker, H Schooley, RT Haubrich, RH Henry, WK Lederman, MM Phair, JP Niu, M Hirsch, MS Merigan, TC Blaschke, TF Simpson, D McLaren, C Rooney, J Salgo, M AF Hammer, SM Katzenstein, DA Hughes, MD Gundacker, H Schooley, RT Haubrich, RH Henry, WK Lederman, MM Phair, JP Niu, M Hirsch, MS Merigan, TC Blaschke, TF Simpson, D McLaren, C Rooney, J Salgo, M TI A trial comparing nucleoside monotherapy with combination therapy in HIV-infected adults with CD4 cell counts from 200 to 500 per cubic millimeter SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; PLACEBO-CONTROLLED TRIAL; CLINICAL-TRIALS; DOUBLE-BLIND; ZIDOVUDINE; EFFICACY; DIDANOSINE; PROTEASE; SAFETY; TYPE-1 AB Background This double-blind study evaluated treatment with either a single nucleoside or two nucleosides in adults infected with human immunodeficiency virus type 1 (HIV-1) whose CD4 cell counts were from 200 to 500 per cubic millimeter. Methods We randomly assigned 2467 HIV-1-infected patients (43 percent without prior antiretroviral treatment) to one of four daily regimens: 600 mg of zidovudine; 600 mg of zidovudine plus 400 mg of didanosine; 600 mg of zidovudine plus 2.25 mg of zalcitabine; or 400 mg of didanosine. The primary end point was a greater than or equal to 50 percent decline in the CD4 cell count, development of the acquired immunodeficiency syndrome (AIDS), or death. Results Progression to the primary end point was more frequent with zidovudine alone (32 percent) than with zidovudine plus didanosine (18 percent; relative hazard ratio, 0.50; P<0.001), zidovudine plus zalcitabine (20 percent; relative hazard ratio, 0.54; P<0.001), or didanosine alone (22 percent; relative hazard ratio, 0.61; P<0.001). The relative hazard ratios for progression to an AIDS-defining event or death were 0.64 (P=0.005) for zidovudine plus didanosine, as compared with zidovudine alone, 0.77 (P=0.085) for zidovudine plus zalcitabine, and 0.69 (P=0.019) for didanosine alone. The relative hazard ratios for death were 0.55 (P=0.008), 0.71 (P=0.10), and 0.51 (P=0.003), respectively. For zidovudine plus zalcitabine, the benefits were limited to those without previous treatment. Conclusions Treatment with zidovudine plus didanosine, zidovudine plus zalcitabine, or didanosine alone slows the progression of HIV disease and is superior to treatment with zidovudine alone. Antiretroviral therapy can improve survival in patients with 200 to 500 CD4 cells per cubic millimeter. C1 HARVARD UNIV,SCH MED,BOSTON,MA. STANFORD UNIV,STANFORD,CA 94305. HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. UNIV COLORADO,DENVER,CO 80202. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. NORTHWESTERN UNIV,CHICAGO,IL 60611. NIAID,DIV AIDS,BETHESDA,MD 20892. MT SINAI MED CTR,NEW YORK,NY 10029. BRISTOL MYERS SQUIBB CO,NEW YORK,NY 10154. HOFFMANN LA ROCHE INC,NUTLEY,NJ 07110. NR 47 TC 631 Z9 640 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 OCT 10 PY 1996 VL 335 IS 15 BP 1081 EP 1090 DI 10.1056/NEJM199610103351501 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA VN399 UT WOS:A1996VN39900001 PM 8813038 ER PT J AU Saravolatz, LD Winslow, DL Collins, G Hodges, JS Pettinelli, C Stein, DS Markowitz, N Reves, R Loveless, MO Crane, L Thompson, M Abrams, D AF Saravolatz, LD Winslow, DL Collins, G Hodges, JS Pettinelli, C Stein, DS Markowitz, N Reves, R Loveless, MO Crane, L Thompson, M Abrams, D TI Zidovudine alone or in combination with didanosine or zalcitabine in HIV-infected patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VIRUS-INFECTION; PHASE-I; THERAPY; RESISTANCE; TIME AB Background We compared two combinations of nucleosides with zidovudine alone in patients with advanced human immunodeficiency virus (HIV) infection. Methods A total of 1102 patients with the acquired immunodeficiency syndrome or fewer than 200 CD4 cells per cubic millimeter were randomly assigned to receive zidovudine alone or zidovudine combined with either didanosine or zalcitabine. Disease progression, survival, toxic effects, and the CD4 cell response were assessed. Results After a median follow-up of 35 months, disease progression or death occurred in 62 percent of the 363 patients assigned to zidovudine plus didanosine, 63 percent of the 367 assigned to zidovudine plus zalcitabine, and 66 percent of the 372 assigned to zidovudine alone (P=0.24). As compared with zidovudine therapy, treatment with zidovudine plus didanosine was associated with a relative risk of disease progression or death of 0.86 (95 percent confidence interval, 0.71 to 1.03), and treatment with zidovudine plus zalcitabine was associated with a relative risk of 0.92 (95 percent confidence interval, 0.76 to 1.10). Survival was similar in the three groups. In a subgroup analysis, combination therapy delayed disease progression or death in patients who had previously received zidovudine for 12 months or less. Therapy with zidovudine plus didanosine resulted in more gastrointestinal adverse effects, and treatment with zidovudine plus zalcitabine, more neuropathy. The mean increases in CD4 cell counts at two months were higher with combination therapy than with zidovudine alone. Conclusions In patients with advanced HIV infection, combination therapy with zidovudine and either didanosine or zalcitabine is not superior to zidovudine therapy alone. However, these combinations may be more effective than zidovudine monotherapy in patients with little or no previous zidovudine treatment. C1 ST JOHNS HOSP,DETROIT,MI. DELAWARE COMMUNITY PROGRAM CLIN RES AIDS,WILMINGTON,DE. UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN 55455. NIAID,DIV AIDS,NIH,BETHESDA,MD 20892. ALBANY MED COLL,ALBANY,NY 12208. HENRY FORD HOSP,DETROIT,MI 48202. DENVER COMMUNITY PROGRAM CLIN RES AIDS,DETROIT,MI. RES & EDUC GRP,PORTLAND,OR. WAYNE STATE UNIV,MED CTR,DETROIT,MI 48202. AIDS RES CONSORTIUM ATLANTA,ATLANTA,GA. COMMUNITY CONSORTIUM SAN FRANCISCO,SAN FRANCISCO,CA. FU NIAID NIH HHS [N01-AI-45231, N01-AI-04045, N01-AI-45227] NR 24 TC 131 Z9 131 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 OCT 10 PY 1996 VL 335 IS 15 BP 1099 EP 1106 DI 10.1056/NEJM199610103351503 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VN399 UT WOS:A1996VN39900003 PM 8813040 ER PT J AU Brechbiel, MW Gansow, OA Pippin, CG Rogers, RD Planalp, RP AF Brechbiel, MW Gansow, OA Pippin, CG Rogers, RD Planalp, RP TI Preparation of the novel chelating agent N-(2-aminoethyl)-trans-1,2-diaminocyclohexane-N,N',N''-pentaacetic acid (H(5)CyDTPA), a preorganized analogue of diethylenetriaminepentaacetic acid (H(5)DTPA), and the structures of Bi-III(CyDTPA)(2-) and Bi-III(H(2)DTPA) complexes SO INORGANIC CHEMISTRY LA English DT Article ID STEREOCHEMICAL ACTIVITY; AQUEOUS-SOLUTION; LONE PAIRS; ANTIBODY; RADIOIMMUNOTHERAPY; CRYSTAL; SIZE C1 NIH,CHEM SECT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NO ILLINOIS UNIV,DEPT CHEM,DE KALB,IL 60115. UNIV NEW HAMPSHIRE,DEPT CHEM,DURHAM,NH 03824. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 25 TC 41 Z9 42 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD OCT 9 PY 1996 VL 35 IS 21 BP 6343 EP & DI 10.1021/ic951326p PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA VL611 UT WOS:A1996VL61100053 ER PT J AU Wasilenko, WJ Palad, AJ Somers, KD Blackmore, PF Kohn, EC Rhim, JS Wright, GL Schellhammer, PF AF Wasilenko, WJ Palad, AJ Somers, KD Blackmore, PF Kohn, EC Rhim, JS Wright, GL Schellhammer, PF TI Effects of the calcium influx inhibitor carboxyamido-triazole on the proliferation and invasiveness of human prostate tumor cell lines SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; CANCER; GROWTH; TRANSFORMATION; DETERMINANTS; TRANSFECTION; L-651,582; PLASMID AB Aberrant cellular signaling is a central feature of malignant cells and a potential target for anti-cancer therapy. Carboxy-amido-triazole (CAI) is a calcium influx inhibitor that alters calcium-sensitive signal transduction pathways and suppresses the proliferative and metastatic potential of malignant cells. We have examined the effects of CAI on several tumor-associated parameters in human prostate cancer cell lines to evaluate the potential of CAI as a signal-transduction therapy agent for advanced-stage prostate cancer. Measuring anchorage-dependent cell growth, continuous application of CAI inhibited the growth of DU-145, PPC-1, PC3 and LNCaP tumor cells with 50% inhibitory concentrations ranging 10-30 mu M. Direct cell enumeration assays revealed that the growth-suppressing activity of CAI toward DU-145 cells was reversible, indicating a cytostatic effect of the drug on tumor cells. The drug also inhibited the proliferation of several immortalized human prostatic epithelial cell lines. The proliferation of HaCaT- and RHEK-1-immortalized keratinocyte cell lines was relatively insensitive to CAI. Additionally, invasion by DU-145, PC3 and PPC-1 cells through Matrigel in vitro was reduced approximately 60-70% by 10 mu M CAI. Other cellular effects of CAI included an attenuation of the elevation of intracellular free calcium in response to bombesin and carbachol in PC3 cells and a marked dose-dependent inhibition of prostate-specific antigen secretion in LNCaP cell cultures. (C) 1996 Wiley-Liss, Inc. C1 EASTERN VIRGINIA MED SCH,DEPT UROL,NORFOLK,VA 23507. EASTERN VIRGINIA MED SCH,DEPT PHARMACOL,NORFOLK,VA 23507. EASTERN VIRGINIA MED SCH,VIRGINIA PROSTATE CTR,NORFOLK,VA 23501. SENTARA CANC INST,NORFOLK,VA. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,MOL ONCOL LAB,FREDERICK,MD. RP Wasilenko, WJ (reprint author), EASTERN VIRGINIA MED SCH,DEPT MICROBIOL & IMMUNOL,NORFOLK,VA 23507, USA. NR 23 TC 46 Z9 49 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD OCT 9 PY 1996 VL 68 IS 2 BP 259 EP 264 DI 10.1002/(SICI)1097-0215(19961009)68:2<259::AID-IJC20>3.0.CO;2-4 PG 6 WC Oncology SC Oncology GA VQ112 UT WOS:A1996VQ11200020 PM 8900438 ER PT J AU Robbins, JB Schneerson, R Anderson, P Smith, DH AF Robbins, JB Schneerson, R Anderson, P Smith, DH TI Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b - Impact on public health and implications for other polysaccharide-based vaccines SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TETANUS TOXOID CONJUGATE; HEMOPHILUS-INFLUENZAE; CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSES; NEISSERIA-MENINGITIDIS; IMMUNOLOGICAL RESPONSES; MECKLENBURG COUNTY; MEMBRANE-PROTEIN; NORTH-CAROLINA; INFANTS AB The development of Haemophilus influenzae type b (Hib) conjugate vaccines has led to the virtual elimination of systemic infections caused by that patnogen, has provided insights into the pathogenesis of and immunity to other capsulated bacteria, and has contributed to the development of new vaccines, Meningitis, a common and serious infection of children, and other infections caused by Hib have been virtually eliminated in countries that have achieved widespread vaccination with Hib conjugates, including the United States, Canada, the United Kingdom, Iceland, Scandinavia, France, and Germany. Hib conjugates have also been shown to be highly effective in developing countries, The principles derived from the use of these vaccines, along with studies of other capsulated pathogens, should allow the rapid inclusion of new polysaccharide-based conjugates into routine vaccination schedules of infants, and should help to realize further reductions in serious systemic infectious diseases. C1 UNIV ROCHESTER,ROCHESTER,NY 14627. DAVID HAMILTON SMITH FDN,NEW YORK,NY. RP Robbins, JB (reprint author), NICHHD,DEV & MOL IMMUN LAB,NIH,BLDG 6,ROOM 424,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 62 TC 122 Z9 127 U1 0 U2 4 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 OCT 9 PY 1996 VL 276 IS 14 BP 1181 EP 1185 DI 10.1001/jama.276.14.1181 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA VL332 UT WOS:A1996VL33200032 PM 8827975 ER PT J AU Freyaldenhoven, TE Cadet, JL Ali, SF AF Freyaldenhoven, TE Cadet, JL Ali, SF TI The dopamine-depleting effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in CD-1 mice are gender-dependent SO BRAIN RESEARCH LA English DT Article DE MPTP; MPP(+); striatal dopamine; gender; CD-I mouse; neurotoxicity ID STRIATAL DOPAMINE; SUBSTANTIA-NIGRA; NEUROTOXIN 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYLPYRIDINIUM ION; CHRONIC PARKINSONISM; SPECIES SENSITIVITY; TRANSGENIC MICE; MOUSE-BRAIN; OXIDASE-B; MPTP AB 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP) is a selective dopaminergic neurotoxin affecting the nigrostriatal system in a variety of species including, rodents, nonhuman primates and humans. There exists, however, a great deal of variability in the sensitivity of different species to the effects of MPTP. The present study was designed to determine whether a significant difference in gender susceptibility to the toxin in CD-I mice might also exist. A dosing regiment of 30 mg/kg MPTP once a day for 3 days (90 mg/kg total dose) in 4-month-old male and female CD-I mice led to a significant depletion of striatal dopamine in both sexes. Two way ANOVA analysis of a time-course generated by measuring striatal dopamine at 4, 12 and 24 h after each dose of MPTP revealed that the initial dopamine reduction is significantly greater in male CD-1 mice (P < 0.001). Further, dopamine levels were reduced to a greater extent in male mice 5 days after the last dose (31% vs. 59% of control; P < 0.02). HPLC analysis using fluorescence detection revealed no difference in the striatal nor the cerebellar levels of MPP(+) between the two sexes, however, accumulation of larger amounts of MPP(+) was observed in the livers of the female mice. These findings suggest that, while female CD-1 mice are more resistant to the dopamine-depleting effects of MPTP, this gender difference is not due to decreased production or accumulation of striatal MPP(+). C1 NATL CTR TOXICOL RES,DIV NEUROTOXICOL,NEUROCHEM LAB,JEFFERSON,AR 72079. UNIV ARKANSAS MED SCI HOSP,DEPT BIOCHEM & MOL BIOL,LITTLE ROCK,AR 72205. NIDA,MOL NEUROPSYCHIAT SECT,NIH,ADDICT RES CTR,BALTIMORE,MD 21224. NR 44 TC 50 Z9 50 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 OCT 7 PY 1996 VL 735 IS 2 BP 232 EP 238 DI 10.1016/0006-8993(96)00598-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA VP317 UT WOS:A1996VP31700006 PM 8911661 ER PT J AU Nomura, T Inoue, K Creveling, CR Komatsu, F Ohta, N Chino, T Karasawa, N Nagatsu, I AF Nomura, T Inoue, K Creveling, CR Komatsu, F Ohta, N Chino, T Karasawa, N Nagatsu, I TI Immunocytochemical localization of aromatic L-amino acid decarboxylase and catechol-O-methyltransferase in blood vessel wall of the human dental pulp SO BRAIN RESEARCH LA English DT Article DE aromatic L-amino acid decarboxylase; catechol-O-methyltransferase; DOPA; dental pulp; human ID ENDOGENOUS L-DOPA; IMMUNOREACTIVE NEURONS; RATS; L-3,4-DIHYDROXYPHENYLALANINE; NEUROTRANSMITTER; NUCLEUS; RELEASE; REGION; MOUSE; BRAIN AB Relatively large amounts of DOPA as compared with the concentration of norepinephrine are found in human dental pulp. AADC and COMT are localized in blood vessel walls of human dental pulp. This localization suggests a functional relationship between COMT and AADC with regard to the metabolism of DOPA. C1 MATSUMOTO DENT COLL,INST DENT SCI,LAB ORAL STRUCT & FUNCT,NAGANO 39907,JAPAN. MATSUMOTO DENT COLL,DEPT PERIODONTOL,NAGANO 39907,JAPAN. NIDDK,OFF TECHNOL DEV,NIH,BETHESDA,MD 20892. MATSUMOTO DENT COLL,DEPT ORAL & MAXILLOFACIAL SURG 1,NAGANO 39907,JAPAN. FUJITA HLTH UNIV,SCH MED,DEPT ANAT,AICHI 47011,JAPAN. NR 22 TC 5 Z9 6 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 OCT 7 PY 1996 VL 735 IS 2 BP 314 EP 316 DI 10.1016/0006-8993(96)00790-1 PG 3 WC Neurosciences SC Neurosciences & Neurology GA VP317 UT WOS:A1996VP31700016 PM 8911671 ER PT J AU Fryer, RH Kaplan, DR Feinstein, SC Radeke, MJ Grayson, DR Kromer, LF AF Fryer, RH Kaplan, DR Feinstein, SC Radeke, MJ Grayson, DR Kromer, LF TI Developmental and mature expression of full-length and truncated TrkB receptors in the rat forebrain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE BDNF; neurotrophin; NT-4/5; telencephalon; trophic factor ID NERVE GROWTH-FACTOR; CILIARY NEUROTROPHIC FACTOR; TYROSINE KINASE RECEPTOR; MESSENGER-RNA EXPRESSION; MOTOR-NEURONS; VISUAL-CORTEX; PROTOONCOGENE PRODUCT; TARGETED DISRUPTION; HIPPOCAMPAL-NEURONS; MOLECULAR-CLONING AB The neurotrophins brain-derived neurotrophic factor (BDNF) and NT-4/5 exert their trophic effects on the nervous system via signaling through trkB receptors. These receptors occur as splice variants of the trkB gene that encodes a full-length receptor containing the signal transducing tyrosine kinase domain as well as truncated forms lacking this domain. Because the importance of the trkB isoforms for development and maturation of the nervous system is unknown, we have examined the expression of trkB receptor isoforms during development of the rat forebrain using 1) a sensitive ribonuclease protection assay to distinguish full-length and truncated trkB transcripts, 2) western blot analysis to characterize developmental changes in trkB proteins, and 3) immunohistochemistry to determine the cellular localization of trkB receptors. In the rat forebrain, adult mRNA levels for full-length trkB are reached by birth, whereas truncated trkB message does not peak until postnatal days 10-15. Western blot analysis indicates that full-length trkB protein is the major form during early development, whereas truncated trkB protein predominates in all forebrain regions of late postnatal and adult rats. These data also suggest that the glycosylation state of these receptors changes during postnatal maturation. TrkB immunoreactivity is present predominately within neurons, where it is localized to axons, cell soma, and dendrites. Strong dendritic immunostaining is particularly evident in certain neuronal populations, such as pyramidal neurons in the hippocampus and in layer V of the neocortex. The dendritic localization of trkB receptors supports the hypothesis that dendrites, as well as axons, are important sites for neurotrophin actions in the central nervous system. (C) 1996 Wiley-Liss, Inc. C1 GEORGETOWN UNIV,MED CTR,DEPT CELL BIOL,WASHINGTON,DC 20007. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT SECT,FREDERICK,MD 21702. UNIV CALIF SANTA BARBARA,NEUROSCI RES INST,SANTA BARBARA,CA 93106. UNIV CALIF SANTA BARBARA,DEPT MOL CELLULAR & DEV BIOL,SANTA BARBARA,CA 93106. MED COLL PENN & HAHNEMANN UNIV,DEPT PSYCHIAT,NEUROSCI RES CTR,PITTSBURGH,PA 15212. RI Grayson, Dennis/K-1447-2015 OI Grayson, Dennis/0000-0002-4544-5869 FU NEI NIH HHS [R01 EY10739]; NINDS NIH HHS [R01 NS31445, 5KO4 NS01647] NR 80 TC 208 Z9 210 U1 2 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 7 PY 1996 VL 374 IS 1 BP 21 EP 40 DI 10.1002/(SICI)1096-9861(19961007)374:1<21::AID-CNE2>3.0.CO;2-P PG 20 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VK709 UT WOS:A1996VK70900002 PM 8891944 ER PT J AU Straus, SE AF Straus, SE TI Chronic fatigue syndrome - ''Biopsychosocial approach'' may be difficult in practice SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material RP Straus, SE (reprint author), NIAID,CLIN INVEST LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 10 TC 14 Z9 14 U1 1 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD OCT 5 PY 1996 VL 313 IS 7061 BP 831 EP 832 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VL559 UT WOS:A1996VL55900003 PM 8870557 ER PT J AU Will, RG Zeidler, M Brown, P Harrington, M Lee, KH Kenney, KL AF Will, RG Zeidler, M Brown, P Harrington, M Lee, KH Kenney, KL TI Cerebrospinal-fluid test for new-variant Creutzfeldt-Jakob disease SO LANCET LA English DT Letter C1 NIH,CNS STUDIES LAB,BETHESDA,MD 20892. CALTECH,DIV BIOL,PASADENA,CA 91125. RP Will, RG (reprint author), WESTERN GEN HOSP,NATL CREUTZFELDT JAKOB DIS SURVEILLANCE UNIT,EDINBURGH EH4 2XU,MIDLOTHIAN,SCOTLAND. RI Crozier, Laura/C-2170-2011 NR 5 TC 54 Z9 54 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 OCT 5 PY 1996 VL 348 IS 9032 BP 955 EP 955 DI 10.1016/S0140-6736(96)24040-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VL097 UT WOS:A1996VL09700041 PM 8843819 ER PT J AU Merrill, RM AF Merrill, RM TI Changes in the use of radical prostatectomy for treating prostate cancer in the USA SO LANCET LA English DT Letter ID CARCINOMA RP Merrill, RM (reprint author), NCI,CANC CONTROL RES PROGRAM,APPL RES BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 10 Z9 10 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 OCT 5 PY 1996 VL 348 IS 9032 BP 963 EP 964 DI 10.1016/S0140-6736(05)65380-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VL097 UT WOS:A1996VL09700058 PM 8843836 ER PT J AU Umar, A Buermeyer, AB Simon, JA Thomas, DC Clark, AB Liskay, RM Kunkel, TA AF Umar, A Buermeyer, AB Simon, JA Thomas, DC Clark, AB Liskay, RM Kunkel, TA TI Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis SO CELL LA English DT Article ID CELL NUCLEAR ANTIGEN; NUCLEOTIDE EXCISION-REPAIR; PROTEIN-PROTEIN INTERACTIONS; SIMPLE REPETITIVE DNA; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; REPLICATION FORK; 2-HYBRID SYSTEM; SHUTTLE VECTORS; TUMOR-CELLS AB A two-hybrid system was used to screen yeast and human expression libraries for proteins that interact with mismatch repair proteins. PCNA was recovered from both libraries and shown in the case of yeast to interact with both MLH1 and MSH2. A yeast strain containing a mutation in the PCNA gene had a strongly elevated mutation rate in a dinucleotide repeat, and the rate was not further elevated in a strain also containing a mutation in MLH1. Mismatch repair activity was examined in human cell extracts using an assay that does not require DNA repair synthesis. Activity was inhibited by p21WAF1 or a p21 peptide, both of which bind to PCNA, and activity was restored to inhibited reactions by addition of PCNA. The data suggest a PCNA requirement in mismatch repair at a step preceding DNA resynthesis. The ability of PCNA to bind to MLH1 and MSH2 may reflect linkage between mismatch repair and replication and may be relevant to the roles of mismatch repair proteins in other DNA transactions. C1 OREGON HLTH SCI UNIV,DEPT MOL & MED GENET,PORTLAND,OR 97201. RP Umar, A (reprint author), NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709, USA. FU NIGMS NIH HHS [GM45413-02] NR 51 TC 451 Z9 463 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD OCT 4 PY 1996 VL 87 IS 1 BP 65 EP 73 DI 10.1016/S0092-8674(00)81323-9 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VL695 UT WOS:A1996VL69500009 PM 8858149 ER PT J AU Godde, JS Kass, SU Hirst, MC Wolffe, AP AF Godde, JS Kass, SU Hirst, MC Wolffe, AP TI Nucleosome assembly on methylated CGG triplet repeats in the Fragile X Mental Retardation gene 1 promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE; CPG SEQUENCES; DNA; TRANSCRIPTION; CHROMATIN; FMR-1; INSTABILITY; TEMPLATES; INVITRO; REGION AB Expansion and methylation of CGG repeat sequences is associated with Fragile X syndrome in humans. We have examined the consequences of CGG repeat expansion and methylation for nucleosome assembly and positioning on the Fragile X Mental Retardation gene 1 (FMR1) gene. Short unmethylated CGG repeats are not particularly favored in terms of affinity for the histone octamer or for positioning of the reconstituted nucleosome. However, upon methylation their affinity for the histone octamer increases and a highly positioned nucleosome assembles with the repeat sequences found adjacent to the nucleosomal dyad. Expansion of these CGG repeats abolishes the preferential nucleosome assembly due to methylation. Thus, the expansion and methylation of these triplet repeats can alter the functional organization of chromatin, which may contribute to alterations in the expression of the FMR1 gene and the disease phenotype. C1 NICHHD,LAB MOL EMBRYOL,NIH,BETHESDA,MD 20892. JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9D4,ENGLAND. NR 50 TC 70 Z9 71 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 OCT 4 PY 1996 VL 271 IS 40 BP 24325 EP 24328 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400004 PM 8798682 ER PT J AU Lee, HY Clair, T Mulvaney, PT Woodhouse, EC Aznavoorian, S Liotta, LA Stracke, ML AF Lee, HY Clair, T Mulvaney, PT Woodhouse, EC Aznavoorian, S Liotta, LA Stracke, ML TI Stimulation of tumor cell motility linked to phosphodiesterase catalytic site of autotaxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEMBRANE GLYCOPROTEIN PC-1; FIBROBLAST GROWTH-FACTOR; HUMAN-MELANOMA CELLS; AMINO-ACID-SEQUENCE; NUCLEOTIDE PYROPHOSPHATASE; CDNA CLONING; RAT-BRAIN; MOLECULAR-CLONING; SURFACE-ANTIGENS; IV COLLAGENASE AB A family of extracellular type I phosphodiesterases has recently been isolated by cDNA cloning, but a physiological function linked to the phosphodiesterase active site has remained unknown, We now present evidence that the phosphodiesterase catalytic site, (201)YMRPVYPTKTFPN(213), is essential for the motility stimulating activity of autotaxin (ATX), one member of the exophosphodiesterase family. Native ATX possesses phosphodiesterase activity at neutral and alkaline pH, binds ATP noncovalently, and undergoes threonine phosphorylation. Homogeneously purified recombinant ATX, based on the teratocarcinoma sequence, retains these same activities, A single amino acid in the phosphodiesterase catalytic site, Thr(210), is found to be necessary for motility stimulation, phosphodiesterase activity, and phosphorylation. Two mutant recombinant proteins, Ala(210)- and Asp(210)-ATX, lack motility stimulation and lack both enzymatic activities; Ser(210)-ATX possesses intermediate activities, Another mutation, with the adjacent lysine (Lys(209)) changed to Leu(209)-ATX, possesses normal motility stimulation with sustained phosphodiesterase activity but exhibits no detectable phosphorylation. This mutation eliminates the phosphorylation reaction and indicates that the dephosphorylated state is an active motility stimulating form of the ATX molecule. By demonstrating that the phosphodiesterase enzymatic site is linked to motility stimulation, these data reveal a novel role for this family of exo/ecto-enzymes and open up the possibility of extracellular enzymatic cascades as a regulatory mechanism for cellular motility. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 33 TC 75 Z9 75 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 4 PY 1996 VL 271 IS 40 BP 24408 EP 24412 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400019 PM 8798697 ER PT J AU Tamami, M Lindholm, PF Brady, JN AF Tamami, M Lindholm, PF Brady, JN TI The retinoblastoma gene product (Rb) induces binding of a conformationally inactive nuclear factor-kappa B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR-IIB; SUSCEPTIBILITY GENE; FACTOR E2F; LARGE-T; PROTEIN; ACTIVATION; TRANSACTIVATION; PHOSPHORYLATION; DOMAIN; P50 AB Nuclear factor-kappa B (NF-KB) regulates expression of several viral and cellular genes including the human immunodeficiency virus long terminal repeat, major histocompatibility complex class I, and interleukin 2R alpha cytokine genes. Here we report that the retinoblastoma gene product (Rb) stimulates binding of the NF-kappa B p50 homodimer. The addition of Rb protein to an in vitro gel shift binding assay stimulated p50 binding greater than 10-fold. Interestingly, by analyzing NF-kappa B-dependent transcription activity in vitro, we demonstrate that Rb suppresses transcriptional activity of p50. Chymotrypsin analysis suggests that Rb induces a conformational change in the NF-kappa B-DNA complex, resulting in binding of a transcriptionally inactive complex, Finally, we demonstrate by coimmunoprecipitation analysis that the Rb-p50 complex is present in Jurkat cell extracts. Our results suggest that Rb may play an important role in regulation of NF-kappa B transcriptional activity. C1 NCI,MOL VIROL LAB,BETHESDA,MD 20892. NR 39 TC 17 Z9 17 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 OCT 4 PY 1996 VL 271 IS 40 BP 24551 EP 24556 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400039 PM 8798717 ER PT J AU Dunsmore, SE Rubin, JS Kovacs, SO Chedid, M Parks, WC Welgus, HG AF Dunsmore, SE Rubin, JS Kovacs, SO Chedid, M Parks, WC Welgus, HG TI Mechanisms of hepatocyte growth factor stimulation of keratinocyte metalloproteinase production SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN SKIN FIBROBLASTS; C-MET RECEPTOR; HUMAN ALVEOLAR MACROPHAGES; FACTOR SCATTER FACTOR; EPITHELIAL-CELLS; MITOGENIC ACTIVITY; TYROSINE KINASE; INTERSTITIAL COLLAGENASE; PROTOONCOGENE PRODUCT; MOLECULAR-CLONING AB Matrix metalloproteinases participate in normal physiologic processes; however, their overproduction has been associated with connective tissue destruction in a variety of pathological states. Migrating basal keratinocytes transiently express collagenase-1 during normal cutaneous reepithelialization. However, the overexpression of both collagenase-1 and stromelysin-1 has been associated with the pathogenesis of chronic nonhealing ulcers, Aberrant expression of metalloproteinases in inflammation is mediated, at least in part, by soluble factors. Since hepatocyte growth factor/scatter factor (HGF/SF) has been reported to promote keratinocyte migration and proliferation, key events in wound repair, and since HGF/SF is produced by dermal fibroblasts and its c-Met receptor is expressed by basal keratinocytes in wounded skin, we have studied the effects of HGF/SF upon keratinocyte metalloproteinase expression. We have found that HGF/SF can stimulate keratinocyte collagenase-1 and stromelysin-1 production in a dose-dependent and matrix dependent manner, Expression of 92-kDa gelatinase was not affected by HGF/SF. We determined that HGF/SF regulation of collagenase-1 expression is transcriptionally mediated and requires tyrosine kinase and protein kinase C activaties. HGF/NK1, a naturally occurring, truncated form of HGF/SF, also stimulates collagenase-1 production, but much less efficiently than does the parent molecule, However, HGF/NK2, another HGF/SF splice variant, as well as heparin, potently inhibit HGF/SF-induced collagenase-1 synthesis, These results indicate that HGF/SF and its naturally occurring splice variants have diverse biological effects on keratinocytes and suggest an additional mechanism whereby HGF/SF may regulate keratinocyte function during wound repair. C1 WASHINGTON UNIV,SCH MED,DEPT MED DERMATOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63110. NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. FU NIAMS NIH HHS [5T32AR07284, AR35805] NR 65 TC 91 Z9 93 U1 0 U2 6 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 OCT 4 PY 1996 VL 271 IS 40 BP 24576 EP 24582 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400043 PM 8798721 ER PT J AU Flodby, P Barlow, C Kylefjord, H Ahrlund-Richter, L Xanthopoulos, KG AF Flodby, P Barlow, C Kylefjord, H Ahrlund-Richter, L Xanthopoulos, KG TI Increased hepatic cell proliferation and lung abnormalities in mice deficient in CCAAT/enhancer binding protein alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SERUM-ALBUMIN GENE; C/EBP-ALPHA; TRANSCRIPTION FACTORS; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; HEPATOCELLULAR-CARCINOMA; LEUCINE ZIPPER; STEM-CELLS; RAT-LIVER; C-MYC AB CCAAT/enhancer binding protein alpha (C/EBP alpha) is a transcription factor that has been implicated in the regulation of cell-specific gene expression mainly in hepatocytes and adipocytes but also in several other terminally differentiated cells. It has been previously demonstrated that the C/EBP alpha protein is functionally indispensable, as inactivation of the C/EBP alpha gene by homologous recombination in mice results in the death of animals homozygous for the mutation shortly after birth (Wang, N., Finegold, M. J., Bradley, A., Ou, C. N., Abdelsayed, S. V., Wilde, M. D., Taylor, L. R., Wilson, D. R., and Darlington, G. J. (1995) Science 269, 1108-1112). Here we show that C/EBP alpha-1-mice have defects in the control of hepatic growth and lung development. The liver architecture is disturbed, with acinar formation, in a pattern suggestive of either regenerating liver or pseudoglandular hepatocellular carcinoma. Pulmonary histology shows hyperproliferation of type II pneumocytes and disturbed alveolar architecture. At the molecular level, accumulation of glycogen and lipids in the liver and adipose tissues is impaired, and the mutant animals are severely hypoglycemic. Levels of c-myc and c-jun RNA are specifically induced by several fold in the livers of the C/EBP alpha -/- animals, indicating an active proliferative stage. Furthermore, immunohistologic detection with an antibody to proliferating cell nuclear antigen/cyclin shows a 5-10 times higher frequency of positively stained hepatocytes in C/EBP alpha -/- liver. These results suggest a critical role for C/EBP alpha in vivo for the acquisition of terminally differentiated functions in liver including the maintenance of physiologic energy homeostasis. C1 KAROLINSKA INST, NOVUM, DEPT BIOSCI, S-14157 HUDDINGE, SWEDEN. CGTB, NATL CTR HUMAN GENOME RES, NIH, BETHESDA, MD 20892 USA. RI Ahrlund-Richter, Lars/C-6226-2012 NR 60 TC 225 Z9 227 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 4 PY 1996 VL 271 IS 40 BP 24753 EP 24760 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400067 PM 8798745 ER PT J AU Minnick, DT Astatke, M Joyce, CM Kunkel, TA AF Minnick, DT Astatke, M Joyce, CM Kunkel, TA TI A thumb subdomain mutant of the large fragment of Escherichia coli DNA polymerase I with reduced DNA binding affinity, processivity, and frameshift fidelity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; CRYSTAL-STRUCTURE; KLENOW FRAGMENT; TEMPLATE-PRIMER; BETA; MISALIGNMENT; MECHANISM; IDENTIFICATION; TERMINATION; REPLICATION AB In Klenow fragment DNA polymerase, a flexible 50-amino acid subdomain at the tip of the thumb which includes two alpha helices has been suggested to interact with the duplex template-primer (Beese, L.S., Derbyshire, V. and Steitz, T.A. (1993) Science 260, 352-355). The present study investigates the properties of Klenow polymerase containing a 24-amino acid deletion (residues 590-613) that removes a portion of the tip of the thumb. The mutant polymerase has relatively normal dNTP binding and catalytic rate. However, its DNA binding affinity is reduced by more than 100-fold relative to the intact polymerase and its ability to conduct processive synthesis is also reduced, Although the mutant polymerase has relatively normal base substitution fidelity, it has strongly reduced frameshift fidelity, being especially error-prone for single nucleotide addition errors in homopolymeric runs. The addition error rateincreases as the length of the reiterated sequence increases, indicative of errors initiated by template-primer strand slippage. These observations suggest a role for the tip of the thumb of Klenow polymerase in determining DNA binding, processivity and frameshift fidelity, perhaps by tracking the minor groove of the duplex DNA. The results are discussed in light of remarkably similar observations with T7 DNA polymerase in the presence or absence of thioredoxin, an accessory subunit that affects these same properties. C1 NIEHS,MOL GENET LAB,NIH,RES TRIANGLE PK,NC 27709. YALE UNIV,DEPT MOL BIOPHYS & BIOCHEM,NEW HAVEN,CT 06520. FU NIGMS NIH HHS [GM-28550] NR 45 TC 64 Z9 64 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 4 PY 1996 VL 271 IS 40 BP 24954 EP 24961 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM674 UT WOS:A1996VM67400098 PM 8798775 ER PT J AU Coop, A Lewis, JW Rice, KC AF Coop, A Lewis, JW Rice, KC TI Direct and simple O-demethylation of thebaine to oripavine SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Letter C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. UNIV BRISTOL,BRISTOL BS8 1TS,AVON,ENGLAND. NR 13 TC 15 Z9 15 U1 1 U2 6 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 OCT 4 PY 1996 VL 61 IS 20 BP 6774 EP 6774 DI 10.1021/jo961473k PG 1 WC Chemistry, Organic SC Chemistry GA VL349 UT WOS:A1996VL34900011 ER PT J AU Jacobs, H Brennan, P Curlin, G Ginsberg, A Adams, M Fleischmann, R Fraser, C Venter, JC Shinnick, T Bishai, W Smith, H Stover, K Hatfull, G AF Jacobs, H Brennan, P Curlin, G Ginsberg, A Adams, M Fleischmann, R Fraser, C Venter, JC Shinnick, T Bishai, W Smith, H Stover, K Hatfull, G TI Comparative sequencing SO SCIENCE LA English DT Letter C1 COLORADO STATE UNIV,FT COLLINS,CO 80523. NIAID,BETHESDA,MD 20892. INST GENOM RES,ROCKVILLE,MD 20850. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30333. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. PATHOGENESIS CORP,SEATTLE,WA 98119. UNIV PITTSBURGH,PITTSBURGH,PA 15260. RP Jacobs, H (reprint author), ALBERT EINSTEIN COLL MED,HOWARD HUGHES MED INST,BRONX,NY 10461, USA. NR 0 TC 6 Z9 6 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 OCT 4 PY 1996 VL 274 IS 5284 BP 17 EP 18 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VK748 UT WOS:A1996VK74800002 ER PT J AU Chiang, C Ying, LTT Lee, E Young, KE Corden, JL Westphal, H Beachy, PA AF Chiang, C Ying, LTT Lee, E Young, KE Corden, JL Westphal, H Beachy, PA TI Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function SO NATURE LA English DT Article ID MOTOR-NEURON INDUCTION; TERMINAL CLEAVAGE PRODUCT; FLOOR PLATE; MOUSE EMBRYO; NOTOCHORD DEVELOPMENT; SCLEROTOME INDUCTION; POLARIZING ACTIVITY; XENOPUS-LAEVIS; EXPRESSION; DROSOPHILA AB Targeted gene disruption in the mouse shows that the Sonic hedgehog (Shh) gene plays a critical role in patterning of vertebrate embryonic tissues, including the brain and spinal cord, the axial skeleton and the limbs. Early defects are observed in the establishment or maintenance of midline structures, such as the notochord and the floorplate, and later defects include absence of distal limb structures, cyclopia, absence of ventral cell types within the neural tube, and absence of the spinal column and most of the ribs. Defects in all tissues extend beyond the normal sites of Shh transcription, confirming the proposed role of Shh proteins as an extracellular signal required for the tissue-organizing properties of several vertebrate patterning centres. C1 JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. RP Chiang, C (reprint author), NIH,LAB MAMMALIAN GENET & DEV,BETHESDA,MD 20892, USA. NR 51 TC 2051 Z9 2094 U1 23 U2 103 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 3 PY 1996 VL 383 IS 6599 BP 407 EP 413 DI 10.1038/383407a0 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL463 UT WOS:A1996VL46300053 PM 8837770 ER PT J AU Wang, XT Culotta, VC Klee, CB AF Wang, XT Culotta, VC Klee, CB TI Superoxide dismutase protects calcineurin from inactivation SO NATURE LA English DT Article ID PHOSPHOPROTEIN PHOSPHATASE; SACCHAROMYCES-CEREVISIAE; ACTIVE-SITE; KINASE; IDENTIFICATION; ADAPTATION; COMPLEXES; GENE AB CALCINEURIN is the only protein phosphatase known to be under the control of Ca2+ and calmodulin(1,2). It is targeted by immuno-suppressive drugs and has a critical role in T-cell activation(3,4). It is specifically inhibited by immunosuppressant immunophilin complexes, which enabled its function in regulating a wide range of cellular responses to Ca2+-mobilizing signals(5,6) to be identified. Calcineurin in situ is 10-20 times more active than in the purified form and is subject to a time- and Ca2+/calmodulin-dependent reversible inactivation that is facilitated by small, heat-stable molecules(7). Here we identify a factor that prevents the inactivation of calcineurin be vitro and in vivo as the enzyme superoxide dismutase, which indicates that inactivation may be the result of oxidative damage to the Fe-Zn active centre of calcineurin. The redox state of iron provides a mechanism to regulate calcineurin activity by desensitizing the enzyme and coupling Ca2+-dependent protein dephosphorylation to the redox state of the cell. The protection of calcineurin against inactivation by superoxide dismutase constitutes a new physiological role for this enzyme which enables the Ca2+-dependent regulation of cellular processes to be modulated by the redox potential. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DIV TOXICOL SCI,BALTIMORE,MD 21205. RP Wang, XT (reprint author), NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892, USA. NR 30 TC 207 Z9 215 U1 0 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD OCT 3 PY 1996 VL 383 IS 6599 BP 434 EP 437 DI 10.1038/383434a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VL463 UT WOS:A1996VL46300061 PM 8837775 ER PT J AU Lindpainter, K Larson, MG Wilson, AF AF Lindpainter, K Larson, MG Wilson, AF TI Absence of association or genetic linkage between the angiotensin-converting-enzyme gene and left ventricular mass - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID HYPERTROPHY C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01702. NATL CTR HUMAN GENOME RES,BALTIMORE,MD 21224. RP Lindpainter, K (reprint author), BRIGHAM & WOMENS HOSP,75 FRANCIS ST,BOSTON,MA 02115, USA. RI Wilson, Alexander/C-2320-2009 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 OCT 3 PY 1996 VL 335 IS 14 BP 1071 EP 1071 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA VL459 UT WOS:A1996VL45900026 ER PT J AU BirchenallRoberts, MC Kim, SJ Bertolette, DC Turley, JM Fu, T Bang, OS Kasper, JJ Yoo, YD Ruscetti, FW AF BirchenallRoberts, MC Kim, SJ Bertolette, DC Turley, JM Fu, T Bang, OS Kasper, JJ Yoo, YD Ruscetti, FW TI P120-v-Abl expression overcomes TGF-beta 1 negative regulation of c-myc transcription but not cell growth SO ONCOGENE LA English DT Article DE v-Abl; E2F-1; RB; c-myc; TGF-beta 1 ID RETINOBLASTOMA GENE-PRODUCT; MURINE LEUKEMIA-VIRUS; TUMOR-SUPPRESSOR PROTEIN; FACTOR-BETA; MOLECULAR-CLONING; TRANS-ACTIVATION; EPITHELIAL-CELLS; KINASE-ACTIVITY; E2F SITE; ABL AB Transformation of interleukin-3 dependent (IL-3) 32D-123 myeloid cells by p120-v-Abl produced the factor-independent 32D-abl cell Line, In 32D-abl cells, myc expression was found to be significantly higher than in the parental cells and was correlated with increased E2F-1 protein expression and DNA binding ability, Surprisingly, in 32D-abl cells, TGF-beta 1, a potent G(1)/S inhibitor of 32D-123 and 32D-abl cell growth, increased E2F transactivation as shown by increased c-myc promoter-CAT and GAL4-E2F-1 activity, In addition, TGF-beta 1 was also found to increase E2F-1 protein levels but had no effect on steady-state retinoblastoma (RE) protein levels or phosphorylation state, In the absence of TGF-beta 1, transient expression of RE in v-Abl expressing cells resulted in decreased c-myc transcription, inhibition of GAL4-E2F-1 driven transactivation and inhibition of cellular proliferation, RE and v-Abl were found to physically asssociate in vivo and in vitro via v-Abl's ATP binding region, In summary, these studies established that in myeloid cells: (1) v-Abl binds RE resulting in increased E2F-1-driven c-myc transcription, and (2) an alternative pathway exists for TGF-beta 1-mediated growth inhibition of v-Abl-transformed cells, in which increased rather than decreased E2F-mediated c-myc transcription is observed. C1 NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NCI, DIV BASIC SCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, LAB LEUKOCYTE BIOL, DIV BASIC SCI, FREDERICK, MD 21702 USA. RP BirchenallRoberts, MC (reprint author), SAIC FREDERICK, INTRAMURAL RES SUPPORT PROGRAM, FREDERICK, MD 21702 USA. NR 63 TC 2 Z9 2 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 3 PY 1996 VL 13 IS 7 BP 1499 EP 1509 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VL384 UT WOS:A1996VL38400015 PM 8875988 ER PT J AU Huang, K Sommers, CL Grinberg, A Kozak, CA Love, PE AF Huang, K Sommers, CL Grinberg, A Kozak, CA Love, PE TI Cloning and characterization of PTP-K1, a novel nonreceptor protein tyrosine phosphatase highly expressed in bone marrow SO ONCOGENE LA English DT Article DE protein tyrosine phosphatase; cDNA cloning; signal transduction ID NUCLEAR-LOCALIZATION; SIGNAL-TRANSDUCTION; SEQUENCE HOMOLOGY; RICH SEQUENCES; PROLINE-RICH; RECEPTOR; FAMILY; CDNA; IDENTIFICATION; DOMAINS AB A novel nonreceptor protein tyrosine phosphatase (PTP), PTP-K1, was identified using a consensus polymerase chain reaction-based approach, The full length cDNA encompasses an open reading frame of 1362 base pairs, predicting a protein of 453 amino acid residues with a molecular mass of 54 kDa, The PTP domain is located in the N-terminal portion of the molecule and shares similar to 50% amino acid identify with two other nonreceptor PTPs: PEP and PTP-PEST, PTP-K1 is preferentially expressed in mouse bone marrow with transcripts of 1.7 kb, 1.9 kb and 3.5 kb, The 1.7 kb transcript was also detected in kidney, lung and ovary, The PTP domain of PTP-K1 was expressed as a fusion protein in bacteria and had intrinsic PTP catalytic activity, Indirect immunofluorescence microscopy in COS-7 cells showed that PTP-K1 was localized to the cytoplasm, Ptp-k1 was mapped to mouse chromosome 1, and was closely linked to the interleukin-1 receptor gene, The high level expression of PTP-K1 mRNA in bone marrow suggests that PTP-K1 may be involved in signal transduction in growth and differentiation of hematopoietic cells. C1 NICHHD,NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NIAID,MOL MICROBIOL LAB,NIH,BETHESDA,MD 20892. NR 41 TC 15 Z9 16 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 3 PY 1996 VL 13 IS 7 BP 1567 EP 1573 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VL384 UT WOS:A1996VL38400024 PM 8875997 ER PT J AU Proud, VK Mussell, HG Kaler, SG Young, DW Percy, AK AF Proud, VK Mussell, HG Kaler, SG Young, DW Percy, AK TI Distinctive Menkes disease variant with occipital horns: Delineation of natural history and clinical phenotype SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE Menkes disease; occipital horn syndrome; copper transport; cutis laxa; pili torti; dopamine-beta-hydroxylase; plasma catechol levels ID COPPER-TRANSPORTING ATPASE; KINKY HAIR DISEASE; CANDIDATE GENE; MUTATIONS; MR; ENCODES; IX AB To delineate further the clinical spectrum of Menkes disease, an X-linked recessive disorder of copper transport, we studied 4 related males, ranging in age from 4-38 years, with a unique phenotype that combines manifestations of classical and mild Menkes disease and occipital horn syndrome (OHS). The propositus, an 18-year-old man, was evaluated following an intracerebral hemorrhage at age 15 years and was noted to have marked hypotonia, motor delay with mental retardation, bladder diverticula, failure to thrive, and diarrhea from infancy; seizures from age 3 years; and abnormal hair (pili torti) and face, cutis laxa, and multiple joint dislocations. Radiographic abnormalities included occipital exostoses, tortuous cerebral blood vessels with multiple branch occlusions, and hammer-shaped clavicles. Biochemical studies demonstrated reduced copper and ceruloplasmin levels in serum, and abnormal plasma catecholamine ratios. We reported previously the molecular defect in this family, a splice-site mutation that predicts formation of approximately 20% of the normal Menkes gene product [Kaler et al., 1994: Nat Genet 18:195-202]. Here, we detail the clinical course and physical features and radiographic findings in these 4 individuals, and compare their phenotype with classical and mild Menkes and OHS. Unusual Menkes disease variants such as this may escape recognition due to anomalies that appear inconsistent with the diagnosis, particularly prolonged survival and later onset of seizures. Males with mental retardation and connective tissue abnormalities should be evaluated for biochemical evidence of defective copper transport. (C) 1996 Wiley-Liss, Inc. C1 CHILDRENS HOSP ALABAMA,DEPT PEDIAT IMAGING,BIRMINGHAM,AL 35233. UNIV ALABAMA,SCH MED,DEPT PEDIAT,DIV NEUROL,LAB MED GENET,BIRMINGHAM,AL. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT MED GENET,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT PEDIAT,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,WASHINGTON,DC. NR 27 TC 31 Z9 31 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 OCT 2 PY 1996 VL 65 IS 1 BP 44 EP 51 DI 10.1002/(SICI)1096-8628(19961002)65:1<44::AID-AJMG7>3.0.CO;2-Y PG 8 WC Genetics & Heredity SC Genetics & Heredity GA VK562 UT WOS:A1996VK56200008 PM 8914740 ER PT J AU Biesecker, LG Abbott, M Allen, J Clericuzio, C Feuillan, P Graham, JM Hall, T Kang, S Olney, AH Lefton, D Neri, G Peters, K Verloes, A AF Biesecker, LG Abbott, M Allen, J Clericuzio, C Feuillan, P Graham, JM Hall, T Kang, S Olney, AH Lefton, D Neri, G Peters, K Verloes, A TI Report from the workshop on Pallister-Hall syndrome and related phenotypes. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material ID CONGENITAL HYPOTHALAMIC HAMARTOBLASTOMA; AUTOSOMAL-DOMINANT TRANSMISSION; SYNDROME TYPE-VI; IMPERFORATE ANUS; HYPOPITUITARISM; HAMARTOMA; DELINEATION; ANOMALIES; ABNORMALITIES; INCLUDE C1 JOHNS HOPKINS UNIV,DEPT MED,BALTIMORE,MD. NYU MED CTR,NEW YORK,NY 10016. UNIV NEW MEXICO,MED CTR,ALBUQUERQUE,NM. NICHHD,NIH,BETHESDA,MD 20892. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. UNIV BRITISH COLUMBIA,VANCOUVER,BC V5Z 1M9,CANADA. UNIV NEBRASKA,SCH MED,OMAHA,NE 68198. UNIV CATTOLICA ROME,IST GENET MED,ROME,ITALY. SART TILMAN UNIV HOSP,CTR HUMAN GENET,LIEGE,BELGIUM. RP Biesecker, LG (reprint author), NATL CTR HUMAN GENOME RES,NIH,49 CONVENT DR,ROOM 4A80,BETHESDA,MD 20892, USA. OI , Alain/0000-0003-4819-0264 NR 37 TC 42 Z9 44 U1 0 U2 2 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 OCT 2 PY 1996 VL 65 IS 1 BP 76 EP 81 DI 10.1002/(SICI)1096-8628(19961002)65:1<76::AID-AJMG12>3.0.CO;2-O PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VK562 UT WOS:A1996VK56200013 PM 8914745 ER PT J AU Stein, U Walther, W Shoemaker, RH AF Stein, U Walther, W Shoemaker, RH TI Reversal of multidrug resistance by transduction of cytokine genes into human colon carcinoma cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TUMOR-NECROSIS-FACTOR; BIOLOGICAL RESPONSE MODIFIERS; P-GLYCOPROTEIN EXPRESSION; FACTOR-ALPHA; MDR1 EXPRESSION; CANCER; LINES; INTERLEUKIN-2; DOXORUBICIN; INTERFERON AB Background: Multidrug resistance can be a major obstacle to successful cancer chemotherapy and is often associated with increased expression of the mdr1 (also known as P-glycoprotein) gene, Some of the proteins produced by the body's immune system, i.e., cytokines such as tumor necrosis factor-alpha (TNF) and interleukin 2 (IL-2), have been shown to modulate multidrug resistance, However, cytokines administered by the conventional intravenous method can cause severe side effects. Transduction of cytokine genes into tumor cells constitutes an alternative approach for production and release of the cytokine proteins in the local tumor microenvironment, which may reduce problems of toxicity associated with systemic administration, Purpose: In this study, we investigated the therapeutic potential of a combination of gene therapy and chemotherapy on the basis of cytokine-mediated modulation of multidrug resistance in human colon carcinoma cells, Methods: Human colon carcinoma cell lines HCT15 and HCT116 were transduced with TNF or IL-2 carrying murine leukemia virus (MLV)-based retroviral vectors. Tumor cell clones were analyzed for cytokine expression by reverse transcriptase-polymerase chain reaction (RT-PCR) and by cytokine-specific enzyme-linked immunosorbent assays (TNF-ELISA or IL-2-ELISA), Expression of mdr1 messenger RNA (mRNA) was investigated using RT-PCR, and P-glycoprotein (Pgp) expression was determined by immunoflow cytometry With the monoclonal antibodies MRK16 and C219. The function of Pgp was analyzed by measuring accumulation of the fluorescent drug doxorubicin by flow cytometry. The XTT-(i.e., [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)]-5-[(phenylamino)carbonyl-2H-tetrazolium hydroxide]-colorimetric cytotoxicity assay was used to determine chemosensitivity of cytokine gene-transfected tumor cells to doxorubicin and vincristine. Statistical significance was determined by the nonparametric Mann-Whitney rank sum test for the flow cytometry experiments (Pgp detection as well as drug uptake assays) and the parametric Student's t test for the chemosensitivity assay (XTT cytotoxicity assay), All P values reported were derived from two-sided statistical tests, Results: Transduction and expression of human TNF and IL-2 in HCT15 and HCT116 human colon carcinoma cell lines were found to reverse multidrug resistance, Both TNF and IL-2 secretion reduced mdr1 expression on the mRNA and Pgp levels (P<.0243). This result was associated with enhancement of doxorubicin accumulation within the cells (P<.0001), The cytokine-mediated effects on mdr1 expression resulted in increased chemosensitivity of the transduced cells to doxorubicin and vincristine (P<.0460). Conclusions and implications: We show that endogenous expression of cytokine genes in tumor cells and after transduction secretion of the related proteins, such as TNF and IL-2, can modulate multidrug resistance in vitro. This modulation enhances the susceptibility of the cells to the cytotoxic drugs, our findings suggest the potential value of combined treatment of resistant tumors with gene therapy and chemotherapy. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT DIAG & CTR,DEV THERAPEUT PROGRAM,FREDERICK,MD. RP Stein, U (reprint author), MAX DELBRUCK CTR MOL MED,ROBERT ROSSLE STR 10,D-13122 BERLIN,GERMANY. NR 43 TC 67 Z9 72 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 OCT 2 PY 1996 VL 88 IS 19 BP 1383 EP 1392 DI 10.1093/jnci/88.19.1383 PG 10 WC Oncology SC Oncology GA VJ725 UT WOS:A1996VJ72500014 PM 8827016 ER PT J AU Ding, I Huang, KD Snyder, ML Cook, J Zhang, L Wersto, N Okunieff, P AF Ding, I Huang, KD Snyder, ML Cook, J Zhang, L Wersto, N Okunieff, P TI Tumor growth and tumor radiosensitivity in mice given myeloprotective doses of fibroblast growth factors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ENDOTHELIAL-CELLS; IN-VIVO; INTERLEUKIN-1; IRRADIATION; PROTECTION AB Background: Radiation at doses high enough to cure cancer also frequently destroys normal tissue. Development of agents that protect normal tissue without also protecting diseased tissue has been difficult. In vivo radioprotection of bone marrow by acidic and basic fibroblast growth factors (FGF(1) and FGF(2), respectively) has recently been demonstrated after whole-body irradiation of C3W/HeN mice. Purpose: Our purpose was to determine whether myeloprotective doses of those growth factors also protect malignant tumors. Methods: First, we investigated the effects of exogenous FGF(1) or FGF(2) (FGF(1/2)) administration (treatment group receiving two intravenous injections of 3 mu g FGF(1/2) per mouse 24 hours and 4 hours before local irradiation of right hind leg and control group receiving two intravenous injections of 0.1 mL of saline) on growth and radiosensitivity of three transplantable murine tumors (one squamous cell carcinoma [SCC-VII] and two sarcomas [KHT and Rif-1]), all of which were grown in C3H/HeN mice. We then evaluated the effect of FGF(1/2) on tumor cell proliferation, cell cycle distribution, and pulmonary metastatic frequency in the mice. Specifically, survival studies were performed in mice treated with 0, 6, 6.5, 7.5, 8.5, 9, or 10 Gy whole-body irradiation with or without FGF(2) (n = 250). Rif-1 (n = 40), KHT (n = 40), and SCC-VII (n = 40) tumors were implanted in the hind leg of mice, and mice were treated with FGF(2) or saline when their tumor-bearing thighs were 9 mm in diameter. In separate experiments (treatment group receiving two injections of 3 mu g each of FGF(2) [6 mu g total] either intravenously or intratumorally 24 hours and 4 hours before local tumor irradiation and control group receiving 0.1 mL saline), tumor growth was followed, and mice were killed to count lung metastases and measure tumor proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine labeling at various times thereafter (three to eight mice per group). Tumor growth curves of untreated and irradiated tumors were determined with and without intravenous or intratumoral FGF(1/2) in SCC-VII tumors (n = 120). Radiation doses to the tumor-bearing leg were 15 and 30 Gy for SCC-VII, 30 Gy for Rif-1, and 15 Gy for KHT. From each experiment, the mean (+/-1 standard error) was calculated from data obtained from three to 20 mice. Statistical tests used included two-tailed Student's t test, the chi-squared test, and Fisher's exact test. All P values represent two-tailed tests of statistical significance. Results: There was no statistically significant difference in tumor growth rate between FGF(2)-treated and saline-treated mice when FGF(2) was administered intravenously at doses and schedules found to be optimally myeloprotective in whole-body irradiation experiments. Intravenous administration of FGF(2) did not induce lung metastases, and it did not augment the S-phase fraction of tumor cells. Likewise, there was no evidence of enhanced cell proliferation as measured by PCNA-labeling index. Intratumoral injection of FGF(1/2) did increase the size of SCC-VII tumors (P<.05 [Student's t test] at 3 days after treatment); however, the radiation response after intratumoral injection of growth factor was not compromised. Conclusion: Low intravenous doses of FGF(1) or FGF(2) appear to protect bone marrow from the toxic effects of radiation without increasing the rates of tumor growth or metastases or decreasing the radiosensitivity of tumors. C1 NCI,RADIAT ONCOL BRANCH,DIV CLIN SCI,NIH,BETHESDA,MD 20892. NR 22 TC 16 Z9 16 U1 1 U2 1 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 OCT 2 PY 1996 VL 88 IS 19 BP 1399 EP 1404 DI 10.1093/jnci/88.19.1399 PG 6 WC Oncology SC Oncology GA VJ725 UT WOS:A1996VJ72500016 PM 8827018 ER PT J AU Parker, DA Levin, BM Harford, TC AF Parker, DA Levin, BM Harford, TC TI Effects of early drinking and an antisocial orientation on the alcohol use of young Russians SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE early drinking; antisocial attitudes; youth ID ADOLESCENT PROBLEM DRINKING; BEHAVIOR; HISTORY AB Drawing upon data from the Survey of Deviant Behavior Among Youth in the Moscow Region of Russia, this paper examines the effects of early drinking behavior and an antisocial orientation on the use of alcohol by young Russians. Using available data from the U.S. National Household Survey of Drug Abuse, the use of alcohol and the effects of early drinking among youth in the Moscow Region and the United States are compared. The analysis of the data from the two surveys indicates that a greater proportion of Russian youth began drinking by the age of 12 but that early drinking is associated with subsequent alcohol use among both Russian and American youth. Although there are no data on an antisocial orientation from the U.S. survey, there are such data from the Russian survey and an analysis of this data indicates that the greatest alcohol use is found among young Russians who began drinking by the age of 12 and who have an antisocial orientation. C1 RUSSIAN ACAD SCI,INST SOCIOL,MOSCOW V71,RUSSIA. NIAAA,ROCKVILLE,MD 20852. RP Parker, DA (reprint author), CALIF STATE UNIV LONG BEACH,DEPT SOCIOL,1250 BELLFLOWER BLVD,LONG BEACH,CA 90840, USA. FU NIAAA NIH HHS [N01-AA-5-1001] NR 22 TC 11 Z9 11 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 1996 VL 20 IS 7 BP 1179 EP 1183 DI 10.1111/j.1530-0277.1996.tb01108.x PG 5 WC Substance Abuse SC Substance Abuse GA VN002 UT WOS:A1996VN00200007 PM 8904967 ER PT J AU Ishii, M Jones, M Shiota, T Heinrich, R Yamada, I Sinclair, B Yoganathan, AP Sahn, DJ AF Ishii, M Jones, M Shiota, T Heinrich, R Yamada, I Sinclair, B Yoganathan, AP Sahn, DJ TI Evaluation of eccentric aortic regurgitation by color Doppler jet and color Doppler-imaged vena contracta measurements: An animal study of quantified aortic regurgitation SO AMERICAN HEART JOURNAL LA English DT Article ID MITRAL REGURGITATION; VALVULAR REGURGITATION; QUANTITATIVE ASSESSMENT; INVITRO; VARIABILITY; SEVERITY; ECHOCARDIOGRAPHY; CONSERVATION; LIMITATIONS; SYSTEM AB To evaluate the utility of measurements of the color Doppler jet area, jet length, and width of the color Doppler-imaged vena contracta (the smallest flow diameter in any part of the flow acceleration field) as methods for quantifying aortic regurgitation (AR), eight sheep with surgically induced AR were studied. AR was quantified as peak and mean regurgitant flow rates, regurgitant stroke volumes, and regurgitant fractions as determined with pulmonary acid aortic electromagnetic flow probes and flowmeters balanced against each other. Simple linear regression analysis between the maximal color jet areas, jet length, and flowmeter data showed only moderately good correlation (jet area: 0.42 less than or equal to r less than or equal to 0.57, SEE = 2.85 cm(2); jet length: 0.42 less than or equal to r less than or equal to 0.59, SEE = 1.23 cm). In contrast, the width of color Doppler-imaged vena contracta was a better indicator of the severity of AR on the basis of the electromagnetic flowmeter methods (0.73 less than or equal to r less than or equal to 0.90, SEE = 0.15 cm). Therefore the color Doppler jet length and jet area methods have limited use for determining AR, whereas the width of the color Doppler-imaged vena contracta can be used for quantifying the severity of AR. C1 NHLBI,LAMS,NIH,BETHESDA,MD 20892. OREGON HLTH SCI UNIV,PORTLAND,OR 97201. GEORGIA INST TECHNOL,ATLANTA,GA 30332. FU NHLBI NIH HHS [HL 43287] NR 30 TC 13 Z9 13 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 1996 VL 132 IS 4 BP 796 EP 804 DI 10.1016/S0002-8703(96)90314-2 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA VK193 UT WOS:A1996VK19300014 PM 8831369 ER PT J AU Fee, E AF Fee, E TI Sexual knowledge, sexual science: The history of attitudes to sexuality - Porter,R, Teich,M SO AMERICAN HISTORICAL REVIEW LA English DT Book Review RP Fee, E (reprint author), NATL LIB MED,BETHESDA,MD 20894, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER HISTORICAL REVIEW PI WASHINGTON PA 400 A ST SE, WASHINGTON, DC 20003 SN 0002-8762 J9 AM HIST REV JI Am. Hist. Rev. PD OCT PY 1996 VL 101 IS 4 BP 1178 EP 1179 DI 10.2307/2169659 PG 2 WC History SC History GA VP497 UT WOS:A1996VP49700013 ER PT J AU Putnam, FW AF Putnam, FW TI Handbook for the assessment of dissociation: A clinical guide - Steinberg,M SO AMERICAN JOURNAL OF CLINICAL HYPNOSIS LA English DT Book Review RP Putnam, FW (reprint author), NIH,UNIT DEV TRAUMATOL,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CLIN HYPNOSIS PI DES PLAINES PA 2200 EAST DEVON AVE SUITE 291, DES PLAINES, IL 60018 SN 0002-9157 J9 AM J CLIN HYPN JI Am. J. Clin. Hypn. PD OCT PY 1996 VL 39 IS 2 BP 154 EP 155 PG 2 WC Psychology, Clinical SC Psychology GA VP523 UT WOS:A1996VP52300009 ER PT J AU Forman, MR Beecher, GR Muesing, R Lanza, E Olson, B Campbell, WS McAdam, P Raymond, E Schulman, JD Graubard, BI AF Forman, MR Beecher, GR Muesing, R Lanza, E Olson, B Campbell, WS McAdam, P Raymond, E Schulman, JD Graubard, BI TI The fluctuation of plasma carotenoid concentrations by phase of the menstrual cycle: A controlled diet study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE menstrual cycle; carotenoids; lipoproteins; controlled diet ID INDUCED NEOPLASTIC TRANSFORMATION; BREAST-CANCER; VITAMIN-A; LIPOPROTEINS; SEPARATION; RETINOIDS AB This is the first controlled diet study to examine the fluctuation of plasma carotenoids, lipoproteins, and serum hormone concentrations by phase of the menstrual cycle. Nonsmoking, premenopausal women (n = 12) with confirmed ovulatory cycles were given a standard diet with 10 mg total carotenoids/d for two cycles under isoenergetic conditions. Blood was drawn for simultaneous measurement of carotenoids, lipoproteins, and hormones on menses days 1-2, 4-6, 11 through 1 d after the luteinizing hormone surge, and 7-8 d after the surge, representing the menses, early and late follicular, and midluteal phases, respectively. Regression modeling with adjustment for plasma cholesterol concentrations was used to compare mean individual and total plasma carotenoid concentrations by phase of the cycle. Plasma carotenoid concentrations were at their lowest at menses and significantly higher thereafter, except for a-carotene. Compared with plasma concentrations at menses, p-carotene peaked (increased by 9%, P = 0.01) in the late follicular phase. Plasma lutein/zeaxanthin and anhydrolutein concentrations were higher by 8-11% (P less than or equal to 0.006) and by 15-31% (P less than or equal to 0.02), respectively, during the last three phases. Plasma lycopene and phytofluene concentrations peaked (increased by 12%, P = 0.004; and by 21%, P = 0.006, respectively) at the midluteal phase. This cyclic fluctuation may affect the estimation of the plasma carotenoid-disease relation in studies of premenopausal women. C1 USDA ARS,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,LIPID RES CLIN LAB,WASHINGTON,DC 20037. NICHHD,BETHESDA,MD 20892. GENET & IN VITRO FERTILIZAT INST,FAIRFAX,VA. RP Forman, MR (reprint author), NCI,DIV CANC PREVENT & CONTROL,CPRP,CPSB,EXECUT PLAZA N,SUITE 211,6130 EXECUT BLVD MSC 732,BETHESDA,MD 20892, USA. NR 32 TC 34 Z9 34 U1 0 U2 2 PU AMER SOC CLIN NUTRITION INC 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 OCT PY 1996 VL 64 IS 4 BP 559 EP 565 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VK569 UT WOS:A1996VK56900005 PM 8839500 ER PT J AU Granter, SR Barnhill, RL Duray, PH AF Granter, SR Barnhill, RL Duray, PH TI Borrelial fasciitis: Diffuse fasciitis and peripheral eosinophilia associated with Borrelia infection SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE Borrelia burgdorferi; Fasciitis; Eosinophilia; lyme disease; borrelial fasciitis; eosinophilic fascitis ID ERYTHEMA CHRONICUM MIGRANS; POLYMERASE CHAIN-REACTION; SCLEROSUS-ET-ATROPHICUS; LYME-DISEASE; BURGDORFERI INFECTION; SPIROCHETAL ORIGIN; SHULMAN SYNDROME; MORPHEA; SKIN; DNA AB We present four cases of diffuse fasciitis (DF) associated with peripheral eosinophilia in which spirochetal organisms were identified. Two patients had borderline positive results on serologic evaluation for Borrelia burgdorferi. Deep biopsy showed dermal sclerosis associated with variable degrees of perivascular mononuclear inflammation. Diffuse fasciitis, septal panniculitis, and myositis with mononuclear cell infiltrates and varying numbers of eosinophils were observed. All cases showed a striking lymphocytic vasculopathy associated with atypical reactive endothelial cells. Using modified Dieterle and Steiner silver stains, multiple organisms were seen in one specimen, a single unequivocal organism detected in two specimens. In one case, no organisms were detected on silver stain; however, organisms were demonstrated using rabbit polyclonal antibodies against B. burgdorferi. B. burgdorferi-specific DNA was identified in one patient by the polymerase chain reaction. These results indicate that some cases of eosinophilic fasciitis are an expression of Lyme disease. We have previously proposed the more specific term ''borrelial fasciitis'' to describe such lesions. C1 HARVARD UNIV,SCH MED,BOSTON,MA. NATL CANC INST,BETHESDA,MD. RP Granter, SR (reprint author), BRIGHAM & WOMENS HOSP,DEPT PATHOL,DIV DERMATOPATHOL,75 FRANCIS ST,BOSTON,MA 02115, USA. NR 43 TC 34 Z9 36 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD OCT PY 1996 VL 18 IS 5 BP 465 EP 473 DI 10.1097/00000372-199610000-00004 PG 9 WC Dermatology SC Dermatology GA VM691 UT WOS:A1996VM69100004 PM 8902092 ER PT J AU Huang, BJ Rodriguez, BL Burchfiel, CM Chyou, PH Curb, JD Yano, K AF Huang, BJ Rodriguez, BL Burchfiel, CM Chyou, PH Curb, JD Yano, K TI Acculturation and prevalence of diabetes among Japanese-American men in Hawaii SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE acculturation; body mass index; diabetes mellitus; diet; life style; risk factors ID CORONARY HEART-DISEASE; MIDDLE-AGED MEN; PHYSICAL-ACTIVITY; GLUCOSE-INTOLERANCE; BIRTH-WEIGHT; PROGRAM; MELLITUS; STROKE; DIET; MORTALITY AB The association between acculturation to a Western lifestyle and prevalence of diabetes was examined among 8,006 Japanese-American men in Hawaii with varying degrees of exposure to traditional Japanese social and cultural lifestyles in 1965-1968. A reduced prevalence of diabetes was observed among the men who had retained a more Japanese lifestyle. These men also reported higher levels of physical activity and consumed more carbohydrates and less fat and animal protein in their diet. An inverse association between diabetes and being born in Japan was observed independent of age, body mass index, physical activity, and percentages of calories from fat or carbohydrates (odds ratios = 0.67 and 0.66, 95% confidence intervals 0.49-0.93 and 0.48-0.91, respectively). The number of total years lived in Japan was inversely associated with prevalent diabetes after controlling for age, body mass index, and physical activity (odds ratio = 0.81, 95% confidence interval 0.68-0.96). Current Oriental diet (compared with Western diet) was inversely associated with prevalent diabetes after controlling for age, body mass index, and physical activity (odds ratio = 0.71, 95% confidence interval 0.50-0.98). These findings suggest that living a Japanese lifestyle is associated with a reduced prevalence of diabetes. C1 NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,EPIDEMIOL RES SECT,HONOLULU,HI. MARSHFIELD MED RES FDN,MARSHFIELD,WI 54449. RP Huang, BJ (reprint author), UNIV HAWAII,HONOLULU HEART PROGRAM,CORP RES,DIV CLIN EPIDEMIOL,SCH MED,347 N KUAKINI ST,HONOLULU,HI 96817, USA. NR 33 TC 69 Z9 70 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 1996 VL 144 IS 7 BP 674 EP 681 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VJ770 UT WOS:A1996VJ77000008 PM 8823064 ER PT J AU Marth, T Feurle, GE AF Marth, T Feurle, GE TI Cutaneous anergy to streptococcal antigens in Whipple's disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID TYPE-3; CELLS C1 UNIV BONN,DRK KRANKENHAUS NEUWIED,D-5300 BONN,GERMANY. RP Marth, T (reprint author), NIH,MUCOSAL IMMUN SECT,BLDG 10,ROOM 11N238,BETHESDA,MD 20892, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 1996 VL 91 IS 10 BP 2254 EP 2255 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL418 UT WOS:A1996VL41800053 PM 8855774 ER PT J AU Havlik, RJ Pahor, M Guralnik, JM Salive, ME Corti, MC AF Havlik, RJ Pahor, M Guralnik, JM Salive, ME Corti, MC TI Comments on Pahor et al's study of calcium channel blockers and cancer - Reply SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Letter ID TRANSPLANTATION; ANTAGONISTS; CELLS RP Havlik, RJ (reprint author), NIA,DEPT EPIDEMIOL,DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20814, USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 1996 VL 9 IS 10 BP 1051 EP 1053 DI 10.1016/0895-7061(96)87754-5 PN 1 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VL726 UT WOS:A1996VL72600022 ER PT J AU Coogan, PF Clapp, RW Newcomb, PA Mittendorf, R Bogdan, G Baron, JA Longnecker, MP AF Coogan, PF Clapp, RW Newcomb, PA Mittendorf, R Bogdan, G Baron, JA Longnecker, MP TI Variation in female breast cancer risk by occupation SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE breast cancer; occupational factors; case-control studies ID UNITED-STATES; ELECTROMAGNETIC-FIELDS; PHYSICAL-ACTIVITY; WOMEN; EXPOSURE; MORTALITY; EPIDEMIOLOGY; ASSOCIATIONS; WORKERS AB Data from a population-based case control study were used to estimate occupation-specific relative risks for female breast cancer, adjusted for established breast cancer risk factors. Breast cancer cases under age 75 were identified from tumor registries in four states. Controls were randomly selected from driver's license and Medicare beneficiary lists. Information on usual occupation and risk factors was obtained by telephone interview. Odds ratios from logistic regression adjusted for age, state, body mass index, benign breast disease, family history of breast cancer, menopausal status, age at menarche, parity, age at first birth, lactation history, education, and alcohol consumption were calculated for each of 26 occupational groups. Complete occupational information was obtained for 6,835 cases and 9,453 controls. Of 26 occupational groups, only ''administrative support occupation'' had a statistically significantly increased risk of breast cancer (OR = 1.15, 95% CI 1.06-1.24). In these data, no specific occupational group had an unusual risk of breast cancer. Increased risks reported elsewhere for nurses and teachers were not corroborated. (C) 1996 Wiley-Liss, Inc. C1 BOSTON UNIV,SCH PUBL HLTH,DEPT ENVIRONM HLTH,BOSTON,MA. UNIV WISCONSIN,CTR COMPREHENS CANC,DEPT HUMAN ONCOL,MADISON,WI. UNIV CHICAGO,PRITZKER SCH MED,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. MAINE BUR HLTH,DIV DIS CONTROL,AUGUSTA,ME. DARTMOUTH COLL SCH MED,DEPT FAMILY & COMMUNITY MED,HANOVER,NH. NATL INST ENVIRONM HLTH SCI,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC. OI Clapp, Richard/0000-0001-8174-0825; Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA 47147, CA 47305] NR 36 TC 44 Z9 44 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 OCT PY 1996 VL 30 IS 4 BP 430 EP 437 DI 10.1002/(SICI)1097-0274(199610)30:4<430::AID-AJIM8>3.0.CO;2-Z PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VK111 UT WOS:A1996VK11100008 PM 8892548 ER PT J AU Heineman, EF Gomez, MR Dosemeci, M Cocco, P AF Heineman, EF Gomez, MR Dosemeci, M Cocco, P TI Methylene chloride and brain cancer: Interpreting a new study in light of existing literature SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter DE methylene chloride; brain cancer; exposure assessment; glioma; solvents ID MORTALITY; EXPOSURE; WORKERS RP Heineman, EF (reprint author), NCI,OCCUPAT STUDIES SECT,EPN ROOM 418,6130 EXECUT BLVD MSC 7364,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 1996 VL 30 IS 4 BP 506 EP 507 DI 10.1002/(SICI)1097-0274(199610)30:4<506::AID-AJIM20>3.0.CO;2-7 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VK111 UT WOS:A1996VK11100020 ER PT J AU Gomez, MR Heineman, E Dosemeci, M Cocco, P AF Gomez, MR Heineman, E Dosemeci, M Cocco, P TI Matrix is a reasonable method to assess exposures SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter DE brain cancer; chlorinated; hydrocarbons; exposure assessment; matrix; methylene chloride; solvents ID CHLORINATED ALIPHATIC-HYDROCARBONS; OCCUPATIONAL EXPOSURE C1 NCI,BETHESDA,MD 20892. IST MED LAVORO,CAGLIARI,ITALY. NR 6 TC 1 Z9 1 U1 0 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 OCT PY 1996 VL 30 IS 4 BP 508 EP 509 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VK111 UT WOS:A1996VK11100021 ER PT J AU Otterson, GA Monahan, BP Harold, N Steinberg, SM Frame, JN Kaye, FJ AF Otterson, GA Monahan, BP Harold, N Steinberg, SM Frame, JN Kaye, FJ TI Clinical significance of the FV:Q(506) mutation in unselected oncology patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACTIVATED PROTEIN-C; FACTOR-V LEIDEN; POOR ANTICOAGULANT RESPONSE; COAGULATION-FACTOR-V; ADDITIONAL RISK FACTOR; VENOUS THROMBOSIS; HYPERCOAGULABLE STATES; MYOCARDIAL-INFARCTION; INHERITED RESISTANCE; DEFICIENT FAMILIES AB PURPOSE: A common germline mutation in the factor V gene (FV:Q(506)) has been associated with hypercoagulability in families with heritable predisposition to thrombosis. We examined the prevalence and clinical significance of the FV:Q(506) mutation in cancer patients. PATIENTS AND METHODS: We performed a retrospective cohort study by examining 353 consecutive, unselected patients in a general hematology/oncology clinic. We ascertained risk factors, obtained the clinical clotting history, and determined the heterozygous or homozygous presence of the FV:Q(506) allele for each patient. RESULTS: We detected a germline mutation in 5.4% (19 of 353) of patients, of whom 18 were heterozygous and 1 was homozygous for the FV:Q(506) mutant allele. In 17 of 18 heterozygous patients, there was no history of venous thrombosis or catheter-associated thrombosis. These asymptomatic patients included 13 patients who had been diagnosed with cancer or leukemia for a mean of 66.2 months (median 69) and had received a variety of local and systemic treatments. In contrast, 1 of 18 heterozygous and 1 of 1 homozygous patients had developed deep vein thrombosis that was associated, respectively, with either recurrent thrombotic events or a strong family history for pulmonary embolus. CONCLUSIONS: Routine screening for the FV:Q(506) mutation in cancer patients without a personal or family history for venous thrombosis is not helpful in guiding management. In contrast, an episode of venous thrombosis in a patient with a mutant germline FV:Q(506) allele was associated with recurrent thrombotic events. These findings suggest that patients heterozygous for the FV:Q(506) allele may require an independent ''susceptibility'' element to manifest a venous hypercoagulable state. In addition, only 2 of 25 clinic patients with a venous clot carried the FV:Q(506) allele suggesting this genetic defect plays a minor role in the hypercoagulable state of cancer. C1 NCI, NAVY ONCOL BRANCH, BETHESDA, MD 20889 USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. NATL NAVAL MED CTR, DIV HEMATOL ONCOL, BETHESDA, MD USA. RI kaye, frederic/E-2437-2011 NR 32 TC 39 Z9 39 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 1996 VL 101 IS 4 BP 406 EP 412 DI 10.1016/S0002-9343(96)00235-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA VN408 UT WOS:A1996VN40800012 PM 8873512 ER PT J AU Macri, CJ Martinez, A Moody, TW Gray, KD Miller, MJ Gallagher, M Cuttitta, F AF Macri, CJ Martinez, A Moody, TW Gray, KD Miller, MJ Gallagher, M Cuttitta, F TI Detection of adrenomedullin, a hypotensive peptide, in amniotic fluid and fetal membranes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 04-10, 1996 CL KAMUELA, HI SP Soc Perinatal Obstetricians DE adrenomedullin; hypotensive peptide; amniotic fluid and membranes ID TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE CELLS; FACTOR-ALPHA; LOCALIZATION; EXPRESSION; IL-1-ALPHA; SECRETION; IL-1-BETA; CLONING; PROTEIN AB OBJECTIVE: Our purpose was to determine whether adrenomedullin, a multifunctional regulatory peptide involved in blood flow regulation and growth stimulation and with antimicrobial activity, was a component of amniotic fluid from second-trimester human fetus and to determine the source of this peptide. STUDY DESIGN: A prospective descriptive study was performed on 134 patients undergoing amniocentesis after genetic counseling, ultrasonography, and infomed consent. Adrenomedullin expression was determined by immunocytochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and in situ reverse transcriptase-polymerase chain reaction in fetal membranes and with radioimmunoassay in amniotic fluid. RESULTS: Radioimmunoassay of the 134 amniotic fluid specimens revealed adrenomedullin-like immunoreactivity in all of them, ranging in concentration from 10 to 300 fmol/25 mu l (170 +/- 62 fmol/25 mu l. Immunocytochemical analysis, Western blot analysis, reverse transcriptase-polymerase chain reaction, and in situ reverse transcriptase-polymerase chain reaction further established the expression of adrenomedullin protein and messenger ribonucleic acid in fetal amniotic membranes, suggesting that this organ is the source of amniotic adrenomedullin. CONCLUSIONS: Our results clearly demonstrate the presence of adrenomedullin in second-trimester human amniotic fluid and adrenomedullin messenger ribonucleic acid and protein in amniotic membranes, suggesting that adrenomedullin is a hormone involved in the maintenance of normal pregnancy. Further studies with these molecular tools are in progress to determine the precise role of this hormone and whether adrenomedullin plays a role in the pathogenesis of various disorders of pregnancy. C1 NATL NAVAL MED CTR, BETHESDA, MD 20889 USA. NCI, BIOMARKERS & PREVENT RES BRANCH, DIV CLIN SCI, NIH, ROCKVILLE, MD USA. RP Macri, CJ (reprint author), UNIFORMED SERV UNIV HLTH SCI, DEPT OBSTET & GYNECOL, ROOM A3080, 4301 JONES BRIDGE RD, BETHESDA, MD 20814 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 25 TC 65 Z9 67 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 OCT PY 1996 VL 175 IS 4 BP 906 EP 911 DI 10.1016/S0002-9378(96)80023-8 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VQ865 UT WOS:A1996VQ86500023 PM 8885746 ER PT J AU Svinarich, DM Bitonti, OM Romero, R Gonik, B AF Svinarich, DM Bitonti, OM Romero, R Gonik, B TI Induction and posttranslational expression of cytokines in a first-trimester trophoblast cell line by lipopolysaccharide SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 04-10, 1996 CL KAMUELA, HI SP Soc Perinatal Obstetricians DE cytokines; trophoblast; infection; immune signaling; lipopolysaccharide ID INTERLEUKIN-6 AB OBJECTIVES: The response to injection by human first-trimester trophoblasts is a poorly understood event. This study was undertaken to determine whether first-trimester trophoblasts are capable of responding to an infection stimulus and mediating an immune response. STUDY DESIGN: HTR-8/SVneo cells were exposed to lipopolysaccharide (1 mu g/ml) or media alone for either 0, 2, 4, 6, 8, or 24 hours. Northern analysis was conducted by use of a panel of antisense cytokine probes. Enzyme-linked immunosorbent assays specific for either interleukin-1 alpha, interleukin-6, interleukin-8, or transforming growth factor-beta 1 were conducted on corresponding cell culture supernatants, and the kinetics of expression were determined. RESULTS: Interleukin-1 alpha, interleukin-6, interleukin-8, and transforming growth factor-beta 1 transcription occurred maximally between 2 and 8 hours of culture in media containing lipopolysaccharide, with a subsequent diminution of response. Enzyme-linked immunosorbent assay analysis corroborated lipopolysaccharide induction seen at the level of transcription, with significant posttranslational expression of these cytokines being detected between 2 and 24 hours in culture (p < 0.01), CONCLUSIONS: Expression of the proinflammatory cytokines interleukin-1 alpha, interleukin-6, interleukin-8 and transforming growth factor-beta 1 strongly support the contention that human first-trimester trophoblasts are capable of responding to an infection stimulus and eliciting an immune response through cytokine-based immune signaling. C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RP Svinarich, DM (reprint author), WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,CS MOTT CTR,275 E HANCOCK AVE,DETROIT,MI 48201, USA. NR 9 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1996 VL 175 IS 4 BP 970 EP 973 DI 10.1016/S0002-9378(96)80034-2 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VQ865 UT WOS:A1996VQ86500034 PM 8885757 ER PT J AU Goldenberg, RL Iams, JD Miodovnik, M VanDorsten, JP Thurnau, G Bottoms, S Mercer, BM Meis, PJ Moawad, AH Das, A Caritis, SN McNellis, D Roberts, JM Hauth, JC Copper, R Northen, A MuellerHeubach, E Swain, M Frye, A Lindheimer, M Jones, P Siddiqi, TA Elder, N Bain, R Thom, E Leuchtenburg, L Fischer, M Paul, RH Kovacs, B Rabello, Y Harger, JH Cotroneo, M Stallings, C Yaffe, SJ Catz, C Klebanoff, M Landon, MB Johnson, F Thurnau, GR Carey, JC Meier, A Newman, RB Collins, BA LeBoeuf, F Sibai, B Mercer, B Ramsey, R Fricke, J Bottoms, SF Dombrowski, MP Norman, GS AF Goldenberg, RL Iams, JD Miodovnik, M VanDorsten, JP Thurnau, G Bottoms, S Mercer, BM Meis, PJ Moawad, AH Das, A Caritis, SN McNellis, D Roberts, JM Hauth, JC Copper, R Northen, A MuellerHeubach, E Swain, M Frye, A Lindheimer, M Jones, P Siddiqi, TA Elder, N Bain, R Thom, E Leuchtenburg, L Fischer, M Paul, RH Kovacs, B Rabello, Y Harger, JH Cotroneo, M Stallings, C Yaffe, SJ Catz, C Klebanoff, M Landon, MB Johnson, F Thurnau, GR Carey, JC Meier, A Newman, RB Collins, BA LeBoeuf, F Sibai, B Mercer, B Ramsey, R Fricke, J Bottoms, SF Dombrowski, MP Norman, GS TI The preterm prediction study: Risk factors in twin gestations SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 04-10, 1996 CL KAMUELA, HI SP Soc Perinatal Obstetricians DE twins; cervical ultrasound; fetal fibronectin ID PREGNANCIES AB OBJECTIVE: Our purpose was to determine the association between the presence of bacterial vaginosis, fetal fibronectin, and a short cervix and the risk of spontaneous preterm birth of twins. STUDY DESIGN: We prospectively screened 147 women with twins at 24 and 28 weeks' gestation for more than 50 potential risk factors for spontaneous preterm birth. We also measured cervical length with ultrasound scans and tested for the presence of bacterial vaginosis. Fetal fibronectin level was evaluated every 2 weeks from 24 to 30 weeks' gestation. Outcomes included spontaneous preterm birth at <32 weeks, <35 weeks, and <37 weeks. RESULTS: Among twin as compared with singleton pregnancies, a cervical length less than or equal to 25 mm was more common at both 24 and 28 weeks, a statistically significant difference. There were no significant differences in most other risk factors. Of the factors evaluated by means of univariate analysis at 24 weeks, only a short cervix (less than or equal to 25 mm) was consistently associated with spontaneous preterm birth. The odds ratios and 95% confidence interval for spontaneous preterm birth at <32 weeks, <35 weeks, and <37 weeks were 6.9 (2.0 to 24.2), 3.2 (1.3 to 7.9), and 2.8 (1.1 to 7.7). At 28 weeks, a cervical length less than or equal to 25 mm was not a strong predictor of spontaneous preterm birth. At both 28 weeks (odds ratio, 9.4; confidence interval, 1.0 to 67.7) and 30 weeks (odds ratio, 46.1; confidence interval, 4.2 to 1381), a positive fetal fibronectin result was significantly associated with spontaneous preterm birth at <32 weeks. Bacterial vaginosis at 24 or 28 weeks was not associated with spontaneous preterm birth of twins. Multivariate analysis confirmed the association between cervical length less than or equal to 25 mm at the 24-week visit and spontaneous preterm birth and also confirmed that at 24 weeks the other risk factors were less consistently and often not statistically significantly associated with spontaneous preterm birth. Of the risk factors evaluated at 28 weeks, only a positive fetal fibronectin was associated with a significantly increased risk for spontaneous preterm birth. CONCLUSIONS: Most known risk factors for spontaneous preterm birth were not significantly associated with spontaneous preterm birth of twins. At 24 weeks, cervical length less than or equal to 25 mm was the best predictor of spontaneous preterm birth at <32 weeks, <35 weeks, and <37 weeks. Of the risk factors evaluated at 28 weeks, fetal fibronectin was the only statistically significant predictor of spontaneous preterm birth at <32 weeks. C1 MAGEE WOMENS HOSP,PITTSBURGH,PA 15213. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC. UNIV CHICAGO,CHICAGO,IL 60637. UNIV CINCINNATI,CINCINNATI,OH 45221. GEORGE WASHINGTON UNIV,CTR BIOSTAT,WASHINGTON,DC 20052. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. NICHHD,BETHESDA,MD 20892. OHIO STATE UNIV,COLUMBUS,OH 43210. UNIV OKLAHOMA,NORMAN,OK 73019. MED UNIV S CAROLINA,CHARLESTON,SC 29425. UNIV TENNESSEE,KNOXVILLE,TN 37996. WAYNE STATE UNIV,DETROIT,MI 48202. UNIV ALABAMA,DEPT OBSTET & GYNECOL,BIRMINGHAM,AL 35233. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD21414, HD21410, HD27860] NR 14 TC 172 Z9 181 U1 0 U2 7 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 OCT PY 1996 VL 175 IS 4 BP 1047 EP 1053 DI 10.1016/S0002-9378(96)80051-2 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VQ865 UT WOS:A1996VQ86500051 PM 8885774 ER PT J AU Klebanoff, MA Nugent, RP Regan, JA AF Klebanoff, MA Nugent, RP Regan, JA TI Group B streptococci and pregnancy - Reply SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter RP Klebanoff, MA (reprint author), NICHHD,DESPR,NIH,6100 BLDG,ROOM 7B03,BETHESDA,MD 20892, USA. NR 2 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 1996 VL 175 IS 4 BP 1085 EP 1085 DI 10.1016/S0002-9378(96)80076-7 PN 1 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VQ865 UT WOS:A1996VQ86500076 ER PT J AU Schwartz, PE Hadjimichael, O Lowell, DM Merino, MJ Janerich, D AF Schwartz, PE Hadjimichael, O Lowell, DM Merino, MJ Janerich, D TI Rapidly progressive cervical cancer: The Connecticut experience SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE rapidly progressive cervical cancer; Papanicolaou smear screening ID SQUAMOUS-CELL CARCINOMA; UTERINE CERVIX AB A review is presented of 15 years of clinical experience working with women who developed cervical cancer within a short interval after the last reported negative Papanicolaou smear. Our initial report concerned isolated cases in which women were diagnosed with invasive cervical cancer within 1 year of a reported normal Papanicolaou smear. Our second report focused on a 10-year review of the Yale-New Haven Hospital experience, during which 40 of 555 women had rapidly progressive invasive disease; 35 cases (87.5%) occurred in women younger than 40 years old and almost all of the 40 diagnosed because of persistent symptoms despite a recent normal Papanicolaou smear. Our final experience is a population-based study of all women in Connecticut who developed cervical cancer between 1985 and 1990. A total of 118 of 481 (24.5%) participants were diagnosed with cervical cancer within 3 years of their last true-negative Papanicolaou smear. Adenocarcinomas occurred in 38 cases (32.2%). These data suggest that rapidly occurring cervical cancer may be a manifestation of endocervical carcinomas that have been inadequately screened. C1 UNIV CONNECTICUT,SCH MED,DEPT EPIDEMIOL,NEW HAVEN,CT 06520. UNIV CONNECTICUT,SCH MED,DEPT PATHOL,NEW HAVEN,CT 06520. NCI,DEPT PATHOL,BETHESDA,MD 20892. RP Schwartz, PE (reprint author), UNIV CONNECTICUT,SCH MED,DEPT OBSTET & GYNECOL,333 CEDAR ST,NEW HAVEN,CT 06520, USA. NR 13 TC 23 Z9 23 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 OCT PY 1996 VL 175 IS 4 BP 1105 EP 1109 DI 10.1016/S0002-9378(96)70012-1 PN 2 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VQ868 UT WOS:A1996VQ86800005 PM 8885794 ER PT J AU Hayashi, T StetlerStevenson, WG Fleming, MV Fishback, N Koss, MN Liotta, LA Ferrans, VJ Travis, WD AF Hayashi, T StetlerStevenson, WG Fleming, MV Fishback, N Koss, MN Liotta, LA Ferrans, VJ Travis, WD TI Immunohistochemical study of metalloproteinases and their tissue inhibitors in the lungs of patients with diffuse alveolar damage and idiopathic pulmonary fibrosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID FIBROBLAST COLLAGENASE INHIBITOR; HUMAN BURN WOUNDS; IV COLLAGENASE; INTERSTITIAL COLLAGENASE; EXTRACELLULAR-MATRIX; MESSENGER-RNA; CELL-LINES; SQUAMOUS-CELL; HUMAN-SKIN; EXPRESSION AB Immunohistochemical and confocal microscopic studies of the localization of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), and type IV collagen were made in lung tissues from patients with normal pulmonary histology (n = 3), diffuse alveolar damage (n = 14), and idiopathic pulmonary fibrosis (n = 12), Pretreatment with pepsin revealed otherwise undetectable MMP- and TIMP-immunoreactive sites. In normal lung, MMP-2, MMP-9, TIMP-1, and TIMP-2 were localized in ciliated cells, endothelial cells, pneumocytes, macrophages, and smooth muscle cells;fibroblasts showed a strong reaction only for MMP-2. Only TIMP-2 showed co-localization with type IV collagen, Myofibroblasts and epithelial cells expressed increased reactivity for MMPs and TIMPs in both disorders, The reactivities for MMPs and TIMPs were stronger in diffuse alveolar damage MMP-2 showed focal co-localization in capillary endothelial and disrupted endothelial basement membranes, suggesting activation of collagenolysis, A protective effect against this lysis was suggested by the extensive co-localization of TIMP-2 with type IV collagen and fibrillar collagens, Alveolar buds showed increased reactivity for MMPs and TIMPs in their lining epithelial cells, myofibroblasts, and their basement membranes; however, their matrices were mostly unreactive. These findings emphasize the complexity of the roles of MMPs and TIMPs is collagen turnover in diffuse alveolar damage and idiopathic pulmonary fibrosis. C1 NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 51 TC 168 Z9 181 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 1996 VL 149 IS 4 BP 1241 EP 1256 PG 16 WC Pathology SC Pathology GA VM314 UT WOS:A1996VM31400018 PM 8863673 ER PT J AU Pietrini, P Furey, ML GraffRadford, N Freo, U Alexander, GE Grady, CL Dani, A Mentis, MJ Schapiro, MB AF Pietrini, P Furey, ML GraffRadford, N Freo, U Alexander, GE Grady, CL Dani, A Mentis, MJ Schapiro, MB TI Preferential metabolic involvement of visual cortical areas in a subtype of Alzheimer's disease: Clinical implications SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GLUCOSE-UTILIZATION; ATROPHY; DIAGNOSIS; DEMENTIA; ASYMMETRIES; CORTEX; PET AB Objective: A subgroup of patients with Alzheimer's disease present with visual disturbances at onset. This study investigated whether specific cortical networks associated with visual processes are preferentially affected in this subgroup and determined the clinical implications of such abnormalities. Method: Regional cerebral glucose metabolic rates were assessed with positron emission tomography and [F-18]2-fluoro-2-deoxy-D-glucose, and general intellectual functions, memory, and visual skills were measured with cognitive tests in patients with probable Alzheimer's disease-10 with and 22 without prominent visual symptoms-and in 25 healthy comparison subjects. Results: Both patient groups showed reduced glucose metabolism in parietal regions and in middle and superior temporal regions in comparison with the healthy subjects. The Alzheimer's disease patients without visual symptoms also showed reductions in inferior temporal, frontal, and limbic structures, as is typical of Alzheimer's disease. In contrast, the patients with visual symptoms had larger metabolic deficits than the patients without visual symptoms in the parietal and occipital cortices (including the primary visual cortex), with a relative sparing of inferior temporal, frontal, and limbic regions. Consistently, the patients with visual symptoms had significantly greater visuospatial deficits and less severe memory impairments than the patients without visual symptoms. Conclusions: Alzheimer's disease patients with visuospatial deficits who are studied while alive have a distinctive regional distribution of cerebral metabolic impairment that is related to specific cognitive deficits and that distinguishes them from patients with typical Alzheimer's disease. These findings imply that regional variations in brain dysfunction can occur in Alzheimer's disease, with differential involvement of cortical systems resulting in distinctive clinical subgroups. C1 MAYO CLIN JACKSONVILLE,DEPT NEUROL,JACKSONVILLE,FL 32224. RP Pietrini, P (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Furey, Maura/H-5273-2013 FU NIA NIH HHS [AG-08031] NR 35 TC 76 Z9 76 U1 1 U2 5 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 OCT PY 1996 VL 153 IS 10 BP 1261 EP 1268 PG 8 WC Psychiatry SC Psychiatry GA VK833 UT WOS:A1996VK83300004 PM 8831432 ER PT J AU Gergen, P AF Gergen, P TI Social class and asthma - Distinguishing between the disease and the diagnosis SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID SOCIOECONOMIC-STATUS; PERSISTENT WHEEZE; DECISION-MAKING; NATIONAL SURVEY; UNITED-STATES; CHILDREN; PREVALENCE; ASSOCIATION; CHILDHOOD; SAMPLE RP Gergen, P (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 19 Z9 19 U1 2 U2 2 PU AMER PUBLIC HEALTH ASSN 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 OCT PY 1996 VL 86 IS 10 BP 1361 EP 1362 DI 10.2105/AJPH.86.10.1361 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VN016 UT WOS:A1996VN01600002 PM 8876501 ER PT J AU Grant, BF Dawson, DA AF Grant, BF Dawson, DA TI Alcohol and drug use, abuse, and dependence among welfare recipients SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB Objectives. This paper presents national estimates of heavy drinking, drug use, and alcohol and drug abuse and/or dependance among recipients of selected welfare programs. Methods. Data from the 1992 National Longitudinal Alcohol Epidemiologic Survey were analyzed. Results. The percentages of welfare recipients using, abusing, or dependent on alcohol or drugs were relatively small and consistent with the general US population and those not receiving welfare benefits. Conclusions. Although a minority of welfare recipients have alcohol or drug problems, substance abuse prevention and treatment services are needed among high-risk sub-groups. RP Grant, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 10 TC 55 Z9 55 U1 0 U2 4 PU AMER PUBLIC HEALTH ASSN 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 OCT PY 1996 VL 86 IS 10 BP 1450 EP 1454 DI 10.2105/AJPH.86.10.1450 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VN016 UT WOS:A1996VN01600019 PM 8876518 ER PT J AU Linet, MS Nyren, O Gridley, G Adami, HO Buckland, JD McLaughlin, JK Fraumeni, JF AF Linet, MS Nyren, O Gridley, G Adami, HO Buckland, JD McLaughlin, JK Fraumeni, JF TI Causes of death among patients surviving at least one year following splenectomy SO AMERICAN JOURNAL OF SURGERY LA English DT Article ID MORTALITY; SEPSIS AB BACKGROUND: TO assess the mortality (mostly long-term sequelae) of patients undergoing splenectomy, we carried out a population-based study in Sweden. METHODS: Using the unique personal identification number assigned to each Swedish resident, we linked centralized hospitalization records with nationwide mortality data, After initially assessing risks within the first 12 months after splenectomy, we excluded deaths during the first year and computed standardized mortality ratios (SMRs) for 1,297 patients splenectomized for external trauma and 991 surgically treated for nonmalignant conditions of adjacent organs who were alive at 12 months following surgery. The general Swedish population was used as the comparison. RESULTS: Both men and women undergoing splenectomy for external trauma had a 1.6-fold (SMR = 1.6) significantly elevated mortality risk, due mainly to circulatory diseases (particularly thromboembolism), alcoholism, digestive disorders. and external causes. Men also had a 28-fold increased mortality from septicemia and an excess of liver cirrhosis (mostly alcohol-related). Patients of both genders splenectomized for nonmalignant conditions had small but significantly elevated mortality overall (SMR = 1.4 to 1.5) reflecting excess risks for malignancies, diseases of blood-forming organs, external causes, and circulatory, respiratory, and digestive disorders, In addition, men had increased mortality from thromboembolism and pneumonia while women experienced elevated risks from septicemia. CONCLUSION: The excess mortality resulted from functional postsplenectomy defects (including sepsis and thromboembolism), behaviors increasing risk of traumatic splenic injury (eg, alcoholism), damage to other organs from the external trauma (eg, traumatic injury to the central nervous system/spinal cord), or the same or recurrent nonmalignant conditions for which surgery was performed (eg, gastric and duodenal ulcers). C1 UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,UPPSALA,SWEDEN. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. INT EPIDEMIOL INST,ROCKVILLE,MD. RP Linet, MS (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,6130 EXECUT BLVD,MSC 7368,EPN 415,BETHESDA,MD 20892, USA. NR 12 TC 23 Z9 25 U1 0 U2 1 PU CAHNERS PUBL CO PI NEW YORK PA 249 WEST 17 STREET, NEW YORK, NY 10011 SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 1996 VL 172 IS 4 BP 320 EP 323 DI 10.1016/S0002-9610(96)00196-1 PG 4 WC Surgery SC Surgery GA VM043 UT WOS:A1996VM04300004 PM 8873521 ER PT J AU Kamel, OW Weiss, LM vandeRijn, M Colby, TV Kingma, DW Jaffe, ES AF Kamel, OW Weiss, LM vandeRijn, M Colby, TV Kingma, DW Jaffe, ES TI Hodgkin's disease and lymphoproliferations resembling Hodgkin's disease in patients receiving long-term low-dose methotrexate therapy SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphoproliferative disorder; Epstein-Barr virus; immunosuppression; methotrexate; rheumatoid arthritis ID EPSTEIN-BARR-VIRUS; REED-STERNBERG CELLS; RHEUMATOID-ARTHRITIS; CYCLOSPORINE-A; LYMPHOMAS; TRANSPLANTATION; IMMUNOSUPPRESSION; IMMUNODEFICIENCY; DERMATOMYOSITIS; MALIGNANCIES AB Recently, it has been shown that patients with rheumatologic diseases who are treated with methotrexate can develop immunosuppression-associated lymphoproliferative disorders. Although a variety of lymphoproliferations have been described in the setting of methotrexate therapy, only rare cases of Hodgkin's disease (HD) have been reported. In this study, we provide a more complete characterization of the spectrum of lymphoproliferations that resemble HD or show features diagnostic of HD that occur in patients receiving long-term low-dose methotrexate therapy. Eight patients were receiving methotrexate for various disorders. Four cases were considered to represent lymphoproliferations resembling HD; the other four cases were diagnosed as HD because they showed diagnostic morphologic and immunophenotypic features. All three patients with lymphoproliferations resembling HD on whom follow-up was available experienced tumor regression with methotrexate withdrawal or with methotrexate withdrawal and steroids; none of these three patients required further therapy. All three patients with HD on whom follow-up was available are alive and free of disease following chemotherapy or radiation therapy. In two of these patients, the tumor persisted or progressed despite discontinuation of methotrexate with observation; the third patient received chemotherapy at the same time methotrexate was stopped. Our findings indicate that a spectrum of lymphoproliferations resembling HD or diagnostic of HD can occur in patients receiving longterm low-dose methotrexate therapy. Recognition of these lymphoproliferative disorders is clinically important because a subset of these neoplasms will completely resolve with discontinuation of methotrexate, thereby obviating the need for chemotherapy or radiation therapy. C1 CITY HOPE NATL MED CTR,DUARTE,CA 91010. UNIV PENN,PHILADELPHIA,PA 19104. MAYO CLIN,SCOTTSDALE,AZ. NATL CANC INST,BETHESDA,MD. RP Kamel, OW (reprint author), STANFORD UNIV,MED CTR,DEPT PATHOL,300 PASTEUR DR,STANFORD,CA 94305, USA. NR 28 TC 87 Z9 87 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 1996 VL 20 IS 10 BP 1279 EP 1287 DI 10.1097/00000478-199610000-00015 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA VJ668 UT WOS:A1996VJ66800015 PM 8827036 ER PT J AU Naritsin, DB Markey, SP AF Naritsin, DB Markey, SP TI Assessment of DNA oxidative damage by quantification of thymidine glycol residues using gas chromatography electron capture negative ionization mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID THYMINE GLYCOL; CHEMICAL-IONIZATION; QUANTITATIVE-DETERMINATION; RAT URINE; BASE; ACID; IDENTIFICATION; METABOLITES; TRYPTOPHAN; ADDUCTS AB A technique to assess DNA oxidative damage by quantification of thymidine glycol residues is described. 2-Methylglycerate was released from thymidine glycol in DNA by alkaline cleavage/borodeuteride reduction, then derivatized to form a combined pentafluorobenzyl-tertbutyldimethylsilyl (PFB-TBDMS) derivative and analyzed by gas chromatography/electron capture negative ionization mass spectrometry. [H-2(4)]Thymine glycol was used as an internal standard. The derivatization chemistry was assessed by using [C-14-methyl]glycerate. Successful esterification was achieved with 75-80% yield using tetrabutylammonium sulfate-assisted anhydrous pentafluorobenzylation. The PFB-TBDMS derivative exhibits excellent chromatographic and detection properties with a detection limit of 41 amol injected on column. Freshly dissolved calf thymus DNA was used to test the method performance. The background level of thymidine glycol detected in this DNA was 11.7 +/- 0.3 x 10(-6) mol thymidine glycol per 1 mol thymidine. The thymidine glycol background in undamaged DNA establishes a lower limit of oxidative damage below which biological oxidation events would not be measured by this method. The method was linear for 4-20 mu g DNA added per tube. The minimum measurable amount of thymidine glycol in DNA sample was 36 fmol. An increased level of thymidine glycol was measured in salmon sperm DNA which had autoxidized during storage in a refrigerated aqueous solution, 71.2 +/- 14.3 x 10(-6) mol thymidine glycol per 1 mol thymidine. (C) 1996 Academic Press, Inc. C1 NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 36 TC 4 Z9 4 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT 1 PY 1996 VL 241 IS 1 BP 35 EP 41 DI 10.1006/abio.1996.0374 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VL138 UT WOS:A1996VL13800007 PM 8921162 ER PT J AU Morikawa, H Kato, K Kimoto, H Ge, P Kirk, KL AF Morikawa, H Kato, K Kimoto, H Ge, P Kirk, KL TI Crystal structure of 2-deoxyascorbic acid SO ANALYTICAL SCIENCES LA English DT Article C1 NIDDK,NIH,BETHESDA,MD 20892. RP Morikawa, H (reprint author), NATL IND RES INST NAGOYA,KITA KU,NAGOYA,AICHI 462,JAPAN. NR 4 TC 1 Z9 1 U1 0 U2 0 PU JAPAN SOC ANALYTICAL CHEM PI TOKYO PA 26-2 NISHIGOTANDA 1 CHOME SHINAGAWA-KU, TOKYO 141, JAPAN SN 0910-6340 J9 ANAL SCI JI Anal. Sci. PD OCT PY 1996 VL 12 IS 5 BP 825 EP 826 DI 10.2116/analsci.12.825 PG 2 WC Chemistry, Analytical SC Chemistry GA VL825 UT WOS:A1996VL82500029 ER PT J AU Gourley, MF Austin, HA Scott, D Yarboro, CH Vaughn, EM Muir, J Boumpas, DT Klippel, JH Balow, JE Steinberg, AD AF Gourley, MF Austin, HA Scott, D Yarboro, CH Vaughn, EM Muir, J Boumpas, DT Klippel, JH Balow, JE Steinberg, AD TI Methylprednisolone and cyclophosphamide, alone or in combination, in patients with lupus nephritis - A randomized, controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE lupus nephritis; methylprednisolone; cyclophosphamide; dose-response relationship, drug; drug therapy, combination ID PULSE CYCLOPHOSPHAMIDE; ERYTHEMATOSUS; THERAPY; AZATHIOPRINE; PREDNISONE; DRUGS; MICE AB Background: Uncertainty exists about the efficacy and toxicity of bolus therapy with methylprednisolone or of the combination of methylprednisolone and cyclophosphamide in the treatment of lupus nephritis. Objective: To determine 1) whether intensive bolus therapy with methylprednisolone is an adequate substitute for bolus therapy with cyclophosphamide and 2) whether the combination of methylprednisolone and cyclophosphamide is superior to bolus therapy with methylprednisolone or cyclophosphamide alone. Design: Randomized, controlled trial with at least 5 years of follow-up. Setting: Government referral-based research hospital. Patients: 82 patients with lupus nephritis who had 10 or more erythrocytes per high-power field, cellular casts, proteinuria (>1 g of protein per day), and a renal biopsy specimen that showed proliferative nephritis. Interventions: Bolus therapy with methylprednisolone (1 g/m(2) body surface area), given monthly for at least 1 year; bolus therapy with cyclophosphamide (0.5 to 1.0 g/m(2) body surface area), given monthly for 6 months and then quarterly; or bolus therapy with both methylprednisolone and cyclophosphamide. Measurements: 1) Renal remission (defined as <10 dysmorphic erythrocytes per high-power field, the absence of cellular casts, and excretion of <1 g of protein per day without doubling of the serum creatinine level), 2) prevention of doubling of the serum creatinine level, and 3) prevention of renal failure requiring dialysis. Results: Renal remission occurred in 17 of 20 patients in the combination therapy group (85%), 13 of 21 patients in the cyclophosphamide group (62%), and 7 of 24 patients in the methylprednisolone group (29%) (P < 0.001). Twenty-eight patients (43%) did not achieve renal remission. By life-table analysis, the likelihood of remission during the study period was greater in the combination therapy group than in the methylprednisolone group (P = 0.028). Combination therapy and cyclophosphamide therapy were not statistically different. Adverse events were amenorrhea (seen in 41% of the cyclophosphamide group, 43% of the combination therapy group, and 7.4% of the methyl prednisolone group), cervical dysplasia (seen in 11% of the cyclophosphamide group, 7.1% of the combination therapy group, and 0% of the methylprednisolone group), avascular necrosis (seen in 11% of the cyclophosphamide group, 18% of the combination therapy group, and 22% of the methylprednisolone group), herpes tester (seen in 15% of the cyclophosphamide group, 21% of the combination therapy group, and 3.7% of the methylprednisolone group) and at least one infection (seen in 26% of the cyclophosphamide group, 32% of the combination therapy group, and 7.4% of the methylprednisolone group). Conclusions: Monthly bolus therapy with methylprednisolone was less effective than monthly bolus therapy with cyclophosphamide. A trend toward greater efficacy with combination therapy was seen. C1 NIH,BETHESDA,MD 20892. NR 33 TC 374 Z9 397 U1 0 U2 3 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 OCT 1 PY 1996 VL 125 IS 7 BP 549 EP & PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA VJ653 UT WOS:A1996VJ65300003 PM 8815753 ER PT J AU Olson, BR Forman, MR Lanza, E McAdam, PA Beecher, G Kimzey, LM Campbell, WS Raymond, EG Brentzel, SL GuttschesEbeling, B AF Olson, BR Forman, MR Lanza, E McAdam, PA Beecher, G Kimzey, LM Campbell, WS Raymond, EG Brentzel, SL GuttschesEbeling, B TI Relation between sodium balance and menstrual cycle symptoms in normal women SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PREMENSTRUAL-SYNDROME; ALDOSTERONE; PROGESTERONE; VASOPRESSIN; PREGNANCY AB Objective: To determine whether sodium balance affects expression of menstrual symptoms. Design: Prospective study of menstrual symptoms during three cycles: a baseline month (usual intake of sodium, 115 mmol/d) followed by 2 months of sodium restriction (intake of sodium, 73.0 mmol/d). Added salt was allowed during the last month, Investigators were aware of the diet sequence. Setting: Outpatient. Meals were prepared by a metabolic kitchen during the 2 months that the participants received salt-restricted diets. Participants: 13 healthy menstruant women. Measurements: Plasma sodium levels, urinary sodium excretion, and plasma renin activity were measured for five time periods during the baseline cycle and the two cycles of salt-restricted diet. Eleven women completed a questionnaire assessing somatic symptoms and sensory cravings at the same time every day during the 3-month study period. Results: Sodium restriction was associated with a mean decrease (+/- one half of the 95% CI) in plasma sodium levels of 0.9 +/- 0.9 mmol/L from a mean of 139.3 mmol/L during the baseline cycle (P = 0.018), a decrease in urinary sodium excretion of 40.3 +/- 18 mmol/d from a mean of 117 mmol/d during the baseline cycle (P = 0.001), and an increase in plasma renin activity of 0.14 +/- 0.08 ng/(L - s) from a mean of 0.28 ng/(L s) during the baseline cycle (P = 0.008). During the luteal phase of the sodium restriction cycle, significant decreases in plasma sodium levels of 1.23 +/- 0.5 mmol/L (from values of 138.8 mmol/L during the follicular phase) and increases in urinary sodium excretion of 27.2 +/- 10 mmol/d (from values of 65.5 mmol/d during the follicular phase) preceded periods when menstrual symptoms were most severe. Ratings of breast tenderness increased sixfold to eightfold in the late luteal phase (P < 0.001) and those of swelling or bloating increased twofold to threefold during early menses (P < 0.001) compared with nadir symptom ratings during each cycle. Sodium cravings increased in the luteal phase of all cycles but were not accompanied by increased sodium intake when access to added salt was allowed. Conclusions: Breast tenderness and bloating did not result from sodium retention in the luteal phase of the menstrual cycle. During normal and sodium-restricted diet cycles, women actually had urinary sodium loss, not retention, during the luteal phase; severity of menstrual symptoms was unchanged. C1 USDA,BELTSVILLE,MD 20705. NCI,NIH,BETHESDA,MD 20892. NR 20 TC 18 Z9 20 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 OCT 1 PY 1996 VL 125 IS 7 BP 564 EP 567 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VJ653 UT WOS:A1996VJ65300005 PM 8815755 ER PT J AU Gradishar, WJ Tallman, MS Abrams, JS AF Gradishar, WJ Tallman, MS Abrams, JS TI High-dose chemotherapy for breast cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED CLINICAL-TRIAL; BONE-MARROW SUPPORT; COMPARING TOTAL MASTECTOMY; ADJUVANT CHEMOTHERAPY; STAGE-II; INTENSIVE CHEMOTHERAPY; RADICAL MASTECTOMY; AUTOLOGOUS MARROW; CELL SUPPORT; HIGH-RISK AB The role of high-dose chemotherapy in the management of women with breast cancer remains one of the most controversial issues in oncology. During the past decade, numerous pilot studies have shown the feasibility of administering high-dose chemotherapy followed by autologous bone marrow transplantation or peripheral blood stem-cell transplantation (referred to as high-dose chemotherapy) to women with metastatic disease. However, it appears that survival improves in few treated patients. This treatment strategy is now being evaluated in the adjuvant setting in patients who are at high risk for developing recurrent disease. The National Cancer Institute has selected two randomized, adjuvant breast cancer trials for its High-Priority Clinical Trials Program. These trials are comparing conventional-dose chemotherapy with high-dose chemotherapy in patients in the early stages of breast cancer who are at high risk for disease recurrence. This paper focuses on the rationale for the randomized studies evaluating adjuvant high-dose chemotherapy in the early stages of breast cancer and reviews the efforts to overcome physician and patient biases so that the trials can be completed. C1 NCI,CLIN INVEST BRANCH,BETHESDA,MD 20892. RP Gradishar, WJ (reprint author), NORTHWESTERN UNIV,CTR CANC,233 E ERIE,SUITE 700,CHICAGO,IL 60611, USA. FU NCI NIH HHS [R21 CA 64487-01] NR 55 TC 32 Z9 32 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 OCT 1 PY 1996 VL 125 IS 7 BP 599 EP 604 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VJ653 UT WOS:A1996VJ65300010 PM 8815759 ER PT J AU Borden, EC Parkinson, D AF Borden, EC Parkinson, D TI Interferons: Effectiveness, toxicities, and costs SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID CHRONIC HEPATITIS-B; ALPHA; THERAPY; CANCER C1 NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. RP Borden, EC (reprint author), UNIV MARYLAND,CTR CANC,22 S GREENE ST,BALTIMORE,MD 21201, USA. NR 19 TC 16 Z9 16 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 OCT 1 PY 1996 VL 125 IS 7 BP 614 EP 616 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA VJ653 UT WOS:A1996VJ65300012 PM 8815761 ER PT J AU Cheson, BD AF Cheson, BD TI Ennui or not ennui, that is the question SO ANNALS OF ONCOLOGY LA English DT Editorial Material ID NON-HODGKINS-LYMPHOMA; LOW-GRADE LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; PHASE-II TRIAL; SINGLE-AGENT; FLUDARABINE; 2-CHLORODEOXYADENOSINE; THERAPY; MITOXANTRONE RP Cheson, BD (reprint author), NCI,CLIN INVEST BRANCH,CANC THERAPY EVALUAT PROGRAM,DIV CANC TREATMENT DIAG & CTR,BETHESDA,MD 20892, USA. NR 37 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 1996 VL 7 IS 8 BP 767 EP 769 PG 3 WC Oncology SC Oncology GA VQ150 UT WOS:A1996VQ15000010 PM 8922188 ER PT J AU Ruxrungtham, K Boone, E Ford, H Driscoll, JS Davey, RT Lane, HC AF Ruxrungtham, K Boone, E Ford, H Driscoll, JS Davey, RT Lane, HC TI Potent activity of 2'-beta-fluoro-2',3'-dideoxyadenosine against human immunodeficiency virus type 1 infection in hu-PBL-SCID mice SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CELLULAR PHARMACOLOGY; HIV; DISEASE; INVITRO; ANALOG; MOUSE; MODEL; AGENT AB A new antiretroviral agent, 2'-beta-fluoro-2',3'-dideoxyadenosine (FddA), is an acid-stable compound whose triphosphate form is a potent reverse transcriptase inhibitor with in vitro anti-human immunodeficiency virus (HN) activity and a favorable pharmacokinetic profile. Severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) provide a useful small-animal model for HIV research, In the present study we utilized this experimental system for the in vivo evaluation of the anti-HIV activity of this new compound when administered prior to infection, Initial studies revealed that, following a challenge with 50 100% tissue culture infective doses of HIV type 1 lymphadenopathy-associated virus, 39 of 42 (93%) control mice developed HIV infection, as evidenced by positive coculture or positive PCR. Administration of zidovudine decreased the infection rate to 5 of 16 (31%), while administration of FddA decreased the infection rate to 0 of 44 (0%), In follow-up controlled studies, the anti-HIV activity of FddA was confirmed, with 18 of 20 control mice shelving evidence of HIV infection, compared with 4 of 20 FddA-treated mice, In addition to having direct anti-HIV effects, FddA was found to have a protective effect on human CD4(+) T cells in the face of HIV infection, Mice treated with FddA were found to have a significantly higher percentage of CD4(+) T cells than controls (10.3% +/- 3.4% versus 0.27% +/- 0.21%; P = 0.01), Thus, FddA, with its potent anti-HN activity in vivo, high oral bioavailability, long intracellular half-life, and ability to preserve CD4(+) cells in the presence of HIV, appears to be a promising agent for clinical investigation. C1 NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 23 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 1996 VL 40 IS 10 BP 2369 EP 2374 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA VK835 UT WOS:A1996VK83500027 PM 8891146 ER PT J AU Foli, A Sogocio, KM Anderson, B Kavlick, M Saville, MW Wainberg, MA Gu, ZX Cherrington, JM Mitsuya, H Yarchoan, R AF Foli, A Sogocio, KM Anderson, B Kavlick, M Saville, MW Wainberg, MA Gu, ZX Cherrington, JM Mitsuya, H Yarchoan, R TI In vitro selection and molecular characterization of human immunodeficiency virus type 1 with reduced sensitivity to 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) SO ANTIVIRAL RESEARCH LA English DT Article DE HIV-1; drug-resistant virus; reverse transcriptase mutations ID REVERSE-TRANSCRIPTASE; ANTIRETROVIRUS ACTIVITY; REPLICATION INVITRO; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; RESISTANCE; INFECTION; MUTATION; 2',3'-DIDEOXYCYTIDINE; DIDEOXYCYTIDINE; AZIDOTHYMIDINE AB 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA) is an acyclic nucleotide with potent in vitro activity against human immunodeficiency virus type 1 (HIV-1). The present study was undertaken to determine whether HIV-1 resistance to PMEA could be generated by in vitro selection and if so, to determine which mutations in reverse transcriptase CRT) were responsible. HIV-1(LA1) was serially passaged for 10 months in the presence of increasing concentrations of PMEA up to a maximum of 40 mu M. After 40 passages, the 50% inhibitory concentration (IC50) of PMEA had increased almost 7-fold from 4.45 to 30.5 mu M. Some cross-resistance to 2',3'-dideoxycytidine (ddC, zalcitabine), 2',3'-dideoxyinosine (ddI, didanosine), and 3'-thiacytidine (3TC, lamivudine) was also observed, but no cross-reactive resistance to 3'-azido-3'-thymidine (AZT, zidovudine). Sequencing of the RT encoding region of each of eight pol clones from resistant isolates revealed a Lys-65 --> Arg (K65R) substitution. HIV with the K65R mutation inserted by site-directed mutagenesis also had decreased sensitivity to PMEA in H9 cells and a similar cross-resistance profile. Thus, HIV can develop decreased sensitivity to PMEA after long-term in vitro exposure and this change is associated with a K65R substitution. Additional studies will be needed to determine whether a similar mutation in HIV RT develops in patients receiving PMEA or its orally bioavailable prodrug adefovir dipivoxil (bis-POM PMEA). C1 NCI,MED BRANCH,BETHESDA,MD 20892. MCGILL UNIV,JEWISH GEN HOSP,AIDS CTR,MONTREAL,PQ H3T 1E2,CANADA. GILEAD SCI INC,FOSTER CITY,CA 94404. NR 37 TC 36 Z9 36 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 1996 VL 32 IS 2 BP 91 EP 98 PG 8 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA VM833 UT WOS:A1996VM83300005 PM 8891168 ER PT J AU Merke, DP Cutler, GB AF Merke, DP Cutler, GB TI Evaluation and management of precocious puberty SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID MCCUNE-ALBRIGHT SYNDROME; HORMONE ANALOG; THERAPY; TESTOLACTONE; EXPERIENCE; HEIGHT; GIRLS RP Merke, DP (reprint author), NICHHD, NATL INST HLTH, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 21 TC 24 Z9 26 U1 0 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 EI 1468-2044 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD OCT PY 1996 VL 75 IS 4 BP 269 EP 271 PG 3 WC Pediatrics SC Pediatrics GA VL990 UT WOS:A1996VL99000001 PM 8984908 ER PT J AU Nielsen, DA Goldman, D Virkkunen, M Tokola, R Rawlings, R Linnoila, M AF Nielsen, DA Goldman, D Virkkunen, M Tokola, R Rawlings, R Linnoila, M TI TPH replication study: Not! SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter ID TRYPTOPHAN-HYDROXYLASE GENE; POLYMORPHISM RP Nielsen, DA (reprint author), NIAAA,DIV INTRAMURAL CLIN & BIOL RES,NEUROGENET LAB,FLOW BLDG,ROOM 2,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 3 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 1996 VL 53 IS 10 BP 964 EP 965 PG 2 WC Psychiatry SC Psychiatry GA VM034 UT WOS:A1996VM03400013 PM 8857875 ER PT J AU Campo, E Jaffe, ES AF Campo, E Jaffe, ES TI Leukemic mantle cell lymphoma can behave in an indolent fashion - Reply SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Letter C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RP Campo, E (reprint author), HOSP CLIN BARCELONA,DEPT ANAT PATHOL,BARCELONA,SPAIN. NR 3 TC 1 Z9 1 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 1996 VL 120 IS 10 BP 905 EP 906 PG 2 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA VV297 UT WOS:A1996VV29700002 ER PT J AU Wilson, PWF Schaefer, EJ Larson, MG Ordovas, JM AF Wilson, PWF Schaefer, EJ Larson, MG Ordovas, JM TI Apolipoprotein E alleles and risk of coronary disease - A meta-analysis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apolipoproteinE; coronary heart disease; meta-analysis; molecular epidemiology ID DENSITY-LIPOPROTEIN CHOLESTEROL; ISCHEMIC-HEART-DISEASE; E POLYMORPHISM; ARTERY DISEASE; MYOCARDIAL-INFARCTION; E PHENOTYPES; POPULATION; LIPIDS; MICE; MEN AB A meta-analysis was undertaken to assess the impact of apolipoprotein E (apo E) alleles (epsilon 2, epsilon 3, and epsilon 4) on coronary disease in 14 published observational studies (9 clinical coronary disease and 5 coronary angiography). In comparison with epsilon 3, the epsilon 4 allele was associated with greater odds for coronary heart disease, and summary estimates of the odds ratios (ORs) and (95% confidence intervals) for both sexes combined were OR=0.98 (0.85-1.14) for epsilon 2 and OR=1.26 (1.13-1.41) for epsilon 4. Separate analyses for men and women showed similar associations. In angiographic studies the relative odds for significant coronary artery disease among both sexes combined was OR=0.76 (0.55-1.05) for epsilon 2 and OR=1.11 (0.88-1.40) for epsilon 4. The overall impression is that epsilon 4 is associated with clinical and coronary disease and that results are similar in men and women. C1 BOSTON UNIV,FRAMINGHAM,MA. TUFTS UNIV,USDA,NUTR CTR,BOSTON,MA 02111. RP Wilson, PWF (reprint author), NHLBI,FRAMINGHAM HEART STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. OI Ordovas, Jose/0000-0002-7581-5680 NR 42 TC 427 Z9 444 U1 0 U2 6 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 1996 VL 16 IS 10 BP 1250 EP 1255 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA VL771 UT WOS:A1996VL77100006 PM 8857921 ER PT J AU Langford, CA Sneller, MC Hallahan, CW Hoffman, GS Kammerer, WA TalarWilliams, C Fauci, AS Lebovics, RS AF Langford, CA Sneller, MC Hallahan, CW Hoffman, GS Kammerer, WA TalarWilliams, C Fauci, AS Lebovics, RS TI Clinical features and therapeutic management of subglottic stenosis in patients with Wegener's granulomatosis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TRACHEA AB Objective. To determine the clinical features and optimal treatment of subglottic stenosis (SGS) in patients with Wegener's granulomatosis (WG). Methods. Review of 43 patients with SGS and treatment of 20 patients with intratracheal dilation-glucocorticoid injection therapy. Results. SGS developed in 43 of 189 patients with WG who were followed up at the National Institutes of Health Clinical Center. The diagnosis of SGS occurred in the absence of other features of active WG in 21 of 43 patients (49%). In 21 patients (49%), SGS began while the patient was receiving systemic immunosuppressive therapy for disease activity involving other sites. Tracheostomy was required in 10 of 18 patients (56%) who were treated with systemic immunosuppressive therapy. In 20 patients treated with intratracheal therapy, none required tracheostomy and 6 with previous tracheostomies were decannulated. Conclusion. SGS often occurs independently of other features of active WG and is frequently unresponsive to systemic immunosuppressive therapy. Intratracheal dilation-injection therapy provides a safe and effective treatment for WG-associated SGS and, in the absence of major organ disease activity, should be used without concomitant systemic immunosuppressive agents. C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NIDOCD,NIH,BETHESDA,MD. RP Langford, CA (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 130 Z9 138 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 1996 VL 39 IS 10 BP 1754 EP 1760 DI 10.1002/art.1780391020 PG 7 WC Rheumatology SC Rheumatology GA VL140 UT WOS:A1996VL14000019 PM 8843868 ER PT J AU McDonald, MP Crawley, JN AF McDonald, MP Crawley, JN TI Galanin receptor antagonist M40 blocks galanin-induced choice accuracy deficits on a delayed-nonmatching-to-position task SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID RAT VENTRAL HIPPOCAMPUS; CENTRAL NERVOUS-SYSTEM; BASAL FOREBRAIN; ALZHEIMERS-DISEASE; WORKING-MEMORY; CHOLINERGIC SYSTEM; NUCLEUS BASALIS; SEPTAL-LESIONS; MEDIAL SEPTUM; BINDING-SITES AB Galanin is a 29-amino acid neuropeptide that coexists with acetylcholine in the medial septum/diagonal band in the rat and impairs choice accuracy on an operant delayed-nonmatching-to-position (DNMTP) working-memory task. M40, a peptidergic galanin antagonist, has previously been shown to block several physiological actions of galanin. The present experiments tested the ability of M40 to block the effects of galanin an DNMTP performance. M40 completely blocked choice-accuracy deficits induced by galanin administration in both the lateral ventricle and ventral hippocampus, at doses of M40 approximately 5-fold the molar dose of galanin. M40 appears to be an effective galanin antagonist in a rodent memory paradigm, indicating that this compound may prove useful in investigating the role of endogenous galanin in learning and memory. RP McDonald, MP (reprint author), NIMH,EXPT THERAPEUT BRANCH,SECT BEHAV NEUROPHARMACOL,BLDG 10,ROOM 4N214,BETHESDA,MD 20892, USA. NR 75 TC 44 Z9 44 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 1996 VL 110 IS 5 BP 1025 EP 1032 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA VQ506 UT WOS:A1996VQ50600016 PM 8919005 ER PT J AU Duka, T Curran, HV Rusted, JM Weingartner, HJ AF Duka, T Curran, HV Rusted, JM Weingartner, HJ TI Perspectives on cognitive psychopharmacology research SO BEHAVIOURAL PHARMACOLOGY LA English DT Review DE attention; attentional resources; benzodiazepines; drugs as tools; memory systems; scopolamine ID SCOPOLAMINE-INDUCED AMNESIA; HUMAN-MEMORY; BENZODIAZEPINE ANTAGONIST; HEALTHY-VOLUNTEERS; WORKING MEMORY; DOSE-RESPONSE; CHOLINERGIC BLOCKADE; EXPLICIT MEMORY; BETA-CARBOLINES; ALZHEIMER-TYPE AB This article discusses new perspectives in the psychopharmacology of cognition and analyses the advantages and disadvantages of using drugs as tools to study the mechanisms underlying memory functions. The use of 'stages' in the processing ofinformation as a means for the analysis of cognitive operations is critically discussed as a rigid approach which can only partially accommodate different cognitive functions. Theoretical models of memory 'systems' and allocation of attentional resources are presented alongside findings from the two types of more commonly used drugs in cognitive psychopharmacology: the benzodiazepines (BZ) and the anticholinergics. In a post-hoc analysis of the effects of BZ and scopolamine on memory and attention, it has become clear that these newer theoretical. models can accommodate most, but not all, of the effects of BZ and scopolamine on cognition. It is suggested that the development of cognitive tasks on the basis of these models and the execution of prospective studies with drugs as tools taking in to account the 'systems' approach to interpretation of data may be more useful for understanding cognitive functions. C1 UNIV LONDON UNIV COLL,LONDON WC1E 6BT,ENGLAND. NIAAA,BETHESDA,MD 20892. RP Duka, T (reprint author), UNIV SUSSEX,BRIGHTON BN1 9QG,E SUSSEX,ENGLAND. NR 65 TC 43 Z9 43 U1 1 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD OCT PY 1996 VL 7 IS 5 BP 401 EP 410 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA VP988 UT WOS:A1996VP98800002 ER PT J AU Funada, M Shippenberg, TS AF Funada, M Shippenberg, TS TI Differential involvement of D1 and D2 dopamine receptors in the expression of morphine withdrawal signs in rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE dopamine receptors; morphine; opioid withdrawal; place conditioning; raclopride; rat; SCH23390 ID PRECIPITATED OPIOID WITHDRAWAL; OPIATE WITHDRAWAL; NUCLEUS-ACCUMBENS; D-1; NALOXONE; ANTAGONISTS; DEPRESSION; ABSTINENCE; DEPENDENCE; CLONIDINE AB The role of dopamine (DA) receptors in the expression of opioid dependence was examined by use of an unbiased conditioned place preference paradigm. Male Sprague-Dawley rats were implanted s.c. with two pellets containing placebo or 75 mg morphine. Animals received one conditioning session with saline and one with the DA D1 receptor antagonist SCH23390 (0.01-0.05 mg, s.c.) or the DA D2 receptor antagonist raclopride (0.25-1.0 mg/kg, s.c.). Conditioning sessions were conducted 4 days after pellet implantation. During each of these sessions, physical signs of withdrawal were quantified. In morphine-pelleted animals, the D2 receptor antagonist raclopride produced conditioned place aversions, with a minimum effective dose of 0.5 mg/kg. Administration of a higher dose also resulted in wet-dog shakes, ptosis and diarrhea in morphine-pelleted animals. This effect was not observed in response to lower doses of raclopride or in placebo-pelleted animals. The D1 receptor antagonist SCH23390 failed to produce conditioned place aversions in either morphine- or placebo-pelleted animals after single-trial conditioning. This antagonist was also ineffective in producing physical withdrawal signs. After two conditioning sessions with SCH23390, both the morphine- and placebo-pelleted animals exhibited a marked aversion for the SCH23390-paired place. However, there was no difference between groups in the magnitude of this effect. These data demonstrate that the acute blockade of D2 receptors produces aversive effects in opioid-dependent animals and that this effect occurs in the presence of few, if any, prototypic physical withdrawal signs. Furthermore, the inability of a selective D1 receptor antagonist to produce conditioned aversive effects or physical signs of withdrawal suggests an important role of D2 as compared to D1 receptors in the expression of morphine withdrawal signs. C1 NIDA,BRAIN IMAGING SECT,DIV INTRAMURAL RES,NATL INST HLTH,BALTIMORE,MD 21224. RP Funada, M (reprint author), NIDA,CLIN PHARMACOL BRANCH,NATL INST HLTH,POB 5180,BALTIMORE,MD 21224, USA. NR 21 TC 28 Z9 28 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD OCT PY 1996 VL 7 IS 5 BP 448 EP 453 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA VP988 UT WOS:A1996VP98800008 ER PT J AU Chariot, A Castronovo, V Le, P Gillet, C Sobel, ME Gielen, J AF Chariot, A Castronovo, V Le, P Gillet, C Sobel, ME Gielen, J TI Cloning and expression of a new HOXC6 transcript encoding a repressing protein SO BIOCHEMICAL JOURNAL LA English DT Article ID DNA-BINDING SPECIFICITY; T-CELL LEUKEMIA; HOMEOBOX GENE; TRANSLOCATION PROTEIN; HOMEOTIC GENES; NUDE-MICE; PRE-B; DROSOPHILA; DIFFERENTIATION; HOMEODOMAINS AB Homeodomain-containing proteins are transcription factors that regulate the co-ordinated expression of multiple genes involved in development, differentiation and malignant transformation. In an attempt to characterize expressed homeobox (HOX) genes in breast cancer cells, we cloned two distinct HOXC6 transcripts from an MCF7 cDNA library. Interestingly, one of them represents a new HOXC6 mRNA encoding a homeodomain-containing protein harbouring a unique N-terminal sequence. Moreover we demonstrate that this HOXC6 transcript is less abundant in human breast cancer cells than in non-tumorigenic cell lines, is detected in breast carcinomas and adjacent tissues and is expressed in a variety of human tumours. In addition, transient co-transfection experiments illustrated that both HOXC6 transcripts encode gene products that repress transcription from a HOX binding sequence in MDA-MB231 cells and co-operate with other HOX gene products such as HOXB7 on their target genes. Taken together, our results suggest that HOXC6 proteins might contribute to the breast cell phenotype through co-operative interactions with other HOX-derived proteins and repression of their target genes. C1 UNIV LIEGE,CHU SART TILMAN,DEPT CLIN CHEM,B-4000 LIEGE,BELGIUM. UNIV LIEGE,CHU SART TILMAN,METASTASIS RES LAB,B-4000 LIEGE,BELGIUM. NCI,NIH,PATHOL LAB,MOL PATHOL SECT,BETHESDA,MD. NR 46 TC 13 Z9 15 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 1996 VL 319 BP 91 EP 97 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM963 UT WOS:A1996VM96300014 PM 8870653 ER PT J AU Hertz, R Nikodem, V BenIshai, A Berman, I Bartana, J AF Hertz, R Nikodem, V BenIshai, A Berman, I Bartana, J TI Thyromimetic mode of action of peroxisome proliferators: Activation of 'malic' enzyme gene transcription SO BIOCHEMICAL JOURNAL LA English DT Article ID ACYL-COA OXIDASE; BETA,BETA'-METHYL-SUBSTITUTED HEXADECANEDIOIC ACID; THYROID-HORMONE; RAT-LIVER; PHOSPHATE POTENTIALS; NUCLEOTIDE-SEQUENCE; FUNCTIONAL-ANALYSIS; RESPONSE ELEMENT; RETINOIC ACID; MESSENGER-RNA AB Peroxisome proliferators induce thyroid-hormone-dependent liver activities, e.g. 'malic' enzyme, mitochondrial glycerol-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, S14 [Hertz, Aurbach, Hashimoto and Bar-Tana (1991) Biochem. J. 274, 745-751]. Here we report that the thyromimetic effect of peroxisome proliferators with respect to 'malic' enzyme results from transcriptional activation of the 'malic' enzyme gene, mediated by binding of the peroxisome proliferator activated receptor (PPAR alpha)/retinoid X receptor (RXR alpha) heterodimer to a 5'-flanking enhancer of the 'malic' enzyme promoter. The enhancer involved is distinct from the thyroid hormone response element of the 'malic' enzyme promoter and is partly homologous with that which mediates transcriptional activation of peroxisomal acyl-CoA oxidase by peroxisome proliferators. Hence transcriptional activation of thyroid-hormone-dependent liver genes by xenobiotic or endogenous amphipathic carboxylates collectively defined as peroxisome proliferators is mediated by a transduction pathway similar to that involved in transcriptional activation of peroxisomal beta-oxidative genes and distinct from that which mediates thyroid hormone action. C1 HEBREW UNIV JERUSALEM,FAC MED,DEPT HUMAN NUTR & METAB,IL-91010 JERUSALEM,ISRAEL. NATL INST HLTH,BETHESDA,MD 20892. NR 31 TC 33 Z9 33 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 1996 VL 319 BP 241 EP 248 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VM963 UT WOS:A1996VM96300035 PM 8870674 ER PT J AU Wang, YX Freedberg, DI Grzesiek, S Torchia, DA Wingfield, PT Kaufman, JD Stahl, SJ Chang, CH Hodge, CN AF Wang, YX Freedberg, DI Grzesiek, S Torchia, DA Wingfield, PT Kaufman, JD Stahl, SJ Chang, CH Hodge, CN TI Mapping hydration water molecules in the HIV-1 Protease/DMP323 complex in solution by NMR spectroscopy SO BIOCHEMISTRY LA English DT Article ID UREA-BASED INHIBITOR; PROTEIN HYDRATION; AQUEOUS-SOLUTION; SELF-DIFFUSION; MACROMOLECULES; RELAXATION; MODEL AB A tetrahedrally hydrogen-bonded structural water molecule, water 301, is seen in the crystal structure of nearly every HIV-1 pretease/inhibitor complex. Although the urea oxygen of the designed inhibitor, DMP323, mimics and replaces water 301, other water molecules are seen in the protease/DMP373 crystal structure. As a first step toward understanding how water molecules may contribute to inhibitor potency and specificity, we have recorded water-NOESY and water-POESY spectra of the protease/DMP323 complex, Cross relaxation rates derived from these spectra, together with interproton distances calculated from the crystal structure of the complex, were used to classify the exchange cross peaks as follows: (A) a direct NOE with a water proton, (B) an indirect NOE with water through a labile protein proton, and (C) direct exchange of an amide proton with water. Type A and B cross peaks were analyzed using three models of water dynamics: (1) two-site exchange, with water molecules randomly hopping between hound and free states, (2) bound water with internal motion, and (3) free diffusion. Using the two-site exchange model to analyze the relaxation data of the type A cross peaks, it was found that the water molecules had short residence times, ca, 500 ps, in contrast with the >9 ns residence time estimated for water 301 In the protease/P9941 complex [Grzesiek et al. (1994) J. Am. Chem. Sec. 116, 1581-1582]. The NMR data are consistent with the X-ray observation that two symmetry-related water molecules, waters 422 and 456, are bound at the DMP323 binding site. Hence, these water molecules may help to stabilize the structure of the complex. Finally, it was found that three buried and hydrogen-bonded Thr hydroxyl protons were in slow exchange with solvent. In contrast, it was found that the DMP323 H4/H5 hydroxyl protons and the Asp25/125 carboxyl protons, which form a buried hydrogen-bonded network at the catalytic site of the protease, are in rapid exchange with solvent, suggesting that solvent can penetrate into the buried protein/inhibitor interface on the millisecond to microsecond time scale. C1 NIDR, STRUCT MOL BIOL UNIT, NIH, BETHESDA, MD 20892 USA. NIDDK, PHYS CHEM LAB, NIH, BETHESDA, MD 20892 USA. NIAMS, PROT EXPRESS LAB, NIH, BETHESDA, MD 20892 USA. DUPONT MERCK PHARMACEUT CO, DEPT CHEM & PHYS SCI, WILMINGTON, DE 19880 USA. NR 27 TC 31 Z9 31 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 1 PY 1996 VL 35 IS 39 BP 12694 EP 12704 DI 10.1021/bi9610764 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VK594 UT WOS:A1996VK59400007 PM 8841113 ER PT J AU Wondrak, EM Louis, JM AF Wondrak, EM Louis, JM TI Influence of flanking sequences on the dimer stability of human immunodeficiency virus type 1 protease SO BIOCHEMISTRY LA English DT Article ID HIV-1 PROTEASE; RETROVIRAL PROTEASES; MECHANISMS; SUBSTRATE; ENZYME AB The maturation of the human immunodeficiency virus type 1 protease (PR) from the Gag-Pol polyprotein is dependent on the intrinsic proteolytic activity of the dimeric Gag-Pol. Herein, we report the kinetics and conformational stabilities of two unique fusion proteins of the protease. In one, X(28)-PR, a random sequence of 28 amino acids (X(28)) was linked to the N terminus of the mature protease, In the second construct, X(28)-Delta TF*PR*Delta Pol, X(28) is fused to the protease which is flanked at both its termini by short sequences (Delta) which correspond to the native sequences of the Gag-Pol precursor. Autoprocessing of the latter protein was prevented by inserting an Ala at the native protease cleavage sites. The measured kinetic parameters and the pH-rate profile of both enzymes are nearly identical to those of the mature protease. However, these fusion proteins are more sensitive to acid and urea denaturation than the mature protease. The decrease in the conformational stability of X(28)-PR and X(28)-Delta TF*PR*Delta Pol is reflected by increases in their apparent dissociation constants (K-d) from <5 nM to approximately 180 and 25 nM, respectively. These results suggest that subunit interactions and hence the dimer stability of the protease domain in the Gag-Pol polyprotein differ from those of the mature protease. The high K-d of X(28)-PR further suggests that addition of non-native sequences to the N terminus of the protease destablizes the dimer. C1 NIDDKD, CELLULAR & DEV BIOL LAB, MOL MECHANISMS DEV SECT, NIH, BETHESDA, MD 20892 USA. NR 17 TC 40 Z9 40 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 1 PY 1996 VL 35 IS 39 BP 12957 EP 12962 DI 10.1021/bi960984y PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VK594 UT WOS:A1996VK59400036 PM 8841142 ER PT J AU Hibbeln, JR Salem, N AF Hibbeln, JR Salem, N TI Risks of cholesterol-lowering therapies SO BIOLOGICAL PSYCHIATRY LA English DT Letter RP Hibbeln, JR (reprint author), NIAAA,DICBR,12501 WASHINGTON AVE,MSC 8205,ROCKVILLE,MD 20852, USA. NR 7 TC 10 Z9 10 U1 1 U2 2 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 OCT 1 PY 1996 VL 40 IS 7 BP 686 EP 687 DI 10.1016/0006-3223(96)00173-4 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VJ929 UT WOS:A1996VJ92900023 PM 8886308 ER PT J AU terHaar, E Rosenkranz, HS Hamel, E Day, BW AF terHaar, E Rosenkranz, HS Hamel, E Day, BW TI Computational and molecular modeling evaluation of the structural basis for tubulin polymerization inhibition by colchicine site agents SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID AUTOMATED STRUCTURE EVALUATION; DEAMINOCOLCHINYL METHYL-ETHER; DNA TOPOISOMERASE-II; ANTIMITOTIC AGENTS; NATURAL-PRODUCTS; ANTITUMOR AGENTS; BINDING-SITE; BIOLOGICAL EVALUATION; ANTICANCER AGENTS; BETA-TUBULIN AB The computer-automated structure evaluation programs MultiCASE and CASE were used to perform a quantitative structure-activity relationship study on tubulin polymerization inhibitors. A learning set of 536 chemicals (202 active, 27 marginal, and 307 inactive), built using IC50 values for inhibition of tubulin polymerization or mitosis from this and previous studies, was used for artificial intelligence self-teaching. The algorithms successfully predicted the activity of agents in the learning set with >90% accuracy. Seventeen MultiCASE and twelve CASE (mostly included in the MultiCASE set) biophores (substructures significantly correlated with activity) were identified with a probability >0.95. Here we present the biophores of podophyllotoxins, colchicinoids, and certain combretastatins, each examined for structure-activity relationships. For the podophyllotoxins and colchicinoids in the learning set, the correlations between observed and predicted potencies were > 0.85. The algorithms recognized the importance of several known site, electronic, and steric effects in the two classes. A predictive QSAR (R(2)=0.98) was developed for combretastatin A-2 and dihydrocombretastatin analogues. The MultiCASE/CASE analyzes were used in combination with molecular models to study relative orientations of colchicine, podophyllotoxin, combretastatin A-4, and steganacin at the colchicine site. This resulted in a new hypothesis, consistent with extensive published experimental data, in which the C-ring and part of the B-ring of colchicine overlap with the A- and B-rings of podophyllotoxin. Consequently, the trimethoxyphenyl rings of colchicine and podophyllotoxin occupied different regions of space, each pointing out from a hydrophobic 'core' occupied by the overlapping biophores. The molecular model of the highly potent combretastatin A-4 could fit into the model binding site in at least three different ways. The developed QSARs were used to identify the potent microtubule stabilizer discodermolide. Its identification, in concert with recently reported findings, suggest potential overlap in the colchicine and paclitaxel binding sites on tubulin. Copyright (C) 1996 Elsevier Science Ltd C1 UNIV PITTSBURGH,INST CANC,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA 15238. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,LAB MOL PHARMACOL,NATL INST HLTH,BETHESDA,MD 20892. UNIV PITTSBURGH,DEPT PHARMACEUT SCI,PITTSBURGH,PA 15238. FU NCI NIH HHS [CA-57288] NR 52 TC 52 Z9 53 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1996 VL 4 IS 10 BP 1659 EP 1671 DI 10.1016/0968-0896(96)00158-7 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA VU125 UT WOS:A1996VU12500010 PM 8931935 ER PT J AU Yu, D Iyer, RP Shaw, DR Lisziewicz, J Li, Y Jiang, ZW Roskey, A Agrawal, S AF Yu, D Iyer, RP Shaw, DR Lisziewicz, J Li, Y Jiang, ZW Roskey, A Agrawal, S TI Hybrid oligonucleotides: Synthesis, biophysical properties, stability studies, and biological activity SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID C-14-LABELED PHOSPHOROTHIOATE OLIGONUCLEOTIDE; OLIGODEOXYRIBONUCLEOSIDE PHOSPHOROTHIOATES; OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES; ANTISENSE OLIGONUCLEOTIDES; PHARMACOKINETICS; AGENTS; PHOSPHODIESTER; CLEAVAGE; ANALOGS; RATS AB We have designed and synthesized hybrid oligonucleotides 2-5, as analogues of oligodeoxynucleoside phosphorothioates, in an effort to have agents with improved 'antisense activity' with reduced phosphorothioate content. The hybrid oligonucleotides contain segments of 2'-O-methyl ribonucleoside phosphoric diesters and oligodeoxynucleoside phosphorothioates. Thus, compared with the 'all' phosphorothioate analogues 1 and 6, the analogues 2-5 showed significantly reduced effect on complement activation. In addition, thermal denaturation studies with complementary RNA revealed that the analogues 2-5 had higher T-m compared with that with oligodeoxynucleoside phosphorothioates. Additionally, the RNA component of the oligo/RNA duplex is efficiently cleaved by RNase H, the site of endonucleolytic cleavage being dictated by the length of the oligodeoxynucleoside phosphorothioate segment. Copyright (C) 1996 Elsevier Science Ltd C1 HYBRIDON INC,WORCESTER,MA 01605. UNIV ALABAMA,CTR COMPREHENS CANC,BIRMINGHAM,AL 35294. NCI,TUMOR CELL BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 35 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 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT PY 1996 VL 4 IS 10 BP 1685 EP 1692 DI 10.1016/0968-0896(96)00160-5 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA VU125 UT WOS:A1996VU12500013 PM 8931938 ER PT J AU Durell, SR Wallqvist, A AF Durell, SR Wallqvist, A TI Atomic-scale analysis of the solvation thermodynamics of hydrophobic hydration SO BIOPHYSICAL JOURNAL LA English DT Article ID FREE-ENERGY CALCULATIONS; MONTE-CARLO SIMULATIONS; MOLECULAR-DYNAMICS; LIQUID WATER; COMPUTER-SIMULATIONS; AQUEOUS-SOLUTION; POLYNOMIAL PATH; INTEGRATION; MODELS; CONVERGENCE AB Molecular dynamics simulations are used to model the transfer thermodynamics of krypton from the gas phase into water, Extra long, nanosecond simulations are required to reduce the statistical uncertainty of the calculated ''solvation'' enthalpy to an acceptable level. Thermodynamic integration is used to calculate the ''solvation'' free energy, which together with the enthalpy is used to calculate the ''solvation'' entropy, A comparison series of simulations are conducted using a single Lennard-Jones sphere model of water to identify the contribution of hydrogen bonding to the thermodynamic quantities. In contrast to the classical ''iceberg'' model of hydrophobic hydration, the favorable enthalpy change for the transfer process at room temperature is found to be due primarily to the strong van der Waals interaction between the solute and solvent, Although some stabilization of hydrogen bonding does occur in the solvation shell, this is overshadowed by a destabilization due to packing constraints. Similarly, whereas some of the unfavorable change in entropy is attributed to the reduced rotational motion of the solvation shell waters, the major component is due to a decrease in the number of positional arrangements associated with the translational motions. C1 SCI APPLICAT INT CORP, NCI, FREDERICK CANC RES & DEV CTR, MATH BIOL LAB, FREDERICK, MD 21702 USA. RP NCI, NIH,MATH BIOL LAB,BLDG 12B,RM B116, 12 S DR, BETHESDA, MD 20892 USA. OI wallqvist, anders/0000-0002-9775-7469 NR 40 TC 32 Z9 32 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1996 VL 71 IS 4 BP 1695 EP 1706 PG 12 WC Biophysics SC Biophysics GA VK295 UT WOS:A1996VK29500004 PM 8889147 ER PT J AU Arispe, N Rojas, E Genge, BR Wu, LNY Wuthier, RE AF Arispe, N Rojas, E Genge, BR Wu, LNY Wuthier, RE TI Similarity in calcium channel activity of annexin V and matrix vesicles in planar lipid bilayers SO BIOPHYSICAL JOURNAL LA English DT Article ID GROWTH-PLATE CARTILAGE; NUCLEATIONAL CORE COMPLEX; BINDING-PROTEINS; MEDIATED MINERALIZATION; EPIPHYSEAL CARTILAGE; ALKALINE-PHOSPHATASE; SELECTIVITY FILTER; ION SELECTIVITY; ANCHORIN-CII; METAL-IONS AB Matrix vesicles (MVs), structures that accumulate Ca2+ during the initiation of mineral formation in growing bone, are rich in annexin V. When MVs are fused with planar phospholipid bilayers, a multiconductance Ca2+ channel is formed, with activity essentially identical to that observed when annexin V is delivered to the bilayer with phosphatidylserine liposomes. Ca2+ currents through this channel, from either MV or annexin V liposomes, are blocked by Zn2+, as is Ca2+ uptake by MV incubated in synthetic cartilage lymph. Blockage by Zn2+ was most effective when applied to the side containing the MV or liposomes. ATP and GTP differentially modulated the activity of this channel: ATP increased the amplitude of the current and the number of conductance states; GTP dramatically reduced the number of events and conductance states, leading to well-defined Ca2+ channel activity from either MV or the annexin V liposomes. In the distinctive effects of ATP, GTP, and Zn2+ on the Ca2+ channel activity observed in both the MV and the liposome systems, the common factor was the presence of annexin V. From this we conclude that Ca2+ entry into MV results from the presence of annexin V in these membrane-enclosed structures. C1 UNIV S CAROLINA,LAB BIOMINERALIZAT RES,DEPT CHEM & BIOCHEM,COLUMBIA,SC 29208. UNIV S CAROLINA,SCH MED,LAB BIOMINERALIZAT RES,COLUMBIA,SC 29208. NIDDKD,NIH,CELL BIOL & GENET LAB,BETHESDA,MD 20892. FU NIAMS NIH HHS [AR-18983] NR 39 TC 63 Z9 64 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 1996 VL 71 IS 4 BP 1764 EP 1775 PG 12 WC Biophysics SC Biophysics GA VK295 UT WOS:A1996VK29500010 PM 8889153 ER PT J AU Carra, JH Murphy, EC Privalov, PL AF Carra, JH Murphy, EC Privalov, PL TI Thermodynamic effects of mutations on the denaturation of T4 lysozyme SO BIOPHYSICAL JOURNAL LA English DT Article ID STAPHYLOCOCCAL NUCLEASE DENATURATION; DIFFERENTIAL SCANNING CALORIMETRY; AMINO-ACID INSERTIONS; PHAGE-T4 LYSOZYME; ALPHA-HELIX; MUTANT FORMS; PROTEIN; T4-LYSOZYME; STABILITY; STATE AB We investigated the folding of substantially destabilized mutant forms of T4 lysozyme using differential scanning calorimetry and circular dichroism measurements. Three mutations in an alpha-helix in the protein's N-terminal region, the alanine insertion mutations S44[A] and K48[A], and the substitution A42K had previously been observed to result in unexpectedly low apparent enthalpy changes of melting, compared to a pseudo-wild-type reference protein. The pseudo-wild-type reference protein thermally unfolds in an essentially two-state manner. However, we found that the unfolding of the three mutant proteins has a reduced cooperativity, which partially explains their lower apparent enthalpy changes. A three-state unfolding model including a discrete intermediate is necessary to describe the melting of the mutant proteins. The reduction in cooperativity must be considered for accurate calculation of the energy changes of folding, Unfolding in two stages reflects the underlying two-subdomain structure of the lysozyme protein family. C1 JOHNS HOPKINS UNIV,DEPT BIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,CTR BIOCALORIMETRY,BALTIMORE,MD 21218. NAT INST ARTHRIT DIABET & DIGEST & KIDNEY DIS,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 48036] NR 30 TC 14 Z9 15 U1 0 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 OCT PY 1996 VL 71 IS 4 BP 1994 EP 2001 PG 8 WC Biophysics SC Biophysics GA VK295 UT WOS:A1996VK29500030 PM 8889173 ER EF