FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mimnaugh, EG Chavany, C Neckers, L AF Mimnaugh, EG Chavany, C Neckers, L TI Polyubiquitination and proteasomal degradation of the p185(c-erbB-2) receptor protein-tyrosine kinase induced by geldanamycin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-PRODUCT P185; HERBIMYCIN-A; BENZOQUINOID ANSAMYCINS; HETEROPROTEIN COMPLEX; STRESS PROTEINS; UBIQUITIN; PATHWAY; INHIBITION; TRANSFORMATION; AMPLIFICATION AB Treatment of SKBr3 human breast carcinoma cells with the benzoquinoid ansamycin, geldanamycin, rapidly depletes p185(c-erbB-2) protein-tyrosine kinase. Loss of p185(c-erbB-2) is initiated by disruption of a heteromeric complex between p185(c-erbB-2) and the 94-kDa glucose-regulated protein, GRP94, to which geldanamycin binds avidly. Here we report that within minutes of exposure to geldanamycin, mature p185(c-erb-2) becomes polyubiquitinated. Treatment of cells with the specific proteasome proteolytic inhibitor, lactacystin, blocked geldanamycin-induced degradation of p185(c-erbB-2) and enhanced the accumulation of polyubiquitinated p185(c-erbB-2). Following geldanamycin and lactacystin treatment, a higher molecular weight form of p185(c-erbB-2), which likely represents ubiquitin-p185(c-erbB-2) conjugates, was detected by anti-p185(c-erbB-2) immunoblotting. Nascent p185(c-erbB-2) synthesized in the presence of geldanamycin is incompletely glycosylated and remains sequestered in the endoplasmic reticulum. While this immature form of the protein is not ubiquitinated in the presence of geldanamycin, its marked, drug-induced instability is nonetheless antagonized by lactacystin. Thus, the rapid depletion of mature p185(c-erbB-2) caused by geldanamycin and the marked, drug-stimulated decrease in half-life of the newly synthesized protein are both mediated by the proteasome, although only the former phenomenon involves polyubiquitination. RP Mimnaugh, EG (reprint author), NCI,CLIN PHARMACOL BRANCH,NIH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 32 TC 353 Z9 358 U1 1 U2 7 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 SEP 13 PY 1996 VL 271 IS 37 BP 22796 EP 22801 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG672 UT WOS:A1996VG67200075 PM 8798456 ER PT J AU Hou, XH Dietrich, J Odum, N Geisler, C AF Hou, XH Dietrich, J Odum, N Geisler, C TI The cytoplasmic tail of Fc gamma RIIIA alpha is involved in signaling by the low affinity receptor for immunoglobulin G SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; PROTEIN-TYROSINE KINASE; EPSILON-RI-GAMMA; T-CELL; ZETA-CHAIN; PHOSPHATASE CD45; CD3-GAMMA CHAIN; MAST-CELLS; IGG FC AB The low affinity receptor for IgG, Fc gamma RIIIA, is a multimeric receptor composed of the ligand binding subunit Fc gamma RIIIA alpha (CD16) in association with the signal-transducing subunits zeta or gamma. Previous studies suggested that the cytoplasmic tail of Fc gamma RIIIA alpha was not required for Fc gamma RIIIA alpha-zeta association or signaling by Fc gamma RIIIA. However, in these studies,the truncated Fc gamma RIIIA alpha chains still expressed the four most membrane-proximal amino acids of the cytoplasmic tail (amino acids 230-233). By successive truncations from the C terminus of Fc gamma RIIIA alpha, we have studied the role played by the membrane-proximal amino acids of the cytoplasmic tail of Fc gamma RIIIA alpha in (i) Fc gamma RIIIA expression, (ii) Fc gamma RIIIA alpha-zeta association, and (iii) signal transduction. We provide evidence that this region is not required for Fc gamma RIIIA expression or Fc gamma RIIIA alpha-zeta association. However, signaling by Fc gamma RIIIA is strictly dependent on the membrane-proximal amino acids in the cytoplasmic tail of Fc gamma RIIIA alpha. Thus, total deletion of the cytoplasmic tail of Fc gamma RIIIA alpha results in a severely impaired tyrosine phosphorylation of phospholipase C-gamma 1, zap, and syk and rise in intracellular free Ca2+ following receptor ligation with specific anti-CD16 monoclonal antibody or Ig-anti-Ig complexes, suggesting that Fc gamma RIIIA alpha-zeta association per se is not sufficient to establish the signal function of Fc gamma RIIIA. In conclusion, the present findings demonstrate that the most membrane-proximal amino acids of the Fc gamma RIIIA alpha cytoplasmic tail play a critical role in ligand-induced signal transduction by the Fc gamma RIIIA alpha-zeta complex. C1 UNIV COPENHAGEN,PANUM INST,INST MED MICROBIOL & IMMUNOL,DK-2200 COPENHAGEN,DENMARK. NIAID,MOL STRUCT LAB,NIH,ROCKVILLE,MD 20892. RI Geisler, Carsten/A-7056-2012 NR 51 TC 12 Z9 12 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 SEP 13 PY 1996 VL 271 IS 37 BP 22815 EP 22822 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG672 UT WOS:A1996VG67200078 PM 8798459 ER PT J AU Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Phillips, ML Kempner, ES Wong, H AF Hill, JS Davis, RC Yang, D Wen, J Philo, JS Poon, PH Phillips, ML Kempner, ES Wong, H TI Human hepatic lipase subunit structure determination SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LIPOPROTEIN-LIPASE; HIGH-DENSITY-LIPOPROTEINS; RECEPTOR-RELATED PROTEIN; AMINO-ACID SEQUENCE; TRIGLYCERIDE LIPASE; RADIATION INACTIVATION; PANCREATIC LIPASE; RAT-LIVER; CHIMERIC LIPASE; MOLECULAR-SIZE AB Chinese hamster ovary cells were stably transfected with a human hepatic lipase (HL) cDNA. The recombinant enzyme was purified from culture medium in milligram quantities and shown to have a molecular weight, specific activity, and heparin affinity equivalent to HL present in human post-heparin plasma. The techniques of intensity light scattering, sedimentation equilibrium, and radiation inactivation were employed to assess the subunit structure of HL. For intensity light scattering, purified enzyme was subjected to size exclusion chromatography coupled to three detectors in series: an ultraviolet absorbance monitor, a differential refractometer, and a light scattering photometer. The polypeptide molecular weight (without carbohydrate contributions) was calculated using the measurements from the three detectors combined with the extinction coefficient of human HL. A single protein peak containing HL activity was identified and calculated to have a molecular mass of 107,000 in excellent agreement with the expected value for a dimer of HL (106.8 kDa). In addition, sedimentation equilibrium studies revealed that HL had a molecular mass (with carbohydrate contributions) of 121 kDa, Finally, to determine the smallest structural unit required for lipolytic activity, HL was subjected to radiation inactivation, Purified HL was exposed to various doses of high energy electrons at -135 degrees C; lipase activity decreased as a single exponential function of the radiation dose to less than 0.01% remaining activity, The target size of functional HL was calculated to be 109 kDa, whereas the size of the structural unit was determined to be 63 kDa. These data indicate that two HL monomer subunits are required for lipolytic activity, consistent with an HL homodimer. A model for active dimeric hepatic lipase is presented with implications for physiological function. C1 UNIV CALIF LOS ANGELES,DEPT MED,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,DEPT CHEM & BIOCHEM,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,INST MOL BIOL,LOS ANGELES,CA 90024. AMGEN INC,THOUSAND OAKS,CA 91320. NIAMS,PHYS BIOL LAB,NIH,BETHESDA,MD 20892. RP Hill, JS (reprint author), W LOS ANGELES VET AFFAIRS MED CTR,LIPID RES LAB,11301 WILSHIRE BLVD,BLDG 113,RM 312,LOS ANGELES,CA 90073, USA. RI Philo, John/A-8804-2009 OI Philo, John/0000-0003-3418-0356 FU NHLBI NIH HHS [HL28481] NR 48 TC 33 Z9 34 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 SEP 13 PY 1996 VL 271 IS 37 BP 22931 EP 22936 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VG672 UT WOS:A1996VG67200093 PM 8798474 ER PT J AU Rice, WG Turpin, JA Schaeffer, CA Graham, L Clanton, D Buckheit, RW Zaharevitz, D Summers, MF Wallqvist, A Covell, DG AF Rice, WG Turpin, JA Schaeffer, CA Graham, L Clanton, D Buckheit, RW Zaharevitz, D Summers, MF Wallqvist, A Covell, DG TI Evaluation of selected chemotypes in coupled cellular and molecular target-based screens identifies novel HIV-1 zinc finger inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEOCAPSID PROTEIN; STRAND TRANSFER; REVERSE TRANSCRIPTION; RNA; SEQUENCE; BINDING; INFECTIVITY; MUTATIONS; MUTANTS AB Conservation of the Cys-Xaa(2)-Cys-Xaa(4)-His-Xaa(4)-Cys retroviral zinc finger sequences and their absolute requirement in both the early and late phases of retroviral replication make these chemically reactive structures prime antiviral targets. We recently reported that select 2,2'-dithiobisbenzamides (DIBAs) chemically modify the zinc finger Cys residues, resulting in release of zinc from the fingers and inhibition of HIV replication. In the current study we surveyed 21 categories of disulfide-based compounds from the chemical repository of the National Cancer Institute for their capacity to act as retroviral zinc finger inhibitors. Aromatic disulfides that exerted anti-HIV activity tended to cluster in the substituted aminobenzene, benzoate, and benzenesulfonamide disulfide subclasses. Only one thiuram derivative exerted moderate anti-HIV activity, while a number of nonaromatic thiosulfones and miscellaneous disulfide congeners were moderately antiviral. Two compounds (NSC 20625 and NSC 4493) demonstrated anti-HIV activity in proliferating T cell cultures and in nonproliferating monocyte/macrophage cultures. The two compounds chemically modified the p7NC zinc fingers in two separate in vitro assays, and interatomic surface molecular modeling docked the compounds efficiently but differentially into the zinc finger domains. The combined efforts of rational drug selection, cell-based screening, and molecular target-based screening led to the identification of zinc finger inhibitors that can now be optimized by medicinal chemistry for the development of biopharmaceutically useful anti-HIV agents. C1 NCI,FREDERICK CANC RES & DEV CTR,ANTI AIDS VIRUS DRUG SCREENING LAB,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21702. UNIV MARYLAND,DEPT CHEM & BIOCHEM,BALTIMORE,MD 21228. NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC SCI,SAIC FREDERICK,FREDERICK,MD 21702. RP Rice, WG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ANTIVIRAL DRUG MECH LAB,DEV THERAPEUT PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. OI wallqvist, anders/0000-0002-9775-7469 FU PHS HHS [N01-C0-56000] NR 32 TC 63 Z9 65 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 SEP 13 PY 1996 VL 39 IS 19 BP 3606 EP 3616 DI 10.1021/jm960375o PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VG688 UT WOS:A1996VG68800002 PM 8809151 ER PT J AU Marquez, VE Siddiqui, MA Ezzitouni, A Russ, P Wang, JY Wagner, RW Matteucci, MD AF Marquez, VE Siddiqui, MA Ezzitouni, A Russ, P Wang, JY Wagner, RW Matteucci, MD TI Nucleosides with a twist. Can fixed forms of sugar ring pucker influence biological activity in nucleosides and oligonucleotides? SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CARBOCYCLIC THYMIDINE; ANTIVIRAL ACTIVITY; NEPLANOCIN-C; ANALOGS; CRYSTAL; INHIBITORS; URACIL AB The sugar moiety of nucleosides in solution is known to exist in a rapid dynamic equilibrium between extreme Northern and Southern conformations as defined in the pseudorotational cycle. In the present work, we describe how the bicyclo[3.1.0]hexane template fixes the ring pucker of 2'-deoxy-methanocarba-nucleosides 1-5 and 12 to values corresponding to either one of these two extreme conformations that are typical of nucleosides. The syntheses of the fixed Northern conformers 1-5 were performed by Mitsunobu coupling of the heterocyclic bases with the chiral carbocyclic alcohol 6 [(1R,2S,4R,5S)-1-[(benzyloxy)methyl]-2-(tert-butyloxy)4-hydroxybicyclo[3.1.0]hexane], while the synthesis of the Southern conformer, (S)-methanocarba-T (12), was reported earlier. Carbocyclic thymidine (carba-T, 13) was used as a reference, flexible carbocyclic nucleoside. Antiviral evaluation of these compounds revealed a very potent antiherpetic activity associated with the Northern thymidine analogue 2, which was more powerful than the reference standard acyclovir against both HSV-1 and HSV-2. (N)-Methanocarba-T (2) was further evaluated as a component of a short oligodeoxynucleotide (ODN) phosphorothioate (5'-CTTCATTTTTTCTTC-3') where all thymidines were replaced by 2. The expected thermodynamic stability resulting from the preorganization of the pseudosugar rings into a Northern conformation, typical of A-DNA, was evident by the increase in T-m of the corresponding DNA/RNA heteroduplex. However, the rigid A-tract ODN caused loss of RNase H recruitment. A detailed conformational analysis of (N)-methanocarba-T (2) and (S)-methanocarba-T (12), as representative examples of conformationally rigid pseudorotational antipodes, revealed that in addition to their different forms of ring pucker, (S)-methanocarba-T appears to be a rather stiff molecule with fewer low-energy conformational states available compared to (N)-methanocarba-T. The syn/anti-energy barrier for these nucleoside analogues is 5-6 kcal/mol higher than for common nucleosides. C1 GILEAD SCI,FOSTER CITY,CA. RP Marquez, VE (reprint author), NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892, USA. NR 32 TC 229 Z9 231 U1 1 U2 8 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 SEP 13 PY 1996 VL 39 IS 19 BP 3739 EP 3747 DI 10.1021/jm960306+ PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA VG688 UT WOS:A1996VG68800013 PM 8809162 ER PT J AU Kligerman, AD Morgan, DL Doerr, CL Milholland, V Tennant, AH AF Kligerman, AD Morgan, DL Doerr, CL Milholland, V Tennant, AH TI Cytogenetic effects in mice of divinylbenzene-55 inhalation SO MUTATION RESEARCH-GENETIC TOXICOLOGY LA English DT Article DE divinylbenzene; cytogenetics; mouse; styrene ID MUTAGENICITY; STYRENE AB Male B6C3F1 mice (8 weeks of age) were exposed by inhalation to divinylbenzene-55 (DVB-55), at target concentrations of 0, 25, 50 and 75 ppm for 6 h per day for 3 days. Following exposure the animals were killed, blood smears were prepared for micronucleus (MN) analysis, and the spleens were removed and cultured for sister chromatid exchange (SCE) and chromosome aberration (CA) analyses. DVB-55 induced a dose-dependent increase in SCE with the two highest doses reaching statistical significance. Similarly, there was a statistically significant although less pronounced increase in the frequency of CAs in splenocytes and MN in polychromatic erythrocytes. There was no indication of toxicity as measured by cell cycle kinetics in the splenocytes or the percentage of polychromatic erythrocytes in the peripheral blood smears. Thus, DVB-55 appears to be a weak genotoxicant in vivo. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP Kligerman, AD (reprint author), US EPA,DIV ENVIRONM CARCINOGENESIS,MAIL DROP 68,RES TRIANGLE PK,NC 27711, USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1218 J9 MUTAT RES-GENET TOX JI Mutat. Res.-Genet. Toxicol. PD SEP 13 PY 1996 VL 370 IS 2 BP 107 EP 113 DI 10.1016/0165-1218(96)00050-X PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA VM859 UT WOS:A1996VM85900005 PM 8879268 ER PT J AU Fleckenstein, AE Kopajtic, TA Boja, JW Carroll, FI Kuhar, MJ AF Fleckenstein, AE Kopajtic, TA Boja, JW Carroll, FI Kuhar, MJ TI Highly potent cocaine analogs cause long-lasting increases in locomotor activity SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine analog; behavior; dopamine transporter ID DOPAMINE TRANSPORTER; HIGH-AFFINITY; REUPTAKE SITES; AMFONELIC ACID; PRIMATE BRAIN; BINDING; TOMOGRAPHY; HYPOTHESIS; SEROTONIN; RECEPTOR AB Three cocaine analogs were compared with cocaine for the capacity to affect: (1) dopamine transporter binding and function; and (2) locomotor activity. RTI-55 (3 beta-[4-iodophenyl]tropane-2 beta-carboxylic acid methyl ester tartrate), RTI-121 (3 beta-[4-iodophenyl]tropan-2 beta-carboxylic acid isopropyl ester hydrochloride) and RTI-130 (3 beta-[4-chlorophenyl-2 beta-[1,2,4-oxadiazol-3-phenyl-5-yl]tropane hydrochloride) competed for [H-3]WIN 35428 binding in rat striatum in vitro, with IC50 values at least 50-fold less than that of cocaine. These analogs inhibited [H-3]dopamine transport into rat striatal synaptosomes, with IC50 values again less (at least 100-fold) than that for cocaine. Intravenous RTI-55, RTI-121 or RTI-130 injection effected dose-related increases in locomotor activity in mice, with estimated relative potencies at least 10-fold greater than that of cocaine. These increases were long lasting: whereas increased activity ceased within 2 h after cocaine administration, increased locomotion was observed at least 10 h after RTI-55, RTI-121, or RTI-130 administration. Parallel line analysis indicated that the slopes of the ascending portion of the RTI-121 and RTI-130 dose-response curves differed from that of cocaine, suggesting the involvement of mechanisms different from that of cocaine. C1 EMORY UNIV,YERKES REG PRIMATE RES CTR,DIV NEUROSCI,ATLANTA,GA 30322. NIDA,INTRAMURAL RES PROGRAM,NIH,BALTIMORE,MD. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NR 27 TC 34 Z9 34 U1 2 U2 3 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 SEP 12 PY 1996 VL 311 IS 2-3 BP 109 EP 114 DI 10.1016/0014-2999(96)00423-2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ942 UT WOS:A1996VJ94200002 PM 8891589 ER PT J AU Mousa, SA Schafer, M Mitchell, WM Hassan, AHS Stein, C AF Mousa, SA Schafer, M Mitchell, WM Hassan, AHS Stein, C TI Local upregulation of corticotropin-releasing hormone and interleukin-1 receptors in rats with painful hindlimb inflammation SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE neuro-immune interaction; analgesia; nociception; opioid; neuropeptide; cytokine ID INFLAMED TISSUE; OPIOID-PEPTIDES; GENE-EXPRESSION; BETA-ENDORPHIN; IMMUNE CELLS; MOUSE SPLEEN; IDENTIFICATION; LOCALIZATION; BINDING; IL-1 AB Opioid peptides derived from immune cells produce analgesia by activating opioid receptors on peripheral sensory nerves in inflammation. Corticotropin-releasing hormone (CRH) and interleukin-1 beta (IL-1 beta) can release these opioids. Here we show that both corticotropin-releasing hormone and interleukin-1 beta elicit receptor-specific antinociception in inflamed paws of rats by an opioid-mediated mechanism. Autoradiographic studies demonstrate I-125-CRH and I-125-IL-1 beta binding sites on immune cells in lymph nodes and inflamed paws. This binding is of high affinity and displaceable by the respective unlabeled agonist and antagonist ligands but not by opioid or adrenergic compounds. I-125-CRH and I-125-IL-1 beta binding sites are absent on nerves and in non-inflamed subcutaneous tissue but their number is greatly enhanced in inflamed paws and lymph nodes. This upregulation of binding sites for the opioid-releasing agents corticotropin-releasing hormone and interleukin-1 beta likely represents part of the body's local response to combat inflammatory pain. C1 NIH,PRECLIN PHARMACOL LLAB,DIV INTRAMURAL RES,NIDA,BALTIMORE,MD 21224. NIDA,NEUROSCI BRANCH,DIV INTRAMURAL RES,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. OI Stein, Christoph/0000-0001-5240-6836 FU NINDS NIH HHS [R01 NS32466] NR 36 TC 55 Z9 55 U1 0 U2 0 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 SEP 12 PY 1996 VL 311 IS 2-3 BP 221 EP 231 DI 10.1016/0014-2999(96)00440-2 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ942 UT WOS:A1996VJ94200016 PM 8891603 ER PT J AU Watson, N Linder, ME Druey, KM Kehrl, JH Blumer, KJ AF Watson, N Linder, ME Druey, KM Kehrl, JH Blumer, KJ TI RGS family members: GTPase-activating proteins for heterotrimeric G-protein alpha-subunits SO NATURE LA English DT Article ID LIPID MODIFICATIONS; CRYSTAL-STRUCTURE; BETA-GAMMA; MECHANISM; HYDROLYSIS; TRANSDUCIN; DEACTIVATION; DESENSITIZATION; INCREASES; AFFINITY AB SIGNALLING pathways using heterotrimeric guanine-nucleotide-binding-proteins (G proteins) trigger physiological responses elicited by hormones, neurotransmitters and sensory stimuli(1,2) GTP binding activates G proteins by dissociating G alpha from G beta gamma subunits, and GTP hydrolysis by G alpha subunits deactivates G proteins by allowing heterotrimers to reform. However, deactivation of G-protein signalling pathways in vivo can occur 10- to 100-fold faster than the rate of GTP hydrolysis of G alpha subunits in vitro(3-8), suggesting that GTPase-activating proteins (GAPs) deactivate G alpha subunits. Here we report that RGS(9,10) (for regulator of G-protein signalling) proteins are GAPs for G alpha subunits. RGS1, RGS4 and GAIP (for G alpha-interacting protein(17)) bind specifically and tightly to G alpha(i) and G alpha(o) in cell membranes treated with GDP and AIF(4)(-), and are GAPs for G alpha(i), G alpha(o) and transducin alpha-subunits, but not for G alpha(s). Thus, these RGS proteins are likely to regulate a subset of the G-protein signalling pathways in mammalian cells. Our results provide insight into the mechanisms that govern the duration and specificity of physiological responses elicited by G-protein-mediated signalling pathways. C1 WASHINGTON UNIV,SCH MED,DEPT CELL BIOL & PHYSIOL,ST LOUIS,MO 63110. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Blumer, Kendall/C-5268-2012 NR 30 TC 422 Z9 424 U1 2 U2 12 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD SEP 12 PY 1996 VL 383 IS 6596 BP 172 EP 175 DI 10.1038/383172a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VG148 UT WOS:A1996VG14800053 PM 8774882 ER PT J AU Stanley, SK Ostrowski, MA Fauci, AS AF Stanley, SK Ostrowski, MA Fauci, AS TI The effects of immunization in human immunodeficiency virus type 1 infection - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID REPLICATION; VACCINATION; ACTIVATION RP Stanley, SK (reprint author), NIAID,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 4 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 SEP 12 PY 1996 VL 335 IS 11 BP 818 EP 819 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VF786 UT WOS:A1996VF78600013 ER PT J AU Cobb, JP Danner, RL AF Cobb, JP Danner, RL TI Nitric oxide and sepsis - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH,BETHESDA,MD 20892. RP Cobb, JP (reprint author), WASHINGTON UNIV,ST LOUIS,MO 63130, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 11 PY 1996 VL 276 IS 10 BP 781 EP 782 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VF219 UT WOS:A1996VF21900017 ER PT J AU Barker, LF Shulman, NR Roderick, MD Hirschman, RJ Ratner, F Diefenbach, WCL Geller, HM AF Barker, LF Shulman, NR Roderick, MD Hirschman, RJ Ratner, F Diefenbach, WCL Geller, HM TI Transmission of serum hepatitis (Reprinted from JAMA, vol 211, pg 1509, 1970) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint AB There is evidence that transmission of serum hepatitis is associated with transmission of virus-like particles, approximately 20 my in diameter, containing the Australia or serum hepatitis (SH) antigen, which is currently referred to as the hepatitis associated antigen (HAA). Virus-like particles containing HAA were in the following materials, inoculation of which produced serum hepatitis: (1) a pool of human plasma, (2) serum obtained during the acute phase of hepatitis from a recipient of the plasma pool, (3) a preparation of human thrombin, and (4) serum from a proved hepatitis carrier. The HAA appeared in the serum samples of 61 individuals inoculated with these materials; serum hepatitis developed in 38 of them. Inoculation of dilutions of the plasma pool showed that serum hepatitis can be transmitted by materials containing HAA in amounts too low to be detected by current techniques. C1 DIV BIOL STAND,BETHESDA,MD. NIAMD,BETHESDA,MD. NIH,BETHESDA,MD 20014. NR 19 TC 10 Z9 10 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 11 PY 1996 VL 276 IS 10 BP 841 EP 844 DI 10.1001/jama.276.10.841 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA VF219 UT WOS:A1996VF21900037 PM 8769597 ER PT J AU Reszka, KJ Bilski, P Chignell, CF AF Reszka, KJ Bilski, P Chignell, CF TI EPR and spin trapping investigations of nitric oxide (center dot NO) from UV irradiated nitrite anions in alkaline aqueous solutions SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RADICALS; NITROMETHANE RP Reszka, KJ (reprint author), NIEHS,MOL BIOPHYS LAB,NIH,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 20 Z9 21 U1 0 U2 2 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 SEP 11 PY 1996 VL 118 IS 36 BP 8719 EP 8720 DI 10.1021/ja960922v PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VG351 UT WOS:A1996VG35100030 ER PT J AU Ross, G Erickson, R Knorr, D Motulsky, AG Parkman, R Samulski, J Straus, SE Smith, BR AF Ross, G Erickson, R Knorr, D Motulsky, AG Parkman, R Samulski, J Straus, SE Smith, BR TI Gene therapy in the United States: A five-year status report SO HUMAN GENE THERAPY LA English DT Article ID AUTOLOGOUS BONE-MARROW; CYSTIC-FIBROSIS; CELLS; MELANOMA; TRANSPLANTATION; MARKING; IMMUNOTHERAPY; ENGRAFTMENT; LYMPHOCYTES; ADENOVIRUS C1 YALE UNIV,SCH MED,DEPT LAB MED,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT PEDIAT,NEW HAVEN,CT 06520. NEW YORK HOSP,PERINATOL CTR,NEW YORK,NY 10021. UNIV ARIZONA,DEPT PEDIAT,TUCSON,AZ 85724. UNIV ARIZONA,DEPT MOL & CELLULAR BIOL,TUCSON,AZ 85724. NIH,OFF RECOMBINANT DNA ACTIVITIES,BETHESDA,MD 20892. UNIV WASHINGTON,SCH MED,DEPT MED,SEATTLE,WA 98195. UNIV WASHINGTON,SCH MED,DEPT GENET,SEATTLE,WA 98195. CHILDRENS HOSP LOS ANGELES,DIV IMMUNOL RES,LOS ANGELES,CA 90027. UNIV N CAROLINA,GENE THERAPY CTR,CHAPEL HILL,NC 27599. NIH,LAB CLIN INVEST ALLERGY & INFECT DIS,BETHESDA,MD 20892. NR 28 TC 93 Z9 95 U1 1 U2 9 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP 10 PY 1996 VL 7 IS 14 BP 1781 EP 1790 DI 10.1089/hum.1996.7.14-1781 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA WD325 UT WOS:A1996WD32500013 PM 8886849 ER PT J AU Vasan, RS Levy, D AF Vasan, RS Levy, D TI The role of hypertension in the pathogenesis of heart failure - A clinical mechanistic overview SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID LEFT-VENTRICULAR HYPERTROPHY; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; ISOLATED SYSTOLIC HYPERTENSION; LONG-TERM PROGNOSIS; BLOOD-PRESSURE; DIASTOLIC FUNCTION; RISK-FACTORS; MILD HYPERTENSION; UNITED-STATES AB Hypertension plays a key role in the evolution of the syndrome of heart failure. Hypertension has been identified as the chief precursor of left ventricular hypertrophy. Hypertensive left ventricular hypertrophy can lead to ventricular diastolic dysfunction; it is also a risk factor for myocardial infarction, which is a principal cause of left ventricular systolic dysfunction, Asymptomatic left ventricular dysfunction, whether systolic or diastolic, culminates in clinically overt heart failure when a threshold is exceeded or when other precipitating factors are superimposed. The onset of overt heart failure heralds a bleak outcome. These structural and functional changes associated with hypertension evolve over decades and are preventable with effective antihypertensive treatment. These observations emphasize the importance of early diagnosis and effective treatment of hypertension to prevent cardiac complications. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, FRAMINGHAM, MA 01701 USA. BETH ISRAEL HOSP, DIV CARDIOL, BOSTON, MA 02215 USA. BETH ISRAEL HOSP, DIV CLIN EPIDEMIOL, BOSTON, MA USA. BOSTON UNIV, SCH MED, BOSTON, MA 02118 USA. NHLBI, BETHESDA, MD 20892 USA. OI Ramachandran, Vasan/0000-0001-7357-5970 NR 159 TC 140 Z9 145 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 9 PY 1996 VL 156 IS 16 BP 1789 EP 1796 DI 10.1001/archinte.156.16.1789 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VF627 UT WOS:A1996VF62700002 PM 8790072 ER PT J AU Sznajder, L Abrahams, C Parry, DM Gierlowski, TC ShoreFreedman, E Schneider, AB AF Sznajder, L Abrahams, C Parry, DM Gierlowski, TC ShoreFreedman, E Schneider, AB TI Multiple schwannomas and meningiomas associated with irradiation in childhood SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DOSE-RESPONSE RELATIONSHIPS; NERVE SHEATH TUMORS; NF2 GENE; NECK IRRADIATION; NEUROFIBROMATOSIS TYPE-2; SPORADIC MENINGIOMAS; LATE CONSEQUENCE; THYROID-CANCER; RADIATION; HEAD AB Objective: To determine the pattern of neural tumors (schwannomas, vestibular schwannomas [acoustic neuromas], and meningiomas) that developed in 3013 people who received radiation treatment with x-ray beam therapy for benign conditions of the head and neck area before their 16th birthday. Methods: The surgical and pathology reports and pathology slides were reviewed for all neural tumors in the cohort. Patients with more than 1 neural tumor were compared with those with 1 neural tumor and those with no neural tumors. Results: There were 7 patients with multiple neural tumors and 63 with single neural tumors. The distribution of tumors in these 2 groups differed. The group with multiple tumors had more spinal nerve root schwannomas, while the group with single tumors had more cranial nerve schwannomas. Six of the 7 patients did not meet the diagnostic criteria for neurofibromatosis type 2. Conclusions: Our findings suggest that host factors that increase susceptibility to radiation may be involved in the development of the multiple neural tumors. Clinically, patients with multiple neural tumors who do not meet the diagnostic criteria for neurofibromatosis type 2 should be questioned about radiation exposure. If exposure is confirmed, then screening for other radiation-related tumors should be initiated. C1 UNIV ILLINOIS, DEPT MED, CHICAGO, IL 60612 USA. UNIV CHICAGO, DEPT PATHOL, CHICAGO, IL 60637 USA. MICHAEL REESE HOSP & MED CTR, DEPT MED, CHICAGO, IL 60616 USA. NCI, NIH, GENET EPIDEMIOL BRANCH, BETHESDA, MD USA. OI Shore-Freedman, Eileen/0000-0001-6194-1814 FU NCI NIH HHS [CA-21518] NR 44 TC 41 Z9 42 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9926 EI 1538-3679 J9 ARCH INTERN MED JI Arch. Intern. Med. PD SEP 9 PY 1996 VL 156 IS 16 BP 1873 EP 1878 DI 10.1001/archinte.156.16.1873 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VF627 UT WOS:A1996VF62700013 PM 8790083 ER PT J AU Grattan, DR Rocca, MS Strauss, KI Sagrillo, CA Selmanoff, M McCarthy, MM AF Grattan, DR Rocca, MS Strauss, KI Sagrillo, CA Selmanoff, M McCarthy, MM TI GABAergic neuronal activity and mRNA levels for both forms of glutamic acid decarboxylase (GAD(65) and GAD(67)) are reduced in the diagonal band of Broca during the afternoon of proestrus SO BRAIN RESEARCH LA English DT Article DE gamma-aminobutyric acid turnover; gonadal steroid; gonadotropin-releasing hormone; hypothalamus; medial preoptic nucleus; rat ID HORMONE-RELEASING HORMONE; MEDIAL PREOPTIC AREA; LHRH-IMMUNOREACTIVE NEURONS; ANTERIOR HYPOTHALAMIC AREA; LUTEINIZING-HORMONE; FEMALE RAT; OVARIECTOMIZED RATS; RECEPTOR AGONISTS; PULSE-GENERATOR; GENE-EXPRESSION AB There is considerable evidence that GABAergic neurons play an important role in the regulation of gonadotropin-releasing hormone (GnRH) secretion, and that these neurons may mediate the feedback actions of gonadal steroids on GnRH neurons. The aim of the present study was to investigate whether endogenous changes in ovarian steroid secretion during the estrous cycle influenced GABAergic neuronal activity in the preoptic region of the hypothalamus, and in other steroid-sensitive brain regions, Intact, adult female rats were sacrificed at various times during the days of metestrus or proestrus, GABAergic neuronal activity was estimated by measuring the rate of accumulation of GABA in microdissected brain regions after pharmacological inhibition of GABA degradation. Concentrations of mRNA for both forms of glutamic acid decarboxylase (GAD(65) and GAD(67)) were quantified in microdissected brain regions by a microlysate ribonuclease protection assay. In the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis (DBB(ovlt)), GABAergic neuronal activity was significantly reduced during the afternoon of proestrus compared with the morning of either proestrus or metestrus. in the lateral septal nucleus, GABAergic neuronal activity was significantly increased in the afternoon of proestrus compared with the morning. There were no significant effects of time of day or day of estrous cycle in the medial preoptic nucleus, median eminence, ventromedial nucleus, suprachiasmatic nucleus, medial septal nucleus, hippocampus (CA1 region), or cingulate cortex. in the DBB(ovlt), mRNA levels for both GAD(65) and GAD(67) were significantly reduced in the afternoon of proestrus compared with the afternoon of metestrus. By contrast, there was no change in GAD(65) and GAD(67), mRNA levels in the cingulate cortex at any of the times examined. These results demonstrate that GABAergic neuronal activity, and mRNA levels for both GAD(65) and GAD(67), are reduced in the DBB(ovlt) during the afternoon of proestrus. These results support the hypothesis that decreased GABAergic neuronal activity in this region plays a major permissive role in the generation and maintenance of the estrogen-induced LH surge. C1 UNIV MARYLAND, SCH MED, DEPT PHYSIOL, CTR STUDIES REPROD, BALTIMORE, MD 21201 USA. NIMH, CLIN SCI LAB, BETHESDA, MD 20892 USA. OI Grattan, Dave/0000-0001-5606-2559 FU NICHD NIH HHS [HD-21351] NR 55 TC 64 Z9 64 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 9 PY 1996 VL 733 IS 1 BP 46 EP 55 DI 10.1016/S0006-8993(96)00532-X PG 10 WC Neurosciences SC Neurosciences & Neurology GA VJ894 UT WOS:A1996VJ89400007 PM 8891247 ER PT J AU Galkina, SI Sudina, GF Margolis, LB AF Galkina, SI Sudina, GF Margolis, LB TI Regulation of intracellular pH by phospholipase A2 and protein kinase C upon neutrophil adhesion to solid substrata SO FEBS LETTERS LA English DT Article DE intracellular pH; adhesion; phospholipase A2; protein kinase C; arachidonic acid; neutrophil ID CELL-ADHESION; H+-ATPASE; ACTIVATION; MACROPHAGES; MODULATION; INHIBITION; EXPRESSION; SECRETION; APOPTOSIS; EXCHANGE AB Adhesion to solid substrata has been shown to increase intracellular pH (pH(i)) of fibroblasts and of other cells (FEBS Lett, (1988) 234, 449-450; Proc, Natl, Acad, Sci, USA (1989) 86, 4525-4529; J. Biol, Chem, (1990) 265, 1327-1332; Exp, Cell Res, (1992) 200, 211-214; FEES Lett, (1995) 374, 17-20), We have found that the inhibitors of PLA2, 4-bromophenacyl bromide and manoalide, completely blocked the increase of pH(i) and spreading of neutrophils upon adhesion to solid substrata, Inhibition of phospholipase C with neomycin or removal of extracellular Ca2+ affects neither neutrophil spreading nor their pH(i), Inhibition of PKC with H-7 or staurosporin increased pH(i), PMA, an activator of PKC, dramatically decreased pH(i) but did not impair the spreading of neutrophils. The effect of arachidonic acid, a product of PLA2 activity, on neutrophil pH(i) and spreading was similar to that of PMA, H-7, an inhibitor of PKC, partially blocked the effect of arachidonic acid (AA) on pH(i). BW755C, an inhibitor of AA metabolism by cyclooxygenase or lipoxygenase, affected neither the pH(i) nor cell spreading, We propose that the increase of pH(i) upon neutrophil adhesion is mediated by PLA2 activity, while PKC decreased pH(i). AA produced by PLA2 activates PKC, thus forming a feedback regulation of pH(i). C1 NICHHD,NIH,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. RP Galkina, SI (reprint author), MOSCOW MV LOMONOSOV STATE UNIV,AN BELOZERSKY INST PHYSICOCHEM BIOL,MOSCOW 119899,RUSSIA. RI Galkina, Svetlana/E-4025-2012; Sud'ina, Galina/E-1053-2012 OI Sud'ina, Galina/0000-0001-7711-3167 NR 31 TC 11 Z9 11 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 SEP 9 PY 1996 VL 393 IS 1 BP 117 EP 120 DI 10.1016/0014-5793(96)00864-2 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VG892 UT WOS:A1996VG89200027 PM 8804438 ER PT J AU Solomon, DA Shea, MT Leon, AC Mueller, TI Coryell, W Maser, JD Endicott, J Keller, MB AF Solomon, DA Shea, MT Leon, AC Mueller, TI Coryell, W Maser, JD Endicott, J Keller, MB TI Personality traits in subjects with bipolar I disorder in remission SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar I disorder; personality trait; personality testing ID SELF-ESTEEM; UNIPOLAR; LITHIUM; ATTRIBUTES; DEPENDENCY; DEPRESSION; THERAPY; MMPI AB This study compared the personality traits of subjects with bipolar I disorder in remission to the personality traits of subjects with no history of any mental illness. Subjects were assessed as part of a prospective, multicenter, naturalistic study of mood disorders, Diagnoses were rendered according to Research Diagnostic Criteria, through use of the Schedule for Affective Disorders and Schizophrenia - Lifetime Version. A total of 30 euthymic bipolar I subjects were compared to 974 never-ill subjects on 17 personality scales selected for their relevance to mood disorders. The subjects with bipolar I disorder in remission had more aberrant scores on 6 of the 17 personality measures, including Emotional Stability, Objectivity, Neuroticism, Ego Resiliency, Ego Control, and Hysterical Factor. These findings indicate that patients with bipolar I disorder in remission have personality traits that differ from those of normal controls. C1 BROWN UNIV,DEPT PSYCHIAT & HUMAN BEHAV,PROVIDENCE,RI 02906. CORNELL UNIV,DEPT PSYCHIAT,NEW YORK,NY 10021. UNIV IOWA,COLL MED,DEPT PSYCHIAT,IOWA CITY,IA 52242. NIMH,BETHESDA,MD 20857. NEW YORK STATE PSYCHIAT INST & HOSP,DEPT RES & TRAINING,NEW YORK,NY 10032. FU NIMH NIH HHS [R01 MH025478] NR 37 TC 36 Z9 36 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD SEP 9 PY 1996 VL 40 IS 1-2 BP 41 EP 48 DI 10.1016/0165-0327(96)00039-0 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VG571 UT WOS:A1996VG57100006 PM 8882913 ER PT J AU Juiz, JM Helfert, RH Bonneau, JM Wenthold, RJ Altschuler, RA AF Juiz, JM Helfert, RH Bonneau, JM Wenthold, RJ Altschuler, RA TI Three classes of inhibitory amino acid terminals in the cochlear nucleus of the guinea pig SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE auditory; immunocytochemistry; GABA; glycine; co-localization ID STEM AUDITORY NUCLEI; SUPERIOR OLIVARY COMPLEX; BRAIN-STEM; GLYCINE-IMMUNOREACTIVITY; IMMUNOCYTOCHEMICAL LOCALIZATION; ELECTRON-MICROSCOPY; SYNAPTIC VESICLES; FINE-STRUCTURE; GLUTAMATE-DECARBOXYLASE; NEURONAL ARCHITECTURE AB Electron microscopic postembedding immunocytochemistry was used to analyze and assess the synaptic distribution of glycine (GLY) and gamma-amino butyric acid (GABA) immunoreactivities in the guinea pig cochlear nucleus (CN). Three classes of endings were identified containing immunolabeling for glycine, GABA, or both glycine and GABA (GLY/GABA). All classes were similar in that the terminals contained pleomorphic vesicles and formed symmetric synapses with their postsynaptic targets. A fourth class, which labeled with neither antibody, contained round vesicles and formed asymmetric synapses. Glycine endings predominated in the ventral CN, while GLY/GABA endings were prevalent in the dorsal CN. GABA endings were the least common and smallest in size. Glycine, GLY/GABA, and GABA endings differed in their proportions and patterns of distribution on the different classes of projection neurons in the CN, including spherical bushy, type I stellate/multipolar, and octopus cells in the ventral CN and fusiform cells in the dorsal CN. The vast majority of anatomically-defined, putative inhibitory endings contain GLY, GABA, or both, suggesting that most of the inhibition in the cochlear nucleus is mediated by these three cytochemically and, probably, functionally distinct classes of endings. The results of this study also suggest that a large proportion of the GABA available for inhibition in the CN coexists in terminals with glycine. (C) 1996 Wiley-Liss, Inc. C1 UNIV MICHIGAN, KRESGE HEARING RES INST, ANN ARBOR, MI 48109 USA. SO ILLINOIS UNIV, SCH MED, DEPT SURG, SPRINGFIELD, IL 62794 USA. SO ILLINOIS UNIV, SCH MED, DEPT PHARMACOL, SPRINGFIELD, IL 62794 USA. NATL INST DEAFNESS & COMMUN DISORDERS, NIH, NEUROCHEM LAB, BETHESDA, MD 20892 USA. RI juiz, jose/G-3025-2015 OI juiz, jose/0000-0002-9668-8983 FU NIDCD NIH HHS [DC00383] NR 95 TC 50 Z9 52 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD SEP 9 PY 1996 VL 373 IS 1 BP 11 EP 26 DI 10.1002/(SICI)1096-9861(19960909)373:1<11::AID-CNE2>3.0.CO;2-G PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA VE376 UT WOS:A1996VE37600002 PM 8876459 ER PT J AU Sun, B Wells, J Goldmuntz, E Silver, P Remmers, EF Wilder, RL Caspi, RR AF Sun, B Wells, J Goldmuntz, E Silver, P Remmers, EF Wilder, RL Caspi, RR TI A simplified, competitive RT-PCR method for measuring rat IFN-gamma mRNA expression SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE reverse transcriptase polymerase chain reaction; housekeeping gene; northern blot analysis; ELISA; DNA mimic; IFN-gamma mRNA; (Rat) ID POLYMERASE CHAIN-REACTION; GENE-EXPRESSION; MESSENGER-RNA; DNA; QUANTITATION; PROTEINS AB We describe an adaptation of competitive RT-PCR to quantitate rat IFN-gamma mRNA expression, An IFN-gamma DNA mimic that shared the same primers and had an identical sequence to the target mRNA except for deletion of 66 nucleotides, was created by a simple PCR amplification from target cDNA. To reduce variations of initial RNA concentrations, beta-actin cDNAs from each target RNA sample were normalized using the densitometric data. A known amount of pretitrated DNA competitor was then used to analyze the relative levels of target cDNA in different samples by PCR co-amplification. The amplification efficiency for both target and competitor remained constant throughout the PCR reaction, and the ratio of target to competitor PCR product remained proportional to the initial ratio of target to competitor. Relative mRNA levels among samples determined by this method were comparable to levels determined by northern blot analysis. They were also comparable to levels of IFN-gamma protein estimated by ELISA. We conclude that this method can be used to estimate the relative abundance of the target mRNA. This method is adaptable to quantitation of other cytokines and is particularly valuable if there are numerous samples, or if the amount of initial mRNA is limited. C1 NEI,SECT IMMUNOREGULAT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NIAMSD,NIH,BETHESDA,MD. NR 12 TC 31 Z9 33 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 SEP 9 PY 1996 VL 195 IS 1-2 BP 139 EP 148 DI 10.1016/0022-1759(96)00099-3 PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA VG477 UT WOS:A1996VG47700017 PM 8814329 ER PT J AU Freedman, L AF Freedman, L TI Bayesian statistical methods - A natural way to assess clinical evidence SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID TRIALS; DESIGN; CANCER RP Freedman, L (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 16 TC 47 Z9 48 U1 0 U2 0 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 SEP 7 PY 1996 VL 313 IS 7057 BP 569 EP 570 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA VG108 UT WOS:A1996VG10800001 PM 8806239 ER PT J AU Robinson, WP Langlois, S Bernasconi, F Clark, S Christian, S Ledbetter, DH GillessenKaesbach, G Horsthemke, B Lerer, I Abeliovich, D Michaelis, R Schuffenhauer, S Schinzel, AA AF Robinson, WP Langlois, S Bernasconi, F Clark, S Christian, S Ledbetter, DH GillessenKaesbach, G Horsthemke, B Lerer, I Abeliovich, D Michaelis, R Schuffenhauer, S Schinzel, AA TI The origin of maternal uniparental disomy 15. SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 UNIV BRITISH COLUMBIA,DEPT MED GENET,VANCOUVER,BC,CANADA. UNIV ZURICH,INST MED GENET,ZURICH,SWITZERLAND. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV ESSEN GESAMTHSCH KLINIKUM,INST HUMAN GENET,D-4300 ESSEN,GERMANY. HEBREW UNIV JERUSALEM,HADASSAH UNIV HOSP,JERUSALEM,ISRAEL. GREENWOOD GENET CTR,GREENWOOD,SC 29646. UNIV MUNICH,KINDERPOLIKLIN,MUNICH,GERMANY. RI Robinson, Wendy/I-9590-2014 OI Robinson, Wendy/0000-0002-2010-6174 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 6 PY 1996 VL 64 IS 4 BP 2 EP 2 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VF014 UT WOS:A1996VF01400011 ER PT J AU Kubota, T Christina, SL Horsthemke, B Ledbetter, DH AF Kubota, T Christina, SL Horsthemke, B Ledbetter, DH TI Advances in both postnatal and prenatal diagnosis for Prader-Willi syndrome (PWS). SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. UNIV ESSEN GESAMTHSCH KLINIKUM,INST HUMAN GENET,D-4300 ESSEN,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 6 PY 1996 VL 64 IS 4 BP 5 EP 5 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VF014 UT WOS:A1996VF01400014 ER PT J AU Okazaki, IJ Kim, HJ Moss, J AF Okazaki, IJ Kim, HJ Moss, J TI Cloning and characterization of a novel membrane-associated lymphocyte NAD:arginine ADP-ribosyltransferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SKELETAL-MUSCLE; DIPHTHERIA-TOXIN; CELLS; RIBOSYLATION; RAT; EXPRESSION; CONSERVATION; TRANSFUSION; PREVENTION; PROTEINS AB Mono-ADP-ribosylation is a post-translational modification of proteins in which the ADP-ribose moiety of NAD is transferred to proteins and is responsible for the toxicity of some bacterial toxins (e.g. cholera toxin and pertussis toxin). NAD:arginine ADP-ribosyltransferases cloned from human and rabbit skeletal muscle and from mouse lymphoma (Yac-1) cells are glycosylphosphatidylinositol-anchored and have similar enzymatic and physical properties; transferases cloned from chicken heterophils and red cells have signal peptides and may be secreted. We report here the cloning and characterization of an ADP-ribosyltransferase (Yac-2), also from Yac-1 lymphoma cells, that differs in properties from the previously identified eukaryotic transferases. The nucleotide and deduced amino acid sequences of the Yac-1 and Yac-2 transferases are 58 and 33% identical, respectively. The Yac-2 protein is membrane-bound but, unlike the Yac-1 enzyme, appears not to be glycosylphosphatidylinositol-anchored. The Yac-1 and Yac-2 enzymes, expressed as glutathione S-transferase fusion proteins in Escherichia coli, were used to compare their ADP-ribosyltransferase and NAD glycohydrolase activities. Using agmatine as the ADP-ribose acceptor, the Yac-1 enzyme was predominantly an ADP-ribosyltransferase, whereas the transferase and NAD glycohydrolase activities of the recombinant Yac-a protein were equivalent. The deduced amino acid sequence of the Yac-2 transferase contained consensus regions common to several bacterial toxin and mammalian transferases and NAD glycohydrolases, consistent with the hypothesis that there is a common mechanism of NAD binding and catalysis among ADP-ribosyltransferases. RP Okazaki, IJ (reprint author), NHLBI,PULM CRIT CARE MED BRANCH,10 CTR DR,MSC 1434,BLDG 10,RM 5N-307,BETHESDA,MD 20892, USA. NR 35 TC 46 Z9 47 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 SEP 6 PY 1996 VL 271 IS 36 BP 22052 EP 22057 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF612 UT WOS:A1996VF61200054 PM 8703012 ER PT J AU Rossig, L Zolyomi, A Catt, KJ Balla, T AF Rossig, L Zolyomi, A Catt, KJ Balla, T TI Regulation of angiotensin II-stimulated Ca2+ oscillations by Ca2+ influx mechanisms in adrenal glomerulosa cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XENOPUS-LAEVIS OOCYTES; CALCIUM OSCILLATIONS; INOSITOL 1,4,5-TRISPHOSPHATE; ENDOPLASMIC-RETICULUM; ACINAR-CELLS; CHANNELS; WAVES; MOBILIZATION; ACTIVATION; METABOLISM AB In adrenal glomerulosa cells, angiotensin II (Ang II) evokes repetitive [Ca2+](i) transients and increases Ca2+ influx through voltage-sensitive calcium channels (VSCCs) as well as the capacitative Ca2+ entry pathway. This study analyzed the relationships between these Ca2+ influx pathways and intracellular Ca2+ signaling in bovine glomerulosa cells, in which Ca2+ oscillation frequency was regulated by Ang II concentration over the range of 50-300 pM. In the absence of external. Ca2+, such oscillations were maintained for prolonged periods of time, but their frequency was significantly reduced (0.23 min(-1) versus 0.38 min(-1)). Restoration of [Ca2+](o) to 0.6 mM increased the frequency of Ca2+ oscillations in cells that showed narrow spikes of constant amplitude and caused a plateau response in cells with broad spikes of rapidly decreasing amplitude. In the presence of Ca2+, nifedipine reduced the frequency of the oscillatory Ca2+ response to 100 pM Ang II by 49%, and BAY K 8644 increased oscillation frequency by 86%, or caused plateau-type responses typical of higher Ang II concentrations. In contrast to their prominent actions on Ca2+ spiking frequency, dihydropyridines caused only minor changes in Ang II (100 pM)-induced inositol phosphate production. Dihydropyridines also had minimal effects on the nonoscillatory Ca2+ signals evoked by high Ang II concentrations (10 nM). These findings indicate that Ca2+ influx through VSCCs modulates the frequency of Ca2+ oscillations induced by low agonist concentrations by a mechanism that does not involve major changes in inositol trisphosphate formation. However, VSCCs make relatively little contribution to the nonoscillatory Ca2+ signals generated by high agonist concentrations, when Ca2+ influx occurs predominantly through the capacitative Ca2+ entry pathway. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. OI Balla, Tamas/0000-0002-9077-3335 NR 36 TC 14 Z9 14 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 SEP 6 PY 1996 VL 271 IS 36 BP 22063 EP 22069 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF612 UT WOS:A1996VF61200056 PM 8703014 ER PT J AU Delporte, C OConnell, BC He, XJ Ambudkar, IS Agre, P Baum, BJ AF Delporte, C OConnell, BC He, XJ Ambudkar, IS Agre, P Baum, BJ TI Adenovirus-mediated expression of aquaporin-5 in epithelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; WATER CHANNELS; GENE-TRANSFER; CDNA; ERYTHROCYTE; SALIVARY; VECTOR AB A recombinant adenovirus coding for rat aquaporin-5 was constructed and plaque purified. The recombinant adenovirus (AdrAQP5) mediated the expression of aquaporin-5 in rat and human salivary cell lines and in dog kidney cells in vitro as demonstrated by Northern blot and Western blot analyses, and by confocal microscopy after immunofluorescent labeling. In kidney cells, expression of the transgene was optimal if cells were infected at their basolateral surface, a phenomenon associated with the distribution of integrin receptors on these cells. The expressed aquaporin-5 protein was functionally active because viral-mediated gene transfer resulted in a significant increase in the osmotically directed net fluid secretion rate across monolayers of kidney cells. AdrAQP5 should provide an efficient and useful means to impart facilitated water permeability to cells lacking such a pathway. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,BALTIMORE,MD 21205. RI Delporte, Christine/A-5733-2012; OI O'Connell, Brian/0000-0003-4529-7664 FU NEI NIH HHS [EY11239]; NHLBI NIH HHS [HL48268, HL33991] NR 23 TC 62 Z9 64 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 SEP 6 PY 1996 VL 271 IS 36 BP 22070 EP 22075 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF612 UT WOS:A1996VF61200057 PM 8703015 ER PT J AU Pan, ZQ Ge, H Amin, AA Hurwitz, J AF Pan, ZQ Ge, H Amin, AA Hurwitz, J TI Transcription-positive cofactor 4 forms complexes with HSSB (RPA) on single-stranded DNA and influences HSSB-dependent enzymatic synthesis of simian virus 40 DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL NUCLEAR ANTIGEN; LARGE TUMOR-ANTIGEN; POLYMERASE-ALPHA; T-ANTIGEN; REPLICATION INVITRO; BINDING-PROPERTIES; SV40 ORIGIN; INITIATION; PROTEIN; DELTA AB The replication of simian virus 40 (SV40) DNA in vitro requires a trimeric single-stranded DNA (ssDNA)-binding protein called HSSB or RPA. HSSB supports the unwinding of DNA containing the SV40 origin in the presence of the viral-encoded T antigen and is required for the initiation of RNA primer synthesis as well as processive elongation of DNA catalyzed by the DNA polymerase delta holoenzyme. In this report we show that the transcription positive cofactor 4 (PC4), a ssDNA-binding protein, forms complexes with HSSB on ssDNA and markedly affects the replication functions of HSSB. PC4 supports T antigen-catalyzed unwinding of SV40 origins in lieu of HSSB but inhibits both RNA primer synthesis and polymerase delta-catalyzed DNA chain elongation reactions. These inhibitory effects can be reversed by the addition of excess HSSB. Depending on the concentration of HSSB, PC4 is capable of either inhibiting or activating SV40 DNA replication measured in both mono- and dipolymerase systems. The possible role of PC4 in the initiation of DNA replication is discussed. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,GRAD PROGRAM MOL BIOL,NEW YORK,NY 10021. RP Pan, ZQ (reprint author), MT SINAI MED CTR,DERALD H RUTTENBERG CANC CTR,NEW YORK,NY 10029, USA. FU NIGMS NIH HHS [GM38559] NR 30 TC 40 Z9 42 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 SEP 6 PY 1996 VL 271 IS 36 BP 22111 EP 22116 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF612 UT WOS:A1996VF61200063 PM 8703021 ER PT J AU Patel, BKR Wang, LM Lee, CC Taylor, WG Pierce, JH LaRochelle, WJ AF Patel, BKR Wang, LM Lee, CC Taylor, WG Pierce, JH LaRochelle, WJ TI Stat6 and Jak1 are common elements in platelet-derived growth factor and interleukin-4 signal transduction pathways in NIH 3T3 fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATORY FACTOR-I; SIMIAN SARCOMA-VIRUS; PROTEIN-TYROSINE KINASES; RECEPTOR GAMMA-CHAIN; DNA-BINDING ACTIVITY; TRANSCRIPTION FACTOR; CYTOKINE RECEPTORS; HEMATOPOIETIC-CELLS; MOLECULAR-CLONING; ELEVATED LEVELS AB Both platelet-derived growth factor (PDGF) and interleukin-4 (IL-4) play major roles in cell proliferation, differentiation, chemotaxis, and other functional responses, Here, we demonstrate that Stat6, previously shown to be activated by only IL-4 and IL-3, becomes activated after PDGF stimulation of NIH 3T3 fibroblasts, PDGF BB, and to a lesser extent PDGF AA, rapidly induced DNA binding activity from NIH 3T3 cell lysates utilizing the immunoglobulin heavy chain germ line a promoter (I epsilon) that specifically binds to StatG in an electrophoretic mobility shift assay. DNA binding activity could be detected within 5 min and reached maximum levels at approximately 20 min in parental NIH 3T3 cells, An identical mobility shift and time course of PDGF-mediated I epsilon binding activity was more pronounced in lysates of NIH 3T3 transfectants overexpressing human Stat6 (NIH 3T3-Stat6), The observed radiolabeled I epsilon mobility shift was competed by unlabeled I epsilon as well as by the beta-casein gene promoter but not by the interferon-alpha-stimulated response element or the interferon-gamma response region of the guanylate-binding protein gene, A StatG specific polyclonal antisera also supershifted the PDGF-induced I epsilon mobility shift, After PDGF BB treatment, a 100-kDa tyrosine phosphorylated species was detected in anti-Stat6 immunoprecipitates. Cycloheximide had little effect on Stat6 tyrosine phosphorylation, In addition to State, Stat5a, and Stat5b, PDGF BE also induced Jak1 tyrosine phosphorylation suggesting a potential pathway for Stat activation, Strikingly, the concurrent addition of IL-4 enhanced PDGF BE-induced I epsilon binding activity, Jak1 tyrosine phosphorylation, and [H-3]thymidine incorporation. These results provide evidence that State and Jak1 are common elements in PDGF and IL-4 signaling pathways and suggest that IL-4 could play a role in potentiating certain known PDGF-induced biological responses. C1 NCI,CELLULAR & MOL BIOL LAB,BETHESDA,MD 20892. NR 62 TC 54 Z9 56 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 SEP 6 PY 1996 VL 271 IS 36 BP 22175 EP 22182 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VF612 UT WOS:A1996VF61200072 PM 8703030 ER PT J AU Bryant, HU Nelson, DL Button, D Cole, HW Baez, MB Lucaites, VL Wainscott, DB Whitesitt, C Reel, J Simon, R Koppel, GA AF Bryant, HU Nelson, DL Button, D Cole, HW Baez, MB Lucaites, VL Wainscott, DB Whitesitt, C Reel, J Simon, R Koppel, GA TI A novel class of 5-HT2A receptor antagonists: Aryl aminoguanidines SO LIFE SCIENCES LA English DT Article DE serotonin; aryl aminoguanidine; 5-HT2A receptor antagonists ID SEROTONIN; RAT; 5-HYDROXYTRYPTAMINE; SUBTYPES; CLASSIFICATION; INHIBITION; BINDING AB Local delivery of serotonin (5-HT) produces a rapid edematous response in soft tissues via increased fluid extravasation which is prevented by 5-HT2 antagonists such as ketanserin or mianserin. Here we report the effects of a new class of aminoguanidine 5-HT2 antagonists, with relative selectivity for 5-HT2A receptors which are potent inhibitors of 5-HT-induced paw edema in the rat. Radioligand binding studies with I-125 DOI On human 5-HT2A and 5-HT2C receptors and with H-3-5-HT on human 5-HT2B receptors demonstrated that, LY314228, and LY320954 displayed some selectivity for the 5-HT2A receptor. When compared to binding at other 5-HT2 receptor subtypes, LY314228 had an 18.6-fold greater affinity for the 5-HT2A site over the 5-HT2B site, and 2.6 fold greater at the 5.HT2C site. LY320954 displayed similar preference for 5-HT2A sites. Both compounds also inhibited 5-HT-induced paw swelling in rats, with ED(50)'s of 6.4 and 4.8 mg/kg (for LY314228 and LY320954, respectively). These studies offer evidence for a novel class of pharmacophores for the 5-HT2 receptor family which show greater relative affinities for the 5-HT2A receptor subclass. C1 ELI LILLY & CO,CENT NERVOUS SYST RES,INDIANAPOLIS,IN 46285. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP Bryant, HU (reprint author), ELI LILLY & CO,LILLY CORP CTR,DIV ENDOCRINE RES,ENDOCRINE RES,D-C 0444,INDIANAPOLIS,IN 46285, USA. NR 19 TC 17 Z9 17 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD SEP 6 PY 1996 VL 59 IS 15 BP 1259 EP 1268 DI 10.1016/0024-3205(96)00449-3 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA VH238 UT WOS:A1996VH23800009 PM 8845011 ER PT J AU Klausner, R AF Klausner, R TI NCI: A lab scientist's view, from the Director's Office SO SCIENCE LA English DT Editorial Material RP Klausner, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD SEP 6 PY 1996 VL 273 IS 5280 BP 1329 EP 1330 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF610 UT WOS:A1996VF61000016 PM 8801626 ER PT J AU Ewald, D Li, MG Efrat, S Auer, G Wall, RJ Furth, PA Hennighausen, L AF Ewald, D Li, MG Efrat, S Auer, G Wall, RJ Furth, PA Hennighausen, L TI Time-sensitive reversal of hyperplasia in transgenic mice expressing SV40 T antigen SO SCIENCE LA English DT Article ID SV40-TRANSFORMED CELLS; GENE-EXPRESSION; ONCOGENES; PROMOTER; PROTEIN; CANCER; GROWTH AB The role of viral oncoprotein expression in the maintenance of cellular transformation was examined as a function of time through controlled expression of simian virus 40 T antigen (TAg), Expression of TAg in the submandibular gland of transgenic mice from the time of birth induced cellular transformation and extensive ductal hyperplasia by 4 months of age, The hyperplasia was reversed when TAg expression was silenced for 3 weeks, When TAg expression was silenced after 7 months, however, the hyperplasia persisted even though TAg was absent, Although the polyploidy of ductal cells could be reversed at 4 months of age, cells at 7 months of age remained polyploid even in the absence of TAg, These results support a model of time-dependent multistep tumorigenesis, in which virally transformed cells eventually lose their dependence on the viral oncoprotein for maintenance of the transformed state. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21201. INST HUMAN VIROL,BALTIMORE,MD 21201. ALBERT EINSTEIN COLL MED,DEPT MOL PHARMACOL,BRONX,NY 10461. KAROLINSKA INST,DEPT PATHOL & ONCOL,S-17176 STOCKHOLM,SWEDEN. ARS,USDA,BELTSVILLE,MD 20705. NIDDKD,BIOCHEM & METAB LAB,NIH,BETHESDA,MD 20892. NR 21 TC 190 Z9 190 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 SEP 6 PY 1996 VL 273 IS 5280 BP 1384 EP 1386 DI 10.1126/science.273.5280.1384 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF610 UT WOS:A1996VF61000041 PM 8703072 ER PT J AU Schuck, P Minton, AP AF Schuck, P Minton, AP TI Analysis of mass transport-limited binding kinetics in evanescent wave biosensors SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SURFACE-PLASMON RESONANCE; OPTICAL BIOSENSOR; MONOCLONAL-ANTIBODIES; HUMAN INTERLEUKIN-5; SH2 DOMAINS; AFFINITY; RECEPTOR; TECHNOLOGY; REPRESSOR; PEPTIDE AB It is shown that currently used methods for analyzing surface plasmon resonance or resonant mirror biosensor data do not adequately take into account the effects of mass transport on the kinetics of ligand association and dissociation. Conventional analyses may yield arbitrary apparent reaction rate constants lying between the mass transport rate constant and the true intrinsic chemical binding rate constants, depending on the choice of ligand concentrations used in the experiments. A new kinetic analysis of biosensor data, based upon a phenomenological two-compartment approximate description of transport, is presented and tested on experimental data and on simulated data generated with a computer model for combined mass transport and reversible binding to a single class of immobilized sites. Results of the analysis indicate the extent to which the experimental binding progress curve is transport controlled and whether or not values of chemical rate constants may be validly extracted from the data. The new analysis is independent of the details of the transport process, simple in its application, and in favorable cases permits determination of the correct values of chemical rate constants that are 10- to 100-fold greater than those that can be correctly evaluated by previous analyses. (C) 1996 Academic Press, Inc. RP Schuck, P (reprint author), NIDDKD,SECT PHYS BIOCHEM,BIOCHEM PHARMACOL LAB,NIH,BETHESDA,MD 20892, USA. OI Schuck, Peter/0000-0002-8859-6966 NR 43 TC 180 Z9 181 U1 1 U2 9 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 SEP 5 PY 1996 VL 240 IS 2 BP 262 EP 272 DI 10.1006/abio.1996.0356 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VJ496 UT WOS:A1996VJ49600012 PM 8811920 ER PT J AU Tsao, LI Su, TP AF Tsao, LI Su, TP TI IP3 receptor antagonist heparin uncompetitively inhibits [H-3](+)-SKF-10047 binding to sigma receptors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sigma receptor; ryanodine; inositol 1,4,5-trisphosphate ID IMPAIRMENT; PRE-084; SITES; BRAIN AB Interaction of a receptors with intracellular Ca2+ channel blocker and modulators was examined. Ryanodine and inositol 1,4,5-trisphosphate (IP3) did not inhibit [H-3](+)-N-allylnormetazocine ([H-3](+)-SKF-10047) binding to sigma receptors from either brain microsomal fractions or liver membrane extracts of the rat. However, the IP3 receptor antagonist heparin inhibited [H-3](+)-SKF-10047 to sigma receptors in an uncompetitive manner with a K-i of 93 mu M. These results suggest that sigma receptors may bear some relationship with IP3 receptor associated proteins or channels. C1 NIA,UNIT PATHOBIOL,MOL NEUROPSYCHIAT SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NR 8 TC 8 Z9 9 U1 0 U2 1 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 SEP 5 PY 1996 VL 311 IS 1 BP R1 EP R2 DI 10.1016/0014-2999(96)00533-X PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VH615 UT WOS:A1996VH61500016 PM 8884243 ER PT J AU Wang, X Brownstein, MJ Young, WS AF Wang, X Brownstein, MJ Young, WS TI Sequence analysis of PG10.2, a gene expressed in the pineal gland and the outer nuclear layer of the retina SO MOLECULAR BRAIN RESEARCH LA English DT Article DE pineal gland; retina; cDNA cloning; polymerase chain reaction; hybridization, in situ; EGF-like repeat ID EPIDERMAL GROWTH-FACTOR; ARBITRARILY PRIMED PCR; FACTOR-LIKE DOMAINS; EGF-LIKE REPEATS; MESSENGER-RNA; DIFFERENTIAL DISPLAY; DROSOPHILA-NOTCH; CHROMOSOMAL LOCALIZATION; NUCLEOTIDE-SEQUENCE; CALCIUM-BINDING AB A cDNA (PG10.2) was cloned from rat using RNA fingerprinting by arbitrarily primed PCR (AP-PCR). Initially, a 145-bp DNA fragment was isolated from a pineal-specific band revealed on a sequencing gel. Riboprobes generated from the DNA fragment were used for hybridization histochemical and Northern analyses. Both techniques indicate a gene (8 kb mRNA) expressed only in the pineal gland and the outer nuclear layer of the retina. Two 4-kb cDNA fragments generated by 5'-RACE (rapid amplification of cDNA ends) and 3'-RACE were obtained using a long template PCR-based RACE technique. DNA sequencing revealed a single long open reading frame (ORF) encoding a predicted protein of 1239 amino acids, containing multiple motifs: a typical signal sequence of 20 amino acids at the NH2-terminus, a long extracellular domain with multiple potential glycosylation sites, a 31-amino-acid transmembrane domain near the COOH-terminus and a 109-amino-acid cytoplasmic tail. There are also two domains similar, but not identical, to EGF-like (epidermal growth factor-like) domains located just upstream of the transmembrane domain. These features suggest that this gene may encode a glycoprotein involved in cell adhesion, growth, and differentiation of pineal and retinal photoreceptor cells. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009; Brownstein, Michael/B-8609-2009 OI Young, W Scott/0000-0001-6614-5112; NR 37 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD SEP 5 PY 1996 VL 41 IS 1-2 BP 269 EP 278 DI 10.1016/0169-328X(96)00107-6 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VF392 UT WOS:A1996VF39200033 PM 8883960 ER PT J AU Wienecke, R Maize, JC Shoarinejad, F Vass, WC Reed, J Bonifacino, JS Resau, JH deGunzburg, J Yeung, RS DeClue, JE AF Wienecke, R Maize, JC Shoarinejad, F Vass, WC Reed, J Bonifacino, JS Resau, JH deGunzburg, J Yeung, RS DeClue, JE TI Co-localization of the TSC2 product tuberin with its target Rap1 in the golgi apparatus SO ONCOGENE LA English DT Article DE tuberous sclerosis; tuberin; localization Rap1; Golgi apparatus ID EKER RAT MODEL; DOMINANTLY INHERITED CANCER; SCLEROSIS TSC2; CYTOPLASMIC DOMAIN; HUMAN NEUTROPHILS; PLASMA-MEMBRANE; MANNOSIDASE-II; GENE-PRODUCT; PROTEINS; COMPLEX AB Tuberin is the protein product of the tuberous sclerosis-2 (TSC2) gene, which is associated with tuberous sclerosis (TSC), a human genetic syndrome characterized by the development of tumors in a variety of tissues, We have previously shown that tuberin is a widely expressed 180 kDa protein which exhibits specific GTPase activating activity in vitro towards the Ras-related Rap1 study we have used affinity-purified antibodies against tuberin to analyse its expression in human and rat tissues and to examine its subcellular localization, Tuberin expression was detected in all adult human tissues tested, with the highest levels found in brain, heart and kidney, organs that are commonly affected in TSC patients, By contrast, in adult rats the highest levels of tuberin were found in brain, liver and testis, Indirect immunofluorescence of tuberin in various cultured cell lines revealed a punctate, mostly perinuclear staining pattern, Double-indirect immunofluorescence analysis sera and anti-tuberin sera and antisera against known Golgi markers (mannosidase-II and furin) revealed that the staining of tuberin was consistent with its localization in the stacks of the Golgi apparatus, In support of this, treatment of cells with brefeldin A, a drug known to cause disassembly of the Golgi apparatus: abolished the perinuclear staining of tuberin, Moreover, conventional and confocal immunofluorescence demonstrated co-localization of tuberin with Rap1, which has previously been localized to the Golgi apparatus, The colocalization of tuberin and Rap1 in vivo strengthens the likelihood that the in vitro catalytic activity of tuberin toward Rap1 plays a physiologically relevant role in the tumor suppressor function of tuberin. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. FOX CHASE CANC CTR,DIV MED SCI,PHILADELPHIA,PA 19111. CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT DERMATOPATHOL,NEW YORK,NY 10021. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIS RES PROGRAM,FREDERICK,MD 21702. INST CURIE,SECT RECH,F-74231 PARIS 05,FRANCE. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 49 TC 90 Z9 90 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 5 PY 1996 VL 13 IS 5 BP 913 EP 923 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VG766 UT WOS:A1996VG76600004 PM 8806680 ER PT J AU SunHoffman, L Aurigemma, RE Sun, B Ruscetti, SK AF SunHoffman, L Aurigemma, RE Sun, B Ruscetti, SK TI Transactivation of the GATA-1 promoter by a myb-ets-containing mouse retrovirus is mediated by CACCC elements SO ONCOGENE LA English DT Article DE ME26 virus; GATA-1 transactivation; CACCC element; Sp1 ID TRANSCRIPTION FACTOR GATA-1; ERYTHROPOIETIN RECEPTOR GENE; LEUKEMIA-VIRUS; FACTOR SP1; BINDING; CELLS; PROTEINS; E26 AB The myb-ets-containing ME26 virus causes erythroleukemia in mice by a novel mechanism involving the inappropriate activation of erythroid-specific genes in hematopoietic precursor cells, We have previously shown that the ME26 viral protein can transactivate the GATA-1 promoter in transient transactivation assays carried out in mouse fibroblasts. The mouse GATA-1 promoter, whose activity is regulated by the GATA-1 protein itself, contains a double GATA consensus sequence at its 5' end and two CACCC elements at its 3' end, both of which are crucial for promoter activity in erythroid cells, as well as a nonconsensus GATA sequence and several putative c-myb and c-ets binding sites, In order to determine which sequences in the GATA-1 promoter are crucial for activation by the ME26 viral protein, we made deletions of the promoter, cloned them into a luciferase expression vector and tested their activity in mouse fibroblasts, which do not express GATA-1, Our results indicate that sequences in the 3' end of the GATA-1 promoter, which include two CACCC elements, are essential for transactivation by ME26 virus, while other upstream sites contribute to full activation by the virus, Mutation of the CACCC sites abolishes ME26 viral transactivation. The interaction of cell extracts containing ME26 viral protein and the GATA-1 promoter fragment containing the two CACCC elements was examined by electrophoretic mobility shift analysis (EMSA) and the results showed no direct interaction between the two, However, we could detect the ubiquitous transcription factor Spl bound to this sequence, These data demonstrate that the CACCC element is necessary for GATA-1 promoter transactivation by ME26 virus and that the viral protein may indirectly transactivate the promoter by binding to Sp1. C1 NCI,MOL ONCOL LAB,FREDERICK,MD 21702. NR 22 TC 6 Z9 6 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 5 PY 1996 VL 13 IS 5 BP 1037 EP 1042 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VG766 UT WOS:A1996VG76600017 PM 8806693 ER PT J AU Bates, S Rowan, S Vousden, KH AF Bates, S Rowan, S Vousden, KH TI Characterisation of human cyclin G(1) and G(2): DNA damage inducible genes SO ONCOGENE LA English DT Article DE cyclins; p53; DNA damage ID PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR P53; TRANSCRIPTIONAL ACTIVATION; IN-VIVO; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; GROWTH ARREST; G1 ARREST; BAX GENE; APOPTOSIS AB Several genes have been identified as targets for transcriptional activation by the p53 tumour suppressor protein. Rodent cyclin G was previously identified as a p53 responsive gene and in order to assess the role played by cyclin G as a mediator of p53 function in humans cells we have isolated full length human cyclin G(1) and identified a related gene designated cyclin G(2). Both human G-cyclins are induced by the DNA damaging agent actinomycin-D and although the induction of cyclin G(1) is clearly p53 dependent, activation of cyclin G(2) expression was observed in the absence of p53. Based on sequence similarity, the G-cyclins and the recently identified cyclin I form a distinct sub-group within the larger cyclin family, possibly reflecting some degree of functional similarity. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 52 TC 120 Z9 129 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 5 PY 1996 VL 13 IS 5 BP 1103 EP 1109 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA VG766 UT WOS:A1996VG76600025 PM 8806701 ER PT J AU Henley, WN Schuebel, KE Nielsen, DA AF Henley, WN Schuebel, KE Nielsen, DA TI Limitations imposed by heteroduplex formation on quantitative RT-PCR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHENOL-CHLOROFORM EXTRACTION; POLYMERASE CHAIN-REACTION; SINGLE-STEP METHOD; TRYPTOPHAN-HYDROXYLASE; RNA ISOLATION; TITRATION; GENE AB RT-PCR, a rapidly emerging technique for the detection of RNA, is being used by many investigators to quantify small amounts of RNA. Accurate quantification of RNA content has been facilitated by the use of competitive amplicons as internal controls. We demonstrate that losses in sensitivity and accuracy are associated with an internal standard having sequence similarity to the primary amplicon. Analysis of PCR products under non-denaturing and denaturing conditions provided evidence that these losses were associated with heteroduplex formation. Subsequent analysis of factors associated with heteroduplex formation provides insights for future development of competitive assays. Assay considerations that can minimize limitations associated with competitive PCR protocols are discussed. (C) 1996 Academic Press, Inc. C1 OHIO UNIV,COLL OSTEOPATH MED,ATHENS,OH 45701. NIAAA,NIH,ROCKVILLE,MD 20852. RP Henley, WN (reprint author), OHIO UNIV,DEPT BIOL SCI,ATHENS,OH 45701, USA. RI Nielsen, David/B-4655-2009 NR 11 TC 36 Z9 37 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 4 PY 1996 VL 226 IS 1 BP 113 EP 117 DI 10.1006/bbrc.1996.1319 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VF935 UT WOS:A1996VF93500018 PM 8806600 ER PT J AU Park, JM Yang, ES Hatfield, DL Lee, BJ AF Park, JM Yang, ES Hatfield, DL Lee, BJ TI Analysis of the selenocysteine tRNA([SER]SEC) gene transcription in vitro using Xenopus oocyte extracts SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHOSERINE TRANSFER-RNA; TRANSFER RNA(SER)SEC GENE; POLYMERASE-III; SNRNA GENES; ELEMENTS; SPECIFICITY; EXPRESSION; INVITRO; BOX AB An in vitro transcription system was devised using a Xenopus oocyte S150 extract for analyzing expression of the Sec tRNA([Ser]Sec) gene. The activator element, located at about -200 that is required for maximal expression of the tRNA([Sec]Sec) gene in vivo, had no effect on tRNA([Ser]Sec) transcription in vitro. In vitro transcription of this gene even tolerated mutations within or deletion of the PSE, showing marked contrast with the requirements observed in vivo. However, the TATA box was indispensable for basal level expression of the gene both in vivo and in vitro. The region spanning from the TATA box to the transcription start point (-33 to -1) was sufficient for Pol III to recognize the tRNA([Ser]Sec) gene promoter in vitro. (C) 1996 Academic Press, Inc. C1 SEOUL NATL UNIV,INST MOL BIOL & GENET,GENET MOL LAB,SEOUL 151742,SOUTH KOREA. NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. NR 14 TC 9 Z9 9 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 SEP 4 PY 1996 VL 226 IS 1 BP 231 EP 236 DI 10.1006/bbrc.1996.1338 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VF935 UT WOS:A1996VF93500037 PM 8806619 ER PT J AU Meyer, GS Jacoby, I Krakauer, H Powell, DW Aurand, J McCardle, P AF Meyer, GS Jacoby, I Krakauer, H Powell, DW Aurand, J McCardle, P TI Gastroenterology workforce modeling SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTERNAL-MEDICINE; UNITED-STATES; MANPOWER AB Objective.-To examine the current supply and distribution of gastroenterologists and project future supply under various scenarios to provide a paradigm for workforce reform. Design.-An analysis of current practices and distribution of gastroenterologists and a demographic model, using the 1992 gastroenterology workforce as a baseline, Main Outcome Measure.-Comparison of current supply, distribution, and practice profiles with past data and future projections, using analyses of data from the 1993 Area Resource File, 1992 Medicare Part B file, age- and sex-specific death and retirement rates from the Bureau of Health Professions, managed care staffing patterns, the National Survey of Internal Medicine Manpower, and the Bureau of the Census. Results.-Rapid growth in the number of US gastroenterologists has resulted in a gastroenterologist-to-population ratio double that used on average by health maintenance organizations. In addition, the work profile of gastroenterologists is shared significantly by primary care physicians and other specialists, with the exception of a few specific and uncommon procedures, Conclusions.-Empirical evidence suggests that, even in the absence of detailed models to describe the desired supply/need balance for gastroenterology, the US health care system and clinicians may benefit from a reduction in gastroenterology training programs. The Gastroenterology Leadership Council endorsed a goal of 25% to 50% reduction in trainee numbers over 5 years, and recent National Resident Matching Program data indicate that a voluntary downsizing process is in full force, This study illustrates a paradigm for workforce planning that could be useful for other medical specialties. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,CTR HLTH CARE QUAL ASSESSMENT,BETHESDA,MD 20814. UNIV TEXAS,MED BRANCH,DEPT INTERNAL MED,GASTROENTEROL LEADERSHIP COUNCIL MANPOWER COMM,GALVESTON,TX 77550. NIH,BETHESDA,MD 20892. RI Powell, Don/K-4774-2014 NR 27 TC 57 Z9 58 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 4 PY 1996 VL 276 IS 9 BP 689 EP 694 DI 10.1001/jama.276.9.689 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA VE233 UT WOS:A1996VE23300006 PM 8769546 ER PT J AU Weliky, DP Tycko, R AF Weliky, DP Tycko, R TI Determination of peptide conformations by two-dimensional magic angle spinning NMR exchange spectroscopy with rotor synchronization SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; ALANYL-GLYCYL-GLYCINE; CRYSTAL-STRUCTURE; PROTEIN; POLYMERS C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. NR 27 TC 106 Z9 106 U1 0 U2 6 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 SEP 4 PY 1996 VL 118 IS 35 BP 8487 EP 8488 DI 10.1021/ja960178e PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VF378 UT WOS:A1996VF37800036 ER PT J AU Felsenfeld, G Boyes, J Chung, J Clark, D Studitsky, V AF Felsenfeld, G Boyes, J Chung, J Clark, D Studitsky, V TI Chromatin structure and gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Colloquium on Biology of Developmental Transcription Control CY OCT 26-28, 1995 CL NATL ACAD SCI, IRVINE, CA HO NATL ACAD SCI ID TRANSCRIBING POLYMERASE; CHROMOSOMAL DOMAINS; GLOBIN GENE; CHICKEN; ENHANCER; TRANSCRIPTION; ELEMENT; LOCUS; CORE AB It is now well understood that chromatin structure is perturbed in the neighborhood of expressed genes. This is most obvious in the neighborhood of promoters and enhancers, where hypersensitivity to nucleases marks sites that no longer carry canonical nucleosomes, and to which transcription factors bind. To study the relationship between transcription factor binding and the generation of these hypersensitive regions, we mutated individual cis-acting regulatory elements within the enhancer that lies between the chicken beta- and epsilon-globin genes. Constructions carrying the mutant enhancer were introduced by stable transformation into an avian erythroid cell line. We observed that weakening the enhancer resulted in creation of two classes of site: those still completely accessible to nuclease attack and those that were completely blocked. This all-or-none behavior suggests a mechanism by which chromatin structure can act to sharpen the response of developmental systems to changing concentrations of regulatory factors, Another problem raised by chromatin structure concerns the establishment of boundaries between active and inactive chromatin domains. We have identified a DNA element at the 5' end of the chicken beta-globin locus, near such a boundary, that has the properties of an insulator; in test constructions, it blocks; the action of an enhancer on a promoter when it is placed between them. We describe the properties and partial dissection of this sequence. A third problem is posed by the continued presence of nucleosomes on transcribed genes, which might prevent the passage of RNA polymerase. We show however, that a prokaryotic polymerase can transcribe through a histone octamer on a simple chromatin template. The analysis of this process reveals that an octamer is capable of transferring from a position in front of the polymerase to one behind, without ever losing its attachment to the DNA. RP Felsenfeld, G (reprint author), NIDDKD,NIH,BETHESDA,MD 20892, USA. RI Studitsky, Vasily/A-9382-2014 NR 19 TC 126 Z9 132 U1 0 U2 6 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 SEP 3 PY 1996 VL 93 IS 18 BP 9384 EP 9388 DI 10.1073/pnas.93.18.9384 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400014 PM 8790338 ER PT J AU SantoniRugiu, E Preisegger, KH Kiss, A Audolfsson, T Shiota, G Schmidt, EV Thorgeirsson, SS AF SantoniRugiu, E Preisegger, KH Kiss, A Audolfsson, T Shiota, G Schmidt, EV Thorgeirsson, SS TI Inhibition of neoplastic development in the liver by hepatocyte growth factor in a transgenic mouse model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCELLULAR-CARCINOMA CELLS; TUMOR CYTOTOXIC FACTOR; SCATTER FACTOR; MET PROTOONCOGENE; FACTOR-ALPHA; C-MYC; FACTOR/SCATTER FACTOR; HUMAN FIBROBLASTS; EPITHELIAL-CELLS; MICE AB Overexpression of the c-myc oncogene is associated with a variety of both human and experimental tumors, and cooperation of other oncogenes and growth factors with the myc family are critical in the evolution of the malignant phenotype. The interaction of hepatocyte growth factor (HGF) with c-myc during hepatocarcinogenesis in a transgenic mouse model has been analyzed. While sustained overexpression of c-myc in the liver leads to cancer, coexpression of HGF and c-myc in the liver delayed the appearance of preneoplastic lesions and prevented malignant conversion. Furthermore, tumor promotion by phenobarbital was completely inhibited in the c-myc/HGF double transgenic mice, whereas phenobarbital was an effective tumor promoter in the c-myc single transgenic mice. The results indicate that HGF may function as a tumor suppressor during early stages of liver carcinogenesis, and suggest the possibility of therapeutic application for this cytokine. C1 NCI,EXPT CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. TOTTORI UNIV,DEPT INTERNAL MED 2,YONAGO,TOTTORI 683,JAPAN. MASSACHUSETTS GEN HOSP,CTR CANC,CHARLESTOWN,MA 02129. NR 57 TC 107 Z9 107 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 SEP 3 PY 1996 VL 93 IS 18 BP 9577 EP 9582 DI 10.1073/pnas.93.18.9577 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400048 PM 8790372 ER PT J AU Madrenas, J Schwartz, RH Germain, RN AF Madrenas, J Schwartz, RH Germain, RN TI Interleukin 2 production, not the pattern of early T-cell antigen receptor-dependent tyrosine phosphorylation, controls anergy induction by both agonists and partial agonists SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T cell; antigen; receptor; major histocompatibility complex class II ID ALTERED PEPTIDE LIGANDS; KINASE-C ACTIVATION; CLONAL ANERGY; COSTIMULATORY SIGNAL; PRESENTING CELLS; PROLIFERATION; TOLERANCE; ABSENCE; PROTEIN; ANTAGONISTS AB Pull activation of T cells requires signaling through the T-cell antigen receptor (TCR) and additional surface molecules interacting with ligands on the antigen-presenting cell. TCR recognition of agonist ligands in the absence of accessory signals frequently results in the induction of a state of unresponsiveness termed anergy. However, even in the presence of costimulation, anergy can be induced by TCR partial agonists. The unique pattern of early receptor-induced tyrosine phosphorylation events induced by partial agonists has led to the hypothesis that altered TCR signaling is directly responsible for the development of anergy. Here we show that energy induction is neither correlated with nor irreversibly determined by the pattern of early TCR-induced phosphorylation. Rather, it appears to result from the absence of downstream events related to interleukin 2 receptor occupancy and/or cell division. This implies that the anergic state can be manipulated independently of the precise pattern of early biochemical changes following TCR occupancy, a finding with implications for understanding the induction of self-tolerance and the use of partial agonist ligands in the treatment of autoimmune diseases. C1 NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892. NIAID,CELLULAR & MOL IMMUNOL,BETHESDA,MD 20892. NR 47 TC 71 Z9 72 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 SEP 3 PY 1996 VL 93 IS 18 BP 9736 EP 9741 DI 10.1073/pnas.93.18.9736 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400076 PM 8790400 ER PT J AU Kordek, R Nerurkar, VR Liberski, PP Isaacson, S Yanagihara, R Gajdusek, DC AF Kordek, R Nerurkar, VR Liberski, PP Isaacson, S Yanagihara, R Gajdusek, DC TI Heightened expression of tumor necrosis factor alpha, interleukin 1 alpha, and glial fibrillary acidic protein in experimental Creutzfeldt-Jakob disease in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE demyelination; reverse transcription-coupled PCR; cytokine ID CENTRAL NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; BOVINE SPONGIFORM ENCEPHALOPATHY; MULTIPLE-SCLEROSIS; WHITE MATTER; ULTRASTRUCTURAL PATHOLOGY; AUTOIMMUNE DEMYELINATION; PANENCEPHALOPATHIC TYPE; TNF-ALPHA; SCRAPIE AB The ultrastructural pathology of myelinated axons in mice infected experimentally with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD) virus is characterized by myelin sheath vacuolation that closely resembles that induced in murine spinal cord organotypic cultures by tumor necrosis factor alpha (TNF-alpha), a cytokine produced by astrocytes and macrophages. To clarify the role of TNF-alpha in experimental CJD, we investigated the expression of TNF-alpha in brain tissues from CJD virus-infected mice at weekly intervals after inoculation by reverse transcription-coupled PCR, Northern and Western blot analyses, and immunocytochemical staining, Neuropathological findings by electron microscopy, as well as expression of interleukin 1 alpha and glial fibrillary acidic protein, were concurrently monitored. As determined by reverse transcription-coupled PCR, the expression of TNF-alpha, interleukin 1 alpha, and glial fibrillary acidic protein was increased by approximately 200-fold in the brains of CJD virus-inoculated mice during the course of disease, By contrast, beta-actin expression remained unchanged. Progressively increased expression of TNF-alpha in CJD virus-infected brain tissues was verified by Northern and Western blot analyses, and astrocytes in areas with striking myelin sheath vacuolation were intensely stained with an antibody against murine TNF-alpha. The collective findings of TNF-alpha overexpression during the course of clinical disease suggest that TNF-alpha may mediate the myelin sheath vacuolation observed in experimental CJD. C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892. RI Kordek, Radzislaw/S-9616-2016 NR 50 TC 75 Z9 77 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 1996 VL 93 IS 18 BP 9754 EP 9758 DI 10.1073/pnas.93.18.9754 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400079 PM 8790403 ER PT J AU Katsafanas, GC Schirmer, EC Wyatt, LS Frenkel, N AF Katsafanas, GC Schirmer, EC Wyatt, LS Frenkel, N TI In vitro activation of human herpesviruses 6 and 7 from latency SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Exanthem subitum; transplantation; bone marrow transplant ID MARROW TRANSPLANT PATIENTS; POLYMERASE CHAIN-REACTION; EXANTHEM-SUBITUM; BONE-MARROW; ANTIGENIC PROPERTIES; CAUSAL AGENT; T-CELLS; INFECTION; CYTOMEGALOVIRUS; REPLICATION AB Human herpesviruses 6 and 7 (HHV-6 and HHV-7) are prevalent lymphotropic viruses that infect more than 80% of children at infancy or during early childhood. Infection ranges from asymptomatic to severe disease. HHV-6B causes exanthem subitum, The virus can be recovered from peripheral blood mononuclear cells during the acute phase of exanthem subitum, but the host remains latently infected throughout life. In immunocompromised patients undergoing kidney, liver, or bone marrow transplantation latent HHV-6B is reactivated, at times causing severe or fatal disease. Here, we describe the establishment of an in vitro system for reactivation of HHV-6B and HHV-7 from latency. HHV-7 is reactivated from latently infected peripheral blood mononuclear cells by T-cell activation. HHV-6B could not be reactivated under similar conditions; however, the latent HHV-6B could be recovered after the cells were infected with HHV-7. Once reactivated, the HHV-6B genomes became prominent and the HHV-7 disappeared. We conclude that HHV-7 can provide a transacting function(s) mediating HHV-6 reactivating from latency. Understanding the activation process is critical for the development of treatments to control the activation of latent viruses so as to avoid these sometimes life threatening infections in transplant recipients. C1 TEL AVIV UNIV,DEPT CELL RES & IMMUNOL,MOL VIROL LAB,IL-69978 TEL AVIV,ISRAEL. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 37 TC 102 Z9 109 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 SEP 3 PY 1996 VL 93 IS 18 BP 9788 EP 9792 DI 10.1073/pnas.93.18.9788 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400085 PM 8790409 ER PT J AU Monack, DM Raupach, B Hromockyj, AE Falkow, S AF Monack, DM Raupach, B Hromockyj, AE Falkow, S TI Salmonella typhimurium invasion induces apoptosis in infected macrophages SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bacterial invasion; programmed cell death; cytotoxicity ID PROGRAMMED CELL-DEATH; SHIGELLA-FLEXNERI; SIGNAL-TRANSDUCTION; EPITHELIAL-CELLS; INTERFERON-GAMMA; FACTOR-RECEPTOR; BACTERIAL; IDENTIFICATION; ENDONUCLEASE; ACTIVATION AB Invasive Salmonella typhimurium induces dramatic cytoskeletal changes on the membrane surface of mammalian epithelial cells and RAW264.7 macrophages as part of its entry mechanism. Noninvasive S. typhimurium strains are unable to induce this membrane ruffling. Invasive S. typhimurium strains invade RAW264.7 macrophages in 2 h with 7- to 10-fold higher levels than noninvasive strains. Invasive S. typhimurium and Salmonella typhi, independent of their ability to replicate intracellularly, are cytotoxic to RAW264.7 macrophages and, to a greater degree, to murine bone marrow-derived macrophages. Here, we show that the macrophage cytotoxicity mediated by invasive Salmonella is apoptosis, as shown by nuclear morphology, cytoplasmic vacuolization, and host cell DNA fragmentation. S. typhimurium that enter cells causing ruffles but are mutant for subsequent intracellular replication also initiate host cell apoptosis. Mutant S. typhimurium that are incapable of inducing host cell membrane ruffling fail to induce apoptosis. The activation state of the macrophage plays a significant role in the response of macrophages to Salmonella invasion, perhaps indicating that the signal or receptor for initiating programmed cell death is upregulated in activated macrophages. The ability of Salmonella to promote apoptosis may be important for the initiation of infection, bacterial survival, and escape of the host immune response. C1 NIH,ROCKY MT LABS,HAMILTON,MT 59840. RP Monack, DM (reprint author), STANFORD UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305, USA. FU NIAID NIH HHS [AI 26195]; NIDDK NIH HHS [DK 38707] NR 35 TC 426 Z9 430 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 1996 VL 93 IS 18 BP 9833 EP 9838 DI 10.1073/pnas.93.18.9833 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400093 PM 8790417 ER PT J AU Smallwood, PM MunozSanjuan, I Tong, P Macke, JP Hendry, SHC Gilbert, DJ Copeland, NG Jenkins, NA Nathans, J AF Smallwood, PM MunozSanjuan, I Tong, P Macke, JP Hendry, SHC Gilbert, DJ Copeland, NG Jenkins, NA Nathans, J TI Fibroblast growth factor (FGF) homologous factors: New members of the FGF family implicated in nervous system development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEAR TRANSLOCATION SEQUENCE; FACTOR MESSENGER-RNAS; NIH 3T3 CELLS; NUCLEOTIDE-SEQUENCE; BINDING-PROTEIN; FACTOR-I; 3-DIMENSIONAL STRUCTURE; GENOMIC ORGANIZATION; MOLECULAR-CLONING; RAT-BRAIN AB Four new members of the fibroblast growth factor (FGF) family, referred to as fibroblast growth factor homologous factors (FHFs), have been identified by a combination of random cDNA sequencing, data base searches, and degenerate PCR Pairwise comparisons between the four FHFs show between 58% and 71% amino acid sequence identity, but each FHF shows less than 30% identity when compared with other FGFs. Like FGF-1 (acidic FGF) and FGF-2 (basic FGF), the FHFs lack a classical signal sequence and contain clusters of basic residues that can act as nuclear localization signals. In transiently transfected 293 cells FHF-1 accumulates in the nucleus and is not secreted. Each FHF is expressed in the developing and adult nervous systems, suggesting a role for this branch of the FGF family in nervous system development and function. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOL BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT OPHTHALMOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. NCI,MAMMALIAN GENET LAB,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 61 TC 269 Z9 279 U1 3 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 1996 VL 93 IS 18 BP 9850 EP 9857 DI 10.1073/pnas.93.18.9850 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400096 PM 8790420 ER PT J AU Ishitani, R Chuang, DM AF Ishitani, R Chuang, DM TI Glyceraldehyde-3-phosphate dehydrogenase antisense oligodeoxynucleotides protect against cytosine arabinonucleoside-induced apoptosis in cultured cerebellar neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE over-expression; neuronal apoptosis; neuroprotection; cerebellar granule cells ID RECEPTOR MESSENGER-RNA; GRANULE CELLS; DEATH; GLUTAMATE; TETRAHYDROAMINOACRIDINE; ACTIVATION; MEMBRANE; BINDING; BRAIN; RAT AB Cytosine arabinonucleoside (AraC) is a pyrimidine antimetabolite that kills proliferating cells by inhibiting DNA synthesis and, importantly, is also an inducer of apoptosis. We recently reported that age-induced apoptotic cell death of cultured cerebellar neurons is directly associated with an over-expression of a particulate 38-kDa protein, identified by us as glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). We now show that the AraC-induced neuronal death of immature cerebellar granule cells in culture is effectively delayed by actinomycin-D, cycloheximide, or aurintricarboxylic acid (a DNase inhibitor), Furthermore, two GAPDH antisense, but not their corresponding sense, oligodeoxyribonucleotides markedly arrested AraC-induced apoptosis. This protection was more effective than that induced by the above-mentioned classical inhibitors of apoptosis. Prior to AraC-induced neuronal death, GAPDH mRNA levels increased by approximate to 2.5-fold, and this mRNA accumulation was blocked by actinomycin-D and the GAPDH antisense (but not sense) oligonucleotide. Like actinomycin-D, a GAPDH antisense oligonucleotide also suppressed the AraC-induced over-expression of the 38-kDa particulate protein (i.e., GAPDH), while the corresponding sense oligonucleotide was totally ineffective. Thus, the present results show that GAPDH over-expression is involved in AraC-induced apoptosis of cultured cerebellar granule cells. C1 NIMH,NATL INST HLTH,BIOL PSYCHIAT BRANCH,MOL NEUROBIOL SECT,BETHESDA,MD 20892. RP Ishitani, R (reprint author), JOSAI UNIV,GRP CELLULAR NEUROBIOL,SAKADO,SAITAMA 35002,JAPAN. NR 29 TC 152 Z9 153 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 3 PY 1996 VL 93 IS 18 BP 9937 EP 9941 DI 10.1073/pnas.93.18.9937 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA VF614 UT WOS:A1996VF61400111 PM 8790435 ER PT J AU Ren, RF Flanders, KC AF Ren, RF Flanders, KC TI Transforming growth factors-beta protect primary rat hippocampal neuronal cultures from degeneration induced by beta-amyloid peptide SO BRAIN RESEARCH LA English DT Article DE transforming growth factor-beta; beta-amyloid peptide; Alzheimers disease; neuroprotection; primary hippocampal neuron; neuroblastoma cell line ID PRECURSOR PROTEIN; MICROGLIAL CELLS; NERVOUS-SYSTEM; MESSENGER-RNA; FACTOR-BETA-1; ALZHEIMER; INVITRO; BRAIN; NEURODEGENERATION; NEUROTOXICITY AB Treatment of primary rat embryo hippocampal neuronal cultures with 10(-5) M beta-amyloid peptide fragment 25-35 (A beta P) for 24 h resulted in a 60% decrease in cell viability as determined by MTT incorporation. When these cells were treated with 0.1-10 ng/ml of either transforming growth factor-beta (TGF-beta) 1, 2 or 3 for 24 h before exposure to A beta P, there was a 2.9-, 1.9-, and 3.2-fold increase in cell survival, respectively, compared to cells treated with A beta P alone. The viability of cells treated with A beta P and 0.1-10 ng/ml TGF-beta was comparable to that of cells not treated with A beta P. The protective effects were less pronounced at lower TGF-beta concentrations. The protective effects of pretreatment with TGF-beta were less striking in mouse CCL-N-2a and human SK-N-SH neuroblastoma cell Lines. When all cells were treated with TGF-beta for 24 h following a 24 h exposure to A beta P, there was a trend toward increased cell viability which was less significant than pretreatment with TGFs-beta. An isoform-specific TGF-beta SELISA showed that primary hippocampal neuronal cultures and the neuroblastoma cell lines secrete all 3 TGF-beta isoforms. Based on our results, we propose that the increased expression of TGF-beta observed in brains of patients with Alzheimer's disease may offer some degree of neuroprotection. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 41 TC 55 Z9 56 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 SEP 2 PY 1996 VL 732 IS 1-2 BP 16 EP 24 DI 10.1016/0006-8993(96)00458-1 PG 9 WC Neurosciences SC Neurosciences & Neurology GA VJ037 UT WOS:A1996VJ03700002 PM 8891264 ER PT J AU Celerin, M Ray, JM Schisler, NJ Day, AW StetlerStevenson, WG Laudenbach, DE AF Celerin, M Ray, JM Schisler, NJ Day, AW StetlerStevenson, WG Laudenbach, DE TI Fungal fimbriae are composed of collagen SO EMBO JOURNAL LA English DT Article DE collagen; fimbriae; fungus; Microbotryum; Ustilago ID CANDIDA-ALBICANS; EXTRACELLULAR-MATRIX; USTILAGO-VIOLACEA; CELL-ADHESION; RECEPTORS; ADHERENCE; PROTEIN; GROWTH; SMUT; ANIMALIA AB Fungal fimbriae are surface appendages that were first described on the haploid cells of the smut fungus, Microbotryum violaceum, They are long (1-20 mu m), narrow (7 nm) flexuous structures that have been implicated in cellular functions such as mating and pathogenesis. Since the initial description, numerous fungi from all five phyla have been shown to produce fimbriae on their extracellular surfaces, The present study analyses the protein component of M.violaceum fimbriae, The N-terminus and three internal amino acid sequences were determined. All four show a strong similarity to sequences which are characteristic of the collagen gene family, Enzymatic digests and immunochemical analyses support this finding, Based on these results, it is suggested that the proteinaceous subunits of fimbriae should be termed fungal collagens, Previously, collagen has been found only among members of the kingdom Animalia where it is the principal component of the animal extracellular matrix and is the most abundant animal protein, The unexpected finding of collagen in the members of the Mycota suggests that it may have evolved from a common ancestor that existed before the divergence of fungi and animals, Further, native fungal fimbriae can function as a mammalian extracellular matrix component, They can act as a substratum which permits animal cells to adhere, spread, and proliferate in a manner similar to animal collagens, The implications of this finding to both phylogeny and pathology are discussed. C1 UNIV WESTERN ONTARIO,DEPT ZOOL,LONDON,ON N6A 5B7,CANADA. NCI,EXTRACELLULAR MATRIX PATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 50 TC 54 Z9 55 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD SEP 2 PY 1996 VL 15 IS 17 BP 4445 EP 4453 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VH004 UT WOS:A1996VH00400001 PM 8887535 ER PT J AU Lai, SY Molden, J Liu, KD Puck, JM White, MD Goldsmith, MA AF Lai, SY Molden, J Liu, KD Puck, JM White, MD Goldsmith, MA TI Interleukin-4-specific signal transduction events are driven by homotypic interactions of the interleukin-4 receptor alpha subunit SO EMBO JOURNAL LA English DT Article DE interleukin-4; JAK-STAT; receptor; signal transduction; specificity ID SEVERE COMBINED IMMUNODEFICIENCY; GAMMA-CHAIN; IL-2 RECEPTOR; FUNCTIONAL COMPONENT; LYMPHOID DEVELOPMENT; TRANSCRIPTION FACTOR; CYTOPLASMIC REGION; BETA-CHAIN; CELLS; CLONING AB Interleukin-4 (IL-4) exerts its effects through a heterodimeric receptor complex (IL-4R), which contains the IL-4R alpha and gamma(c) subunits, IL-4R alpha also functions with other partner subunits in several receptor types, including the IL-13 receptor, To examine the roles of the individual subunits within IL-4R complexes, we employed a chimeric system that recapitulates native IL-4R function as verified by the activation of the kinases, JAK1 and JAK3, and induction of STAT-6. When a mutant gamma(c) subunit in which the four cytoplasmic tyrosines were converted to phenylalanine was paired with the cytoplasmic domain of the IL-4R alpha chain, specificity within the JAK-STAT pathway was not altered, Signaling events were examined further in cells expressing the IL-4R alpha chimera alone without the gamma(c) chimera, Ligand-induced homodimerization of these receptors activated the IL-4 signaling program despite the absence of gamma(c), including induction of JAK1 and STAT-6, phosphorylation of the insulin-related substrate 1 and cellular proliferation, Thus, homotypic interactions of the IL-4R alpha subunit are sufficient for the initiation and determination of IL-4-specific signaling events, and such interactions may be integral to signaling through IL-4R complexes. C1 UNIV CALIF SAN FRANCISCO,SCH MED,GLADSTONE INST VIROL & IMMUNOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,DEPT MED,SAN FRANCISCO,CA 94143. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA. FU NIGMS NIH HHS [GM54351-01] NR 53 TC 71 Z9 72 U1 0 U2 0 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 SEP 2 PY 1996 VL 15 IS 17 BP 4506 EP 4514 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VH004 UT WOS:A1996VH00400008 PM 8887542 ER PT J AU Raynal, P Kuijpers, G Rojas, E Pollard, HB AF Raynal, P Kuijpers, G Rojas, E Pollard, HB TI Rise in nuclear calcium translocates annexins IV and V to the nuclear envelope SO FEBS LETTERS LA English DT Article DE annexin; Ca2+; Nucleus; 85-kDa cytosolic; phospholipase A(2) ID ENDOTHELIAL-CELLS AB Following incubation of human fibroblasts with Ca2+ ionophore A23187, we found strong immunofluorescence labelling of the nuclear envelope by annexin IV antibody. Using confocal imaging of cells loaded with Fluo-3, we showed that A23187 generates an intense and sustained rise of Ca2+ in the nucleus, By contrast, stimulation without extracellular Ca2+ produces only a brief rise in nuclear Ca2+ that does not promote annexin IV translocation to the nuclear envelope, and compounds that induce only a transient increase of nuclear Ca2+ do not support translocation of annexin IV. In addition, annexin V was also translocated to the nuclear envelope by A23187, but distribution of annexins I, II, VI and VII is unaffected, In in vitro assays with isolated nuclei, annexin V was also found to bind to the nuclear envelope in a Ca (2+)-dependent manner, These results demonstrate that the translocation to the nuclear envelope of different types of Ca2+-regulated proteins is directly triggered by a major rise of Ca2+ in the nucleus. C1 NIDDKD,CELL BIOL & GENET LAB,NIH,BETHESDA,MD 20892. NR 11 TC 35 Z9 35 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 SEP 2 PY 1996 VL 392 IS 3 BP 263 EP 268 DI 10.1016/0014-5793(96)00827-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VF855 UT WOS:A1996VF85500014 PM 8774858 ER PT J AU Malhotra, AK Goldman, D Ozaki, N Rooney, W Clifton, A Buchanan, RW Breier, A Pickar, D AF Malhotra, AK Goldman, D Ozaki, N Rooney, W Clifton, A Buchanan, RW Breier, A Pickar, D TI Clozapine response and the 5HT(2C)Cys(23)Ser polymorphism SO NEUROREPORT LA English DT Article DE 5HT(2C) receptor; amino acid substitution; clozapine; schizophrenia; genotype; association study; allele AB THE, presence of the 5HT(2C) receptor allele, Ser(23), has recently been reported to predict favorable response to the antipsychotic drug, clozapine. This finding is of interest as Ser(23), compared with the more abundant Cys(23), alters pharmacological characteristics of the receptor and therefore may provide insights into the mechanism of action of antipsychotic drugs. We determined 5HT(2C) receptor genotype at the Cys(23)Ser locus in 66 subjects participating in double-blind studies of clozapine. There was no relationship between Ser(23) and clozapine response (p = 0.30, Fisher's exact) nor was there any effect of Ser(23) upon absolute levels of psychiatric symptoms after 10 weeks of clozapine treatment (t = -0.57, p = 0.57). These data suggest that this 5HT(2C) receptor polymorphism is not associated with clozapine response. C1 NIAAA, NEUROGENET LAB, BETHESDA, MD 20892 USA. UNIV MARYLAND, MARYLAND PSYCHIAT RES CTR, DEPT PSYCHIAT, SCH MED, BALTIMORE, MD 21201 USA. RP NIMH, EXPT THERAPEUT BRANCH, 10 CTR DR, BLDG 10, ROOM 4N212, BETHESDA, MD 20892 USA. RI Ozaki, Norio/M-8908-2014; Goldman, David/F-9772-2010 OI Ozaki, Norio/0000-0002-7360-4898; Goldman, David/0000-0002-1724-5405 NR 6 TC 51 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0959-4965 EI 1473-558X J9 NEUROREPORT JI Neuroreport PD SEP 2 PY 1996 VL 7 IS 13 BP 2100 EP 2102 DI 10.1097/00001756-199609020-00007 PG 3 WC Neurosciences SC Neurosciences & Neurology GA WD441 UT WOS:A1996WD44100009 PM 8930967 ER PT J AU Li, CY Peoples, RW Weight, FF AF Li, CY Peoples, RW Weight, FF TI Acid pH augments excitatory action of ATP on a dissociated mammalian sensory neuron SO NEUROREPORT LA English DT Article DE pH; ATP; ion channels; P2X purinoceptors; acidification; alkalinization; sensory neuron; pain ID EXTRACELLULAR ATP; RECEPTOR; PROTONS; CELLS AB ATP stimulates nociceptive neurons via an action on ligand-gated ion channels. Since tissue injury and inflammation result in both localized acidosis and release of ATP, we studied the effect of acid pH on ATP-gated ion channels in rat nodose ganglion neurons. Lowering pH dramatically increased membrane depolarization and action potential firing elicited by ATP. ATP-activated current was enhanced by acid pH and suppressed by alkaline pH. A pH of 7.2 produced the half-maximal effect. Acidification increased the apparent affinity of the receptor for ATP, as evidenced by a parallel shift of the ATP concentration-response curve to the left. The observations suggest that the localized acidosis associated with tissue injury may enhance pain perception via an action on ATP-gated ion channels on mammalian sensory neurons. RP Li, CY (reprint author), NIAAA,MOL & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 23 TC 28 Z9 29 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 2 PY 1996 VL 7 IS 13 BP 2151 EP 2154 DI 10.1097/00001756-199609020-00018 PG 4 WC Neurosciences SC Neurosciences & Neurology GA WD441 UT WOS:A1996WD44100020 PM 8930978 ER PT J AU Ren, K Ruda, MA AF Ren, K Ruda, MA TI Descending modulation of Fos expression after persistent peripheral inflammation SO NEUROREPORT LA English DT Article DE pain; nociception; c-fos; spinal transection; descending inhibition ID SPINAL-CORD; NOXIOUS-STIMULATION; RAT; NEURONS; INHIBITION; PROTEIN; INCREASE; PAIN AB THE effects of spinal transection on Fos protein expression following complete Freund's adjuvant-induced hindpaw inflammation and hyperalgesia were studied. Fos-like immunoreactivity (LI) was used as a measure of neuronal activity in dorsal horn nociceptive pathways. Induction of Fos-LI in spinally transected rats with 3 days of hindpaw inflammation was significantly increased in ipsilateral lumbar (L4,5) spinal cord, when compared with control animals with Similar inflammation but an intact spinal cord. The contralateral side of spinally transected rats also showed significant induction of Fos-LI compared to the non-inflamed side of control rats. Since Fos induction provides an indication of the level of neuronal activity in response to a given stimulus, these results suggest that the net effect of brain stem descending pathways is to dampen central hyperexcitability in the spinal cord induced by tissue inflammation and hyperalgesia. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. NR 20 TC 64 Z9 64 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 2 PY 1996 VL 7 IS 13 BP 2186 EP 2190 DI 10.1097/00001756-199609020-00026 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WD441 UT WOS:A1996WD44100028 PM 8930986 ER PT J AU Tang, Y Aigner, TG AF Tang, Y Aigner, TG TI Release of cerebral acetylcholine increases during visually mediated behavior in monkeys SO NEUROREPORT LA English DT Article DE memory; recognition; rhinal cortex; hippocampus; temporal cortex; acetylcholine; microdialysis; monkeys ID BASAL FOREBRAIN; ALZHEIMERS-DISEASE; RECOGNITION MEMORY; NUCLEUS BASALIS; RHESUS-MONKEYS; CHOLINERGIC INNERVATION; SENILE DEMENTIA; SYSTEM; HIPPOCAMPUS; IMPAIRMENT AB EXTRACELLULAR levels of acetylcholine in inferior temporal cortex (IT), perirhinal cortex (PR), and dentate gyrus (DG) of the hippocampus were monitored using in vivo microdialysis in rhesus monkeys performing two behavioral tasks. Performance on a visual recognition task was associated with 26%, 41% and 24% increases in acetylcholine overflow in IT, PR and DG, respectively, compared with pre-test baseline levels. Performance on a memory-independent task was associated with increases in acetylcholine release of 24%, 34% and 7% above baseline in IT, PR and DG, respectively. The PR-DG differences were significant, but the others were not. The results provide biochemical evidence for cerebral cholinergic system activation during visually mediated behavior in non-human primates, and are consistent with the view that such activation is a prerequisite for visual recognition memory. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NR 21 TC 21 Z9 24 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 2 PY 1996 VL 7 IS 13 BP 2231 EP 2235 DI 10.1097/00001756-199609020-00034 PG 5 WC Neurosciences SC Neurosciences & Neurology GA WD441 UT WOS:A1996WD44100037 PM 8930995 ER PT J AU Horowitz, MS AF Horowitz, MS TI Educational loan repayment/forgiveness programs: A creative solution to a serious problem SO ACADEMIC MEDICINE LA English DT Editorial Material RP Horowitz, MS (reprint author), NIH,OFF LOAN REPAYMENT & SCHOLARSHIP,OFF INTRAMURAL RES,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1996 VL 71 IS 9 BP 986 EP 987 DI 10.1097/00001888-199609000-00014 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA VH214 UT WOS:A1996VH21400020 PM 9125987 ER PT J AU Endrizzi, J Zhang, GY Xiong, WFC Hurley, JH Remington, SJ Colman, RF AF Endrizzi, J Zhang, GY Xiong, WFC Hurley, JH Remington, SJ Colman, RF TI Crystallization and preliminary diffraction analysis of porcine heart mitochondrial NADP(+)-dependent isocitrate dehydrogenase SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; PIG-HEART; 3-ISOPROPYLMALATE DEHYDROGENASE; BINDING-SITE; ENZYME; DIMERIZATION; NUCLEOTIDES; COENZYMES; MECHANISM; SEQUENCE AB Isocitrate dehydrogenases [isocitrate:NAD(P)(+) oxidoreductase (decarboxylating), E.C. 1.1.1.42] are ubiquitous metabolic enzymes which occur in all living organisms. The NADP(+)-dependent mitochondrial isocitrate dehydrogenase from pig heart has been crystallized from polyethylene glycol/sodium sulfate mixtures in the presence of Mg2+ and isocitrate. The crystals belong to space group C2 with a=137.0, b=113.4, c=65.0 Angstrom and beta=98.5 degrees, and diffract to at least 2.4 Angstrom resolution. There are two protein monomers per asymmetric unit which are related by non-crystallographic twofold symmetry. C1 UNIV OREGON,INST MOL BIOL,EUGENE,OR 97403. NIDDKD,NIH,MOL BIOL LAB,BETHESDA,MD 20892. UNIV DELAWARE,DEPT CHEM & BIOCHEM,NEWARK,DE 19716. NR 22 TC 4 Z9 4 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD SEP 1 PY 1996 VL 52 BP 1024 EP 1026 DI 10.1107/S0907444996006154 PN 5 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA VM251 UT WOS:A1996VM25100020 PM 15299615 ER PT J AU Drusano, GL Aweeka, F Gambertoglio, J Jacobson, M Polis, M Lane, HC Eaton, C MartinMunley, S AF Drusano, GL Aweeka, F Gambertoglio, J Jacobson, M Polis, M Lane, HC Eaton, C MartinMunley, S TI Relationship between foscarnet exposure, baseline cytomegalovirus (CMV) blood culture and the time to progression of CMV retinitis in HIV-positive patients SO AIDS LA English DT Article DE cytomegalovirus retinitis; foscarnet; pharmacodynamics ID IMMUNODEFICIENCY-VIRUS INFECTION; CONTROLLED TRIAL; AIDS; ZIDOVUDINE AB Objective: To determine some of the factors influencing the time to progression of cytomegalovirus (CMV) retinitis among HIV-infected patients being treated with foscarnet. Design: A retrospective analysis of two open-label Phase I/II studies in multiple university hospitals. Patients were studied in both inpatient and outpatient settings. Patients: Of the patients in the databases examined, 31 had adequate pharmacokinetic information and 29 had information on outcome and the other patient covariates. Intervention: After induction therapy with foscarnet at a dose of 60 mg/kg three times daily was completed, patients had maintenance therapy with 60-120 mg/kg foscarnet once daily. poses were subsequently adjusted for changed estimated creatinine clearance. Measurements: The measured endpoint was time to progression of CMV retinitis. The independent variables examined to determine influence on time to progression included mean peak foscarnet concentration, mean area under the concentration-time curve (AUG) for foscarnet, the positive or negative outcome of a baseline blood culture for CMV, the initial CP4 cell count for a patient and the peak CP4 cell count observed during maintenance therapy. Results: A wide range (-10-fold) of foscarnet AUC was observed, even though only a fourfold dose range was employed, and doses were altered for changing estimated creatinine clearance. in a multivariate Cox model, only AUC and the status of the baseline CMV blood culture significantly affected the time to progression of the retinitis. Conclusion: The AUC produced by a dose of foscarnet has a wide interindividual range. The AUC of foscarnet significantly altered time to progression of the retinitis. However, patients with positive baseline CMV blood cultures had a significantly more shallow dose-response curve. This indicates that the added risk of nephrotoxicity which is present with aggressive foscarnet dosing might be best borne by the subgroup of patients with a positive CMV blood culture at baseline. C1 ALBANY MED COLL,DEPT PHARMACOL,ALBANY,NY 12208. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. ASTRA USA INC,WESTBOROUGH,MA. RP Drusano, GL (reprint author), ALBANY MED COLL,DIV CLIN PHARMACOL,DEPT MED,ALBANY,NY 12208, USA. OI Polis, Michael/0000-0002-9151-2268 NR 16 TC 6 Z9 6 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1996 VL 10 IS 10 BP 1113 EP 1119 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VE790 UT WOS:A1996VE79000009 PM 8874628 ER PT J AU Easterbrook, PJ Farzadegan, H Hoover, DR Palenicek, J Chmiel, JS Kaslow, RA Saah, AJ AF Easterbrook, PJ Farzadegan, H Hoover, DR Palenicek, J Chmiel, JS Kaslow, RA Saah, AJ TI Racial differences in rate of CD4 decline in HIV-1-infected homosexual men SO AIDS LA English DT Article DE racial minorities; black race; CD4 lymphocyte count; HIV-1 p24 antigen; immune complex dissociation ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTER AIDS COHORT; HIV P24 ANTIGEN; ETHNIC-DIFFERENCES; IMMUNE-COMPLEXES; INFECTION; RACE; LYMPHOCYTES; AFRICAN; INDIVIDUALS AB Objective: To determine whether racial differences exist in the rate of CD4 lymphocyte decline in HIV-1-infected homosexual men. Design: Prospective cohort study. Study population: Non-Hispanic white (n = 321) and black (n = 102) HIV-1-seropositive homosexual and bisexual men were recruited from the Baltimore/ Washington, DC metropolitan areas between 1984-1985 and 1987-1990, and evaluated semiannually. Main measurements: Changes in CD4 lymphocyte count and CD4 percentage over time were analysed using linear regression methods for the 271 white and 69 black participants who had at least four semiannual CD4 lymphocyte measurements. Results: Rate of decline in CD4 lymphocyte count over 6 months was much slower among black than white seroprevalent men at all levels of baseline CD4 count (baseline 201-400x10(6)/l: +0.24 versus -17.7x10(6)/l; 401-600x10(6)/l: -11.3 versus -23.9x10(6)/l; 601-800x10(6)/l: -15.1 versus -35.2x10(6)/l; > 800x10(6)/l: -4.3 versus -42.7x10(6)/l for black versus white, respectively), although this was only statistically significant for the lowest and highest strata of baseline CD4 count. These racial differences persisted after adjustment for recruitment period (1984-1985 or 1987-1990), follow-up duration, age and zidovudine therapy or Pneumocystis carinii pneumonia prophylaxis. Similar findings were observed among the 70 white and 11 black seroconverters. Black participants were also less likely than a subgroup of white participants matched on baseline CD4 lymphocyte count to be HIV-1 p24 antigen-positive. However, after acid dissociation of samples initially p24 antigen-negative, there were no significant differences in the prevalence of p24 antigenemia at enrollment or after 1 year of follow-up. Conclusions: This analysis suggests a more gradual decline in CD4 lymphocyte count among black than white Americans. The clinical significance of and reasons for this are unclear, but the lower prevalence of p24 antigenemia due to immune complexing among black Americans suggests that racial differences in the immune response to HIV may exist. Additional studies are needed to validate these findings in a larger cohort of non-whites, and to assess their relationship with other measures of cell-mediated immune function. C1 JOHNS HOPKINS SCH HYG & PUBL HLTH,BALTIMORE,MD. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. NIAID,BETHESDA,MD 20892. FU PHS HHS [N01-AL-72632, N01-AL-72631, N01-AL-72634] NR 31 TC 28 Z9 28 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1996 VL 10 IS 10 BP 1147 EP 1155 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VE790 UT WOS:A1996VE79000014 PM 8874633 ER PT J AU Poole, WK Fulkerson, W Lou, Y Kvale, P Hopewell, PC Hirschtick, R Glassroth, J Rosen, M Mangura, B Wallace, J Markowitz, N Stansell, J Turner, J Osmond, D Mossar, M Meiselman, L Manghisi, KK Cardozo, C Kalb, TH Reichman, LB Jenkins, S Hanson, C Dowell, F OToole, M LeMaire, B Richer, B Au, J Coulson, A Clemente, V Shapiro, B Saravolatz, LD Johnson, C Huitsing, J Krystoforski, A Rao, AV Clayton, K Hansen, N Jordan, M Thompson, J Myers, D LaVange, L Katzin, J Wilcosky, T Game, S Kalica, A Peavy, H Wittes, J Follmann, DA Wise, R Cherniack, R Ware, JH Bartlett, JG Connett, JE Daniele, RP French, JF Goebel, FD Snider, DE Turino, GN AF Poole, WK Fulkerson, W Lou, Y Kvale, P Hopewell, PC Hirschtick, R Glassroth, J Rosen, M Mangura, B Wallace, J Markowitz, N Stansell, J Turner, J Osmond, D Mossar, M Meiselman, L Manghisi, KK Cardozo, C Kalb, TH Reichman, LB Jenkins, S Hanson, C Dowell, F OToole, M LeMaire, B Richer, B Au, J Coulson, A Clemente, V Shapiro, B Saravolatz, LD Johnson, C Huitsing, J Krystoforski, A Rao, AV Clayton, K Hansen, N Jordan, M Thompson, J Myers, D LaVange, L Katzin, J Wilcosky, T Game, S Kalica, A Peavy, H Wittes, J Follmann, DA Wise, R Cherniack, R Ware, JH Bartlett, JG Connett, JE Daniele, RP French, JF Goebel, FD Snider, DE Turino, GN TI Overall and cause-specific mortality in a cohort of homo-/bisexual men, injecting drug users, and female partners of HIV-infected men SO AIDS LA English DT Article DE HIV survival analysis; HIV risk groups; AIDS; mortality; cause-specific mortality ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEW-YORK-CITY; DISEASE PROGRESSION; SURVIVAL; DEATH; AIDS; EXPERIENCE; WOMEN; RISK AB Objective: To study the overall and cause-specific HIV-related mortality in a cohort of HIV-seropositive subjects according to transmission category, race/ethnicity, sex and severity of immunosuppression. Design: A cohort of 1129 HIV-seropositive homo-/bisexual men, injecting drug users, and female partners of HIV-infected men were enrolled at six centers in San Francisco, Los Angeles, Chicago, Newark, Detroit and New York between 1 November 1988 and 1 November 1989. Subjects were evaluated every 6 months at least until 31 March 1994. Methods: The analyses of overall mortality for the subgroups of interest were performed with Kaplan-Meier plots and Cox proportional hazards models. Cause-specific analyses were performed on the primary cause of death using rates per 100 person-years of exposure. Results and Conclusions: Baseline severity of immunosuppression is the strongest predictor of mortality. There were no statistically significant differences in overall HIV-related mortality among transmission categories, race/ethnicity groups or sexes. There were differences, however, in cause-specific mortality among the different risk groups. C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. DUKE UNIV,MED CTR,DURHAM,NC. HENRY FORD HOSP,DETROIT,MI 48202. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NORTHWESTERN UNIV,CHICAGO,IL 60611. MED COLL PENN & HAHNEMANN UNIV,PHILADELPHIA,PA. BETH ISRAEL MED CTR,NEW YORK,NY 10003. UNIV MED & DENT NEW JERSEY,NEWARK,NJ 07103. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV MED & DENT NEW JERSEY HOSP,NEW JERSEY MED SCH,NEWARK,NJ. HENRY FORD HOSP,DETROIT,MI 48202. JOHNS HOPKINS UNIV,NHLBI,BALTIMORE,MD 21218. FU NHLBI NIH HHS [N01-HR7-8029, N01-HR7-6030, N01-HR7-6031] NR 35 TC 13 Z9 13 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1996 VL 10 IS 11 BP 1257 EP 1264 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VH722 UT WOS:A1996VH72200012 PM 8883588 ER PT J AU Bulterys, M Goedert, JJ AF Bulterys, M Goedert, JJ TI From biology to sexual behaviour - Towards the prevention of mother-to-child transmission of HIV SO AIDS LA English DT Editorial Material DE AIDS; HIV; perinatal transmission; sexual behavior; pregnancy ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; INFECTION; WOMEN; TWINS; RISK C1 NCI,VIRAL EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP Bulterys, M (reprint author), UNIV NEW MEXICO,SCH MED,CTR POPULAT HLTH,2400 TUCKER AVE,ALBUQUERQUE,NM 87131, USA. NR 24 TC 7 Z9 8 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD SEP PY 1996 VL 10 IS 11 BP 1287 EP 1289 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA VH722 UT WOS:A1996VH72200016 PM 8883592 ER PT J AU Radebaugh, TS Buckholtz, NS Khachaturian, ZS AF Radebaugh, TS Buckholtz, NS Khachaturian, ZS TI Fisher Symposium: Strategies for the prevention of Alzheimer disease - Overview of research planning meeting III SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Editorial Material DE Alzheimer disease; prevention; epidemiology; clinical trials AB Even though the prospect for preventing Alzheimer disease seems remote now, a plan must be developed to reach this goal in order to avoid a fiscal crisis in the health care system. The goals of delaying Alzheimer disease and eventually preventing it will become possible as more is learned about the brain mechanisms and risk factors involved. In response to a 1994 Congressional report, the National Institute on Aging in cooperation with the Zachary and Elizabeth M. Fisher Medical Foundation sponsored a workshop to address potential strategies for the prevention of Alzheimer disease. The workshop helped to identify the necessary resources and the types of technical problems involved in developing methods to prevent Alzheimer disease. This volume presents the position papers which served as the springboard for the discussions at the workshop, out of which developed a number of specific recommendations including new epidemiological studies for well defined population groups, identification of high risk populations for treatment and prevention studies, and coupling of new questions and add-on investigations to in-progress studies. C1 NIA,NEUROSCI & NEUROPSYCHOL AGING PROGRAM,NIH,BETHESDA,MD 20892. NATL INST NURSING RES,NIH,BETHESDA,MD. NR 1 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD FAL PY 1996 VL 10 SU 1 BP 1 EP 5 DI 10.1097/00002093-199601031-00001 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA VF274 UT WOS:A1996VF27400001 PM 8876779 ER PT J AU Dimitrov, NV MeyerLeece, C McMillan, J Gilliland, D Perloff, M Malone, W AF Dimitrov, NV MeyerLeece, C McMillan, J Gilliland, D Perloff, M Malone, W TI Plasma alpha-tocopherol concentrations after supplementation with water- and fat-soluble vitamin E SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE vitamin E; water-soluble vitamins; kinetics; humans; bioavailability ID POLYETHYLENE GLYCOL-1000 SUCCINATE; E-DEFICIENCY; TRANSFER PROTEIN; INTESTINAL-ABSORPTION; BINDING-PROTEIN; RAT-LIVER; HUMANS; BIOAVAILABILITY; ACETATE; RRR AB The objective of this study was to examine differences in plasma alpha-tocopherol concentrations after oral administration of pharmacologic doses of vitamin E to normal healthy subjects as RRR-alpha-tocopheryl glycol 1000 succinate (TPGS; water-miscible form) and RRR-alpha-tocopheryl acetate (TA; fat-soluble form). The study was designed to evaluate the administration of three different single doses and multiple doses for 4 wk with both preparations. Administration of 400 IU (269 mg), 800 nr (537 mg), and 1200 IU (807 mg) TPGS as a single dose resulted in slight elevation of plasma alpha-tocopherol concentrations. Administration of multiple daily doses at all three amounts of TPGS for 28 consecutive days resulted in a slight elevation of plasma alpha-tocopherol concentrations. A significant increase in plasma alpha-tocopherol concentrations was observed after ingestion of a single dose or equivalent multiple doses of TA at all three doses. As reported in the Literature, in cases of cholestasis and other forms of lipid malabsorption, oral administration of TPGS is the treatment of choice. It appears that for normal adults and patients with normal lipid absorption, fat-soluble forms of vitamin E are preferable for therapeutic and prophylactic uses. C1 NCI, DCPC, CHEMOPREVENT BRANCH, ROCKVILLE, MD USA. RP MICHIGAN STATE UNIV, DEPT MED, B-220 LIFE SCI BLDG, E LANSING, MI 48824 USA. FU NCI NIH HHS [N01-CN-85104] NR 41 TC 12 Z9 12 U1 0 U2 2 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1996 VL 64 IS 3 BP 329 EP 335 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VE607 UT WOS:A1996VE60700011 PM 8780342 ER PT J AU Levine, M AF Levine, M TI Fruits and vegetables: There is no substitute SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material ID ASCORBIC-ACID RP Levine, M (reprint author), NIDDKD,MOL & CLIN NUTR SECT,DIABET BRANCH,NIH,BLDG 10,ROOM 4D-52-MSC1372,BETHESDA,MD 20892, USA. NR 13 TC 1 Z9 1 U1 0 U2 1 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 SEP PY 1996 VL 64 IS 3 BP 381 EP 382 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VE607 UT WOS:A1996VE60700020 PM 8780351 ER PT J AU Yanovski, SZ Hubbard, VS Lukaski, HC Heymsfield, SB AF Yanovski, SZ Hubbard, VS Lukaski, HC Heymsfield, SB TI Bioelectrical impedance analysis in body composition measurement - Proceedings of a National Institutes of Health Technology Assessment Conference held in Bethesda, MD, December 12-14, 1994 - Introduction SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material C1 COLUMBIA UNIV, ST LUKES ROOSEVELT HOSP CTR, COLL PHYS & SURG, OBES RES CTR, NEW YORK, NY USA. USDA ARS, GRAND FORKS HUMAN NUTR RES CTR, GRAND FORKS, ND 58202 USA. NIDDKD, NUTR SCI BRANCH, NIH, BETHESDA, MD 20892 USA. RP NIDDKD, DIV DIGEST DIS & NUTR, NIH, BETHESDA, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1996 VL 64 IS 3 SU S BP 387 EP 387 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VE984 UT WOS:A1996VE98400001 ER PT J AU Davis, JW Grandinetti, A Waslien, CI Ross, GW White, LR Morens, DM AF Davis, JW Grandinetti, A Waslien, CI Ross, GW White, LR Morens, DM TI Observations on serum uric acid levels and the risk of idiopathic Parkinson's disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE mortality; Parkinson's disease; uric acid ID SUBSTANTIA-NIGRA; CIGARETTE-SMOKING; GLUTATHIONE; HYPOTHESIS; OXIDATION; FERRITIN; HAWAII; METALS; BRAINS; IRON AB Uric acid, an antioxidant found in high concentrations in serum and in the brain, has been hypothesized to protect against oxidative damage and cell death in Parkinson's disease, The authors tested this hypothesis among men participating in a 30-year prospective study known as the Honolulu Heart Program, Serum uric acid was measured in 7,968 men at the baseline examination held from 1965 to 1968, Of these men, 92 subsequently developed idiopathic Parkinson's disease (IPD), In analyses adjusted for age and smoking, men with uric acid concentrations above the median at enrollment had a 40% reduction in IPD incidence (rate ratio (RR) = 0.6; 95% confidence interval (CI) 0.4-1.0), Reduced IPD incidence rates persisted in analyses restricted to nonsmokers (RR = 0.5; 95% CI 0.3-1.0) and cases younger than age 75 years (RR = 0.5; 95% CI 0.3-0.9), Incidence rates were not notably affected when analyses were restricted to cases that occurred more than 5 years after uric acid measurement (RR = 0.6; 95% CI 0.4-1.0). Inclusion of known or computed correlates of uric acid in regression models did not substantially change risk of IPD, This study provides prospective evidence of an association between uric acid and reduced occurrence of IPD and indicates that further investigations of this association are warranted. C1 UNIV HAWAII,SCH PUBL HLTH,PROGRAM EPIDEMIOL,HONOLULU,HI 96822. HAWAII OSTEOPOROSIS CTR,HONOLULU,HI. EAST WEST CTR,HONOLULU,HI 96848. UNIV HAWAII,SCH MED,DEPT INTERNAL MED,HONOLULU,HI. US DEPT VET AFFAIRS,HONOLULU,HI. NIA,NIH,HONOLULU,HI. UNIV HAWAII,SCH MED,DEPT TROP MED,HONOLULU,HI. NR 21 TC 114 Z9 119 U1 0 U2 8 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 SEP 1 PY 1996 VL 144 IS 5 BP 480 EP 484 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VE900 UT WOS:A1996VE90000007 PM 8781463 ER PT J AU Boyer, BA Barakat, LP AF Boyer, BA Barakat, LP TI Mothers of children with leukemia: Self-reported and observed distress and coping during painful pediatric procedures SO AMERICAN JOURNAL OF FAMILY THERAPY LA English DT Article ID MEDICAL PROCEDURES; ADULTS; ADAPTATION; STRESS AB Self-reported maternal coping, self-rated maternal distress, and observed distress and coping behaviors were assessed during lumbar punctures (LP) with families of 45 patients with leukemia. Mothers' subscale means for Ways of Coping Scale (WCS) were significantly higher for 4 of 8 dimensions in this sample than for a stressed community sample. Mothers displayed almost no overt distress, but reported moderate distress both before and after the procedure. Planful problem-solving and self-controlling coping strategies showed correlations of moderate magnitude with observed maternal coping. In regression analyses, mothers' observed distress and coping were most strongly related to patient age and patients' observed distress and coping. Findings are discussed in terms of identifying mothers at risk for greater distress and the difficulties in coping with procedures throughout childhood leukemia treatment. C1 CHILDRENS HOSP PHILADELPHIA,DIV ONCOL,PHILADELPHIA,PA 19104. NCI,BETHESDA,MD 20892. VILLANOVA UNIV,VILLANOVA,PA 19085. RP Boyer, BA (reprint author), MERCY CATHOLIC MED CTR,MSB MEZZANINE,DIV BEHAV MED,1500 LANSDOWNE AVE,DARBY,PA 19023, USA. NR 32 TC 7 Z9 7 U1 1 U2 2 PU BRUNNER/MAZEL INC PI NEW YORK PA 19 UNION SQUARE WEST, NEW YORK, NY 10003 SN 0192-6187 J9 AM J FAM THER JI Am. J. Fam. Ther. PD FAL PY 1996 VL 24 IS 3 BP 227 EP 241 DI 10.1080/01926189608251036 PG 15 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA VQ682 UT WOS:A1996VQ68200004 ER PT J AU Takagi, H Shimoda, R Uehara, M Takayama, H Yamada, T Ojima, T Abe, T Mori, M Takehara, K Suka, K Nagamine, T Yamasaki, S Barber, A AF Takagi, H Shimoda, R Uehara, M Takayama, H Yamada, T Ojima, T Abe, T Mori, M Takehara, K Suka, K Nagamine, T Yamasaki, S Barber, A TI Hepatocellular carcinoma with pleural metastasis complicated by hemothorax SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID RUPTURE AB Hemothorax can be caused by rupture of hepatocellular carcinoma (HCC). Hemoperitoneum is a well-known cause of death caused by rupture of a primary HCC lesion. Rupture of a HCC metastasis has not been adequately described. This is the first report of a HCC patient who died of hemothorax due to rupture of a pleural metastasis. The patient, a woman, died in respiratory failure 2 wk after rupture of her HCC metastasis in the pleura. Autopsy revealed moderately differentiated HCC in the liver, lung, and pleura, We discuss treatment options for ruptured pleura-based HCC metastases. C1 MAEBASHI RED CROSS HOSP,DEPT GASTROENTEROL,MAEBASHI,GUMMA 371,JAPAN. HOSP TSUKIJI,NATL CANC CTR,DEPT SURG,TOKYO,JAPAN. NATL CANC INST,MATH BIOL LAB,BETHESDA,MD. RP Takagi, H (reprint author), GUNMA UNIV,SCH MED,DEPT INTERNAL MED 1,SHOWAMACHI 3-39,MAEBASHI,GUMMA 371,JAPAN. NR 10 TC 6 Z9 6 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 SEP PY 1996 VL 91 IS 9 BP 1865 EP 1866 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VF823 UT WOS:A1996VF82300042 PM 8792722 ER PT J AU Lebowitz, BD AF Lebowitz, BD TI Diagnosis and treatment of depression in late life - An overview of the NIH Consensus Statement SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article AB Depression among elderly persons is widespread and is often undiagnosed and untreated. In the absence of a reliable clinical diagnostic test, an attentive clinical evaluation is essential. Depressive illness in late life should be treated vigorously with antidepressants; electroconvulsive treatment has been found to be effective; and psychosocial approaches are also useful. The current system of care is fragmented and inadequate, and staff at residential and other facilities are often ill-equipped to recognize and manage depression. RP Lebowitz, BD (reprint author), NIMH,MENTAL DISORDERS AGING RES BRANCH,5600 FISHERS LANE,ROOM 18-101,ROCKVILLE,MD 20857, USA. NR 1 TC 38 Z9 38 U1 0 U2 3 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 1996 VL 4 IS 4 SU 1 BP S3 EP S6 PG 4 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA VN701 UT WOS:A1996VN70100002 ER PT J AU Niederehe, G AF Niederehe, G TI Psychosocial treatments with depressed older adults - A research update SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID GROUP COGNITIVE THERAPY; GERIATRIC DEPRESSION; SPOUSE-CAREGIVERS; MAJOR DEPRESSION; PSYCHOTHERAPIES; EFFICACY; LIFE AB Psychotherapeutic techniques can benefit elderly, depressed patients when the special needs of this population are taken into account in designing and implementing therapy Plans. Combination treatment with mediation and psychotherapy may be the optimum therapy in this population, and it deserves greater research attention. The author discusses some of the key conclusions reached by the 1991 National Institutes of Health Consensus Development Conference on Diagnosis and Treatment of Depression in Late Life, some of the studies the Conference examined and subsequent studies that support or raise questions about those conclusions. RP Niederehe, G (reprint author), NIMH,5600 FISHERS LANE,ROOM 18-101,ROCKVILLE,MD 20857, USA. NR 43 TC 20 Z9 20 U1 1 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD FAL PY 1996 VL 4 IS 4 SU 1 BP S66 EP S78 PG 13 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA VN701 UT WOS:A1996VN70100009 ER PT J AU Parry, DM MacCollin, MM KaiserKupfer, MI Pulaski, K Nicholson, HS Bolesta, M Eldridge, R Gusella, JF AF Parry, DM MacCollin, MM KaiserKupfer, MI Pulaski, K Nicholson, HS Bolesta, M Eldridge, R Gusella, JF TI Germ-line mutations in the neurofibromatosis 2 gene: Correlations with disease severity and retinal abnormalities SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BILATERAL ACOUSTIC NEUROFIBROMATOSIS; TUMOR-SUPPRESSOR GENE; NF2 GENE; TYPE-2 NEUROFIBROMATOSIS; PIGMENT EPITHELIUM; ADENOMATOUS POLYPOSIS; COMBINED HAMARTOMA; OCULAR FUNDUS; SCHWANNOMAS; DELETION AB Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign neural tumors, and cataracts. Patients in some families develop many tumors at an early age and have rapid clinical progression, whereas in other families, patients may not have symptoms until much later and vestibular schwannomas may be the only tumors. The NF2 gene has been cloned from chromosome 22q; most identified germ-line mutations result in a truncated protein and severe NF2. To look for additional mutations and clinical correlations, we used SSCP analysis to screen DNA from 32 unrelated patients. We identified 20 different mutations in 21 patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice site mutations, and 1 large in-frame deletion. Clinical information on 47 patients from the 21 families included ages at onset and at diagnosis, numbers of meningiomas, spinal and skin tumors, and presence of cataracts and retinal abnormalities. We compared clinical findings in patients with nonsense or frameshift mutations to those with splice-site mutations. When each patient was considered as an independent random event, the two groups differed (P less than or equal to .05) for nearly every variable. Patients with nonsense or frameshift mutations were)lounger at onset and at diagnosis and had a higher frequency and mean number of tumors, supporting the correlation between nonsense and frameshift mutations and severe NF2. When each family was considered as an independent random event, statistically significant differences between the two groups were observed only for mean ages at onset and at diagnosis. A larger data set is needed to resolve these discrepancies. We observed retinal hamartomas and/or epiretinal membranes in nine patients from five families with four different nonsense mutations. This finding, which may represent a new genotype-phenotype correlation, merits further study. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,NIH,BETHESDA,MD 20892. US PHS,BETHESDA,MD. MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROGENET UNIT,BOSTON,MA 02114. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. UNIV MARYLAND,DEPT MEASUREMENT STAT & EVALUAT,COLLEGE PK,MD 20742. RP Parry, DM (reprint author), NCI,GENET EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 400,6130 EXECUT BLVD MSC7360,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-15602, N01-CP-33060, N01-CP-40500] NR 58 TC 142 Z9 144 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1996 VL 59 IS 3 BP 529 EP 539 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA VN625 UT WOS:A1996VN62500006 PM 8751853 ER PT J AU Wang, SB DeteraWadleigh, SD Coon, H Sun, CE Goldin, LR Duffy, DL Byerley, WF Gershon, ES Diehl, SR AF Wang, SB DeteraWadleigh, SD Coon, H Sun, CE Goldin, LR Duffy, DL Byerley, WF Gershon, ES Diehl, SR TI Evidence of linkage disequilibrium between schizophrenia and the SCA1 CAG repeat on chromosome 6p23 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID SCHIZOAFFECTIVE DISORDER; MICROSATELLITE LOCI; GENETIC DISSECTION; COMPLEX TRAITS; SUSCEPTIBILITY; ASSOCIATION; WORKSHOP; DISEASE; TYPE-1; FAMILY C1 NIDR,MOL EPIDEMIOL & DIS INDICATORS BRANCH,DEODP,NIH,BETHESDA,MD 20892. NIMH,CLIN NEUROGENET BRANCH,NIH,BETHESDA,MD 20892. UNIV UTAH,SCH MED,DEPT PSYCHIAT,SALT LAKE CITY,UT 84112. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. RI Duffy, David/B-7392-2013 OI Duffy, David/0000-0001-7227-632X NR 43 TC 29 Z9 30 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1996 VL 59 IS 3 BP 731 EP 736 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VN625 UT WOS:A1996VN62500028 PM 8751875 ER PT J AU Tayebi, N Cushner, S Sidransky, E AF Tayebi, N Cushner, S Sidransky, E TI Differentiation of the glucocerebrosidase gene from pseudogene by long-template PCR: Implications for Gaucher disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID MUTATIONS C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 9 TC 30 Z9 31 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1996 VL 59 IS 3 BP 740 EP 741 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA VN625 UT WOS:A1996VN62500031 PM 8751878 ER PT J AU Neumann, HPH Bender, B Zauner, I Berger, DP Eng, C Brauch, H Zbar, B AF Neumann, HPH Bender, B Zauner, I Berger, DP Eng, C Brauch, H Zbar, B TI Monogenetic hypertension and pheochromocytoma SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE pheochromocytoma; hereditary hypertension; Von Hippel-Lindau disease; multiple endocrine neoplasia type 2; proto-oncogenes; tumor suppressor genes ID MULTIPLE ENDOCRINE NEOPLASIA; VONHIPPEL-LINDAU DISEASE; TUMOR-SUPPRESSOR GENE; MEDULLARY-THYROID CARCINOMA; TYROSINE KINASE DOMAIN; RET PROTOONCOGENE; GERMLINE MUTATIONS; POINT MUTATION; VHL DISEASE; MEN 2A AB Hypertension attributable to pheochromocytoma is a very attractive model for the elucidation of the pathogenesis of hypertension, Sixteen different point mutations in the RET proto-oncogene and 30 mutations in the Von Hippel-Lindau (VHL) tumor suppressor gene have been identified so far associated with expression of pheochromocytoma, Each of these mutations initiates either the syndrome of multiple endocrine neoplasia type 2 (MEN 2) (MEN 2A and MEN 2B) or the VHL disease, Certain mutations in both genes are associated with the presence of pheochromocytoma. In general, these pheochromocytomas produce catecholamines that result in hypertension, Therefore, analysis for germline mutations in these genes are of practical value, because susceptibility to these diseases can be predicted in as yet clinically unaffected relatives. (C) 1996 by the National Foundation, Inc. C1 UNIV FREIBURG, DEPT HYPERTENS & NEPHROL, FREIBURG, GERMANY. HARVARD UNIV, SCH MED, DANA FARBER CANC INST, BOSTON, MA 02115 USA. UNIV CAMBRIDGE, CRC, HUMAN CANC GENET GRP, CAMBRIDGE CB2 1TN, ENGLAND. TECH UNIV MUNICH, DEPT PATHOL, D-8000 MUNICH, GERMANY. NCI, FREDERICK, MD 21701 USA. OI Eng, Charis/0000-0002-3693-5145 NR 25 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 1996 VL 28 IS 3 BP 329 EP 333 DI 10.1016/S0272-6386(96)90488-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA VG429 UT WOS:A1996VG42900002 PM 8804229 ER PT J AU Held, PJ Port, FK Webb, RL Wolfe, RA Bloembergen, WE Turenne, MN Hirth, R Young, EW Ojo, AO Strawderman, RL Woods, JD Tedeschi, PJ Carroll, CE HulbertShearon, T Zhang, QL Levine, GN Hatcher, D Jones, CA Greer, JW Agodoa, LYC AF Held, PJ Port, FK Webb, RL Wolfe, RA Bloembergen, WE Turenne, MN Hirth, R Young, EW Ojo, AO Strawderman, RL Woods, JD Tedeschi, PJ Carroll, CE HulbertShearon, T Zhang, QL Levine, GN Hatcher, D Jones, CA Greer, JW Agodoa, LYC TI Excerpts from the United States Renal Data System 1996 Annual Data Report SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Review ID LONG-TERM COMPLICATIONS; DIALYSIS PATIENTS; DISEASE PATIENTS; PERITONEAL-DIALYSIS; KIDNEY-TRANSPLANTS; HEMODIALYSIS-PATIENTS; ALLOGRAFT SURVIVAL; MORTALITY-RATES; MORBIDITY; THERAPY C1 UNIV MICHIGAN, UDRDS COORDINATING CTR, ANN ARBOR, MI 48109 USA. RP Held, PJ (reprint author), DKUHD, NIDDK, NIH, BETHESDA, MD 20892 USA. NR 143 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD SEP PY 1996 VL 28 IS 3 SU 2 BP S1 EP S165 DI 10.1016/S0272-6386(96)90572-7 PG 165 WC Urology & Nephrology SC Urology & Nephrology GA VH150 UT WOS:A1996VH15000001 ER PT J AU Mathis, L Donovan, M Stegmann, B AF Mathis, L Donovan, M Stegmann, B TI Your guide to nursing opportunities in Florida and Georgia SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 NIH,BETHESDA,MD 20892. ST FRANCIS CTR,CHILDRENS PROGRAM,WASHINGTON,DC. RP Mathis, L (reprint author), NCI,PEDIAT HIV PSYCHOSOCIAL SUPPORT PROGRAM,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD SEP PY 1996 VL 96 IS 9 BP 56 EP & PG 5 WC Nursing SC Nursing GA VF618 UT WOS:A1996VF61800020 ER PT J AU Schmidt, PJ Gindoff, PR Baron, DA Rubinow, DR AF Schmidt, PJ Gindoff, PR Baron, DA Rubinow, DR TI Basal and stimulated gonadotropin levels in the perimenopause SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE perimenopause; gonadotropins; bioactivity ID HORMONE-RELEASING HORMONE; LUTEINIZING-HORMONE; MENSTRUAL-CYCLE; WOMEN; SERUM; RADIOIMMUNOASSAY; PROGESTERONE; ESTROGEN; OLDER; AGE AB OBJECTIVE: We investigated whether perimenopausal menstrual cycle irregularity is associated with increased gonadotropin immunoactivity, bioactivity, or the bioactivity/immunoactivity ratio at baseline and after short-term stimulation with gonadotropin-releasing hormone. STUDY DESIGN: Subjects consisted of four groups: (1) young regular cycling women (<35 year; old), older women (>35 years) with (2) regular or (3) irregular menstrual cycles, and (4) postmenopausal women. Ganadotropin-releasing hormone stimulation tests (100 mu g intravenous gonadotropin-releasing hormone) were performed in the National Institute of Mental Hearth outpatient clinic during the follicular phase of the menstrual cycle or randomly in postmenopausal women. RESULTS: Perimenopausal women had baseline follicle-stimulating hormone and luteinizing hormone levels and stimulated follicle-stimulating hormone levels (area under the curve) that were similar to those of postmenopausal women and significantly greater than those of control (younger and older) women. Postmenopausal women had significantly greater baseline levels of luteinizing hormone bioactivity than did the other three groups. The bioactivity/immunoactivity ratio in the postmenopausal women was significantly greater than those in the perimenopausal and older cycling women, which were similar. No change in the bioactivity/immunoactivity ratio was seen after gonadotropin-releasing hormone stimulation in any group. CONCLUSIONS: Although the perimenopause is associated with increases in baseline and stimulated gonadotropin levels similar to those seen after the menopause, significantly increased baseline Luteinizing hormone bioactivity and the bioactivity/immunoactivity ratio are seen only after the menopause. C1 GEORGE WASHINGTON UNIV, DEPT OBSTET & GYNECOL, WASHINGTON, DC USA. RP Schmidt, PJ (reprint author), NIMH, SECT BEHAV ENDOCRINOL,BIOL PSYCHIAT BRANCH, BLDG 10,ROOM 3N238,10 CTR DR, MSC 1276, BETHESDA, MD 20892 USA. NR 24 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 1996 VL 175 IS 3 BP 643 EP 650 PN 1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VR785 UT WOS:A1996VR78500022 PM 8828428 ER PT J AU Berchuck, A Cirisano, F Lancaster, JM Schildkraut, JM Wiseman, RW Futreal, A Marks, JR AF Berchuck, A Cirisano, F Lancaster, JM Schildkraut, JM Wiseman, RW Futreal, A Marks, JR TI Role of BRCA1 mutation screening in the management of familial ovarian cancer SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE BRCA1 gene; familial ovarian cancer; breast cancer ID BREAST-CANCER; SUSCEPTIBILITY GENE; PROPHYLACTIC OOPHORECTOMY; GERMLINE MUTATIONS; WOMEN; CHROMOSOME; CARCINOMA; REGISTRY; HISTORY; LINKAGE AB Families with multiple cases or ovarian cancer have long been observed, and in the past prophylactic oophorectomy has been advocated for women with a history of ovarian cancer in two first-degree relatives. It is now thought that >90% of familial ovarian cancer is due to inherited mutations in the BRCA1 breast-ovarian cancer susceptibility gene on chromosome 17q. BRCA1 testing is being performed in several academic medical centers on a research basis and is also now commercially available. With the ability to identify inherited mutations in BRCA1, prophylactic oophorectomy and other interventions intended to decrease cancer mortality can be offered specifically to women who carry a mutation, but the optimal strategy for decreasing cancer mortality in BRCA1 families has not yet been determined. To facilitate further clinical and basic research in this field, our group and others have established multidisciplinary hereditary breast-ovarian cancer clinics that offer a wide range of services including BRCA1 testing, genetic counseling, and cancer prevention and treatment. C1 DUKE UNIV,MED CTR,DEPT CANC CONTROL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT SURG,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT GENET,DURHAM,NC 27710. NIEHS,NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD. RP Berchuck, A (reprint author), DUKE UNIV,MED CTR,DIV GYNECOL ONCOL,DEPT OBSTET & GYNECOL,BOX 3079,DURHAM,NC 27710, USA. FU NCI NIH HHS [CA 55640] NR 61 TC 21 Z9 21 U1 0 U2 1 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 SEP PY 1996 VL 175 IS 3 BP 738 EP 746 PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VR785 UT WOS:A1996VR78500038 PM 8828444 ER PT J AU Baumrind, S Korn, EL Boyd, RL AF Baumrind, S Korn, EL Boyd, RL TI Apical root resorption in orthodontically treated adults SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article ID INCISORS; TEETH AB This study analyzed the relationship in orthodontically treated adults between upper central incisor displacement measured on lateral cephalograms and apical root resorption measured on anterior periapical x-ray films, A multiple linear regression examined incisor displacements ii four directions (retraction, advancement, intrusion, and extrusion) as independent variables, attempting to account for observed differences in the dependent variable, resorption. Mean apical resorption was 1.36 mm (sd +/- 1.46, n = 73). Mean horizontal displacement of the apex was -0.83 mm (sd +/- 1.74, n = 67); mean vertical displacement was 0.19 mm (sd +/- 1.48, n = 67). The regression coefficients for the intercept and for retraction were highly significant; those for extrusion, intrusion, and advancement were not. At the 95% confidence level, an average of 0.99 mm (se = +/- 0.34) of resorption was implied in the absence of root displacement and an average of 0.49 mm (se = +/- 0.14) of resorption was implied per millimeter of retraction. R(2) for all four directional displacement variables (DDVs) taken together was only 0.20, which implied that only a relatively small portion of ft-ie observed apical resorption could be accounted for by tooth displacement alone. In a secondary set of univariate analyses, the associations between apical resorption and each of 14 additional treatment-related variables were examined. Only Gender, Elapsed Time, and Total Apical Displacement displayed statistically significant associations with apical resorption. Additional multiple regressions were then performed in which the data for each of these three statistically significant variables were considered separately, with the data for the four directional displacement variables. The addition of information on Elapsed Time or Total Apical Displacement did not explain a significant additional portion of the variability in apical resorption, On the other hand, the addition of information on Gender to the information on the four directional displacement variables yielded an R(2) value of 0.35, which indicated that these variables taken together could account for approximately a third of the observed variability in apical resorption in this sample. C1 UNIV MED & DENT NEW JERSEY,NEWARK,DE. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. UNIV PACIFIC,DIV ORTHODONT,SAN FRANCISCO,CA. NCI,CLIN TRIALS SECT,BIOMETR RES BRANCH,BETHESDA,MD. FU NIDCR NIH HHS [DE08713] NR 16 TC 82 Z9 100 U1 1 U2 7 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD SEP PY 1996 VL 110 IS 3 BP 311 EP 320 DI 10.1016/S0889-5406(96)80016-3 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VH017 UT WOS:A1996VH01700017 PM 8814033 ER PT J AU Steeg, PS Clare, SE Lawrence, JA Zhou, Q AF Steeg, PS Clare, SE Lawrence, JA Zhou, Q TI Molecular analysis of premalignant and carcinoma in situ lesions of the human breast SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID C-ERBB-2 ONCOGENE EXPRESSION; P53 PROTEIN EXPRESSION; IN-SITU; ESTROGEN-RECEPTOR; NEU ONCOGENE; INSITU; CANCER; DISEASE; BENIGN; OVEREXPRESSION C1 NCI,WOMENS CANC SECT,PATHOL LAB,BETHESDA,MD 20892. NR 46 TC 30 Z9 30 U1 0 U2 1 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 SEP PY 1996 VL 149 IS 3 BP 733 EP 738 PG 6 WC Pathology SC Pathology GA VE590 UT WOS:A1996VE59000001 PM 8780376 ER PT J AU Muschel, RJ Tykocinski, M Padarathsingh, M AF Muschel, RJ Tykocinski, M Padarathsingh, M TI Link between tumor progression, proteases, and cell motility - Pathology B workshop SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Editorial Material C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT PATHOL,CLEVELAND,OH 44106. NIH,DIV RES GRANTS,BETHESDA,MD 20892. RP Muschel, RJ (reprint author), UNIV PENN,DEPT PATHOL & LAB MED,RM 269 J MORGAN BLDG,PHILADELPHIA,PA 19104, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 SEP PY 1996 VL 149 IS 3 BP 1073 EP 1076 PG 4 WC Pathology SC Pathology GA VE590 UT WOS:A1996VE59000034 PM 8780409 ER PT J AU Bortner, CD Cidlowski, JA AF Bortner, CD Cidlowski, JA TI Absence of volume regulatory mechanisms contributes to the rapid activation of apoptosis in thymocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE flow cytometry; regulatory volume increase; regulatory volume decrease; cell shrinkage ID CELL-VOLUME; DNA FRAGMENTATION; DEOXYRIBONUCLEIC-ACID; ANISOTONIC MEDIA; SUICIDE PROCESS; FLOW-CYTOMETRY; S49 CELLS; DEATH; GLUCOCORTICOIDS; CALCIUM AB A common event that occurs during apoptosis is a loss of cell volume, but little information is available on its role in the cell death process. Lymphocytes undergo apoptosis in response to glucocorticoids and exhibit cell shrinkage, nuclear condensation, internucleosomal DNA fragmentation, and apoptotic body formation. Interestingly, only cells that exhibit a loss in cell volume degrade their DNA. To determine if physical shrinkage was sufficient to initiate apoptosis, S49 Neo lymphocytes were cultured in hypertonic medium. The normal osmolarity (similar to 300 mosM) of tissue culture medium was increased to either 550 or 800 mosM, using impermeant sugars such as mannitol and sucrose or NaCl. These hypertonic conditions led to a rapid killing of S49 Neo cells. Evaluation of the mode of cell death revealed that these hypertonic conditions resulted in apoptosis. Unlike glucocorticoid-induced cell death, hypertonically induced apoptosis did not require protein synthesis. When S49 Neo cells were cultured under hypotonic conditions, the cells swelled but apoptosis did not occur. Analysis of several cell types revealed that all lymphoid cells examined (S49 Neo, CEM-C7, primary thymocytes) undergo apoptosis in response to hypertonic conditions, whereas several other cell types (L cells, COS, HeLa, GH(3)) did not. Although these nonlymphoid cells showed a similar initial reduction in cell volume in response to hypertonic conditions, they subsequently maintained volume or regulated back to a near normal cell volume. These data indicate that thymic lymphoid cells have the machinery in place for rapid induction of apoptosis in response to physical shrinkage, whereas other cell types resist shrinkage-induced apoptosis by the activation of cell volume regulatory mechanisms. C1 NIEHS, LAB INTEGRAT BIOL, RES TRIANGLE PK, NC 27709 USA. NR 36 TC 146 Z9 155 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 1996 VL 271 IS 3 BP C950 EP C961 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VH052 UT WOS:A1996VH05200031 PM 8843726 ER PT J AU Serrano, CV Fraticelli, A Paniccia, R Teti, A Noble, B Corda, S Faraggiana, T Ziegelstein, RC Zweier, JL Capogrossi, MC AF Serrano, CV Fraticelli, A Paniccia, R Teti, A Noble, B Corda, S Faraggiana, T Ziegelstein, RC Zweier, JL Capogrossi, MC TI pH dependence of neutrophil-endothelial cell adhesion and adhesion molecule expression SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE acidosis; alkalosis; hydrogen ion; inflammation; ischemia ID MYOCARDIAL-ISCHEMIA; ANOXIA REOXYGENATION; REPERFUSION INJURY; FLOW; ADHERENCE; ACIDOSIS; ACIDIFICATION; ADHESIVENESS; GENERATION; MODULATION AB Neutrophil adhesion to the vascular endothelium is enhanced during tissue ischemia and/or inflammation, conditions that are associated with tissue acidosis. This study examined the effects of hypercarbic acidosis (10 or 20% CO2) and of hypocarbic alkalosis (0% CO2) on human neutrophil CD18 and human aortic endothelial cell intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molucule-1 (VCAM-1), and E-selectin expression quantified by flow cytometry. Acidosis with 20% CO2 for 4 h decreased ICAM-1 to 60.6 +/- 9.7% of control. In contrast, alkalosis with 0% CO2 for 4 h enhanced ICAM-1 expression to 143.8 +/- 10.1% of control. There was no pH dependence of VCAM-1, or E-selectin expression. Tumor necrosis factor-alpha (TNF-alpha; 10 ng/ml) increased endothelial ICAM-1, E-selectin, and VCAM-1; under these conditions, acidosis with 20% CO2 blunted both ICAM-1 and E-selectin surface expression compared with 5% CO2-, TNF-alpha-treated cells. Hypercarbic acidosis with 20% CO2 increased neutrophil CD18 expression and enhanced neutrophil adhesion. This latter effect was inhibited by neutrophil pretreatment with an anti-CD18 monoclonal antibody. In contrast, when only endothelial cells were preincubated with the hypercarbic buffer, neutrophil adhesion diminished to 55.6 +/- 7.8% of control. The results suggest that acidosis generated during tissue ischemia/inflammation may induce CD18-mediated neutrophil adhesion despite a decrease in ICAM-1 expression. C1 NIA, CTR GERONTOL RES, CARDIOVASC SCI LAB, NIH, BALTIMORE, MD 21224 USA. JOHNS HOPKINS UNIV, SCH MED,JOHNS HOPKINS BAYVIEW MED CTR,DEPT MED, DIV CARDIOL, BALTIMORE, MD 21224 USA. INRCA ANCONA, LAB CARDIOL SPERIMENTALE, I-60131 ANCONA, ITALY. UNIV AQUILA, DIPARTIMENTO MED SPERIMENTALE, I-67100 LAQUILA, ITALY. IRCCS, IST DERMOPAT IMMACOLATA, LAB PATOL VASC, I-00167 ROME, ITALY. RI Serrano Junior, Carlos Vicente/I-2729-2013 FU NHLBI NIH HHS [HL-52315, HL-38324] NR 37 TC 57 Z9 59 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 1996 VL 271 IS 3 BP C962 EP C970 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA VH052 UT WOS:A1996VH05200032 PM 8843727 ER PT J AU Papanicolaou, DA Petrides, JS Tsigos, C Bina, S Kalogeras, KT Wilder, R Gold, PW Deuster, PA Chrousos, GP AF Papanicolaou, DA Petrides, JS Tsigos, C Bina, S Kalogeras, KT Wilder, R Gold, PW Deuster, PA Chrousos, GP TI Exercise stimulates interleukin-6 secretion: Inhibition by glucocorticoids and correlation with catecholamines SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE stress; inflammatory cytokines ID PITUITARY-ADRENAL AXIS; NF-KAPPA-B; RECOMBINANT INTERLEUKIN-6; TREADMILL EXERCISE; EXPRESSION INVIVO; GENE-EXPRESSION; HUMANS; RESPONSES; ENDOTOXIN; STRESS AB In experimental animals, stress and catecholamines stimulate endogenous interleukin-6 (IL-6) secretion, whereas glucocorticoids inhibit it. To examine whether physical stress alters the secretion of IL-6 in humans, and to what extent this is correlated with catecholamines and modified by glucocorticoids, we performed high-intensity treadmill exercise test runs on 15 male volunteers, in a double-blind crossover design, after pretreatment with placebo, hydrocortisone, or dexamethasone. Plasma epinephrine and norepinephrine concentrations peaked 15 min after the start of exercise, whereas plasma IL-6 concentrations peaked twice, 15 min and 45 min after the onset of the test run. There was no difference in either the epinephrine or norepinephrine peaks among the three treatments, but the net area under the curve for IL-6 was smaller after hydrocortisone or dexamethasone than after placebo and smaller after dexamethasone than after hydrocortisone. A positive correlation was observed between peak plasma epinephrine or norepinephrine and IL-6 levels at 15 min. These findings suggest that IL-6 secretion is stimulated during exercise, possibly by catecholamines, whereas exogenous glucocorticoids attenuate this effect without affecting the catecholamine levels. C1 UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20814 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT ANESTHESIOL, BETHESDA, MD 20814 USA. NIAMSD, ARTHRIT & RHEUMATISM BRANCH, NIH, BETHESDA, MD 20892 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT MIL & EMERGENCY MED, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 31 TC 174 Z9 176 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 1996 VL 271 IS 3 BP E601 EP E605 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA VH198 UT WOS:A1996VH19800026 PM 8843757 ER PT J AU Sollott, SJ Ziman, BD Warshaw, DM Spurgeon, HA Lakatta, EG AF Sollott, SJ Ziman, BD Warshaw, DM Spurgeon, HA Lakatta, EG TI Actomyosin interaction modulates resting length of unstimulated cardiac ventricular cells SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiac cells; intracellular calcium concentration ID SKELETAL-MUSCLE MYOSIN; 2,3-BUTANEDIONE MONOXIME; CONTRACTILE ACTIVATION; BUTANEDIONE MONOXIME; MAMMALIAN MYOCARDIUM; IN-VITRO; MYOCYTES; CA2+; TENSION; CALCIUM AB We sought to determine whether resting or diastolic cardiac myocyte length during low stimulation rates is regulated by myofilament interaction. Cytosolic Ca2+ concentration ([Ca2+](i), via indo 1 fluorescence) and length, in the presence and absence of 2,3-butanedione monoxime (BDM), a potent inhibitor of force production in striated muscle, were measured in rat and guinea pig cardiac myocytes at rest and after electrical stimulation. In tetanized cells BDM reduced steady contraction amplitudes for a given [Ca2+](i). In an actomyosin-sliding filament assay without Ca2+ or regulatory proteins, BDM decreased actin filament velocity along myosin. BDM increased both diastolic and resting cell lengths without changes in [Ca2+](i). The resting cell length also increased when [Ca2+](i) was reduced by removing extracellular Ca2+, an effect further enhanced by BDM and by loading cells with the intracellular Ca2+ chelator, 1,2-bis(2-amino-phenoxy)ethane-N,N,N' N,N,N',N'-tetraacetic acid-acetoxymethyl-ester. Thus myofilament interaction is present in cardiac cells, both at rest or during low rates of stimulation, and this myofilament interaction is regulated, in part, by the ambient [Ca2+](i). C1 JOHNS HOPKINS MED INST, DEPT MED, DIV CARDIOL, BALTIMORE, MD 21224 USA. UNIV VERMONT, DEPT MOL PHYSIOL & BIOPHYS, BURLINGTON, VT 05401 USA. RP Sollott, SJ (reprint author), NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 47 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD SEP PY 1996 VL 271 IS 3 BP H896 EP H905 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA VH789 UT WOS:A1996VH78900010 PM 8853323 ER PT J AU Ecelbarger, CA Terris, J Hoyer, JR Nielsen, S Wade, JB Knepper, MA AF Ecelbarger, CA Terris, J Hoyer, JR Nielsen, S Wade, JB Knepper, MA TI Localization and regulation of the rat renal Na+-K+-2Cl(-) cotransporter, BSC-1 SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE thick ascending limb; Henle's loop; sodium chloride transport; vasopressin; furosemide; Brattleboro rat; urinary concentrating mechanism; Tamm-Korsfall protein; aquaporin-2; water channel ID THICK ASCENDING LIMB; TAMM-HORSFALL GLYCOPROTEIN; K-CL COTRANSPORTER; RABBIT KIDNEY; HENLES LOOP; CHLORIDE TRANSPORT; MOLECULAR-CLONING; BRATTLEBORO RAT; SODIUM-CHLORIDE; NACL TRANSPORT AB To investigate the role of the thick ascending limb (TAL) Na+-K+-2Cl(-) cotransporter in regulation of water excretion, we have prepared a peptide-derived polyclonal antibody based on the cloned cDNA sequence of the rat type 1 bumetanide-sensitive cotransporter, BSC-1 (also termed ''NKCC-2''). Immunoblots revealed a single broad 161-kDa band in membrane fractions of rat renal outer medulla and cortex but not from rat colon or parotid gland. A similar protein was labeled in mouse kidney. Immunoperoxidase immunohistochemistry in rat kidney revealed labeling restricted to the medullary and cortical TAL segments. Because long-term regulation of urinary concentrating ability may depend on regulation of Na+-K+-2Cl(-) cotransporter abundance, we used immunoblotting to evaluate the effects of several in vivo factors on expression levels of BSC-1 protein in rat kidney outer medulla. Chronic oral saline loading with 0.16 M NaCl markedly increased BSC-1 abundance. However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance. Chronic furosemide infusion caused a 9-kDa upward shift in apparent molecular mass and an apparent increase in expression level. These results support the previous identification of BSC-1 as the TAL Na+-K+-2Cl- transporter and demonstrate that the expression of this transporter is regulated. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PHYSIOL, BETHESDA, MD 20814 USA. UNIV MARYLAND, SCH MED, DEPT PHYSIOL, BALTIMORE, MD 21201 USA. UNIV PENN, CHILDRENS HOSP, SCH MED, DEPT PEDIAT, PHILADELPHIA, PA 19104 USA. AARHUS UNIV, INST ANAT, DEPT CELL BIOL, DK-8000 AARHUS, DENMARK. FU NIDDK NIH HHS [DK-08832, DK-32839] NR 44 TC 179 Z9 180 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD SEP PY 1996 VL 271 IS 3 BP F619 EP F628 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA VH215 UT WOS:A1996VH21500016 PM 8853424 ER PT J AU Miller, DS Letcher, S Barnes, DM AF Miller, DS Letcher, S Barnes, DM TI Fluorescence imaging study of organic anion transport from renal proximal tubule cell to lumen SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE carboxyfluorescein diacetate; confocal microscopy; fluorescein; fluorescence microscopy; Fundulus heteroclitus; glutathione conjugates; kidney; killifish; monochlorobimane; video image analysis ID RAT HEPATOCYTES; SECRETION; DERIVATIVES; GLUTATHIONE; SPECIFICITY; INHIBITION; MECHANISMS; VESICLES; KIDNEY; ACIDS AB The mechanisms driving organic anion transport from cell to lumen were studied in intact killifish proximal tubules using fluorescence microscopy. Three fluorescent substrates were used as follows: 1) fluorescein (FL); 2) carboxyfluorescein (CF), generated intracellularly from carboxyfluorescein diacetate (CFDA); and 3) bimane-S conjugates, generated intracellularly by conjugation of monochlorobimane (MCB) with glutathione (GSH) and subsequent metabolism. The latter two substrates bypassed the basolateral uptake mechanism, allowing direct study of luminal transport mechanisms. At steady state! for all three substrates, luminal fluorescence was two to three times higher than cellular fluorescence. With FL as substrate, addition of p-aminohippurate (PAH) or probenecid to the incubation medium reduced cellular and luminal fluorescence to roughly the same extent. With CFDA or MCB as substrate, PAH and probenecid only slightly reduced cellular fluorescence but greatly reduced luminal fluorescence. MCB blocked transport of FL from cell to lumen; CFDA blocked transport of bimane-S conjugates from cell to lumen. Finally, depolarizing tubule cells with high-potassium medium did not affect the steady-state lumen-to-cell distribution of FL, CF, or bimane-S conjugates. These results show that organic anion transport from cell to lumen is mediated and uphill but not sensitive to the electrical potential difference across the luminal membrane. C1 MT DESERT ISL BIOL LAB, SALSBURY COVE, ME 04672 USA. RP Miller, DS (reprint author), NIEHS, CELLULAR & MOL PHARMACOL LAB, INTRACELLULAR REGULAT SECT, NATL INST HLTH, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 29 TC 45 Z9 45 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrolyte Physiol. PD SEP PY 1996 VL 271 IS 3 BP F508 EP F520 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA VH215 UT WOS:A1996VH21500004 PM 8853412 ER PT J AU Finnegan, LP AF Finnegan, LP TI The NIH women's health initiative its evolution and expected contributions to women's health SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material RP Finnegan, LP (reprint author), NIH,OFF DIS PREVENT,OFF DIRECTOR,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 5 TC 11 Z9 11 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP-OCT PY 1996 VL 12 IS 5 BP 292 EP 293 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VQ477 UT WOS:A1996VQ47700002 PM 8909634 ER PT J AU Breen, N Figueroa, JB AF Breen, N Figueroa, JB TI Stage of breast and cervical cancer diagnosis in disadvantaged neighborhoods: A prevention policy perspective SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE breast neoplasms; cervical cancer; poverty; cancer; African Americans; Hispanic Americans; cancer staging; socioeconomic factors; socioeconomic status ID HEALTH INTERVIEW SURVEY; SOCIOECONOMIC-STATUS; SCREENING MAMMOGRAPHY; UNITED-STATES; BLACK-WOMEN; HOME CARE; COMMUNITY; SURVIVAL; INCOME; RATES AB Introduction: Public health research on cancer and socioeconomic status (SES) has shown that higher SES is related to greater access to services. Using neighborhood-level measures of SES, we test hypotheses related to stage of breast and cervical cancer diagnosis. Methods: SEER data on women diagnosed with breast or cervical cancer in 1989 and 1990 in San Francisco, Atlanta, and Detroit were matched with 1990 Census tract data. Cases were grouped as ''in situ'' or ''invasive'' at diagnosis. Using multivariate logistic regression in two separate models, we investigated whether residence in a poverty-tract or, alternatively, a disadvantaged neighborhood is associated with increased likelihood of diagnosis with invasive tumors. Results: Living in a socioeconomically disadvantaged neighborhood was a strong, consistent predictor of invasive cancer. Living in a neighborhood with a high proportion of households in poverty was also a significant predictor for cervical cancer. Conclusions: Our results suggest specific neighborhoods that would benefit from clinical interventions. Lack of economic and social resources constrains individuals living in these neighborhoods from taking advantage of interventions targeting individual behavior. Thus, interventions in the small proportion of disadvantaged neighborhoods, we argue, need to target the entire community. Further, policy reform at the community level becomes more feasible when need can be specified for a particular census tract. RP Breen, N (reprint author), NIH,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 313,BETHESDA,MD 20892, USA. NR 55 TC 50 Z9 50 U1 3 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD SEP-OCT PY 1996 VL 12 IS 5 BP 319 EP 326 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA VQ477 UT WOS:A1996VQ47700008 PM 8909640 ER PT J AU Lenfant, C AF Lenfant, C TI National Asthma Education and Prevention Program Task Force report on the cost effectiveness, quality of care, and financing of asthma care - National Asthma Education and Prevention Program Coordinating Committee - Foreword SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NATL ASTHMA EDUC & PREVENT PROGRAM COORDINATING C,BETHESDA,MD. RP Lenfant, C (reprint author), NHLBI,BLDG 10,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD SEP PY 1996 VL 154 IS 3 SU S BP S81 EP S81 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA VH146 UT WOS:A1996VH14600001 ER PT J AU Carney, JA Stratakis, CA AF Carney, JA Stratakis, CA TI Ductal adenoma of the breast and the Carney complex SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Letter ID ENDOCRINE OVERACTIVITY; SPOTTY PIGMENTATION; MYXOMAS C1 NICHHD,NIH,BETHESDA,MD 20892. RP Carney, JA (reprint author), MAYO CLIN & MAYO FDN,200 1ST ST SW,ROCHESTER,MN 55905, USA. NR 6 TC 23 Z9 23 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 SEP PY 1996 VL 20 IS 9 BP 1154 EP 1155 DI 10.1097/00000478-199609000-00014 PG 2 WC Pathology; Surgery SC Pathology; Surgery GA VD613 UT WOS:A1996VD61300014 PM 8764753 ER PT J AU Nelson, RA Gorelick, DA Keenan, RM Carmona, GN Covi, L AF Nelson, RA Gorelick, DA Keenan, RM Carmona, GN Covi, L TI Cardiovascular interactions of desipramine, fluoxetine, and cocaine in cocaine-dependent outpatients SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID INTRAVENOUS COCAINE; MAINTENANCE; HUMANS; ABUSE AB The authors investigated the subacute cardiovascular effects of cocaine use alone and with antidepressants. At study entry, 55 cocaine-dependent (DSM-III-R) patients with cocaine-positive urines had slightly higher resting heart rates and blood pressures than 36 patients with cocaine-negative urines, which achieved significance (P < 0.05) for three of eleven parameters. A repeated-measures analysis of medication-compliant patients found no significant cardiovascular differences between cocaine-positive and cocaine-negative urine conditions for either desipramine (n = 10) or fluoxetine (n = 20). Cocaine use appears to produce minimal subacute cardiovascular effects, which are not accentuated by desipramine or fluoxetine, in physically healthy cocaine-dependent patients. C1 NIDA,DIV INTRAMURAL RES,TREATMENT BRANCH,NIH,BALTIMORE,MD 21224. NR 17 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD FAL PY 1996 VL 5 IS 4 BP 321 EP 326 PG 6 WC Substance Abuse SC Substance Abuse GA VQ248 UT WOS:A1996VQ24800006 ER PT J AU Sang, CN Gracely, RH Max, MB Bennett, GJ AF Sang, CN Gracely, RH Max, MB Bennett, GJ TI Capsaicin-evoked mechanical allodynia and hyperalgesia cross nerve territories - Evidence for a central mechanism SO ANESTHESIOLOGY LA English DT Article DE measurement techniques, sensory testing; nerves, blockade; pain, allodynia, capsaicin-evoked; pain, hyperalgesia, capsaicin-evoked ID RECEPTOR ANTAGONIST KETAMINE; CHRONIC NEUROPATHIC PAIN; NEUROGENIC HYPERALGESIA; POSTHERPETIC NEURALGIA; INTRADERMAL INJECTION; CENTRAL SENSITIZATION; C-NOCICEPTORS; DOUBLE-BLIND; HUMAN SKIN; PLACEBO AB Background: The finding in some patients with neuropathic pain that mechanical allodynia (pain evoked by light touch) and hyperalgesia (supranormal pain evoked by painful stimuli) extend beyond the territory of a single nerve or spinal sensory root (extraterritorial pain) often prompts a diagnosis of psychiatric illness. The hypothesis that focal nociceptive input in a single nerve territory can result in allodynia and hyperalgesia in a nerve territory adjacent to the input was investigated in normal human subjects. Methods: On separate days, 13 healthy volunteers each received left radial and ulnar nerve blocks. After block of either nerve, sensation remaining for three classes of afferents (A beta low-threshold mechanoreceptors, A delta nociceptors, and C polymodal nociceptors) allowed inference of the nerve territory of the adjacent nerve, and the area of overlapping innervation. On a third day, 1,000 mu g intradermal capsaicin was administered into a site such that C-nociceptor input was confined to the ulnar nerve territory. Areas of brush allodynia and pinprick hyperalgesia were determined. Results: Spread of brush allodynia beyond all three borders of the ulnar nerve territory occurred in 9 of 13 patients (for these subjects, range 5-28 mm), whereas spread of pinprick hyperalgesia beyond all borders of the ulnar nerve territory occurred in 12 of 13 subjects (range 1-31 mm). Spread of brush allodynia beyond the A beta border of the ulnar nerve territory occurred in 10 of 13 subjects (range 4-35 mm); and spread of pinprick hyperalgesia beyond the A delta border of the ulnar nerve territory occurred in 12 of 13 subjects (range 1-31 mm). Conclusions: It is concluded that activation of C-nociceptors evokes a state of central sensitization that may manifest itself by the appearance of extraterritorial pain abnormalities. RP Sang, CN (reprint author), NIDR,NIH,PAIN RES CLIN,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 10,ROOM 3C-407,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 32 TC 77 Z9 77 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3 BP 491 EP 496 DI 10.1097/00000542-199609000-00007 PG 6 WC Anesthesiology SC Anesthesiology GA VK280 UT WOS:A1996VK28000009 PM 8853078 ER PT J AU Bambha, K Moody, E Skolnick, P AF Bambha, K Moody, E Skolnick, P TI Chronic exposure of mice to isoflurane results modulation of GABA(A) receptor function SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,DEPT ANESTHESIOL,BALTIMORE,MD 21287. NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A708 EP A708 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600708 ER PT J AU Moody, E Bambha, K Skolnick, P AF Moody, E Bambha, K Skolnick, P TI Nitrous oxide does not modulate GABA(A) receptors in mouse cortical tissue SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,DEPT ANESTHESIOL,BALTIMORE,MD 21287. NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A707 EP A707 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600707 ER PT J AU Njoku, DB Pohl, LR Martin, JL AF Njoku, DB Pohl, LR Martin, JL TI The cysteine conjugate beta-lyase pathway of metabolism may not be the major cause of nephrotoxicity after compound A exposure to rats SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,DEPT ANESTHESIOL,BALTIMORE,MD 21218. NIH,LAB MOL IMMUNOL,BETHESDA,MD 20892. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A363 EP A363 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600363 ER PT J AU Schafer, M Mousa, S Zhang, Q Carter, L Stein, C AF Schafer, M Mousa, S Zhang, Q Carter, L Stein, C TI Peripheral opioid analgesia is triggered by locally expressed corticotropin-releasing factor. SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 NIDA,PRECLIN PHARMACOL LAB,DIR,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DEPT ANESTHESIOL,BALTIMORE,MD 21224. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A717 EP A717 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600717 ER PT J AU Weinger, MB Stuart, JS Schulteis, G Piercy, M Maldonado, R Roques, BP Rice, K Koob, GF AF Weinger, MB Stuart, JS Schulteis, G Piercy, M Maldonado, R Roques, BP Rice, K Koob, GF TI Systemically-active delta opioid agonists have a favorable dose-effect profile in rats SO ANESTHESIOLOGY LA English DT Meeting Abstract ID BUBU; MU C1 UNIV CALIF SAN DIEGO, DEPT ANESTHESIOL, LA JOLLA, CA 92093 USA. Scripps Res Inst, RES INST, DEPT NEUROPHARMACOL, LA JOLLA, CA 92037 USA. UNIV PARIS 05, PARIS, FRANCE. NIDDK, BETHESDA, MD 20892 USA. VET AFFAIRS MED CTR, SAN DIEGO, CA 92161 USA. RI Maldonado, Rafael/F-5657-2014; koob, george/P-8791-2016 OI Maldonado, Rafael/0000-0002-4359-8773; NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1996 VL 85 IS 3A SU S BP A656 EP A656 PG 1 WC Anesthesiology SC Anesthesiology GA VM466 UT WOS:A1996VM46600656 ER PT J AU Guralnik, JM AF Guralnik, JM TI Assessing the impact of comorbidity in the older population SO ANNALS OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Epidemiology - Rethinking Disease: Implications for Epidemiology CY SEP 12-13, 1994 CL ROSYLYN, VA SP Amer Coll Epidemiol DE comorbidity; aging; chronic disease; disability ID CO-MORBIDITY; BREAST-CANCER; DISEASE; SURVIVAL; WOMEN AB Comorbidity is common in the older population. A variety of assessment techniques have been used for measurement of comorbidity and have demonstrated the association of increased level of comorbidity with a variety of adverse health outcomes. The most basic measure of comorbidity is a sum of the number of conditions present. Two general approaches have been used to incorporate disease severity measures into comorbidity indices: assignment of severity scores to all relevant conditions with summation of these scores, and assignment of comorbidity severity based on the most severe comorbid disease present. Each of these approaches has strengths and limitations. Research focusing on an index condition and associated comorbidity has been valuable in describing the impact of comorbidity in a number of different disease states. (C) 1996 by Elsevier Science Inc. RP Guralnik, JM (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,3C-309,BETHESDA,MD 20892, USA. NR 20 TC 132 Z9 134 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 1996 VL 6 IS 5 BP 376 EP 380 DI 10.1016/S1047-2797(96)00060-9 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VQ684 UT WOS:A1996VQ68400004 PM 8915467 ER PT J AU Yancik, R Havlik, RJ Wesley, MN Ries, L Long, S Rossi, WK Edwards, BK AF Yancik, R Havlik, RJ Wesley, MN Ries, L Long, S Rossi, WK Edwards, BK TI Cancer and comorbidity in older patients: A descriptive profile SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE cancer; elderly; comorbidity; aging ID ICD-9-CM ADMINISTRATIVE DATA; TRANSURETHRAL RESECTION; HOSPITAL MORTALITY; MEDICAL CONDITIONS; PROSTATIC-CANCER; APACHE-III; AGE; DIAGNOSIS; SEVERITY; STAGE AB In 1992, the National Institute on Aging (NIA) and the National Cancer Institute (NCI) initiated a study to assess the prevalence of comorbid conditions in elderly patients with cancer. Seven cancer sites were selected for the study: breast, cervix, ovary, prostate, colon, stomach, and urinary bladder. This report on similar to 7600 patients in the study sample describes the NIA/NCI approach to developing information on comorbidity in elderly patients and addresses the chronic disease burden (i.e., comorbidity) and severity for six particular conditions: arthritis, chronic obstructive pulmonary disease (COPD), diabetes, gastrointestinal problems, heart-related conditions, and hypertension. Data on comorbidity were collected by abstracting information from hospital medical records. Patients were registered in six geographic areas of the NCI Surveillance, Epidemiology, and End Results (SEER) Program. A satisfied random sample of patients aged 55 to 64, 65 to 74, and 75 years or older with the index cancers were selected. Comorbidity data were matched with data from the conventional SEER monitoring system. Analyses showed that hypertension is the most prevalent condition and is also much more common as a current management problem rather than as history for the NIA/NCI SEER Study patients. Heart conditions varied slightly in the percentage of severity reported, but percentages for all rumors remained within a range of 13 to 26% for current and past categories. A similar range was observed for arthritis, with the higher percentage seen in the current problem category. For episodic complaints (e.g., gastrointestinal problems), a medical history was more common, except for cancers that involve complaints associated with the malignancy (e.g., colon and stomach cancers and, to a lesser extent, ovarian cancer). COPD and diabetes were less prevalent. Analyses currently under way will determine the impact of a patient's comorbidity burden on the cancer care continuum of diagnosis, treatment, and survival. The broad and independent effects of chronic conditions, singly and in combination, are being examined. (C) 1996 by Elsevier Science Inc. C1 INFORMAT MANAGEMENT SERV INC, SILVER SPRING, MD USA. NCI, NIH, BETHESDA, MD 20892 USA. RP Yancik, R (reprint author), NIA, CANC SECT,GERIATR PROGRAM,NIH,BLDG 31,ROOM 5C05, 31 CTR DR MSC 2292, BETHESDA, MD 20892 USA. NR 40 TC 136 Z9 138 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 EI 1873-2585 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD SEP PY 1996 VL 6 IS 5 BP 399 EP 412 DI 10.1016/S1047-2797(96)00063-4 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VQ684 UT WOS:A1996VQ68400008 PM 8915471 ER PT J AU Whitley, RJ Weiss, H Gnann, JW Tyring, S Mertz, GJ Pappas, PG Schleupner, CJ Hayden, F Wolf, J Soong, SJ Laughlin, C Gnann, J Sherrill, L Pappas, P Greenberg, S Couch, R Wolfe, J Basler, E Orengo, I Liu, HC Pollard, R Savoia, M Oxman, MN Fine, D Mangi, R Kessler, H Peacock, J Tilles, J Flowers, F Beutner, K AF Whitley, RJ Weiss, H Gnann, JW Tyring, S Mertz, GJ Pappas, PG Schleupner, CJ Hayden, F Wolf, J Soong, SJ Laughlin, C Gnann, J Sherrill, L Pappas, P Greenberg, S Couch, R Wolfe, J Basler, E Orengo, I Liu, HC Pollard, R Savoia, M Oxman, MN Fine, D Mangi, R Kessler, H Peacock, J Tilles, J Flowers, F Beutner, K TI Acyclovir with and without prednisone for the treatment of herpes zoster - A randomized, placebo-controlled trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ORAL ACYCLOVIR; POSTHERPETIC NEURALGIA; THERAPY; FAMCICLOVIR; EFFICACY AB Objective: To determine the effect of acyclovir and prednisone treatment of herpes tester on chronic pain and quality-of-life outcomes. Design: Randomized, double-blind, placebo-controlled study with a 2 x 2 factorial design. Setting: 15 university hospitals or affiliated clinics. Patients: 208 immunocompetent patients older than 50 years of age who had localized herpes tester that developed less than 72 hours before study enrollment. Intervention: Acyclovir or a matched placebo was administered orally, 800 mg five times daily, for 21 days. Prednisone or a matched placebo was administered orally at 60 mg/d for the first 7 days, 30 mg/d for days 8 to 14, and 15 mg/d for days 15 to 21. The four treatments regimens given were acyclovir plus prednisone; acyclovir plus prednisone placebo; prednisone plus acyclovir placebo; and placebos for both acyclovir and prednisone. Measurements: Patients were monitored daily for the first 28 days for lesion healing, resolution of pain, return to usual activity, and return to uninterrupted sleep. Monitoring was then done monthly for 6 months. Patients documented analgesic requirements each day, and adverse events and laboratory abnormalities were recorded at each clinic visit. An intention-to-treat analysis was used. Results: Patients were randomly allocated to receive one of the four regimens. Demographic characteristics were similar for each group. Time to total crusting and healing was accelerated for patients receiving acyclovir plus prednisone compared with patients receiving two placebos; the risk ratios were 2.27 (95% CI, 1.46 to 3.55) for total crusting and 2.07 (Cl, 1.26 to 3.38) for healing. Similarly, compared with the placebo group, patients receiving acyclovir plus prednisone had accelerated time to cessation of acute neuritis (risk ratio, 3.02 [Cl, 1.42 to 6.41]), time to return to uninterrupted sleep (risk ratio, 2.12 [Cl, 1.25 to 3.58]); time to return to usual daily activity (risk ratio, 3.22 [Cl, 1.92 to 5.40]); and time to cessation of analgesic therapy (risk ratio, 3.15 [Cl, 1.69 to 5.89]). In the acyclovir plus prednisone group, resolution of pain during the 6 months after disease onset did not statistically differ from that in the other groups. No important clinical or laboratory adverse events occurred in any group. Conclusions: In relatively healthy persons older than 50 years of age who have localized herpes tester, combined acyclovir and prednisone therapy can improve quality of life. C1 NIAID,NIH,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PEDIAT,CENT UNIT,BIRMINGHAM,AL 35233. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV KANSAS,KANSAS CITY,KS. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. UNIV OKLAHOMA,OKLAHOMA CITY,OK. HOSP ST RAPHAEL,NEW HAVEN,CT. RUSH PRESBYTERIAN ST LUKES MED CTR,CHICAGO,IL. WAKE FOREST UNIV,WINSTON SALEM,NC 27109. UNIV CALIF IRVINE,IRVINE,CA 92717. UNIV FLORIDA,GAINESVILLE,FL. SOLANO DERMATOL,SOLANO BEACH,CA. BURROUGHS WELLCOME CO,RES TRIANGLE PK,NC 27709. INFECT DIS RES,FAIRFAX,VA. HENNEPIN CTY MED CTR,MINNEAPOLIS,MN. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35233. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35233. UNIV ALABAMA,CTR COMPREHENS CANC,BIRMINGHAM,AL 35294. UNIV TEXAS,MED BRANCH,DEPT MICROBIOL,GALVESTON,TX 77550. UNIV NEW MEXICO,SCH MED,ALBUQUERQUE,NM 87131. UNIV VIRGINIA,SALEM,VA 24153. VET AFFAIRS MED CTR,SALEM,VA 24153. UNIV VIRGINIA,MED CTR,CHARLOTTESVILLE,VA 22908. FU NIAID NIH HHS [N01-AI-12667, N01-AI-15113, N01-AI-62554] NR 20 TC 225 Z9 232 U1 0 U2 4 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 SEP 1 PY 1996 VL 125 IS 5 BP 376 EP 383 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA VE079 UT WOS:A1996VE07900004 PM 8702088 ER PT J AU MacCollin, M Braverman, N Viskochil, D Ruttledge, M Davis, K Ojemann, R Gusella, J Parry, DM AF MacCollin, M Braverman, N Viskochil, D Ruttledge, M Davis, K Ojemann, R Gusella, J Parry, DM TI A point mutation associated with a severe phenotype of neurofibromatosis 2 SO ANNALS OF NEUROLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; NF2 GENE; TYPE-2 NEUROFIBROMATOSIS; RB1 GENE; APC GENE; POLYPOSIS; IDENTIFICATION; RETINOBLASTOMA; INDIVIDUALS AB Neurofibromatosis 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other nonmalignant tumors of the brain, spinal cord, and peripheral nerves. Although the average age of onset of NF2 is 20 years, some individuals may become symptomatic in childhood. We studied 5 unrelated NF2 patients who became symptomatic before age 13. All 5 had multiple tumors in addition to vestibular schwannoma, and none had a positive family history. Sequence analysis of the NF2 gene revealed identical nonsense mutation of exon 6 in 3 patients. Because this mutation destroys a restriction enzyme recognition site, genomic DNA from the 2 other children was directly tested for this change and identical alterations were detected. Although the work of our laboratory and others has not, in general, detected identical mutations in unrelated patients, this mutation seems to occur particularly frequently in the pediatric population and thus may be associated with an especially severe phenotype. Restriction analysis in children with NF2 may be a cost effective way of identifying their mutation. Further work is needed to characterize the effects of this change on the NF2 protein product and its relationship to this severe phenotype. C1 MASSACHUSETTS GEN HOSP,DEPT NEUROL,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,DEPT NEUROSURG,BOSTON,MA 02114. MASSACHUSETTS GEN HOSP,NEUROGENET UNIT,BOSTON,MA 02114. JOHNS HOPKINS CTR MED GENET,BALTIMORE,MD. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV UTAH,DEPT PEDIAT,SALT LAKE CITY,UT. MCGILL UNIV,CTR RES NEUROSCI,MONTREAL,PQ H3A 2T5,CANADA. NR 29 TC 10 Z9 10 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1996 VL 40 IS 3 BP 440 EP 445 DI 10.1002/ana.410400313 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VG795 UT WOS:A1996VG79500012 PM 8797533 ER PT J AU Sznol, E Zwierzina, H AF Sznol, E Zwierzina, H TI Immune monitoring of cancer vaccines - Report on a workshop held at the 9th NCI-EORTC Symposium on new drugs in cancer therapy SO ANNALS OF ONCOLOGY LA English DT Editorial Material DE cancer vaccines; immunotherapy; monitoring C1 UNIV INNSBRUCK, INNERE MED KLIN, A-6020 INNSBRUCK, AUSTRIA. RP Sznol, E (reprint author), NCI, INVEST DRUG BRANCH, CANC THERAPY EVALUAT PROGRAM, DIV CANC TREATMENT DIAG & CTR, ROCKVILLE, MD 20852 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD SEP PY 1996 VL 7 IS 7 BP 667 EP 670 PG 4 WC Oncology SC Oncology GA VL799 UT WOS:A1996VL79900010 ER PT J AU Khaled, HM ElMawla, NG ElSaid, A Hamza, MR Gaafar, R ElAttar, I AbuRabia, A Magrath, I AF Khaled, HM ElMawla, NG ElSaid, A Hamza, MR Gaafar, R ElAttar, I AbuRabia, A Magrath, I TI Combination chemotherapy for advanced bilharzial bladder carcinoma SO ANNALS OF ONCOLOGY LA English DT Article DE bilharziasis; bladder cancer; chemotherapy AB Background: Carcinoma of the bilharzial bladder, the most common cancer in Egyptian patients has been, until recently, largely treated by surgery. We have studied the activity of a series of single agents in phase II trials and identified a number of active agents. Here we report the results of a trial in which therapeutic combinations of the most active agents were administered in alternating cycles to patients who had never received chemotherapy. Patients and methods: The study included 30 patients with histologically proven inoperable (20), recurrent (5, 2 of whom subsequently developed metastases), or metastatic disease (5). There were 27 males and 3 females, with a median age of 48.5 years (range 29-65 years). Fourteen patients had squamous cell carcinoma, 12 had transitional cell carcinoma, 2 had adenocarcinoma, and the remaining 2 had undifferentiated carcinoma. Chemotherapy consisted of epidoxorubicin (120 mg/sqm i.v. d1) and vincristine (1.4 mg/sqm i.v., days 1 and 8) alternating with etoposide (100 mg/sqm i.v. infusion over 1 hour, days 1 to 5) and ifosfamide (1800 mg/sqm i.v. infusion over 2 hours, days 1 to 5). Mesna was given as a uroprotector at 40% of the ifosfamide dose at 0, 4, and 8 hours after the ifosfamide infusion. Courses were repeated every 3-4 weeks. Results: Among the 22 evaluable patients, 8 (36.5%) had a partial and one (4.5%), a complete response, giving a response rate of 46%. Three more patients had responses that were less than a partial remission, and 6 patients showed disease stabilisation on chemotherapy. Toxicities were tolerable and consisted mainly of myelosuppression. Results were further analysed in relation to pathologic subtype, disease status at the start of chemotherapy, and the delivered dose intensity. No relationship was found between any of these parameters and response to therapy. Conclusion: Advanced bilharzial bladder cancer is relatively sensitive to combination chemotherapy, but complete remission and prolonged survival is rare in this subgroup of patients with advanced disease. Further studies will be needed to determine the relative efficacy of single agents and drug combinations. C1 NATL CANC INST,DEPT SURG,CAIRO,EGYPT. NATL CANC INST,DEPT BIOSTAT,CAIRO,EGYPT. NATL CANC INST,DEPT RADIODIAG,CAIRO,EGYPT. NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. RP Khaled, HM (reprint author), NATL CANC INST,DEPT MED ONCOL,CAIRO,EGYPT. NR 7 TC 10 Z9 10 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 SEP PY 1996 VL 7 IS 7 BP 751 EP 754 PG 4 WC Oncology SC Oncology GA VL799 UT WOS:A1996VL79900023 PM 8905036 ER PT J AU Jaskowiak, N Norton, JA Alexander, HR Doppman, JL Shawker, T Skarulis, M Marx, S Spiegel, A Fraker, DL AF Jaskowiak, N Norton, JA Alexander, HR Doppman, JL Shawker, T Skarulis, M Marx, S Spiegel, A Fraker, DL TI A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 116th Annual Scientific Session of the American-Surgical-Association CY APR 18-20, 1996 CL PHOENIX, AZ SP Amer Surg Assoc ID PERSISTENT PRIMARY HYPERPARATHYROIDISM; RECURRENT HYPERPARATHYROIDISM; LOCALIZATION PROCEDURES; SURGERY; GLANDS; MANAGEMENT; EXPLORATION; STRATEGY; DISEASE; SCANS AB Objectives The authors evaluate the results of preoperative imaging protocols and surgical re-exploration in a series of patients with missed parathyroid adenomas after failed initial procedures for primary hyperparathyroidism. Background The success rate is lower and the complication rate is increased in patients undergoing reoperation for primary hyperparathyroidism compared with initial procedures. Scarring and distortion of tissue planes plus the potential for ectopic gland location leads to this worsened outcome. Methods Two hundred eighty-eight consecutive patients with persistent/recurrent hyperparathyroidism were treated at a single institution after a failed procedure or procedures at outside institutions, Two hundred twenty-two of these patients (77%) were believed to have a missed single adenoma, and these patients underwent 228 operations and 227 preoperative work-ups. Preoperative evaluation consisted of a combination of four noninvasive imaging studies--neck ultrasound, nuclear medicine scan, neck and mediastinal computed tomography scan, and neck and mediastinal magnetic resonance imaging. Based on the noninvasive testing alone, 27% patients underwent surgery whereas the other patients underwent invasive studies, including selective angiography (58%), selective venous sampling for parathyroid hormone (43%), or percutaneous aspiration of suspicious lesions (15%). Results Abnormal parathyroid adenomas were found in 209 of 222 initial procedures and 6 of 6 second procedures, with an overall success rate in terms of resolution of hypercalcemia in 97% (215/222) of patients. The single most common site of missed adenoma glands was in the tracheal-esophageal groove in the posterior superior mediastinum (27%). The most common ectopic sites for parathyroid adenomas are thymus (17%), intrathyroidal (10%), undescended glands (8.6%), carotid sheath (3.6%), and the retroesophageal space (3.2%). The most sensitive and specific noninvasive imaging test is the sestamibi subtraction scan, with 67% true-positive and no false-positive results. The rate of true-positive and false-positive results for ultrasound, computed tomography, magnetic resonance imaging, and technetium thallium scans were 48%/21%, 52%/16%, 48%/14%, and 42%/8%, respectively. The incidence of injury to the recurrent laryngeal nerve was 1.3%. Conclusions A single missed parathyroid adenoma is the most common cause for a failed initial parathyroid operation. Appropriate use of preoperative imaging tests and knowledge of the potential location of parathyroid adenomas can lead to very high cure rates with minimal morbidity. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. WASHINGTON UNIV,DEPT SURG,ST LOUIS,MO. RP Jaskowiak, N (reprint author), UNIV PENN,MED CTR,DEPT SURG,DIV SURG ONCOL,3400 SPRUCE ST,4TH FLOOR SILVERSTEIN,PHILADELPHIA,PA 19104, USA. NR 44 TC 131 Z9 132 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 1996 VL 224 IS 3 BP 308 EP 320 DI 10.1097/00000658-199609000-00007 PG 13 WC Surgery SC Surgery GA VG494 UT WOS:A1996VG49400012 PM 8813259 ER PT J AU Kopreski, MS Witters, L Brennan, WA Buckwalter, EA Chinchilli, VM Demers, LM Lipton, A AF Kopreski, MS Witters, L Brennan, WA Buckwalter, EA Chinchilli, VM Demers, LM Lipton, A TI Protein tyrosine kinase activity in breast cancer and its relation to prognostic indicators SO ANTICANCER RESEARCH LA English DT Article DE breast cancer; epidermal growth factor; HER-2/neu; prognostic indicators; protein tyrosine kinase ID C-ERBB-2 AMPLIFICATION; CLINICAL-SIGNIFICANCE; ESTROGEN-RECEPTORS; RECURRENT DISEASE; MAMMARY-CARCINOMA; ALLELIC LOSS; EXPRESSION; HER-2/NEU; ONCOGENE; OVEREXPRESSION AB Tyrosine kinase dependent oncogenes and growth factor receptors are of prognostic importance in breast cancel, but the relation of cytosolic protein tyrosine kinase (PTK) activity to traditional prognostic indicators is poorly defined. We determined cytosolic PTK activity in tumor extracts of 61 women with invasive beast cancel; including 51 primary specimens and 12 nodal oi metastatic specimens, 7 women with in situ breast cancel; and 8 control breast specimens. PTK activity (pmol/min/mg) was measured in a dot blot assay using phosphotyrosine antibodies to detect phosphorylated tyrosyl residues in the tissue extracts. Compared with control specimens (mean PTK=20.5), tyrosine kinase activity was significantly greater in invasive primary cancels (mean PTK=298.1; p=0.0008), and nodal/metastatic specimens (mean PTK=491.5; p=0.0009). PTK levels of invasive cancels did not correlate with age (p=0.36), tumor size (p=0.83), nodal status (p=0.37), estrogen receptor status (p=0.66), or progesterone receptor status (p=0.09). Thus, while tyrosine kinase activity is increased in breast cancer; correlations with traditional prognostic indicators were not found. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,SCH MED,DEPT MED,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,SCH MED,DEPT PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,SCH MED,DEPT PATHOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,SCH MED,DEPT BIOSTAT & EPIDEMIOL,HERSHEY,PA 17033. NCI,SAIC FREDERICK,CLIN RES BRANCH,FREDERICK,MD 21701. NR 33 TC 11 Z9 11 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 1996 VL 16 IS 5B BP 3037 EP 3041 PG 5 WC Oncology SC Oncology GA VQ153 UT WOS:A1996VQ15300001 PM 8920763 ER PT J AU ChoChung, YS AF ChoChung, YS TI Protein kinase A-directed antisense restrains cancer growth: Sequence-specific inhibition of gene expression SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Review ID RI-ALPHA-SUBUNIT; MAMMARY EPITHELIAL-CELLS; SELECTIVE CAMP ANALOGS; HL-60 LEUKEMIA-CELLS; CYCLIC-AMP ANALOGS; REGULATORY SUBUNIT; BINDING-PROTEINS; ADENOSINE-MONOPHOSPHATE; DOWN-REGULATION; MESSENGER-RNA AB Increased expression of the RI(alpha) subunit of cAMP-dependent protein kinase type I has been shown in human cancer cell lines, in primary tumors, in cells after transformation, and in cells upon stimulation of growth. The sequence-specific inhibition of RI(alpha) gene expression by an antisense oligodeoxynucleotide results in the differentiation of leukemia cells and growth arrest of cancer cells of epithelial origin, A single-injection RI(alpha) antisense treatment in vivo also causes a reduction in RI(alpha) expression and inhibition of tumor growth. Tumor cells behave like untransformed cells by making less protein kinase type I. The RI(alpha) antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to restrain neoplastic growth in vivo. RP ChoChung, YS (reprint author), NCI,CELLULAR BIOCHEM SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 51 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD FAL PY 1996 VL 6 IS 3 BP 237 EP 244 DI 10.1089/oli.1.1996.6.237 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA VP250 UT WOS:A1996VP25000014 PM 8915509 ER PT J AU Buckheit, RW FliakasBoltz, V Russell, JD Snow, M Pallansch, LA Yang, SS Bader, JP Khan, TN Zanger, M AF Buckheit, RW FliakasBoltz, V Russell, JD Snow, M Pallansch, LA Yang, SS Bader, JP Khan, TN Zanger, M TI A diarylsulphone non-nucleoside reverse transcriptase inhibitor with a unique sensitivity profile to drug-resistant virus isolates SO ANTIVIRAL CHEMISTRY & CHEMOTHERAPY LA English DT Article DE combination anti-HIV activity; cross-resistance; diarylsulphones; non-nucleoside reverse transcriptase inhibitors ID ANTI-HIV ACTIVITY; HUMAN-IMMUNODEFICIENCY; NONNUCLEOSIDE INHIBITORS; BINDING-SITE; HIV-1-SPECIFIC INHIBITORS; OXATHIIN CARBOXANILIDE; TIBO DERIVATIVES; VIRAL RESISTANCE; TYPE-1; NEVIRAPINE AB Structure-activity relationship evaluations with a series of diarylsulphone non-nucleoside reverse transcriptase (RT) inhibitors indicated that the steric properties of the molecule and compound lipophilicity primarily contributed to the overall level of activity of the compounds against human immunodeficiency virus type 1 (HIV-1). The most active compounds in the diarylsulphone series had an orthonitro group and yielded anti-HIV activity at sub-micromolar concentrations, Compounds of the diarylsulphone class exhibited antiviral properties similar to other members of the pharmacologic class of HIV-1 specific nonnucleoside reverse transcriptase inhibitors, including activity in a wide variety of established and primary human cells, activity against a wide variety of laboratory and clinical virus isolates, and activity when challenged at high multiplicity of infection. Synergistic inhibition of HIV-1 was observed when the diarylsulphone NSC 667952 was used with the nucleoside analogues AZT, ddl, 3TC and d4T, the protease inhibitor KNI 272 and the sulphonated dye resobene; additive effects were observed when NSC 667952 was used with the nucleoside analogue ddC and other non-nucleoside RT inhibitors. The diarylsulphones exhibited a unique sensitivity profile when evaluated against both virus isolates and purified reverse transcriptase containing non-nucleoside reverse transcriptase inhibitor resistance-engendering mutations. Unlike other members of the class of nonnucleoside compounds, NSC 667952 remained active against virus isolates with the L100I amino acid change in the RT, The compound was, however, highly sensitive to Y181C, K103N and K101E amino acid changes in the RT. The diarylsulphone selected for resistant virus populations which possessed the Y181C amino acid change in the reverse transcriptase and which exhibited enhanced sensitivity to the non-nucleoside inhibitors calanolide A and costatolide. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. PHILADELPHIA COLL PHARM & SCI,PHILADELPHIA,PA 19104. RP Buckheit, RW (reprint author), FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21701, USA. NR 39 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0956-3202 J9 ANTIVIR CHEM CHEMOTH JI Antivir. Chem. Chemother. PD SEP PY 1996 VL 7 IS 5 BP 243 EP 252 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology GA VH801 UT WOS:A1996VH80100004 ER PT J AU Hoagwood, K Koretz, D AF Hoagwood, K Koretz, D TI Embedding prevention services within systems of care: Strengthening the nexus for children SO APPLIED & PREVENTIVE PSYCHOLOGY LA English DT Article DE children; mental health; prevention; research; services; system of care ID MENTAL-HEALTH-SERVICES; ANTISOCIAL-BEHAVIOR; COMMUNITY; FAMILY; STATE; PSYCHOPATHOLOGY; PREVALENCE; CHALLENGES; PATTERNS; TRIALS AB System-of-care models that offer a continuum of integrated mental health services for children are being widely implemented in local communities. Preventive services, arising from the theoretically grounded prevention sciences, are an important but neglected component of this model. Studies of the use of mental health services by children are reviewed, and an integrative model is proposed to incorporate prevention services as a component of the child mental health service system. Construction of the prevention sciences has followed a linear phase model that has advantages and disadvantages for bridging prevention sciences and services research. As prevention science progresses into broader held tests of its effectiveness, studies of child services can be informative, especially in advancing the applicability and dissemination of research findings. Future directions are outlined to strengthen the nexus between services research and prevention science, and to construct a new genre of prevention services research. RP Hoagwood, K (reprint author), NIMH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 69 TC 21 Z9 21 U1 1 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0962-1849 J9 APPL PREV PSYCHOL JI Appl. Prev. Psychol. PD FAL PY 1996 VL 5 IS 4 BP 225 EP 234 DI 10.1016/S0962-1849(96)80014-X PG 10 WC Psychology, Clinical; Psychology, Applied SC Psychology GA VP242 UT WOS:A1996VP24200003 ER PT J AU Powledge, TM Rose, M AF Powledge, TM Rose, M TI The great DNA hunt SO ARCHAEOLOGY LA English DT Article RP Powledge, TM (reprint author), NATL INST HLTH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ARCHAEOLOGICAL INST PI NEW YORK PA 135 WILLIAM ST, NEW YORK, NY 10038-3805 SN 0003-8113 J9 ARCHAEOLOGY JI Archaeology PD SEP-OCT PY 1996 VL 49 IS 5 BP 36 EP & PG 9 WC Archaeology SC Archaeology GA VE533 UT WOS:A1996VE53300023 ER PT J AU Kowlessur, D Citron, BA Kaufman, S AF Kowlessur, D Citron, BA Kaufman, S TI Recombinant human phenylalanine hydroxylase: Novel regulatory and structural properties SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID RAT-LIVER; ESCHERICHIA-COLI; BIOCHEMICAL-CHARACTERIZATION; PHENYLKETONURIA; PHOSPHORYLATION; DEHYDRATASE; PROTEINS; HYPERPHENYLALANINEMIA; 4-MONOOXYGENASE; PURIFICATION AB Recombinant human liver phenylalanine hydroxylase (PAH) expressed in Escherichia coli has been purified to homogeneity. The recombinant enzyme exists in solution as a mixture of 80% tetramers and 20% dimers. A study of the kinetic properties of the enzyme indicates that compared to the recombinant and the native rat liver enzymes, the recombinant human enzyme is in an activated state, This conclusion is supported by the finding that its catalytic activity is only marginally stimulated by incubation with either phenylalanine or lysolecithin. In contrast, the native and the recombinant rat liver enzymes are activated 8- to 25-fold, respectively, when preincubated with phenylalanine or lysolecithin. In the absence of activators, the ratio of the hydroxylase activity in the presence of 6-methyl-5,6,7,8-tetrahydropterin compared to the activity in the presence of (6R)-5,6,7,8-tetrahydrobiopterin (BH4), which is an index of the state of activation of the enzyme, is 4 for the human recombinant PAH compared to a value of 12 for the recombinant rat liver enzyme. Furthermore, the K-m for phenylalanine in the presence of BH4 is 0.050 mM, a value that is one-fifth that of the recombinant rat liver enzyme. Covalent modification of the human enzyme by phosphorylation with protein kinase A provides further evidence that the human enzyme is in a substantially activated state. Phosphorylation, which results in the incorporation of 0.6 mol of phosphate/mol of subunit, leads to only a modest activation of 1.5-fold compared to about a 3-fold activation seen after phosphorylation of the native and the recombinant rat liver enzymes. Moreover, the recombinant human liver enzyme is less sensitive than the rat liver enzyme to stimulation by lysolecithin when tryptophan is the substrate. Just as is true for the rat liver enzyme, the apparent K-m values for tryptophan and phenylalanine vary with the pterin cofactor employed. The ability of 7-tetrahydrobiopterin (7-BH4) to substitute for the natural cofactor tetrahydrobiopterin has been studied in vitro. The apparent K-m for 7-BH4 for the recombinant human enzyme is 0.2 mM and the K-m for phenylalanine is 0.05 mM. The hydroxylase reaction is severely inhibited by 7-BH4 in the presence of physiological concentrations of BH4. This inhibition can be overcome by a decrease in the concentration of phenylalanine, The implications of these novel properties of human PAH for phenylalanine homoestasis in man are discussed. RP Kowlessur, D (reprint author), NIMH,NEUROCHEM LAB,NIH,ROOM 3D30,BLDG 36,BETHESDA,MD 20892, USA. NR 37 TC 20 Z9 20 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1996 VL 333 IS 1 BP 85 EP 95 DI 10.1006/abbi.1996.0367 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD629 UT WOS:A1996VD62900011 PM 8806757 ER PT J AU Krause, RJ Ripp, SL Sausen, PJ Overby, LH Philpot, RM Elfarra, AA AF Krause, RJ Ripp, SL Sausen, PJ Overby, LH Philpot, RM Elfarra, AA TI Characterization of the methionine S-Oxidase activity of rat liver and kidney microsomes: Immunochemical and kinetic evidence for FM03 being the major catalyst SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE flavin-containing monooxygenases; methionine S-oxidase; S-benzyl-L-cysteine S-oxidase; methionine metabolism; S-benzyl-L-cysteine metabolism; sulfoxidation reactions; rat FMO1; rat FMO3 ID FLAVIN-CONTAINING MONOOXYGENASE; ADULT HUMAN LIVER; ESCHERICHIA-COLI; MULTIPLE FORMS; HUMAN-TISSUES; RABBIT LIVER; EXPRESSION; PURIFICATION; PROTEINS; CLONING AB Methionine is oxidized to methionine sulfoxide by rat liver and kidney microsomes in an O-2- and NADPH-dependent manner, In all microsomal assays, no methionine sulfone was detected, Use of a monoclonal antibody to rat liver cytochrome P-450 reductase, various cytochrome P-450 and peroxidase inhibitors, antioxidants, and competitive flavin-containing monooxygenase (FRIO) substrates suggested that methionine sulfoxidation was exclusively mediated by FMOs. At 5 mM methionine, the d-isomer of methionine sulfoxide was preferentially detected over the I-isomer in both liver (ratio, 5:1) and kidney microsomes (ratio, 12:1); however, at 30 to 40 mM methionine concentrations, the diastereomeric ratio was reduced to approximately 3:1 in both tissues, The V-max/K-m ratios determined for the liver and kidney microsomes were similar, Because cDNA-expressed rabbit FMO3 and FMO1 were previously shown to preferentially catalyze methionine and S-benzyl-L-cysteine (SEC) sulfoxidations, respectively, these substrates were used to isolate two distinct S-oxidase activities from the same rat liver microsomal preparation, The purified activities have apparent molecular weights of approximately 55 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The findings that the methionine S-oxidase reacted intensely with antibodies raised against rabbit FMO3 and the SEC S-oxidase reacted intensely with antibodies raised against rabbit FMO1 provide evidence for these activities being associated with FMO3 and FMO1, respectively, The apparent methionine K-m determined with the purified methionine S-oxidase was 3.4 mrcz, whereas the apparent methionine K-m determined with the purified SEC S-oxidase was 48 mM, The methionine sulfoxide d:l diastereomeric ratio obtained with methionine S-oxidase was 15:1, whereas the diastereomeric ratio obtained with SEC S-oxidase was only 2:1. These results provide strong evidence for the expression of both FMO1 and FMO3 in rat liver microsomes and suggest that FMO3 is the major catalyst of methionine sulfoxidation in rat liver and kidney microsomes. (C) 1996 Academic Press, Inc. C1 UNIV WISCONSIN,DEPT COMPARAT BIOSCI,MADISON,WI 53706. UNIV WISCONSIN,CTR ENVIRONM TOXICOL,MADISON,WI 53706. NIEHS,CELLULAR & MOL PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. FU NIDDK NIH HHS [DK44295]; NIEHS NIH HHS [T32 ES07015] NR 41 TC 34 Z9 34 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1996 VL 333 IS 1 BP 109 EP 116 DI 10.1006/abbi.1996.0370 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD629 UT WOS:A1996VD62900014 PM 8806760 ER PT J AU FitzGerald, CT FernandezSalguero, P Gonzalez, FJ Nebert, DW Puga, A AF FitzGerald, CT FernandezSalguero, P Gonzalez, FJ Nebert, DW Puga, A TI Differential regulation of mouse Ah receptor gene expression in cell lines of different tissue origins SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HYDROCARBON HYDROXYLASE INDUCTION; RETINOIC ACID; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; EPIDERMAL-CELLS; STEM-CELLS; DIOXIN; TOXICITY; GROWTH; MICE; CLONING AB The dioxin-binding Ah receptor (AHR) is a ligand-activated transcription factor that regulates the expression of several drug-metabolizing enzymes and has been implicated in immunosuppression, teratogenesis, cell-specific hyperplasia, and certain types of malignancies and toxicities. In order to examine tissue-specific regulation of the mouse Ah receptor gene (Ahr), we studied chimeric deletion constructs, containing the Ahr 5' flanking region and the firefly luciferase reporter gene (Luc). Transient transfection assays were performed in five established mouse cell lines: Hepa-1c1c7 (derived from hepatoma), JB6-C1 41-5a (epidermis), MLE-12 (lung epithelium), F9 (embryonal carcinoma), and NIH/3T3 (fibroblasts). Treatment of the cell lines included: dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), retinoic acid (RA), cyclic adenosine 3':5'-monophosphate (cAMP), or 12-O-tertrdecanoylphorbol 13-acetate (TPA). Expression levels another, this finding was also confirmed by measurements of AHR mRNA steady-state levels. In all cell lines except F9 cells, maximal constitutive expression was observed with constructs containing 78 bp of Ahr promoter sequences, which include several putative binding sites for the transcription factor Sp1. In contrast, in F9 cells, inclusion of sequences between -174 and -78 resulted in a fourfold stimulation of constitutive expression, suggesting that other transcription factors are important in Ahr gene expression in these cells. In MLE-12 and 41-5a cells, expression was significantly decreased by treatment with dioxin, RA, cAMP, or TPA. A similar inhibitory effect was observed in cAMP-treated MLE-12 and F9 cells; this result was confirmed by RT-PCR measurements of AHR mRNA steady-state levels. These results indicate that both up- and down-regulation of the Ahr gene occur and exhibit tissue- and cell-type specificity. (C) 1996 Academic Press, Inc. C1 UNIV CINCINNATI,MED CTR,DEPT ENVIRONM HLTH,CTR ENVIRONM GENET,CINCINNATI,OH 45267. UNIV CINCINNATI,MED CTR,DEV BIOL GRAD PROGRAM,CINCINNATI,OH 45267. NCI,MOL CARCINOGENESIS LAB,NATL INST HLTH,BETHESDA,MD 20892. RI Puga, Alvaro/B-7676-2008; OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU NIEHS NIH HHS [R01 ES06273, R01 ES06811, P30 ES06096] NR 57 TC 51 Z9 52 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1996 VL 333 IS 1 BP 170 EP 178 DI 10.1006/abbi.1996.0378 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD629 UT WOS:A1996VD62900022 PM 8806768 ER PT J AU Netto, LES Stadtman, ER AF Netto, LES Stadtman, ER TI The iron-catalyzed oxidation of dithiothreitol is a biphasic process: Hydrogen peroxide is involved in the initiation of a free radical chain of reactions SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE thiols; dithiothreitol; metals; oxidation; hydrogen peroxide; iron ID SUPEROXIDE; PROTEINS; GLUTATHIONE; GENERATION; OXYGEN; AUTOXIDATION; MECHANISMS; CYSTEINE; TOXICITY; PEPTIDES AB Dithiothreitol (DTT) is the most common agent used to reduce disulfide bonds in proteins. In the presence of transition metals and O-2, however, DTT can induce oxidative damage in biomolecules. By means of polarographic measurements, it was established that the DTT oxidation catalyzed by Fe3+ is a biphasic process, characterized by a lag phase of several minutes during which O-2 is consumed at a slow rate, by a mechanism involving the DTT-dependent reduction of Fe3+ to Fe2+ and the conversion of O-2 to H2O2. Some lines of evidence indicate that the reduction of Fe3+ is the rate-limiting step: (i) The replacement of Fe3+ with Fe2+ leads to a decrease in the length of the lag phase. (ii) The rate of Fe2+ formation by DTT is the same as the initial rate of O-2 uptake. (iii) The rate of sulfhydryl oxidation under anaerobic conditions is very slow. EDTA stimulates the iron-catalyzed oxidation of DTT probably by accelerating Fe3+ reduction. The lag phase is followed by a rapid uptake of O-2 involving both O-2(.-)-dependent and O-2(.-)-independent free radical reactions, which can proceed, albeit more slowly, in the absence of H2O2 (i.e., in the presence of catalase). Glutamine synthetase is inactivated faster when added during the phase of rapid O-2 uptake than when added before the beginning of the reaction. In both cases, catalase protects the enzyme, suggesting that only reactive species generated by H2O2 decomposition are able to induce the inactivation. (C) 1996 Academic Press, Inc. C1 NHLBI,BIOCHEM LAB,IR,NATL INST HLTH,BETHESDA,MD 20892. RI Netto, Luis/A-3783-2008 OI Netto, Luis/0000-0002-4250-9177 NR 43 TC 59 Z9 59 U1 0 U2 17 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 SEP 1 PY 1996 VL 333 IS 1 BP 233 EP 242 DI 10.1006/abbi.1996.0386 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA VD629 UT WOS:A1996VD62900030 PM 8806776 ER PT J AU Mazor, M Ghezzi, F Cohen, J Hershkovitz, R Tolosa, JE Levy, J Leiberman, JR AF Mazor, M Ghezzi, F Cohen, J Hershkovitz, R Tolosa, JE Levy, J Leiberman, JR TI Maternal plasma and amniotic fluid dehydroepiandrosterone-sulfate concentrations in preterm labor and delivery SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Article DE dehydroepiandrosterone-sulfate; preterm labor; amniotic fluid; plasma; parturition ID HUMAN-FETAL MEMBRANES; HUMAN PARTURITION; ESTRONE SULFATE; TERM; DECIDUA; CELLS; PROSTAGLANDINS; SULFOHYDROLASE; ENDOMETRIUM; CHORION AB The purpose of this study was to determine whether preterm parturition is associated with changes in maternal plasma and amniotic fluid dehydroepiandrosterone-sulfate concentrations. A cross sectional study was constructed according to the gestational age at admission and response to tocolysis. Group 1 consisted of women admitted with preterm labor and intact membranes between 28 and 31 weeks and 6 days gestational age (n=40). Group 2 included 40 patients with preterm labor between 32 and 36 weeks gestational age. Both groups were classified into two subgroups: preterm delivery within seven days of admission and term delivery. Commercially available immunoassay kits validated for amniotic fluid analysis of DHEA-S, were used to measure maternal plasma and amniotic fluid DHEA-S concentrations. Maternal plasma DHEA-S concentrations were significantly higher in women with preterm labor who delivered preterm than in those who delivered at term. (Group 1: median 800 ng/ml [range 100-1100] vs. median 200 ng/ml [70-800], P<0.001; Group 2: median 850 ng/ml [300-1700] vs. median 300 ng/ml [90-1100], P<0.001). In contrast, no significant differences were detected in amniotic fluid DHEA-S concentrations. Our data suggest that the rise in maternal plasma DHEA-S concentrations observed in patients with preterm labor may be related to the effects of stress during labor. C1 NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RP Mazor, M (reprint author), BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,CLIN BIOCHEM UNIT,DEPT OBSTET & GYNECOL,IL-84101 BEER SHEVA,ISRAEL. OI Ghezzi, Fabio/0000-0003-3949-5410 NR 27 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0932-0067 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD SEP PY 1996 VL 259 IS 1 BP 7 EP 12 DI 10.1007/BF02505302 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VR585 UT WOS:A1996VR58500002 PM 8933923 ER PT J AU DelaRosa, A Mikhak, B Steeg, PS AF DelaRosa, A Mikhak, B Steeg, PS TI Identification and characterization of the promoter for the human metastasis suppressor gene nm23-H1 SO ARCHIVES OF MEDICAL RESEARCH LA English DT Article; Proceedings Paper CT 1st Carlos-Fernandez-Tomas Meeting on Molecular Biomedicine CY JAN 19-20, 1995 CL MEXICO CITY, MEXICO SP CINVESTAV DE nm23; transcription factors; CTF/NF1; AP-7; Ets ID NUCLEOSIDE DIPHOSPHATE KINASE; TRANSCRIPTION FACTOR; MELANOMA-CELLS; BREAST-CANCER; EXPRESSION; PROTEIN; TUMORS; DNA; PROLIFERATION; AMPLIFICATION AB The nm23-H1 gene, localized to chromosome 17q21-22, has been demonstrated in transfection experiments to significantly inhibit the metastatic potential of melanoma and breast carcinoma cell lines. In this study, we report the isolation, sequencing and partial characterization of the nm23-H1 promoter. The nm23-H1 promoter has no TATA box, but it contains a number of sequences which may bind known transcriptional regulatory proteins (AP-1, CTF/NF1, ACAAAG, and Ets). We have also identified two nonconsensus transcriptional start sites within one of the Ets binding sites. Nuclear proteins from HeLa cells bound specifically to a 95 bp region of the nm23-H1 promoter which harbors the CTF/NF1 recognition consensus sequence, suggesting that CTF/NF1 may play a role in nm23-H1 expression. C1 NCI,PATHOL LAB,WOMENS CANC SECT,BETHESDA,MD 20892. NR 41 TC 8 Z9 8 U1 0 U2 0 PU INST MEXICANO SEGURO PI MEXICO D F PA SOCIAL APDO POSTAL 73-032, MEXICO D F 03020, MEXICO SN 0188-0128 J9 ARCH MED RES JI Arch. Med. Res. PD FAL PY 1996 VL 27 IS 3 BP 395 EP 401 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VF996 UT WOS:A1996VF99600022 PM 8854401 ER PT J AU Chew, EY Klein, ML Ferris, FL Remaley, NA Murphy, RP Chantry, K Hoogwerf, BJ Miller, D AF Chew, EY Klein, ML Ferris, FL Remaley, NA Murphy, RP Chantry, K Hoogwerf, BJ Miller, D TI Association of elevated serum lipid levels with retinal hard exudate in diabetic retinopathy - Early treatment diabetic retinopathy study (ETDRS) report 22 SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MELLITUS AB Objective: To evaluate the relationship between serum lipid levels, retinal hard exudate, and visual acuity in patients with diabetic retinopathy. Design: Observational data from the Early Treatment Diabetic Retinopathy Study. Participants: Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study, the first 2709 enrolled had serum lipid levels measured. Main Outcome Measures: Baseline fasting serum lipid levels, best-corrected visual acuity, and assessment of retinal thickening and hard exudate from stereoscopic macular photographs. Results: Patients with elevated total serum cholesterol levels or serum low-density lipoprotein cholesterol levels at baseline were twice as likely to have retinal hard exudates as patients with normal levels. These patients were also at higher risk of developing hard exudate during the course of the study. The risk of losing visual acuity was associated with the extent of hard exudate even after adjusting for the extent of macular edema. Conclusions: These data demonstrate that elevated serum lipid levels are associated with an increased risk of retinal hard exudate in persons with diabetic retinopathy. Although retinal hard exudate usually accompanies diabetic macular edema, increasing amounts of exudate appear to be independently associated with an increased risk of visual impairment. Lowering elevated serum lipid levels has been shown to decrease the risk of cardiovascular morbidity. The observational data from the Early Treatment Diabetic Retinopathy Study suggest that lipid lowering may also decrease the risk of hard exudate formation and associated vision loss in patients with diabetic retinopathy. Preservation of vision may be an additional motivating factor for lowering serum lipid levels in persons with diabetic retinopathy and elevated serum lipid levels. C1 OREGON HLTH SCI UNIV,CASEY EYE INST,PORTLAND,OR 97201. RETINA INST MARYLAND,BALTIMORE,MD. CLEVELAND OHIO CLIN FDN,CLEVELAND,OH. CTR DIS CONTROL & PREVENT,ATLANTA,GA 30341. RP Chew, EY (reprint author), NEI,NIH,BLDG 31,ROOM 6A52,31 CTR DR,MSC 2510,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z99 EY999999] NR 31 TC 294 Z9 309 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD SEP PY 1996 VL 114 IS 9 BP 1079 EP 1084 PG 6 WC Ophthalmology SC Ophthalmology GA VF908 UT WOS:A1996VF90800004 PM 8790092 ER PT J AU Rogan, WJ AF Rogan, WJ TI Pollutants in breast milk SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Review ID POLYCHLORINATED-BIPHENYLS PCBS; DICHLORODIPHENYL DICHLOROETHENE DDE; PARA-DIOXINS PCDDS; ADIPOSE-TISSUE; FOLLOW-UP; CHLORINATED HYDROCARBONS; N-NITROSODIMETHYLAMINE; PESTICIDE-RESIDUES; PREVIOUS LACTATION; PORPHYRIA TURCICA AB Objective: To review data on the occurrence and toxicity of the commonly reported pesticides and industrial environmental pollutant chemicals in breast milk. Data Sources: Continuous automated literature surveillance plus contact with investigators and governmental agencies. Selections: For data on occurrence, the most recent data from the largest data sets on the most representative donors were used. For data on toxicity, the primary report that was publicly available was used. Delta Extraction: When necessary, data were reexpressed or concentrations were rescaled. The original investigator was contacted if necessary. Data Synthesis: Although pollutant chemicals are readily detected in most human milk worldwide, there is little evidence for consequent morbidity in nurslings. There have been several mass poisonings in which chemicals that were transmitted through breast milk clearly affected children who were breast-fed, and there is some evidence chat prenatal exposure to background levels resulted in mild developmental delay and that lactation per se was disturbed. Conclusions: Breast-feeding is recommended despite the presence of chemical residues. The prenatal period in the child and the initiation of lactation in the mother may be sensitive periods to the toxicity of the chemicals that are considered here, and the potential for poisoning at higher levels is clear. However, in the vast majority of women, the benefits of breast-feeding appear to outweigh the risks, and those who advise women about infant nutrition should continue to support breast-feeding. RP Rogan, WJ (reprint author), NIEHS,POB 12233,MAIL DROP A3-04,RES TRIANGLE PK,NC 27709, USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 102 TC 36 Z9 36 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD SEP PY 1996 VL 150 IS 9 BP 981 EP 990 PG 10 WC Pediatrics SC Pediatrics GA VF470 UT WOS:A1996VF47000017 PM 8790132 ER PT J AU deBlois, D Viswanathan, M Su, JE Clowes, AW Saavedra, JM Schwartz, SM AF deBlois, D Viswanathan, M Su, JE Clowes, AW Saavedra, JM Schwartz, SM TI Smooth muscle DNA replication in response to angiotensin II is regulated differently in the neointima and media at different times after balloon injury in the rat carotid artery - Role of AT(1) receptor expression SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE vascular smooth muscle; DNA replication; angiotensin II receptors; neointima ID FIBROBLAST GROWTH-FACTOR; CONVERTING ENZYME-INHIBITION; VASCULAR INJURY; CELLULAR PROLIFERATION; CATHETER INJURY; TRANSFORMING GROWTH-FACTOR-BETA-1; HYPERTENSIVE RAT; GENE-EXPRESSION; GUINEA-PIGS; FACTOR-BETA AB We have reported that angiotensin II (Ang II) infusion to rats during the third and fourth weeks after vascular injury stimulates DNA replication in a larger proportion of smooth muscle cells (SMCs) in the arterial neointima than in the underlying media or the normal arterial media. Whether this increased responsiveness to Ang II is a transient or stable property of neointimal cells after vascular injury remained unclear. The present study examined smooth muscle DNA replication in response to Ang II infusion (250 ng . kg(-1). min(-1) for 2 weeks) at 3 to 4, 9 to 10, or 27 to 28 weeks after balloon injury to the rat carotid artery. Control rats received Ringer's lactate. BrdU (0.8 mg . kg(-1). d(-1)) was coinfused to label replicating DNA. The increased replicative response to Ang II in the neointima versus the normal arterial media did not persist beyond the period of rapid lesion growth shortly after injury, even in neointimal areas without endothelial regeneration. By 9 to ID weeks after injury, replication frequencies were comparable in the neointima and the normal arterial wall. In the presence of a regenerated endothelium, neointimal DNA replication was lowered but not abolished. After the early period, however, the most marked difference may be the loss of ability of medial SMCs to respond mitogenically to systemic Ang II. As a consequence, Ang II-induced DNA replication in injured arteries was greater in the neointima than in the underlying media at all times studied after injury. DNA replication levels correlated with AT(1) receptor levels in the injured artery neointima but not media, as shown by receptor binding in vascular sections at 3 and 10 weeks after injury. The growth response to systemic Ang II is differentially regulated in adjacent smooth muscle layers in the injured arterial wall in vivo via mechanisms that include, but are not restricted to, the regulation of AT(1) receptor expression in SMCs. C1 UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT SURG,SEATTLE,WA 98195. NIMH,PHARMACOL SECT,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL 26405, HL 42270] NR 58 TC 24 Z9 27 U1 0 U2 1 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 SEP PY 1996 VL 16 IS 9 BP 1130 EP 1137 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA VF888 UT WOS:A1996VF88800005 PM 8792766 ER PT J AU Gabelli, C Bilato, C Martini, S Tennyson, GE Zech, LA Corsini, A Albanese, M Brewer, HB Crepaldi, G Baggio, G AF Gabelli, C Bilato, C Martini, S Tennyson, GE Zech, LA Corsini, A Albanese, M Brewer, HB Crepaldi, G Baggio, G TI Homozygous familial hypobetalipoproteinemia - Increased LDL catabolism in hypobetalipoproteinemia due to a truncated apolipoprotein B species, Apo B-87(Padova) SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE lipoproteins; apolipoprotein B; cholesterol metabolism; atherosclerosis ID DENSITY LIPOPROTEIN-RECEPTOR; NORMOTRIGLYCERIDEMIC ABETALIPOPROTEINEMIA; DNA; POLYMERASE; PROTEINS; PLASMA AB Mutations on the apolipoprotein (apo) B gene that interfere with the full-length translation of the apoB molecule are associated with familial hypobetalipoproteinemia (FHBL), a disease characterized by the reduction of plasma apoB and LDL cholesterol. In this report, we describe an FHBL kindred carrying a unique truncated apoB form, apoB-87(Padova). Sequence analysis of amplified genomic DNA identified a single G deletion at nucleotide 12 032, which shifts the translation reading frame and causes a termination at amino acid 3978. Two homozygous subjects and seven heterozygous relatives were studied. Although homozygous individuals had only trace amounts of LDL, they were virtually free from the symptoms typical of homozygous FHBL subjects. We investigated the in vivo turnover of radiolabeled normal apoB-100 LDL and apoB-87 LDL in one homozygous patient and two normal control subjects. ApoB-87 LDL showed a similar metabolism in all three subjects, with a fractional catabolic rate more than double that of normal LDL. The rate of entry of apoB-87 in the LDL compartment was also markedly decreased compared with normal apoB-100. The increased in vivo catabolism of apoB-87 LDL was paralleled in vitro by a 2.5-fold increased ability of these particles to inhibit the uptake and degradation of normal apoB-100 LDL by normal human cultured fibroblasts. These results indicate that apoB-87 LDL has an enhanced ability to interact with the LDL receptor; the increased apoB catabolism contributes to the hypobetalipoproteinemia and may explain the mild expression of the disease in the two homozygous individuals. C1 NHLBI,MOL DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV MILAN,INST PHARMACOL SCI,MILAN,ITALY. RP Gabelli, C (reprint author), UNIV PADUA,INST INTERNAL MED,VIA GIUSTINIANI 2,I-35128 PADUA,ITALY. OI Corsini, Alberto/0000-0002-9912-9482 NR 35 TC 19 Z9 19 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 1996 VL 16 IS 9 BP 1189 EP 1196 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA VF888 UT WOS:A1996VF88800013 PM 8792774 ER PT J AU Shah, J Gerber, L Fleisher, T McGarvey, C Brown, M Adams, S Gilbert, J Danoff, J AF Shah, J Gerber, L Fleisher, T McGarvey, C Brown, M Adams, S Gilbert, J Danoff, J TI Effect of change in peak torque and total work on lymphocyte subpopulations (CD4 T cells, CD8 T cells, and natural killer cells) in healthy men. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 10 EP 10 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300010 ER PT J AU Livneh, A Drenth, JPH Klasen, IS Langevitz, P George, J Kastner, DL Pras, M vanderMeer, JWM AF Livneh, A Drenth, JPH Klasen, IS Langevitz, P George, J Kastner, DL Pras, M vanderMeer, JWM TI Familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D syndrome (HIDS) are two diseases with distinct features. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. UNIV NIJMEGEN ST RADBOUD HOSP,DEPT MED,NL-6500 HB NIJMEGEN,NETHERLANDS. UNIV NIJMEGEN ST RADBOUD HOSP,LABS CLIN CHEM,NL-6500 HB NIJMEGEN,NETHERLANDS. NIAMS,BETHESDA,MD. RI Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013 OI van der Meer, Jos/0000-0001-5120-3690 NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 138 EP 138 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300138 ER PT J AU Tassiulas, IO Aksentiievich, I Kim, Y Gourley, MF Boumoas, DT AF Tassiulas, IO Aksentiievich, I Kim, Y Gourley, MF Boumoas, DT TI Angiotensin converting enzyme (ACE) polymorphisms in patients with systemic lupus erythematosus (SLE). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 502 EP 502 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300502 ER PT J AU Pillemer, S Fowler, S Tilley, B Alarcon, G Heyse, S Trentham, D Neuner, R Clegg, D Leisen, J Cooper, S Duncan, H Tuttleman, M AF Pillemer, S Fowler, S Tilley, B Alarcon, G Heyse, S Trentham, D Neuner, R Clegg, D Leisen, J Cooper, S Duncan, H Tuttleman, M TI Limited joint counts in a rheumatoid arthritis (RA) clinical trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HENRY FORD HLTH SCI CTR,DETROIT,MI 48202. NIAMS,BETHESDA,MD 20892. UNIV ALABAMA,BIRMINGHAM,AL 35294. NIAID,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02215. SUNY HLTH SCI CTR,BROOKLYN,NY 12903. UNIV UTAH,MED CTR,SALT LAKE CITY,UT 84132. HENRY FORD HOSP,DETROIT,MI 48202. UNIV VERMONT,BURLINGTON,VT 05401. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 540 EP 540 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300540 ER PT J AU Kotake, S Schumacher, HR Yarboro, CH Arayssi, TK Pando, JA Kanik, KS Gourley, MF Klippel, JH Wilder, RL AF Kotake, S Schumacher, HR Yarboro, CH Arayssi, TK Pando, JA Kanik, KS Gourley, MF Klippel, JH Wilder, RL TI In vivo gene expression of type 1 and type 2 cytokines in synovial tissues from patients in early stages of rheumatoid, reactive and undifferentiated arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,PHILADELPHIA,PA 19104. NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 545 EP 545 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300545 ER PT J AU Longman, RE Remmers, EF Cannon, G Griffiths, M Walder, RL AF Longman, RE Remmers, EF Cannon, G Griffiths, M Walder, RL TI Localization of genetic loci controlling antibody response to autologous collagen in rats with collagen-induced arthritis (CIA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NATL INST HLTH,BETHESDA,MD 20892. UNIV UTAH,VET AFFAIRS MED CTR,RES SERV,SALT LAKE CITY,UT 84132. UNIV UTAH,DEPT MED RHEUMATOL,SALT LAKE CITY,UT 84132. NR 0 TC 1 Z9 1 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 SEP PY 1996 VL 39 IS 9 SU S BP 546 EP 546 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300546 ER PT J AU Wilder, RL Elenkov, IJ Papanicolaou, DA Chrousos, GP AF Wilder, RL Elenkov, IJ Papanicolaou, DA Chrousos, GP TI Effects of glucocorticoids and catecholamines on human interleukin-12 and interleukin-10 production: Implications for the effect of stress on autoimmune rheumatic diseases and TH1/TH2 cytokine balance. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NICHHD,DEB,NIH,BETHESDA,MD 20892. NIAMS,ARB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 605 EP 605 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300607 ER PT J AU Arayssi, TK Schumacher, HR AF Arayssi, TK Schumacher, HR TI Closed needle biopsy of small joints in patients with synovitis: Development and testing of a new biopsy needle SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV PENN,VET ADM MED CTR,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 782 EP 782 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300783 ER PT J AU Pillemer, S Fowler, S Tilley, B Alarcon, G Hevse, S Trentham, D Neuner, R Clegg, D Leisen, J Cooper, S Duncan, H Tuttleman, M AF Pillemer, S Fowler, S Tilley, B Alarcon, G Hevse, S Trentham, D Neuner, R Clegg, D Leisen, J Cooper, S Duncan, H Tuttleman, M TI Comparison of response criteria in a rheumatoid arthritis trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,BETHESDA,MD 20892. HENRY FORD HLTH SYST,DETROIT,MI 48202. UNIV ALABAMA,BIRMINGHAM,AL 35294. NIAID,BETHESDA,MD 20892. BETH ISRAEL HOSP,BOSTON,MA 02215. SUNY HLTH SCI CTR,BROOKLYN,NY 12903. UNIV UTAH,MED CTR,SALT LAKE CITY,UT 84132. HENRY FORD HOSP,DETROIT,MI 48202. UNIV VERMONT,BURLINGTON,VT 05401. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 783 EP 783 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300784 ER PT J AU Kawahito, Y Griffiths, MM Cannon, GW Longman, RE Gulko, P Remmers, EF Wilder, RL AF Kawahito, Y Griffiths, MM Cannon, GW Longman, RE Gulko, P Remmers, EF Wilder, RL TI Role of MHC and non-MHC genes in determining onset and/or severity or collagen (CIA) and adjuvant arthritis (PA) in rats SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. VET ADM MED CTR,SALT LAKE CITY,UT 84148. UNIV UTAH,SALT LAKE CITY,UT 84148. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 799 EP 799 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300800 ER PT J AU Horton, W Balakir, R Precht, P Plato, CC Tobin, JD LethbridgeCejku, M Hochberg, MC Meek, L Doege, K AF Horton, W Balakir, R Precht, P Plato, CC Tobin, JD LethbridgeCejku, M Hochberg, MC Meek, L Doege, K TI Association between an aggrecan polymorphic allele and bilateral hand osteoarthritis in elderly white men: Data from the Baltimore longitudinal study of aging (BLSA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. SHRINERS HOSP CRIPPLED CHILDREN,PORTLAND,OR 97201. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 841 EP 841 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300842 ER PT J AU Gerber, L Furst, G Drinkard, B Dale, J Straus, S AF Gerber, L Furst, G Drinkard, B Dale, J Straus, S TI Assessment of fatigue in patients with rheumatoid arthritis. Polymyositis and chronic fatigue syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 896 EP 896 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300897 ER PT J AU Saaibi, DL Arayssi, T Gowin, KM Branigan, PJ Gerard, HC Hudson, AP Klippel, JH Schumacher, HR AF Saaibi, DL Arayssi, T Gowin, KM Branigan, PJ Gerard, HC Hudson, AP Klippel, JH Schumacher, HR TI Clinical spectrum of arthritis associated with chlamydia pneumoniae in synovium. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,COLL MED,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NIAMS,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 937 EP 937 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300938 ER PT J AU Gerard, HC Branigan, PJ Arayssi, T Klippel, JH Schumacher, HR Hudson, AP AF Gerard, HC Branigan, PJ Arayssi, T Klippel, JH Schumacher, HR Hudson, AP TI Viability of Chlamydia pneumoniae in synovial tissue of arthritis patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED COLL PENN & HAHNEMANN UNIV,DVA MED CTR,PHILADELPHIA,PA. UNIV PENN,SCH MED,PHILADELPHIA,PA 19104. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 938 EP 938 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300939 ER PT J AU Kotake, S Schumacher, HR Branigan, P Hudson, A Gerard, H Yarboro, CH Arayssi, TK Pando, JA Kanik, KS Gourley, MF Klippel, JH Wilder, RL AF Kotake, S Schumacher, HR Branigan, P Hudson, A Gerard, H Yarboro, CH Arayssi, TK Pando, JA Kanik, KS Gourley, MF Klippel, JH Wilder, RL TI In vivo cytokine gene expression in chlamydia DNA positive synovial tissues from recent-onset arthritis patients. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 940 EP 940 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300941 ER PT J AU Bulbul, R Davis, J Yarboro, C Gourley, M Klippel, J Arayssi, T Branigan, P Hudson, A Rothfuss, S Schumacher, HR AF Bulbul, R Davis, J Yarboro, C Gourley, M Klippel, J Arayssi, T Branigan, P Hudson, A Rothfuss, S Schumacher, HR TI Treatment responses in chlamydia trachomatis associated arthritis: An observational study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV PENN,VET ADM MED CTR,PHILADELPHIA,PA 19104. NIAMS,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 942 EP 942 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300943 ER PT J AU Gulko, PS Arayssi, TK Davis, JC Pando, J Yarboro, C Branigan, PJ Hudson, A Kastner, DL Klippel, JH Wilder, RL Schumacher, HR AF Gulko, PS Arayssi, TK Davis, JC Pando, J Yarboro, C Branigan, PJ Hudson, A Kastner, DL Klippel, JH Wilder, RL Schumacher, HR TI Variable HLA A2 but not B27 frequency among recent-onset arthritis patients positive or negative for chlamydia trachomatis in the synovium. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 944 EP 944 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300945 ER PT J AU Arayssi, TK Gulko, PS Davis, JC Yarboro, CH Pando, JA Gourley, MF Wilder, RL Klippel, JH Schumacher, HR AF Arayssi, TK Gulko, PS Davis, JC Yarboro, CH Pando, JA Gourley, MF Wilder, RL Klippel, JH Schumacher, HR TI Pathogenetic role of enteric pathogens in early undifferentiated arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV PENN,VAMC,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 953 EP 953 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300954 ER PT J AU Rider, L Sonies, B Sapper, D Solomon, B Katona, I George, S Lindsley, C White, P Miller, F AF Rider, L Sonies, B Sapper, D Solomon, B Katona, I George, S Lindsley, C White, P Miller, F TI Swallowing and oral motor abnormalities are frequent in juvenile idiopathic inflammatory myopathy (JIIM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,CTR CLIN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 983 EP 983 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300984 ER PT J AU Hicks, JE Siegel, KL Miller, FW Rider, LG AF Hicks, JE Siegel, KL Miller, FW Rider, LG TI Muscle strength in key lower extremity muscles predicts walking speed in juvenile idiopathic inflammatory myopathy (JIIM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 989 EP 989 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88300990 ER PT J AU Duna, GF Cotch, MF Galperin, C Hoffman, D Hoffman, GS AF Duna, GF Cotch, MF Galperin, C Hoffman, D Hoffman, GS TI Wegener's granulomatosis (WG): Role of environmental exposures. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CLEVELAND CLIN FDN,CLEVELAND,OH 44195. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1028 EP 1028 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301029 ER PT J AU Wainstein, E Edberg, J Csernok, E Sneller, M Hoffman, G Keystone, E Gross, W Salmon, J Kimberly, R AF Wainstein, E Edberg, J Csernok, E Sneller, M Hoffman, G Keystone, E Gross, W Salmon, J Kimberly, R TI Fc gamma RIIIb alleles predict renal dysfunction in wegeners granulomatosis (WG). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CORNELL UNIV,COLL MED,HOSP SPECIAL SURG,NEW YORK,NY. UNIV LUBECK,D-2400 LUBECK,GERMANY. NIAID,NIH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,CLEVELAND,OH 44195. UNIV TORONTO,WELLESLEY HOSP,TORONTO,ON M4Y 1J3,CANADA. NR 0 TC 1 Z9 1 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 SEP PY 1996 VL 39 IS 9 SU S BP 1100 EP 1100 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301101 ER PT J AU Langford, CA Fauci, AS TalarWilliams, C Sneller, MC AF Langford, CA Fauci, AS TalarWilliams, C Sneller, MC TI Treatment of Wegener's granulomatosis with methotrexate and glucocorticoids: Update on rate of relapse SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1102 EP 1102 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301103 ER PT J AU Johnson, EM Wells, MC AF Johnson, EM Wells, MC TI Herbal therapy - A growing health care trend: Considerations for culturally sensitive practice SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1126 EP 1126 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301127 ER PT J AU Schachter, LA Wisnieski, JJ Denburg, MR Michael, AR Ginzler, EM Kimberly, RP Salmon, JE AF Schachter, LA Wisnieski, JJ Denburg, MR Michael, AR Ginzler, EM Kimberly, RP Salmon, JE TI Antibodies to the collagen like region of CLQ in systemic lupus erythematosus: Likely contributors to renal disease. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 CASE WESTERN RESERVE UNIV,VET ADM MED CTR,CLEVELAND,OH 44106. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. NIAMS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1347 EP 1347 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301348 ER PT J AU Davis, JC Klippel, J Boumpas, D Yarboro, C Larsen, A Scott, D AF Davis, JC Klippel, J Boumpas, D Yarboro, C Larsen, A Scott, D TI 2'chloroxyadenosine (Cda) treatment in lupus nephritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1358 EP 1358 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301359 ER PT J AU LethbridgeCejku, M Hochberg, MC Scott, WW Plato, CC Tobin, JD AF LethbridgeCejku, M Hochberg, MC Scott, WW Plato, CC Tobin, JD TI History of knee surgery increases the odds of knee osteoarthritis: Data from the Baltimore longitudinal study of aging (BLSA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. JOHNS HOPKINS MED INST, BALTIMORE, MD 21205 USA. NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 1405 EP 1405 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301406 ER PT J AU LethbridgeCejku, M Hochberg, MC Scott, WW Plato, CC Tobin, JD AF LethbridgeCejku, M Hochberg, MC Scott, WW Plato, CC Tobin, JD TI Radiographic features of knee osteoarthritis and knee pain predict total knee replacement: Data from the Baltimore longitudinal study of aging (BLSA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND, SCH MED, BALTIMORE, MD 21201 USA. JOHNS HOPKINS MED INST, BALTIMORE, MD 21224 USA. NIA, CTR GERONTOL RES, BALTIMORE, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 EI 1529-0131 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD SEP PY 1996 VL 39 IS 9 SU S BP 1408 EP 1408 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301409 ER PT J AU Bhardwaj, N Seder, RA Reddy, A Feldman, MV AF Bhardwaj, N Seder, RA Reddy, A Feldman, MV TI Interleukin 12 enhances human CD8+ cytolytic T cell responses. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 ROCKEFELLER UNIV,HOSP SPECIAL SURG,NEW YORK,NY 10021. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1425 EP 1425 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301426 ER PT J AU Hagiwara, E Pando, J Ishigatsubo, Y Klinman, D AF Hagiwara, E Pando, J Ishigatsubo, Y Klinman, D TI Abnormal ratio of type 1: Type 2 cytokine secreting cells in patients with primary Sjogren's syndrome. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 YOKOHAMA CITY MED SCH,YOKOHAMA,KANAGAWA,JAPAN. NIH,CTR BIOL,FDA,BETHESDA,MD 20892. NIAMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1561 EP 1561 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301561 ER PT J AU Nakabayashi, T Dang, H Kong, LP Letterio, JJ Geiser, AG Talal, N AF Nakabayashi, T Dang, H Kong, LP Letterio, JJ Geiser, AG Talal, N TI MHC class II antigen expression is a factor for development of autoimmune phenotype in TGF-beta 1 knockout mice. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV TEXAS,HLTH SCI CTR,AUDIE L MURPHY MEM VET HOSP,SAN ANTONIO,TX 78284. NEI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1568 EP 1568 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301568 ER PT J AU Rosin, M Yarboro, C Nuzzo, V Klippel, J Gourley, M AF Rosin, M Yarboro, C Nuzzo, V Klippel, J Gourley, M TI Corticosteroid (CS) effects on bone mineral density (BMD) in patients with systemic lupus erythematosus (SLE). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1587 EP 1587 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301587 ER PT J AU Fraenkel, L LaValley, M McAlindon, T Chaisson, C Roubenoff, R Harris, T Felson, D AF Fraenkel, L LaValley, M McAlindon, T Chaisson, C Roubenoff, R Harris, T Felson, D TI Association of peripheral monocyte derived interleukin 1 beta (IL1) and tumor necrosis factor alpha (TNF) with osteoarthritis (OA). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 BOSTON UNIV,CTR ARTHRITIS,BOSTON,MA 02118. TUFTS UNIV,BOSTON,MA 02111. NIA,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1629 EP 1629 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301629 ER PT J AU Scott, WW Ma, L Pillemer, SR Jacobssen, L delPuente, A Knowler, WC Bennett, PH AF Scott, WW Ma, L Pillemer, SR Jacobssen, L delPuente, A Knowler, WC Bennett, PH TI Population-based prevalence estimates of erosions in rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21287. LUND UNIV,MALMO,SWEDEN. UNIV NAPLES FEDERICO II,NAPLES,ITALY. NIDDKD,NIH,PHOENIX,AZ 85014. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1639 EP 1639 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301639 ER PT J AU Gulko, PS Arayssi, TK Davis, JC Pando, J Yarboro, C Kastner, DL Klippel, JH Wilder, RL Schumacher, HR AF Gulko, PS Arayssi, TK Davis, JC Pando, J Yarboro, C Kastner, DL Klippel, JH Wilder, RL Schumacher, HR TI Role of HLA typing in diagnosis and prediction of one year outcome of patients with recent-onset synovitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. UNIV PENN,PHILADELPHIA,PA 19104. VAMC,PHILADELPHIA,PA 19104. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1670 EP 1670 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301670 ER PT J AU Summers, RM Choyke, PL White, P George, S Katona, I Lindsley, C Miller, FW Rider, LG AF Summers, RM Choyke, PL White, P George, S Katona, I Lindsley, C Miller, FW Rider, LG TI Exercise increases STIR MRI signal intensity in juvenile dermatomyositis (JDM). SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,CTR CLIN,BETHESDA,MD 20892. OI Miller, Frederick/0000-0003-2831-9593 NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1688 EP 1688 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301688 ER PT J AU Hirsch, R Lin, JP Scott, WW Ma, L Pillemer, SR Kastner, DL Jacobsson, L Knowler, WC Bale, SJ AF Hirsch, R Lin, JP Scott, WW Ma, L Pillemer, SR Kastner, DL Jacobsson, L Knowler, WC Bale, SJ TI Construction in a native American population: Application to an analysis of familial clustering of rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21287. LUND UNIV,MALMO,SWEDEN. NIDDK,NIH,PHOENIX,AZ 85014. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1692 EP 1692 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301692 ER PT J AU Nietert, P Sutherland, S Silver, R Pandey, J Dosemeci, M AF Nietert, P Sutherland, S Silver, R Pandey, J Dosemeci, M TI Occupational solvent exposure - A risk factor for systemic sclerosis? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,ENVIRONM HAZARDS ASSESSMENT PROGRAM,CHARLESTON,SC 29425. NCI,ROCKVILLE,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 39 IS 9 SU S BP 1740 EP 1740 PG 1 WC Rheumatology SC Rheumatology GA VH883 UT WOS:A1996VH88301738 ER PT J AU Lambre, CR Aufderheide, M Bolton, RE Fubini, B Haagsman, HP Hext, PM Jorissen, M Landry, Y Morin, JP Nemery, B Nettesheim, P Pauluhn, J Richards, RJ Vickers, AEM Wu, R AF Lambre, CR Aufderheide, M Bolton, RE Fubini, B Haagsman, HP Hext, PM Jorissen, M Landry, Y Morin, JP Nemery, B Nettesheim, P Pauluhn, J Richards, RJ Vickers, AEM Wu, R TI In vitro tests for respiratory toxicity - The report and recommendations of ECVAM Workshop 18 SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Editorial Material ID TRACHEAL EPITHELIAL-CELLS; RAT LUNG; PRIMARY CULTURES; PULMONARY TOXICOLOGY; CLARA CELLS; IN-VITRO; II CELL; METABOLISM; DIFFERENTIATION; INVITRO C1 FRAUNHOFER INST TOXICOL & AEROSOL RES,D-3000 HANNOVER 61,GERMANY. UNIV EDINBURGH,INST OCCUPAT MED,EDINBURGH EH8 9SU,MIDLOTHIAN,SCOTLAND. UNIV TURIN,DIPARTIMENTO CHIM INORGAN CHIM FIS,I-10125 TURIN,ITALY. UNIV UTRECHT,VET BIOCHEM LAB,NL-3508 TD UTRECHT,NETHERLANDS. ZENECA CENT TOXICOL LAB,MACCLESFIELD SK10 4TJ,CHESHIRE,ENGLAND. UNIV HOSP CAMPUS GATHUISBERG,CTR HUMAN GENET,B-3000 LOUVAIN,BELGIUM. UNIV ROUEN,INSERM U295,F-76803 ST ETIENNE,FRANCE. KATHOLIEKE UNIV LEUVEN,LABORATORIUM PNEUMOL,B-3000 LOUVAIN,BELGIUM. NIEHS,RES TRIANGLE PK,NC 27709. BAYER AG,ABT INHALAT TOXIKOL,PHARMAFORSCHUNGZENTRUM,D-42096 WUPPERTAL,GERMANY. UNIV WALES COLL CARDIFF,DEPT BIOCHEM,CARDIFF CF1 1ST,S GLAM,WALES. SANDOZ PHARMA LTD,CH-4002 BASEL,SWITZERLAND. UNIV CALIF DAVIS,CALIF REG PRIMATE RES CTR,DAVIS,CA 95616. FAC PHARM,INSERM,CJF N9105,F-67401 ILLKIRCH GRAFFENS,FRANCE. RP Lambre, CR (reprint author), INERIS,DEPT TOXICOL ECOTOXICOL,BP 2,F-60550 VERNEUIL,FRANCE. RI Haagsman, Henk/F-8919-2010; Nemery, Benoit/D-1224-2013 NR 64 TC 20 Z9 20 U1 0 U2 0 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM, NOTTS, ENGLAND NG1 4EE SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD SEP-OCT PY 1996 VL 24 IS 5 BP 671 EP 681 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA VT361 UT WOS:A1996VT36100013 ER PT J AU Gause, BL Longo, DL AF Gause, BL Longo, DL TI Treatment of relapsed Hodgkin's disease SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; COLONY-STIMULATING FACTOR; HIGH-DOSE CHEMOTHERAPY; 1ST COMPLETE REMISSION; TERM FOLLOW-UP; COMBINATION CHEMOTHERAPY; SALVAGE CHEMOTHERAPY; AUTOLOGOUS TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; PLATELET RECOVERY C1 NCI,NIH,DIV CLIN SCI,CLIN RES BRANCH,FREDERICK,MD 21701. FREDERICK MEM HOSP,REG CANC CTR,FREDERICK,MD 21701. RP Gause, BL (reprint author), NCI,NIH,DIV CLIN SCI,CLIN RES BRANCH,BETHESDA,MD 20892, USA. NR 62 TC 6 Z9 6 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD SEP PY 1996 VL 9 IS 3 BP 559 EP 572 DI 10.1016/S0950-3536(96)80027-8 PG 14 WC Hematology SC Hematology GA VP456 UT WOS:A1996VP45600010 PM 8922246 ER PT J AU Hallett, M AF Hallett, M TI The role of the cerebellum in motor learning is limited SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Editorial Material ID MODULATION AB Motor learning can be divided into adaptation and skill learning. The cerebellum plays the major role in adaptation learning, which can be described as context-response linkage. Motor skill learning is development of a new ability such as a sequence of motor actions. Skill learning can occur in patients with cerebellar lesions. Cortical mechanisms play a major role in development of skills. RP Hallett, M (reprint author), NINCDS,HUMAN MOTOR CONTROL SECT,NIH,BLDG 36,RM 4D04,BETHESDA,MD 20892, USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD SEP PY 1996 VL 19 IS 3 BP 453 EP & PG 0 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA WL417 UT WOS:A1996WL41700026 ER PT J AU Dimitrov, M Grafman, J Kosseff, P Wachs, J Alway, D Higgins, J Litvan, I Lou, JS Hallett, M AF Dimitrov, M Grafman, J Kosseff, P Wachs, J Alway, D Higgins, J Litvan, I Lou, JS Hallett, M TI Preserved cognitive processes in cerebellar degeneration SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE cerebellum; cognition; attention; memory; spatial processing ID CEREBRAL BLOOD-FLOW; MENTAL ACTIVITY; HYPOTHESIS; ATTENTION; BEHAVIOR; ATROPHY; BRAIN AB Aspects of cognitive processing in patients with cerebellar degeneration (CD) were studied in order to examine the validity of recent findings that CD patients demonstrate deficits in visuospatial cognition and verbal-associative learning. Two groups of patients with CD were compared to stratified matched control groups on tests examining selective visual attention, visual spatial attention, mental. rotation of geometric designs, and memory for the temporal order of words they were previously exposed to. CD patients performed similarly to their matched controls across all tasks, These results indicate that the reported cognitive deficits of CD patients are quite selective and need further specification in order to more fully describe their relationship to cerebellar dysfunction. C1 NINCDS,COGNIT NEUROSCI SECT,NIH,BETHESDA,MD 20892. NINCDS,CLIN NEUROGENET UNIT,NIH,BETHESDA,MD 20892. NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,NIH,BETHESDA,MD 20892. NINCDS,NIH,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 35 TC 30 Z9 30 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD SEP PY 1996 VL 79 IS 1-2 BP 131 EP 135 DI 10.1016/0166-4328(96)00007-1 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA VH444 UT WOS:A1996VH44400014 PM 8883824 ER PT J AU Sundaresan, M Yu, ZX Ferrans, VJ Sulciner, DJ Gutkind, JS Irani, K GoldschmidtClermont, PJ Finkel, T AF Sundaresan, M Yu, ZX Ferrans, VJ Sulciner, DJ Gutkind, JS Irani, K GoldschmidtClermont, PJ Finkel, T TI Regulation of reactive-oxygen-species generation in fibroblasts by Rac1 SO BIOCHEMICAL JOURNAL LA English DT Article ID GTP-BINDING PROTEINS; NADPH OXIDASE; DNA-BINDING; HYDROGEN-PEROXIDE; REDOX REGULATION; ACTIVATION; CELLS; EXPRESSION; H2O2; SUPEROXIDE AB In a variety of non-phagocytic cell types, there is a marked increase in intracellular levels of reactive oxygen species (ROS), including superoxide and H2O2, after ligand stimulation. We demonstrate that in NIH 3T3 cells transient expression of constitutively activated forms of the small GTP-binding proteins Ras or Rac1 leads to a significant increase in intracellular ROS. An increase in intracellular ROS is also demonstrated after growth factor [platelet-derived growth factor (PDGF) or epidermal growth factor (EGF)] or cytokine [tumour necrosis factor-alpha (TNF-alpha) or interleukin (IL)-1 beta] stimulation of NIH 3T3 cells. Expression of a dominant negative allele of Rac1 inhibits the rise in ROS seen after Ras expression or after stimulation by either growth factors or cytokines, These results provide the first demonstration of the pathway by which ligand stimulation of ROS occurs in non-phagocytic cells and suggest that the family of Ras-related small GTP-binding proteins may function as regulators of the intracellular redox state. C1 NHLBI,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. NHLBI,PATHOL SECT,NIH,BETHESDA,MD 20892. NIDR,MOL SIGNALLING UNIT,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,BALTIMORE,MD 21287. RI Gutkind, J. Silvio/A-1053-2009 NR 36 TC 366 Z9 375 U1 0 U2 8 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1996 VL 318 BP 379 EP 382 PN 2 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH412 UT WOS:A1996VH41200002 PM 8809022 ER PT J AU Takeuchi, H Kanematsu, T Misumi, Y Yaakob, HB Yagisawa, H Ikehara, Y Watanabe, Y Tan, Z Shears, SB Hirata, M AF Takeuchi, H Kanematsu, T Misumi, Y Yaakob, HB Yagisawa, H Ikehara, Y Watanabe, Y Tan, Z Shears, SB Hirata, M TI Localization of a high-affinity inositol 1,4,5-trisphosphate/inositol 1,4,5,6-tetrakisphosphate binding domain to the pleckstrin homology module of a new 130 kDa protein: Characterization of the determinants of structural specificity SO BIOCHEMICAL JOURNAL LA English DT Article ID PHOSPHOLIPASE-C; PH DOMAIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; TRISPHOSPHATE; ANALOGS; RECOGNITION; PHOSPHATASE; C-DELTA(1); MEMBRANES; KINASE AB We have previously identified a novel 130 kDa protein (p130) which binds Ins(1,4,5)P-3 and shares 38 % sequence identity with phospholipase C-delta(1) [Kanematsu, Misumi, Watanabe, Ozaki, Koga, Iwanaga, Ikehara and Hirata (1996) Biochem. J. 313, 319-325]. We have now transfected COS-1 cells with genes encoding the entire length of the molecule or one of several truncated mutants, in order to locate the region for binding of Ins(1,4,5)P-3. Deletion of N-terminal residues 1 16-232, the region which corresponds to the pleckstrin homology (PH) domain of the molecule, completely abolished binding activity. This result was confirmed when the PH domain itself (residues 95-232), isolated from a bacterial expression system, was found to bind [H-3]Ins(1,4,5)P-3. We also found that Ins(1,4,5,6)P-4 was as efficacious as Ins(1,4,5)P-3 in displacing [H-3]Ins(1,4,5)P-3, suggesting that these two polyphosphates bind to p130 with similar affinity. This conclusion was confirmed by direct binding studies using [H-3]Ins(1,4,5,6)P-4 with high specific radioactivity which we prepared ourselves. Binding specificity was also examined with a variety of inositol phosphate derivatives. As is the case with other PH domains characterized to date, we found that the 4,5-vicinal phosphate pair was an essential determinant of ligand specificity. However, the PH domain of p130 exhibited some novel features. For example, the 3- and/or 6-phosphates could also contribute to overall binding; this contrasts with some other PH domains where these phosphate groups decrease ligand affinity by imposing a steric constraint. Secondly, a free monoester 1-phosphate substantially increased binding affinity, which is a situation so far unique to the PH domain of p130. C1 KYUSHU UNIV, FAC DENT, DEPT BIOCHEM, FUKUOKA 81282, JAPAN. KYUSHU UNIV, FAC DENT, DEPT MAXILLOFACIAL SURG, FUKUOKA 81282, JAPAN. FUKUOKA UNIV, FAC MED, DEPT BIOCHEM, FUKUOKA 81480, JAPAN. HIMEJI INST TECHNOL, FAC SCI, DEPT LIFE SCI, HIMEJI, HYOGO 67812, JAPAN. EHIME UNIV, FAC ENGN, DEPT APPL CHEM, MATSUYAMA, EHIME 790, JAPAN. NIEHS, CELLULAR & MOL PHARMACOL LAB, INOSITOL LIPID SECT, RES TRIANGLE PK, NC 27709 USA. NR 36 TC 50 Z9 52 U1 1 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1996 VL 318 BP 561 EP 568 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH412 UT WOS:A1996VH41200027 PM 8809047 ER PT J AU Civelek, VN Deeney, JT Shalosky, NJ Tornheim, K Hansford, RG Prentki, M Corkey, BE AF Civelek, VN Deeney, JT Shalosky, NJ Tornheim, K Hansford, RG Prentki, M Corkey, BE TI Regulation of pancreatic beta-cell mitochondrial metabolism: Influence of Ca2+, substrate and ADP SO BIOCHEMICAL JOURNAL LA English DT Article ID GLYCEROL-PHOSPHATE DEHYDROGENASE; INDUCED INSULIN-SECRETION; SKELETAL-MUSCLE EXTRACTS; ACYL-COA ESTERS; CA2+-DEPENDENT ACTIVATION; GLYCOLYTIC OSCILLATIONS; ELECTRICAL-ACTIVITY; HEXOSE METABOLISM; CALCIUM-IONS; MALONYL-COA AB To gain insight into the regulation of pancreatic beta-cell mitochondrial metabolism, the direct effects on respiration of different mitochondrial substrates, variations in the ATP/ADP ratio and free Ca2+ were examined using isolated mitochondria and permeabilized clonal pancreatic beta-cells (HIT). Respiration from pyru vate was high and not influenced by Ca2+ in State 3 or under various redox states and fixed values of the ATP/ADP ratio; nevertheless, high Ca2+ elevated pyridine nucleotide fluorescence, indicating activation of pyruvate dehydrogenase by Ca2+. Furthermore, in the presence of pyruvate, elevated Ca2+ stimulated CO2 production from pyruvate, increased citrate production and efflux from the mitochondria and inhibited CO2 production from palmitate. The latter observation suggests that beta-cell fatty acid oxidation is not regulated exclusively by malonyl-CoA but also by the mitochondrial redox state. alpha-Glycerophosphate (alpha-GP) oxidation was Ca2+-dependent with a half-maximal rate observed at around 300 nM Ca2+. We have recently demonstrated that increases in respiration precede increases in Ca2+ in glucose-stimulated clonal pancreatic beta-cells (HIT), indicating that Ca2+ is not responsible for the initial stimulation of respiration [Civelek, Deeney, Kubik, Schultz, Tornheim and Corkey (1996) Biochem. J. 315, 1015-1019]. It is suggested that respiration is stimulated by increased substrate (alpha-GP and pyruvate) supply together with oscillatory increases in ADP [Nilsson, Schultz, Berggren, Corkey and Tornheim (1996) Biochem. J. 314, 91-94]. The rise in Ca2+, which in itself may not significantly increase net respiration, could have the important functions of (1) activating the alpha-GP shuttle, to maintain an oxidized cytosol and high glycolytic flux; (2) activating pyruvate dehydrogenase, and indirectly pyruvate carboxylase, to sustain production of citrate and hence the putative signal coupling factors, malonyl-CoA and acyl-CoA; and (3) increasing mitochondrial redox state to implement the switch from fatty acid to pyruvate oxidation. C1 BOSTON UNIV,MED CTR,DIABET & METAB UNIT,EVANS DEPT MED,BOSTON,MA 02118. BOSTON UNIV,MED CTR,DEPT BIOCHEM,BOSTON,MA 02118. NIA,ENERGY METAB & BIOENERGET SECT,NIH,FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. UNIV MONTREAL,DEPT NUTR,MOL NUTR UNIT,MONTREAL,PQ H3C 3J7,CANADA. OI Civelek , Vildan N./0000-0002-2942-6609 FU NIDDK NIH HHS [DK35914, DK31559] NR 45 TC 61 Z9 63 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 1 PY 1996 VL 318 BP 615 EP 621 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH412 UT WOS:A1996VH41200035 PM 8809055 ER PT J AU Morita, K Tomares, SM Pollard, HB AF Morita, K Tomares, SM Pollard, HB TI Enhancement by F-actin of MgATP-dependent dopamine uptake into isolated chromaffin granules SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE chromaffin granule; dopamine uptake; F-actin; microfilament network ID CATECHOLAMINE TRANSPORT; STORAGE VESICLES; ADRENAL-MEDULLA; MEMBRANE; FLUXES; ATPASE; MODEL; CELLS AB Interaction of chromaffin granules with the microfilament network in the cytoplasmic space of adrenal medullary cells has been proposed, but the influence of chromaffin granule-microfilament interaction on granule function has not yet been studied. In the present study, the effect of F-actin on dopamine uptake into isolated chromaffin granules was examined. The MgATP-dependent component of dopamine uptake was significantly enhanced by F-actin. In contrast, catecholamine efflux from the granules was not significantly altered by F-actin under the conditions in which the enhancement of MgATP-dependent dopamine uptake was observed. These findings suggest that the interaction of chromaffin granules with the microfilament network results in the enhancement of MgATP-dependent dopamine uptake into the granules, thus modulating the accumulation and storage of catecholamines in the adrenal medullary cell. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 21 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD SEP PY 1996 VL 40 IS 1 BP 61 EP 66 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VK200 UT WOS:A1996VK20000007 PM 8886270 ER PT J AU Mansfield, E Pastan, I FitzGerald, DJ AF Mansfield, E Pastan, I FitzGerald, DJ TI Characterization of RFB4-Pseudomonas exotoxin A immunotoxins targeted to CD22 on B-cell malignancies SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RICIN-A-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; PSEUDOMONAS-EXOTOXIN; PHASE-I; ANTITUMOR-ACTIVITY; RECOMBINANT FORM; VARIABLE DOMAINS; TUMOR-CELLS; BONE-MARROW; LYMPHOMA AB To develop an immunotoxin for the treatment of B-cell malignancies, we constructed several candidate conjugates with RFB4, a B-cell specific anti-CD22 IgG(1), and truncated forms of Pseudomonas exotoxin (PE). The four versions of PE included PE35 and PE35KDEL, which were linked to RFB4 via a disulfide bond, and PE38 and PE38KDEL, which were linked via a thioether bond. The PE35 truncated forms, which are fully active in ADP ribosylation and lack receptor binding sequences, do not require intracellular proteolytic cleavage in order to be active. PE35KDEL has the consensus endoplasmic reticulum retention signal, KDEL, replacing the wild type PE C-terminal sequence, REDLK. The PE38 forms retain all of domain II and therefore require cleavage to be active within cells. Cytotoxicity experiments on CD22-positive cell lines revealed that the PE35 conjugates were more active than the PE38 versions and the presence of the KDEL sequence generally enhanced toxicity by 5-10-fold compared to that of REDLK. The RFB4-PE35KDEL immunotoxin was most active in cytotoxicity assays against Burkitt's lymphoma cell lines such as Daudi and CA46 (IC50 = 0.2 ng/mL) and displayed little cytotoxicity toward human vascular endothelial cells (IC50 > 20 mu g/mL). Results of experiments conducted in nude mice showed that both RFB4-PE35KDEL and RFB4-PE35 could inhibit the development of subcutaneous CA46 tumors. C1 NCI,MOL BIOL LAB,DCBDC,NIH,BETHESDA,MD 20892. NR 30 TC 34 Z9 35 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD SEP-OCT PY 1996 VL 7 IS 5 BP 557 EP 563 DI 10.1021/bc960043y PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA VK976 UT WOS:A1996VK97600008 PM 8889017 ER PT J AU Benjamin, J Gershon, ES AF Benjamin, J Gershon, ES TI Genetic discoveries in human behavior: Small effect genes loom large SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID BIPOLAR AFFECTIVE-DISORDER; MANIC-DEPRESSIVE ILLNESS; COMPLEX TRAITS; SUSCEPTIBILITY GENE; VULNERABILITY LOCUS; MAJOR DEPRESSION; LINKAGE ANALYSIS; SCHIZOPHRENIA; MARKERS; CHROMOSOME-18 C1 BEN GURION UNIV NEGEV,IL-84105 BEER SHEVA,ISRAEL. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RP Benjamin, J (reprint author), SOROKA MED CTR,POB 151,IL-84101 BEER SHEVA,ISRAEL. NR 34 TC 8 Z9 8 U1 1 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 SEP 1 PY 1996 VL 40 IS 5 BP 313 EP 316 DI 10.1016/0006-3223(96)00278-8 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VF237 UT WOS:A1996VF23700001 PM 8874832 ER PT J AU Johnson, EO Kamilaris, TC Carter, CS Calogero, AE Gold, PW Chrousos, GP AF Johnson, EO Kamilaris, TC Carter, CS Calogero, AE Gold, PW Chrousos, GP TI The biobehavioral consequences of psychogenic stress in a small, social primate (Callithrix jacchus jacchus) SO BIOLOGICAL PSYCHIATRY LA English DT Article DE common marmoset; psychogenic stress; ACTH; cortisol; HPA axis ID CORTICOTROPIN-RELEASING-FACTOR; CORTICOSTEROID-BINDING GLOBULIN; PITUITARY-ADRENAL AXIS; RHESUS-MONKEYS; BEHAVIORAL HOMEOSTASIS; CORTISOL SECRETION; CUSHINGS-DISEASE; SQUIRREL-MONKEY; DOSE-RESPONSE; HORMONE AB The biobehavioral consequences of psychogenic stress were examined using neuroendocrine and ethological methods in a captive colony of common marmosets (Callithrix jacchus jacchus), Specifically, hypothalamic-pituitary-adrenal (HPA) axis reactivity was evaluated as a function of gender and social status in four consecutive social environments [(I) stable heterosexual pairs; (2) isolation; (3) unstable peer groups; and (4) stable peer groups], by measuring both basal plasma cortisol, adrenocorticotropic hormone (ACTH) and P-endorphin concentrations and responsiveness of these hormones to dexamethasone, ovine corticotropin-releasing hormone (oCRH) and ACTH(1-24). Socially stressful conditions, such as isolation and peer group formation, were associated with increased HPA axis function and behavioral arousal, and individual profiles were related to gender and social status. Hormonal levels prior to group formation predicted subsequent status in peer groups. Basal morning concentrations of plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression, were sensitive indices of HPA axis arousal during periods of social stress. The context-dependent development of hormonal and behavioral profiles, reminiscent of depression and/or anorexia nervosa, suggests that the common marmoset may be a useful model of psychiatric hypercortisolism. C1 NICHHD,SECT PEDIAT ENDOCRINOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. UNIV MARYLAND,DEPT ZOOL,COLLEGE PK,MD 20742. FU NIMH NIH HHS [5F31 MH-09594-03] NR 49 TC 71 Z9 72 U1 2 U2 8 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 SEP 1 PY 1996 VL 40 IS 5 BP 317 EP 337 DI 10.1016/0006-3223(95)00397-5 PG 21 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VF237 UT WOS:A1996VF23700002 PM 8874833 ER PT J AU Fay, MP AF Fay, MP TI Rank invariant tests for interval censored data under the grouped continuous model SO BIOMETRICS LA English DT Article DE coarsened at random; grouped data; ordered categorical data; weighted log-rank ID PROPORTIONAL HAZARDS MODEL; FAILURE TIME DATA; REGRESSION-ANALYSIS; COARSE DATA; IGNORABILITY; LIKELIHOOD; AIDS AB This paper creates rank invariant score tests for grouped or interval censored data. This generalizes Finkelstein (1986, Biometrics 42, 845-854), who derived score tests for interval censored data assuming proportional hazards. We frame the problem as a linear rank test of a shift in location with a known error distribution. We discuss adjustments to the test that may be required when the number of observation times is large. We offer a graphical test of the assumption of the location shift model and discuss an alternative interpretation of the test using the logistic error when the location shift assumption does not hold. RP Fay, MP (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,SUITE 344,6130 EXECUT BLVD,MSC 735,BETHESDA,MD 20892, USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 27 TC 32 Z9 33 U1 0 U2 6 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1996 VL 52 IS 3 BP 811 EP 822 DI 10.2307/2533044 PG 12 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VF838 UT WOS:A1996VF83800003 PM 8805758 ER PT J AU Troendle, JF AF Troendle, JF TI A permutational step-up method of testing multiple outcomes SO BIOMETRICS LA English DT Article DE adjusted p value; familywise error rate; power; step-up procedure; test statistic ID BONFERRONI PROCEDURE; ENDPOINTS AB This paper describes a permutational step-up multiple comparison procedure to adjust the p values from k related hypotheses. The method is applicable when two groups of subjects are being compared on each of k outcomes. It is related to the step-down method of Westfall and Young (1993, Resampling-Based Multiple Testing: Examples and Methods for P-Value Adjustment, Volume 1) and Troendle (1995, Journal of the American Statistical Association 90, 370-378) and is an alternative to the analytic step-up method of Dunnett and Tamhane (1992, Journal of the American Statistical Association. 87, 162-170), which requires a specific distribution and correlation structure. By conditioning on the data observed, this permutational method avoids any specific distribution or correlation assumption. It is shown very generally that the method asymptotically controls the familywise probability of a type I error. RP Troendle, JF (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BLDG 6100,ROOM 7B13,BETHESDA,MD 20892, USA. NR 15 TC 21 Z9 21 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1996 VL 52 IS 3 BP 846 EP 859 DI 10.2307/2533047 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VF838 UT WOS:A1996VF83800006 PM 8805759 ER PT J AU Zhou, HB Weinberg, CR AF Zhou, HB Weinberg, CR TI Modeling conception as an aggregated Bernoulli outcome with latent variables via the EM algorithm SO BIOMETRICS LA English DT Article DE aggregated Bernoulli outcomes; EM algorithm; fertility; generalized estimating equations; latent variables; marginal analysis ID LONGITUDINAL DATA; OVULATION; PREGNANCY; TEMPERATURE; INTERCOURSE; PROBABILITY; SURVIVAL; BABY; SEX AB We describe a general method for analyzing aggregated Bernoulli outcomes. The research is motivated by an epidemiological reproductive study where the outcome was whether pregnancy was detected in a woman's particular menstrual cycle and the Bernoulli ''trials'' corresponded to days with intercourse during the cycle. Each cycle is either ''viable'' or not, i.e., is or is not susceptible to conception. We develop an EM algorithm approach to maximizing the observed-data pseudo-likelihood, based on a set of unobservable latent outcomes linked to the specific days with intercourse. This method is flexible in that it allows one to model effects of covariates on the susceptibility factor and on the latent outcomes. Application of the method to fertility studies enables one to investigate covariates with a long-term or transient effect on the daily conception probability. A complication is that most couples contribute more than one cycle in a prospective study. A generalized estimating equation approach adjusts for the dependency among outcomes within individual couples. The method can be applied in any setting where dependency among Bernoulli trials is induced by a susceptibility factor and the trial outcomes are only observable in the aggregate. RP Zhou, HB (reprint author), NIEHS,STAT & BIOMATH BRANCH,MD A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 33 Z9 33 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1996 VL 52 IS 3 BP 945 EP 954 DI 10.2307/2533055 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VF838 UT WOS:A1996VF83800014 PM 8805762 ER PT J AU Freedman, L Midthune, D Brown, C AF Freedman, L Midthune, D Brown, C TI Statistical analysis of animal cancer chemoprevention experiments - Reply SO BIOMETRICS LA English DT Letter RP Freedman, L (reprint author), NCI,BIOMETRY BRANCH,DCPC,EXECUT PLAZA N,SUITE 344,BETHESDA,MD 20882, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 1996 VL 52 IS 3 BP 1157 EP 1157 PG 1 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA VF838 UT WOS:A1996VF83800038 ER PT J AU Scarborough, A Su, TL Leteutre, FF Pommier, Y Chou, TC AF Scarborough, A Su, TL Leteutre, FF Pommier, Y Chou, TC TI DNA interaction and topoisomerase II inhibition by the antitumor agent 3'-(9-acridinylamino)-5'-hydroxymethylaniline and derivatives SO BIOORGANIC CHEMISTRY LA English DT Article ID CLEAVAGE ACTIVITY; BINDING; COMPLEX; INTERCALATOR; AMSACRINE; DRUGS AB Cleavage and cytotoxicity assays have been used to show that 3'-(9-acridinylamino)5'-hydroxymethylaniline (AHMA) is a potent antileukemic agent that inhibits topoisomerase II-mediated relaxation of supercoiled DNA and promotes the topoisomerase II-mediated cleavage of DNA al a subset of the cleavage sites of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA). Equilibrium binding data show a larger binding constant for the more cytotoxic derivatives for binding to poly(dA-dT)(2) as compared to poly(dG-dC)(2), but greater cooperativity for binding to poly(dG-dC)2 and a steric barrier to binding caused by the size of the 5'-hydroxymethyl substituent. Circular dichroism shows a more intercalated binding geometry on poly(dc-dC)(2) for 1'-substituted derivatives when compared to AHMA and derivatives with a free 1'-amino group, which is absent with poly(dA-dT)(2) and calf thymus DNA and is indicative of specific interactions with CC-rich areas in natural DNA for AHMA and derivatives with free 1'-amino groups which may stabilize the drug-DNA complex. (C) 1996 Academic Press, Inc. C1 MEM SLOAN KETTERING CANC CTR,MOL PHARMACOL & THERAPEUT PROGRAMS,NEW YORK,NY 10021. CORNELL UNIV,GRAD SCH MED SCI,NEW YORK,NY 10021. NCI,MOL PHARMACOL LAB,BETHESDA,MD 20205. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 NR 28 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 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD SEP PY 1996 VL 24 IS 3 BP 229 EP 241 DI 10.1006/bioo.1996.0021 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA VL841 UT WOS:A1996VL84100003 ER PT J AU Tummino, PJ Prasad, JVNV Ferguson, D Nouhan, C Graham, N Domagala, JM Ellsworth, E Gajda, C Hagen, SE Lunney, EA Para, KS Tait, BD Pavlovsky, A Erickson, JW Gracheck, S McQuade, TJ Hupe, DJ AF Tummino, PJ Prasad, JVNV Ferguson, D Nouhan, C Graham, N Domagala, JM Ellsworth, E Gajda, C Hagen, SE Lunney, EA Para, KS Tait, BD Pavlovsky, A Erickson, JW Gracheck, S McQuade, TJ Hupe, DJ TI Discovery and optimization of nonpeptide HIV-1 protease inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE HIV protease; nonpeptide inhibitor; pyran-2-ones; 5,6-dihydropyran-2-ones; structure-based design ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMPETITIVE-INHIBITION; ASPARTIC PROTEINASE; RATIONAL DESIGN; BINDING; POTENT; MECHANISM; SPECIFICITY; MODE AB Several small, achiral nonpeptide inhibitors of HIV-1 protease with low micromolar activity were identified by mass screening of the Parke-Davis compound library. Two of the compounds, structurally similar, were both found to be competitive and reversible inhibitors [compound 1, 4-hydroxy-3-(3-phenoxypropyl)-1-benzopyran-2-one: K-i = 1.0 mu M; compound 2, 4-hydroxy-6- phenyl-3-(phenylthio)-pyran-2-one: K-i = 1.1 mu M]. These inhibitors were chosen as initial leads for optimization of in vitro inhibitory activity based on molecular modeling and X-ray crystallographic structural data. While improvements in inhibitory potency were small with analogues of compound 1, important X-ray crystallographic structural information of the enzyme-inhibitor complex was gained. When bound, 1 was found to displace H(2)O301 in the active site while hydrogen bonding to the catalytic Asps and Ile50 and Ile150. The pyranone group of compound 2 was found to bind at the active site in the same manner, with the 6-phenyl and the 3-phenylthio occupying P1 and P1', respectively. The structural information was used to develop design strategies to reach three or four of the internal pockets, P2-P2'. This work led to analogues of diverse structure with high potency (IC50 < 10 nM) that contain either one or no chiral centers and remain nonpeptidic. The highly potent compounds possess less anti-HIV activity in cellular assays than expected, and current optimization now focuses on increasing cellular activity. The value of the HIV-1 protease inhibitors described is their potential as better pharmacological agents with a different pattern of viral resistance development, relative to the peptidic inhibitors in human clinical trials. Copyright (C) 1996 Elsevier Science Ltd C1 WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,DEPT BIOCHEM,ANN ARBOR,MI 48105. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,DEPT CHEM,ANN ARBOR,MI 48105. WARNER LAMBERT PARKE DAVIS,PARKE DAVIS PHARMACEUT RES,DEPT INFECT DIS,ANN ARBOR,MI 48105. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 41 TC 25 Z9 25 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 SEP PY 1996 VL 4 IS 9 BP 1401 EP 1410 DI 10.1016/0968-0896(96)00134-4 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA VL856 UT WOS:A1996VL85600003 PM 8894098 ER PT J AU Randad, RS Lubkowska, L Silva, AM Guerin, DMA Gulnik, SV Yu, B Erickson, JW AF Randad, RS Lubkowska, L Silva, AM Guerin, DMA Gulnik, SV Yu, B Erickson, JW TI Structure-based design of achiral, nonpeptidic hydroxybenzamide as a novel P2/P2' replacement for the symmetry-based HIV protease inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CRYSTAL-STRUCTURE; INFECTIVITY; RESISTANCE; COMPLEX; AIDS AB A combination of structure-activity studies, kinetic analysis, X-ray crystallographic analysis, and modeling were employed in the design of a novel series of HIV-1 protease (HIV PR) inhibitors. The crystal structure of a complex of HIV PR with SRSS-2,5-bis[N-(tert-butyloxycarbonyl)amino]-3,4-dihydroxy-1,6-diphenylhexane (1) delineated a crucial water-mediated hydrogen bond between the tert-butyloxy group of the inhibitor and the amide hydrogen of Asp29 of the enzyme. Achiral, nonpeptidic 2-hydroxyphenylacetamide and 9-hydroxybenzamide groups were modeled as novel P2/P2' ligands to replace the crystallographic water molecules and to provide direct interactions with the NH groups of the Asp29/129 residues. Indeed, the symmetry-based inhibitors 7 and 19, possessing 3-hydroxy and 3-aminobenzamide, respectively, as a P2/P2' ligand, were potent inhibitors of HIV PR. The benzamides were superior in potency to the phenylacetamides and have four fewer rotatable bonds. An X-ray crystal structure of the HIV PR/7 complex at 2.1 Angstrom resolution revealed an asymmetric mode of binding, in which the 3-hydroxy group of the benzamide ring makes the predicted interaction with the backbone NH of Asp29 on one side of the active site only. An unexpected hydrogen bond with the Gly148 carbonyl group, resulting from rotation of the aromatic ring out of the amide plane, was observed on the other side. The inhibitory potencies of the benzamide compounds were found to be sensitive to the nature and position of substituents on the benzamide ring, and can be rationalized on the basis of the structure of the HIV PR/7 complex. These results partly confirm our initial hypothesis and suggest that optimal inhibitor designs should satisfy a requirement for providing polar interactions with Asp29 NH, and should minimize the conformational entropy loss on binding by reducing the number of freely rotatable bonds in inhibitors. Copyright (C) 1996 Elsevier Science Ltd C1 NCI, FREDERICK CANC RES & DEV CTR, STRUCT BIOCHEM PROGRAM, SAIC FREDERICK, FREDERICK, MD 21702 USA. RI Guerin, Diego /N-4486-2014; OI Guerin, Diego M.A./0000-0001-8504-9636 NR 36 TC 5 Z9 5 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD SEP PY 1996 VL 4 IS 9 BP 1471 EP 1480 DI 10.1016/0968-0896(96)00140-X PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA VL856 UT WOS:A1996VL85600009 PM 8894104 ER PT J AU Mazur, J Jernigan, RL Sarai, A AF Mazur, J Jernigan, RL Sarai, A TI Constructing optimal backbone segments for joining fixed DNA base pairs SO BIOPHYSICAL JOURNAL LA English DT Article ID DISTANCE GEOMETRY METHOD; B-DNA; MOLECULAR-CONFORMATION; NUCLEIC-ACIDS; ENERGY; TRANSITION; SIMULATION; RELAXATION; DYNAMICS; SEQUENCE AB A method is presented to link a sequence of space-fixed base pairs by the sugar-phosphate segments of single nucleotides and to evaluate the effects in the backbone caused by this positioning of the bases, The entire computational unit comprises several nucleotides that are energy-minimized, subject to constraints imposed by the sugar-phosphate backbone segments being anchored to space-fixed base pairs, The minimization schemes are based on two stages, a conjugate gradient method followed by a Newton-Raphson algorithm. Because our purpose is to examine the response, or relaxation, of an artificially stressed backbone, it is essential to be able to obtain, as closely as possible, a lowest minimum energy conformation of the backbone segment in conformational space, For this purpose, an algorithm is developed that leads to the generation of an assembly of many local energy minima. From these sets of local minima, one conformation corresponding to the one with the lowest minimum is then selected and designated to represent the backbone segment at its minimum. The effective electrostatic potential of mean force is expressed in terms of adjustable parameters that incorporate solvent screening action in the Coulombic interactions between charged backbone atoms; these parameters are adjusted to obtain the best fit of the nearest-neighbor phosphorous atoms in an x-ray structure. C1 NCI,MATH BIOL LAB,DBS,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK BIOMED SUPER COMP LAB,FREDERICK,MD 21701. RIKEN,LIFE SCI CTR,TSUKUBA,IBARAKI 305,JAPAN. RI Jernigan, Robert/A-5421-2012 FU NCI NIH HHS [N01-CO-74102] NR 40 TC 4 Z9 4 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 SEP PY 1996 VL 71 IS 3 BP 1493 EP 1506 PG 14 WC Biophysics SC Biophysics GA VF097 UT WOS:A1996VF09700035 PM 8874023 ER PT J AU Sarai, A Jernigan, RL Mazur, J AF Sarai, A Jernigan, RL Mazur, J TI Interdependence of conformational variables in double-helical DNA SO BIOPHYSICAL JOURNAL LA English DT Article ID B-DNA; SEQUENCE DEPENDENCE; NUCLEIC-ACIDS; DODECAMER; DYNAMICS; POLY(DG).POLY(DC); FLEXIBILITY; SIMULATION; TRANSITION; MORPHOLOGY AB DNA exhibits conformational polymorphism, with the details depending on the sequence and its environment. To understand the mechanisms of conformational polymorphism and these transitions, we examine the interrelationships among the various conformational variables of DNA. In particular, we examine the stress-strain relation among conformational variables, describing base-pair morphology and their effects on the backbone conformation, For the calculation of base pairs, we use the method previously developed to calculate averages over conformational variables of DNA. Here we apply this method to calculate the Boltzmann averages of conformational variables for fixed values of one particular conformational variable, which reflects the strain in the structure responding to a particular driving stress, This averaging over all but one driving variable smooths the usual rough energy surface to permit observation of the effects of one conformational variable at a time. The stress-strain analyses of conformational variables of base pair slide, twist, and roll, which exhibit characteristic changes during the conformational transition of DNA, have shown that the conformational changes of base pairs are strongly correlated with one another. Furthermore, the stress-strain relations are not symmetrical with respect to these variables, i.e., the response of one coordinate to another is different from the reverse direction, We also examine the effect of conformational changes in base-pair variables on the sugar-backbone conformation by using the minimization method we developed. The conformational changes of base pairs affect the sugar pucker and other dihedral angles of the backbone of DNA, but each variable affects the sugar-backbone differently, In particular, twist is found to have the most influence in affecting the sugar pucker and backbone conformation. These calculated conformational changes in base pairs and backbone segments are consistent with experimental observations and serve to validate the calculation method. C1 NCI,MATH BIOL LAB,DBS,NIH,BETHESDA,MD 20892. RIKEN,LIFE SCI CTR,TSUKUBA,IBARAKI 305,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK BIOMED SUPER COMP LAB,FREDERICK,MD 21701. RI Jernigan, Robert/A-5421-2012 NR 39 TC 9 Z9 9 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD SEP PY 1996 VL 71 IS 3 BP 1507 EP 1518 PG 12 WC Biophysics SC Biophysics GA VF097 UT WOS:A1996VF09700036 PM 8874024 ER PT J AU Arnold, MM Srivastava, S Fredenburgh, J Stockard, CR Myers, RB Grizzle, WE AF Arnold, MM Srivastava, S Fredenburgh, J Stockard, CR Myers, RB Grizzle, WE TI Effects of fixation and tissue processing on immunohistochemical demonstration of specific antigens SO BIOTECHNIC & HISTOCHEMISTRY LA English DT Article DE antigen retrieval; biomarkers; fixation; immunohistochemistry ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; TUMOR-ASSOCIATED GLYCOPROTEIN-72; ADENOCARCINOMA; EXPRESSION AB Identification of biomarkers in archival tissues using immunochemistry is becoming increasingly important for determining the diagnosis and prognosis of tumors, for characterizing preinvasive neoplastic changes in glandular tissues such as prostate, for evaluating the response of tumors and preinvasive neoplastic changes to certain therapies (i.e., as a surrogate intermediate end point), for selecting patients who are candidates for specific therapies (e.g., immunotherapy) and for retrospective studies. For detecting specific biomarkers it is important to understand the limitations imposed by the fixation methods and processing of the tissues. This study was designed to determine the effects of fixation on the detection in archival paraffin blocks of selected antigens postulated to be important in tumor biology. We evaluated the antigens TGF alpha, p185(erbB-2), broad spectrum keratins, p53, and TAG-72 (B72.3). Fixatives evaluated included standard preparations of neutral buffered formalin, acid formalin, zinc formalin, alcoholic formalin, ethanol, methanol, and Bouin's fixative. We found that in general neutral buffered formalin is the poorest fixative for maintaining antigen recognition by immunohistochemistry and that no single fixative was best for all antigens. The dehydrating (coagulant) fixatives (e.g., ethanol and methanol) preserved immunorecognition of p53 and broad spectrum keratins best while the slow cross-linking fixatives (e.g., unbuffered zinc formalin) were best for demonstrating TGF alpha and p185(erbB-2) Fixatives other than neutral buffered formalin produced equivalent recognition of the epitope of TAG-72 by B72.3. In formalin fixed archival tissues, only a portion of the antigen signal can be detected by routine immunohistologic methods. C1 UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. SANTA ROSA MEM HOSP,DEPT PATHOL,SANTA ROSA,CA 95405. NCI,BETHESDA,MD 20892. RICHARD ALLAN MED INC,KALAMAZOO,MI. UNIV ALABAMA,BIRMINGHAM,AL. FU NCI NIH HHS [N01-CN-15340-2] NR 14 TC 69 Z9 69 U1 1 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1052-0295 J9 BIOTECH HISTOCHEM JI Biotech. Histochem. PD SEP PY 1996 VL 71 IS 5 BP 224 EP 230 DI 10.3109/10520299609117164 PG 7 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA VL671 UT WOS:A1996VL67100002 PM 8896794 ER PT J AU Cereseto, A Diella, F Mulloy, JC Cara, A Michieli, P Grassmann, R Franchini, G Klotman, ME AF Cereseto, A Diella, F Mulloy, JC Cara, A Michieli, P Grassmann, R Franchini, G Klotman, ME TI P53 functional impairment and high p21(waf1/cip1) expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells SO BLOOD LA English DT Article ID TROPICAL SPASTIC PARAPARESIS; LEUKEMIA-LYMPHOMA VIRUS; TUMOR-SUPPRESSOR GENE; HTLV-1 TAX PROTEIN; HUMAN RETROVIRUS; CYCLIN KINASES; MESSENGER-RNA; DNA-DAMAGE; ACTIVATION; MUTATIONS AB Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral as well as dysregulated cellular proteins in transformation. We investigated the potential role of the tumor suppressor gene p53 and of the p53-regulated gene, p21(waf1/cip1) (wild-type p53 activated fragment 1/ cycling dependent kinases [cdks] interacting protein 1), in HTLV-l-infected T cells. We have found that the majority of HTLV-l-infected T cells have the wild-type p53 gene. However, its function in HTLV-l-transformed cells appears to be impaired, as shown by the lack of appropriate p53-mediated responses to ionizing radiation (IR). Interestingly, the expression of the p53 inducible gene, p21(waf1/cip1), is elevated at the messenger ribonucleic acid and protein levels in all HTLV-I-infected T-cell lines examined as well as in Taxi-1, a human T-cell line stably expressing Tax, Additionally, Tax induces upregulation of a p21(waf1/cip1) promoter-driven luciferase gene in p53 null cells, and increases p21(waf1/cip1) expression in Jurkat T cells. These findings suggest that the Tax protein is at least partially responsible for the p53-independent expression of p21(waf1/cip1) in HTLV-l-infected cells. Dysregulation of p53 and p21(waf1/cip1) proteins regulating cell-cycle progression, may represent an important step in HTLV-l-induced T-cell transformation. (C) 1996 by The American Society of Hematology. C1 NCI,TUMOR CELL BIOL LAB,NIH,BETHESDA,MD 20892. NCI,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. NCI,CELLULAR & MOL BIOL LAB,NIH,BETHESDA,MD 20892. UNIV ERLANGEN NURNBERG,INST KLIN & MOL VIROL,D-8520 ERLANGEN,GERMANY. RI Michieli, Paolo/A-2588-2011; klotman, mary/A-1921-2016; Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 69 TC 126 Z9 127 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 SEP 1 PY 1996 VL 88 IS 5 BP 1551 EP 1560 PG 10 WC Hematology SC Hematology GA VE234 UT WOS:A1996VE23400003 PM 8781409 ER PT J AU Lee, SB Rao, AK Lee, KH Yang, X Bae, YS Rhee, SG AF Lee, SB Rao, AK Lee, KH Yang, X Bae, YS Rhee, SG TI Decreased expression of phospholipase C-beta 2 isozyme in human platelets with impaired function SO BLOOD LA English DT Article ID TYROSINE PHOSPHORYLATION; C ISOZYMES; CALCIUM MOBILIZATION; BOVINE BRAIN; ACTIVATION; PURIFICATION; CLONING; C-GAMMA-2; RECEPTOR AB Platelets from a patient with a mild inherited bleeding disorder and abnormal platelet aggregation and secretion show reduced generation of inositol 1,4,5-trisphosphate, mobilization of intracellular Ca2+, and phosphorylation of pleckstrin in response to several G protein mediated agonists, suggesting a possible defect at the level of phospholipase C (PLC) activation (see accompanying report), A procedure was developed that allows quantitation of platelet PLC isozymes. After fractionation of platelet extracts by high-performance liquid chromatography, 7 out of 10 known PLC isoforms were detected by immunoblot analysis. The amount of these isoforms in normal platelets decreased in the order PLC-gamma 2 > PLC-beta 2 > PLC-beta 3 > PLC-beta 1 > PLC-gamma 1 > PLC-delta 1 > PLC-beta 4. Compared with normal platelets, platelets from the patient contained approximately one-third the amount of PLC-beta 2, whereas PLC-beta 4 was increased threefold, These results suggest that the impaired platelet function in the patient in response to multiple G protein mediated agonists is attributable to a deficiency of PLC-beta 2. They document for the first time a specific PLC isozyme deficiency in human platelets and provide an unique opportunity to understand the role of different PLC isozymes in normal platelet function. (C) 1996 by The American Society of Hematology. C1 NHLBI,LAB CELL SIGNALING,NIH,BETHESDA,MD 20892. TEMPLE UNIV,SCH MED,SOL SHERRY THROMBOSIS RES CTR,PHILADELPHIA,PA 19122. TEMPLE UNIV,SCH MED,DEPT MED,PHILADELPHIA,PA 19122. FU NHLBI NIH HHS [K07HL02658, T32HL07777] NR 29 TC 64 Z9 64 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 SEP 1 PY 1996 VL 88 IS 5 BP 1684 EP 1691 PG 8 WC Hematology SC Hematology GA VE234 UT WOS:A1996VE23400018 PM 8781424 ER PT J AU Aoshima, M Nunoi, H Shimazu, M Shimizu, S Tatsuzawa, O Kenney, RT Kanegasaki, S AF Aoshima, M Nunoi, H Shimazu, M Shimizu, S Tatsuzawa, O Kenney, RT Kanegasaki, S TI Two-exon skipping due to a point mutation in p67-phox-deficient chronic granulomatous disease SO BLOOD LA English DT Article ID PHAGOCYTE NADPH OXIDASE; RESPIRATORY BURST OXIDASE; P67(PHOX) GENE; CYTOCHROME-B; LIGHT CHAIN; BINDING; COMPONENT; EXPRESSION; CLONING; PROTEIN AB The cytosolic 67-kD protein in phagocytes (p67-phox) and B lymphocytes is one of essential components of the superoxide-generating system in these cells, and its defect causes an autosomal recessive type of chronic granulomatous disease (CGD). We performed mutation analysis of p67-phox mRNA from a CGD patient who lacks the protein and found an in-frame deletion from nucleotide 694 to 879, which corresponds to the entire sequence of exons 8 and 9. This sequence encodes one of two Src homology 3 domains and a part of proline-rich domain in p67-phox and lack of these domains seem to have influenced stability of this protein. To know causative reason for the deletion, we analyzed genomic DNA for p87-phox using two sets of primers that covered exons 8 and 9 with adjacent introns. The DNA fragments from the patient were shown to be same in length as those from control. However, the single-strand conformation-polymorphism analysis of the fragments showed that a patient's specimen that included the splice junction of exon 9 exhibited different mobility from the control. By sequencing of the fragment, a homozygous G to A replacement at position +1 of intron 9 was found to be a sole mutation, which reduced the matching score of the splicing sequence to the consensus calculated according to the formula proposed by Shapiro and Senapathy (Nucleic Acids Res 15:7155, 1987). The reduced matching score at the splice doner site (5' splice site) of intron 9 and the original low matching score at the acceptor site (3' splice site) of intron 7 may explain the skipping of exon 8 and 9, and another predicted mechanism is discussed on the basis of Shapiro and Senapathy's hypothesis. (C) 1996 by The American Society of Hematology. C1 UNIV TOKYO,INST MED SCI,MINATO KU,TOKYO 108,JAPAN. MITSUBISHI YUKA BIOCHEM LAB INC,TOKYO,JAPAN. NATL CTR PEDIAT TREATMENT,SETAGAYA KU,TOKYO,JAPAN. NIAID,NIH,BETHESDA,MD 20892. NR 39 TC 23 Z9 24 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 SEP 1 PY 1996 VL 88 IS 5 BP 1841 EP 1845 PG 5 WC Hematology SC Hematology GA VE234 UT WOS:A1996VE23400037 PM 8781442 ER PT J AU Rajapakse, JC Giedd, JN Rumsey, JM Vaituzis, AC Hamburger, SD Rapoport, JL AF Rajapakse, JC Giedd, JN Rumsey, JM Vaituzis, AC Hamburger, SD Rapoport, JL TI Regional MRI measurements of the corpus callosum: A methodological and developmental study SO BRAIN & DEVELOPMENT LA English DT Article DE corpus callosum; magnetic resonance imaging; brain imaging; interhemispheric communication; shape measurement ID DEFICIT-HYPERACTIVITY DISORDER; SEXUAL DIMORPHISM; MORPHOMETRIC ANALYSIS; SCHIZOPHRENIA; MORPHOLOGY; SIZE; HANDEDNESS; GENDER; DOMINANCE; CHILDHOOD AB A technique for quantifying the midsagittal size and shape of the corpus callosum (CC) from magnetic resonance brain scans is presented. The technique utilizes the distances to the ventral and dorsal boundaries of small sectors of the CC from a reference point to compute the size and shape parameters of the CC and its subdivisions, Intrarater and interrater interclass correlation coefficients for the area measurements ranged from 0.88 to 0.99. Correlations between these automated measures and those obtained by pixel counting were equally high, The corpus callosa of 104 (57 male and 47 female) right-handed healthy children and adolescents, ages 4-18, were examined in relation to age and sex, Corpus callosum growth was most striking for the splenium and isthmus with some changes in the midbody regions, The area and perimeter of these regions increased, shapes became more compact, and the boundaries became more regular with age. The length and curvature at the anterior and posterior regions of the CC increased more rapidly in males than in females, These significant and consistent results indicate that the method is reliable and sensitive to developmental changes of the CC. RP Rajapakse, JC (reprint author), NIMH,CHILD PSYCHIAT BRANCH,NIH,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Rohlf, F/A-8710-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 70 TC 63 Z9 67 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0387-7604 J9 BRAIN DEV-JPN JI Brain Dev. PD SEP-OCT PY 1996 VL 18 IS 5 BP 379 EP 388 DI 10.1016/0387-7604(96)00034-4 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA VL171 UT WOS:A1996VL17100006 PM 8891233 ER PT J AU De Luca, LM Scita, G AF De Luca, LM Scita, G TI Ha-ras oncogene transformation abolishes retinoic acid-induced reduction of intracellular fibronectin SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT 4th Brazilian Symposium on Extracellular Matrix CY SEP 08-11, 1996 CL ANGRA DOS REIS, BRAZIL DE retinoic acid; differentiation; cell growth; extracellular matrix; fibronectin; Ha-ras p21 protein transformation ID MESSENGER-RNA LEVELS; HUMAN-LEUKEMIA CELLS; BREAST-CANCER CELLS; TERATOCARCINOMA CELLS; LAMININ RECEPTOR; EXPRESSION; GENE; FIBROBLASTS; DIFFERENTIATION; TRANSCRIPTION AB All-trans-retinoic acid (RA) is a master regulator of cell differentiation and in this process it greatly influences cell adhesion and the elaboration of the extracellular matrix. Therefore, we were interested in the effect of RA on the biosynthesis of fibronectin (FN). RA reduced the level of intracellular FN in a time- and concentration-dependent fashion in NIH-3T3 cells, but not in NIH-3T3 cells transformed by an activated Ha-ras oncogene. Since the steady-state level of FN transcripts did not change after treatment of the cells with RA for various times or concentrations, RA probably acts at the translational level. In NIH-3T3 cells, RA had distinct effects on different receptors, from decreasing retinoic acid receptor (RAR)alpha to increasing RAR beta expression to no effect on RAR gamma. Transfomation of NIH-3T3 cells with an activated Ha-ras oncogene downmodulated RAR expression and also abolished responsiveness to RA. A variety of approaches permitted the following conclusions: 1) RA-dependent FN downmodulation is mediated by RARs, 2) retinoid X receptors (RXRs) mediate the observed reduction of RAR alpha by RA, and 3) the blockade of RA responsiveness by Ha-ras-transfected cells cannot be overcome by overexpression of RAR alpha. These studies have identified fibronectin and RAR alpha as RA targets in fibroblast cells and have shown that oncogenic transformation renders the cells resistant to RA action. RP De Luca, LM (reprint author), NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NIH, NIH BLDG 37,ROOM 3A-17, 37 CONVERT DR, BETHESDA, MD 20892 USA. RI Scita, GIORGIO/J-9670-2012; OI Scita, Giorgio/0000-0001-7984-1889 NR 45 TC 1 Z9 1 U1 0 U2 2 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD SEP PY 1996 VL 29 IS 9 BP 1127 EP 1131 PG 5 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA VF231 UT WOS:A1996VF23100006 PM 9181055 ER PT J AU Monnet, FP deCosta, BR Bowen, WD AF Monnet, FP deCosta, BR Bowen, WD TI Differentiation of sigma ligand-activated receptor subtypes that modulate NMDA-evoked [H-3]-noradrenaline release in rat hippocampal slices SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE N-methyl-D-aspartate (NMDA); sigma receptors; ED-737; ED-1008; NE-100; 1,3-di(2-tolyl)guanidine (DTG); (+)-pentazocine; haloperidol; ED-1063; rat hippocampus ID METHYL-D-ASPARTATE; INDUCED NEURONAL ACTIVATION; GUINEA-PIG BRAIN; H-3 NOREPINEPHRINE RELEASE; NORADRENALINE RELEASE; BINDING-SITES; REDUCED HALOPERIDOL; ANTIPSYCHOTIC-DRUGS; DORSAL HIPPOCAMPUS; CEREBRAL-CORTEX AB 1 It is now widely accepted that there are two classes of sigma (sigma) binding sites, denoted sigma(1) and sigma(2), and recently sigma(3) subtype has been proposed. Selective sigma(1) and sigma(2) receptor agonists are known to modulate the neuronal response to N-methyl-D-aspartate (NMDA) in vivo and in vitro. To identify the site of action of a series of recently synthesised high affinity sigma ligands, the present in vitro series of experiments was carried out on NMDA-evoked [H-3]-noradrenaline ([H-3]-NA) overflow from preloaded hippocampal slices of the rat. 2 The ligands (+)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl) cyclohexylamine (BD-737) and (+)-pentazocine, considered as the prototypic sigma(1) agonists, potentiated the NMDA response from 10 nM to 100 nM. This potentiation faded between 100 nM and 1 mu M ligand concentrations. On the other hand, 1,3-di(2-tolyl)guanidine (DTG), a mixed sigma(1)/sigma(2) agonist, at concentrations greater than 100 nM inhibited the NMDA-evoked [H-3]-NA release. Spiperone, considered as active on putative sigma(3) receptors, was without effect on the NMDA response, or on the potentiating effect of BD-737. 3 The high affinity sigma antagonists haloperidol and 1[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (BD-1063), inactive by themselves on the NMDA-induced response, at concentrations above 30 nM totally prevented the potentiating effect of (+)-pentazocine (100 nM) as well as the inhibitory effect of DTG (300 nM) on NMDA-evoked [H-3]-NA release. Whereas haloperidol and BD-1063, at concentrations <1 mu M, were inactive on the potentiating effect of BD-737 (100 nM). 4 4-(4-Chlorophenyl)-alpha-4-fluorophenyl-4-hydroxy-1-piperidinebutanol (reduced haloperidol), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD-1008), inactive by themselves on the NMDA-evoked [H-3]-NA release, failed to reverse the effects of (+)-pentazocine and DTG, but at concentrations of 30 nM to 1 mu M antagonised the BD-737-induced potentiation of the NMDA response. Conversely, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) blocked the effects of (+)-pentazocine as well as those of BD-737, but not those of DTG. 5 The present results provide in vitro functional evidence for a sigma receptor type preferentially sensitive to BD-737, reduced haloperidol, BD-1008 and also to NE-100, that differs from the already identified sigma(1), sigma(2) and sigma(3) sites. C1 ASSISTANCE PUBL HOP PARIS,DPIM,DELEGAT RECH CLIN,F-75004 PARIS,FRANCE. CNRS,UPR 2212,F-91198 GIF SUR YVETTE,FRANCE. NIDDKD,MED CHEM LAB,NIH,BETHESDA,MD 20892. RP Monnet, FP (reprint author), INSERM,U33,80 RUE GEN LECLERC,F-94276 LE KREMLIN BICETR,FRANCE. NR 52 TC 55 Z9 57 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 1996 VL 119 IS 1 BP 65 EP 72 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VE792 UT WOS:A1996VE79200011 PM 8872358 ER PT J AU Szallasi, A Jonassohn, M Acs, G Biro, T Acs, P Blumberg, PM Sterner, O AF Szallasi, A Jonassohn, M Acs, G Biro, T Acs, P Blumberg, PM Sterner, O TI The stimulation of capsaicin-sensitive neurones in a vanilloid receptor-mediated fashion by pungent terpenoids possessing an unsaturated 1,4-dialdehyde moiety SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE isovelleral; pungent terpenoids; unsaturated dialdehydes; resiniferatoxin; capsaicin; capsazepine; vanilloid receptors; novel vanilloids ID H-3 RESINIFERATOXIN BINDING; CHEMICAL DEFENSE; COMPETITIVE ANTAGONIST; SULFHYDRYL-REAGENTS; HOT TASTE; RAT; DIALDEHYDES; ANTIFEEDANT; ANALOGS; HUMANS AB 1 The irritant fungal terpenoid isovelleral caused protective eye-wiping movements in the rat upon intraocular instillation and showed cross-tachyphylaxis with capsaicin, the pungent principle in hot pepper. 2 Isovelleral induced a dose-dependent calcium uptake by rat dorsal root ganglion neurones cultured in vitro with an EC(50) of 95 nM, which was fully inhibited by the competitive vanilloid receptor antagonist capsazepine. 3 Isovelleral inhibited specific binding of [H-3]-resiniferatoxin (RTX), an ultrapotent capsaicin analogue, to rat trigeminal ganglion or spinal cord preparations with an IC50 of 5.2 mu M; in experiments in which the concentration of [H-3]-RTX was varied, isovelleral changed both the apparent affinity (from 16 pM to 37 pM) and the co-operativity index (from 2.1 to 1.5), but not the B-max. 4 The affinity of isovelleral for inducing calcium uptake or inhibiting RTX binding was in very good agreement with the threshold dose (2.2. nmol) at which it provoked pungency on the human tongue. 5 For a series of 14 terpenoids with an unsaturated 1,4-dialdehyde, a good correlation was found between pungency on the human tongue and affinity for vanilloid receptors on the rat spinal cord. 6 The results suggest that isovelleral-like compounds produce their irritant effect by interacting with vanilloid receptors on capsaicin-sensitive sensory neurones. Since these pungent diterpenes are structurally distinct from the known classes of vanilloids, these data provide new insights into structure-activity relations and may afford new opportunities for the development of drugs targeting capsaicin-sensitive pathways. C1 LUND UNIV,DEPT ORGAN CHEM 2,LUND,SWEDEN. KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL,STOCKHOLM,SWEDEN. NCI,BETHESDA,MD 20892. NR 60 TC 48 Z9 48 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD SEP PY 1996 VL 119 IS 2 BP 283 EP 290 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG298 UT WOS:A1996VG29800017 PM 8886410 ER PT J AU Guiney, PD Cook, PM Casselman, JM Fitzsimmons, JD Simonin, HA Zabel, EW Peterson, RE AF Guiney, PD Cook, PM Casselman, JM Fitzsimmons, JD Simonin, HA Zabel, EW Peterson, RE TI Assessment of 2,3,7,8-tetrachlorodibenzo-p-dioxin induced sac fry mortality in lake trout (Salvelinus namaycush) from different regions of the Great Lakes SO CANADIAN JOURNAL OF FISHERIES AND AQUATIC SCIENCES LA English DT Article ID LIFE-STAGE MORTALITY; DIBENZO-P-DIOXIN; RAINBOW-TROUT; POLYCHLORINATED-BIPHENYLS; ONCORHYNCHUS-MYKISS; SALMO-GAIRDNERI; TCDD TOXICITY; FISH; EGGS; CONGENERS AB Background levels of TCDD toxic equivalents (TEs) in lake trout (Salvelinus namaycush) eggs (calculated using fish-specific toxicity equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs)) were higher for two locations in Lake Ontario than Lake Superior and a hatchery (10.5-10.9 versus 0.3 and 0.05 pg TE/g egg). Despite the higher contamination of Lake Ontario eggs, sac fry mortality was uniformly low for all eggs. This is consistent with TCDD toxicity equivalence concentrations (TECs) of all eggs being less than the TCDD no observable adverse effect level (NOAEL) for Lake Superior lake trout sac fry mortality (34 pg TCDD/g egg). Eggs exposed in the laboratory to [H-3]TCDD and maintained at either 8 or 8-3-8 degrees C had similar sac fry mortalities. For all sources of eggs, [3H]TCDD-induced sac fry mortality was associated with blue sac disease, which was not affected by water temperature, and resulted in similar LD(50) values (42-72 pg[H-3]TCDD/g egg). Thus, lack of sac fry mortality in wild Lake Ontario lake trout eggs was not caused by lack of responsiveness to TCDD but rather was attributable to egg TECs being below the TCDD NOAEL for sac fry mortality. C1 UNIV WISCONSIN,NIEHS,AQUAT BIOMED CTR,MILWAUKEE,WI 53204. US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,MID CONTINENT ECOL DIV,DULUTH,MN 55804. BAYFIELD INST,GREAT LAKES LAB FISHERIES & AQUAT SCI,BURLINGTON,ON L7R 4A6,CANADA. NEW YORK DEPT ENVIRONM CONSERVAT,ROME,NY 13440. UNIV WISCONSIN,CTR ENVIRONM TOXICOL,MADISON,WI 53706. CTR ENVIRONM TOXICOL,MADISON,WI 53706. SCH PHARM,MADISON,WI 53706. ONTARIO MINIST NAT RESOURCES,GLENORA FISHERIES RES STN,PICTON,ON K0K 2T0,CANADA. NR 54 TC 23 Z9 25 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0706-652X J9 CAN J FISH AQUAT SCI JI Can. J. Fish. Aquat. Sci. PD SEP PY 1996 VL 53 IS 9 BP 2080 EP 2092 DI 10.1139/cjfas-53-9-2080 PG 13 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA WE259 UT WOS:A1996WE25900017 ER PT J AU Danion, JM Weingartner, H Singer, L AF Danion, JM Weingartner, H Singer, L TI Is cognitive psychopathology plausible? Illustrations from memory research SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE cognitive psychopathology; memory disorders; benzodiazepines; schizophrenia; depression; cognitive remediation ID HEALTHY-VOLUNTEERS; RECOGNITION MEMORY; EXPLICIT MEMORY; IMPLICIT MEMORY; CLINICAL DEPRESSION; INDUCED AMNESIA; SCHIZOPHRENIA; LORAZEPAM; DIAZEPAM; BENZODIAZEPINES AB Objective: To examine the strengths and weaknesses of cognitive psychopathology through the specific examples of the memory impairments associated with the administration of benzodiazepines, with schizophrenia, and with depression. Method: These examples are analyzed with reference to a model of memory based on the principle of division between specialized and central processing structures. A basic contention is that it is useful to consider 2 broad classes of processes-automatic, associative, or sensory/perceptual processes on the one hand and intentional, strategic, or reflective processes on the other hand-as being separate. Results: The functional mechanisms of the memory impairments associated with these conditions are beginning to be identified, and there is preliminary evidence that a deficit in an elementary computation may have dramatic consequences on highest cognitive functions. There is also evidence that certain memory impairments are linked to specific dysfunctional outcomes in everyday life. By showing that specific rate-limiting factors of cognitive performance can be identified and are amenable to cognitive interventions, existing data open the door for theoretically and empirically based cognitive remediation of mental disorders. Conclusion: The bulk of available evidence (albeit limited) makes the enterprise of cognitive psychopathology quite plausible and convincing. C1 PUBL HLTH SERV,DEPT HLTH & HUMAN SERV,NIH,BETHESDA,MD. RP Danion, JM (reprint author), HOP UNIV STRASBOURG,INSERM U405,PSYCHIAT CLIN,1 PL HOP,F-67091 STRASBOURG,FRANCE. NR 70 TC 4 Z9 4 U1 5 U2 6 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA SUITE 200, 237 ARGYLE AVE, OTTAWA ON K2P 1B8, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD SEP PY 1996 VL 41 IS 7 SU 1 BP S5 EP S13 PG 9 WC Psychiatry SC Psychiatry GA VH881 UT WOS:A1996VH88100002 PM 8884046 ER PT J AU Newcomb, PA Longnecker, MP Storer, BE Mittendorf, R Baron, J Clapp, RW TrenthamDietz, A Willett, WC AF Newcomb, PA Longnecker, MP Storer, BE Mittendorf, R Baron, J Clapp, RW TrenthamDietz, A Willett, WC TI Recent oral contraceptive use and risk of breast cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; oral contraceptives; United States ID YOUNG-WOMEN; SWEDEN; AGE; AGREEMENT; HISTORIES; NORWAY AB We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States, Cases (n = 6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire, Controls (n = 9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years), Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview, After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR] = 1.1, 95 percent confidence interval [CI] = 1.0-1.2), Total duration of use also was not related to risk, There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI = 0.9-1.9), However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR = 2.0, CI = 1.1-3.9), Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index kg/m(2)) less than 20.4, RR = 1.7, CI = 1.1-2.8, While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. UNIV CHICAGO,DEPT OBSTET & GYNECOL,PRITZKER SCH MED,CHICAGO,IL 60637. DARTMOUTH COLL SCH MED,DEPT FAMILY & COMMUNITY MED,HANOVER,NH. BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA 02215. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH MED,CHANNING LAB,CAMBRIDGE,MA 02138. BRIGHAM & WOMENS HOSP,DEPT MED,BOSTON,MA 02115. RP Newcomb, PA (reprint author), UNIV WISCONSIN,CTR COMPREHENS CANC,1300 UNIV AVE,4780,MADISON,WI 53706, USA. OI Clapp, Richard/0000-0001-8174-0825; Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [R01 CA 47147, R01 CA 47305] NR 37 TC 24 Z9 24 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1996 VL 7 IS 5 BP 525 EP 532 DI 10.1007/BF00051885 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VL256 UT WOS:A1996VL25600006 PM 8877050 ER PT J AU Weiss, HA Devesa, SS Brinton, LA AF Weiss, HA Devesa, SS Brinton, LA TI Laterality of breast cancer in the United States SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; laterality; risk factors; United States ID MAMMOGRAPHIC FEATURES; RISK; AUGMENTATION; SIZE AB Breast cancer laterality of over 250,000 cases from the Surveillance, Epidemiology, and End Results (SEER) program in the United States was studied in relation to gender, race, tumor stage, histology, age at diagnosis, year of diagnosis, estrogen receptor status, and marital status. The data, which include all invasive and in situ breast cancer cases in the SEER program during the years 1973-92, confirm results from other studies of an overall five percent excess of left-sided disease in women. The excess occurs for all races and stages of disease, and for invasive disease, the excess increases with age, There was no significant variation in the laterality of invasive disease over time, though for in situ tumors, the left-sided excess was significantly greater during the years 1978-82 than in other periods. No excess of left-sided breast cancer was observed among men. There is no evidence that detection bias plays a major role, and although the left breast is slightly larger, on average, than the right, there is little evidence that breast size is associated with breast cancer risk. The reason for the left-sided excess among women remains unclear. RP Weiss, HA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,EXECUT PLAZA NORTH RM 443,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 22 TC 35 Z9 36 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1996 VL 7 IS 5 BP 539 EP 543 DI 10.1007/BF00051887 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VL256 UT WOS:A1996VL25600008 PM 8877052 ER PT J AU Merrill, RM Feuer, EJ AF Merrill, RM Feuer, EJ TI Risk adjusted cancer-incidence rates (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE hysterectomy; incidence; lifetime risk; prevalence; United States; uterine cancers ID BREAST-CANCER; PREVALENCE; LUNG; HYSTERECTOMY; MORTALITY AB A risk-adjusted method is proposed for estimating cancer incidence rates from data collected by the Surveillance, Epidemiology, and End Results (SEER) program of the US National Cancer Institute, Unlike the conventional incidence-rate estimates reported by SEER, this method considers only the first primary cancer, and adjusts for population-based cancer prevalence, as well as for surgical procedures which remove an individual from risk of developing a given cancer. Thus, risk-adjusted incidence-rates more accurately reflect the average cancer risk for individuals in the cancer-free, at-risk population, The results of the analysis indicate that, in general, incidence-rate estimates are fairly similar between the conventional and risk-adjusted methods, However, this is not the case for certain cancer sites which may have: (i) a high number of subsequent primary cancers (e.g., melanomas-skin); (ii) a high cancer prevalence proportion (e.g., prostate cancer); (iii) a high number of subsequent primary cancers and prevalence proportion (e.g., female breast); or (iv) a high prevalence of removal of the organ in question (e.g., cervical and uterine cancers), For example, by applying the risk-adjusted incidence method for in situ and invasive cervical cancer, we found that in the period 1990-92 the age-adjusted incidence-rate estimate increased from 57.8 to 66.3 (15 percent) per 100,000 person-years; the greatest increase in the incidence-rate estimate occurred for women aged 65 to 69 years, from 40.1 to 63.2 (58 percent) per 100,000 person-years; and the lifetime risk of developing cervical cancer increased from 4.6 (1 in 22) to 5.5 (1 in 18) percent. C1 NCI,CANC CONTROL RES PROGRAM,APPL RES BRANCH,BETHESDA,MD 20892. RP Merrill, RM (reprint author), NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,9000 ROCKVILLE PIKE,EPN 313,BETHESDA,MD 20892, USA. NR 32 TC 26 Z9 32 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD SEP PY 1996 VL 7 IS 5 BP 544 EP 552 DI 10.1007/BF00051888 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VL256 UT WOS:A1996VL25600009 PM 8877053 ER PT J AU Landi, MT Zocchetti, C Bernucci, I Kadlubar, FF Tannenbaum, S Skipper, P Bartsch, H Malaveille, C Shields, P Caporaso, NE Vineis, P AF Landi, MT Zocchetti, C Bernucci, I Kadlubar, FF Tannenbaum, S Skipper, P Bartsch, H Malaveille, C Shields, P Caporaso, NE Vineis, P TI Cytochrome P4501A2: Enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CAFFEINE URINARY METABOLITES; BLADDER-CANCER; JAPANESE POPULATION; HEMOGLOBIN ADDUCTS; CIGARETTE-SMOKING; DRUG-METABOLISM; ODDS RATIO; HUMAN LUNG; SMOKERS AB Cytochrome P4501A2 (CYP1A2) activity may be related to bladder cancer risk through metabolic activation of aromatic amines, such as 4-aminobiphenyl (ABP), to reactive intermediates that can form DNA and hemoglobin (Hb) adducts, In the context of a study on smoking and bladder cancer risk, 97 healthy male volunteers were investigated, CYP1A2-dependent N-oxidation activity was measured using a molar ratio of urinary caffeine metabolites [(paraxanthine + 1,7-dimethyluric acid)/caffeine] obtained between the fourth and fifth h after drinking a standardized cup of coffee, N-Oxidation activity was induced by blond tobacco smoke, meat consumption the dinner before the test, or more than four cups of coffee a day, The regular use of medication appeared associated with a decrease in N-oxidation levels. Age and alcohol consumption were not related with CYP1A2 activity, A polymorphic distribution of the CYP1A2 and N-acetyltransferase-2 (determined by the caffeine metabolite ratio 5-acetylamino-6-formylamino-3-methyluracil:1-methylxanthine) phenotypes was examined in relation to susceptibility to ABP-Hb adduct formation, Rapid oxidizers and subjects with the combined slow acetylator-rapid oxidizer phenotype showed the highest ABP-Hb adduct levels at a low smoking dose, Blond tobacco smokers exhibited higher adduct levels compared with black tobacco smokers, after adjustment for the quantity of cigarettes smoked. At the highest levels of smoking exposure, no major difference in ABP-Hb adduct levels was found among the different combinations of CYP1A2 and N-acetyltransferase-2 phenotypes, In a subset of only 45 available samples, no association was seen between the ABP-Hb adduct levels and the glutathione S-transferase M1 genotype. C1 IST CLIN PERFEZIONAMENTO, I-20122 MILAN, ITALY. UNIV TURIN, DIPARTIMENTO SCI BIOMED & ONCOL UMANA, I-10126 TURIN, ITALY. NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. MIT, CAMBRIDGE, MA 02139 USA. GERMAN CANC RES CTR, D-69120 HEIDELBERG, GERMANY. INT AGCY RES CANC, F-69372 LYON, FRANCE. NIH, NATL CANC INST, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. NIH, NATL CANC INST, GENET EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. RP Landi, MT (reprint author), UNIV MILAN, EPIDEMIOL RES CTR, EPOCA, VIA S BARNABA 8, I-20122 MILAN, ITALY. RI Shields, Peter/I-1644-2012 NR 47 TC 58 Z9 59 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1996 VL 5 IS 9 BP 693 EP 698 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VF687 UT WOS:A1996VF68700005 PM 8877060 ER PT J AU Giusti, RM Maloney, EM Hanchard, B Morgan, OS Steinberg, SM Wachter, H Williams, E Cranston, B Fuchs, D Manns, A AF Giusti, RM Maloney, EM Hanchard, B Morgan, OS Steinberg, SM Wachter, H Williams, E Cranston, B Fuchs, D Manns, A TI Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HTLV-I; HIV-1 INFECTION; CEREBROSPINAL-FLUID; RISK-FACTORS; NEOPTERIN; TRYPTOPHAN; BETA-2-MICROGLOBULIN; ANTIBODIES; LEUKEMIA; JAMAICA AB Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction, Biomarkers of immune activation may correlate with perturbations of immune function associated,vith these diseases. We conducted a pilot cross-sectional study to assess four candidate biomarkers of immune activation, beta(2)-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus type I (HTLV-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica, Mean levels of beta(2)-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups, Mean tryptophan levels were significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups, No significant differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups, Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration, In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients, This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- and HTLV-I+ individuals, Neopterin and tryptophan mag be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients. C1 NATL CANC INST, VIRAL EPIDEMIOL BRANCH, DIV CANC EPIDEMIOL & GENET, ROCKVILLE, MD 20852 USA. NCI, DIV CLIN SCI, BIOSTAT & DATA MANAGEMENT SECT, BETHESDA, MD 20892 USA. UNIV W INDIES, DEPT PATHOL & MED, KINGSTON 7, JAMAICA. UNIV INNSBRUCK, INST MED CHEM & BIOCHEM, A-6020 INNSBRUCK, AUSTRIA. FU PHS HHS [31006, 40548] NR 32 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1996 VL 5 IS 9 BP 699 EP 704 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VF687 UT WOS:A1996VF68700006 PM 8877061 ER PT J AU Longnecker, MP Bernstein, L Bird, CL Yancey, AK Peterson, JC AF Longnecker, MP Bernstein, L Bird, CL Yancey, AK Peterson, JC TI Measurement of organochlorine levels in postprandial serum or in blood collected in serum separator tubes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB Whether organochlorine blood levels in fasting and postprandial specimens provide equivalent measures of exposure and the extent to which collecting blood in tubes containing material to separate serum and blood cells corrupts the specimen are unclear, In this paper, we present data from two studies that address both of these issues, In the first study, 27 women provided fasting blood in plain, silicone-coated Vacutainer tubes (red-topped) and in similar tubes containing serum separator gel (SSTs), as well as a postprandial specimen in a red-topped tube, The specimens collected in SSTs were left to stand overnight, with the gel in contact with the sample, In the second study, the blood of 12 industrial incinerator workers was collected in red-topped tubes and in SSTs, Blood in SSTs was left in contact with the gel for 5 days, Serum organochlorine residue levels ([1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] (DDE)) and polychlorinated biphenyls) in samples collected in red-topped tubes were highly correlated with levels measured in samples collected in SSTs (all Pearson r values were greater than or equal to 0.79). Postprandial and fasting organochlorine levels were also highly correlated (Pearson r values greater than or equal to 0.89). Our results indicate that timing of the collection of blood in relation to meals and use of SSTs to collect blood specimens did not greatly affect the relative classification of subjects with respect to serum level of DDE or polychlorinated biphenyls, The longer the specimen was in contact with the SST gel, however, the lower the level of organochlorine that was detected and, at least for DDE, the greater the misclassification caused. C1 UNIV SO CALIF,DEPT PREVENT MED,LOS ANGELES,CA 90089. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT COMMUNITY HLTH SCI,LOS ANGELES,CA 90024. PACIFIC TOXICOL LAB,LOS ANGELES,CA 90025. RP Longnecker, MP (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233 MD A3-05,RES TRIANGLE PK,NC 27709, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NICHD NIH HHS [N01-HD-3-3175]; NIEHS NIH HHS [R01 ES07084] NR 11 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1996 VL 5 IS 9 BP 753 EP 755 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VF687 UT WOS:A1996VF68700013 PM 8877068 ER PT J AU Kadlubar, FF Young, JF Lang, NP Caporaso, NE Sinha, R Landi, MT AF Kadlubar, FF Young, JF Lang, NP Caporaso, NE Sinha, R Landi, MT TI Correspondence re: Letter to the editor by B.K. Wang and W. Kalow on CYP1A2 phenotyping using caffeine. Cancer Epidemiol Biomarkers & Prev, vol 5, pg 231, 1996 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID URINARY METABOLITES C1 ARKANSAS CANC RES CTR,LITTLE ROCK,AR 72205. NCI,BETHESDA,MD 20892. UNIV MILAN,EPIDEMIOL RES CTR,EPOCA,I-20122 MILAN,ITALY. RP Kadlubar, FF (reprint author), NATL CTR TOXICOL RES,DIV MOL EPIDEMIOL,3900 NCTR RD HFT-100,JEFFERSON,AR 72079, USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD SEP PY 1996 VL 5 IS 9 BP 757 EP 758 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA VF687 UT WOS:A1996VF68700014 PM 8877069 ER PT J AU Moore, SK Zambrano, N Lynch, HT Lipkin, M Kopelovich, L AF Moore, SK Zambrano, N Lynch, HT Lipkin, M Kopelovich, L TI Absence of germline mutations in exons 5-9 of the p53 gene in patients with Li-Fraumeni-like (SBLA) and familial adenomatous polyposis heritable cancer syndromes SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; CULTURED SKIN FIBROBLASTS; BREAST-CANCER; EXPRESSION; CHILDREN; CELLS; DNA; PREVALENCE; NEOPLASMS; SPECTRUM AB Although acquired mutations in the human p53 gene occur in many tumor types, germline mutations are rare. An exception is the occurrence of germline p53 mutations in a fraction of families afflicted with the Li-Fraumeni syndrome (LFS). Previous studies from our laboratory demonstrated increased levels of wild type p53 protein in skin fibroblasts (SF) of patients from heritable cancer syndrome, including familial adenomatous polyposis (FAP), neurofibromatosis type 1 (NF1), and bilateral retinoblastoma (bRB) (Kopelovich and DeLeo, 1984,1986). Here, we further address the association between germline p53 alterations and genetic predisposition to cancer in the SBLA syndrome and in FAP. DNA sequencing and single-stranded conformational polymorphism analysis (SSCP) were utilized to screen for the presence of mutations within exons 5-9 of the p53 gene in SF and in benign tumors. Thus we observed no germline mutations in exons 5-9 of the p53 gene in SF from SBLA or FAP patients, including the Gardner variant. In addition, we observed no acquired mutations in exons 5-9 of the p53 gene in benign tumors from FAP patients. In conclusion, we found no association between germline p53 mutations and SBLA or FAP. How mechanisms that involve nonmutational activation of the p53 protein might affect genetic predisposition to cancer remains to be established. C1 VET ADM MED CTR,BAY PINES,FL 33504. US FDA,CTR DRUG EVALUAT & RES,DIV METAB & ENDOCRINE DRUG PROD,ROCKVILLE,MD 20857. NATL CANC INST,NATL INST HLTH,CELL BIOL LABS,BETHESDA,MD. CREIGHTON CANC CTR,OMAHA,NE. CREIGHTON UNIV,SCH MED,DEPT PREVENT MED,OMAHA,NE 68178. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. UNIV S FLORIDA,COLL MED,DEPT BIOL MOL,TAMPA,FL. UNIV S FLORIDA,DEPT PATHOL,TAMPA,FL. RI Zambrano, Nicola/B-9352-2014 OI Zambrano, Nicola/0000-0001-9395-3481 NR 44 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD SEP PY 1996 VL 90 IS 2 BP 125 EP 129 DI 10.1016/S0165-4608(96)00072-6 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA VJ108 UT WOS:A1996VJ10800006 PM 8830720 ER PT J AU Tsukui, T Hildesheim, A Schiffman, MH Lucci, J Contois, D Lawler, P Rush, BB Lorincz, AT Corrigan, A Burk, RD Qu, WM Marshall, MA Mann, D Carrington, M Clerici, M Shearer, GM Carbone, DP Scott, DR Houghten, RA Berzofsky, JA AF Tsukui, T Hildesheim, A Schiffman, MH Lucci, J Contois, D Lawler, P Rush, BB Lorincz, AT Corrigan, A Burk, RD Qu, WM Marshall, MA Mann, D Carrington, M Clerici, M Shearer, GM Carbone, DP Scott, DR Houghten, RA Berzofsky, JA TI Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: Correlation with cervical pathology SO CANCER RESEARCH LA English DT Article ID IMMUNE-RESPONSES; LEISHMANIA-MAJOR; T-CELL; INTRAEPITHELIAL NEOPLASIA; SEROPOSITIVE INDIVIDUALS; TRANSPLANTATION IMMUNITY; SEZARY-SYNDROME; B-LYMPHOCYTES; TH2 SUBSETS; INFECTION AB Human papillomavirus (HPV) is believed to be the major cause of cervical cancer. To investigate whether a cellular immune response, especially a T helper type 1 response, is related to the natural defense against HPV-related cervical lesions, the interleukin 2 response of peripheral blood lymphocytes in vitro to overlapping peptides from HPV-16 E6 and E7 oncoproteins was compared with the degree of cervical cytological abnormality among 140 women in a cross-sectional study. We compared 66 women diagnosed with low-grade squamous intraepithelial lesions (LSIL), 21 with high-grade squamous intraepithelial lesions (HSIL), and 28 with invasive cervical cancer with 25 women who were cytologically normal but previously HPV-16 DNA positive. The fraction showing strong interleukin 2 production against HPV-16 peptides was greatest among cytologically normal women (35%) and declined with increasing disease severity [LSIL] (20%), HSIL (17%), and cancer patients (7%); chi(2) test P for the trend = 0.02], whereas the responses against a recall influenza antigen were not significantly different among groups. Our finding suggests that a T helper lymphocyte type 1 response to HPV antigens is associated with disease status. This result may reflect a targeted effect of the disease on immune function or a protective effect of the immune response against disease progression. C1 NCI,MOL IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,BETHESDA,MD 20892. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,EXPT IMMUNOL BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED SCH,DALLAS,TX 75235. KAISER PERMANENTE,PORTLAND,OR 97227. DIGENE DIAGNOST,SILVER SPRING,MD 20904. YESHIVA UNIV ALBERT EINSTEIN COLL MED,BRONX,NY 10461. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21702. TORREY PINES INST MOL STUDIES,SAN DIEGO,CA 92121. NR 54 TC 106 Z9 118 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 SEP 1 PY 1996 VL 56 IS 17 BP 3967 EP 3974 PG 8 WC Oncology SC Oncology GA VE083 UT WOS:A1996VE08300023 PM 8752165 ER PT J AU Pass, HI Mew, DJY Carbone, M Matthews, WA Donington, JS Baserga, R Walker, CL Resnicoff, M Steinberg, SM AF Pass, HI Mew, DJY Carbone, M Matthews, WA Donington, JS Baserga, R Walker, CL Resnicoff, M Steinberg, SM TI Inhibition of hamster mesothelioma tumorigenesis by an antisense expression plasmid to the insulin-like growth factor-1 receptor SO CANCER RESEARCH LA English DT Article ID FACTOR-I RECEPTOR; CELL-LINES; IGF-1 RECEPTOR; T-ANTIGEN; TRANSFORMATION; PROLIFERATION; TUMORS; RNA AB We evaluated the effect of antisense insulin-like growth factor (IGF) receptor transcripts on the proliferation and tumorigenicity in an SV40-induced, immunocompetent hamster mesothelioma model (H9A). Expression of IGF-1 and IGF-1 receptor (IGP-1R) genes was identified from H9A RNA using reverse transcription-PCR and Northern analysis. H9A cells were electroporated with inducible expression vectors (under the transcriptional control of heat shock promoter HSP70) containing a cDNA fragment corresponding to base pairs 1-309 of IGF-1R in the sense or antisense orientation to generate the respective clones A3 sense or B9 antisense, The expression vector in genomic DNA was detected with PCR analysis as a 173-bp fragment on ethidium bromide gels. The effects of the expression vectors were then evaluated in vitro under active (at 39 degrees C) or inactive (at 34 degrees C) conditions. At 39 degrees C, the B9 antisense transfectants demonstrated significantly less proliferation than A3 sense transfectants (P-2 < 0.02), At 34 degrees C, cell growth of A3 sense- and B9 antisense-transfected cells was not significantly different. In vivo tumorigenicity was evaluated in hamsters inoculated with 10(5) A3 sense- or B9 antisense-transfected cells. The A3 sense clones resulted in greater numbers of tumors in vivo compared to the B9 antisense clone (P-2 = 0.0001). When genomic DNA from tumors that developed in A3 sense and B9 antisense animals was analyzed for the expression vectors, a 173-bp fragment amplified from the expression vector was identified in the sense tumors but not in antisense B9 or wild-type H9A tumors, indicating a loss of the vector from the antisense clones that proliferated in vivo. The inhibitory effect of IGF-1R antisense transcripts on hamster mesothelioma demonstrated in this study by decreased growth and tumorigenicity in vitro and in vivo may have implications for the therapy of human mesothelioma. C1 NCI,BIOSTAT SECT,NIH,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,SMITHVILLE,TX 78957. JEFFERSON MED COLL,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. RP Pass, HI (reprint author), NCI,THORAC ONCOL SECT,NIH,BLDG 10,ROOM 2B07,BETHESDA,MD 20892, USA. FU NIGMS NIH HHS [GM-33694]; PHS HHS [06658] NR 36 TC 53 Z9 53 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 1996 VL 56 IS 17 BP 4044 EP 4048 PG 5 WC Oncology SC Oncology GA VE083 UT WOS:A1996VE08300035 PM 8752177 ER PT J AU Howe, SR Pass, HI Ethier, SP Matthews, WJ Walker, C AF Howe, SR Pass, HI Ethier, SP Matthews, WJ Walker, C TI Presence of an insulin-like growth factor I autocrine loop predicts uterine fibroid responsiveness to tamoxifen SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER PATIENTS; REPRODUCTIVE-TRACT LEIOMYOMATA; DOMINANTLY INHERITED CANCER; MESSENGER RIBONUCLEIC-ACID; FACTOR-BINDING-PROTEINS; SMOOTH-MUSCLE TUMORS; EKER RAT MODEL; GENE-EXPRESSION; CELL-LINES; DEOXYRIBONUCLEIC-ACID AB Uterine leiomyoma is an estrogen-responsive tumor, and the present studies examine the ability of the antiestrogen tamoxifen to modulate leiomyoma cell growth, Tamoxifen is an effective form of hormonal therapy for breast cancer, although the mechanism by which tamoxifen inhibits tumor growth is not well understood and may involve mechanisms other than the action of tamoxifen as an estrogen antagonist. Tamoxifen was found to inhibit the proliferation of three of five leiomyoma-derived cell lines (ELT cell lines) in vitro, including an estrogen receptor-negative cell line. The ability of tamoxifen to decrease leiomyoma growth was found to correlate with expression of insulin-like growth factor I (IGF-I) by the tumor cells, suggesting that the inhibitory effects of tamoxifen were associated with expression of this growth factor. The existence of an IGF-I autocrine loop in the cells was investigated, because transcripts for both IGF-I and its cognate receptor were expressed in the tamoxifen-responsive cell lines. An IGF-I RIA demonstrated secreted IGF-I protein in serum-free medium conditioned by the IGF-I-expressing cell line ELT 3, and this same medium supported the growth of IGF-requiring MCF-10A cells, indicating the presence of biologically active IGF-I in the conditioned medium. Exogenous IGF-I stimulated ELT 3 cell proliferation, confirming that this growth factor is mitogenic for leiomyoma cells, IGF-I neutralizing antibody inhibited ELT 3 growth, indicating that the levels of IGF-I produced by the leiomyoma cells were physiologically significant. These data demonstrate the existence of an IGF-I autocrine loop in tamoxifen-sensitive leiomyoma cells, supporting the hypothesis that the presence of an IGF-I autocrine loop predicts uterine fibroid responsiveness to tamoxifen. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CARCINOGENESIS,SCI PK RES DIV,SMITHVILLE,TX 78957. NCI,THORAC ONCOL SECT,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109. FU NCI NIH HHS [CA66324]; NCPDCID CDC HHS [NCI 72253] NR 62 TC 17 Z9 17 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 SEP 1 PY 1996 VL 56 IS 17 BP 4049 EP 4055 PG 7 WC Oncology SC Oncology GA VE083 UT WOS:A1996VE08300036 PM 8752178 ER PT J AU Bian, JH Wang, YL Smith, MR Kim, H Jacobs, C Jackman, J Kung, HF Colburn, NH Sun, Y AF Bian, JH Wang, YL Smith, MR Kim, H Jacobs, C Jackman, J Kung, HF Colburn, NH Sun, Y TI Suppression of in vivo tumor growth and induction of suspension cell death by tissue inhibitor of metalloproteinases (TIMP)-3 SO CARCINOGENESIS LA English DT Article ID B16-F10 MELANOMA-CELLS; ERYTHROID-POTENTIATING ACTIVITY; TIMP GENE FAMILY; MATRIX METALLOPROTEINASES; NASOPHARYNGEAL CARCINOMA; MOLECULAR-CLONING; POINT MUTATION; 21-KDA PROTEIN; IN-VIVO; EXPRESSION AB Tissue inhibitor of metalloproteinases-3(TIMP-3), a novel member of TIMP family genes, has been recently cloned and shown to be expressed in preneoplastic but not in neoplastic mouse JB6 epidermal cells (Sun ed al. 1994 Cancer Res., 54, 11139), This down regulation of the gene appears to be attributable at least in part to alteration of gene methylation (Sun et al, 1995 J. Biol. Chem., 270, 19312), Little is known, however, about the role of TIMP-3 in human cancers, We screened several human tumor cell lines for TIMP-3 expression and found that a colon carcinoma line, DLD-1, did not express TIMP-3, If down regulation of TIMP-3 is causally related to carcinogenesis, re-expression by transfection may reverse the tumor cell phenotype, We therefore overexpressed human TIMP-3 in DLD-1 cells, TIMP-3 transfectants showed a serum-dependent growth inhibition in monolayer culture and a decreased growth potential in nude mice in a manner dependent on the level of TIMP-3 expression, A transfectant expressing a high level of active hTIMP-3 completely lost the ability to form tumors following s.c. injection into nude mice, We also tested TIMP-3 expressing cells and neocontrol TIMP-3 negative cells for their ability to grow in liquid suspension culture, since both cells grew in semi-solid soft agar, As compared to neocontrol cells, TIMP-3 overexpressors formed large aggregates, followed by cell death, This effect was not mimicked by BB94, a broad MMP inhibitor, We conclude from this study that (i) TIMP-3 overexpression in human colon carcinoma cells induces growth arrest in low serum conditions and inhibits in vivo tumor growth and (ii) the TIMP-3-induced large aggregate formation and subsequent cell death under suspension growth cannot be explained by its MMP inhibitory activity. C1 PARKE DAVIS PHARMACEUT RES,DEPT MOL BIOL,ANN ARBOR,MI 48105. NCI,CELL BIOL SECT,VIRAL CARCINOGENESIS LAB,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. GEORGETOWN UNIV,DEPT BIOCHEM & MOL BIOL,WASHINGTON,DC. NCI,LAB BIOCHEM PHYSIOL,DIV BASIC SCI,FCRDC,FREDERICK,MD 21701. NR 43 TC 126 Z9 129 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1996 VL 17 IS 9 BP 1805 EP 1811 DI 10.1093/carcin/17.9.1805 PG 7 WC Oncology SC Oncology GA VH728 UT WOS:A1996VH72800004 PM 8824499 ER PT J AU Hansen, LA Trempus, CS Mahler, JF Tennant, RW AF Hansen, LA Trempus, CS Mahler, JF Tennant, RW TI Association of tumor development with increased cellular proliferation and transgene overexpression, but not c-Ha-ras mutations, in v-Ha-ras transgenic Tg.AC mice SO CARCINOGENESIS LA English DT Article ID MOUSE SKIN; GENE; ONCOGENE; CHROMOSOME-7; PROGRESSION; EXPRESSION; PAPILLOMAS; NEOPLASIA; CARCINOMA; PROMOTER AB The transgenic mouse line Tg.AC carries a v-Ha-ras gene fused to a fetal (zeta) globin promoter and uniquely responds to chemical carcinogens and tumor promoters by the induction of epidermal papillomas, Although the transgene was not constitutively expressed in non-tumor-bearing tissues, expression was induced by exposure to selected chemicals. Tg.AC transgenic mice on the FVB/N background developed occasional spontaneous tumors, including odontomas, squamous cell carcinoma of the salivary gland, leukemias and a rare ovarian yolk sac carcinoma, Both spontaneous and induced tumors are associated with expression of the transgene and, as determined by in situ hybridization, transgene expression is localized to proliferative areas of the tumors, Sequence analysis of the endogenous c-Ha-ras gene in both induced and spontaneous tumors revealed no mutations in codons 12, 59 or 61, These results suggest that expression of the v-Ha-ras transgene induces proliferation of specific cells in diverse tissues which then acquire neoplastic properties. C1 NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,RES TRIANGLE PK,NC 27709. NIEHS,LAB EXPT PATHOL,RES TRIANGLE PK,NC 27709. NR 30 TC 45 Z9 45 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1996 VL 17 IS 9 BP 1825 EP 1833 DI 10.1093/carcin/17.9.1825 PG 9 WC Oncology SC Oncology GA VH728 UT WOS:A1996VH72800007 PM 8824502 ER PT J AU Katoh, T Nagata, N Kuroda, Y Itoh, H Kawahara, A Kuroki, N Ookuma, R Bell, DA AF Katoh, T Nagata, N Kuroda, Y Itoh, H Kawahara, A Kuroki, N Ookuma, R Bell, DA TI Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma SO CARCINOGENESIS LA English DT Article ID STOMACH-CANCER; COLON-CANCER; LUNG-CANCER; DELETION; THETA; EXPOSURE; BLADDER; COMMON; RISK; MU AB Genes coding for the glutatione S-transferase M1 (GSTM1) and Theta 1 (GSTT1) proteins are polymorphic in humans and these genes are absent, or homozygous null, in 10-60% of different ethnic populations, These enzymes catalyze the conjugation of glutathione to numerous carcinogenic chemicals and previous epidemiologic studies have associated the null genotypes of these GST genes with higher risk of cancer, In this study the frequency of GSTM1 and GSTT1 null genotypes was determined in Japanese patients with gastric adenocarcinoma and colorectal adenocarcinoma and compared to frequencies determined in a community-based control group, The frequency of the null GSTM1 genotype in patients with gastric adenocarcinoma (56.8%) showed a statistically significant increase compared to the control group frequency (43.6%) (odds ratio (OR) = 1.70; 95% CI, 1.05-2.76), The frequency of GSTM1 null individuals was also higher among all colorectal adenocarcinoma cases, but this increase did not reach statistical significance, After grouping by tumor site, the GSTM1 null genotype was a risk factor among the subgroup with distal colorectal tumors (61.1%) (OR = 2.03; 95% CI, 1.06-3.90), No consistent. difference was observed between smoking patients and corresponding controls for the frequency of the GSTM1 null genotype for either cancer, although a large risk (OR = 5.76; 95% CI 1.18-28.3) was associated with the GSTM1 null genotype in the low smoking group of gastric adenocarcinoma patients, On the other hand, no statistically significant differences were observed in the frequency of null GSTT1 genotypes in gastric (47.5%) or colorectal (48.5%) adenocarcinoma patients when compared with the control population (44.4%), These results suggest that the GSTM1 null genotype may be associated with susceptibility to gastric adenocarcinoma and distal colorectal adenocarcinoma in Japanese; however, the associations observed were relatively weak and additional studies will be needed to confirm these findings. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV OCCUPAT & ENVIRONM HLTH,SCH MED TECHNOL,BRANCH PUBL HLTH,KITAKYUSHU,FUKUOKA 807,JAPAN. UNIV OCCUPAT & ENVIRONM HLTH,SCH MED,DEPT SURG 1,KITAKYUSHU,FUKUOKA 807,JAPAN. MITSUBISHI KAGAKU HOSP,DEPT SURG,KITAKYUSHU,FUKUOKA,JAPAN. NR 29 TC 209 Z9 220 U1 0 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1996 VL 17 IS 9 BP 1855 EP 1859 DI 10.1093/carcin/17.9.1855 PG 5 WC Oncology SC Oncology GA VH728 UT WOS:A1996VH72800011 PM 8824506 ER PT J AU BurkhartSchultz, KJ Thompson, CL Jones, IM AF BurkhartSchultz, KJ Thompson, CL Jones, IM TI Spectrum of somatic mutation at the hypoxanthine phosphoribosyltransferase (hprt) gene of healthy people SO CARCINOGENESIS LA English DT Article ID HUMAN LYMPHOCYTES-T; MUTANT FREQUENCY; GUANINE PHOSPHORIBOSYLTRANSFERASE; HUMAN-POPULATION; MISMATCH RECOGNITION; MOLECULAR ANALYSES; CLONING ASSAY; CODING REGION; BLOOD-CELLS; SKIN-CANCER AB Understanding the significance of somatic mutations requires knowledge of the mutations that occur in vivo in healthy people, The molecular characterization of mutations in the hypoxanthine phosphoribosyltransferase (hprt) gene in 217 independent T-lymphocyte mutants from 172 donors, including smoking and non-smoking males and females, reveals a broad spectrum of in vivo somatic mutation occurring in a population of healthy people, Identification of the DNA alteration in individual mutant clones was accomplished using either one or a combination of multiplex polymerase chain reaction analysis of genomic DNA, sequencing of cDNA, and genomic DNA sequencing, The total spectrum consists of 59% (128/217) base substitutions: 126 simple and two tandem CC>TT base substitutions; 39% (85/217) deletion/insertion type mutations: 30 frameshifts, 26 small (3-200 basepairs) and 27 large deletions, and two duplications; and the remaining 2% (4/217) complex mutations involving the deletion of one to 11 basepairs which are replaced by 1 to 10 basepairs, No significant difference was detected between the base substitution spectra for the smokers and the non-smokers, Analysis of the number of mutations occurring at any one base position led to the identification of three hotspots for mutations at basepairs 197, 508 and 617, in the hprt gene coding region, Spontaneous deamination of CpG may be implicated in the creation of basepair 508 as a hotspot since all mutations detected are C>T transitions resulting in the nonsense mutation, TAG, At basepairs 197 and 617 both G>T transversions and G>A transitions were found indicating that at least two mechanisms were involved in creating mutations at these positions, Comparison of the mutation spectra from two populations can provide insight into the origin of the mutations, This study provides an excellent base for comparison of mutation spectra in other human populations. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RP BurkhartSchultz, KJ (reprint author), LAWRENCE LIVERMORE NATL LAB,BIOL & BIOTECHNOL RES PROGRAM,POB 808,L-452,LIVERMORE,CA 94551, USA. FU NIEHS NIH HHS [Y01-ES-80171] NR 54 TC 45 Z9 45 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD SEP PY 1996 VL 17 IS 9 BP 1871 EP 1883 DI 10.1093/carcin/17.9.1871 PG 13 WC Oncology SC Oncology GA VH728 UT WOS:A1996VH72800013 PM 8824508 ER PT J AU Giordano, M Takashima, H Poltorak, M Geller, HM Freed, WJ AF Giordano, M Takashima, H Poltorak, M Geller, HM Freed, WJ TI Constitutive expression of glutamic acid decarboxylase (GAD) by striatal cell lines immortalized using the tsA58 allele of the SV40 large T antigen SO CELL TRANSPLANTATION LA English DT Article DE SV40 large T antigen; striatal cells; cell lines; GABA; transplantation ID NERVE GROWTH-FACTOR; REGION-SPECIFIC DIFFERENTIATION; NEURONAL DIFFERENTIATION; INTRACEREBRAL TRANSPLANTATION; MEMBRANE DEPOLARIZATION; CHOLINERGIC NEURONS; SUBSTANTIA-NIGRA; CULTURED NEURONS; PROGENITOR CELLS; GENE-TRANSFER AB Rodent striatal cells were immortalized using the A58 temperature-sensitive allele of the SV40 large T antigen. Seventy-eight clones and 10 mixed cultures were characterized at the nonpermissive and permissive temperatures. Based on morphology and expression of proteins, cells were classified into three primary types, with types b and c expressing some neuronal characteristics. Type a cells have an epithelial-like morphology with coarse cytoplasmic extensions and occasional fine processes. These cells express vimentin, do not grow well under serum-free conditions and, when confluent, form a uniform monolayer. Type b cells have a polygonal shape and usually extend multiple thin processes. These cells possess large nuclei with multiple nucleoli and do not express vimentin. Type c cells have a fibroblast-like appearance, are unipolar or multipolar, and their soma is smaller than that of type b cells. Type c cells do not express vimentin, and when confluent form a uniform monolayer. Some type b and c clones express NCAM and MAP-2. Several type b and c cell lines were found to consistently express glutamic acid decarboxylase (GAD) immunoreactivity under several tissue culture conditions. Selected cell lines were transplanted into the intact adult rat rain in several locations. Cells survived well for 15 wk and did not form tumors. The proteins expressed in vivo were similar to those expressed in vitro. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,SECT PRECLIN NEUROSCI,WASHINGTON,DC 20032. OI Giordano, Magda/0000-0002-4335-7953; Geller, Herbert/0000-0002-7048-6144 FU NINDS NIH HHS [NS24168] NR 66 TC 21 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD SEP-OCT PY 1996 VL 5 IS 5 BP 563 EP 575 DI 10.1016/0963-6897(96)00027-9 PG 13 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA VJ541 UT WOS:A1996VJ54100005 PM 8889215 ER PT J AU Gelboin, HV Goldfarb, I Krausz, KW Grogan, J Korzekwa, KR Gonzalez, FJ Shou, MG AF Gelboin, HV Goldfarb, I Krausz, KW Grogan, J Korzekwa, KR Gonzalez, FJ Shou, MG TI Inhibitory and noninhibitory monoclonal antibodies to human cytochrome P450 2E1 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN LIVER-MICROSOMES; RAT-LIVER; CDNA-EXPRESSION; IN-VITRO; N-NITROSODIMETHYLAMINE; METABOLIC-ACTIVATION; BENZENE METABOLISM; MICE; BIOTRANSFORMATION; OXIDATION AB A panel of 17 hybridomas producing (MAbs) against human cytochrome P450 2E1 (h2E1) was generated by immunizing mice with baculovirus-expressed h2E1. All 17 hybridoma clones gave positive ELISA or immunoblots with either baculovirus- or vaccinia virus-expressed h2E1. Two of the latter were further developed due to their desirable characteristics. MAb 1-73-18 was found to be a powerful inhibitor of P450 h2E1; however, it did not yield a positive immunoblot. MAb 2-106-12 was found to be noninhibitory but formed a strong positive immunoblot with P450 h2E1. These MAbs to h2E1 were highly specific and did not recognize six other human P450s as tested with ELISA or immunoblot analyses. The MAbs to baculovirus-expressed h2E1 also reacted with h2E1 expressed from a vaccinia virus vector system as well as with microsomal fractions of human and acetone-treated rat liver. MAb 1-73-18 inhibited h2E1 enzyme activity catalyzing the metabolism of phenanthrene by 85%, p-nitroanisole by 99%, 4-methylanisole by 60-80%, toluene by 90%, and chlorzoxazone by 90%. The inhibitory MAb 1-73-18 is uniquely useful for determining the contribution of h2E1 to the metabolism of h2E1 substrates in human liver containing multiple P450s. The quantitatively determined contribution of h2E1 to the metabolism of the above substrates ranged from 25% to 75%. Thus, h2E1 was responsible for the following percentages of the total metabolism in human liver: p-nitroanisole (35%), phenanthrene (23%), methylanisole to cresol (25%), methylanisole to methoxybenzyl alcohol(12%), toluene (40%), and chlorzoxazone (72%). The MAb 2-106-12 forming a strong immunoblot is useful for determining the amount of h2E1 protein in a tissue. Thus the utility of the inhibitory and immunoblot positive MAbs is complementary and can determine both the contribution of h2E1 to the metabolism of specific substrates and the amount of h2E1 protein in human tissue. The analyses of metabolism with the inhibitory MAb 1-73-18 can be generalized and applicable to all h2E1 substrates. RP Gelboin, HV (reprint author), NCI,MOL CARCINOGENESIS LAB,NIH,BLDG 37,9000 ROCKVILLE PIKE,ROOM 3E24,BETHESDA,MD 20892, USA. NR 54 TC 25 Z9 25 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 1996 VL 9 IS 6 BP 1023 EP 1030 DI 10.1021/tx9600154 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA VF546 UT WOS:A1996VF54600016 PM 8870991 ER PT J AU Uhrikova, D Gawrisch, K Yaradaikin, S Balgavy, P AF Uhrikova, D Gawrisch, K Yaradaikin, S Balgavy, P TI The forces between phospholipid bilayers charged by the alkylammonium ion SO CHEMICKE LISTY LA English DT Article DE alkylammonium bromide; phosphatidylcholine bilayers; hydration force ID DEFORMATION C1 NIH,BIOPHYS CHEM LAB,ROCKVILLE,MD 20852. JOINT INST NUCL RES,NEUTRON PHYS LAB,DUBNA 141980,RUSSIA. RP Uhrikova, D (reprint author), COMENIUS UNIV BRATISLAVA,FAC PHARM,BRATISLAVA 83232,SLOVAKIA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU CHEMICKE LISTY PI PRAGUE 6 PA PELLEOVA 24, PRAGUE 6, CZECH REPUBLIC 160 00 SN 0009-2770 J9 CHEM LISTY JI Chem. Listy PD SEP PY 1996 VL 90 IS 9 BP 626 EP 627 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA VG968 UT WOS:A1996VG96800063 ER PT J AU Nieto, FJ Adam, E Sorlie, P Farzadegan, H Melnick, JL Comstock, GW Szklo, M AF Nieto, FJ Adam, E Sorlie, P Farzadegan, H Melnick, JL Comstock, GW Szklo, M TI Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; viruses; risk factors; carotid arteries; follow-up studies ID SOLID-PHASE RADIOIMMUNOASSAY; CORONARY HEART-DISEASE; ARTERIAL-WALLS; POTENTIAL ROLE; VIRUS; HERPESVIRUS; ANTIBODY; CELLS; PATHOGENESIS; CHOLESTEROL AB Background Animal studies as well as clinical and cross-sectional epidemiological studies in humans have suggested a possible role of cytomegalovirus (CMV) and other herpesvirus infections in the development of cardiovascular disease. Methods and Results The present report is based on a case-control study nested within a historical cohort. The case group comprised 150 individuals with elevated carotid intimal-medial thickness (IMT) measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities (ARIC) Study (1987 through 1992). The control group comprised 150 age- and sex-matched individuals with low IMT. Antibody titers for CMV and herpesvirus 1 and 2 were determined in sera obtained in 1974 as part of a community-wide survey conducted in Washington County, Maryland. Case subjects had higher mean CMV antibody titers in 1974 sera than control subjects, although the difference was not statistically significant when adjusted for other cardiovascular risk factors. There was evidence of a graded relation between the odds of intimal-medial thickening and the levels of CMV antibodies that remained significant after adjustment for the main cardiovascular risk factors (P=.013). The adjusted odds ratio for a high CMV antibody titer (a positive/negative value greater than or equal to 20) compared with a positive/negative value <4 was 5.3 (95% confidence interval, 1.5 to 18.0). Conclusions The results from this first population-based cohort study of CMV infection and carotid IMT are compatible with the hypothesis of a causal role of CMV in atherosclerosis. C1 BAYLOR COLL MED,DIV MOL VIROL,HOUSTON,TX 77030. NHLBI,NIH,BETHESDA,MD 20892. RP Nieto, FJ (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,615 N WOLFE ST,BALTIMORE,MD 21205, USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 41 TC 209 Z9 215 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 SEP 1 PY 1996 VL 94 IS 5 BP 922 EP 927 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VE237 UT WOS:A1996VE23700012 PM 8790026 ER PT J AU Rodriguez, BL Sharp, DS Abbott, RD Burchfiel, CM Masaki, K Chyou, PH Huang, B Yano, K Curb, JD AF Rodriguez, BL Sharp, DS Abbott, RD Burchfiel, CM Masaki, K Chyou, PH Huang, B Yano, K Curb, JD TI Fish intake may limit the increase in risk of coronary heart disease morbidity and mortality among heavy smokers - The Honolulu Heart Program SO CIRCULATION LA English DT Article DE coronary disease; smoking; fatty acids; follow-up studies; epidemiology ID POLYUNSATURATED FATTY-ACIDS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; THROMBOXANE FORMATION; PLASMA-FIBRINOGEN; PLATELET-FUNCTION; BLOOD-PRESSURE; DOUBLE-BLIND; DIETARY; OIL AB Background Research has shown that fish consumption limits damage to the lungs caused by cigarette smoking, possibly by the effects of fish on arachidonic acid metabolism. We explored this fish-smoking interaction using coronary heart disease (CHD) incidence and mortality as the outcome. Methods and Results The Honolulu Heart Program began in 1965 to follow a cohort of 8006 Japanese-American men aged 45 to 65 years who lived on Oahu, Hawaii, in 1965. Fish intake was measured at baseline by use of a questionnaire. For current smokers at baseline (n=3310) who reported low fish intake (<2 times/wk), age-adjusted 23-year CHD mortality rates increased with the number of cigarettes smoked per day (2.3, 3.1, and 6.9 per 1000 person-years for men who smoked <20, 20 to 30, and >30 cigarettes/d, respectively; trend test P<.0001). Among current smokers whose fish intake was high (greater than or equal to 2 times/wk), CHD mortality rates showed no relation with cigarettes/d (3.7, 3.2, and 3.7 per 1000 person-years for the corresponding levels of smoking). A Cox proportional hazards model based on current smokers, adjusted for age, years in Japan, calories/d, alcohol intake, physical activity index, years smoked, hypertension, and serum cholesterol, blood glucose, and uric acid levels, was examined. In the high-smoking group, the risk factor-adjusted relative risk (RR) for CHD mortality among those with high fish intake was half that of those with low fish consumption (RR=0.5, 95% confidence interval=0.28 to 0.91). A Cox model that adjusted for similar risk factors confirmed a significant interaction of cigarettes/d and fish intake (P<.01) on CHD mortality. Analyses for CHD incidence showed similar results. Conclusions Despite the findings of this investigation, the public health message for smokers continues to be to stop smoking. However, an interaction between fish intake and cigarette smoking is biologically plausible and deserves further investigation. The study of this phenomenon may shed light on the biological mechanisms by which cigarette smoking leads to CHD. C1 UNIV HAWAII,JOHN A BURNS SCH MED,DIV CLIN EPIDEMIOL,HONOLULU,HI 96822. UNIV HAWAII,JOHN A BURNS SCH MED,DIV GERIATR MED,HONOLULU,HI 96822. NHLBI,HONOLULU HEART PROGRAM,NIH,HONOLULU,HI. UNIV VIRGINIA,DEPT BIOSTAT,CHARLOTTESVILLE,VA. RP Rodriguez, BL (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 39 TC 98 Z9 100 U1 0 U2 5 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 1 PY 1996 VL 94 IS 5 BP 952 EP 956 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VE237 UT WOS:A1996VE23700017 PM 8790031 ER PT J AU Lazarous, DF Shou, M Scheinowitz, M Hodge, E Thirumurti, V Kitsiou, AN Stiber, JA Lobo, AD Hunsberger, S Guetta, E Epstein, SE Unger, EF AF Lazarous, DF Shou, M Scheinowitz, M Hodge, E Thirumurti, V Kitsiou, AN Stiber, JA Lobo, AD Hunsberger, S Guetta, E Epstein, SE Unger, EF TI Comparative effects of basic fibroblast growth factor and vascular endothelial growth factor on coronary collateral development and the arterial response to injury SO CIRCULATION LA English DT Article DE angiogenesis; collateral circulation muscle, smooth; growth substances ID MUSCLE CELL-PROLIFERATION; BLOOD-FLOW MEASUREMENTS; INTIMAL HYPERPLASIA; PERMEABILITY FACTOR; THERAPEUTIC ANGIOGENESIS; ISCHEMIC MYOCARDIUM; MITOGEN; MODEL; ATHEROSCLEROSIS; ANGIOPLASTY AB Background We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) enhance canine coronary collateral development when administered for greater than or equal to 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, a fundamental component of atherosclerosis. VEGF, an endothelial cell-specific mitogen and vascular permeability factor, could have deleterious effects related to vascular hyperpermeability. The present investigation had two aims: (1) to ascertain whether brief (7-day) systemic arterial treatment with bFGF or VEGF would improve myocardial collateral perfusion and (2) to determine whether these peptides induce neointimal accumulation in vivo. Methods and Results Dogs were subjected to ameroid-induced occlusion of the left circumflex coronary artery and randomized to bFGF 1.74 mg (n=9), VEGF 0.72 mg (n=9), or saline (n=10) as a daily left atrial bolus (days 10 to 16). Additional dogs were randomized to VEGF 0.72 mg (n=6) or saline (n=5); however, treatment was delayed by 1 week. Coincident with the institution of treatment, all dogs underwent balloon denudation injury of the iliofemoral artery. bFGF markedly increased max collateral flow but did not exacerbate neointimal accumulation. VEGF had no discernible effect on maximal collateral flow, but it exacerbated neointimal thickening after vascular injury. Conclusions Short-term treatment with bFGF enhanced collateral development without increasing neointimal accumulation at sites of vascular injury. Although VEGF did not increase collateral development as administered in this study, it significantly exacerbated neointimal accumulation. These data provide support for the clinical investigation of bFGF in selected patients with ischemic heart disease. C1 NHLBI,BIOSTAT RES BRANCH,NIH,BETHESDA,MD 20892. RP Lazarous, DF (reprint author), NHLBI,EXPT PHYSIOL & PHARMACOL SECT,CARDIOL BRANCH,NIH,BLDG 10,ROOM 7B15,10 CTR DR,MSC 1650,BETHESDA,MD 20892, USA. NR 40 TC 277 Z9 291 U1 3 U2 11 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 1 PY 1996 VL 94 IS 5 BP 1074 EP 1082 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VE237 UT WOS:A1996VE23700035 PM 8790049 ER PT J AU Wyszynski, DF Beaty, TH Maestri, NE AF Wyszynski, DF Beaty, TH Maestri, NE TI Genetics of nonsyndromic oral clefts revisited SO CLEFT PALATE-CRANIOFACIAL JOURNAL LA English DT Review DE birth defects; cleft lip; cleft palate; genetics; malformations ID GROWTH-FACTOR-ALPHA; COMPLEX SEGREGATION ANALYSIS; AUTOSOMAL MAJOR LOCUS; PRADER-WILLI SYNDROME; BIRTH-DEFECTS; NO EVIDENCE; HOMEOTIC TRANSFORMATION; POSSIBLE ASSOCIATION; BAMHI POLYMORPHISM; ANGELMAN SYNDROME AB Nonsyndromic oral clefts are among the most common birth defects, affecting approximately 1 in 1000 Caucasian newborns, In recent decades, many investigators have used genetic and epidemiologic methods to identify etiologic factors, but results have often been inconclusive or contradictory, Etiologic heterogeneity is undoubtedly a major component in these birth defects, and there may not be a single answer to this problem, Here, we describe the main features of published studies pointing out their strengths and limitations, Additionally, we give insight into current methods for detecting the presence of interaction between genetic markers and environmental exposures in the etiology of oral clefts. C1 NIH,MED GENET BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. RP Wyszynski, DF (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205, USA. FU NIDCR NIH HHS [R01-DE10293] NR 133 TC 127 Z9 130 U1 0 U2 6 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 1055-6656 J9 CLEFT PALATE-CRAN J JI Cleft Palate-Craniofac. J. PD SEP PY 1996 VL 33 IS 5 BP 406 EP 417 DI 10.1597/1545-1569(1996)033<0406:GONOCR>2.3.CO;2 PG 12 WC Dentistry, Oral Surgery & Medicine; Surgery SC Dentistry, Oral Surgery & Medicine; Surgery GA VK162 UT WOS:A1996VK16200008 PM 8891372 ER PT J AU HofmannLehmann, R Fehr, D Grob, M Elgizoli, M Packer, C Martenson, JS OBrien, SJ Lutz, H AF HofmannLehmann, R Fehr, D Grob, M Elgizoli, M Packer, C Martenson, JS OBrien, SJ Lutz, H TI Prevalence of antibodies to feline parvovirus, calicivirus, herpesvirus, coronavirus, and immunodeficiency virus and of feline leukemia virus antigen and the interrelationship of these viral infections in free-ranging lions in east Africa SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID LINKED IMMUNOSORBENT-ASSAY; ETOSHA-NATIONAL-PARK; PHYLOGENETIC ASPECTS; NONDOMESTIC FELIDS; GENETIC-VARIATION; ACINONYX-JUBATUS; CHEETAH; PERITONITIS; LENTIVIRUS; WILD AB While viral infections and their impact are well studied in domestic cats, only limited information is available on their occurrence in free-ranging lions. The goals of the present study were (i) to investigate the prevalence of antibodies to feline calicivirus (FCV), herpesvirus (FHV), coronavirus (FCoV), parvovirus (FPV), and immunodeficiency virus (FIV) and of feline leukemia virus (FeLV) antigen in 311 serum samples collected between 1984 and 1991 from lions inhabiting Tanzania's national parks and (ii) to evaluate the possible biological importance and the interrelationship of these viral infections. Antibodies to FCV, never reported previously in free-ranging lions, were detected in 70% of the sera. In addition, a much higher prevalence of antibodies to FCoV (57%) was found than was previously reported in Etosha National Park and Kruger National Park. Titers ranged from 25 to 400. FeLV antigen was not detectable in any of the serum samples. FCoV, FCV FHV, and FIV were endemic in the Serengeti, while a transient elevation of FPV titers pointed to am outbreak of FPV infection between 1985 and 1987. antibody titers to FPV and FCV were highly prevalent its the Serengeti (FPV, 75%; FCV, 67%) but not in Ngorongoro Crater (FPV, 27%; FCV, 2%). These differences could be explained by the different habitats and biological histories of the two populations and by the well-documented absence of immigration of lions from the Serengeti plains into Ngorongoro Crater after 1965. These observations indicate that, although the pathological potential of these viral infections seemed not to be very high in free-ranging lions, relocation of seropositive animals by humans to seronegative lion populations must be considered very carefully. C1 VET AG,CH-8021 ZURICH,SWITZERLAND. UNIV MINNESOTA,COLL BIOL SCI,DEPT ECOL EVOLUT & BEHAV,ST PAUL,MN 55108. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP HofmannLehmann, R (reprint author), UNIV ZURICH,DEPT INTERNAL VET MED,CLIN LAB,WINTERTHURERSTR 260,CH-8057 ZURICH,SWITZERLAND. RI Hofmann-Lehmann, Regina/C-6528-2009 NR 54 TC 69 Z9 70 U1 2 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1996 VL 3 IS 5 BP 554 EP 562 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VG961 UT WOS:A1996VG96100012 PM 8877134 ER PT J AU Hartman, AB VanDeVerg, LL Mainhart, CR Tall, BD SmithGill, SJ AF Hartman, AB VanDeVerg, LL Mainhart, CR Tall, BD SmithGill, SJ TI Specificity of monoclonal antibodies elicited by mucosal infection of BALB/c mice with virulent Shigella flexneri 2a SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID EVOKE KERATOCONJUNCTIVITIS; ESCHERICHIA-COLI; CLONES BINDING; GUINEA-PIGS; ANTIGENS; VACCINE; PROTECTION; EPITOPE; SONNEI; LIPOPOLYSACCHARIDES AB Protective immunity against shigellosis is thought to be determined by the O-antigen side chains of the lipopolysaccharide (LPS) molecule, To study possible common protective epitopes, monoclonal antibodies reacting with Shigella flexneri 2a LPS were generated from BALB/c mice infected ocularly with the virulent serotype 2a strain S. flexneri 2457T and tested against a panel of S. flexneri LPSs by enzyme-linked immunosorbent and immunoblot assays, Four monoclonal antibodies were identified, all of which showed restricted specificity patterns. Three different patterns of reactivity to LPS possessing the 3,4 group antigen were seen: (i) 2a only, (ii) 2a and 5a, and (iii) 2a, 4a, 5a, and Y. These results have implications for designing a Shigella vaccine that will be protective against related serotypes. Electron microscopy studies showed that the monoclonal antibodies bind to the bacterial surface in a patchy pattern, suggesting their potential use for examining the LPS distribution on the sun-face of the bacteria. C1 NIH,GENET LAB,BETHESDA,MD 20892. US FDA,CTR FOOD SAFETY & APPL NUTR,WASHINGTON,DC 20204. RP Hartman, AB (reprint author), WALTER REED ARMY INST RES,DEPT ENTER INFECT,WASHINGTON,DC 20307, USA. OI Tall, Ben/0000-0003-0399-3629 NR 34 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1996 VL 3 IS 5 BP 584 EP 589 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VG961 UT WOS:A1996VG96100018 PM 8877140 ER PT J AU Heller, T Yin, SR Tsarev, SA Purcell, RH Emerson, SU AF Heller, T Yin, SR Tsarev, SA Purcell, RH Emerson, SU TI False-positive serologic test resulting from a probable yeast infection in a chimpanzee SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article AB Sera used to identify putative hepatitis E viral proteins expressed in Pischia pastoris produced a false-positive reaction because of antibodies to a yeast protein. This report illustrates a potential problem when serological reagents ase used in combination with recombinant proteins expressed in yeast. RP Heller, T (reprint author), NIAID,HEPATITIS VIRUSES SECT,INFECT DIS LAB,NIH,BLDG 7,RM 206,7 CTR DR,MSC 0740,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD SEP PY 1996 VL 3 IS 5 BP 614 EP 615 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VG961 UT WOS:A1996VG96100026 PM 8877148 ER PT J AU Hagiwara, E Adams, EM Plotz, PH Klinman, DM AF Hagiwara, E Adams, EM Plotz, PH Klinman, DM TI Abnormal numbers of cytokine producing cells in patients with polymyositis and dermatomyositis SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE polymyositis; dermatomyositis; cytokines ID SYSTEMIC LUPUS-ERYTHEMATOSUS; IDIOPATHIC INFLAMMATORY MYOPATHIES; RHEUMATOID-ARTHRITIS; IL-6; INTERLEUKIN-6; MUSCLE; BLOOD; QUANTITATION; LYMPHOCYTES; EXPRESSION AB Objective: To examine the constitutive pattern of cytokine production inpatients with polymyositis (PM) and dermatomyositis (DM). Methods. PBMC secreting the type 1 cytokines IL-2 and IFN gamma and the type 2 cytokines IL-6 and IL-10 were monitored by ELlspot assay. Results: The frequency of IFN gamma-secreting PBMC was reduced 2 - 20 fold in patients with PM and DM when compared to normal controls (p < 0.01). This change correlated inversely with disease activity (p < 0.01). PM and DM were also characterized by increased numbers of cells secreting IL-10. Patients with DM had fewer IL-2 (p < 0.03) and more IL-6 (p < 0.006) secreting cells than normal controls or patients with other myopathies. Conclusions: Abnormal patterns of cytokine production characterize patients with PM and DM. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,SECT RETROVIRAL IMMUNOL,BETHESDA,MD 20892. NIAMDSD,ARTHRITIS & RHEUMATISM BRANCH,NIH,BETHESDA,MD. NR 41 TC 16 Z9 18 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD SEP-OCT PY 1996 VL 14 IS 5 BP 485 EP 491 PG 7 WC Rheumatology SC Rheumatology GA VL365 UT WOS:A1996VL36500003 PM 8913649 ER PT J AU Scherf, U Benhar, I Webber, KO Pastan, I Brinkmann, U AF Scherf, U Benhar, I Webber, KO Pastan, I Brinkmann, U TI Cytotoxic and antitumor activity of a recombinant tumor necrosis Factor-B1(Fv) fusion protein on Le(Y) antigen-expressing human cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID FACTOR-ALPHA; FACTOR TNF; LYMPHOTOXIN; ANTIBODY; FV; MALIGNANCIES; IMMUNOTOXINS; REGRESSION; FORMS; LYSIS AB We have constructed a fusion protein composed of tumor necrosis factor alpha (TNF-alpha) fused at its COOH terminus to the scFv region of monoclonal antibody (mAb) B1, an antibody that recognizes Le(Y) antigen present on many human cancer cells, Our rationale for fusing the scFv to the COOH terminus of TNF was to diminish the binding of the fusion protein to TNF receptors because the COOH terminus of TNF is involved in binding, and thus to partially inactivate (detoxify) the molecule. The Fv region should then target and accumulate the fusion protein on cancer cells, which should compensate for the reduced binding affinity of the TNF moiety and lead to selective killing of TNF-sensitive antigen-expressing cancer cells. The fusion protein was expressed in Escherichia coli and found in insoluble inclusion bodies, After refolding and purification by anion exchange, Ni-NTA affinity, and size-exclusion chromatography, we obtained monomeric TNF-B1(Fv). This molecule binds to Le(Y) antigen on cancer cells with the same affinity as B1(scFv) and B1(scFv) immunotoxins but with significantly lower affinity to the TNF receptor compared to the TNF trimer. TNF-B1(Fv) is very toxic to Le(Y) antigen-expressing cancer cells that are sensitive to TNF (e.g., MCF-7 breast or CRL-1739 gastric cancer cells). This cytotoxicity is antibody targeted and TNF mediated because it can be prevented (as shown on MCF-7 cells) by an antibody competing for Le(Y) antigen binding and by an antibody that neutralizes TNF-alpha. TNF-B1(FV) kills TNF-alpha-sensitive cells that do not express the target antigen only at much higher doses than TNF trimer, and it does not kill Le(Y)-bearing but TNF-alpha-resistant cells. TNF-B1(Fv) can cause significant tumor regression of MCF-7 tumor xenografts in mice at doses that are not toxic to the mice. Thus, the reduced binding of the TNF moiety to TNF receptors, combined with binding of the B1(Fv) portion to Le(Y) antigen, makes TNF-B1(Fv) an agent for selective killing of Le(Y)-expressing TNF-sensitive cancer cells. C1 NCI,NIH,MOL BIOL LAB,DIV BASIC SCI,BETHESDA,MD 20892. NR 36 TC 22 Z9 23 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD SEP PY 1996 VL 2 IS 9 BP 1523 EP 1531 PG 9 WC Oncology SC Oncology GA VH107 UT WOS:A1996VH10700012 PM 9816329 ER PT J AU Kong, LP Dunn, GD Keefer, LK Korthuis, RJ AF Kong, LP Dunn, GD Keefer, LK Korthuis, RJ TI Nitric oxide reduces tumor cell adhesion to isolated rat postcapillary venules SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE cancer; endothelium; invasion; melanoma cells; metastasis ID VASCULAR ENDOTHELIUM; RELAXING FACTOR; FLOW CONDITIONS; PLATELET-AGGREGATION; CANCER METASTASIS; GUANYLATE-CYCLASE; INTERLEUKIN-1; PHARMACOLOGY; ACTIVATION; INVITRO AB Adhesion of circulating tumor cells to microvascular endothelium plays an important role in tumor metastasis to distant organs. The purpose of this study was to determine whether nitric oxide (NO) would attenuate tumor cell adhesion (TCA) to naive or Lipopolysaccharide (LPS)-treated postcapillary venules. A melanoma cell line, RPMI 1846, was shown to be much more adhesive to postcapillary venules isolated from rat mesentery than to corresponding precapillary arterioles, Although venules exposed to LPS for 4 h demonstrated an increased adhesivity for the melanoma cells, TCA to LPS-treated arterioles was not altered. Isolated venules exposed to DETA/NO (1 mM), an NO donor, for 30 min prior to tumor cell perfusion prevented the increment in adhesion induced by LPS and attenuated TCA to naive postcapillary venules. While L-arginine (100 mu M), an NO precursor, failed to decrease TCA to naive postcapillary venules, this treatment abolished LPS-stimulated TCA to postcapillary venules. The effect of L-arginine was reversed by administration of N-omega-nitro-L-arginine methyl ester (L-NAME, 100 mu M), an NO synthase (NOS) inhibitor. These observations indicate that both exogenous and endogenous NO modulate TCA to postcapillary venules. To assess the role of NO-induced activation of cGMP in the reduction in TCA produced by DETA/NO, two additional series of experiments were conducted. In the first series, LY-83583 (10 mu M), a guanylyl cyclase inhibitor, was shown to completely reverse the effect of DETA/NO on TCA to both naive and LPS-activated postcapillary venules. On the other hand, administration of 8-bromoguanosine 3',5'-cyclic monophosphate (8-B-cGMP) (1 mM), a cell permeant cGMP analog, mimicked the effect of DETA/NO and reduced TCA to LPS-stimulated postcapillary venules. These data suggest that (a) tumor cells are more likely to adhere to postcapillary venules than to corresponding precapillary arterioles, (b) LPS enhances TCA to postcapillary venules, (c) both exogenously applied (DETA/NO) and endogenously generated (L-arginine) NO attenuate the enhanced adhesion induced by LPS, but only DETA/NO reduced TCA to naive postcapillary venules, and (d) the NO-induced reduction in TCA to LPS-activated postcapillary venules occurs by a cGMP-dependent mechanism. C1 LOUISIANA STATE UNIV,MED CTR,DEPT PHYSIOL,SHREVEPORT,LA 71130. LOUISIANA STATE UNIV,MED CTR,DEPT SURG,SHREVEPORT,LA 71130. SCH MED,SHREVEPORT,LA. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NHLBI NIH HHS [HL-48646] NR 31 TC 41 Z9 42 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD SEP PY 1996 VL 14 IS 4 BP 335 EP 343 DI 10.1007/BF00123392 PG 9 WC Oncology SC Oncology GA VP589 UT WOS:A1996VP58900002 PM 8878407 ER PT J AU Bergan, R Kyle, E Nguyen, P Trepel, J Ingui, C Neckers, L AF Bergan, R Kyle, E Nguyen, P Trepel, J Ingui, C Neckers, L TI Genistein-stimulated adherence of prostate cancer cells is associated with the binding of focal adhesion kinase to beta-1-integrin SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE adhesion; focal adhesion kinase; genistein; integrin; prostate ID PROTEIN-TYROSINE KINASE; CYTOSKELETAL ORGANIZATION; EXTRACELLULAR-MATRIX; GROWTH-FACTOR; 3T3 CELLS; PHOSPHORYLATION; PP125(FAK); TUMORS; DIET; MEN AB The isoflavinoid genistein is a protein-tyrosine kinase inhibitor which has been identified as a putative cancer prevention agent, Its consumption is associated with a low incidence of clinical metastatic prostate cancer in the face of a sustained high incidence of organ-confined prostate cancer, We therefore undertook studies to examine genistein's effect upon tell adhesion as one possible mechanism by which it could be acting as an antimetastatic: agent, A morphogenic analysis revealed that genistein caused cell flattening in a variety of cell lines: PC3-M, PC3, and DU-145 prostate carcinoma cells, as well as MCF-7 breast carcinoma cells, Mechanistic studies focused on the highly metastatic PC3-M cell Line, and revealed that cell flattening was accompanied by an increase in cell adhesion, Further investigations demonstrated that focal adhesion kinase (FAK) accumulated in areas of focal cell attachment, and that this accumulation occurred only when cells were actively undergoing genistein-mediated morphologic change, Concurrent formation of a complex between the cell attachment molecule, beta-1-integrin, and FAK was shown to occur, and to correlate with transient activation of FAK activity, Genistein is presented as a novel investigative tool for use in the study of molecular events involved in the process of cell adhesion. C1 NCI,NIH,MED BRANCH,BETHESDA,MD 20892. RP Bergan, R (reprint author), NCI,NIH,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 42 TC 70 Z9 73 U1 0 U2 1 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD SEP PY 1996 VL 14 IS 4 BP 389 EP 398 DI 10.1007/BF00123398 PG 10 WC Oncology SC Oncology GA VP589 UT WOS:A1996VP58900008 PM 8878413 ER PT J AU Gonzalez, CE Venzon, D Lee, S Mueller, BU Pizzo, PA Walsh, TJ AF Gonzalez, CE Venzon, D Lee, S Mueller, BU Pizzo, PA Walsh, TJ TI Virus: A case-control study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISSEMINATED FUNGAL-INFECTIONS; RISK-FACTORS; CANDIDA-PARAPSILOSIS; LYMPHOCYTE SUBSETS; CANCER-PATIENTS; CHILDREN; COLONIZATION; FUNGEMIA; EPIDEMIOLOGY AB To define the risk factors related to the occurrence of fungemia in children infected with human immunodeficiency virus (HIV), we performed a matched case-control study. During a 6-year period (1987-1993), fungemia developed in 22 (6.3%) of 347 HIV-infected children observed at the Pediatric Branch of the National Cancer Institute, Each of these 22 cases was matched by age and gender with three controls. Multiple logistic regression indicated that the best predictor of fungemia in this population was the presence of a central venous catheter placed for > 90 days (P < .00001), followed by a group of risk factors composed of 10 independent variables adjusted for a CD4 cell count of < 100/mu L (P < .045). Those variables included treatment with more than three antibiotics, treatment with more than three parenteral antibiotics, > 30 days of antibiotic treatment, bacterial infections, > 30 days in the hospital, hypoalbuminemia, C3 (Centers for Disease Control and Prevention) classification of HIV infection, and malnourishment. We conclude that prolonged placement of central venous catheters is the most important risk factor for fungemia in HIV-infected children and that the risk of fungemia is further influenced by antibacterial therapy, catheter manipulation, and host response. C1 NCI,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 47 TC 31 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1996 VL 23 IS 3 BP 515 EP 521 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VF947 UT WOS:A1996VF94700016 PM 8991477 ER PT J AU Schnittman, SM Pierce, PF AF Schnittman, SM Pierce, PF TI Potential role of lamivudine (3TC) in the clearance of chronic hepatitis B virus infection in a patient coinfected with human immunodeficiency virus type 1 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID REPLICATION C1 GEORGETOWN UNIV,SCH MED,DEPT MED,DIV INFECT DIS,WASHINGTON,DC. RP Schnittman, SM (reprint author), NIAID,DIV AIDS,NIH,6003 EXECUT BLVD,ROOM 2C22,ROCKVILLE,MD 20852, USA. NR 5 TC 14 Z9 14 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP PY 1996 VL 23 IS 3 BP 638 EP 639 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VF947 UT WOS:A1996VF94700037 PM 8879794 ER PT J AU Asthana, S Greig, NH Holloway, HW Raffaele, KC Berardi, A Schapiro, MB Rapoport, SI Soncrant, TT AF Asthana, S Greig, NH Holloway, HW Raffaele, KC Berardi, A Schapiro, MB Rapoport, SI Soncrant, TT TI Clinical pharmacokinetics of arecoline in subjects with Alzheimer's disease SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CHOLINERGIC AGONIST ARECOLINE; SENILE DEMENTIA; CEREBRAL-CORTEX; VERBAL MEMORY; INFUSION; PHYSOSTIGMINE; IMPROVEMENT; RECEPTORS; THERAPY; SYSTEM AB Objective: To study the pharmacokinetics and pharmacodynamics of intravenously. Methods: Plasma arecoline concentrations were measured during and after high-dose (i,e., 5 mg intravenously over 30 minutes) and up to 2 weeks of continuous multiple-dose steady-state intravenous infusions of arecoline in 15 subjects with mild to moderate Alzheimer's disease. During multiple-dose infusions, the dose of arecoline was escalated from 0.5 to 40 mg/day. Psychometric tests were administered at baseline and every other dose to determine an ''optimal dose'' for each subject. This dose then was administered for 1 week using a randomized, placebo-controlled, double-blind, crossover design. Plasma drug concentrations were measured by GC-MS. Results: The optimal dose of arecoline varied fourfold across subjects (4 mg/day, n = 6; 16 mg/day, n = 3) with mean plasma half-lives of 0.95 +/- 0.54 and 9.3 +/- 4.5 (SD) minutes. Clearance and volume of distribution were 13.6 +/- 5.8 L/min and 205 +/- 170 (SD) L, respectively. At the dose that optimized memory, the mean plasma level was 0.31 +/- 0.14 (SD) ng/ml, and it predicted the optimal dose in all subjects. Conclusions: Because optimal dose variation is due to differing plasma kinetics, the plasma arecoline level measured at a single infusion rate can be used to choose the optimal dose fur memory enhancement in patients with Alzheimer's disease. C1 NIA, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. NR 37 TC 30 Z9 31 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD SEP PY 1996 VL 60 IS 3 BP 276 EP 282 DI 10.1016/S0009-9236(96)90054-5 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VK935 UT WOS:A1996VK93500005 PM 8841150 ER PT J AU Witebsky, FG KruczakFilipov, P AF Witebsky, FG KruczakFilipov, P TI Identification of mycobacteria by conventional methods SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID RAPIDLY GROWING MYCOBACTERIA; CHELONAE-LIKE ORGANISM; SP-NOV; PRESUMPTIVE IDENTIFICATION; CERVICAL LYMPHADENITIS; TUBERCULOSIS COMPLEX; EMERGING PATHOGEN; CORD FORMATION; AVIUM COMPLEX; INFECTION AB Conventional methods used in the authors' laboratory for identifying human mycobacterial pathogens are presented. in sufficient detail so that the procedures can be performed in the diagnostic laboratory. A brief account of the disease presentations of the different mycobacterial species is provided. Tabular summaries of the significant phenotypic features of these mycobacterial pathogens are presented. C1 WARREN G MAGNUSON CLIN CTR,MICROBIOL SERV,DEPT CLIN PATHOL,NIH,BETHESDA,MD. NR 65 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD SEP PY 1996 VL 16 IS 3 BP 569 EP & PG 34 WC Medical Laboratory Technology SC Medical Laboratory Technology GA VG152 UT WOS:A1996VG15200005 PM 8866181 ER PT J AU Lamb, ME AF Lamb, ME TI Fatherhood: Contemporary theory, research, and social policy - Marsiglio,W SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP Lamb, ME (reprint author), NICHHD,SECT SOCIAL & EMOT DEV,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD SEP PY 1996 VL 41 IS 9 BP 911 EP 911 PG 1 WC Psychology, Multidisciplinary SC Psychology GA VG956 UT WOS:A1996VG95600030 ER PT J AU Calle, EE Heath, CW MiracleMcMahill, HL Coates, RJ Liff, JM Franceschi, S Talamini, R Chantarakul, N Koetsawang, S Rachawat, D Morabia, A Schuman, I Stewart, W Szklo, M Bain, C Schofield, F Siskind, V Band, P Coldman, AJ Gallagher, RP Hislop, TG Yang, P Duffy, SW Kolonel, LM Nomura, AMY Oberle, MW Ory, HW Peterson, HB Wilson, HG Wingo, PA Ebeling, K Kunde, D Nishan, P Colditz, G Martin, N Pardthaisong, T Silpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C McMichael, AJ Rohan, T Ewertz, M Paul, C Skegg, DCG Spears, GFS Boyle, P Evstifeeva, T Daling, JR Malone, K Noonan, EA Stanford, JL Thomas, DB Weiss, NS White, E Andrieu, N Bremond, A Clavel, F Gairard, B Lansac, J Piana, L Renaud, R Fine, SRP Cuevas, HR Ontiveros, P Palet, A Salazar, SB Aristizabel, N Cuadros, A Bachelot, A Le, MG Deacon, J Peto, J Taylor, CN Alfandary, E Modan, B Ron, E Friedman, GD Hiatt, RA Bishop, T Kosmelj, K PrimicZakelj, M Ravnihar, B Stare, J Beeson, WL Fraser, G Allen, DS Bulbrook, RD Cuzick, J Fentiman, IS Hayward, JL Wang, DY Hanson, RL Leske, MC Mahoney, MC Nasca, PC Varma, AP Weinstein, AL Moller, TR Olsson, H Ranstam, J Goldbohm, RA vandenBrandt, PA Apelo, RA Baens, J delaCruz, JR Javier, B Lacaya, LB Ngelangel, CA LaVecchia, C Negri, E Marbuni, E Ferraroni, M Gerber, M Richardson, S Segala, C Gatei, D Kenya, P Kungu, A Mati, JG Brinton, LA Hoover, R Schairer, C Spirtas, R Lee, HP Rookus, MA vanLeeuwen, FE Schoenberg, JA Gammon, MD Clarke, EA Jones, L McPherson, K Neil, A Vessey, M Yeates, D Beral, V Bull, D Crossley, B Hermon, C Jones, S Key, T Lewis, C Reeves, G Smith, P Collins, R Doll, R Peto, R Hannaford, P Kay, C RoseroBixby, L Yuan, JM Wei, HY Yun, T Zhiheng, C Berry, G Booth, JC Jelihovsky, T MacLennan, R Shearman, R Wang, QS Baines, CJ Miller, AB Wall, C Lund, E Stalsberg, H Dabancens, A Martinez, L Molina, R Salas, O Alexander, FE Hulka, BS Chilvers, CED Bernstein, L Haile, RW PaganiniHill, A Pike, MC Ross, RK Ursin, G Yu, MC Adami, HO Bergstrom, R Longnecker, MP Newcomb, P Farley, TMN Holck, S Meirik, O AF Calle, EE Heath, CW MiracleMcMahill, HL Coates, RJ Liff, JM Franceschi, S Talamini, R Chantarakul, N Koetsawang, S Rachawat, D Morabia, A Schuman, I Stewart, W Szklo, M Bain, C Schofield, F Siskind, V Band, P Coldman, AJ Gallagher, RP Hislop, TG Yang, P Duffy, SW Kolonel, LM Nomura, AMY Oberle, MW Ory, HW Peterson, HB Wilson, HG Wingo, PA Ebeling, K Kunde, D Nishan, P Colditz, G Martin, N Pardthaisong, T Silpisornkosol, S Theetranont, C Boosiri, B Chutivongse, S Jimakorn, P Virutamasen, P Wongsrichanalai, C McMichael, AJ Rohan, T Ewertz, M Paul, C Skegg, DCG Spears, GFS Boyle, P Evstifeeva, T Daling, JR Malone, K Noonan, EA Stanford, JL Thomas, DB Weiss, NS White, E Andrieu, N Bremond, A Clavel, F Gairard, B Lansac, J Piana, L Renaud, R Fine, SRP Cuevas, HR Ontiveros, P Palet, A Salazar, SB Aristizabel, N Cuadros, A Bachelot, A Le, MG Deacon, J Peto, J Taylor, CN Alfandary, E Modan, B Ron, E Friedman, GD Hiatt, RA Bishop, T Kosmelj, K PrimicZakelj, M Ravnihar, B Stare, J Beeson, WL Fraser, G Allen, DS Bulbrook, RD Cuzick, J Fentiman, IS Hayward, JL Wang, DY Hanson, RL Leske, MC Mahoney, MC Nasca, PC Varma, AP Weinstein, AL Moller, TR Olsson, H Ranstam, J Goldbohm, RA vandenBrandt, PA Apelo, RA Baens, J delaCruz, JR Javier, B Lacaya, LB Ngelangel, CA LaVecchia, C Negri, E Marbuni, E Ferraroni, M Gerber, M Richardson, S Segala, C Gatei, D Kenya, P Kungu, A Mati, JG Brinton, LA Hoover, R Schairer, C Spirtas, R Lee, HP Rookus, MA vanLeeuwen, FE Schoenberg, JA Gammon, MD Clarke, EA Jones, L McPherson, K Neil, A Vessey, M Yeates, D Beral, V Bull, D Crossley, B Hermon, C Jones, S Key, T Lewis, C Reeves, G Smith, P Collins, R Doll, R Peto, R Hannaford, P Kay, C RoseroBixby, L Yuan, JM Wei, HY Yun, T Zhiheng, C Berry, G Booth, JC Jelihovsky, T MacLennan, R Shearman, R Wang, QS Baines, CJ Miller, AB Wall, C Lund, E Stalsberg, H Dabancens, A Martinez, L Molina, R Salas, O Alexander, FE Hulka, BS Chilvers, CED Bernstein, L Haile, RW PaganiniHill, A Pike, MC Ross, RK Ursin, G Yu, MC Adami, HO Bergstrom, R Longnecker, MP Newcomb, P Farley, TMN Holck, S Meirik, O TI Breast cancer and hormonal contraceptives: Further results SO CONTRACEPTION LA English DT Article ID REQUIRING PROLONGED OBSERVATION; ORAL-CONTRACEPTIVES; RISK-FACTORS; FINAL REPORT; PREMENOPAUSAL WOMEN; YOUNG-WOMEN; AGE; POPULATION; ESTROGEN; PATTERNS AB The Collaborative Group on Hormonal Factors in Breast Cancer has brought together and reanalysed the worldwide epidemiological evidence on breast cancer risk and use oi hormonal contraceptives. Original data from 54 studies, representing about 90% of the information available on the topic, were collected, checked and analysed centrally. The 54 studies were performed in 26 countries and include a total of 53,297 women with breast cancer and 100,239 women without breast cancer. The studies were varied in their design, setting and timing. Most information came from case-control studies with controls chosen from the general population; most women resided in Europe or North America and most cancers were diagnosed during the 1980s. Overall 41% of the women with breast cancer and 40% of the women without breast cancer had used oral contraceptives at some time: the median age at first use was 26 years, the median duration of use was 3 years, the median year of first use was 1968, the median time since first use was 16 years, and the median time since last use was 9 years. The main findings, summarised elsewhere,I are that there is a small increase in the risk of having breast cancer diagnosed in current users of combined oral contraceptives and in women who had stopped use in the past 10 years but that there is no evidence of an increase in the risk more than 10 years after stopping use. In addition, the cancers diagnosed in women who had used oral contraceptives tended to be less advanced clinically than the cancers diagnosed in women who had not used them. Despite the large number of possibilities investigated, few factors appeared to modify the main findings either in recent or in past users. For recent users who began use before age 20 the relative risks are higher than for recent users who began at older ages. For women whose use of oral contraceptives ceased more than 10 years before there was some suggestion of a reduction in breast cancer risk in certain subgroups, with a deficit of tumors that had spread beyond the breast, especially among women who had used preparations containing the highest doses of oestrogen and progestogen. These findings are unexpected and need to be confirmed. Although these data represent most of the epidemiologi cal evidence on the topic to date, there is still insufficient information to comment reliably about the effects of specific types of oestrogen or of progestogen. What evidence there is suggests, however, no major differences in the effects for specific types of oestrogen or of progestogen and that the pattern of risk associated with use of hormonal contraceptives containing progestogens alone may be similar to that observed for preparations containing both oestrogens and progestogens. On the basis of these results, there is little difference between women who have and have not used combined oral contraceptives in terms of the estimated cumulative number of breast cancers diagnosed during the period from starting use up to 20 rears after stopping. The cancers diagnosed in women who have used oral contraceptives are, however, less advanced clinically than the cancers diag nosed in never users. Further research is needed to establish whether the associations described here are due to earlier diagnosis of breast cancer in women who have used oral contraceptives, to the biological effects of the hormonal contraceptives or to a combination of both. Little information is as yet available about the effects on breast cancer risk of oral contraceptive use that ceased more than 20 years before and as such data accumulate it will be necessary to reexamine the worldwide evidence. C1 RADCLIFFE INFIRM, IMPERIAL CANC RES FUND, CANC EPIDEMIOL UNIT, OXFORD OX2 6HE, ENGLAND. AMER CANC SOC, ATLANTA, GA 30329 USA. EMORY UNIV, ATLANTA, GA 30322 USA. AVIANO CANC CTR, PORDENONE, ITALY. MAHIDOL UNIV, BANGKOK 10700, THAILAND. JOHNS HOPKINS UNIV, BREAST TUMOR COLLABORAT STUDY, BALTIMORE, MD 21218 USA. UNIV QUEENSLAND, BRISBANE, QLD, AUSTRALIA. BRITISH COLUMBIA CANC AGCY, VANCOUVER, BC, CANADA. MRC, BIOSTAT UNIT, CAMBRIDGE, ENGLAND. UNIV HAWAII, CTR CANC RES, HONOLULU, HI 96822 USA. CTR DIS CONTROL & PREVENT, ATLANTA, GA 30333 USA. CENT INST CANC RES, BERLIN, GERMANY. HARVARD UNIV, SCH MED,BRIGHAM & WOMENS HOSP,CHANNING LAB, NURSES HLTH STUDY RES GRP, CAMBRIDGE, MA 02138 USA. CHIANG MAI UNIV, CHIANG MAI 50000, THAILAND. CHULALONGKORN UNIV, BANGKOK 10330, THAILAND. CSIRO, DIV HUMAN NUTR, ADELAIDE, SA 5000, AUSTRALIA. DANISH CANC SOC, AARHUS, DENMARK. UNIV OTAGO, DUNEDIN, NEW ZEALAND. EUROPEAN INST ONCOL, MILAN, ITALY. FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA. INSERM, FRENCH MULTICTR BREAST STUDY, F-75654 PARIS 13, FRANCE. HOSP GEN MEXICO SA, MEXICO CITY, DF, MEXICO. INST GUSTAVE ROUSSY, INSERM, F-94805 VILLEJUIF, FRANCE. INST CANC RES, SUTTON, SURREY, ENGLAND. ISRAEL CHAIM SHEBA MED CTR, TEL HASHOMER, ISRAEL. KAISER PERMANENTE, OAKLAND, CA USA. IMPERIAL CANC RES FUND, GENET EPIDEMIOL LAB, LEEDS, W YORKSHIRE, ENGLAND. INST ONCOL, LJUBLJANA, SLOVENIA. LOMA LINDA UNIV, LOMA LINDA, CA 92350 USA. IMPERIAL CANC RES FUND, LONDON WC2A 3PX, ENGLAND. LONG ISL BREAST CANC STUDY, LONG ISL CITY, NY USA. UNIV LUND HOSP, S-22185 LUND, SWEDEN. UNIV LIMBURG, NL-6200 MD MAASTRICHT, NETHERLANDS. UNIV PHILIPPINES, MANILA, PHILIPPINES. IST RIC FARMACOL MARIO NEGRI, MILAN, ITALY. UNIV MILAN, IST STAT MED & BIOMETRIA, I-20122 MILAN, ITALY. IST NAZL TUMORI, DIV STAT MED & BIOMETRA, I-20133 MILAN, ITALY. CTR CANC, MONTPELLIER, FRANCE. INSERM, MONTPELLIER, FRANCE. NAIROBI CTR RES REPROD, NAIROBI, KENYA. NCI, BETHESDA, MD 20892 USA. NICHHD, BETHESDA, MD 20892 USA. NATL UNIV SINGAPORE, SINGAPORE 117548, SINGAPORE. NETHERLANDS CANC INST, AMSTERDAM, NETHERLANDS. NEW JERSEY STATE DEPT HLTH, TRENTON, NJ 08625 USA. COLUMBIA UNIV, SCH PUBL HLTH, NEW YORK, NY USA. ONTARIO CANC TREATMENT & RES FDN, TORONTO, ON, CANADA. DEPT PUBL HLTH & PRIMARY CARE, OXFORD, ENGLAND. IMPERIAL CANC RES FUND, MRC, BHF CLIN TRIAL SERV UNIT, OXFORD, ENGLAND. IMPERIAL CANC RES FUND, MRC, EPIDEMIOL STUDIES UNIT, OXFORD, ENGLAND. ROYAL COLL GEN PRACTITIONERS, ORAL CONTRACEPT STUDY, LONDON, ENGLAND. UNIV COSTA RICA, SAN JOSE, COSTA RICA. SHANGHAI INST PLANNED PARENTHOOD RES, SHANGHAI, PEOPLES R CHINA. UNIV SYDNEY, DEPT PUBL HLTH, SYDNEY, NSW 2006, AUSTRALIA. TIANJIN CANC INST, TIANJIN, PEOPLES R CHINA. UNIV TORONTO, DEPT PREVENT MED & BIOSTAT, TORONTO, ON, CANADA. UNIV TROMSO, TROMSO, NORWAY. UNIV CHILE, SANTIAGO, CHILE. UNIV EDINBURGH, EDINBURGH EH8 9YL, MIDLOTHIAN, SCOTLAND. UNIV N CAROLINA, SCH PUBL HLTH, CHAPEL HILL, NC USA. UNIV NOTTINGHAM, NOTTINGHAM NG7 2RD, ENGLAND. UNIV SO CALIF, LOS ANGELES, CA 90089 USA. UNIV UPPSALA, S-75105 UPPSALA, SWEDEN. UNIV WISCONSIN, CTR COMPREHENS CANC, MADISON, WI 53706 USA. WHO, UNDP,UNFPA,WORLD BANK, SPECIAL PROGRAMME RES DEV & TRAINING H, GENEVA, SWITZERLAND. RI Ranstam, Jonas/A-4386-2009; Beral, Valerie/B-2979-2013; Negri, Eva/B-7244-2013; Clavel-Chapelon, Francoise/G-6733-2014; Brinton, Louise/G-7486-2015; Colditz, Graham/A-3963-2009; Ferraroni, Monica/D-6548-2017 OI Ranstam, Jonas/0000-0002-8287-7273; Negri, Eva/0000-0001-9712-8526; Brinton, Louise/0000-0003-3853-8562; Colditz, Graham/0000-0002-7307-0291; Ferraroni, Monica/0000-0002-4542-4996 NR 70 TC 1 Z9 1 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD SEP PY 1996 VL 54 IS 3 SU S BP S1 EP S106 PG 106 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA VN552 UT WOS:A1996VN55200002 ER PT J AU Blesa, R Mohr, E Miletich, RS Hildebrand, K Sampson, M Chase, TN AF Blesa, R Mohr, E Miletich, RS Hildebrand, K Sampson, M Chase, TN TI Cerebral metabolic changes in Alzheimer's disease: Neurobehavioral patterns SO DEMENTIA LA English DT Article DE Alzheimer's disease; cerebral glucose metabolism; behavioral neuroanatomy; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; GLUCOSE-METABOLISM; SENILE DEMENTIA; HUMAN-BRAIN; PET; ABNORMALITIES; DIAGNOSIS; DISORDERS; CORTEX AB Regional cerebral glucose metabolism was surveyed in 37 Alzheimer's disease (AD) patients and 21 normal controls using positron emission tomography. Where possible, brain regions were specified according to their neurobehavioral function rather than as anatomically demarcated structures. Absolute metabolic values revealed significant differences (p < 0.05) between AD patients and controls for whole brain and the more superior supratentorial brain slices. Normalized values (region/brain stem) showed the most striking declines (p < 0.001) in the association cortex (heteromodal region -21%; unimodal region -19%) and the primary sensory-motor cortex (-13%), with motor, auditory, and visual areas more affected than somatosensory areas. Limbic and paralimbic systems were equally affected (-14%; -11%; p < 0.001). Thalamus, striatum, cerebellum and brain stem were minimally or not affected. Neurobehaviorally defined hypometabolic regions largely parallel affected areas noted in anatomic and previous metabolic studies, with the possible exception of metabolic deficits in the primary sensory-motor complex. Conceivably, brain areas unaffected morphologically by the pathophysiological processes of AD may become dysfunctional due to a disruption of connectivity between regions. C1 UNIV OTTAWA, FAC MED NEUROL, OTTAWA CIVIC HOSP, OTTAWA, ON, CANADA. ELISABETH BRUYERE HLTH CTR, OTTAWA, ON, CANADA. DENT NEUROL INST, BUFFALO, NY USA. NINCDS, EXPT THERAPEUT BRANCH, NIH, BETHESDA, MD 20892 USA. RP Blesa, R (reprint author), UNIV BARCELONA, SERV NEUROL, HOSP CLIN & PROV, VILLARROEL 170, E-08036 BARCELONA, SPAIN. RI Sampson, Margaret/A-9128-2011; OI Sampson, Margaret/0000-0003-2550-9893 NR 51 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1013-7424 J9 DEMENTIA JI Dementia PD SEP-OCT PY 1996 VL 7 IS 5 BP 239 EP 245 DI 10.1159/000106886 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VE929 UT WOS:A1996VE92900002 PM 8872413 ER PT J AU Skrtic, D Antonucci, JM Eanes, ED AF Skrtic, D Antonucci, JM Eanes, ED TI Improved properties of amorphous calcium phosphate fillers in remineralizing resin composites SO DENTAL MATERIALS LA English DT Article ID CEMENTS AB Objectives. The rationale for this study was based on the hypothesis that the mechanical strength of methacrylate composites containing the bioactive filler, amorphous calcium phosphate, can be enhanced by synthesizing this filler in the presence of glass-forming agents. Specifically this study was conducted to prepare composites with zirconia- and silica-modified amorphous calcium phosphate fillers, and to determine whether the remineralization potential from the release of calcium and phosphate ions and the mechanical properties of the corresponding methacrylate composites were enhanced. Methods. The modified amorphous calcium phosphates were synthesized at pH 10.5 by mixing 800 mmol/L Ca(NO3)(2) solutions and either 250 mmol/L zirconyl chloride (ZrOCl2) or 4.4 mol/L tetraethoxysilane (TEOS) solutions with solutions containing 525 mmol/L Na2HPO4 and 11 mmol/L Na4P2O7. After washing and drying, the amorphous calcium phosphates were mixed with visible light-activated resins and photopolymerized to form composite disks that were then examined for their ability to release Ca2+ and total ionic phosphate (PO43- + HPO42- + H2PO4, hereafter indicated as PO4) by immersion in HEPES-buffered (pH 7.4) saline at 37 degrees C. Solution ion concentrations were compared at regular intervals up to 265 h. Biaxial flexural strengths of the composites before and after immersion were compared, and significant differences were established by Student's t test (p < 0.05). Results. Both ZrOCl2- and TEOS-modified amorphous calcium phosphate composite disks released Ca2+ and PO4 ions at sustained levels requisite for remineralization to occur. The transformation of amorphous calcium phosphate into hydroxyapatite within the composites was also retarded, particularly in the case of amorphous calcium phosphate modified with ZrOCl2. Biaxial flexure strength values of composite disks showed that TEOS- and ZrOCl2-amorphous calcium phosphate-filled composites increased in strength by 33% and 21% before immersion and by 25% and 27% after immersion, respectively, compared to unmodified amorphous calcium phosphate composites (controls). All strength increases except TEOS after immersion were significant (p<0.05). Significance. Properly modified amorphous calcium phosphate fillers can be used to prepare bioactive composites with enhanced mechanical properties for more demanding dental applications without compromising their remineralizing potential. C1 NIDR,RES ASSOCIATE PROGRAM,BETHESDA,MD 20892. NATL INST STAND & TECHNOL,DENT & MED MAT GRP,DIV POLYMER,GAITHERSBURG,MD 20899. NR 26 TC 72 Z9 75 U1 1 U2 15 PU ACAD DENTAL MATERIALS PI DALLAS PA BAYLOR COLLEGE DENTISTRY, 3302 GASTON AVE, DALLAS, TX 75266-0677 SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD SEP-NOV PY 1996 VL 12 IS 5-6 BP 295 EP 301 DI 10.1016/S0109-5641(96)80037-6 PG 7 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA WB402 UT WOS:A1996WB40200002 PM 9170997 ER PT J AU Rankin, T Familari, M Lee, E Ginsberg, A Dwyer, N BlanchetteMackie, J Drago, J Westphal, H Dean, J AF Rankin, T Familari, M Lee, E Ginsberg, A Dwyer, N BlanchetteMackie, J Drago, J Westphal, H Dean, J TI Mice homozygous for an insertional mutation in the Zp3 gene lack a zona pellucida and are infertile SO DEVELOPMENT LA English DT Article DE zona pellucida; infertility; ZP3 sperm receptor; zona-free oocytes; disruption of the corona radiata; Zp3 null mutant mice ID SPERM-EGG INTERACTION; MOUSE OOCYTES; MONOCLONAL-ANTIBODIES; MAMMALIAN OOGENESIS; RECEPTOR ACTIVITY; ACROSOME REACTION; GRANULOSA-CELLS; INVITRO; FERTILIZATION; GLYCOPROTEIN AB Mammalian oocytes synthesize and secrete a zona pellucida that surrounds the growing oocytes, ovulated eggs and pre-implantation embryos, The extracellular zona matrix is composed of three glycoproteins (ZP1, ZP2, ZP3) that are involved in folliculogenesis, species-specific fertilization, and passage of the early embryo down the oviduct, We have established a mouse line in which Zp3 has been inactivated by homologous recombination with an insertional mutation, Neither Zp3 transcripts nor ZP3 protein was detected in female mice homozygous for the mutation (Zp3(-/-)), whereas both ZP1 and ZP2 were present in mutant oocytes, Homozygous mutant Zp3(-/-) mice had follicles with germinal-vesicle-intact oocytes but that lacked a zona pellucida matrix and had a disorganized corona radiata, Although mutant oocytes underwent germinal vesicle breakdown (GVBD) prior to ovulation, the cumulus-oocyte complex was markedly disrupted and the oocytes were often separate from the cumulus cells, After hormone-induced ovulation, cumulus masses were present in the oviducts of homozygous mutant mice, but zona-free eggs were observed in only half of the females and, in these, less than 10% of the normal mumber of eggs were detected, No zona-free 2-cell embryos were recovered from homozygous mutant Zp3(-/-) female mice after mating with males proven to be fertile, and none became visibly pregnant or produced offspring, These results demonstrate that a genetic defect in a zona pellucida gene causes infertility and, given the conserved nature of the zona pellucida, a similar phenotype is expected in other mammals. C1 NICHHD,NIH,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NIDDK,NIH,LAB CELL BIOCHEM & BIOL,BETHESDA,MD 20892. RP Rankin, T (reprint author), NIDDK,NIH,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 41 TC 201 Z9 203 U1 1 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD SEP PY 1996 VL 122 IS 9 BP 2903 EP 2910 PG 8 WC Developmental Biology SC Developmental Biology GA VJ075 UT WOS:A1996VJ07500032 PM 8787763 ER PT J AU Haynes, JI Duncan, MK Piatigorsky, J AF Haynes, JI Duncan, MK Piatigorsky, J TI Spatial and temporal activity of the alpha B-crystallin small heat shock protein gene promoter in transgenic mice SO DEVELOPMENTAL DYNAMICS LA English DT Article DE crystallin; development; heat shock; promoter; transgenic mouse ID LOOP-HELIX PROTEIN; SKELETAL-MUSCLE; A-CRYSTALLIN; LENS CRYSTALLINS; DEVELOPMENTAL REGULATION; NONLENTICULAR TISSUES; ROSENTHAL FIBERS; MOUSE EMBRYOS; EXPRESSION; STRESS AB In order to study the spatial and temporal activity of the mouse alpha B-crystallin/small heat shock gene promoter during embryogenesis, we generated mice harboring a transgene consisting of approximately 4 kbp of alpha B-crystallin promoter sequence fused to the Escherichia coli lacZ reporter gene. beta-galactosidase activity was first observed in the heart rudiment of 8.5 days post coitum (d.p.c.) embryos. An identical expression pattern was obtained for the endogenous alpha B-crystallin gene by whole mount in situ hybridization. At 9.5 d.p.c., beta-galactosidase activity was detected in the lens placode, in the myotome of the somites, in Rathke's pouch (future anterior pituitary), and in some regions of oral ectoderm. We also examined the stress inducibility of the alpha B-crystallin promoter in vivo. Injection of sodium arsenite into mice resulted in increased endogenous alpha B-crystallin expression in the adrenal gland and possibly the liver. Our results indicate that visualization of B-galactosidase activity provides an accurate reflection of endogenous alpha B-crystallin expression and demonstrate that the complex developmental pattern of mouse alpha B-crystallin gene expression is regulated at the transcriptional level. This expression pattern, coupled with the present literature which addresses functions of the protein, suggests a role for the alpha B-crystallin/small heat shock protein in intermediate filament turnover and cellular remodeling which occur during normal development and differentiation. (C) 1996 Wiley-Liss, Inc. C1 NEI, MOL & DEV BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 80 TC 44 Z9 45 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 EI 1097-0177 J9 DEV DYNAM JI Dev. Dyn. PD SEP PY 1996 VL 207 IS 1 BP 75 EP 88 DI 10.1002/(SICI)1097-0177(199609)207:1<75::AID-AJA8>3.0.CO;2-T PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA VE849 UT WOS:A1996VE84900008 PM 8875078 ER PT J AU Sokoloff, L Takahashi, S Gotoh, J Driscoll, BF Law, MJ AF Sokoloff, L Takahashi, S Gotoh, J Driscoll, BF Law, MJ TI Contribution of astroglia to functionally activated energy metabolism SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT 2nd International Conference on Brain Energy Metabolism - Molecules to Man CY AUG 06-11, 1995 CL HEINRICH-FABRI-INST, BLAUBEUREN, GERMANY SP Deut Forschungsgemeinsch, Int Soc Neurochem, State Baden Wurttemberg, Hermann & Lilly Schilling Fdn Med Res, S Karger AG, Basel, Knoll AG, Ludwigshafen, Bayer AG, Wuppertal HO HEINRICH-FABRI-INST DE astrocyte; [C-14]deoxyglucose; glutamate; Na+,K+-ATPase; potassium; sodium ID CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; GLUCOSE-UTILIZATION; CULTURED ASTROCYTES; EXTRACELLULAR POTASSIUM; ELECTRICAL-STIMULATION; GLUTAMATE TRANSPORTER; DEOXYGLUCOSE UPTAKE; ATPASE ACTIVITY; CELLULAR-LEVEL AB Studies of local glucose utilization in neural tissues in vivo with the autoradiographic [C-14]deoxyglucose method have demonstrated that energy metabolism increases almost linearly with the degree of functional activation, i.e. spike frequency, in the terminal projection zones of activated pathways. The increased metabolism is found in neuropil and is minimal or undetectable in neuronal cell bodies. Electrical stimulation, increased extracellular [K+] ([K+](o)), or opening of Na+ channels with veratridine stimulates metabolism in neural tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+,K+-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to mediate the function-related increase in energy metabolism. The metabolic activation is, therefore, not directly related to the functional activity itself but to processes operating to recover from that activity. The limited spatial resolution of the [C-14]DG method precludes identification of cellular elements in neuropil participating in the metabolic activation, e.g. axonal terminals, dendrites, or astrocytic processes enveloping the synapses. We have, therefore, attempted to simulate in vitro conditions to be expected from functional activation and increased spike activity in vivo, e.g. increased extracellular [K+], intracellular [Na+], or extracellular neurotransmitter levels, and examined their effects on glucose metabolism in neurons and astroglia in culture. Increased [K+](o) stimulated [C-14]DG phosphorylation in neuronal and mixed neuronal-astroglial cultures, but not in astroglial cultures assayed in bicarbonate buffer; it did occasionally stimulate metabolism in astroglia when assayed in HEPES or phosphate buffers, but these effects were variable and inconsistent. Veratridine (75 mu M) stimulated [C-14]DG phosphorylation in neurons and astroglia; these stimulations were blocked by 1 mM ouabain or 10 mu M tetrodotoxin (TTX), which blocks voltage-dependent Na+ channels. The Na+ ionophore monensin (10 mu M) doubled the rate of metabolism, a stimulation that was only partially blocked by ouabain and unaffected by TTX. L-Glutamate (500 mu M) stimulated [C-14]DC phosphorylation in astroglia, but this stimulation was probably secondary to Na+ uptake into the cells via a sodium/glutamate co-transporter because it was not blocked by inhibitors of NMDA or non-NMDA receptors but was absent in Na+-free medium. These results indicate that astroglia con tribute to the increased energy metabolism in neuropil during functional activation by mechanisms that promote Na+ entry into the cells. RP Sokoloff, L (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,1A-05,36 CONVENT DR,MSC 4030,BETHESDA,MD 20892, USA. RI Takahashi, Shinichi/L-3454-2013 NR 51 TC 20 Z9 20 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD SEP-DEC PY 1996 VL 18 IS 5-6 BP 343 EP 352 DI 10.1159/000111427 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA VQ957 UT WOS:A1996VQ95700004 ER PT J AU Beattie, GM Rubin, JS Mally, MI Otonkoski, T Hayek, A AF Beattie, GM Rubin, JS Mally, MI Otonkoski, T Hayek, A TI Regulation of proliferation and differentiation of human fetal pancreatic islet cells by extracellular matrix, hepatocyte growth factor, and cell-cell contact SO DIABETES LA English DT Article ID GENE-EXPRESSION; MICE; NICOTINAMIDE; INSULIN AB Ex vivo expansion of human fetal pancreatic endocrine cells is important for biological studies and as a potential tissue source for transplantation in insulin-deficient states. In tissue culture experiments involving the use of hepatocyte growth factor/scatter factor and selected extracellular matrices, we obtained a 30-fold increase in cell number of human fetal pancreatic epithelial cells. This proliferation in monolayer culture was associated with marked downregulation of insulin and glucagon gene expression. However, gene expression increased when the cells were combined into three-dimensional aggregates, suggesting that cell-cell contact mediated mechanisms regulate the transcription of islet-specific genes, a process enhanced by nicotinamide (NIC). After transplantation into nude mice, either as cell suspensions or aggregates, only the cell aggregates treated with NIC developed into mature functional islet-like structures. These are the first experiments to describe the interactions of specific matrices and growth factors in the ex vivo expansion of human fetal pancreatic cells, and they also show the importance of cell aggregates in the context of cellular and molecular events that might positively influence islet cell transplantation. C1 UNIV CALIF SAN DIEGO, DEPT PEDIAT, ISLET RES LAB, LA JOLLA, CA 92037 USA. UNIV CALIF SAN DIEGO, WHITTIER INST, LA JOLLA, CA USA. NCI, CELLULAR & MOL BIOL LAB, BETHESDA, MD 20892 USA. RI Otonkoski, Timo/F-1189-2011 FU NIDDK NIH HHS [R01-DK-39087] NR 25 TC 122 Z9 124 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD SEP PY 1996 VL 45 IS 9 BP 1223 EP 1228 DI 10.2337/diabetes.45.9.1223 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF529 UT WOS:A1996VF52900013 PM 8772726 ER PT J AU Norman, RA Leibel, RL Chung, WK PowerKehoe, L Chua, SC Knowler, WC Thompson, DB Bogardus, C Ravussin, E AF Norman, RA Leibel, RL Chung, WK PowerKehoe, L Chua, SC Knowler, WC Thompson, DB Bogardus, C Ravussin, E TI Absence of linkage of obesity and energy metabolism to markers flanking homologues of rodent obesity genes in Pima Indians SO DIABETES LA English DT Article ID QUANTITATIVE TRAIT; SIB PAIRS; OB GENE; MICE; PROTEIN; HUMANS; NIDDM; LOCUS; RNA AB The homologues of single genes that cause obesity in rodents are suggested as candidate genes for modulation of body composition in humans. Among these genes are the four mouse mutations-diabetes (db), obesity (ob), tubby (tub), and yellow agouti (A(Y)). Variation in the human counterparts to these genes (OB, DB, TUB, and ASP, respectively) may contribute to human obesity, which is thought to have a substantial genetic component. To initially assess the potential contribution of these genes to human obesity, we examined polymorphic DNA markers that, by virtue of syntenic relationships to appropriate regions of the mouse genome, should be closely linked to the human counterparts of these genes. Using combined data from 716 Pima Indians comprising 217 nuclear families, we have tested a number of polymorphic microsatellite markers (three at DB, two at OB, five at TUB, and three at ASP) for sib-pair linkage to BMI, percentage body fat, resting metabolic rate, 24-h energy expenditure, and 24-h respiratory quotient. No significant linkages were found in an analysis of all sibships or in an analysis restricted to discordant sib pairs. C1 NIDDKD,DIABET & ARTHRIT EPIDEMIOL SECT,NIH,PHOENIX,AZ. ROCKEFELLER UNIV,HUMAN BEHAV & METAB LAB,NEW YORK,NY 10021. RP Norman, RA (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,NIH,4212 N 16TH ST,RM 541,PHOENIX,AZ 85016, USA. FU NCRR NIH HHS [1 P41 RR03655]; NICHD NIH HHS [HD28047]; NIDDK NIH HHS [DK26687] NR 36 TC 59 Z9 59 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD SEP PY 1996 VL 45 IS 9 BP 1229 EP 1232 DI 10.2337/diabetes.45.9.1229 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF529 UT WOS:A1996VF52900014 PM 8772727 ER PT J AU Narayan, KMV Pettitt, DJ Hanson, RL Bennett, PH Fernandes, RJ deCourten, M Rose, FA Knowler, WC AF Narayan, KMV Pettitt, DJ Hanson, RL Bennett, PH Fernandes, RJ deCourten, M Rose, FA Knowler, WC TI Familial aggregation of medial arterial calcification in Pima Indians with and without diabetes SO DIABETES CARE LA English DT Article ID RISK-FACTORS; MELLITUS; DISEASE; PROTEINURIA; OBESITY; INDEX AB OBJECTIVE - Little is known about medial arterial calcification (MAC) other than its association with age, sex, diabetes, and diabetes complications Familial aggregation of this disorder was studied to determine the importance of potential genetic factors and to assess whether such familial aggregation was independent of that of diabetes. RESEARCH DESIGN AND METHODS - Members of 1,256 Pima Indian nuclear families with 3,339 offspring were examined radiologically for MAC of the feet. Multiple logistic regression analyses were used to compare the presence of the disorder in a parent with the presence of MAC in an offspring and to determine whether familial aggregation of MAC was independent of parental diabetes. RESULTS - Controlled for age, sex, diabetes, serum cholesterol, and blood pressure, offspring of one parent with MAC had 3.3 (95% CI 1.5-7.6) times the odds of MAC as did offspring of parents without MAC, and offspring with both parents affected had an even higher risk (odds ratio, 8.1; 95% CI 3.4-18.8). Controlled for offspring age and sex and for parental age and diabetes, parental MAC was associated with the disorder in offspring (P < 0.001), but the effect of parental diabetes on MAC in the offspring was not significant when controlled for parental MAC (P = 0.36). Furthermore, offspring of nondiabetic parents with MAC, controlled for age, sex, diabetes, and diabetes duration, had 1.7 (95% CI 0.9-3.1) times the odds of MAC than did offspring of diabetic parents with MAC. CONCLUSIONS - Independent of parental age and diabetes and offspring age, sex, diabetes, and diabetes complications, parental MAC confers an increased risk of MAC in offspring. These findings suggest that the factors responsible for the Familial clustering of MAC may be different from those for diabetes. RP Narayan, KMV (reprint author), NIDDK,DIABET & ARTHRIT EPIDEMIOL SECT,PHOENIX EPIDEMIOL & CLIN RES BRANCH,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Narayan, K.M. Venkat /J-9819-2012; Hanson, Robert/O-3238-2015; de Courten, Maximilian/B-3300-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405; Hanson, Robert/0000-0002-4252-7068; de Courten, Maximilian/0000-0001-9997-9359 NR 32 TC 9 Z9 9 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1996 VL 19 IS 9 BP 968 EP 971 DI 10.2337/diacare.19.9.968 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VE982 UT WOS:A1996VE98200009 PM 8875090 ER PT J AU Naryan, KMV Hanson, RL Pettitt, DJ Bennett, PH Knowler, WC AF Naryan, KMV Hanson, RL Pettitt, DJ Bennett, PH Knowler, WC TI A two-step strategy for identification of high-risk subjects for a clinical trial of prevention of NIDDM SO DIABETES CARE LA English DT Article ID FASTING PLASMA-GLUCOSE; DEPENDENT DIABETES-MELLITUS; BODY-FAT DISTRIBUTION; GLYCOSYLATED HEMOGLOBIN; PIMA-INDIANS; FOLLOW-UP; INSULIN; OBESITY; TOLERANCE; MODELS AB OBJECTIVE - To evaluate 2-h plasma glucose (2HPG), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA(1)), a combination of FPG and HbA(1) (FPG-HbA(1)), and other factors as screening tests for identifying high-risk subjects for a clinical trial of prevention of NIDDM and to identify strategies to minimize the total number of oral glucose tolerance tests (OGTTs) required to reemit eligible subjects to the trial. RESEARCH DESIGN END METHODS - One thousand, one hundred and eight nondiabetic Pima Indians aged 25-64 years were followed for up to 5 years, and factors predicting NIDDM, defined by World Health Organization criteria (2HPG greater than or equal to 11.1 mmol/l), were assessed using Cox's proportional hazards analysis. Various threshold values of FPG, HbA(1), and FPG-HbA(1) were determined, which, when combined with an OGTT, identified subjects with impaired glucose tolerance (IGT) (2HPG greater than or equal to 7.8 and <11.1 mmol/l) at a number of specified risks for developing NIDDM in 5 years. The value of each of the three tests was then assessed by calculating (for each threshold) the numbers To be screened, the numbers requiring an OGTT, and the sample size of IGT subjects needed to detect a 33% reduction in NIDDM by an experimental intervention at a power of 80%. RESULTS - During a median of 4.3 years of follow-up, 91 (8.2%) of the 1,108 nondiabetic subjects developed NIDDM. The estimated 5-year cumulative incidence rate was 13.5%. Each of the variables, 2HPG, FPG, HbA(1), FPG-HbA(1), BMI, IGT, and systolic (sBP), diastolic (dBP), and mean (MBP) blood pressures, predicted NIDDM (P < 0.05 for each) when controlled for age and sex. In a stepwise proportional hazards analysis model, 2HPG and FPG-HbA, (P < 0.001 for each) were selected as the best set of predictors of NIDDM and of fasting hyperglycemia (FPG greater than or equal to 7.8 mmol/l). CONCLUSIONS - A two-step strategy, in which high-risk individuals are first identified by FPG or FPG-HbA, and then the OGTT is used to select subjects with IGT, requires fewer OGTTs than when using 2HPG as the initial screening test without substantially increasing the numbers that would need to be screened. Such a strategy also offers the advantage of reducing the necessary sample size and is therefore an effective, efficient, and convenient method of identifying eligible subjects for a clinical trial of prevention of NIDDM. RP Naryan, KMV (reprint author), NIDDKD,DAES,PECRB,1550 E INDIAN SCH RD,PHOENIX,AZ 85014, USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 36 TC 0 Z9 0 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD SEP PY 1996 VL 19 IS 9 BP 972 EP 978 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VE982 UT WOS:A1996VE98200010 ER PT J AU Fedorko, DP Williams, EC AF Fedorko, DP Williams, EC TI Evaluation of two commercial microtiter cytotoxin assays for the detection of Clostridium difficile toxin B in stool specimens SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID ENZYME-IMMUNOASSAY; DIAGNOSIS; DISEASE; DIARRHEA AB Two commercial microtiter cytotoxin assays using a fibroblast cell line (Bartels, Baxter Diagnostics, Inc., Deerfield, IL) and an epithelial cell line (Cytotoxi Test, Advanced Clinical Diagnostics, Toledo, OH) were evaluated for their ability to detect Clostridium difficile toxin B in stool specimens. After 48 hours, the assays had comparable sensitivity (90 versus 92%) and specificity (99 versus 98%). Although nor statistically significant, the Bartels assay detected more toxin-positive specimens at 24 hours (84 versus 72%, P = 0.089, Fisher's Exact Test) and the Cytotoxi assay had fewer nonspecific reactions requiring repeat testing (2.2 versus 1.1%, P = 0.186, Fisher's Exact Test). Both cytotoxin assays had comparable analytic performance. (C) 1996 Elsevier Science Inc. RP Fedorko, DP (reprint author), NIH,DEPT CLIN PATHOL,WARREN G MAGNUSON CLIN CTR,MICROBIOL SERV,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 15 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 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD SEP PY 1996 VL 26 IS 1 BP 47 EP 51 DI 10.1016/S0732-8893(96)00172-1 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA VV371 UT WOS:A1996VV37100010 PM 8950530 ER PT J AU Minowa, MT Lee, SH Mouradian, MM AF Minowa, MT Lee, SH Mouradian, MM TI Autoregulation of the human D-1A dopamine receptor gene by cAMP SO DNA AND CELL BIOLOGY LA English DT Article ID AGONIST-INDUCED DESENSITIZATION; MOLECULAR-CLONING; PARKINSONS-DISEASE; RESPONSE ELEMENT; BINDING-PROTEINS; PROMOTER REGION; MESSENGER-RNA; EXPRESSION; D1; TRANSCRIPTION AB Stimulation of the D-1A dopamine receptor increases intracellular cAMP concentration and down-regulates the receptor protein, We evaluated the possibility that this second messenger system could affect the expression of the D-1A gene as a positive autoregulatory mechanism, Treatment of the D-1A-expressing cells SK-NMC with 100 mu M dopamine resulted in an initial increase in steady-state levels of the D-1A mRNA beginning at 30 min, followed by decline below the baseline and then recovery by 24 hr, Forskolin/IBMX (100 mu M each) treatment also resulted in a decline followed by recovery, To determine if these changes in D-1A message levels are due to transcriptional control, transient expression assays were done using reporter gene constructs of the human D-1A gene 5'-flanking region, Forskolin/IBMX treatment for 19 hr resulted in a four- to sevenfold increase in trans-activation of the human D-1A gene promoter, Two cAMP-responsive regions in exon 1 of this gene with nuclear protein binding sites within both regions were identified, The segment of the D-1A gene between these two cAMP-responsive regions contained two additional DNA-protein interaction sites, one of which bound to nuclear factors considerably stronger following forskolin/IBMX treatment, Several consensus sequences for classical transcription factors known to mediate the cAMP response, such as CREB, AP2, and AP1, are found in the human D-1A gene, However, the location of all but one AP2 site in other parts of this gene and lack of AP2 expression in SK-N-MC cells suggest that these factors are unlikely to transduce this response, Thus, dopamine treatment results in delayed cAMP-mediated trans-activation of the D-1A gene via an indirect mechanism. C1 NINCDS,GENET PHARMACOL UNIT,ETB,NIH,BETHESDA,MD 20892. OI Mouradian, M. Maral/0000-0002-9937-412X NR 36 TC 11 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD SEP PY 1996 VL 15 IS 9 BP 759 EP 767 DI 10.1089/dna.1996.15.759 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA VL198 UT WOS:A1996VL19800006 PM 8836034 ER PT J AU Dawson, DA Archer, LD Grant, BF AF Dawson, DA Archer, LD Grant, BF TI Reducing alcohol-use disorders via decreased consumption: A comparison of population and high-risk strategies SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article AB This study compared three alternative scenarios for effecting a 25% reduction in U.S. alcohol consumption in terms of their respective impacts on the prevalence of alcohol abuse and dependence. The three approaches were (1) an overall 25% reduction in the volume of ethanol intake for all current drinkers, (2) an equivalent absolute reduction taken only among drinkers whose current intake ever exceeds moderate drinking guidelines, and (3) an equivalent reduction taken only among drinkers whose current intake usually exceeds moderate drinking guidelines. The per-occasion cutpoint for moderate consumption was set at the intake level demonstrated to produce psychomotor impairment, and was based on each individual's total body water level. The impact of reducing consumption on the prevalence of alcohol use disorders was estimated by means of a logistic regression model that adjusted for sociodemographic characteristics, family history of alcoholism, and age at first drink, and that took into account interactions between the consumption and other variables. Taking an overall 25% reduction in intake resulted in the same decrease in the prevalence of abuse and dependence (21.7%) as was achieved by taking an equal volume of reduction among only those drinkers whose consumption usually exceeded the moderate drinking cutpoint. Restricting the reduction in consumption to those drinkers whose consumption ever exceeded this cutpoint resulted in a slightly greater reduction in alcohol use disorders, 24.6%. RP Dawson, DA (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,WILLCO BLDG,SUITE 514,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 28 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD SEP PY 1996 VL 42 IS 1 BP 39 EP 47 DI 10.1016/0376-8716(96)01260-4 PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA VF132 UT WOS:A1996VF13200005 PM 8889402 ER PT J AU Shin, Y Daly, JW Jacobson, KA AF Shin, Y Daly, JW Jacobson, KA TI Activation of phosphoinositide breakdown and elevation of intracellular calcium in a rat RBL-2H3 mast cell line by adenosine analogs: Involvement of A(3)-adenosine receptors? SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE adenosine receptors; phosphoinositides; calcium; xanthines ID N-6-BENZYLADENOSINE-5'-URONAMIDES; RESPONSIVENESS AB A variety of adenosine analogs activate phosphoinositide breakdown in a rat RBL-2H3 mast cell line. it is presumed that an A(3)-adenosine receptor is involved, since the phosphoinositide response is insensitive to xanthines. However, the very potent A(3)-receptor agonist 2-chloro-N-6-iodobenzyl-N-methylcarboxamidoadenosine (2-Cl-IBMECA) with an EC(50) of 4.1 mu M is about twofold less potent (and less efficacious) than N-ethylcarboxamidoadenosine (NECA) with an EC(50) of 2.1 mu M. The other agents consisting of N-6-p-aminophenylethyladenosine (APNEA), N-6-iodobenzylMECA (IB-MECA), N-6-R-phenylisopropyladenosine (R-PIA), 2-chloroadenosine, N-6-benzyladenosine, N-6-cyclohexyladenosine (CHA), N-6-cyclohexylNECA (CHNECA), 2-(p-carboxyethylphenylethylaminoNECA (CGS 21680), 1,3-dibutylxanthine 7-riboside-5'-N-methylcarboxamide (DBXRM), adenosine, and 8-bromoadenosine are all nearly equipotent with EC(50) values of 5.5-13.9 mu M. The rank order of potencies of the analogs in causing an elevation of intracellular calcium is quite different. The potent A(3) receptor agonists 2-Cl-IBMECA and IB-MECA with EC(50) values of 0.07 and 0.11 mu M, respectively, are about fourfold more potent than N-6-cyclohexylNECA and about 15-fold more potent than NECA. The other analogs are comparable or somewhat less potent than NECA, some are less efficacious, and 8-bromoadenosine is inactive. The results suggest that stimulation of phosphoinositide breakdown by adenosine analogs in RBL-2H3 cells as measured by IP1 accumulation is not predictive of IP3-mediated elevations of intracellular calcium. Rank order of potency for the calcium response is consonant with intermediacy of A(3)-adenosine receptors, while the former, as measured by [H-3]IP1-formation, probably reflects contributions from both an A(3)-mediated response and some other mechanism. Combinations of subthreshold concentrations of 2-Cl-IBMECA with either the A(1)-selective agonist CHA or the A(2A)-selective agonist CGS 21680 caused a marked stimulation of phosphoinositide breakdown, providing further evidence for dual mechanisms. The selective A(3)-adenosine receptor antagonist 3,6-dichloro-2'-(isopropyloxy)-4'-methylflavone (MRS 1067) inhibits 2-Cl-IBMECA- and NECA-elicited elevation of calcium levels, and had differential effects on phosphoinositide breakdown, blocking [H-3]IP3 accumulation and either blocking (NECA) or having no effect (2-Cl-IBMECA) on [H-3]IP1 accumulation. (C) 1997 Wiley-Liss, Inc. C1 NIDDKD,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] NR 18 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD SEP PY 1996 VL 39 IS 1 BP 36 EP 46 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA WF906 UT WOS:A1996WF90600005 PM 23087534 ER PT J AU Torchin, CD McNeilly, PJ Kapetanovic, IM Strong, JM Kupferberg, HJ AF Torchin, CD McNeilly, PJ Kapetanovic, IM Strong, JM Kupferberg, HJ TI Stereoselective metabolism of a new anticonvulsant drug candidate, losigamone, by human liver microsomes SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID ENANTIOMER-ENANTIOMER INTERACTION; RAT; (S)-PROPAFENONE; (R)-PROPAFENONE; PHARMACOLOGY; MECHANISM; ISOMERS AB Losigamone (LSG) is a new candidate anticonvulsant drug undergoing preclinical and clinical development. Metabolism of racemic (+/-)-LSG and its two enantiomers, AO-242 [(+)-LSG] and AO-294 [(-)-LSG], was studied using human liver microsomes and recombinant cytochrome P450 isozymes. HPLC with both UV and electrochemical detection was used for analysis of the incubation media. Five metabolites (M1, M2, M3, M4, and M5) were generated from racemic (+/-)-LSG by both human liver microsomes and recombinant enzymes. Stereoselective metabolism was observed when each enantiomer was incubated separately with human liver microsomes. M1 was the major metabolite produced from (+)-LSG, whereas M3, M4, and M5 were primarily produced from (-)-LSG. The production of M1 from (+)-LSG was markedly inhibited by (-)-LSG, indicating a metabolic enantiomer/enantiomer interaction. (+/-)-LSG enantiomers were selectively metabolized by recombinant cytochrome P450 2A6, and the metabolism of (+)-LSG and (-)-LSG by human liver microsomes was preferentially inhibited by coumarin, a cytochrome P450 2A6-selective compound. C1 NINCDS,EPILEPSY BRANCH,NIH,BETHESDA,MD 20892. US FDA,CTR DRUG EVALUAT & RES,OFF PHARMACEUT SCI,DIV CLIN PHARMACOL RES,ROCKVILLE,MD 20857. NR 23 TC 29 Z9 29 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 1996 VL 24 IS 9 BP 1002 EP 1008 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VH337 UT WOS:A1996VH33700012 PM 8886611 ER PT J AU Darbyshire, JF Iyer, KR Grogan, J Korzekwa, KR Trager, WF AF Darbyshire, JF Iyer, KR Grogan, J Korzekwa, KR Trager, WF TI Selectively deuterated warfarin - Substrate probe for the mechanism of aromatic hydroxylation catalyzed by cytochrome P450 SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID NIH SHIFT; FENTONS REAGENT; ARENE OXIDES; PEROXYDISULFATE; METABOLISM; OXIDATION; MICROSOMES; EXPRESSION; CHEMISTRY; PATHWAY AB The effect of branch pathways on the observed intramolecular isotope effect and deuterium retention associated with 6- and 7-hydroxylation of selectively monodeuterated (R)- and (S)-warfarin with cytochrome P450 (CYP) 2C9 and CYP1A2 were studied, cDNA-expressed CYP2C9 was incubated with enantiomerically pure (S)-7d(1)- and (S)-6d(1)-warfarin, and expressed CYP1A2 was incubated with enantiomerically pure (R)-7d(1) and (R)-6d(1)-warfarin. A high degree of deuterium retention was observed in all metabolites, independent of the stereochemistry of the substrate or CYP isoform. No deuterium kinetic isotope effect was observed for the formation of 6-hydroxy- or 7-hydroxywarfarin in the case of the (S)-6d(1)-warfarin metabolism by CYP2C9, or for the formation of 6-hydroxy-, 7-hydroxy-, and 8-hydroxywarfarin in the case of the (R)-6d(1)-warfarin metabolism by CYP1A2. Deuterium isotope effects of 1.17 and 1.23 accompanied formation of 7-hydroxywarfarin from (S)-7d(1)-warfarin by CYP2C9 and from (R)-7d(1)-warfarin by CYP1A2, respectively. These observations are consistent with the addition-rearrangement pathway for aromatic hydroxylation, in which a triplet-like active oxygen species initially adds to the pi system, resulting in a tetrahedral intermediate, The intermediate subsequently rearranges to generate the phenol, the final product of the reaction. C1 UNIV WASHINGTON,SCH PHARM,DEPT MED CHEM,SEATTLE,WA 98195. NCI,MOL CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM 36922] NR 39 TC 21 Z9 22 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD SEP PY 1996 VL 24 IS 9 BP 1038 EP 1045 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VH337 UT WOS:A1996VH33700018 PM 8886617 ER PT J AU Vandell, DL AF Vandell, DL TI Characteristics of infant child care: Factors contributing to positive caregiving SO EARLY CHILDHOOD RESEARCH QUARTERLY LA English DT Article ID FAMILY; QUALITY AB At 6 months of age, 576 infants were observed during 2 half-days in five types of nonmaternal child care (centers, child care homes, in-home sitters, grandparents, and fathers). Settings were assessed in terms of their structural characteristics (group size, child-adult ratio, physical environment) and caregivers' characteristics (formal education, specialized training, child care experience, and beliefs about child rearing). In addition, caregivers' interactions with infants were observed. Caregivers were rated as providing more positive caregiving when group sizes and child-adult ratios were smaller and when caregivers held less-authoritarian beliefs about child rearing. Significant differences were associated with type of care arrangement. Child-adult ratios and group sizes were largest in centers and smallest in informal in-home care (with fathers, grandparents, and in-home sitters); specialized training was highest in centers. Small group sizes, low child adult ratios, caregivers' nonauthoritarian child-rearing beliefs, and safe, clean, and stimulating physical environments were consistently associated with positive caregiving behaviors within each of these different types of settings. C1 NICHHD,BETHESDA,MD 20892. PENN STATE UNIV,UNIVERSITY PK,PA 16802. TEMPLE UNIV,PHILADELPHIA,PA 19122. UNIV ARKANSAS,FAYETTEVILLE,AR 72701. UNIV CALIF IRVINE,IRVINE,CA 92717. UNIV KANSAS,LAWRENCE,KS 66045. UNIV NEW HAMPSHIRE,DURHAM,NH 03824. UNIV N CAROLINA,CHAPEL HILL,NC. UNIV PITTSBURGH,PITTSBURGH,PA 15260. UNIV TEXAS,DALLAS,TX 75230. VANDERBILT UNIV,NASHVILLE,TN 37240. WELLESLEY COLL,WELLESLEY,MA 02181. UNIV VIRGINIA,CHARLOTTESVILLE,VA 22903. UNIV WASHINGTON,SEATTLE,WA 98195. RP Vandell, DL (reprint author), UNIV WISCONSIN,WISCONSIN CTR EDUC RES,1025 W JOHNSON ST,MADISON,WI 53706, USA. NR 50 TC 17 Z9 18 U1 0 U2 18 PU ABLEX PUBL CORP PI NORWOOD PA 355 CHESTNUT ST, NORWOOD, NJ 07648 SN 0885-2006 J9 EARLY CHILD RES Q JI Early Childhood Res. Q. PD SEP PY 1996 VL 11 IS 3 BP 269 EP 306 DI 10.1016/S0885-2006(96)90009-5 PG 38 WC Education & Educational Research; Psychology, Developmental SC Education & Educational Research; Psychology GA VT154 UT WOS:A1996VT15400001 ER PT J AU Yarmola, E Sokoloff, H Chrambach, A AF Yarmola, E Sokoloff, H Chrambach, A TI The relative contributions of dispersion and diffusion to band spreading (resolution) in gel electrophoresis SO ELECTROPHORESIS LA English DT Article DE band spreading; resolution; diffusion; dispersion; agarose gel electrophoresis ID DNA; COEFFICIENTS; APPARATUS; WIDTH AB DNA of approximately 2 kbp in length was previously found not to diffuse significantly in 1-1.5% agarose gels in the absence of an electric field, but to disperse during electrophoresis (Yarmola, E., Chrambach, A., Electrophoresis 1995, 16, 345-349). Accordingly, a process distinct from diffusion, and responsible for band spreading with migration time in gel electrophoresis, was defined as dispersion. Correspondingly, the diffusion coefficient, D(diff), was distinguished from a dispersion coefficient, D(disp). For DNA of approximately 1, 2 and 3 kbp, D(diff) and D(disp) were measured in agarose gel electrophoresis (1.0% SeaKem GTG). In that order of DNA length, D(disp)/D(diff) was found to increase from 5 to 15 to 45, showing that with increasing DNA length, time-dependent band spreading, and thus resolution in gel electrophoresis, is governed predominantly by dispersion, not diffusion. It is assumed that the essential part of electrophoretic dispersion is due to entanglement of the DNA molecule in the gel. Indirect evidence for such an entanglement derives from the observation of peak asymmetry and its interpretation by the Giddings-Weiss model. C1 NIH,THEORET & PHYS BIOL LAB,MACROMOL ANAL SECT,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BETHESDA,MD 20892. RUSSIAN ACAD SCI,VA ENGELHARDT MOL BIOL INST,LAB BIOPOLYMER PHYS,MOSCOW,RUSSIA. NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. NR 16 TC 25 Z9 25 U1 1 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD SEP PY 1996 VL 17 IS 9 BP 1416 EP 1419 DI 10.1002/elps.1150170904 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA VP140 UT WOS:A1996VP14000003 PM 8905256 ER PT J AU RabadanDiehl, C Kiss, A Camacho, C Aguilera, G AF RabadanDiehl, C Kiss, A Camacho, C Aguilera, G TI Regulation of messenger ribonucleic acid for corticotropin releasing hormone receptor in the pituitary during stress SO ENDOCRINOLOGY LA English DT Article ID MEDIAN-EMINENCE; ADRENOCORTICOTROPIN SECRETION; ARGININE VASOPRESSIN; DOWN-REGULATION; ADRENAL AXIS; RESPONSES; RAT; DESENSITIZATION; EXPRESSION; CRF AB The mechanism regulating pituitary CRH receptors during stress was studied by analysis of the changes in CRH receptor messenger RNA (mRNA) and CRH binding after acute and repeated stress and CRH and vasopressin (VP) administration in intact and adrenalectomized rats. Acute stress caused time- and stress type-dependent changes in pituitary CRH receptor expression. In situ hybridization studies shelved biphasic changes in CRH receptor mRNA after immobilization stress for 1 h and decreases by 2 h (P < 0.01). Increases (P < 0.01) were seen 4 and 8 h after the initiation of the stress, and a return to near basal levels by 12 and 18 h. A different pattern, with a decrease by 4 h (P < 0.01) and levels similar to controls after 12 and 18 h, was observed after a single ip injection of hypertonic saline (1.5 M NaCl). Binding autoradiography showed significant increases in pituitary CRH binding 4, 10, and 12 h after immobilization stress, but significant decreases 4, 12, and 18 h after ip hypertonic saline. In contrast, repeated immobilization or ip hypertonic saline for 8 or 14 days increased pituitary CRH receptor mRNA, and CRH binding was decreased. To determine the role of hypothalamic CRH and VP on these stress-induced changes, rats were injected for 14 days with CRH, VP, or their combination at doses mimicking stress levels in pituitary portal circulation (1 mu g/day sc). Repeated injection of CRH or VP increased CRH receptor mRNA and CRH binding (P < 0.05). CRH receptor mRNA levels further increased after combined administration of CRH and VP (P < 0.01), but CRH binding showed a tendency to decrease. The role of glucocorticoids on CRH receptor regulation was studied by analysis of the effects of stress on CRH receptor mRNA and CRH binding in adrenalectomized (ADX) rats with and without corticosterone replacement in the drinking water. Although in 6-day ADX rats pituitary CRH receptor mRNA levels were markedly reduced after acute immobilization, glucocorticoid replacement restored the stimulatory effect of stress to levels observed in intact fats. Similarly, a single sc injection of CRH (1 mu g) decreased CRH receptor mRNA in ADX rats but not in glucocorticoid-replaced ADX rats. CRH binding showed the expected decrease after ADX and was unchanged after stress or CRH injection. The increased pituitary CRH receptor mRNA after stress suggests that stress-induced CRH receptor down-regulation is due to increased receptor occupancy and internalization rather than to a decrease in receptor synthesis. The data suggest that increased hypothalamic secretion of CRH and VP mediates the delayed up-regulatory effect of stress on CRH receptor mRNA, and that resting levels of glucocorticoids are required for this effect. In addition, increased VP levels are permissive for the down-regulation of CRH binding induced by chronic pituitary exposure to stress levels of CRH. C1 NICHHD,SECT ENDOCRINE PHYSIOL,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 33 TC 41 Z9 41 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1996 VL 137 IS 9 BP 3808 EP 3814 DI 10.1210/en.137.9.3808 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VD086 UT WOS:A1996VD08600028 PM 8756551 ER PT J AU Feuillan, PP Aguilera, G AF Feuillan, PP Aguilera, G TI Regulation of aldosterone in the 7-day-old rat SO ENDOCRINOLOGY LA English DT Article ID ANGIOTENSIN-II RECEPTORS; ADRENAL-CORTEX; SYNTHASE CYTOCHROME-P-450; MOLECULAR-CLONING; STRESS; ADRENOCORTICOTROPIN; SODIUM; BIOSYNTHESIS; GLOMERULOSA; SUPPRESSION AB Little is known about mineralocorticoid regulation in the neonate, Here, adrenocortical function in 7-day-old Sprague-Dawley rats was studied by measuring the effects of angiotensin II (Ang II) and ACTH on serum aldosterone (ALDO), corticosterone, and cytochrome P-450 ALDO synthetase and 11 beta-hydroxylase messenger RNA (mRNA) levels with and without dexamethasone (DEX) treatment. In the absence of DEX, serum ALDO was unchanged after 5 mu g/kg, but increased 2- to 12-fold after 50 mu g/kg, Ang II and 9- to 36-fold after 5 U/kg ACTH. After 4 days of exposure to exogenous ACTH, basal and Ang II-stimulated ALDO were markedly decreased. Basal plasma corticosterone was near or below the assay detection limit and did not change after Ang II, but increased significantly after ACTH administration. After treatment with 200 mu g/kg DEX, basal serum ALDO fell to below the assay detection limit at 1 h, the responses to 50 mu g/kg Ang II were attenuated at 1 and 4 h and were undetectable at 18 h. Preincubation of 7-day-old dispersed adrenal glomerulosa cells with 100 nM DEX for 2 h did not decrease basal or stimulated ALDO production. In situ hybridization studies revealed that cytochrome P-450 ALDO synthetase mRNA was confined to the subcapsular zona glomerulosa, whereas cytochrome P-450 11 beta-hydroxylase mRNA was present only in the zona fasciculata-reticularis. DEX caused a time-dependent decrease in P-450 ALDO synthetase mRNA (91 +/- 36, 77 +/- 6%, 60 +/- 13%, and 38 +/- 19% of the control value at 1, 4, 8, and 16 h, respectively), an effect that was not prevented by ACTH replacement. Only minimal decreases in P-450 11 beta-hydroxylase mRNA levels were observed 18 h after DEX treatment. Hence, the sensitivity of ALDO responses to Ang II in the 7-day-old rat was markedly reduced in vivo, but not in vitro. In addition, DEX markedly reduced ALDO secretion, an effect that was associated with a decrease in cytochrome P-450 ALDO synthetase mRNA. RP Feuillan, PP (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 35 TC 9 Z9 9 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD SEP PY 1996 VL 137 IS 9 BP 3992 EP 3998 DI 10.1210/en.137.9.3992 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VD086 UT WOS:A1996VD08600053 PM 8756576 ER PT J AU Ward, MH Mark, SD Cantor, KP Weisenburger, DD CorreaVillasenor, A Zahm, SH AF Ward, MH Mark, SD Cantor, KP Weisenburger, DD CorreaVillasenor, A Zahm, SH TI Drinking water nitrate and the risk of non-Hodgkin's lymphoma SO EPIDEMIOLOGY LA English DT Article DE non-Hodgkin's lymphoma; nitrate; drinking water; diet ID PARAFFIN-EMBEDDED TISSUE; N-NITROSO COMPOUNDS; GASTRIC-CANCER; UNITED-STATES; DIETARY FACTORS; TIME TRENDS; VITAMIN-C; LEUKEMIA; EXPOSURE; MISCLASSIFICATION AB The increasing incidence of non-Hodgkin's lymphoma (NHL) in the United States is only partially explained by known risk factors. Nitrate is a contaminant of drinking water in many rural areas. We evaluated its association with NHL after accounting for dietary nitrate intake. For 156 cases and 527 controls who used Nebraska community supplies, average nitrate exposure was estimated from 1947 through 1979. Long-term consumption of community water with average nitrate levels in the highest quartile (greater than or equal to 4 mg per liter nitrate-nitrogen) was positively associated with risk [odds ratio (OR)=2.0; 95% confidence interval (CI)=1.1-3.6]. Dietary nitrate, which came mainly from vegetables, was not associated with NHL risk, after adjusting for vitamin C and carotene intakes. Persons with a lower intake of vitamin C were at slightly higher risk of developing NHL than persons whose daily intake was greater than or equal to 130 mg, for all levels of intake of drinking water nitrate; our findings were similar for the combined effect of water nitrate and carotene intake. Nitrate levels in private wells were measured at the time of the interview for 51 cases and 150 controls but were not associated with the risk of NHL after adjusting for pesticide use on the farm. These findings indicate that long-term exposure to elevated nitrate levels in drinking water may contribute to the risk of NHL. RP Ward, MH (reprint author), NCI,OCCUPAT STUDIES SECT,DIV CANC EPIDEMIOL & GENET,6130 EXECUT BLVD,EPN 418,BETHESDA,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 49 TC 142 Z9 148 U1 4 U2 16 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1996 VL 7 IS 5 BP 465 EP 471 DI 10.1097/00001648-199609000-00002 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VC739 UT WOS:A1996VC73900003 PM 8862975 ER PT J AU Weinberg, CR Moledor, ES Umbach, DM Sandler, DP AF Weinberg, CR Moledor, ES Umbach, DM Sandler, DP TI Imputation for exposure histories with gaps, under an excess relative risk model SO EPIDEMIOLOGY LA English DT Article DE missing data; radon; exposure assessment; imputation ID RESIDENTIAL RADON EXPOSURE; LUNG-CANCER; REGRESSION; WOMEN AB In reconstructing exposure histories needed to calculate cumulative exposures, gaps often occur. Our investigation was motivated by case control studies of residential radon exposure and lung cancer, where half or more of the targeted homes may not be measurable. Investigators have adopted various schemes for imputing exposures for such gaps. We first undertook simulations to assess the performance of five such methods under an excess relative risk model, in the presence of random missingness and under assumed independence among the true exposure levels for different epochs of exposure (houses). Assuming no other source of measurement error, one of the methods performed without bias and with coverage of nominally 95% confidence intervals that was close to 95%. This method assigns to the missing residences the arithmetic mean across all measured control residences. We show that its good properties can be explained by the fact that this approach produces approximate ''Berkson errors.'' To take advantage of predictive information that might exist about the missing epochs of exposure, one might prefer to carry out the imputations within strata. In further simulations, we asked whether the method would still perform well if imputations were carried out within many strata. It does, and much of the lost statistical power/precision can be recovered if the stratification system is moderately predictive of the missing exposures. Thus, observed control mean imputation provides a way to impute missing exposures without corrupting the study's validity; and stratifying the imputations can enhance precision. The technique is applicable in other settings where exposure histories contain gaps. RP Weinberg, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,MD A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Sandler, Dale/0000-0002-6776-0018 NR 15 TC 50 Z9 52 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1996 VL 7 IS 5 BP 490 EP 497 DI 10.1097/00001648-199609000-00006 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VC739 UT WOS:A1996VC73900007 PM 8862979 ER PT J AU Chow, WH Devesa, SS AF Chow, WH Devesa, SS TI Underreporting and misclassification of urinary tract cancer cases on death certificates SO EPIDEMIOLOGY LA English DT Article DE death certificates; tumor registry; case ascertainment; neoplasms; kidney; kidney pelvis; bladder ID UNITED-STATES; LUNG-CANCER; MORTALITY; ACCURACY; SMOKING AB We compared the diagnoses for deceased cases with urinary tract cancer reported to the Surveillance, Epidemiology, and End Results (SEER) program with their underlying cause of death reported on death certificates. Deaths for a substantial proportion of cases were ascribed to noncancer causes (bladder, 48%; kidney, 28%; renal pelvis, 37%; and other urinary tract, 38%), which decreased with advancing stage at diagnosis and increased with length of survival. In general, cancer deaths were more likely to be recorded to the predominant subsite within an organ. Only 5.5% of renal pelvis cancer patients were recorded to have died of their illness, whereas 33.7% of their deaths were reported as due to kidney cancer. On the other hand, over 85% of urinary tract cancer deaths reported on the death certificates were confirmed by SEER diagnosis, although the extent of agreement varied by stage at diagnosis and age at death for kidney and renal pelvis cancers. C1 NCI,DIV CANC EPIDEMIOL & GENET,BIOSTAT BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852. NR 17 TC 13 Z9 13 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 1996 VL 7 IS 5 BP 517 EP 520 DI 10.1097/00001648-199609000-00011 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VC739 UT WOS:A1996VC73900012 PM 8862984 ER PT J AU Mellemkjaer, L Linet, MS Gridley, G Frisch, M Moller, H Olsen, JH AF Mellemkjaer, L Linet, MS Gridley, G Frisch, M Moller, H Olsen, JH TI Rheumatoid arthritis and cancer risk SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE rheumatoid arthritis; cancer risk; hospital discharge register; follow-up study ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MORTALITY; NEOPLASMS; SCLEROSIS; LYMPHOMA AB The aim of this study was to examine the cancer pattern in a large group of patients with rheumatoid arthritis (RA). A follow-up study of cancer incidence in RA was conducted within a cohort of 20 699 patients recorded in the Danish Hospital Discharge Register during 1977-1987 by linkage with the Danish Cancer Registry through 1991. There were consistent excesses of non-Hodgkin's lymphoma and Hodgkin's disease in both sexes and during both early and late periods of follow-up. Risks for lung cancer and non-melanoma skin cancer were also increased, with no predilection for any specific histological subtype, while risks for colorectal cancer and female breast cancer were reduced. The cancer pattern seen among Danish RA patients largely supports findings from two earlier Nordic investigations. Thus, there seem to be consistent positive associations between RA and non-Hodgkin's lymphoma, Hodgkin's disease and lung cancer and a consistent negative association with colorectal cancer. Copyright (C) 1996 Elsevier Science Ltd C1 NCI,DIV CANC EPIDEMIOL & GENET,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. STATE SERUM INST,DANISH EPIDEMIOL CTR,COPENHAGEN,DENMARK. CTR RES HLTH & SOCIAL STAT,COPENHAGEN,DENMARK. RP Mellemkjaer, L (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRANDBLVD 49,DK-2100 COPENHAGEN O,DENMARK. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 FU NCI NIH HHS [MAO NO1-CP-85639-04] NR 30 TC 257 Z9 261 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1996 VL 32A IS 10 BP 1753 EP 1757 DI 10.1016/0959-8049(96)00210-9 PG 5 WC Oncology SC Oncology GA VK144 UT WOS:A1996VK14400037 PM 8983286 ER PT J AU Lewis, KC Zech, LA Phang, JM AF Lewis, KC Zech, LA Phang, JM TI Effects of chronic administration of N-(4-hydroxyphenyl)retinamide (4-HPR) in rats on vitamin A metabolism in the eye SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE N-(4-hydroxyphenyl)retinamide; vitamin A metabolism; retinoid supplementation; kinetic analysis; compartmental modelling ID SYNTHETIC RETINOID FENRETINIDE; BREAST-CANCER PATIENTS; PLASMA RETINOL; PROSTATE-CANCER; BINDING PROTEIN; TOLERABILITY; PREVENTION; TAMOXIFEN; ANALOG AB The retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) effectively inhibits cancer in a variety of tissues. In contrast to many other retinoids, the toxicity problems associated with administration of 4-HPR have been found to be minimal or absent. However, the effects of 4-HPR upon normal metabolism of native physiological forms of vitamin A in vivo have not been adequately investigated. To understand better the interaction between 4-HPR and the native physiological forms of vitamin A, the present study examines the effects of long-term administration of 4-HPR upon normal vitamin A metabolism in the eyes. Male Sprague-Dawley rats were fed either a control diet sufficient in vitamin A (CON group; 0.8 retinol equivalents [RE]/g diet; n = 28) or a CON diet supplemented with 4-HPR (CON + 4-HPR group; 1173 mu g 4-HPR/g diet; n = 28). Following an i.v. dose of physiologically radiolabelled retinol, associated with its normal plasma transport complex, the vitamin A content and radioactivity of the plasma and eyes were examined at different times over a 41 day period. Mean plasma retinol levels measured during the study period were significantly reduced in the CON + 4-HPR group as compared with the CON group (23.5 +/- 7.0 and 50.3 +/- 5.3 [mean +/- S.D.]mu g/dl, respectively). From approximately 7 days post-dosing, vitamin A levels in the eyes of the 4-HPR-treated group steadily decreased such that by the end of the study, they were only approximately one-fifth those of the CON group (0.098 +/- 0.075 and 0.50 +/- 0.053 RE, respectively). Kinetic analysis of vitamin A turnover in the eyes indicated that there was no apparent down-regulation of the fraction of vitamin A leaving this tissue on a daily basis; these values were found to be similar in both groups, averaging 0.104 +/- 0.0393 and 0.113 +/- 0.0373 per day (mean +/- fractional standard deviation [F.S.D.]) for the CON and CON + 4-HPR groups, respectively. At the same time, the flow of vitamin A through the eyes was significantly decreased in the CON + 4-HPR group eyes (0.0162 +/- 0.101 mu g/day) as compared with the CON group (0.0604 +/- 0.0672 mu g/day). Our results suggest that compensatory mechanisms that would normally function to conserve depleting ocular vitamin A stores may be blocked in the 4-HPR-treated animals and further, that the 4-HPR itself appears to be interfering with the normal uptake and/or metabolism of vitamin A in the eye. These findings may help to provide at least a partial explanation for the visual impairment problems that have been reported in human trials that include long-term administration of 4-HPR. C1 NCI, MATH BIOL LAB, NIH, BETHESDA, MD 20892 USA. RP Lewis, KC (reprint author), NCI, FREDERICK CANC RES & DEV CTR, LAB NUTR & MOL REGULAT, POB B, FREDERICK, MD 21702 USA. NR 25 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD SEP PY 1996 VL 32A IS 10 BP 1803 EP 1808 DI 10.1016/0959-8049(96)00197-9 PG 6 WC Oncology SC Oncology GA VK144 UT WOS:A1996VK14400044 PM 8983293 ER PT J AU Kyrtopoulos, SA Souliotis, VL Chhabra, SK Anderson, LM AF Kyrtopoulos, SA Souliotis, VL Chhabra, SK Anderson, LM TI DNA damage studies related to the assessment of the role of N-nitroso compounds in human cancer SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article; Proceedings Paper CT 13th Annual ECP Symposium N-Nitroso Compounds in Human Cancer - Current Status and Future Trends CY OCT 16-17, 1995 CL LONDON, ENGLAND SP European Canc Prevent Org ID TOBACCO-SPECIFIC NITROSAMINES; BLOOD LEUKOCYTE DNA; GENETIC POLYMORPHISMS; ALCOHOL-CONSUMPTION; ESOPHAGEAL CANCER; GASTRIC-CANCER; BRAIN-TUMORS; RISK-FACTORS; IN-VIVO; ETHANOL C1 NCI, COMPARAT CARCINOGENESIS LAB, FREDERICK CANC RES & DEV CTR, FT FREDERICK, MD USA. RP Kyrtopoulos, SA (reprint author), NATL HELLEN RES FDN, INST BIOL RES & BIOTECHNOL, LAB CHEM CARCINOGENESIS, GR-11635 ATHENS, GREECE. NR 47 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 EI 1473-5709 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD SEP PY 1996 VL 5 SU 1 BP 109 EP 114 DI 10.1097/00008469-199609001-00023 PG 6 WC Oncology SC Oncology GA VY390 UT WOS:A1996VY39000023 PM 8972304 ER PT J AU Bell, MD Taub, DD Kunkel, SJ Strieter, RM Foley, R Gauldie, J Perry, VH AF Bell, MD Taub, DD Kunkel, SJ Strieter, RM Foley, R Gauldie, J Perry, VH TI Recombinant human adenovirus with rat MIP-2 gene insertion causes prolonged PMN recruitment to the murine brain SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE inflammation; chemokines; tachyphylaxis; blood-brain barrier ID CENTRAL-NERVOUS-SYSTEM; T-CELL SUBSETS; MONOCLONAL-ANTIBODY; ALZHEIMERS-DISEASE; ENDOTHELIAL-CELLS; MEDIATED TRANSFER; INVIVO; MACROPHAGE; EXPRESSION; VECTOR AB Single injections of recombinant cytokines/chemokines into tissue have provided insights into their possible roles during the inflammatory response. Adenoviral technology may allow us to mimic the in vivo situation more closely, with protein generated in a continuous but transient fashion. Replication-deficient human type 5 adenovirus containing a rat macrophage inflammatory protein-2 (MIP-2) gene insertion and cytomegalovirus promoter was injected into the mouse brain to investigate the inflammatory response to continuous overproduction of MIP-2. Adenovirus with a LacZ gene insertion expressing beta-galactosidase was used as a control. At doses of 10(4) to 10(7) plaque-forming units, a minimal inflammatory response was detected to the LacZ virus, with leukocyte recruitment that was restricted to the injection site. A dose of 10(7) plaque-forming units of both the LacZ and the MIP-2 vector produced extensive transgene product expression that persisted for at least 7 days. Astrocytes, recognized by their morphology, were the predominant cell type expressing MIP-2 and beta-galactosidase. A dose of 10(7) plaque-forming units of MIP-2 vector caused dramatic polymorphonuclear leukocyte (PMN) recruitment to the brain parenchyma after 2 days. PMN recruitment was still observed after 4 and 7 days, but had become more localized to the injection site and was associated with numerous foam-like macrophages. At both 2 and 7 days the blood-brain barrier was breached in the region of leukocyte recruitment. Despite the extent of leukocyte recruitment there were no overt signs of neuronal degeneration or demyelination. Our findings demonstrate that continuous production of MIP-2 in the CNS results in persistent PMN recruitment to the brain parenchyma with no evidence of tachyphylaxis. The lack of PMN recruitment to the brain parenchyma following CNS injury may be a result of deficient production of PMN chemoattractants. C1 UNIV OXFORD,DEPT PHARMACOL,OXFORD OX1 3QT,ENGLAND. SAIC,NCI CANC RES,FREDERICK,MD. SAIC,DEV CTR,FREDERICK,MD. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI. MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON,CANADA. FU Wellcome Trust NR 52 TC 38 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 1996 VL 8 IS 9 BP 1803 EP 1811 DI 10.1111/j.1460-9568.1996.tb01324.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA VK344 UT WOS:A1996VK34400002 PM 8921271 ER PT J AU Melzer, P Smith, CB AF Melzer, P Smith, CB TI Plasticity of metabolic whisker maps in somatosensory brainstem and thalamus of mice with neonatal lesions of whisker follicles SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE neonatal plasticity,; mouse; trigeminal brainstem; thalamic ventrobasal complex; quantitative autoradiographic deoxyglucose method ID STEM SUBNUCLEUS INTERPOLARIS; INFRAORBITAL NERVE TRANSECTION; VIBRISSAE REPRESENTATION; CYTOCHROME-OXIDASE; TRIGEMINAL SYSTEM; PRIMARY AFFERENTS; NUCLEAR-COMPLEX; BARREL CORTEX; ADULT-RAT; MOUSE AB We employed the autoradiographic deoxyglucose method to study metabolic whisker maps of the adult mouse somatosensory brainstem and thalamus after the neonatal removal of left whisker follicles C1, C2 and C3. Left whiskers B1-3 and D1-3 were deflected to metabolically activate the somatosensory pathway. Unoperated mice that were stimulated in the same fashion served as controls, Whisker stimulation resulted in an ipsilateral increase in metabolic activity in the three trigeminal brainstem structures in which the whiskers are represented topologically by segments of high cytochrome oxidase activity, i.e. subnucleus caudalis, subnucleus interpolaris and nucleus principalis. In the two subnuclei of mice with lesions and of controls, there was an increase in metabolic activity of the representations of the deflected whiskers, whereas the metabolic activity of representations A1-3 and E1-3 was low. Apart from these similarities, the metabolic activation of the representations originally representing whiskers C1-3 was remarkably greater in mice with lesions than in controls. This increase reached statistical significance in subnucleus caudalis and approached statistical significance in subnucleus interpolaris. In nucleus principalis the deprived territory was only partially activated and the degree of metabolic activation was less than in the subnuclei. In the thalamic ventrobasal complex of mice with lesions metabolic activity was unpatterned whereas two areas of metabolic activation were distinct in controls. Hence, the removal of whisker follicles in newborn mice resulted in the suppression of localized metabolic responses to whisker stimulation in the thalamus, whereas in the brainstem stimulus-related activity was prominent and the deprived territory became responsive to the stimulation of whisker follicles adjacent to the lesion. Apparently, the modification of the whisker representation at the first synapse of the pathway induces a diminution of localized responsivity in the thalamus. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 43 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD SEP PY 1996 VL 8 IS 9 BP 1853 EP 1864 DI 10.1111/j.1460-9568.1996.tb01329.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA VK344 UT WOS:A1996VK34400007 PM 8921276 ER PT J AU Spiegel, S Scott, SW BowmanVance, V Tam, Y Galiakparov, NN Rosner, A AF Spiegel, S Scott, SW BowmanVance, V Tam, Y Galiakparov, NN Rosner, A TI Improved detection of prunus necrotic ringspot virus by the polymerase chain reaction SO EUROPEAN JOURNAL OF PLANT PATHOLOGY LA English DT Article DE ilarvirus; PCR; peach; PNRSV; virus detection ID LINKED IMMUNOSORBENT-ASSAY; YELLOW MOSAIC-VIRUS; NUCLEOTIDE-SEQUENCE; PCR; ILARVIRUSES; TREES; DNA AB The reverse transcription - polymerase chain reaction (RT-PCR) technique was used for detection of prunus necrotic ringspot virus in dormant peach trees which tested negative by ELISA. Total RNA extracted from bark tissue, using a lithium chloride based method, were used for reverse transcription and subsequent amplification of viral sequences. The PCR product, about 300 base pairs in size, was analyzed by gel electrophoresis and visualized by ethidium bromide staining. In some cases, PCR products were not clearly visible in the stained gel and became distinct only following hybridisation with a P-32-labelled virus specific probe. The RT-PCR assay described in this paper is sensitive enough for detection of PNRSV in dormant woody bark tissue and could be incorporated into testing protocols during post-entry quarantines for rapid initial screening of imported budwood and in virus elimination programs. C1 CLEMSON UNIV,DEPT PLANT PATHOL & PHYSIOL,CLEMSON,SC 29634. UNIV S CAROLINA,DEPT BIOL SCI,COLUMBIA,SC 29208. NATL BIOTECHNOL CTR,INST BIOCHEM & MOL BIOL,ALMATY,KAZAKHSTAN. RP Spiegel, S (reprint author), AGR RES ORG,VOLCANI CTR,DEPT VIROL,IL-50250 BET DAGAN,ISRAEL. NR 20 TC 59 Z9 65 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-1873 J9 EUR J PLANT PATHOL JI Eur. J. Plant Pathol. PD SEP PY 1996 VL 102 IS 7 BP 681 EP 685 DI 10.1007/BF01877249 PG 5 WC Agronomy; Plant Sciences; Horticulture SC Agriculture; Plant Sciences GA VJ951 UT WOS:A1996VJ95100009 ER PT J AU Shefer, VI Talan, MI Engel, BT AF Shefer, VI Talan, MI Engel, BT TI Heat loss during cold exposure in adult and aged C57BL/6J mice SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE aging; thermoregulation; cold exposure; metabolic heat production; heat toss; colonic temperature; mice ID SKIN BLOOD-FLOW; STRESS; RESPONSES; BODY; RATS AB Metabolic heat production (MHP), colonic temperature (Tco), and nonevaporative (dry) heat loss were measured in ADULT and AGED C57BL/6J male mice during cold exposure. Dry heat loss was assessed as a differential temperature (Td) between incoming and outgoing air through the chamber for indirect calorimetry. The average Td during cold exposure normalized to surface area for ADULT mice was significantly higher than that for the AGED animals (0.0618 +/- 0.0003 degrees C/cm(2) and 0.0553 +/- 0.0005 degrees C/cm(2), respectively). Linear regression analysis showed that at the same Tco AGED mice showed lower values of Td normalized to surface area, indicating that at the same body temperature they were losing less heat than ADULT animals. It was concluded that age-related decline in cold tolerance in mice is not due to a lack of ability to reduce heat loss during cold exposure. On the contrary, AGED animals had lower heat loss in comparison with ADULT. We suggest that augmentation of heat conservation mechanisms is an adaptive response to diminishing cold-induced heat production. C1 NIA,BEHAV SCI LAB,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 21 TC 2 Z9 2 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP-OCT PY 1996 VL 31 IS 5 BP 597 EP 604 DI 10.1016/0531-5565(96)00009-5 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA VH325 UT WOS:A1996VH32500006 PM 9415115 ER PT J AU Kodavanti, UP Jaskot, RH Bonner, J Badgett, A Dreher, KL AF Kodavanti, UP Jaskot, RH Bonner, J Badgett, A Dreher, KL TI Eosinophilic lung inflammation in particulate-induced lung injury: Technical consideration in isolating RNA for gene expression studies SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE eosinophils; inflammation; lung tissue; particles; ribonucleases; RNA isolation ID CATIONIC PROTEIN; RIBONUCLEASE; ASTHMA; OZONE; AIR; PROTEOGLYCAN; MACROPHAGES; LYMPHOCYTES; EXTRACTION; NEUROTOXIN AB Particulate and other pollutant exposures are associated with lung injury and inflammation. The purpose of this study was to develop an approach by which intact RNA could be obtained from inflamed lung tissue from particulate-exposed animals in order to correlate injury with specific gene expression. Male Sprague Dawley (SD) and Fischer-344 (F-344) rats were intratracheally instilled with saline or residual oil fly ash (ROFA) instillation, lungs were either lavaged or used for RNA isolation. ROFA exposure produced an increase in bronchoalveolar lavage fluid (BALF) neutrophils in both SD and F-344 rats. A time-dependent increase in eosinophils occurred only in SD rats but not in F-344 rats. Extraction if inflamed pulmonary tissue having a high influx of eosinophils for RNA using the conventional acid guanidinium thiocyanate phenol-chloroform (AGPC) procedure failed to provide undergraded RNA suitable for RT-PCR and Northern blot analysis of beta-actin mRNA expression. Mixing intact total RNA from saline control rat lungs with degraded RNA samples from inflamed lung yielded a gel profile of degraded RNA, indicating the presence of ribonuclease-like activity in the RNA extracted from lung tissues having eosinophil influx. Evidently, the conventional AGPC procedure failed to completely remove ribonuclease activity associated with ROFA-induced pulmonary eosinophil influx. This study reports a single-step modification to the AGPC extraction method that does not require additional reagents or additional precipitation steps for extracting undergraded RNA from nuclease-rich inflamed lung tissue. The aqueous layer resulting from mixing homogenate and chloroform is extracted a second time using an equal volume of AGPC buffer followed by addition of chloroform and centrifugation. This simple aqueous phase is then treated as described in the conventional RNA extraction protocol. This simple aqueous phase is then treated as described in the conventional RNA extraction protocol. This sample and convenient modification does not require multiple precipitations of RNA and yields undergraded RNA from inflamed lung tissue with a slightly higher A(260)/A(280) ratio without affecting overall RNA recovery. The results indicate that undergraded RNA could not be isolated using the routine ROFA exposure. The degraded RNA preparations were unsuitable for gene expression studies. However, undergraded RNA can be isolated from these tissues by modifying the original AGPC RNA extraction procedure, which is suitable for gene expression analysis using northern blot and RT-PCR techniques. C1 US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,EXPT TOXICOL DIV,PULM TOXICOL BRANCH,RES TRIANGLE PK,NC 27711. NATL INST ENVIRONM HLTH SCI,PULM PATHOBIOL SECT,RES TRIANGLE PK,NC. NR 28 TC 21 Z9 21 U1 0 U2 1 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD SEP-OCT PY 1996 VL 22 IS 5 BP 541 EP 554 DI 10.3109/01902149609046041 PG 14 WC Respiratory System SC Respiratory System GA VJ555 UT WOS:A1996VJ55500004 PM 8886758 ER PT J AU Dong, WM Lewtas, J Luster, MI AF Dong, WM Lewtas, J Luster, MI TI Role of endotoxin in tumor necrosis factor alpha expression from alveolar macrophages treated with urban air particles SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE alveolar macrophage; diesel particles; endotoxin; inflammatory cytokines; lung inflammation; urban air particles ID PULMONARY TOXICITY; LUNG INFLAMMATION; DUST EXPOSURE; GROWTH-FACTOR; COTTON DUST; POLLUTION; RELEASE; INHALATION; CYTOKINE; LIPOPOLYSACCHARIDE AB The effects of urban air and diesel particles on inflammatory cytokine gene expression, tumor necrosis factor alpha (TNF-alpha) in particular, were studied in rat alveolar macrophages. TNF-alpha, interleukin (IL)-1, IL-6, cytokine-induced neutrophil chemoattractant (CINC), and macrophage inflammatory protein (MIP)-2 gene expression and TNF-alpha secretion were increased in cells treated with 50 to 200 mu g/mL of urban air particles in a concentration-related manner. There was no cytokine induction by diesel particles at any of the concentrations tested. Cytokine expression was not related to reactive oxygen species since antioxidants, such as catalase, TMTU, or DMSO, had not effect on TNF-alpha secretion. However, cytokine induction by urban air particles was completely prevented by polymyxin B, an antibiotic capable of neutralizing bacterial lipopolysaccharide (LPS) activities. Furthermore, LPS was detected on the urban air particles, but not on diesel particle. These results suggest that activation of cytokine gene expression and secretion in rat alveolar macrophages by urban air particles is due to the presence of endotoxin on the particles. C1 US EPA, HUMAN STUDIES DIV, CHAPEL HILL, NC USA. NIOSH, TOXICOL & MOL BIOL BRANCH, MORGANTOWN, WV USA. RP Dong, WM (reprint author), NIEHS, ENVIRONM IMMUNOL & NEUROBIOL SECT, C1-04, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 48 TC 49 Z9 49 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD SEP-OCT PY 1996 VL 22 IS 5 BP 577 EP 592 DI 10.3109/01902149609046043 PG 16 WC Respiratory System SC Respiratory System GA VJ555 UT WOS:A1996VJ55500006 PM 8886760 ER PT J AU Varmus, H AF Varmus, H TI Untitled SO FASEB JOURNAL LA English DT Editorial Material RP Varmus, H (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1996 VL 10 IS 11 BP 1237 EP 1240 PG 4 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA VJ717 UT WOS:A1996VJ71700002 ER PT J AU Thorgeirsson, SS AF Thorgeirsson, SS TI Liver regeneration .9. Hepatic stem cells in liver regeneration SO FASEB JOURNAL LA English DT Article DE growth factors; liver stem cell biology; stem cell activation; hepatocytes; bile duct epithelial cells; liver parenchyma; oval cells; partial hepatectomy; proliferation; differentiation ID GROWTH-FACTOR-ALPHA; CHOLINE-DEFICIENT DIET; BILIARY EPITHELIAL-CELLS; ADULT-RAT LIVER; OVAL CELLS; CHEMICAL HEPATOCARCINOGENESIS; FETOPROTEIN EXPRESSION; MONOCLONAL-ANTIBODIES; C-KIT; DIFFERENTIATION AB The concept that the Liver contains epithelial cells that share some of the major properties of stem cells of the well-characterized, stem cell-fed lineages found in bone marrow, intestinal epithelium, and epidermis is now well supported, Nevertheless, the population dynamics of the major types of liver epithelial cells, hepatocytes, and bile epithelia display a striking difference from the population dynamics of the classic stem cell systems, The focus of this review is on recent studies of the activation and expansion of liver stem cells in vivo and the role these cells may play in regeneration of the liver. The requirement for a selective and sustained expression of growth factors during the early stages of stem cell activation is highlighted, In addition, results are presented supporting the hypothesis that after loss of liver mass, both the quiescent stem cells as well as the residual differentiated hepatocytes and bile duct epithelial cells are activated to proliferate, However, significant contribution of the stem cells to the regeneration process only occurs under circumstances in which the residual differentiated cells are functionally compromised and/or cannot proliferate. RP Thorgeirsson, SS (reprint author), NCI,NIH,EXPT CARCINOGENESIS LAB,DIV BASIC SCI,BLDG 37,ROOM 3C28,37 CONVENT DR MSC4255,BETHESDA,MD 20892, USA. NR 68 TC 235 Z9 253 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 1996 VL 10 IS 11 BP 1249 EP 1256 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA VJ717 UT WOS:A1996VJ71700004 PM 8836038 ER PT J AU Pennington, JAT AF Pennington, JAT TI Issues of food description SO FOOD CHEMISTRY LA English DT Article; Proceedings Paper CT 2nd International Food Data Base Conference on Food Composition Research - The Broader Context CY AUG 28-30, 1995 CL LAHTI, FINLAND ID INTERNATIONAL INTERFACE STANDARD; DATABASES AB Food names and descriptions identify and distinguish among foods listed in databases. Descriptive terms may be captured in free form with the food name and in faceted systems. The INFOODS Food Description System is faceted with free text. The International Interface (which includes LANGUAL) is a faceted system with standardized vocabulary. Faceted systems provide a checklist to fully describe foods, and they allow for retrievals and matching of foods among databases. On-line dictionaries can be used to clarify implicit and complex food names. Relevant descriptive information varies among foods and food types. Information about cooking methods, ingredients, recipes, cuisine and preparation location is important to fully define some foods. Sample descriptions (as opposed to food descriptions) identify the products analysed in the laboratory. Market share and default entries should be clearly identified. Pictures of foods (hard-copy or computerized) are useful for product identification. A universal system to describe foods will enhance the sharing and exchange of food composition data. Published by Elsevier Science Ltd C1 US FDA,WASHINGTON,DC 20204. RP Pennington, JAT (reprint author), NIH,BLDG 10,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0308-8146 J9 FOOD CHEM JI Food Chem. PD SEP PY 1996 VL 57 IS 1 BP 145 EP 148 DI 10.1016/0308-8146(96)00152-5 PG 4 WC Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Chemistry; Food Science & Technology; Nutrition & Dietetics GA VR298 UT WOS:A1996VR29800023 ER PT J AU Ahmed, AE Jacob, S Ghanayem, BI AF Ahmed, AE Jacob, S Ghanayem, BI TI Comparative disposition of acrylonitrile and methacrylonitrile: Quantitative whole-body autoradiographic studies in rats SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID 2-CYANOETHYLENE OXIDE; URINARY-EXCRETION; METABOLISM; MICE; GLUTATHIONE; TOXICITY; WORKERS; INVITRO; TISSUE; MECHANISM AB Following intravenous administration of an equimolar (0.216 mmol/kg) radioactive dose of acrylonitrile (2-[C-14]VCN, 11.5 mg/ kg) or methacrylonitrile (2-[C-14]MeVCN, 14.5 mg/kg), the tissue distribution, covalent interaction, and elimination were compared (at 5 min to 48 hr) in male Fischer 344 rats using whole-body autoradiography (WBA). Autoradiographs obtained from freeze-dried or acid-extracted sections of animals treated with 2-[C-14]VCN showed that radioactivity accumulated in the liver, lung, bone marrow, adipose tissues, kidney, gastrointestinal tract, and spleen. In animals treated with 2-[C-14]MeVCN, the respiratory tissues contained high levels of C-14 at an early period (5 min), while the gastrointestinal mucosa, adrenal cortex, liver, and kidney contained high levels of radioactivity at later periods (8, 24, and 48 hr). Quantitatively, lower uptake and irreversible interactions of C-14 were observed in autoradiographs of rats treated with 2-[C-14]MeVCN compared with those treated with 2-[C-14]VCN. Rats given 2-[C-14]VCN eliminated only 27% of administered radioactivity (exhaled air, urine, and feces), whereas rats treated with 2-[C-14]MeVCN eliminated, by all routes, 65% of the total radioactive dose. Both WBA and elimination studies indicated that 2-[C-14]VCN and/or its metabolites were rapidly distributed, extensively bound, and slowly eliminated from tissues. 2-[C-14]MeVCN and/or its metabolites, however, were rapidly distributed and eliminated, mostly via the lung. The study indicated that the substitution of a methyl group on the alpha-carbon of the alpha-beta unsaturated aliphatic nitrile VCN, to form MeVCN, imparted qualitative and quantitative differences in the disposition of these two compounds. (C) 1996 Society of Toxicology C1 UNIV TEXAS,MED BRANCH,DEPT PATHOL,GALVESTON,TX 77555. NIEHS,RES TRIANGLE PK,NC 27709. RP Ahmed, AE (reprint author), UNIV TEXAS,MED BRANCH,CTR CANC,PHARMACOKINET LAB,GALVESTON,TX 77555, USA. FU NIEHS NIH HHS [ES-01871] NR 48 TC 10 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1996 VL 33 IS 1 BP 49 EP 59 DI 10.1006/faat.1996.0142 PG 11 WC Toxicology SC Toxicology GA VF995 UT WOS:A1996VF99500007 PM 8812221 ER PT J AU Freeman, GB Dill, JA Johnson, JD Kurtz, PJ Parham, F Mathews, HB AF Freeman, GB Dill, JA Johnson, JD Kurtz, PJ Parham, F Mathews, HB TI Comparative absorption of lead from contaminated soil and lead salts by weanling fischer 344 rats SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID PHYSIOLOGICALLY-BASED MODELS; BONE-SEEKING ELEMENTS; LOW DIETARY CALCIUM; BIOAVAILABILITY; BLOOD; DISPOSITION; TOXICITY; KINETICS; ACETATE AB A 44-day dosed feed study was performed to compare the bioavailability of lead from contaminated soil versus two lead salts and the effect of soil on gastrointestinal absorption of ingested lead. Male Fischer rats (approximately 4 weeks of age) received lead, 17, 42, or 127 ppm, in the form of lead acetate, lead sulfide, lead-contaminated soil, or combinations thereof in the diet for 7, 15, or 44 days, Control soil was added to the diets of some animals to determine how it might alter lead bioavailability, Blood Delta-aminolevulinic acid dehydratase (Delta-ALAD) and blood, bone, kidney, and liver lead were determined in groups of animals at each time-point, Blood Delta-ALAD was inhibited in a dose-dependent manner and to the greatest degree in the lead acetate and lead acetate/control soil groups, followed by the lead sulfide and lead-contaminated soil groups, Bone and tissue lead levels increased in a dose-dependent manner and were greatest in animals receiving lead acetate and significantly less in animals receiving lead sulfide and lead-contaminated soil. Blood lead levels were generally greatest by 7 days and stabilized at lower levels thereafter, Bone lead concentration-time patterns did not demonstrate the biphasic change seen with tissues and continued to increase in most treatment groups through the course of the study, The presence of soil in the diet clearly attenuated the absorption of lead acetate, but had little effect on the absorption of lead sulfide. Results of these studies confirm previous observations that lead absorption is highly dependent on the form of lead ingested and the matrix in which it is ingested, More important, these studies demonstrate that lead in soil may be significantly less available than estimated by current default assumptions and that the presence of soil may decrease the availability of lead from lead salts on which the default assumptions are based. Results presented here also demonstrate that the weanling rat may represent an appropriate model that could be used to obtain relatively rapid and economical estimates of the availability of lead in complex matrices such as soil. (C) 1996 Society of Toxicology. C1 PACIFIC NW LAB, RICHLAND, WA 99352 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. RP Freeman, GB (reprint author), BATTELLE MEM INST, 505 KING AVE, COLUMBUS, OH 43210 USA. NR 41 TC 34 Z9 37 U1 0 U2 10 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD SEP PY 1996 VL 33 IS 1 BP 109 EP 119 DI 10.1006/faat.1996.0148 PG 11 WC Toxicology SC Toxicology GA VF995 UT WOS:A1996VF99500013 PM 8812247 ER PT J AU Drake, JW Crow, JF AF Drake, JW Crow, JF TI Recollections of Howard Temin (1934-1994) SO GENETICS LA English DT Item About an Individual C1 UNIV WISCONSIN,GENET LAB,MADISON,WI 53706. RP Drake, JW (reprint author), NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 5 Z9 5 U1 2 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 1996 VL 144 IS 1 BP 1 EP 6 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VE252 UT WOS:A1996VE25200001 PM 8878668 ER PT J AU Goldman, ASH Lichten, M AF Goldman, ASH Lichten, M TI The efficiency of meiotic recombination between dispersed sequences in Saccharomyces cerevisiae depends upon their chromosomal location SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; GENE CONVERSION; HETERODUPLEX DNA; YEAST; MEIOSIS; MOLECULES; FREQUENCY; IDENTIFICATION; INITIATION; KARYOTYPE AB To examine constraints imposed on meiotic recombination by homologue pairing, we measured the frequency of recombination between mutant alleles of the ARG4 gene contained in pBR322-based inserts. Inserts were located at identical loci on homologues (allelic recombination) or at different loci on either homologous or heterologous chromosomes (ectopic recombination). Ectopic recombination between interstitially located inserts on heterologous chromosomes had an efficiency of 6-12% compared to allelic recombination. By contrast, ectopic recombination between interstitial inserts located on homologues had relative efficiencies of 47-99%. These finding suggest that when meiotic ectopic recombination occurs, homologous chromosomes are already colocalized. The efficiency of ectopic recombination between inserts on homologues decreased as the physical distance between insert sites was increased. This result is consistent with the suggestion that during meiotic recombination, homologues are not only close to each other, but also are aligned end to end. Finally, the efficiency of ectopic recombination between inserts near telomeres (within 16 kb) was significantly greater than that observed with inserts > 50 kb from the nearest telomere. Thus, at the time of recombination, there may be a special relationship between the ends of chromosomes not shared with interstitial regions. RP Goldman, ASH (reprint author), NCI,NIH,DIV BASIC SCI,BIOCHEM LAB,BLDG 37 ROOM 4D11,37 CONVENT DR MSC 4255,BETHESDA,MD 20892, USA. NR 42 TC 98 Z9 98 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 1996 VL 144 IS 1 BP 43 EP 55 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA VE252 UT WOS:A1996VE25200005 PM 8878672 ER PT J AU Perry, WL Nakamura, T Swing, DA Secrest, L Eagleson, B Hustad, CM Copeland, NG Jenkins, NA AF Perry, WL Nakamura, T Swing, DA Secrest, L Eagleson, B Hustad, CM Copeland, NG Jenkins, NA TI Coupled site-directed mutagenesis/transgenesis identifies important functional domains of the mouse agouti protein SO GENETICS LA English DT Article ID STIMULATING-HORMONE-RECEPTOR; HUMAN HOMOLOG; ECTOPIC EXPRESSION; N-GLYCOSYLATION; YELLOW MICE; GENE; MUTATIONS; CLONING; LOCUS; SECRETION AB The agouti locus encodes a novel paracrine signaling molecule containing a signal sequence, an N-linked glycosylation site, a central lysine-rich basic domain, and a C-terminal tail containing 10 cysteine (Cys) residues capable of forming five disulfide bonds. When overexpressed, agouti causes a number of pleiotropic effects including yellow coat and adult-onset obesity. Numerous studies suggest that agouti causes yellow coat color by antagonizing the binding of alpha-melanocyte-stimulating hormone (alpha-MSH) to the alpha-MSH-(melanocortin-1) receptor. With the goal of identifying functional domains of agouti important for its diverse biological activities, we have generated 14 agouti mutations by in vit ro site-directed mutagenesis and analyzed these mutations in transgenic mice for their effects on coat color and obesity. These studies demonstrate that the signal sequence, the N-linked glycosylation site, and the C-terminal Cys residues are important for full biological activity, while at least a portion of the lysine-rich basic domain is dispensable for normal function. They also show that the same functional domains of agouti important in coat color determination are important for inducing obesity, consistent with the hypothesis that agouti induces obesity by antagonizing melanocortin binding to other melanocortin receptors. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 53 TC 43 Z9 44 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 1996 VL 144 IS 1 BP 255 EP 264 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA VE252 UT WOS:A1996VE25200024 PM 8878691 ER PT J AU Boguski, M Chakravarti, A Gibbs, R Green, E Myers, RM AF Boguski, M Chakravarti, A Gibbs, R Green, E Myers, RM TI The end of the beginning: The race to begin human genome sequencing SO GENOME RESEARCH LA English DT Editorial Material C1 CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. BAYLOR COLL MED,HOUSTON,TX 77030. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. STANFORD UNIV,SCH MED,STANFORD,CA 94305. RP Boguski, M (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD SEP PY 1996 VL 6 IS 9 BP 771 EP 772 DI 10.1101/gr.6.9.771 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VJ575 UT WOS:A1996VJ57500001 PM 8889545 ER PT J AU Makalowski, W Zhang, JH Boguski, MS AF Makalowski, W Zhang, JH Boguski, MS TI Comparative analysis of 1196 orthologous mouse and human full-length mRNA and protein sequences SO GENOME RESEARCH LA English DT Article ID 3' UNTRANSLATED REGION; Y-CHROMOSOME; CDNA CLONE; GENE; DNA; EXPRESSION; EVOLUTION; FAMILY; ALIGNMENT; DIVERSITY AB A large set of mRNA and encoded protein sequences, from orthologous murine and human genes, was compiled to analyze statistical, biological, and evolutionary properties of coding and noncoding transcribed sequences. Protein sequence conservation varied between 36% and 100% identity, with an average value of 85%. The average degree of nucleotide sequence identity for the corresponding coding sequences was also similar to 85%, whereas 5' and 3' untranslated regions (UTRs) were less conserved, with aligned identities of 67% and 69%, respectively. For some mouse and human genes, nucleotide sequences are more highly conserved than the encoded protein sequences. A subset of 32 sequences, consisting of only mouse/human protein pairs for which the human sequence represents a positionally cloned disease gene, had properties very similar to the larger data set, suggesting that our data are representative of the genome as a whole. With respect to sequence conservation, two interesting outliers are the breast cancel (BRCA1) gene product and the testis-determining factor (SRY), both of which display among the lowest degrees of sequence identity. The occurrence of both introns and repetitive elements (e.g., Alu, B1) in 5' and 3' UTRs was also studied. These results provide one benchmark for the ''comparative genomics'' of mice and humans, with practical implications for the cross-referencing, of transcript maps. Also, they should prove useful in estimating the additional sampling diversity provided by mouse EST sequencing projects designed to complement the existing human cDNA collection. RP Makalowski, W (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BETHESDA,MD 20894, USA. RI Makalowski, Wojciech/I-2843-2016 NR 45 TC 162 Z9 169 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD SEP PY 1996 VL 6 IS 9 BP 846 EP 857 DI 10.1101/gr.6.9.846 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA VJ575 UT WOS:A1996VJ57500007 PM 8889551 ER PT J AU Bertuzzi, S Sheng, HZ Copeland, NG Gilbert, DJ Jenkins, NA Taira, M Dawid, IB Westphal, H AF Bertuzzi, S Sheng, HZ Copeland, NG Gilbert, DJ Jenkins, NA Taira, M Dawid, IB Westphal, H TI Molecular cloning, structure, and chromosomal localization of the mouse LIM/homeobox gene Lhx5 SO GENOMICS LA English DT Article ID CYSTEINE-RICH PROTEIN; LIM-DOMAIN; CAENORHABDITIS-ELEGANS; DNA STRUCTURES; DROSOPHILA; HOMEODOMAIN; SEQUENCES; BINDING; MEMBER; FAMILY AB Lhx5, the mouse ortholog of the Xenopus Xlim-5, is a LIM/homeobox gene expressed in the central nervous system during both embryonic development and adulthood. During development its domain of expression is mainly localized at the most anterior portion of the neural tube, and it precedes the morphological differentiation of the forebrain; for this reason we believe that Lhx5 could play an important role in forebrain patterning. Here we present the structural organization and the chromosomal localization of the Lhx5 gene. The gene is composed of five exons spanning more than 10 kb of genomic sequence. The first and second LIM domains are encoded by the first and second exon, while the codons of the homeobox are split between the third and the fourth exons. The structure of Lhx5 is similar to that of other LIM/homeodomain proteins, Lhx1/lim1 and Lhx3/lim3, but differs from that of of her LIM genes, such as mec3 and LMO1/Rbtn1, in which the codons for the LIM domains are interrupted by introns. We have mapped Lhx5 to the central region of mouse chromosome 5. (C) 1996 Academic Press, Inc. C1 NICHHD,LAB MAMMALIAN GENES & DEV,NIH,BETHESDA,MD 20892. NICHHD,GENET MOL LAB,NIH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 38 TC 19 Z9 20 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 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1996 VL 36 IS 2 BP 234 EP 239 DI 10.1006/geno.1996.0458 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VH187 UT WOS:A1996VH18700002 PM 8812449 ER PT J AU Ding, YP Remmers, EF Du, Y Longman, RE Goldmuntz, EA Zha, HB Kotake, S Cannon, GW Griffiths, MM Wilder, RL AF Ding, YP Remmers, EF Du, Y Longman, RE Goldmuntz, EA Zha, HB Kotake, S Cannon, GW Griffiths, MM Wilder, RL TI Genetic maps of polymorphic DNA loci on rat chromosome 1 SO GENOMICS LA English DT Article ID SINGLE LINKAGE GROUP; MICROSATELLITE MARKERS; FORM; CONSERVATION; MOUSE AB Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome I were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes, Six markers for live genes, gamma-aminobutyric acid receptor beta 3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor beta 1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that a large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. (C) 1996 Academic Press, Inc. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,NIH,BETHESDA,MD 20892. UNIV UTAH,DIV RHEUMATOL,SALT LAKE CITY,UT 84148. VET AFFAIRS MED CTR,RES SERV,SALT LAKE CITY,UT 84148. NR 37 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 1 PY 1996 VL 36 IS 2 BP 320 EP 327 DI 10.1006/geno.1996.0468 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VH187 UT WOS:A1996VH18700012 PM 8812459 ER PT J AU Takenoshita, S Hagiwara, K Nagashima, M Gemma, A Bennett, WP Harris, CC AF Takenoshita, S Hagiwara, K Nagashima, M Gemma, A Bennett, WP Harris, CC TI The genomic structure of the gene encoding the human transforming growth factor beta type II receptor (TGF-beta RII) SO GENOMICS LA English DT Article ID MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; CARCINOMA-CELLS; MUTATIONS; COLON; INHIBITION; EXPRESSION; PROTEIN; CLONING; KINASE AB The genomic structure of the human transforming growth factor-beta type II receptor gene (TGF-beta RII) was determined by two PCR-based methods, the ''long distance sequencer'' method and the ''promoter finder'' method. Genomic fragments containing exons and adjacent introns were amplified by PCR, and the nucleotide sequences were determined by direct sequencing and subcloning sequencing. The TGF-beta RII protein is encoded by 567 codons in 7 exons, This is the first report about the genomic structure of a gene that belongs to the serine/threonine kinase type II receptor subfamily. Knowledge of the genomic structure of the TGF-beta RII gene will facilitate investigation of the TGF-beta signaling pathway in normal human cells and of the aberrations occurring during carcinogenesis. (C) 1996 Academic Press, Inc. C1 NCI,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 18 TC 36 Z9 40 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 SEP 1 PY 1996 VL 36 IS 2 BP 341 EP 344 DI 10.1006/geno.1996.0471 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA VH187 UT WOS:A1996VH18700015 PM 8812462 ER PT J AU Johansen, C Chow, WH Jorgensen, T Mellemkjaer, L Engholm, G Olsen, JH AF Johansen, C Chow, WH Jorgensen, T Mellemkjaer, L Engholm, G Olsen, JH TI Risk of colorectal cancer and other cancers in patients with gall stones SO GUT LA English DT Article DE gall stones; cholecystectomy; obesity; colorectal cancer ID FECAL BILE-ACIDS; GALLBLADDER-DISEASE; LARGE BOWEL; CHOLECYSTECTOMY; GALLSTONES; CARCINOMA; CHOLELITHIASIS; ASSOCIATION; COHORT; COLON AB Background-The occurrence of gall stones has repeatedly been associated with an increased risk for cancer of the colon, but risk associated with cholecystectomy remains unclear. Aims-To evaluate the hypothesis in a nationwide cohort of more than 40 000 gall stone patients with complete follow up including information of cholecystectomy and obesity. Patients-in the population based study described here, 42 098 patients with gall stones in 1977-1989 were identified in the Danish Hospital Discharge Register. Methods-These patients were linked to the Danish Cancer Registry to assess their risks for colorectal and other cancers during follow up to the end of 1992. Results-The analysis showed a modest increase in the number of cancers at all sites combined (n=3940; RR, 1.07; 95% confidence intervals (CI), 1.0 to 1.1). A weak association was found for cancer of the colon (n=360; RR, 1.09; 95% CI 1.0 to 1.2), which remained unchanged when analysed by sex, anatomical subsite, and duration of follow up. Multivariate analysis with adjustment for cholecystectomy and clinically defined obesity did not change these estimates to any significant extent. Excess risks were found for cancers of the pancreas and the small intestine. A non-significant increased risk for breast cancer was seen in women five years after initial discharge for gall stones. Conclusion-A borderline significant association was seen between gall stones and cancer of the colon, and for cancer of pancreas and small intestine as well as for breast cancer in women. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,DIV CANC ETIOL,BETHESDA,MD 20892. UNIV COPENHAGEN,BISPEBJERG HOSP,SURG DEPT K,COPENHAGEN,DENMARK. RP Johansen, C (reprint author), DANISH CANC SOC,DIV CANC EPIDEMIOL,STRAND BLVD 49,DK-2100 COPENHAGEN O,DENMARK. NR 32 TC 32 Z9 33 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0017-5749 J9 GUT JI Gut PD SEP PY 1996 VL 39 IS 3 BP 439 EP 443 DI 10.1136/gut.39.3.439 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA VL303 UT WOS:A1996VL30300018 PM 8949651 ER PT J AU Meslin, EM AF Meslin, EM TI Final report: White House Advisory Committee on Human Radiation Experiments SO HASTINGS CENTER REPORT LA English DT Book Review RP Meslin, EM (reprint author), NIH,NATL CTR HUMAN GENOME RES,ELSI,RES PROGRAM,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD SEP-OCT PY 1996 VL 26 IS 5 BP 34 EP 36 DI 10.2307/3528469 PG 3 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA VM226 UT WOS:A1996VM22600018 PM 11644871 ER PT J AU SansonFisher, R Redman, S Hancock, L Halpin, S Clarke, P Schofield, M Burton, R Hensley, M Gibberd, R Reid, A Walsh, R Girgis, A Burton, L McClintock, A Carter, R Donner, A Green, S AF SansonFisher, R Redman, S Hancock, L Halpin, S Clarke, P Schofield, M Burton, R Hensley, M Gibberd, R Reid, A Walsh, R Girgis, A Burton, L McClintock, A Carter, R Donner, A Green, S TI Developing methodologies for evaluating community-wide health promotion SO HEALTH PROMOTION INTERNATIONAL LA English DT Article DE community; evaluation; health promotion ID NATIONAL-CANCER-INSTITUTE; SAMPLE-SIZE REQUIREMENTS; STANFORD 5-CITY PROJECT; CLUSTER RANDOMIZATION; INTERVENTION TRIALS; DISEASE; DESIGNS; SMOKING; MODEL AB There has been growing recognition that health promotion programs which target whole communities are more likely to be effective in changing health behaviour. However, studies evaluating the impact of communitywide health promotion programs rarely use adequate methodology. Randomised control trials where multiple whole communities are randomly assigned to control and intervention groups are optimum if evaluators hope to validly attribute changes in health behaviour to the intervention. However, such trials present a number of difficulties including cost and feasibility limitations and the evolving nature of statistical techniques. This paper proposes applying a fairly well-accepted phased evaluation approach to the evaluation of community participation programs, using three defined phases. Phase I consists of small-scale studies to develop the measures and assess acceptability and feasibility of the intervention; Phase 2 consists of studies in a small number of communities designed to trial the intervention in the real world; Phase 3 studies use an appropriate number of entire communities to provide valid evidence of efficacy of the intervention. It is suggested that criteria be resolved to identify adequate studies at each stage and that advantages and limitations of Phase I and 2 studies be clearly identified. The paper describes the major design, sampling and analysis considerations for a Phase 3 study. C1 UNIV NEWCASTLE,FAC MED & HLTH SCI,WALLSEND,NSW 2287,AUSTRALIA. AUSTRALIAN INST HLTH,CANBERRA,ACT,AUSTRALIA. NSW CANC COUNCIL,SYDNEY,NSW,AUSTRALIA. UNIV WESTERN ONTARIO,LONDON,ON N6A 3K7,CANADA. NCI,BETHESDA,MD 20892. RI parkinson, lynne/C-1949-2008; Girgis, Afaf/G-8660-2011; Schofield, Margot/B-6771-2008; OI Girgis, Afaf/0000-0003-4101-4006; Schofield, Margot/0000-0003-0543-5751; Clarke, Philip/0000-0002-7555-5348; Parkinson, Lynne/0000-0001-9433-9555 NR 36 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0957-4824 J9 HEALTH PROMOT INT JI Health Promot. Int. PD SEP PY 1996 VL 11 IS 3 BP 227 EP 236 DI 10.1093/heapro/11.3.227 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VH921 UT WOS:A1996VH92100009 ER PT J AU Mizuta, K Iwasa, KH Tachibana, M Benos, DJ Lim, DJ AF Mizuta, K Iwasa, KH Tachibana, M Benos, DJ Lim, DJ TI Amiloride-sensitive Na+ channel-like immunoreactivity in the luminal membrane of some non-sensory epithelia of the inner ear (vol 88, pg 199, 1995) SO HEARING RESEARCH LA English DT Correction, Addition RP Mizuta, K (reprint author), NIH,BLDG 9,9 CTR DR,MSC 0922,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD SEP 1 PY 1996 VL 98 IS 1-2 BP 180 EP 180 DI 10.1016/0378-5955(96)00025-1 PG 1 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA VH191 UT WOS:A1996VH19100018 ER PT J AU Jacobowitz, DM Winsky, L DeteraWadleigh, SD AF Jacobowitz, DM Winsky, L DeteraWadleigh, SD TI Cellular expression of MAP 2 kinase in rat brain SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; ELECTROCONVULSIVE SHOCK; STIMULATED PROTEIN; ERK1; INSULIN; HIPPOCAMPUS; FIBROBLASTS; ASSOCIATION; RECEPTOR AB The cellular localization of microtubule-associated protein (MAP) 2 kinase mRNA in rat brain was examined by in situ hybridization histochemistry using a synthetic oligonucleotide probe. MAP 2 kinase was expressed in both neuronal and non-neuronal cells. Areas of high density of mRNA label by the MAP 2 kinase probe appeared to be associated with high cellular packing density. Thus, MAP 2 kinase expression was particularly high in regions such as the locus coeruleus, the piriform cortex, the dentate gyrus granule cell layer, pyramidal cells of the hippocampus, the mitral cells of the olfactory bulb, and the large motor neurons of the V and VII nerves. This apparent ubiquitous distribution suggests an important role of MAP 2 kinase in the cellular functions in most cells of the adult brain. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. RP Jacobowitz, DM (reprint author), NIMH,CLIN SCI LAB,ROOM 3D-48,10 CTR DR MSC 1266,BETHESDA,MD 20892, USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-5564 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD SEP PY 1996 VL 106 IS 3 BP 303 EP 310 DI 10.1007/s004180050046 PG 8 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA VL054 UT WOS:A1996VL05400005 PM 8897071 ER PT J AU Giollant, M Bertrand, S Verrelle, P Tchirkov, A duManoir, S Ried, T Mornex, F Dore, JF Cremer, T Malet, P AF Giollant, M Bertrand, S Verrelle, P Tchirkov, A duManoir, S Ried, T Mornex, F Dore, JF Cremer, T Malet, P TI Characterization of double minute chromosomes' DNA content in a human high grade astrocytoma cell line by using comparative genomic hybridization and fluorescence in situ hybridization SO HUMAN GENETICS LA English DT Article ID MOLECULAR CYTOGENETIC ANALYSIS; HUMAN GLIOMAS; SOLID TUMORS; INSITU HYBRIDIZATION; AMPLIFICATION; LOSSES; GAINS AB The presence of double minute chromosomes (dmin) in cancer cells is known to be correlated with gene amplifications. In human high grade astrocytomas or glioblastomas, about 50% of cytogenetically characterized cases display dmin. G5 is a cell line which has been established from a human glioblastoma containing multiple dmin. In order to identify the DNA content of these dmin, three techniques were successively used: conventional cytogenetic analysis, comparative genomic hybridization (CGH), and fluorescent in situ hybridization (FISH). The karyotype of G5 cells showed numerical chromosome changes (hypertriploidy), several marker chromosomes, and multiple dmin. CGH experiments detected two strong DNA amplification areas located in 9p21-22 and 9p24, as well as an underrepresentation of chromosomes 6, 10, 11, 13, 14, and 18q. By using FISH with a chromosome 9-specific painting probe to metaphase chromosomes of the G5 cell line, dmin were shown to contain DNA sequences originating from chromosome 9. This study demonstrates the usefulness of a combination of classical karyotyping, CGH, and FISH to identify the chromosomal origin of amplified DNA sequences in dmin. C1 FAC MED,LAB HISTOL EMBRYOL & CYTOGENET,F-63001 CLERMONT FERRAN,FRANCE. CTR LEON BERARD,INSERM,F-69373 LYON,FRANCE. CTR JEAN PERRIN,CLERMONT FERRAN,FRANCE. INSERM U71,CLERMONT FERRAN,FRANCE. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV HEIDELBERG,INST ANTHROPOL & HUMAN GENET,D-6900 HEIDELBERG,GERMANY. NR 20 TC 19 Z9 19 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 1996 VL 98 IS 3 BP 265 EP 270 DI 10.1007/s004390050205 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA VA115 UT WOS:A1996VA11500003 PM 8707292 ER PT J AU Glavac, D Neumann, HPH Wittke, C Jaenig, H Masek, O Streicher, T Pausch, F Engelhardt, D Plate, KH Hofler, H Chen, F Zbar, B Brauch, H AF Glavac, D Neumann, HPH Wittke, C Jaenig, H Masek, O Streicher, T Pausch, F Engelhardt, D Plate, KH Hofler, H Chen, F Zbar, B Brauch, H TI Mutations in the VHL tumor suppressor gene and associated lesions in families with von Hippel-Lindau disease from central Europe SO HUMAN GENETICS LA English DT Article ID GERMLINE MUTATIONS; SOMATIC MUTATIONS; IDENTIFICATION; PHENOTYPE; CARCINOMA; SYSTEM; DNA AB von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome predisposing to retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma and pancreatic tumors. Clinically two types of the disease can be distinguished: VHL type 1 (without pheochromocytoma) and VHL type 2 (with pheochromocytoma). We report VHL germline mutations and trends in phenotypic variation in families from central Europe. We identified 28 mutations in 53/65 (81.5%) families with 18 (64%) mutations being unique to this population. Whereas types and distribution of mutations as well as a strong correlation of missense mutations with the VHL 2 phenotype were similar to those identified in other populations, these families have provided new insights into the molecular basis for variability in the VHL 2 phenotype. Seven different missense mutations in exons 1 and 3 varied in their biological consequences from a minimal VHL 2 phenotype with pheochromocytoma only to a full VHL 2 phenotype with RCC and pancreatic lesion. These findings contribute to a better understanding of the fundamental mechanisms of VHL disease and its phenotypic variability. Further, we have provided rapid VHL screening for the families in central Europe, which has resulted in improved diagnosis and clinical management. C1 UNIV WOMANS CLIN EPPENDORF, LAB ONCOL, D-20246 HAMBURG, GERMANY. TECH UNIV MUNICH, INST PATHOL, LAB MOL PATHOL, D-81675 MUNICH, GERMANY. INST PATHOL, FAC MED, LAB MOL PATHOL, SL-61115 LJUBLJANA, SLOVENIA. UNIV FREIBURG, DIV NEPHROL & HYPERTENS, DEPT MED, D-79106 FREIBURG, GERMANY. ZLIN HOSP, CZ-76275 ZLIN, CZECH REPUBLIC. BOYNICE HOSP, SK-97201 BOJNICE, SLOVAKIA. UNIV MUNICH, DIV ENDOCRINOL, DEPT MED, D-81366 MUNICH, GERMANY. UNIV FREIBURG, DEPT NEUROPATHOL, NEUROCTR, D-79106 FREIBURG, GERMANY. PROGRAM RESOURCES SCI APPLICAT INT CORP, NATL CANC INST, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES FACIL, IMMUNOBIOL LAB, FREDERICK, MD 21701 USA. NR 21 TC 82 Z9 84 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD SEP PY 1996 VL 98 IS 3 BP 271 EP 280 DI 10.1007/s004390050206 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA VA115 UT WOS:A1996VA11500004 PM 8707293 ER PT J AU Sidhar, SK Clark, J Gill, S Hamoudi, R Crew, AJ Gwilliam, R Ross, M Linehan, WM Birdsall, S Shipley, J Cooper, CS AF Sidhar, SK Clark, J Gill, S Hamoudi, R Crew, AJ Gwilliam, R Ross, M Linehan, WM Birdsall, S Shipley, J Cooper, CS TI The t(X;l)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene SO HUMAN MOLECULAR GENETICS LA English DT Article ID HELIX-LOOP-HELIX; TUMOR-SUPPRESSOR GENE; CHROMOSOMAL TRANSLOCATIONS; ONCOGENIC CONVERSION; ACTIVATION DOMAINS; FUSION; CYTOGENETICS; BREAKPOINT; ENHANCER; ADENOCARCINOMA AB The specific chromosomal translocation t(X;1)(p11,2;q21,2) has been observed in human papillary renal cell carcinomas, In this study we demonstrated that this translocation results in the fusion of a novel gene designated PRCC at 1q21,2 to the TFE3 gene at Xp11,2, TFE3 encodes a member of the basic helix-loop-helix (bHLH) family of transcription factors originally identified by its ability to bind to mu E3 elements in the immunoglobin heavy chain intronic enhancer, The translocation is predicted to result in the fusion of the N-terminal region of the PROC protein, which includes a proline-rich domain, to the entire TFE3 protein, Notably the generation of the chimaeric PRCC-TFE3 gene appears to be accompanied by complete loss of normal TFE3 transcripts, This work establishes that the disruption of transcriptional control by chromosomal translocation is important in the development of kidney carcinoma in addition to its previously established role in the aetiology of sarcomas and leukaemias. C1 INST CANC RES,HADDOW LABS,MOL CARCINOGENESIS SECT,SUTTON SM2 5NG,SURREY,ENGLAND. INST CANC RES,HADDOW LABS,CELL BIOL & EXPT PATHOL SECT,SUTTON SM2 5NG,SURREY,ENGLAND. INST CANC RES,HADDOW LABS,CANC GENE CLONING LAB,SUTTON SM2 5NG,SURREY,ENGLAND. SANGER CTR,CAMBRIDGE CB10 1RQ,ENGLAND. NCI,UROL ONCOL SECT,BETHESDA,MD 20892. ST VINCENT HOSP,GARVAN INST,SYDNEY,NSW,AUSTRALIA. FU Wellcome Trust NR 37 TC 157 Z9 165 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD SEP PY 1996 VL 5 IS 9 BP 1333 EP 1338 DI 10.1093/hmg/5.9.1333 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA VF767 UT WOS:A1996VF76700016 PM 8872474 ER PT J AU EmmertBuck, MR AF EmmertBuck, MR TI Cathepsin D and prognosis in breast cancer: One piece of a larger puzzle? SO HUMAN PATHOLOGY LA English DT Editorial Material ID IMMUNOHISTOCHEMISTRY; EXPRESSION; CARCINOMA; CELLS RP EmmertBuck, MR (reprint author), NCI,PATHOL LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 23 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1996 VL 27 IS 9 BP 869 EP 871 DI 10.1016/S0046-8177(96)90211-7 PG 3 WC Pathology SC Pathology GA VG735 UT WOS:A1996VG73500001 PM 8816879 ER PT J AU Przygodzki, RM Moran, CA Suster, S Khan, MA Swalsky, PA Bakker, A Koss, MN Finkelstein, SD AF Przygodzki, RM Moran, CA Suster, S Khan, MA Swalsky, PA Bakker, A Koss, MN Finkelstein, SD TI Primary mediastinal and testicular seminomas: A comparison of K-ras-2 gene sequence and p53 immunoperoxidase analysis of 26 cases SO HUMAN PATHOLOGY LA English DT Article DE mediastinal seminoma; testicular seminoma; p53 immunohistochemistry; K-ras; polymerase chain reaction; sequence analysis; topographic genotyping ID GERM-CELL TUMORS; LUNG-CANCER; MUTATIONS; EXPRESSION; SUPPRESSOR; PROTEIN AB Primary mediastinal seminomas (MS) are rare tumors. Histologically, they are similar to their counterpart in the gonads. The survival rate has varied from 50% to 85% in different series. However, large series of these tumors primarily in the mediastinum are lacking. At the molecular level, a few reports document K-ras mutations in up to 40% of testicular seminomas (TS), localized predominantly to codon 12. Reports on TS p53 immunohistochemistry (IHC) range from negative to overexpression approaching 90% of cases, and by sequence analysis one small series showed a 23% mutation rate. To date, no analyses have been performed for either K-ras mutations or p53 immunohistochemical expression in primary MS. The authors studied 13 cases each of primary MS and TS from archival formalin-fixed, paraffin-embedded sections in which adequate tumor sampling and clinical history, including serological studies, and histological, histochemical, and LHC staining, were performed to confirm the diagnosis. p53 immunoperoxidase staining using citrate buffer/microwave antigen retrieval was performed. Topographic genotyping was performed on 5-mu m-thick tissue sections up to 17 years old, in which the neoplastic cell population was sampled. Additionally, multiple sites within a given cases were sampled to determine clonality of the tumor cell population. Polymerase chain reaction and subsequent sequence analysis of the K-ras-2 exon-1 gene was used for mutation analysis. Focal weak staining with p53 MC was observed in 4 of 13 (31%) MS and 10 of 13 (77%) TS cases, with all remaining cases being negative (P < .05). Only one MS case (8%) showed K-ras mutation (codon 13 GGC > GAG; glycine > aspartate), which is in contrast to 2 of the TS cases (15%), showing codon 12 mutations. All the remaining cases were wild type. Therefore, primary mediastinal seminomas appear to be different in their K-ras sequence and p53 immunostain profile from TS. Codon mutation type may be useful in determining primary versus metastatic origin of a mediastinal seminoma. C1 ARMED FORCES INST PATHOL,DEPT PULM & MEDIASTINAL PATHOL,WASHINGTON,DC 20306. NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. MT SINAI MED CTR,DEPT PATHOL & LAB MED,MIAMI BEACH,FL 33140. UNIV PITTSBURGH,MED CTR,DEPT PATHOL,PITTSBURGH,PA. OI Przygodzki, Ronald/0000-0002-1238-262X NR 24 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD SEP PY 1996 VL 27 IS 9 BP 975 EP 979 DI 10.1016/S0046-8177(96)90227-0 PG 5 WC Pathology SC Pathology GA VG735 UT WOS:A1996VG73500017 PM 8816895 ER PT J AU Parmer, RJ Le, H Kailasam, MT Wilson, AF OConnor, DT AF Parmer, RJ Le, H Kailasam, MT Wilson, AF OConnor, DT TI Impaired baroreflex sensitivity is associated with blood pressure elevation and dyslipidemia in families with essential hypertension SO HYPERTENSION LA English DT Meeting Abstract C1 VET ADM MED CTR,DEPT MED,SAN DIEGO,CA 92161. VET ADM MED CTR,CTR GENET MOL,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NATL CTR HUMAN GENOME RES,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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1996 VL 28 IS 3 BP 2 EP 2 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VF997 UT WOS:A1996VF99700032 ER PT J AU Zeng, GY Quon, MJ AF Zeng, GY Quon, MJ TI Direct measurement of nitric oxide from endothelial cells in response to insulin SO HYPERTENSION LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 1996 VL 28 IS 3 BP 57 EP 57 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VF997 UT WOS:A1996VF99700084 ER PT J AU Wange, RL Samelson, LE AF Wange, RL Samelson, LE TI Complex complexes: Signaling at the TCR SO IMMUNITY LA English DT Review ID CELL ANTIGEN-RECEPTOR; PROTEIN-TYROSINE KINASE; SEVERE COMBINED IMMUNODEFICIENCY; C-CBL PROTOONCOGENE; TANDEM SH2 DOMAINS; JURKAT T-CELLS; ZETA-CHAIN; PHOSPHATIDYLINOSITOL 3'-KINASE; ACTIVATION MOTIFS; ADAPTER PROTEIN RP Wange, RL (reprint author), NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892, USA. NR 80 TC 419 Z9 424 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 1996 VL 5 IS 3 BP 197 EP 205 DI 10.1016/S1074-7613(00)80315-5 PG 9 WC Immunology SC Immunology GA VJ797 UT WOS:A1996VJ79700002 PM 8808675 ER PT J AU Saxena, RK Collins, GD Chrest, JF Adler, WH AF Saxena, RK Collins, GD Chrest, JF Adler, WH TI Bcl-2 transfection protects Hut78 cell line from different types of cytotoxic effector cells SO IMMUNOLOGY LETTERS LA English DT Article DE Bcl-2 transfection; Hut78 cell line; cytoxic effector cells ID MEDIATED CYTOTOXICITY; MEMBRANE PROTEIN; DEATH; PERFORIN; PATHWAYS AB The human T lymphoma cell line Hut78 was transfected with Bc1-2 gene or with control G418 Neomycin resistance-conferring plasmid. Bc1-2 transfected and Neomycin selected Hut78 cells expressed about ten-fold greater Bcl-2 protein than the neo-transfected controls. Susceptibility of Bc1-2-transfected Hut78 cells to human NK cells, human mixed lymphocyte reaction-generated cytotoxic effector cells, and mouse cytotoxic spleen cells generated by immunization with Hut78 cells was examined. In all systems tested, Bc1-2-transfected Hut78 target cells were significantly less susceptible to lysis than the neo-transfected control target cells, These results suggest that in Hut78 cells, Bc1-2 gene product may confer partial resistance to different types of cytotoxic effector mechanisms. C1 NIA,GRC,CLIN IMMUNOL SECT,NIA,BALTIMORE,MD. RP Saxena, RK (reprint author), JAWAHARLAL NEHRU UNIV,SCH LIFE SCI,NEW DELHI 110067,INDIA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD SEP PY 1996 VL 52 IS 2-3 BP 95 EP 98 DI 10.1016/0165-2478(96)02590-4 PG 4 WC Immunology SC Immunology GA VP090 UT WOS:A1996VP09000006 PM 8905402 ER PT J AU Tine, JA Lanar, DE Smith, DM Wellde, BT Schultheiss, P Ware, LA Kauffman, EB Wirtz, RA DeTaisne, C Hui, GSH Chang, SP Church, P Hollingdale, MR Kaslow, DC Hoffman, S Guito, KP Ballou, WR Sadoff, JC Paoletti, E AF Tine, JA Lanar, DE Smith, DM Wellde, BT Schultheiss, P Ware, LA Kauffman, EB Wirtz, RA DeTaisne, C Hui, GSH Chang, SP Church, P Hollingdale, MR Kaslow, DC Hoffman, S Guito, KP Ballou, WR Sadoff, JC Paoletti, E TI NYVAC-Pf7: A poxvirus-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria SO INFECTION AND IMMUNITY LA English DT Article ID GENETICALLY ENGINEERED POXVIRUSES; SPOROZOITE SURFACE PROTEIN-2; RECOMBINANT SERA PROTEIN; LETHAL JEV INFECTION; VIRUS GLYCOPROTEIN-D; ASEXUAL BLOOD STAGES; CIRCUMSPOROZOITE PROTEIN; PROTECTIVE IMMUNITY; AOTUS MONKEYS; ESCHERICHIA-COLI AB The highly attenuated NYVAC vaccinia virus strain has been utilized to develop a multiantigen, multistage vaccine candidate for malaria, a disease that remains a serious global health problem and for which no highly effective vaccine exists. Genes encoding seven Plasmodium falciparum antigens derived from the sporozoite (circumsporozoite protein and sporozoite surface protein 2), liver (liver stage antigen 1), blood (merozoite surface protein 1, serine repeat antigen, and apical membrane antigen 1), and sexual (25-kDa sexual-stage antigen) stages of the parasite life cycle were inserted into a single NYVAC genome to generate NYVAC-P17. Each of the seven antigens was expressed in NYVAC-Pf7-infected culture cells, and the genotypic and phenotypic stability of the recombinant virus was demonstrated. When inoculated into rhesus monkeys, NYVAC-Pf7 was safe and well tolerated. Antibodies that recognize sporozoites, liver, blood, and sexual stages of P. falciparum were elicited. Specific antibody responses against four of the P. falciparum antigens (circumsporozoite protein, sporozoite surface protein 2, merozoite surface protein 1, and 25-kDa sexual-stage antigen) were characterized. The results demonstrate that NYVAC-Pf7 is an appropriate candidate vaccine for further evaluation in human clinical trials. C1 VIROGENET CORP,TROY,NY 12180. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. PASTEUR MERIEUX SERUMS & VACCINS,F-69280 MARCY LETOILE,FRANCE. UNIV HAWAII,JOHN A BURNS SCH MED,DEPT TROP MED & MED MICROBIOL,HONOLULU,HI 96816. USN,MED RES INST,MALARIA PROGRAM,BETHESDA,MD 20889. UNIV LEEDS,DEPT BIOL,LEEDS LS2 9JT,W YORKSHIRE,ENGLAND. NIAID,MALARIA RES LAB,BETHESDA,MD 20892. CONNAUGHT LABS INC,SWIFTWATER,PA 18370. RI Lanar, David/B-3560-2011 NR 95 TC 99 Z9 104 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 1996 VL 64 IS 9 BP 3833 EP 3844 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VE443 UT WOS:A1996VE44300055 PM 8751936 ER PT J AU Beekmann, SE Engler, HD Collins, AS Canosa, J Henderson, DK Freifeld, A AF Beekmann, SE Engler, HD Collins, AS Canosa, J Henderson, DK Freifeld, A TI Rapid identification of respiratory viruses: Impact on isolation practices and transmission among immunocompromised pediatric patients SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID SHELL VIAL CULTURE; SYNCYTIAL VIRUS; DIRECT IMMUNOFLUORESCENCE; ENZYME-IMMUNOASSAY; VIRAL-INFECTIONS; INFLUENZA-A; RHINOVIRUSES; PREVENTION; DIAGNOSIS AB OBJECTIVE: To determine whether empiric isolation of patients with acute respiratory virus infection symptoms could be discontinued when preliminary shell vial cultures were negative, and the impact of this approach on hospital resources. DESIGN: In 1993, we retrospectively reviewed respiratory virus test results from 1992 to 1993 and extended data collection prospectively through the 1993 to 1994 season. The rapid test and 48-hour shell vial results were com pared to a standard of rapid test plus 5-day shell vial culture results to determine the sensitivity and specificity of these ''preliminary'' results. SETTING: A 400-bed tertiary referral research hospital. PATIENTS: Patients from any inpatient unit or clinic with acute respiratory virus infection symptoms who had a specimen submitted for respiratory virus culture. Patients were placed on empiric respiratory isolation culture pending culture results. RESULTS: The overall sensitivity of the combined rapid and 48-hour culture results in adults and children was 97%. All 15 pediatric patients with respiratory syncytial virus infection who had specimens submitted on first suspicion of respiratory virus infection were positive by rapid test. Culture results were positive within 48 hours for 100% of patients with influenza A (15 patients), influenza B (6), and parainfluenza (18) viruses. Of 59 pediatric inpatients who were isolated empirically awaiting 5-day culture results, 31 (52%) ultimately were determined to be culture negative. CONCLUSIONS: Empiric isolation of symptomatic children can be discontinued at 48 hours when both the rapid test and the early culture results are negative. Our institution would have saved 93 days of unnecessary isolation over 2 years had such a policy been in place. C1 NCI,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. NCI,HOSP EPIDEMIOL SERV,BETHESDA,MD. NCI,MICROBIOL SERV,BETHESDA,MD. NCI,DEPT CLIN PATHOL,BETHESDA,MD. NCI,CTR CLIN,BETHESDA,MD. NR 22 TC 15 Z9 15 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD SEP PY 1996 VL 17 IS 9 BP 581 EP 586 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA VG245 UT WOS:A1996VG24500007 PM 8880230 ER PT J AU Cohen, JI AF Cohen, JI TI Varicella-zoster virus - The virus SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID IMMEDIATE-EARLY PROTEIN; READING FRAME-10 PROTEIN; REPLICATION IN-VITRO; VACCINE STRAIN OKA; FUNCTIONALLY DISTINCT; ACTIVATION DOMAIN; BINDING PROTEIN; GENE-EXPRESSION; HERPES; GLYCOPROTEIN AB Varicella-zoster virus (VZV) causes chickenpox and herpes tester. After acute infection the virus becomes latent in dorsal root and trigeminal ganglia for the lifetime of the individual. The viral genome encodes about 70 proteins, at least three of which are thought to be expressed during latency in humans. VZV grows in cell culture, but is very cell-associated; it is relatively difficult to obtain high titers of cell-free virus. RP Cohen, JI (reprint author), NIH,CLIN INVEST LAB,BLDG 10,ROOM 11N214,BETHESDA,MD 20892, USA. NR 63 TC 9 Z9 9 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD SEP PY 1996 VL 10 IS 3 BP 457 EP & DI 10.1016/S0891-5520(05)70308-1 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA VB586 UT WOS:A1996VB58600002 PM 8856347 ER PT J AU Wilbur, WJ AF Wilbur, WJ TI Human subjectivity and performance limits in document retrieval SO INFORMATION PROCESSING & MANAGEMENT LA English DT Article ID TEXT RETRIEVAL; SYSTEM; KNOWLEDGE AB Test sets for the document-retrieval task composed of human relevance judgments have been constructed that allow one to compare human performance directly with that of automatic methods and that place absolute limits on performance by any method, Current retrieval systems are found to generate only about half of the information allowed by these absolute limits. The data presented here strongly suggest that most of the improvement that could be achieved consistent with these limits can only be achieved by incorporating specific subject information into retrieval systems. Published by Elsevier Science Ltd RP Wilbur, WJ (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BLDG 38A,RM 85806,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 31 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4573 J9 INFORM PROCESS MANAG JI Inf. Process. Manage. PD SEP PY 1996 VL 32 IS 5 BP 515 EP 527 DI 10.1016/0306-4573(96)00028-3 PG 13 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA VJ870 UT WOS:A1996VJ87000002 ER PT J AU Huang, LY vanMeerwijk, JPM Bikoff, EK Germain, RN AF Huang, LY vanMeerwijk, JPM Bikoff, EK Germain, RN TI Comparison of thymocyte development in normal and invariant chain-deficient mice provides evidence that maturation-related changes in TCR and co-receptor levels play a critical role in cell fate SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE deletion; lymphocyte; MHC class II; superantigen ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-II MOLECULES; IMMATURE CD4+CD8+ THYMOCYTES; POSITIVE SELECTION; TRANSGENIC MICE; T-CELLS; TOLERANCE INDUCTION; PARTIAL AGONISTS; CD8+ THYMOCYTES; EXPRESSION AB Cells of invariant chain-deficient mice show a substantial decrease in cell surface MHC class II protein expression, as well as a change in the occupancy of the expressed class II molecules. Taking advantage of recent advances in phenotypic identification of transitional populations of developing thymocytes, the effects of these changes in MHC class II on positive and negative selection were reanalyzed. A marked (similar to 6-fold) reduction in CD4 single-positive mature cells was seen in H-2(b) mutant mice, yet there was little change in the number of CD4(hi)CD8(int)TCR(int) cells, a population containing the cells from which mature CD4(+) cells derive. In normal mice expressing I-E and MMTV-encoded vSAG, V-beta-specific negative selection occurred at a later point in the maturation pathway for cells showing greater expression of CD8 than CD4. In invariant chain-deficient mice, vSAG-mediated negative selection was diminished in general and what deletion still occurred was seen in more mature populations as compared to wild-type mice, Taken together, the decrease in MHC class II expression in invariant chain mutant mice and these alterations in the timing of thymocyte deletion provide strong support for an avidity model of negative selection, Perhaps more importantly, they emphasize the importance of the increasing TCR expression, the changing co-receptor levels and the movement from one antigen-presenting cell to another that accompany T cell maturation in determining the fate of developing thymocytes. C1 NIAID,LYMPHOCYTE BIOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,DEPT MOL & CELL BIOL,CAMBRIDGE,MA 02138. RI van Meerwijk, Joost/K-1345-2014 NR 55 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD SEP PY 1996 VL 8 IS 9 BP 1429 EP 1440 DI 10.1093/intimm/8.9.1429 PG 12 WC Immunology SC Immunology GA VJ306 UT WOS:A1996VJ30600012 PM 8921421 ER PT J AU Lamb, ME Hershkowitz, I Sternberg, KJ Esplin, PW Hovav, M Manor, T Yudilevitch, L AF Lamb, ME Hershkowitz, I Sternberg, KJ Esplin, PW Hovav, M Manor, T Yudilevitch, L TI Effects of investigative utterance types on Israeli children's responses SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID STATEMENTS; VALIDITY; MEMORY AB This field study is concerned with the effect of interviewing style on children's reports of sexual abuse. Detailed psycholinguistic analyses of 22 front-line interviews of 5- to 11-year-old Israeli children by a number of interviewers focused on the length (number of words) and richness (number of new details) provided in responses to different types of utterances by the interviewers. As predicted, open-ended invitations yielded significantly longer and more detailed responses than directive, leading, or suggestive utterances, regardless of age. The younger children provided briefer and less detailed responses, however. These findings underscore the value of open-ended prompts in investigative interviews. C1 ISRAELI MINIST LABOR & SOCIAL AFFAIRS, JERUSALEM, ISRAEL. RP Lamb, ME (reprint author), NICHHD, SECT SOCIAL & EMOT DEV, 9190 ROCKVILLE PIKE, BETHESDA, MD 20814 USA. NR 27 TC 121 Z9 121 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD SEP PY 1996 VL 19 IS 3 BP 627 EP 637 DI 10.1177/016502549601900310 PG 11 WC Psychology, Developmental SC Psychology GA VF325 UT WOS:A1996VF32500010 ER PT J AU Malinda, KM Kleinman, HK AF Malinda, KM Kleinman, HK TI The laminins SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE basement membrane; extracellular matrix; laminin; cell attachment protein; biological activity ID GLYCOPROTEIN; SEQUENCES AB The laminins are a family of extracellular matrix glycoproteins localized in the basement membrane that separates epithelial cells from the underlying stroma. They are also found in basement membrane surrounding fat, muscle and peripheral nerve cells. The laminins are large trimeric glycoproteins comprising three disulphide-bonded chains. They are the first extracellular matrix molecules to be observed in the developing embryo and have potent biological activities. In addition, there have been new developments in the number and localization of the homologues of the laminin chains and the role of laminin in neuromuscular disease. Their primary role is in cell-matrix attachment, but many additional biological activities, including promoting cell growth and migration, tumour growth and metastases, neurite outgrowth, nerve regeneration, wound repair and graft survival, have been demonstrated. Many of these biological activities are duplicated by proteolytic fragments of laminin and by small laminin-derived synthetic peptides. These laminin-derived peptides may be useful clinical reagents for accelerating wound healing with minimal scarring or for blocking tumour metastases. Copyright (C) 1996 Elsevier Science Ltd C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 9 TC 106 Z9 108 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD SEP PY 1996 VL 28 IS 9 BP 957 EP 959 DI 10.1016/1357-2725(96)00042-8 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VV043 UT WOS:A1996VV04300001 PM 8930117 ER PT J AU Jacobs, I Lancaster, J AF Jacobs, I Lancaster, J TI The molecular genetics of sporadic and familial epithelial ovarian cancer SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Review DE familial; genetics; ovarian cancer ID EPIDERMAL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; POLYMERASE CHAIN-REACTION; FACTOR RECEPTOR EXPRESSION; TUMOR-NECROSIS-FACTOR; K-RAS PROTOONCOGENE; FREQUENT LOSS; P53 GENE; PROTO-ONCOGENE; BREAST-CANCER AB Progress in investigating the molecular basis of cancer has been rapid during recent years and has resulted in important advances in understanding ovarian carcinogenesis. These include the isolation of highly penetrant cancer susceptibility genes and the identification of alterations in other genetic elements involved in cell growth, differentiation and DNA repair. The first section of this review describes the epidemiology and genetics of familial ovarian cancer and the identification of the BRCA1 gene associated with breast/ovarian cancer and of the DNA repair genes associated with the Lynch II syndrome. The risk of cancer associated with germ line abnormalities of these genes and the management options for women with a family history of ovarian cancer are discussed. The second section describes genetic abnormalities associated with sporadic ovarian cancer. Although a detailed multistep pathway of sporadic ovarian carcinogenesis cannot yet be described a number of specific abnormalities have now been documented. These include abnormalities of growth factors (M-CSF, TGF-beta), growth factor receptors (c-fins, EGFR, Her-2/neu), genes involved in signal transduction (Ki-ras), and genes involved in transcriptional regulation (c-myc, p53) and loss of heterozygosity at various chromosomal loci. The final section of the review discusses the genetics of metastatic disease, candidate precursor lesions for ovarian cancer and the field change hypothesis of ovarian carcinogenesis. C1 UNIV CAMBRIDGE,CRC,HUMAN CANC GENET UNIT,CAMBRIDGE CB2 1TN,ENGLAND. NIEHS,NIH,RES TRIANGLE PK,NC. RP Jacobs, I (reprint author), ST BARTHOLOMEWS HOSP,DEPT GYNAECOL ONCOL,LONDON EC1A 7BE,ENGLAND. RI Jacobs, Ian/F-1743-2013 OI Jacobs, Ian/0000-0002-8112-4624 NR 157 TC 11 Z9 11 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD SEP-OCT PY 1996 VL 6 IS 5 BP 337 EP 355 DI 10.1046/j.1525-1438.1996.06050337.x PG 19 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA VB621 UT WOS:A1996VB62100001 ER PT J AU Munoz, KA BallardBarbash, R Graubard, B Swanson, CA Schairer, C Kahle, LL AF Munoz, KA BallardBarbash, R Graubard, B Swanson, CA Schairer, C Kahle, LL TI Recall of body weight and body size estimation in women enrolled in the breast cancer detection and demonstration project (BCDDP) SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE body height; body mass index; body weight; body size perception; pictorials ID OBESITY; HEIGHT; POPULATION; ATTITUDES; ACCURACY; VALIDITY; FAT; OLD AB OBJECTIVE: To examine the relationship between body mass index (BMI) and pictorial representations of body size in women from young adulthood to late mid-life. DESIGN: Retrospective, descriptive study of BMI and pictorial estimation of body size. SUBJECTS: 5,807 women age 33-77 years enrolled in the National Cancer Institute's and American Cancer Society's Breast Cancer Detection and Demonstration Project (BCDDP). MEASUREMENTS: Body weight and height were measured in 1973. In 1977, a subset of the cohort recalled their usual height and weight at 10 y intervals starting at age 20. In 1987, subjects reported their usual and current weight and selected one of nine pictorials best representing their body size at ages 15, 25, 40, 50 and +60 y. RESULTS: For the cohort, and among White women, Pearson correlations between recalled BMI (Kg/M(2)) and pictorials for each decade ranged from 0.62-0.67 and was 0.80 for current BMI and current pictorial. The range of correlations between pictorials and recalled BMI for other race/ethnic groups were 0.72-0.87 (Black), 0.53-0.75 (Hispanic) and 0.28-0.87 (Asian). Among a subset of women with data on measured BMI, recalled BMI and pictorials at specific ages, the correlation between pictorials and measured BMI was 0.75, compared to the correlation between recalled BMI and measured BMI which was 0.89. CONCLUSION: Correlations are higher between recalled BMI and measured BMI compared to the correlation between pictorials and measured BMI. Therefore, estimates of body size by pictorials alone may not be appropriate for epidemiological investigations. Alternate uses of pictorials may include assessment body weight in low literate populations or in instances where body weight is not or has not been measured. C1 NCI,BIOMETRY BRANCH,DIV CANC PREVENT & CONTROL,NIH,BETHESDA,MD 20892. NIH,ENVIRONM EPIDEMIOL BRANCH,DIV CANC EPIDEMIOL & GENET,BETHESDA,MD 20892. INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD. RP Munoz, KA (reprint author), NCI,APPL RES BRANCH,DIV CANC PREVENT & CONTROL,NIH,EXECUT PLAZA N,ROOM 343,BETHESDA,MD 20892, USA. NR 20 TC 19 Z9 20 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD SEP PY 1996 VL 20 IS 9 BP 854 EP 859 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA VE562 UT WOS:A1996VE56200011 PM 8880354 ER PT J AU Greig, JR Miller, RW Okunieff, P AF Greig, JR Miller, RW Okunieff, P TI An approach to dose measurement for total body irradiation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE dose measurement; total body irradiation; diodes; quality assurance; treatment verification ID SYSTEM AB Purpose: An approach is proposed to allow the interpretation of diode measurements on patients receiving total body irradiation (TBI) in opposed lateral fields as midplane dose measurements. Methods and Materials: This technique consists of making measurements on both entrance and exit sides of any ray path along which the midplane dose is desired, The diode on the entrance side is calibrated so that its output is indicative of the dose delivered at the depth of maximum dose along the ray, The diode on the exit side is calibrated so that its output represents the dose that would have been delivered to that depth had the medium (the patient) been semi-infinite. Because these two measurements Lie along the same ray, they are related by a simple depth-dose equation from which the effective absorption coefficient (mu(eff)) can be determined. The dose at the midplane is calculated using this mu(eff) in a similar equation. Results: The validity of this approach was checked with measurements at isocenter and at the TBI distance using a polystyrene phantom. In both cases, the calculated midplane dose was within reasonable experimental error (range similar to+/-2% on average) of the measured dose, Measurements on eight patients showed the excellent reproducibility of entrance surface measurements (standard deviation [SD] similar to+/-1%), compared to that of midplane measurements (SD similar to+/-4%) and exit surface measurements (SD similar to less than or equal to 8%). Midplane doses determined from these equations confirmed that dose inhomogeneity using this opposed lateral technique is on the order of +/-10% aith highest doses delivered to the calves and lowest to the lungs. Conclusion: Recent measurements made on TBI patients have shown that a commercial eight-diode system can be used successfully to measure the dose delivered to the midplane within an accuracy of similar to+/-4%. The reproducibility of entrance surface measurements (similar to+/-1%) shows that such measurements provide the accuracy required for quality assurance purposes. Copyright (C) 1996 Elsevier Science Inc. RP Greig, JR (reprint author), NCI,RADIAT ONCOL BRANCH,DIV CLIN SCI,NATL INST HLTH,BLDG 10,ROOM B3-B69,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 7 TC 6 Z9 7 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 1996 VL 36 IS 2 BP 463 EP 468 DI 10.1016/S0360-3016(96)00268-4 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VN740 UT WOS:A1996VN74000024 PM 8892472 ER PT J AU Ellwein, LB Drummond, MF AF Ellwein, LB Drummond, MF TI Economic analysis alongside clinical trials - Bias in the assessment of economic outcomes SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article AB Clinical trial randomization schemes to control patient characteristics that can influence clinical response are not sufficient to control for their effects on operational efficiency and cost within the provider institution. This variation can result in biased economic findings when patients are allowed to select a provider themselves. C1 UNIV YORK,CTR HLTH ECON,YORK YO1 5DD,N YORKSHIRE,ENGLAND. RP Ellwein, LB (reprint author), NEI,BLDG 31,RM 6A04,BETHESDA,MD 20892, USA. NR 9 TC 22 Z9 23 U1 0 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD FAL PY 1996 VL 12 IS 4 BP 691 EP 697 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA WE150 UT WOS:A1996WE15000011 PM 9136476 ER PT J AU Wu, YQ Becerra, SP AF Wu, YQ Becerra, SP TI Proteolytic activity directed toward pigment epithelium-derived factor in vitreous of bovine eyes implications of proteolytic processing SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE bovine eyes; pigment epithelium-derived factor; serine proteinases; serpins; vitreous humor ID PLASMINOGEN-ACTIVATOR; ALPHA-1-PROTEINASE INHIBITOR; IV COLLAGENASE; STROMELYSIN; PROTEINS; BINDING; MATRIX; CELLS; PA AB Purpose. Experiments were designed to identify proteolytic activities that cleave pigment epithelium-derived factor (PEDF), a member of the serpin (serine protease inhibitor) family. Methods. Proteins in vitreous humor from bovine eyes were analyzed by Western blot with antiserum to human recombinant PEDF protein, Protein fractionation was by ammonium sulfate saturation and by S-Sepharose column chromatography. Proteolytic activities were determined by gelatin zymography and by solution assays against PEDF or chromogenic peptide substrates, Results. PEDF protein was identified and purified to near homogeneity from vitreous humor of bovine eyes. Limited proteolysis showed that the vitreal protein has a protease-sensitive region at its serpin-exposed peptide loop. Proteolytic activities that cleave the PEDF 49.5 kDa-polypeptide were identified only when proteins from these extracts were separated by 45% to 70% ammonium sulfate fractionation (P-70). The degradation product had an apparent molecular weight of 46 kDa. This result is consistent with cleavage at the serpin-exposed loop. The PEDF-cleavage activity in P-70 was inhibited specifically by the serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF), but not by aprotinin, EDTA, or pepstatin. The vitreal P-70 extracts contained 49- and 53-kDa gelatinolytic activities that also were inhibited by AEBSF and not by EDTA, aprotinin, or pepstatin. The PEDF-cleavage activity did not hydrolyze substrates fur thrombin, factor Xa, alpha-chymotrypsin, trypsin, or plasmin, nor did it immunoreact with antibody to urokinase plasminogen activator. Conclusions. These data indicated that vitreous has a serine-proteolytic activity associated with a novel 49/53-kDa enzyme that cleaves the PEDF protein in a serpinase fashion. In addition to cleavage in vitro, these proteases might play a role in modulating PEDF in vivo. C1 NEI, NIH, RETINAL CELL & MOL BIOL LAB, BETHESDA, MD 20892 USA. NR 27 TC 50 Z9 54 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1996 VL 37 IS 10 BP 1984 EP 1993 PG 10 WC Ophthalmology SC Ophthalmology GA VG343 UT WOS:A1996VG34300013 PM 8814138 ER PT J AU Krausz, E Augusteyn, RC Quinlan, RA Reddan, JR Russell, P Sax, CM Graw, J AF Krausz, E Augusteyn, RC Quinlan, RA Reddan, JR Russell, P Sax, CM Graw, J TI Expression of crystallins, Pax6, filensin, CP49, MIP, and MP20 in lens-derived cell lines SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cell culture; crystallins; cytoskeleton; gene expression; membrane protein ID ALPHA-A-CRYSTALLIN; FIBER CELL; EPITHELIAL-CELLS; MEMBRANE-PROTEIN; GROWTH-FACTOR; EYE LENS; GENE; MOUSE; PROMOTER; TISSUES AB Purpose. Cell lines are the systems of choice to analyze cellular functions related to the particular organ system. For lens research, three cell lines are widely used: N/N1003A (derived from rabbit lenses), alpha TN4, and NKR-11 (both of murine origin). The aim of the current study was to characterize these particular cell lines with respect to their expression of genes that are considered to be lens specific or expressed preferentially in the lens, such as crystallins, Pax6, Filensin, CP49, MIP, and MP20. Methods. alpha A- and alpha B-crystallin cDNA from rabbit lenses were sequenced. The expression of various genes was analyzed by reverse transcription-polymerase chain reaction using specific primers and mRNA from three lens-derived cell lines. For control, the expression of the selected genes was compared in nonlenticular tissues of mouse as well as in non-lens-derived murine cell lines (EF43, NIH-3T3, and L929). Results. None of the transcripts for beta B2-crystallin, gamma-crystallins, MIP, MP20, filensin, and CP49 could be detected in the lens-derived cell lines. Transcripts for alpha A-crystallin were amplified in alpha TN4, but not in N/N1003A and NKR-11. cells. Pax6, a master control gene of eye develop ment, is expressed in all three lens-derived cell lines and, additionally, in cell lines of neuronal origin, but not in corneal endothelial cells and in the currently used control cell lines. Conclusions. Three cell lines of lenticular origin were tested for expression of genes that were found abundantly in the lens. The observed expression of Pax6 in all lens-derived cell lines allows their use in the analysis of corresponding signal chains. C1 GSF FORSCHUNGSZENTRUM UNWELT & GESUNDHEIT, INST SAUGETIERGENET, D-85785 OBERSCHLEISSHEIM, GERMANY. NATL VISION RES INST, CARLTON, AUSTRALIA. UNIV DUNDEE, INST MED RES, DEPT BIOCHEM, DUNDEE, SCOTLAND. OAKLAND UNIV, DEPT BIOL SCI, ROCHESTER, MI USA. NEI, NIH, BETHESDA, MD 20892 USA. RI Graw, Jochen/D-9336-2013; Quinlan, Roy/A-1348-2012; OI Quinlan, Roy/0000-0003-0644-4123; Graw, Jochen/0000-0003-0298-9660 FU NEI NIH HHS [EY00362]; Wellcome Trust NR 42 TC 35 Z9 39 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 1996 VL 37 IS 10 BP 2120 EP 2128 PG 9 WC Ophthalmology SC Ophthalmology GA VG343 UT WOS:A1996VG34300027 PM 8814151 ER PT J AU Hannaway, C AF Hannaway, C TI The western medical tradition: 800 BC to AD 1800 - Conrad,LI, Neve,M, Nutton,V, Porter,R, Wear,A SO ISIS LA English DT Book Review RP Hannaway, C (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0021-1753 J9 ISIS JI Isis PD SEP PY 1996 VL 87 IS 3 BP 528 EP 529 DI 10.1086/357584 PG 2 WC History & Philosophy Of Science SC History & Philosophy of Science GA VP808 UT WOS:A1996VP80800020 ER PT J AU Lucier, GW Portier, CJ AF Lucier, GW Portier, CJ TI New cancer risk guidelines SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Letter RP Lucier, GW (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD FAL PY 1996 VL 13 IS 1 BP 10 EP 10 PG 1 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA VM203 UT WOS:A1996VM20300009 ER PT J AU Goldberger, BA Cone, EJ Kadehjian, L AF Goldberger, BA Cone, EJ Kadehjian, L TI Unsuspected ethanol ingestion through soft drinks and flavored beverages SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Letter C1 NIDA,NIH,ADDICT RES CTR,BALTIMORE,MD 21224. RP Goldberger, BA (reprint author), UNIV FLORIDA,COLL MED,DIAGNOST REFERAL LABS,2310 SW 13TH ST,GAINESVILLE,FL 32608, USA. NR 3 TC 9 Z9 9 U1 0 U2 1 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD SEP PY 1996 VL 20 IS 5 BP 332 EP 333 PG 2 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA VD329 UT WOS:A1996VD32900012 PM 8872245 ER PT J AU Li, LH Wine, RN Chapin, RE AF Li, LH Wine, RN Chapin, RE TI 2-Methoxyacetic acid (MAA)-induced spermatocyte apoptosis in human and rat testes: An in vitro comparison SO JOURNAL OF ANDROLOGY LA English DT Article DE 2-methoxyethanol; human; rat; seminiferous tubules; apoptosis; calcium ID GLYCOL MONOMETHYL ETHER; EXPERIMENTAL HUMAN EXPOSURE; ETHYLENE-GLYCOL; SEMINIFEROUS TUBULES; TESTICULAR TOXICITY; 2-METHOXYETHANOL ME; ALKOXYACETIC ACIDS; MONOALKYL ETHERS; GUINEA-PIGS AB 2-Methoxyethanol (2-ME) produces adverse reproductive effects in humans at an exposure level that is about 60-fold lower (2.6 mg/m(3)) than the concentration toxic to rat testes (167 mg/m(3)), suggesting that humans are much more sensitive to the testicular toxicity of 2-ME than rats. Previous studies found that 2-ME-induced germ cell death seen in vivo could be faithfully mimicked in vitro only in cultured seminiferous tubules, using the active metabolite methoxyacetic acid (MAA). To test whether human testis per se is more sensitive than rat testis to MAA, we compared the responses of cultured rat seminiferous tubules (RSTs) and human testicular tissues (HTT) in vitro. Degeneration in spermatocytes was observed in RSTs 19 hours after a 5-hour exposure to MAA at and above 1 mM. The dying germ cells showed necrotic-like morphology, as seen in vivo. Germ cells in HTT were also killed by doses greater than or equal to 1 mM, although the dying germ cells appeared apoptotic, rather than necrotic. For both species, doses lower than 1 mM were without visible effect. Interestingly, agarose gel electrophoresis of DNA from tubules of both species showed internucleosomal DNA fragmentation after MAA treatment, indicating that MAA induced apoptosis in both human and rat germ cells, though the dying cells showed different morphology in the two species. Furthermore, MAA-induced germ cell apoptosis in both species could be significantly attenuated by calcium channel blockers such as nifedipine or verapamil, which inhibit calcium movement through plasma membranes. In conclusion, the results suggest that: 1) human testis is equally sensitive to MAA compared to rat testis; and 2) MAA induces germ cell apoptosis both in human and rat, probably through similar, calcium-dependent mechanism(s). The precise steps in this germ cell apoptosis are under investigation. C1 NIEHS,REPROD TOXICOL GRP,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. OI Chapin, Robert/0000-0002-5997-1261 NR 34 TC 47 Z9 48 U1 1 U2 1 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD SEP-OCT PY 1996 VL 17 IS 5 BP 538 EP 549 PG 12 WC Andrology SC Endocrinology & Metabolism GA VV826 UT WOS:A1996VV82600012 PM 8957698 ER PT J AU Lam, KS Hesler, GA Gustavson, DR Berry, RL Tomita, K MacBeth, JL Ross, J Miller, D Forenza, S AF Lam, KS Hesler, GA Gustavson, DR Berry, RL Tomita, K MacBeth, JL Ross, J Miller, D Forenza, S TI Pyrrolosporin A, a new antitumor antibiotic from Micromonospora sp C39217-R109-7 .1. Taxonomy of producing organism, fermentation and biological activity SO JOURNAL OF ANTIBIOTICS LA English DT Article AB Strain C39217-R109-7 (ATCC 53791) is an actinomycete strain isolated from a soil sample collected at Puerto Viejo, Peru. It produces a new antitumor antibiotic, designated pyrrolosporin A. Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Micromonospora sp. C39217-R109-7. Pyrrolosporin A shows antimicrobial activity against Gram-positive bacteria and it is weakly active against Gram-negative bacteria. Pyrrolosporin A prolongs the life span of mice inoculated with P388 leukemia cells. C1 FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Lam, KS (reprint author), BRISTOL MYERS SQUIBB PHARMACEUT RES INST,5 RES PKWY,WALLINGFORD,CT 06492, USA. NR 9 TC 16 Z9 16 U1 1 U2 1 PU JAPAN ANTIBIOT RES ASSN PI TOKYO PA 2 20 8 KAMIOSAKI SHINAGAWA KU, TOKYO 141, JAPAN SN 0021-8820 J9 J ANTIBIOT JI J. Antibiot. PD SEP PY 1996 VL 49 IS 9 BP 860 EP 864 PG 5 WC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Immunology; Microbiology; Pharmacology & Pharmacy GA VJ736 UT WOS:A1996VJ73600004 PM 8931718 ER PT J AU Selbie, WS Caldwell, GE AF Selbie, WS Caldwell, GE TI A simulation study of vertical jumping from different starting postures SO JOURNAL OF BIOMECHANICS LA English DT Article DE jumping; simulation; optimization; modeling; forward dynamics ID BIARTICULAR MUSCLES; COORDINATION; MOVEMENTS; ENERGY; MODEL AB This paper addresses the question of whether maximal vertical jump height depends on initial jumping posture. A direct dynamics computer simulation approach was used to avoid subject preference and practice effects. The human body was modeled as four rigid segments connected by ideal hinge joints, with movement constrained to the sagittal plane and driven by three single-joint torque actuators. Maximal height jumps were found for each of 125 different intial postures. For each initial posture, the optimal pattern of joint torque actuator onset times was found using a multidimensional simplex algorithm searching for maximal jump height. The model results revealed that maximal jump height is relatively insensitive io initial posture, but that the pattern of joint torque onset times necessary to effect these optimal heights varies considerably. Model kinematics indicate that the variability in onset times is necessary to allow the body to re-orient itself in different ways during the downward countermovement phase. This variable re-orientation strategy is followed by a more stereotyped upward thrust phase that is similar despite the differences in starting postures. Model center of mass, joint and segmental kinematics show many features found in experimental studies of jumping, despite the exclusive use of single joint torque actuators. However, a proximal-to-distal sequence of joint coordination was not found, possibly because of the omission of antagonist and bi-articular muscles. The results suggest that similar vertical jump heights should be obtained using a wide range of initial starting positions. Copyright (C) 1996 Published by Elsevier Science Ltd. C1 UNIV MASSACHUSETTS,DEPT EXERCISE SCI,BIOMECH LAB,AMHERST,MA 01003. NIDCD,VOICE & SPEECH SECT,NIH,BETHESDA,MD. NR 22 TC 41 Z9 41 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD SEP PY 1996 VL 29 IS 9 BP 1137 EP 1146 DI 10.1016/0021-9290(96)00030-9 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA VD998 UT WOS:A1996VD99800003 PM 8872270 ER PT J AU Webb, CP Lane, K Dawson, AP VandeWoude, GF Warn, RM AF Webb, CP Lane, K Dawson, AP VandeWoude, GF Warn, RM TI C-Met signalling in an HGF/SF-insensitive variant MDCK cell line with constitutive motile/invasive behaviour SO JOURNAL OF CELL SCIENCE LA English DT Article DE Met; HGF/SF; scattering; MDCK-1; tyrosine phosphorylation ID HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE RECEPTOR; FACTOR SCATTER FACTOR; EPITHELIAL-CELLS; TRANSFORMING ACTIVITY; REGULATORY SITE; HERBIMYCIN-A; PROTOONCOGENE; PROTEIN; PHOSPHORYLATION AB The Met protein is a receptor tyrosine kinase for hepatocyte growth factor/scatter factor (HGF/SF), a multifunctional growth factor with mitogenic, motogenic and morphogenic properties, A morphologically altered variant of the MDCK cell line, MDCK-1, spontaneously exhibits a number of features associated with a partial HGF/SF-Met induced phenotype (less adhesive colonies in culture, enhanced invasion and motility, nascent tubule formation), but paradoxically does not respond to HGF/SF treatment. Although the overall cell surface expression and distribution of Met were found to be similar in parental MDCK cells and the MDCK-1 cell line, p145(met) autophosphorylation (+/- HGF/SF) was significantly reduced in MDCK-1 cells in vitro and in vivo when compared with parental MDCK cells, In contrast, EGF induced cell proliferation and EGF receptor autophosphorylation to similar levels in both cell lines, The basal levels of protein tyrosine phosphorylation were higher in MDCK-1 cells when compared with parental MDCK cells, including that of two prominent proteins with molecular masses of similar to 185 kDa and 220 kDa, Moreover, both p185 and p220 are present and tyrosine phosphorylated in Met immunoprecipitates from MDCK-1 cells (+/- HGF/SF), but not parental MDCK cells, In addition,Met immunocomplexes from MDCK-1 cells exhibited an approximately 3-fold increased tyrosine kinase activity in vitro when compared with MDCK cells, correlating with the higher basal levels of total phosphotyrosine. Treatment of MDCK-1 cells with the tyrosine kinase inhibitor herbimycin A reverted the cell phenotype to a more MDCK-like morphology in culture, with a concomitant reduction in the tyrosine phosphorylation predominantly of p220. Taken together these data suggest that aberrations in Met activity and associated signalling render MDCK-1 cells insensitive to HGF/SF, and may also mediate alterations in MDCK-1 cell behaviour. C1 MRC CTR,IMPERIAL CANC RES FUND,CELL INTERACT LABS,CAMBRIDGE CB2 2QH,ENGLAND. ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RP Webb, CP (reprint author), UNIV E ANGLIA,SCH BIOL SCI,NORWICH NR4 7TJ,NORFOLK,ENGLAND. RI Webb, Craig/I-8123-2012 NR 47 TC 16 Z9 16 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 1996 VL 109 BP 2371 EP 2381 PN 9 PG 11 WC Cell Biology SC Cell Biology GA VJ466 UT WOS:A1996VJ46600017 PM 8886986 ER PT J AU Raj, GV Cupp, C Khalili, K Kim, SJ Amini, S AF Raj, GV Cupp, C Khalili, K Kim, SJ Amini, S TI Soluble factors secreted by activated T-lymphocytes modulate the transcription of the immunosuppressive cytokine TGF-beta 2 in glial cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE GLRP; T-lymphocyte; immune response; central nervous system ID GROWTH-FACTOR-BETA; CENTRAL-NERVOUS-SYSTEM; DNA-BINDING ACTIVITY; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-2; DIFFERENTIAL EXPRESSION; GLIOBLASTOMA CELLS; SUPPRESSOR FACTOR; IMMUNE-RESPONSES; RNA EXPRESSION AB Coordination of the immune response to injury or disease in the brain is postulated to involve bi-directional discourse between the immune system and the central nervous system. This cross communication involves soluble mediators, including various growth factors, cytokines, and neuropeptides. In this report, we demonstrate that the supernatant from activated T-lymphocytes is able to induce the transcription of a potent cytokine, TGF-beta 2 in glial cells. The activating stimulus invokes signaling mechanisms distinct from known kinase or protease pathways. Activation of TGF-beta 2 transcription correlates with the loss of binding activity for an 80 kDa glial labile repressor protein, GLRP, to a responsive region within the TGF-beta 2 promoter. Although GLRP shares some characteristics with the inducible transcription factor AP-1, it appears to be distinct from known AP-1 family members. These data along with previous observations demonstrating the potent immunosuppressive activity of TGF-beta 2, support a model for a feedback mechanism between the activated T-lymphocytes and astrocytes via TGF-beta 2 to regulate the immune response. (C) 1996 Wiley-Liss, Inc. C1 THOMAS JEFFERSON UNIV,JEFFERSON INST MOL MED,DEPT BIOCHEM & MOL BIOL,MOL NEUROVIROL SECT,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. NR 56 TC 5 Z9 5 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD SEP 1 PY 1996 VL 62 IS 3 BP 342 EP 355 DI 10.1002/(SICI)1097-4644(199609)62:3<342::AID-JCB5>3.0.CO;2-R PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VF240 UT WOS:A1996VF24000005 PM 8872606 ER PT J AU Ramsey, NF Kirkby, BS VanGelderen, T Berman, KF Duyn, JH Frank, JA Mattay, VS VanHorn, JD Esposito, G Moonen, CTW Weinberger, DR AF Ramsey, NF Kirkby, BS VanGelderen, T Berman, KF Duyn, JH Frank, JA Mattay, VS VanHorn, JD Esposito, G Moonen, CTW Weinberger, DR TI Functional mapping of human sensorimotor cortex with 3D BOLD fMRI correlates highly with (H2O)-O-15 PET rCBF SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE PRESTO; positron emission tomography; functional magnetic resonance imaging; human brain; motor cortex; BOLD ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; HUMAN BRAIN; SENSORY STIMULATION; CORTICAL AREAS; MRI TECHNIQUE; MOTOR AREAS; MOVEMENTS; ACTIVATION; ARM AB Positron emission tomography (PET) functional imaging is based on changes in regional cerebral blood flow (rCBF). Functional magnetic resonance imaging (fMRI) is based on a variety of physiological parameters as well as rCBF. This study is aimed at the cross validation of three-dimensional (3D) fMRI, which is sensitive to changes in blood oxygenation, with oxygen-15-labeled water ((H2O)-O-15) PET. Nine normal subjects repeatedly performed a simple finger opposition task during fMRI scans and during PET scans. Within-subject statistical analysis revealed significant (''activated'') signal changes (p < 0.05, Bonferroni corrected for number of voxels) in contralateral primary sensorimotor- cortex (PSM) in all subjects with fMRI and with PET. With both methods, 78% of all activated voxels were located in the PSM. Overlap of activated regions occurred in all subjects (mean 43%, SD 26%). The size of the activated regions in PSM with both methods was highly correlated (rho = 0.87, p < 0.01). The mean distance between centers of mass of the activated regions in the PSM for fMRI versus PET was 6.7 mm (SD 3.0 mm). Average magnitude of signal change in activated voxels in this region, expressed as z-values adapted to timeseries, z(t), was similar (fMRI 5.5, PET 5.3). Results indicate that positive blood oxygen level-dependent (BOLD) signal changes obtained with 3D principles of echo shifting with a train of observations (PRESTO) fMRI are correlated with rCBF, and that sensitivity of fMRI can equal that of (H2SO)-S-15 PET. C1 NIMH,CLIN BRAIN DISORDERS BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NATL INST HLTH,IN VIVO NMR RES CTR,BETHESDA,MD. NATL INST HLTH,LAB DIAGNOST RADIOL RES,BETHESDA,MD. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 30 TC 98 Z9 98 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1996 VL 16 IS 5 BP 755 EP 764 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA VE555 UT WOS:A1996VE55500001 PM 8784221 ER PT J AU Pierpaoli, C Alger, JR Righini, A Mattiello, J Dickerson, R Pres, DD Barnett, A DiChiro, G AF Pierpaoli, C Alger, JR Righini, A Mattiello, J Dickerson, R Pres, DD Barnett, A DiChiro, G TI High temporal resolution diffusion MRI of global cerebral ischemia and reperfusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain; diffusion-weighted imaging; echo planar imaging; ischemia; magnetic resonance imaging; metabolism; white matter ID CAT BRAIN; WATER DIFFUSION; BLOOD-FLOW; STROKE; NMR; ENERGY; ECHO; RECOVERY; RATS; SPECTROSCOPY AB Although brain ischemia has been extensively studied using diffusion-weighted magnetic resonance imaging, most studies performed so far have not had adequate time resolution to follow the temporal changes in the water apparent diffusion coefficient (ADC) in hyperacute ischemia. Using diffusion echo planar imaging, we obtained ADC maps (calculated from measurements made with 8 b-values) with a time resolution of 43 s in a feline model of global brain ischemia and reperfusion. Different protocols were performed: 10-min hypoperfusion, 10- and 22-min ischemia followed by reperfusion, and cardiac arrest. ADC values were obtained from white matter of the internal capsule and from the thalamus, Cortical gray matter measurements were not deemed reliable due to the close proximity of CSF in the cortical sulci. Following occlusion, the ADC declined in the thalamus to < 2 SD of its normal baseline value within 1.5-2.5 min. This decay was exponential with a time constant (tau +/- SD) of 6.0 +/- 2.6 min; no further decrease in the ADC was observed IO min following ischemia. Following reperfusion, in animals that showed ADC recovery, the ADC began increasing immediately, returning to its preischemic value in similar to 15 min. No significant ADC changes were observed during hypoperfusion. Following cardiac arrest, the decay of ADC was more rapid in the thalamus (tau = 2.6 +/- 0.6 min) than in white matter (tau = 6.6 +/- 1.8 min). We observed that the ADC at 40 min after cardiac arrest was similar to the ADC at 10 min after ischemia. Given that all animals subjected to 10-min ischemic episodes showed ADC recovery with reperfusion, doubt is cast on whether it is possible to define a threshold value of the ADC below which brain tissue is irreversibly damaged. Finally, despite variability in the time constants of the ADC decay induced by ischemia, the ADC values at 10 min were very similar in all the animals. This suggests that when blood flow is diminished sufficiently to induce an ADC reduction, differences in pel-fusion affect the rapidity of the decrease but not the final asymptotic value reached. C1 NATL INST HLTH, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD USA. NATL INST HLTH, IN VIVO NMR CTR, NCRR, BETHESDA, MD USA. UNIV CALIF LOS ANGELES, DEPT RADIOL SCI, LOS ANGELES, CA 90024 USA. RP NINCDS, NEUROIMAGING BRANCH,NIH,RM 1C227,BLDG 10, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Pierpaoli, Carlo/E-1672-2011 NR 45 TC 83 Z9 84 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD SEP PY 1996 VL 16 IS 5 BP 892 EP 905 PG 14 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA VE555 UT WOS:A1996VE55500013 PM 8784233 ER PT J AU Pastor, RW Zwanzig, R Szabo, A AF Pastor, RW Zwanzig, R Szabo, A TI Diffusion limited first contact of the ends of a polymer: Comparison of theory with simulation SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID CONTROLLED INTRACHAIN REACTIONS AB The mean first passage time for the close approach of the ends of a polymer is investigated by computer simulation of the Brownian dynamics of a Rouse model. There are N bonds, of length b, and the contact distance is a. The results for N=50, 75, and 100 are compared with theoretical predictions by Wilemski and Fixman (WF), and by Szabo, Schulten, and Schulten (SSS). Theory differs from simulation by a factor of 1.3 to 3 when a is comparable to b but improves considerably when a is reduced. Closest agreement is obtained at a/b = 0.1 for WF with a delta function sink, where theory is within the statistical error (approximate to 5%) of the simulation for each case. C1 NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Pastor, RW (reprint author), US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,1401 ROCKVILLE PIKE,ROCKVILLE,MD 20852, USA. RI Szabo, Attila/H-3867-2012 NR 12 TC 108 Z9 108 U1 1 U2 16 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 1 PY 1996 VL 105 IS 9 BP 3878 EP 3882 DI 10.1063/1.472208 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA VD768 UT WOS:A1996VD76800056 ER PT J AU Cutler, GB AF Cutler, GB TI Treatment of congenital adrenal hyperplasia: The case for new medical approaches SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID PRECOCIOUS PUBERTY RP Cutler, GB (reprint author), NICHHD, NIH, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1996 VL 81 IS 9 BP 3185 EP 3186 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF804 UT WOS:A1996VF80400011 ER PT J AU Yanovski, JA Yanovski, SZ Friedman, TC Loh, YP Jayasvasti, V Cutler, GB Chrousos, GP AF Yanovski, JA Yanovski, SZ Friedman, TC Loh, YP Jayasvasti, V Cutler, GB Chrousos, GP TI Etiology of the differences in corticotropin-releasing hormone-induced adrenocorticotropin secretion of black and white women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; DEXAMETHASONE SUPPRESSION; PRECURSOR; ASSAY; MEN AB After iv oCRH, plasma immunoreactive ACTH (ACTH-IR) is significantly greater in blacks than in whites; however, there is no corresponding increase in cortisol secretion. To test the hypothesis that there are black-white differences in adrenal responsiveness to ACTH that underlie this phenomenon, weight-, age-, and education-matched black (n = 10) and white (n = 10) women were iv infused with 5 differing doses of ACTH(1-24) (0, 0.003, 0.01, 0.1, and 1 mu g/kg) with measured plasma cortisol and DHEA. To test the alternative hypothesis that greater post-CRH plasma ACTH-IR in blacks is caused by qualitative differences in circulating ACTH-immunoreactive peptides, we collected pre- and post-CRH plasma from 5 black and 5 white women and measured ACTH-IR after sample fractionation, using high-pressure liquid chromatography. There were no racial differences in adrenal responsiveness to differing doses of ACTH(1-24) and no differences in the distribution of the forms of ACTH-IR before CRH. After CRH, whites had predominant ACTH-IR peaks at the retention times of ACTH(1-39) and ACTH(1-39) sulfoxide, whereas blacks had prominent peaks at several additional retention times. The post-CRH ratio of intact to total ACTH was significantly lower in blacks than in whites (0.27 +/- 0.17 vs. 0.71 +/- 0.17, P < 0.003). We conclude that there are qualitative differences in post-CRH circulating ACTH-IR in blacks and whites, leading to a greater immunoreactive to bioactive ACTH ratio in blacks. Such differences in the circulating forms of ACTH can account for greater CRH-stimulated ACTH-IR in blacks. C1 NICHHD, OFF DIRECTOR, CTR CLIN, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NIDDKD, DIV DIGEST DIS & NUTR, BETHESDA, MD 20892 USA. NICHHD, DEV NEUROBIOL LAB, NIH, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, CEDARS SINAI MED CTR,SCH MED,DEPT MED, DIV ENDOCRINOL, LOS ANGELES, CA 90048 USA. RP Yanovski, JA (reprint author), NICHHD, DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262, MSC 1862, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 17 TC 19 Z9 19 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 1996 VL 81 IS 9 BP 3307 EP 3311 DI 10.1210/jc.81.9.3307 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA VF804 UT WOS:A1996VF80400036 PM 8784088 ER PT J AU Scott, WA Brambilla, D Siwak, E Beatty, C Bremer, J Coombs, RW Farzadegan, H Fiscus, SA Hammer, SM Hollinger, FB Khan, N Rasheed, S Reichelderfer, PS AF Scott, WA Brambilla, D Siwak, E Beatty, C Bremer, J Coombs, RW Farzadegan, H Fiscus, SA Hammer, SM Hollinger, FB Khan, N Rasheed, S Reichelderfer, PS TI Evaluation of an infectivity standard for real-time quality control of human immunodeficiency virus type 1 quantitative micrococulture assays SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; CLINICAL-TRIALS GROUP; PLASMA VIREMIA; HIV-1; CULTURE; MICROCULTURE; INDIVIDUALS; SUSCEPTIBILITY; LYMPHOCYTES AB Quantitative micrococulture assays of cryopreserved human immunodeficiency virus type 1-infected cell suspensions and culture supernatants were compared among seven assay sites. There was no significant change in titer during 1 year of storage. The overall standard deviation for infected cell suspensions was approximately 0.8 log(10) virus titer. A method for detecting deviant assay results was developed and was used to identify two donor cell preparations (n = 54) that gave consistently low titers. C1 NEW ENGLAND RES INST, WATERTOWN, MA 02192 USA. BAYLOR COLL MED, DIV MOL VIROL, HOUSTON, TX 77030 USA. UNIV MINNESOTA, DEPT MED, MINNEAPOLIS, MN 55455 USA. RUSH PRESBYTERIAN ST LUKES MED CTR, DEPT IMMUNOL & MICROBIOL, CHICAGO, IL 60612 USA. UNIV WASHINGTON, PACIFIC MED CTR, SEATTLE, WA 98144 USA. JOHNS HOPKINS UNIV, DEPT MED, BALTIMORE, MD 21205 USA. UNIV N CAROLINA, DEPT MICROBIOL & IMMUNOL, CHAPEL HILL, NC 27599 USA. HARVARD UNIV, NEW ENGLAND DEACONESS HOSP, SCH MED, BOSTON, MA 02215 USA. MARYLAND MED METPATH, BALTIMORE, MD 21227 USA. UNIV SO CALIF, DEPT PATHOL, LOS ANGELES, CA 90032 USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. RP Scott, WA (reprint author), UNIV MIAMI, SCH MED, DEPT BIOCHEM & MOL BIOL, POB 016129, MIAMI, FL 33101 USA. FU NIAID NIH HHS [AI27535, AI27551, AI25868] NR 32 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 1996 VL 34 IS 9 BP 2312 EP 2315 PG 4 WC Microbiology SC Microbiology GA VD335 UT WOS:A1996VD33500053 PM 8862609 ER PT J AU Clark, VP Hillyard, SA AF Clark, VP Hillyard, SA TI Spatial selective attention affects early extrastriate but not striate components of the visual evoked potential SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; INTERNATIONAL 10-20 SYSTEM; HUMAN BRAIN; ELECTROPHYSIOLOGICAL EVIDENCE; CURRENT-DENSITY; CORTEX; AREAS; TASK; MODULATION; MECHANISMS AB The effects of spatial selective attention on sensory processing in visual cortical areas were investigated by means of visual evoked potential (VEP) recordings and source localization techniques. Patterned stimuli were rapidly presented in random order to the left and right visual fields while subjects maintained central fixation and attended to one visual field at a time. Attended stimuli evoked enhanced P1 (100-130 msec) and N1 (120-200 msec) components of the VEP, whereas no effects of attention were observed on the C1 (50-100 msec) or P2 (200-240 msec) components. Spatiotemporal dipole modeling of the early VEP sources was carried out in relation to MRI-defined cortical anatomy. The dipolar generator of the CI component was found to lie in calcarine cortex, the human homologue of area Vl,whereas the attention-sensitive P1 generator was localized to ventral-lateral occipital cortex, within extrastriate area 19. These results support the hypothesis that spatial attention does not affect the initial activity evoked in area V1 but rather produces an enhancement within extrastriate visual areas of sensory signals arising from stimuli at attended locations. C1 UNIV CALIF SAN DIEGO,DEPT NEUROSCI,LA JOLLA,CA 92093. NIMH,NIH,BETHESDA,MD 20892. RI Clark, Vincent/B-3343-2010; Martin Arevalo, Elisa/L-4472-2014 OI Clark, Vincent/0000-0002-9151-2102; Martin Arevalo, Elisa/0000-0002-4546-6440 NR 68 TC 337 Z9 347 U1 10 U2 45 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD SEP PY 1996 VL 8 IS 5 BP 387 EP 402 DI 10.1162/jocn.1996.8.5.387 PG 16 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA VG437 UT WOS:A1996VG43700002 PM 23961943 ER PT J AU Buvat, I Freedman, NMT Dilsizian, V Bacharach, SL AF Buvat, I Freedman, NMT Dilsizian, V Bacharach, SL TI Realignment of emission contaminated attenuation maps with uncontaminated attenuation maps for attenuation correction in PET SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE emission computed tomography; image registration; attenuation correction ID TRANSMISSION MEASUREMENTS; SCANS; TOMOGRAPHY AB Purpose: We investigated aligning a transmission (T) scan with a subsequent emission contaminated transmission (T + E) scan. This would permit correction for patient motion and thereby use of a single T scan to correct E scans taken hours or days apart. Method: Scans from 15 patients were used to produce 200 T scans contaminated with two levels of either [F-18]fluorodeoxyglucose or [N-13]ammonia E data. Known misalignments were introduced between each T + E scan and the corresponding T scan, and each pair was subsequently realigned, Realignment errors were compared with those obtained for uncontaminated T scans. Results: The realignment errors increase with the contamination level and depend slightly on the contaminant. However, even at the highest level of contamination studied, the mean absolute translation errors remained less than the voxel size and the mean absolute rotation errors were <2.5 degrees. Conclusion: A T + E scan can be accurately realigned with a T scan. This suggests that attenuation correction could be performed by using a high quality T scan taken days or hours earlier and aligning this T scan with a short T scan taken immediately after E imaging. C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. CNRS,U66 INSERM,PARIS,FRANCE. NR 8 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 1996 VL 20 IS 5 BP 848 EP 854 DI 10.1097/00004728-199609000-00037 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VG359 UT WOS:A1996VG35900037 PM 8797931 ER PT J AU Skrtic, D Hailer, AW Takagi, S Antonucci, JM Eanes, ED AF Skrtic, D Hailer, AW Takagi, S Antonucci, JM Eanes, ED TI Quantitative assessment of the efficacy of amorphous calcium phosphate/methacrylate composites in remineralizing caries-like lesions artificially produced in bovine enamel SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amorphous calcium phosphate; caries; enamel; methacrylate composites; remineralization ID FLUORIDE MOUTHRINSE; INVITRO; TRANSFORMATION; PROGRESSION; DENTIFRICE; PH AB Recent studies show that methacrylate-based composites with amorphous calcium phosphate (ACP) as a filler can release supersaturating levels of calcium and phosphate ions in proportions favorable for apatite formation. These findings suggest that such composites could be effectively used as coatings for remineralizing teeth damaged by tooth decay. To examine this hypothesis, we tested composites in vitro for their efficacy to remineralize artificially formed caries-like lesions in extracted bovine incisors. Single 120-mu m-thick sagittal tooth sections were placed in holders that exposed only the carious enamel surface. The exposed surfaces were coated with a 1-mm- to 1.5-mm-thick layer of the composite containing, by mass, 40% apatite, silica, or P2O74--stabilized ACP and 60% photoactivated resin comprised of Bis-GMA, TEGDMA, HEMA, and ZrM. The photocured composite-coated sections were immersed either in a remineralizing solution for 4 weeks at 37 degrees C (static model) or cyclically immersed in demineralizing (0.5 h) and remineralizing solutions (11.5 h) for 2 weeks (dynamic model). Quantitative digital image analysis of matched 102 mu m x 220 mu m areas from contact microradiographs taken of the sections before and after immersion showed that lesions coated with ACP-filled composites fractionally recovered 71% +/- 33% of their lost mineral compared with 14% +/- 13% for apatite controls in the static model and 38% +/- 16% compared with -6% +/- 24% in the dynamic model. The results suggest that sealants based on ACP-filled methacrylate composites have the potential to remineralize carious enamel lesions. C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. NIST,AMER DENT ASSOC HLTH FDN,PAFFENBARGER RES CTR,GAITHERSBURG,MD 20899. NIST,DENT & MED MAT GRP,DIV POLYMERS,GAITHERSBURG,MD 20899. FU NIDCR NIH HHS [DEO5354] NR 23 TC 96 Z9 97 U1 0 U2 4 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD SEP PY 1996 VL 75 IS 9 BP 1679 EP 1686 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VX041 UT WOS:A1996VX04100010 PM 8952621 ER PT J AU McConkey, GA Li, J Rogers, MJ Seeley, DC Graczyk, TK Cranfield, MR McCutchan, TF AF McConkey, GA Li, J Rogers, MJ Seeley, DC Graczyk, TK Cranfield, MR McCutchan, TF TI Parasite diversity in an endemic region for avian malaria and identification of a parasite causing penguin mortality SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE Culex; mosquito; Plasmodium relictum; ribosomal RNA; RT-PCR; Spheniscus demersus ID PLASMODIUM-FALCIPARUM; SPHENISCUS-DEMERSUS; MOSQUITO; ACID; RNA AB Understanding the population structure of Plasmodium parasites is essential for malaria intervention. A survey of parasites in vectors and host infections was conducted in an area of intense mortality due to malaria in a captive penguin (Spheniscus demersus) colony, using a novel method for identification of Plasmodium species by amplification of ribosomal sequences in DNA or RNA. Three phylogenetically distinct groups of avian Plasmodium were detected in mosquitoes (Culex) collected at the study site (Baltimore Zoo, Baltimore, MD) during a period of high transmission. One of the three clades of Plasmodium was found to be prevalent in penguins monitored through the malaria transmission season and consistent with morphological identification as Plasmodium relictum. This parasite sequence was directly associated with the death of a penguin. Thus, a complete transmission cycle is defined at this site. Phylogenetic comparison of ribosomal sequences to an authenticated reference strain of Plasmodium relictum indicates that this is not the parasite causing death in the penguins, suggesting that different parasites may be morphologically indistinguishable. C1 NIAID,GROWTH & DEV SECT,LAB PARASIT DIS,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT MOL MICROBIOL & IMMUNOL,BALTIMORE,MD 21205. BALTIMORE ZOO,DEPT MED,BALTIMORE,MD 21217. JOHNS HOPKINS UNIV,SCH MED,DEPT COMPARAT MED,BALTIMORE,MD 21205. NR 24 TC 21 Z9 21 U1 1 U2 10 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1996 VL 43 IS 5 BP 393 EP 399 DI 10.1111/j.1550-7408.1996.tb05049.x PG 7 WC Microbiology SC Microbiology GA VC050 UT WOS:A1996VC05000005 PM 8822810 ER PT J AU Angus, CW Klivington, D Wyman, J Kovacs, JA AF Angus, CW Klivington, D Wyman, J Kovacs, JA TI Nucleic acid vaccination against Toxoplasma gondii in mice SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshops on Opportunistic Protists CY JUN 11-15, 1996 CL TUCSON, AZ SP Bayer Corp, Bio Merieux, Burroughs Wellcome Fund, Charles River Labs, Ciba Geigy Corp, Glaxo Wellcome Inc, Heska Corp, Hoechst Roussel Agri Vet Co, Meridian Diagnost Inc, NIAID, NHLBI, Pfizer Inc, TAP Holdings RP Angus, CW (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 4 TC 13 Z9 13 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1996 VL 43 IS 5 BP S117 EP S117 DI 10.1111/j.1550-7408.1996.tb05034.x PG 1 WC Microbiology SC Microbiology GA VC050 UT WOS:A1996VC05000097 PM 8822899 ER PT J AU Mei, Q Kovacs, JA Hildebrand, B Angus, CW AF Mei, Q Kovacs, JA Hildebrand, B Angus, CW TI Expression of the major surface glycoprotein of rat-derived Pneumocystis carinii by recombinant baculovirus SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article; Proceedings Paper CT 4th International Workshops on Opportunistic Protists CY JUN 11-15, 1996 CL TUCSON, AZ SP Bayer Corp, Bio Merieux, Burroughs Wellcome Fund, Charles River Labs, Ciba Geigy Corp, Glaxo Wellcome Inc, Heska Corp, Hoechst Roussel Agri Vet Co, Meridian Diagnost Inc, NIAID, NHLBI, Pfizer Inc, TAP Holdings RP Mei, Q (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892, USA. NR 3 TC 4 Z9 4 U1 0 U2 0 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD SEP-OCT PY 1996 VL 43 IS 5 BP S31 EP S31 DI 10.1111/j.1550-7408.1996.tb04968.x PG 1 WC Microbiology SC Microbiology GA VC050 UT WOS:A1996VC05000031 PM 8822835 ER PT J AU Arenberg, DA Kunkel, SL Polverini, PJ Morris, SB Burdick, MD Glass, MC Taub, DT Iannettoni, MD Whyte, TI Strieter, RM AF Arenberg, DA Kunkel, SL Polverini, PJ Morris, SB Burdick, MD Glass, MC Taub, DT Iannettoni, MD Whyte, TI Strieter, RM TI Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NORMAL HUMAN KERATINOCYTES; PLATELET FACTOR-IV; X-C CHEMOKINE; TUMOR-GROWTH; IN-VIVO; BRONCHOGENIC-CARCINOMA; INDUCED ANGIOGENESIS; ALPHA-INTERFERON; GENE-EXPRESSION; T-CELLS AB The success of solid tumor growth and metastasis is dependent upon angiogenesis. Neovascularization within the tumor is regulated, in part, by a dual and opposing system of angiogenic and angiostatic factors. We now report that IP-10, a recently described angiostatic factor, is a potent angiostatic factor that regulates non-small cell lung cancer (NSCLC)-derived angiogenesis, tumor growth, and spontaneous metastasis. We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA). In contrast, levels of IP-10 were equivalent in either normal lung tissue or adenocarcinoma specimens. The neoplastic cells in specimens of SCCA were the predominant cells that appeared to express IP-10 by immunolocalization. Neutralization of IP-10 in SCCA tumor specimens resulted in enhanced tumor-derived angiogenic activity. Using a model of human NSCLC tumorigenesis in SCID mice, we found that NSCLC tumor growth was inversely correlated with levels of plasma or tumor-associated IP-10. IP-10 in vitro functioned as neither an autocrine growth factor nor as an inhibitor of proliferation of the NSCLC cell lines. Reconstitution of intratumor IP-10 for a period of 8 wk resulted in a significant inhibition of tumor growth, tumor-associated angiogenic activity and neovascularization, and spontaneous lung metastases; whereas, neutralization of IP-10 for 10 wk augmented tumor growth. These findings support the notion that tumor-derived IP-10 is an important endogenous angiostatic factor in NSCLC. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,DIV PULM & CRIT CARE,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH DENT,SECT ORAL PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT PATHOL,ANN ARBOR,MI 48109. NCI,MOL IMMUNOREGULAT LAB,FREDERICK,MD 21702. UNIV MICHIGAN,DEPT SURG,THORAC SURG SECT,ANN ARBOR,MI 48109. OI Arenberg, Douglas/0000-0001-7707-5092 FU NCI NIH HHS [CA66180, CA72543]; NHLBI NIH HHS [HL50057] NR 58 TC 284 Z9 291 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 1 PY 1996 VL 184 IS 3 BP 981 EP 992 DI 10.1084/jem.184.3.981 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA VG868 UT WOS:A1996VG86800020 PM 9064358 ER PT J AU Rickard, TC Bourne, LE AF Rickard, TC Bourne, LE TI Some tests of an identical elements model of basic arithmetic skills SO JOURNAL OF EXPERIMENTAL PSYCHOLOGY-LEARNING MEMORY AND COGNITION LA English DT Article ID MENTAL MULTIPLICATION; COGNITIVE MECHANISMS; DYSCALCULIA; RETRIEVAL; FACTS AB Two experiments tested an identical elements model of the organization of basic arithmetic skills (T. C. Rickard, A. F. Healy, & L. E. Bourne, 1994). This model assumes, a distinct abstract representation for each unique combination of the basic elements (i.e., the operands and the required operation) of a problem. Participants practiced multiplication and division problems and were then tested on various altered versions of these problems. Experiment 1 confirmed the prediction of no positive transfer when the presented elements of a test problem do not exactly match those of a practice problem. Experiment 2 confirmed the prediction that there is complete transfer when the elements of the test problem match exactly with those of a practice problem. Experiment 2 also confirmed that there is both perceptually specific and nonspecific speed-up with practice. Implications for number processing and arithmetic are discussed. C1 UNIV COLORADO,DEPT PSYCHOL,BOULDER,CO 80309. RP Rickard, TC (reprint author), NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,NIH,BLDG 10,ROOM 5S209,10 CTR DR MSC1440,BETHESDA,MD 20892, USA. NR 22 TC 62 Z9 62 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0278-7393 J9 J EXP PSYCHOL LEARN JI J. Exp. Psychol.-Learn. Mem. Cogn. PD SEP PY 1996 VL 22 IS 5 BP 1281 EP 1295 DI 10.1037/0278-7393.22.5.1281 PG 15 WC Psychology; Psychology, Experimental SC Psychology GA VF054 UT WOS:A1996VF05400015 PM 8805822 ER PT J AU Byrne, G Suomi, SJ AF Byrne, G Suomi, SJ TI Individual differences in object manipulation in a colony of tufted capuchins SO JOURNAL OF HUMAN EVOLUTION LA English DT Article DE cebus; capuchins; behavior; object manipulation; tool use; individual differences ID MONKEYS CEBUS-APELLA; TOOL USE; SENSORIMOTOR INTELLIGENCE; EXPLORATORY-BEHAVIOR; HAND PREFERENCE; ACQUISITION; ADAPTATIONS; APES AB Individual differences in object manipulation were studied in 42 captive tufted capuchins (Cebus apella) in seven social groups. Object manipulation was recorded in the homecage with familiar and novel objects. Juveniles were more manipulative than adults, and no overall sex differences were observed in object manipulation. Baseline manipulation of familiar objects in the homecage was significantly correlated with manipulation of novel objects when they were introduced. Along with a wide range of interest in objects, there was considerable stability in individual differences across situations, such that most animals could be classified as to their ''style'' of object use. The influence of those manipulative styles on whether or not individuals can learn to use tools remains to be explored. (C) 1996 Academic Press Limited RP Byrne, G (reprint author), NICHHD,COMPARAT ETHOL LAB,NIH,ANIM CTR,POOLESVILLE,MD 20837, USA. NR 39 TC 16 Z9 17 U1 1 U2 9 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0047-2484 J9 J HUM EVOL JI J. Hum. Evol. PD SEP PY 1996 VL 31 IS 3 BP 259 EP 267 DI 10.1006/jhev.1996.0060 PG 9 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA VH487 UT WOS:A1996VH48700004 ER PT J AU Anderson, DE Dhokalia, A Parsons, DJ Bagrov, AY AF Anderson, DE Dhokalia, A Parsons, DJ Bagrov, AY TI High end tidal CO2 association with blood pressure response to sodium loading in older adults SO JOURNAL OF HYPERTENSION LA English DT Article DE blood pressure; breathing; carbon dioxide; end tidal CO2; digitalis-like factor; hypertension; sodium chloride ID SALT SENSITIVITY; ESSENTIAL-HYPERTENSION; IMMUNOREACTIVE FACTOR; INHIBITORY ACTIVITY; DOGS; HYPOXIA; HUMANS; PLASMA; PUMP AB Objective To test the hypothesis that blood pressure of older adults with high resting end tidal CO2 (PETCO(2)) is sensitive to high dietary intake of sodium chloride. Design and methods Forty-four Caucasian men and women, aged 41-79 years (mean +/- SEM 55.5 +/- 1.4), restricted their dietary intake of sodium chloride for 11 days and ingested sodium chloride capsules (an additional 190 mmol sodium/day) during the last seven of those days, On days 1, 4 and 11, resting PETCO(2) and blood pressure were monitored for 25 min in the laboratory, followed by ambulatory blood pressure monitoring in the natural environment for 24 h, Overnight urine samples were obtained at days 4 and 11 to estimate excretion of sodium and of an endogenous digitalis-like factor (EDLF) that is sensitive to changes in plasma volume, Results Individual resting PETCO, remained stable within and between laboratory monitoring sessions and was correlated with urinary excretion of the endogenous digitalislike factor, both before and after the period of high sodium intake, The high-sodium diet was associated with increased urinary sodium excretion and body weight in all quartiles of PETCO(2). The high-sodium diet produced significant increases in resting and in 24 h systolic blood pressures in the upper two quartiles of the PETCO(2) distribution, and significant increases in resting and in 24 h diastolic blood pressures in the highest PETCO(2) quartile only, Conclusion These findings indicate that blood pressure sensitivity to sodium loading is differentially associated with high resting PETCO(2) in older adults, A high PETCO(2) may be an index of a dynamic steady state that influences sodium transport mechanisms. RP Anderson, DE (reprint author), NIA,GERONTOL RES CTR,NIH,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21093, USA. NR 38 TC 15 Z9 15 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD SEP PY 1996 VL 14 IS 9 BP 1073 EP 1079 DI 10.1097/00004872-199609000-00005 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA VK711 UT WOS:A1996VK71100005 PM 8986906 ER PT J AU Yewdell, JW Anton, LC Bennink, JR AF Yewdell, JW Anton, LC Bennink, JR TI Defective ribosomal products (DRiPs) - A major source of antigenic peptides for MHC class I molecules? SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTES; CELLS; PATHWAY AB MHC class I molecules predominantly bind to peptides derived from a cytosolic pool of polypeptides. Little is known about the nature of the polypeptides that serve as substrates for peptidogenic cytosolic proteases. We propose that a significant source of self and viral peptides are defective ribosomal products (DRiPs), which consist of prematurely terminated polypeptides and misfolded polypeptides produced from translation of bona fide mRNAs in the proper reading frame. DRiPs are produced entropically, due to the inevitable imperfections inherent to protein synthesis or folding, To accelerate recognition of cells harboring intracellular parasites such as viruses, DRiP formation may be enhanced by changes in the cellular physiology induced by infection or by exposure of cells to cytokines released at the site of inflammation. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X NR 21 TC 247 Z9 249 U1 1 U2 13 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 1996 VL 157 IS 5 BP 1823 EP 1826 PG 4 WC Immunology SC Immunology GA VF753 UT WOS:A1996VF75300002 PM 8757297 ER PT J AU Conlon, KC Anver, MR Longo, DL Ortaldo, JR Murphy, WJ AF Conlon, KC Anver, MR Longo, DL Ortaldo, JR Murphy, WJ TI Adoptive immunotherapy involving recombinant human M-CSF and R24 anti-melanoma antibody induces human T-cell infiltration into human melanoma xenografts SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE M-CSF; MoAbs; trafficking; human T cells ID COLONY-STIMULATING FACTOR; MOLECULAR MECHANISMS; METASTATIC MELANOMA; MONOCLONAL-ANTIBODY; PHASE-I; LYMPHOCYTES; CANCER; LYSIS; INTERLEUKIN-2; MIGRATION AB Directed motion toward and infiltration of tumor masses by effector cells is essential for successful adoptive immunotherapy. A human/SCLD mouse chimeric system was used to examine whether an antirumor antibody and recombinant human monocyte colony-stimulating factor (rhM-CSF) could promote human T-cell infiltration of a human tumor in vivo. Fourteen days after subcutaneous injection of the human melanoma cell line M-14 into SCID recipients, several adoptive immunotherapy regimens were initiated using activated human T cells, an anti-melanoma monoclonal antibody (MoAb) (R24), and rhM-CSF. Effects on tumor growth and human T-cell infiltration into the tumor were assessed. Compared with other treatment groups, only mice treated with the combination of activated human T cells, anti-tumor MoAb, and rhM-CSF demonstrated a significant cellular infiltrate in the melanoma. Immunohistology demonstrated human T cells present in the tumor up to 7 days after injection, Groups treated with rhRANTES or rmGM-CSF in place of rhM-CSF exhibited markedly less human T-cell infiltration. Additionally, only mice treated with human T cells, R24, and rhM-CSF demonstrated a significant antitumor response in vivo. This model suggests that activated human T cells can be specifically targeted to in vivo tumor sites by combined treatment with an antitumor antibody and rhM-CSF. C1 SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. SAIC FREDERICK,PATHOL HISTOTECH LAB,FREDERICK,MD. SAIC FREDERICK,EXPT IMMUNOL LAB,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,FREDERICK,MD 21701. NR 33 TC 4 Z9 3 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 1996 VL 19 IS 5 BP 317 EP 323 DI 10.1097/00002371-199609000-00001 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA VU227 UT WOS:A1996VU22700001 PM 8941871 ER PT J AU Player, MA Barracchini, KC Simonis, TB Rivoltini, L Arienti, F Castelli, C Mazzocchi, A Belli, F Parmiani, G Marincola, FM AF Player, MA Barracchini, KC Simonis, TB Rivoltini, L Arienti, F Castelli, C Mazzocchi, A Belli, F Parmiani, G Marincola, FM TI Differences in frequency distribution of HLA-A2 subtypes between North American and Italian white melanoma patients: Relevance for epitope specific vaccination protocols SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE melanoma; melanoma antigens; HLA ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; SEQUENCE-SPECIFIC PRIMERS; CLASS-I MOLECULES; PEPTIDE BINDING; CELL-LINES; A-LOCUS; ANTIGEN; IDENTIFICATION; DNA AB Cytotoxic T lymphocytes (CTL) associated in vivo with tumor regression recognize the product of nonmutated genes expressed by most melanoma cells as peptides bound to human leukocyte antigen (KLA) molecules. Multiple HLA-A*0201 restricted peptides derived from melanoma associated antigens (MAA) have been described, and peptide-based vaccination protocols against melanoma are being developed worldwide for the treatment of HLA-A2 melanoma patients based on the assumption that most serologically typed HLA-A2+ individuals will be suitable for such vaccinations. Serologic typing of HLA-A2, however, encompasses a family of at least 17 related alleles recognized by molecular typing techniques and differing at one or more functional residues of the HLA class I molecule. We have recently shown that naturally occurring single-residue variants of HLA-A*0201 are responsible for significant differences in CTL response to MAA-peptide stimulation. Existing data fur HLA-A*02 subtype frequencies among whites (who are most affected by melanoma) derive from analyses of Northern European and North American populations that are of similar heritage and predict an exceedingly rare (<5%) frequency of non-HLA-A*0201 alleles. Melanoma, however, affects other white populations in which the prevalence of HLA-Ar*02 alleles could be more variable. This study was done to identify HLA-A*02 subtypes and their prevalence in two ancestrally different white melanoma populations. HLA-A*02 subtype frequencies were compared by polymerase chain reaction between serologically HLA-A2+ melanoma patients referred for treatment to the Istituto Nazionale Tumori of Milan (n = 93), Italy or to the National Cancer Institute, Bethesda, MD, U.S.A. (n = 100). This analysis demonstrated differences in subtype specificity and distribution between the two populations, with a significantly higher percentage of non-HLA-A*0201 subtypes in the Italian population. Only 2% of serologically HLA-A2+ Northern American white melanoma patients did not express HLA-Ar*201. In contrast, 15% of HLA-A2+ Italian patients were not HLA-A*0201 (p(2) value = 0.001). As allele-specific/peptide-based vaccination protocols are presently pursued at several institutions, a proportion of patients might be inappropriately enrolled basing their eligibility on serologically defined HLA-typing. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. IST NAZL TUMORI,DEPT EXPT ONCOL D,I-20133 MILAN,ITALY. RI castelli, chiara/K-6899-2012; OI castelli, chiara/0000-0001-6891-8350; Rivoltini, Licia/0000-0002-2409-6225 NR 43 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 1996 VL 19 IS 5 BP 357 EP 363 DI 10.1097/00002371-199609000-00005 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA VU227 UT WOS:A1996VU22700005 PM 8941875 ER PT J AU Fenton, RG Steis, RG Madara, K Zea, AH Ochoa, AC Janik, JE Smith, JW Gause, BL Sharfman, WH Urba, WJ Hanna, MG DeJager, RL Coyne, MX Crouch, RD Gray, P Beveridge, J Creekmore, SP Holmlund, J Curti, BD Sznol, M Longo, DL AF Fenton, RG Steis, RG Madara, K Zea, AH Ochoa, AC Janik, JE Smith, JW Gause, BL Sharfman, WH Urba, WJ Hanna, MG DeJager, RL Coyne, MX Crouch, RD Gray, P Beveridge, J Creekmore, SP Holmlund, J Curti, BD Sznol, M Longo, DL TI A phase I randomized study of subcutaneous adjuvant IL-2 in combination with an autologous tumor vaccine in patients with advanced renal cell carcinoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE immunization; immunotherapy; T cell; vaccine; IL-2 ID ACTIVE SPECIFIC IMMUNOTHERAPY; MELANOMA-CELLS; T-CELLS; LYMPHOCYTES-T; INTERLEUKIN-2; GENE; COSTIMULATION; MOLECULES; ANTIGENS; IMMUNITY AB We performed a prospective, randomized study to determine whether subcutaneous administration of interleukin-2 (IL-2) in combination with an autologous renal cell vaccine is feasible and can potentiate antitumor immunity. Seventeen patients with metastatic renal cell carcinoma underwent surgical resection with preparation of an autologous tumor cell vaccine. Patients were vaccinated intradermally twice at weekly intervals with 10(7) irradiated tumor cells plus bacillus Calmette-Guerin, and once with 10(7) tumor cells alone. Patients were randomized to one of three groups: no adjuvant IL-2, low-dose. IL-2 (1.2 x 10(6) IU/m(2)), or high-dose IL-2 (1.2 x 10(7) IU/m(2)). IL-2 was administered subcutaneously on the day of vaccination and the subsequent 4 days. Immune response was monitored by delayed-type hypersensitivity (DTH) response to tumor cells as compared with normal autologous renal cells. Sixteen of 17 patients received vaccine therapy. Four patients developed cellular immunity specific for autologous tumor cells as measured by DTH responses; two had received no lL-2 and two had received high-dose: IL-2. There were two partial responses (PR) noted, both in patients who received high-dose IL-2. One responding patient was DTH(+) and one was negative. A third patient who was DTH(+) after vaccination with no IL-2 had a dramatic PR after receiving IL-2 subcutaneously in a subsequent protocol. Prospective testing of response to recall antigens indicated that only 5 of 12 tested patients were positive, including both clinical responders. These data suggest that subcutaneously administered adjuvant IL-2 does not dramatically augment the immunologic response to autologous renal cell vaccines as determined by the development of tumor-specific DTH response. C1 ATLANTA CANC CARE,ATLANTA,GA. FREDERICK MEM HOSP,CLIN RES BRANCH,FT DETRICK,MD. SAIC,CLIN SERV PROGRAM,FT DETRICK,MD. UNIV MICHIGAN,MED CTR,ANN ARBOR,MI 48109. FRANCIS SCOTT KEY MED CTR,DEPT MED,BALTIMORE,MD 21224. PROVIDENCE MED CTR,EARLE CHILES RES INST,PORTLAND,OR. PER IMMUNE INC,ROCKVILLE,MD. NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. RP Fenton, RG (reprint author), NCI,FREDERICK CANC RES & DEV CTR,CLIN RES BRANCH,POB B,BLDG 567,ROOM 207,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 28 TC 15 Z9 15 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 1996 VL 19 IS 5 BP 364 EP 374 DI 10.1097/00002371-199609000-00006 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA VU227 UT WOS:A1996VU22700006 PM 8941876 ER PT J AU Marincola, FM AF Marincola, FM TI Possible biases in referral pattern to NIH and their effect on HLA association studies SO JOURNAL OF IMMUNOTHERAPY LA English DT Letter RP Marincola, FM (reprint author), NCI,SURG BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP PY 1996 VL 19 IS 5 BP 384 EP 385 DI 10.1097/00002371-199609000-00009 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA VU227 UT WOS:A1996VU22700009 ER PT J AU Lang, DR Guerrant, RL AF Lang, DR Guerrant, RL TI Summary of the 31st United States Japan joint conference on cholera and related diarrheal diseases SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 UNIV VIRGINIA,DIV GEOG MED,CHARLOTTESVILLE,VA. RP Lang, DR (reprint author), NIAID,NIH,ENTER DIS BRANCH,SOLAR BLDG,ROOM 3A21,6003 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1996 VL 174 IS 3 BP 451 EP 455 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VE493 UT WOS:A1996VE49300001 PM 8769599 ER PT J AU Steel, C Guinea, A Ottesen, EA AF Steel, C Guinea, A Ottesen, EA TI Evidence for protective immunity to Bancroftian filariasis in the Cook Islands SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN LYMPHATIC FILARIASIS; PAPUA-NEW-GUINEA; ENDEMIC FILARIASIS; PACIFIC ISLAND; INFECTION; DYNAMICS; ANTIGEN; AREA; IMMUNOGLOBULIN; IDENTIFICATION AB To challenge the concept of protective immunity in lymphatic filariasis, 19 adult residents of a Wuchereria bancrofti-endemic island who had been diagnosed 17 years earlier as putatively immune endemic normals (PI/EN) were reexamined, Even with continued exposure to infection, all 19 had maintained their apparent infection-free status. Studies to define the mechanisms underlying this putative immunity revealed that cellular immune responses (including proliferation; generation of interleukin [IL]-2, IL-5, IL-10, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) to adult- and microfilarial-stage antigens, hut not antibody responses, were markedly greater than those of 20 age-matched, infected patients. Furthermore, the PI/EN group was comprised of high- and low-responding persons who were clinically indistinguishable. These findings provide evidence that protective immunity to lymphatic filariasis does occur and that it is probably T cell-mediated. C1 DEPT HLTH,MAUKE,COOK ISLANDS. RP Steel, C (reprint author), NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. NR 28 TC 37 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1996 VL 174 IS 3 BP 598 EP 605 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VE493 UT WOS:A1996VE49300021 PM 8769619 ER PT J AU Glass, RI Lang, DR Ivanoff, BN Compans, RW AF Glass, RI Lang, DR Ivanoff, BN Compans, RW TI Introduction: Rotavirus from basic research to a vaccine SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID YOUNG-CHILDREN; PROTECTION; IMMUNIZATION; INFECTION; DIARRHEA C1 EMORY UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,ATLANTA,GA 30322. NIAID,DIV MICROBIOL & INFECT DIS,NIH,BETHESDA,MD 20892. WHO,GLOBAL PROGRAMME VACCINES,VACCINE RES & DEV,CH-1211 GENEVA,SWITZERLAND. RP Glass, RI (reprint author), CTR DIS CONTROL & PREVENT,VIRAL GASTROENTERITIS SECT,NATL CTR INFECT DIS,ATLANTA,GA 30341, USA. RI Compans, Richard/I-4087-2013 OI Compans, Richard/0000-0003-2360-335X NR 18 TC 15 Z9 17 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1996 VL 174 SU 1 BP S1 EP S2 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VE910 UT WOS:A1996VE91000001 PM 8752282 ER PT J AU Kapikian, AZ Hoshino, Y Chanock, RM PerezSchael, I AF Kapikian, AZ Hoshino, Y Chanock, RM PerezSchael, I TI Efficacy of a quadrivalent rhesus rotavirus-based human rotavirus vaccine aimed at preventing severe rotavirus diarrhea in infants and young children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 5th Rotavirus Vaccine Workshop CY OCT 16-17, 1995 CL CTR DIS CONTROL & PREVENT, BETHESDA, MD SP Ctr Dis Control & Prevent, NIAIS, NIH, Emory Univ Sch Med HO CTR DIS CONTROL & PREVENT ID GASTROENTERITIS; REACTOGENICITY; RESTRICTION; INFECTION; IMMUNITY; AGENT AB The most extensively explored strategy for rotavirus vaccination has been the Jennerian approach, which uses an antigenically related rotavirus strain from an animal host as the immunogen to induce protection against the 4 epidemiologically important group A rotavirus VP7 serotypes. Because this approach has shown limited efficacy, a modified Jennerian approach was developed with the goal of achieving broader antigenic coverage, Four VP7 serotypes were incorporated into a quadrivalent vaccine comprised of three rhesus-human rotavirus reassortants, each with 10 rhesus rotavirus genes and 1 human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity; the rhesus rotavirus itself provides coverage for VP7 serotype 3. This approach appears quite promising for preventing severe rotavirus diarrhea, including those episodes that lead to dehydration. Additional strategies under development stress the role not only of human rotavirus VP7 but also of human rotavirus VP4, the other outer capsid protein that also induces neutralizing antibodies. C1 CENT UNIV VENEZUELA,CARACAS,VENEZUELA. RP Kapikian, AZ (reprint author), NIAID,INFECT DIS LAB,NIH,BLDG 7,ROOM 103,7 CTR DR MSC 0720,BETHESDA,MD 20892, USA. NR 38 TC 89 Z9 99 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1996 VL 174 SU 1 BP S65 EP S72 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VE910 UT WOS:A1996VE91000012 PM 8752293 ER PT J AU Lang, DR Glass, RI Compans, RW AF Lang, DR Glass, RI Compans, RW TI Summary of the Fifth Rotavirus Vaccine Workshop SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material C1 EMORY UNIV,SCH MED,ATLANTA,GA. NIAID,DIV MICROBIOL & INFECT DIS,NIH,BETHESDA,MD 20892. RP Lang, DR (reprint author), CTR DIS CONTROL & PREVENT,VIRAL GASTROENTERITIS SECT,NATL CTR INFECT DIS,ATLANTA,GA 30341, USA. RI Compans, Richard/I-4087-2013 OI Compans, Richard/0000-0003-2360-335X NR 0 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP PY 1996 VL 174 SU 1 BP S3 EP S4 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA VE910 UT WOS:A1996VE91000002 PM 8752283 ER PT J AU Bouloc, A Walker, P Grivel, JC Vogel, J Katz, SI AF Bouloc, A Walker, P Grivel, JC Vogel, J Katz, SI TI Dendritic cells in intracutaneous DNA immunization. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 5 EP 5 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000032 ER PT J AU Roden, R Kirnbauer, R Lowy, D Schiller, J AF Roden, R Kirnbauer, R Lowy, D Schiller, J TI In vitro generation of infectious papillomavirus and assessment of serological cross-reactivity. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD. UNIV VIENNA,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 8 EP 8 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000039 ER PT J AU Boni, R Zhuang, Z Albuquerque, A Vortmeyer, A Duray, P AF Boni, R Zhuang, Z Albuquerque, A Vortmeyer, A Duray, P TI Allelic deletion detected on chromosome 1p and chromosome 9p in microdissected dysplastic nevus lesions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ZURICH HOSP,DEPT DERMATOL,CH-8091 ZURICH,SWITZERLAND. NCI,DEPT PATHOL,NIH,BETHESDA,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 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 71 EP 71 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000098 ER PT J AU Courtois, S Woodworth, CD Degreef, H Garmyn, M AF Courtois, S Woodworth, CD Degreef, H Garmyn, M TI Retroviral-mediated wild-type p53 expression suppresses tumorigenesis and allows G1 arrest after UVB in human squamous carcinoma cells. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 CATHOLIC UNIV LEUVEN,DEPT DERMATOL,B-3000 LOUVAIN,BELGIUM. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 144 EP 144 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000173 ER PT J AU Richard, G Whyte, YM Smith, L Itin, P Hohl, D Wollina, U Epstein, E Lin, JP Bale, SJ AF Richard, G Whyte, YM Smith, L Itin, P Hohl, D Wollina, U Epstein, E Lin, JP Bale, SJ TI Linkage studies in erythrokeratodermias: Fine mapping, genetic heterogeneity, and analysis of candidate genes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD. UNIV BASEL,DEPT DERMATOL,CH-4003 BASEL,SWITZERLAND. BEAUMONT HOSP,DEPT DERMATOL,LAUSANNE,SWITZERLAND. UNIV JENA,DEPT DERMATOL,D-6900 JENA,GERMANY. UNIV CALIF SAN FRANCISCO,GEN HOSP,DEPT DERMATOL,SAN FRANCISCO,CA 94143. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 202 EP 202 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000232 ER PT J AU Jakob, T Udey, MC AF Jakob, T Udey, MC TI Intercellular adhesion in aggregates of murine fetal skin-derived dendritic cell precursors is mediated by E-cadherin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 231 EP 231 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000259 ER PT J AU Hertl, M Amagai, M Ishii, K Karr, R Katz, SI AF Hertl, M Amagai, M Ishii, K Karr, R Katz, SI TI T cell responses to the extracellular portion (EC1-5) of desmoglein 3 (Dsg 3) are restricted by polymorphisms of the beta 1-chain of HLA-DR and by HLA-DQ molecules. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 RHEIN WESTFAL TH AACHEN,DEPT DERMATOL,D-5100 AACHEN,GERMANY. KEIO UNIV,TOKYO,JAPAN. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. GD SEARLE & CO,ST LOUIS,MO. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 290 EP 290 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000321 ER PT J AU Kraemer, KH AF Kraemer, KH TI Xeroderma pigmentosum knockout mice: An immunologic tale SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID DNA-REPAIR; EXCISION REPAIR; IMMUNE FUNCTION; SKIN-CANCER; GENE; TRICHOTHIODYSTROPHY; CELLS RP Kraemer, KH (reprint author), NCI,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 18 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 291 EP 292 DI 10.1111/1523-1747.ep12362992 PG 2 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000001 PM 8751958 ER PT J AU Hengge, UR Walker, PS Foster, RA Himmler, A Vogel, JC AF Hengge, UR Walker, PS Foster, RA Himmler, A Vogel, JC TI Eradication of canine oral papillomatosis via intralesional naked IFN-A DNA: Results of a double-blind trial. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. UNIV ESSEN GESAMTHSCH,DEPT DERMATOL,D-4300 ESSEN 1,GERMANY. BENDER & CO,VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 348 EP 348 PG 1 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000377 ER PT J AU Yang, JM Nam, K Park, KB Kim, WS Moon, KC Koh, JK Steinert, PM Lee, ES AF Yang, JM Nam, K Park, KB Kim, WS Moon, KC Koh, JK Steinert, PM Lee, ES TI A novel H1 mutation in the keratin 1 chain in epidermolytic hyperkeratosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE type II keratin; H1 subdomain; ichthyosis ID INTERMEDIATE FILAMENTS; DISEASE; GENE; DOMAINS AB We report a novel mutation in a case of epidermolytic hyperkeratosis that results in a proline for arginine substitution in the penultimate residue position of the H1 subdomain of the keratin 1 chain, which is near the beginning of the rod domain. This causes a severe clinical disease classified as PS-2. Therefore, the H1 subdomain is probably equally important for the maintenance of keratin intermediate filament integrity as the rod domain. Since earlier concepts had implied that mutations in the H1 subdomain produce milder disease, this case suggest that attempts to correlate mutations with disease presentation remain problematic. C1 SAMSUNG BIOMED RES INST,BASIC RES CTR,SEOUL,SOUTH KOREA. ASAN MED CTR,DEPT DERMATOL,SEOUL,SOUTH KOREA. NIAMSD,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. RP Yang, JM (reprint author), SAMSUNG MED CTR,DEPT DERMATOL,KANGNAM KU,50 IL WON DONG,SEOUL 135230,SOUTH KOREA. NR 24 TC 14 Z9 14 U1 2 U2 4 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 1996 VL 107 IS 3 BP 439 EP 441 PG 3 WC Dermatology SC Dermatology GA VD790 UT WOS:A1996VD79000026 PM 8751983 ER PT J AU Zhou, LX Pihlstrom, B Hardwick, JP Park, SS Wrighton, SA Holtzman, JL AF Zhou, LX Pihlstrom, B Hardwick, JP Park, SS Wrighton, SA Holtzman, JL TI Phenytoin metabolism by the gingiva of normal humans: The possible role of reactive metabolites of phenytoin in the initiation of gingival hyperplasia. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV MINNESOTA,DEPT MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT PHARMACOL,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,SCH DENT,MINNEAPOLIS,MN 55455. VET AFFAIRS MED CTR,MINNEAPOLIS,MN. NE OHIO UNIV,COLL MED,ROOTSTOWN,OH 44272. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. ELI LILLY & CO,INDIANAPOLIS,IN 46285. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 1996 VL 44 IS 7 BP A343 EP A343 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA VE473 UT WOS:A1996VE47300022 ER PT J AU Calderon, SN Bertha, CM Gutkind, JS Xu, H Partilla, JS Rothman, RB Rice, KC AF Calderon, SN Bertha, CM Gutkind, JS Xu, H Partilla, JS Rothman, RB Rice, KC TI Probes for narcotic receptor mediated phenomena .22. Synthesis and characterization of optically pure [H-3](+)-4-[(alpha R)-alpha-((2S,5R)-4-propyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N-diethylbenzamide, [H-3]SNC 121, a novel high affinity and selective ligand for delta opioid receptors SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE [H-3](+)-4-[(alpha-((2S,5R)-4-propyl-2,5-dimethyl-1-piperazinyl)-3-metho xybenzyl]-N,N-diethylbenzamide ([H-3]SNC 121); delta opioid receptors; SNC 80; [H-3]SNC 121 ID AGONIST; ANALGESIA AB The synthesis of unlabelled and labelled SNC 121, a selective nonpeptide ligand for the delta opioid receptor is reported. [H-3]SNC 121 of specific activity of 26.8 Ci/mmol, was synthesized by catalytic tritiation of the optically pure precursor SNC 80. C1 NIDA,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NIDR,NIH,BETHESDA,MD 20892. RP Calderon, SN (reprint author), NIDDKD,MED CHEM LAB,BLDG 8,RM B1-23,BETHESDA,MD 20892, USA. RI Gutkind, J. Silvio/A-1053-2009 NR 14 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD SEP PY 1996 VL 38 IS 9 BP 847 EP 850 DI 10.1002/(SICI)1099-1344(199609)38:9<847::AID-JLCR900>3.0.CO;2-N PG 4 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA VD399 UT WOS:A1996VD39900008 ER PT J AU Wang, RF Rosenberg, SA AF Wang, RF Rosenberg, SA TI Human tumor antigens recognized by T lymphocytes: Implications for cancer therapy SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE cyclin-dependent kinase 4; beta-catenin; autoimmune disease; interleukin-2 ID DIFFERENTIAL-AVIDITY MODEL; HUMAN GENE MAGE-3; HUMAN-MELANOMA; INFILTRATING LYMPHOCYTES; IN-VITRO; METASTATIC MELANOMA; HLA-A2 MELANOMAS; BREAST-CANCER; MESSENGER-RNA; IMMUNODOMINANT PEPTIDE AB The adoptive transfer of cytotoxic T lymphocytes (CTLs) derived from tumor-infiltrating lymphocytes (TIL) along with interleukin-2 (IL-2) into autologous patients with cancer resulted in the objective regression of tumor, indicating that these CTLs recognized cancer rejection antigens on tumor cells. In the past year, a number of such tumor antigens were isolated by the use of cDNA expression systems and biochemical approaches. The majority of tumor antigens identified to date have been found to be nonmutated, self proteins. This raises important questions regarding the mechanism of antitumor activity and autoimmune disease. Several tumor-specific mutated tumor antigens have also been recently identified, which include cell cyclin-dependent kinase 4 (CDK4) and beta-eatenin. For the first time, a novel human cancer antigen was recently found to be generated by the use of an alternative open reading frame of the previously identified tyrosinase-related protein-1 (TRP-1) gene. The identification of human tumor rejection antigens provides new opportunities for the development of therapeutic strategies against cancer. The potential clinical applications of these tumor antigens will be discussed. RP Wang, RF (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 120 TC 37 Z9 39 U1 0 U2 3 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 SEP PY 1996 VL 60 IS 3 BP 296 EP 309 PG 14 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VH464 UT WOS:A1996VH46400002 PM 8830785 ER PT J AU Xu, LL Warren, MK Rose, WL Gong, WH Wang, JM AF Xu, LL Warren, MK Rose, WL Gong, WH Wang, JM TI Human recombinant monocyte chemotactic protein and other c-c chemokines bind and induce directional migration of dendritic cells in vitro SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE binding; chemotaxis ID MULTIPLE LEUKOCYTE RECEPTORS; COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; MOLECULAR-BIOLOGY; MCP3 INTERACTS; CYTOKINES; IDENTIFICATION; PROGENITORS; EXPRESSION; FAMILY AB Because dendritic cells (DC) are the most potent antigen-presenting cells involved in many pathophysiological responses, we investigated the effect of chemokines on the migration of these cells in an effort to determine whether chemokines may contribute to the initiation of immune responses. CD34(+) progenitor cells isolated from umbilical cord blood were grown in suspension cultures with cytokines and expanded 50- to 100-fold. A variable proportion of the cells expressed markers consistent with DC. The proportion of CD1a(+) DC was increased when the cells were cultured with interleukin-4 (IL-4). These cells expressed specific binding sites for C-C and C-X-C chemokines. Cells cultured with or without IL-4 had similar binding profiles. All C-C chemokines tested, including monocyte chemotactic protein (MCP)-1, MCP-2, MCP-3, macrophage inflammatory protein-1 alpha (MIP1 alpha), MIP-1 beta, and RANTES, induced migration of DC-enriched cells cultured with or without IL-4 with MCP-3 being the most potent chemoattractant. Phenotypic analysis of cell migrating in response to C-C chemokines showed that CD1a(+) cells were indeed attracted across the polycarbonate filters, and there was no preferential attraction of contaminating CD14(+) monocytes by C-C chemokines. DC-enriched cells also expressed specific binding sites for IL-8 and NAP2, which failed to induce cell migration. Our results suggest that C-C chemokines may participate in the recruitment of DC to amplify host defense. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD 21701. OTSUKA AMER PHARMACEUT INC,MARYLAND RES LABS,ROCKVILLE,MD. NCI,FREDERICK CANC RES & DEV CTR,DIV BASIC RES,MOL IMMUNOREGULAT LAB,FREDERICK,MD. NR 30 TC 190 Z9 195 U1 0 U2 5 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 SEP PY 1996 VL 60 IS 3 BP 365 EP 371 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA VH464 UT WOS:A1996VH46400010 PM 8830793 ER PT J AU Kahn, RA Terui, T Randazzo, PA AF Kahn, RA Terui, T Randazzo, PA TI Effects of acid phospholipids on ARF activities: Potential roles in membrane traffic SO JOURNAL OF LIPID MEDIATORS AND CELL SIGNALLING LA English DT Article; Proceedings Paper CT Satellite Symposium of the 15th International-Society-for-Neurochemistry on Lipid Messengers in the Nervous System CY JUN 28-30, 1995 CL TOKYO, JAPAN SP Int Soc Neurochem, Nagai Fdn, Tokyo DE ADP-ribosylation factors (ARF); regulatory GTP binding proteins; phosphatidylinositol 4,5-bisphosphate (PIP2); GTPase activating protein (GAP); phospholipase D (PLD) ID ADP-RIBOSYLATION FACTOR; GTP-BINDING-PROTEIN; ENDOPLASMIC-RETICULUM; GOLGI TRANSPORT; BREFELDIN-A; EXCHANGE; COP AB ADP-ribosylation factors are a family of approximate to 21 kDa GTP binding proteins which have been implicated as ubiquitous regulators of multiple steps in both exocytic and endocytic membrane traffic in mammals and yeast. Reversible membrane associations are thought to be an essential component in the physiological actions of ARF and are regulated by GTP binding. ARFs are unique among the superfamily of GTP binding proteins in having a strict dependence on phospholipids for nucleotide exchange. In addition, ARF proteins were found to bind phospatidylinositol 4,5-bisphosphate (PIP2) specifically. PIP2 was found to increase the rate of GDP dissociation and stabilize the nucleotide-free form of the protein. The previously described requirements for PIP2 in the ARF stimulated phospholipase D (PLD) activity and ARF GTPase activating protein (ARF GAP) assays provide the basis for a model in which PIP2 acts as a cofactor in one or more ARF pathways. There are potentially two distinct phospholipid binding sites each of which are coupled to the nucleotide binding site of ARFs. RP Kahn, RA (reprint author), NCI,BIOL CHEM LAB,DTP,DCT,NIH,BLDG 37,ROOM 5D-02,BETHESDA,MD 20892, USA. NR 22 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0929-7855 J9 J LIPID MEDIAT CELL JI J. Lipid Mediat. Cell Signal. PD SEP PY 1996 VL 14 IS 1-3 BP 209 EP 214 DI 10.1016/0929-7855(96)00527-5 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VN203 UT WOS:A1996VN20300028 PM 8906564 ER PT J AU Gaynor, PM Zhang, WY Salehizadeh, B Pettiford, B Kruth, HS AF Gaynor, PM Zhang, WY Salehizadeh, B Pettiford, B Kruth, HS TI Cholesterol accumulation in human cornea: Evidence that extracellular cholesteryl ester-rich lipid particles deposit independently of foam cells SO JOURNAL OF LIPID RESEARCH LA English DT Article DE atherosclerosis; lipoproteins; apoE; apoA-I; apoB; corneal arcus ID LOW-DENSITY-LIPOPROTEIN; HUMAN ATHEROSCLEROTIC LESIONS; PLASMA LIPOPROTEINS; APOLIPOPROTEIN-E; ARCUS; MACROPHAGES; IDENTIFICATION; BINDING; INTIMA; ATHEROGENESIS AB The cornea is a connective tissue site where lipid accumulates as a peripheral arcus lipoides. We found that cholesterol, in predominantly esterified form, progressively accumulated with age in the peripheral corneas of 20- to 90-yr-old individuals. Ultrastructural studies showed extracellular solid spherical lipid particles (<200 nm in diameter) enmeshed between collagen fibers. Immunostaining showed significant apoE and apoA-I, but very little apoB in the peripheral cornea. Lipid particles were extracted from minced corneas into a buffer and subjected to isopycnic density gradient centrifugation. The lipid particles had a density <1.02 g/ml, contained >75% of their cholesterol in esterified form, and were distributed in two populations with average diameters of 22 +/- 5 nm (SD) and 79 +/- 26 nm. Gel-filtration chromatographic analysis of the corneal lipid particles showed that most cholesterol eluted with the larger particles and these larger particles lacked apoB. ApoA-I was associated with lipid particles the size of HDL. Most apoE was associated with lipid particles larger than the apoA-I-containing lipid particles and smaller than the large lipid particles that carried most of the corneal cholesterol. jlr Thus, the cholesteryl ester-rich lipid particles that accumulate in the cornea are 1) similar to lipid particles previously localized within and isolated from human atherosclerotic lesions, 2) accumulate without foam cells, and 3) may be derived from low density lipoproteins that have lost their apoB and fused. C1 NHLBI,SECT EXPT ATHEROSCLEROSIS,NIH,BETHESDA,MD 20892. NR 60 TC 29 Z9 30 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 1996 VL 37 IS 9 BP 1849 EP 1861 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH359 UT WOS:A1996VH35900003 PM 8895051 ER PT J AU Myhre, AM Takahashi, N Blomhoff, R Breitman, TR Norum, KR AF Myhre, AM Takahashi, N Blomhoff, R Breitman, TR Norum, KR TI Retinoylation of proteins in rat liver, kidney, and lung in vivo SO JOURNAL OF LIPID RESEARCH LA English DT Article DE retinoic acid; retinol all-trans-retinoic acid; protein acylation ID RETINOIC ACID RECEPTOR; THIOREDOXIN REDUCTASE; 13-CIS-RETINOIC ACID; CELL-LINES; C-JUN; BINDING; ACYLATION; LEUKEMIA; 17-BETA-ESTRADIOL; DIFFERENTIATION AB Retinoylation (retinoic acylation) is a posttranslational modification of proteins occurring in a variety of cell types in vitro. This study was done to examine whether retinoylation occurs in vivo. We found that in retinol-deficient rats, radiolabeled retinol or retinoic acid was incorporated into the liver, kidney, and lung in a form that was not removed by extraction with CHCl3:CH3OH. About 98% of the radiolabeled retinoid was acid-soluble after digestion with proteinase K indicating that it was covalently bound to protein. About 50% of the retinoid covalently bound to liver and kidney protein was removed by mild hydrolysis with CH3OH-KOH. Methyl retinoate, all-trans-retinoic acid, and polar metabolites of retinoic acid accounted for essentially all of the retinoids released. We conclude that retinoylation of protein occurs in vivo primarily via the formation of an ester bond. C1 UNIV OSLO,INST NUTR RES,FAC MED,N-0316 OSLO,NORWAY. NCI,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 36 TC 32 Z9 33 U1 0 U2 0 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 1996 VL 37 IS 9 BP 1971 EP 1977 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA VH359 UT WOS:A1996VH35900015 PM 8895063 ER PT J AU GarzinoDemo, A Chen, M Lusso, P Berneman, Z DiPaolo, JA AF GarzinoDemo, A Chen, M Lusso, P Berneman, Z DiPaolo, JA TI Enhancement of TAT-induced transactivation of the HIV-1 LTR by two genomic fragments of HHV-6 SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE cervical carcinoma; AIDS; papillomavirus ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN HERPESVIRUS-6 INFECTION; HUMAN PAPILLOMAVIRUS INFECTION; LONG TERMINAL REPEAT; MARROW TRANSPLANTATION; CERVICAL NEOPLASIA; IDENTIFICATION; GENE; CELLS; WOMEN AB Clinical and experimental observations suggest that human herpesvirus-6 (HHV-6), a T-lymphotropic herpesvirus, may act as a cofactor in the acquired immunodeficiency syndrome (AIDS). Moreover, a possible role of HHV-6 in the increased incidence and severity of cervical carcinoma in human immunodeficiency virus (HIV)-infected women was suggested by the recent observation that HHV-6 can infect cervical carcinoma cells, accelerating their tumorigenicity in vivo. Therefore, the ability of four HHV-6 genomic clones derived from HHV-6 to transactivate the long terminal repeat (LTR) of HIV-1 in two cervical carcinoma cell lines and in a T-lymphoid cell line was tested. Two HHV-6 clones, pZVH-14 and pZVB-70, which were previously shown to increase the expression of human papillomavirus (HPV)-transforming genes, were, per se, weak transactivators of the HIV-1 LTR. However, an increased effect occurred when these clones were combined with the HIV-1 transactivator TAT-1. No such effect was seen with two other HHV-6 clones used as controls. Analysis with HIV-1 LTR deletion mutants indicated that this enhancing effect requires the presence of elements contained in both the enhancer region and the TAT activation region (TAR) of HIV-1. This data may have implications for the potential role of HHV-6 in AIDS and AIDS-related cervical carcinoma. (C) 1996 Wiley-Liss, Inc. C1 NCI, BIOL LAB, BETHESDA, MD 20892 USA. NCI, TUMOR CELL BIOL LAB, BETHESDA, MD 20892 USA. UNIV ANTWERP, LAB EXPT HEMATOL, ANTWERP, BELGIUM. NR 36 TC 9 Z9 9 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0146-6615 EI 1096-9071 J9 J MED VIROL JI J. Med. Virol. PD SEP PY 1996 VL 50 IS 1 BP 20 EP 24 DI 10.1002/(SICI)1096-9071(199609)50:1<20::AID-JMV5>3.0.CO;2-V PG 5 WC Virology SC Virology GA VM302 UT WOS:A1996VM30200005 PM 8890036 ER PT J AU Timbs, MM Spring, KR AF Timbs, MM Spring, KR TI Hydraulic properties of MDCK cell epithelium SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE water permeability; compliance; confocal microscopy; cell volume; fluorescence ID LATERAL INTERCELLULAR SPACES; RAT PROXIMAL TUBULE; WATER PERMEABILITY; MODEL; TRANSPORT; PH; MONOLAYERS; ABSORPTION; PATHWAYS; VOLUME AB The water permeability of the apical and basolateral cell membranes and the compliance of the lateral intercellular spaces (LIS) of MDCK monolayers were measured on confluent cultures grown on permeable supports. Cell membrane water permeabilities were determined, using quantitative differential interference light microscopy, from the rate of cell volume decrease after exposure to a hyperosmotic bathing solution. Both membranes exhibited osmotic water permeabilities (P-OSM) of -10 mu m/sec, comparable to that of unmodified lipid bilayers. The compliance of the cell membranes forming the lateral intercellular space (LIS) between cells was determined from the pressure-volume relation. Confocal microscopy of fluorescent labeling of the basolateral cell membranes was used to delineate the LIS geometry as transepithelial hydrostatic pressure was varied. The LIS were poorly deformable as a function of transepithelial hydrostatic pressure until a pressure of greater than or equal to 8 cm H2O (basolateral > apical) was reached where catastrophic failure of intercellular connections occurred. The compliance of the LIS was calculated from the geometry changes at pressures <8 cm H2O and ranged from 0.05-0.11 cm H2O-1, comparable to that previously predicted in mathematical models of the rat proximal tubule. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,NIH,BETHESDA,MD 20892. NR 31 TC 27 Z9 27 U1 2 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD SEP PY 1996 VL 153 IS 1 BP 1 EP 11 DI 10.1007/s002329900104 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA VE243 UT WOS:A1996VE24300001 PM 8694902 ER PT J AU Lee, CM Stevens, LA Hsu, HC Tsai, SC Lee, YT Moss, J Vaughan, M AF Lee, CM Stevens, LA Hsu, HC Tsai, SC Lee, YT Moss, J Vaughan, M TI Expression in human endothelial cells of ADP-ribosylation factors, 20-kDa guanine nucleotide-binding proteins involved in the initiation of vesicular transport SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE ADP-ribosylation factors; human umbilical vein endothelial cells; quantitative polymerase chain reaction; guanine nucleotide-binding proteins ID POLYMERASE CHAIN-REACTION; CHOLERA-TOXIN; MESSENGER-RNA; FACTOR-III; FACTOR-I; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; GOLGI MEMBRANES; FACTORS ARFS; BREFELDIN-A AB ADP-ribosylation factors (ARFs) are similar to 20-kDa, guanine nucleotide-binding proteins, initially discovered as stimulators of cholera toxin ADP-ribosyltransferase activity and subsequently shown to participate in vesicular trafficking, Five of the six mammalian ARFs have been identified inhuman tissues by molecular cloning. They Fall into three classes (class I: ARFs 1-3; class II: ARFs 4, 5; class III: ARF 6) based on deduced amino acid sequence, size, phylogenetic analysis, and gene structure. Similar to the rab family of similar to 20 kDa guanine nucleotide-binding proteins, the ARFs appear to function in specific trafficking pathways, The presence of a specific ARF might serve as a marker for that pathway, To verify expression of ARF mRNA and protein in human umbilical vein endothelial cells, immunoreactivity using antibodies specific for each ARF class, quantitative polymerase chain reaction (PCR) using ARF-specific, internal cRNA standards containing unique restriction enzyme cleavage sites introduced by point mutations, and Northern analysis with probes specific for ARPs 1, and 3-6, were utilized. PCR and northern analysis were in agreement in showing that amounts of mRNA for ARF 1 and XRF 4 were similar and higher than those of ARF 3 and ARF 5 which were greater than ARF 6, Primarily, Class I ARF proteins were detected by immunoreactivity, with the majority in the supernatant fraction, The relative expression of ARFs in endothelial cells thus differs from that in neuronal tissues where it had been found that ARF 3 is the predominant species. C1 NHLBI, PULM CRIT CARE MED BRANCH, NIH, BETHESDA, MD 20892 USA. NATL TAIWAN UNIV HOSP, DEPT INTERNAL MED, TAIPEI 10016, TAIWAN. OI LEE, CHII-MING/0000-0002-1075-5787 NR 42 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 1996 VL 28 IS 9 BP 1911 EP 1920 DI 10.1006/jmcc.1996.0184 PG 10 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA VK818 UT WOS:A1996VK81800009 PM 8899550 ER PT J AU Zhang, J Clark, JR Herman, EH Ferrans, VJ AF Zhang, J Clark, JR Herman, EH Ferrans, VJ TI Doxorubicin induced apoptosis in spontaneously hypertensive rats: Differential effects in heart, kidney and intestine, and inhibition by ICRF-187 SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE doxorubicin toxicity; ICRF-187; apoptosis; cardiomyopathy; nephropathy ID PROGRAMMED CELL-DEATH; TOPOISOMERASE-II; DNA-DAMAGE; BIS(2,6-DIOXOPIPERAZINE) DERIVATIVES; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; TUMOR-CELLS; ADRIAMYCIN; INDUCTION; GROWTH AB The occurrence of apoptosis in heart, kidney and small intestine was investigated in spontaneously hypertensive rats (SHR) treated with doxorubicin (1 mg/kg/week for 6, 9 and 12 weeks) with and without pretreatment with the iron chelator ICRF-187 [(+)1,2-bis(3.5-dioxopiperazinyl-1-yl)propane] (25 mg/kg, i.p., given 30 min before doxorubicin). Animals receiving either ICRF-187 alone or saline were used as controls, Cells undergoing apoptosis were identified ultrastructurally and by staining using the nick-end labeling method, The results obtained by counting cells with positive nick-end labeling showed that, when given in cumulative doses of 9 and 12 (but not 6) mg/kg, doxorubicin induced significant toxicity in the heart, kidneys and intestine in association with apoptosis in epithelial cells of the intestinal mucosa and renal tubules but not in cardiac myocytes. At these doses, nick end labeling in the heart was confined to occasional endothelial cells, interstitial dendritic cells and macrophages. The frequency of doxorubicin-induced apoptosis in renal and intestinal epithelial cells was decreased by pretreatment of the SHR with ICRF-187. Our data support the concept that the chronic cardiomyopathy induced by doxorubicin is not mediated by apoptosis of the cardiac myocytes. (C) 1996 Academic Press Limited C1 NHLBI, PATHOL SECT, NIH, BETHESDA, MD 20892 USA. US FDA, DIV RES & TESTING, LAUREL, MD 20708 USA. NR 47 TC 96 Z9 97 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD SEP PY 1996 VL 28 IS 9 BP 1931 EP 1943 DI 10.1006/jmcc.1996.0186 PG 13 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA VK818 UT WOS:A1996VK81800011 PM 8899552 ER PT J AU Jeffers, M Rong, S VandeWoude, GF AF Jeffers, M Rong, S VandeWoude, GF TI Hepatocyte growth factor scatter factor Met signaling in tumorigenicity and invasion/metastasis SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE hepatocyte growth factor scatter factor; Met; tumorigenicity; invasion; metastasis ID CARCINOMA CELL-LINES; RECEPTOR TYROSINE KINASE; HUMAN PANCREATIC-CANCER; C-MET; EPITHELIAL-CELLS; FACTOR/SCATTER FACTOR; HGF RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PROTOONCOGENE PRODUCT; AUTOCRINE STIMULATION AB Hepatocyte growth factor/scatter factor (HCF/SF) is a pleiotropic effector of cells expressing the Met tyrosine kinase receptor. While HGF/SF-Met signaling clearly plays a role in a variety of normal cellular processes, this signaling pathway has also been implicated in the generation and metastatic spread of tumors. This review discusses in detail several model systems that have been developed to investigate the role of HGF/SF-Met signaling in malignancy and describes additional data regarding the expression of these molecules in human tumors. Collectively the findings support a role for this receptor-ligand pair in human malignancy. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 106 TC 234 Z9 243 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD SEP PY 1996 VL 74 IS 9 BP 505 EP 513 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA VG430 UT WOS:A1996VG43000004 PM 8892055 ER PT J AU Pengsuparp, T Serit, M Hughes, SH Soejarto, DD Pezzuto, JM AF Pengsuparp, T Serit, M Hughes, SH Soejarto, DD Pezzuto, JM TI Specific inhibition of human immunodeficiency virus type 1 reverse transcriptase mediated by soulattrolide, a coumarin isolated from the latex of Calophyllum teysmannii SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID HIGH-LEVEL RESISTANCE; RAIN-FOREST TREE; SELECTIVE-INHIBITION; HIV-1 REPLICATION; NATURAL-PRODUCTS; ESCHERICHIA-COLI; ZIDOVUDINE AZT; DNA-POLYMERASE; DERIVATIVES; 3'-AZIDO-3'-DEOXYTHYMIDINE AB Soulattrolide (1), a coumarin isolated from Calophyllum teysmannii latex, was found to be a potent inhibitor of HIV-1 reverse transcriptase (RT) with an IC50 of 0.34 mu M. Inhibition was remarkably specific, with no appreciable activity being observed toward HIV-2 RT, AMV RT, RNA polymerase, or DNA polymerases alpha or beta. C1 UNIV ILLINOIS,COLL PHARM,DEPT MED CHEM & PHARMACOGNOSY,PROGRAM COLLABORAT RES PHARMACEUT SCI,CHICAGO,IL 60612. CHULALONGKORN UNIV,FAC PHARMACEUT SCI,DEPT BIOCHEM,BANGKOK 10330,THAILAND. UNIV MALAYSIA SARAWAK,FAC RESOURCE SCI & TECHNOL,KOTA SAMARAHAN 94300,SARAWAK,MALAYSIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 37 TC 38 Z9 42 U1 0 U2 2 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 SEP PY 1996 VL 59 IS 9 BP 839 EP 842 DI 10.1021/np960399y PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VK429 UT WOS:A1996VK42900004 PM 8864237 ER PT J AU Manfredi, KP Britton, M Vissieche, V Pannell, LK AF Manfredi, KP Britton, M Vissieche, V Pannell, LK TI Three new Naphthyldihydroisoquinoline alkaloids from Ancistrocladus tectorius SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ACETOGENIC ISOQUINOLINE ALKALOIDS; TRADITIONAL MEDICINAL-PLANTS; ABBREVIATUS; KORUPENSIS; THAILAND AB Three new 5-1'-linked naphthyldihydroisoquinoline alkaloids (1-3) have been isolated from the organic extract of Ancistrocladus tectorius. The gross structures of the compounds have been established using 1D and 2D NMR spectroscopy and difference NOE experiments. The absolute stereochemistry of 1, 2, and 3 was determined from CD spectral comparison and chemical degradation, Evidence is presented to show that two of the compounds exist exclusively in the keto form at C-8 of the isoquinoline system (2b, 3b). C1 NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. RP Manfredi, KP (reprint author), UNIV NO IOWA,DEPT CHEM,CEDAR FALLS,IA 50613, USA. NR 19 TC 12 Z9 13 U1 0 U2 0 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 SEP PY 1996 VL 59 IS 9 BP 854 EP 859 DI 10.1021/np960410u PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VK429 UT WOS:A1996VK42900007 PM 8864239 ER PT J AU Dai, JR Hallock, YF Cardellina, JH Gray, GN Boyd, MR AF Dai, JR Hallock, YF Cardellina, JH Gray, GN Boyd, MR TI Triangulynes A-H and triangulynic acid, new cytotoxic polyacetylenes from the marine sponge Pellina triangulata SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID SEMITUBULOSA; SCREEN AB Nine new polyacetylenes, triangulynes A-H (1-8) and triangulynic acid (9), have been isolated from the marine sponge Pellina triangulata (Oceanapiidae) through cytotoxicity-guided fractionation. Structural elucidations and stereochemistry assignments were based on chemical and spectral studies. C1 NCI,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,DIAG & CTR,FREDERICK,MD 21702. NR 17 TC 34 Z9 34 U1 0 U2 5 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 SEP PY 1996 VL 59 IS 9 BP 860 EP 865 DI 10.1021/np960366i PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VK429 UT WOS:A1996VK42900008 PM 8991958 ER PT J AU Rabemanantsoa, A Ranarivelo, Y Andriantsiferana, M Tillequin, F Silverton, JV Garraffo, HM Spande, TF Yeh, HJC Daly, JW AF Rabemanantsoa, A Ranarivelo, Y Andriantsiferana, M Tillequin, F Silverton, JV Garraffo, HM Spande, TF Yeh, HJC Daly, JW TI A new secotrinervitane diterpene isolated from soldiers of the Madagascan termite species, Nasutitermes canaliculatus SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID DEFENSE SECRETIONS; INTERSPECIFIC VARIATION; CHEMICAL-COMPOSITION; HOSPITALITERMES; ISOPTERA AB Reported herein is the X-ray crystallographic structure of a novel 10-oxygenated secotrinervitane diterpene, 3 alpha,10 alpha-diacetoxy-7,16-secotrinervita-7,11,15(17)-triene (4), from soldiers of the endemic Madagascan termite Nasutitermes canaliculatus, which was compared with an energy-minimized structure obtained by computer molecular modeling. We also report H-1- and C-13-NMR and MS data for this new diterpene. C1 NIDDKD,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NIDDKD,ANALYT CHEM LAB,NIH,BETHESDA,MD 20892. UNIV ANTANANARIVO,LAB CHIM ORGAN PROD NAT,ANTANANARIVO 101,MALAGASY REPUBL. UNIV PARIS 05,FAC PHARM,URA CNRS 1310,LAB PHARMACOGNOSIE,F-75006 PARIS,FRANCE. NR 29 TC 3 Z9 3 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 SEP PY 1996 VL 59 IS 9 BP 883 EP 886 DI 10.1021/np960374z PG 4 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA VK429 UT WOS:A1996VK42900015 PM 8864240 ER PT J AU Palinkas, LA Houseal, M Rosenthal, NE AF Palinkas, LA Houseal, M Rosenthal, NE TI Subsyndromal seasonal affective disorder in Antarctica SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID LIGHT THERAPY; PREVALENCE; INDIVIDUALS; DEPRESSION; BEHAVIOR; SYMPTOMS; SAMPLE; WINTER; MOOD AB The seasonality of depressed mood was examined in 70 men and women who spent the 1991 austral winter at three American research stations in Antarctica. Seasonal Pattern Assessment Questionnaire global seasonality scores increased significantly from late summer (February/March) to midwinter (July/August; p < .001). Only one case of seasonal affective disorder (SAD) was found during midwinter, but the prevalence of subsyndromal SAD increased significantly, from 10.5 to 28.4 per 100, during this period. Station latitude was significantly associated with SAD-specific symptoms and global Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version scores in midwinter and in early spring (October). The results suggest that even clinically normal individuals are likely to experience symptoms of subsyndromal SAD in high latitude environments, that these variations become more pronounced with increasing latitude, and that they can be detected through repeated administrations of instruments such as the Seasonal Pattern Assessment Questionnaire and Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version. C1 TEXAS TECH UNIV,DEPT PSYCHIAT,LUBBOCK,TX. NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. RP Palinkas, LA (reprint author), UNIV CALIF SAN DIEGO,DEPT FAMILY & PREVENT MED,9500 GILMAN DR,LA JOLLA,CA 92093, USA. NR 33 TC 36 Z9 39 U1 4 U2 6 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 SEP PY 1996 VL 184 IS 9 BP 530 EP 534 DI 10.1097/00005053-199609000-00003 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VH796 UT WOS:A1996VH79600003 PM 8831642 ER PT J AU Luo, Y Sunderland, T Wolozin, B AF Luo, Y Sunderland, T Wolozin, B TI Physiologic levels of beta-amyloid activate phosphatidylinositol 3-kinase with the involvement of tyrosine phosphorylation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE neuron; Wortmannin; Alzheimer's disease; lipids; signal transduction ID NERVE GROWTH-FACTOR; PRECURSOR PROTEIN; TRK PROTOONCOGENE; INSULIN-RECEPTOR; 85-KDA SUBUNIT; PC12 CELLS; PEPTIDE; KINASE; INHIBITION; NEURONS AB The beta-amyloid protein (A beta) peptide plays an important role in Alzheimer's disease, but the potential actions of physiologic levels of A beta (225-625 pM) have not been explored. We recently showed that picomolar doses of A beta can stimulate tyrosine phosphorylation of neuronal cells and now show that leads to the activation of the lipid kinase phosphatidylinositol 3-kinase (PI3 kinase), Three independent lines of evidence support the hypothesis that A beta is activating PI3 kinase through a tyrosine kinase-mediated mechanism, Immunoblotting studies show that A beta induces tyrosine phosphorylation of p85 as well as association of the p85 subunit of PI3 kinase with tyrosine-phosphorylated proteins. Studies of membrane proteins show that A beta induces a translocation of p85 to membrane-bound glycoproteins, which are likely to be receptors, Finally, direct studies of PI3 kinase activity in both anti-phosphotyrosine immunocomplexes and wheal germ agglutinin precipitates show that A beta increases formation of the product of PI3 kinase. Wortmannin, a selective inhibitor of PI3 kinase, blocks this A beta-stimulated PI3 kinase activity. Thus, physiologic levels of A beta stimulate tyrosine phosphorylation and PI3 kinase activity. C1 NIMH,SECT GERIATR PSYCHIAT,BETHESDA,MD 20892. NR 40 TC 33 Z9 33 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 SEP PY 1996 VL 67 IS 3 BP 978 EP 987 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VD232 UT WOS:A1996VD23200011 PM 8752103 ER PT J AU Bernard, M Klein, DC AF Bernard, M Klein, DC TI Retinoic acid increases hydroxyindole-O-methyltransferase activity and mRNA in human Y-79 retinoblastoma cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE hydroxyindole-O-methyltransferase; melatonin; Y-79 retinoblastoma; retinoic acid ID MELATONIN PRODUCTION; NUCLEAR RECEPTOR; PINEAL-GLAND; BINDING; GENE; DIFFERENTIATION; PHOTORECEPTORS; EXPRESSION; DOPAMINE; BUTYRATE AB Hydroxyindole-O-methyltransferase (HIOMT) plays an important role as the final enzyme in the synthesis of melatonin. Here we present the first evidence that retinoic acid (RA) stereoisomers are potent regulators of HIOMT in the human retinoblastoma-derived Y-79 cell line. Treatment with all-trans-, 13-cis-, and 9-cis-RA induced a gradual IO-fold increase in HIOMT activity and mRNA, without changing the levels of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase, actin, S-antigen, and interphotoreceptor retinoid-binding protein. These findings point to the possibility that RA may play a physiological role in the regulation of human HIOMT. C1 NICHHD,SECT NEUROENDOCRINOL,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 38 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 1996 VL 67 IS 3 BP 1032 EP 1038 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA VD232 UT WOS:A1996VD23200017 PM 8752109 ER PT J AU Sundar, KS Kamarajul, LS Dingfelder, J McMahon, J Bitonte, RA Gollapudi, S Wilson, WH Kong, LY Hong, JS Lee, JE AF Sundar, KS Kamarajul, LS Dingfelder, J McMahon, J Bitonte, RA Gollapudi, S Wilson, WH Kong, LY Hong, JS Lee, JE TI Endogenous opioids and HIV-1 infection SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 3rd Annual Symposium on AIDS, Drugs of Abuse and the Neuroimmune Axis CY NOV 09-11, 1995 CL SAN DIEGO, CA C1 E TOWNE OBGYN,CHAPEL HILL,NC. EVE CLIN,LOS ANGELES,CA. UNIV CALIF IRVINE,DEPT MED,IRVINE,CA 92717. NIEHS,MOL NEUROSCI LAB,RES TRIANGLE PK,NC 27709. RP Sundar, KS (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710, USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD SEP PY 1996 VL 69 IS 1-2 BP 46 EP 47 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA VK244 UT WOS:A1996VK24400032 ER PT J AU Chikwendu, A McBain, CJ AF Chikwendu, A McBain, CJ TI Two temporally overlapping ''delayed-rectifiers'' determine the voltage-dependent potassium current phenotype in cultured hippocampal interneurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID STRATUM-LACUNOSUM-MOLECULARE; INHIBITORY POSTSYNAPTIC POTENTIALS; CENTRAL-NERVOUS-SYSTEM; CA1 PYRAMIDAL CELLS; RAT HIPPOCAMPUS; ORIENS-ALVEUS; AMINOPYRIDINE BLOCK; MEMBRANE-PROPERTIES; SYNAPTIC RESPONSES; K+ CHANNELS AB 1. Whole cell voltage-clamp recordings were used to characterize the calcium-independent ''delayed-rectifier'' potassium currents of gamma-aminobutyric acid (GABA)-positive stratum radiatum-lacunosum-moleculare (st. L-M) interneurons in primary culture derived from neonate rats [postnatal day 5-7 (P5-P7)]. 2. Two distinct current phenotypes were observed, which we termed ''sustained'' and ''slowly inactivating.'' Despite possessing similar voltage-dependent activation properties, currents differed in their time-dependent inactivation properties and their kinetics of activation and deactivation. The phenotypes of the observed currents did not change during the time in vitro. The total current phenotype observed in any cell likely resulted from the temporal overlap of the two current components expressed in different relative proportions. 3. Externally applied 4-aminopyridine (4-AP) selectively blocked the slowly inactivating current component, by a use-dependent, but voltage-independent mechanism, suggesting that channel activation is required for 4-AP to interact with its binding site. In contrast, the sustained current component was unaffected by 4-AP. 4. Both the slowly inactivating and sustained current phenotypes were sensitive to externally applied tetraethylammonium (TEA). The IC50 Of block by TEA was lower in cells expressing predominantly the sustained current component. 5. Currents recorded in the presence of internally applied TEA were of a slowly inactivating phenotype, suggesting that [TEA](i) preferentially blocked the sustained current component. 6. When test pulses were preceded by a prepulse to -100 mV, a transient A-type current component was observed, but in contrast to pyramidal neurons and other interneuron types, this transient current contributed only a minor component to the total initial peak current. 7. In conclusion, two distinct, temporally overlapping potassium current phenotypes were observed on st. L-M interneurons. The overall phenotype was determined by the relative proportion of each current component. The absence of a prominent transient current suggests that the two delayed-rectifier currents play a critical role in determining the firing characteristics of these interneurons. C1 NICHHD,UNIT CELLULAR & SYNAPT PHYSIOL,LAB CELLULAR & MOL NEUROPHYSIOL,LCMN,BETHESDA,MD 20892. NR 49 TC 13 Z9 14 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1996 VL 76 IS 3 BP 1477 EP 1490 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VL117 UT WOS:A1996VL11700010 PM 8890268 ER PT J AU Krauzlis, RJ Miles, FA AF Krauzlis, RJ Miles, FA TI Transitions between pursuit eye movements and fixation in the monkey: Dependence on context SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SMOOTH-PURSUIT; INITIATION; FIELD; MICROSTIMULATION; STIMULATION; GENERATION; TRACKING; LESIONS AB 1. We compared the visuomotor processing underlying the onset and offset of pursuit by recording the eye movements of three monkeys as they smoothly tracked a target that was initially at rest, started to move suddenly at a constant velocity along the horizontal meridian, and then stopped. We presented this sequence of target motions in two different contexts. In the first context the target sometimes stopped after 500 ms, but on other interleaved trials the target either continued moving at a constant velocity, slowed down, speeded up, or reversed direction. In the second context the target always stopped, but the duration of the preceding constant velocity was randomized from 500 to 700 ms. 2. The dynamics of the eye velocity during the offset of pursuit were markedly different in the two experiments. When the target stopped only sometimes, the decrease in eye velocity at the offset of pursuit often overshot zero, producing a brief, small reversal in the direction of pursuit before eye speed settled to zero. When the target always stopped, the decrease in eye velocity at the offset of pursuit followed a more gradual transition toward zero with no overshoot. Thus the eye velocity profiles obtained in the first experiment contradict, whereas those obtained in the second experiment confirm, previous characterizations of the offset of pursuit as an exponential decay toward zero eye speed. 3. To investigate the basis of the different eye velocity profiles obtained in the two experiments, we probed the state of transmission along the visuomotor pathways for pursuit with the use of small perturbations in the motion of the target. We used perturbations consisting of 1 degrees step changes in target position superimposed on the constant velocity motion of the target, on the basis of previous findings that such perturbations elicit saccades during fixation but smooth changes in eye speed during maintained pursuit. Single perturbations were imposed at regularly spaced intervals on separate interleaved trials during the onset, maintenance, and offset of pursuit. 4. Perturbations imposed during the onset and maintenance of pursuit had similar effects regardless of whether the target stopped only sometimes or always. In both experiments, perturbations that stepped the target in the direction opposite to the constant velocity of the target produced decreases in eye speed; perturbations in the same direction produced neglible or inconsistent changes in eye speed. The changes in eye speed caused by perturbations were largest for those perturbations introduced within the first 100 ms after the start of target motion, before the onset of the smooth eye movement, and became progressively smaller as target motion continued. The largest changes in eye speed were therefore caused by those perturbations imposed during periods of large retinal slip and by those perturbations whose direction opposed that slip. 5. Perturbations imposed during the offset of pursuit had different effects depending on whether the target stopped only sometimes or always. When the target stopped only sometimes, forward perturbations produced large increases in eye speed, whereas backward perturbations produced negligible or inconsistent changes in eye speed. Thus the visuomotor processing underlying the offset of pursuit in this experiment strongly resembled that underlying the onset of pursuit: in both cases, those perturbations in the direction opposing large retinal slip produced the largest effects. In contrast, when the target always stopped, neither forward nor backward perturbations imposed during the offset of pursuit produced large changes in eye speed. This indicates that the visuomotor processing underlying the offset of pursuit in this experiment was different from the processing underlying the onset of pursuit. 6. Perturbations also produced changes in the frequency of saccades, although these effects were less consistent than the changes in pursuit eye speed. During the onset of pursuit, such effects as did occur were similar in the two experiments: perturbations in the same direction as the motion of the target increased the frequency of saccades, whereas perturbations in the opposite direction either decreased the frequency of saccades or had no effect. In contrast, during the offset of pursuit, perturbations had different effects on saccadic frequency, dependent on whether the target stopped only sometimes or always. When the target stopped only sometimes, backward perturbations increased the frequency of saccades, whereas forward perturbations decreased the frequency of saccades. However, when the target always stopped, there was little difference between the effects of forward and backward perturbations on saccades. Thus the effects of the perturbations on the programming of saccades complemented the effects on smooth eye velocity. 7. Our data indicate that the visuomotor processing underlying the offset of pursuit can be either very similar to or very different from that underlying the onset of pursuit. These results raise doubts about the previous proposal that the onset and offset of pursuit are mediated by different mechanisms. For parsimony, we suggest that the onset and offset of pursuit are mediated by a single mechanism, but that the transmission of visual and motor signals through this mechanism can vary during pursuit. We present simulations to demonstrate that a model incorporating this suggestion can account for the variety of eye velocity profiles observed during the onset and offset of pursuit. RP Krauzlis, RJ (reprint author), NIH,SENSORIMOTOR RES LAB,BLDG 49,RM 2A-50,BETHESDA,MD 20892, USA. NR 34 TC 50 Z9 51 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 1996 VL 76 IS 3 BP 1622 EP 1638 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA VL117 UT WOS:A1996VL11700023 PM 8890281 ER PT J AU George, MS Wassermann, EM Post, RM AF George, MS Wassermann, EM Post, RM TI Transcranial magnetic stimulation: A neuropsychiatric tool for the 21st century SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Review ID HUMAN MOTOR CORTEX; LONG-TERM POTENTIATION; BRAIN-STIMULATION; CORTICAL HYPEREXCITABILITY; MAJOR DEPRESSION; EPILEPTIC FOCI; INDUCTION; ACTIVATION; RESPONSES; SAFETY AB Neuroscientists have constantly sought new methods of evaluating brain function, with progressive improvement in the last century in imaging brain structure and function. However, except for direct surgical stimulation, neuropsychiatrists can only infer causality between the signal obtained on an image and a behavior or disease. Transcranial magnetic stimulation (TMAS) is a new, noninvasive technique for directly stimulating cortical neurons. It has been used to map attention, memory, movement, speech, and vision. Preliminary investigations have also used rapid-rate TMS to improve motor speed in Parkinson's disease and mood in depression. TMS is likely to be an important future neuropsychiatric tool. C1 MED UNIV S CAROLINA, DEPT PSYCHIAT, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT NEUROL, CHARLESTON, SC 29425 USA. RALPH H JOHNSON VET AFFAIRS HOSP, DEPT PSYCHIAT, CHARLESTON, SC USA. NINCDS, HUMAN MOTOR CONTROL SECT, BETHESDA, MD 20892 USA. NIMH, BIOL PSYCHIAT BRANCH, BETHESDA, MD 20892 USA. RP George, MS (reprint author), MED UNIV S CAROLINA, DEPT RADIOL, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. NR 109 TC 109 Z9 114 U1 0 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 1996 VL 8 IS 4 BP 373 EP 382 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA VQ816 UT WOS:A1996VQ81600001 PM 9116472 ER PT J AU Maccaferri, G McBain, CJ AF Maccaferri, G McBain, CJ TI Long-term potentiation in distinct subtypes of hippocampal nonpyramidal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE hippocampus; interneurons; LTP; plasticity; GABAergic; CA1 ID LACUNOSUM-MOLECULARE INTERNEURONS; PROTEIN-KINASE ACTIVITY; EXCITATORY POSTSYNAPTIC CURRENTS; GOLGI-ELECTRON-MICROSCOPE; WHOLE-CELL RECORDINGS; RAT HIPPOCAMPUS; SYNAPTIC TRANSMISSION; AREA CA1; GLUTAMATE RECEPTORS; PYRAMIDAL NEURONS AB We have investigated NMDA receptor-dependent long-term potentiation (LTP) in distinct subtypes of nonpyramidal neurons of the CA1 hippocampus using induction protocols that permitted the differentiation between a direct form of LTP and plasticity resulting simply from the ''passive propagation'' of LTP occurring on CA1 pyramidal neurons. Two types of stratum (st.) oriens/alveus interneurons received passive propagation of synaptic potentiation via the recurrent collaterals of CA1 pyramidal cells, but neither subtype possessed direct plasticity. In st, radiatum, two distinct classes of cells were observed: st. radiatum interneurons that showed neither direct nor propagated forms of synaptic plasticity, and ''giant cells'' for which EPSPs were robustly potentiated after a pairing protocol. This potentiation is similar to the LTP described in pyramidal cells, and its induction requires NMDA receptor activation, Thus, a large heterogeneity of synaptic plasticity exists in morphologically distinct neurons and suggests that complex changes in the CA1 network properties will occur after the induction of LTP. C1 NICHHD,UNIT CELLULAR & SYNAPT PHYSIOL,LAB CELLULAR & MOL NEUROPHYSIOL,BETHESDA,MD 20892. NR 64 TC 105 Z9 105 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 SEP 1 PY 1996 VL 16 IS 17 BP 5334 EP 5343 PG 10 WC Neurosciences SC Neurosciences & Neurology GA VG898 UT WOS:A1996VG89800006 PM 8757246 ER PT J AU Meredith, RF Partridge, EE Alvarez, RD Khazaeli, MB Plott, G Russell, CD Wheeler, RH Liu, TP Grizzle, WE Schlom, J LoBuglio, AF AF Meredith, RF Partridge, EE Alvarez, RD Khazaeli, MB Plott, G Russell, CD Wheeler, RH Liu, TP Grizzle, WE Schlom, J LoBuglio, AF TI Intraperitoneal radioimmunotherapy of ovarian cancer with lutetium-177-CC49 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE ovarian cancer; radioimmunotherapy; lutetium-177-CC49 ID B72.3 MONOCLONAL-ANTIBODY; CARCINOMA; THERAPY; CHEMOTHERAPY; IRRADIATION; EXPERIENCE; SURVIVAL; TRIAL AB Twelve ovarian cancer patients who failed chemotherapy entered a Phase I trial of intraperitoneal Lu-177-CC49 antibody. Methods: Patients had disease confined to the abdominal cavity +/- retroperitoneal lymph nodes, adequate organ function and no previous radiation. Results: Side effects included mild discomfort with administration (1/12), delayed transient arthralgia (2/12), and mild marrow suppression (calculated marrow doses of 11-54 cGy). The maximum tolerated dose has not been reached with levels of 10, 18, 25 and 30 mCi/m(2). Radioimmunoscintigraphy revealed localization consistent with tumor in 11 of 12 patients. One of eight patients with gross disease had > 50% tumor reduction after therapy, while six progressed and one went off study with stable disease. Of patients with microscopic or occult disease, one relapsed at 10 mo and three remain without evidence of disease after 18 mo. Conclusion: Intraperitoneal radioimmunotherapy with Lu-177-CC49 is well tolerated and appears to have antitumor activity against chemotherapy-resistant ovarian cancer in the peritoneal cavity. C1 UNIV ALABAMA,DEPT RADIAT ONCOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT OBSTET GYNECOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT NUCL MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PATHOL,BIRMINGHAM,AL 35294. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [1 R55 CA/OD67828-01, CM 87215]; NCRR NIH HHS [MOI RR 00032] NR 34 TC 92 Z9 93 U1 0 U2 4 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 SEP PY 1996 VL 37 IS 9 BP 1491 EP 1496 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VF797 UT WOS:A1996VF79700024 PM 8790200 ER PT J AU Pentlow, KS Graham, MC Lambrecht, RM Daghighian, F Bacharach, SL Bendriem, B Finn, RD Jordan, K Kalaigian, H Karp, JS Robeson, WR Larson, SM AF Pentlow, KS Graham, MC Lambrecht, RM Daghighian, F Bacharach, SL Bendriem, B Finn, RD Jordan, K Kalaigian, H Karp, JS Robeson, WR Larson, SM TI Quantitative imaging of iodine-124 with PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; iodine-124; quantitative imaging ID POSITRON EMISSION TOMOGRAPHY; MONOCLONAL-ANTIBODIES; COMPUTED-TOMOGRAPHY; PERFORMANCE-CHARACTERISTICS; NEURO-BLASTOMA; BREAST-CANCER; HUMAN TUMOR; I-124; RADIOIMMUNOTHERAPY; DOSIMETRY AB PET is potentially very useful for the accurate in vivo quantitation of time-varying biological distributions of radiolabeled antibodies over several days. The short half-lives of most commonly used positron-emitting nuclides make them unsuitable for this purpose. Iodine-124 is a positron emitter with a half-life of 4.2 days and appropriate chemical properties. It has not been widely used because of a complex decay scheme including several high energy gamma rays. However, measurements made under realistic conditions on several different PET scanners have shown that satisfactory imaging and quantitation can be achieved. Methods: Whole-body and head-optimized scanners with different detectors (discrete BGO, block BGO and BaF2 time-of-flight), different septa and different correction schemes were used. Measurements of resolution, quantitative linearity and the ability to quantitatively image spheres of different sizes and activities in different background activities were made using phantoms. Results: Compared with conventional PET nuclides, resolution and quantitation were only slightly degraded. Sphere detectability was also only slightly worse if imaging time was increased to compensate for the lower positron abundance. Conclusion: Quantitative imaging with I-124 appears to be possible under realistic conditions with various PET scanners. C1 MEM SLOAN KETTERING CANC CTR,DEPT RADIOL,NEW YORK,NY 10021. N SHORE UNIV HOSP,MANHASSET,NY. NIH,BETHESDA,MD 20892. BROOKHAVEN NATL LAB,UPTON,NY 11973. HANNOVER MED SCH,HANNOVER,GERMANY. HOSP UNIV PENN,PHILADELPHIA,PA 19104. KING FAISAL SPECIALIST HOSP & RES CTR,RIYADH 11211,SAUDI ARABIA. RP Pentlow, KS (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 34 TC 122 Z9 122 U1 0 U2 6 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 SEP PY 1996 VL 37 IS 9 BP 1557 EP 1562 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VF797 UT WOS:A1996VF79700043 PM 8790218 ER PT J AU Pennington, JAT AF Pennington, JAT TI Intakes of minerals from diets and foods: Is there a need for concern? SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on New Approaches, Endpoints and Paradigms for RDAs of Mineral Elements CY SEP 10-12, 1995 CL GRAND FORKS, ND SP USDA, ARS, Grand Forks Human Nutr Res Ctr & Sch Med, Univ N Dakota DE minerals; mineral intakes; mineral status; Total Diet Study; humans AB Continuous monitoring of the food supply through the Total Diet Studies allows for the identification of changes and trends in the mineral content of foods resulting from agricultural or manufacturing practices. The studies also allow for the estimation of average daily intakes of minerals and a comparison of these intakes with Recommended Dietary Allowances. The Total Diet Studies use a small number of foods (core foods) to represent the U.S. food supply. The core foods are purchased four times per year, prepared for consumption, and analyzed for 11 nutritional minerals. The food composition data are then merged with food consumption data from national surveys to provide estimates of daily intakes of minerals for selected age-sex groups. Results of the 1982-1991 Total Diet Studies indicated that average intakes of potassium, phosphorus, selenium, iodine and manganese were adequate. Sodium could not be adequately assessed because the studies did not include discretionary salt. Intakes of calcium, magnesium, iron, zinc and copper were below recommended intakes for some age-sex groups. Studies based on clinical and biochemical measurements confirm that calcium, iron and zinc are of concern for segments of the U.S. population. There are conflicting opinions about the need for concern for copper and magnesium. RP Pennington, JAT (reprint author), NIDDK,DNRC,NIH,NATCHER BLDG,ROOM 5AN-32A,45 CTR DR,MSC 6600,BETHESDA,MD 20892, USA. NR 15 TC 15 Z9 18 U1 0 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 SEP PY 1996 VL 126 IS 9 SU S BP S2304 EP S2308 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA VG826 UT WOS:A1996VG82600003 ER PT J AU NobleTopham, SE Burrow, SR Eppert, K Kandel, RA Meltzer, PS Bell, RS Andrulis, IL AF NobleTopham, SE Burrow, SR Eppert, K Kandel, RA Meltzer, PS Bell, RS Andrulis, IL TI SAS is amplified predominantly in surface osteosarcoma SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID SOFT-TISSUE SARCOMAS; GENE AMPLIFICATION; C-MYC; N-MYC; MDM2; ONCOGENE; PROTEIN; REGION; DNA; CANCER AB The development of several types of human tumors is related to amplification of genes that are involved in cell growth. The protein products of these genes give the cells a selective growth advantage. The q13-15 region of chromosome 12 is frequently altered in human sarcomas, and the SAS gene has been identified in an amplification unit mapping to this region. Gene amplification of SAS was analyzed to determine the frequency of genetic alteration of this gene in osteosarcoma. Using Southern blot analysis as well as quantitative polymerase chain reaction. SAS was found to be amplified in 10 (36%) of 28 osteosarcomas. Gene amplification was evaluated in subtypes of osteosarcoma. All seven surface osteosarcomas displayed amplified SAS. In contrast, SAS was amplified in only two (13%) of 15 intramedullary osteosarcomas. The finding that all surface osteosarcomas demonstrated SAS gene amplification suggests that this gene may play a role in the pathogenesis of osteosarcoma subtypes and that surface osteosarcoma may be genetically different from high-grade intramedullary osteosarcoma. C1 MT SINAI HOSP,SAMUEL LUNENFELD RES INST,TORONTO,ON M5G 1X5,CANADA. MT SINAI HOSP,DEPT PATHOL & LAB MED,TORONTO,ON M5G 1X5,CANADA. MT SINAI HOSP,DIV ORTHOPAED SURG,TORONTO,ON M5G 1X5,CANADA. UNIV TORONTO,TORONTO,ON,CANADA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Andrulis, Irene/E-7267-2013; Kandel, Rita/E-2149-2017 OI Kandel, Rita/0000-0003-4047-3913 NR 33 TC 21 Z9 23 U1 0 U2 0 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD SEP PY 1996 VL 14 IS 5 BP 700 EP 705 DI 10.1002/jor.1100140504 PG 6 WC Orthopedics SC Orthopedics GA VP972 UT WOS:A1996VP97200003 PM 8893761 ER PT J AU Mueller, BU Sei, S Anderson, B Luzuriaga, K Farley, M Venzon, DJ TudorWilliams, G Schwartzentruber, DJ Fox, C Sullivan, JL Pizzo, PA AF Mueller, BU Sei, S Anderson, B Luzuriaga, K Farley, M Venzon, DJ TudorWilliams, G Schwartzentruber, DJ Fox, C Sullivan, JL Pizzo, PA TI Comparison of virus burden in blood and sequential lymph node biopsy specimens from children infected with human immunodeficiency virus SO JOURNAL OF PEDIATRICS LA English DT Article ID TYPE-1 INFECTION; NEVIRAPINE; THERAPY; ZIDOVUDINE; PHARMACOKINETICS; RESERVOIRS; RESISTANCE; DISEASE; TISSUES; CELLS AB Background: Lymph nodes serve as reservoirs for the replication of human immunodeficiency virus (HIV) type 1. Comparison of serial measurements of virus burden in lymph nodes and peripheral blood after a change in antiretroviral therapy may provide insights into pathogenic mechanisms and permit a more accurate assessment of a therapeutic response. Study design: Nevirapine was added to the drug regiment of eight children with HIV infection treated with the combination of zidovudine and didanosine who had increasing levels of serum p24 antigen. Lymph node biopsies were performed at entry and after 12 weeks of therapy. Results: Neither CD4 counts nor p24 antigen level correlated with the degree of viremia as measured by ribonucleic acid copy numbers in plasma. Correlations were found between HIV DNA copy number in peripheral blood mononuclear cells and HIV DNA copy number in lymph nodes (p=0.02), as well as between peripheral blood CD4 counts and lymph node architecture. The HIV signals in the lymph nodes conformed to the anatomic organization of apical light zones in the germinal centers; however, in more advanced disease stages, organized germinal centers disappeared as evidenced by a decline in the extent of the follicular dendritic network. Conclusions: Lymph node biopsies in this small number of HIV-infected children revealed a progressive loss of an organized architecture, especially of the follicular dendritic network. This correlated with a progressive loss of CD4(+) cells but not with other measures of disease stage, including viral load, as measured by ribonucleic acid copy numbers. C1 NCI, SURG BRANCH, NIH, BETHESDA, MD 20892 USA. MOL HISTOL LABS, GAITHERSBURG, MD USA. UNIV MASSACHUSETTS, MED CTR, DEPT PEDIAT, WORCESTER, MA USA. RP Mueller, BU (reprint author), NCI, PEDIAT BRANCH,BIOSTAT & DATA MANAGEMENT SECT,NIH, BLDG 10,ROOM 13N240, 10 CTR DR MSC 1928, BETHESDA, MD 20892 USA. RI Venzon, David/B-3078-2008 FU NIAID NIH HHS [AI 32907] NR 29 TC 10 Z9 10 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD SEP PY 1996 VL 129 IS 3 BP 410 EP 418 DI 10.1016/S0022-3476(96)70074-4 PG 9 WC Pediatrics SC Pediatrics GA VK798 UT WOS:A1996VK79800014 PM 8804331 ER PT J AU Malatynska, E Wang, Y Knapp, RJ Waite, S Calderon, S Rice, K Hruby, VJ Yamamura, HI Roeske, WR AF Malatynska, E Wang, Y Knapp, RJ Waite, S Calderon, S Rice, K Hruby, VJ Yamamura, HI Roeske, WR TI Human delta opioid receptor: Functional studies on stably transfected Chinese hamster ovary cells after acute and chronic treatment with the selective nonpeptidic agonist SNC-80 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID H-3 NALTRINDOLE BINDING; MESSENGER-RNA; HIGH-AFFINITY; EXPRESSION; TOLERANCE; ANALOGS; ENKEPHALIN; D-PEN5>ENKEPHALIN; DESENSITIZATION; ENKEPHALIN AB The SNC-80 series of nonpeptidic agonists for the delta-opioid receptor are being developed as potential analgesic drugs. It is important to understand their acute and chronic effects at human delta-opioid receptors. Thus, we measured the ability of SNC-80 and [D-Pen(2),4'-Cl-Phe(4),D-Pen(5)]enkephalin to inhibit forskolin-stimulated adenylyl cyclase activity in recombinant Chinese hamster ovary cells stably expressing the cloned human delta-opioid receptor. The calculated EC(50) values for [D-Pen(2),4'-Cl-Phe(4),D-Pen(5)]enkephalin and SNC-80 were 0.6 +/- 0.1 nM and 6.3 +/- 0.1 nM, respectively. Pretreatment of these cells with SNC-80 (100 nM) for 24 hr produced 1) a time-dependent reduction of delta receptor density, as measured by radioligand binding studies with [H-3]naltrindole; 2) a shift in the EC(50) value of SNC-80 from 7.7 +/- 4.2 nM to 44.1 +/- 12 nM, as measured by the cyclic AMP assay; 3) a reduction in the maximum inhibition of adenylyl cyclase activity from 86% to 48%; 4) a marked increase in the forskolin stimulation of basal cyclic AMP accumulation by nearly 100% (from 442 pmol/mg of protein to 824 pmol/mg of protein); and 5) a 5-fold increase in forskolin-stimulated cyclic AMP accumulation after addition of naltrindole. These studies showed that SNC-80 produced desensitization and down-regulation of human delta-opioid receptors in recombinant Chinese hamster ovary cells after chronic treatment and that this effect was associated with an increase in adenylyl cyclase activity. C1 UNIV ARIZONA, HLTH SCI CTR, DEPT MED, TUCSON, AZ 85724 USA. UNIV ARIZONA, HLTH SCI CTR, DEPT PHARMACOL, TUCSON, AZ 85724 USA. UNIV ARIZONA, HLTH SCI CTR, DEPT CHEM, TUCSON, AZ 85724 USA. UNIV ARIZONA, HLTH SCI CTR, DEPT BIOCHEM, TUCSON, AZ 85724 USA. UNIV ARIZONA, HLTH SCI CTR, DEPT PSYCHIAT, TUCSON, AZ 85724 USA. UNIV ARIZONA, HLTH SCI CTR, PROGRAM NEUROSCI, TUCSON, AZ 85724 USA. NIDDKD, NIH, BETHESDA, MD 20892 USA. FU NIDA NIH HHS [DA08657, DA04248, DA06284] NR 37 TC 41 Z9 41 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 1996 VL 278 IS 3 BP 1083 EP 1089 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ018 UT WOS:A1996VJ01800013 PM 8819489 ER PT J AU Lakritz, J Chang, AM Weir, A Nishio, S Philpot, R Hyde, D Buckpitt, A Plopper, C AF Lakritz, J Chang, AM Weir, A Nishio, S Philpot, R Hyde, D Buckpitt, A Plopper, C TI Cellular and metabolic basis of clara cell tolerance to multiple doses of cytochrome P450-activated cytotoxicants .1. Bronchiolar epithelial reorganization and expression of cytochrome P450 monooxygenases in mice exposed to multiple doses of naphthalene SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DEPENDENT TOLERANCE; MICRODISSECTED AIRWAYS; PULMONARY TOXICITY; COVALENT BINDING; RATS; LUNG; OZONE; HAMSTERS; ENZYMES; PROTEIN AB The objectives of this study were to quantitatively define alterations in the epithelial populations and expression of cytochrome P450 monooxygenases in distal airways which are associated with the tolerance resulting from repeated exposure of mice to the acute Clara cell toxicant, naphthalene. Bronchiolar epithelium of mice treated daily for 7 days with an acutely cytotoxic dose of naphthalene (200 mg/kg/day) quantitatively resembles the bronchiolar epithelium of control animals in terms of proportions of ciliated and nonciliated cells and nuclear and cytoplasmic volumes. Subsequent treatment of tolerant animals with higher doses (300 mg/kg) does not produce the same Clara cell injury observed in previously untreated mice after a single treatment with 300 mg/kg. After repeated exposures to naphthalene, cellular expression of immunoreactive cytochrome P450 monooxygenases 2B and 2F, P450 reductase and Clara cell secretory protein significantly decreased in bronchiolar epithelium. Although metabolism of naphthalene to the 1R,2S-naphthalene oxide is depressed in microsomes derived from whole-lung homogenates of tolerant animals, metabolism of naphthalene in distal airways isolated by microdissection is unchanged from the controls at saturating substrate concentrations. When substrate concentrations are less than the apparent K-m for naphthalene (<0.05 mM), the rate of naphthalene metabolite production is markedly lower in distal airways of tolerant mice compared with controls. Covalent binding of reactive naphthalene metabolites in lungs of tolerant mice is also unchanged from control. In conclusion, after repeated exposure to short-term cytotoxic doses of naphthalene, distal bronchioles of tolerant mice 1) are lined by epithelium which resembles that of controls; 2) express lower levels of P450 proteins; 3) have reduced levels of naphthalene monooxygenase activity, but only at less than saturating concentrations and 4) have no decrease in covalent binding of reactive metabolites to proteins. C1 UNIV CALIF DAVIS,SCH VET MED,DEPT ANAT CELL BIOL & PHYSIOL,DAVIS,CA 95616. UNIV CALIF DAVIS,SCH VET MED,DEPT MOL BIOSCI,DAVIS,CA 95616. UNIV CALIF DAVIS,SCH MED,DEPT COMMUNITY & INT HLTH,DAVIS,CA 95616. NIEHS,CELLULAR & MOL PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RI Lakritz, Jeffrey/E-3456-2011; OI Lakritz, Jeffrey/0000-0003-2143-0416 FU NIEHS NIH HHS [ES04311, ES04699, ES05578] NR 38 TC 28 Z9 28 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 SEP PY 1996 VL 278 IS 3 BP 1408 EP 1418 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VJ018 UT WOS:A1996VJ01800052 PM 8819528 ER PT J AU Horowitz, AM Goodman, HS Yellowitz, JA Nourjah, PA AF Horowitz, AM Goodman, HS Yellowitz, JA Nourjah, PA TI The need for health promotion in oral cancer prevention and early detection SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT National Strategic Planning Conference for the Prevention and Control of Oral and Pharyngeal Cancer CY AUG 07-09, 1996 CL CHICAGO, IL DE oral cancer; prevention and early detection; health promotion; provider knowledge and practices; public knowledge and practices; policy ID PHARYNGEAL CANCER; SMOKING CESSATION; EARLY DIAGNOSIS; NECK-CANCER; PHYSICIANS; KNOWLEDGE; MEDICINE; TOBACCO; ALCOHOL; CAVITY AB Objectives: This review paper provides a rationale for using health promotion to help reduce morbidity and mortality due to oral cancers by identifying barriers to prevention and early detection of these cancers and discussing strategies for change. Methods: A literature review of the following areas was conducted: epidemiology of and risk factors for oral cancers; knowledge, opinions, and practices of health care providers and the public regarding prevention, early detection, and control of oral cancers; and policies and regulations that either enhance or act as barriers to the prevention and early detection of oral cancers. Results: Overall, the public is iii-informed about risk factors for and signs and symptoms of oral cancers and relatively few US adults have had an oral cancer examination. Further, health care providers are remiss in providing oral cancer examinations and detecting early oral cancers. Conclusions: To achieve the 13 oral cancer objectives contained in ''Healthy People 2000,'' health care providers and the public must know the risk factors for these cancers as well as their signs and symptoms. Further, health care providers need to provide oral cancer examinations routinely and competently. Equally important, the public needs to know that an examination for oral cancer is available and that they can request one routinely. Thus, a vigorous agenda that includes education, policy, and research initiatives is needed to enhance oral cancer prevention and early detection. C1 MARYLAND DEPT HLTH & MENTAL HYG,BALTIMORE,MD. UNIV MARYLAND,SCH DENT,BALTIMORE,MD 21201. RP Horowitz, AM (reprint author), NIDR,NIH,NATCHER BLDG,ROOM 3AN-44B,45 CTR DR,MSC 6401,BETHESDA,MD 20892, USA. NR 124 TC 59 Z9 64 U1 0 U2 6 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1996 VL 56 IS 6 BP 319 EP 330 DI 10.1111/j.1752-7325.1996.tb02459.x PG 12 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA WQ025 UT WOS:A1996WQ02500004 PM 9089527 ER PT J AU Horowitz, AM Nourjah, PA AF Horowitz, AM Nourjah, PA TI Factors associated with having oral cancer examinations among US adults 40 years of age or older SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article; Proceedings Paper CT 74th General Session of the International-Association-for-Dental-Research CY MAR 13-17, 1996 CL SAN FRANCISCO, CA SP Int Assoc Dent Res DE oral cancer examination; knowledge of risk factors for oral cancers; National Health interview Survey ID KNOWLEDGE; RESIDENTS AB Objectives: This study describes factors associated with having an oral cancer examination among US adults 40 years of age or older. Methods: Data used in this study are from the Cancer Control supplement of the 1992 National Health Interview Survey, which included questions about having had an oral cancer screening examination and knowledge of risk factors for oral cancers. The survey was administered to a national sample 18 years of age and older (n=12,035). Questions regarding beliefs and opinions about cancers in general also were asked and their associations with responses to having had an oral cancer examination studied. Analyses are limited to those respondents 40 years of age and older (n=6,538). Results: Fifteen percent of the adults reported having had an oral cancer examination. Of these, 48 percent had the exam during the past year and 31 percent had an exam one to three years ago. Respondents who were above the poverty level, white, non-Hispanic, 40 to 64 years of age, and who had more than a high school education and a higher level of knowledge about risk factors for oral cancer were more likely to have had an oral cancer examination. Conclusions: These findings demonstrate the need for vigorous health education and health promotion interventions aimed at health care providers and the public to increase knowledge about risk factors for oral cancers and to increase oral cancer examinations. RP Horowitz, AM (reprint author), NIDR,NIH,NATCHER BLDG,45 CTR DR,MSC 6401,ROOM 3AN-44B,BETHESDA,MD 20892, USA. NR 20 TC 68 Z9 69 U1 0 U2 0 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD FAL PY 1996 VL 56 IS 6 BP 331 EP 335 DI 10.1111/j.1752-7325.1996.tb02460.x PG 5 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA WQ025 UT WOS:A1996WQ02500005 PM 9089528 ER PT J AU Brown, BS Nurco, DN Tims, FM AF Brown, BS Nurco, DN Tims, FM TI Report of a conference on HIV/AIDS and drug abuse treatment SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Editorial Material DE HIV; drug abuse treatment; criminal justice programming; outreach; treatment policy C1 UNIV N CAROLINA, WILMINGTON, NC 28401 USA. UNIV MARYLAND, SCH MED, DEPT PSYCHIAT, BALTIMORE, MD 21201 USA. NIDA, HLTH SERV RES BRANCH, LEXINGTON, KY 40583 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD SEP-OCT PY 1996 VL 13 IS 5 BP 373 EP 374 DI 10.1016/S0740-5472(96)00107-9 PG 2 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA WX586 UT WOS:A1996WX58600001 ER PT J AU Lazarova, Z Yancey, KB AF Lazarova, Z Yancey, KB TI Reactivity of autoantibodies from patients with defined subepidermal bullous diseases against 1 mol/L salt-split skin - Specificity, sensitivity, and practical considerations SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID LUPUS-ERYTHEMATOSUS; PEMPHIGOID ANTIGEN; LAMINA-LUCIDA; AUTO-ANTIGEN; IMMUNOFLUORESCENCE; ANTIBODIES; PROTEIN; IDENTIFICATION; ACQUISITA; EPILIGRIN AB Background: Circulating IgG anti-basement membrane autoantibodies from patients with subepidermal bullous diseases can be categorized on the basis of their pattern of reactivity against 1 mol/L sodium chloride (NaCl)-split skin. Objective: The purpose of this study was to define by immunochemical techniques the specific antigen(s) targeted by IgG autoantibodies from a group of patients with subepidermal blistering diseases and then (1) prospectively determine which side(s) of 1 mol/L NaCl-split skin is (are) bound by these patients' autoantibodies, (2) compare the sensitivity of intact and 1 mol/L NaCl-split skin for the detection of these autoantibodies; and (3) devise a practical method to distinguish patients with antiepiligrin cicatricial pemphigoid from those with other subepidermal blistering diseases. Methods: Investigative techniques included direct and indirect immunofluorescence microscopy, immunoprecipitation studies, and immunoblotting. Results: These studies identified 14 patients whose sera immunoprecipitate bullous pemphigoid antigens 1, 2, or both. These patients' circulating Ige anti-basement membrane autoantibodies bind the epidermal (n = 11), epidermal and dermal (n = 2), or dermal (n = 1) sides of 1 mol/L NaCl-split skin by indirect immunofluorescence microscopy. In contrast, IgG from all patients with autoantibodies directed against type VII collagen (n = 5) or epiligrin (n = 6) bind only the dermal side of I mol/L NaCl-split skin. In all but one patient in this series, 1 mol/L NaCl-split skin proved to be a more sensitive test substrate than intact human skin for detection of circulating IgG anti-basement membrane autoantibodies. Patients with antiepiligrin cicatricial pemphigoid were distinguished from other patients in that their circulating autoantibodies bound epidermal basement membrane in the skin of primates but not small mammals. Conclusion: NaCl-split skin (1 mol/L) of various species is a sensitive and practical indirect immunofluorescence microscopy test substrate for the evaluation of patients with IgG anti-basement membrane autoantibodies and evaluation of subepidermal bullous diseases. C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 18 TC 39 Z9 39 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 1996 VL 35 IS 3 BP 398 EP 403 DI 10.1016/S0190-9622(96)90604-0 PN 1 PG 6 WC Dermatology SC Dermatology GA VF215 UT WOS:A1996VF21500006 PM 8784276 ER PT J AU Brown, LJ Winn, DM White, BA AF Brown, LJ Winn, DM White, BA TI Dental caries, restoration and tooth conditions in US adults, 1988-1991 SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID LONGEVITY AB This article provides estimates of dental caries experience and selected restorative and tooth conditions among U.S. adults, obtained from Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey, Between 1988 and 1991, 94 percent of adults in the United States showed evidence of past or present coronal caries, Based on the data collected, the authors estimate that about 40.5 percent, or 61.6 million, dentate adults had at least one tooth or tooth space that could potentially benefit from professional treatment, Minimally, it is estimated that 135.6 million teeth or tooth spaces among U.S. adults may benefit from professional treatment. These estimates supplement information available from the DMF index to provide a broader profile of the impact of dental caries on permanent teeth of U.S. adults. C1 NIDR,US PUBL HLTH SERV,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,BETHESDA,MD 20892. RP Brown, LJ (reprint author), NIDR,ANALYT STUDIES & HLTH ASSESSMENT BRANCH,DIV EPIDEMIOL & ORAL DIS PREVENT,NIH,NATCHER BLDG,BETHESDA,MD 20892, USA. NR 25 TC 22 Z9 22 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 SEP PY 1996 VL 127 IS 9 BP 1315 EP 1325 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VG395 UT WOS:A1996VG39500018 PM 8854607 ER PT J AU Slavkin, HC AF Slavkin, HC TI An update on HIV AIDS 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 SEP PY 1996 VL 127 IS 9 BP 1401 EP 1404 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VG395 UT WOS:A1996VG39500031 PM 8854620 ER PT J AU Rozzini, R Ferrucci, L Losonczy, K Havlik, RJ Guralnik, JM AF Rozzini, R Ferrucci, L Losonczy, K Havlik, RJ Guralnik, JM TI Protective effect of chronic NSAID use on cognitive decline in older persons. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALZHEIMERS-DISEASE; ESTABLISHED POPULATIONS; CLINICAL-TRIAL; ASSOCIATION; THERAPY; INDOMETHACIN; DYSFUNCTION; DEMENTIA; ASPIRIN AB OBJECTIVE: To verify whether chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective effect against cognitive decline in older persons. DESIGN: Prospective study with a 3-year observation period. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). SUBJECTS: A population-based sample of 7671 subjects who received an in-person interview at the sixth annual follow-up. Persons with documented NSAID use at the time of the interview and 3 years before were considered chronic users (21%), while all other persons were considered as nonusers. MAIN OUTCOME MEASURE: Change over time in cognitive function assessed as the number of correct answers to a 9-item version of the Short Portable Mental Status Questionnaire (SPMSQ). RESULTS: For every level of SPMSQ score measured at the beginning of the observation period, the mean SPMSQ score after 3 years was higher in chronic NSAID users than in nonusers. Cognitive function at the end of the observation period was significantly higher in chronic NSAID users than in controls, adjusting for initial SPMSQ score and potential confounders. Older age, female gender, education, and history of cerebrovascular disease were also independent predictors of lower SPMSQ score. In the multivariate analysis, the magnitude of the protective effect estimated for NSAID use was comparable to a difference in age of 3.5 years. The percentage of persons who started above a specific SPMSQ score cut-point and deteriorated below that cut-point over a 3-year period was significantly lower in chronic NSAID users than in nonusers (30.2% vs 34.3%, P = .03, for decline below SPMSQ score of 8 and 12.3% vs 14.4% for decline below SPMSQ score of 6, P = .04). After controlling for potential confounders, the relative risk of cognitive declining in chronic NSAID users compared with nonusers was 0.82 (95% Confidence Interval: 0.69-0.98) for a decline below a score of 8, and 0.80 (95% CI: 0.66-0.98) for a decline below a score of 6. CONCLUSIONS: These results support the association between NSAID use and reduction in cognitive decline in older persons. Ultimately, randomized controlled trials must be done to prove a beneficial effect definitively. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. P RICHIEDEI HOSP,GERIATR EVALUAT & REHABIL UNIT,GUSSAGO,BS,ITALY. NATL RES INST,DEPT GERIATR,FLORENCE,ITALY. NR 28 TC 59 Z9 59 U1 0 U2 3 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 SEP PY 1996 VL 44 IS 9 BP 1025 EP 1029 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VF440 UT WOS:A1996VF44000001 PM 8790225 ER PT J AU Pahor, M Guralnik, JM Havlik, RJ Carbonin, P Salive, ME Ferrucci, L Corti, MC Hennekens, CH AF Pahor, M Guralnik, JM Havlik, RJ Carbonin, P Salive, ME Ferrucci, L Corti, MC Hennekens, CH TI Alcohol consumption and risk of deep venous thrombosis and pulmonary embolism in older persons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR; SEVERE GASTROINTESTINAL HEMORRHAGE; CORONARY HEART-DISEASE; MODERATE ALCOHOL; MYOCARDIAL-INFARCTION; PLATELET-AGGREGATION; VEIN THROMBOSIS; UNITED-STATES; MORTALITY; STROKE AB OBJECTIVES: To assess whether low to moderate alcohol consumption decreases the risk of deep venous thrombosis and pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Three communities of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: A total of 7959 persons aged 68 years or older. MEASUREMENTS: The incidence of deep venous thrombosis and pulmonary embolism was assessed by surveying hospital discharge diagnoses and deaths from 1985 through 1992. Those participants who estimated they used alcohol less than 1 time, on average, in the past month, less than 1 ounce per day, and 1 ounce or more per day were compared with those who reported no alcohol intake in the past year. Age, gender, race, body mass index, smoking, education, income, disability, cognitive function, arterial pressure, medication use, baseline chronic conditions, number of hospital admissions in past year, and occurrence of disease during follow-up were examined as possible confounders. RESULTS: During 48,035 person-years of follow-up, 155 events were observed (35 deep venous thromboses and 123 pulmonary emboli). Compared with non-drinkers, after adjusting for potential confounding variables, the relative risks (95% confidence interval) for deep venous thrombosis and pulmonary embolism associated with increasing alcohol consumption levels were 0.7 (0.4-1.1), 0.6 (0.4-0.9), and 0.5 (0.2-1.1), respectively (P for trend = .004). The results were unchanged after stratifying on health status and disability. CONCLUSIONS: Low to moderate alcohol consumption is associated with a decreased risk of deep venous thrombosis and pulmonary embolism in older persons. C1 UNIV CATTOLICA SACRO CUORE,DEPT INTERNAL MED & GERIATR,ROME,ITALY. NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. NATL INST RES & CARE ELDERLY,DEPT GERIATR,FLORENCE,ITALY. HARVARD UNIV,SCH MED,DEPT PREVENT MED,BOSTON,MA 02115. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2107, N01-AG-0-2106] NR 61 TC 22 Z9 23 U1 0 U2 2 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 SEP PY 1996 VL 44 IS 9 BP 1030 EP 1037 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VF440 UT WOS:A1996VF44000002 PM 8790226 ER PT J AU Haydar, Z Fleg, JL Tobin, JD Vaitkevicius, PV Harman, SM Blackman, MR AF Haydar, Z Fleg, JL Tobin, JD Vaitkevicius, PV Harman, SM Blackman, MR TI Aging, not circulating IGF-1, influences aerobic capacity in healthy women and men. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21224. NIA,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1996 VL 44 IS 9 BP P293 EP P293 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VF440 UT WOS:A1996VF44000363 ER PT J AU Stevens, TE Harman, SM Adler, WA Pyle, RS StClair, C Gusenoff, J Blackman, MR AF Stevens, TE Harman, SM Adler, WA Pyle, RS StClair, C Gusenoff, J Blackman, MR TI The inter relationships between spontaneous nocturnal cortisol secretion and peripheral lymphocyte number and function differ in healthy elderly women and men. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract C1 NIA,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 1996 VL 44 IS 9 BP P298 EP P298 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VF440 UT WOS:A1996VF44000368 ER PT J AU Rodgers, RPC AF Rodgers, RPC TI Java and its future in biomedical computing SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Review AB Java, a new object-oriented computing language related to C++, is receiving considerable attention due to its use in creating network-sharable, platform-independent software modules (known as ''applets'') that can be used with the World Wide Web. The Web has rapidly become the most commonly used information-retrieval tool associated with the global computer network known as the Internet, and Java has the potential to further accelerate the Web's application to medical problems. Java's potentially wide acceptance due to its Web association and its own technical merits also suggests that it may become a popular language for non-Web-based, object-oriented computing. RP Rodgers, RPC (reprint author), US NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,COMP SCI BRANCH,BETHESDA,MD 20894, USA. NR 7 TC 8 Z9 8 U1 1 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 1996 VL 3 IS 5 BP 303 EP 307 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA VJ042 UT WOS:A1996VJ04200001 PM 8880677 ER PT J AU Austin, HA Vaughan, EM Boumpas, DT Klippel, JH Balow, JE AF Austin, HA Vaughan, EM Boumpas, DT Klippel, JH Balow, JE TI Lupus membranous nephropathy: Controlled trial of prednisone, pulse cyclophosphamide, and cyclosporine A. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NATL INST HLTH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0411 EP A0411 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400410 ER PT J AU Austin, HA Vaughan, EM Boumpas, DT Balow, JE AF Austin, HA Vaughan, EM Boumpas, DT Balow, JE TI Randomized trial of pulse cyclophosphamide and prednisone vs prednisone alone in idiopathic membranous nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NATL INST HLTH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0410 EP A0410 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400409 ER PT J AU Berl, T Perez, AG Siriwardana, G DuBois, S Heasley, L AF Berl, T Perez, AG Siriwardana, G DuBois, S Heasley, L TI Role of JUN-N terminal kinase (JNK) in the response to hypertonicity (H) in inner medullary collecting duct (IMCD) cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV COLORADO,SCH MED,DENVER,CO. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0249 EP A0249 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400248 ER PT J AU Bird, JE Durham, SK Giancarli, MR Gitlitz, P Pandya, D Barton, D Mozes, MM Kopp, JB AF Bird, JE Durham, SK Giancarli, MR Gitlitz, P Pandya, D Barton, D Mozes, MM Kopp, JB TI Captopril (CAP) ameliorates nephropathy in HIV-transgenic mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB,PRINCETON,NJ. NIDDK,NIH,BETHESDA,MD. RI Mozes, Miklos/E-9003-2011 NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 7 IS 9 BP A3019 EP A3019 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07403013 ER PT J AU Bottinger, EP Jakubczak, J Roberts, I Mumy, M Hemmati, P Wakefield, LM Merlino, G Roberts, AB AF Bottinger, EP Jakubczak, J Roberts, I Mumy, M Hemmati, P Wakefield, LM Merlino, G Roberts, AB TI Increased deposition of extracellular matrix and cross-regulation of TGF-beta isoforms in transgenic mice with targeted overexpression of dominant negative mutant TGF-beta receptors. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,LC,NIH,BETHESDA,MD 20892. NCI,LMB,NIH,BETHESDA,MD 20892. UNIV MANCHESTER,MANCHESTER,LANCS,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2526 EP A2526 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402521 ER PT J AU Bottinger, EP Roberts, I Factor, V Tsang, M Weatherbee, J Thorgeirsson, S Roberts, AB Wakefield, L Kopp, J AF Bottinger, EP Roberts, I Factor, V Tsang, M Weatherbee, J Thorgeirsson, S Roberts, AB Wakefield, L Kopp, J TI Improved renal function and histology in TGF beta 1 transgenic mice treated with recombinant TGF beta 1 latency-associated peptide (LAP). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NCI,LC,BETHESDA,MD 20892. NCI,LEC,BETHESDA,MD 20892. NIDDK,BETHESDA,MD. RES & DEV SYST,MINNEAPOLIS,MN. UNIV MANCHESTER,MANCHESTER,LANCS,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1895 EP A1895 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401891 ER PT J AU Cusumano, A Bodkin, NL Hansen, BC Kopp, JB AF Cusumano, A Bodkin, NL Hansen, BC Kopp, JB TI Glomerular morphometry of normal and spontaneously diabetic rhesus monkeys. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,DEPT PHYSIOL,OBES & DIABET RES CTR,BALTIMORE,MD 21201. NIDDK,NIH,KIDNEY DIS SECT,BETHESDA,MD. RI Hansen, Barbara/J-8723-2012 OI Hansen, Barbara/0000-0001-9646-3525 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2420 EP A2420 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402415 ER PT J AU Daugirdas, J Greene, T Levin, H Maroni, B Schulman, G Star, R AF Daugirdas, J Greene, T Levin, H Maroni, B Schulman, G Star, R TI Modeled/anthropometric volume ratios: Effect of age, race, and different formulas. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1305 EP A1305 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401301 ER PT J AU Daugirdas, J Greene, T Depner, T Gotch, F Keshaviah, P Star, R AF Daugirdas, J Greene, T Depner, T Gotch, F Keshaviah, P Star, R TI Estimation of double pool volume from single pool urea distribution volume. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1304 EP A1304 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401300 ER PT J AU Depner, TA Cheung, AK Daugirdas, JT Gotch, FA Greene, T Leypoldt, JK AF Depner, TA Cheung, AK Daugirdas, JT Gotch, FA Greene, T Leypoldt, JK TI Adjustments required to accurately predict in vivo hemodialysis urea clearance from in vitro derived constants. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1308 EP A1308 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401304 ER PT J AU Doi, SQ Jacot, TA He, CJ Hirszel, P Striker, GE Striker, LJ AF Doi, SQ Jacot, TA He, CJ Hirszel, P Striker, GE Striker, LJ TI Growth hormone (GH) increases inducible nitric oxide synthase (INOS) expression in cultured mouse mesangial cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NIDDK,RCBS,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1909 EP A1909 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401905 ER PT J AU Feng, Z Striker, GE Jacot, T Lenz, O Striker, LJ AF Feng, Z Striker, GE Jacot, T Lenz, O Striker, LJ TI Stimulation of bovine growth hormone (bGH) expression in bGH mesangial cells results in increased extracellular matrix (ECM) gene mRNA levels. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,NIH,RCBS,BETHESDA,MD. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1996 VL 7 IS 9 BP A2426 EP A2426 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402421 ER PT J AU Ferraris, JD Williams, CK Jung, KY Bedford, JJ Burg, MB GarciaPerez, A AF Ferraris, JD Williams, CK Jung, KY Bedford, JJ Burg, MB GarciaPerez, A TI Ore, eukaryotic minimal essential osmotic response element: The aldose reductase (AR) gene in hyperosmotic stress. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,LKEM,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 2 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 SEP PY 1996 VL 7 IS 9 BP A0259 EP A0259 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400258 ER PT J AU Fierlbeck, W Palkovits, M Geiger, H AF Fierlbeck, W Palkovits, M Geiger, H TI Effects of inhibition of ANP-degradation in DOCA-salt hypertensive rats. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV NURNBERG,MED CLIN 4,NURNBERG,GERMANY. NIH,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1413 EP A1413 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401409 ER PT J AU Frokiaer, J Marples, D Monster, B Jensen, UB Knepper, MA Nielsen, S AF Frokiaer, J Marples, D Monster, B Jensen, UB Knepper, MA Nielsen, S TI Downregulation of aquaporin-2 (AQP2) protein and mRNA expression parallel functional changes of renal water excretion in unilateral ureteral obstruction SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,AARHUS,DENMARK. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0092 EP A0092 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400091 ER PT J AU Ginns, SM Knepper, MA Ecelbarger, CA Terris, J He, X Coleman, RA Wade, JB AF Ginns, SM Knepper, MA Ecelbarger, CA Terris, J He, X Coleman, RA Wade, JB TI Secretory isoform of bumetanide-sensitive ion cotransporter immunolocalizes to renal intercalated cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NIDR,NIH,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0029 EP A0029 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400028 ER PT J AU Goebel, J Ghosh, P Mikovits, J Boineau, F Ukah, F Young, H Robey, F Lowry, RP AF Goebel, J Ghosh, P Mikovits, J Boineau, F Ukah, F Young, H Robey, F Lowry, RP TI CD4-ligand binding extinguishes IL-2 receptor signaling & modulates expression of the Th1-effector phenotype. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 TULANE UNIV,NEW ORLEANS,LA 70118. UNIV S ALABAMA,MOBILE,AL 36688. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A3194 EP A3194 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07403188 ER PT J AU He, CJ Stitt, A Striker, L Hattori, M Vlassara, H AF He, CJ Stitt, A Striker, L Hattori, M Vlassara, H TI Low expression of AGE-receptor-1 in NOD mouse mesangial cells: Possible link to diabetic nephropathy. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 PICOWER INST MED RES,MANHASSET,NY. NIDDK,RCBS,MDB,BETHESDA,MD. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A3123 EP A3123 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07403117 ER PT J AU Hugo, C Pichler, RH Roberts, DD Couser, WG Johnson, RJ AF Hugo, C Pichler, RH Roberts, DD Couser, WG Johnson, RJ TI Differential effects of thrombospondin 1 (TSP1) peptides in experimental mesangial proliferative disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIH,PATHOL LAB,BETHESDA,MD 20892. UNIV WASHINGTON,SEATTLE,WA 98195. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2438 EP A2438 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402433 ER PT J AU Jacot, JL Jacot, TA McKenzie, JE Striker, L AF Jacot, JL Jacot, TA McKenzie, JE Striker, L TI Role of Nitric Oxide in modulating cortical and medullary renal blood flow in neonatal piglets. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NEI,NIH,BETHESDA,MD 20892. NIDDK,NIH,BETHESDA,MD 20892. USUHS,DEPT PHYSIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1575 EP A1575 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401571 ER PT J AU Jacot, TA Striker, GE StetlerStevenson, MA Striker, LJ AF Jacot, TA Striker, GE StetlerStevenson, MA Striker, LJ TI Decreased mesangial cell MMP-9 as a cause of sclerosis in mice transgenic for bovine growth hormone (bGH). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,RENAL CELL BIOL SECT,NIH,BETHESDA,MD. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2546 EP A2546 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402541 ER PT J AU Kishore, BK Mandon, B Nielsen, S Knepper, MA AF Kishore, BK Mandon, B Nielsen, S Knepper, MA TI Tagmin-6 is expressed in the collecting duct principal cell: A possible molecular switch in vasopressin-induced water channel trafficking SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. UNIV AARHUS,AARHUS,DENMARK. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0325 EP A0325 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400324 ER PT J AU Kishore, DK Terris, JM Knepper, MA AF Kishore, DK Terris, JM Knepper, MA TI Ultramicro-determination of vasopressin-regulated urea transporter protein in microdissected tubule segments: Effect of low-protein diet. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1996 VL 7 IS 9 BP A0101 EP A0101 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400100 ER PT J AU Kovbasnjuk, O Spring, O AF Kovbasnjuk, O Spring, O TI Regulation of tight junction (TJ) sodium permeability in MDCK cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,LKEM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 7 IS 9 BP A0182 EP A0182 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400181 ER PT J AU Le, HV Kailasam, MT Cervenka, JH Wilson, AF OConnor, DT Parmer, RJ AF Le, HV Kailasam, MT Cervenka, JH Wilson, AF OConnor, DT Parmer, RJ TI Sympathetic nervous system reactivity to cold stress in families with essential hypertension: Racial differences and evidence for heritability. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VAMC,DEPT MED,SAN DIEGO,CA. VAMC,CTR MOL GENET,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NATL CTR HUMAN GENOME RES,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1512 EP A1512 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401508 ER PT J AU Lenz, O Striker, GE Killen, PD Striker, LJ AF Lenz, O Striker, GE Killen, PD Striker, LJ TI Contribution of glomerular endothelial, epithelial and mesangial cells to extracellular matrix turnover in vitro. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,MDB,RCBS,NIH,BETHESDA,MD. UNIV MICHIGAN,ANN ARBOR,MI 48109. RI Lenz, Oliver/M-4672-2016 OI Lenz, Oliver/0000-0003-2997-3976 NR 0 TC 0 Z9 0 U1 1 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 SEP PY 1996 VL 7 IS 9 BP A2562 EP A2562 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402557 ER PT J AU Leypoldt, JK Cheung, AK Clark, WR Daugirdas, JT Gotch, FA Greene, T Levin, NW AF Leypoldt, JK Cheung, AK Clark, WR Daugirdas, JT Gotch, FA Greene, T Levin, NW TI Characterization of low and high flux dialyzers with reuse in the hemo study: Interim report. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1345 EP A1345 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401341 ER PT J AU Maroni, B Burkart, J Burrowes, J Cockram, D Drabik, M Dwyer, J Kusek, J Makoff, R Paranandi, L Powers, S Rocco, M AF Maroni, B Burkart, J Burrowes, J Cockram, D Drabik, M Dwyer, J Kusek, J Makoff, R Paranandi, L Powers, S Rocco, M TI Baseline nutritional characteristics of the HEMO study participants: Interim report SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDKD,HEMODIALYSIS STUDY,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1041 EP A1041 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401037 ER PT J AU Marples, D Monster, B Frokiaer, J Knepper, MA Nielsen, S AF Marples, D Monster, B Frokiaer, J Knepper, MA Nielsen, S TI Thirsting reverses the polyuria and decreased aquaporin-2 (AQP2) expression associated with continuous treatment with a V2 receptor antagonist. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,AARHUS,DENMARK. UNIV LEEDS,LEEDS,W YORKSHIRE,ENGLAND. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0108 EP A0108 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400107 ER PT J AU Monster, B Marples, D Frokiaer, J Jensen, UB Knepper, MA Nielsen, S AF Monster, B Marples, D Frokiaer, J Jensen, UB Knepper, MA Nielsen, S TI Short-term effects of the V2-receptor antagonist OPC31260 on AQP mRNA expression and subcellular distribution of AQP2 protein in rat kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 AARHUS UNIV,AARHUS,DENMARK. UNIV LEEDS,LEEDS,W YORKSHIRE,ENGLAND. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0109 EP A0109 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400108 ER PT J AU Nielsen, S Marples, D Monster, B Valtin, H Morris, J Knepper, MA AF Nielsen, S Marples, D Monster, B Valtin, H Morris, J Knepper, MA TI Downregulation of aquaporin-2 (AQP2) water channel protein in polyuric DI+/+ mice with constitutively high levels of cAMP-phosphodiesterase activity. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 UNIV AARHUS,AARHUS,DENMARK. UNIV LEEDS,LEEDS,W YORKSHIRE,ENGLAND. UNIV OXFORD,OXFORD,ENGLAND. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0114 EP A0114 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400113 ER PT J AU Ota, K Wada, J Kumar, A StetlerStevenson, WG Kanwar, YS AF Ota, K Wada, J Kumar, A StetlerStevenson, WG Kanwar, YS TI CDNA cloning of murine membrane-type matrix metalloproteinase-1 and its role in metanephric organogenesis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2581 EP A2581 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402576 ER PT J AU Parmer, RJ Le, H Kailasam, MT Wilson, AF OConnor, DT AF Parmer, RJ Le, H Kailasam, MT Wilson, AF OConnor, DT TI Impaired baroreflex sensitivity is associated with blood pressure elevation and dyslipidemia in families with essential hypertension. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 VAMC,DEPT MED,SAN DIEGO,CA. VAMC,CTR MOL GENET,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. NATL CTR HUMAN GENOME RES,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1519 EP A1519 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401515 ER PT J AU Ray, PE Rakusan, T Owens, J Xu, L Cook, A Davis, H Bryant, J Kher, K AF Ray, PE Rakusan, T Owens, J Xu, L Cook, A Davis, H Bryant, J Kher, K TI Increased basic FGF levels in the circulation of children with HIV associated renal disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 CHILDRENS NATL MED CTR,CRI,WASHINGTON,DC 20010. NIDR,ANIM CARE UNIT,VET RESOURCES PROGRAM,NIH,BETHESDA,MD 20892. INST HUMAN VIROL,BALTIMORE,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0480 EP A0480 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400479 ER PT J AU Schachter, LA Wisnieski, JJ Denburg, MR Michael, AR Gourley, MF Kimberly, RP Salmon, JE AF Schachter, LA Wisnieski, JJ Denburg, MR Michael, AR Gourley, MF Kimberly, RP Salmon, JE TI Antibodies to Clq in systemic lupus erythematosus are potential contributors to renal disease. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 CORNELL UNIV,MED CTR,NEW YORK,NY 10021. CASE WESTERN RESERVE UNIV,VET ADM MED CTR,CLEVELAND,OH 44106. NIAMS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2670 EP A2670 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402664 ER PT J AU Shrivastav, S Bryant, JL Kopp, JB AF Shrivastav, S Bryant, JL Kopp, JB TI Functional T cells are not required for renal disease in HIV-transgenic mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,KIDNEY DIS SECT,NIH,BETHESDA,MD. UNIV MARYLAND,INST HUMAN VIROL,BALTIMORE,MD 21201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2496 EP A2496 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402491 ER PT J AU Tassiulas, IO Boumpas, DT Vaughan, E Fleisher, TA Piscetelli, S Kim, Y Puccino, F Balow, JE Austin, HA AF Tassiulas, IO Boumpas, DT Vaughan, E Fleisher, TA Piscetelli, S Kim, Y Puccino, F Balow, JE Austin, HA TI A pilot study of low-dose fludarabine in membranous nephropathy refractory to therapy. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NATL INST HLTH,BETHESDA,MD. NR 0 TC 0 Z9 0 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 SEP PY 1996 VL 7 IS 9 BP A2679 EP A2679 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402673 ER PT J AU Verbalis, JG Ecelbarger, CA Knepper, MA Nielsen, S Olson, BR Baker, EA AF Verbalis, JG Ecelbarger, CA Knepper, MA Nielsen, S Olson, BR Baker, EA TI The vasopressin-escape phenomenon is associated with marked downregulation of aquaporin-2 water channel expression SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. AARHUS UNIV,AARHUS,DENMARK. GEORGETOWN UNIV,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0090 EP A0090 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400089 ER PT J AU Vukicevic, S Kopp, JB Luyten, FP Sampath, TK AF Vukicevic, S Kopp, JB Luyten, FP Sampath, TK TI Induction of nephrogenic mesenchyme by OP-1 (BMP-7). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIDDK,BETHESDA,MD. UNIV ZAGREB,ZAGREB 41000,CROATIA. NIDR,NIH,BETHESDA,MD 20892. CREAT BIOMOL INC,HOPKINTON,MA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A1791 EP A1791 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07401787 ER PT J AU Weiss, RA AF Weiss, RA TI Cadmium chloride induces B7.1 expression in murine renal tubular cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A2391 EP A2391 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07402387 ER PT J AU Zayas, CF Platt, A Eckman, J Elsas, L Clark, WS Mitch, WE Guasch, A AF Zayas, CF Platt, A Eckman, J Elsas, L Clark, WS Mitch, WE Guasch, A TI Prevalence and predictors of glomerular involvement in sickle cell anemia SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract C1 EMORY UNIV,SCH PUBL HLTH,DIV RENAL,DIV MED GENET,ATLANTA,GA. EMORY UNIV,NIH,SICKLE CELL CTR,ATLANTA,GA 30322. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 1996 VL 7 IS 9 BP A0780 EP A0780 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA VK074 UT WOS:A1996VK07400777 ER PT J AU Hoofnagle, JH Lau, D Conjeevaram, H Kleiner, D DiBisceglie, AM AF Hoofnagle, JH Lau, D Conjeevaram, H Kleiner, D DiBisceglie, AM TI Prolonged therapy of chronic hepatitis C with ribavirin SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE antivirals; chronic hepatitis; gallstones; haemolysis; hepatitis C virus; nucleoside analogue ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; COMBINATION THERAPY; INTERFERON-ALFA; TOLERANCE; VIRUS AB Therapy with ribavirin for 6-12 months is associated with decreases in serum aminotransferases in some patients with chronic hepatitis C. We have assessed the practicality and safety of prolonged therapy with ribavirin. Six patients with chronic hepatitis C were given 1000-1200 mg of ribavirin daily for 24 months. Serum aminotransferases and hepatitis C virus (HCV) RNA levels were monitored during and after therapy. Liver biopsies were carried out before and at the end of treatment. With therapy, mean serum alanine aminotransferase (ALT) levels fell from 161 U/L to 45 U/L at 12 months and to 39 U/L at 24 months. HCV RNA levels did not change. Liver histology improved in five and was unchanged in one patient. When therapy was stopped, aminotransferases rose to pretreatment levels. Side effects included mild fatigue and headaches. Two patients developed gallstones during therapy, perhaps caused by the chronic haemolysis that occurred in all patients. In conclusion, prolonged therapy with ribavirin can result in sustained improvements in serum aminotransferases and hepatic histology in a proportion of patients with chronic hepatitis C. Ribavirin therapy does not cause decreases in viraemia and, therefore, probably must be continued indefinitely to provide lasting benefit. The advantages of such therapy must be weighed against possible long-term side-effects. C1 NATL CANC INST,NATL INST HLTH,PATHOL LAB,BETHESDA,MD. RP Hoofnagle, JH (reprint author), NIDDK,NIH,LIVER DIS SECT,DIGEST DIS BRANCH,BLDG 10,ROOM 9B16,BETHESDA,MD 20892, USA. OI Kleiner, David/0000-0003-3442-4453 NR 20 TC 53 Z9 57 U1 0 U2 2 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 SEP PY 1996 VL 3 IS 5 BP 247 EP 252 DI 10.1111/j.1365-2893.1996.tb00050.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA VM114 UT WOS:A1996VM11400004 PM 8914004 ER PT J AU Roden, RBS Greenstone, HL Kirnbauer, R Booy, FP Jessie, J Lowy, DR Schiller, JT AF Roden, RBS Greenstone, HL Kirnbauer, R Booy, FP Jessie, J Lowy, DR Schiller, JT TI In vitro generation and type-specific neutralization of a human papillomavirus type 16 virion pseudotype SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; L2 CAPSID PROTEINS; BOVINE PAPILLOMAVIRUS; L1 PROTEIN; MONOCLONAL-ANTIBODIES; INSECT CELLS; MOUSE CELLS; EXPRESSION; DNA; INVITRO AB We report a system for generating infectious papillomaviruses in vitro that facilitates the analysis of papillomavirus assembly, infectivity, and serologic relatedness. Cultured hamster BPHE-1 cells harboring autonomously replicating bovine papillomavirus type 1 (BPV1) genomes were infected with recombinant Semliki Forest viruses that express the structural proteins of BPV1, When plated on C127 cells, extracts from cells expressing L1 and L2 together induced numerous transformed foci that could be specifically prevented by BPV neutralizing antibodies, demonstrating that BPV infection was responsible for the focal transformation. Extracts from BPHE-1 cells expressing L1 or L2 separately were not infectious. Although Semliki Forest virus-expressed L1 self-assembled into virus-like particles (VLPs), viral DNA was detected in particles only when L2 was coexpressed with L1, indicating that genome encapsidation requires L2. Expression of human papillomavirus type 16 (HPV16) L1 and L2 together in BPHE-1 cells also yielded infectious virus. These pseudotyped virions were neutralized by antiserum to HPV16 VLPs derived from European (114/K) or African (Z-1194) HPV16 variants but not by antisera to BPV VLPs, to a poorly assembling mutant HPV16 L1 protein, or to VLPs of closely related genital HPV types. Extracts from BPHE-1 cells coexpressing BPV L1 and HPV16 L2 or HPV16 L1 and BPV L2 were not infectious. We conclude that (i) mouse C127 cells express the cell surface receptor for HPV16 and are able to uncoat HPV16 capsids; (ii) if a papillomavirus DNA packaging signal exists, then it is conserved between the BPV and HPV16 genomes; (iii) functional L1-L2 interaction exhibits type specificity; and (iv) protection by HPV virus-like particle vaccines is likely to be type specific. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. UNIV VIENNA,SCH MED,DEPT DERMATOL,DIV IMMUNOL ALLERGY & INFECT DIS,A-1090 VIENNA,AUSTRIA. LIFE TECHNOL INC,GAITHERSBURG,MD 20884. NR 46 TC 211 Z9 219 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 SEP PY 1996 VL 70 IS 9 BP 5875 EP 5883 PG 9 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500019 PM 8709207 ER PT J AU Tabernero, C Zolotukhin, AS Valentin, A Pavlakis, GN Felber, BK AF Tabernero, C Zolotukhin, AS Valentin, A Pavlakis, GN Felber, BK TI The posttranscriptional control element of the simian retrovirus type 1 forms an extensive RNA secondary structure necessary for its function SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 REV PROTEIN; PFIZER MONKEY VIRUS; VIRAL MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; RESPONSIVE ELEMENT; MOLECULAR CLONE; GENE-PRODUCT; EXPRESSION; IDENTIFICATION AB It was previously shown that a 240-nucleotide (nt) RNA element (cis-acting transactivation element [CTE]) located between the env gene and the 3' long terminal repeat of simian retrovirus type 1 (SRV-1) can functionally replace posttranscriptional activation directed by Rev and the Rev-responsive element (RRE) when inserted into a Rev- and RRE-deficient molecular clone of human immunodeficiency virus type 1, resulting in efficient virus replication. Here, we analyze the molecular and structural requirements for function of this RNA element, Deletion mutagenesis demonstrated that the core element spans 173 nt, SRV-2 and Mason-Pfizer monkey virus have highly homologous elements, which function similarly when inserted into the Rev/RRE-deficient human immunodeficiency virus type 1, Computer prediction indicated that the core CTEs of all three viruses have similar extensive secondary structures, Mutagenesis of the SRV-1 CTE revealed that both sequence and secondary structure are essential for function. Nuclease probing of the SRV-1 CTE further supported the genetic analysis and confirmed the predicted structural features of the RNA element, Sequence analysis of the 240-nt SRV-1 CTE, after continuous long-term propagation of the Rev-independent viruses, revealed that the genetically defined core element remained unchanged, while regions outside the core CTE underwent deletions or duplications, These data further support our in vitro mutagenesis data and demonstrate the importance of the sequence and structure of the SRV-1 CTE for appropriate function. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. NR 37 TC 92 Z9 92 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 SEP PY 1996 VL 70 IS 9 BP 5998 EP 6011 PG 14 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500034 PM 8709222 ER PT J AU Blake, M Niklinski, J Zajac-Kaye, M AF Blake, M Niklinski, J Zajac-Kaye, M TI Interactions of the transcription factors MIBP1 and RFX1 with the EP element of the hepatitis B virus enhancer SO JOURNAL OF VIROLOGY LA English DT Article ID C-MYC GENE; SV40 ENHANCER; HEPATOCELLULAR-CARCINOMA; BINDING-PROTEIN; NUCLEAR FACTOR; 1ST INTRON; RXR-ALPHA; EF-C; COMPLEX; EXPRESSION AB We previously demonstrated that MIBP1 and RFX1 polypeptides associate in vivo to form a complex that binds to the MIF-1 element in the c-myc gene and the major histocompatibility complex class II X-box recognition sequence. We now show that the EP element, a key regulatory sequence within hepatitis B virus enhancer I, also associates with MIBP1 and RFX1. Using polyclonal antisera directed against either oligonucleotide-purified MIBP1 or a peptide derived from the major histocompatibility complex class II promoter-binding protein RFX1, we showed that MIBP1 and RFX1 are both present in the DNA-protein complexes at the EP site. In addition, while the EP element can act cooperatively with several adjacent elements to transactivate hepatitis B virus expression, we demonstrated that the EP site alone can repress transcription of simian virus 40 promoter in a position- and orientation-independent manner, suggesting a silencer function in hepatocarcinoma cells. C1 NIH, BIOL CHEM LAB, BETHESDA, MD 20892 USA. SCH MED, DEPT THORAC SURG, BIALYSTOK, POLAND. NR 44 TC 12 Z9 13 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 SEP PY 1996 VL 70 IS 9 BP 6060 EP 6066 PG 7 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500041 PM 8709229 ER PT J AU Kuo, LL Fearns, R Collins, PL AF Kuo, LL Fearns, R Collins, PL TI The structurally diverse intergenic regions of respiratory syncytial virus do not modulate sequential transcription by a dicistronic minigenome SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; ANTIGENIC SUBGROUP-A; MESSENGER-RNA; GENE-OVERLAP; GENOME ORGANIZATION; SENDAI VIRUS; SEQUENCES; PROTEIN; ATTENUATION; REPLICATION AB The first nine genes of respiratory syncytial virus (RSV), a nonsegmented negative-strand RNA virus, are separated by intergenic regions which range in size from 1 to 52 nucleotides for strain A2 and lack obvious consensus elements except that each ends in an A (genome sense). Their significance for gene expression was investigated by using RSV-CAT-LUC RNA, a helper-dependent cDNA-encoded dicistronic analog of RSV genomic RNA in which the viral genes were replaced by a negative-sense copy of the translational open reading frame (ORF) encoding chloramphenicol acetyltransferase (CAT) as the upstream, leader-proximal gene and that encoding luciferase (LUG) as the downstream gene, These foreign ORFs were flanked by the RSV gene-start (GS) and gene-end (G-E) transcription signals and separated by the naturally occurring G/F intergenic region, The RSV-GAT-LUC minigenome was synthesized in vitro and transfected into RSV-infected cells, and synthesis of the CAT and LUC mRNAs was monitored by enzyme assay and Northern (RNA) blot hybridization, Surprisingly, substitution of each of the other naturally occurring RSV intergenic regions in turn did not significantly alter the absolute or relative amounts of the two mRNAs, Substitution of a nonnatural 10-nucleotide intergenic region, or elimination of the intergenic region altogether, also had little effect on the level of expression of the two genes. Four of the minigenome variants containing naturally occurring intergenic regions were modified further by replacing part of the LUC ORF with a second copy of the CAT ORF, so that each of the two mRNAs would hybridize equally with a CAT-specific probe and their relative molar amounts could be determined. The level of expression of the downstream gene was 0.30 to 0.36 that of the upstream one. This determined the magnitude of RSV transcriptional polarity across a gene pair and confirmed that this value was very similar among the various intergenic regions. Minigenome transcription also yielded a CAT-LUG readthrough mRNA at a level 0.10 to 0.13 that of the LUC mRNA, In summary, the structurally diverse RSV intergenic regions do not appear to play a role in modulating RSV gene expression. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 31 TC 50 Z9 51 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 SEP PY 1996 VL 70 IS 9 BP 6143 EP 6150 PG 8 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500051 PM 8709239 ER PT J AU Nunn, MF Marsh, JW AF Nunn, MF Marsh, JW TI Human immunodeficiency virus type 1 Nef associates with a member of the p21-activated kinase family SO JOURNAL OF VIROLOGY LA English DT Article ID GTP-BINDING PROTEINS; T-CELLS; GENE-PRODUCT; NUCLEAR-LOCALIZATION; MUTATIONAL ANALYSIS; NONDIVIDING CELLS; MOLECULAR-CLONING; PLASMA-MEMBRANE; MATRIX PROTEIN; HUMAN PLACENTA AB Although human immunodeficiency virus (HIV) Nef is essential for the induction of AIDS, its biochemical function has remained an enigma. In this study, HIV Nef protein is shown to associate with a serine-threonine kinase that recognizes histone H4 as a substrate, is serologically related to rat p21-activated kinase (PAK), and is specifically activated by Rac and Cdc42. These characteristics define the Nef-associated kinase as belonging to the PAK family. PAKs initiate kinase cascades in response to environmental stimuli, and their identification as a target of Nef implicates these signaling molecules in HIV pathogenesis and provides a novel target for clinical intervention. C1 NIMH,MOL BIOL LAB,BETHESDA,MD 20892. NR 59 TC 133 Z9 134 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 SEP PY 1996 VL 70 IS 9 BP 6157 EP 6161 PG 5 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500053 PM 8709241 ER PT J AU Turpin, JA Terpening, SJ Schaeffer, CA Yu, G Glover, CJ Felsted, RL Sausville, EA Rice, WG AF Turpin, JA Terpening, SJ Schaeffer, CA Yu, G Glover, CJ Felsted, RL Sausville, EA Rice, WG TI Inhibitors of human immunodeficiency virus type 1 zinc fingers prevent normal processing of Gag precursors and result in the release of noninfectious virus particles SO JOURNAL OF VIROLOGY LA English DT Article ID ACID-BINDING-PROTEINS; MURINE LEUKEMIA-VIRUS; VIRAL MESSENGER-RNA; CYS-HIS BOX; NUCLEOCAPSID PROTEIN; STRAND TRANSFER; HIV-1 PROTEASE; 3-DIMENSIONAL STRUCTURE; N-MYRISTOYLTRANSFERASE; REVERSE TRANSCRIPTION AB The Cys-Xaa(2)-Cys-Xaa(4)-His-Xaa(4)-Cys zinc fingers of retroviral nucleo cap sid proteins are prime antiviral targets because of conservation of the Cys and His chelating residues and the absolute requirement of these fingers in both early and late phases of retroviral replication. We previously reported that certain disulfide-substituted benzamides (DIBAs) chemically modify the Cys residues of the fingers, resulting in inhibition of human immunodeficiency virus type 1 (HIV-1) replication (W. G. Rice, J. G. Supko, L. Malspeis, R. W. Buckheit, Jr., D. Clanton, M. Bu, L. Graham, C. A. Schaeffer, J. A. Turpin, J. Domagala, R. Gogliotti, J. P. Bader, S. M. Halliday, L. Coren, R. C. Sowder II, L. O. Arthur, and L. E. Henderson, Science 270:1194-1197, 1995). We now examine the consequences of the interaction of DIBAs,vith the zinc fingers of the HIV-1 p7 nucleocapsid protein and its pr55(gag) precursor. In HIV-1-infected U1 cells, DIBAs inhibited the release of infectious virions, and even under conditions in which virion particles were produced, the particles were noninfectious. DIBAs caused abnormal processing of Gag precursors, and the inhibitory effect on processing was not due to inhibition of the HIV-1 protease enzyme or Pr55(gag) myristoylation. Rather, the defect in processing was due to the formation of intermolecular cross-linkages among the zinc fingers of adjacent Gag molecules, rendering the precursors no longer recognizable by HIV-1 protease. Likewise, DIBAs caused intermolecular cross-linkage among recombinant Pr55(gag) packaged into pseudovirions, thereby generating modified precursors that were resistant to the action of protease. Thus, DIBAs chemically modified the mutationally intolerant retroviral zinc fingers in infected cells, interrupting protease-mediated maturation of virions and leading ultimately to the production of compromised virions. C1 NCI,FREDERICK CANC RES & DEV CTR,DEV THERAPEUT PROGRAM,LAB ANTIVIRAL DRUG MECHAN,SAIC FREDERICK,FREDERICK,MD 21702. NCI,BIOL CHEM LAB,DIV BASIC SCI,BETHESDA,MD 20892. FU PHS HHS [N01-C0-56000] NR 59 TC 66 Z9 68 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 SEP PY 1996 VL 70 IS 9 BP 6180 EP 6189 PG 10 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500056 PM 8709244 ER PT J AU Semmes, OJ Jeang, KT AF Semmes, OJ Jeang, KT TI Localization of human T-cell leukemia virus type 1 Tax to subnuclear compartments that overlap with interchromatin speckles SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTIONAL CONTROL REGION; PRE-MESSENGER-RNA; HTLV-I TAX; HEAT-SHOCK; NUCLEAR RIBONUCLEOPROTEINS; MEDIATED TRANSACTIVATION; MAMMALIAN SPLICEOSOME; ACTIVATOR PROTEIN; BINDING-SITES; HELA-CELLS AB Tax, the virally encoded activator of the human T-cell leukemia virus type 1 long terminal repeats, regulates the expression of many cellular genes. This protein has been implicated in transformation events leading to the development of adult T-cell leukemia. Because subcellular localization contributes importantly to protein function, we determined the compartment(s) within the cell in which Tax is found. Using confocal microscopy, we found that Tax localizes to subnuclear domains which overlap with structures previously identified as interchromatin granules or spliceosomal speckles. These Tax speckled structures are coincident with a subset of nuclear transcriptional hot spots. Disruption of the Tax speckled structures by heat shock revealed the existence of different populations of Tax. One population of Tax is tightly associated with nuclear speckles. A second population exists outside of the speckles and is transcriptionally active for some promoters. RP Semmes, OJ (reprint author), NIAID,MOL MICROBIOL LAB,MOL VIROL SECT,BETHESDA,MD 20892, USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 63 TC 91 Z9 93 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 SEP PY 1996 VL 70 IS 9 BP 6347 EP 6357 PG 11 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500075 PM 8709263 ER PT J AU Bender, BS Rowe, CA Taylor, SF Wyatt, LS Moss, B Small, PA AF Bender, BS Rowe, CA Taylor, SF Wyatt, LS Moss, B Small, PA TI Oral immunization with a replication-deficient recombinant vaccinia virus protects mice against influenza SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; MUCOSAL IMMUNE-SYSTEM; A VIRUS; INTRACELLULAR NEUTRALIZATION; RESPIRATORY-INFECTION; HETEROTYPIC IMMUNITY; ENTERIC IMMUNIZATION; RABIES GLYCOPROTEIN; PASSIVE TRANSFER; THIRD-WORLD AB Mice immunized with two intragastrically administered doses of a replication deficient recombinant vaccinia virus containing the hemagglutinin and nucleoprotein genes from H1N1 influenza virus developed serum anti-H1 immunoglobulin G (IgG) antibody that completely protected the lungs from challenge with H1N1. Almost all of the mice given two intragastric doses also developed mucosal anti-H1 IgA antibody, and those with high anti-H1 IgA titers had completely protected noses. Intramuscular injection of the vaccine protected the lungs but not the noses from challenge. We also found that the vaccine enhanced recovery from infection caused by a shifted (H3N2) influenza virus, probably through the induction of nucleoprotein-specific cytotoxic T-lymphocyte activity. A replication-deficient, orally administered, enteric-coated, vaccinia virus-vectored vaccine might safely protect humans against influenza. C1 UNIV FLORIDA, COLL MED, DEPT MED, GAINESVILLE, FL 32610 USA. UNIV FLORIDA, COLL MED, DEPT MOL GENET & MICROBIOL, GAINESVILLE, FL 32610 USA. UNIV FLORIDA, COLL MED, DEPT PATHOL & LAB MED, GAINESVILLE, FL 32610 USA. NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. RP Bender, BS (reprint author), VET AFFAIRS MED CTR, GRECC 182, GAINESVILLE, FL 32608 USA. NR 73 TC 78 Z9 81 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 1996 VL 70 IS 9 BP 6418 EP 6424 PG 7 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500086 PM 8709274 ER PT J AU Willey, RL Shibata, R Freed, EO Cho, MW Martin, MA AF Willey, RL Shibata, R Freed, EO Cho, MW Martin, MA TI Differential glycosylation, virion incorporation, and sensitivity to neutralizing antibodies of human immunodeficiency virus type 1 envelope produced from infected primary T-lymphocyte and macrophage cultures SO JOURNAL OF VIROLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; N-LINKED GLYCANS; GP120 V3 LOOP; POLYLACTOSAMINOGLYCAN MODIFICATION; MONONUCLEAR PHAGOCYTES; GLYCOPROTEIN GP120; HIV-INFECTION; SOLUBLE CD4; HTLV-III; CELLS AB Two primary cell targets for human immunodeficiency virus type 1 (HIV-1) infection in vivo are CD4(+) T lymphocytes and monocyte-derived macrophages (MDM). HIV-1 encodes envelope glycoproteins which mediate virus entry into these cells. We have utilized infected and radiolabelled primary peripheral blood mononuclear cell (PBMC) and MDM cultures to examine the biochemical and antigenic properties of the HIV-1 envelope produced in these two cell types. The gp120 produced in MDM migrates as a broad, diffuse band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels compared with that of the more homogeneous gp120 released from PBMCs. Glycosidase analyses indicated that the diffuse appearance of the MDM gp120 is due to the presence of asparagine linked carbohydrates containing lactosaminoglycans, a modification not observed with the gp120 produced in PBMCs. Neutralization experiments, using isogeneic PBMC and MDM-derived macrophage-tropic HIV-1 isolates, indicate that 8- to 10-fold more neutralizing antibody, directed against the viral envelope, is required to block virus produced from MDM. These results demonstrate that HIV-1 released from infected PBMC and MDM cultures differs in its biochemical and antigenic properties. RP Willey, RL (reprint author), NIAID,MOL MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 54 TC 56 Z9 56 U1 0 U2 2 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 SEP PY 1996 VL 70 IS 9 BP 6431 EP 6436 PG 6 WC Virology SC Virology GA VB415 UT WOS:A1996VB41500088 PM 8709276 ER PT J AU Perfetti, R Wang, YH Shuldiner, AR Egan, JM AF Perfetti, R Wang, YH Shuldiner, AR Egan, JM TI Molecular investigation of age-related changes in mouse endocrine pancreas SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID MESSENGER RIBONUCLEIC-ACID; GLUCOSE-TOLERANCE; ENVIRONMENTAL-FACTORS; NUCLEOTIDE-SEQUENCE; INSULIN-SECRETION; RAT; GLUCOKINASE; RELEASE; GENE AB Aging is an etiologic factor in non-insulin-dependent diabetes mellitus. While the effect of aging on insulin secretion has been described by several classic studies, the characterization of the molecular basis of beta-cell abnormalities is stilt under way. We recently demonstrated in rats that aging is associated not only with a reduction in insulin secretion but also with diminished levels of intracellular insulin content and the mRNA for insulin. In this study, we investigated whether the molecular abnormalities previously described in the rat beta cell were also present in the mouse (C57BL/dJ). Total cellular RNA was isolated from individual pancreata of 3-, 9-, and 30-month-old mice (n = 6 per age group), Samples were subjected to slot-blot analysis by using homologous probes for insulin, glucagon, somatostatin, glucose transporter-2 (glut-2), glucokinase, elastase-I, and beta-actin. We observed a progressive age-dependent decrease in insulin mRNA levels: insulin mRNA levels decreased by 40% with age (p = .007). This paralleled decreases in glut-2 (p = .001) mRNA levels, but it was in contrast with glucokinase mRNA levels which increased markedly (p = .0003). Somatostatin mRNA levels were unchanged, glucagon mRNA levels decreased modestly (p = .01), and mRNA levels for elastase-I and beta-actin increased with age (p = .0001 for either one). In summary, a appears that in the mouse a progressive decline in the activity of the endocrine pancreas occurs with aging. This phenomenon seems to affect only the beta cells and not the alpha or delta cells of the islet of Langerhans or the exocrine pancreas. This progressive decline may represent the biological features of the age-dependent risk for the development of diabetes. C1 JOHNS HOPKINS UNIV, SCH MED, DIV GERIATR MED & GERONTOL, BALTIMORE, MD USA. RP Perfetti, R (reprint author), NIA, DIABET UNIT,LAB CLIN PHYSIOL,NIH,GERONTOL RES CTR, ROOM 2B02, 4940 AVE, BALTIMORE, MD 21224 USA. NR 29 TC 4 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1996 VL 51 IS 5 BP B331 EP B336 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VN951 UT WOS:A1996VN95100005 PM 8808981 ER PT J AU Perfetti, R Egan, JM Zenilman, ME Shuldiner, AR AF Perfetti, R Egan, JM Zenilman, ME Shuldiner, AR TI Differential expression of reg-I and reg-II genes during aging in the normal mouse SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PANCREATIC THREAD PROTEIN; XENOPUS-LAEVIS; RIBONUCLEIC-ACID; STONE PROTEIN; B-CELL; RAT; SEQUENCE; PREPROINSULIN; REGENERATION; AMELIORATION AB A cDNA termed reg (for regenerating gene) has been isolated from a rat pancreatic DMA library, peg expression has been shown to correlate with changes in beta cell mass and function. This finding has been recently challenged by studies showing a non-beta-cell-dependent regulation of reg expression. All studies to date, however, have neglected the fact that two nonallelic reg genes (reg-I and reg-II) exist in several species. In studying the regulation of each individual copy gene, we investigated reg-I and -II gene expression in a naturally occurring modification of beta-cell physiology normal aging. RNA was isolated from individual pancreata of 1-, 3-, 9-, 20-, and 30-month-old C5BL/6J mice (n greater than or equal to 3 per group) and subjected to slot-blot analysis using homologous probes for reg-I, reg-II, insulin, and elastase-1. A progressive age-dependent decrease in total reg mRNA levels (reg-I and -II) was detected. At 30 months of age, total reg mRNA levels were approximately 45% of the level detected in 1-month-old mice (p = .01). This paralleled the decrease in insulin mRNA levels (p = .01), which fell below 50%; by contrast, mRNA levels for elastase-1 increased with age (p = .05). Analysis of RNA isolated from purified islets did not reveal any mRNA for reg, suggesting that in the normal mouse, reg is primarily a product of the exocrine pancreas. Reg mRNA were detectable in RNA extracts from stomach, duodenum, and small intestine. By hybridization bf total pancreatic RNA with oligonucleotide probes which specifically recognize reg-I or reg-II sequences, we show that reg-I mRNA levels declined with age (p = .001) while reg-II mRNA levels remained unchanged These data demonstrate that in mouse pancreas the two nonallelic reg genes are differentially expressed during aging and that the decrease in reg-I mRNA levels parallels the decrease in insulin gene expression. Differential regulation of reg-I and reg-II genes may explain the presence of conflicting data in the current literature. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT SURG,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DIV GERIAT MED & GERONTOL,BALTIMORE,MD 21205. RP Perfetti, R (reprint author), NIA,DIABET UNIT,LAB CLIN PHYSIOL,NIH,GERONTOL RES CTR,ROOM 2B02,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 29 TC 14 Z9 14 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 1996 VL 51 IS 5 BP B308 EP B315 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA VN951 UT WOS:A1996VN95100002 PM 8808978 ER PT J AU Jaffer, FA Wen, H Balaban, RS Wolff, SD AF Jaffer, FA Wen, H Balaban, RS Wolff, SD TI A method to improve the B-0 homogeneity of the heart in vivo SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; shimming; cardiac; homogeneity AB A homogeneous static (B-0) magnetic field is required for many NMR experiments such as echo planar imaging, localized spectroscopy, and spiral scan imaging, Although semi-automated techniques have been described to improve the B-0 field homogeneity, none has been applied to the in vivo heart, The acquisition of cardiac field maps is complicated by motion, blood flow, and chemical shift artifact from epicardial fat, To overcome these problems, an ungated three-dimensional (3D) chemical shift image (CSI) was collected to generate a time and motion-averaged B-0 field map, B-0 heterogeneity in the heart was minimized by using a previous algorithm that solves for the optimal shim coil currents for an input field map, using up to third-order current-bounded shims (1). The method improved the B-0 homogeneity of the heart in all 11 normal volunteers studied, After application of the algorithm to the un-shimmed cardiac field maps, the standard deviation of proton frequency decreased by 43%, the magnitude H-1 spectral linewidth decreased by 24%, and the peak-peak gradient decreased by 35%. Simulations of the high-order (second- and third-order) shims in B-0 field correction of the heart show that high order shims are important, resulting for nearly half of the improvement in homogeneity for several subjects. The T-2* of the left ventricular anterior wall before and after field correction was determined at 4.0 Tesla. Finally, results show that cardiac shimming is of benefit in cardiac P-31 NMR spectroscopy and cardiac echo planar imaging. C1 NHLBI,CARDIAC ENERGET LAB,NIH,BETHESDA,MD 20892. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010; OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997; Jaffer, Farouc/0000-0001-7980-384X FU NCRR NIH HHS [RR-02305] NR 10 TC 28 Z9 28 U1 0 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1996 VL 36 IS 3 BP 375 EP 383 DI 10.1002/mrm.1910360308 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VE627 UT WOS:A1996VE62700007 PM 8875407 ER PT J AU Lee, JM Barry, JA AF Lee, JM Barry, JA TI Influence of membrane lipid packing on T-2-weighted magnetic resonance images: Study of relaxation parameters in model membrane systems SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE soft tissue contrast; lipid; relaxation, toluene ID TOLUENE ABUSE; PHOSPHOLIPID-BILAYERS; HYDROCARBON CHAINS; SIGNAL INTENSITY; MR-IMAGES; H-2 NMR; WATER; PHOSPHATIDYLCHOLINE; SPECTROSCOPY; EQUILIBRIUM AB The detailed mechanisms leading to soft tissue contrast in MRI are not known, To explore the physical basis for this phenomena, the effect of acyl chain packing of phospholipid model membranes on water proton relaxation were investigated at 20 MHz at 40 degrees C, Three variables affecting lipid packing were examined: chain composition, toluene concentration, and pH/ionic strength, It is demonstrated that the T-2 of water protons is strongly influenced by changes in lipid packing, while T-1 is generally insensitive to these variables, It is also shown that small changes in water content (7 wt%) altered both T-1 and T-2 in all systems studied, The results suggest that the physical properties of biological membranes in tissues are an important factor in determining T-2. C1 NIH,LAB DIAGNOT RADIOL RES,BETHESDA,MD 20892. NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,BETHESDA,MD 20892. NR 43 TC 7 Z9 7 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD SEP PY 1996 VL 36 IS 3 BP 420 EP 426 DI 10.1002/mrm.1910360314 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA VE627 UT WOS:A1996VE62700013 PM 8875413 ER PT J AU Forlino, A Wang, Q Marini, JC AF Forlino, A Wang, Q Marini, JC TI Combined effect of a null allele and a non-collagenous insertion in COL1A1 mRNA is responsible for the severe phenotype in a family affected by osteogenesis imperfecta. SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 1 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 176 EP 177 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600061 ER PT J AU Grassi, G Marini, JC AF Grassi, G Marini, JC TI Hammerhead ribozymes achieve allele-specific cleavage of collagen mRNA in vitro from patients affected by osteogenesis imperfect. SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 1 U2 2 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 176 EP 176 DI 10.1016/S0945-053X(96)90062-1 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600060 ER PT J AU Cohen, IR Gajko, A Marini, JC AF Cohen, IR Gajko, A Marini, JC TI Expression and regulation of type I collagen and other matrix components in osteogenesis imperfecta osteoblasts. SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NICHHD,SECT CONNECT TISSUE DISORDERS,HDB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 177 EP 178 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600063 ER PT J AU Forlino, A Marini, JC AF Forlino, A Marini, JC TI Unusual electrophoretic mobility of alpha 2(I) collagen chain caused by a Gly421 to asp substitution in a lethal case of osteogenesis imperfecta. SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 177 EP 177 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600062 ER PT J AU Yeowell, HN Walker, LC Yeowell, MN Pinnell, SR AF Yeowell, HN Walker, LC Yeowell, MN Pinnell, SR TI Compound heterozygosity for a nonsense mutation and an exon deletion in the lysyl hydroxylase gene of a patient with Ehlers Danlos Syndrome type VI. SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 185 EP 185 DI 10.1016/S0945-053X(96)90080-3 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600079 ER PT J AU Robey, PG Kuznetsov, S Satomura, K IbarakiOConnor, DK Rowe, D Benayahu, D RIminucci, M Fisher, LW Young, MF Kerr, J AF Robey, PG Kuznetsov, S Satomura, K IbarakiOConnor, DK Rowe, D Benayahu, D RIminucci, M Fisher, LW Young, MF Kerr, J TI Biochemical characterization of marrow stromal fibroblasts. SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 NIDR,BONE RES BRANCH,NIH,BETHESDA,MD 20892. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 1 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 187 EP 187 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600082 ER PT J AU Horwitz, EM Prockop, DJ Marini, J Fitzpatrick, LA Pyeritz, R Sussman, M Orchid, P Brenner, MK AF Horwitz, EM Prockop, DJ Marini, J Fitzpatrick, LA Pyeritz, R Sussman, M Orchid, P Brenner, MK TI Treatment of severe osteogenesis imperfecta by allogeneic bone marrow transplantation. SO MATRIX BIOLOGY LA English DT Meeting Abstract C1 ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN USA. THOMAS JEFFERSON UNIV, PHILADELPHIA, PA 19107 USA. NICHHD, NIH, BETHESDA, MD USA. MAYO CLIN, ROCHESTER, MN USA. MED COLL PENN & HAHNEMANN UNIV, PHILADELPHIA, PA USA. OREGON HLTH SCI UNIV, SHRINERS HOSP CRIPPLED CHILDREN, PORTLAND, OR 97201 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. RI Pyeritz, Reed/A-1364-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 3 BP 188 EP 188 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ836 UT WOS:A1996VJ83600084 ER PT J AU Sakai, LY Burgeson, RE Olsen, BR Rowe, DW Gordon, SL AF Sakai, LY Burgeson, RE Olsen, BR Rowe, DW Gordon, SL TI Current knowledge and research directions in heritable disorders of connective tissue SO MATRIX BIOLOGY LA English DT Editorial Material ID MICROFIBRIL-ASSOCIATED GLYCOPROTEIN; MULTIPLE EPIPHYSEAL DYSPLASIA; NEONATAL MARFAN-SYNDROME; GROWTH-FACTOR RECEPTOR-3; MUTATED COLLAGEN GENE; EGF-LIKE DOMAIN; OSTEOGENESIS IMPERFECTA; TRANSGENIC MICE; FIBRILLIN GENE; EXTRACELLULAR MICROFIBRILS C1 OREGON HLTH SCI UNIV,SHRINERS HOSP CRIPPLED CHILDREN,PORTLAND,OR 97201. HARVARD UNIV,DEPT DERMATOL,CUTANEOUS BIOL RES CTR,CHARLESTOWN,MA. MASSACHUSETTS GEN HOSP,CHARLESTOWN,MA. HARVARD UNIV,SCH MED,DEPT CELL BIOL,BOSTON,MA 02115. UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,FARMINGTON,CT. OSIRIS THERAPEUT INC,BALTIMORE,MD. NIAMS,MUSCULOSKELETAL BRANCH,NIH,BETHESDA,MD. RP Sakai, LY (reprint author), OREGON HLTH SCI UNIV,DEPT BIOCHEM & MOL BIOL,PORTLAND,OR 97201, USA. NR 90 TC 5 Z9 5 U1 0 U2 2 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 1996 VL 15 IS 4 BP 211 EP 229 DI 10.1016/S0945-053X(96)90113-4 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VJ837 UT WOS:A1996VJ83700001 PM 8892222 ER PT J AU Okabe, S ForsbergNilsson, K Spiro, AC Segal, M McKay, RDG AF Okabe, S ForsbergNilsson, K Spiro, AC Segal, M McKay, RDG TI Development of neuronal precursor cells and functional postmitotic neurons from embryonic stem cells in vitro SO MECHANISMS OF DEVELOPMENT LA English DT Article DE embryonic stem cell; central nervous system; neuronal precursor cell; in vitro culture; synapse ID FIBROBLAST GROWTH-FACTOR; RAT HIPPOCAMPAL-NEURONS; MONOCLONAL-ANTIBODIES; TARGETED MUTATION; NERVOUS-SYSTEM; HOMEOBOX GENES; RETINOIC ACID; IN-VITRO; DIFFERENTIATION; CULTURE AB To understand the mechanism of the sequential restriction of multipotency of stem cells during development, we have established culture conditions that allow the differentiation of neuroepithelial precursor cells from embryonic stem (ES) cells. A highly enriched population of neuroepithelial precursor cells derived from ES cells proliferates in the presence of basic fibroblast growth factor (bFGF). These cells differentiate into both neurons and glia following withdrawal of bFGF By further differentiating the cells in serum-containing medium, the neurons express a wide variety of neuron-specific genes and generate both excitatory and inhibitory synaptic connections. The expression pattern of position-specific neural markers suggests the presence of a variety of central nervous system (CNS) neuronal cell types. These findings indicate that neuronal precursor cells can be isolated from ES cells and that these cells can efficiently differentiate into functional post-mitotic neurons of diverse CNS structures. C1 NINCDS,NIH,LMB,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT NEUROBIOL,IL-76100 REHOVOT,ISRAEL. NR 44 TC 535 Z9 577 U1 3 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD SEP PY 1996 VL 59 IS 1 BP 89 EP 102 DI 10.1016/0925-4773(96)00572-2 PG 14 WC Developmental Biology SC Developmental Biology GA VL192 UT WOS:A1996VL19200008 PM 8892235 ER PT J AU Clancy, CM McAllister, JW AF Clancy, CM McAllister, JW TI Quality measurement and improvement among primary care practitioners - Results from a multisite, randomized, controlled test - Preface SO MEDICAL CARE LA English DT Editorial Material C1 AHCPR,CTR OUTCOMES & EFFECTIVENESS RES,ROCKVILLE,MD 20852. CTR INFORMAT TECHNOL,AGCY HLTH CARE POLICY & RES,ROCKVILLE,MD 20852. RP Clancy, CM (reprint author), AHCPR,CTR PRIMARY CARE RES,2101 E JEFFERSON ST,SUITE 502,ROCKVILLE,MD 20852, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD SEP PY 1996 VL 34 IS 9 SU S BP SS1 EP SS2 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA VG253 UT WOS:A1996VG25300001 ER PT J AU Tuttle, MS Nelson, SJ AF Tuttle, MS Nelson, SJ TI A poor precedent SO METHODS OF INFORMATION IN MEDICINE LA English DT Editorial Material ID SYSTEM AB The single greatest impediment to the successful leveraging of computer-based patient records (CPRs) is the difficulty of creating and maintaining comparable patient descriptions. Specifically, it will be hard to justify the investment required to deploy CPRs widely if the patient descriptions they store are not comparable across successive releases of controlled health-care vocabularies. Thus, it is necessary to solve the controlled health-care vocabulary update problem for CPRs before the comparability of patient descriptions can be sustained. What may seem to be a narrow technical problem of interest only to maintainers of health-care enterprise systems is, instead, a central problem of medical informatics. Cimino's ''Formal descriptions and adaptive mechanisms for changes in controlled medical vocabularies'' describes a classification of the changes appearing in the 1994 Edition of the International Classification of Diseases (ICD-9-CM). His paper describes the conversion of differences detected between the 1993 and 1994 releases of ICD-9-CM and a conversion of the elements of the classification into the required formal changes to the Medical Entities Dictionary (MED), part of the CPR in use at Columbia Presbyterian Medical Center. Because the process of detecting differences begins with an empirical analysis of the ASCII representations of the 1993 and 1994 releases of ICD-9-CM, it is impossible for a computer program to infer the intent of the changes that caused the differences; instead, a content expert must infer the intent and then update the MED accordingly. A typical task is to infer whether a change in naming also reflects a change in the meaning named. While Cimino's methods and their execution are exemplary in every respect, they nevertheless constitute a kind of ''reverse engineering'' - an ad hoc attempt to infer intent from details. Reverse engineering of changes to controlled medical vocabularies is a poor precedent. Such methods should be viewed as necessary short-term expedients only, and all parties concerned should work toward an incremental plan by which the intent of changes to controlled health-care vocabularies can be made both explicit and machine processible. Only then can the comparability of patient descriptions be sustained. C1 NATL LIB MED, BETHESDA, MD 20894 USA. RP Tuttle, MS (reprint author), LEXICAL TECHNOL INC, 1000 ATLANTIC AVE, SUITE 106, ALAMEDA, CA 94501 USA. NR 40 TC 13 Z9 13 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0026-1270 J9 METHOD INFORM MED JI Methods Inf. Med. PD SEP PY 1996 VL 35 IS 3 BP 211 EP 217 PG 7 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA VP332 UT WOS:A1996VP33200014 PM 8952305 ER PT J AU Porcella, SF Belland, RJ Judd, RC AF Porcella, SF Belland, RJ Judd, RC TI Identification of an EF-Tu protein that is periplasm-associated and processed in Neisseria gonorrhoeae SO MICROBIOLOGY-SGM LA English DT Article DE Neisseria gonorrhoeae; tufA; EF-Tu; processing ID ELONGATION-FACTOR-TU; GONOCOCCAL OUTER-MEMBRANE; ESCHERICHIA-COLI; CATHEPSIN-G; GENES; EXPRESSION; SEQUENCE; DNA; MUTATIONS; CLEAVAGE AB A 44 kDa protein is a dominant component of periplasmic extracts of Neisseria gonorrhoeae. Peptide sequence generated from a cyanogen-bromide-cleaved fragment of this protein indicated sequence homology with elongation factor-Tu (EF-Tu). Polyclonal antiserum was made against the 44 kDa protein purified from periplasm extracts of N. gonorrhoeae. The preabsorbed antiserum was immunoblotted against whole-cell lysates on two-dimensional gels. A 44 kDa protein and a smaller 37 kDa protein were recognized by this antiserum. A N. gonorrhoeae lambda phage DNA library was screened and a clone expressing a 44 kDa protein was identified. The DNA insert in this clone contained several genes homologous to genes contained in the str operon of Escherichia coli. One ORF product with a calculated molecular mass of 43 kDa was highly homologous to the EF-TuA of E. coli. A synthetic peptide antiserum specific for a portion of the C terminus of EF-Tu confirmed that the 37 kDa protein in whole-cell lysates of N. gonorrhoeae was a processed form of EF-Tu. Deletion of the tufA gene homologue in N. gonorrhoeae was attempted but was unsuccessful. C1 NIAID, ROCKY MT LABS, NIH, HAMILTON, MT 59840 USA. UNIV MONTANA, DIV BIOL SCI, MISSOULA, MT 59812 USA. RP UNIV TEXAS, SW MED SCH, DEPT MICROBIOL, DALLAS, TX 75235 USA. FU PHS HHS [R01 A121236] NR 46 TC 19 Z9 24 U1 1 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD SEP PY 1996 VL 142 BP 2481 EP 2489 PN 9 PG 9 WC Microbiology SC Microbiology GA VH925 UT WOS:A1996VH92500018 PM 8828215 ER PT J AU Tilly, K Fuhrman, J Campbell, J Samuels, DS AF Tilly, K Fuhrman, J Campbell, J Samuels, DS TI Isolation of Borrelia burgdorferi genes encoding homologues of DNA-binding protein HU and ribosomal protein S20 SO MICROBIOLOGY-UK LA English DT Article DE lyme disease; Borrelia burgdorferi; integration host factor (IHF); HU protein ID INTEGRATION HOST FACTOR; HISTONE-LIKE PROTEIN; SITE-SPECIFIC RECOMBINATION; LYME-DISEASE AGENT; ESCHERICHIA-COLI; LINEAR PLASMIDS; RHODOBACTER-CAPSULATUS; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING AB Linear DMA with covalently closed ends is the predominant form of DNA in the spirochaete Borrelia burgdorferi. All bacteria examined to date have small DNA-binding proteins related to the Escherichia coli IHF and HU proteins that appear to play roles in DNA compaction and replication, but such proteins had not been isolated from bacteria with linear genomes. We found a single gene in B. burgdorferi (named hbb) whose product (named Hbb) complements the defects for lambda DNA packaging found in E. coli strains mutant in the genes for IHF and HU. The sequence of the predicted B. burgdorferi protein is similar to those of HU and IHF-like proteins in other bacteria. The gene appears to be in an operon with the order rpsT-hbb-orfH, where the rpsT gene is a homologue of the E. coli gene encoding ribosomal protein S20 and the orfH gene encodes a protein of unknown function. This operon is located upstream of the previously identified B. burgdorferi rho homologue. C1 NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,HAMILTON,MT 59840. RP Tilly, K (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 NR 65 TC 21 Z9 22 U1 0 U2 0 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 SEP PY 1996 VL 142 BP 2471 EP 2479 PN 9 PG 9 WC Microbiology SC Microbiology GA VH925 UT WOS:A1996VH92500017 PM 8828214 ER PT J AU Martayan, A Fiscella, M Setini, A Ciccarelli, G Feriotto, G Gambari, R Beretta, A Siccardi, AG Appella, E Giacomini, P AF Martayan, A Fiscella, M Setini, A Ciccarelli, G Feriotto, G Gambari, R Beretta, A Siccardi, AG Appella, E Giacomini, P TI Synthesis of free HLA-A, -B, -C heavy chains in the beta(2)-microglobulin deficient kidney carcinoma cell line KJ29 SO MINERVA BIOTECNOLOGICA LA English DT Article; Proceedings Paper CT 6th Workshop on Synthetic Oligonucleotides in Molecular Biology and Biotechnology CY FEB 08-09, 1996 CL FERRARA, ITALY SP Ferrara Univ, Biotechnol Ctr, Ferrara Univ, Dept Biochem & Molec Biol DE HLA-C antigens; beta(2)microglobulin; free heavy chains ID CLASS-I MOLECULES; SURFACE EXPRESSION; BETA-2-MICROGLOBULIN; H-2DB; PEPTIDES; ANTIGENS; BINDING AB A novel beta(2)-microglobulin (beta(2)m) deficient kidney carcinoma cell line, KJ29, has been selected to assess the influence of beta(2)m on the intracellular accumulation and post-translational modifications of HLA-A, -B, -C molecules. HLA-A2, -B27, -CW1 molecules synthesized by KJ29 cells have been compared to heavy chains synthesized in transfectants expressing a large stoichiometric excess of beta(2)m. We show that HLA-A2 and B27 free heavy chains are unstable in absence of beta(2)m, and capable of nearly complete assembly in beta(2)m transfectants. At variance, HLA-CW1 heavy chains are relatively stable, and their assembly with beta(2)m is largely incomplete both in the presence and the absence of beta(2)m. Free HLA-B27 heavy chains display, in beta(2)m defective cells, an altered molecular weight and a lon or absent sialilation, suggesting an altered biosynthesis and intracellular transport, At variance, HLA-CW1 heavychain components are neuraminidase insensitive, No changes are apparent in either the molecular weight or the net charge of HLA-CW1 upon transfection with beta(2)m. These results demonstrate distinctive biochemical properties of HLA-C molecules, and suggest that at least HLA-CW1, and, possibly, other alleles at. the HLA-C locus, might be relatively refractory to those defects in the assembly of class I molecules which impair their intracellular traffic. C1 CRS,REGINA ELENA INST,IMMUNOL LAB,I-00158 ROME,ITALY. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. DIBIT S RAFFAELE,MILAN,ITALY. UNIV FERRARA,CTR BIOTECHNOL,I-44100 FERRARA,ITALY. RI Gambari, Roberto/F-9555-2015; Giacomini, Patrizio/K-5217-2016 OI Gambari, Roberto/0000-0001-9205-6033; Giacomini, Patrizio/0000-0001-6109-1709 NR 18 TC 1 Z9 1 U1 0 U2 2 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1120-4826 J9 MINERVA BIOTECNOL JI Minerva Biotechnol. PD SEP PY 1996 VL 8 IS 3 BP 160 EP 164 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VN044 UT WOS:A1996VN04400010 ER PT J AU Kumar, S Green, GA TeruyaFeldstein, J Raffeld, M Jaffe, ES AF Kumar, S Green, GA TeruyaFeldstein, J Raffeld, M Jaffe, ES TI Use of CD23 (BU38) on paraffin sections in the diagnosis of small lymphocytic lymphoma and mantle cell lymphoma SO MODERN PATHOLOGY LA English DT Article DE CD23; mantle cell lymphoma; paraffin section immunostaining; small lymphocytic lymphoma ID INTERMEDIATE DIFFERENTIATION; EXPRESSION AB The CD23 antigen is a low-affinity immunoglubulin E receptor that is expressed during B-cell activation, Recently, it has been shown to be of diagnostic utility in distinguishing between small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL), two entities that can have similar morphologic and immunophenotypic features, Such studies, however, generally required viable cells in cell suspension or cryostat sections for detection of CD23, We evaluated staining for the CD23 antigen in paraffin sections, using BU38, an antibody that detects a fixation-resistant epitope of the antigen. We analyzed 44 SLLs, 3 lymphoplasmacytoid lymphomas, and 39 MCLs, Staining was performed on formalin- or B5-fixed paraffin-embedded tisssue sections using L26 (CD20), CD3, Leu22 (CD43), and BU38 (CD23) antibodies, All of the cases were of B-cell phenotype (CD20+), and 42/44 SLLs, 3/3 lymphoplasmacytoid lymphomas, and 33/39 MCLs coexpressed the CD43 antigen. CD23 was positive in 41 (93%) of 44 SLLs. The majority of neoplastic cells (75% or more) stained positively, with a membranous pattern of staining. The staining was moderate in intensity and easily interpreted, Only 1/39 MCLs and 1/3 lymphoplasmacytoid lymphomas were CD23 positive. CD23-positive follicular dendritic cells were, however, present in all of the MCLs, either in residual follicles or in large, disordered meshworks, These results demonstrate that the BU38 antibody can detect CD23 on the cells of SLLs in paraffin sections and that this antibody can have diagnostic utility in routine diagnosis. C1 NCI,HEMATOPATHOL SECT,PATHOL LAB,NIH,BETHESDA,MD 20892. NR 17 TC 47 Z9 47 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD SEP PY 1996 VL 9 IS 9 BP 925 EP 929 PG 5 WC Pathology SC Pathology GA VG382 UT WOS:A1996VG38200007 PM 8878025 ER PT J AU deCastro, FA Ward, GE Jambou, R Attal, G Mayau, V Jaureguiberry, G BraunBreton, C Chakrabarti, D Langsley, G AF deCastro, FA Ward, GE Jambou, R Attal, G Mayau, V Jaureguiberry, G BraunBreton, C Chakrabarti, D Langsley, G TI Identification of a family of Rab G-proteins in Plasmodium falciparum and a detailed characterisation of pfrab6 SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Rab GTPases; Rab6, traffic; secretion; Plasmodium falciparum; malaria ID BINDING PROTEIN; GOLGI; TRANSPORT; PARASITE; GTPASES; GLYCOSYLATION; ERYTHROCYTES; EXPRESSION; CLONING; STAGE AB As a first step towards developing a set of compartment-specific probes for studying protein trafficking in the malaria-infected erythrocyte, we describe here a family of Plasmodium falciparum Rab proteins. We characterise in detail P. falciparum Rab6 (PfRab6) a marker which in other cells is specific for the Golgi/trans Golgi network. Although PfRab6 mRNA is expressed throughout the intraerythrocytic cycle, maximal expression occurs at the trophozoite stage. Immunofluorescence microscopy shows that the distribution of PfRab6 changes during the final stages of parasite maturation, coalescing into multiple foci, each of which is associated with the nucleus of a forming daughter parasite. C1 INST PASTEUR,DEPT IMMUNOL,URA CNRS 1960,UNIT EXPT PARASITOL,F-75015 PARIS,FRANCE. NIAID,PARASIT DIS LAB,NIH,BETHESDA,MD 20892. INSERM U13,F-75019 PARIS,FRANCE. INST PASTEUR,ANTANANARIVO,MALAGASY REPUBL. INST PASTEUR,DEPT IMMUNOL,URA CNRS 1960,UNIT SOMAT GENET,F-75015 PARIS,FRANCE. UNIV CENT FLORIDA,DEPT MOL BIOL & MICROBIOL,ORLANDO,FL 32816. NR 37 TC 62 Z9 63 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 SEP PY 1996 VL 80 IS 1 BP 77 EP 88 DI 10.1016/0166-6851(96)02670-9 PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VG237 UT WOS:A1996VG23700007 PM 8885224 ER PT J AU Cappello, M Hawdon, JM Jones, BF Kennedy, WP Hotez, PJ AF Cappello, M Hawdon, JM Jones, BF Kennedy, WP Hotez, PJ TI Ancylostoma caninum anticoagulant peptide: Cloning by PCR and expression of soluble, active protein E-coli SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE hookworm; ancylostoma; anticoagulant; factor Xa; serine protease inhibitors; Ascaris ID CHYMOTRYPSIN ELASTASE; FACTOR XA; INHIBITOR; HOOKWORM; INVITRO; ENZYME AB Ancylostoma caninum Anticoagulant Peptide (AcAP) is the major anticoagulant activity present in extracts of adult Ancylostoma caninum hookworms. This 8.7 kDa protein is a potent and specific inhibitor of human coagulation factor Xa. Using PCR, we have isolated a cDNA encoding for AcAP from an adult A. caninum cDNA library. The 5' end of the AcAP cDNA was identified by reverse transcription PCR (RT-PCR) using A. caninum cDNA and a 5' primer corresponding to a nematode spliced leader sequence. The AcAP cDNA was expressed in E. coli using a prokaryotic expression vector, and the recombinant fusion protein (rAcAP) was purified to homogeneity using nickel resin affinity chromatography and reverse phase HPLC. Purified rAcAP is comparable to the native protein in inhibitory activity, with an apparent equilibrium inhibitory dissociation constant (K-i*) for the inhibition of factor Xa of 265 +/- 71 pM. The purified protein also prolongs the prothrombin and partial thromboplastin times of human plasma in a dose dependent manner. C1 YALE UNIV,SCH MED,DEPT EPIDEMIOL,MED HELMINTHOL LAB,NEW HAVEN,CT 06520. NIDDKD,CHEM PHYS LAB,NIH,BETHESDA,MD 20892. RP Cappello, M (reprint author), YALE UNIV,SCH MED,DEPT PEDIAT,MED HELMINTHOL LAB,501 LEPH,60 COLL ST,NEW HAVEN,CT 06520, USA. FU NIAID NIH HHS [R29 AI32726, 1 K11 AI01299-01] NR 20 TC 36 Z9 37 U1 0 U2 2 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 SEP PY 1996 VL 80 IS 1 BP 113 EP 117 DI 10.1016/0166-6851(96)02658-8 PG 5 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA VG237 UT WOS:A1996VG23700010 PM 8885227 ER PT J AU Clemens, KE Piras, G Radonovich, MF Choi, KS Duvall, JF DeJong, J Roeder, R Brady, JN AF Clemens, KE Piras, G Radonovich, MF Choi, KS Duvall, JF DeJong, J Roeder, R Brady, JN TI Interaction of the human T-cell lymphotropic virus type 1 tax transactivator with transcription factor IIA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID NF-KAPPA-B; HTLV-I TAX; RNA-POLYMERASE-II; ELEMENT-BINDING PROTEIN; RECEPTOR GENE-EXPRESSION; HORMONE-RELATED PROTEIN; SERUM RESPONSE FACTOR; IMMEDIATE-EARLY GENES; LONG TERMINAL REPEAT; LEUKEMIA-VIRUS AB The Tax protein of human T-cell lymphotropic virus type 1 (HTLV-1) is a 40-kDa transcriptional activator which is critical for HTLV-1 gene regulation and virus-induced cellular transformation. Tax is localized to the DNA through its interaction with the site-specific activators cyclic AMP-responsive element-binding protein, NF-kappa B, and serum response factor. It has been suggested that the recruitment of Tax to the DNA positions Tax for interaction with the basal transcriptional machinery. On the basis of several independent assays, we now report a physical and functional interaction between Tax and the transcription factor, TFIIA. First, Tax was found to interact with the 35-kDa (alpha) subunit of TFIIA in the yeast two-hybrid interaction system. Importantly, two previously characterized mutants with point mutations in Tax, M32 (Y196A, K197S) and M41 (N287A, P288S), which were shown to be defective in Tax-activated transcription were unable to interact with TFIIA in this assay. Second, a glutathione-S-transferase (GST) affinity-binding assay showed that the interaction of holo-TFIIA with GST-Tax was 20-fold higher than that observed with either the GST-Tax M32 activation mutant or the GST control. Third, a coimmunoprecipitation assay showed that in HTLV-1-infected human T lymphocytes, Tax and TFIIA were associated. Finally, TFIIA facilitates Tax transactivation in vitro and in vivo. In vitro transcription studies showed reduced levels of Tax-activated transcription in cell extracts depleted of TFIIA. In addition, transfection of human T lymphocytes with TFIIA expression vectors enhanced Tax-activated transcription of an HTLV-1 long terminal repeat-chloramphenicol acetyltransferase reporter construct. Our study suggests that the interaction of Tax with the transcription factor TFIIA may play a role in Tax-mediated transcriptional activation. C1 NCI,MOL VIROL LAB,BETHESDA,MD 20892. UNIV TEXAS,DEPT BIOL,RICHARDSON,TX 75080. ROCKEFELLER UNIV,NEW YORK,NY 10021. NR 113 TC 45 Z9 46 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 SEP PY 1996 VL 16 IS 9 BP 4656 EP 4664 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700008 PM 8756622 ER PT J AU Ye, JP Cippitelli, M Dorman, L Ortaldo, JR Young, HA AF Ye, JP Cippitelli, M Dorman, L Ortaldo, JR Young, HA TI The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: Inhibition of AP1 binding and activation of a silencer element SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; SERUM RESPONSE FACTOR; IL-2 GENE-EXPRESSION; ZINC FINGER PROTEIN; TRANSCRIPTION FACTOR; C-JUN; MEDIATES INDUCTION; ADENOVIRUS E1A; T-CELLS; SITE AB Our group has previously reported that the nuclear factor Yin-Yang 1 (YY1), a ubiquitous DNA-binding protein, is able to interact with a silencer element (BE) in the gamma interferon (IFN-gamma) promoter region, In this study, we demonstrated that YY1 can directly inhibit the activity of the IFN-gamma promoter by interacting with multiple sites in the promoter, In cotransfection assays, a YY1 expression vector significantly inhibited IFN-gamma promoter activity, Mutation of the YY1 binding site in the native IFN-gamma promoter was associated with an increase in the IFN-gamma promoter activity, Analysis of the DNA sequences of the IFN-gamma promoter revealed a second functional YY1 binding site (BED) that overlaps with an AP1 binding site. In this element, AP1 enhancer activity was suppressed by YY1. Since the nuclear level of YY1 does not change upon cell activation, our data support a model that the nuclear factor YY1 acts to suppress basal IFN-gamma transcription by interacting with the promoter at multiple DNA binding sites, This repression can occur through two mechanisms: (i) cooperation with an as-yet-unidentified AP2-like repressor protein and (ii) competition for DNA binding,vith the transactivating factor AP1. C1 NCI,FCRDC,FREDERICK,MD 21702. SAIC,DIV BASIC SCI,EXPT IMMUNOL LAB,FREDERICK,MD. SAIC,INTRAMURAL RES SUPPORT PROGRAM,FREDERICK,MD. OI CIPPITELLI, Marco/0000-0002-9620-538X NR 54 TC 136 Z9 137 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 SEP PY 1996 VL 16 IS 9 BP 4744 EP 4753 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700018 PM 8756632 ER PT J AU Ludwig, RL Bates, S Vousden, KH AF Ludwig, RL Bates, S Vousden, KH TI Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR P53; WILD-TYPE P53; TRANSCRIPTIONAL ACTIVATION; CYCLE ARREST; DNA-BINDING; P53-MEDIATED APOPTOSIS; MONOCLONAL-ANTIBODIES; GROWTH ARREST; G(1) ARREST; HELA-CELLS AB The p53 tumor suppressor protein is a sequence-specific transcriptional activator, a function which contributes to cell cycle arrest and apoptosis induced by p53 in appropriate cell types. analysis of a series of p53 point mutants has revealed the potential for selective loss of the ability to transactivate some, but not all, cellular p53-responsive promoters. p53 175P and p53 181L are tumor-derived p53 point mutants which were previously characterized as transcriptionally active. Both mutants retained the ability to activate expression of the cyclin-dependent kinase inhibitor p21(cip/waf1), and this activity correlated with the ability to induce a G(1) cell cycle arrest. However, an extension of this survey to include other p53 targets showed that p53 175P was defective in the activation of p53-responsive sequences derived from the bar promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3) promoter, while p53 181L showed loss of the ability to activate a promoter containing IGF-BP3 box B sequences. Failure to activate transcription was also reflected in the reduced ability of the mutants to bind the p53-responsive DNA sequences present in these promoters. These specific defects in transcriptional activation correlated with the impaired apoptotic function displayed by these mutants, and the results suggest that activation of cell cycle arrest genes by p53 can be separated from activation of genes with a role in mediating the p53 apoptotic response. The cellular response to p53 activation may therefore depend, at least in part, on which group of p53-responsive genes become transcriptionally activated. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 56 TC 234 Z9 237 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 SEP PY 1996 VL 16 IS 9 BP 4952 EP 4960 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700040 PM 8756654 ER PT J AU Doro, U Sakaguchi, K Appella, E Ashwell, JD AF Doro, U Sakaguchi, K Appella, E Ashwell, JD TI Mutational analysis of lck in CD45-negative T cells: Dominant role of tyrosine 394 phosphorylation in kinase activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CD45 PHOSPHOTYROSINE PHOSPHATASE; N-TERMINAL REGION; PROTEIN-KINASE; ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; CATALYTIC ACTIVITY; CROSS-LINKING; MICE LACKING; P56LCK; ACTIVATION AB The CD45 tyrosine phosphatase has been reported to activate the src family tyrosine kinases Lck and Fyn by dephosphorylating regulatory COOH-terminal tyrosine residues 505 and 528, respectively, However, recent studies with CD45(-) T-cell lines have found that despite the fact that Lck and Fyn were constitutively hyperphosphorylated, the tyrosine kinase activity of both enzymes was actually increased, In the present study, phosphoamino acid analysis revealed that the increased phosphorylation of Lck in CD45(-) YAC-1 T cells was restricted to tyrosine residues, To understand the relationship between tyrosine phosphorylation and Lck kinase activity, CD45(-) YAC-1 cells were transfected with forms of Lck in which tyrosines whose phosphorylation is thought to regulate enzyme activity (Tyr-192, Tyr-394, Tyr-505, or both Tyr-394 and Tyr-505) were replaced with phenylalanine. While the Y-to-F mutation at position 192 (192-Y-->F) had little effect, the 505-Y-->F mutation increased enzymatic activity, In contrast, the 394-Y-->F mutation decreased the kinase activity to very low levels, an effect that the double mutation, 394-Y-->F and 505Y-->F, could not reverse. Phosphopeptide analysis of tryptic digests of Lck from CD45(-) YAC-1 cells revealed that it is hyperphosphorylated on two tyrosine residues, Tyr-505 and, to a lesser extent, Tyr-394. The purified and enzymatically active intracellular portion of CD45 dephosphorylated Lck Tyr-394 in vitro, These results demonstrate that in addition to Tyr-505, CD45 can dephosphorylate Tyr-394, and that in the absence of CD45 the hyperphosphorylation of Tyr-394 can cause an increase in the kinase activity of Lck despite the inhibitory hyperphosphorylation of Tyr-505, Therefore, Lck kinase activity is determined by the balance of activating and inhibitory tyrosine phosphorylations that are, in turn, regulated by CD45. C1 NCI,LAB IMMUNE CELL BIOL,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 54 TC 73 Z9 74 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 SEP PY 1996 VL 16 IS 9 BP 4996 EP 5003 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700044 PM 8756658 ER PT J AU Ogryzko, VV Hirai, TH Russanova, VR Barbie, DA Howard, BH AF Ogryzko, VV Hirai, TH Russanova, VR Barbie, DA Howard, BH TI Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POSITION-EFFECT VARIEGATION; HUMAN-DIPLOID FIBROBLASTS; HOST DNA-SYNTHESIS; SODIUM-BUTYRATE; DROSOPHILA-MELANOGASTER; REPLICATIVE SENESCENCE; GENE-EXPRESSION; RETINOBLASTOMA PROTEIN; TRANSCRIPTIONAL STATES; SIMIAN VIRUS-40 AB Human diploid fibroblasts (HDF) complete a limited number of cell divisions before entering a growth arrest state that is termed replicative senescence. Two histone deacetylase inhibitors, sodium butyrate and trichostatin A, dramatically reduce the HDF proliferative life span in a manner that is dependent on one or more cell doublings in the presence of these agents. Cells arrested and subsequently released from histone deacetylase inhibitors display markers of senescence and exhibit a persistent G(1) block but remain competent to initiate a round of DNA synthesis in response to simian virus 40 T antigen. Average telomere length in prematurely arrested cells is greater than in senescent cells, reflecting a lower number of population doublings completed by the former. Taken together, these results support the view that one component of HDF senescence mimics a cell cycle-dependent drift in differentiation state and that propagation of HDF in histone deacetylase inhibitors accentuates this component. C1 NICHHD,LAB MOL GROWTH REGULAT,BETHESDA,MD 20892. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 91 TC 185 Z9 192 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 1996 VL 16 IS 9 BP 5210 EP 5218 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA VC897 UT WOS:A1996VC89700064 PM 8756678 ER PT J AU Uverskii, VN Ptitsyn, OB AF Uverskii, VN Ptitsyn, OB TI Three-stage equilibrium unfolding of small globular proteins by strong denaturants .1. Carbonic anhydrase B SO MOLECULAR BIOLOGY LA English DT Article DE carbonic anhydrase B; protein folding; intermediate states; molten globule; pre-molten globule; conformational transitions ID MOLTEN-GLOBULE; ALPHA-LACTALBUMIN; CIRCULAR-DICHROISM; CONFORMATIONAL TRANSITIONS; GUANIDINE-HYDROCHLORIDE; ACID DENATURATION; FOLDING PATHWAY; COMPACT STATE; SIDE-CHAINS; INTERMEDIATE AB Circular dichroism, enzymic assays, fluorescence, and high-performance gel permeation were used to demonstrate that, unlike all previously studied cases, equilibrium unfolding of carbonic anhydrase B induced with guanidinium hydrochloride at low temperature is a three-stage process: first the protein molecule assumes the molten globule state, then at higher denaturant concentrations it converts into a less compact state (''pre-molten globule''), and finally the molecule is completely unfolded. Thus, a new equilibrium intermediate, pre-molten globule, is discerned. C1 NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. NR 45 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU, 233 SPRING ST, NEW YORK, NY 10013 SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD SEP-OCT PY 1996 VL 30 IS 5 BP 672 EP 678 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG844 UT WOS:A1996WG84400003 ER PT J AU Uverskii, VN Ptitsyn, OB AF Uverskii, VN Ptitsyn, OB TI Three-stage equilibrium unfolding of small globular proteins by strong denaturants .2. beta-lactamase and general model SO MOLECULAR BIOLOGY LA English DT Article DE protein folding; intermediate states; molten globule; pre-molten globule; conformational transitions ID CARBONIC-ANHYDRASE-B; MOLTEN-GLOBULE; ALPHA-LACTALBUMIN; CONFORMATIONAL TRANSITIONS; GUANIDINE-HYDROCHLORIDE; SECONDARY STRUCTURE; CIRCULAR-DICHROISM; FOLDING PATHWAY; COMPACT STATE; INTERMEDIATE AB Equilibrium unfolding of staphylococcal beta-lactamase induced with guanidinium hydrochloride at 4 degrees C was studied by circular dichroism, enzymic assays, fluorescence, and high-performance gel permeation. Like in the case of carbonic anhydrase B, it proved to be a three-stage process involving at least two intermediate states: molten globule and its folding precursor (''pre-molten globule'' or partly folded state) with structural properties intermediate between those of molten globule and random coil. The new intermediate is supposed to be an equilibrium analog of the first kinetic intermediate observed in protein folding. C1 NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. RP Uverskii, VN (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,MOSCOW REGION,RUSSIA. NR 47 TC 1 Z9 1 U1 1 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU, 233 SPRING ST, NEW YORK, NY 10013 SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD SEP-OCT PY 1996 VL 30 IS 5 BP 679 EP 684 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA WG844 UT WOS:A1996WG84400004 ER PT J AU Urbanek, M Goldman, D Long, JC AF Urbanek, M Goldman, D Long, JC TI The apportionment of dinucleotide repeat diversity in native Americans and Europeans: A new approach to measuring gene identity reveals asymmetric patterns of divergence SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE gene identity; dinucleotide repeats; Native Americans; Europeans ID POPULATION-STRUCTURE; HUMAN-EVOLUTION; LINKAGE MAP; MITOCHONDRIAL; POLYMORPHISMS; FREQUENCIES; HAPLOTYPES; MIGRATIONS; LINEAGES; WORLD AB The purpose of this paper is to assess the extent of gene identity and differentiation at 33 dinucleotide repeat loci (377 total alleles) within acid among three European and three Native American populations. In order to do this, we show that a maximum-likelihood method proposed for phylogenetic trees (Cavalli-Sforza and Piazza 1975) can be used to estimate gene identity (Nei 1987) with respect to any hierarchical structure. This method allows gene differentiation to be evaluated with respect to any internal node of a hierarchy, It also allows a generalization of F- and G-statistics to situations with unequal expected levels of differentiation. Our principal finding is that levels of genetic differentiation are unique to specific populations and levels of nesting. The populations of European origin show very little internal differentiation; moreover, their continental average is close to the total population defined by the aggregate of Europeans and Native Americans. By contrast, the Native American populations show moderate levels of internal differentiation, and a great distance between their continental average and the total. The results of analyses of subsets of loci that were selected to have high gene diversities in either Europeans or Native Americans closely parallel those from the total set of loci. This suggests that the principal results are unlikely to be caused by a European ascertainment bias in locus selection. In summary, our findings demonstrate that partitions of gene diversity into within- and between-populations components are heavily biased by the populations analyzed and the models fitted. Optimistically, however, more information is available to analyze population history and evolution by quantifying, as we have done, the uniqueness of patterns of differentiation. C1 NIAAA,NEUROGENET LAB,NIH,ROCKVILLE,MD 20852. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 44 TC 47 Z9 47 U1 1 U2 2 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 SEP PY 1996 VL 13 IS 7 BP 943 EP 953 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA VE169 UT WOS:A1996VE16900006 PM 8752003 ER PT J AU Saitoh, H Cooke, CA Burgess, WH Earnshaw, WC Dasso, M AF Saitoh, H Cooke, CA Burgess, WH Earnshaw, WC Dasso, M TI Direct and indirect association of the small GTPase ran with nuclear pore proteins and soluble transport factors: Studies in Xenopus laevis egg extracts SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID BINDING PROTEIN; COMPLEX PROTEIN; RAN/TC4 GTPASE; CYTOSOLIC FACTORS; IMPORT SUBSTRATE; DNA-REPLICATION; IDENTIFICATION; LOCALIZATION; RCC1; NUCLEOPORINS AB Ran is a small GTPase that is required for protein import, mRNA export, and the maintenance of nuclear structures. To gain a better understanding of Ran's role in the nucleus, we have sought to use Xenopus egg extracts for the purification and characterization of proteins that interact with it. This was done through a simple-affinity assay, examining which proteins from egg extracts bound with a high affinity to a glutathione-S-transferase-Ran fusion protein (GST-Ran). We found that GST-Ran associates specifically with at least 10 extract proteins. We determined the identities of six Ran-interacting proteins (Rips), and found that they include RanBP2/Nup358, Nup153, Importin beta, hsc70, RCC1, and RanBP1. On the basis of peptide sequence, a seventh Rip (p88) seems to be similar but not identical to Fug1/RanGAP1, the mammalian Ran-GTPase-activating protein. Gel filtration analysis of endogenous extract proteins suggests that Importin beta acts as a primary GTP-Ran effector. Both Ran and Importin beta are coimmunoprecipitated by anti-p340(RanBP2) antibodies in the presence of nonhydrolyzable GTP analogues, suggesting that Ran-Importin beta complexes interact with p340(RanBP2). Two Other Rips, p18 and p88, are coprecipitated with p340(RanBP2) in, a nucleotide-independent manner. Analysis of the Ran-GTPase pathway in Xenopus extracts allows the examination of interactions between Ran-associated proteins under conditions that resemble in vivo conditions more closely than in assays with purified components, and it thereby allows additional insights into the molecular mechanism of nuclear transport. C1 NICHHD,MOL EMBRYOL LAB,NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT ANAT & CELL BIOL,BALTIMORE,MD 21205. HOLLAND LAB,DEPT MOL BIOL,ROCKVILLE,MD 20855. OI Dasso, Mary/0000-0002-5410-1371 NR 58 TC 49 Z9 50 U1 0 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 1996 VL 7 IS 9 BP 1319 EP 1334 PG 16 WC Cell Biology SC Cell Biology GA VH314 UT WOS:A1996VH31400001 PM 8885229 ER PT J AU Dabholkar, MD Berger, MS Vionnet, JA Overton, L Thompson, C BostickBruton, F Yu, JJ Silber, JR Reed, E AF Dabholkar, MD Berger, MS Vionnet, JA Overton, L Thompson, C BostickBruton, F Yu, JJ Silber, JR Reed, E TI Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and adjacent non-neoplastic brain SO MOLECULAR CARCINOGENESIS LA English DT Article DE ERCC3; ERCCG; malignant brain tissues ID DNA EXCISION-REPAIR; PIGMENTOSUM GROUP-F; XERODERMA-PIGMENTOSUM; TRANSCRIPTION FACTOR; COCKAYNES-SYNDROME; CHROMOSOME 19Q; GENE; EXPRESSION; HELICASE; PROTEINS AB Nucleotide excision repair (NER) is an ordered process in nonmalignant cells, in both human and nonhuman systems. We previously reported that in human brain, there is discordant mRNA expression of excision repair cross-complementing (ERCC) 1 and ERCC2 in malignant tissues, concurrent with excellent concordance of these genes in nonmalignant tissues from the same patients. Here we have extended these studies to compare low-grade tumors to high-grade tumors and to include ERCC3 (which links DNA repair with DNA transcription) and ERCC6 (which is essential for gene-specific repair). Glial tumor and adjacent normal brain specimens from 19 individuals were studied. Paired malignant and nonmalignant tissues were obtained from 12 of these patients. For ERCC3, there was excellent concordance of mRNA expression between malignant and nonmalignant tissues from the same individuals (P = 0.003). For ERCC6, no concordance was observed (P = 0.314). Tumor tissue from patients with high-grade gliomas exhibited marked discordance of mRNA expression patterns in situations in which good concordance was observed in tumor tissue from low-grade gliomas. We previously established that malignant brain tumors show increased disorder of genes in the NER process, as compared with nonmalignant tissues. These data suggest that increasing disorder in the NER process may occur as cells move from low-grade to high-grade malignancy. (C) 1996 Wiley-Liss, Inc. C1 NCI,CLIN PHARMACOL BRANCH,NIH,MED OVARIAN CANC SECT,BETHESDA,MD 20892. UNIV WASHINGTON,MED CTR,DEPT NEUROL SURG,SEATTLE,WA 98195. NR 26 TC 15 Z9 16 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1996 VL 17 IS 1 BP 1 EP 7 DI 10.1002/(SICI)1098-2744(199609)17:1<1::AID-MC1>3.0.CO;2-M PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA VP108 UT WOS:A1996VP10800001 PM 8876669 ER PT J AU Adler, V Dolan, LR Kim, J Pincus, M Barrett, JC Ronai, Z AF Adler, V Dolan, LR Kim, J Pincus, M Barrett, JC Ronai, Z TI Changes in jun N-terminal kinase activation by stress during aging of cultured normal human fibroblasts SO MOLECULAR CARCINOGENESIS LA English DT Article DE cellular aging; stress response; jun N-terminal kinases ID SENESCENT HUMAN FIBROBLASTS; HUMAN-DIPLOID FIBROBLASTS; REPLICATIVE SENESCENCE; BINDING-ACTIVITY; DNA-SYNTHESIS; IN-VITRO; TRANSCRIPTION; CELLS; AP-1; AGE AB The molecular changes associated with the aging process include the reduced activity of transcription factors (such as AP-1) and an impaired response to stress, which has been well documented in the case of the heat-shock (HS) response. Using human diploid fibroblasts of early and late passages as an in vitro model for aging, we elucidated changes in the activation of jun N-terminal kinases (JNKs), which play an important role in the mammalian stress response. We Sound that early-passage cells exhibited a greater degree of JNK activation in response to HS and ultraviolet (UV) C light treatments than did late-passage cells. Decreased JNK activation was dependent on the number of passages but was not affected by varying doses of UV irradiation. Analysis of protein kinase A, mitogen-activated protein kinase, and src-related tyrosine kinases revealed no decreased activities in aged cells, indicating a selective rather than generalized decrease in kinase activities during aging. A further understanding of this impaired activation of JNK may provide insights into the mechanisms of stress response and cellular aging. (C) 1996 Wiley-Liss, Inc. C1 AMER HLTH FDN,MOL CARCINOGENESIS PROGRAM,VALHALLA,NY 10595. VET AFFAIRS MED CTR,DEPT PATHOL,BROOKLYN,NY. NATL INST ENVIRONM HLTH SCI,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC. OI RONAI, ZEEV/0000-0002-3859-0400 NR 34 TC 5 Z9 5 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD SEP PY 1996 VL 17 IS 1 BP 8 EP 12 DI 10.1002/(SICI)1098-2744(199609)17:1<8::AID-MC2>3.0.CO;2-F PG 5 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA VP108 UT WOS:A1996VP10800002 PM 8876670 ER PT J AU deCastro, M Elliot, S Kino, T Bamberger, C Karl, M Webster, E Chrousos, GP AF deCastro, M Elliot, S Kino, T Bamberger, C Karl, M Webster, E Chrousos, GP TI The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGR beta): Tissue levels, mechanism of action, and potential physiologic role SO MOLECULAR MEDICINE LA English DT Article ID HEAT-SHOCK PROTEIN; DOMINANT-NEGATIVE ACTIVITY; PITUITARY-ADRENAL AXIS; VARIANT ALPHA-2; RESISTANCE; DOMAIN; TRANSCRIPTION; LOCALIZATION; COMPETITION; GENES AB Background: Alternative splicing of the transcripts of the human glucocorticoid receptor gene results in two mutually exclusive products, the classic, ligand-binding glucocorticoid receptor (hGR alpha), and a dominant negative non-ligand-binding isoform, hGR beta. Materials and Methods: We examined the existence of and quantified both hGR alpha and hGR beta isoforms in a panel of human tissues, as well as in intact and fractionated HeLa cells, using specific quantitative Western blots and/or immunocytochemistry. We studied the potential interactions of hGR beta with heat shock protein (hsp) 90 and/or hGR alpha using cross immunoadsorption/precipitation procedures followed by Western blots. Results: For the first time, we demonstrated the natural existence of the hGR beta protein, which was widely expressed in human tissues. The ratio of immunoreactive hGR alpha to hGR beta varied from 0.2 to 1.0 among different tissues, and was approximately 0.2 in HeLa cells. In the latter, both isoforms were distributed in the cytoplasm and nucleus in the absence of the hormonal ligand, and translocated into the nucleus after addition of dexamethasone. The cytosolic and nuclear hGR alpha-to-hGR beta ratio remained the same before and after dexamethasone exposure, suggesting that upon activation the two isoforms translocated into the nucleus in equal proportions. hGR alpha-and hGR beta-specific antibodies cross-adsorbed and precipitated cytosolic and nuclear glucocorticoid hGR alpha and hGR beta, respectively, as well as hsp90, suggesting that hGR alpha: and hGR beta are in complex with hsp90 and/or each other. Conclusions: The hGR beta protein is widely expressed throughout the human body and present mostly in the cytoplasm of human cells, in complex with hsp90 and other proteins. In the presence of glucocorticoid, hGR beta probably heterodimerizes with ligand-bound hGR alpha and translocates into the nucleus to act as a dominant negative inhibitor of the classic receptor. RP deCastro, M (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,NIH,BLDG 10,ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Castro, Margaret/A-4918-2009 NR 35 TC 125 Z9 126 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 SEP PY 1996 VL 2 IS 5 BP 597 EP 607 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VL189 UT WOS:A1996VL18900008 PM 8898375 ER PT J AU Waterman, SR Small, PLC AF Waterman, SR Small, PLC TI Identification of sigma(s)-dependent genes associated with the stationary-phase acid-resistance phenotype of Shigella flexneri SO MOLECULAR MICROBIOLOGY LA English DT Article ID PROTEIN H-NS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; NUCLEOTIDE-SEQUENCE; VIBRIO-CHOLERAE; SIGMA-FACTOR; EXPRESSION; GROWTH; RPOS; PH AB Shigella flexneri grown to stationary phase has the ability to survive for several hours at pH 2.5. This acid resistance, which may contribute to the low infective dose associated with shigellosis, is dependent upon the expression of the stationary-phase-specific sigma factor sigma(s). Using random TnphoA and TnlacZ mutagenesis we isolated five acid-sensitive mutants of S. flexneri, which had lost their ability to survive at pH 2.5 for 2 h in vitro. Each transposon insertion with flanking S. flexneri DNA was cloned and sequenced. Database searches indicated that two TnlacZ mutants had an insertion within the hdeA gene, which is the first gene in the hdeAB operon. Acid resistance was restored in one of these mutants by a plasmid carrying the entire hdeAB operon. Further sequence analysis from the remaining TnlacZ and two TnphoA mutants demonstrated that they all had insertions within a previously unidentified open reading frame (ORF), which is directly downstream from the gadB gene. This putative ORF encodes a protein that has homology to a number of inner membrane amino acid antiporters. A 1.8 kb polymerase chain reaction (PCR) product containing this gene was cloned, which was able to restore acid resistance in each mutant. These fusions were induced during entry into late exponential phase and were positively regulated by RpoS. We confirmed that the expression of the acid-resistance phenotype in acidified minimal media was dependent upon the supplementation of glutamic acid and that this glutamate-dependent system was RpoS regulated. Southern hybridization revealed that both the gadC and hdeAB loci are absent in Salmonella. An rpoS deletion mutant of S. flexneri was also constructed to confirm the important role played by this gene in acid resistance. This rpoS(-) derivative was extremely acid sensitive. Two-dimensional gel electrophoresis of this mutant revealed that it no longer expressed 27 proteins in late log phase that were present in its isogenic parent. These data indicate that the expression of acid resistance in S. flexneri may be multifactorial and involve proteins located at different subcellular locations. RP Waterman, SR (reprint author), NIAID,ROCKY MT LABS,MICROSCOPY BRANCH,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 41 TC 119 Z9 124 U1 2 U2 14 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 1996 VL 21 IS 5 BP 925 EP 940 DI 10.1046/j.1365-2958.1996.00058.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VH131 UT WOS:A1996VH13100005 PM 8885264 ER PT J AU Davis, MA Radnedge, L Martin, KA Hayes, F Youngren, B Austin, SJ AF Davis, MA Radnedge, L Martin, KA Hayes, F Youngren, B Austin, SJ TI The P1 ParA protein and its ATPase activity play a direct role in the segregation of plasmid copies to daughter cells SO MOLECULAR MICROBIOLOGY LA English DT Article ID UNIT-COPY MINIPLASMIDS; ESCHERICHIA-COLI; BACTERIAL PLASMIDS; PARTITION PROTEIN; CLONING VECTORS; BINDING DOMAIN; HOST FACTOR; SEQUENCE; ENCODES; REGION AB The P1 ParA protein is an ATPase that recognizes the parA promoter region where it acts to autoregulate the P1 parA-parB operon. The ParB protein is essential for plasmid partition and recognizes the cis-acting partition site parS. The regulatory role of ParA is also essential because a controlled level of Pare protein is critical for partition. However, we show that this regulatory activity is not the only role for ParA in partition. Efficient partition can be achieved without autoregulation as long as Par protein levels are kept within a range of low values. The properties of ParA mutants in these conditions showed that ParA is essential for some critical step in the partition process that is independent of par operon regulation. The putative nucleotide-binding site for the ParA ATPase was identified and disrupted by mutation. The resulting mutant was substantially defective for autoregulation and completely inactive for partition in a system in which the need for autoregulation is abolished. Thus, the ParA nucleotide-binding site appears to be necessary both for the repressor activity of ParA and for some essential step in the partition process itself. We propose that the nucleotide-bound form of the enzyme adopts a configuration that favours binding to the operator, but that the ATPase activity of ParA is required for some energetic step in partition of the plasmid copies to daughter cells. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. CENT CONNECTICUT STATE UNIV,DEPT BIOL SCI,NEW BRITAIN,CT 06050. NR 26 TC 67 Z9 68 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 1996 VL 21 IS 5 BP 1029 EP 1036 DI 10.1046/j.1365-2958.1996.721423.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA VH131 UT WOS:A1996VH13100013 PM 8885272 ER PT J AU Ryu, DY Levi, PE FernandezSalguero, P Gonzalez, FJ Hodgson, E AF Ryu, DY Levi, PE FernandezSalguero, P Gonzalez, FJ Hodgson, E TI Piperonyl butoxide and acenaphthylene induce cytochrome P450 1A2 and 1B1 mRNA in aromatic hydrocarbon-responsive receptor knock-out mouse liver SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN CYP1A2 GENE; AH-RECEPTOR; METHYLENEDIOXYPHENYL COMPOUNDS; B6C3F1 MICE; EXPRESSION; ISOZYMES; TRANSCRIPTION; IDENTIFICATION; METABOLISM; ISOSAFROLE AB It has been suggested that acenaphthylene (ACN), piperonyl butoxide (PBO) and other methylenedioxyphenyl (benzodioxole) compounds can function as aromatic hydrocarbon-responsive receptor (AHR)-independent inducers of the cytochrome P450 (CYP) 1A2 in mouse liver. Although much indirect evidence has supported this hypothesis, direct proof was lacking until the present study. PBO and ACN were used to examine the expression of CYP1A1, CYP1A2 and CYP1B1 in mouse liver. These three CYP isozymes are included in the AHR battery of proteins. In this study, AHR knock-out mice were dosed intraperitoneally with PBO (200 mg/kg) or ACN (100 mg/kg). Induction of hepatic CYP1A1 by PBO or ACN was not detected by northern blots. In contrast, both CYP1A2 and CYP1B1 mRNA, constitutively expressed at low levels in this tissue, were induced by each compound in the livers of AHR knockout mice. In addition, the use of heterogenous nuclear RNA reverse transcription-polymerase chain reaction procedures revealed that the transcriptional activities of CYP1A2 were increased by PBO and ACN treatments. These results show that AHR-independent pathway(s) can be involved in induction of CYP1A2 and CYP1B1. C1 N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NCI,NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 FU NIEHS NIH HHS [ES00044] NR 44 TC 84 Z9 86 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 SEP PY 1996 VL 50 IS 3 BP 443 EP 446 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG935 UT WOS:A1996VG93500001 PM 8794879 ER PT J AU Lobaugh, LA Eisfelder, B Gibson, K Johnson, GL Putney, JW AF Lobaugh, LA Eisfelder, B Gibson, K Johnson, GL Putney, JW TI Constitutive activation of a phosphoinositidase C-linked G protein in murine fibroblasts decreases agonist-stimulated Ca2+ mobilization SO MOLECULAR PHARMACOLOGY LA English DT Article ID INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; NIH 3T3 CELLS; PHOSPHOLIPASE-C; ALPHA-SUBUNIT; MALIGNANT TRANSFORMATION; DOWN-REGULATION; GROWTH; EXPRESSION; 1,3,4-TRISPHOSPHATE; TRISPHOSPHATE AB We compared Ca2+ signaling and inositol polyphosphate metabolism in NIH-3T3 cells stably transfected with cDNA encoding either the wild-type G protein G(16) alpha subunit or a GTPase-deficient alpha(16) subunit (Q212L-alpha(16)). Constitutive activation of phosphoinositidase C (PIG) in cells expressing Q212L-alpha(16) was demonstrated by 1) an increased basal level of [H-3]inositol polyphosphates, 2) an enhanced rate of [H-3]inositol polyphosphate accumulation in cells treated with 10 mM LiCl, and 3) an increased rate of incorporation of [H-3]inositol into cell lipids. Q212L-alpha(16) cells had a diminished cell growth rate. Basal intracellular Ca2+ concentration was equivalent in Fura-2 acetoxymethyl ester-loaded Q212L-alpha(16) cells compared with controls; however, calcium release in Q212L-alpha(16) cells exposed to ionomycin, ATP (a G protein-linked agonist), or platelet-derived growth factor (a tyrosine kinase-linked agonist) was decreased. Permeabilized, Ca-45-loaded Q212L-alpha(16) cells released less Ca-45 at each concentration of inositol-l,4,5-trisphosphate than did control cells. Accordingly, the total amount of inositol trisphosphate (IP3) receptor protein was decreased in Q212L-alpha(16) cells relative to controls. These data demonstrate that Q212L-alpha(16) cells maintain physiological levels of cytoplasmic calcium and partially loaded Ca2+ stores in the face of constitutively active PIG. This is accomplished, at least in part, by down-regulation of IP3 receptor number. Thus, diminution in cell growth rate in Q212L-alpha(16) cells seems to be attributable to a combination of at least two effects: a direct effect of PIC activation leading to partial depletion of Ca2+ stores and an indirect, adaptive response resulting in a decreased IP3 receptor number. C1 NIEHS,CELLULAR & MOL PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709. NATL JEWISH CTR IMMUNOL & RESP MED,DEPT PEDIAT,DENVER,CO 80206. NR 43 TC 12 Z9 12 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 SEP PY 1996 VL 50 IS 3 BP 493 EP 500 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG935 UT WOS:A1996VG93500008 PM 8794886 ER PT J AU Jiang, QL VanRhee, AM Kim, JH Yehle, S Wess, J Jacobson, KA AF Jiang, QL VanRhee, AM Kim, JH Yehle, S Wess, J Jacobson, KA TI Hydrophilic side chains in the third and seventh transmembrane helical domains of human A(2A) adenosine receptors are required for ligand recognition SO MOLECULAR PHARMACOLOGY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; MUSCARINIC ACETYLCHOLINE-RECEPTORS; BETA-ADRENERGIC-RECEPTOR; BINDING-SITE; SPECIES-DIFFERENCES; SERINE RESIDUES; MOLECULAR-BASIS; AMINO-ACIDS; RAT; IDENTIFICATION AB Hydrophilic residues of the G protein-coupled human A(2A) adenosine receptor that are potentially involved in the binding of the ribose moiety of adenosine were targeted for mutagenesis. Residues in a T(88)QSS(91) sequence in the third transmembrane helical domain (TM3) were individually replaced with alanine and other amino acids. Two additional serine residues in TMT that were previously shown to be involved in ligand binding were mutated to other uncharged, hydrophilic amino acids. The binding affinity of agonists at T88 mutant receptors was greatly diminished, although the receptors were well expressed and bound antagonists similar to the wild-type receptor. Thus, mutations that are specific for diminishing the affinity of ribose-containing ligands (i.e., adenosine agonists) have been identified in both TM3 and TM7. The T88A and T88S mutant receptor fully stimulated adenylyl cyclase, with the dose-response curves to CGS 21680 highly shifted to the right. A Q89A mutant gained affinity for all agonist and antagonist ligands examined in binding and functional assays. Q89 likely plays an indirect role in ligand binding. S90A, S91A, and S277C mutant receptors displayed only moderate changes in ligand affinity. A S281N mutant gained affinity for all adenosine derivatives (agonists), but antagonist affinity was generally diminished, with the exception of a novel tetrahydrobenzothiophenone derivative. C1 NIDDK,NIH,MOL RECOGNIT SECT,BETHESDA,MD 20892. NIDDK,NIH,DRUG RECEPTOR INTERACT SECT,BETHESDA,MD 20892. NIDDK,NIH,LAB BIOORGAN CHEM,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 52 TC 71 Z9 71 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD SEP PY 1996 VL 50 IS 3 BP 512 EP 521 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG935 UT WOS:A1996VG93500011 PM 8794889 ER PT J AU Iimuro, Y Bradford, BU Gao, WS Kadiiska, M Mason, RP Stefanovic, B Brenner, DA Thurman, RG AF Iimuro, Y Bradford, BU Gao, WS Kadiiska, M Mason, RP Stefanovic, B Brenner, DA Thurman, RG TI Detection of alpha-hydroxyethyl free radical adducts in the pancreas after chronic exposure to alcohol in the rat SO MOLECULAR PHARMACOLOGY LA English DT Article ID INTRAGASTRIC ETHANOL INFUSION; CULTURED HUMAN-FIBROBLASTS; LIPID-PEROXIDATION; LONG-TERM; KUPFFER CELLS; LIVER; INVIVO; GENE; ESR; POTENTIATION AB Chronic pancreatitis is characterized by inflammation and fibrosis leading to tissue destruction; in industrialized nations, alcohol abuse is the cause of 70-80% of cases of pancreatitis in adults. The purpose of the current work was to determine whether free radical adducts are produced by the pancreas during Vie early phases of chronic exposure to ethanol. Accordingly, rats were chronically led ethanol using the model of continuous enteral infusion developed by Tsukamoto et al. [Am. J, Physiol. 247: R595-R599 (1984)], Histological evaluation revealed only mild acinar steatosis and spotty necrosis after 4 weeks of alcohol treatment; the pancreatic enzymes lipase and amylase were not elevated, Furthermore, no fibrosis was detected, nor were there differences in pancreatic collagen alpha 1(I) mRNA levels between ?he dietary control and ethanol-treated groups. After 4 weeks, rats were injected with the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (1 g/kg intravenously), and pancreatic secretions were collected over a 4-hr period. A six-line free radical adduct spectrum indicative of a carbon-centered free radical was detected in pancreatic secretions and in Folch extracts of pancreatic tissue by electron spin resonance spectroscopy. Control experiments ruled out ex vivo radical formation. This study represents the first detection of radical adducts in pancreatic secretions. When [C-13]ethanol (3 g/kg intragastrically) was administered, a definitive 12-line spectrum was detected in pancreatic secretions, demonstrating that the alpha-hydroxyethyl radical adduct was formed in the pancreas from [C-13]ethanol. interestingly only a six-line signal was detected in tissue extracts under these conditions. Free radicals, therefore, are formed in the pancreas during the early phases of chronic alcohol intake in rats before the development of overt pathology. C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT MED,CHAPEL HILL,NC 27599. NIEHS,NIH,RES TRIANGLE PK,NC. FU NIAAA NIH HHS [AA09156, AA03624]; NIGMS NIH HHS [GM41804] NR 36 TC 21 Z9 21 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 SEP PY 1996 VL 50 IS 3 BP 656 EP 661 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA VG935 UT WOS:A1996VG93500029 PM 8794907 ER PT J AU Gold, PW Wong, ML Chrousos, GP Licinio, J AF Gold, PW Wong, ML Chrousos, GP Licinio, J TI Stress system abnormalities in melancholic and atypical depression: Molecular, pathophysiological, and therapeutic implications SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; MESSENGER-RNA LEVELS; CENTRAL NERVOUS-SYSTEM; TYROSINE-HYDROXYLASE; RAT-BRAIN; BIOCHEMICAL MANIFESTATIONS; FACTOR RECEPTORS; HORMONE; SECRETION C1 NICHHD, BETHESDA, MD USA. RP NIMH, CLIN NEUROENDOCRINOL BRANCH, NIH, BLDG 10-2D46, 19 CTR DR MSC 1284, BETHESDA, MD 20892 USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 45 TC 55 Z9 56 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 1996 VL 1 IS 4 BP 257 EP 264 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VV910 UT WOS:A1996VV91000001 PM 9118349 ER PT J AU Negrao, AB Licinio, J AF Negrao, AB Licinio, J TI Stress-responsive neuropeptides in major depression SO MOLECULAR PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; HORMONE; VASOPRESSIN; DISEASE; CRF RP Negrao, AB (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BLDG 10,RM 2D49,10 CTR DR,MSC 1284,BETHESDA,MD 20892, USA. RI Negrao, Andre Brooking/C-9526-2014; Licinio, Julio/L-4244-2013 OI Negrao, Andre Brooking/0000-0002-8133-6723; Licinio, Julio/0000-0001-6905-5884 NR 20 TC 2 Z9 2 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 SEP PY 1996 VL 1 IS 4 BP 300 EP 301 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VV910 UT WOS:A1996VV91000005 PM 9118353 ER PT J AU Wong, ML AlShekhlee, A Bongiorno, PB Esposito, A Khatri, P Sternberg, EM Gold, PW Licinio, J AF Wong, ML AlShekhlee, A Bongiorno, PB Esposito, A Khatri, P Sternberg, EM Gold, PW Licinio, J TI Localization of urocortin messenger RNA in rat brain and pituitary SO MOLECULAR PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; FACTOR-RECEPTOR; EXPRESSION; DISEASE; SHEEP; GLAND; AXIS AB Pituitary function is regulated by hypothalamic releasing hormones secreted into hypophyseal-portal blood. A new hypothesis is that pituitary function might also be regulated at the local level by releasing hormones synthesized within the pituitary. Here we show that the pituitary expresses high levels of the gene encoding for urocortin. We suggest that urocortin synthesized by the pituitary may modulate pituitary function, and that adrenocorticotropic hormone (ACTH) secretion is dependent on input not only from the hypothalamus as previously described, but it may also be regulated by urocortin synthesized locally. Urocortin binds to the corticotropin-releasing hormone (CRH) receptor type I (CRH-RI) with high affinity and potently stimulates pituitary-adrenal function. Our group and others have previously localized high levels of CRH-R1 mRNA in the pituitary. Using a S-35-labeled rat urocortin riboprobe we have now localized urocortin mRNA in rat brain and pituitary. The finding of urocortin gene expression in the pituitary may help explain why proopiomelanocortin (POMC) mRNA levels are not decreased during hypothalamo-pituitary disconnection, and also describes a new level of complexity in the regulation of hypothalamo-pituitary function. Future studies should consider the possibility that pituitary function might be regulated at the local level by urocortin. RP Wong, ML (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BLDG 10,RM 2D46,10 CTR DR MSC 1284,BETHESDA,MD 20892, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 18 TC 73 Z9 75 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 SEP PY 1996 VL 1 IS 4 BP 307 EP 312 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA VV910 UT WOS:A1996VV91000008 PM 9118356 ER PT J AU Shigeta, H Newbold, RR McLachlan, JA Teng, C AF Shigeta, H Newbold, RR McLachlan, JA Teng, C TI Estrogenic effect on the expression of estrogen receptor, COUP-TF, and lactoferrin mRNA in developing mouse tissues SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE estrogen receptor; COUP-TF; lactoferrin; development; estrogen target tissues; gene regulation ID PROMOTER TRANSCRIPTION FACTOR; RETINOIC ACID RECEPTORS; LACTOTRANSFERRIN GENE; REPRODUCTIVE-TRACT; THYROID-HORMONE; ELEMENTS; PROTEIN; UTERUS; REGION; CYCLE AB We have previously demonstrated that lactoferrin (LF) is a major estrogen-inducible protein in the mouse uterus. The increase of LF mRNA after estrogen treatment (>300 fold) is the result of a complex interplay among transcription factors acting on the estrogen response element (ERE) of the LF gene. Two transcription factors - the estrogen receptor (ER) and the chicken ovalbumin upstream promoter transcription factor (COUP-TF) - play opposing roles in the estrogen responsiveness of the LF gene promoter-reporter constructs in transiently transfected human endometrial carcinoma cells, The ratio of ER/COUP-TF in the transfected cells appears to be critical for estrogen-stimulated LF gene promoter activity (Liu et al, 1993), In the current study, ER and COUP-TF mRNA levels are examined and related to LF mRNA expression in various mouse tissues, including the developing uterus with/without estrogen stimulation. Results show that LF mRNA and protein are expressed in various tissues during development, but the potent synthetic estrogen, diethylstilbestrol (DES), does not increase LF mRNA expression in nonreproductive tissues such as liver, spleen, and lung. In contrast, in developing neonatal reproductive tract tissues, DES increases LF mRNA and protein expression as previously reported in immature and mature uterine tissues. DES, however, did not affect ER and COUP-TF expression in developing uterine tissues. Although the uterus has a high ratio of ER/COUP-TF as compared to other tissues examined, COUP-TF may not be the only regulator for LF gene expression in this particular tissue since COUP-TF remains constant during development and following DES treatment. These data point to the complexity of differential expression of LF gene in estrogen responsive and nonresponsive tissues during development. (C) 1996 Wiley-Liss, Inc. C1 NIEHS,GENE REGULAT GRP,REPROD & DEV TOXICOL LAB,ENVIRONM BIOL PROGRAM,RES TRIANGLE PK,NC 27709. NIEHS,DEV ENDOCRINOL SECT,REPROD TOXICOL GRP,LAB TOXICOL,ENVIRONM TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. TULANE UNIV,CTR BIOENVIRONM RES,NEW ORLEANS,LA 70118. NR 25 TC 26 Z9 26 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD SEP PY 1996 VL 45 IS 1 BP 21 EP 30 DI 10.1002/(SICI)1098-2795(199609)45:1<21::AID-MRD3>3.0.CO;2-U PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA VF008 UT WOS:A1996VF00800003 PM 8873065 ER PT J AU Cupler, EJ Otero, C Hench, K Luciano, C Dalakas, MC AF Cupler, EJ Otero, C Hench, K Luciano, C Dalakas, MC TI Acetylcholine receptor antibodies as a marker of treatable fatigue in HIV-1 infected individuals SO MUSCLE & NERVE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MYASTHENIA-GRAVIS; MYOPATHY; IMMUNE C1 NINCDS,NEUROMUSCULAR DIS SECT,NIH,BETHESDA,MD 20892. NINCDS,EMG SECT,NIH,BETHESDA,MD. NINR,CLIN THERAPEUT LAB,NIH,BETHESDA,MD. NR 20 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD SEP PY 1996 VL 19 IS 9 BP 1186 EP 1188 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA VC635 UT WOS:A1996VC63500021 PM 8761282 ER PT J AU Zeiger, E Ashby, J Bakale, G Enslein, K Klopman, G Rosenkranz, HS AF Zeiger, E Ashby, J Bakale, G Enslein, K Klopman, G Rosenkranz, HS TI Prediction of Salmonella mutagenicity SO MUTAGENESIS LA English DT Article ID NATIONAL-TOXICOLOGY-PROGRAM; NCI/NTP-SCREENED CHEMICALS; KE TEST; RODENT CARCINOGENICITY; STRUCTURAL BASIS; 44 CHEMICALS; TYPHIMURIUM; BIOASSAYS; ASSAY; NONCARCINOGENS AB The ability of a number of prediction systems was examined to determine how well they could predict Salmonella mutagenicity. The prediction systems included two computer-based systems (CASE(C) and TOPKAT(C)), the measurement of a physiochemical parameter (k(e)) and the use of structural alerts by an expert chemist. The computer-based systems operators and the chemist were supplied with the structures of 100 chemicals that had been tested for mutagenicity in the Salmonella test; the actual chemicals were needed for the physiochemical measurement, None of the participants was provided with the chemical names or Salmonella test results prior to submitting their predictions. The three systems that predicted the mutagenicity from the structure of the chemicals produced equivalent results (71-76% concordance with the Salmonella results); the physiochemical system produced a lower (60-61%) concordance. C1 ZENECA CENT TOXICOL LAB,MACCLESFIELD,CHESHIRE,ENGLAND. CASE WESTERN RESERVE UNIV,DEPT RADIOL,CLEVELAND,OH 44106. HLTH DESIGN INC,ROCHESTER,NY. CASE WESTERN RESERVE UNIV,DEPT CHEM,CLEVELAND,OH 44106. UNIV PITTSBURGH,DEPT ENVIRONM & OCCUPAT HLTH,PITTSBURGH,PA. RP Zeiger, E (reprint author), NIEHS,EXPT TOXICOL BRANCH,WC-05,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 48 Z9 52 U1 1 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 1996 VL 11 IS 5 BP 471 EP 484 DI 10.1093/mutage/11.5.471 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA VG666 UT WOS:A1996VG66600008 PM 8921509 ER PT J AU Buzard, GS AF Buzard, GS TI Studies of oncogene activation and tumor suppressor gene inactivation in normal and neoplastic rodent tissue SO MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY LA English DT Review DE oncogene; suppressor gene; mutation; rodent; model; p53; Rb; genotoxic ID MOUSE-LIVER TUMORS; RENAL MESENCHYMAL TUMORS; SQUAMOUS-CELL CARCINOMAS; CHRONIC ACTIVE HEPATITIS; NITROSO-N-METHYLUREA; RAT P53 GENE; K-RAS; HEPATOCELLULAR CARCINOMAS; RETINOBLASTOMA GENE; TRANSGENIC MICE AB Emerging short-term bioassays for chemically-induced carcinogenesis are dependent for their relevance to human risk assessment on the degree of coincidence of human and rodent tumor pathways. Since these pathways do not always converge, these new tests may have a number of unanticipated pitfalls. Models of liver and renal tumors are described. The results from Rb and p53 tumor suppressor gene transgenic animals are compared to human tumor syndromes. The question of mutagenic and epigenetic fingerprints of chemicals versus the cell-specific selection of spontaneous mutations is debated. Examples of specific pitfalls, such as the recently discovered Helicobacter hepaticus promoted liver tumors in mice are presented, The rat pseudogenes for p53 and the rare role of p53 in most important rodent tumor models other than epithelial tumors present experimental quandaries. The differential effects of carcinogens during various stages of rodent perinatal and adult development are also discussed. It is concluded that the pathways of both animal models and their human counterparts should be better identified so that realistic endpoint markers can be chosen for human carcinogenic risk assessment. RP Buzard, GS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC,INTRAMURAL RES SUPPORT PROGRAM,BLDG 538,ROOM 205-D,POB B,FREDERICK,MD 21702, USA. NR 110 TC 12 Z9 12 U1 0 U2 1 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 SEP PY 1996 VL 365 IS 1-3 SI SI BP 43 EP 58 DI 10.1016/S0165-1110(96)90011-1 PG 16 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA VP854 UT WOS:A1996VP85400004 PM 8898988 ER PT J AU Cunningham, ML AF Cunningham, ML TI Role of increased DNA replication in the carcinogenic risk of nonmutagenic chemical carcinogens SO MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY LA English DT Article DE hepatocellular proliferation; peroxisome proliferation; hepatocarcinogenesis; nonmutagenic carcinogen; rodent-specific carcinogenesis; pleiotropic effect ID HEPATIC PEROXISOME PROLIFERATION; B6C3F1 MICE; RAT-LIVER; HEPATOCARCINOGEN METHAPYRILENE; HEPATOCELLULAR PROLIFERATION; MUTAGENIC NONCARCINOGENS; CELL-PROLIFERATION; MOUSE-LIVER; F344 RATS; OXAZEPAM AB DNA replication is not an error-free process; therefore induction of cell proliferation with the requisite increase in DNA replication may be an important mechanism by which carcinogenesis can be induced by chemicals. Data presented in this overview indicate a positive association between increased cell proliferation and carcinogenesis, and illustrate the value of performing mechanistic studies such as cell proliferation assays in conjunction with short-term tests to further investigate the results of cancer bioassays. Whereas chemically-induced cell proliferation per se may not be sufficient to induce carcinogenesis, it creates a favorable environment for tumor development. There are two types of chemically-induced cell proliferation, mitogenic and cytotoxic, and they have different consequences regarding the mechanism of carcinogenesis of a chemical. Mitogenic chemical such as phenobarbital, oxazepam, and the peroxisome proliferating agents exert a short-term cell proliferative response that may exert its primary effect in carcinogenesis at the promotion stages. It is not clear at what stage(s) cytotoxic agents such as methapyrilene, alpha(2u)-globulin inducers or saccharin exert their effects in carcinogenesis. A confounding factor in evaluation of cell proliferation in risk assessments is the production of chemical specific pleiotropic effects that may contribute to the carcinogenicity of a chemical. It is clear that mechanistic studies performed to understand the relationship of sex, species and dose in rodent carcinogenicity assays of chemicals is critical for the extrapolation of such data for human health assessments, RP Cunningham, ML (reprint author), NIEHS, EXPT TOXICOL PROGRAM, CHEM BRANCH, MAIL DROP B3-10, RES TRIANGLE PK, NC 27709 USA. NR 58 TC 48 Z9 48 U1 0 U2 0 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 SEP PY 1996 VL 365 IS 1-3 SI SI BP 59 EP 69 DI 10.1016/S0165-1110(96)90012-3 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA VP854 UT WOS:A1996VP85400005 PM 8898989 ER PT J AU Tennant, RW Spalding, J French, JE AF Tennant, RW Spalding, J French, JE TI Evaluation of transgenic mouse bioassays for identifying carcinogens and noncarcinogens SO MUTATION RESEARCH-REVIEWS IN GENETIC TOXICOLOGY LA English DT Article DE transgenic mouse; bioassay model; carcinogenesis; p53 heterozygote; Tg center dot Ac ID TUMOR-SUPPRESSOR GENES; CELL-CYCLE CHECKPOINT; P53-DEFICIENT MICE; INDUCED TUMORIGENESIS; SKIN; P53; ONCOGENES; MODELS; INITIATION AB Data supporting the use of transgenic lines to identify carcinogens and noncarcinogens are thus far based on a limited number of chemicals for which there are also long-term bioassay results in rats and/or mice. Six chemicals have been tested in the heterozygous p53-deficient mice and 13 in the Tg . AC line. The results show that the p53(def) responds rapidly to mutagenic carcinogens and the Tg . AC responds rapidly to both mutagenic and nonmutagenic carcinogens. Neither transgenic line responded to the noncarcinogens that were tested. The p53(def) line failed to respond to two nonmutagenic carcinogens (N-methyloacrylamide and reserpine), the Tg . AC line failed to respond to ethyl acrylate, a nonmutagenic chemical that induced tumors of the forestomach when administered by gavage, and to triethanolamine that caused an increase in hepatocellular tumors in B6C3F1 mice via skin painting. Both of the latter chemicals are examples of highly specific responses related to either route of administration or to strain susceptibility. Further efforts to evaluate the range of chemicals to which these transgenic lines respond are currently in progress. RP Tennant, RW (reprint author), NIEHS,LAB ENVIRONM CARCINOGENESIS & MUTAGENESIS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 36 TC 114 Z9 116 U1 1 U2 1 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 SEP PY 1996 VL 365 IS 1-3 SI SI BP 119 EP 127 DI 10.1016/S0165-1110(96)90016-0 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA VP854 UT WOS:A1996VP85400009 PM 8898993 ER PT J AU Sikorski, RS Peters, R AF Sikorski, RS Peters, R TI Clinical trials on the web SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP Sikorski, RS (reprint author), HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD SEP PY 1996 VL 14 IS 9 BP 1170 EP 1170 DI 10.1038/nbt0996-1170 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA VF843 UT WOS:A1996VF84300043 ER PT J AU Tachibana, M Takeda, K Nobukuni, Y Urabe, K AF Tachibana, M Takeda, K Nobukuni, Y Urabe, K TI Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics SO NATURE GENETICS LA English DT Article ID LOOP-HELIX PROTEIN; MICROPHTHALMIA GENE; TRANSCRIPTION FACTOR; HUMAN HOMOLOG; MAMMALIAN TYROSINASE; MOUSE FIBROBLASTS; MOLECULAR-BASIS; PAIRED DOMAIN; MUTATIONS; DIFFERENTIATION AB MITF (microphthalmia-associated transcription factor) encodes a transcription factor with a basic-helix-loop-helix-zipper (bHLH-Zip) motif. MITF mutations occur in patients with Waardenburg syndrome type 2, a disorder associated with melanocyte abnormalities. Here we show that ectopic expression of MITF converts NIH/3T3 fibroblasts into cells with characteristics of melanocytes. MITF transfectants formed foci of morphologically altered cells, which resemble those induced by oncogenes, but did not exhibit malignant phenotypes. Instead, they contained dendritic cells that express melanogenic marker proteins such as tyrosinase and tyrosinase-related protein 1. Most cloned cells of MITF transfectants exhibited dendritic morphology and expressed melanogenic markers, but such properties were not observed in cells transfected with closely related TFE3 cDNA. Our findings indicate that MITF is critically involved in melanocyte differentiation. C1 NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,MOL & CELLULAR BIOL LAB,BETHESDA,MD 20892. RP Tachibana, M (reprint author), NIDOCD,GENET MOL LAB,NIH,5 RES COURT,ROCKVILLE,MD 20850, USA. NR 61 TC 197 Z9 207 U1 2 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 SEP PY 1996 VL 14 IS 1 BP 50 EP 54 DI 10.1038/ng0996-50 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA VF611 UT WOS:A1996VF61100020 PM 8782819 ER PT J AU Gailani, MR StahleBackdahl, M Leffell, DJ Glynn, M Zaphiropoulos, PG Pressman, C Unden, AB Dean, M Brash, DE Bale, AE Toftgard, R AF Gailani, MR StahleBackdahl, M Leffell, DJ Glynn, M Zaphiropoulos, PG Pressman, C Unden, AB Dean, M Brash, DE Bale, AE Toftgard, R TI The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas SO NATURE GENETICS LA English DT Letter ID TUMOR-SUPPRESSOR; GORLIN SYNDROME; GENE; PROTEIN; LOCALIZATION; CHROMOSOME-9; ASSOCIATION; MUTATIONS; HEDGEHOG; RNA C1 YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT PAEDIAT,NEW HAVEN,CT 06520. KAROLINSKA HOSP,DEPT DERMATOL,S-17176 STOCKHOLM,SWEDEN. KAROLINSKA INST,NOVUM,DEPT BIOSCI,S-14157 HUDDINGE,SWEDEN. KAROLINSKA INST,NOVUM,CTR NUTR & TOXICOL,S-14157 HUDDINGE,SWEDEN. FREDERICK NATL CANC INST,HUMAN GENET SECT,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [K11CA60199, R01CA57605]; NICHD NIH HHS [1-P30-HD27757-01] NR 30 TC 508 Z9 515 U1 4 U2 16 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 SEP PY 1996 VL 14 IS 1 BP 78 EP 81 DI 10.1038/ng0996-78 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VF611 UT WOS:A1996VF61100024 PM 8782823 ER PT J AU Remmers, EF Longman, RE Du, Y OHare, A Cannon, GW Griffiths, MM Wilder, RL AF Remmers, EF Longman, RE Du, Y OHare, A Cannon, GW Griffiths, MM Wilder, RL TI A genome scan localizes five non-MHC loci controlling collagen-induced arthritis in rats SO NATURE GENETICS LA English DT Letter ID RHEUMATOID-ARTHRITIS; EXPERIMENTAL-MODEL; IMMUNE-RESPONSE; II COLLAGEN; DISEASE-SUSCEPTIBILITY; IMMUNOGENETIC CONTROL; AUTOIMMUNE-DISEASES; GENETIC DISSECTION; MOUSE CHROMOSOME-6; BB RAT C1 UNIV UTAH,VET AFFAIRS MED CTR,RES SERV,SALT LAKE CITY,UT 84132. UNIV UTAH,DEPT MED RHEUMATOL,SALT LAKE CITY,UT 84132. RP Remmers, EF (reprint author), NIAMSD,INFLAMMATORY JOINT DIS SECT,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892, USA. NR 30 TC 181 Z9 184 U1 0 U2 2 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 SEP PY 1996 VL 14 IS 1 BP 82 EP 85 DI 10.1038/ng0996-82 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VF611 UT WOS:A1996VF61100025 PM 8782824 ER PT J AU Ning, Y Roschke, A Smith, ACM Macha, M Precht, K Riethman, H Ledbetter, DH Flint, J Horsley, S Regan, R Kearney, L Knight, S Kvaloy, K Brown, WRA AF Ning, Y Roschke, A Smith, ACM Macha, M Precht, K Riethman, H Ledbetter, DH Flint, J Horsley, S Regan, R Kearney, L Knight, S Kvaloy, K Brown, WRA TI A complete set of human telomeric probes and their clinical application SO NATURE GENETICS LA English DT Letter ID ENDONUCLEASE RARE CLEAVAGE; HUMAN-CHROMOSOMES; DNA FRAGMENTS; SEQUENCE ORGANIZATION; PHYSICAL ANALYSIS; TRANSLOCATION; CLONING; VECTOR; GENE; ARM C1 NIH,DIAGNOST DEV BRANCH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. JOHN RADCLIFFE HOSP,INST MOL MED,OXFORD OX3 9DU,ENGLAND. UNIV OXFORD,DEPT BIOCHEM,OXFORD OX1 3QU,ENGLAND. NR 33 TC 253 Z9 256 U1 0 U2 2 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 SEP PY 1996 VL 14 IS 1 BP 86 EP 89 DI 10.1038/ng0996-86 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VF611 UT WOS:A1996VF61100026 ER PT J AU Risinger, JI Umar, A Boyd, J Berchuck, A Kunkel, TA Barrett, JC AF Risinger, JI Umar, A Boyd, J Berchuck, A Kunkel, TA Barrett, JC TI Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair SO NATURE GENETICS LA English DT Letter ID DNA MISMATCH REPAIR; SIMPLE REPETITIVE DNA; MICROSATELLITE INSTABILITY; CELL-LINE; TUMOR-CELLS; GENE; YEAST; CARCINOMAS; TRACTS; GTBP C1 NIEHS,MOL GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOL CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM GENET & MOL BIOL,CHAPEL HILL,NC 27599. UNIV PENN,MED CTR,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. DUKE UNIV,DIV GYNECOL ONCOL,DEPT OBSTET & GYNECOL,DURHAM,NC 27710. NR 39 TC 158 Z9 159 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 SEP PY 1996 VL 14 IS 1 BP 102 EP 105 DI 10.1038/ng0996-102 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA VF611 UT WOS:A1996VF61100030 PM 8782829 ER PT J AU Fauci, AS AF Fauci, AS TI Resistance to HIV-1 infection: It's in the genes SO NATURE MEDICINE LA English DT Editorial Material RP Fauci, AS (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 28 Z9 28 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 SEP PY 1996 VL 2 IS 9 BP 966 EP 967 DI 10.1038/nm0996-966 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VF497 UT WOS:A1996VF49700023 PM 8782446 ER PT J AU Leonard, WJ AF Leonard, WJ TI STATs and cytokine specificity SO NATURE MEDICINE LA English DT Editorial Material ID PHOSPHORYLATION; TRANSCRIPTION; RECEPTOR; TYROSINE; IL-4 RP Leonard, WJ (reprint author), NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892, USA. NR 20 TC 38 Z9 40 U1 0 U2 1 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD SEP PY 1996 VL 2 IS 9 BP 968 EP 969 DI 10.1038/nm0996-968 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VF497 UT WOS:A1996VF49700024 PM 8782447 ER PT J AU Neurath, MF Pettersson, S zumBuschenfelde, KHM Strober, W AF Neurath, MF Pettersson, S zumBuschenfelde, KHM Strober, W TI Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice SO NATURE MEDICINE LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; RECEPTOR MUTANT MICE; CELL-PROLIFERATION; TRANSCRIPTIONAL ACTIVATION; TARGETED DISRUPTION; ULCERATIVE-COLITIS; GENE INHIBITION; EXPRESSION; ALPHA; DNA AB Chronic intestinal inflammation induced by 2,4,6,-trinitrobenzene sulfonic acid (TNBS) is characterized by a transmural granulomatous colitis that mimics some characteristics of human Crohn's disease. Here, we show that the transcription factor NF-kappa S p65 was strongly activated in TNBS-induced colitis and in colitis of interleukin-10-deficient mice. Local administration of p65 antisense phosphorothioate oligonucleotides abrogated clinical and histological signs of colitis and was more effective in treating TNBS-induced colitis than single or daily administration of glucocorticoids. The data provide direct evidence for the central importance of p65 in chronic intestinal inflammation and suggest a potential therapeutic utility of p65 antisense oligonucleotides as a novel molecular approach for the treatment of patients with Crohn's disease. C1 KAROLINSKA INST,CTR BIOTECHNOL,S-14157 HUDDINGE,SWEDEN. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. RP Neurath, MF (reprint author), UNIV MAINZ,MED CLIN 1,IMMUNOL LAB,LANGENBECKSTR 1,D-55101 MAINZ,GERMANY. RI Pettersson, Sven/F-9511-2015 NR 47 TC 623 Z9 642 U1 2 U2 17 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 SEP PY 1996 VL 2 IS 9 BP 998 EP 1004 DI 10.1038/nm0996-998 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA VF497 UT WOS:A1996VF49700034 PM 8782457 ER PT J AU Grobler, JA Essen, LO Williams, RL Hurley, JH AF Grobler, JA Essen, LO Williams, RL Hurley, JH TI C2 domain conformational changes in phospholipase C-delta 1 SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; SYNAPTOTAGMIN-I; BINDING; CALCIUM; ISOZYMES; TRANSITION; CALMODULIN; REFINEMENT; MEMBRANES; PROGRAM AB The structure of the PH-domain truncated core of rat phosphoinositide-specific phospholipase C-delta 1 has been determined at 2.4 Angstrom, resolution and compared to the structure previously determined in a different crystal form. The stereochemical relationship between the EF, catalytic, and CZ domains is essentially identical, The Ca2+ analogue Sm3+ binds at two sites between the jaws of the C2 domain. Sm3+ binding ejects three lysine residues which bridge the gap between the jaws and occupy the Ca2+ site in the apoenzyme, triggering a conformational change in the jaws. The distal sections of the C2 jaws move apart, opening the mouth by 9 Angstrom and creating a gap large enough to bind a phospholipid headgroup. C1 NIDDKD, MOL BIOL LAB, NIH, BETHESDA, MD 20892 USA. MRC CTR, CTR PROT ENGN, CAMBRIDGE CB2 2QH, ENGLAND. RI Essen, Lars-Oliver/L-3862-2016 OI Essen, Lars-Oliver/0000-0003-4272-4026 FU Medical Research Council [MC_U105184308] NR 45 TC 101 Z9 103 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD SEP PY 1996 VL 3 IS 9 BP 788 EP 795 DI 10.1038/nsb0996-788 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA VF280 UT WOS:A1996VF28000013 PM 8784353 ER PT J AU Ma, JY Brewer, HB Potter, H AF Ma, JY Brewer, HB Potter, H TI Alzheimer A beta neurotoxicity: Promotion by antichymotrypsin, ApoE4; Inhibition by A beta-related peptides SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; amyloid; inflammation; acute phase response; ACT; apoE; IL-1 ID AMYLOID PRECURSOR PROTEIN; HEREDITARY CEREBRAL-HEMORRHAGE; APOLIPOPROTEIN-E GENOTYPE; FIBRIL FORMATION; DISEASE LOCUS; SENILE PLAQUES; MISSENSE MUTATIONS; TYPE-4 ALLELE; LUNG-DISEASE; CONGO-RED AB Two inflammation-associated proteins found in the Alzheimer amyloid deposits-alpha(1)-antichymotrypsin (ACT) and apolipoprotein E4 (apoE4)-have been shown to be genetic risk factors for the development of Alzheimer's disease and to promote the polymerization of the A beta peptide into amyloid filaments in vitro. In the present study, we show that ACT and apoE4 increase the neurotoxicity of the A beta peptide in parallel with their promotion of filament formation. Preincubation of ACT or apoE4 with small A beta-related peptides, or of apoE4 with apoE2, abrogated their subsequent ability to promote both the formation and the neurotoxicity of A beta filaments. These results indicate that ACT and apoE4 may play a stimulatory role in the formation of neurotoxic amyloid in Alzheimer's disease, and that their amyloid promoting activity can be blocked by inhibitory peptides. C1 HARVARD UNIV,SCH MED,DEPT NEUROBIOL,BOSTON,MA 02115. NHLBI,NIH,BETHESDA,MD 20892. NR 88 TC 78 Z9 79 U1 0 U2 1 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 SEP-OCT PY 1996 VL 17 IS 5 BP 773 EP 780 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA VK447 UT WOS:A1996VK44700014 PM 8892351 ER PT J AU Tedeschi, G Bertolino, A Lundbom, N Bonavita, S Patronas, NJ Duyn, JH Metman, LV Chase, TN DiChiro, G AF Tedeschi, G Bertolino, A Lundbom, N Bonavita, S Patronas, NJ Duyn, JH Metman, LV Chase, TN DiChiro, G TI Cortical and subcortical chemical pathology in Alzheimer's disease as assessed by multislice proton magnetic resonance spectroscopic imaging SO NEUROLOGY LA English DT Article ID WHITE MATTER CHANGES; ACETYL-L-ASPARTATE; N-ACETYLASPARTATE; MR SPECTROSCOPY; IN-VIVO; H-1-NMR SPECTROSCOPY; RAT-BRAIN; DEMENTIA; DISTRIBUTIONS; ACID AB Background: Multislice proton magnetic resonance spectroscopic imaging (1H-MRSI) permits the simultaneous acquisition of N-acetylaspartate (NA), choline (Cho), creatine/phosphocreatine (Cre), and lactate (Lac) signal intensities from four 15-mm slices divided into 9.84-ml single-volume elements. NA is inferred to be a neuron-specific molecule, whereas Cho mainly reflects glycerophosphocholine and phosphocholine, compounds involved in phospholipid metabolism. Objective: To assess whether 1H-MRSI could detect a regional pattern of cortical and subcortical involvement in the brain of Alzheimer's disease (AD) patients. Methods: 1H-MRSI was performed in 15 patients with probable AD and 15 age-matched healthy controls. Regions of interest (ROIs) were selected from frontal (FC), temporal (TC), parietal (PC), occipital, and insular cortices, subcortical white matter (WM), and thalamus. Results: In AD patients, we found a significant reduction of NA/Cre in the FC, TC, and PC and a significant reduction of Cho/Cre in the WM. Conclusions: This 1H-MRSI study of AD patients shows a regional pattern of neuronal damage in the associative cor tices, as revealed by significant reduction of NA/Cre in the FC, TC, and PC, and regional derangement of phospholipid metabolism, as revealed by significant reduction of Cho/Cre in the WM. C1 NINCDS,EXPT THERAPEUT BRANCH,NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NINCDS,LAB DIAGNOST RADIOL RES,NIH,BETHESDA,MD 20892. RP Tedeschi, G (reprint author), NINCDS,NEUROIMAGING BRANCH,NIH,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C227,10 CTR DR,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010; Bertolino, Alessandro/O-6352-2016 OI Bertolino, Alessandro/0000-0002-1251-1380 NR 45 TC 53 Z9 53 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 SEP PY 1996 VL 47 IS 3 BP 696 EP 704 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA VG596 UT WOS:A1996VG59600015 PM 8797467 ER PT J AU Cochran, EJ Bennett, DA Cervenakova, L Kenney, K Bernard, B Foster, NL Benson, DF Goldfarb, LG Brown, P AF Cochran, EJ Bennett, DA Cervenakova, L Kenney, K Bernard, B Foster, NL Benson, DF Goldfarb, LG Brown, P TI Familial Creutzfeldt-Jakob disease with a five-repeat octapeptide insert mutation SO NEUROLOGY LA English DT Article ID PRION PROTEIN GENE; AMYLOID PRECURSOR GENE; 144-BASE-PAIR INSERTION; DNA POLYMORPHISM; PRNP GENE; INSOMNIA; DIAGNOSIS; FEATURES; DEMENTIA AB We report a familial form of Creutzfeldt-Jakob disease, associated with a unique insert mutation of the PRNP gene in an American family of Ukrainian origin. Ten family members exhibited early age at onset and long-duration illnesses characterized primarily by personality changes, cognitive impairment, and spasticity. The proband, presenting at age 42 years, exhibited a fairly stable, nonprogressive course over 7 years, followed by precipitous decline and death in the eighth year. Other affected family members exhibited marked clinical heterogeneity. Each tested affected member had an insert mutation consisting of five extra octapeptide repeats between codons 51 and 91 of the PRNP gene on chromosome 20. Examination of two autopsy cases showed classic spongiform change, neuronal loss and astrocytosis in one case, and minimal pathologic abnormality in the other case. This report documents a new insert mutation of the PRNP gene, and confirms the early age of onset, characteristically prolonged clinical course, and clinical and pathologic heterogeneity seen in such mutations. C1 RUSH PRESBYTERIAN ST LUKES MED CTR,DEPT PATHOL,CHICAGO,IL 60612. NINCDS,NIH,CNS STUDIES LAB,BETHESDA,MD. UNIV MICHIGAN,MED CTR,MICHIGAN ALZHEIMERS DIS RES CTR,DEPT NEUROL,ANN ARBOR,MI. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. RP Cochran, EJ (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH ALZHEIMERS DIS CTR,DEPT NEUROL SCI,TECH 2000-SUITE 200,CHICAGO,IL 60612, USA. FU NIA NIH HHS [AG08671, AG09466, AG10161] NR 27 TC 50 Z9 51 U1 1 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD SEP PY 1996 VL 47 IS 3 BP 727 EP 733 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA VG596 UT WOS:A1996VG59600019 PM 8797471 ER PT J AU Nichelli, P Alway, D Grafman, J AF Nichelli, P Alway, D Grafman, J TI Perceptual timing in cerebellar degeneration SO NEUROPSYCHOLOGIA LA English DT Article; Proceedings Paper CT AAN Meeting CY MAY 01-07, 1994 CL WASHINGTON, DC DE cerebellum; time perception; time estimation; scalar timing theory; timing ID TEMPORAL MEMORY; INTERNAL CLOCK; TIME; BISECTION; REPRESENTATION; INVOLVEMENT; HIPPOCAMPAL; LESIONS AB This study examined rime perception in 12 patients with cerebellar degeneration (CD) and in 13 normal controls (NC). We used a time bisection procedure with four interval conditions (100-900 msec; 8-32 sec; 100-600 msec; 100-325 msec). Each subject's bisection point, discrimination ability (the Weber ratio) and precision (the inverse of the proportion of unexplained variance) was calculated for each condition. CD patients' performance on the 100-900 msec time bisection condition suggested a possible time discrimination deficit, which was confirmed with intervals in the range of 100-600 msec. Time discrimination was normal on the 100-325 msec condition and impaired on the 8-32 sec bisection task. However, when discriminating long intervals, CD patients also showed a precision deficit, which points to impaired sustained attention and/or decision processes. Our findings corroborate the view that cerebellar timing processes are not limited to the motor system but are also used in perceptual computations. Copyright (C) 1996 Elsevier Science Ltd. C1 NINCDS,COGNIT NEUROSCI SECT,NIH,MNB,BETHESDA,MD 20892. UNIV MODENA,DIPARTIMENTO PATOL NEUROPSICOSENSORIALE,I-41100 MODENA,ITALY. RI Nichelli, Paolo/F-7336-2015; OI Nichelli, Paolo/0000-0001-9756-6796; Grafman, Jordan H./0000-0001-8645-4457 NR 38 TC 125 Z9 126 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD SEP PY 1996 VL 34 IS 9 BP 863 EP 871 DI 10.1016/0028-3932(96)00001-2 PG 9 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA UW225 UT WOS:A1996UW22500003 PM 8822733 ER PT J AU Chen, G Manji, HK Wright, CB Hawver, DB Potter, WZ AF Chen, G Manji, HK Wright, CB Hawver, DB Potter, WZ TI Effects of valproic acid on beta-adrenergic receptors, G-proteins, and adenylyl cyclase in rat C6 glioma cells SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE valproic acid; beta-adrenergic receptor; guanine-nucleotide-binding protein; adenylyl cyclase; protein kinase C; anticonvulsant; lithium; bipolar affective disorder ID BIPOLAR AFFECTIVE-DISORDER; CEREBRAL-CORTEX; KINASE-C; LITHIUM INVITRO; DOWN-REGULATION; BRAIN; DESIPRAMINE; FORSKOLIN; BINDING; MECHANISMS AB Valproic acid (VPA) is an anticonvulsant drug with demonstrated efficacy in the treatment of mania. In the present study, we found that chronic exposure of rat C6 glioma cells to VPA induces a coordinate decrease in multiple components of the beta-adrenergic receptor- (beta-AR) coupled cyclic adenosine 3'-5'-monophosphate (cAMP) generating system. Chronic VPA decreased the number of beta-ARs in a time- and concentration-dependent manner; the decrease of beta-ARs was largely beta(1)-AR selective and affected beta-ARs in both the high- and low-affinity states. Chronic VPA also significantly attenuated receptor- and postreceptor-stimulated cAMP production, [H-3]forskolin binding sites, immunolabeling of G alpha(s) 45, and cholera toxin catalyzed ADP-ribosylation of G alpha(s) 52 and 45. Although the precise underlying mechanisms remain to be elucidated, such profound long-term changes in the functioning of this key signaling pathway may help explain the antimanic effects of chronic VPA treatment and are worthy of further study. C1 WAYNE STATE UNIV, SCH MED, DEPT PSYCHIAT & BEHAV NEUROSCI, DETROIT, MI 48201 USA. NIMH, CLIN PHARMACOL SECT, EXPT THERAPEUT BRANCH, NIH, BETHESDA, MD 20892 USA. RP WAYNE STATE UNIV, SCH MED, DEPT PSYCHIAT & BEHAV NEUROSCI, MOL PATHOPHYSIOL PROGRAM, DETROIT, MI 48201 USA. RI Chen, Guang/A-2570-2017 NR 52 TC 36 Z9 36 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1996 VL 15 IS 3 BP 271 EP 280 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VD482 UT WOS:A1996VD48200006 PM 8873110 ER PT J AU Adinoff, B Anton, R Linnoila, M Guidotti, A Nemeroff, CB Bissette, G AF Adinoff, B Anton, R Linnoila, M Guidotti, A Nemeroff, CB Bissette, G TI Cerebrospinal fluid concentrations of corticotropin-releasing hormone (CRH) and diazepam-binding inhibitor (DBI) during alcohol withdrawal and abstinence SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alcohol withdrawal; alcoholism; diazepam binding inhibitor; corticotropin releasing hormone; GABA receptor; HPA axis ID PITUITARY-ADRENAL AXIS; FACTOR-LIKE IMMUNOREACTIVITY; ETHANOL WITHDRAWAL; BENZODIAZEPINE ANTAGONIST; DEPRESSED-PATIENTS; FACTOR RECEPTORS; RAT; REVERSES; ANXIETY; BRAIN AB The neuropeptides diazepam binding inhibitor (DBI) and corticotropin-releasing hormone (CRH) elicit anxietylike symptoms when administered intracerebroventricularly to laboratory animals. Because of the similarities between the symptoms of certain anxiety states and the alcohol withdrawal syndrome, we hypothesized that increased secretion of either of these endogenous neuropeptides may, at least in part, be responsible for the symptoms of alcohol withdrawal. We therefore measured DBI and CRH concentrations in cerebrospinal fluid (CSF) of 15 alcohol-dependent patients during acute withdrawal (Day 1) and again at 3 week's abstinence (Day 21). In addition, plasma concentrations of cortisol were measured to evaluate the relationship between pituitary-adrenal axis activation and CSF CRH concentrations. CSF CRH (p < .04), but not CSF DBI, was significantly higher on Day 1 than on Day 21. Although there was a significant decrease in plasma cortisol from Day 1 to Day 21 (p < .001), a significant correlation between CSF CRH and plasma cortisol concentrations was not observed at either time point. Neither CSF neuropeptide correlated with clinical measures of withdrawal severity. These tentative findings may implicate CRH, but not DBI, in the pathogenesis of alcohol withdrawal. Alternately, the central release of CRH and DBI may not be adequately reflected in lumbar CSF. C1 UNIV TEXAS, SW MED CTR, DEPT PSYCHIAT, DALLAS, TX USA. MED UNIV S CAROLINA, DEPT PSYCHIAT, CHARLESTON, SC 29425 USA. NIAAA, DICBR, CLIN STUDIES LAB, BETHESDA, MD 20892 USA. NATHAN S KLINE INST PSYCHIAT RES, CTR NEUROPHARMACOL, ORANGEBURG, NY 10962 USA. EMORY UNIV, SCH MED, DEPT PSYCHIAT & BEHAV SCI, ATLANTA, GA USA. UNIV MISSISSIPPI, DEPT PSYCHIAT, JACKSON, MS 39216 USA. RP Adinoff, B (reprint author), VET ADM MED CTR, 116A, 4500 S LANCASTER RD, DALLAS, TX 75216 USA. FU NIMH NIH HHS [MH-42088] NR 43 TC 52 Z9 54 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1996 VL 15 IS 3 BP 288 EP 295 DI 10.1016/0893-133X(95)00212-V PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VD482 UT WOS:A1996VD48200008 PM 8873112 ER PT J AU Eisenhofer, G Lenders, JWM HarveyWhite, J Ernst, M Zametkin, A Murphy, DL Kopin, IJ AF Eisenhofer, G Lenders, JWM HarveyWhite, J Ernst, M Zametkin, A Murphy, DL Kopin, IJ TI Differential inhibition of neuronal and extraneuronal monoamine oxidase SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE monoamine oxidase; monoamine oxidase inhibitors; catecholamines; metabolism; norepinephrine; normetanephrine ID METABOLISM; PLASMA; 3,4-DIHYDROXYPHENYLALANINE; NOREPINEPHRINE; CATECHOLAMINES; LOCALIZATION; MOCLOBEMIDE; (-)DEPRENYL; CLORGYLINE; BRAIN AB This study examined whether the neuronal and extraneuronal sites of action of two monoamine oxidase (MAO) inhibitors, l-deprenyl and debrisoquin, could be distinguished by their effects on plasma concentrations of catecholamine metabolites. Plasma concentrations of the intraneuronal deaminated metabolite of norepinephrine, dihydroxyphenylglycol (DHPG), were decreased by 77% after debrisoquin and by 64% after l-deprenyl administration. Plasma concentrations of the extraneuronal O-methylated metabolite of norepinephrine, normetanephrine, were increased substantially more during treatment with l-deprenyl than with debrisoquin (255% compared to a 27% increase). The comparable decreased in plasma concentrations of DHPG indicate a similar inhibition of intraneuronal MAO by both drugs. Much larger increases in normetanephrine after l-deprenyl than after debrisoquin are consistent with a site of action of the latter drug directed at the neuronal rather than the extraneuronal compartment. Thus, differential changes in deaminated and O-methylated amine metabolites allows identification of neuronal and extraneuronal sites of action of MAO inhibitors. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIMH,CHILD PSYCHIAT BRANCH,NIH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,NIH,BETHESDA,MD 20892. UNIV NIJMEGEN ST RADBOUD HOSP,DEPT MED,DIV GEN INTERNAL MED,NL-6500 HB NIJMEGEN,NETHERLANDS. RI Lenders, J.W.M./L-4487-2015 NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 1996 VL 15 IS 3 BP 296 EP 301 DI 10.1016/0893-133X(95)00233-4 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA VD482 UT WOS:A1996VD48200009 PM 8873113 ER PT J AU Bell, MD Taub, DD Perry, VH AF Bell, MD Taub, DD Perry, VH TI Overriding the brain's intrinsic resistance to leukocyte recruitment with intraparenchymal injections of recombinant chemokines SO NEUROSCIENCE LA English DT Article DE chemokines; inflammation; leukocyte recruitment; blood-brain barrier; hippocampus; MIP-2 ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERCELLULAR-ADHESION MOLECULE; ACUTE INFLAMMATORY RESPONSE; CENTRAL-NERVOUS-SYSTEM; MONOCLONAL-ANTIBODY; CEREBRAL-ISCHEMIA; MESSENGER-RNA; POLYMORPHONUCLEAR LEUKOCYTES; DIFFERENTIAL REGULATION; ENDOTHELIAL-CELLS AB Following the intracranial injection of lipopolysaccharide or during acute neuronal degeneration, there is a paucity of polymorphonuclear leukocyte recruitment to the brain parenchyma and a delay in monocyte recruitment. The present study investigates whether the injection of specific leukocyte chemoattractants into the murine central nervous system can override this intrinsic resistance. Recombinant alpha-(IL-8/NAP-1, MIP-2, IP-10) and beta-chemokines (MCP-I, RANTES) were injected into the murine hippocampus and leukocyte recruitment was assessed histologically. Injections were also made into the dermis of the hind flank for comparison. At doses of I mu g, MCP-I was found to be the most potent monocyte chemoattractant in the brain parenchyma and skin with IP-IO and RANTES producing minimal monocyte recruitment to both sites. In contrast IL-8, and MIP-2 provoked dramatic polymorphonuclear leukocyte recruitment in both the central nervous system and skin. The polymorphonuclear leukocyte recruitment was associated with a breaching of the blood-brain barrier that was particularly severe after MIP-2. Both L-8 and MIP-2 induced blood-brain barrier breakdown could be attenuated by prior depletion of the circulating leukocytes. The regulation of polymorphonuclear leukocyte chemoattractants in the brain parenchyma during injury and infection is an important area for future studies. Copyright (C) 1996 Published by Elsevier Science Ltd. C1 UNIV OXFORD,DEPT PHARMACOL,OXFORD OX1 3QT,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,SAIC,FREDERICK,MD 21702. FU Wellcome Trust NR 40 TC 133 Z9 133 U1 0 U2 7 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 SEP PY 1996 VL 74 IS 1 BP 283 EP 292 DI 10.1016/0306-4522(96)00083-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA UZ332 UT WOS:A1996UZ33200023 PM 8843093 ER EF