FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Liu, XB Ambudkar, IS AF Liu, XB Ambudkar, IS TI Characteristics of a store-operated calcium-permeable channel - Sarcoendoplasmic reticulum calcium pump function controls channel gating SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID JURKAT T-LYMPHOCYTES; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; CAPACITATIVE CA2+ ENTRY; CURRENT I-CRAC; HTRP3 CHANNELS; CELLS; ACTIVATION; RELEASE; DEPLETION; INSP(3) AB We examined the single channel properties and regulation of store-operated calcium channels (SOCC). In human submandibular gland cells, carbachol (CCh) induced flickery channel activity while thapsigargin (Tg) induced burst-like activity, with relatively lower open probability (NPo) and longer mean open time. Tg- and CCh-activated channels were permeable to Na+ and Ba2+, but not to NTUDG, in the absence of Ca2+. The channels exhibited similar Ca2+, Na2+, and Ba2+ conductances and were inhibited by 2-aminoethoxydiphenylborate, xestospongin C, Gd3+, and La3+. CCh stimulated flickery activity changed to burst-like activity by (i) addition of Tg, (ii) using Na+ instead of Ca2+, (iii) using Ca2+-free bath solution, or (iv) buffering [Ca2+](i) with BAPTA-AM. Buffering [Ca2+](i) induced a 2-fold increase in NPo of Tg-stimulated SOCC. Reducing free [Ca2+] in the endoplasmic reticulum with the divalent cation chelator, N,N,N ' ,N ' -tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), induced burst-like channel activity similar to that seen with CCh + Tg. Thus, SOCC is activated by stimulation of muscarinic receptors, inhibition of the sarcoendoplasmic Ca2+ pump, and lowering [Ca2+] in the internal store. Importantly, SOCC activity depends on [Ca2+](i) and the free [Ca2+] in the internal store. These novel findings reveal that SERCA plays a major role in the gating of SOCC by (i) refilling the internal Ca2+ store(s) and (ii) decreasing the [Ca2+](i)-dependent inhibition. C1 NIDCR, GTTB, Secretory Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Ambudkar, IS (reprint author), NIDCR, GTTB, Secretory Physiol Sect, NIH, Bldg 10,Rm 1N-113, Bethesda, MD 20892 USA. NR 39 TC 41 Z9 42 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 29891 EP 29898 DI 10.1074/jbc.M103283200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000039 PM 11395504 ER PT J AU Arron, JR Vologodskaia, M Wong, BR Naramura, M Kim, N Gu, H Choi, Y AF Arron, JR Vologodskaia, M Wong, BR Naramura, M Kim, N Gu, H Choi, Y TI A positive regulatory role for Cbl family proteins in tumor necrosis factor-related activation-induced cytokine (TRANCE) and CD40L-mediated Akt activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; KAPPA-B ACTIVATION; N-TERMINAL KINASE; C-CBL; DENDRITIC CELLS; IN-VIVO; TYROSINE PHOSPHORYLATION; RING FINGER; T-CELLS; PHOSPHATIDYLINOSITOL-3 KINASE AB Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE) is a TNF family member essential for osteoclast differentiation, and it induces the activation and survival of osteoclasts and mature dendritic cells. We recently demonstrated that TRANCE activates Akt via a mechanism involving TRANCE receptor (TRANCE-R)/RANK, TRAF6, and c-Src. Here, we show that TRANCE-R and CD40 recruit TRAF6, Cbl family-scaffolding proteins, and the phospholipid kinase phosphatidylinositol 3-kinase in a ligand-dependent manner. The recruitment of Cbl-b and c-Cbl to TRANCE-R, is dependent upon the activity of Src-family kinases. TRANCE and CD40L-mediated Akt activation is defective in Cbl-b -/- dendritic cells, and CD40L-mediated Akt activation is defective in c-Cbl -/- B cells. These findings implicate Cbl family proteins as not only negative regulators of signaling but as positive modulators of TNF receptor superfamily signaling as well. C1 Rockefeller Univ, Immunol Lab, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. RP Choi, Y (reprint author), Rockefeller Univ, Immunol Lab, New York, NY 10021 USA. FU NIAID NIH HHS [AI-44264]; NIGMS NIH HHS [GM-07739] NR 45 TC 91 Z9 94 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 30011 EP 30017 DI 10.1074/jbc.M100414200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000054 PM 11406619 ER PT J AU Langland, G Kordich, J Creaney, J Goss, KH Lillard-Wetherell, K Bebenek, K Kunkel, TA Groden, J AF Langland, G Kordich, J Creaney, J Goss, KH Lillard-Wetherell, K Bebenek, K Kunkel, TA Groden, J TI The Bloom's syndrome protein (BLM) interacts with MLH1 but is not required for DNA mismatch repair SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNDROME GENE-PRODUCT; WERNERS-SYNDROME GENES; SACCHAROMYCES-CEREVISIAE; HOLLIDAY JUNCTIONS; TOPOISOMERASE-III; HELICASE ACTIVITY; SYNDROME CELLS; REPLICATION; RECOMBINATION; ASSOCIATION AB Bloom's syndrome (BS) is a rare autosomal recessive disorder characterized by pre- and postnatal growth deficiency, immunodeficiency, and a tremendous predisposition to a wide variety of cancers. Cells from BS individuals are characterized by a high incidence of chromosomal gaps and breaks, elevated sister chromatid exchange, quadriradial formations, and locus-specific mutations. BS is the consequence of mutations that lead to loss of function of BLM, a gene encoding a helicase with homology to the RecQ helicase family. To delineate the role of BLM in DNA replication, recombination, and repair we used a yeast two-hybrid screen to identify potential protein partners of the BLM helicase. The C terminus of BLM interacts directly with MLH1 in the yeast-two hybrid assay; far Western analysis and co-immunoprecipitations confirmed the interaction. Cell extracts deficient in BLM were competent for DNA mismatch repair. These data suggest that the BLM helicase and MLH1 function together in replication, recombination, or DNA repair events independent of single base mismatch repair. C1 Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Howard Hughes Med Inst, Cincinnati, OH 45267 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Groden, J (reprint author), Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. OI Goss, Kathleen/0000-0002-7379-5639 FU NCI NIH HHS [CA63507, CA59268-06A1]; NIEHS NIH HHS [ES06096] NR 29 TC 75 Z9 75 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 30031 EP 30035 DI 10.1074/jbc.M009664200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000057 PM 11325959 ER PT J AU Espey, MG Miranda, KM Thomas, DD Wink, DA AF Espey, MG Miranda, KM Thomas, DD Wink, DA TI Distinction between nitrosating mechanisms within human cells and aqueous solution SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; S-NITROSYLATION; IN-VIVO; KINETICS; OXYGEN; OXIDATION; GLUTATHIONE; THIOLS; INHIBITION; SUPEROXIDE AB The quintessential nitrosating species produced during NO autoxidation is N2O3. Nitrosation of amine, thiol, and hydroxyl residues can modulate critical cell functions. The biological mechanisms that control reactivity of nitrogen oxide species formed during autoxidation of nano- to micromolar levels of NO were examined using the synthetic donor NaEt2NN(O)NO (DEA/NO), hum an tumor cells, and 4,5-diaminofluorescein (DAF). Both the disappearance of NO and formation of nitrosated product from DAF in aerobic aqueous buffer followed second order processes; however, consumption of NO and nitrosation within intact cells were exponential. An optimal ratio of DEA/NO and 2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (PTIO) was used to form N2O3 through the intermediacy of NO2. This route was found to be most reflective of the nitrosative mechanism within intact cells and was distinct from the process that occurred during autoxidation of NO in aqueous media. Manipulation of the endogenous scavengers ascorbate and glutathione indicated that the location, affinity, and concentration of these substances were key determinants in dictating nitrosative susceptibility of molecular targets. Taken together, these findings suggest that the functional effects of nitrosation may be organized to occur within discrete domains or compartments. Nitrosative stress may develop when scavengers are depleted and this architecture becomes compromised. Although NO2 was not a component of aqueous NO autoxidation, the results suggest that the intermediacy of this species may be a significant factor in the advent of either nitrosation or oxidation chemistry in biological systems. C1 NCI, Radiat Biol Branch, NIH, Div Clin Sci, Bethesda, MD 20892 USA. RP Espey, MG (reprint author), NCI, Radiat Biol Branch, NIH, Div Clin Sci, Bldg 10,Rm B3-B69, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 52 TC 116 Z9 118 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 30085 EP 30091 DI 10.1074/jbc.M101723200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000065 PM 11404354 ER PT J AU Dimitrov, AS Xiao, XD Dimitrov, DS Blumenthal, R AF Dimitrov, AS Xiao, XD Dimitrov, DS Blumenthal, R TI Early intermediates in HIV-1 envelope glycoprotein-mediated fusion triggered by CD4 and co-receptor complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEMBRANE-FUSION; INFLUENZA HEMAGGLUTININ; CONFORMATIONAL-CHANGES; ATOMIC-STRUCTURE; LIPID BILAYERS; VIRAL MEMBRANE; COILED COILS; TYPE-1 GP120; SOLUBLE CD4 AB An early step in the process of HIV-1 entry into target cells is the activation of its envelope glycoprotein (GP120-GP41) to a fusogenic state upon binding to target cell CD4 and cognate co-receptor. Incubation of human immunodeficiency virus (HIV)-1 Env-expressing cells with an excess of CD4 and co-recepeptor-bearing target cells resulted in an influx of an impermeant nucleic acid-staining fluorescent dye into the Env-expressing cells. The dye influx occurred concomitant with cell fusion. No influx of dye into target cells was observed if they were incubated with an excess of Env-expressing cells. The permeabilization of Env-expressing cells was also triggered by CD4.co-receptor complexes attached to Protein G-Sepharose beads in the absence of target cells. The CD4 and co-receptor-induced permeabilization of Env-expressing cells occurred with the same specificity with respect to co-receptor usage as cell fusion. Natural ligands for the co-receptors and C-terminal GP41 peptide inhibitors of HIV-1 fusion blocked this effect. Our results indicate that the process of HIV-1 Env-mediated fusion is initiated by the destabilization of HIV-1 Env-expressing membranes. Further elucidation of these early intermediates may help identify and develop potential inhibitors of HIV-1 entry into cells. C1 NCI, Canc Res Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RP Blumenthal, R (reprint author), NCI, Canc Res Ctr, Lab Expt & Computat Biol, NIH, POB B,Bldg 469,Rm 216A,Miller Dr, Frederick, MD 21702 USA. NR 64 TC 43 Z9 45 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 30335 EP 30341 DI 10.1074/jbc.M103788200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000096 PM 11397808 ER PT J AU Montagnani, M Chen, H Barr, VA Quon, MJ AF Montagnani, M Chen, H Barr, VA Quon, MJ TI Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; RAT ADIPOSE-CELLS; ENDOTHELIAL GROWTH-FACTOR; PROTEIN-KINASE-B; LYSOPHOSPHATIDIC ACID; MICE LACKING; CA2+-INDEPENDENT ACTIVATION; THYMIDINE INCORPORATION; RECEPTOR SUBSTRATE-1; TRANSLOCATION AB Vasodilator actions of insulin are mediated by activation of endothelial nitric-oxide synthase (eNOS) and subsequent production of NO. Phosphatidylinositol 3-kinase and Akt play important roles in insulin-signaling pathways leading to production of NO in vascular endothelium. Here we dissected mechanisms whereby insulin activates eNOS by using the fluorescent dye DAF-2 to directly measure NO production in single cells. Insulin caused a rapid increase in intracellular NO in NIH-3T3(IR) cells transiently transfected with eNOS.. The stimulation of NO production by lysophosphatidic, acid (LPA) was abrogated by pretreatment of cells with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Remarkably, in the same cells, insulin-stimulated production of NO was unaffected. However, cells expressing the eNOS-S1179A mutant (disrupted Akt phosphorylation site) did not produce detectable NO in response to insulin, whereas the response to LPA was Similar to that observed in cells expressing wild-type eNOS. Moreover, production of NO in response to insulin was blocked by coexpression. of an inhibitory mutant of Akt, whereas the response to LPA was unaffected. Phosphorylation of eNOS at Ser(1179) was observed only in response to treatment with insulin, but not with LPA. Interestingly, platelet-derived growth factor treatment of cells activated Akt but not eNOS. Results from human vascular endothelial cells were qualitatively similar to those obtained in transfected NIH-3T3(IR) cells, although the magnitude of the responses was smaller. We conclude that insulin regulates eNOS activity using a Ca2+-independent mechanism requiring phosphorylation. of eNOS by Akt. Importantly, phosphorylation-dependent mechanisms that enhance eNOS activity can operate independently from Ca2+-dependent mechanisms. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Rm 8C-218,10 Ctr Dr,MSC 1755, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; montagnani, monica/0000-0002-5697-8185; Quon , Michael /0000-0002-5289-3707 NR 50 TC 334 Z9 350 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 30392 EP 30398 DI 10.1074/jbc.M103702200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000103 PM 11402048 ER PT J AU Ogushi, K Wada, A Niidome, T Mori, N Oishi, K Nagatake, T Takahashi, A Asakura, H Makino, S Hojo, H Nakahara, Y Ohsaki, M Hatakeyama, T Aoyagi, H Kurazono, H Moss, J Hirayama, T AF Ogushi, K Wada, A Niidome, T Mori, N Oishi, K Nagatake, T Takahashi, A Asakura, H Makino, S Hojo, H Nakahara, Y Ohsaki, M Hatakeyama, T Aoyagi, H Kurazono, H Moss, J Hirayama, T TI Salmonella enteritidis FliC (flagella filament protein) induces human beta-defensin-2 mRNA production by Caco-2 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; PSEUDOMONAS-AERUGINOSA; EPITHELIAL-CELLS; HUMAN MONOCYTES; BETA-DEFENSINS; TYPHI FLAGELLA; EXPRESSION; ACTIVATION; INDUCTION; ALPHA AB Antimicrobial peptides are crucial for host defense at mucosal surfaces. Bacterial factors responsible for induction of human beta -defensin-2 (hBD-2) mRNA expression in Caco-2 human carcinoma cells were determined. Salmonella enteritidis, Salmonella typhimurium, Salmonella typhi, Salmonella dublin, and culture supernatants of these strains induced hBD-2 mRNA expression in Caco-2 human carcinoma cells. Using luciferase as a reporter gene for a similar to2.1-kilobase pair hBD-2 promoter, the hBD-2-inducing factor in culture supernatant of S. enteritidis was isolated. The supernatant factor was heat-stable and proteinase-sensitive. After purification by anion exchange and gel filtration chromatography, the hBD-2-inducing factor was identified as a 53-kDa monomeric protein with the amino-terminal sequence AQVINTNSLSLLTQNNLNK, which is identical to that of the flagella filament structural protein (FliC) of S. enteritidis. Consistent with this finding, the 53-kDa protein reacted with anti-FliC antibody, which prevented its induction of hBD-2 mRNA in Caco-2 cells. In agreement, the hBD-2-inducing activity in culture supernatant was completely neutralized by anti-FliC antibody. In gel retardation analyses, FliC increased binding of NF-kappaB (p65 homodimer) to hBD-2 gene promoter sequences. We conclude that S. enteritidis FliC induces hBD-2 expression in Caco-2 cells via NF-kappaB activation and thus plays an important role in up-regulation of the innate immune response. C1 Nagasaki Univ, Dept Bacteriol, Nagasaki 8528523, Japan. Nagasaki Univ, Dept Prevent Med & AIDS Res, Nagasaki 8528523, Japan. Nagasaki Univ, Inst Trop Med, Dept Internal Med, Nagasaki 8528523, Japan. Nagasaki Univ, Dept Appl Chem, Fac Engn, Nagasaki 8528523, Japan. Univ Tokushima, Sch Med, Dept Nutr, Tokushima 7708503, Japan. Obihiro Univ Agr & Vet Med, Dept Vet Microbiol, Obihiro, Hokkaido 0808555, Japan. Tokai Univ, Dept Ind Chem, Hiratsuka, Kanagawa 2591292, Japan. Okayama Univ, Sch Med, Fac Hlth Sci, Okayama 7008558, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Dept Bacteriol, Sakamoto, Nagasaki 8528523, Japan. RI Niidome, Takuro/F-1508-2010; OI Niidome, Takuro/0000-0002-8070-8708; Hatakeyama, Tomomitsu/0000-0002-9505-1980 NR 27 TC 105 Z9 112 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 30521 EP 30526 DI 10.1074/jbc.M011618200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000120 PM 11387317 ER PT J AU Lee, CH Chung, JH AF Lee, CH Chung, JH TI The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE CHECKPOINT; DEPENDENT PROTEIN-KINASE; FHA DOMAIN; CATALYTIC SUBUNIT; CRYSTAL-STRUCTURE; HUMAN CDC25C; ATM PROTEIN; CHK2; LINKAGE; CDS1 AB hCds1 (Chk2) (1-4) is an evolutionarily conserved kinase that functions in DNA damage response and cell cycle checkpoint. The Cds1 family of kinases are activated by a family of large phosphatidylinositol 3-kinase-like kinases. In humans, ataxia telangiectasia-mutated (ATM) (5) and ataxia-telangiectasia and Rad3-related (6) kinases activate hCds1 by phosphorylating Thr(68) (7-9). hCds1 and Cds1-related kinases contain the FHA (fork. head-associated) domain (10), which appears to be important for integrating the DNA damage signal. It is not known how ATM phosphorylation activates hCds1 function and whether the phosphorylation is linked to the FHA. Here, we demonstrate that the hCds1-FHA domain is essential for Thr(68) phosphorylation. Thr(68) phosphorylation, in turn, is required for ionizing radiation-induced autophosphorylation of two amino acid residues in hCds1, Thr(383) and Thr(387). These two amino acid residues, located in the activation loop of hCds1, are conserved in hCds1-related kinases and are essential for hCds1 activity. Thus, the hCds1-FRA domain mediates a chain of phosphorylation events on hCds1, which includes phosphorylation by ATM and hCds1 autophosphorylation, in response to DNA damage. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Dept Pathol, Brain Korea Projects Med Sci 21, Seoul 120752, South Korea. RP Chung, JH (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 10-7D13,10 Ctr Dr, Bethesda, MD 20892 USA. NR 33 TC 111 Z9 115 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 30537 EP 30541 DI 10.1074/jbc.M104414200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000122 PM 11390408 ER PT J AU Siebenlist, U AF Siebenlist, U TI Signal transduction - Barriers come down SO NATURE LA English DT Editorial Material C1 NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAID, Immunoregulat Lab, Bldg 10, Bethesda, MD 20892 USA. NR 4 TC 10 Z9 12 U1 0 U2 0 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 9 PY 2001 VL 412 IS 6847 BP 601 EP 602 DI 10.1038/35088174 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 460PP UT WOS:000170318000026 PM 11493905 ER PT J AU Albrecht, MA Bosch, RJ Hammer, SM Liou, SH Kessler, H Para, MF Eron, J Valdez, H Dehlinger, M Katzenstein, DA AF Albrecht, MA Bosch, RJ Hammer, SM Liou, SH Kessler, H Para, MF Eron, J Valdez, H Dehlinger, M Katzenstein, DA CA AIDS Clin Trials Grp 364 Study Team TI Nelfinavir, efavirenz, or both after the failure of nucleoside treatment of HIV infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; PRIOR ANTIRETROVIRAL THERAPY; CD4 CELL COUNTS; COMBINATION THERAPY; CUBIC MILLIMETER; CONTROLLED TRIAL; DRUG-RESISTANCE; PLUS INDINAVIR; LAMIVUDINE; ZIDOVUDINE AB Background: The optimal antiretroviral treatment for patients who have human immunodeficiency virus (HIV) viremia despite treatment with nucleoside reverse-transcriptase inhibitors (nucleoside analogues) remains uncertain. We studied treatment with regimens that combined two nucleoside analogues, at least one of which was new, with the protease inhibitor nelfinavir, the nonnucleoside reverse-transcriptase inhibitor efavirenz, or both. Methods: The study included 195 patients who had been treated with nucleoside analogues only, and had a plasma HIV type 1 (HIV-1) RNA level of at least 500 copies per milliliter. Patients were randomly assigned to receive, in addition to two nucleoside analogues, nelfinavir, efavirenz, or nelfinavir plus efavirenz. The primary end point was a plasma HIV-1 RNA level of less than 500 copies per milliliter at week 16. A secondary end point was the composite of the HIV-1 RNA levels measured at weeks 40 and 48. Results: At week 16 and at weeks 40 and 48, the proportions of patients in whom a plasma HIV-1 RNA level of less than 500 copies per milliliter was achieved were, respectively, 81 percent and 74 percent in the nelfinavir-plus-efavirenz group, 69 percent and 60 percent in the efavirenz group, and 64 percent and 35 percent in the nelfinavir group. Quadruple therapy resulted in a higher rate of viral suppression in both the short term (P=0.03) and the long term (P=0.001) than did triple therapy with nelfinavir. Triple therapy with efavirenz conferred a higher rate of long-term suppression than triple therapy with nelfinavir (P=0.004). Quadruple therapy also achieved a higher rate of virologic suppression than triple therapy with efavirenz (P=0.008). Conclusions: In HIV-infected patients previously treated with nucleoside analogues, treatment with nelfinavir plus efavirenz and at least one new nucleoside analogue achieves a higher rate of viral suppression than do regimens with nucleoside analogues and nelfinavir or efavirenz alone. (N Engl J Med 2001;345:398-407. Copyright (C) 2001 Massachusetts Medical Society. C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Rush Med Coll, Chicago, IL 60612 USA. Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Univ N Carolina, Chapel Hill, NC USA. Case Western Reserve Univ, Sch Med, Cleveland, OH USA. NIAID, HIV Res Branch, Div AIDS, Bethesda, MD 20892 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Albrecht, MA (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 1 Deaconess Rd,Kennedy 6, Boston, MA 02215 USA. FU NIAID NIH HHS [AI-25924, AI-27664]; PHS HHS [U01 A127659] NR 24 TC 97 Z9 98 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 9 PY 2001 VL 345 IS 6 BP 398 EP 407 DI 10.1056/NEJM200108093450602 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 460EJ UT WOS:000170295000002 PM 11496850 ER PT J AU Pine, DS Walkup, JT Greenhill, L AF Pine, DS Walkup, JT Greenhill, L CA Res Unit Pediat Psychopharmacology TI Fluvoxamine for the treatment of anxiety disorders in children and adolescents. Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID RISK C1 NIMH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21287 USA. Columbia Univ, New York, NY 10032 USA. RP Pine, DS (reprint author), NIMH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 9 PY 2001 VL 345 IS 6 BP 466 EP 467 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 460EJ UT WOS:000170295000019 ER PT J AU Fan, SJ Yuan, RQ Ma, YX Xiong, JB Meng, QH Erdos, M Zhao, JN Goldberg, ID Pestell, RG Rosen, EM AF Fan, SJ Yuan, RQ Ma, YX Xiong, JB Meng, QH Erdos, M Zhao, JN Goldberg, ID Pestell, RG Rosen, EM TI Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding SO ONCOGENE LA English DT Article DE BRCA1; retinoblastoma; RB; p107; p130; p300 ID TUMOR-SUPPRESSOR; RETINOBLASTOMA PROTEIN; CELL-CYCLE; HISTONE DEACETYLASE; ALPHA-SUBUNIT; GENE-PRODUCT; P53; APOPTOSIS; TRANSCRIPTION; PROLIFERATION AB The tumor suppressor activity of the BRCA1 gene product is due, in part, to functional interactions with other tumor suppressors, including p53 and the retinoblastoma (RB) protein. RB binding sites on BRCA1 were identified in the C-terminal BRCT domain (Yarden and Brody, 1999) and in the N-terminus (aa 304-394) (Aprelikova et al., 1999). The N-terminal site contains a consensus RB binding motif, LXCXE (aa 358-362), but the role of this motif in RB binding and BRCA1 functional activity is unclear. In both in vitro and in vivo assays, we found that the BRCA1:RB interaction does not require the BRCA1 LXCXE motif, nor does it require an intact A/B binding pocket of RB. In addition, nuclear co-localization of the endogenous BRCA1 and RB proteins was observed. Over-expression of wild-type BRCA1 (wtBRCA1) did not cause cell cycle arrest but did cause down-regulation of expression of RB, p107, p130, and other proteins (e.g., p300), associated with increased sensitivity to DNA-damaging agents. In contrast, expression of a full-length BRCA1 with an LXCXE inactivating mutation (LXCXE-->RXRXH) failed to down-regulate RB, blocked the down-regulation of RB by wtBRCA1, induced chemoresistance, and abrogated the ability of BRCA1 to mediate tumor growth suppression of DU-145 prostate cancer cells. wtBRCA1-induced chemosensitivity was partially reversed by expression of either Rb or p300 and fully reversed by co-expression of Rb plus p300. Our findings suggest that: (I) disruption of the LXCXE motif within the N-terminal RB binding region alters the biologic function of BRCA1; and (2) over-expression of BRCA1 inhibits the expression of RB and RB family (p107 and p130) proteins. C1 Albert Einstein Coll Med, Long Isl Jewish Med Ctr, Dept Radiat Oncol, New Hyde Pk, NY 11040 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Radiat Oncol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Div Hormone Dependent Tumor Biol, Bronx, NY 10461 USA. RP Fan, SJ (reprint author), Albert Einstein Coll Med, Long Isl Jewish Med Ctr, Dept Radiat Oncol, Long Isl Campus,270-05 76th Ave, New Hyde Pk, NY 11040 USA. FU NCI NIH HHS [R01-CA82599, R01-CA80000]; NIEHS NIH HHS [R01-ES09169] NR 51 TC 34 Z9 36 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 9 PY 2001 VL 20 IS 35 BP 4827 EP 4841 DI 10.1038/sj.onc.1204666 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 459VH UT WOS:000170271800007 PM 11521194 ER PT J AU Lerman, C Caporaso, NE Bush, A Zheng, YL Audrain, J Main, D Shields, PG AF Lerman, C Caporaso, NE Bush, A Zheng, YL Audrain, J Main, D Shields, PG TI Tryptophan hydroxylase gene variant and smoking behavior SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE genetics; tobacco; smoking; nicotine ID POLYMORPHISM; SUICIDALITY AB Approximately 50% of the variance in smoking behavior is attributable to genetic factors. Genes in the serotonin system are plausible candidates because of serotonin's role in mood regulation. The present study examined the association of smoking behavior with a polymorphism in the TPH gene, which codes for a rate limiting enzyme in the biosynthesis of serotonin. A polymorphism in intron 7 has been linked with a variety of traits involving poor impulse control. Participants in this study were 249 Caucasian smokers and 202 nonsmokers recruited through newspaper advertisements. Smokers completed smoking history and nicotine dependence assessments. The overall frequencies of the A- and C-allele were 42% and 58%, respectively. There was no association of TPH alleles with smoking status. However, case series analysis indicated that individuals with the A/A genotype started smoking at age 15.6 years, compared with 17.3 years among smokers with other genotypes. This association was significant in a multivariate regression model controlling for age, education, body mass index (BAH), alcohol use, and medication use. This finding is consistent with previous studies relating the A-allele to impulsive behavior and suggests that it may predispose to early smoking initiation. Future family-based studies are needed to con-firm this finding. Published 2001 Wiley-Liss, Inc(dagger). C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Div Canc Epidemiol & Genet, Washington, DC 20007 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 USA. NCI, Div Canc Epidemiol & Genet, Pharmacogenet Sect, Rockville, MD USA. Univ Penn Hlth Solences, Dept Psychiat, Philadelphia, PA 19104 USA. RP Lerman, C (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Div Canc Epidemiol & Genet, 2233 Wisconsin Ave NW,Suite 317, Washington, DC 20007 USA. RI Shields, Peter/I-1644-2012 NR 11 TC 57 Z9 58 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD AUG 8 PY 2001 VL 105 IS 6 BP 518 EP 520 DI 10.1002/ajmg.1476 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 459HG UT WOS:000170244500006 PM 11496367 ER PT J AU Simons-Morton, DG Blair, SN King, AC Morgan, TM Applegate, WB O'Toole, M Haskell, WL Albright, CL Cohen, SJ Ribisl, PM Shih, JH AF Simons-Morton, DG Blair, SN King, AC Morgan, TM Applegate, WB O'Toole, M Haskell, WL Albright, CL Cohen, SJ Ribisl, PM Shih, JH CA Writing Grp Activity Counseling Tr TI Effects of physical activity counseling in primary care - The activity counseling trial: A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ALL-CAUSE MORTALITY; AMERICAN-HEART-ASSOCIATION; CARDIORESPIRATORY FITNESS; ACTIVITY PROGRAMS; HEALTH PROMOTION; CARDIAC REHABILITATION; CLINICAL CARDIOLOGY; EXERCISE; MEN; WOMEN AB Context Physical activity is important for health, yet few studies have examined the effectiveness of physical activity patient counseling in primary care. Objective To compare the effects of 2 physical activity counseling interventions with current recommended care and with each other in a. primary care setting. Design The Activity Counseling Trial, a randomized controlled trial with recruitment in 1995-1997, with 24 months of follow-up. Setting Eleven primary care facilities affiliated with 3 US clinical research centers. Participants Volunteer sample of 395 female and 479 male inactive primary care patients aged 35 to 75 years without clinical cardiovascular disease. Interventions Participants were randomly assigned to 1 of 3 groups: advice (n=292), which included physician advice and written educational materials (recommended care); assistance (n=293),,which included all the components received by the advice group plus interactive mail and behavioral counseling at physician visits; or counseling (n=289), which included the assistance and advice group components plus regular telephone counseling and behavioral classes. Main Outcome Measures Cardiorespiratory fitness, measured by maximal oxygen uptake ((V)over dotO(2)max) and self-reported total physical activity, measured by a 7-day Physical Activity Recall, compared among the 3 groups and analyzed separately for men and women at 24 months. Results At 24 months, 91.4% of the sample had completed physical activity and 77.6% had completed cardiorespiratory fitness measurements. For women at 24 months, (V)over dotO(2)max was significantly higher in the assistance group than in the advice group (mean difference, 80.7 mL/min; 99.2% confidence interval [CI], 8.1-153.2 mL/min) and in the counseling group than in the advice group (mean difference, 73.9 mL/min; 99.2% CI, 0.9-147.0 mL/min), with no difference between the counseling and assistance groups and no significant differences in reported total physical activity. For men, there were no significant between-group differences in cardiorespiratory fitness or total physical activity. Conclusions Two patient counseling interventions differing in type and number of contacts were equally effective in women in improving cardiorespiratory fitness over 2 years compared with recommended care. In men, neither of the 2 counseling interventions was more effective than recommended care. C1 NHLBI, Clin Applicat & Prevent Program, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Inst Aerobics Res, Dallas, TX USA. San Diego State Univ, San Diego, CA 92182 USA. Brown Univ, Providence, RI 02912 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Univ Tennessee, Memphis, TN USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27109 USA. Penn Med Labs, Washington, DC USA. RP Simons-Morton, DG (reprint author), NHLBI, Clin Applicat & Prevent Program, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. NR 56 TC 224 Z9 228 U1 3 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 8 PY 2001 VL 286 IS 6 BP 677 EP 687 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 459VE UT WOS:000170271500023 ER PT J AU Krylov, DM Koonin, EV AF Krylov, DM Koonin, EV TI A novel family of predicted retroviral-like aspartyl proteases with a possible key role in eukaryotic cell cycle control SO CURRENT BIOLOGY LA English DT Letter ID PROTEIN; SEQUENCE; YEAST C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 21 TC 32 Z9 32 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 7 PY 2001 VL 11 IS 15 BP R584 EP R587 DI 10.1016/S0960-9822(01)00357-8 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 461HZ UT WOS:000170360000004 PM 11516960 ER PT J AU Zaks-Zilberman, M Zaks, TZ Vogel, SN AF Zaks-Zilberman, M Zaks, TZ Vogel, SN TI Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (Taxol (TM)) in murine and human breast cancer cell lines SO CYTOKINE LA English DT Article DE breast cancer; inflammatory genes; LPS; macrophages; paclitaxel ID COLONY-STIMULATING FACTOR; NECROSIS-FACTOR PRODUCTION; MONOPHOSPHORYL LIPID-A; HUMAN OVARIAN-CANCER; NF-KAPPA-B; MESSENGER-RNA; NITRIC-OXIDE; IN-VIVO; MACROPHAGES; EXPRESSION AB In murine macrophages, the anti-tumor agent, paclitaxel, induces expression of a wide variety of inflammatory and anti-inflammatory genes, and causes cytokine secretion via signaling pathways that overlap with those engaged by lipopolysaccharide (LPS), the endotoxic component of Gram-negative bacteria. Using semi-quantitative RT-PCR for detection of gene expression, coupled with ELISA for the detection of secreted gene products, we analyzed the responsiveness of an extensive panel of cytokine and non-cytokine genes to induction by paclitaxel and LPS in the murine DA-3 breast cancer line. A subset of the genes examined (e.g., G-CSF, MIP-2, iNOS, and EL-1 beta, and GM-CSF) was upregulated >3-20-fold by both LPS and paclitaxel in the DA-3 cell line, while IP-10 mRNA was induced by paclitaxel, but not by LPS. In the human MDA-MB-231 breast cancer cell line, LPS also increased mRNA levels for both GM-CSF and IP-10 significantly, while, paclitaxel increased IP-10 mRNA levels with delayed kinetics and failed to induce GM-CSF mRNA. Co-cultures of murine breast cancer cells and macrophages, stimulated with IFN-gamma plus either paclitaxel or LPS, resulted in augmented release of nitric oxide. As both GM-CSF and IP-10 have been implicated in tumor rejection in vivo through either indirect actions on the host immune system or by inhibiting tumor angiogenesis, our data strengthen the hypothesis that tumor cell-derived inflammatory mediators may, in part, underlie the anti-tumor efficacy of paclitaxel in breast cancer. (C) 2001 Academic Press. C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Vogel, SN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU NIAID NIH HHS [AI-18797] NR 53 TC 54 Z9 59 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1043-4666 J9 CYTOKINE JI Cytokine PD AUG 7 PY 2001 VL 15 IS 3 BP 156 EP 165 DI 10.1006/cyto.2001.0935 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 473WA UT WOS:000171070700005 PM 11554785 ER PT J AU Epand, RF Yip, CM Chernomordik, LV LeDuc, DL Shin, YK Epand, RM AF Epand, RF Yip, CM Chernomordik, LV LeDuc, DL Shin, YK Epand, RM TI Self-assembly of influenza hemagglutinin: studies of ectodomain aggregation by in situ atomic force microscopy SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE atomic force microscopy; membrane fusion; bromelain-cleaved hemagglutinin; protein-lipid interactions ID INDUCED CONFORMATIONAL CHANGE; SIALO-SUGAR CHAINS; VIRUS HEMAGGLUTININ; MEMBRANE-FUSION; LOW-PH; GANGLIOSIDES; RESOLUTION; MECHANISM; KINETICS; PROTEINS AB We have used in situ tapping mode atomic force microscopy (AFM) to study the structural morphology of two fragments of the influenza hemagglutinin protein bound to supported bilayers. The two proteins that we studied are the bromelain-cleaved hemagglutinin (BHA), corresponding to the full ectodomain of the hemagglutinin protein. and FHA2, the 127 amino acid N-terminal fragment of the HA2 subunit of the hemagglutinin protein. While BHA is water soluble at neutral pH and is known to bind to membranes via specific interactions with a viral receptor, FHA2 can only be solubilized in water with an appropriate detergent. Furthermore, FHA2 is known to readily bind to membranes at neutral pH in the absence of a receptor. Our in situ AFM studies demonstrated that, when bound to supported bilayers at neutral pH, both these proteins are self-assembled as single trimeric molecules. In situ acidification resulted in further lateral association of the FHA2 without a large perturbation of the bilayer. In contrast, BHA remained largely unaffected by acidification, except in areas of exposed mica where it is aggregated. Remarkably, these results are consistent with previous observations that FHA2 promotes membrane fusion while BHA only induces liposome leakage at low pH. The results presented here are the first example of in situ imaging of the ectodomain of a viral envelope protein allowing characterization of the real-time self-assembly of a membrane fusion protein. (C) 2001 Elsevier Science BN. All rights reserved. C1 McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. Univ Toronto, Dept Chem Engn & Appl Chem, Inst Biomat & Biomed Engn, Toronto, ON M5S 3G9, Canada. NICHD, Sect Membrane Biol, LCMB, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. Iowa State Univ Sci & Technol, Dept Biochem & Biophys, Ames, IA 50011 USA. RP Epand, RM (reprint author), McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. OI Yip, Christopher/0000-0003-4507-556X NR 37 TC 27 Z9 29 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD AUG 6 PY 2001 VL 1513 IS 2 BP 167 EP 175 DI 10.1016/S0005-2736(01)00350-9 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 457LF UT WOS:000170138000007 PM 11470088 ER PT J AU McPartland, J Di Marzo, V De Petrocellis, L Mercer, A Glass, M AF McPartland, J Di Marzo, V De Petrocellis, L Mercer, A Glass, M TI Cannabinoid receptors are absent in insects SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cannabinoid receptors; neurotransmitters; anandamide; tetrahydrocannabinol; GTP gamma s; fatty acid amide hydrolase; sequencing analysis; insects; Cannabis ID ACID AMIDE HYDROLASE; APIS-MELLIFERA BRAIN; LYSINE RESIDUE; BINDING; ENDOCANNABINOIDS; RAT; CB1; MODULATION; ANANDAMIDE; WIN55212-2 AB The endocannabinoid system exerts an important neuromodulatory role in mammals. Knockout mice lacking cannabinoid (CB) receptors exhibit significant morbidity. The endocannabinoid system also appears to be phylogenetically ancient-it occurs in mammals, birds, amphibians, fish, sea urchins, leeches, mussels, and even the most primitive animal with a nerve network, the Hydra. The presence of CB receptors, however, has not been examined in terrestrial invertebrates (or any member of the Ecdysozoa). Surprisingly, we found no specific binding of the synthetic CB ligands [H-3]CP55,940 and [H-3]SR141716A in a panel of insects: Apis mellifera, Drosophila melanogaster, Gerris marginatus, Spodoptera frugiperda, and Zophobas atratus. A lack of functional CB receptors was confirmed by the inability of tetrahydrocannabinol (THC) and HU210 to activate G-proteins in insect tissues, utilizing a guanosine-5'-O-(3- [(35)]thio)-triphosphate (GTP gammaS) assay. No orthologs of human CB receptors were located in the Drosophila genome, nor did we find orthologs of fatty acid amide hydrolase. This loss of CB receptors appears to be unique in the field of comparative neurobiology. No other known mammalian neuroreceptor is understood to be missing in insects. We hypothesized that CB receptors were lost in insects because of a dearth of ligands; endogenous CB ligands are metabolites of arachidonic acid, and insects produce little or no arachidonic acid or endocannabinoid ligands, such as anandamide, J. Comp. Neurol. 436: 423-429, 2001. (C) 2001 Wiley-Liss, Inc. C1 GW Pharmaceut Ltd, Salisbury SP4 0JQ, Wilts, England. CNR, Ist Chim Mol Interesse Biol, Endocannabinoid Res Grp, I-80072 Naples, Italy. CNR, Ist Cibernet, I-80072 Naples, Italy. Univ Otago, Dept Zool, Dunedin, New Zealand. NIDCD, Cell Biol Lab, Rockville, MD 20850 USA. RP McPartland, J (reprint author), UNITEC, Fac Hlth & Environm Sci, Private Bag 92025, Auckland, New Zealand. OI Mercer, Alison/0000-0001-8110-4247; Glass, Michelle/0000-0002-5997-6898 NR 45 TC 45 Z9 48 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 6 PY 2001 VL 436 IS 4 BP 423 EP 429 DI 10.1002/cne.1078 PG 7 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 450PK UT WOS:000169752200004 PM 11447587 ER PT J AU Valenzuela, JG Belkaid, Y Garfield, MK Mendez, S Kamhawi, S Rowton, ED Sacks, DL Ribeiro, JMC AF Valenzuela, JG Belkaid, Y Garfield, MK Mendez, S Kamhawi, S Rowton, ED Sacks, DL Ribeiro, JMC TI Toward a defined anti-Leishmania vaccine targeting vector antigens: Characterization of a protective salivary protein SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE DNA vaccine; salivary gland; sand fly; Leishmania; leishmaniasis ID CUTANEOUS LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS; RHODNIUS-PROLIXUS; HISTAMINE-BINDING; MAJOR INFECTION; NATURAL MODEL; SAND FLIES; MICE; IMMUNITY; MECHANISM AB Lcislunania parasites are transmitted to their vertebrate hosts by infected phlebotomine sand fly bites. Sand fly saliva is known to enhance Leislimania infection, while immunity to the saliva protects against infection as determined by coinoculation of parasites with vector salivary gland homogenates (SGHs) or by infected sand fly bites (Kamhawi, S., Y. Belkaid, G. Modi, E. Rowton, and D. Sacks. 2000. Science. 290:1351-1354). We have now characterized nine salivary proteins of Phlebotomus papatasi, the vector of Leishmania major. One of these salivary proteins, extracted from SDS gels and having an apparent mol wt of 15 kD, was able to protect vaccinated mice challenged with parasites plus SGH. A DNA vaccine containing the cDNA for the predominant 15-kD protein (named SP15) provided this same protection. Protection lasted at least 3 ino after immunization. The vaccine produced both intense humoral and delayed-type hypersensitivity (DTH) reactions. B cell-deficient mice immunized with the SP15 plasmid vaccine successfully controlled Leislimania infection when injected with Leislimania plus SGH. These results indicate that DTH response against saliva provides most or all of the protective effects of this vaccine and that salivary gland proteins or their cDNAs are viable vaccine targets against leishmaniasis. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Res Technol Branch, Rockville, MD 20852 USA. Walter Reed Army Inst Res, Dept Entomol, Washington, DC 20307 USA. RP Ribeiro, JMC (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Rm 4-126, Bethesda, MD 20892 USA. RI Rowton, Edgar/A-1975-2011; Rowton, Edgar/A-4474-2012; OI Rowton, Edgar/0000-0002-1979-1485; Ribeiro, Jose/0000-0002-9107-0818 NR 45 TC 231 Z9 237 U1 0 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 6 PY 2001 VL 194 IS 3 BP 331 EP 342 DI 10.1084/jem.194.3.331 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 461UQ UT WOS:000170382200012 PM 11489952 ER PT J AU Lee, CG Kinoshita, K Arudchandran, A Cerritelli, SM Crouch, RJ Honjo, T AF Lee, CG Kinoshita, K Arudchandran, A Cerritelli, SM Crouch, RJ Honjo, T TI Quantitative regulation of class switch recombination by switch region transcription SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE secondary structures; recombinase; artificial constructs; tet inducible promoter; B lymphoma line ID CYTIDINE DEAMINASE AID; HEAVY-CHAIN SWITCH; SOMATIC HYPERMUTATION; DNA-SEQUENCES; B-CELLS; IMMUNOGLOBULIN; GENE; EXPRESSION; MUTATION; PROMOTER AB The isotype specificity of immunoglobulin (Ig) class switching is regulated by a cytokine which induces transcription of a specific switch (S) region, giving rise to so-called germline transcripts. Although previous studies have demonstrated that germline transcription of an S region is required for class switch recombination (CSR) of that particular S region, it has not been shown whether the level of S region transcription affects the efficiency of CSR. We addressed this question by using an artificial DNA construct containing a constitutively transcribed mu switch (S mu) region and an alpha switch (S alpha) region driven by a tetracycline-responsive promoter. The construct was introduced into a switch-inducible B lymphoma line and the quantitative correlation between Sot region transcription and class switching efficiency was evaluated. The level of Su transcription was linearly correlated with CSR efficiency, reaching a plateau at saturation. On the other hand, we failed to obtain the evidence to support involvement of either RNA-DNA heteroduplex or trans germline transcripts in CSR Taken together, it is likely that S region transcription and/or transcript processing in situ may be required for CSR. We propose that because of the unusual properties of S region DNA, transcription induces the DNA to transiently be single stranded, permitting secondary structure(s) to form. Such structures may be recognition targets of a putative class switch recombinase. C1 Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Honjo, T (reprint author), Kyoto Univ, Grad Sch Med, Dept Med Chem, Sakyo Ku, Kyoto 6068501, Japan. RI Honjo, Tasuku/N-4470-2016 NR 44 TC 48 Z9 48 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD AUG 6 PY 2001 VL 194 IS 3 BP 365 EP 373 DI 10.1084/jem.194.3.365 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 461UQ UT WOS:000170382200015 PM 11489955 ER PT J AU Ben-Shaul, V Lomnitski, L Nyska, A Zurovsky, Y Bergman, M Grossman, S AF Ben-Shaul, V Lomnitski, L Nyska, A Zurovsky, Y Bergman, M Grossman, S TI The effect of natural antioxidants, NAO and apocynin, on oxidative stress in the rat heart following LPS challenge SO TOXICOLOGY LETTERS LA English DT Article DE heart; LPS; oxidative stress; NADPH oxidase; superoxide dismutase ID WATER-SOLUBLE ANTIOXIDANT; SEPTIC SHOCK; LIPID-PEROXIDATION; ISCHEMIA-REPERFUSION; LABORATORY MODELS; IMPROVES SURVIVAL; FREE-RADICALS; IN-VIVO; LIPOPOLYSACCHARIDE; ENDOTOXIN AB Oxidative damage plays a key role in septic shock induced by lipopolysaccharide (LPS) which is known to enhance the formation of reactive oxygen species (ROS). In this study, biochemical parameters indicative of oxidative stress were tested in the rat heart following LPS challenge, with and without pretreatment with the antioxidants NAO (natural antioxidant) and apocynin. NAO is a natural antioxidant isolated and purified from spinach and its main components are flavonoids and coumaric acid derivatives. Treatment with LPS alone significantly (P < 0.05) increased the malondialdehyde (MDA) level in heart, both in cytosolic and mitochondrial fractions by 1.5- and 2.4-fold, respectively, and in plasma (2.66 fold). In the heart homogenate, the level of hydroperoxides also increased significantly (P < 0.05). In addition, LPS treatment significantly (P < 0.05) increased NADPH oxidase activity in the heart microsomal fraction by approximately 10-fold compared to control. Pretreatment for 7 days with either apocynin or NAO prior to the LPS challenge significantly (P < 0.05) improved rat survival, decreased MDA levels in both fractions and decreased microsomal NADPH-oxidase activity, compared to LPS alone. Catalase (CAT) activity slightly increased at 24 h post-LPS injection in LPS group and returned to the control level in the apocynin treated group. No meaningful changes were indicated for glutathione peroxidase activity among all the treatment groups. The activities - of cytosolic and mitochondrial superoxide dismutase (SOD) enzymes significantly (P < 0.05) increased approximately 20% in the LPS-treated group, compared to control. Apocynin significantly (P < 0.05) decreased SOD level in the mitochondrial fraction with no effect on the cytosolic fraction; whereas, NAO had no important effect on SOD level in both fractions. The beneficial pretreatment effects of the antioxidants against oxidative stress in the rat heart presented in this study may suggest a potential chemopreventive effect of this compound in sepsis prevention. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NIEHS, Res Triangle Pk, NC 27709 USA. RP Grossman, S (reprint author), Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. EM grossms@mail.biu.ac.il NR 46 TC 76 Z9 77 U1 0 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG 6 PY 2001 VL 123 IS 1 BP 1 EP 10 DI 10.1016/S0378-4274(01)00369-1 PG 10 WC Toxicology SC Toxicology GA 469ET UT WOS:000170802200001 PM 11514100 ER PT J AU Lavery, JV Boyle, J Dickens, BM Maclean, H Singer, PA AF Lavery, JV Boyle, J Dickens, BM Maclean, H Singer, PA TI Origins of the desire for euthanasia and assisted suicide in people with HIV-1 or AIDS: a qualitative study SO LANCET LA English DT Article ID TERMINALLY ILL; NETHERLANDS; ATTITUDES; DEATH; CARE; CAREGIVERS AB Background Euthanasia and assisted suicide, and policies to address them are the subjects of contentious debate in many countries. However, the question of why people desire euthanasia or assisted suicide has not been coherently answered. We aimed to answer this question in a specific group of patients. Methods We did a qualitative study of 32 people with HIV-1 or AIDS, who were enrolled in the HIV-1 Ontario Observational Database at Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada. We elicited participants' experiences of deliberation about euthanasia or assisted suicide, and the meaning of these experiences with in-depth, face-to-face interviews. We analysed our data with grounded theory methods. Findings Participants' desire for euthanasia and assisted suicide were affected by two main factors: disintegration, which resulted from symptoms and loss of function; and loss of community, which we defined as progressive diminishment of opportunities to initiate and maintain close personal relationships. These factors resulted in perceived loss of self. Euthanasia and assisted suicide were seen by participants as means of limiting loss of self. Interpretation These determinants of desire for euthanasia or assisted suicide in people with HIV-1 or AIDS have implications for the debate on these practices, and development of policies to regulate them. C1 Univ Toronto, Joint Ctr Bioeth, Toronto, ON, Canada. Queens Univ, Queens Hlth Policy Res Unit, Kingston, ON, Canada. Univ Toronto, Fac Law, Dept Philosophy, Toronto, ON M5S 1A1, Canada. Univ Toronto, Fac Publ Hlth Sci, Toronto, ON M5S 1A1, Canada. Univ Toronto, Ctr Res Womens Hlth, Toronto, ON M5S 1A1, Canada. Univ Toronto, Dept Med, Toronto, ON M5S 1A1, Canada. Univ Hlth Network, Toronto, ON, Canada. RP Lavery, JV (reprint author), NIH, Fogarty Int Ctr, Div Adv Studies & Policy Anal, Bldg 16, Bethesda, MD 20892 USA. RI Lavery, James/E-5254-2012 NR 30 TC 57 Z9 57 U1 1 U2 12 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD AUG 4 PY 2001 VL 358 IS 9279 BP 362 EP 367 DI 10.1016/S0140-6736(01)05555-6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 459DE UT WOS:000170235100010 PM 11502315 ER PT J AU Wellner, RB Baum, BJ AF Wellner, RB Baum, BJ TI Polarized sorting of aquaporins 5 and 8 in stable MDCK-II transfectants SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE aquaporin; MDCK; cultured epithelial cell; apical membrane; basolateral membrane; water transport ID EPITHELIAL-CELLS; WATER CHANNELS; LACRIMAL GLANDS; RAT SALIVARY; EXPRESSION; MEMBRANE; IMMUNOLOCALIZATION; SECRETION; BIOLOGY AB Localization of aquaporin (AQP) water channels to either apical or basolateral membranes is important for various epithelial functions. We have established MDCK-II cell transfectants stably expressing AQP5 (RW5 cells) or AQP8 (RW8 cells). The expression of both AQPs was confirmed by the results of immunofluorescence microscopy and immunoblot analysis. When grown on polycarbonate filters, osmotically-obliged transepithelial water flow across RW5 and RW8 monolayers was similar to3-fold greater than that occurring across a monolayer of the parental cell line. Importantly, results of confocal immunofluorescence microscopy studies showed that AQP5 sorted to the apical membranes of RW5 cells. In contrast, AQP8 sorted to the basolateral membranes of RW8 cells. This is the first report of (i) stable epithelial cell cultures exhibiting a functional, polarized distribution of AQPs 5 and 8, and (ii) a basolateral localization of AQP8 in a polarized epithelial cell. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Wellner, RB (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1A01,10 Ctr Dr,MSC 1190, Bethesda, MD 20892 USA. NR 33 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 3 PY 2001 VL 285 IS 5 BP 1253 EP 1258 DI 10.1006/bbrc.2001.5287 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 460GY UT WOS:000170300900030 PM 11478792 ER PT J AU Alileche, A Goldman, CK Waldmann, TA AF Alileche, A Goldman, CK Waldmann, TA TI Differential effects of IL-2 and IL-15 on expression of IL-2 receptor alpha SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE IL-2; IL-15; receptor; expression; transcription; translocation; cytokines; cytokines receptors; cellular activation; NK cells ID T-CELL LEUKEMIA; BLOOD MONONUCLEAR-CELLS; ACTIVATED KILLER-CELLS; TUMOR NECROSIS FACTOR; LINE YT-CELLS; INTERLEUKIN-2 RECEPTOR; MESSENGER-RNA; TAC ANTIGEN; INTRACYTOPLASMIC DETECTION; LYMPHOCYTES-T AB IL-2 and IL-15 have overlapping functions since they share the IL-2R beta gamma receptor complex. However, each cytokine has a private a receptor namely IL-2R alpha for IL-2 and IL-15R alpha for IL-15. As a consequence the effects of the two cytokines may differ. We describe the differential effects of the two cytokines regarding the induction of cell surface expression of the IL-2R alpha subunit on YT-1 cells. Both cytokines induced transcription of the IL-2R alpha gene. Furthermore translation of IL-2R alpha leading to intracellular expression of the receptor was observed following either IL-2 or IL-15 addition. However, only IL-15 was associated with the induction of cell surface expression of IL-2R alpha. With IL-2 there appears to be an impediment to the translocation of IL-2R alpha to the cell membrane. Since surface expression of IL-2R alpha is a key element in the formation of the high affinity IL-2 receptor, translocation of IL-2R alpha to the membrane represents another level of control of the immune response in addition to regulation of IL-2R alpha transcription and translation. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, NIH, 10 Ctr Dr 1374,Rm 4N115,Bldg 10, Bethesda, MD 20892 USA. NR 44 TC 16 Z9 17 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 3 PY 2001 VL 285 IS 5 BP 1302 EP 1308 DI 10.1006/bbrc.2001.5332 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 460GY UT WOS:000170300900037 PM 11478799 ER PT J AU Hu, B Copeland, NG Gilbert, DJ Jenkins, NA Kilimann, MW AF Hu, B Copeland, NG Gilbert, DJ Jenkins, NA Kilimann, MW TI The paralemmin protein family: Identification of paralemmin-2, an isoform differentially spliced to AKAP2/AKAP-KL, and of palmdelphin, a more distant cytosolic relative SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE paralemmin; membrane dynamics; gene structure; AKAP; A kinase anchor protein; protein kinase A; differential splicing; mouse genetics; chromosomal mapping; fusion protein ID MEMBRANE AB Paralemmin is a protein implicated in plasma membrane dynamics. Here we describe the identification of two new paralemmin-related proteins. A partial paralemmin homolog, palmdelphin, is predominantly cytosolic, unlike paralemmin which is lipid-anchored to the plasma membrane through a C-terminal CaaX motif. We have mapped the mouse palmdelphin gene to distal chromosome 3 between Amy2 and Abcd3, in a region homologous to human chromosome 1p22-p21 where the human palmdelphin gene is located. We have also identified a second paralemmin isoform, paralemmin-2. It is expressed from a gene on human chromosome 9q31-q33 which ends only 33 kb upstream of the gene encoding the protein kinase A-binding protein, AKAP2/AKAP-KL. The closely adjacent paralemmin-2 and AKAP2 genes are functionally linked in a very unusual manner. Chimeric mRNAs are expressed, apparently by RNA readthrough and differential splicing, that encode natural fusion proteins in which either the N-terminal coiled-coil region or nearly the complete sequence of paralemmin-2 except its C-terminal CaaX motif is fused to AKAP2/AKAP-KL. The N-terminal coiled-coil region is conserved in paralemmin-1, paralemmin-2/AKAP2, palmdelphin and a fourth, uncharacterized gene, suggesting that it is a modular functional domain. (C) 2001 Academic Press. C1 Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Kilimann, MW (reprint author), Ruhr Univ Bochum, Inst Physiol Chem, Univ Str 150, D-44780 Bochum, Germany. NR 8 TC 16 Z9 22 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 3 PY 2001 VL 285 IS 5 BP 1369 EP 1376 DI 10.1006/bbrc.2001.5329 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 460GY UT WOS:000170300900047 PM 11478809 ER PT J AU Konu, O Kane, JK Barrett, T Vawter, MP Chang, RY Ma, JZ Donovan, DM Sharp, B Becker, KG Li, MD AF Konu, O Kane, JK Barrett, T Vawter, MP Chang, RY Ma, JZ Donovan, DM Sharp, B Becker, KG Li, MD TI Region-specific transcriptional response to chronic nicotine in rat brain SO BRAIN RESEARCH LA English DT Article DE microarray; normalization; mRNA expression; brain; nicotine; pathway ID PROTEIN-KINASE PATHWAY; GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; TUMOR-SUPPRESSOR; FOS PROTEIN; RECEPTORS; PTEN/MMAC1; DISCOVERY; CANCER; DRUGS AB Even though nicotine has been shown to modulate mRNA expression of a variety of genes, a comprehensive high-throughput study of the effects of nicotine on the tissue-specific gene expression profiles has been lacking in the literature. In this study, cDNA microarrays containing 1117 genes and ESTs were used to assess the transcriptional response to chronic nicotine treatment in rat, based on four brain regions, Le. prefrontal cortex (PFC), nucleus accumbens (NAs), ventral tegmental area (VTA), and amygdala (AMYG). On the basis of a non-parametric resampling method, an index (called jackknifed reliability index, JRI) was proposed, and employed to determine the inherent measurement error across multiple arrays used in this study. Upon removal of the outliers, the mean correlation coefficient between duplicate measurements increased to 0.978+/-0.0035 from 0.941+/-0.045. Results from principal component analysis and pairwise correlations suggested that brain regions studied were highly similar in terms of their absolute expression levels, but exhibited divergent transcriptional responses to chronic nicotine administration. For example, PFC and NAs were significantly more similar to each other (r=07; p<10(-14-)) than to either VTA or AMYG. Furthermore, we confirmed our microarray results for two representative genes, i.e. the weak inward rectifier K+ channel (TWIK-1), and phosphate and tensin homolog (PTEN) by using real-time quantitative RT-PCR technique. Finally, a number of genes, involved in MAPK, phosphatidylinositol, and EGFR signaling pathways, were identified and proposed as possible targets in response to nicotine administration. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Tennessee, Dept Pharmacol, Coll Med, Memphis, TN 38163 USA. NIDA, NIH, Baltimore, MD 21224 USA. Univ Tennessee, Div Biostat, Dept Prevent Med, Coll Med, Memphis, TN 38163 USA. NIA, NIH, Baltimore, MD 21224 USA. RP Li, MD (reprint author), Univ Tennessee, Dept Pharmacol, Coll Med, 874 Union Ave, Memphis, TN 38163 USA. OI Becker, Kevin/0000-0002-6794-6656 FU NIDA NIH HHS [R01 DA013783, R01-DA12844, R01 DA013783-04, R01-DA13783, R01 DA012844-01, R01 DA012844] NR 56 TC 76 Z9 80 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD AUG 3 PY 2001 VL 909 IS 1-2 BP 194 EP 203 DI 10.1016/S0006-8993(01)02685-3 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 466CM UT WOS:000170626800021 PM 11478936 ER PT J AU Groves, FD Sinha, D Kayhty, H Goedert, JJ Levine, PH AF Groves, FD Sinha, D Kayhty, H Goedert, JJ Levine, PH TI Haemophilus influenzae type b serology in childhood leukaemia: A case-control study SO BRITISH JOURNAL OF CANCER LA English DT Article DE leukaemia; child; serology; Haemophilus influenzae type b; case-control study ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CONJUGATE VACCINE; NATURAL-HISTORY; CHILDREN; RISK; INFANTS; DISEASE; TRIAL AB Antibody to Haemophilus influenzae type b (Hib) polysaccharide (PRP) was measured in 42 children with acute lymphoblastic leukaemia (ALL) and 42 non-leukaemic hospital controls. Modelling anti-PRP concentrations as a function of age revealed that the slopes of the trend lines differed significantly between cases and controls (P = 0.05); anti-PRP concentrations were lower among younger cases, and higher among older cases, than among controls of the same ages. (C) 2001 Cancer Research Campaign. C1 Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. NCI, Biostat Branch, Rockville, MD USA. Natl Publ Hlth Inst, Lab Vaccine Immunol, Helsinki, Finland. NCI, Viral Epidemiol Branch, Rockville, MD USA. RP Groves, FD (reprint author), Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG 3 PY 2001 VL 85 IS 3 BP 337 EP 340 DI 10.1054/bjoc.2001.1903 PG 4 WC Oncology SC Oncology GA 461MU UT WOS:000170368700005 PM 11487261 ER PT J AU El Khadem, HS Shalaby, MA Coxon, B AF El Khadem, HS Shalaby, MA Coxon, B TI The cations and anions of cyclobutanetetraone poly(phenylhydrazones) SO CARBOHYDRATE RESEARCH LA English DT Article DE anions; bathochromic shift; cations; cyclobutanetetraone poly(phenylhydrazones); enolization; hypsochromic shift; NMR spectroscopy; UV-Vis spectrophotometry ID SQUARIC ACID; PHENYLHYDRAZINE AB Six cyclobutanetetraone poly(arylhydrazones) have been treated with acids and bases, and the structures of the resulting anions and cations studied by UV-Vis absorption and NMR spectroscopy. In acid media, all the hydrazones studied formed cations, which exhibited bathochromic shifts due to the extension of their resonance systems. However, in bases, only some (those which could enolize) formed anions that exhibited hypsochromic shifts; the others were unaltered. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 American Univ, Dept Chem, Washington, DC 20016 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Div Biotechnol, Gaithersburg, MD 20899 USA. RP El Khadem, HS (reprint author), American Univ, Dept Chem, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD AUG 3 PY 2001 VL 334 IS 1 BP 61 EP 70 DI 10.1016/S0008-6215(01)00168-9 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 462ZX UT WOS:000170453300007 PM 11470251 ER PT J AU Steudel, R Steudel, Y Miaskiewicz, K AF Steudel, R Steudel, Y Miaskiewicz, K TI Does the interconversion of polysulfur compounds proceed via hypervalent intermediates? - An ab initio MO study SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article; Proceedings Paper CT 9th International Conference on Inorganic Ring Systems (IRIS-IX) CY JUL 23-28, 2000 CL SAARLAND UNIV, SAARLAND, GERMANY SP Deutsch Forsch Gemeinsch, Fonds Chem Ind, BASF, Acros Organ, Simga Aldrich, Wacker Chemie, Stoe & Co, Gordon & Breach Publishers, John Wiley & Sons, Royal Soc Chem, Minist Bild, Kultur & Wissensch, Totto Loto HO SAARLAND UNIV DE ab initio calculations; hypervalent compounds; sulfur; thermodynamics; transition states ID DENSITY-FUNCTIONAL THEORY; SULFUR-SULFUR BONDS; LIQUID SULFUR; THERMAL POLYMERIZATION; MOLECULAR-STRUCTURE; TRANSITION-STATES; CRYSTAL; HPLC; ELIMINATION; ENERGIES AB Ab initio MO calculations at the CCSD(T)/6-311++G(2df,p)//MP2/6-311++G** level have been carried out to determine the reaction energies and Gibbs energies of the homolytic dissociation of the S-S bonds in the chainlike sulfanes H2Sn (n = 2-4). Good agreement with the experimental data is observed. At the same level of theory, the formation of the hypothetical sulfuranes H2S(SH)(2), H2S(SSH)(2), and S(SH)(4) from H2S and the mentioned sulfanes has been studied. Species of this type had been proposed as intermediates in the interconversion reactions of poly-sulfur compounds (e.g.. formation of S-7 from S-8 and vice versa). The three sulfuranes serve here as model compounds. On the basis of the Gibbs energies and activation energies at 298 K. it is shown that the formation of the three sulfuranes from sulfanes requires too much energy and activation energy to successfully compete with homolytic dissociation reactions. In addition, the formation of the methyl-substituted sulfurane S(SMe)(4) from the sulfanes Me2S2 and Me2S3, was studied to elucidate the mechanism of the formal exchange of sulfur atoms between poly-sulfane molecules. However, both the reaction energy of 199 kJ mol(-1) and the activation energy of 287 kJ mol(-1) calculated at the MP2/6-31G* level, are much higher than the homolytic dissociation energy of the S-S bonds in chain- and ringlike polysulfur compounds. such as Me2S4 (140 kJ mol(-1)) and sulfur homo-cycles (150 kJ mol(-1)). Therefore, it is concluded that the observed interconversion reactions of sulfur rings and of chainlike polysulfanes do not proceed via sulfurane-type intermediates. Instead, these reactions will take place by a radical chain mechanism at high temperatures, while at temperatures below 100 degreesC they are most probably initiated either by traces of nucleophiles that are present as impurities or by the polar surface groups usually present on the walls of the vessels used. C1 Tech Univ Berlin, Inst Chem, Sekr C2, D-10623 Berlin, Germany. NCI, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Steudel, R (reprint author), Tech Univ Berlin, Inst Chem, Sekr C2, D-10623 Berlin, Germany. NR 53 TC 10 Z9 10 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PD AUG 3 PY 2001 VL 7 IS 15 BP 3281 EP 3290 DI 10.1002/1521-3765(20010803)7:15<3281::AID-CHEM3281>3.0.CO;2-B PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 463JN UT WOS:000170473500009 PM 11531113 ER PT J AU Samuel, W Kutty, RK Nagineni, S Gordon, JS Prouty, SM Chandraratna, RAS Wiggert, B AF Samuel, W Kutty, RK Nagineni, S Gordon, JS Prouty, SM Chandraratna, RAS Wiggert, B TI Regulation of stearoyl coenzyme a desaturase expression in human retinal pigment epithelial cells by retinoic acid SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED GENE-EXPRESSION; COA DESATURASE; RECEPTOR-ALPHA; FATTY-ACIDS; DIFFERENTIAL DISPLAY; 3T3-L1 PREADIPOCYTES; X RECEPTOR; HETERODIMERS; LIGAND; LIVER AB Stearoyl-CoA desaturase (SCD) is a regulatory enzyme involved in the synthesis of the monounsaturated fatty acids palmitoleate and oleate. The regulation of SCD is of physiological importance because the ratio of saturated fatty acids to unsaturated fatty acids is thought to modulate membrane fluidity. Differential display analysis of retinal pigment epithelial (ARPE-19) cells identified SCD as a gene regulated by retinoic acid. Two SCD transcripts of 3.9 and 5.2 kilobases in size were found to be expressed in these cells by Northern blot analysis. All-trans-retinoic acid (all-trans-RA) increased SCD mRNA expression in a dose- and time-dependent manner; a similar to7-fold increase was observed with 1 mum all-trans-RA at 48 h. SCD m-RNA expression was also increased by 9-cis-retinoic acid (9-cis-RA) as well as 4-(E-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid (TT-NPB), a retinoic acid receptor (RAR)-specific agonist. AGN194301, a RAR alpha -specific antagonist, suppressed the SCD expression induced by all-trans-RA, TTNPB, and 9-cis-RA. These results indicate the involvement of RAR alpha in the induction of SCD expression by retinoic acid. However, AGN194204, a RXR (retinoid X receptor) pan agonist, also increased SCD mRNA expression. This increase was not blocked by AGN194301, suggesting that an RAR-independent mechanism may also be involved. Thus, SCD expression in retinal pigment epithelial cells is regulated by retinoic acid, and the regulation appears to be mediated through RAR and RXR. C1 NEI, Biochem Sect, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20878 USA. Johnson & Johnson Consumer Prod Inc, Skin Biol Tech Resource Ctr, Skillman, NJ 08558 USA. Allergan Pharmaceut Inc, Retinoid Res, Dept Chem, Irvine, CA 92713 USA. Allergan Pharmaceut Inc, Retinoid Res, Dept Biol, Irvine, CA 92713 USA. RP Samuel, W (reprint author), NEI, LRCMB, NIH, Rm 338,6 Ctr Dr, Bethesda, MD 20892 USA. NR 42 TC 36 Z9 37 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 28744 EP 28750 DI 10.1074/jbc.M103587200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000015 PM 11397803 ER PT J AU Utani, A Nomizu, M Matsuura, H Kato, K Kobayashi, T Takeda, U Aota, S Nielsen, PK Shinkai, H AF Utani, A Nomizu, M Matsuura, H Kato, K Kobayashi, T Takeda, U Aota, S Nielsen, PK Shinkai, H TI A unique sequence of the laminin alpha 3 G domain binds to heparin and promotes cell adhesion through syndecan-2 and -4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT G-DOMAIN; BASEMENT-MEMBRANES; EPITHELIAL-CELLS; INTEGRIN ALPHA-3-BETA-1; EPIDERMOLYSIS-BULLOSA; DYSTROGLYCAN BINDING; PERIPHERAL-NERVE; GAMMA-2 CHAIN; VII COLLAGEN; GENE LAMC2 AB Laminin-5, consisting of the alpha3, beta3, and gamma2 chains, is localized in the skin basement membrane and supports the structural stability of the epidermo-dermal linkage and regulates various cellular functions. The alpha chains of laminins have been shown to have various biological activities. In this study, we identified a sequence of the alpha3 chain C-terminal globular domain (LG1-LG5 modules) required for both heparin binding and cell adhesion using recombinant proteins and synthetic peptides. We found that the LG3 and LG4 modules have activity for heparin binding and that LG4 has activity for cell adhesion. Studies with synthetic peptides delineated the A3G75aR sequence (NSFMALYLSKGR, residues 1412-1423) within LG4 as a major site for both heparin and cell binding. Substitution mutations in LG4 and A3G75aR identified the Lys and Arg of the A3G75aR sequence as critical for these activities. Cell adhesion to LG4 and A3G75aR was inhibited by heparitinase I treatment of cells, suggesting that cell binding to the A3G75aR site was mediated by cell surface heparan sulfate proteoglycans. We showed by affinity chromatography that syndecan-2 from fibroblasts bound to LG4. Solid-phase assays confirmed that syndecan-2 interacted with the A3G75aR peptide sequence. Stably transfected 293T cells with expression vectors for syndecan-2 and -4, but not glypican-1, specifically adhered to LG4 and A3G75aR. These results indicate that the A3G75aR sequence within the laminin alpha3 LG4 module is responsible for cell adhesion and suggest that syndecan-2 and -4 mediate this activity. C1 Chiba Univ, Sch Med, Dept Dermatol, Chuou Ku, Chiba 260, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 060, Japan. Biomol Engn Res Inst, Suita, Osaka 565, Japan. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Utani, A (reprint author), Chiba Univ, Sch Med, Dept Dermatol, Chuou Ku, 1-8-1 Inohana, Chiba 260, Japan. NR 52 TC 102 Z9 104 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 28779 EP 28788 DI 10.1074/jbc.M101420200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000020 PM 11373281 ER PT J AU Jourd'heuil, D Jourd'heuil, FL Kutchukian, PS Musah, RA Wink, DA Grisham, MB AF Jourd'heuil, D Jourd'heuil, FL Kutchukian, PS Musah, RA Wink, DA Grisham, MB TI Reaction of superoxide and nitric oxide with peroxynitrite - Implications for peroxynitrite-mediated oxidation reactions in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FREE-RADICAL FORMATION; TYROSINE NITRATION; SIMULTANEOUS GENERATION; CHEMISTRY; (NO)-N-CENTER-DOT; DECOMPOSITION AB Peroxynitrite (ONOO-/ONOOH), the product of the diffusion-limited reaction of nitric oxide ((NO)-N-.) with superoxide (O-2(radical anion)), has been implicated as an important mediator of tissue injury during conditions associated with enhanced (NO)-N-. and O-2(radical anion) production. Although several groups of investigators have demonstrated substantial oxidizing and cytotoxic activities of chemically synthesized peroxynitrite, others have proposed that the relative rates of (NO)-N-. and production may be critical in determining the reactivity of peroxynitrite formed in situ (Miles, A. M., Bohle, D. S., Glassbrenner, P. A., Hansert, B., Wink, D. A., and Grisham, At B. (1996) J. Biol. Chem. 271, 40-47). In the present study, we examined the mechanisms by which excess O-2(radical anion) or (NO)-N-. production 2 inhibits peroxynitrite-mediated oxidation reactions. Peroxynitrite was generated in situ by the co-addition of a chemical source of (NO)-N-., spermineNONOate, and an enzymatic source of O-2(radical anion), xanthine oxidase, with either hypoxanthine or lumazine as a substrate. We found that the oxidation of the model compound dihydrorhodamine by peroxynitrite occurred via the free radical intermediates OH and NO2, formed during the spontaneous decomposition of peroxynitrite and not via direct reaction with peroxynitrite. The inhibitory effect of excess O-2(radical anion) on the oxidation of dihydrorhodamine could not be ascribed to the accumulation of the peroxynitrite scavenger urate produced from the oxidation of hypoxanthine by xanthine oxidase. A biphasic oxidation profile was also observed upon oxidation of NADH by the simultaneous generation of (NO)-N-. and O-2(radical anion). Conversely, the oxidation of glutathione, which 2 occurs via direct reaction with peroxynitrite, was not affected by excess production of (NO)-N-.. We conclude that the oxidative processes initiated by the free radical intermediates formed from the decomposition of peroxynitrite, are inhibited by excess production of (NO)-N-. or O-2(radical anion), whereas oxidative pathways involving a direct reaction with peroxynitrite are not altered. The physiological implications of these findings are discussed. C1 Albany Med Coll, Ctr Cardiovasc Sci, Albany, NY 12208 USA. SUNY Albany, Dept Chem, Albany, NY 12222 USA. NCI, Tumor Biol Sect, Radiat Biol Branch, Bethesda, MD 20892 USA. Louisiana State Univ, Med Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71130 USA. RP Jourd'heuil, D (reprint author), Albany Med Coll, Ctr Cardiovasc Sci, 47 New Scotland Ave,MC8, Albany, NY 12208 USA. RI Kutchukian, Peter/A-9826-2016 OI Kutchukian, Peter/0000-0002-5684-1971 NR 27 TC 143 Z9 146 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 28799 EP 28805 DI 10.1074/jbc.M102341200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000022 PM 11373284 ER PT J AU Puri, N Majumdar, A Cuenoud, B Natt, F Martin, P Boyd, A Miller, PS Seidman, MM AF Puri, N Majumdar, A Cuenoud, B Natt, F Martin, P Boyd, A Miller, PS Seidman, MM TI Targeted gene knockout by 2 '-O-aminoethyl modified triplex forming oligonucleotides SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEQUENCE-SPECIFIC RECOGNITION; PHOTO-CROSS-LINKING; DOUBLE-STRANDED DNA; DOUBLE-HELICAL DNA; MAMMALIAN-CELLS; 3RD STRAND; EXONUCLEASE RESISTANCE; BACKBONE COMPOSITION; BIOLOGICAL-ACTIVITY; PURINE-MOTIF AB Triplex forming oligonucleotides (TFOs) are of interest because of their potential for facile gene targeting. However, the failure of TFOs to bind target sequences at physiological pH and Mg2+ concentration has limited their biological applications. Recently, pyrimidine TFOs with 2 ' -O-aminoethyl (AE) substitutions were shown to have enhanced kinetics and stability of triplex formation (Cuenoud, B., Casset, F., Husken, D., Natt, F., Wolf, R. M., Altmann, K. H., Martin, P., and Moser H. E. (1998) Angew. Chem. Int, Ed. 37,1288-1291). We have prepared psoralen-linked TFOs with varying amounts of the AE-modified residues, and have characterized them in biochemical assays in vitro, and in stability and HPRT gene knockout assays in vivo. The AE TFOs showed higher affinity for the target in vitro than a TFO with uniform 2 ' -OMe substitution, with relatively little loss of affinity when the assay was performed in reduced Mg2+. Once formed they were also more stable in "physiological" buffer, with the greatest affinity and stability displayed by the TFO with all but one residue in the AE format. However, TFOs with lesser amounts of the AE modification formed the most stable triplexes in vivo, and showed the highest HPRT gene knockout activity. We conclude that the AE modification can enhance the biological activity of pyrimidine TFOs, but that extensive substitution is deleterious. C1 NIA, LMG, NIH, Baltimore, MD 21224 USA. Novartis Horshan Res Ctr, Horsham RH12 4AB, W Sussex, England. Novartis Pharma Ltd, CH-4002 Basel, Switzerland. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. RP Seidman, MM (reprint author), NIA, LMG, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 57 TC 49 Z9 49 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 28991 EP 28998 DI 10.1074/jbc.M103409200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000049 PM 11389147 ER PT J AU Raghavan, SC Kirsch, IR Lieber, MR AF Raghavan, SC Kirsch, IR Lieber, MR TI Analysis of the V(D)J recombination efficiency at lymphoid chromosomal translocation breakpoints SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; DEVELOPMENTAL STAGE; JOINING SIGNALS; CLUSTER REGION; GENE; LOCUS; RECEPTOR; DELTA AB Chromosomal translocations and deletions are among the major events that initiate neoplasia. For lymphoid chromosomal translocations, misrecognition by the RAG (recombination activating gene) complex of V(D)J recombination is one contributing factor that has long been proposed. The chromosomal translocations involving LMO2 (t(11;14)(p13;q11)), Ttg-1 (t(11;14)(p15;q11)), and Hox11 (t(10;14)(q24;q11)) are among the clearest examples in which it appears that a D or J segment has synapsed with an adventitious heptamer/nonamer at a gene outside of one of the antigen receptor loci. The interstitial deletion at 1p32 involving SIL (SCL-interrupting locus)/SCL (stem cell leukemia) is a case involving two non-V(D)J sites that have been suggested to be V(D)J recombination mistakes. Here we have used our human extrachromosomal substrate assay to formally test the hypothesis that these regions are V(D)J recombination misrecognition sites and, more importantly, to quantify their efficiency as V(D)J recombination targets within the cell. We find that the LMO2 fragile site functions as a 12-signal at an efficiency that is only 27-fold lower than that of a consensus 12-signal. The Ttg-1 site functions as a 23-signal at an efficiency 530-fold lower than that of a consensus 23-signal. Hox11 failed to undergo recombination as a 12. or 23-signal and was at least 20,000-fold less efficient than consensus signals. SIL has been predicted to function as a 12-signal and SCL as a 23-signal. However, we find that SH, actually functions as a 23-signal. These results provide a formal demonstration that certain chromosomal fragile sites can serve as RAG complex targets, and they determine whether these sites function as 12- versus 23-signals. These results quantify one of the three major factors that determine the frequency of these translocations in T-cell acute lymphocytic leukemia. C1 Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Biol Sci, Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. NCI, Med Branch, NIH, Bethesda, MD 20889 USA. NCI, Dept Genet, NIH, Bethesda, MD 20889 USA. RP Lieber, MR (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, Rm 5428,1441 Eastlake Ave, Los Angeles, CA 90089 USA. NR 49 TC 91 Z9 94 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29126 EP 29133 DI 10.1074/jbc.M103797200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000067 PM 11390401 ER PT J AU Tsai, HF Fujii, I Watanabe, A Wheeler, AH Chang, YC Yasuoka, Y Ebizuka, Y Kwon-Chung, KJ AF Tsai, HF Fujii, I Watanabe, A Wheeler, AH Chang, YC Yasuoka, Y Ebizuka, Y Kwon-Chung, KJ TI Pentaketide melanin biosynthesis in Aspergillus fumigatus requires chain-length shortening of a heptaketide precursor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYKETIDE SYNTHASE GENE; NIDULANS WA GENE; COLLETOTRICHUM-LAGENARIUM; HETEROLOGOUS EXPRESSION; VIRULENCE; CLONING; ORYZAE; PKS1; IDENTIFICATION; TRANSFORMATION AB Chain lengths and cyclization patterns of microbial polyketides are generally determined by polyketide synthases alone. Fungal polyketide melanins are often derived from a pentaketide 1,8-dihydroxynaphthalene, and pentaketide synthases are used for synthesis of the upstream pentaketide precursor, 1,3,6,8-tetrahydroxynaphthalene (1,3,6,8-THN). However, Aspergillus fumigatus, a human fungal pathogen, uses a heptaketide synthase (Alb1p) to synthesize its conidial pigment through a pentaketide pathway similar to that which produces 1,8-dihydroxynaphthalene-melanin. In this study we demonstrate that a novel protein, Ayg1p, is involved in the formation of 1,3,6,8-THN by chain-length shortening of a heptaketide precursor in A. fumigatus. Deletion of the ayg1 gene prevented the accumulation of 1,3,6,8-THN suggesting the involvement of ayg1 in 1,3,6,8-THN production. Genetic analyses of double-gene deletants suggested that Ayg1p catalyzes a novel biosynthetic step downstream of Alb1p and upstream of Arp2p (1,3,6,8-THN reductase). Further genetic and biochemical analyses of the reconstituted strains carrying alb1, ayg1, or alb1 + ayg1 indicated that Ayg1p is essential for synthesis of 1,3,6,8-THN in addition to Alb1p. Cell-free enzyme assays, using the crude Ayg1p protein extract, revealed that Ayg1p enzymatically shortened the heptaketide product of Alb1p to 1,3,6,8-THN. Thus, the protein Ayg1p facilitates the participation of a heptaketide synthase in a pentaketide pathway via a novel polyketide-shortening mechanism in A fumigatus. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. USDA ARS, Cotton Pathol Res Unit, College Stn, TX 77845 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Clin Invest Lab, NIH, Bldg 10,Rm 11C304,10 Ctr Dr,MSC 1882, Bethesda, MD 20892 USA. NR 37 TC 79 Z9 85 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29292 EP 29298 DI 10.1074/jbc.M101998200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000088 PM 11350964 ER PT J AU Erlenbach, I Kostenis, E Schmidt, C Serradeil-Le Gal, C Raufaste, D Dumont, ME Pausch, MH Wess, J AF Erlenbach, I Kostenis, E Schmidt, C Serradeil-Le Gal, C Raufaste, D Dumont, ME Pausch, MH Wess, J TI Single amino acid substitutions and deletions that alter the G protein coupling properties of the V2 vasopressin receptor identified in yeast by receptor random mutagenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHEROMONE RESPONSE PATHWAY; NEPHROGENIC DIABETES-INSIPIDUS; SIGNAL-TRANSDUCTION; MOLECULAR-BASIS; ALPHA-SUBUNIT; HORMONE-RECEPTOR; C5A RECEPTOR; WILD-TYPE; SELECTIVITY; BINDING AB To facilitate structure-function relationship studies of the V2 vasopressin receptor, a prototypical G(s)-coupled receptor, we generated V2 receptor-expressing yeast strains (Saccharomyces cerevisiae) that required arginine vasopressin-dependent receptor/G protein coupling for cell growth. V2 receptors heterologously expressed in yeast were unable to productively interact with the endogenous yeast G protein alpha subunit, Gpa1p, or a mutant Gpa1p subunit containing the C-terminal G alpha (q) sequence (Gq5). In contrast, the V2 receptor efficiently coupled to a Gpa1p/G alpha (s) hybrid subunit containing the C-terminal Gas sequence (Gs5), indicating that the V2 receptor retained proper G protein coupling selectivity in yeast. To gain insight into the molecular basis underlying the selectivity of V2 receptor/G protein interactions, we used receptor saturation random mutagenesis to generate a yeast library expressing mutant V2 receptors containing mutations within the second intracellular loop. A subsequent yeast genetic screen of about 30,000 mutant receptors yielded four mutant receptors that, in contrast to the wild-type receptor, showed substantial coupling to Gq5. Functional analysis of these mutant receptors, followed by more detailed site-directed mutagenesis studies, indicated that single amino acid substitutions at position Met(145) in the central portion of the second intracellular loop of the V2 receptor had pronounced effects on receptor/G protein coupling selectivity. We also observed that deletion of single amino acids N-terminal of Met145 led to misfolded receptor proteins, whereas single amino acid deletions C-terminal of Met(145) had no effect on V2 receptor function. These findings highlight the usefulness of combining receptor random mutagenesis and yeast expression technology to study mechanisms governing receptor/G protein coupling selectivity and receptor folding. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Sanofi Synthelabo Rech, Exploratory Res Dept, F-31036 Toulouse, France. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. Wyeth Ayerst Res, Dept Neurosci, Princeton, NJ 08543 USA. RP Wess, J (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05, Bethesda, MD 20892 USA. NR 52 TC 43 Z9 44 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29382 EP 29392 DI 10.1074/jbc.M103203200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000100 PM 11375990 ER PT J AU Singh, SK Rozycki, J Ortega, J Ishikawa, T Lo, J Steven, AC Maurizi, MR AF Singh, SK Rozycki, J Ortega, J Ishikawa, T Lo, J Steven, AC Maurizi, MR TI Functional domains of the ClpA and ClpX molecular chaperones identified by limited proteolysis and deletion analysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SENSITIVE FUSION PROTEIN; ATP-DEPENDENT PROTEASES; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ARCHAEAL CHAPERONIN; TERMINAL DOMAIN; DEGRADATION; THERMOSOME; TARGETS; COMPLEX AB Escherichia coli ClpA and ClpX are ATP-dependent protein unfoldases that each interact with the protease, ClpP, to promote specific protein degradation. We have used limited proteolysis and deletion analysis to probe the conformations of ClpA and ClpX and their interactions with ClpP and substrates. ATP gammaS binding stabilized ClpA and ClpX such that that cleavage by lysylendopeptidase C occurred at only two sites. Both proteins were cleaved within in a loop preceding an a-helix-rich C-terminal domain. Although the loop varies in size and composition in Clp ATPases, cleavage occurred within and around a conserved triad, IG(FIL). Binding of ClpP blocked this cleavage, and prior cleavage at this site rendered both ClpA and ClpX defective in binding and activating ClpP, suggesting that this site is involved in interactions with ClpP. ClpA was also cut at a site near the junction of the two ATPase domains, whereas the second cleavage site in ClpX lay between its N-terminal and ATPase domains. ClpP did not block cleavage at these other sites. The N-terminal domain of ClpX dissociated upon cleavage, and the remaining ClpX DeltaN remained as a hexamer, associated with ClpP, and expressed ATPase, chaperone, and proteolytic activity. A truncated mutant of ClpA lacking its N-terminal 153 amino acids also formed a hexamer, associated with ClpP, and expressed these activities. We propose that the N-terminal domains of ClpX and ClpA lie on the outside ring surface of the holoenzyme complexes where they contribute to substrate binding or perform a gating function affecting substrate access to other binding sites and that a loop on the opposite face of the ATPase rings stabilizes interactions with ClpP and is involved in promoting ClpP proteolytic activity. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,1B07, Bethesda, MD 20892 USA. RI Ishikawa, Takashi/E-5023-2017 OI Ishikawa, Takashi/0000-0002-1976-7477 NR 41 TC 86 Z9 90 U1 3 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29420 EP 29429 DI 10.1074/jbc.M103489200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000104 PM 11346657 ER PT J AU Chen, PL Hutter, D Yang, XL Gorospe, M Davis, RJ Liu, YS AF Chen, PL Hutter, D Yang, XL Gorospe, M Davis, RJ Liu, YS TI Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the phosphatase catalytically SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-REGULATED KINASE; DUAL-SPECIFICITY PHOSPHATASES; TYROSINE-PHOSPHATASE; CRYSTAL-STRUCTURE; IN-VIVO; HEAT-SHOCK; C-JUN; STRESS; DOMAIN; EXPRESSION AB MKP-2 is a member of the mitogen-activated protein (MAP) kinase phosphatase family which has been suggested to play an important role in the feedback control of MAP kinase-mediated gene expression. Although MKP-2 preferentially inactivates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) MAP kinase subfamilies, the mechanisms underlying its own regulation remain unclear. In this report, we have examined the MKP-2 interaction with and catalytic activation by distinct MAP kinase subfamilies. We found that the catalytic activity of MKP-2 was enhanced dramatically by ERK and JNK but was affected only minimally by p38. By contrast, p38 and ERK bound MKP-2 with comparably strong affinities, whereas JNK and MKP-2 interacted very weakly. Through site-directed mutagenesis, we defined the ERK/p38-binding site as a cluster of arginine residues in the NH2-terminal domain of MKP-2. Mutation of the basic motif abrogated its interaction with both ERK and p38 and severely compromised the catalytic activation of MKP-2 by these kinases. Unexpectedly, such mutations had little effect on JNK-triggered catalytic activation. Both in vitro and in vivo, wild type MKP-2 effectively inactivated ERK2 whereas MKP-2 mutants incapable of binding to ERK/p38 did not. Finally, in addition to its role as a docking site for ERK and p38, the MKP-2 basic motif plays a role in regulating its nuclear localization. Our studies provided a mechanistic explanation for the substrate preference of MKP-2 and suggest that catalytic activation of MKP-2 upon binding to its substrates is crucial for its function. C1 NIA, Mol & Cellular Biol Lab, NIH, Baltimore, MD 21224 USA. Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Program Mol Med,Dept BIochem & Mol Biol, Worcester, MA 01605 USA. RP Liu, YS (reprint author), NIA, Mol & Cellular Biol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 53 TC 72 Z9 73 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29440 EP 29449 DI 10.1074/jbc.M103463200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000106 PM 11387337 ER PT J AU Louis, JM Bewley, CA Clore, GM AF Louis, JM Bewley, CA Clore, GM TI Design and properties of N-CCG-gp41, a chimeric gp41 molecule with nanomolar HIV fusion inhibitory activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; 44 KDA ECTODOMAIN; ENVELOPE GLYCOPROTEIN; COILED-COIL; INACTIVATING PROTEIN; SECONDARY STRUCTURE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ATOMIC-STRUCTURE; CYANOVIRIN-N AB The design and characterization of a chimeric protein, termed N-CCG-gp41, derived from the ectodomain of human immunodeficiency virus (HIV), type I gp41 is described. N-CCG-gp41 features an exposed trimeric coiled-coil comprising the N-terminal helices of the gp41 ectodomain. The trimeric coiled-coil is stabilized both by fusion to a minimal thermostable ectodomain of gp41 and by engineered intersubunit disulfide bonds. N(CCG)gp41 is shown to inhibit HIV envelope-mediated cell fusion at nanomolar concentrations with an IC., of 16.1 +/- 2.8 nM. It is proposed that N-CCG-gp41 targets the exposed C-terminal region of the gp41 ectodomain in its pre-hairpin intermediate state, thereby preventing the formation of the fusogenic form of the gp41 ectodomain, which comprises a highly stable trimer of hairpins arranged in a six-helix bundle. N-CCG-gp41 has potential as a therapeutic agent for the direct inhibition of HIV cell entry, as an anti-HIV vaccine, and as a component of a rapid throughput assay for screening for small molecule inhibitors of HIV envelope-mediated cell fusion. It is anticipated that antibodies raised against N-CCG-gp41 may target the trimeric coiled-coil of N-terminal helices of the gp41 ectodomain that is exposed in the pre-hairpin intermediate state in a manner analogous to peptides derived from the C-terminal helix of gp41 that are currently in clinical trials. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5,Rm B1-301, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 34 TC 86 Z9 93 U1 2 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29485 EP 29489 DI 10.1074/jbc.C100317200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000111 PM 11418583 ER PT J AU Kadyrov, FA Drake, JW AF Kadyrov, FA Drake, JW TI Conditional coupling of leading-strand and lagging-strand DNA synthesis at bacteriophage T4 replication forks SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GP41 FORMS; HELICASE; PROTEIN; POLYMERASE; PURIFICATION; HOLOENZYME; SEQUENCE; COMPLEX AB Eight proteins encoded by bacteriophage T4 are required for the replicative synthesis of the leading and lagging strands of T4 DNA. We show here that active T4 replication forks, which catalyze the coordinated synthesis of leading and lagging strands, remain stable in the face of dilution provided that the gp44/62 clamp loader, the gp45 sliding clamp, and the gp32 ssDNA-binding protein are present at sufficient levels after dilution. If any of these accessory proteins is omitted from the dilution mixture, uncoordinated DNA synthesis occurs, and/or large Okazaki fragments are formed. Thus, the accessory proteins must be recruited from solution for each round of initiation of lagging-strand synthesis. A modified bacteriophage T7 DNA polymerase (Sequenase) can replace the T4 DNA polymerase for leading-strand synthesis but not for well coordinated lagging-strand synthesis. Although T4 DNA polymerase has been reported to self-associate, gel-exclusion chromatography displays it as a monomer in solution in the absence of DNA. It forms no stable holoenzyme complex in solution with the accessory proteins or with the gp41-gp61 helicase-primase. Instead, template DNA is required for the assembly of the T4 replication complex, which then catalyzes coordinated synthesis of leading and lagging strands in a conditionally coupled manner. C1 NIEHS, Lab Mol Genet E3 01, NIH, Res Triangle Pk, NC 27709 USA. RP Kadyrov, FA (reprint author), NIEHS, Lab Mol Genet E3 01, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 30 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29559 EP 29566 DI 10.1074/jbc.M101310200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000121 PM 11390383 ER PT J AU Mittelstadt, PR Ashwell, JD AF Mittelstadt, PR Ashwell, JD TI Inhibition of AP-1 by the glucocorticoid-inducible protein GILZ SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; NUCLEAR RECEPTOR COACTIVATOR; STEROID-HORMONE RECEPTORS; FAS LIGAND EXPRESSION; T-CELL HYBRIDOMA; TRANSCRIPTION FACTORS; DNA-BINDING; NEGATIVE REGULATION; C-JUN; FUNCTIONAL ANTAGONISM AB The immunosuppressive effects of glucocorticoids arise largely by inhibition of cytokine gene expression, which has been ascribed to interference between the glucocorticoid receptor and transcription factors such as AP-1 and NF-kappaB as well as by competition for common coactivators. Here we show that glucocorticoid-induced inhibition of interleukin-2 mRNA expression in activated normal T cells required new protein synthesis, suggesting that this phenomenon is secondary to expression of glucocorticoid-regulated genes. One of the most prominent glucocorticoid-induced genes is glucocorticoid-induced leucine zipper (GILZ), which has been reported to inhibit activation-induced up-regulation of Fas ligand (FasL) mRNA. Indeed, transient expression of GILZ in Jurkat T cells blocked induction of a reporter construct driven by the FasL promoter. This could be accounted for by GILZ-mediated inhibition of Egr-2 and Egr-3, NFAT/AP-1-inducible transcription factors that bind a regulatory element in the FasL promoter and up-regulate FasL expression. GILZ also potently inhibited AP-1-driven and IL-2 promoter-driven reporter constructs, and recombinant GILZ specifically interacted with c-Fos and c-Jun in vitro and inhibited the binding of active AP-1 to its target DNA. Whereas homodimerization of GILZ required the presence of its leucine zipper, the interaction with c-Fos and c-Jun occurred through the N-terminal 60-amino acid region of GILZ. Thus, GILZ represents a glucocorticoid-induced gene product that can inhibit a variety of activation-induced events, at least in part by direct interference with AP-1, and is therefore a candidate for a mediator of glucocorticoid-induced immunosuppression. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Rm 1B-40,Bdg 10, Bethesda, MD 20892 USA. NR 59 TC 175 Z9 188 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 3 PY 2001 VL 276 IS 31 BP 29603 EP 29610 DI 10.1074/jbc.M101522200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 461BX UT WOS:000170346000127 PM 11397794 ER PT J AU Carroll, ML Roy-Engel, AM Nguyen, SV Salem, AH Vogel, E Vincent, B Myers, J Ahmad, Z Nguyen, L Sammarco, M Watkins, WS Henke, J Makalowski, W Jorde, LB Deininger, PL Batzer, MA AF Carroll, ML Roy-Engel, AM Nguyen, SV Salem, AH Vogel, E Vincent, B Myers, J Ahmad, Z Nguyen, L Sammarco, M Watkins, WS Henke, J Makalowski, W Jorde, LB Deininger, PL Batzer, MA TI Large-scale analysis of the Alu Ya5 and Yb8 subfamilies and their contribution to human genomic diversity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Alu insertion polymorphism; gene conversion; computational biology ID DNA-SEQUENCES; INSERTION POLYMORPHISMS; TRANSPOSABLE ELEMENTS; HUMAN-POPULATION; GENE CONVERSION; FAMILY MEMBERS; Y-CHROMOSOME; EVOLUTION; REPEATS; AMPLIFICATION AB We have utilized computational biology to screen GenBank for the presence of recently integrated Ya5 and Yb8 Alu family members. Our analysis identified 2640 Ya5 Alu family members and 1852 Yb8 Alu family members from the draft sequence of the human genome. We selected a set of 475 of these elements for detailed analyses. Analysis of the DNA sequences from the individual Alu elements revealed a low level of random mutations within both subfamilies consistent with the recent origin of these elements within the human genome. Polymerase chain reaction assays were used to determine the phylogenetic distribution and human genomic variation associated with each Alu repeat. Over 99 % of the Ya5 and Yb8 Alu family members were restricted to the human genome and absent from orthologous positions within the genomes of several non-human primates, confirming the recent origin of these Alu subfamilies in the human genome. Approximately 1 % of the analyzed Ya5 and Yb8 Alu family members had integrated into previously undefined repeated regions of the human genome. Analysis of mosaic Yb8 elements suggests gene conversion played an important role in generating sequence diversity among these elements. Of the 475 evaluated elements, a total of 106 of the Ya5 and Yb8 Alu family members were polymorphic for insertion presence/absence within the genomes of a diverse array of human populations. The newly identified Alu insertion polymorphisms will be useful tools for the study of human genomic diversity. (C) 2001 Academic Press. C1 Louisiana State Univ, Dept Biol Sci, Biol Computat & Visualizat Ctr, Baton Rouge, LA 70803 USA. Louisiana State Univ, Hlth Sci Ctr, Stanley S Scott Canc Ctr, Dept Pathol,Neurosci Ctr Excellence, New Orleans, LA 70112 USA. Louisiana State Univ, Hlth Sci Ctr, Stanley S Scott Canc Ctr, Dept Genet Biochem & Mol Biol,Neurosci Ctr Excell, New Orleans, LA 70112 USA. Tulane Univ, Hlth Sci Ctr, Dept Environm Hlth Sci, Tulane Canc Ctr, New Orleans, LA 70112 USA. Univ Utah, Hlth Sci Ctr, Dept Human Genet, Salt Lake City, UT 84112 USA. Inst Blutgrp Forsch, D-50501 Cologne, Germany. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Alton Ochsner Med Fdn & Ochsner Clin, Mol Genet Lab, New Orleans, LA 70121 USA. RP Batzer, MA (reprint author), Louisiana State Univ, Dept Biol Sci, Biol Computat & Visualizat Ctr, 508 Life Sci Bldg, Baton Rouge, LA 70803 USA. EM mbatzer@lsu.edu RI Makalowski, Wojciech/I-2843-2016; OI Deininger, Prescott/0000-0002-1067-3028; Engel, Astrid/0000-0002-8884-4544 FU NIGMS NIH HHS [R01 GM45668, R01 GM59290] NR 47 TC 114 Z9 118 U1 0 U2 7 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 3 PY 2001 VL 311 IS 1 BP 17 EP 40 DI 10.1006/jmbi.2001/4847 PG 24 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 460UG UT WOS:000170326500003 PM 11469855 ER PT J AU Barry, CE Lee, RE Protopova, M AF Barry, CE Lee, RE Protopova, M TI Use of genomic information in the development of new drugs against Mycobacterium tuberculosis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIAID, Tuberculosis Res Sect, NIH, Rockville, MD 20852 USA. RI Barry, III, Clifton/H-3839-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 299-MEDI BP U692 EP U692 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003627 ER PT J AU Berkin, A Coxon, B Robbins, JB Schneerson, R Pozsgay, V AF Berkin, A Coxon, B Robbins, JB Schneerson, R Pozsgay, V TI Toward a synthetic glycoconjugate vaccine against meningitis caused by Neisseria meningitidis A. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 99-CARB BP U176 EP U176 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000867 ER PT J AU Brooks, BR Lee, YS Cheatham, TE AF Brooks, BR Lee, YS Cheatham, TE TI QM/MM techniques for examining enzyme mechanisms: Free energies by the Replica/Path method. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD USA. Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 63-COMP BP U392 EP U392 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001962 ER PT J AU Cheng, Y Rau, DC Chik, J Prud'homme, RK AF Cheng, Y Rau, DC Chik, J Prud'homme, RK TI Structure and intermolecular interactions between polysaccharide chains: An osmotic stress and x-ray scattering study. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. NIH, Struct Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 104-PMSE BP U356 EP U356 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690101975 ER PT J AU Chernyak, AY Karavano, A Ogawa, Y Kovac, P AF Chernyak, AY Karavano, A Ogawa, Y Kovac, P TI Conjugating oligosaccharides to proteins by squaric acid diester chemistry: Rapid monitoring of the progress of conjugation, and recovery of the unused ligand. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Ciphergen Biosyst Inc, Palo Alto, CA USA. Fuji Chem Ind Co Ltd, Toyama, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 63-CARB BP U171 EP U171 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000831 ER PT J AU Das, D Brooks, BR Billings, EM AF Das, D Brooks, BR Billings, EM TI Quantum mechanical/molecular mechanical study using Gaussian charges and the double link atom method. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NHLBI, NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 116-COMP BP U400 EP U400 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690002013 ER PT J AU Davies, KM Price, SE Lorenzo, P Hrabie, JA Saavedra, JE AF Davies, KM Price, SE Lorenzo, P Hrabie, JA Saavedra, JE TI Micellar binding and catalysis of nitric oxide dissociation from zwitterionic diazeniumdiolates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. NCI, SAIC, FCRDC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 119-COLL BP U331 EP U331 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001706 ER PT J AU Doerge, DR Delclos, KB Newbold, RR AF Doerge, DR Delclos, KB Newbold, RR TI Genistein distribution in target tissues from dietary exposure in adult rats and evidence for modulation of endocrine function. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Toxicol Lab, Dev Endocrinol Sect, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 118-AGFD BP U44 EP U44 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000118 ER PT J AU Elisseeff, JH Kleinman, HK Yamada, Y AF Elisseeff, JH Kleinman, HK Yamada, Y TI Synthesis and biological response of novel composite hydrogels based on alginate and cartilage extracellular matrix (cartrigel). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Inst Dental & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 30-PMSE BP U344 EP U344 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690101901 ER PT J AU Fox, BM Kohlhagen, G Pommier, Y Cushman, M AF Fox, BM Kohlhagen, G Pommier, Y Cushman, M TI Design and synthesis of novel non-camptothecin topoisomerase I poisons. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 61-MEDI BP U649 EP U649 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003389 ER PT J AU Gallardo-Williams, MT Harris, MW Dunson, DB Fernando, R Collins, BJ AF Gallardo-Williams, MT Harris, MW Dunson, DB Fernando, R Collins, BJ TI Correlation between boron uptake by bones and hair in ovariectomized rats. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIEHS, Dept Chem, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 144-ENVR BP U442 EP U442 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690002265 ER PT J AU Garde, S Hummer, G Pratt, LR AF Garde, S Hummer, G Pratt, LR TI Effect of chain length on microscopic density fluctuations and solvation in polymeric fluids. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Rensselaer Polytech Inst, Dept Chem Engn, Troy, NY 12180 USA. NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. RI Pratt, Lawrence/H-7955-2012; Hummer, Gerhard/A-2546-2013 OI Pratt, Lawrence/0000-0003-2351-7451; Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 268-PMSE BP U381 EP U381 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690102139 ER PT J AU Goel, A Appella, E Inman, J AF Goel, A Appella, E Inman, J TI Design and synthesis of novel thioesters as inhibitors for IV-1NCp7 protein. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Cell Biol Lab, Chem Sect, Bethesda, MD 20892 USA. NIH, Immunol Lab, Chem Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 144-MEDI BP U663 EP U663 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003472 ER PT J AU Gorokhov, A Johnson, EF Negishi, M Perera, L Darden, T Pedersen, LG AF Gorokhov, A Johnson, EF Negishi, M Perera, L Darden, T Pedersen, LG TI Model of mouse cytochrome P450 2A4 in solution. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA USA. NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 10-MEDI BP U640 EP U640 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003338 ER PT J AU Horkay, F Tasaki, I Basser, PJ AF Horkay, F Tasaki, I Basser, PJ TI Effect of monovalent-multivalent cation exchange on the thermodynamic properties of polyacrylate hydrogels. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Lab Integrat & Med Biophys, NICHD, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 533-POLY BP U335 EP U335 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690101863 ER PT J AU Horkay, F Uriarte, RJ Hecht, AM Geissler, E AF Horkay, F Uriarte, RJ Hecht, AM Geissler, E TI Neutron scattering investigations on fluorosilicone gels. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Gen Elect Corp, Corp Res & Dev Ctr, Fairfield, CT USA. Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, F-38041 Grenoble, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 100-POLY BP U256 EP U256 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690101430 ER PT J AU Hsin, LW Tian, XR Webster, EL Coop, A Caldwell, TM Jacobson, AE Chrousos, GP Gold, PW Habib, KE Ayala, A Eckelman, WC Contoreggi, C Rice, KC AF Hsin, LW Tian, XR Webster, EL Coop, A Caldwell, TM Jacobson, AE Chrousos, GP Gold, PW Habib, KE Ayala, A Eckelman, WC Contoreggi, C Rice, KC TI Synthesis, hydrophilicity, and corticotropin-releasing hormone type 1 receptor (CRHR1) binding affinity of substituted pyrrolopyrimidines. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, LMC, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Pharmaceut Sci, College Pk, MD 20742 USA. NICHHD, Pediat Endocrinol Sect, PREB, NIH, Bethesda, MD USA. Ctr Clin, PET Dept, NIH, Bethesda, MD USA. NIDA, Mol Neurobiol Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 41-MEDI BP U646 EP U646 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003369 ER PT J AU Jacobson, KA Barak, D Moro, S AF Jacobson, KA Barak, D Moro, S TI Use of molecular modeling and mutagenesis in docking of ligands to GPCRs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. Univ Padua, Dept Pharmaceut Sci, Padua, Italy. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 184-COMP BP U410 EP U410 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690002081 ER PT J AU Kunos, G AF Kunos, G TI Endocannabinoids: Emerging role in cardiovascular and neuroendocrine regulation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 292-MEDI BP U690 EP U691 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003620 ER PT J AU Lai, CC Kelley, JA AF Lai, CC Kelley, JA TI Quantitative evaluation of large-volume sample stacking for the analysis of synthetic and biological nucleotide mixtures by capillary electropheresis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 123-ANYL BP U98 EP U98 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000425 ER PT J AU Lee, K Ravi, G Ji, XD Marquez, VE Jacobson, KA AF Lee, K Ravi, G Ji, XD Marquez, VE Jacobson, KA TI Ring-constrained (N)-methanocarba adenosines as adenosine receptor agonists: Independent 5 '-uronamide and 2 '-deoxy modifications. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK, LBC, Mol Recognit Sect, Bethesda, MD 20892 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 199-MEDI BP U673 EP U673 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003527 ER PT J AU Lukianova, OA Chepanoske, CL Golinelli, MP David, SS AF Lukianova, OA Chepanoske, CL Golinelli, MP David, SS TI Participation of Arg143 of DNA repair enzyme MutY in damage recognition and removal. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Utah, Dept Chem, Salt Lake City, UT 84112 USA. Lawrence Livermore Natl Lab, Livermore, CA USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 169-BIOL BP U143 EP U143 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000683 ER PT J AU Luzzio, FA Figg, WD Mayorov, AV Kruger, EA AF Luzzio, FA Figg, WD Mayorov, AV Kruger, EA TI Thalidomide metabolites and analogs, part 3: Synthesis and antiangiogenic activity of the teratogenic and TNF-alpha-modulatory thalidomide analog EM-12. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Louisville, Louisville, KY 40292 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 264-MEDI BP U685 EP U685 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003592 ER PT J AU Ma, DS Lu, F Overstreet, T Milenic, DE Brechbiel, MW AF Ma, DS Lu, F Overstreet, T Milenic, DE Brechbiel, MW TI Novel chelating agents for potential clinical applications of copper. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 162-INOR BP U570 EP U570 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690002890 ER PT J AU Milner, JA Knowles, L AF Milner, JA Knowles, L TI Molecular targets for allyl sulfur compounds in neoplastic cells. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Div Canc Prevent & Control, Nutr Sci & Res Grp, Bethesda, MD 20892 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 133-AGFD BP U46 EP U46 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000133 ER PT J AU Nicklaus, MC Ihlenfeldt, WD Filimonov, D Poroikov, VV AF Nicklaus, MC Ihlenfeldt, WD Filimonov, D Poroikov, VV TI Computer-assisted mechanism-of-action analysis of large databases, including 250,000 chemical compounds registered by NCI. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, NIH, Frederick, MD 21702 USA. Univ Erlangen Nurnberg, Inst Organ Chem, Comp Chem Ctr, D-8520 Erlangen, Germany. Russian Acad Med Sci, Inst Biomed Chem, Moscow, Russia. RI Poroikov, Vladimir/O-2769-2013 OI Poroikov, Vladimir/0000-0001-7937-2621 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 91-CINF BP U279 EP U279 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001443 ER PT J AU Pais, GCG Merchand, C Pommier, Y Neamati, N Burke, TR AF Pais, GCG Merchand, C Pommier, Y Neamati, N Burke, TR TI Investigation of modifications in the beta-diketo acid side chain of aryl beta-diketo acid-family HIV-1 integrase inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. NIH, NCI, Mol Pharmacol Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 104-MEDI BP U657 EP U657 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003432 ER PT J AU Pozsgay, V Berkin, A AF Pozsgay, V Berkin, A TI Lipophilic benzyl ether-type protecting groups in oligosaccharide synthesis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NICHD, LDMI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 70-CARB BP U172 EP U172 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000838 ER PT J AU Pozsgay, V AF Pozsgay, V TI Synthesis of oligosaccharide-based glycoconjugate vaccines. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NICHD, LDMI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 50-CARB BP U169 EP U169 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000818 ER PT J AU Preusch, PC AF Preusch, PC TI NIH Metals in Medicine initiative. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, Natl Inst Gen Med Sci, Pharmacol Physiol & Biol Chem Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 190-INOR BP U575 EP U575 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690002918 ER PT J AU Puri, N Majumdar, A Cuenoud, B Natt, F Martin, P Miller, PS Seidman, M AF Puri, N Majumdar, A Cuenoud, B Natt, F Martin, P Miller, PS Seidman, M TI Targeted gene knockouts in mammalian cell cultures by 2 '-O-aminoethyl-modified triplex forming oligonucleotides. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 18-CARB BP U163 EP U163 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000786 ER PT J AU Rogers, ME AF Rogers, ME TI NIGMS/NIH support for collaborative research. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NIGMS, Pharmacol Physiol & Biol Chem Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 19-WCC BP U440 EP U440 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467EU UT WOS:000170690102426 ER PT J AU Stadtman, ER AF Stadtman, ER TI Modification of proteins by lipid peroxidation products. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NHLBI, Biochem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 16-TOXI BP U288 EP U288 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001475 ER PT J AU Tang, Y Nicklaus, MC AF Tang, Y Nicklaus, MC TI Refined model of the HIV-1 integrase-viral DNA complex used for inhibitor docking studies. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NCI, Med Chem Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 100-COMP BP U397 EP U397 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001997 ER PT J AU Tuntiwechapikul, W Kerwin, SM Salazar, M AF Tuntiwechapikul, W Kerwin, SM Salazar, M TI Novel cytosine-selective DNA alkylation by an aza-enediyne: Sequence specificity studies and proposed mechanisms. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI, Chem Sect, Cell Biol Lab, Bethesda, MD 20892 USA. NIH, Immunol Lab, Chem Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 143-MEDI BP U663 EP U663 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003471 ER PT J AU Weisz, A Murphy, CM Mazzola, EP Ito, Y AF Weisz, A Murphy, CM Mazzola, EP Ito, Y TI Preparation of starting materials for components of the color additive D&C Yellow No. 10 (Quinoline Yellow). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 83-AGFD BP U37 EP U38 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690000083 ER PT J AU Yager, JD Goodman, JE Lavigne, JA Chen, J AF Yager, JD Goodman, JE Lavigne, JA Chen, J TI COMT polymorphism and mitochondrial estrogen receptor in estrogen carcinogenesi. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 81-TOXI BP U300 EP U300 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690001540 ER PT J AU Yan, SQ Sigano, DM Nicklaus, MC Marquez, VE AF Yan, SQ Sigano, DM Nicklaus, MC Marquez, VE TI Molecular modeling studies of potential inhibitors against protein kinase C. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RI Sigano, Dina/M-6144-2014 OI Sigano, Dina/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 106-COMP BP U398 EP U398 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690002003 ER PT J AU Zhang, XC Merchand, C Pommier, Y Burke, TR AF Zhang, XC Merchand, C Pommier, Y Burke, TR TI Examination of chicoric acid and CAPE variants of beta-diketo acid-family HIV-1 integrase inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH, NCI, Med Chem Lab, FCRDC, Frederick, MD 21702 USA. NIH, NCI, Mol Pharmacol Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG PY 2001 VL 222 MA 102-MEDI BP U656 EP U656 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 467ET UT WOS:000170690003430 ER PT J AU Johansen, C Mellemkjaer, L Frisch, M Kjaer, SK Gridley, G Olsen, JH AF Johansen, C Mellemkjaer, L Frisch, M Kjaer, SK Gridley, G Olsen, JH TI Risk for anogenital cancer and other cancer among women hospitalized with gonorrhea SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE cancer; epidemiology; gonorrhea ID CERVICAL INTRAEPITHELIAL NEOPLASIA; SEXUALLY-TRANSMITTED INFECTION AB Background. We investigated the relationship between infections with Neisseria gonorrhoeae and anogenital and other cancers. Methods. Nationwide and population based register linkage study utilizing prospectively notified information. The observed numbers of cancers among the women were compared with those expected on the basis of national incidence rates. Results. In a cohort of 4440 women hospitalized for gonorrhea we observed a total of 227 cases of cervical intraepithelial neoplasia grade III (CIN III), with 103 expected (standardized incidence ratio (SIR), 2,2; 95% confidence interval (CI), 1.9-2.5). No significantly increased risk for other anogenital cancers or cancer at other sites was seen. Conclusions. These results support the view that the observed association between gonorrheal infection and subsequent cervical preneoplasia is due mainly to surveillance bias. However, our results also indicate that women hospitalized with a N. gonorrhoeae infection will benefit from the compliance with the regular Pap smear screening programs. C1 Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen O, Denmark. State Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Johansen, C (reprint author), Danish Canc Soc, Inst 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 [N01-CP-85639-04] NR 20 TC 5 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD AUG PY 2001 VL 80 IS 8 BP 757 EP 761 DI 10.1034/j.1600-0412.2001.080008757.x PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 467XC UT WOS:000170728200015 PM 11531621 ER PT J AU Strober, W Fuss, I Kitani, A AF Strober, W Fuss, I Kitani, A TI Regulation of experimental mucosal inflammation SO ACTA ODONTOLOGICA SCANDINAVICA LA English DT Article; Proceedings Paper CT Conference on New Frontiers in Oral Immunological Diseases CY FEB 23-27, 2001 CL LILLEHAMMER, NORWAY DE Crohn disease; cytokines; Th cells ID CD4(+) T-CELLS; INTERLEUKIN-10-DEFICIENT MICE; INTESTINAL INFLAMMATION; EXPERIMENTAL COLITIS; ORAL TOLERANCE; DISEASE; BETA; SUPPRESSION; INDUCTION; ANTIGENS AB Studies conducted over the past 10 years have provided ample evidence that many. types of inflammations arising from basic abnormalities, of immune regulation art, ultimately 'funneled' through it Th1 or Th2 T cell-mediated immune reaction. Thus, by understanding these types of reactions and, in particular, by identifying their natural checkpoints, one can control the inflammation regardless of its more basic causes. A case in point is the inflammatory disease of thc intestine known as Crohn disease, a disease now thought to be due to one or more abnormalities leading to an excessive immune response to elements of the bacterial microflora of the gut. Both ill murine models and by study of Crohn disease itself, we have shown that Crohn inflammation is due to a Th1 T-cell abnormality involving overproduction of interleukin (IL)-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha. In addition, we and others have shown that treatment of mice with anti-IL-12 or other agents that downregulate the level of IL-12 secretion can have a dramatic effect on the inflammation. This is because anti-IL-12 administration leads to apoptosis of activated Th1 T cells. A second checkpoint of Th1 T-cell-mediated inflammation involves its downregulation by the suppressor cytokine, transforming growth factor (TGF)-beta. Wr have been delivering TGF-beta to mice with experimental intestinal inflammation, using several novel approaches. In particular, we have successfully treated such mice with intranasally administered DNA encoding active TGF-beta. Another approach currently under investigation is delivery of TGF-beta by gene therapy. These and other developments in the understanding of inflammation paint it bright future For cytokine-based therapeutic agents. It is now apparent that these therapies are not only effective and safe but also potentially longlasting. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 19 TC 11 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6357 J9 ACTA ODONTOL SCAND JI Acta Odontol. Scand. PD AUG PY 2001 VL 59 IS 4 BP 244 EP 247 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 470ZC UT WOS:000170901500009 PM 11570528 ER PT J AU Allen, JP Litten, RZ Strid, N Sillanaukee, P AF Allen, JP Litten, RZ Strid, N Sillanaukee, P TI The role of biomarkers in alcoholism medication trials SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE biomarkers; outcome measures; alcohol treatment; clinical trial; biochemical markers ID CARBOHYDRATE-DEFICIENT TRANSFERRIN; PLACEBO-CONTROLLED TRIAL; GAMMA-GLUTAMYL-TRANSFERASE; DOUBLE-BLIND; CONSUMMATORY BEHAVIORS; OUTPATIENT ALCOHOLICS; BIOLOGICAL MARKERS; DEPENDENCE; ACAMPROSATE; NALTREXONE AB Background: Increasingly, biomarkers are being incorporated into the research design of clinical trials on medications to reduce drinking in alcoholics. To date, however, there has been little analysis of the unique roles that biomarkers can play in such investigations or of the practical and conceptual considerations that surround their best use in this context. Methods: Clinical trials of alcoholism medications published between 1985 and the present were abstracted to determine how biomarkers were used and how changes in them related to self-report measures of drinking. Results: Six uses of biomarkers were identified: determination of subjects to be included or excluded in the trial; description of baseline sample characteristics; primary and secondary outcome assessment; corroboration of self-reports of drinking status; specification of patients likely to respond to the medication; and evaluation of drug safety. Conclusion: Use of biomarkers in such studies appears warranted, particularly as an objective source of information on treatment efficacy that can be considered with patient self-report measures of drinking status. Biomarkers related to liver functioning also can assist in determination of drug safety for medications metabolized by the liver. C1 NIAAA, Rockville, MD 20852 USA. NS Associates, Stentorp, Sweden. Tampere Univ, Tampere Univ Hosp, Sch Med, Res Unit, Tampere, Finland. RP Allen, JP (reprint author), NIAAA, Willco Bldg 505,6000 Execut Blvd,MSC 7003, Rockville, MD 20852 USA. NR 40 TC 28 Z9 29 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2001 VL 25 IS 8 BP 1119 EP 1125 PG 7 WC Substance Abuse SC Substance Abuse GA 463CA UT WOS:000170458200005 PM 11505042 ER PT J AU Stinson, FS Grant, BF Dufour, MC AF Stinson, FS Grant, BF Dufour, MC TI The critical dimension of ethnicity in liver cirrhosis mortality statistics SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE mortality; cirrhosis; Hispanic origin ID DRINKING PATTERNS AB Background: In 1997, Ever cirrhosis was the 10th leading cause of death in the United States. Beginning in the 1950s, liver cirrhosis mortality rates have been consistently higher for black than for white men and women. There has been a gradual adoption of the recommendation that all death certificates include information on the Hispanic origin of decedents, with universal adoption in the 1997 data year. It is the purpose of this study to examine the extent to which relative risks for cirrhosis mortality might shift for different demographic groups when Hispanic origin is considered along with the race and sex of the decedent. Methods: Age-adjusted death rates were calculated for liver cirrhosis by using public-use data files produced by the National Center for Health Statistics. Trends in cirrhosis mortality rates from 1991 through 1997 are shown for white Hispanic, white non-Hispanic, black Hispanic, and black non-Hispanic men and women. Results: In 1997, white Hispanic men show the highest cirrhosis mortality rates over the period examined, followed by black non-Hispanic and white non-Hispanic men, white Hispanic women, and black non-Hispanic and white non-Hispanic women. Among Hispanic decedents, the largest group was of Mexican ancestry, with large numbers being born outside the United States and having low education levels. Conclusions: The findings of higher risk for cirrhosis mortality among white men and women of Hispanic origin serve to focus new attention on these demographic groups. Collateral analyses of other causes of death do not support alternate explanations of these findings as artifacts of demographic misclassification. Future studies of amounts and patterns of alcohol consumption should include Hispanic origin among demographic factors examined. C1 NIAAA, Div Biometry & Epidemiol, NIH, Bethesda, MD 20892 USA. RP Stinson, FS (reprint author), NIAAA, Div Biometry & Epidemiol, NIH, 6000 Execut Blvd,Ste 514, Bethesda, MD 20892 USA. FU NIAAA NIH HHS [N0AA82014] NR 18 TC 87 Z9 90 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD AUG PY 2001 VL 25 IS 8 BP 1181 EP 1187 PG 7 WC Substance Abuse SC Substance Abuse GA 463CA UT WOS:000170458200013 PM 11505049 ER PT J AU Prasad, A Koh, KK Schenke, WH Mincemoyer, R Csako, G Fleischer, TA Brown, M Selvaggi, TA Quyyumi, AA AF Prasad, A Koh, KK Schenke, WH Mincemoyer, R Csako, G Fleischer, TA Brown, M Selvaggi, TA Quyyumi, AA TI Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-ARTERY DISEASE; APPARENTLY HEALTHY-MEN; SOLUBLE L-SELECTIN; ENDOTHELIAL-CELLS; LEUKOCYTE ADHESION; DIABETIC-PATIENTS; HEART-DISEASE; IN-VIVO; EXPRESSION; ICAM-1 AB Background Inflammation is a central feature of coronary artery disease (CAD) that is characterized by increased expression of cellular adhesion molecules with the exception of L-selectin. L-selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so that it appears to be decreased in CAD. The renin-angiotensin system (RAS) is implicated in atherogenesis and up-regulates these molecules. Objectives The aim of this study was to investigate the effect of angiotensin type I (ATI) receptor antagonism on serum and leukocyte adhesion molecule expression in patients with CAD. Blood samples were collected from 31 patients before and after 8 weeks of treatment with losartan (44 +/-2 mg/d, mean SE), an ATI receptor antagonist. We measured serum intercellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-leukocyte adhesion molecule, and C-reactive protein (CRP). By flow cytometry, we also measured the expression of leukocyte CD11a, CD11b, CD11c, CD18, CD31, CD49d, and CD62L (L-selectin) in 13 patients. Results Treatment with losartan decreased systolic blood pressure (141 +/-3 vs 135 +/-4 mm Hg, P =.04) and increased plasma renin activity (1.2 +/-0.4 vs 2.7 +/-0.5 ng/mL/h, P=.001). There was a significant increase in L-selectin expression an monocytes (86 +/-6 vs 118 +/- 10 MESF units, P=.007), lymphocytes (52 +/- 10 vs 79 +/-8, P=.01), and granulocytes (124 +/-7 vs 156 +/- 18, P =.056). However, there were no changes in the other leukocyte and serum adhesion molecules or CRP. Conclusions These findings suggest that AT1 receptor antagonism selectively modulates L-selectin expression on leukocytes and that endogenous stimulation of AT1 receptors by the RAS contributes to the activation of leukocytes and decreased expression of L-selectin in CAD. C1 NHLBI, NIH, Cardiol Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), NHLBI, NIH, Cardiol Branch, Bldg 10,Room 7B15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 35 TC 53 Z9 61 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 2001 VL 142 IS 2 BP 248 EP 253 DI 10.1067/mhj.2001.116699 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 459XC UT WOS:000170275900010 PM 11479463 ER PT J AU Lederman, RJ Mendelsohn, FO Santos, R Phillips, HR Stack, RS Crowley, JJ AF Lederman, RJ Mendelsohn, FO Santos, R Phillips, HR Stack, RS Crowley, JJ TI Primary renal artery stenting: Characteristics and outcomes after 363 procedures SO AMERICAN HEART JOURNAL LA English DT Article ID RECURRENT PULMONARY-EDEMA; BALLOON ANGIOPLASTY; BLOOD-PRESSURE; SURGICAL REVASCULARIZATION; ISCHEMIC NEPHROPATHY; RENOVASCULAR HYPERTENSION; RANDOMIZED TRIAL; STENOSIS; DISEASE; PLACEMENT AB Background Stenting improves the acute results of percutaneous balloon angioplasty for atherosclerotic renal artery stenosis. Predictors of benefit and angiographic restenosis are not well understood. We describe the technical and clinical success of renal artery stenting in a large consecutive series of patients with hypertension or renal insufficiency. We identify clinical, procedural, and anatomic factors that might influence outcome, restenosis, and survival. Methods Primary renal artery stenting was performed in 300 consecutive patients who underwent 363 stent procedures in 358 arteries. Angiograms were analyzed quantitatively. Clinical and angiographic follow-up data are available after a median of 16.0 months. Results At baseline, 87% of patients had hypertension, and 37% had chronic renal insufficiency. The mean age was 70 years (interquartile range 63.1-74.6) years. The stenosis was unilateral in 49% and bilateral in 48% and involved a solitary functioning kidney in 3.6%. The stenting procedure was successful in all attempts. There were no procedural deaths or emergency renal surgical procedures. Postprocedure azotemia was seen in 45 of 363 (12%) procedures but persisted in only 6 patients (2%), all of whom had baseline renal insufficiency. Systolic and diastolic blood pressures were significantly reduced (systolic blood pressure from 164.0 +/- 28.7 to 142.4 +/- 19.1 mm Hg, P <.001). At follow-up, 70% of patients had improved blood pressure control regardless of renal function. In patients with baseline renal insufficiency, 19% had improvement in serum creatinine levels at follow-up, 54% had stabilization, and 27% had deterioration. Follow-up mortality was 10% and was predicted by baseline creatinine levels (odds ratio 1.72 for each 1 mg/dL creatinine increment, 95% confidence interval 1. 13-2.49) and extent of coronary artery disease (odds ratio 1.66 for each diseased coronary artery, 95% confidence interval 1.03-2.67). Angiographic restenosis was found in 21% of 102 patients overall and was less common (12%) in arteries with a reference caliber >4.5 mm (P<.01 vs caliber <4.5 mm). Neither poststenotic dilation nor severity of angiographic stenosis predicted clinical outcome. Conclusions Primary renal artery stenting can be performed safely with nearly uniform technical success. The majority of patients with hypertension or renal insufficiency derive benefit. Follow-up mortality is 5-fold higher in patients with baseline renal insufficiency. Clinical and angiographic features did not predict blood pressure or renal functional outcome. Restenosis is more common in renal arteries with a reference caliber less than 4.5 mm. C1 Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. Univ Michigan Hlth Syst, Dept Internal Med, Div Cardiol, Ann Arbor, MI USA. RP Lederman, RJ (reprint author), NHLBI, NIH, 10 Ctr Dr,Room B1 D219, Bethesda, MD 20892 USA. OI lederman, robert/0000-0003-1202-6673 NR 46 TC 165 Z9 179 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD AUG PY 2001 VL 142 IS 2 BP 314 EP 323 DI 10.1067/mhj.2001.116958 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 459XC UT WOS:000170275900019 PM 11479472 ER PT J AU Kwiatkowska, HY AF Kwiatkowska, HY TI Family art therapy: Experiments with a new technique SO AMERICAN JOURNAL OF ART THERAPY LA English DT Article C1 NIMH, Art Therapy Dept, Baltimore, MD USA. Sculpture Ctr, New York, NY USA. RP Kwiatkowska, HY (reprint author), NIMH, Art Therapy Dept, Baltimore, MD USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER J ART THERAPY PI MONTPELIER PA VERMONT COLL OF NORWICH UNIV, MONTPELIER, VT 05602 USA SN 0007-4764 J9 AM J ART THER JI mm. J. Art. Ther. PD AUG PY 2001 VL 40 IS 1 BP 27 EP 39 PG 13 WC Rehabilitation SC Rehabilitation GA 464CL UT WOS:000170515500004 ER PT J AU Pearson, TA Stone, EJ Grundy, SM McBride, PE Van Horn, L Tobin, BW AF Pearson, TA Stone, EJ Grundy, SM McBride, PE Van Horn, L Tobin, BW CA NAA Collaborative Grp TI Translation of nutritional sciences into medical education: the Nutrition Academic Award Program SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE medical education; nutrition education; curriculum; medical students; residents; clinical competence; Nutrition Academic Award Program ID AMERICAN-HEART-ASSOCIATION; HEALTH-CARE PROFESSIONALS; GUIDELINES; CHOLESTEROL; PHYSICIANS; CURRICULUM; STATEMENT; NETWORKS; DISEASE; SCHOOLS AB For the past 40 y the scientific community has decried the inadequacy of the training of physicians and other health professionals in the subject of human nutrition. In 1997 the National Heart, Lung, and Blood Institute developed the Nutrition Academic Award (NAA) Program, an initiative to improve nutrition training across a network of US medical schools. The purpose of this funding, which began in 1998, is to support the development and enhancement of nutrition curricula for medical students. residents. and practicing physicians to learn principles and practice skills in nutrition. The NAA recipients developed the Nutrition Curricular Guide for Training Physicians, a plan to incorporate clinical guidelines into physician practice skills, create educational and assessment practice tools. and evaluate curricula, materials, and teaching tools. Dissemination of NAA activities and materials will be facilitated by a national website. presentations and publications, and consultants and advisors from the NAA nutrition education programs. The NAA Program constitutes a major new effort to enhance nutrition knowledge and skills among health care providers and to effectively apply the science of human nutrition to clinical medicine. This article describes the purpose and aims of the NAA Program, the organizational structure of the network of recipients, a profile of the recipients and individual programs at 21 medical schools. the various strategies to overcome barriers in training physicians in human nutrition, and collaborative and dissemination efforts. C1 Univ Rochester, Sch Med & Dent, Dept Community & Prevent Med, Rochester, NY USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Northwestern Univ, Sch Med, Dept Prevent Med, Evanston, IL USA. Mercer Univ, Sch Med, Div Basic Med Sci, Macon, GA 31207 USA. RP Pearson, TA (reprint author), Univ Rochester, Sch Med, Dept Community & Prevent Med, 601 Elmwood Ave, Rochester, NY 14642 USA. FU NHLBI NIH HHS [HL03943, HL03924, HL03965, HL03967, HL043051] NR 43 TC 37 Z9 38 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2001 VL 74 IS 2 BP 164 EP 170 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 457GQ UT WOS:000170129100005 PM 11470716 ER PT J AU Michaud, DS Giovannucci, E Willett, WC AF Michaud, DS Giovannucci, E Willett, WC TI Validity of dietary assessment - Reply to B Watzl and G Rechkemmer SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID CANCER; FRUIT C1 Natl Canc Inst, Nutrit Epidemiol Branch, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. RP Michaud, DS (reprint author), Natl Canc Inst, Nutrit Epidemiol Branch, Rockville, MD 20852 USA. RI Michaud, Dominique/I-5231-2014 NR 3 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2001 VL 74 IS 2 BP 273 EP 274 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 457GQ UT WOS:000170129100026 ER PT J AU El-Serag, HB Richardson, PA Everhart, JE AF El-Serag, HB Richardson, PA Everhart, JE TI The role of diabetes in hepatocellular carcinoma: A case-control study among United States veterans SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID PRIMARY LIVER-CANCER; C VIRUS-INFECTION; HEPATITIS-C; RISK-FACTORS; MULTIVARIATE-ANALYSIS; CIRRHOSIS; MELLITUS; PROGRESSION; DISEASE; TAIWAN AB OBJECTIVE: Diabetes mellitus (DM) has been reported to increase the risk of hepatocellular carcinoma (HCC). We carried out a case-control study to examine the role of DM while controlling for several known risk factors of HCC. METHODS: All hospitalized patients with primary liver cancer (PLC) during 1997-1999 were identified in the computerized database of the Department of Veterans Affairs, the Patient Treatment File. Controls without cancer were randomly assigned from the Patient Treatment File during the same time period. The inpatient and outpatient files were searched for several conditions including DM, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic cirrhosis, autoimmune hepatitis, hemochromatosis, and nonspecific cirrhosis. Adjusted odds ratios (OR) were calculated in a multivariable logistic regression model. RESULTS: We identified 823 patients with PLC and 3459 controls. The case group was older (62 yr [+/- 10] vs 60 [+/- 11], p < 0.0001). had more men (99% vs 97%. 0.0004), and a greater frequency of nonwhites (66% vs 71%, 0.0009) compared with controls. However, HCV- and HBV-infected patients were younger among cases than controls. Risk factors that were significantly more frequent among PLC cases included HCV (34% vs 5%, p < 0.0001), HBV (11% vs 2%. p < 0.0001), alcoholic cirrhosis (47% vs 6%, p < 0.0001). hemochromatosis (2% vs 0.3%, p < 0.0001), autoimmune hepatitis (5% vs 0.5%. p < 0.0001), and diabetes (33% vs 30%. p = 0.059). In the multivariable logistic regression, diabetes was associated with a significant increase in the adjusted OR of PLC (1.57, 1.08-2.28, p = 0.02) in the presence of HCV, HBV. or alcoholic cirrhosis. Without markers of chronic liver disease, the adjusted OR for diabetes and PLC was not significantly increased (1.08, 0.86-1.18. p = 0.4). There was an increase in the HCV adjusted OR (17.27, 95% CI = 11.98-24.89) and HBV (9.22, 95% Cl = 4.52-18.80) after adjusting for the younger age of HCV- and HBV-infected cases. The combined presence of HCV and alcoholic cirrhosis further increases the risk with an adjusted OR of 79.21 (60.29-103.41). The population attributable fraction for HCV among hospitalized veterans was 44.8%, whereas that of alcoholic cirrhosis was 51%. CONCLUSION: DM increased the risk of PLC only in the presence of other risk factors such as hepatitis C or B or alcoholic cirrhosis. Hepatitis C infection and alcoholic cirrhosis account for most of PLC among veterans. C1 Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDKD, NIDDK, Bethesda, MD USA. RP El-Serag, HB (reprint author), Vet Affairs Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 38 TC 154 Z9 156 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD AUG PY 2001 VL 96 IS 8 BP 2462 EP 2467 DI 10.1111/j.1572-0241.2001.04054.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 462TA UT WOS:000170434800036 PM 11513191 ER PT J AU Lu, KM Lee, MH Hazard, S Brooks-Wilson, A Hidaka, H Kojima, H Ose, L Stalenhoef, AFH Mietinnen, T Bjorkhem, I Bruckert, E Pandya, A Brewer, HB Salen, G Dean, M Srivastava, A Patel, SB AF Lu, KM Lee, MH Hazard, S Brooks-Wilson, A Hidaka, H Kojima, H Ose, L Stalenhoef, AFH Mietinnen, T Bjorkhem, I Bruckert, E Pandya, A Brewer, HB Salen, G Dean, M Srivastava, A Patel, SB TI Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DIETARY-CHOLESTEROL; ABSORPTION; XANTHOMATOSIS; IDENTIFICATION; PROTEINS; CLONING AB Sitosterolemia is a rare autosomal recessive disorder characterized by (a) intestinal hyperabsorption of all sterols, including cholesterol and plant and shellfish sterols, and (b) impaired ability to excrete sterols into bile. Patients with this disease have expanded body pools of cholesterol and very elevated plasma plant-sterol species and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. In previous studies, we have mapped the STSL locus to human chromosome 2p21. Recently, we reported that a novel member of the ABC-transporter family, named "sterolin-1" and encoded by ABCG5, is mutated in 9 unrelated families with sitosterolemia; in the remaining 25 families, no mutations in sterolin-1 could be identified. We identified another ABC transporter, located <400 bp upstream of sterolin-1, in the opposite orientation. Mutational analyses revealed that this highly homologous protein, termed "sterolin-2" and encoded by ABCG8, is mutated in the remaining pedigrees. Thus, two highly homologous genes, located in a head-to-head configuration on chromosome 2p21, are involved as causes of sitosterolemia. These studies indicate that both sterolin-1 and sterolin-2 are indispensable for the regulation of sterol absorption and excretion. Identification of sterolin-1 and sterolin-2 as critical players in the regulation of dietary-sterol absorption and excretion identifies a new pathway of sterol transport. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, STR 541, Charleston, SC 29403 USA. Med Univ S Carolina, Biomol Comp Resource, Charleston, SC 29403 USA. Xenon Genet Inc, Vancouver, BC, Canada. Sanyo Elect Grp Hlth Insurance Assoc, Osaka, Japan. Shiga Univ Med Sci, Dept Med 3, Otsu, Shiga 52021, Japan. Univ Oslo, Rikshosp, Lipid Res Clin, N-0027 Oslo, Norway. Univ Nijmegen Hosp, Dept Med, Div Gen Internal Med, NL-6500 HB Nijmegen, Netherlands. Univ Helsinki, Cent Hosp, Dept Internal Med, Helsinki, Finland. Huddinge Univ, Karolinska Inst, Div Clin Chem, Huddinge, Sweden. Hop La Pitie Salpetriere, Dept Endocrinol, Paris, France. Virginia Commonwealth Univ, Dept Human Genet, Richmond, VA USA. NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Div Gastroenterol, Newark, NJ 07103 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. RP Patel, SB (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, STR 541, 114 Doughty St, Charleston, SC 29403 USA. RI Dean, Michael/G-8172-2012; Tang, Macy/B-9798-2014; Brooks-Wilson, Angela/E-9399-2012; Stalenhoef, A.F.H./H-8094-2014; OI Dean, Michael/0000-0003-2234-0631; Brooks-Wilson, Angela/0000-0003-1009-6408; Bjorkhem, Ingemar/0000-0001-6087-9190; Patel, Shailendra/0000-0003-0046-5513 FU NCRR NIH HHS [M01 RR001070, MO1 RR01070-25]; NHLBI NIH HHS [R01 HL060613, HL60616] NR 35 TC 184 Z9 200 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2001 VL 69 IS 2 BP 278 EP 290 DI 10.1086/321294 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 456XN UT WOS:000170108200004 PM 11452359 ER PT J AU Aksentijevich, I Galon, J Soares, M Mansfield, E Hull, K Oh, HH Goldbach-Mansky, R Dean, J Athreya, B Reginato, AJ Henrickson, M Pons-Estel, B O'Shea, JJ Kastner, DL AF Aksentijevich, I Galon, J Soares, M Mansfield, E Hull, K Oh, HH Goldbach-Mansky, R Dean, J Athreya, B Reginato, AJ Henrickson, M Pons-Estel, B O'Shea, JJ Kastner, DL TI The tumor-necrosis-factor receptor-associated periodic syndrome: New mutations in TNFRSF1A, ancestral origins, genotype-phenotype studies, and evidence for further genetic heterogeneity of periodic fevers SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; ENCODING MEVALONATE KINASE; TNF RECEPTOR; CHROMOSOME 12P13; COMPLEX; IDENTIFICATION; LOCALIZATION; AMYLOIDOSIS; DISEASES; LINKAGE AB Mutations in the extracellular domain of the 55-kD tumor-necrosis factor (TNF) receptor (TNFRSF1A), a key regulator of inflammation, define a periodic-fever syndrome, TRAPS (TNF receptor-associated periodic syndrome [MIM 142680]), which is characterized by attacks of fever, sterile peritonitis, arthralgia, myalgia, skin rash, and/or conjunctivitis; some patients also develop systemic amyloidosis. Elsewhere we have described six disease-associated TNFRSF1A mutations, five of which disrupt extracellular cysteines involved in disulfide bonds; four other mutations have subsequently been reported. Among 150 additional patients with unexplained periodic fevers, we have identified four novel TNFRSF1A mutations (H22Y, C33G, S86P, and c. 193-14 G-->A), one mutation (C30S) described by another group, and two substitutions (P46L and R92Q) present in similar to1% of control chromosomes. The increased frequency of P46L and R92Q among patients with periodic fever, as well as functional studies of TNFRSF1A, argue that these are low- penetrance mutations rather than benign polymorphisms. The c. 193-14 G-->A mutation creates a splice-acceptor site upstream of exon 3, resulting in a transcript encoding four additional extracellular amino acids. T50M and c. 193-14 G-->A occur at CpG hotspots, and haplotype analysis is consistent with recurrent mutations at these sites. In contrast, although R92Q also arises at a CpG motif, we identified a common founder chromosome in unrelated individuals with this substitution. Genotype-phenotype studies identified, as carriers of cysteine mutations, 13 of 14 patients with TRAPS and amyloidosis and indicated a lower penetrance of TRAPS symptoms in individuals with noncysteine mutations. In two families with dominantly inherited disease and in 90 sporadic cases that presented with a compatible clinical history, we have not identified any TNFRSF1A mutation, despite comprehensive genomic sequencing of all of the exons, therefore suggesting further genetic heterogeneity of the periodic-fever syndromes. C1 NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Sect Lymphocyte Cell Biol, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. Inst Curie, Lab Immunol Cellulaire & Clin, INSERM, U255, Paris, France. duPont Hosp Children, Div Rheumatol, Wilmington, DE USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Cooper Univ Med Ctr, Dept Med,Rheumatol Sect, Camden, NJ 08103 USA. Valley Childrens Hosp, Pediat Arthrit Ctr, Madera, CA USA. Sanatorio Parque, Rosario, Santa Fe, Argentina. RP Aksentijevich, I (reprint author), NIAMSD, Genet Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N214, Bethesda, MD 20892 USA. NR 33 TC 203 Z9 210 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2001 VL 69 IS 2 BP 301 EP 314 DI 10.1086/321976 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 456XN UT WOS:000170108200006 PM 11443543 ER PT J AU Xu, JF Zheng, SQL Hawkins, GA Faith, DA Kelly, B Isaacs, SD Wiley, KE Chang, BL Ewing, CM Bujnovszky, P Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB AF Xu, JF Zheng, SQL Hawkins, GA Faith, DA Kelly, B Isaacs, SD Wiley, KE Chang, BL Ewing, CM Bujnovszky, P Carpten, JD Bleecker, ER Walsh, PC Trent, JM Meyers, DA Isaacs, WB TI Linkage and association studies of prostate cancer susceptibility: Evidence for linkage at 8p22-23 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TUMOR-SUPPRESSOR GENE; COLORECTAL-CANCER; ALLELIC LOSS; LUNG-CANCER; DELETION; HETEROZYGOSITY; CHROMOSOME-8; CARCINOMAS; TESTS; EXPRESSION AB Multiple lines of evidence have implicated the short arm of chromosome 8 as harboring genes important in prostate carcinogenesis. Although most of this evidence comes from the identification of frequent somatic alterations of 8p loci in prostate cancer cells (e.g., loss of heterozygosity), studies have also suggested a role for 8p genes in mediation of inherited susceptibility to prostate cancer. To further examine this latter possibility, we performed linkage analyses, in 159 pedigrees affected by hereditary prostate cancer (HPC), using 24 markers on the short arm of chromosome 8. In the complete set of families, evidence for prostate cancer linkage was found at 8p22-23, with a peak HLOD of 1.84 (P = .004), and an estimate of the proportion of families linked (alpha) of 0.14, at D8S1130. In the 79 families with average age at diagnosis >65 years, an allele-sharing LOD score of 2.64 (P = .005) was observed, and six markers spanning a distance of 10 cM had LOD scores >2.0. Interestingly, the small number of Ashkenazi Jewish pedigrees (n = 11) analyzed in this study contributed disproportionately to this linkage. Mutation screening in HPC probands and association analyses in case subjects (a group that includes HPC probands and unrelated case subjects) and unaffected control subjects were carried out for the putative prostate cancer-susceptibility gene, PG1, previously localized to the 8p22-23 region. No statistical differences in the allele, genotype, or haplotype frequencies of the SNPs or other sequence variants in the PG1 gene were observed between case and control subjects. However, case subjects demonstrated a trend toward higher homozygous rates of less-frequent alleles in all three PG1 SNPs, and overtransmission of a PG1 variant to case subjects was observed. In summary, these results provide evidence for the existence of a prostate cancer-susceptibility gene at 8p22-23. Evaluation of the PG1 gene and other candidate genes in this area appears warranted. C1 Johns Hopkins Hosp, Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21287 USA. Wake Forest Univ, Bowman Gray Sch Med, Ctr Human Genom, Winston Salem, NC USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Isaacs, WB (reprint author), Johns Hopkins Hosp, Johns Hopkins Med Inst, Dept Urol, Marburg 115,600 N Wolfe St, Baltimore, MD 21287 USA. RI Xu, Jun/B-7351-2012 FU NCI NIH HHS [CA58236, P50 CA058236] NR 36 TC 102 Z9 107 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2001 VL 69 IS 2 BP 341 EP 350 DI 10.1086/321967 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 456XN UT WOS:000170108200009 PM 11443539 ER PT J AU Kelley, MJ Korczak, JF Sheridan, E Yang, XH Goldstein, AM Parry, DM AF Kelley, MJ Korczak, JF Sheridan, E Yang, XH Goldstein, AM Parry, DM TI Familial chordoma, a tumor of notochordal remnants, is linked to chromosome 7q33 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MULTILOCUS LINKAGE ANALYSIS; INHERITANCE; LOCUS AB Chordoma is a rare tumor originating from notochordal remnants that is usually diagnosed during midlife. We performed a genomewide analysis for linkage in a family with 10 individuals affected by chordoma. The maximum two-point LOD score based on only the affected individuals was 2.21, at recombination fraction 0, at marker D7S2195 on chromosome 7q. Combined analysis of additional members of this family (11 affected individuals) and of two unrelated families (one with 2 affected individuals and the other with 3 affected individuals), with 20 markers on 7q, showed a maximum two-point LOD score of 4.05 at marker D7S500. Multipoint analysis based on only the affected individuals gave a maximum LOD score of 4.78, with an approximate 2-LOD support interval from marker D7S512 to marker D7S684. Haplotype analysis of the three families showed a minimal disease-gene region from D7S512 to D7S684, a distance of 11.1 cM and similar to7.1 Mb. No loss of heterozygosity was found at markers D7S1804, D7S1824, and D7S2195 in four tumor samples from affected family members. These results map a locus for familial chordoma to 7q33. Further analysis of this region, to identify this gene, is ongoing. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Duke Univ, Dept Med, Durham, NC USA. Vet Affairs Hosp, Durham, NC USA. Karmanos Canc Inst, Epidemiol Sect, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Internal Med, Detroit, MI 48201 USA. St James Univ Hosp, Leeds LS9 7TF, W Yorkshire, England. RP Parry, DM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7124,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. OI Kelley, Michael/0000-0001-9523-6080 FU BLRD VA [I01 BX000458]; NCRR NIH HHS [P41 RR003655, RR03655]; PHS HHS [263-MQ-013900] NR 18 TC 43 Z9 44 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD AUG PY 2001 VL 69 IS 2 BP 454 EP 460 DI 10.1086/321982 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 456XN UT WOS:000170108200021 PM 11452362 ER PT J AU Anderson, DE Scuteri, A Agalakova, N Parsons, DJ Bagrov, AY AF Anderson, DE Scuteri, A Agalakova, N Parsons, DJ Bagrov, AY TI Racial differences in resting end-tidal CO2 and circulating sodium pump inhibitor SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE African American; blood pressure; end-tidal CO2; hypertension; sodium ID BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; MARINOBUFAGENIN-LIKE; VOLUME EXPANSION; INTRACELLULAR PH; SALT SENSITIVITY; BLACKS; ASSOCIATION; PLASMA; DOGS AB Previous studies have shown that high end-tidal CO, (PetCO(2)) is a marker for sodium sensitivity of blood pressure (BP) in White Americans, and that the BP of African Americans is more sensitive to high sodium intake than that of whites. The present study tested the hypothesis that resting PetCO(2) is higher in normotensive African Americans than in whites. Resting end-tidal CO2 of 395 white and 125 African American participants in the Baltimore Longitudinal Study on Aging was monitored for 20 min with a respiratory gas monitor, and BP and heart rate were recorded every 5 min by oscillometric methodology. Twenty-four-hour urinary excretion of a circulating sodium pump inhibitor marinobufagenin-like compound (MBG), which increases when plasma volume is expanded, was also analyzed by fluoroimmunoassay in racial groups. Mean resting PetCO(2) of African American men was higher than that of white men (38.1 +/- 0.5 v 36.4 +/- 0.3 mm Hg), and resting PetCO(2) of African American women was higher than that of white women (37.7 +/- 0.3 v 36.2 +/- 0.3 rum Hg). The differences were not significant in either men or women less than 50 years old, but were substantial in both men and women more than 50 years. Twenty-four-hour urinary excretion of MBG was higher in white (2.7 +/- 0.2 pmol) than in African American (2.1 +/- 0.2 pmol) participants, and high PetCO(2) was a significant independent predictor of high MBG excretion in African Americans, These data are consistent with the hypothesis that the higher resting PetCO(2) in African Americans plays a role in slower urinary excretion of sodium, greater BP sensitivity to high sodium intake, and increased prevalence of chronic hypertension. (C) 2001 American Journal of Hypertension. Ltd. C1 NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Anderson, DE (reprint author), NIA, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD AUG PY 2001 VL 14 IS 8 BP 761 EP 767 DI 10.1016/S0895-7061(01)02163-X PN 1 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 458JK UT WOS:000170191100005 PM 11497191 ER PT J AU Hayes, RB Yin, SN Dosemeci, M Linet, M AF Hayes, RB Yin, SN Dosemeci, M Linet, M TI Benzene and lymphohematopoietic malignancies in humans SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Review DE benzene; leukemia; exposure assessment; lymphohematopoietic malignancies; epidemiology ID NATIONAL-CANCER-INSTITUTE; INDUSTRY WIDE MORTALITY; DOSE-RELATED INCIDENCE; EXPOSED WORKERS; CHROMOSOMAL-ABERRATIONS; OCCUPATIONAL EXPOSURE; MULTIPLE-MYELOMA; RUBBER INDUSTRY; APLASTIC-ANEMIA; RISK ASSESSMENT AB Background Quantitative evaluations of benzene-associated risk for cancer have relied primarily on findings from a cohort study of highly exposed U.S. rubber workers. An epidemiologic investigation in China (NCI/CAPM study) extended quantitative evaluations of cancer risk to a broader range of benzene exposures, particularly at lower levels. Methods We review the evidence implicating benzene in the etiology of hematopoietic disorders, clarify methodologic aspects of the NCI/CAPM study, and examine the study in the context of the broader literature on health effects associated with occupational benzene exposure. Results Quantitative relationships for cancer risk from China and the U.S. show a relatively smooth increase in risk for acute myeloid leukemia and related conditions over a broad dose range of benzene exposure (below 200 ppm-years mostly from the China study and above 200 ppm-years mostly from the U.S. study). Conclusions Risks of acute myeloid leukemia and other malignant and nonmalignant hematopoietic disorders associated with benzene exposure in China are consistent with other information about benzene exposure, hematotoxicity, and cancer risk, extending evidence for hematopoietic cancer risks to levels substantially lower than had previously been established. Published 2001 Wiley-Liss, Inc. C1 NCI, Div Canc epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Prevent Med, Beijing 100052, Peoples R China. RP Hayes, RB (reprint author), NCI, Div Canc epidemiol & Genet, EPS 8114, Bethesda, MD 20892 USA. NR 106 TC 69 Z9 71 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 2001 VL 40 IS 2 BP 117 EP 126 DI 10.1002/ajim.1078 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 462TW UT WOS:000170436700001 PM 11494338 ER PT J AU Ji, BT Silverman, DT Stewart, PA Blair, A Hoover, R AF Ji, BT Silverman, DT Stewart, PA Blair, A Hoover, R TI Re: Occupational exposure to pesticides and pancreatic cancer. 2001. Ji B.-T., Silverman D.T., Stewart P.A., Blair A., Swanson G.M., Baris D., Greenberg R.D., Hayes R., Brown L.M., Lillemoe K.D., Schoenberg J.B., Pottern L.M., Schwartz A.G., Hoover R. Am. J. Ind. Med. 39:92-99 SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter C1 NCI, Div Cant Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ji, BT (reprint author), NCI, Div Cant Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 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 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD AUG PY 2001 VL 40 IS 2 BP 225 EP 226 DI 10.1002/ajim.1092 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 462TW UT WOS:000170436700015 ER PT J AU Baksh, FK Finkelstein, SD Swalsky, PA Stoner, GL Ryschkewitsch, CF Randhawa, P AF Baksh, FK Finkelstein, SD Swalsky, PA Stoner, GL Ryschkewitsch, CF Randhawa, P TI Molecular genotyping of BK and JC viruses in human polyomavirus-associated interstitial nephritis after renal transplantation SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 10-17, 2000 CL NEW ORLEANS, LOUISIANA SP US & Canadian Acad Pathol DE BK virus (BKV); JC virus (JCV); polyomavirus; allograft; kidney; sequencing; mutations; genotypes; interstitial nephritis; renal transplantation (Tx) ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; HEMORRHAGIC CYSTITIS; DNA-SEQUENCES; PRIMATE POLYOMAVIRUSES; COMPLETE GENOMES; AIDS PATIENT; HUMAN URINE; INFECTION; RECIPIENTS; DISEASE AB The human polyomaviruses BK virus (BKV) and JC virus (JCV) have been linked to ureteric stenosis and allograft interstitial nephritis, but molecular characterization of the species involved has not been performed. We studied paraffin-embedded renal tissue from 19 cases of allograft viral interstitial nephritis. Histological sections were subjected to polymerase chain reaction amplification using consensus, BKV-, and JCV-specific primers, with subsequent DNA sequencing for strain determination. BKV was present in all (100%) interstitial nephritis kidneys and placed in genotypes corresponding to serological groups I (n = 11), 11 (n = 1), and IV (n = 5). Fourteen of 17 isolates (82%) showed sequence variations in the viral capsid protein-1 (VP1) capsid region, with predicted changes in the encoded amino acids and sometimes with potential implications for the secondary and tertiary structure of the corresponding protein molecules. An additional case showed a previously reported glutamine --> leucine T-antigen region mutation. JCV was seen in seven interstitial nephritis kidneys (37%), with types 4 (n = 3), 3A (n = 2), and 2A (n = 1) identified. Most white individuals with asymptomatic infection are reported to shed type 1 JCV in the urine. Simian 40 polyomavirus was not Identified in any case. These observations may have pathogenic relevance to the development of an extremely refractory form of polyomavirus interstitial nephritis seen after kidney transplantation. (C) 2001 by the National Kidney Foundation, Inc. C1 Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA. NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. RP Randhawa, P (reprint author), Univ Pittsburgh, Presbyterian Univ Hosp, Med Ctr, Div Transplantat Pathol,Dept Pathol, 200 Lothrop St, Pittsburgh, PA 15213 USA. NR 66 TC 85 Z9 87 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD AUG PY 2001 VL 38 IS 2 BP 354 EP 365 DI 10.1053/ajkd.2001.26101 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 458PX UT WOS:000170204700016 PM 11479162 ER PT J AU Porter, AE Auth, J Prince, M Ghidini, A Brenneman, DE Spong, CY AF Porter, AE Auth, J Prince, M Ghidini, A Brenneman, DE Spong, CY TI Optimization of cytokine stability in stored amniotic fluid SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE amniotic fluid; cytokines; stability; interleukin-6; angiogenin; vascular endothelial growth factor ID TUMOR-NECROSIS-FACTOR; GESTATIONAL-AGE; INTERLEUKIN-6 LEVELS; PRETERM DELIVERY; MIDTRIMESTER; ANGIOGENIN; LABOR; ALPHA AB OBJECTIVE: Many studies use stored amniotic, fluid samples to assay cytokines and other proteins for outcome-based research; however, there is little information on the optimal methods of storage. The objective of our study was to evaluate cytokine stability In amniotic fluid stored at different temperatures both with and without a proteolytic enzyme inhibitor. STUDY DESIGN: Patients undergoing midtrimester genetic amniocentesis for routine indications gave consent for the study. After the sample was centrifuged, the acellular portion of the sample was mixed to homogeneity and aliquoted in 0.5-mL increments and stored for 1 year at 4 degreesC, -20 degreesC, and -80 degreesC with and without the protease inhibitor aprotinin. Enzyme-linked immunoassays for angiogenin, interleukin-6, and vascular endothelial growth factor were performed simultaneously on each aliquot. RESULTS: Thirty samples were assayed for each storage condition. Results were calculated as the percentage of its own sister aliquot stored at -80 degreesC without aprotinin. In all samples, there was a significant relation between storage temperature and cytokine levels, with the lowest levels found at 4 degreesC and the highest at -80 degreesC (angiogenin, P = .004; interleukin-6, P < .001; vascular endothelial growth factor, P = .02). The addition of aprotinin improved stability only for angiogenin at all temperatures (all P < .05). CONCLUSIONS: Degradation of cytokines occurs when amniotic fluid samples are stored for prolonged periods at temperatures greater than -80 degreesC. The addition of a protease Inhibitor helps stem the degradation of some cytokines. C1 NICHD, SDMP, LDN, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC 20057 USA. RP Spong, CY (reprint author), NICHD, SDMP, LDN, NIH, Bldg 49,Room 5A-38,MSC 4480,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2001 VL 185 IS 2 BP 459 EP 462 DI 10.1067/mob.2001.115106 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 465XL UT WOS:000170615200050 PM 11518909 ER PT J AU Spong, CY Porter, AE Queenan, JT AF Spong, CY Porter, AE Queenan, JT TI Management of isoimmunization in the presence of multiple maternal antibodies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE isoimmunization; multiple maternal antibodies; Queenan curve; erythroblastosis fetalis; management AB OBJECTIVE: Evaluation and management of patients with multiple maternal antibody isoimmunization is unclear. The presence of greater than or equal to 1 maternal antibody may suggest a worse scenario. The objective of this study was 2-fold: first, to determine whether the presence of multiple antibodies predicts a more severe course than single antibodies and second, to determine the utility of the Queenan curves/protocol In evaluating multiple-antibody isoimmunization. STUDY DESIGN: Amniotic fluid Delta OD450 measurements were obtained from the antenatal testing logbook and confirmed by chart review. Cases were categorized by antibody type and clinical outcomes obtained by chart review. RESULTS: Twenty-four pregnancies with isoimmunization and multiple maternal antibodies were Identified; of these, 17 had 2 antibodies (anti-D and -C in 13; anti-D and -E In 1; anti-D and -Jka in 1; anti-c and -E in 1; and anti-c and -Jka in 1), and 7 had > 2 antibodies (anti-D, -C, and -E in 4; anti-D, -C, and -N In 1; anti-c, -E, and -FYA in 1; and anti-E, -K, -Fya, -S, and -C in 1). Eleven patients (46%) required at least 1 Intrauterine fetal transfusion (mean initial fetal hematocrit, 15%; range, 4.9%-24%). In those not transfused, no Delta OD450 measurements occurred in the Queenan "fetal death risk" zone. Poorest outcomes (multiple transfusions/hydrops/fetal demise) were in patients with anti-D and anti-C, with or without anti-E. The absence of anti-D was associated with no need for fetal transfusions. The overall transfusion rate was significantly higher compared with a group of 57 isoimmunization patients with only anti-D (46% vs 25%, P less than or equal to .05). CONCLUSIONS: The presence of anti-D appears to be the most significant factor guiding the course of isoimmunization with multiple antibodies. The presence of another antibody with anti-D appears to significantly increase the need for intrauterine fetal transfusions. The Queenan protocol can successfully treat patients with multiple maternal red blood cell antibodies. C1 NICHD, PPB, CRMC,Sect Dev & Mol Pharmacol, NIH,Lab Dev Neurobiol, Bethesda, MD 20892 USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC 20057 USA. RP Spong, CY (reprint author), NICHD, PPB, CRMC,Sect Dev & Mol Pharmacol, NIH,Lab Dev Neurobiol, 6100 Execut Blvd,Rm 4B03, Bethesda, MD 20892 USA. NR 9 TC 17 Z9 18 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2001 VL 185 IS 2 BP 481 EP 484 DI 10.1067/mob.2001.115999 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 465XL UT WOS:000170615200054 PM 11518913 ER PT J AU Goldenberg, RL Klebanoff, M Carey, JC MacPherson, C AF Goldenberg, RL Klebanoff, M Carey, JC MacPherson, C CA Natl Inst Child Hlth Human Dev Mat TI Metronidazole treatment of women with a positive fetal fibronectin test result SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE fetal fibronectin; bacterial vaginosis; preterm birth ID BACTERIAL VAGINOSIS; PRETERM PREDICTION; DELIVERY AB Eighty-nine women with either bacterial vaginosis, Trichomonas vaginalis, or both, who also had a positive fetal fibronectin test result were randomized to two courses of metronidazole treatment as part of a Maternal-Fetal Medicine Network Units study of the National Institute of Child Health and Human Development. In this subgroup analysis, compared with the placebo group, women who were treated with metronidazole had a nonsignificant reduction in spontaneous preterm birth from 14.6% to 8.3%. C1 Univ Alabama Birmingham, Birmingham, AL USA. NICHHD, Bethesda, MD 20892 USA. Oklahoma Univ, Oklahoma City, OK USA. George Washington Univ, Ctr Biostat, Washington, DC USA. RP Goldenberg, RL (reprint author), Univ Alabama Birmingham, Birmingham, AL USA. FU NICHD NIH HHS [U10 HD 27917, U10 HD27915, U10 HD 27869, U10 HD27860, U10 HD34210, U10 HD27905, U10 HD36801, U10 HD 21410, U10 HD34208, U10 HD34136, U10 HD 21414, U10 HD27861, U10 HD34122, U10 HD34116] NR 5 TC 21 Z9 21 U1 0 U2 2 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 AUG PY 2001 VL 185 IS 2 BP 485 EP 486 DI 10.1067/mob.2001.115998 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 465XL UT WOS:000170615200055 PM 11518914 ER PT J AU Okamoto, Y Chaves, A Chen, JC Kelley, R Jones, K Weed, HG Gardner, KL Gangi, L Yamaguchi, M Klomkleaw, W Nakayama, T Hamlin, RL Carnes, C Altschuld, R Bauer, J Hai, T AF Okamoto, Y Chaves, A Chen, JC Kelley, R Jones, K Weed, HG Gardner, KL Gangi, L Yamaguchi, M Klomkleaw, W Nakayama, T Hamlin, RL Carnes, C Altschuld, R Bauer, J Hai, T TI Transgenic mice with cardiac-specific expression of activating transcription factor 3, a stress-inducible gene, have conduction abnormalities and contractile dysfunction SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MYOSIN HEAVY-CHAIN; PRESSURE-OVERLOAD HYPERTROPHY; MESSENGER-RNA; DILATED CARDIOMYOPATHY; RYANODINE RECEPTORS; KINASE ACTIVATION; HEART; INDUCTION; PROMOTER; MYOCYTES AB Activating transcription factor 3 (ATF3) is a member of the CREB/ATF family of transcription factors. Previously, we demonstrated that the expression of the ATF3 gene is induced by many stress signals. In this report, we demonstrate that expression of ATF3 is induced by cardiac ischemia coupled with reperfusion (ischemia-reperfusion) in both cultured cells and an animal model. Transgenic mice expressing ATF3 under the control of the alpha -myosin heavy chain promoter have atrial enlargement, and atrial and ventricular hypertrophy. Microscopic examination showed myocyte degeneration and fibrosis. Functionally, the transgenic heart has reduced contractility and aberrant conduction. Interestingly, expression of sorcin, a gene whose product inhibits the release of calcium from sarcoplasmic reticulum, is increased in these transgenic hearts. Taken together, our results indicate that expression of ATF3, a stress-inducible gene, in the heart leads to altered gene expression and impaired cardiac function. C1 Ohio State Univ, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Ohio State Univ, Neurobiotechnol Ctr, Columbus, OH 43210 USA. Ohio State Univ, Dept Pharm, Columbus, OH 43210 USA. Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. Ohio State Univ, Dept Vet Biosci, Columbus, OH 43210 USA. NCI, Ctr Adv Technol, Gaithersburg, MD USA. Univ Cincinnati, Dept Pharmacol & Cell Biophys, Cincinnati, OH USA. RP Hai, T (reprint author), Ohio State Univ, Dept Mol & Cellular Biochem, Room 148,Rightmire Hall,1060 Carmack Rd, Columbus, OH 43210 USA. RI Hai, Tsonwin/H-4480-2011; Carnes, Cynthia/C-9540-2012; Hai, Tsonwin/E-3185-2011 OI Hai, Tsonwin/0000-0003-4510-0315; Carnes, Cynthia/0000-0003-0420-6973; Hai, Tsonwin/0000-0003-4510-0315 FU NHLBI NIH HHS [R01 HL59791]; NIDDK NIH HHS [R01 DK064938]; NIEHS NIH HHS [R01 ES08690, R01 ES008690] NR 43 TC 59 Z9 62 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2001 VL 159 IS 2 BP 639 EP 650 DI 10.1016/S0002-9440(10)61735-X PG 12 WC Pathology SC Pathology GA 461GL UT WOS:000170356500028 PM 11485922 ER PT J AU Wang, WH Wang, SB Nishanian, EV Cintron, AD Wesley, RA Danner, RL AF Wang, WH Wang, SB Nishanian, EV Cintron, AD Wesley, RA Danner, RL TI Signaling by eNOS through a superoxide-dependent p42/44 mitogen-activated protein kinase pathway SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE signal transduction; tumor necrosis factor-alpha; reactive oxygen species; endothelial nitric oxide synthase ID NITRIC-OXIDE SYNTHASE; SMOOTH-MUSCLE CELLS; ENDOTHELIAL-CELLS; HUMAN-NEUTROPHILS; ALPHA PRODUCTION; SHEAR-STRESS; U937 CELLS; GENERATION; EXPRESSION; PHOSPHORYLATION AB Expression of endothelial nitric oxide synthase (eNOS) in transfected U-937 cells upregulates phorbol 12-myristate 13-acetate (PMA)-induced tumor necrosis factor-alpha (TNF-alpha) production through a superoxide (O-2(-))-dependent mechanism. Because mitogen-activated protein kinases (MAPK) have been shown to participate in both reactive oxygen species signaling and TNF-alpha regulation, their possible role in eNOS-derived O-2(-) signal transduction was examined. A redox-cycling agent, phenazine methosulfate, was found to both upregulate TNF-alpha (5.8 +/- 1.0 fold; P = 0.01) and increase the phosphorylation state of p42/44 MAPK (3.1 +/- 0.2 fold; P = 0.01) in PMA-differentiated U-937 cells. Although S-nitroso-N-acetylpenicillamine, a nitric oxide (NO) donor, also increased TNF-alpha production, NO exposure led to phosphorylation of p38 MAPK, not p42/44 MAPK. Upregulation of TNF-alpha production by eNOS transfection was associated with increases in activated p42/44 MAPK (P = 0.001), whereas levels of phosphorylated p38 MAPK were unaffected. Furthermore, cotransfection with Cu/Zn superoxide dismutase, which blocks TNF-alpha upregulation by eNOS, also abolished the effects on p42/44 MAPK. Expression of Gln(361)eNOS, a mutant that produces O-2(-) but not NO, still resulted in p42/44 MAPK phosphorylation. In contrast, two NADPH binding site deletion mutants of eNOS that lack oxidase activity had no effect on p42/44 MAPK. Finally, PD-98059, a p42/44 MAPK pathway inhibitor, blocked TNF-alpha upregulation by eNOS (P = 0.02). Thus O-2(-) produced by eNOS increases TNF-alpha production via a mechanism that involves p42/44 MAPK activation. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Danner, RL (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 41 TC 14 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD AUG PY 2001 VL 281 IS 2 BP C544 EP C554 PG 11 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 449XG UT WOS:000169712000018 PM 11443053 ER PT J AU Korzick, DH Holiman, DA Boluyt, MO Laughlin, MH Lakatta, EG AF Korzick, DH Holiman, DA Boluyt, MO Laughlin, MH Lakatta, EG TI Diminished alpha(1)-adrenergic-mediated contraction and translocation of PKC in senescent rat heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE myocardium; signal transduction; cell surface receptors; aging; receptors for activated C kinase ID PROTEIN-KINASE-C; CARDIAC MYOCYTES; ALPHA-1-ADRENERGIC RECEPTORS; PHOSPHOLIPASE-C; VENTRICULAR MYOCARDIUM; ISOFORM EXPRESSION; BINDING-PROTEIN; MESSENGER-RNAS; AGE; ACTIVATION AB Myocardial reserve function declines with aging due in part to reduced alpha- and beta -adrenergic receptor (AR)-mediated contractile augmentation. Whereas specific age-associated deficits in beta -AR signaling have been identified, it is not known which components of the alpha (1)-AR signaling cascade, e.g., protein kinase C (PKC) and associated anchoring proteins (receptors for activated C kinase; RACKs), underlie deficits in alpha (1)-AR contractile function with aging. We therefore assessed cardiac contraction (dP/dt) in Langendorff perfused hearts isolated from adult (5 mo) and senescent (24 mo) Wistar rats following maximal alpha (1)-AR stimulation with phenylephrine (PE), and we measured the subcellular distribution of PKC alpha and PKC epsilon, and their respective anchoring proteins RACK1 and RACK2 by Western blotting. The maximum dP/dt response to PE (10(-5) M) was significantly reduced by 41% in 24-mo-old vs. 5-mo-old (P < 0.01). Inhibitory effects of PKC blockade (chelerythrine; 10 M) on dP/dt following alpha (1)-AR stimulation with PE observed in adult hearts were absent in 24-mo-old hearts (P < 0.01). In 5-mo-old hearts, PE elicited reductions in soluble PKC and PKC epsilon levels, while increasing particulate PKC alpha and PKC epsilon levels to a similar extent. In contrast, soluble PKC alpha and PKC epsilon levels in 24-mo-old hearts were increased in response to PE; particulate PKC epsilon and PKC alpha were unchanged or reduced and associated with significant reductions in particulate RACK1 and RACK2. The results indicate, for the first time, that selective translocation of PKC alpha and PKC epsilon in response to alpha (1)-AR stimulation is disrupted in the senescent myocardium. That age-related reductions in particulate RACK1 and RACK2 levels were also observed provide evidence that alterations in PKC-anchoring proteins may contribute to impaired PKC translocation and defective alpha (1)-AR contraction in the aged rat heart. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Missouri, Dept Vet Biomed Sci, Columbia, MO 65211 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, 4940 Eastern Ave,Box 13, Baltimore, MD 21224 USA. FU NHLBI NIH HHS [P01-HL-52490]; NIA NIH HHS [KO1-AG-00875]; NICHD NIH HHS [T32-HD-07460] NR 52 TC 38 Z9 40 U1 0 U2 2 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 AUG PY 2001 VL 281 IS 2 BP H581 EP H589 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 451XZ UT WOS:000169829200015 PM 11454560 ER PT J AU McKenzie, TL Stone, EJ Feldman, HA Epping, JN Yang, MH Strikmiller, PK Lytle, LA Parcel, GS AF McKenzie, TL Stone, EJ Feldman, HA Epping, JN Yang, MH Strikmiller, PK Lytle, LA Parcel, GS TI Effects of the CATCH physical education intervention - Teacher type and lesson location SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE child; exercise; health promotion; physical fitness ID CARDIOVASCULAR HEALTH; ADOLESCENT TRIAL; CHILDREN; STUDENTS; CONTEXT; DIET AB Background: Substantial differences exist in how and where physical education (PE) is conducted in elementary schools throughout the United States. Few effectiveness studies of large-scale interventions to improve PE have been reported. Design: Multicenter randomized trial. Setting/participants: The Child and Adolescent Trial for Cardiovascular Health (CATCH) was implemented in PE classes in 96 schools (56 intervention, 20 control) in four study centers: California, Louisiana, Minnesota, and Texas. Intervention: The 2.5-year PE intervention consisted of professional development sessions, curricula, and follow-up consultations. Main Outcome Measures: Intervention effects oil student physical activity and lesson context in PE were examined by teacher type (PE specialists and classroom teachers) and lesson location (indoors and outdoors). Results: Differential effects by teacher type and lesson location were evidenced for both physical activity and lesson context. Observations of 2016 lessons showed that intervention schools provided more moderate-to-vigorous physical activity (p=0.002) and vigorous physical activity (p=0.02) than controls. Classroom teachers improved physical activity relatively more than PE specialists, but PE specialists still provided longer lessons and more physical activity. Classroom teachers increased lesson length (p=0.02) and time for physical fitness (p=0.03). Conclusions: The intervention improved PE of both specialists' and classroom teachers' lessons. States and districts should ensure that the most qualified staff teaches PE. Interventions need to be tailored to meet local needs and conditions, including teacher type and location of lessons. C1 San Diego State Univ, Dept Exercise & Nutr Sci, San Diego, CA 92182 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NHLBI, Bethesda, MD 20892 USA. New England Res Inst, Watertown, MA 02172 USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. RP McKenzie, TL (reprint author), San Diego State Univ, Dept Exercise & Nutr Sci, San Diego, CA 92182 USA. FU NHLBI NIH HHS [U01HL39852, U01HL39880, U01HL39906, U01HL39927]; PHS HHS [U0139870] NR 24 TC 65 Z9 66 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD AUG PY 2001 VL 21 IS 2 BP 101 EP 109 DI 10.1016/S0749-3797(01)00335-X PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 455FE UT WOS:000170016200004 PM 11457629 ER PT J AU Hartos, JL Nissen, WJ Simons-Morton, BG AF Hartos, JL Nissen, WJ Simons-Morton, BG TI Acceptability of the checkpoints parent-teen driving agreement - Pilot test SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE accident prevention; accidents, traffic; adolescence; parenting; primary prevention ID CRASH INVOLVEMENT; YOUNG DRIVERS; PASSENGERS; RISK AB Background: Parent-teen driving agreements are potentially important tools to facilitate parental management of teen driving and reduce adolescent driving risk. The Checkpoints Parent-Teen Driving Agreement (Checkpoints P-TDA) was designed so that parents could initially impose strict limitations on teen driving in high-risk driving conditions (e.g., at night and with teen passengers) and gradually increase driving privileges over time as teens demonstrate responsible driving behavior. Methods: To assess the acceptability of the format and content of the Checkpoints P-TDA, it was pilot tested with a convenience sample of 47 families recruited as their teens tested for a driver's license at five private driving schools in Connecticut. Family members were interviewed at the driving schools about potential limits on teen driving, asked to use the driving agreement, and re-interviewed within 3 months about acceptability of the driving agreement and initial driving limits placed on teens. Results: Most families (38 of 47) used and liked the agreement. In addition, most parents placed the recommended strict initial limits on teen driving related to driving related to driving unsupervised at night, with teen passengers, and on high-speed roads. Moreover, parents reported placing more strict limits on their teens' driving than they originally intended. Conclusions: The results showed promise for the acceptability of the Checkpoints P-TDA, which will be tested statewide. (C) 2001 American Journal of Preventive Medicine. C1 NICHHD, Prevent Res Branch, Bethesda, MD 20892 USA. Preusser Res Grp Inc, Trumbull, CT USA. RP Hartos, JL (reprint author), NICHHD, Prevent Res Branch, 6100 Execut Blvd,Room 7B05,MSC 7510, Bethesda, MD 20892 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [1-HD-8-3285] NR 16 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD AUG PY 2001 VL 21 IS 2 BP 138 EP 141 DI 10.1016/S0749-3797(01)00330-0 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 455FE UT WOS:000170016200009 PM 11457634 ER PT J AU DeVinney, BJ Berman, CM Rasmussen, KLR AF DeVinney, BJ Berman, CM Rasmussen, KLR TI Changes in yearling rhesus monkeys' relationships with their mothers after sibling birth SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE sibling birth; Macaca mulatta; juveniles; mother-offspring relationships ID MACAQUES MACACA-MULATTA; SOCIAL SEPARATION; BEHAVIOR; FIRSTBORNS; LACTATION; PATTERNS; PLAY AB The birth of a new sibling is believed to signify an abrupt and important transition in a young primate's relationship with its mother - one that is of potential importance from at least three theoretical perspectives: attachment theory, parent-offspring conflict theory, and dynamic assessment models. This study examines changes in relationships between free-ranging yearling rhesus monkeys (Macaca mulatta) and their mothers concomitant with the birth of the mother's next infant, and tests predictions derived from each theoretical perspective. We observed 31 yearling rhesus on Cayo Santiago, Puerto Rico, 3 months before and 3 months after their siblings' births, using focal animal sampling methods. Changes in measures related to mother-yearling interaction and yearling distress were examined using repeated-measures analysis of variance. After sibling birth, mothers and yearlings abruptly reduced amounts of time in contact and increased amounts of time at a distance and out of sight of one another. Mothers and yearlings played approximately equal roles in bringing about decreases in proximity, and yearlings took the primary roles in bringing about decreases in contact. Rates of maternal aggression toward yearlings increased immediately and markedly after birth, possibly providing yearlings with early cues regarding subsequent decreased levels of maternal care. There were no marked increases in overt signs of yearling distress (e.g., vocalizations or tantrums) following the births. We conclude that yearlings generally acquiesced to reduced levels of care, responding behaviorally with increased independence and maturity. In this sense, our study provides preliminary support for dynamic assessment models over attachment theory and parent-offspring conflict theory models. (C) 2001 Wiley-Liss, Inc. C1 SUNY Coll Buffalo, Dept Anthropol, Buffalo, NY 14222 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. Caribbean Primate Res Ctr, Punta Santiago, PR USA. RP DeVinney, BJ (reprint author), NICHD, Lab Comparat Ethol, POB 529, Poolesville, MD 20837 USA. FU NCRR NIH HHS [RR-03460] NR 41 TC 12 Z9 12 U1 5 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2001 VL 54 IS 4 BP 193 EP 210 DI 10.1002/ajp.1030 PG 18 WC Zoology SC Zoology GA 457GY UT WOS:000170129800002 PM 11468750 ER PT J AU Kumra, S Sporn, A Hommer, DW Nicolson, R Thaker, G Israel, E Lenane, M Bedwell, J Jacobsen, LK Gochman, P Rapoport, JL AF Kumra, S Sporn, A Hommer, DW Nicolson, R Thaker, G Israel, E Lenane, M Bedwell, J Jacobsen, LK Gochman, P Rapoport, JL TI Smooth pursuit eye-tracking impairment in childhood-onset psychotic disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID QUANTITATIVE-ANALYSIS; SCHIZOPHRENIA-PATIENTS; QUALITATIVE RATINGS; OCULOMOTOR MEASURES; MONOZYGOTIC TWINS; MOVEMENTS; PERFORMANCE; DYSFUNCTION; ABNORMALITIES; ADOLESCENCE AB Objective: Although childhood-onset schizophrenia is relatively rare, a sizable group of children with severe emotional disturbances have transient psychotic symptoms that fall outside of current syndrome boundaries. The relationship of this group of children to those with childhood-onset schizophrenia and other childhood psychiatric disorders is unclear. In this study, the authors compared smooth pursuit eye tracking, a biological trait marker associated with schizophrenia, of children and adolescents with psychotic disorder not otherwise specified to that of children with childhood-onset schizophrenia and healthy comparison subjects, Method: By means of infrared oculography, smooth pursuit eye movements during a 17 degrees /second visual pursuit task were quantitatively and qualitatively compared in 55 young adolescents (29 with childhood-onset schizophrenia and 26 with psychotic disorder not otherwise specified) and their respective independent healthy comparison groups (a total of 38 healthy subjects). Results: Subjects with childhood-onset schizophrenia had qualitatively poorer eye tracking, higher root mean square error, lower gain, and a greater frequency of catch-up saccades than healthy children. Subjects with psychotic disorder not otherwise specified also had qualitatively poorer eye tracking, higher root mean square error, and lower gain than healthy children, but saccade frequency did not differ significantly. Conclusions: Children with childhood-onset schizophrenia exhibit a pattern of eye-tracking dysfunction similar to that reported for adult patients. Similar abnormalities were seen in the subjects with psychotic disorder not otherwise specified except that they did not exhibit a greater frequency of catch-up saccades. Prospective longitudinal neurobiological and clinical follow-up studies of both groups are currently underway to further validate the distinction between these two disorders. Also, family studies are planned to establish whether eye-tracking dysfunction represents a trait- or state-related phenomenon in subjects with psychotic disorder not otherwise specified. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Rm 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. RI Thaker, Gunvant/B-1112-2009; Nicolson, Robert/E-4797-2011 NR 52 TC 20 Z9 20 U1 5 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD AUG PY 2001 VL 158 IS 8 BP 1291 EP 1298 DI 10.1176/appi.ajp.158.8.1291 PG 8 WC Psychiatry SC Psychiatry GA 459JG UT WOS:000170246800020 PM 11481165 ER PT J AU Theerman, P AF Theerman, P TI Readers respond to "Cholera in Paris" - Theerman responds SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2001 VL 91 IS 8 BP 1170 EP 1170 DI 10.2105/AJPH.91.8.1170-a PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BT UT WOS:000170345600005 ER PT J AU Helfand, WH Lazarus, J Theerman, P AF Helfand, WH Lazarus, J Theerman, P TI "... so that others may walk": The March of Dimes SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Theerman, P (reprint author), Natl Lib Med, Hist Med Div, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 4 Z9 4 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2001 VL 91 IS 8 BP 1190 EP 1190 DI 10.2105/AJPH.91.8.1190 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BT UT WOS:000170345600014 PM 11499100 ER PT J AU Hunt, CE AF Hunt, CE TI Sudden infant death syndrome and other causes of infant mortality - Diagnosis, mechanisms, and risk for recurrence in siblings SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review ID OBSTRUCTIVE SLEEP-APNEA; NONACCIDENTAL HEAD-INJURY; LIFE-THREATENING EVENTS; SUBSEQUENT SIBLINGS; SYNDROME VICTIMS; CHILD-ABUSE; MUNCHAUSEN-SYNDROME; VENTILATORY-CONTROL; INTRAALVEOLAR HEMORRHAGE; FAMILIAL AGGREGATION C1 Med Coll Ohio, Dept Pediat, Toledo, OH 43699 USA. Childrens Mercy Hosp, Toledo, OH USA. RP Hunt, CE (reprint author), NHLBI, Natl Ctr Sleep Disorders Res, Rockledge Ctr 2, Room 10038,6701 Rockledge Dr,MSC 7920, Bethesda, MD 20892 USA. NR 143 TC 53 Z9 57 U1 4 U2 10 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 1 PY 2001 VL 164 IS 3 BP 346 EP 357 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 466NG UT WOS:000170651200005 PM 11500332 ER PT J AU Carr, EA Theon, AP Madewell, BR Hitchcock, ME Schlegel, R Schiller, JT AF Carr, EA Theon, AP Madewell, BR Hitchcock, ME Schlegel, R Schiller, JT TI Expression of a transforming gene (E5) of bovine papillomavirus in sarcoids obtained from horses SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID EQUINE LEUKOCYTE ANTIGENS; CELLULAR DNA-SYNTHESIS; TYPE-1; ONCOPROTEIN; PROTEIN; TUMORS; VIRUS; FIBROBLASTS; ACTIVATION; COMPONENT AB Objective To determine expression of a transforming gene (E5) of bovine papillomavirus in sarcoids, other tumors, and normal skin samples collected from horses with and without sarcoids. Sample Population-23 sarcoids and 6 samples of normal skin obtained from 16 horses with sarcoids, 2 samples of normal skin and 2 papillomas obtained from horses without sarcoids, and 1 papilloma obtained from a cow. Procedure-Protein was extracted from tissue samples collected from horses and incubated with agarose beads covalently coupled to Staphylococcus aureus protein A and an anti-E5 polyclonal antibody. Following incubation, proteins were eluted from the beads and electrophoresed on a 14% polyacrylamide gel and transferred to a polyvinylidene difluoride membrane. The E5 protein was detected by use of western blot analysis, using a chemiluminescence detection system. Results-All 23 sarcoids had positive results for expression of E5 protein. Quantity of viral protein appeared to vary among sarcoids. All other tissues examined had negative results for E5 protein. Highest expression for E5 protein was observed in biologically aggressive fibroblastic variants of sarcoids, compared with expression in quiescent tumors. Conclusions and Clinical Relevance This study documented that activation and expression of the E5 gene is evident in sarcoids obtained from horses. These data support the conclusion that infection with bovine papillomavirus is important in the initiation or progression of sarcoids in horses. Treatment strategies designed to increase immune recognition of virally infected cells are warranted. C1 Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA. Canc Res Program, Calif Dept Hlth Serv, Sacramento, CA 94234 USA. Georgetown Univ, Sch Med, Dept Pathol, Washington, DC 20007 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Carr, EA (reprint author), Michigan State Univ, Sch Vet Med, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA. NR 52 TC 60 Z9 63 U1 1 U2 7 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD AUG PY 2001 VL 62 IS 8 BP 1212 EP 1217 DI 10.2460/ajvr.2001.62.1212 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 458JH UT WOS:000170190900005 PM 11497440 ER PT J AU Lublin, M Danforth, DN AF Lublin, M Danforth, DN TI Iatrogenic gallbladder perforation: Conservative management by percutaneous drainage and cholecystostomy SO AMERICAN SURGEON LA English DT Article ID LIVER-BIOPSY; BILE PERITONITIS; COMPLICATIONS; ASCITES AB Gallbladder perforation is an uncommon complication of percutaneous liver biopsy. Diagnosis is usually made clinically and management has traditionally been by cholecystectomy. We report a case of gallbladder perforation secondary to percutaneous liver biopsy diagnosed by dimethyl iminodiacetic acid (HIDA) scan and managed successfully by percutaneous drainage and cholecystostomy. This case illustrates the role of conservative management in selected cases of gallbladder perforation. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B38, Bethesda, MD 20892 USA. NR 23 TC 5 Z9 5 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD AUG PY 2001 VL 67 IS 8 BP 760 EP 763 PG 4 WC Surgery SC Surgery GA 460HQ UT WOS:000170302500010 PM 11510578 ER PT J AU Boja, ES Fales, HM AF Boja, ES Fales, HM TI Overalkylation of a protein digest with iodoacetamide SO ANALYTICAL CHEMISTRY LA English DT Article AB Cystine linkages in proteins are often opened with reducing agents, sometimes to improve their digestion, often to eliminate disulfide linkages from complicating analysis of the digest. After reduction, the sulfhydryls are usually reacted with iodoacetamide (IAM), iodoacetic acid (IAA), or another electrophile to prevent reformation of disulfide linkages in a random manner. When the amount of protein may be reliably estimated, side reactions from excess IAM or IAA can be avoided. When this is not so, removal of excess iodoalkane can be accomplished by RPLC, by dialysis, or simply by allowing a reducing thiol to consume any excess. In mass spectrometric analysis of proteins isolated by 1D or 2D gels, removal of the excess iodoalkane is often accomplished simply by washing the gel prior to proteolytic digestion. During a recent study of the glutathionylation site mapping of actin, IAM was used to block any residual sulfhydryl groups remaining on the protein so that they would not displace glutathione from its initial site. In addition, to avoid losses due to actin polymerization du-ring dialysis, the MI was allowed to remain during the digestion. This further ensured that any sulfhydryl groups liberated during the digestion would be similarly blocked by the MI. Under these conditions, we observed the peptides to undergo N- as well as S-carbamidomethylation. In examining a series of other peptides alkylated with IAM in this way, we have found N-alkylation to be the rule rather than the exception and even O-alkylation was detected. The main sites to which the carbamidomethyl group attaches to the peptides have been located with LC-MS2 using an ion trap mass spectrometer and found to be the N-terminal amino group. A simple expedient to prevent such reactions when an excess of reducing agent must be avoided is to run the alkylation in the presence of a thioether such as 2,2 ' -thiodiethanol rather than a thiol. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Fales, HM (reprint author), NHLBI, NIH, 10 Ctr Dr,MSC 1676, Bethesda, MD 20892 USA. NR 16 TC 76 Z9 77 U1 1 U2 41 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 1 PY 2001 VL 73 IS 15 BP 3576 EP 3582 DI 10.1021/ac0103423 PG 7 WC Chemistry, Analytical SC Chemistry GA 459WL UT WOS:000170274400018 PM 11510821 ER PT J AU Martin, JL Keegan, MT Vasdev, GMS Nyberg, SL Bourdi, M Pohl, LR Plevak, DJ AF Martin, JL Keegan, MT Vasdev, GMS Nyberg, SL Bourdi, M Pohl, LR Plevak, DJ TI Fatal hepatitis associated with isoflurane exposure and CYP2A6 autoantibodies SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Midwest Anesthesia Residents Conference CY APR 17, 1999 CL COLUMBUS, OHIO ID ENDOPLASMIC-RETICULUM AUTOANTIBODIES; HALOTHANE HEPATITIS; CYTOCHROME-P450 2E1; ANTIBODIES; ENFLURANE; HEPATOTOXICITY; ANESTHESIA; METABOLISM; DRUG; AUTOANTIGEN C1 Mayo Clin, Dept Anesthesiol, Rochester, MN 55905 USA. Mayo Clin, Dept Surg, Rochester, MN 55905 USA. Johns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Plevak, DJ (reprint author), Mayo Clin, Dept Anesthesiol, 200 1st St SW, Rochester, MN 55905 USA. NR 30 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2001 VL 95 IS 2 BP 551 EP 553 DI 10.1097/00000542-200108000-00043 PG 3 WC Anesthesiology SC Anesthesiology GA 459EJ UT WOS:000170237800039 PM 11506133 ER PT J AU Schroeder, JR Latkin, CA Hoover, DR Curry, AD Knowlton, AR Celentano, DD AF Schroeder, JR Latkin, CA Hoover, DR Curry, AD Knowlton, AR Celentano, DD TI Illicit drug use in one's social network and in one's neighborhood predicts individual heroin and cocaine use SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE social environment; social support; crime; heroin dependence; cocaine-related disorders ID OPIATE ADDICTION; RELAPSE AB PURPOSE: The nature of competing social environmental factors' influence on substance abuse is unclear. A longitudinal study was undertaken to determine the relative power of social network and neighborhood characteristics to predict continuing illicit drug use. METHODS: Three hundred forty-two inner-city adults with a history of injection drug use were followed for I year; their heroin and cocaine use were assessed semiannually. Multiple logistic regression models were fit to determine the degree to which social network and neighborhood characteristics, assessed at baseline, predicted continuing heroin and/or cocaine use throughout the study period. RESULTS: Two hundred thirty-six (69%) participants reported continuing heroin and/or cocaine use. Drug use by members of the social network was a stronger predictor of participants' continuing drug use (OR = 4.31, 95% Cl 2.51 to 7.40) than was a high level of drug-related arrests in the participant's neighborhood (OR = 2.41, 95% Cl 1.24 to 4.71) after adjusting for drug treatment and demographic variables. Both seemed to have independent effects on study participants' drug use. CONCLUSIONS: These findings reiterate the importance of breaking ties with drug-using associates, even for those who reside in high-risk environments. Further work is needed to develop interventions that increase drug users' success in altering social network composition or also treat drug-using network members. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Rutgers State Univ, Dept Stat, New Brunswick, NJ 08903 USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Schroeder, JR (reprint author), NIDA, Intramural Res Program, Clin Pharmacol & Therapeut Res Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA09951, DA04334, DA08335] NR 18 TC 64 Z9 64 U1 4 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 2001 VL 11 IS 6 BP 389 EP 394 DI 10.1016/S1047-2797(01)00225-3 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 459WK UT WOS:000170274300005 PM 11454498 ER PT J AU Hughes, R Bensa, S Willison, H Van den Bergh, P Comi, G Illa, I Nobile-Orazio, E van Doorn, P Dalakas, M Bojar, M Swan, A AF Hughes, R Bensa, S Willison, H Van den Bergh, P Comi, G Illa, I Nobile-Orazio, E van Doorn, P Dalakas, M Bojar, M Swan, A CA INCAT Grp TI Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy SO ANNALS OF NEUROLOGY LA English DT Article ID DOUBLE-BLIND; PLASMA-EXCHANGE; INTEROBSERVER AGREEMENT; CYCLOSPORINE-A; CROSS-OVER; POLYNEUROPATHY; THERAPY; IMPROVEMENT AB This multicenter, randomized, double-blind, crossover trial compared a six week course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous immunoglobulin (IVIg) 2.0 g/kg given over one to two days for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty-four of the thirty-two randomized patients completed both treatment periods. Both treatments produced significant improvements in the primary outcome measure, change in an 11-point disability scale two weeks after randomization. There was slightly, but not significantly, more improvement after Mg than with prednisolone, the mean difference between the groups in change in disability grade being 0.16 (95% CI = -0.35 to 0.66). There were also slightly, but not significantly, greater improvements favoring Mg in the secondary outcome measures: time to walk 10 meters after two weeks and improvement in disability grade after six weeks. Results may have been biased against Mg by the eight patients who did not complete the second arm of the trial. A serious adverse event (psychosis) attributable to treatment occurred in one patient while on prednisolone and in none with Mg. C1 Guys Kings & St Thomas Sch Med, Dept Neuroimmunol, Guys Hosp, London SE1 9RT, England. Univ Glasgow, So Gen Hosp, Dept Neurol, Glasgow, Lanark, Scotland. Univ Catholique Louvain, Clin Univ St Luc, Neurol Serv, B-1200 Brussels, Belgium. Osped San Raffaele, Dipartimento Sci & Technol, Biomed Clin Neurol 4, Milan, Italy. Hosp Univ Sta Creu & St Pau, Serv Neurol, Barcelona, Spain. Univ Milan, Osped Maggiore Policlin, Inst Clin Neurol, Milan, Italy. Erasmus Med Ctr Rotterdam, Dept Neurol, Rotterdam, Netherlands. Univ Athens, Sch Med, Eginit Univ Hosp, Athens, Greece. NIH, Neuromusc Dis Sect, Bethesda, MD 20892 USA. Charles Univ Hosp, Sch Med 2, Prague, Czech Republic. PHLS, Stat Unit, London, England. RP Hughes, R (reprint author), Guys Kings & St Thomas Sch Med, Dept Neuroimmunol, Guys Hosp, London SE1 9RT, England. RI Nobile-Orazio, Eduardo/B-7915-2013 NR 31 TC 366 Z9 376 U1 1 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2001 VL 50 IS 2 BP 195 EP 201 DI 10.1002/ana.1088 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 459HA UT WOS:000170243900009 PM 11506402 ER PT J AU Gianni, L Dombernowsky, P Sledge, G Martin, M Amadori, D Arbuck, SG Ravdin, P Brown, M Messina, M Tuck, D Weil, C Winograd, B AF Gianni, L Dombernowsky, P Sledge, G Martin, M Amadori, D Arbuck, SG Ravdin, P Brown, M Messina, M Tuck, D Weil, C Winograd, B TI Cardiac function following combination therapy with paclitaxel and doxorubicin: An analysis of 657 women with advanced breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; cardiac toxicity; doxorubicin; paclitaxel ID COLONY-STIMULATING FACTOR; PHASE-I; PLUS DOXORUBICIN; RISK-FACTORS; CARDIOTOXICITY; DEXRAZOXANE; ADRIAMYCIN; TRIAL; I/II AB Background: To determine the cardiotoxicity of paclitaxel (T) plus doxorubicin (A) combination therapy in women with advanced breast cancer. To define a dose range of A for use in AT. Patients and methods: The effect of cumulative A dose on risk of congestive heart failure (CHF) and alterations of myocardial contractility (left ventricular ejection fraction [LVEF] decrease greater than or equal to 20% or to < 50%) was estimated from pooled data from 10 trials of AT. Results: Thirty-one of 657 patients (4.7%) developed CHF at a median of 6.6 months (range 0.3-24.6) after initiation of AT. CHF was stabilized in 29 patients at a median of 17.3 months after diagnosis (range 4.1-31.2 months). The risk of developing CHF was less than or equal to5% at a total A dose less than or equal to 380 mg/m(2). In patients who received a total A dose > 440 mg/m(2), the incidence of CHF was > 25% but similar to that of A monotherapy. The risk of CHF was similar in women receiving AT or A monotherapy at a dose less than or equal to 380 mg/m(2) (2%-3%). LVEF progressively decreased in patients who received AT, especially at a cumulative A dose > 380 mg/m(2). LVEF decreases were more frequent in patients who later developed CHF, but the majority of CHF patients did not experience LVEF alterations prior to symptoms. LVEF recovered after discontinuation of A in 25 of 67 women who developed LVEF < 50%. Conclusion: The reported cardiac effects are consistent with anthracycline-related cardiotoxicity. AT is associated with a cardiac risk similar to that of A monotherapy up to a cumulative A dose of 340-380 mg/m(2). C1 Ist Nazl Tumori, Unit Med Oncol A, I-20133 Milan, Italy. Univ Copenhagen Hosp, Dept Oncol, DK-2100 Copenhagen, Denmark. Univ Indianapolis, Med Ctr, Indianapolis, IN USA. Hosp Univ San Carlos, Madrid, Spain. Osped Morgagni Peirantoni, Forli, Italy. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, New York, NY 10154 USA. RP Gianni, L (reprint author), Ist Nazl Tumori, Unit Med Oncol A, Via Venezian 1, I-20133 Milan, Italy. EM gianni@istitutotumori.mi.it NR 23 TC 53 Z9 53 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 EI 1569-8041 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2001 VL 12 IS 8 BP 1067 EP 1073 DI 10.1023/A:1011655503511 PG 7 WC Oncology SC Oncology GA 467VT UT WOS:000170725000022 PM 11583187 ER PT J AU Nguyen, DM Lorang, D Chen, GA Stewart, JH Tabibi, E Schrump, DS AF Nguyen, DM Lorang, D Chen, GA Stewart, JH Tabibi, E Schrump, DS TI Enhancement of paclitaxel-mediated cytotoxicity in lung cancer cells by 17-allylamino geldanamycin: In vitro and in vivo analysis SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 29-31, 2001 CL NEW ORLEANS, LOUISIANA SP Soc Thorac Surgeons ID EPIDERMAL GROWTH-FACTOR; HUMAN-BREAST-CANCER; OVEREXPRESSION; CARCINOMA; ADENOCARCINOMA; ANGIOGENESIS; C-ERBB-2/NEU; INVOLVEMENT; MODULATION; MECHANISMS AB Background. It has previously been demonstrated that 17-allylamino geldanamycin (17-AAG) enhances paclitaxel-mediated cytotoxicity and downregulates vascular endothelial factor expression in non-small cell lung cancer. This project was designed to evaluate the tumoricidal and antiangiogeneic effects of 17-AAG and paclitaxel in H358 non-small cell lung cancer cells grown as xenografts in nude mice. Methods. In vitro cytotoxic drug combination effects were evaluated by (4, 5-dimethylthiazo-2-yl)-2, 5-diphenyl tetrazolium bromide-based proliferation assays. The combinations of 17-AAG and paclitaxel were administered intraperitoneally in nude mice bearing H358 tumor xenografts. Tumor volumes were measured weekly. Tumor expression of erbB2, vascular endothelial cell growth factor, von Willebrand factor (tumor microvasculature), and activated caspase 3 (apoptosis) were determined by immunohistochemistry. Results. Five- to 22-fold enhancement of paclitaxel cytotoxicity was achieved by paclitaxel + 17-AAG combination that was paralleled with marked induction of apoptosis. This combination treatment profoundly sup-pressed tumor growth and significantly prolonged survival of mice bearing H358 xenografts. Immunohistochemical staining of tumor tissues indicated profound reduction of vascular endothelial cell growth factor expression associated with reduction of microvasculature in tumors treated with 17-AAG. Apoptotic cells were more abundant in tumors treated with 17-AAG + paclitaxel than in those treated with 17-AAG or paclitaxel alone. Conclusions. Concurrent exposure of H358 cells to 17-AAG and paclitaxel resulted in supraadditive growth inhibition effects in vitro and in vivo. Analysis of molecular markers of tumor tissues indicated that therapeutic drug levels could be achieved with this chemotherapy regimen leading to significant biological responses. Moreover, 17-AAG-mediated suppression of vascular endothelial cell growth factor production by tumor cells may contribute to the antitumor effects of this drug combination in vivo. (C) 2001 by The Society of Thoracic Surgeons. C1 NCI, Sect Thorac Oncol, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Metab Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Pharmaceut Resources Branch,Div Canc Therapeut &, NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), NCI, Sect Thorac Oncol, Surg Branch, NIH, Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. FU NCI NIH HHS [K08 CA131482] NR 25 TC 62 Z9 65 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2001 VL 72 IS 2 BP 371 EP 378 DI 10.1016/S0003-4975(01)02787-4 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 462UC UT WOS:000170437300014 PM 11515869 ER PT J AU Pettit, GR Moser, BR Boyd, MR Schmidt, JM Pettit, RK Chapuis, JC AF Pettit, GR Moser, BR Boyd, MR Schmidt, JM Pettit, RK Chapuis, JC TI Antineoplastic agents 460. Synthesis of combretastatin A-2 prodrugs SO ANTI-CANCER DRUG DESIGN LA English DT Article DE antineoplastic activity; combretastatin A-2 prodrug; phosphate esters ID P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; IN-VIVO; PHOSPHATE; TUBULIN; BINDING; TUMORS AB The original synthesis of combretastatin A-2 (1a) was modified to provide an efficient scale-up procedure for obtaining this antineoplastic stilbene. Subsequent conversion to a useful prodrug was accomplished by phosphorylation employing in situ formation of dibenzylchlorophosphite followed by cleavage of the benzyl ester protective groups with bromotrimethylsilane to afford the phosphoric acid intermediate 11. The latter was immediately treated with sodium methoxide to complete a practical route to the disodium phosphate prodrug (2a). The phosphoric acid precursor (11) of phosphate 2a was employed in a parallel series of reactions to produce a selection of metal and ammonium cation prodrug candidates. Each of the phosphate salts (2a-q) was evaluated with respect to relative solubility behavior, cancer cell growth inhibition and antimicrobial activity. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. NCI, Lab Drug Discovery Res & Dev, DTP, DCTD,Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 872404, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA44344-05-12] NR 35 TC 15 Z9 15 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD AUG PY 2001 VL 16 IS 4-5 BP 185 EP 193 PG 9 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA 562YL UT WOS:000176226500002 PM 12049477 ER PT J AU Parr, AL Myers, TG Holbeck, SL Loh, YLJ Allegra, CJ AF Parr, AL Myers, TG Holbeck, SL Loh, YLJ Allegra, CJ TI Thymidylate synthase as a molecular target for drug discovery using the National Cancer Institute's Anticancer Drug Screen SO ANTI-CANCER DRUGS LA English DT Article DE COMPARE analysis; NCI Anticancer Drug Screen; thymidylate synthase; UNIDRUG ID CELL-LINES AB Thymidylate synthase (TS) is a critical cellular target for cancer chemotherapeutics, particularly the fluoropyrimidine and antifolate classes of antineoplastic agents. One of the primary mechanisms of clinical insensitivity to these agents is through the overexpression of the target enzyme, TS. Thus, there is a need for the development of agents which selectively target TS-overexpressing malignant cells. To this end, we conducted a search for agents which potentially selectively target TS-overexpressing cells using two separate algorithms for identifying such compounds in the NCI Drug Repository by comparing cytotoxicity profiles of 30 000 compounds with the TS expression levels measured by Western blot analysis in 53 cell lines. Using the traditional COMPARE analysis we were unable to identify compounds which maintain a selective ability to kill high TS-expressing cells in a subsequent four cell line validation assay. A new algorithm, termed COMPARE Effect Clusters analysis, enabled the Identification of a particular drug cluster which contained compounds that maintained a selective ability to kill TS-overexpressing cell lines in the validation assay. While the identified compounds were selectively cytotoxic to TS-overexpressing cells, we found that they were not specifically targeting TS as a mechanism of action. Apparently, the overexpression of TS was providing a marker for sensitivity. This identified class of compounds which appears to be selectively cytotoxic against cells which overexpress TS may be useful for the development of therapeutics for those whose cancers overexpress TS de novo. [(C) 2001 Lippincott Williams & Wilkins.]. C1 NCI, Med Branch, Bethesda, MD 20889 USA. NCI, Informat Technol Branch, Dev Therapeut Program, Bethesda, MD 20889 USA. RP Parr, AL (reprint author), NCI, Natl Naval Med Ctr, 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD AUG PY 2001 VL 12 IS 7 BP 569 EP 574 DI 10.1097/00001813-200108000-00002 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 464YV UT WOS:000170561700002 PM 11487712 ER PT J AU Wheat, LJ Cloud, G Johnson, PC Connolly, P Goldman, M Le Monte, A Fuller, DE Davis, TE Hafner, R AF Wheat, LJ Cloud, G Johnson, PC Connolly, P Goldman, M Le Monte, A Fuller, DE Davis, TE Hafner, R CA AIDS Clin Trials Grp Mycoses Study Grp NIAID TI Clearance of fungal burden during treatment of disseminated histoplasmosis with liposomal amphotericin B versus itraconazole SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CAPSULATUM ANTIGEN AB Animal studies have shown that fungal burden correlates with survival during treatment with new antifungal therapies for histoplasmosis. The purpose of this report is to compare the clearance of fungal burden in patients,vith histoplasmosis treated with liposomal amphotericin B versus itraconazole, In two separate closed clinical trials that evaluated the efficacy of liposomal amphotericin B and itraconazole treatment of disseminated histoplasmosis in patients with ALDS, blood was cultured for fungus and blood and urine were tested for Histoplasma: antigen, The clinical response rates were similar; 86% with liposomal amphotericin B (n = 51) versus 85% with itraconazole (n = 59). Of the patients with positive blood cultures at enrollment, after 2 weeks of therapy cultures were negative in over 85% of the liposomal amphotericin B group versus 53% of the itraconazole group (P = 0.0008). Furthermore, after 2 weeks, median antigen levels in serum fell by 1.6 U in the liposomal amphotericin B group versus 0.1 U in the itraconazole group (P = 0.02), and those in urine fell by 2.1 U in the liposomal amphotericin B group and 0.2 U in the itraconazole group (P = 0.0005). The more rapid clearance of fungemia supports the use of liposomal amphotericin B rather than itraconazole for initial treatment of moderately severe or severe histoplasmosis. C1 Indiana Univ, Sch Med, Histopasmosis Reference Lab, Indianapolis, IN 46202 USA. Vet Affairs Med Ctr, Indianapolis, IN USA. Univ Alabama, Birmingham, AL USA. Univ Texas, Sch Med, Houston, TX USA. NIAID, Div Aids, Rockville, MD USA. RP Wheat, LJ (reprint author), Indiana Univ, Sch Med, Histopasmosis Reference Lab, 1001 W 10th St, Indianapolis, IN 46202 USA. FU NCRR NIH HHS [N01-RR0255A]; NIAID NIH HHS [AI25859, U01 AI025859] NR 6 TC 36 Z9 37 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2001 VL 45 IS 8 BP 2354 EP 2357 DI 10.1128/AAC.45.8.2354-2357.2001 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 454YQ UT WOS:000169999700024 PM 11451696 ER PT J AU Mischiati, C Jeang, KT Feriotto, G Breda, L Borgatti, M Bianchi, N Gambari, R AF Mischiati, C Jeang, KT Feriotto, G Breda, L Borgatti, M Bianchi, N Gambari, R TI Aromatic polyamidines inhibiting the Tat-induced HIV-1 transcription recognize structured TAR-RNA SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID DNA-PROTEIN INTERACTIONS; GENE-EXPRESSION; TRANS-ACTIVATION; T-CELLS; BINDING; AMIDINOPHENOXYNEOPENTANE; REPLICATION; INITIATION; DRUGS; BULGE AB We have investigated the effects of aromatic polyamidines on HIV-1 transcription. We found a block to Tat-induced HIV-1 transcription assessed by inhibition of CAT activity in RL3T1 cells at a concentration lower than the IC50 value, suggesting that molecules with three (TAPB) and four (TAPP) benzamidine rings could be useful against HIV-1. In contrast, aromatic polyamidines with only two benzamidine rings (DAPP) did not block Tat-induced transcription. We reasoned that this effect could be due to binding of TAPB and TAPP to HIV-1 TAR RNA. By EMSA and filter binding assays, we studied possible interactions of aromatic polyamidines with HIV-1 TAR RNA. Wild-type TAR RNA or TAR RNA with mutations in the stem or bulge sequences, but retaining the stem-loop structure, was used to define the RNA-binding activities of these compounds. Our data suggest that aromatic polyamidines with two (DAPP) and four (TAPP) benzamidine rings, respectively, do not bind to TAR RNA or bind without sequence selectivity. Interestingly, an aromatic polyamidine with three benzamidine rings (TAPB) recognizes the wild-type TAR RNA in a specific manner. Furthermore, we found that introduction of one halogen atom into the benzamidine rings strongly increases the RNA-binding activity of these compounds. C1 Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Mischiati, C (reprint author), Univ Ferrara, Dept Biochem & Mol Biol, Via L Borsari N 46, I-44100 Ferrara, Italy. RI Jeang, Kuan-Teh/A-2424-2008; Gambari, Roberto/F-9555-2015; Borgatti, Monica/G-2611-2015; Bianchi, Nicoletta/H-1902-2015 OI Gambari, Roberto/0000-0001-9205-6033; Borgatti, Monica/0000-0001-8470-2496; Bianchi, Nicoletta/0000-0001-9280-6017 NR 30 TC 20 Z9 22 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD AUG PY 2001 VL 11 IS 4 BP 209 EP 217 DI 10.1089/108729001317022214 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 470LQ UT WOS:000170873800002 PM 11572598 ER PT J AU Bhargava, R Schaeberle, MD Fernandez, DC Levin, IW AF Bhargava, R Schaeberle, MD Fernandez, DC Levin, IW TI Novel route to faster Fourier transform infrared spectroscopic imaging SO APPLIED SPECTROSCOPY LA English DT Article DE FT-IR; imaging; focal plane array; signal-to-noise ratio; hyperspectral data cube; step-scan; continuous scan; rapid scan; data collection; trigger method ID PLANE ARRAY DETECTOR; MICROSCOPY; SYSTEMS; TISSUES AB Fourier transform infrared (FT-IR) spectroscopic imaging microscopy couples a focal plane array (FPA) detector, integrated within an infrared microscope assembly, to an interferometer for attaining a multiplex/multichannel signal detection advantage. While this configuration should enable the acquisition of spatially resolved spectra over the entire field of view of a sample in the time that it takes a conventional FT-IR spectrometer to record a single spectrum, data acquisition in an imaging modality is an intrinsically slower process. We present a novel collection technique for step-scan, micro-imaging spectrometers that both allows large numbers of samples to be imaged rapidly and provides higher signal-to-noise ratios (SNRs) for given experimental time intervals. For example, data may be collected in as little as one minute, while SNRs greater than 800 are achieved for data acquired in less than 10 min. Imaging data acquired in the proposed, more rapid approach exhibit no loss in fidelity compared to data recorded by the conventional imaging techniques. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. OI Bhargava, Rohit/0000-0001-7360-994X NR 19 TC 17 Z9 18 U1 0 U2 4 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD AUG PY 2001 VL 55 IS 8 BP 1079 EP 1084 DI 10.1366/0003702011952983 PG 6 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 473QG UT WOS:000171056400018 ER PT J AU Agbuya, PG Sherman, NE Moen, LK AF Agbuya, PG Sherman, NE Moen, LK TI Proteolytic processing of the human T-cell lymphotropic virus 1 reverse transcriptase: Identification of the N-terminal cleavage site by mass spectrometry SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE human T-cell lymphotropic virus; retrovirus; reverse transcriptase; proteolytic processing; LC-MS; MS/MS ID COMPLETE NUCLEOTIDE-SEQUENCE; BOVINE LEUKEMIA-VIRUS; TROPICAL SPASTIC PARAPARESIS; HTLV-I; SYNDROME RETROVIRUS; ESCHERICHIA-COLI; CLINICAL ENTITY; PROTEASE GENE; POL GENES; TYPE-1 AB Human T-cell lymphotropic virus 1 (HTLV-1) is a type C human retrovirus, which is the causative agent of Adult T-cell Leukemia and other diseases. The reverse transcriptase of HTLV-1 (E.C. 2.7.7.49) is synthesized as part of a Gag-Pro-Pol precursor protein, and the mature Gag, Pro, and Pol proteins, including the reverse transcriptase, are created by proteolytic processing catalyzed by the viral protease. The location of the proteolytic cleavage site, which creates the N-terminus of mature HTLV-1 reverse transcriptase, has not been previously identified. By using sequence comparisons of several retroviral polymerases, as well as information about the location of the ribosomal frameshift, we tentatively identified this N-terminal processing site. PCR amplification was used to construct a clone, which spans a region of the pro-pol junction of HTLV-1, to produce a recombinant Pro-Pol protein spanning the locations of those cleavage sites proposed by others as well as the one identified by our sequence alignment. Cleavage of the recombinant Pro-Pol protein by HTLV-1 protease generated a 5.5-kDa fragment. Analysis of this fragment by capillary LC-MS and MS/MS revealed the N-terminal cleavage site to be between Leu(147)-Pro(148) of the pro ORF. This is the first physical identification of the authentic amino acid sequence of the reverse transcriptase of HTLV-1. The data reported here provides a basis for further investigation of the function and structural aspects of protein-nucleic interaction. (C) 2001 Academic Press. C1 Old Dominion Univ, Dept Chem & Biochem, Norfolk, VA USA. Univ Virginia, Biomol Res Facil, WM Keck Biomed Mass Spectrometry Lab, Charlottesville, VA USA. RP Moen, LK (reprint author), NIGMS, NIH, 45 Center Dr,1AS-13H, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA71091] NR 49 TC 3 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 1 PY 2001 VL 392 IS 1 BP 93 EP 102 DI 10.1006/abbi.2001.2432 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 460GA UT WOS:000170298800013 PM 11469799 ER PT J AU Taimi, M Breitman, TR Takahashi, N AF Taimi, M Breitman, TR Takahashi, N TI Cyclic AMP-dependent protein kinase isoenzymes in human myeloid leukemia (HL60) and breast tumor (MCF-7) cells SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cyclic AMP-dependent protein kinase; HL60 cells; MCF-7 cells; PKA regulatory subunit; 8-chloro-cyclic AMP ID ADENOSINE 3'-5'-MONOPHOSPHATE-INDUCING AGENTS; CHINESE-HAMSTER OVARY; A ANCHORING PROTEIN; REGULATORY SUBUNITS; RETINOIC ACID; INDUCED-DIFFERENTIATION; ACTIVE METABOLITE; GROWTH-INHIBITION; DOWN-REGULATION; CAMP AB Combinations of retinoic acid (RA) and cAMP mediate many biological responses in a large variety of cell types. While the basis for the apparent synergistic effects of RA and cAMP are not clearly defined, it is likely that activation of PKA by cAMP is involved. However, literature reports concerning the identity of PKA isoforms in HL60 and MCF-7 cells are conflicting. The purpose of the present investigation is to identify PKA isoforms in HL60 and MCF-7 cells. Utilization of high-performance anion-exchange liquid chromatography, immunoblotting, and 8-azido-cAMP photoaffinity binding resulted in the finding that HL60 cells contain PKA types I alpha and II alpha, while MCF-7 cells contain PKA types I alpha, II alpha, and II beta. PKA type I alpha in both HL60 and MCF-7 cells eluted from columns as two well-separated peaks. One peak eluted at a low salt concentration in agreement with previous reports. The second HL60 PKA type la peak eluted at a salt concentration intermediate between that eluting the first peak and that eluting PKA type II alpha and contained approximately 62% of the total RI alpha protein. However, the second MCF-7 PKA type la peak contained approximately 66% of the total RI alpha protein and co-eluted with PKA types II alpha and II beta. This "contamination" of PKA type II fractions with PKA type I has led, in some cases, to interpretations that may need reevaluation. (C) 2001 Academic Press. C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Takahashi, N (reprint author), Hoshi Univ, Fac Pharmaceut Sci, Dept Hlth Chem, Sinagawa Ku, 4-41 Ebara 2 Chome, Tokyo 1428501, Japan. NR 55 TC 10 Z9 10 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 1 PY 2001 VL 392 IS 1 BP 137 EP 144 DI 10.1006/abbi.2001.2443 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 460GA UT WOS:000170298800018 PM 11469804 ER PT J AU Bing, EG Burnam, A Longshore, D Fleishman, JA Sherbourne, CD London, AS Turner, BJ Eggan, F Beckman, R Vitiello, B Morton, SC Orlando, M Bozzette, SA Ortiz-Barron, L Shapiro, M AF Bing, EG Burnam, A Longshore, D Fleishman, JA Sherbourne, CD London, AS Turner, BJ Eggan, F Beckman, R Vitiello, B Morton, SC Orlando, M Bozzette, SA Ortiz-Barron, L Shapiro, M TI Psychiatric disorders and drug use among human immunodeficiency virus-infected adults in the United States SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; QUALITY-OF-LIFE; HIV-INFECTION; SUBSTANCE USE; COMMUNITY SAMPLE; HOMOSEXUAL MEN; GAY MEN; PREVALENCE; DEPRESSION; ILLNESS AB Background: There have been no previous nationally representative estimates of the prevalence of mental disorders and drug use among adults receiving care for human immunodeficiency virus (HIV) disease in the United States. it is also not known which clinical and sociodemographic factors are associated with these disorders. Subjects and Methods: We enrolled a nationally representative probability sample of 2864 adults receiving care for HIV in the United States in 1996. Participants were administered a brief structured psychiatric instrument that screened for psychiatric disorders (major depression, dysthymia, generalized anxiety disorders, and panic attacks) and drug use during the previous 12 months. Sociodemographic and clinical factors associated with screening positive for any psychiatric disorder and drug dependence were examined in multivariate logistic regression analyses. Results: Nearly half of the sample screened positive for a psychiatric disorder, nearly 40% reported using an illicit drug other than marijuana, and more than 12% screened positive for drug dependence during the previous 12 months. Factors independently associated with screening positive for a psychiatric disorder included number of HIV-related symptoms, illicit drug use, drug dependence, heavy alcohol use, and being unemployed or disabled. Factors independently associated with screening positive for drug dependence included having many HIV-related symptoms, being younger, being heterosexual, having frequent heavy alcohol use, and screening positive for a psychiatric disorder. Conclusions: Many people infected with HIV may also have psychiatric and/or drug dependence disorders. Clinicians may need to actively identify those at risk and work with policymakers to ensure the availability of appropriate care for these treatable disorders. C1 Charles R Drew Univ Med & Sci, Ctr AIDS Res Educ & Serv, Los Angeles, CA 90059 USA. Charles R Drew Univ Med & Sci, Collaborat Alcohol Res Ctr, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, Dept Gen Internal Med, Los Angeles, CA USA. Michigan State Univ, Coll Med, E Lansing, MI 48824 USA. Univ Calif San Diego, Sch Med, Vet Affairs San Diego Healthcare Syst, Hlth Serv Res & Dev Unit, San Diego, CA 92103 USA. RAND Corp, Stat Grp, Santa Monica, CA USA. NIMH, Bethesda, MD 20892 USA. AIDS Coordinators Off, Los Angeles, CA USA. Univ Penn, Dept Med, Div Gen Med, Philadelphia, PA 19104 USA. Kent State Univ, Dept Sociol, Kent, OH 44242 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Univ Calif Los Angeles, Los Angeles Drug Abuse Res Ctr, Los Angeles, CA USA. RP Bing, EG (reprint author), Charles R Drew Univ Med & Sci, Ctr AIDS Res Educ & Serv, 1651 E 120th St, Los Angeles, CA 90059 USA. FU AHRQ HHS [U-01HS08578]; NIAAA NIH HHS [AA11899]; NIMH NIH HHS [MH00990] NR 45 TC 578 Z9 586 U1 5 U2 30 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2001 VL 58 IS 8 BP 721 EP 728 DI 10.1001/archpsyc.58.8.721 PG 8 WC Psychiatry SC Psychiatry GA 459JH UT WOS:000170246900001 PM 11483137 ER PT J AU Burnam, MA Bing, EG Morton, SC Sherbourne, C Fleishman, JA London, AS Vitiello, B Stein, M Bozzette, SA Shapiro, MF AF Burnam, MA Bing, EG Morton, SC Sherbourne, C Fleishman, JA London, AS Vitiello, B Stein, M Bozzette, SA Shapiro, MF TI Use of mental health and substance abuse treatment services among adults with HIV in the United States SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATIONAL PROBABILITY SAMPLES; LOW-PREVALENCE DISEASES; QUALITY-OF-LIFE; PSYCHIATRIC-DISORDERS; INFECTION; COST; PSYCHOPATHOLOGY; HISTORY; WOMEN AB Background: The need for mental health and substance abuse services is great among those with human immunodeficiency virus (HIV), but little information is available on services used by this population or on individual factors associated with access to care. Methods: Data are from the HIV Cost and Services Utilization Study, a national probability survey of 2864 HIV-infected adults receiving medical care in the United States in 1996. We estimated 6-month use of services for mental health and substance abuse problems and examined socioeconomic, HIV illness, and regional factors associated with use. Results: We estimated that 61.4% of 231 400 adults under care for HIV used mental health or substance abuse services: 1.8% had hospitalizations, 3.4% received residential substance abuse treatment, 26.0% made individual mental health specialty visits, 15.2% had group mental health treatment, 40.3% discussed emotional problems with medical providers, 29.6% took psychotherapeutic medications, 5.6% received outpatient substance abuse treatment, and 12.4% participated in substance abuse self-help groups. Socioeconomic factors commonly associated with poorer access to health services predicted lower likelihood of using mental health outpatient care, but greater likelihood of receiving substance abuse treatment services. Those with less severe HIV illness were less likely to access services. Persons living in the Northeast were more likely to receive services. Conclusions: The magnitude of mental health and substance abuse care provided to those with known HIV infection is substantial, and challenges to providers should be recognized. Inequalities in access to care are evident, but differ among general medical, specialty mental health, and substance abuse treatment sectors. C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif Los Angeles, Dept Med, Div Gen Internal Med, Los Angeles, CA 90024 USA. Vet Adm Med Ctr, La Jolla, CA 90034 USA. Rhode Isl Hosp, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. NIMH, NIH, Bethesda, MD 20892 USA. Kent State Univ, Dept Sociol, Kent, OH 44242 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Charles R Drew Univ Med & Sci, Collaborat Alcohol Res Ctr, Los Angeles, CA 90059 USA. Charles R Drew Univ Med & Sci, Ctr AIDS Res Educ & Serv, Los Angeles, CA 90059 USA. RP Burnam, MA (reprint author), RAND Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. FU AHRQ HHS [U-01HS08578]; NIAAA NIH HHS [AA11899]; NIMH NIH HHS [MH00990] NR 28 TC 110 Z9 111 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2001 VL 58 IS 8 BP 729 EP 736 DI 10.1001/archpsyc.58.8.729 PG 8 WC Psychiatry SC Psychiatry GA 459JH UT WOS:000170246900002 PM 11483138 ER PT J AU Loeb, MJ De Loof, A Gelman, DB Hakim, RS Jaffe, H Kochansky, JP Meola, SM Schoofs, L Steel, C Vafopoulou, X Wagner, RM Woods, CW AF Loeb, MJ De Loof, A Gelman, DB Hakim, RS Jaffe, H Kochansky, JP Meola, SM Schoofs, L Steel, C Vafopoulou, X Wagner, RM Woods, CW TI Testis ecdysiotropin, an insect gonadotropin that induces synthesis of ecdysteroid SO ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY LA English DT Article; Proceedings Paper CT International Congress of Entomology CY AUG 20-26, 2000 CL IGUASSU FALLS, BRAZIL DE male reproduction; neuropeptide; ecdysteroid; cell signaling; immunocytochemistry ID LYMANTRIA-DISPAR; GYPSY-MOTH; PROTHORACICOTROPIC HORMONE; MANDUCA-SEXTA; LARVAL TESTES; BOMBYX-MORI; SPERMIOGENESIS; ARMYWORM; SHEATHS; CELLS AB Testes of lepidoptera synthesized ecdysteroid in a somewhat different temporal pattern than the prothoracic glands that release ecdysteroid to the hemolymph. Brain extracts from Heliothis virescens and Lymantria dispar induced testes to synthesize ecdysteroid, but did not affect prothoracic glands. The testis ecdysiotropin (LTE) was isolated from L. dispar pupal brains by a series of high-pressure chromatography steps. Its sequence was Ile-Ser-Asp-Phe-Asp-Glu-Tyr-Glu-Pro-Leu-Asn-Asp-Ala-Asp-Asn-Asn-Glu-Val-Leu-Asp-Phe-OH, of molecular mass 2,473 Daltons. The predominant signaling pathway for LTE was via Gi protein, IP3, diacylglycerol and PKC; a modulating pathway, apparently mediated by an angiotensin II-like peptide, was controlled via G. protein, cAMP, and PKA. Testis ecdysteroid caused isolated testis sheaths to also synthesize a growth factor that induced development of the male genital tract. The growth factor appeared to be a glycoprotein similar to vertebrate alpha-l-glycoprotein. A polyclonal antibody to LTE indicated LTE-like peptide in L. dispar brain medial neurosecretory cells, the suboesophageal, and other ganglia, and also in its target organ, the testis sheath. LTE immunoreactivity was also seen in testis sheaths of Rhodnius prolixus. LTE-like immunoactivity was also detected in developing optic lobes, antennae, frontal ganglia, and elongating spermatids of developing L. dispar pupae. This may indicate that LTE has a role in development as well as stimulation of testis ecdysteroid synthesis. C1 USDA ARS, Beltsville Agr Res Ctr, Insect Biocontrol Lab, Beltsville, MD 20705 USA. Zool Inst, Louvain, Belgium. Howard Univ, Dept Anat, Washington, DC USA. NIH, Bethesda, MD USA. USDA ARS, Food Anim Protect Res Lab, College Stn, TX USA. York Univ, Dept Biol, Toronto, ON, Canada. USDA ARS, Biol Control Insects Res Lab, Columbia, MO USA. Univ Maryland, College Pk, MD USA. RP Loeb, MJ (reprint author), USDA ARS, Beltsville Agr Res Ctr, Insect Biocontrol Lab, Bldg 011A,Rm 211,Barc W, Beltsville, MD 20705 USA. NR 26 TC 18 Z9 24 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0739-4462 J9 ARCH INSECT BIOCHEM JI Arch. Insect Biochem. Physiol. PD AUG PY 2001 VL 47 IS 4 SI SI BP 181 EP 188 DI 10.1002/arch.1050 PG 8 WC Biochemistry & Molecular Biology; Entomology; Physiology SC Biochemistry & Molecular Biology; Entomology; Physiology GA 457ZK UT WOS:000170168700003 PM 11462222 ER PT J AU Christen, WG Glynn, RJ Ajani, UA Schaumberg, DA Chew, EY Buring, JE Manson, JE Hennekens, CH AF Christen, WG Glynn, RJ Ajani, UA Schaumberg, DA Chew, EY Buring, JE Manson, JE Hennekens, CH TI Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; SENILE MACULAR DEGENERATION; CHOROIDAL BLOOD-FLOW; TREATMENT DIABETIC-RETINOPATHY; RISK-FACTORS; CARDIOVASCULAR-DISEASE; PHOTODYNAMIC THERAPY; CIGARETTE-SMOKING; 5-YEAR INCIDENCE; NEOVASCULARIZATION AB Objective: To examine the development of age-related maculopathy (ARM) in a large-scale trial of low-dose aspirin treatment. Methods: The Physicians' Health Study I was a randomized, double-masked, placebo-controlled trial of low-dose aspirin (325 mg every other day) and beta carotene (50 mg every other day) in the prevention of cardiovascular disease and cancer conducted among 22 071 US male physicians aged 40 to 84 years in 1982. A total of 21216 participants did not report ARM at baseline, were followed up for at least 7 years, and are included in this analysis. Main Outcome Measures: Total ARM, defined as a self-report confirmed by medical record evidence of an initial diagnosis subsequent to randomization, and ARM with vision loss, defined as total ARM but with vision loss to 20/30 or worse attributable to ARM. Results: Early termination of the randomized aspirin component of the Physicians' Health Study I, after an average of 60.2 months of treatment and follow-up due to a statistically extreme 44% reduced risk of first myocardial infarction, resulted in a far lower number of incident cases of ARM during the aspirin treatment period than would have accrued without early termination. Thus, during an average of 60.2 months of follow-up, a total of 117 cases of ARM were confirmed, including 57 cases responsible for vision loss to 20/30 or worse. There were 51 cases of ARM in the aspirin group and 66 in the placebo group (relative risk, 0.77; 95% confidence interval, 0.54-1.11). For ARM, with vision loss, there were 25 cases in the aspirin group and 32 in the placebo group (relative risk, 0.78; 95% confidence interval, 0.46-1.32). Conclusions: These randomized trial data tend to exclude any large beneficial effect of 5 years of low-dose aspirin treatment on ARM. However, a smaller, but potentially important, beneficial effect cannot be ruled out and would require testing in randomized trials of adequate size and duration. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Prevent Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NEI, Bethesda, MD 20892 USA. RP Christen, WG (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU Intramural NIH HHS [Z99 EY999999]; NCI NIH HHS [CA 34944, CA 40360]; NEI NIH HHS [K23 EY000365, EY 06633, K23 EY000365-04, K23 EY000365-05]; NHLBI NIH HHS [HL 26490, HL 34595] NR 69 TC 43 Z9 47 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2001 VL 119 IS 8 BP 1143 EP 1149 PG 7 WC Ophthalmology SC Ophthalmology GA 460GD UT WOS:000170299100005 PM 11483080 ER PT J AU Seddon, JM Rosner, B Sperduto, RD Yannuzzi, L Haller, JA Blair, NP Willett, W AF Seddon, JM Rosner, B Sperduto, RD Yannuzzi, L Haller, JA Blair, NP Willett, W TI Dietary fat and risk for advanced age-related macular degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; CORONARY HEART-DISEASE; MACULOPATHY; REPRODUCIBILITY; WOMEN AB Objective: To evaluate the relationship between intake of total and specific types of fat and risk for advanced age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults. Design: A multicenter eye disease case-control study Setting: Five US clinical ophthalmology centers. Patients: Case subjects included 349 individuals (age range, 55-80 years) with the advanced, neovascular stage of AMD diagnosed within 1 year of their enrollment into the study who resided near a participating clinical center. Control subjects included 504 individuals without AMD but with other ocular diseases. Controls were from the same geographic areas as cases and were frequency-matched to cases by age and sex. Main Outcome Measures: Relative risk for AMD according to level of fat intake, controlling for cigarette smoking and other risk factors. Results: Higher vegetable fat consumption was associated with an elevated risk for AMD. After adjusting for age, sex, education, cigarette smoking, and other risk factors, the odds ratio (OR) was 2.22 (95% confidence interval [ CI] 1.32-3.74) for persons in the highest vs those in the lowest quintiles of intake (P for trend, .007). The risk for AMD was also significantly elevated for the highest vs lowest quintiles of intake of monounsaturated (OR, 1.71) and polyunsaturated (OR, 1.86) fats (Ps for trend, .03 and .03, respectively). Higher consumption of linoleic acid was also associated with a higher risk for AMD (P for trend, .02). Higher intake of omega -3 fatty acids was associated with a lower risk for AMD among individuals consuming diets low in linoleic acid, an omega -6 fatty acid (P for trend, .05; P for continuous variable,.03). Similarly, higher frequency of fish intake tended to reduce risk for AMD when the diet was low in linoleic acid (P for trend, .05). Conversely, neither omega -3 fatty acids nor fish intake were related to risk for AMD among people with high levels of linoleic acid intake. Conclusion: Higher intake of specific types of fat-including vegetable, monounsaturated, and polyunsaturated fats and linoleic acid-rather than total fat intake may be associated with a greater risk for advanced AMD. Diets high in omega -3 fatty acids and fish were inversely associated with risk for AMD when intake of linoleic acid was low. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NEI, Dept Epidemiol & Clin Res, Bethesda, MD 20892 USA. Manhattan Eye Ear & Throat Hosp, Dept Ophthalmol, New York, NY 10021 USA. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. Univ Illinois, Chicago, IL USA. RP Seddon, JM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY09972] NR 21 TC 222 Z9 234 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD AUG PY 2001 VL 119 IS 8 BP 1191 EP 1199 PG 9 WC Ophthalmology SC Ophthalmology GA 460GD UT WOS:000170299100013 PM 11483088 ER PT J AU Chen, AH Stephan, DA Hasson, T Fukushima, K Nelissen, CM Chen, AF Jun, AI Ramesh, A Van Camp, G Smith, RJH AF Chen, AH Stephan, DA Hasson, T Fukushima, K Nelissen, CM Chen, AF Jun, AI Ramesh, A Van Camp, G Smith, RJH TI MYO1F as a candidate gene for nonsyndromic deafness, DFNB15 SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID MYOSIN-VIIA GENE; UNCONVENTIONAL MYOSINS; RECESSIVE DEAFNESS; MOUSE; MUTATIONS; MAPS; 1B AB Background: Earlier studies have mapped the autosomal recessive nonsyndromic deafness locus, DFNB15, to chromosomes 3q21.3-q25.2 and 19p13.3-13.1, identifying one of these chromosomal regions (or possibly both) as the site of a deafness-causing gene. Mutations in unconventional myosins cause deafness in mice and humans. One unconventional myosin, myosin 1F (MYO1F), is expressed in the cochlea and maps to chromosome 19p13.3-13.2. Objective: To evaluate MYO1F as a candidate gene for deafness at the DFNB15 locus by determining its genomic structure and screening each exon for deafness-causing mutations to identify possible allele variants of MYO1F segregating in the DFNB15 family. Methods: We used radiation hybrid mapping to localize MYO1F on chromosome arm 19p. We next determined its genomic structure using multiple long-range polymerase chain reaction experiments. Using these data, we completed mutation screening using single-stranded conformational polymorphism analysis and direct sequencing of affected and nonaffected persons in the original DFNB15 family. Results: Radiation hybrid mapping placed MYO1F in the DFNB15 interval, establishing it as a positional candidate gene. Its genomic structure consists of 24 coding exons. No mutations or genomic rearrangements were found in the original DFNB15 family, making it unlikely that MYO1F is the disease-causing gene in this kindred. Conclusions: Although we did not find MYO1F allele variants in one family with autosomal recessive nonsyndromic hearing loss, the gene remains an excellent candidate for hereditary hearing impairment. Given its wide tissue expression, MYO1F might cause syndromic deafness. C1 Univ Iowa, Dept Pediat & Otolaryngol, Iowa City, IA USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Dept Biol, New Haven, CT USA. Okayama Univ, Sch Med, Dept Otolaryngol, Okayama, Japan. Univ Madras, Dept Genet, Madras, Tamil Nadu, India. Univ Antwerp, Dept Med Genet, B-2020 Antwerp, Belgium. RP Smith, RJH (reprint author), Univ Iowa Hosp & Clin, Dept Otorhinolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. RI Van Camp, Guy/F-3386-2013 OI Van Camp, Guy/0000-0001-5105-9000 NR 21 TC 13 Z9 13 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD AUG PY 2001 VL 127 IS 8 BP 921 EP 925 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 459JB UT WOS:000170246300002 PM 11493199 ER PT J AU Hunt, CE Durham, JK Guess, SJ Kapuniai, LE Golub, H AF Hunt, CE Durham, JK Guess, SJ Kapuniai, LE Golub, H CA Collaborative Home Infant Monitori TI Telephone subsidy - An effective incentive for successful participation in home memory monitor study SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID INFANT-DEATH-SYNDROME AB Context: The Collaborative Home Infant Monitoring Evaluation (CHIME) study enrolled healthy term infants and 3 groups of infants considered to be at increased risk for sudden infant death syndrome to evaluate apnea and bradycardia events in the home. Mother-infant pairs without a telephone were ineligible for enrollment. Objective: To determine whether mother-infant pairs who were offered a telephone subsidy would agree to enroll in CHIME and achieve protocol compliance rates comparable with those of matched subjects able to afford telephones. Design: Thirty-one telephone subsidy subjects were retrospectively compared with 55 control subjects matched for study group, site, birth weight, and maternal race, age, and education. Setting: Collaborative Home Infant Monitoring Evaluation clinical research centers in Honolulu, Hawaii, and Toledo, Ohio. Intervention: Provision of telephone subsidy to otherwise eligible enrollees for CHIME. Main Outcome Measures: Frequency of compliance with protocol requirements for follow-up evaluations and for extent of home monitoring. Results: Subsidy subjects achieved protocol completion rates that were comparable with those of control subjects, for developmental assessments at 56 and 92 weeks postconceptional age (PCA), and for the polysomnogram. Unexpectedly, however, subsidy subjects were more likely to have a developmental assessment at 44 weeks PCA (P=.02), as well as a cry analysis (P=.04). They were also more likely to use the CHIME home monitor for more hours during weeks 2 through 5 (P=.004), have a higher percentage using the monitor for 10 or more hours per week during weeks 2 through 5 (P=.009), and have a higher total number of days of monitor use throughout 6 months (P<001). Mean cost of the subsidy was $3.25 per day of monitor use, and monitor use per day was directly related to total cost of the subsidy (P=.02). Conclusions: Telephone subsidy is an effective financial incentive. At least within the context of the CHIME study, telephone subsidy enhanced access to health care, and in some categories it resulted in enhanced protocol compliance. C1 Med Coll Ohio, Dept Pediat, Toledo, OH 43699 USA. Univ Hawaii, Dept Pediat, Honolulu, HI 96822 USA. Kapiolani Med Ctr Women & Children, Honolulu, HI 96822 USA. Boston Univ, Dept Pediat, Boston, MA 02215 USA. Boston Univ, Dept Epidemiol, Boston, MA 02215 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. RP Hunt, CE (reprint author), NHLBI, Natl Ctr Sleep Disorders Res, NIH, 2 Rockledge Ctr,6701 Rockledge Dr,Suite 10038,MSC, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD 34625, HD 28791, HD 29056, HD 29060, HD 29067, HD 29071, HD 29073] NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2001 VL 155 IS 8 BP 954 EP 959 PG 6 WC Pediatrics SC Pediatrics GA 459EB UT WOS:000170237100015 PM 11483125 ER PT J AU Ardans, JA Blum, A Mangan, PR Wientroub, S Cannon, RO Wahl, LM AF Ardans, JA Blum, A Mangan, PR Wientroub, S Cannon, RO Wahl, LM TI Raloxifene-mediated increase in matrix metalloproteinase-1 production by activated monocytes SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; matrix metalloproteinases; monocytes; plaque; raloxifene ID HUMAN ATHEROSCLEROTIC PLAQUES; POSTMENOPAUSAL WOMEN; MACROPHAGE; MECHANISMS; RISK AB Matrix metalloproteinases (MMPs), proteolytic enzymes produced by monocytes, may contribute to atherosclerotic arterial wall remodeling and to plaque rupture. Because estrogen influences the synthesis of MMPs, we examined the effect of raloxifene, a selective estrogen receptor modulator, on monocyte MMP production. Human primary blood monocytes treated with raloxifene (10 mu mol/L) in the presence of lipopolysaccharide (LPS) or tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor induced a 2- to 3-fold increase in MMP-1 production by monocytes. The enhancement of MMP-1 production by raloxifene in LPS-activated monocytes occurred through a cyclooxygenase-2- and prostaglandin E-2-independent mechanism. Additionally, compared with monocytes acquired during the placebo phase, peripheral blood monocytes from 5 of 6 healthy postmenopausal women treated with raloxifene (60 mg daily for 1 month) in a clinical trial produced significantly higher levels of MMP-1 when the monocytes were activated with LPS. Furthermore, serum obtained during the raloxifene phase from 4 of these subjects, when added to control monocytes, significantly enhanced LPS-induced MMP-1 production compared with that from serum obtained during the placebo phase. In summary, raloxifene increases the production of MMP-1 in activated monocytes; this effect may be favorable in atherosclerotic arterial wall remodeling but unfavorable for plaque stability. C1 NIDCR, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Orthoped Pediat, IL-69978 Tel Aviv, Israel. RP Wahl, LM (reprint author), NIDCR, Immunopathol Sect, NIH, Bldg 30,Room 325,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 15 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD AUG PY 2001 VL 21 IS 8 BP 1265 EP 1268 DI 10.1161/hq0801.095083 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 463YZ UT WOS:000170506000006 PM 11498451 ER PT J AU Hull, KM Griffith, L Kuncl, RW Wigley, FM AF Hull, KM Griffith, L Kuncl, RW Wigley, FM TI A deceptive case of amyloid myopathy - Clinical and magnetic resonance imaging features SO ARTHRITIS AND RHEUMATISM LA English DT Article ID PRIMARY SYSTEMIC AMYLOIDOSIS AB Amyloid myopathy is a well-described, increasingly recognized clinical entity. Similar to inflammatory myopathies, amyloid myopathy presents with proximal muscle weakness and can be associated with elevated levels of muscle enzymes. We report the case of a 58-year-old woman who, at presentation to her physician with proximal muscle weakness and congestive heart failure, was antinuclear antibody positive and had muscle biopsy findings "consistent with inflammatory myopathy." She was referred to Johns Hopkins University Medical Center with the diagnosis of polymyositis. Further investigation revealed a monoclonal gammopathy, a unique patterning of subcutaneous fat reticulation and hypodense bone marrow changes on magnetic resonance imaging (MRI), and an endocardial biopsy sample that was positive for light chain amyloid deposition. Paraffin sections of the muscle biopsy sample from the time of her original presentation were obtained, and Congo red staining showed diffuse amyloid deposition throughout the sample, but no inflammation. This case not only illustrates that proximal muscle weakness due to primary amyloid myopathy (as found in light chain amyloidosis and transthyretin amyloidosis) can mimic that of polymyositis, but also shows that unique findings on MRI can alert the clinician to the diagnosis of amyloidosis prior to muscle biopsy. C1 NIAMS, NIH, ARB, Bethesda, MD 20892 USA. Johns Hopkins Univ, Med Ctr, Baltimore, MD 21218 USA. RP Hull, KM (reprint author), NIAMS, NIH, ARB, Bldg 10,Room 9S205,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2001 VL 44 IS 8 BP 1954 EP 1958 DI 10.1002/1529-0131(200108)44:8<1954::AID-ART333>3.0.CO;2-S PG 5 WC Rheumatology SC Rheumatology GA 498BZ UT WOS:000172491100029 PM 11508448 ER PT J AU Wilson, A Hickie, I Hadzi-Pavlovic, D Wakefield, D Parker, G Straus, SE Dale, J McCluskey, D Hinds, G Brickman, A Goldenberg, D Demitrack, M Blakely, T Wessely, S Sharpe, M Lloyd, A AF Wilson, A Hickie, I Hadzi-Pavlovic, D Wakefield, D Parker, G Straus, SE Dale, J McCluskey, D Hinds, G Brickman, A Goldenberg, D Demitrack, M Blakely, T Wessely, S Sharpe, M Lloyd, A TI What is chronic fatigue syndrome? Heterogeneity within an international multicentre study SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE chronic fatigue; somatization; latent class ID PROLONGED FATIGUE; PRIMARY-CARE; DOUBLE-BLIND; DEFINITION; FIBROMYALGIA; DISTRESS; CRITERIA; TWIN AB Objective: We sought to compare the characteristics of patients presenting with chronic fatigue (CF) and related syndromes in eight international centres and to subclassify these subjects based on symptom profiles. The validity of the subclasses was then tested against clinical data. Method: Subjects with a clinical diagnosis of CF completed a 119-item self-report questionnaire to provide clinical symptom data and other information such as illness course and functional impairment. Subclasses were generated using a principal components-like analysis followed by latent profile analysis (LPA). Results: 744 subjects returned complete data sets (mean age 40.8 years, mean length of illness 7.9 years, female to male ratio 3:1). Overall, the subjects had a high rate of reporting typical CF symptoms (fatigue, neuropsychological dysfunction, sleep disturbance). Using LPA, two subclasses were generated. Class one (68% sample) was characterized by: younger age, lower female to male ratio; shorter episode duration; less premorbid, current and familial psychiatric morbidity; and, less functional disability. Class two subjects (32%) had features more consistent with a somatoform illness. There was substantial variation in subclass prevalences between the study centres (Class two range 6-48%). Conclusions: Criteria-based approaches to the diagnosis of CF and related syndromes do not select a homogeneous patient group. While substratification of patients is essential for further aetiological and treatment research, the basis for allocating such subcategories remains controversial. C1 St George Hosp & Community Hlth Serv, Acad Dept Psychiat, Kogarah, NSW 2217, Australia. Univ New S Wales, Sydney, NSW, Australia. NIAID, Bethesda, MD 20892 USA. Royal Victoria Hosp, Belfast BT12 6BA, Antrim, North Ireland. Univ Miami, Coral Gables, FL 33124 USA. Newton Wellesley Hosp, Arthrit Fibrositis Ctr, Boston, MA USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ London Kings Coll, Sch Med, London WC2R 2LS, England. Univ Edinburgh, Edinburgh, Midlothian, Scotland. RP Hickie, I (reprint author), St George Hosp & Community Hlth Serv, Acad Dept Psychiat, 7 Chapel St, Kogarah, NSW 2217, Australia. RI Wessely, Simon/A-8713-2008; Demitrack, Mark/I-7697-2013 NR 28 TC 76 Z9 76 U1 1 U2 8 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0004-8674 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD AUG PY 2001 VL 35 IS 4 BP 520 EP 527 DI 10.1046/j.1440-1614.2001.00888.x PG 8 WC Psychiatry SC Psychiatry GA 479MY UT WOS:000171409200138 PM 11531735 ER PT J AU Burgdorf, J Knutson, B Panksepp, J Ikemoto, S AF Burgdorf, J Knutson, B Panksepp, J Ikemoto, S TI Nucleus accumbens amphetamine microinjections unconditionally elicit 50-kHz ultrasonic vocalizations in rats SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID LABORATORY RATS; SHORT CALLS; REWARD; BRAIN; BEHAVIOR; DOPAMINE; REINFORCEMENT; ANTICIPATION AB The authors have hypothesized that, in adult rats, 50-kHz ultrasonic vocalizations (USVs) index a state characterized by high arousal and expectations of reward. This study was conducted to investigate whether dopamine agonism of the nucleus accumbens (NAcc) could evoke such an appetitive state, by examining the effects of NAcc amphetamine (AMPH) microinjections on USVs. Intra-NAcc AMPH injections (0.3, 1.0, 3.0, 10.0 mug unilaterally) produced robust, dose-dependent increases in 50-kHz USVs, which could not be accounted for by concomitant increases in locomotor activity (LA). However, AMPH injections into dorsal control caudate putamen sites produced a modest, dose-dependent increase in LA without significant increases in 50-kHz USVs. These findings indicate that NAcc AMPH microinjections selectively evoke 50-kHz USVs in rats, supporting the notion that dopamine elevations in the NAcc may unconditionally elicit a state of reward anticipation. C1 NIDA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Clin Studies, NIH, Bethesda, MD 20892 USA. Bowling Green State Univ, Dept Psychol, Bowling Green, OH 43403 USA. RP Knutson, B (reprint author), Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. OI Ikemoto, Satoshi/0000-0002-0732-7386; Knutson, Brian/0000-0002-7669-426X NR 31 TC 131 Z9 132 U1 0 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD AUG PY 2001 VL 115 IS 4 BP 940 EP 944 DI 10.1037//0735-7044.115.4.940 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 471DD UT WOS:000170911600020 PM 11508733 ER PT J AU Holmes, A Iles, JP Mayell, SJ Rodgers, RJ AF Holmes, A Iles, JP Mayell, SJ Rodgers, RJ TI Prior test experience compromises the anxiolytic efficacy of chlordiazepoxide in the mouse light/dark exploration test SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE light/dark exploration test; animal model of anxiety; test experience; retesting; chlordiazepoxide; injection effects; mice ID ELEVATED PLUS-MAZE; ONE-TRIAL TOLERANCE; WHITE TEST BOX; 2-COMPARTMENT BLACK; ANIMAL-MODELS; PHARMACOLOGICAL CHARACTERIZATION; 5-HT1A RECEPTOR; ANXIETY-STATES; MALE-MICE; BEHAVIOR AB It is now well established that prior test experience can alter behavioural baselines and attenuate/abolish the anxiolytic efficacy of benzodiazepines in the elevated plus-maze paradigm. In View of evidence that different models of anxiety measure qualitatively distinct forms of anxiety-like behaviour, it is important to establish whether the effects of prior experience extend to other widely-used tests. The present study assessed the behavioural and pharmacological sequelae of a single undrugged prior exposure to the light/dark exploration (L/D) test in mice, using ethological scoring methods. One group of adult male Swiss-Webster mice was given a single undrugged exposure to the L/D test 24 h prior to drug testing, while another group was completely naive to the apparatus. On test day, half the animals in each experiential condition were treated with saline and half with an anxiolytic dose (10 mg/kg) of chlordiazepoxide (CDP). When administered to test-naive animals, CDP induced a clear reduction in anxiety-like behaviour as evidenced by significant increases in exploration of the light compartment (line crossings, % line crossings, and % time) as well as reductions in stretched attend postures (SAPs) and the proportion of SAPs displayed toward the light compartment. The behavioural specificity of these effects was confirmed by the absence of a drug effect on line crossings in the dark compartment, total rearing and grooming. In complete contrast, with the sole exception of a decrease in total SAPs, CDP was without significant behavioural effect in test-experienced mice. As prior test experience did not significantly alter behavioural baselines in the L/D test, a second experiment was designed to investigate the possibility that handling/intraperitoneal injection may have precluded detection of experientially-induced changes in baseline behaviour. Results showed that handling/injection had no effect upon L/D behavioural profiles in either test-naive or test-experienced subjects, and confirmed that prior experience itself did not modify the primary indices of anxiety in this test. Present data indicate that prior test experience seriously compromises the anxiolytic efficacy of CDP (10 mg/kg) in the mouse L/D test and, together with recent findings in the four-plate test, appear to confirm that an experientially-induced reduction in sensitivity to the anxiolytic effects of benzodiazepines is by no means unique to the elevated plus-maze. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Leeds, Sch Psychol, Ethopharmacol Lab, Leeds LS2 9JT, W Yorkshire, England. RP Holmes, A (reprint author), NIMH, Expt Therapeut Branch, Sect Behav Neuropharmacol, Bldg 10,Rm 4D11, Bethesda, MD 20892 USA. NR 68 TC 66 Z9 68 U1 0 U2 4 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 AUG 1 PY 2001 VL 122 IS 2 BP 159 EP 167 DI 10.1016/S0166-4328(01)00184-X PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 454VK UT WOS:000169992300005 PM 11334646 ER PT J AU Chen, ZG Eggerman, TL Patterson, AP AF Chen, ZG Eggerman, TL Patterson, AP TI Phosphorylation is a regulatory mechanism in apolipoprotein B mRNA editing SO BIOCHEMICAL JOURNAL LA English DT Article DE APOBEC-1; kinase; mutation; quantification ID PROTEIN-KINASE-C; MESSENGER-RNA; CATALYTIC SUBUNIT; MOLECULAR-CLONING; RAT-LIVER; SUBCELLULAR-LOCALIZATION; ETHANOL ALTERS; ENZYME-COMPLEX; GROWTH-HORMONE; APOBEC-1 AB The editing of apolipoprotein B (apoB) mRNA is under tissue-specific, developmental and metabolic regulation. We found that multiple protein kinase inhibitors or activators increased apoB mRNA editing up to 2.5-fold in Caco-2 cells and 3-8-fold in McA7777 and FAO rat cells respectively. The phosphorylation-agent-induced modulation is independent of the apolipoprotein B editing catalytic subunit 1 (APOBEC-1) and of apoB mRNA expression levels, indicating the involvement of a protein modification, such as phosphorylation, regulating the cellular editing of apoB mRNA. Transient expression of protein kinase C-theta more than doubled apoB mRNA editing in FAO cells. Chronic exposure to ethanol, a treatment known to increase the expression of protein kinases and to change protein phosphorylation status, increased apoB mRNA editing in FAO cells up to 2.5-fold without increasing the mRNA abundance of APOBEC-1. The elimination of potential phosphorylation sites 47 and 72 of human APOBEC-1 decreased its activity to approx. one-eighth of control levels by a Ser(47) --> Ala mutation, but more than doubled the activity by a Ser(72) --> Ala mutation. The activity modulation was reversed by a Ser Asp mutation at sites 47 and 72, which introduced a phosphorylation-like carbonic acid group. Both human APOBEC-1 dephosphorylated by alkaline phosphase and the Ser(47),(72)-to-alanine double mutant protein demonstrated a shifted isoelectric focusing pattern compared with the wild type, indicating phosphorylation at these sites. Taken together, these results suggest that phosphorylation might be an important mechanism in the regulation of apoB mRNA editing. C1 NHLBI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Patterson, AP (reprint author), NHLBI, NIH, 6000 Execut Blvd,Suite 302, Bethesda, MD 20892 USA. NR 64 TC 12 Z9 13 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 2001 VL 357 BP 661 EP 672 DI 10.1042/0264-6021:3570661 PN 3 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 462DQ UT WOS:000170405800006 PM 11463337 ER PT J AU Mattson, MP Chan, SL Camandola, S AF Mattson, MP Chan, SL Camandola, S TI Presenilin mutations and calcium signaling defects in the nervous and immune systems SO BIOESSAYS LA English DT Article ID AMYLOID-PRECURSOR PROTEIN; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; FAMILIAL ALZHEIMERS-DISEASE; BETA-PEPTIDE; HIPPOCAMPAL-NEURONS; INTRACELLULAR CALCIUM; MUTANT PRESENILIN-1; RYANODINE RECEPTOR; BINDING PROTEIN; PC12 CELLS AB Presenilin-1 (PS1) is thought to regulate cell differentiation and survival by modulating the Notch signaling pathway. Mutations in PS1 have been shown to cause early-onset inherited forms of Alzheimer's disease (AD) by a gain-of-function mechanism that alters proteolytic processing of the amyloid precursor protein (APP) resulting in increased production of neurotoxic forms of amylold beta -peptide. The present article considers a second pathogenic mode of action of PS1 mutations, a defect in cellular calcium signaling characterized by overfilling of endoplasmic reticulum (ER) calcium stores and altered capacitive calcium entry; this abnormality may impair synaptic plasticity and sensitize neurons to apoptosis and excitotoxicity. The calcium signaling defect has also been documented in lymphocytes, suggesting a contribution of immune dysfunction to the pathogenesis of AD. A better understanding of the calcium signaling defect resulting from PS1 mutations may lead to the development of novel preventative and therapeutic strategies for disorders of the nervous and immune systems. (C) 2001 John Wiley & Sons, Inc. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 90 TC 49 Z9 53 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD AUG PY 2001 VL 23 IS 8 BP 733 EP 744 DI 10.1002/bies.1103 PG 12 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 459XR UT WOS:000170277200010 PM 11494322 ER PT J AU Pine, DS Fyer, A Grun, J Phelps, EA Szeszko, PR Koda, V Li, W Ardekani, B Maguire, EA Burgess, N Bilder, RM AF Pine, DS Fyer, A Grun, J Phelps, EA Szeszko, PR Koda, V Li, W Ardekani, B Maguire, EA Burgess, N Bilder, RM TI Methods for developmental studies of fear conditioning circuitry SO BIOLOGICAL PSYCHIATRY LA English DT Article DE fear conditioning; development; anxiety; neuroscience; fMRI ID ANXIETY DISORDERS; HUMAN AMYGDALA; POTENTIATION; ADOLESCENTS; HIPPOCAMPUS; STARTLE; RISK; FMRI AB Psychophysiologic studies use air puff as an aversive stimulus to document abnormal fear conditioning in children of parents with anxiety disorders. This study used functional magnetic resonance imaging (fMRI) to examine changes in amygdala activity during air-puff conditioning among adults. Blood oxygen level-dependent (BOLD) signal was monitored in seven adults during 16 alternating presentations of two different colored lights (CS+ vs. CS-), one of which was consistently paired with an aversive air puff. A region-of-interest analysis demonstrated differential change in BOLD signal in the right but not left amygdala across CS+ versus CS- viewing. The amygdala is engaged by pairing of a light with an air puff. Given that prior studies relate air-puff conditioning to risk for anxiety in children, these methods may provide an avenue for directly studying the developmental neurobiology of fear conditioning. (C) 2001 Society of Biological Psychiatry. C1 NIMH, Intramural Res Program, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NYU, New York, NY USA. UCL, Neurol Inst, Wellcome Dept Cognit Neurol, London, England. UCL, Inst Cognit Neurosci, London, England. UCL, Dept Anat, London, England. Nathan S Kline Inst, Ctr Adv Brain Imaging, Orangeburg, NY USA. Hillside Hosp, Div N Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA. RP Pine, DS (reprint author), NIMH, Intramural Res Program, Bldg 1,Room B3-10, Bethesda, MD 20892 USA. RI Burgess, Neil/B-2420-2009; Szeszko, Philip/G-9336-2013; Bilder, Robert/A-8894-2008 OI Burgess, Neil/0000-0003-0646-6584; Bilder, Robert/0000-0001-5085-7852 FU NIMH NIH HHS [MH-01391] NR 23 TC 40 Z9 40 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 2001 VL 50 IS 3 BP 225 EP 228 DI 10.1016/S0006-3223(01)01159-3 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 463AJ UT WOS:000170454400010 PM 11513822 ER PT J AU Sukharev, S Durell, SR Guy, HR AF Sukharev, S Durell, SR Guy, HR TI Structural models of the MscL gating mechanism SO BIOPHYSICAL JOURNAL LA English DT Article ID MECHANOSENSITIVE CHANNEL MSCL; ESCHERICHIA-COLI; ION-CHANNEL; LARGE-CONDUCTANCE; HELIX PACKING; OSMOTIC DOWNSHOCK; SINGLE RESIDUE; PROTEINS; ENERGIES; TENSION AB Three-dimensional structural models of the mechanosensitive channel of large conductance, MscL, from the bacteria Mycobacterium tuberculosis and Escherichia coli were developed for closed, intermediate, and open conformations. The modeling began with the crystal structure of M. tuberculosis MscL, a homopentamer with two transmembrane a-helices, M1 and M2, per subunit. The first 12 N-terminal residues, not resolved in the crystal structure, were modeled as an amphipathic a-he(ix, called S1. A bundle of five parallel S1 helices are postulated to form a cytoplasmic gate. As membrane tension induces expansion, the tilts of M1 and M2 are postulated to increase as they move away from the axis of the pore. Substantial expansion is postulated to occur before the increased stress in the S1 to M1 linkers pulls the S1 bundle apart. During the opening transition, the S1 helices and C-terminus amphipathic a-helices, S3, are postulated to dock parallel to the membrane surface on the perimeter of the complex. The proposed gating mechanism reveals critical spatial relationships between the expandable transmembrane barrel formed by M1 and M2, the gate formed by S1 helices, and "strings" that link Sts to M1s. These models are consistent with numerous experimental results and modeling criteria. C1 NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RP Guy, HR (reprint author), NCI, Lab Expt & Computat Biol, NIH, Bldg 12,Room B105,12 South Dr, Bethesda, MD 20892 USA. EM bg4y@nih.gov FU NINDS NIH HHS [NS39314] NR 40 TC 153 Z9 160 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2001 VL 81 IS 2 BP 917 EP 936 PG 20 WC Biophysics SC Biophysics GA 457TB UT WOS:000170152000026 PM 11463635 ER PT J AU Tekle, E Astumian, RD Friauf, WA Chock, PB AF Tekle, E Astumian, RD Friauf, WA Chock, PB TI Asymmetric pore distribution and loss of membrane lipid in electroporated DOPC vesicles SO BIOPHYSICAL JOURNAL LA English DT Article ID ELECTRIC-FIELD; CELL-MEMBRANES; MODELING ELECTROPORATION; MESOPHYLL PROTOPLASTS; ERYTHROCYTE-GHOSTS; BILAYER VESICLES; SINGLE-CELL; KINETICS; ELECTROPERMEABILIZATION; DEFORMATION AB An externally applied electric field across vesicles leads to transient perforation of the membrane. The distribution and lifetime of these pores was examined using 1,2-di-oleoyl-sn-glycero-3-phosphocholine (DOPC) phospholipid vesicles using a standard fluorescent microscope. The vesicle membrane was stained with a fluorescent membrane dye, and upon field application, a single membrane pore as large as similar to7 mum in diameter was observed at the vesicle membrane facing the negative electrode. At the anode-facing hemisphere, large and visible pores are seldom found, but formation of many small pores is implicated by the data. Analysis of pre- and post-field fluorescent vesicle images, as well as images from negatively stained electron micrographs, indicate that pore formation is associated with a partial loss of the phospholipid bilayer from the vesicle membrane. Up to similar to 14% of the membrane surface could be lost due to pore formation. Interestingly, despite a clear difference in the size distribution of the pores observed, the effective porous areas at both hemispheres was approximately equal. Ca2+ influx measurements into perforated vesicles further showed that pores are essentially resealed within similar to 165 ms after the pulse. The pore distribution found in this study is in line with an earlier hypothesis (E. Tekle, R. D. Astumian, and P. B. Chock, 1994, Proc. Natl. Acad. Sci. U.S.A. 91:11512-11516) of asymmetric pore distribution based on selective transport of various fluorescent markers across electroporated membranes. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Univ Chicago, Dept Surg, Plast & Reconstruct Surg Sect, Chicago, IL 60637 USA. RP Tekle, E (reprint author), NHLBI, Biochem Lab, NIH, 50 South Dr,Room 2127,MSC 8012, Bethesda, MD 20892 USA. NR 48 TC 61 Z9 68 U1 0 U2 11 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2001 VL 81 IS 2 BP 960 EP 968 PG 9 WC Biophysics SC Biophysics GA 457TB UT WOS:000170152000029 PM 11463638 ER PT J AU Binder, H Gawrisch, K AF Binder, H Gawrisch, K TI Dehydration induces lateral expansion of polyunsaturated 18 : 0-22 : 6 phosphatidylcholine in a new lamellar phase SO BIOPHYSICAL JOURNAL LA English DT Article ID INFRARED DICHROISM INVESTIGATIONS; HUMIDITY TITRATION CALORIMETRY; X-RAY-DIFFRACTION; LIPID BILAYERS; ACYL-CHAIN; DOCOSAHEXAENOIC ACID; MAGNETIC-RESONANCE; WATER PERMEABILITY; DIENE GROUPS; H-2 NMR AB To gain a better understanding of the biological role of polyunsaturated phospholipids, infrared (1R) linear dichroism, NMR, and x-ray diffraction studies have been conducted on the lyotropic phase behavior and bilayer dimensions of sn-1 chain perdeuterated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC-d35), a mixed-chain saturated (18:0)-polyunsaturated (22:6 omega3) lipid. SDPC films were hydrated at definite values of temperature (T) and relative humidity (RN). In excess water, the lipid forms exclusively lamellar phases in the temperature range 0-50 degreesC. Upon dehydration the lipid undergoes the main phase transition between the liquid-crystalline (L-alpha) and gel (L-beta) phase at T < 15 degreesC. Both the saturated and polyunsaturated chains adopt a stretched conformation in the La phase, presumably the all-trans (stearoyl) and angle iron or helical (docosahexaenoyl) one. A new fluid lamellar phase (L-alpha(')) was found in partially hydrated samples at T > 15 degreesC. SDPC membranes expand laterally and contract vertically in the L-alpha(') phase when water was removed. This tendency is in sharp contrast to typical dehydration-induced changes of membrane dimensions. The slope of the phase transition lines in the RH-T phase diagram reveal that the lyotropic L-alpha(')-L-alpha and L-beta-L-alpha transitions are driven by enthalpy and entropy, respectively The possible molecular origin of the phase transitions is discussed. The properties of SDPC are compared with that of membranes of monounsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC-d31). C1 Univ Leipzig, Inst Med Phys & Biophys, D-04103 Leipzig, Germany. NIAAA, NIH, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Binder, H (reprint author), Univ Leipzig, Inst Med Phys & Biophys, Liebigstr 27, D-04103 Leipzig, Germany. NR 52 TC 30 Z9 31 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2001 VL 81 IS 2 BP 969 EP 982 PG 14 WC Biophysics SC Biophysics GA 457TB UT WOS:000170152000030 PM 11463639 ER PT J AU Chik, JK Parsegian, VA AF Chik, JK Parsegian, VA TI The entropically favored osmotic "compression" of sickle cell hemoglobin gels SO BIOPOLYMERS LA English DT Article DE hard sphere; monomeric hemoglobin; sickle cell hemoglobin; polymerization; gelation; osmotic compressibility ID BEHAVIOR; HELICES AB Contrary to the accurate, hard-sphere depiction of monomeric hemoglobin in solution, sickle cell hemoglobin (HbS) polymerization/gelation requires attention to molecular interactions. From the temperature dependence of the osmotic compressibility of HbS gels, we were able to extract the entropy increase for concentrating HbS in this phase. Normalized per mole of water removed, the entropy increase from gel compression DeltaS(gel) in four times the previously measured DeltaS(trans), for the transition from monomeric HbS solution to HbS gel. The positive entropy change cannot emerge from the assembly of hard spheres but can indicate remodeling of HbS gibers driven by release of ordered water. The fourfold difference in DeltaS(gel) and DeltaS(trans) suggest that the act of initial fiber/gel formation from monomeric solution differs from the process of further polymerization due to tighter packing within the gel phase. (C) 2001 John Wiley & Sons, Inc. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Parsegian, VA (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bldg 12A,Room 2041, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD AUG PY 2001 VL 59 IS 2 BP 120 EP 124 DI 10.1002/1097-0282(200108)59:2<120::AID-BIP1011>3.0.CO;2-M PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 447JQ UT WOS:000169568500006 PM 11373725 ER PT J AU Kohgo, S Mitsuya, H Ohrui, H AF Kohgo, S Mitsuya, H Ohrui, H TI Synthesis of the L-enantiomer of 4 ''-C-ethynyl-2 '-deoxycytidine SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE 4 '-C-ethynyl-2 '-deoxycytidine; L-configuration nucleosides; anti-HIV activity ID HIV AB The L-enantiomer of 4'-C-ethynyl-2'-deoxycytidine (2) was synthesized, but did not show any activity against HIV-1 up to 100 muM. C1 Tohoku Univ, Grad Sch Agr Sci, Div Life Sci, Aoba Ku, Sendai, Miyagi 9818555, Japan. Kumamoto Univ, Sch Med, Dept Immunopathol & Internal Med 2, Kumamoto 8608556, Japan. NCI, Med Branch, Div Clin Sci, Expt Retrovirol Sect, Bethesda, MD 20892 USA. RP Ohrui, H (reprint author), Tohoku Univ, Grad Sch Agr Sci, Div Life Sci, Aoba Ku, 1-1 Tsutsumidori Amamiyamachi, Sendai, Miyagi 9818555, Japan. EM ohrui@biochem.tohoku.ac.jp NR 9 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD AUG PY 2001 VL 65 IS 8 BP 1879 EP 1882 DI 10.1271/bbb.65.1879 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA 469HH UT WOS:000170808100029 PM 11577734 ER PT J AU Szmania, S Galloway, A Bruorton, M Musk, P Aubert, G Arthur, A Pyle, H Hensel, N Ta, N Lamb, L Dodi, T Madrigal, A Barrett, J Henslee-Downey, J van Rhee, F AF Szmania, S Galloway, A Bruorton, M Musk, P Aubert, G Arthur, A Pyle, H Hensel, N Ta, N Lamb, L Dodi, T Madrigal, A Barrett, J Henslee-Downey, J van Rhee, F TI Isolation and expansion of cytomegalovirus-specific cytotoxic T lymphocytes to clinical scale from a single blood draw using dendritic cells and HLA-tetramers SO BLOOD LA English DT Article ID ALLOGENEIC BONE-MARROW; TRANSPLANT RECIPIENTS; GANCICLOVIR PROPHYLAXIS; PROTEIN PP65; VIRUS INFECTION; CUTTING EDGE; RISK-FACTORS; DISEASE; ANTIGEN; IDENTIFICATION AB Cytomegalovirus (CMV) reactivation in immunocompromised recipients of allogeneic stem cell transplantation is a cause of morbidity and mortality from viral pneumonitis. Antiviral drugs given to reactivating patients have reduced the mortality from CMV but have toxic side effects and do not always prevent late CMV disease. Cellular immunotherapy to prevent CMV disease Is less toxic and could provide prolonged protection. However, a practical approach to generating sufficient quantities of CMV-specific cytotoxic T cells (CTLs) Is required. This study describes a system for generating sufficient CMV-specific CTLs for adoptive immunotherapy of HLA-A*0201 bone marrow transplant recipients from 200 mL donor blood. Donor monocytes are used to generate dendritic cells (DCs) in medium with autologous plasma, interleukin 4, granulocyte-macrophage colony-stimulating factor, and CD40 ligand, The DCs are pulsed with the immunodominant HLA-A*0201-restricted CMV peptide pp65(495-503), and incubated with donor T cells. These cultures are restimulated twice with peptide-pulsed lymphoblastoid cell lines (LCLs) or CD40-ligated B cells and purified with phycoerythrin (PE)-labeled pp65(495-503)/ HLA-A*0201 tetramers by flow sorting, or with anti-PE paramagnetic beads. The pure tetramer-positive population is then rapidly expanded to obtain sufficient cells for clinical immunotherapy. The expanded CTLs are more than 80% pure, of memory phenotype, with a Tc1 cytokine profile. They efficiently kill CMV-infected fibroblasts and express the integrin VLA-4, suggesting that the CTLs could cross endothelial barriers. This technique is reproducible and could be used for generating CMV-specific CTLs to prevent CMV disease after allogeneic blood and marrow transplantation. C1 Palmetto Hlth Alliance, S Carolina Canc Ctrcan, Div Transplantat Med, Columbia, SC USA. Univ S Carolina, Sch Med, Columbia, SC USA. NHLBI, Hematol Branch, Bone Marrow Transplant Unit, NIH, Bethesda, MD 20892 USA. Anthony Nolan Res Inst, London, England. RP van Rhee, F (reprint author), Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. NR 39 TC 110 Z9 111 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2001 VL 98 IS 3 BP 505 EP 512 DI 10.1182/blood.V98.3.505 PG 8 WC Hematology SC Hematology GA 456QY UT WOS:000170094800005 PM 11468143 ER PT J AU Nicot, C Mulloy, JC Ferrari, MG Johnson, JM Fu, KS Fukumoto, R Trovato, R Fullen, J Leonard, WJ Franchini, G AF Nicot, C Mulloy, JC Ferrari, MG Johnson, JM Fu, KS Fukumoto, R Trovato, R Fullen, J Leonard, WJ Franchini, G TI HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells SO BLOOD LA English DT Article ID VIRUS TYPE-I; RECEPTOR-BETA-CHAIN; OPEN READING FRAMES; HUMAN T-CELLS; TAX PROTEIN; HIV-1 NEF; CONSTITUTIVE ACTIVATION; PRIMARY LYMPHOCYTES; VIRAL INFECTIVITY; CYCLE ARREST AB The p12(1) protein, encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 (HTLV-1), Is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi. Although p121 contains 4 minimal proline-rich, src homology 3-binding motifs (PXXP), a characteristic commonly found in proteins involved in signaling pathways, it has not been known whether p121 has a role in modulating intracellular signaling pathways. This study demonstrated that p121 binds to the cytoplasmic domain of the Interleukin-2 receptor (IL-2R) beta chain that is involved in the recruitment of the Jak1 and Jak3 kinases. As a result of this interaction, p121 increases signal transducers and activators of transcription 5 (STAT5) DNA binding and transcriptional activity and this effect depends on the presence of both IL-2R beta and gamma (c). chains and Jak3. Transcluction of primary human peripheral blood mononuclear cells (PB-MCs) with a human immunodeficiency virus type 1-based retroviral vector expressing p121 also resulted in increased STAT5 phosphorylation and DNA binding. However, p121 could increase proliferation of human PBMCs only after stimulation of T-cell receptors by treatment of cells with low concentrations of aCD3 and alpha CD28 antibodies. In addition, the proliferative advantage of p12(1)-transduced PBMCs was evident mainly at low concentrations of IL-2. Together, these data indicate that p121 may confer a proliferative advantage on HTLV-1-infected cells in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of Infected T cells in vivo. (C) 2001 by The American Society of Hematology. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. NR 59 TC 78 Z9 80 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2001 VL 98 IS 3 BP 823 EP 829 DI 10.1182/blood.V98.3.823 PG 7 WC Hematology SC Hematology GA 456QY UT WOS:000170094800046 PM 11468184 ER PT J AU Mansfield, E Chae, JJ Komarow, HD Brotz, TM Frucht, DM Aksentijevich, I Kastner, DL AF Mansfield, E Chae, JJ Komarow, HD Brotz, TM Frucht, DM Aksentijevich, I Kastner, DL TI The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments SO BLOOD LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; SYNDROME GENE-PRODUCT; POLYMORPHONUCLEAR LEUKOCYTES; INFLAMMATORY MEDIATORS; ARP2/3 COMPLEX; L-SELECTIN; IN-VITRO; COLCHICINE; EXPRESSION; INHIBITION AB Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever and intense inflammation. FMF attacks are unique in their sensitivity to the microtubule inhibitor colchicine, contrasted with their refractoriness to the anti-Inflammatory effects of glucocorticoids. The FMF gene, MEFV was recently identified by positional cloning; it Is expressed at high levels in granulocytes and monocytes. The present study investigated the subeelfular localization of the normal gene product, pyrin. These experiments did not support previously proposed nuclear or Golgi localizations. In-stead fluorescence microscopy demonstrated colocalization of full-length GFP-and epitope-tagged pyrin with microtubules; this was markedly accentuated in paclitaxel-treated cells. Moreover, immunoblot analysis of precipitates of stabilized microtubules with recombinant pyrin demonstrated a direct interaction in vitro. Pyrin expression did not affect the stability of microtubules. Deletion constructs showed that the unique N-terminal domain of pyrin is necessary and sufficient for colocalization, whereas disease-associated mutations in the C-terminal B30.2 (rfp) domain did not disrupt this interaction. By phalloidin staining, a colocalization of pyrin with actin was also observed in perinuclear filaments and in peripheral lamellar ruffles. The proposal is made that pyrin regulates inflammatory responses at the level of leukocyte cytoskeletal organization and that the unique therapeutic effect of colchicine in FMF may be dependent on this interaction. (C) 2001 by The American Society of Hematology. C1 NIAMSD, Genet Sect, NIH, Bethesda, MD 20892 USA. NIAMSD, Lymphocyte Cell Biol Sect, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Mansfield, E (reprint author), NIAMSD, Genet Sect, NIH, Bldg 10,Rm 9N210,10 Ctr Dr,MSC-1820, Bethesda, MD 20892 USA. RI Brotz, Tilmann/R-6599-2016 OI Brotz, Tilmann/0000-0001-8212-459X NR 68 TC 107 Z9 118 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2001 VL 98 IS 3 BP 851 EP 859 DI 10.1182/blood.V98.3.851 PG 9 WC Hematology SC Hematology GA 456QY UT WOS:000170094800050 PM 11468188 ER PT J AU Daley, T Metcalfe, DD Akin, C AF Daley, T Metcalfe, DD Akin, C TI Association of the Q576R polymorphism in the interleukin-4 receptor alpha chain with indolent mastocytosis limited to the skin SO BLOOD LA English DT Article ID HUMAN MAST-CELLS; BLOOD MONONUCLEAR-CELLS; C-KIT; CATALYTIC DOMAIN; MUTATION; EXPRESSION; TRYPTASE; IL-4; SEVERITY; DISEASE AB Gain-of-function mutations in c-kit, which appear to contribute to mast cell hyperplasia, have been detected in both limited and aggressive forms of mastocytosis, suggesting that other mutations or polymorphisms may contribute to the clinical phenotype. Because addition of interleukin-4 (IL-4) to mast cell cultures Is reported to induce apoptosis, the hypothesis was considered that individuals carrying the gal n-of-function polymorphism Q576R in the cytoplasmic domain of the alpha -subunit of the IL-4 receptor (IL-4R) might be relatively resistant to the gain-of-function mutation In c-kit. To assess this possibility, 36 patients with either cutaneous or systemic mastocytosis were studied for association with the Q576R polymorphism. The 0576R polymorphism was found more frequently in those with disease limited to skin and who exhibited lower levels of surrogate disease markers. These data suggest that the Q576R IL-4R alpha- chain polymorphism may mitigate disease expression and confer a better prognosis in patients with mastocytosis. (C) 2001 by The American Society of Hematology. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Akin, C (reprint author), NIAID, Lab Allerg Dis, NIH, MSC 1881,Bldg 10,Rm 11C205, Bethesda, MD 20892 USA. NR 14 TC 38 Z9 41 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2001 VL 98 IS 3 BP 880 EP 882 DI 10.1182/blood.V98.3.880 PG 3 WC Hematology SC Hematology GA 456QY UT WOS:000170094800054 PM 11468192 ER PT J AU Eliez, S Blasey, CM Freund, LS Hastie, T Reiss, AL AF Eliez, S Blasey, CM Freund, LS Hastie, T Reiss, AL TI Brain anatomy, gender and IQ in children and adolescents with fragile X syndrome SO BRAIN LA English DT Article DE fragile X syndrome; MRI; brain development; FMR1 ID MENTAL-RETARDATION; YOUNG BOYS; MALES; PROTEIN; FEMALES; FMR-1; PERFORMANCE; INSTABILITY; INVOLVEMENT; MATURATION AB This study utilized MRI data to describe neuroanatomical morphology in children and adolescents with fragile X syndrome, the most common inherited cause of developmental disability. The syndrome provides a model for understanding how specific genetic factors can influence both neuroanatomy and cognitive capacity. Thirty-seven children and adolescents with fragile X syndrome received an MRI scan and cognitive testing. Scanning procedures and analytical strategies were identical to those reported in an earlier study of 85 typically developing children, permitting a comparison with a previously published template of normal brain development. Regression analyses indicated that there was a normative age-related decrease in grey matter and an increase in white matter. However, caudate and ventricular CSF volumes were significantly enlarged, and caudate volumes decreased with age. Rates of reduction of cortical grey matter were different for males and females. IQ scores were not significantly correlated with volumes of cortical and subcortical grey matter, and these relationships were statistically different from the correlational patterns observed in typically developing children. Children with fragile X syndrome exhibited several typical neurodevelopmental patterns. Aberrations in volumes of subcortical nuclei, gender differences in rates of cortical grey matter reduction and an absence of correlation between grey matter and cognitive performance provided indices of the deleterious effects of the fragile X mutation on the brain's structural organization. C1 Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford Behav Neurogenet Res Ctr, Stanford, CA 94305 USA. NICHHD, Rockville, MD USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. RP Eliez, S (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford Behav Neurogenet Res Ctr, 401 Quarry Rd, Stanford, CA 94305 USA. NR 53 TC 79 Z9 81 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2001 VL 124 BP 1610 EP 1618 DI 10.1093/brain/124.8.1610 PN 8 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 462ZY UT WOS:000170453400013 PM 11459752 ER PT J AU Abrams, JS AF Abrams, JS TI Overview of the US consensus conference on adjuvant therapy for breast cancer SO BREAST LA English DT Article; Proceedings Paper CT 7th International Conference on Adjuvant Therapy of Primary Breast Cancer CY FEB 21-24, 2001 CL ST GALLEN, SWITZERLAND SP UICC, SAK ID RANDOMIZED-TRIALS; TAMOXIFEN; WOMEN; CHEMOTHERAPY; TUMORS; CYCLOPHOSPHAMIDE; FLUOROURACIL; METHOTREXATE; SURVIVAL; PROJECT C1 NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diagnosis, Rockville, MD 20852 USA. RP Abrams, JS (reprint author), NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diagnosis, 6130 Execut Blvd,EPN 7040, Rockville, MD 20852 USA. EM jablx@nih.gov NR 40 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 EI 1532-3080 J9 BREAST JI Breast PD AUG PY 2001 VL 10 SU 3 BP 139 EP 146 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 460ND UT WOS:000170312900023 ER PT J AU Silverstone, AM AF Silverstone, AM TI The state of the ecosystem on Anticosti Island, Quebec SO CANADIAN VETERINARY JOURNAL-REVUE VETERINAIRE CANADIENNE LA English DT Article ID WHITE-TAILED DEER; HEALTH AB The state of the ecosystem of Anticosti Island, Quebec, was studied by veterinary students (n = 17) and faculty (n = 4) in the summer of 1999. The field of ecosystem health is an integrative science requiring the expertise of professionals in several disciplines, including socioeconomic, ecological, biophysical, human health, and animal health (1). C1 Univ Prince Edward Isl, Atlantic Vet Coll, Charlottetown, PE C1A 4P3, Canada. RP Silverstone, AM (reprint author), NCI, Dept Expt Transplantat & Immunol, NIH, Bldg 10,Rm 12N226,MSC 1907, Bethesda, MD 20892 USA. NR 16 TC 0 Z9 0 U1 0 U2 3 PU CANADIAN VET MED ASSOC PI OTTAWA PA 339 BOOTH ST ATTN: KIMBERLY ALLEN-MCGILL, OTTAWA, ONTARIO K1R 7K1, CANADA SN 0008-5286 J9 CAN VET J JI Can. Vet. J.-Rev. Vet. Can. PD AUG PY 2001 VL 42 IS 8 BP 638 EP 641 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 463JE UT WOS:000170472700008 PM 11519275 ER PT J AU Meredith, RF Alvarez, RD Partridge, EE Khazaeli, MB Lin, CY Macey, DJ Austin, JM Kilgore, LC Grizzle, WE Schlom, J LoBuglio, AF AF Meredith, RF Alvarez, RD Partridge, EE Khazaeli, MB Lin, CY Macey, DJ Austin, JM Kilgore, LC Grizzle, WE Schlom, J LoBuglio, AF TI Intraperitoneal radioimmunochemotherapy of ovarian cancer: A phase I study SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE radioimmunotherapy; antibody; chemotherapy ID MONOCLONAL-ANTIBODY; RADIOIMMUNOTHERAPY; INTERFERON; TOXICITY; CARCINOMA; CC49; TRIAL; TAXOL; PHARMACOKINETICS; LU-177-CC49 AB A phase I trial was designed to examine the feasibility of combining interferon and Taxol with intraperitoneal radioimmunotherapy (Lu-177-CC49). Patients with recurrent or persistent ovarian cancer confined to the abdominal cavity after first line therapy, Karnofsky, performance status > 60, adequate liver, renal and hematologic function, and tumor that reacted with CC49 antibody were enrolled. Human recombinant alpha interferon (IFN) was administered as 4 subcutaneous injections of 3 X 10(6) U on alternate days beginning 5 days before RIT to increase the expression of the tumor-associated antigen, TAG-72. The addition of IFN increased hematologic toxicity such that the maximum tolerated dose (MTD) of the combination was 40 mCi/m(2) compared to Lu-177-CC49 alone (45 mCi/m(2)). Taxol, which has radiosensitizing effects as well as antitumor activity against ovarian cancer, was given intraperitoneally (IP) 48 hrs before RIT. It was initiated at 25 mg/m(2) and escalated at 25 mg/m(2) increments to 100 mg/m(2). Subsequent groups of patients were treated with IFN + 100 mg/m(2) Ta-vol + escalating doses of Lu-177-CC49. Three or more patients were treated in each dose group and 34 patients were treated with the 3-agent combination. Therapy was well tolerated with the expected reversible hematologic toxicity. The MTD for Lu-177-CC49 was 40 mCi/m(2) when given with IFN + 100 mg/m(2) Taxol. Interferon increased the effective whole body half-time of radioactivity and the whole body radiation dose. Taxol did not have a significant effect on pharmacokinetic or dosimetry, parameters. Four of 17 patients with CT measurable disease had a partial response (PR) and 4 of 27 patients with non-measurable disease have Progression-free intervals of 18+, 21+, 21+, and 37+ months. The combination of intraperitoneal Taxol chemotherapy (100 mg/m(2)) with RIT using Lu-177-CC49 and interferon was well tolerated, with bone marrow suppression as the dose-limiting toxicity. C1 Univ Alabama, Ctr Comprehens Canc, Wallace Tumor Inst 117, Dept Radiat Oncol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Dept Pathol, Birmingham, AL 35294 USA. Natl Canc Inst, Bethesda, MD USA. RP Meredith, RF (reprint author), Univ Alabama, Ctr Comprehens Canc, Wallace Tumor Inst 117, Dept Radiat Oncol, 1530 3rd Ave S, Birmingham, AL 35294 USA. FU NCI NIH HHS [CM 87215, 1R01 CA 0D67828-01]; NCRR NIH HHS [M01 RR00032] NR 35 TC 59 Z9 62 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD AUG PY 2001 VL 16 IS 4 BP 305 EP 315 DI 10.1089/108497801753131381 PG 11 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 478LJ UT WOS:000171347400005 PM 11603001 ER PT J AU Nagano, J Kono, S Preston, DL Mabuchi, K AF Nagano, J Kono, S Preston, DL Mabuchi, K TI A prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan) SO CANCER CAUSES & CONTROL LA English DT Article DE antioxidants; cancer incidence; green tea; polyphenols; prospective studies ID ATOMIC-BOMB SURVIVORS; ESOPHAGEAL CANCER; STOMACH-CANCER; RISK-FACTORS; GASTRIC-CANCER; POLYPHENOLS; POPULATION; SHANGHAI; CHINA; ALCOHOL AB Objectives: Laboratory and animal studies have shown a protective effect of green tea on cancer of different sites, but epidemiological evidence is limited and inconclusive. This prospective study in Japan examined the association between green tea consumption and cancer incidence. Methods: Subjects were 38,540 people (14,873 men, mean age 52.8 years; 23,667 women, mean age 56.8 years) who responded to a mail survey carried out between 1979 and 1981. A self-administered questionnaire ascertained consumption frequency of green tea using precoded answers (never, once per day, twice to four times per day, and five or more times per day). Follow-up continued until 31 December 1994. The study analyzed solid cancers (n = 3881); hematopoietic cancers (188); cancers of all sites combined (4069); and cancer of specific sites with more than 100 cases, i.e. stomach (901), colon (432), rectum (193), liver (418), gallbladder (122), pancreas (122), lung (436), breast (281), and bladder (122). Poisson regression was used to allow for city, gender, age, radiation exposure, smoking status, alcohol drinking, body-mass index, education level, and calendar time. Results: Green tea consumption was virtually unrelated to incidence of cancers under study. The relative risks of all cancers for those consuming green tea twice to four times per day and five or more times per day were 1.0 (95% confidence interval 0.91-1.1) and 0.98 (0.88-1.1), respectively, as compared with those consuming green tea once per day or less. Conclusion: Our findings do not provide evidence that regular green tea consumption is related to reduced cancer risks. C1 Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, Hiroshima 7320815, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Prevent Med, Higashi Ku, Fukuoka 8128582, Japan. Kyushu Univ, Inst Hlth Sci, Kasuga, Fukuoka 8168580, Japan. Radiat Effects Res Fdn, Dept Stat, Minami Ku, Hiroshima 7320815, Japan. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Nagano, J (reprint author), Radiat Effects Res Fdn, Dept Epidemiol, Minami Ku, Hijiyama Pk 5-2, Hiroshima 7320815, Japan. RI U-ID, Kyushu/C-5291-2016 NR 38 TC 109 Z9 112 U1 3 U2 17 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2001 VL 12 IS 6 BP 501 EP 508 DI 10.1023/A:1011297326696 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 455XC UT WOS:000170052200003 PM 11519758 ER PT J AU Waddell, BL Zahm, SH Baris, D Weisenburger, DD Holmes, F Burmeister, LF Cantor, KP Blair, A AF Waddell, BL Zahm, SH Baris, D Weisenburger, DD Holmes, F Burmeister, LF Cantor, KP Blair, A TI Agricultural use of organophosphate pesticides and the risk of non-Hodgkin's lymphoma among male farmers (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE cancer; diazinon; farmers; herbicides; insecticides; non-Hodgkin's lymphoma ID PROXY RESPONDENTS; LEUKEMIA; IOWA; MINNESOTA; CANCER; MEN; DIAGNOSES; EXPOSURE AB Objective: Data from three population-based case-control studies conducted in Kansas, Nebraska, Iowa, and Minnesota were pooled to evaluate the relationship between the use of organophosphate pesticides and non-Hodgkin's lymphoma (NHL) among white male farmers. Methods: The data set included 748 cases of non-Hodgkin's lymphoma and 2236 population-based controls. Telephone or in-person interviews were utilized to obtain information on the use of pesticides. Odds ratios (OR) adjusted for age, state of residence, and respondent status, as well as other pesticide use where appropriate, were estimated by logistic regression. Results: Use of organophosphate pesticides was associated with a statistically significant 50% increased risk of NHL, but direct interviews showed a significantly lower risk (OR = 1.2) than proxy interviews (OR = 3.0). Among direct interviews the risk of small lymphocytic lymphoma increased with diazinon use (OR = 2.8), after adjustment for other pesticide exposures. Conclusions: Although we found associations between the risk of NHL and several groupings and specific organophosphate pesticides, larger risks from proxy respondents complicate interpretation. Associations, however, between reported use of diazinon and NHL, particularly diffuse and small lymphocytic lymphoma, among subjects providing direct interviews are not easily discounted. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Nebraska, Sch Med, Omaha, NE 68198 USA. Univ Iowa, Sch Med, Iowa City, IA 52242 USA. Univ Kansas, Sch Med, Kansas City, KS USA. RP Blair, A (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Room 8118, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 29 TC 65 Z9 68 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2001 VL 12 IS 6 BP 509 EP 517 DI 10.1023/A:1011293208949 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 455XC UT WOS:000170052200004 PM 11519759 ER PT J AU Michaud, DS Augustsson, K Rimm, EB Stampfer, MJ Willett, WC Giovannucci, E AF Michaud, DS Augustsson, K Rimm, EB Stampfer, MJ Willett, WC Giovannucci, E TI A prospective study on intake of animal products and risk of prostate cancer SO CANCER CAUSES & CONTROL LA English DT Article DE cohort study; dairy intake; prostate cancer; red meat intake ID FOOD FREQUENCY QUESTIONNAIRE; DIETARY-FAT; COHORT; REPRODUCIBILITY; CONSUMPTION; VALIDITY; CALCIUM; ACIDS; MEN AB Objective: Association between animal products and prostate cancer have been observed in numerous observational studies, but it is not clear whether the high fat content of these foods or some other component accounts for these associations. We examine these associations among 51,529 men who contributed detailed dietary data. Methods: Participants of the Health Professionals Follow-Up Study completed a semiquantitative food-frequency questionnaire in 1986, and subsequently in 1990 and 1994. Other data on potential risk factors were collected at baseline and in subsequent questionnaires during follow-up. Between 1986 and 1996, 1897 total cases of prostate cancer (excluding stage A(1)) and 249 metastatic cancers were identified. We used pooled logistic regression for analyses of diet and prostate cancer. Results: Intakes of total meat, red meat, and dairy products were not associated with risk of total or advanced prostate cancer. An elevated risk for metastatic prostate cancer was observed with intake of red meat (relative risk (RR) = 1.6 for top vs. bottom quintile comparison, 95% confidence interval (CI) = 1.0-2.5); this association was slightly attenuated after controlling for saturated and alpha -linolenic fatty acids (RR = 1.5, 95% CI = 0.88-2.5). Processed meats, bacon and beef, pork or lamb as a main dish each contributed to an elevated risk of metastatic prostate cancer. Dairy product intake increased risk of metastatic prostate cancer (RR = 1.4, 95% CI = 0.91-2.2 for top vs. bottom quintile comparison), but no association remained after controlling for calcium and other fatty acids. A high intake in both red meat and dairy product was associated with a statistically significant two-fold elevation in risk of metastatic prostate cancer, compared to low intake of both products; however, most of the excess risk could be explained by known nutritional components of these foods. Conclusions: Intakes of red meat and dairy products appear to be related to increased risk of metastatic prostate cancer. While known nutrients, such as calcium and fatty acids, may explain most of the dairy association observed, it appears that a portion of the risk of metastatic prostate cancer associated with red meat intake remains unexplained. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. RP Michaud, DS (reprint author), NCI, 6120 Execut Blvd,EPS Rm 7026, Rockville, MD 20852 USA. RI Michaud, Dominique/I-5231-2014 FU NCI NIH HHS [CA 55075]; NHLBI NIH HHS [HL 35464] NR 30 TC 141 Z9 145 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2001 VL 12 IS 6 BP 557 EP 567 DI 10.1023/A:1011256201044 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 455XC UT WOS:000170052200009 PM 11519764 ER PT J AU Yeowell-O'Connell, K Rothman, N Waidyanatha, S Smith, MT Hayes, RB Li, GL Bechtold, WE Dosemeci, M Zhang, LP Yin, SN Rappaport, SM AF Yeowell-O'Connell, K Rothman, N Waidyanatha, S Smith, MT Hayes, RB Li, GL Bechtold, WE Dosemeci, M Zhang, LP Yin, SN Rappaport, SM TI Protein adducts of 1,4-benzoquinone and benzene oxide among smokers and nonsmokers exposed to benzene in China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BENZOQUINONE ADDUCTS; HEMOGLOBIN ADDUCTS; ALBUMIN ADDUCTS; BONE-MARROW; HYDROQUINONE; METABOLITES; CATECHOL; URINE; BLOOD; RATS AB Hemoglobin (Hb) and albumin (Alb) adducts of the benzene metabolites benzene oxide (BO) and 1,4-benzoquinone (1,4-BQ) were analyzed by gas chromatography-mass spectrometry in 43 exposed workers and 44 unexposed controls from Shanghai, China, as part of a larger cross-sectional study of benzene biomarkers. When subjects were divided into controls (n = 44) and workers exposed to less than or equal to 31 ppm (n 21) and > 31 ppm (n = 22) of benzene, median 1,4-BQ-Alb adducts were 2110, 5850, and 13,800 pmol/g Alb, respectively (correlation with exposure: Spearman r = 0.762; P < 0.0001); median BO-Alb adducts were 106, 417, and 2400 pmol/g Alb, respectively (Spearman r = 0.877; P < 0.0001); and median BO-Hb adducts were 37.1, 50.5, and 136 pmol/g Hb, respectively (Spearman r = 0.757; P < 0.0001). To our knowledge, this is the first observation that adducts of 1,4-BQ are significantly correlated with benzene exposure. When compared on an individual basis, Alb adducts of 1,4-BQ and BO and Hb adducts of BO were highly correlated with each other and with urinary phenol and hydroquinone (P < 0.0001 for all of the comparisons). Although detectable in the assays, Hb adducts of 1,4-BQ and both Hb and Alb adducts of 1,2-BQ produced erratic results and are not reported. Interestingly, cigarette smoking increased Alb adducts of 1,4-BQ but not of BO, suggesting that benzene from cigarette smoke was not the primary contributor to the 1,4-BQ adducts. C1 Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Acad Prevent Med, Inst Occupat Med, Beijing 100050, Peoples R China. Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. RP Rappaport, SM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Environm Sci & Engn, CB 7400, Chapel Hill, NC 27599 USA. FU NIEHS NIH HHS [P42ES04705, P42ES05948] NR 37 TC 36 Z9 37 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2001 VL 10 IS 8 BP 831 EP 838 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 460UZ UT WOS:000170328100003 PM 11489749 ER PT J AU Lipkus, IM Klein, WMP Rimer, BK AF Lipkus, IM Klein, WMP Rimer, BK TI Communicating breast cancer risks to women using different formats SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID UNCERTAINTY; PROBABILITIES; AMBIGUITY; DECISION AB Using a pre-post test design with a baseline, laboratory, and a 6-month follow-up, we communicated women's objective breast cancer risks, based on the Gail Model, using two formats: (a) range of risks (e.g., risk of breast cancer can be as low as 1% and as high as 5%); and (b) as a point estimate (e.g., your risk of breast cancer is 3%). We examined how these presentations individually and jointly affected women's perceived lifetime breast cancer risks. Overall, providing risk estimates either as a range of risks or as a point estimate lowered women's perceived lifetime risks compared with women who did not get information presented this way shortly after receipt of this information relative to baseline. At the 6-month follow-up, perceptions of lifetime risks generally returned to their baseline values. Overall, women viewed their risk feedback, whether presented as a point estimate or as a range of risks, as equally credible, trustworthy, accurate, and personally relevant. These results suggest that women evaluate risk feedback containing either point estimates or range of risks as equally acceptable. Both formats lead to short-term reductions in perceived risk (i.e., greater accuracy). C1 Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Risk Commun Lab, Durham, NC 27701 USA. Colby Coll, Waterville, ME 04901 USA. NCI, Bethesda, MD 20892 USA. RP Lipkus, IM (reprint author), 905 W Main St,Box 34, Durham, NC 27713 USA. FU NCI NIH HHS [CA72099-05] NR 17 TC 40 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2001 VL 10 IS 8 BP 895 EP 898 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 460UZ UT WOS:000170328100011 PM 11489757 ER PT J AU David-Beabes, GL Lunn, RM London, SJ AF David-Beabes, GL Lunn, RM London, SJ TI No association between the XPD (Lys751Gln) polymorphism or the XRCC3 (Thr241Met) polymorphism and lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. RP David-Beabes, GL (reprint author), POB 12233,MD C2-04, Res Triangle Pk, NC 27709 USA. NR 5 TC 113 Z9 118 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2001 VL 10 IS 8 BP 911 EP 912 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 460UZ UT WOS:000170328100015 PM 11489761 ER PT J AU Peters, KF Menaker, TJ Wilson, PL Hadley, DW AF Peters, KF Menaker, TJ Wilson, PL Hadley, DW TI The Human Genome Project: An update SO CANCER NURSING LA English DT Article DE Human Genome Project; genetic map; sequencing ID GENE; BREAST AB The mapping, sequencing, and analysis of the human genome that has occurred during the last decade through the Human Genome Project are providing fundamental advances for basic science and medicine. Genomic information is providing insights into causes of, susceptibility to, and protection from cancer and a host of other diseases. Already, information generated by the Human Genome Project has been incorporated into the care of cancer patients. Perhaps more so than other types of medical information, genetic knowledge can have profound implications for individuals, families, and society. As a result, nursing professionals in clinical and academic settings are being called upon to identify and deliberate medical, social, ethical, and legal issues stemming from Human Genome Project advancements. The purpose of this article is to review the goals and implications of the Human Genome Project to further prepare cancer nurses to actively participate in the deliberations, research, and clinical activities evolving from the Human Genome Project. C1 NIH, Med Genet Branch, NHGRI, Bethesda, MD 20892 USA. Penn State Univ, University Pk, PA 16802 USA. Howard Univ, Washington, DC 20059 USA. RP Hadley, DW (reprint author), NIH, Med Genet Branch, NHGRI, 10 Ctr Dr,MSC 1852,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 U1 4 U2 40 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD AUG PY 2001 VL 24 IS 4 BP 287 EP 292 DI 10.1097/00002820-200108000-00007 PG 6 WC Oncology; Nursing SC Oncology; Nursing GA 459DN UT WOS:000170235900006 PM 11502037 ER PT J AU Dong, G Chen, Z Li, ZY Yeh, NT Bancroft, CC Van Waes, C AF Dong, G Chen, Z Li, ZY Yeh, NT Bancroft, CC Van Waes, C TI Hepatocyte growth factor/scatter factor-induced activation of MEK and PI3K signal pathways contributes to expression of proangiogenic cytokines interleukin-8 and vascular endothelial growth factor in head and neck squamous cell carcinoma SO CANCER RESEARCH LA English DT Article ID FACTOR SCATTER FACTOR; RECEPTOR TYROSINE KINASE; C-MET; TUMOR ANGIOGENESIS; MAP KINASE; IN-VIVO; COLORECTAL-CANCER; EPITHELIAL-CELLS; MELANOMA-CELLS; HUMAN GLIOMAS AB The proangiogenic activity of hepatocyte growth factor (HGF)/scatter factor has been closely associated with its ability to stimulate endothelial cell chemotaxis, migration, proliferation, and capillary format on. However, the potential of HGF as a paracrine factor in regulating the expression of angiogenesis factors by tumor cells is not widely appreciated. We observed that increased HGF was correlated with higher levels of angiogenesis factors interleukin (IL)-8 and vascular endothelial growth factor (VEGF) in serum of patients with head and neck squamous cell carcinoma (HNSCC) as compared with that in normal volunteers and hypothesized that HGF may regulate angiogenesis factor production by tumor cells through the activation of its receptor c-Met, which is expressed by HNSCC cells. To test this hypothesis, we examined the effect of HGF treatment on IL-8 and VEGF expression by a panel of primary keratinocytes and HNSCC lines. HGF induced a significant dose-dependent increase in IL-8 and/or VEGF cytokine production in eight HNSCC lines tested, which is not observed in normal keratinocytes. In addition, HGF increased mRNA expression of IL-8 in 3 of 6 and VEGF in 5 of 6 HNSCC lines. The increase in induction of these factors by HGF corresponded to an increase in phosphorylation of c-Met in HNSCC. HGF-induced phosphorylation of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) pathway substrate p42/p44(erk) and phosphatidylinositol 3 ' -kinase (PI3K) pathway substrate Akt provided evidence or downstream activation of MEK and PI3K pathways in HNSCC. Inhibitors of MEK (U0126) and PI3K (LY294002) blocked p42/p44(erk) and Akt, respectively, and partially blocked HGF-induced production of IL-8 and VEGF, whereas the combination of U0126 and LY294002 completely inhibited expression of IL-8 and VEGF by UMSCC-11A. Our results demonstrate that HGF can promote expression of angiogenesis factors in tumor cells through both MEK- and PI3K-dependent pathways. Understanding HGF/Met paracrine regulatory mechanisms between tumor and host cells may provide critical information for targeting of therapies against angiogenesis. C1 Natl Inst Deafness & Other Commun, Head & Neck Surg Branch, Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. RP Dong, G (reprint author), Natl Inst Deafness & Other Commun, Head & Neck Surg Branch, Tumor Biol Sect, NIH, Bldg 10,Room 5D55,MSC-1419,10 Ctr Dr, Bethesda, MD 20892 USA. EM dongg@nided.nih.gov FU NIDCD NIH HHS [Z01-DC-0016] NR 60 TC 204 Z9 218 U1 2 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2001 VL 61 IS 15 BP 5911 EP 5918 PG 8 WC Oncology SC Oncology GA 458KZ UT WOS:000170194700037 PM 11479233 ER PT J AU Singh, R Leuratti, C Josyula, S Sipowicz, MA Diwan, BA Kasprzak, KS Schut, HAJ Marnett, LJ Anderson, LM Shuker, DEG AF Singh, R Leuratti, C Josyula, S Sipowicz, MA Diwan, BA Kasprzak, KS Schut, HAJ Marnett, LJ Anderson, LM Shuker, DEG TI Lobe-specific increases in malondialdehyde DNA adduct formation in the livers of mice following infection with Helicobacter hepaticus SO CARCINOGENESIS LA English DT Article ID CHRONIC ACTIVE HEPATITIS; LIPID-PEROXIDATION PRODUCTS; A/JCR MICE; BACTERIAL PATHOGEN; MALONALDEHYDE; DAMAGE; TUMORS; PYRIMIDOPURINONE; MUTAGENICITY; ACIDS AB Helicobacter hepaticus infection is associated with chronic hepatitis and the development of liver tumours in mice. The underlying mechanism of this liver carcinogenesis is not clear but the oxidative stress associated with H. hepaticus infection may result in induction of lipid peroxidation and the generation of malondialdehyde. Malondialdehyde can react with deoxyguanosine in DNA resulting in the formation of the cyclic pyrimidopurinone N-1,N-2 malondialdehyde-deoxyguanosine (M(1)dG) adduct. This adduct has the potential to cause mutations that may ultimately lead to liver carcinogenesis. The objective of this study was to determine the control and infection-related levels of M(1)dG in the liver DNA of mice over time, using an immunoslot-blot procedure. The level of M(1)dG in control A/J mouse livers at 3, 6, 9 and 12 months averaged 37.5, 36.6, 24.8 and 30.1 adducts per 10(8) nucleotides, respectively. Higher levels of M(1)dG were detected in the liver DNA of H. hepaticus infected A/JCr mice, with levels averaging 40.7, 47.0, 42.5 and 52.5 adducts per 10(8) nucleotides at 3, 6, 9 and 12 months, respectively. There was a significant age dependent increase in the level of M(1)dG in the caudate and median lobes of the A/JCr mice relative to control mice. A lobe specific distribution of the M(1)dG adduct in both infected and control mice was noted, with the left lobe showing the lowest level of the adduct compared with the right and median lobes at all time points. In a separate series of mice experimentally infected with H. hepaticus, levels of 8-hydroxy-deoxyguanosine were significantly greater in the median compared with the left lobe at 12 weeks after treatment. In conclusion, these results suggest that M(1)dG occurs as a result of oxidative stress associated with H. hepaticus infection of mice, and may contribute to liver carcinogenesis in this model. C1 Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England. Open Univ, Dept Chem, Milton Keynes MK7 6AA, Bucks, England. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. NCI, Comparat Carcinogenesis Lab, Div Basic Sci, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Vanderbilt Univ, Sch Med, Dept Biochem & Chem, Ctr Mol Toxicol, Nashville, TN 37232 USA. RP Singh, R (reprint author), Univ Leicester, MRC, Toxicol Unit, Hodgkin Bldg,POB 138,Lancaster Rd, Leicester LE1 9HN, Leics, England. RI Singh, Raj/A-5398-2011 FU NCI NIH HHS [CA77839] NR 32 TC 32 Z9 34 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2001 VL 22 IS 8 BP 1281 EP 1287 DI 10.1093/carcin/22.8.1281 PG 7 WC Oncology SC Oncology GA 463HV UT WOS:000170471800022 PM 11470759 ER PT J AU Pal, A Gu, YJ Herzog, C Srivastava, SK Zimniak, P Ji, XH Singh, SV AF Pal, A Gu, YJ Herzog, C Srivastava, SK Zimniak, P Ji, XH Singh, SV TI Role of arginine 216 in catalytic activity of murine Alpha class glutathione transferases mGSTAl-1 and mGSTA2-2 toward carcinogenic diol epoxides of polycyclic aromatic hydrocarbons SO CARCINOGENESIS LA English DT Article ID S-TRANSFERASE; EXCEPTIONAL ACTIVITY; OPTICAL ENANTIOMERS; ELLAGIC ACID; HUMAN-LIVER; DNA-DAMAGE; RAT-LIVER; CONJUGATION; MUTAGENICITY; REFINEMENT AB Murine class Alpha glutathione (GSH) transferase A1-1 (mGSTA1-1) is unique among mammalian Alpha class GSTs due to its exceptionally high catalytic activity toward (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene [(+)-anti-BPDE], which is the activated metabolite of an environmentally relevant carcinogen, benzo[a] pyrene (BP). However, the molecular basis for high catalytic activity of mGSTA1-1 toward (+)-anti-BPDE is not clear. In the present study, we demonstrate that an arginine residue at position 216, which is conserved in some but not all mammalian class Alpha GSTs, plays an important role in catalytic activity of mGSTA1-1 toward (+)-anti-BPDE and carcinogenic diol epoxides of other environmentally relevant polycyclic aromatic hydrocarbons (PAHs). The catalytic efficiency (k(cat)/K-m) of mGSTA1-1 for the GSH conjugation of (+)-anti-BPDE (108/mM/s) was reduced by about 58 % upon replacement of arginine 216 with alanine (R216A). This was mainly due to a significantly lower Vma for the R216A mutant of mGSTA1-1 compared with wildtype mGSTA1-1. The R216A mutation also resulted in a statistically significant reduction (> 70%) in specific activity of mGSTA1-1 toward racemic anti-diol epoxides of chrysene and benzo[c]phenanthrene (anti-CDE and anti-B[c]PDE, respectively). The catalytic activity of mGSTA2-2, which is a close structural homologue of mGSTA1-1, was also reduced upon R216A mutation. The results of the present study clearly indicate that an arginine residue at position 216 is critical for catalytic activity of mGSTA1-1 and mGSTA2-2 toward carcinogenic diol epoxide metabolites of various PAHs that are abundant in the environment and suspected human carcinogens. C1 Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA 15261 USA. Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. McClellan VA Hosp Med Res, Little Rock, AR 72205 USA. NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Singh, SV (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol, 3550 Terrace St, Pittsburgh, PA 15261 USA. RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [CA76348, CA55589] NR 42 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2001 VL 22 IS 8 BP 1301 EP 1305 DI 10.1093/carcin/22.8.1301 PG 5 WC Oncology SC Oncology GA 463HV UT WOS:000170471800025 PM 11470762 ER PT J AU Kumar, S Nussinov, R AF Kumar, S Nussinov, R TI How do thermophilic proteins deal with heat? SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE thermostability; salt bridges; electrostatics; adaptation; protein. temperature; structure ID COLD-SHOCK PROTEIN; COMPLETE GENOME SEQUENCE; ARCHAEON PYROCOCCUS-FURIOSUS; AMINO-ACID-RESIDUES; ION-PAIR NETWORKS; CRYSTAL-STRUCTURE; THERMOTOGA-MARITIMA; SALT BRIDGES; THERMAL-STABILITY; GLUTAMATE-DEHYDROGENASE AB Recent years have witnessed an explosion of sequence and structural information for proteins from hyperthermophilic and thermophilic organisms. Complete genome sequences are available for many hyperthermophilic archaeons. Here, we review some recent studies on protein thermostability along with work from our laboratory. A large number of sequence and structural factors are thought to contribute toward higher intrinsic thermal stability of proteins from these organisms. The most consistent are surface loop deletion, increased occurrence of hydrophobic residues with branched side chains and an increased proportion of charged residues at the expense of uncharged polar residues. The energetic contribution of electrostatic interactions such as salt bridges and their networks toward protein stability can be stabilizing or destabilizing. For hyperthermophilic proteins, the contribution is mostly stabilizing. Macroscopically, improvement in electrostatic interactions and strengthening of hydrophobic cores by branched apolar residues increase the enthalpy change between the folded and unfolded states of a thermophilic protein. At the same time, surface loop deletion contributes to decreased conformational entropy and decreased heat capacity change between the folded and unfolded states of the protein. C1 NCI, Intramural Res Support Program, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, SAIC, Frederick Canc Res & Dev Ctr, Bldg 469,Rm 151, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 122 TC 260 Z9 269 U1 7 U2 56 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD AUG PY 2001 VL 58 IS 9 BP 1216 EP 1233 DI 10.1007/PL00000935 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 474CQ UT WOS:000171087100005 PM 11577980 ER PT J AU Behar, TN Smith, SV Kennedy, RT Mckenzie, JM Maric, I Barker, AL AF Behar, TN Smith, SV Kennedy, RT Mckenzie, JM Maric, I Barker, AL TI GABA(B) receptors mediate motility signals for migrating embryonic cortical cells SO CEREBRAL CORTEX LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; RAT-BRAIN; NEURONAL MIGRATION; NMDA RECEPTORS; BINDING-SITES; SPINAL-CORD; MOUSE-BRAIN; EXPRESSION; TAURINE; SYSTEM AB During development, postmitotic neurons migrate from germinal regions into the cortical plate (cp), where lamination occurs. In rats, GABA is transiently expressed in the cp. near target destinations for migrating neurons. In vitro GABA stimulates neuronal motility, suggesting cp cells release GABA, which acts as a chemoattractant during corticogenesis. Pharmacological studies indicate GABA stimulates migration via GABA(B)-receptor (GABA(B)-R) activation. Using immunohistochemistry. RT-PCR and Western blotting, we examined embryonic cortical cell expression of GABA(B)-Rs in vivo. At E17, GABA(B)-R1(+) cells were identified in the ventricular zone (vz) and cp. RT-PCR and Western blotting demonstrated the presence of GABA(B)-R1a and GABA(B)-R1b mRNA and proteins. Using immunocytochemistry, GABA(B)-R expression was examined in vz and cp cell dissociates before and after migration to GABA in an in vitro chemotaxis assay. GABA-induced migration resulted in an increase of GABAs-R+ cells in the migrated population. While <20% of each starting dissociate was GABA(B)-R+. >70% of migrated cells were immunopositive. We used a microchemotaxis assay to analyze cp cell release of diffusible chemotropic factor(s). In vitro, cp dissociates induced vz cell migration in a cell density-dependent manner that was blocked by micromolar saclofen (a GABA(B)-R antagonist). HPLC demonstrated cp cells release micromolar levels of GABA and taurine in several hours. Micromolar levels of both molecules stimulated cell migration that was blocked by micromolar saclofen. Thus, migratory cortical cells express GABA(B)-Rs, cp cells release GABA and taurine, and both molecules stimulate cortical cell movement. Together these findings suggest GABA and/or taurine act as chemoattractants for neurons during rat cortical histogenesis via mechanisms involving GABA(B)-Rs. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Chem, Gainesville, FL 32611 USA. RP Barker, AL (reprint author), NINDS, Neurophysiol Lab, NIH, Bldg 36,Rm 2C02, Bethesda, MD 20892 USA. RI Kennedy, Robert/G-9095-2016 OI Kennedy, Robert/0000-0003-2447-7471 FU NINDS NIH HHS [NS38476] NR 36 TC 92 Z9 94 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2001 VL 11 IS 8 BP 744 EP 753 DI 10.1093/cercor/11.8.744 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 455TT UT WOS:000170044400007 PM 11459764 ER PT J AU Chelazzi, L Miller, EK Duncan, J Desimone, R AF Chelazzi, L Miller, EK Duncan, J Desimone, R TI Responses of neurons in macaque area V4 during memory-guided visual search SO CEREBRAL CORTEX LA English DT Article ID INFERIOR TEMPORAL CORTEX; PRIMATE PREFRONTAL CORTEX; SACCADE TARGET SELECTION; FRONTAL EYE FIELD; NEURAL MECHANISMS; RHESUS-MONKEY; VISUOTOPIC ORGANIZATION; EXTRASTRIATE CORTEX; DIRECTED ATTENTION; LESIONS AB In a typical scene with many different objects, attentional mechanisms are needed to select relevant objects for visual processing and control over behavior. To test the role of area V4 in the selection of objects based on non-spatial features, we recorded from V4 neurons in the monkey, using a visual search paradigm. A cue stimulus was presented at the center of gaze, followed by a blank delay period. After the delay, a two-stimulus array was presented extrafoveally, and the monkey was rewarded for detecting the target stimulus matching the cue. The array was composed of one 'good' stimulus (effective in driving the cell when presented alone) and one 'poor' stimulus (ineffective in driving the cell when presented alone). When the choice array was presented in the receptive field (RF) of the neuron, many calls showed suppressive interactions between the stimuli as well as strong attention effects. Within 150-200 ms of array onset, responses to the array were determined by the target stimulus. If the target was the good stimulus, the response to the array became equal to the response to the good stimulus presented alone. If the target was the poor stimulus, the response approached the response to that stimulus presented alone. Thus the influence of the nontarget stimulus was filtered out. These effects were reduced or eliminated when the poor stimulus was located outside the RF and, therefore, no longer competing for the cell's response. Overall, the results support a 'biased competition' model of attention, according to which objects in the visual field compete for representation in the cortex, and this competition is biased in favor of the behaviorally relevant object. C1 Univ Verona, Physiol Sect, Dept Neurol & Vis Sci, I-37121 Verona, Italy. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. MIT, Dept Brain & Cognit Sci, RIKEN MIT Neurosci Res Ctr, Ctr Learning & Memory, Cambridge, MA 02139 USA. MRC, Cognit & Brain Sci Unit, Cambridge, England. RP Chelazzi, L (reprint author), Univ Verona, Physiol Sect, Dept Neurol & Vis Sci, Str Grazie 8, I-37121 Verona, Italy. RI Chelazzi, Leonardo/B-6084-2011 OI Chelazzi, Leonardo/0000-0001-8566-0611 NR 44 TC 191 Z9 202 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD AUG PY 2001 VL 11 IS 8 BP 761 EP 772 DI 10.1093/cercor/11.8.761 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 455TT UT WOS:000170044400009 PM 11459766 ER PT J AU Ramos, LA Sayer, JM Yagi, H Shah, JH Dipple, A Jerina, DM AF Ramos, LA Sayer, JM Yagi, H Shah, JH Dipple, A Jerina, DM TI Effect of benzo-ring hydroxyl groups on site-specific mutagenesis by tetrahydrobenzo[a]pyrene adducts at N-6 of deoxyadenosine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SINGLE-STRANDED VECTOR; NUCLEOSIDE ADDUCTS; EPOXIDES; CIS; STEREOSELECTIVITY; CONSEQUENCES; MUTAGENICITY; REPLICATION; METABOLISM; FREQUENCY AB We have previously investigated the mutations induced on replication in Escherichia coli of the M13mp7L2 genome containing each of the eight possible adducts derived from the four optically active 7,8-diol 9,10-epoxide metabolites of benzo[a]pyrene (B[a]P) by alkylation of a specific deoxyadenosine (dAdo) residue at N-6. Observed mutational frequencies depended in part on the relative spatial orientations of the three hydroxyl groups in these adducts. To determine how the presence or absence of these hydroxyl groups affects mutational response, we have synthesized 16-mer oligonucleotides with the same sequence as one of those previously studied with the diol epoxide adducts, but containing B[a]P-dAdo adducts in which two or all three of the adduct hydroxyl groups were replaced by hydrogen. Transfection of the adducted M13 constructs into SOS-induced Escherichia coli consistently gave fewer infective centers than the control construct, with viabilities ranging from 8.4 to 44.9% relative to control. In general, decreasing the number of adduct hydroxyls decreased the total frequency of substitution mutations induced. For all but one of the present adducts, the total mutational frequency was lower than that for any of the previously reported diol epoxide adducts in the same sequence. Remarkably, this (9S,10R)-adduct with cis orientation of the dAdo residue and the 9-OH group gave the highest mutational frequency of all the B[a]P adducts studied in this sequence, including the diol epoxide adducts. With the present adducts, A --> T transversions predominated, with smaller numbers of A --> G transitions and even fewer A --> C transversions. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. RP Jerina, DM (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 32 TC 6 Z9 6 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD AUG PY 2001 VL 14 IS 8 BP 1082 EP 1089 DI 10.1021/tx010076o PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 467HG UT WOS:000170695900017 PM 11511182 ER PT J AU Slonim, AD Ognibene, FP AF Slonim, AD Ognibene, FP TI Enchancing patient safety for pediatric bronchoscopy - Alternatives to conscious sedation SO CHEST LA English DT Editorial Material ID LARYNGEAL MASK AIRWAY; FIBEROPTIC BRONCHOSCOPY; CHILDREN; MIDAZOLAM; KETAMINE C1 Childrens Natl Med Ctr, Dept Crit Care Med, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Performance Improvement, Washington, DC 20010 USA. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Washington, DC 20052 USA. RP Slonim, AD (reprint author), Childrens Natl Med Ctr, Dept Crit Care Med, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 12 TC 3 Z9 5 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2001 VL 120 IS 2 BP 341 EP 342 DI 10.1378/chest.120.2.341 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 462DM UT WOS:000170405500007 PM 11502626 ER PT J AU Sausville, EA AF Sausville, EA TI Combining cytotoxics and 17-allylamino, 17-demethoxygeldanamycin: Sequence and tumor biology matters - Commentary re: P. Munster et al., modulation of Hsp90 function by ansamycins sensitizes breast cancer cells to chemotherapy-induced apoptosis in an RB- and schedule-dependent manner. Clin. Cancer Res., 7: 2228-2236, 2001. SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-PRODUCT P185; PROTEIN-KINASE; BENZOQUINOID ANSAMYCINS; ANTITUMOR-ACTIVITY; DT-DIAPHORASE; GELDANAMYCIN; UCN-01; AGENT; FLAVOPIRIDOL; DEGRADATION C1 NCI, Dev Therapeut Program, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, 6130 Execut Blvd,Room 8018, Rockville, MD 20852 USA. NR 32 TC 31 Z9 31 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 2001 VL 7 IS 8 BP 2155 EP 2158 PG 4 WC Oncology SC Oncology GA 460VB UT WOS:000170328300001 PM 11489788 ER PT J AU Gilbert, J Baker, SD Bowling, MK Grochow, L Figg, WD Zabelina, Y Donehower, RC Carducci, MA AF Gilbert, J Baker, SD Bowling, MK Grochow, L Figg, WD Zabelina, Y Donehower, RC Carducci, MA TI A phase I dose escalation and bioavailability study of oral sodium phenylbutyrate in patients with refractory solid tumor malignancies SO CLINICAL CANCER RESEARCH LA English DT Article ID TRANSCRIPTIONAL UP-REGULATION; HISTONE DEACETYLASE; AGENT PHENYLACETATE; PROSTATE-CANCER; DIFFERENTIATION; ANALOGS; CELLS AB Purpose: Phenylbutyrate (PB) is an aromatic fatty acid with multiple mechanisms of action including histone deacetylase inhibition. Preclinically, PB demonstrates both cytotoxic and differentiating effects at a concentration of 0.5 mm. We conducted a Phase I trial of p.o. PB patients with refractory solid tumor malignancies to evaluate toxicity, pharmacokinetic parameters, and feasibility of p.o. administration. Experimental Design: Twenty-eight patients with refractory solid tumor malignancies were enrolled on this dose-escalation to maximally tolerated dose trial. Five dose levels of PB were studied: 9 g/day (n = 4), 18 g/day (n = 4), 27 g/day (n = 4), 36 g/day (n = 12), and 45 g/day (n = 4). Pharmacokinetic studies were performed and included an p.o. bioavailability determination. Compliance data were also collected. Results: The recommended Phase II dose is 27 g/day. Overall the drug was well tolerated with the most common toxicities being grade 1-2 dyspepsia and fatigue. Nonoverlapping dose-limiting toxicities of nausea/vomiting and hypocalcemia were seen at 36 g/day. The p.o. bioavailability of PB was 78% for all dose levels, and the biologically active concentration of 0.5 mm was achieved at all dose levels. Compliance was excellent with 93.5% of all possible doses taken. No partial remission or complete remission was seen, but 7 patients had stable disease for more than 6 months while on the drug. Conclusions: PB (p.o.) is well tolerated and achieves the concentration in vivo that has been shown to have biological activity in vitro. PB may have a role as a cytostatic agent and should be additionally explored in combination with cytotoxics and other novel drugs. C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Div Med Oncol & Expt Therapeut, Baltimore, MD 21231 USA. NIH, Bethesda, MD 20892 USA. RP Carducci, MA (reprint author), Johns Hopkins Oncol Ctr, 1 M88 Bunting Blaunstein Canc Res Bldg,1650 Orlea, Baltimore, MD 21231 USA. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [R01 CA-75525, UO1 CA 70095]; NCRR NIH HHS [MO1 RR00052] NR 20 TC 166 Z9 175 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 2001 VL 7 IS 8 BP 2292 EP 2300 PG 9 WC Oncology SC Oncology GA 460VB UT WOS:000170328300017 PM 11489804 ER PT J AU Gore, SD Weng, LJ Zhai, S Figg, WD Donehower, RC Dover, GJ Grever, M Griffin, CA Grochow, LB Rowinsky, EK Zabalena, Y Hawkins, EK Burks, K Miller, CB AF Gore, SD Weng, LJ Zhai, S Figg, WD Donehower, RC Dover, GJ Grever, M Griffin, CA Grochow, LB Rowinsky, EK Zabalena, Y Hawkins, EK Burks, K Miller, CB TI Impact of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID TRANS-RETINOIC ACID; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOCYTIC-LEUKEMIA; FETAL HEMOGLOBIN; PHASE-I; APOPTOSIS; CELLS; PHENYLACETATE; MARROW AB Sodium phenylbutyrate (PB) is an aromatic fatty acid with cytostatic and differentiating activity against malignant myeloid cells (ID50, 1-2 mM). Higher doses induce apoptosis. Patients with myelodysplasia (n = 11) and acute myeloid leukemia (n = 16) were treated with PB as a 7-day continuous infusion repeated every 28 days in a Phase I dose escalation study. The maximum tolerated dose was 375 mg/kg/day; higher doses led to dose-limiting reversible neuro-cortical toxicity. At the maximum tolerated dose, PB was extremely well tolerated, with no significant toxicities; median steady-state plasma concentration at this dose was 0.29 +/- 0.16 mm. Although no patients achieved complete or partial remission, four patients achieved hematological improvement (neutrophils in three, platelet transfusion-independence in one). Other patients developed transient increases in neutrophils or platelets and decrements in circulating blasts. Monitoring of the percentage of clonal cells using centromere fluorescence in situ hybridization over the course of PB administration showed that hematopoiesis remained clonal. Hematological response was often associated with increases in both colony-forming units-granulocyte-macrophage and leukemic colony-forming units. PB administration was also associated with increases in fetal erythrocytes. These data document the safety of continuous infusion PB and provide preliminary evidence of clinical activity in patients with myeloid malignancies. C1 Inst Drug Dev, San Antonio, TX 78229 USA. NCI, Pharmacokinet Sect, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. RP Gore, SD (reprint author), Johns Hopkins Oncol Ctr, 1650 Orleans St,Room 288, Baltimore, MD 21231 USA. RI Figg Sr, William/M-2411-2016 FU NCI NIH HHS [CA 15396, R01 CA067803, R01 CA67803]; NCRR NIH HHS [RR00052] NR 32 TC 84 Z9 87 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG PY 2001 VL 7 IS 8 BP 2330 EP 2339 PG 10 WC Oncology SC Oncology GA 460VB UT WOS:000170328300022 PM 11489809 ER PT J AU Hall, PD Virella, G Willoughby, T Atchley, DH Kreitman, RJ Frankel, AE AF Hall, PD Virella, G Willoughby, T Atchley, DH Kreitman, RJ Frankel, AE TI Antibody response to DT-GM, a novel fusion toxin consisting of a truncated diphtheria toxin (DT) linked to human granulocyte-macrophage colony stimulating factor (GM), during a phase I trial of patients with relapsed or refractory acute myeloid leukemia SO CLINICAL IMMUNOLOGY LA English DT Article DE huGMCSF diphtheria toxin fusion protein; myeloid leukemia; antibody ID LONG-TERM SURVIVAL; ONCOLOGY-GROUP; INTERLEUKIN-2; EXPERIENCE; RECEPTOR; PROTEIN AB We are conducting a Phase I trial of a fusion toxin (DT-GM) for the treatment of relapsed or refractory acute myeloid leukemia (AML). The fusion toxin consists of a truncated diphtheria toxin (DT) linked to human granulocyte-macrophage colony stimulating factor (GM). Prior to beginning the Phase I trial, our first goal was to determine whether healthy controls and adult AMI, patients had preexisting antibodies able to inhibit DT-GM. Sera from 5 of the 9 controls completely neutralized DT-GM by an in vitro bioassay to assess the inhibition of DT-GM. Sera from 43 patients with AML were tested by bioassay and a specific enzymoimmunoassay (EIA) for anti-DT-GM antibodies. Forty-two of 43 samples were positive by EIA, and 5 patients (11.6%) showed complete neutralization of DT-GM in the bioassay. Anti-DT-GM concentrations were significantly higher in samples demonstrating neutralization than in samples demonstrating no neutralization (P = 0.003). In the Phase I trial of DT-GM prior to therapy, none of 28 patients exhibited neutralization by bioassay, but 89% were positive by EIA. After the first course of DT-GM, 23% developed neutralizing antibodies by the bioassay, and 64% of patients exhibited an increase in their anti-DT-GM antibody concentrations by EIA. Further studies are needed to determine the clinical impact of the anti-DT-GM antibodies and whether the neutralization bioassay can be replaced by our EU. (C) 2001 Academic Press. C1 Med Univ S Carolina, Coll Pharm, Charleston, SC 29425 USA. Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Canc Biol, Winston Salem, NC 27106 USA. RP Hall, PD (reprint author), Med Univ S Carolina, Coll Pharm, 280 Calhoun St,Box 250142, Charleston, SC 29425 USA. FU NCI NIH HHS [CA76178] NR 14 TC 38 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD AUG PY 2001 VL 100 IS 2 BP 191 EP 197 DI 10.1006/clim.2001.5066 PG 7 WC Immunology SC Immunology GA 460JQ UT WOS:000170304800009 PM 11465948 ER PT J AU Abbott, KC Agodoa, LY AF Abbott, KC Agodoa, LY TI Etiology of bacterial septicemia in chronic dialysis patients in the United States SO CLINICAL NEPHROLOGY LA English DT Article DE septicemia; African American; female; complications; hemodialysis; USRDS; age; albumin; hemoglobin; weight; diabetes; Staphylococcus; Streptococcus; gram-negative; pneumococcus; pseudomonas ID CHRONIC-HEMODIALYSIS PATIENTS; LONG-TERM HEMODIALYSIS; RISK-FACTORS; BACTEREMIA; MORTALITY; SEPSIS; DEFINITION; MANAGEMENT; INFECTIONS AB Aims: Previous studies have identified risk factors for and mortality associated with hospitalized septicemia (septicemia) in patients with end-stage renal disease (ESRD). However, the etiologies of septicemia in this population have not been determined. Methods: 327,993 patients in the United States Renal Data System initiated on ESRD therapy between January 1, 1992, and June 30, 1997, who never received renal transplants were analyzed in a retrospective registry study of hospitalized cases of septicemia (ICD9 038.x). Results: Of the study population, 43,441 (13.2%) had septicemia. In logistic regression analysis, septicemia was associated with female gender, African American race, ESRD due to diabetes and obstruction/chronic pyelonephritis, increased age, and hemodialysis (vs. peritoneal dialysis). Polycystic kidney disease and glomerulonephritis were associated with decreased risk of septicemia. At initiation of dialysis, higher hemoglobin, and lower weight, creatinine, and albumin were associated with septicemia. Among patients with septicemia, the leading specified etiologies were Staphylococcus (34%) and miscellaneous Gramnegative rods (21.7%). Etiologies of septicemia were significantly associated with hemodialysis (Gram-positives and Pneumococcus), female gender (Gram-negatives except Pseudomonas), African American race (Staphylococcus), and diabetes (global). Hemodialysis (vs. peritoneal dialysis) and Staphylococcus as an etiology of septicemia were associated with repeated hospitalizations for septicemia. Septicemia was independently associated with patient mortality, and African Americans and females with septicemia were at disproportionately greater risk of mortality. Conclusions: This study identifies significant associations between septicemia and female gender, African American race, hemodialysis, and higher hemoglobin. Significant associations between etiologies of septicemia and patient subgroups are also identified. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDDK, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. OI Abbott, Kevin/0000-0003-2111-7112 NR 23 TC 40 Z9 44 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD AUG PY 2001 VL 56 IS 2 BP 124 EP 131 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 492TK UT WOS:000172183500006 PM 11522089 ER PT J AU Wassermann, EM Lisanby, SH AF Wassermann, EM Lisanby, SH TI Therapeutic application of repetitive transcranial magnetic stimulation: a review SO CLINICAL NEUROPHYSIOLOGY LA English DT Review DE depression; Parkinson's disease; treatment; clinical trials; motor cortex; prefrontal cortex ID DORSOLATERAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; REFRACTORY DEPRESSED-PATIENTS; RESISTANT MAJOR DEPRESSION; AMYGDALA-KINDLED SEIZURES; LONG-TERM POTENTIATION; HUMAN MOTOR CORTEX; RAT-BRAIN; ELECTROCONVULSIVE-THERAPY; PARKINSONS-DISEASE AB Transcranial magnetic stimulation (TMS), a non-invasive means of electrically stimulating neurons in the human cerebral cortex, is able to modify neuronal activity locally and at distant sites when delivered in series or trains of pulses. Data from stimulation of the motor cortex suggest that the type of effect on the excitability of the cortical network depends on the frequency of stimulation. These data, as well as results from studies in rodents, have been generalized across brain areas and species to provide rationales for using repetitive TMS (rTMS) to treat various brain disorders, most notably depression. Research into clinical applications for TMS remains active and has the potential to provide useful data, but, to date, the results of blinded, sham-controlled trials do not provide clear evidence of beneficial effects that replace or even match the effectiveness of conventional treatments in any disorder. In this review, we discuss the clinical and scientific bases for using rTMS as treatment, and review the results of trials in psychiatric and neurological disorders to date. (C) 2001 Elsevier Science Ireland Ltd. AE rights reserved. C1 NINDS, Brain Stimulat Unit, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Dept Biol Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Wassermann, EM (reprint author), NINDS, Brain Stimulat Unit, 10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 123 TC 306 Z9 333 U1 6 U2 43 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD AUG PY 2001 VL 112 IS 8 BP 1367 EP 1377 DI 10.1016/S1388-2457(01)00585-5 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 459MF UT WOS:000170253600002 PM 11459676 ER PT J AU Garvey, MA Ziemann, U Becker, DA Barker, CA Bartko, JJ AF Garvey, MA Ziemann, U Becker, DA Barker, CA Bartko, JJ TI New graphical method to measure silent periods evoked by transcranial magnetic stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE cortical silent period; graphics; statistical process control; transcranial magnetic stimulation; physiologic measurement ID STATISTICAL PROCESS-CONTROL; PARKINSONS-DISEASE; CORTICAL STIMULATION; BRAIN-STIMULATION; INHIBITION; POTENTIALS; DISORDER; MUSCLE; HUMANS AB Objectives: Manual methods of measuring duration of cortical silent periods (CSP) evoked by transcranial magnetic stimulation (TMS) depend upon subjective visual estimation of onset and offset. Because of this, the measurements are susceptible to poor rater reliability. We describe a graphical method to measure silent periods with greater precision. The statistical process underlying this new method is simple and particularly suited to signal detection in serially dependent data. Methods: TMS-evoked silent periods were recorded in 13 healthy subjects. Two investigators subjectively measured silent period duration on each subject to estimate rater reliability. Using the graphical method, the mean and 99.76% variation limits of pre-stimulus electromyogram (EMG) activity were computed. Each averaged trial was displayed and CSP onset and offset detected when post-stimulus EMG activity moved outside the 99.76% limits. Results: Maximum variation in silent period duration was 21.8 ms between the two investigators' subjective measurements. Silent period duration measured with the graphical method closely approximated measurements obtained using the manual method. It was possible to automate the procedure. Conclusions: This graphical method allowed precise measurement of CSP duration, independent of subjective estimations of onset or offset points. Further studies are necessary to determine if this method can provide a framework for other physiologic measures. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Pediat Movement Disorders Unit, NIH, Bethesda, MD 20892 USA. RP Garvey, MA (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Pediat Movement Disorders Unit, NIH, 10 Ctr Dr,4N208,MSC 1255, Bethesda, MD 20892 USA. RI Barker, Christopher/I-9477-2012 NR 30 TC 86 Z9 86 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD AUG PY 2001 VL 112 IS 8 BP 1451 EP 1460 DI 10.1016/S1388-2457(01)00581-8 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 459MF UT WOS:000170253600011 PM 11459685 ER PT J AU Jobe, JB Smith, DM Ball, K Tennstedt, SL Marsiske, M Willis, SL Rebok, GW Morris, JN Helmers, KF Leveck, MD Kleinman, K AF Jobe, JB Smith, DM Ball, K Tennstedt, SL Marsiske, M Willis, SL Rebok, GW Morris, JN Helmers, KF Leveck, MD Kleinman, K TI ACTIVE: A cognitive intervention trial to promote independence in older adults SO CONTROLLED CLINICAL TRIALS LA English DT Article DE cognitive decline; activities of daily living; behavioral intervention ID ELDERLY PERSONS; DRIVERS; IMPAIRMENT; PERFORMANCE; COMPETENCE; MORTALITY; EFFICACY; CRASH; RISK; AGE AB The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial is a randomized, controlled, single-masked trial designed to determine whether cognitive training interventions (memory, reasoning, and speed of information processing), which have previously been found to be successful at improving mental abilities under laboratory or small-scale field conditions, can affect cognitively based measures of daily functioning. Enrollment began during 1998; 2-year follow-up will be completed by January 2002. Primary outcomes focus on measures of cognitively demanding everyday functioning, including financial management, food preparation, medication use, and driving. Secondary outcomes include health-related quality of life, mobility, and health-service utilization. Trial participants (n = 2832) are aged 65 and over, and at entry into the trial, did not have significant cognitive, physical, or functional decline. Because of its size and the carefully developed rigor, ACTIVE may serve as a guide for future behavioral medicine trials of this nature. Published by Elsevier Science Inc. 2001. C1 NIA, Behav & Social Res Program, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. New England Res Inst, Watertown, MA 02172 USA. Wayne State Univ, Inst Gerontol, Detroit, MI 48202 USA. Wayne State Univ, Dept Psychol, Detroit, MI 48202 USA. Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16802 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. NINR, Bethesda, MD 20892 USA. RP Jobe, JB (reprint author), NHLBI, Behav Med Res Grp, Sch Med, 6701 Rockledge Dr,MSC 7936, Bethesda, MD 20892 USA. OI Marsiske, Michael/0000-0001-5973-2116 FU NIA NIH HHS [R37 AG024102, T32 AG000048, U01 AG014260, U01 AG014263, U01 AG014276, U01 AG014276-04, U01 AG014276-05, U01 AG014276-05S1, U01 AG014276-05S2, U01 AG014276-05S3, U01 AG014276-06A1, U01 AG014276-07, U01 AG014276-07S1, U01 AG014276-08, U01 AG014276-08S1, U01 AG014282, U01 AG014289, U01AG14260, U01AG14263, U01AG14276, U01AG14282, U01AG14289]; NINR NIH HHS [U01 NR004507, U01 NR004508, U01NR04507, U01NR04508] NR 76 TC 182 Z9 183 U1 5 U2 29 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD AUG PY 2001 VL 22 IS 4 BP 453 EP 479 DI 10.1016/S0197-2456(01)00139-8 PG 27 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 463GP UT WOS:000170469000009 PM 11514044 ER PT J AU Lustig, B Jeang, KT AF Lustig, B Jeang, KT TI Biological applications of hammerhead ribozymes as anti-viral molecules SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; HAIRPIN RIBOZYME; GENE-THERAPY; CRYSTAL-STRUCTURE; RNA TRANSFECTION; CANCER-THERAPY; STEM-CELLS; HIV-1; EXPRESSION; CATALYSIS AB Ribozymes are catalytic RNAs that can cleave substrate RNAs in a sequence specific manner. Here we survey, in brief, the structure of hammerhead and hairpin ribozymes and discuss their applications as molecular antiviral molecules for HIV-1. C1 San Jose State Univ, Dept Chem, San Jose, CA 95192 USA. NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), San Jose State Univ, Dept Chem, San Jose, CA 95192 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 65 TC 4 Z9 4 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD AUG PY 2001 VL 8 IS 10 BP 1181 EP 1187 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 452RM UT WOS:000169872600004 PM 11472235 ER PT J AU Adah, SA Bayly, SF Cramer, H Silverman, RH Torrence, PF AF Adah, SA Bayly, SF Cramer, H Silverman, RH Torrence, PF TI Chemistry and biochemistry of 2 ',5 '-oligoadenylate-based antisense strategy SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID CHRONIC MYELOGENOUS LEUKEMIA; SYNCYTIAL VIRUS-REPLICATION; UNFOLDED PROTEIN RESPONSE; INTERFERON-TREATED CELLS; DOUBLE-STRANDED-RNA; MESSENGER-RNA; RIBONUCLEASE-L; 2-5A ANTISENSE; THERAPEUTIC AGENTS; GENE-EXPRESSION AB This review describes the application of a natural defense mechanism to develop effective agents for the post-transcriptional control of gene expression. 2-5A is a unique 2 ' ,5 ' -phosphodiester bond linked oligoadenylate, (pp)p5 ' A2 ' (p5 'A)(n) , that is elaborated in virus-infected interferon-treated cells. The 2-5A system is an RNA degradation pathway that is an important mechanistic component of interferon's action against certain viruses. It may also play a role in the anticellular effects of interferon and in general RNA decay. A major player in the 2-5A-system is the latent and constitutive 2-5A-dependent ribonuclease (RNase L) which upon activation by 2-5A, degrades RNA. This RNase I, enzyme can be recruited for antisense therapeutics by linking it to an appropriate oligonucleotide targeted to a chosen RNA. Syntheses of 2-5A, its analogues, 2-5A-antisense, and its modifications are detailed herein. Applications of 2-5A-antisense to particular targets such as HIV, PKR, chronic myelogenous leukemia, telomerase, and respiratory syncytical virus are described. C1 No Arizona Univ, Dept Chem, Flagstaff, AZ 86011 USA. Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. Gemini Technol Inc, Cleveland, OH 44106 USA. NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Torrence, PF (reprint author), No Arizona Univ, Dept Chem, Flagstaff, AZ 86011 USA. NR 145 TC 29 Z9 35 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD AUG PY 2001 VL 8 IS 10 BP 1189 EP 1212 PG 24 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 452RM UT WOS:000169872600005 PM 11472236 ER PT J AU Hicke, L Lippincott-Schwartz, J AF Hicke, L Lippincott-Schwartz, J TI Membranes and sorting - Editorial overview SO CURRENT OPINION IN CELL BIOLOGY LA English DT Editorial Material C1 Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hicke, L (reprint author), Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2153 Sheridan Rd, Evanston, IL 60208 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 2001 VL 13 IS 4 BP 429 EP 430 DI 10.1016/S0955-0674(00)00232-5 PG 2 WC Cell Biology SC Cell Biology GA 451UX UT WOS:000169821700008 ER PT J AU Robinson, MS Bonifacino, JS AF Robinson, MS Bonifacino, JS TI Adaptor-related proteins SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID SYNAPTIC VESICLE ENDOCYTOSIS; POLARIZED EPITHELIAL-CELLS; PIGMENT GRANULE BIOGENESIS; HERMANSKY-PUDLAK-SYNDROME; GAMMA-ADAPTIN; AP-3 ADAPTER; DROSOPHILA-MELANOGASTER; SORTING SIGNALS; STONED LOCUS; MOLECULAR CHARACTERIZATION AB Two new adaptor-related protein complexes, AP-3 and AP-4, have recently been identified, and both have been implicated in protein sorting at the trans-Golgi network (TGN) and/or endosomes. In addition, two families of monomeric proteins with adaptor-related domains, the GGAs and the stoned B family, have also been identified and shown to act at the TGN and plasma membrane, respectively. Together with the two conventional adaptors, AP-1 and AP-2, these proteins may act to direct different types of cargo proteins to different post-Golgi membrane compartments. C1 Univ Cambridge, Dept Clin Biochem, Cambridge CB2 2XY, England. Univ Cambridge, Wellcome Trust Ctr Study Mol Mechanisms Dis, Cambridge CB2 2XY, England. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Robinson, MS (reprint author), Univ Cambridge, Dept Clin Biochem, Cambridge CB2 2XY, England. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 88 TC 369 Z9 381 U1 0 U2 8 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 2001 VL 13 IS 4 BP 444 EP 453 DI 10.1016/S0955-0674(00)00235-0 PG 10 WC Cell Biology SC Cell Biology GA 451UX UT WOS:000169821700011 PM 11454451 ER PT J AU Danino, D Hinshaw, JE AF Danino, D Hinshaw, JE TI Dynamin family of mechanoenzymes SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID GUANYLATE-BINDING PROTEIN-1; CLATHRIN-MEDIATED ENDOCYTOSIS; MITOCHONDRIAL-DNA MAINTENANCE; DOMINANT OPTIC ATROPHY; HUMAN MXB PROTEIN; ARABIDOPSIS-THALIANA; SUBCELLULAR-LOCALIZATION; NUCLEOTIDE-BINDING; TARGET STRUCTURES; NERVE-TERMINALS AB The dynamin family of proteins is continually growing, and in recent years members have been localized to areas of mitochondrial fission, plant phragmoplasts and chloroplasts, and viral ribonucleoprotein complexes. All the dynamin-like proteins examined to-date appear to assemble into oligomers, such as rings or spirals; however, it remains to be determined if a global mechanism of action exists. Even the role of dynamin in vesicle formation remains controversial as to whether it behaves as a molecular switch or as a mechanochemical enzyme. C1 NIH, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA. RP Danino, D (reprint author), NIH, Lab Cell Biochem & Biol, Bldg 8,Room 419,MSC 0851,8 Ctr Dr, Bethesda, MD 20892 USA. RI Danino, Dganit/D-6832-2016 OI Danino, Dganit/0000-0002-9782-4940 NR 71 TC 144 Z9 145 U1 0 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 2001 VL 13 IS 4 BP 454 EP 460 DI 10.1016/S0955-0674(00)00236-2 PG 7 WC Cell Biology SC Cell Biology GA 451UX UT WOS:000169821700012 PM 11454452 ER PT J AU Huttner, WB Zimmerberg, J AF Huttner, WB Zimmerberg, J TI Implications of lipid microdomains for membrane curvature, budding and fission - Commentary SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID CLATHRIN-MEDIATED ENDOCYTOSIS; SYNAPTIC VESICLES; INFLUENZA HEMAGGLUTININ; LYSOPHOSPHATIDIC ACID; BILAYER-MEMBRANES; PLASMA-MEMBRANE; NERVE-TERMINALS; CHOLESTEROL; DYNAMIN; PROTEIN AB Recent studies have highlighted the importance of monolayer and bilayer curvature for the budding and fission of biological membranes. Other lines of research, addressing the structure of planar biological membranes, have revealed the existence of cholesterol-based membrane microdomains. Here, we comment on the Significance of microdomains for curved membranes, with special emphasis on budding and fission. C1 Max Planck Inst Mol Cell Biol & Genet, D-01307 Dresden, Germany. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Huttner, WB (reprint author), Max Planck Inst Mol Cell Biol & Genet, Pfotenhauerstr 108, D-01307 Dresden, Germany. NR 63 TC 162 Z9 163 U1 1 U2 17 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD AUG PY 2001 VL 13 IS 4 BP 478 EP 484 DI 10.1016/S0955-0674(00)00239-8 PG 7 WC Cell Biology SC Cell Biology GA 451UX UT WOS:000169821700015 PM 11454455 ER PT J AU Jankovic, D Sher, A Yap, G AF Jankovic, D Sher, A Yap, G TI Th1/Th2 effector choice in parasitic infection: decision making by committee SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CD4(+) T-CELLS; LEISHMANIA-MAJOR INFECTION; IN-VIVO; TRYPANOSOMA-CRUZI; DENDRITIC CELLS; TOXOPLASMA-GONDII; CYTOKINE PROFILE; TH2 RESPONSES; IFN-GAMMA; NIPPOSTRONGYLUS-BRASILIENSIS AB Parasitic infections frequently result in highly polarized CD4(+) T cell responses characterized by dominant Th1 or Th2 cytokine production profiles. Although previously thought to be strictly dependent on signaling by the differentiative cytokines, IL-12 and IL-4, recent data indicate that this polarization may be primarily decided instead by a series of different factors intrinsic to the pathogen-antigen-presenting-cell interaction that influence T cell priming. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. RP Jankovic, D (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 61 TC 57 Z9 59 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2001 VL 13 IS 4 BP 403 EP 409 DI 10.1016/S0952-7915(00)00234-X PG 7 WC Immunology SC Immunology GA 448UP UT WOS:000169648600004 PM 11498295 ER PT J AU Mascola, JR Nabel, GJ AF Mascola, JR Nabel, GJ TI Vaccines for the prevention of HIV-1 disease SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; IMMUNE-RESPONSES; RHESUS MACAQUES; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; DENDRITIC CELLS; TYPE-1 ENVELOPE; DNA VACCINE; ANTIRETROVIRAL TREATMENT AB Clinical investigation in humans and experimental lentivirus infection in nonhuman primates have advanced our understanding of immune responses that control HIV-1 disease. Recently, immunization approaches in macaques have shown that the immune response can control viremia and improve clinical outcome. When such vaccine strategies are formulated to be similarly immunogenic in humans, they could form the basis for the development of candidate AIDS vaccines that would prevent infection. suppress progression to disease or reduce HIV-1 transmission in humans. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 72 TC 53 Z9 53 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2001 VL 13 IS 4 BP 489 EP 495 DI 10.1016/S0952-7915(00)00246-6 PG 7 WC Immunology SC Immunology GA 448UP UT WOS:000169648600016 PM 11498307 ER PT J AU Lee, LM Henderson, DK AF Lee, LM Henderson, DK TI Emerging viral infections SO CURRENT OPINION IN INFECTIOUS DISEASES LA English DT Review ID SIMIAN IMMUNODEFICIENCY VIRUS; HEPATITIS-C VIRUS; CREUTZFELDT-JAKOB-DISEASE; BOVINE SPONGIFORM ENCEPHALOPATHY; HEALTH-CARE WORKERS; HANTAVIRUS PULMONARY SYNDROME; HUMAN-HERPESVIRUS 6; T-CELL DEPLETION; WEST-NILE-VIRUS; KAPOSIS-SARCOMA AB The past decade has witnessed the emergence of several significant viral pathogens and the further evolution of additional viral pathogens. Transmitted by a variety of differing routes, these organisms have presented substantial intellectual challenges to medicine of the 20th and 21st centuries. As perhaps the benchmark pathogen of the past decade, HIV has provided medicine and society with a most formidable opponent, and one that has yet to be fully conquered. Nonetheless, a variety of additional viral pathogens have also perplexed medicine over the past 10-15 years. Curr Opin Infect Dis 14:467-480, (C) 2001 Lippincott Williams & Wilkins. C1 NIH, Warren Grant Magnuson Clin Ctr, Off Deputy Director Clin Care, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Off Deputy Director Clin Care, Bldg 10 Room 2C 146,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 184 TC 12 Z9 12 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7375 J9 CURR OPIN INFECT DIS JI Curr. Opin. Infect. Dis. PD AUG PY 2001 VL 14 IS 4 BP 467 EP 480 PG 14 WC Infectious Diseases SC Infectious Diseases GA 456EA UT WOS:000170069100012 PM 11964867 ER PT J AU Rossouw, JE AF Rossouw, JE TI Early risk of cardiovascular events after commencing hormone replacement therapy SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review ID FACTOR-V-LEIDEN; CORONARY HEART-DISEASE; ACTIVATED PROTEIN-C; MYOCARDIAL-INFARCTION; POSTMENOPAUSAL WOMEN; VENOUS THROMBOSIS; VASCULAR-DISEASE; YOUNG-WOMEN; ESTROGEN; MUTATION C1 NHLBI, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, 1 Rockledge Ctr,Suite 300,6705 Rockledge Dr, Bethesda, MD 20892 USA. NR 30 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD AUG PY 2001 VL 12 IS 4 BP 371 EP 375 DI 10.1097/00041433-200108000-00001 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 456JK UT WOS:000170079200001 PM 11507320 ER PT J AU Carlton, JMR Fidock, DA Djimde, A Plowe, CV Wellems, TE AF Carlton, JMR Fidock, DA Djimde, A Plowe, CV Wellems, TE TI Conservation of a novel vacuolar transporter in Plasmodium species and its central role in chloroquine resistance of P-falciparum SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID MALARIA PARASITES; FERRIPROTOPORPHYRIN-IX; DIGESTIVE VACUOLE; DRUG-RESISTANCE; GENE; ANTIMALARIALS; MECHANISM; IDENTIFICATION; HEMATIN; PROTEIN AB Chloroquine resistance in Plasmodium falciparum has recently been shown to result from mutations in the novel vacuolar transporter, PfCRT Field studies have demonstrated the importance of these mutations in clinical resistance. Although a pfcrt ortholog has been identified in Plasmodium vivax, there is no association between in vivo chloroquine resistance and codon mutations in the P. vivax gene. This is consistent with lines of evidence that suggest alternative mechanisms of chloroquine resistance among various malaria parasite species. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Res, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Univ Mali, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali. Univ Maryland, Sch Med, Malaria Sect, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NIAID, Malaria Genet Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA. RP Carlton, JMR (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Res, Bldg 45,45 Ctr Dr, Bethesda, MD 20892 USA. OI Fidock, David/0000-0001-6753-8938 FU NIAID NIH HHS [R01 AI050234] NR 54 TC 36 Z9 38 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD AUG PY 2001 VL 4 IS 4 BP 415 EP 420 DI 10.1016/S1369-5274(00)00228-9 PG 6 WC Microbiology SC Microbiology GA 463BY UT WOS:000170458000010 PM 11495804 ER PT J AU Chan, FKM Siegel, RM Zacharias, D Swofford, R Holmes, KL Tsien, RY Lenardo, MJ AF Chan, FKM Siegel, RM Zacharias, D Swofford, R Holmes, KL Tsien, RY Lenardo, MJ TI Fluorescence resonance energy transfer analysis of cell surface receptor interactions and signaling using spectral variants of the green fluorescent protein SO CYTOMETRY LA English DT Article DE FRET; flow cytometry; GFP; TNF receptor; PLAD ID PHYSICAL ASSOCIATION; APOPTOSIS; FAS; AGGREGATION; ACTIVATION; DOMAIN; FADD; CD4 AB Background: Fluorescence resonance energy transfer (FRET) is a powerful technique for measuring molecular interactions at Angstrom distances. We present a new method for FRET that utilizes the unique spectral properties of variants of the green fluorescent protein (GFP) for large-scale analysis by flow cytometry. Methods: The proteins of interest are fused in frame separately to the cyan fluorescent protein (CFP) or the yellow fluorescent protein (YFP). FRET between these differentially tagged fusion proteins is analyzed using a dual-laser FACSVantage cytometer. Results: We show that homotypic interactions between individual receptor chains of tumor necrosis factor receptor (TNTFR) family members can be detected as FRET from CFP-tagged receptor chains to YFP-tagged receptor chains. Noncovalent molecular complexation can be detected as FRET between fusions of CFP and YFP to either the intracellular or extracellular regions of the receptor chains. The specificity of the assay is demonstrated by the absence of FRET between heterologous receptor pairs that do not biochemically associate with each other. Interaction between a TNFR-like receptor (Fas/CD95/Apo-1) and a downstream cytoplasmic signaling component (FADD) can also be demonstrated by flow cytometric FRET analysis. Conclusions: The utility of spectral variants of GFP in flow cytometric FRET analysis of membrane receptors is demonstrated. This method of analyzing FRET allows probing of noncovalent molecular interactions that involve both the intracellular and extracellular regions of membrane proteins as well as proteins within the cells. Unlike biochemical methods, FRET allows the quantitative determination of noncovalent molecular associations at Angstrom ngstrom level in living cells. Moreover, flow cytometry allows quantitative analyses to be carried out on a cell-by-cell basis on large number of cells. Cytometry 44: 361-368, 2001. Published 2001 Witey-Liss, Inc.dagger C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Flow Cytometry Sect, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311, Bethesda, MD 20892 USA. RI Siegel, Richard/C-7592-2009; Chan, Francis/E-9647-2014; OI Siegel, Richard/0000-0001-5953-9893; Chan, Francis/0000-0002-4803-8353; Darzynkiewicz, Zbigniew/0000-0002-2040-7081; Chan, Francis K.L./0000-0001-7388-2436 NR 23 TC 82 Z9 85 U1 0 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD AUG 1 PY 2001 VL 44 IS 4 BP 361 EP 368 DI 10.1002/1097-0320(20010801)44:4<361::AID-CYTO1128>3.0.CO;2-3 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 460JB UT WOS:000170303500009 PM 11500853 ER PT J AU Nishinakamura, R Matsumoto, Y Nakao, K Nakamura, K Sato, A Copeland, NG Gilbert, DJ Jenkins, NA Scully, S Lacey, DL Katsuki, M Asashima, M Yokota, T AF Nishinakamura, R Matsumoto, Y Nakao, K Nakamura, K Sato, A Copeland, NG Gilbert, DJ Jenkins, NA Scully, S Lacey, DL Katsuki, M Asashima, M Yokota, T TI Murine homolog of SALL1 is essential for ureteric bud invasion in kidney development SO DEVELOPMENT LA English DT Article DE Sall1; kidney; Townes-Brocks syndrome; mouse ID TOWNES-BROCKS-SYNDROME; MICE LACKING GDNF; HOMEOTIC GENE SPALT; EPITHELIAL TRANSFORMATION; METANEPHRIC MESENCHYME; MOLECULAR-CLONING; DROSOPHILA EMBRYO; TYROSINE KINASE; NERVOUS-SYSTEM; RENAL AGENESIS AB SALL1 is a mammalian homolog of the Drosophila region-specific homeotic gene spalt (sal); heterozygous mutations in SALL1 in humans lead to Townes-Brocks syndrome. We have isolated a mouse homolog of SALL1 (Sall1) and found that mice deficient in Sall1 die in the perinatal period and that kidney agenesis or severe dysgenesis are present. Sall1 is expressed in the metanephric mesenchyme surrounding ureteric bud; homozygous deletion of Sall1 results in an incomplete ureteric bud outgrowth, a failure of tubule formation in the mesenchyme and an apoptosis of the mesenchyme. This phenotype is likely to be primarily caused by the absence of the inductive signal from the ureter, as the Sall1-deficient mesenchyme is competent with respect to epithelial. differentiation. Sall1 is therefore essential for ureteric bud invasion, the initial key step for metanephros development. C1 Univ Tokyo, Inst Med Sci, Div Stem Cell Regulat, Tokyo 1088639, Japan. Univ Tokyo, Inst Med Sci, Lab DNA Biol & Embryo Engn, Tokyo 1088639, Japan. Univ Tokyo, Dept Life Sci, Tokyo 1538902, Japan. Natl Canc Inst, Mouse Canc Genet Program, Frederick, MD 21702 USA. Amgen Inc, Dept Pathol, Thousand Oaks, CA 91320 USA. RP Nishinakamura, R (reprint author), Univ Tokyo, Inst Med Sci, Div Stem Cell Regulat, 4-6-1 Shirokanedai, Tokyo 1088639, Japan. RI Yokota, Takashi/F-6021-2011; Yokota, Takashi/J-8483-2015 NR 45 TC 210 Z9 215 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD AUG PY 2001 VL 128 IS 16 BP 3105 EP 3115 PG 11 WC Developmental Biology SC Developmental Biology GA 469QG UT WOS:000170825900006 PM 11688560 ER PT J AU Ma, GT Soloveva, V Tzeng, SJ Lowe, LA Pfendler, KC Iannaccone, PM Kuehn, MR Linzer, DIH AF Ma, GT Soloveva, V Tzeng, SJ Lowe, LA Pfendler, KC Iannaccone, PM Kuehn, MR Linzer, DIH TI Nodal regulates trophoblast differentiation and placental development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE differentiation; giant cell; nodal; placenta; trophoblast ID LEFT-RIGHT ASYMMETRY; GIANT-CELLS; LACTOGEN-I; MOUSE PLACENTA; TRANSCRIPTION FACTOR; MESODERM FORMATION; MOLECULAR-CLONING; GENE FAMILY; EXPRESSION; PROTEIN AB Nodal has been thought to be an embryo-specific factor that regulates development, but nodal is also expressed in the mouse placenta beginning at midgestation, specifically in the spongiotrophoblasts. in an insertional null nodal mutant, not only is embryonic development disrupted, but mouse placental development is also grossly altered with the loss of the diploid spongiotrophoblasts and labyrinth and an expansion of the polyploid giant cell layer. A hypomorphic mutation in nodal results in an expansion of the giant cell and spongiotrophoblast layers, and a decrease in labyrinthine development. Expression of nodal in trophoblast cell cultures is sufficient to inhibit trophoblast giant cell differentiation, demonstrating that nodal can act directly on trophoblasts. The mechanism of nodal action includes the inhibition of junB gene transcription. These results suggest that nodal may be involved in redirecting trophoblast fate towards the midgestational expansion of the labyrinth region while maintaining the thin layer of trophoblast giant cells and the underlying layer of spongiotrophoblasts that form the boundary between the maternal and extraembryonic compartments. (C) 2001 Academic Press. C1 Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60614 USA. Childrens Mem Inst Educ & Res, Chicago, IL 60614 USA. RP Linzer, DIH (reprint author), Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, 2153 Sheridan Rd, Evanston, IL 60208 USA. RI Kuehn, Michael/A-4573-2014; OI Kuehn, Michael/0000-0002-7703-9160; Tzeng, Shiang-Jong/0000-0003-1633-020X FU NCI NIH HHS [CA60553]; NCRR NIH HHS [RR13168]; NICHD NIH HHS [HD29962, P30 HD28048]; NIEHS NIH HHS [ES10549] NR 50 TC 53 Z9 54 U1 2 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2001 VL 236 IS 1 BP 124 EP 135 DI 10.1006/dbio.2001.0334 PG 12 WC Developmental Biology SC Developmental Biology GA 456XZ UT WOS:000170109200012 PM 11456449 ER PT J AU Ito, Y Sarkar, P Mi, QG Wu, N Bringas, P Liu, YH Reddy, S Maxson, R Deng, CX Chai, Y AF Ito, Y Sarkar, P Mi, QG Wu, N Bringas, P Liu, YH Reddy, S Maxson, R Deng, CX Chai, Y TI Overexpression of Smad2 reveals its concerted action with Smad4 in regulating TGF-beta-mediated epidermal homeostasis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE skin; Smad2 transgenic; Smad4; TGF-beta signaling; tooth ID TRANSFORMING-GROWTH-FACTOR; TRANSGENIC MICE; TOOTH FORMATION; II RECEPTOR; IN-VITRO; EXPRESSION; SKIN; DIFFERENTIATION; INHIBITION; LACKING AB Members of the transforming growth factor-beta (TGF-beta) superfamily are critical regulators for epithelial growth and can alter the differentiation of keratinocytes. Transduction of TGF-beta signaling depends on the phosphorylation and activation of Smad proteins by heteromeric complexes of ligand-specific type I and II receptors. To understand the function of TGF-beta and activin-specific Smad, we generated transgenic mice that overexpress Smad2 in epidermis under the control of keratin 14 promoter. Overexpression of Smad2 increases endogenous Smad4 and TGF-beta1 expression while heterozygous loss of Smad2 reduces their expression levels, suggesting a concerted action of Smad2 and -4 in regulating TGF-beta signaling during skin development. These transgenic mice have delayed hair growth, underdeveloped ears, and shorter tails. In their skin, there is severe thickening of the epidermis with disorganized epidermal architecture, indistinguishable basement membrane, and dermal fibrosis. These abnormal phenotypes are due to increased proliferation of the basal epidermal cells and abnormalities in the program of keratinocyte differentiation. The ectodermally derived enamel structure is also abnormal. Collectively, our study presents the first in vivo evidence that, by providing an auto-feedback in TGF-beta signaling, Smad2 plays a pivotal role in regulating TGF-beta -mediated epidermal homeostasis. (C) 2001 Academic Press. C1 Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ So Calif, Norris Hosp & Res Inst, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. RP Chai, Y (reprint author), Univ So Calif, Sch Dent, Ctr Craniofacial Mol Biol, 2250 Alcazar St,CSA 103, Los Angeles, CA 90033 USA. RI deng, chuxia/N-6713-2016 FU NIDCR NIH HHS [DE12711, DE12941] NR 62 TC 45 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 1 PY 2001 VL 236 IS 1 BP 181 EP 194 DI 10.1006/dbio.2001.0332 PG 14 WC Developmental Biology SC Developmental Biology GA 456XZ UT WOS:000170109200016 PM 11456453 ER PT J AU Pham, V Roman, BL Weinstein, BM AF Pham, V Roman, BL Weinstein, BM TI Isolation and expression analysis of three zebrafish angiopoietin genes SO DEVELOPMENTAL DYNAMICS LA English DT Article DE angiopoietin-1; angiopoietin-2; angiopoietin-like-3; zebrafish; hypochord; vascular development ID RECEPTOR TYROSINE KINASES; IN-SITU HYBRIDIZATION; ENDOTHELIAL-CELLS; TIE2 RECEPTOR; ANGIOGENESIS; NOTOCHORD; SURVIVAL; LIGANDS; XENOPUS; ANGPT1 AB The Tie1 and Tie2 receptor tyrosine kinases and the Tie2 ligands, the angiopoietins, play critical roles in vertebrate vascular embryogenesis, helping to mediate the interaction between endothelial cells and the pericytes or vascular smooth muscle cells that envelop and support them. We have obtained full-length cDNA sequences for zebrafish orthologs of angiopoietin-1 (ang1), angiopoietin-2 (ang2), and angiopoietin-like-3 (angpt13). Ang1 is expressed in head ventral mesenchyme, in the ventromedial region of somites, in mesenchyme surrounding trunk axial vessels, and in the hypochord, a transient embryonic structure of endodermal origin that has been implicated in dorsal aorta assembly in both zebrafish and Xenopus. Ang2 is expressed in head and anterior trunk ventral mesenchyme and the-developing pronephric glomeruli. Angpt13 is expressed in the yolk syncytial layer. (C) 2001 Wiley-Liss, Inc. C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Weinstein, BM (reprint author), NICHD, Mol Genet Lab, NIH, Bldg 6B,Room 309,6 Ctr Dr, Bethesda, MD 20892 USA. OI Roman, Beth/0000-0002-1250-1705 FU NICHD NIH HHS [ZO1-HD-01011] NR 22 TC 33 Z9 35 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD AUG PY 2001 VL 221 IS 4 BP 470 EP 474 DI 10.1002/dvdy.1157 PG 5 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 457RB UT WOS:000170149600013 PM 11500985 ER PT J AU Gautier, JF Wilson, C Weyer, C Mott, D Knowler, WC Cavaghan, M Polonsky, KS Bogardus, C Pratley, RE AF Gautier, JF Wilson, C Weyer, C Mott, D Knowler, WC Cavaghan, M Polonsky, KS Bogardus, C Pratley, RE TI Low acute insulin secretory responses in adult offspring of people with early onset type 2 diabetes SO DIABETES LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; PIMA-INDIANS; METABOLIC CHARACTERISTICS; C-PEPTIDE; MELLITUS; NIDDM; INDIVIDUALS; MUTATIONS; GENE; PATHOGENESIS AB The offspring of Pima Indians with early onset type 2 diabetes are at high risk for developing diabetes at an early age. This risk is greater among those whose mothers were diabetic during pregnancy. To define the metabolic abnormalities predisposing individuals in these high-risk groups to diabetes, we conducted a series of studies to measure insulin secretion and insulin action in healthy adult Pima Indians. In 104 normal glucose-tolerant subjects, acute insulin secretory response (AIR) to a 25-g intravenous glucose challenge correlated with the age at onset of diabetes in the mother (r = 0.23, P = 0.03) and, in multiple regression analyses, the age at onset of diabetes in the father (P = 0.02), after adjusting for maternal age at onset and after allowing for an interaction between these terms. In contrast, insulin action (hyperinsulinemic glucose clamp) did not correlate with the age at onset of diabetes in the parents. To determine whether early onset diabetes in the parents affected insulin secretion in the offspring across a range of glucose concentrations, responses to a stepped glucose infusion were measured in 23 subjects. Insulin secretion rates were lower in individuals whose mothers had developed diabetes before 35 years of age (n = 8) compared with those whose parents remained nondiabetic until at least 49 years of age (n = 15) (average insulin secretory rates: geometric mean [95% Cl] 369 [209-652] vs. 571 [418-780] pmol/min, P = 0.007). Finally, the AIR was lower in individuals whose mothers were diabetic during pregnancy (n = 8) than in those whose mothers developed diabetes at an early age but after the birth of the subject (n = 41) (740 [510-1,310] vs. 1,255 [1,045-1,505] pmol/l, P < 0.02). Thus, insulin secretion is lower in normal glucose tolerant offspring of people with early onset type 2 diabetes. This impairment may be worsened by exposure to a diabetic environment in utero. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Indian Hlth Serv, Phoenix Indian Med Ctr, Phoenix, AZ USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Pratley, RE (reprint author), Novartis Pharmaceut, 59 Rt 10, E Hanover, NJ 07936 USA. FU NIDDK NIH HHS [DK 20595] NR 32 TC 78 Z9 82 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD AUG PY 2001 VL 50 IS 8 BP 1828 EP 1833 DI 10.2337/diabetes.50.8.1828 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 456RU UT WOS:000170096700021 PM 11473045 ER PT J AU Pratley, RE Weyer, C AF Pratley, RE Weyer, C TI The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus SO DIABETOLOGIA LA English DT Review DE insulin action; insulin secretion; Type II diabetes mellitus; impaired glucose tolerance; pathogenesis ID HEPATIC GLUCOSE-PRODUCTION; PIMA-INDIANS; BETA-CELL; RISK-FACTORS; METABOLIC CHARACTERISTICS; CHRONIC HYPERGLYCEMIA; GLUCAGON-SECRETION; DOSE-RESPONSE; FATTY-ACIDS; EARLY-PHASE AB Patients with Type II (non-insulin-dependent) diabetes mellitus manifest abnormalities in insulin action and insulin secretion. It is widely accepted that insulin resistance is an early finding, evident before the onset of hyperglycaemia and predictive of the subsequent development of diabetes. Whether abnormalities in insulin secretion also precede and predict diabetes has been debated. However, recent studies clearly indicate that early insulin secretion plays a critical role in maintaining normal glucose homeostasis. Cross-sectional analyses show that acute insulin secretory responses (Ally) to intravenous glucose are lower in subjects with impaired glucose tolerance and those at high risk for developing diabetes. Prospectively, a low AIR predicts the development of diabetes in several populations. In longitudinal studies, AIR declines dramatically as patients progress from normal to impaired glucose tolerance and ultimately to diabetes. Early insulin secretion is important for the rapid and efficient suppression of endogenous glucose production after a meal. Thus, loss of early insulin secretion initially leads to post-prandial hyperglycaemia which, as the disease progresses, worsens to clinical hyperglycaemia. Strategies that enhance early insulin secretion improve glucose tolerance and represent a novel and more physiologic approach to improving glycaemic control in patients with Type II diabetes mellitus. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. RP Pratley, RE (reprint author), Nova Pharmaceut Corp, 59 Route 10, E Hanover, NJ 07936 USA. NR 98 TC 236 Z9 282 U1 2 U2 14 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2001 VL 44 IS 8 BP 929 EP 945 DI 10.1007/s001250100580 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467DX UT WOS:000170686800001 PM 11484070 ER PT J AU Tack, CT Goldstein, DS AF Tack, CT Goldstein, DS TI Sympathetic blockade increases insulin-induced vasodilatation and glucose uptake SO DIABETOLOGIA LA English DT Meeting Abstract C1 Univ Nijmegen, Med Ctr, Div Gen Internal Med, Nijmegen, Netherlands. NINCDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RI Tack, Cees/A-2368-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD AUG PY 2001 VL 44 SU 1 MA 186 BP A49 EP A49 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MA UT WOS:000170706200188 ER PT J AU Hiraiwa, H Chou, JY AF Hiraiwa, H Chou, JY TI Glucocorticoids activate transcription of the gene for the glucose-6-phosphate transporter, deficient in glycogen storage disease type 1b SO DNA AND CELL BIOLOGY LA English DT Article ID CHROMOSOME 11Q23; RECEPTOR; IB; TRANSLOCASE; SEQUENCE; PROTEINS; SYSTEM; HNF-1; MICE AB Deficiencies in the glucose-6-phosphate transporter (G6PT) cause glycogen storage disease type 1b (GSD-1b), a heritable metabolic disorder. The G6PT protein translocates glucose-6-phosphate from the cytoplasm to the lumen of the endoplasmic reticulum, where glucose-6-phosphatase metabolizes it to glucose and phosphate. Therefore, G6PT and glucose-6-phosphatase work in concert to maintain glucose homeostasis. To delineate the control of G6PT gene expression, we first demonstrated that transcription of the gene requires hepatocyte nuclear factor la. Consequently, hepatocyte nuclear factor la-null mice manifest a G6PT deficiency like that of GSD-1b patients. In this study, we delineated the role of glucocorticoids in the transcription of the G6PT gene. We showed that the basal G6PT promoter is contained within nucleotides -369 to -1 upstream of the translation start site, which contains three activation elements. Further, we demonstrated that glucocorticoids activate G6PT transcription and that glucocorticoid action is mediated through a glucocorticoid response element within activation element-2 of the promoter. Taken together, the results suggest that glucocorticoids play a pivotal role in regulating the G6PT gene. C1 NICHHD, Heritable Disorders Branch, Sect Cellular Differentiat, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHHD, Heritable Disorders Branch, Sect Cellular Differentiat, NIH, Bldg 10,Room 9S241, Bethesda, MD 20892 USA. NR 32 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD AUG PY 2001 VL 20 IS 8 BP 447 EP 453 DI 10.1089/104454901316976073 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 470ZY UT WOS:000170903400001 PM 11560776 ER PT J AU Jing, NJ Marchand, C Guan, YL Liu, J Pallansch, L Lackman-Smith, C De Clercq, E Pommier, Y AF Jing, NJ Marchand, C Guan, YL Liu, J Pallansch, L Lackman-Smith, C De Clercq, E Pommier, Y TI Structure-activity of inhibition of HIV-1 integrase and virus replication by G-quartet oligonucleotides SO DNA AND CELL BIOLOGY LA English DT Article ID TETRAD-FORMING OLIGONUCLEOTIDES; DRUG DESIGN; IN-VITRO; POTENT; TYPE-1 AB As novel anti-HIV agents, the G-tetrad-forming oligonucleotides have been explored for their structure-activity relations with regard to inhibition of integrase (IN) (N. Jing, Expert Opin. Investig. Drugs (2000) 9, 1777-1785). We have now developed two families of G-quartet oligonucleotides: T40217-T40222, with potential formation of a tail-to-tail G-quartet dimer, and T40224-T40227, with phosphorothioate (PT) linkages in the guanine loops. The results obtained from biophysical measurements and the assays of the inhibition of HIV-1 IN and virus replication demonstrated that an increase in the length of the G-quartet structure from a monomer (15 Angstrom) to a tail-to-tail dimer (47 Angstrom) does not distinctly disrupt the inhibition of HIV-1 IN activity or the inhibition of HIV-1 replication in cell cultures. G-quartet oligonucleotides were observed to induce molecular aggregation of HIV-1 IN and interrupt the binding of viral DNA to HIV-1 IN. Also, PT substitutions did not confer any advantages compared with the regular phosphodiesters for the inhibition of HIV-1 replication by intramolecular G-quartets. The G-quartet motif is the primary requirement for the remarkable nuclease resistance and pronounced biological efficacy of these oligonucleotides. C1 Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD USA. Rega Inst, Louvain, Belgium. RP Jing, NJ (reprint author), Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. RI Marchand, Christophe/D-8559-2016 FU NIGMS NIH HHS [GM60153] NR 17 TC 15 Z9 15 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD AUG PY 2001 VL 20 IS 8 BP 499 EP 508 DI 10.1089/104454901316976136 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 470ZY UT WOS:000170903400007 PM 11560782 ER PT J AU Brown, SG Kim, YC Kim, SA Jacobson, KA Burnstock, G King, BF AF Brown, SG Kim, YC Kim, SA Jacobson, KA Burnstock, G King, BF TI Actions of a series of PPADS analogs at P2X(1) and P2X(3) receptors SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE purinoceptor; P2X receptor; ion channel; nucleotide; ATP; antagonist ID DIINOSINE PENTAPHOSPHATE; ADENINE-NUCLEOTIDES; XENOPUS-LAEVIS; VAS-DEFERENS; ECTO-ATPASE; ANTAGONIST; RESPONSES; OOCYTES; P-2Y-PURINOCEPTORS; P-2X-PURINOCEPTORS AB Seven PPADS (Pyridoxal-5'- Phosphate 6-Azophenyl 2',4'-DiSulfonate) analogs were investigated at Group 1 P2X receptors expressed in Xenopus oocytes. All seven analogs potently inhibited P2X, (IC50 range, 5-32 nM) and P2X(3) (IC50 range, 22-345 nM), the two Group I P2X receptor subtypes. Analogs showed greater inhibitory activity where the pyridoxal moiety of PPADS contained a 5'-phosphonate group, rather than a 5'-phosphate group. Analogs also showed greater potency where disulfonate groups were removed from, or substituted at, the azophenyl moiety. The most active analog was MRS 2257 (pyridoxal-5'-phosphonate 6-azophenyl 3',5'-bismethylenephosphonate) at P2X(1) (IC50, 5 nM) and P2X(3) (IC50, 22 nM) receptors, being 14-fold and 10-fold more potent than PPADS itself. MRS 2257 produced a nonsurmountable inhibition when tested against a range of ATP concentrations, although blockade was reversed by about 85% after 20 minutes of washout. TNP-ATP and Ip(5)I were equipotent with MRS 2257 at P2X1 receptors, whereas TNP-ATP was 64-fold more potent than MRS 2257 at P2X3 receptors. In conclusion, the PPADS template can be altered at the pyridoxal and phenyl moieties to produce P2X1 and P2X3 receptor antagonists showing higher potency and greater degree of reversibility than the parent compound at these Group I P2X receptors. (C) 2001 Wiley-Liss, Inc. C1 RF & UCMS, Auton Neurosci Inst, London NW3 2PF, England. NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP King, BF (reprint author), RF & UCMS, Auton Neurosci Inst, Royal Free Campus,Rowland Hill St, London NW3 2PF, England. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031127-01, Z99 DK999999] NR 36 TC 15 Z9 15 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD AUG PY 2001 VL 53 IS 4 BP 281 EP 291 DI 10.1002/ddr.1197 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 485UU UT WOS:000171783100006 PM 27134334 ER PT J AU Elfenbein, JL Fisher, RA Wei, S Morell, RJ Stewart, C Friedman, TB Friderici, K AF Elfenbein, JL Fisher, RA Wei, S Morell, RJ Stewart, C Friedman, TB Friderici, K TI Audiologic aspects of the search for DFNA20: A gene causing late-onset, progressive, sensorineural hearing loss SO EAR AND HEARING LA English DT Article ID NON-SYNDROMIC DEAFNESS; NONSYNDROMIC DEAFNESS; DOMINANT DEAFNESS; MAPS; IMPAIRMENT; LOCUS; MUTATION; FORM; LINKAGE; 4P16.3 AB Objective: The purpose of this research was to identify the gene responsible for a novel form of nonsyndromic, late-onset, bilateral, progressive, sensorineural hearing loss in a Michigan family of English descent. This report describes the audiologic aspects of the search. Design: Fifty-eight members of the family served as subjects for the study. Family pedigree information was gathered from family interviews, family records, birth and death registration records and census data. Audiologic evaluation was used to describe the hearing loss (phenotype) and classify family members as affected or unaffected based on hearing status. These data then were used in a linkage analysis, a process in which the inheritance of a trait is compared with the inheritance of genetic markers and statistically significant associations are sought. Results. The team mapped the hearing loss to the long arm of chromosome 17 at band 17q25. The pattern of inheritance is autosomal dominant. The search for the gene is continuing using a candidate gene approach. Conclusions: The hearing loss demonstrated by this mid-Michigan family is a novel form of nonsyndromic, genetic, late-onset, bilateral, progressive, sensorineural hearing loss. The locus of the gene, the 20th for autosomal dominant hearing loss, is at band 17q25 of chromosome 17. C1 Michigan State Univ, Dept Audiol & Speech Sci, E Lansing, MI 48824 USA. Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. NIDCD, Mol Genet Lab, NIH, Rockville, MD USA. Profess Hearing Consultants, E Lansing, MI USA. RP Elfenbein, JL (reprint author), Michigan State Univ, Dept Audiol & Speech Sci, E Lansing, MI 48824 USA. OI Morell, Robert/0000-0003-1537-7356 FU NIDCD NIH HHS [Z01 DC 00035-02, Z01 DC 00039-02] NR 39 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-0202 J9 EAR HEARING JI Ear Hear. PD AUG PY 2001 VL 22 IS 4 BP 279 EP 288 DI 10.1097/00003446-200108000-00003 PG 10 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 465GE UT WOS:000170580600003 PM 11527035 ER PT J AU Yefimov, S Yergey, AL Chrambach, A AF Yefimov, S Yergey, AL Chrambach, A TI Sequential electroelution and mass spectroscopic identification of intact sodium dodecyl sulfate-proteins labeled with 5(6)-carboxyfluorescein-N-hydroxysuccinimide ester SO ELECTROPHORESIS LA English DT Article DE electroelution; sodium dodecyl sulfate-proteins; 5(6)-carboxyfluorescein-N-hydroxysuccinimide ID POLYACRYLAMIDE-GEL-ELECTROPHORESIS; AUTOMATED HPGE-1000 APPARATUS; IMPROVED RESOLUTION; SDS-PROTEIN; RECOVERY; SPECTROMETRY; SEPARATION; BANDS; STEP AB A gel electrophoresis apparatus capable of scanning the migration path fluorometrically and of computer-directed electroelution of bands was applied to the mass spectrometric identification of sequentially electroeluted 5(6)-carboxyfluorescein-N-hydrosuccinimide ester (FLUOS)-labeled sodium dodedyl sulfate (SDS)-proteins. The masses of four electroeluted SDS-proteins under study determined by matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) spectrometry are changed by 1% due to their reaction with FLUOS in a 1:5 molar ratio of protein:label, allowing for the identification of the labeled intact proteins on the basis of mass. More importantly, the partial (10 or 50%) derivatization of proteins with FLUOS does not preclude their tryptic hydrolysis, and identification of the protein on the basis of the mass spectrometric analysis of its tryptic peptides. Potentially, the procedure allows for the automated mass spectrometric identification of SDS-proteins globally labeled with FLUOS and electrophoretically separated, without need for any gel sectioning. C1 NICHHD, Macromol Anal Sect, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Mol Biophys, Sect Mass Spectrometry & Metab, NIH, Bethesda, MD USA. RP Chrambach, A (reprint author), NICHHD, Macromol Anal Sect, NIH, Bldg 10,Rm 9D50, Bethesda, MD 20892 USA. NR 23 TC 1 Z9 1 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD AUG PY 2001 VL 22 IS 14 BP 2881 EP 2887 DI 10.1002/1522-2683(200108)22:14<2881::AID-ELPS2881>3.0.CO;2-H PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 471GR UT WOS:000170920900008 PM 11565783 ER PT J AU Boehm, J He, YS Greiner, A Staudt, L Wirth, T AF Boehm, J He, YS Greiner, A Staudt, L Wirth, T TI Regulation of BOB.1/OBF.1 stability by SIAH SO EMBO JOURNAL LA English DT Article DE B cell; BOB.1; OBF.1; coactivator; SIAH; ubiquitin ligase ID CELL-SPECIFIC COACTIVATOR; GERMINAL-CENTER FORMATION; OCA-B; FUNCTIONAL-CHARACTERIZATION; MURINE HOMOLOG; T-CELLS; TRANSCRIPTION; EXPRESSION; BINDING; GENE AB The BOB.1/OBF.1 coactivator is critically involved in mediating octamer-dependent transcriptional activity in B lymphocytes. Mice lacking this coactivator show various defects in B-cell development, most notably they completely lack germinal centers. Consistent with this phenotype, BOB.1/OBF.1 levels are massively upregulated in germinal center B cells as compared with resting B cells. We have addressed the mechanism of upregulation and found that only a minor part of this regulation can be attributed to increased levels of BOB.1/OBF.1-specific mRNA. Apparently, BOB.1/OBF.1 is also regulated at the protein level. In support of this suggestion we have been able to identify two related BOB.1/OBF.1 interacting proteins, SIAH1 and SIAH2, in a yeast two-hybrid screen. SIAH1 and SIAH2 are known regulators of protein stability. Cotransfection experiments revealed that coexpression of SIAH results in a destabilization of BOB.1/OBF.1 protein without affecting mRNA levels. Furthermore, proteasome inhibitors block the degradation of BOB.1/OBF.1 protein. Finally, B-cell receptor crosslinking also resulted in the degradation of BOB.1/OBF.1 and consequently reduced transcriptional activation of BOB.1/OBF.1-dependent reporters. C1 Univ Wurzburg, Inst Med Srahlenkunde & Zellforschung, MSZ, D-97078 Wurzburg, Germany. Univ Ulm, Dept Physiol Chem, D-89081 Ulm, Germany. Pathol Inst, D-97080 Wurzburg, Germany. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Wirth, T (reprint author), Univ Wurzburg, Inst Med Srahlenkunde & Zellforschung, MSZ, Versbacher Str 5, D-97078 Wurzburg, Germany. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 47 TC 68 Z9 74 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 1 PY 2001 VL 20 IS 15 BP 4153 EP 4162 DI 10.1093/emboj/20.15.4153 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 462DZ UT WOS:000170406600027 PM 11483518 ER PT J AU Pacak, K Palkovits, M AF Pacak, K Palkovits, M TI Stressor specificity of central neuroendocrine responses: Implications for stress-related disorders SO ENDOCRINE REVIEWS LA English DT Review ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CORTICOTROPIN-RELEASING-FACTOR; C-FOS EXPRESSION; INSULIN-INDUCED HYPOGLYCEMIA; ROSTRAL VENTROLATERAL MEDULLA; RAT SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; CENTRAL AMYGDALOID NUCLEUS; PITUITARY-ADRENAL AXIS; VASOPRESSIN MESSENGER-RNA AB Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Neuromorphol Lab, H-1094 Budapest, Hungary. RP Pacak, K (reprint author), NICHHD, NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 504 TC 507 Z9 546 U1 8 U2 39 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD AUG PY 2001 VL 22 IS 4 BP 502 EP 548 DI 10.1210/er.22.4.502 PG 47 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 461TD UT WOS:000170378800004 PM 11493581 ER PT J AU Servoss, SJ Lee, SJ Gibney, G Gozes, I Brenneman, DE Hill, JM AF Servoss, SJ Lee, SJ Gibney, G Gozes, I Brenneman, DE Hill, JM TI IGF-I as a mediator of VIP/activity-dependent neurotrophic factor-stimulated embryonic growth SO ENDOCRINOLOGY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; CULTURED MOUSE EMBRYOS; GENE-EXPRESSION; BINDING-SITES; ENVELOPE PROTEIN; NERVOUS-SYSTEM; MESSENGER-RNA; RECEPTOR GENE; INSULIN; MICE AB IGF-I and the IGF-I receptor are necessary for normal embryonic growth. VIP is an important regulator of early postimplantation growth and acts indirectly through the release of other factors, including activity-dependent neurotrophic factor. The relationship of IGF-I growth regulation to VIP/activity-dependent neurotrophic factor-stimulated growth was examined with whole cultured embryonic d 9.5 mouse embryos. Somite numbers and DNA and protein contents were measured in embryos treated with IGF-1, anti-IGF-I, VIP, activity-dependent neurotrophic factor, and anti-activity-dependent neurotrophic factor-14 (antiserum to an activity-dependent neurotrophic factor agonist). IGF-I mRNA content was measured after incubation with and without VIP for 30 and 60 min using competitive RT-PCR. IGF-1 induced a significant, dose-dependent increase in growth as measured by somite number, DNA levels, and protein content. Furthermore, anti-IGF-I inhibited embryonic growth and also prevented exogenous IGF-mediated growth. Both VIP- and activity-dependent neurotrophic factor-stimulated growth were blocked by anti-IGF-I, whereas anti-activity-dependent neurotrophic factor-14 had no detectable effect on IGF-I-induced growth. Treatment with VIP resulted in a 2-fold increase in embryonic IGF-I mRNA. These data suggest that IGF-I is a downstream mediator of VIP and activity-dependent neurotrophic factor in a regulatory pathway coordinating embryonic growth and that VIP may function as a regulator of IGF-I gene expression in the embryo. C1 NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Hill, JM (reprint author), NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jh139h@nih.gov NR 53 TC 23 Z9 26 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2001 VL 142 IS 8 BP 3348 EP 3353 DI 10.1210/en.142.8.3348 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 459ZC UT WOS:000170280500010 PM 11459777 ER PT J AU Chandrashekar, V Bartke, A Awoniyi, CA Tsai-Morris, CH Dufau, ML Russell, LD Kopchick, JJ AF Chandrashekar, V Bartke, A Awoniyi, CA Tsai-Morris, CH Dufau, ML Russell, LD Kopchick, JJ TI Testicular endocrine function in GH receptor gene disrupted mice SO ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; LUTEINIZING-HORMONE RECEPTORS; TRANSGENIC MICE; PITUITARY-FUNCTION; DWARF MICE; SULFATED GLYCOPROTEIN-2; SERTOLI CELLS; SNELL DWARF; ADULT-RATS; SPERMATOGENESIS AB The consequences of disruption of GH receptor gene in GH receptor knockout mice on testicular function were evaluated. Adult male GH receptor knockout mice and their normal siblings were divided in to two subgroups and treated with either saline or ovine LH (0.3 mug/g BW) in saline. One hour after saline or LH administration, blood was obtained via heart puncture. Plasma IGF-I, LH, FSH, PRL, androstenedione, and testosterone levels were measured by RIAs. Testicular LH and PRL receptor numbers as well as pituitary LH beta -subunit and testicular sulfated glycoprotein-2 mRNA levels were measured. Also, testicular morphometric analysis was performed. Unlike in normal, wild-type mice, the circulating IGF-l was undetectable in GH receptor knockout mice. The plasma PRL levels were (P < 0.01) higher in GH receptor knockout mice than in their normal siblings. The basal LH secretion was similar in normal and GH receptor knockout mice. However, the circulating FSH levels were lower (P < 0.001) in GH receptor gene disrupted mice. Administration of LH resulted in a significant (P < 0.001) increase in plasma testosterone levels in both GH receptor knockout and normal mice. However, this testosterone response was attenuated (P < 0.01) in GH receptor knockout mice. Plasma androstenedione responses were similar in both GH receptor knockout and normal mice. Testicular LH and PRL receptor numbers were significantly decreased in GH receptor knockout mice. The results of the morphometric analysis of the testis revealed that the Leydig cell volume per testis was reduced in mice with GH receptor gene disruption. The steady-state of LH beta -subunit and testicular sulfated glycoprotein-2 mRNA levels were not different in GH receptor knockout mice relative to their normal siblings. The present in vivo study demonstrates that in GH receptor knockout mice, LH action on the testis in terms of testosterone secretion is significantly attenuated and suggests that this is due to a decrease in the number of testicular LH receptors. The reduced number of PRL receptors may contribute to the diminished responsiveness of testicular steroidogenesis to LH by decreased ability to convert androstenedione to testosterone. These changes are most likely due to the absence of circulating IGF-I. These findings provide evidence that systemic IGF-I plays a major modulatory role in testicular endocrine function. C1 So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Denver, CO 80262 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, Athens, OH 45701 USA. Ohio Univ, Edison Biotechnol Inst, Dept Biomed Sci, Athens, OH 45701 USA. RP Chandrashekar, V (reprint author), So Illinois Univ, Sch Med, Dept Physiol, Life Sci 2 Bldg, Carbondale, IL 62901 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X FU NICHD NIH HHS [HD-37672, HD-37950] NR 55 TC 31 Z9 32 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2001 VL 142 IS 8 BP 3443 EP 3450 DI 10.1210/en.142.8.3443 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 459ZC UT WOS:000170280500022 PM 11459789 ER PT J AU Xu, SY Zhu, BT Turan, V Rusyn, I Thurman, R Peters, JM Gonzalez, FJ Conney, AH AF Xu, SY Zhu, BT Turan, V Rusyn, I Thurman, R Peters, JM Gonzalez, FJ Conney, AH TI PPAR alpha-dependent induction of liver microsomal esterification of estradiol and testosterone by a prototypical peroxisome proliferator SO ENDOCRINOLOGY LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; SPECIES-DIFFERENCES; METABOLISM; CYTOCHROME-P-450; CARCINOGENESIS; MICE; GENE AB Fatty acyl-coenzyme A:estradiol acyltransferase in liver microsomes catalyzes the formation of estradiol fatty acid esters. These estrogen esters are extremely lipophilic and have prolonged hormonal activity because they are slowly metabolized and slowly release estradiol. Our previous studies showed that treatment of female rats with clofibrate or gemfibrozil (peroxisome proliferators commonly used as hypolipidemic drugs) markedly stimulated the liver microsomal esterification of estradiol. Although clofibrate administration is a potent inducer of liver microsomal fatty acyl-coenzyme A.-estradiol acyltransferase in rats, it is a poor inducer in mice. In contrast to these observations, Wy-14,643 (an exceptionally potent prototypical peroxisome proliferator) is a strong inducer of fatty acyl-coenzyme A:estradiol acyltransferase in mice. To explore the role of PPAR alpha in the induction of fatty acyl-coenzyme A:estradiol acyltransferase and fatty acyl-coenzyme A:testosterone acyltransferase activities by peroxisome proliferators, we fed 0.1% Wy-14,643 to female wild-type and PPARa null mice for 11 d. The liver microsomal acyl-coenzyme A:estradiol acyltransferase and acyl-coenzyme A:testosterone acyltransferase activities were increased 4- to 5-fold in wild-type mice fed Wy-14,643, but no increase was observed in null mice. These results demonstrate that induction of acyl-coenzyme A:estradiol acyltransferase and acyl-coenzyme A:testosterone acyltransferase activities by a prototypical peroxisome proliferator is dependent on PPAR alpha. C1 Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, Piscataway, NJ 08854 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Penn State Univ, Ctr Mol Toxicol, Dept Vet Sci, University Pk, PA 16802 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Conney, AH (reprint author), Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. RI Peters, Jeffrey/D-8847-2011; Rusyn, Ivan/S-2426-2016 NR 16 TC 12 Z9 12 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2001 VL 142 IS 8 BP 3554 EP 3557 DI 10.1210/en.142.8.3554 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 459ZC UT WOS:000170280500035 PM 11459802 ER PT J AU Frendo, JL Therond, P Bird, T Massin, N Muller, F Guibourdenche, J Luton, D Vidaud, M Anderson, WB Evain-Brion, D AF Frendo, JL Therond, P Bird, T Massin, N Muller, F Guibourdenche, J Luton, D Vidaud, M Anderson, WB Evain-Brion, D TI Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation SO ENDOCRINOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; IN-VITRO DIFFERENTIATION; GROWTH-FACTOR RECEPTOR; HUMAN-PLACENTA; HUMAN CYTOTROPHOBLAST; DOWNS-SYNDROME; VILLOUS CYTOTROPHOBLAST; OXIDATIVE STRESS; HUMAN-PREGNANCY; EXPRESSION AB The syncytiotrophoblast is the major component of the human placenta, involved in feto-maternal exchanges and secretion of pregnancy-specific hormones. Multinucleated syncytiotrophoblast arises from fusion of mononuclear cytotrophoblast cells. In trisomy 21-affected placentas, we recently have shown that there is a defect in syncytiotrophoblast formation and a decrease in the production of pregnancy-specific hormones. Due to the role of oxygen free radicals in trophoblast cell differentiation, we investigated the role of the key antioxidant enzyme, copper/zinc superoxide dismutase, encoded by chromosome 21 in in vitro trophoblast differentiation. We first observed that overexpression of superoxide dismutase in normal cytotrophoblasts impaired syncytiotrophoblast formation. This was associated with a significant decrease in mRNA transcript levels and secretion of hCG and other hormonal markers of syncytiotrophoblast. We confirmed abnormal cell fusion by overexpression of green fluorescence protein-tagged superoxide dismutase in cytotrophoblasts. In addition, a significant decrease in syncytin transcript levels was observed in superoxide dismutase-transfected cells. We then examined superoxide dismutase expression and activity in isolated trophoblast cells from trisomy 21-affected placentas. Superoxide dismutase mRNA expression (P<0.05), protein levels (P<0.01), and activity (P<0.05) were significantly higher in trophoblast cells isolated from trisomy 21-affected placentas than in those from normal placentas. These results suggest that superoxide dismutase overexpression may directly impair trophoblast cell differentiation and fusion, and superoxide dismutase overexpression in Down's syndrome may be responsible at least in part for the failure of syncytiotrophoblast formation observed in trisomy 21-affected placentas. C1 Univ Paris 05, Fac Sci Pharmaceut & Biol, INSERM, U427, F-75270 Paris, France. Univ Paris 05, Fac Sci Pharmaceut & Biol, Lab Biochim Metab & Clin, F-75270 Paris, France. Univ Paris 05, Fac Sci Pharmaceut & Biol, Genet Mol Lab, F-75270 Paris, France. NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Hop Ambroise Pare, Serv Biochim, F-92104 Boulogne, France. Hop Robert Debre, Serv Hormonol, F-75019 Paris, France. Hop Robert Debre, Serv Gynecol Obstet, F-75019 Paris, France. RP Evain-Brion, D (reprint author), Fac Sci Pharmaceut & Biol Paris, INSERM, U427, 4 Ave Observ, F-75270 Paris 06, France. OI Frendo, Jean-Louis/0000-0003-0118-5556 NR 67 TC 65 Z9 66 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2001 VL 142 IS 8 BP 3638 EP 3648 DI 10.1210/en.142.8.3638 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 459ZC UT WOS:000170280500046 PM 11459813 ER PT J AU Kanno, J Onyon, L Haseman, J Fenner-Crisp, P Ashby, J Owens, W AF Kanno, J Onyon, L Haseman, J Fenner-Crisp, P Ashby, J Owens, W TI The OECD program to validate the rat uterotrophic bioassay to screen compounds for in vivo estrogenic responses: Phase 1 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE endocrine disruption; estrogen; rat uterus; uterotrophic ID SPRAGUE-DAWLEY RATS; ASSAY AB The Organisation for Economic Co-operation and Development has completed the first phase of an international validation program for the rodent uterotrophic bioassay. This uterotrophic bioassay is intended to identify the in vivo activity of compounds that are suspected agonists or antagonists of estrogen. This information could, for example, be used to help prioritize positive compounds for further testing. Using draft protocols, we tested and compared two model systems, the immature female rat and the adult ovariectomized rat. Data from 19 participating laboratories using a high-potency reference agonist, ethinyl estradiol (EE), and an antagonist, ZM 189,154, indicate no substantive performance differences between models. All laboratories and an protocols successfully detected increases in uterine weights using EE in phase 1. These significant uterine weight increases were achieved under a variety of experimental conditions (e.g., strain, diet, housing protocol, bedding, vehicle). For each protocol, there was generally good agreement among laboratories with regard to the actual EE doses both in producing the first significant increase in uterine weights and achieving the maximum uterine response. Furthermore, the Hill equation appears to model the dose response satisfactorily and indicates general agreement based on calculated effective dose (ED)(10) and ED50 within and among laboratories. The feasibility of an antagonist assay was also successfully demonstrated. Therefore, both models appear robust, reproducible, and transferable across laboratories for high-potency estrogen agonists such as EE. For the next phase of the OECD validation program, both models will be tested against a battery of weak, partial estrogen agonists. C1 Natl Inst Hlth Sci, Tokyo 158, Japan. OECD, Environm Hlth & Safety Div, Paris, France. NIEHS, Res Triangle Pk, NC 27709 USA. US EPA, Washington, DC 20460 USA. Syngenta Cent Toxicol Lab, Macclesfield, Cheshire, England. Procter & Gamble Co, Human & Environm Safety, Cincinnati, OH 45253 USA. RP Owens, W (reprint author), Procter & Gamble Co, Human & Environm Safety, POB 538707, Cincinnati, OH 45253 USA. NR 23 TC 132 Z9 140 U1 0 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2001 VL 109 IS 8 BP 785 EP 794 DI 10.2307/3454820 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 470BZ UT WOS:000170851700021 PM 11564613 ER PT J AU Vojta, PJ Randels, SP Stout, J Muilenberg, M Burge, HA Lynn, H Mitchell, H O'Connor, GT Zeldin, DC AF Vojta, PJ Randels, SP Stout, J Muilenberg, M Burge, HA Lynn, H Mitchell, H O'Connor, GT Zeldin, DC TI Effects of physical interventions on house dust mite allergen levels in carpet, bed, and upholstery dust in low-income, urban homes SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergen avoidance; asthma; environmental intervention; house dust mite; indoor allergens ID DER-P-I; BRONCHIAL HYPERREACTIVITY; ASTHMA; AVOIDANCE; EXPOSURE; CHILDREN; DISORDERS; CHILDHOOD; INFANCY AB House dust mite allergen exposure is a postulated risk factor for allergic sensitization, asthma development, and asthma morbidity; however, practical and effective methods to mitigate these allergens from low-income, urban home environments remain elusive. The purpose of this study was to assess the feasibility and effectiveness of physical interventions to mitigate house dust mite allergens in this setting. Homes with high levels of house dust mite allergen (Der f1 + Der p 1 greater than or equal to 10 mug/g dust by enzyme-linked immunosorbent assay) in the bed, bedroom carpet, and/or upholstered furniture were enrolled in the study. Carpets and upholstered furniture were subjected to a single treatment of either dry steam cleaning plus vacuuming (carpet only) or intensive vacuuming alone. Bed interventions consisted of complete encasement of the mattress, box spring, and pillows plus either weekly professional or in-home laundering of nonencased bedding. Dust samples were collected at baseline and again at 3 days (carpet and upholstery only) and 2, 4, and 8 weeks posttreatment. We compared pretreatment mean allergen concentrations and loads to posttreatment values and performed between-group analyses after adjusting for differences in the pretreatment means. Both dry steam cleaning plus vacuuming and vacuuming alone resulted in a significant reduction in carpet house dust mite allergen concentration and load (p < 0.05). Levels approached pretreatment values by 4 weeks posttreatment in the intensive vacuuming group, whereas steam cleaning plus vacuuming effected a decrease that persisted for up to 8 weeks. Significant decreases in bed house dust mite allergen concentration and load were obtained in response to encasement and either professional or in-home laundering (p < 0.001). Between-group analysis revealed significantly less postintervention house dust mite allergen load in professionally laundered compared to home-laundered beds (P < 0.05). Intensive vacuuming and dry steam cleaning both caused a significant reduction in allergen concentration and load in upholstered furniture samples (p < 0.005). Based on these data, we conclude that physical interventions offer practical, effective means of reducing house dust mite allergen levels in low-income, urban home environments. C1 NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Rho Inc, Chapel Hill, NC USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, 111 Alexander Dr,Mail Drop D2-02, Res Triangle Pk, NC 27709 USA. OI O'Connor, George/0000-0002-6476-3926 NR 35 TC 38 Z9 41 U1 1 U2 5 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2001 VL 109 IS 8 BP 815 EP 819 DI 10.2307/3454824 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 470BZ UT WOS:000170851700025 PM 11564617 ER PT J AU Padilla-Banks, E Jefferson, WN Newbold, RR AF Padilla-Banks, E Jefferson, WN Newbold, RR TI The immature mouse is a suitable model for detection of estrogenicity in the uterotropic bioassay SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE complement C3; dose-response modeling; endocrine disruptors; endocrine modulators; environmental estrogens; estrogens; lactoferrin; risk assessment extrapolations; uterotropic bioassay ID I SCREENING BATTERY; SPRAGUE-DAWLEY RATS; ASSAY; LACTOFERRIN; SENSITIVITY; UTERUS; VITRO; GENE; VIVO; 17-BETA-ESTRADIOL AB The traditional rodent uterotropic response assay has been incorporated into the U.S. Environmental Protection Agency's screening and testing program for environmental endocrine-disrupting chemicals (EDCs). While much effort continues to focus on determining protocol variables, few studies compare uterotropic responses in rats, a species commonly used in toxicologic testing, with other rodent species. In this study, we compared uterine responses in immature outbred CD-1 mice and Sprague-Dawley rats. After three daily subcutaneous injections with 17 beta -estradiol (0.1-500 mug/kg/day), immature mice and rats demonstrated a similar dose-response increase in absolute uterine wet weight and uterine weight:body weight ratio. Further, morphologic and biochemical parameters of estrogenicity, including uterine epithelial cell height and number, gland number, and induction of estrogen-responsive proteins lactoferrin and complement C3, minor wet weight increases. We conclude that mice are as well suited as rats for the uterotropic bioassay. Because of the advantages of using mice, including lower costs, less space required, and smaller amounts of compound needed for tests, mice should be given appropriate consideration in testing paradigms for EDCs. C1 NIEHS, Dev Endocrinol Sect, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol Sect, Toxicol Lab, Environm Toxicol Program, MD E4-02, Res Triangle Pk, NC 27709 USA. EM newbold1@niehs.nih.gov NR 36 TC 44 Z9 54 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2001 VL 109 IS 8 BP 821 EP 826 DI 10.2307/3454825 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 470BZ UT WOS:000170851700026 PM 11564618 ER PT J AU Aguilella, VM Bezrukov, SM AF Aguilella, VM Bezrukov, SM TI Alamethicin channel conductance modified by lipid charge SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE surface charge; double layer; lipid titration; protein electrostatics ID PHOSPHOLIPID SURFACE-CHARGE; ION CHANNELS; MEMBRANE INTERACTIONS; K+ CHANNEL; GRAMICIDIN; MODEL; ELECTROSTATICS; TRANSDUCTION; DIFFUSION; PEPTIDES AB The membrane surface charge modifies the conductance of ion channels by changing the electric potential and redistributing the ionic composition in their vicinity. We have studied the effects of lipid charge on the conductance of a multi-state channel formed in planar lipid bilayers by the peptide antibiotic alamethicin. The channel conductance was measured in two lipids: in a neutral dioleoylphosphatidylethanolamine (DOPE) and a negatively charged dioleoylphosphatidylserine (DOPS). The charge state of DOPS was manipulated by the pH of the membrane-bathing solution. We find that at high salt concentrations (e.g., 2 M NaCl) the effect of the lipid charge is below the accuracy of our measurements. However, when the salt concentration in the membrane-ba thing solution is decreased , the surface charge manifests itself as an increase in the conductance of the first two channel levels that correspond to the smallest conductive alamethicin aggregates. Our analysis shows that both the salt and pH dependence of the surface charge effect can be rationalized within the nonlinear Poisson-Boltzmann approach. Given channel conductance in neutral lipids, we use different procedures to account for the surface charge (e.g., introduce averaging over the channel aperture and take into account Na+ adsorption to DOPS heads), but only one adjustable parameter: an effective distance from the nearest lipid charge to the channel mouth center. We show that this distance varies by 0.3-0.4 nm upon channel transition from the minimal conducting aggregate (level LO) to the next larger one (level LI). This conclusion is in accord with a simple geometrical model of alamethicin aggregation. C1 Univ Jaume 1, Dept Ciencias Expt, Castellon De La Plana 12080, Spain. Nichhd, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. RP Aguilella, VM (reprint author), Univ Jaume 1, Dept Ciencias Expt, Ap 224, Castellon De La Plana 12080, Spain. EM aguilell@uji.es RI Aguilella, Vicente/B-7592-2008 OI Aguilella, Vicente/0000-0002-2420-2649 NR 42 TC 30 Z9 31 U1 0 U2 9 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD AUG PY 2001 VL 30 IS 4 BP 233 EP 241 PG 9 WC Biophysics SC Biophysics GA 462VM UT WOS:000170440500001 PM 11548125 ER PT J AU Kao, C Kiesewetter, D Jagoda, E Ma, Y Ravasi, L Szajek, L Eckelman, W AF Kao, C Kiesewetter, D Jagoda, E Ma, Y Ravasi, L Szajek, L Eckelman, W TI Radiosynthesis, metabolism, and biodistribution of [Br-76]bromopaclitaxel ([Br-76]BPAC), a potential PET tracer for paclitaxel SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 NIH, Positron Emiss Tomog Dept, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD AUG PY 2001 VL 28 IS 8 SU S MA OS136 BP 996 EP 996 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 464HZ UT WOS:000170528300138 ER PT J AU Catafau, AM Endres, CJ Gay, O Dogan, AS Hilton, J Cherstniakova, S Rothman, RB Rice, KC Shin, L Cantilena, LR Wong, DF AF Catafau, AM Endres, CJ Gay, O Dogan, AS Hilton, J Cherstniakova, S Rothman, RB Rice, KC Shin, L Cantilena, LR Wong, DF TI GBR12909 dopamine transporter occupancy: Are 11C-Cocaine and 11C-WIN35,428 PET measurements comparable? SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, Natl Inst Drug Abuse, IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD AUG PY 2001 VL 28 IS 8 SU S MA PS226 BP 1133 EP 1133 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 464HZ UT WOS:000170528300664 ER PT J AU Jahoda, CAB Oliver, RF Reynolds, AJ Forrester, JC Gillespie, JW Cserhalmi-Friedman, PB Christiano, AM Horne, KA AF Jahoda, CAB Oliver, RF Reynolds, AJ Forrester, JC Gillespie, JW Cserhalmi-Friedman, PB Christiano, AM Horne, KA TI Trans-species hair growth induction by human hair follicle dermal papillae SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE hair follicle; dermal papilla; epithelial-mesenchymal interactions; induction ID OUTER ROOT SHEATH; BETA-CATENIN; EAR WOUNDS; CELLS; MICE; EXPRESSION; VIBRISSA; CYCLE; SKIN; RAT AB A series of experimental bioassays has shown that the dermal papilla of the adult rodent vibrissa hair follicle retains unique inductive properties. In view of the many phenotypic and functional differences between specific hair follicle types, and the growing interest in hair follicle biology and disease, it remains important to establish that the human hair follicle dermal papilla has equivalent capabilities. In this study we tested the ability of human hair follicle papillae to induce hair growth when implanted into transected, athymic mouse vibrissa follicles. The implanted papillae that interacted with mouse follicle epithelium created new fibre-producing follicle end bulbs. The origin of the papillae in the recombinant structures was confirmed using laser capture microdissection and human specific gender determination by PCR. The demonstration that intact adult human dermal papillae can induce hair growth has implications for molecular analysis of basic hair growth mechanisms, particularly since the study involved common epithelial-mesenchymal signalling and recognition properties across species. It also improves the prospects for a cell-based clinical approach to hair follicle disorders. C1 Univ Durham, Dept Biol Sci, Durham DH1 3LE, England. Univ Dundee, Dept Biol Sci, Dundee DD1 4HN, Scotland. Ninewells Hosp, Dept Surg, Dundee DD1 9SY, Scotland. NCI, Pathol Lab, Bethesda, MD 20895 USA. Columbia Univ, Dept Dermatol, New York, NY 10027 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. RP Jahoda, CAB (reprint author), Univ Durham, Dept Biol Sci, South Rd, Durham DH1 3LE, England. NR 55 TC 35 Z9 48 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD AUG PY 2001 VL 10 IS 4 BP 229 EP 237 DI 10.1034/j.1600-0625.2001.100402.x PG 9 WC Dermatology SC Dermatology GA 463GD UT WOS:000170468000002 PM 11493311 ER PT J AU Cheng, QF Rao, PV Zigler, JS AF Cheng, QF Rao, PV Zigler, JS TI Effect of perillic acid, a putative isoprenylation inhibitor, on the cultured rat lens SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE perillic acid; lovastatin; isoprenylation; lens; cataract; farnesyl; geranylgeranyl ID GTP-BINDING PROTEINS; COA REDUCTASE INHIBITORS; SMOOTH-MUSCLE CELLS; INDUCE APOPTOSIS; ALCOHOL; LOVASTATIN; CANCER; MONOTERPENES; CATARACTS; GROWTH AB Previous studies have demonstrated that agents affecting the cholesterol synthetic pathway can have cataractogenic effects. We have suggested that opacification of cultured lenses resulting from exposure to the cholesterol-lowering agent lovastatin is caused by inhibition of isoprenylation of small GTPases. To test that hypothesis we have investigated the effects of perillic acid, an agent reported to inhibit isoprenylation, on rat lenses in organ culture. Perillic acid caused dose and time dependent opacification of cultured lenses. While the opacities appeared grossly similar to those produced by lovastatin, they differed dramatically when analysed histologically. It also produced marked morphological changes to lens epithelial cells in culture. Analysis of small GTPases in the perillic acid treated cells failed to detect any accumulation in the water soluble fraction as would be expected if isoprenylation was inhibited. Further, studies on the isoprenylation of radiolabelled isoprenoids into proteins in cultured lenses showed no significant decrease following perillic acid exposure. It was concluded that perillic acid causes cataract in this system by a mechanism different from lovastatin and that inhibition of isoprenylation is unlikely to be a primary factor in the perillic acid cataract. C1 NEI, Lab Mechanisms Ocular Dis, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. RP Zigler, JS (reprint author), NEI, Lab Mechanisms Ocular Dis, 6 Ctr Dr,MSC 2735, Bethesda, MD 20892 USA. FU NEI NIH HHS [EY-12201] NR 40 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2001 VL 73 IS 2 BP 239 EP 245 DI 10.1006/exer.2001.1030 PG 7 WC Ophthalmology SC Ophthalmology GA 454VH UT WOS:000169992100010 PM 11446774 ER PT J AU Sarabi, A Chang, CF Wang, Y Hoffer, BJ Morales, M AF Sarabi, A Chang, CF Wang, Y Hoffer, BJ Morales, M TI Time course study of GFR alpha-1 expression in an animal model of stroke SO EXPERIMENTAL NEUROLOGY LA English DT Article DE GDNF; stroke; ischemia; receptors ID NEUROTROPHIC FACTOR PROTECTS; C-RET; RAT-BRAIN; CORTICAL INFARCTION; TOPICAL APPLICATION; GABAERGIC NEURONS; RECEPTOR-ALPHA; FACTOR GDNF; ISCHEMIA; INJURY AB Previous studies have shown that intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) reduces ischemia-mediated cerebral infarction. The biological effects of GDNF are mediated by GDNF-family receptor alpha -1 (GFR alpha -1) and c-Ret. In this study, we examined the levels of expression of GFR alpha -1 and c-Pet in a rat model of stroke. Adult Sprague-Dawley rats were anesthetized with chloral hydrate. The right middle cerebral artery was ligated at its distal branch for 90 min. Animals were sacrificed at 0, 6,12, and 24 h after reperfusion and levels of expression of GFR alpha -1 and c-Ret mRNA were determined by in situ hybridization histochemistry. We found that GFR alpha -1 mRNA was up-regulated in CAS, dentate gyrus (DG), cortex, and striatum. The peak of up-regulation in DG was 6 h after reperfusion. GFR alpha -1 mRNA levels in CA3 were gradually up-regulated over the 24-h reperfusion period. In cortex, GFR alpha -1 mRNA was up-regulated at all time points; however, the peak of up-regulation was observed at 0 and 24 h after reperfusion. In striatum, an initial up-regulation of GFR alpha -1 was found at 0 h after ischemia. In striatum., up-regulation of c-Ret mRNA was detected as early as 0 h after reperfusion. A gradual increase was found at 6, 12, and 24 h after reperfusion. In conclusion, our results indicate that there are both regional and temporal differences in up-regulation of GFR alpha -1 and c-Ret after ischemia. Since GDNF is neuroprotective, up-regulation of GFR alpha -1 and c-Ret could enhance the responsiveness to GDNF and reduce neuronal damage. The selective up-regulation of GFR alpha -1 and c-Ret in different brain areas suggests that there may be regional differences in GDNF-induced neuroprotection in stroke. (C) 2001 Academic Press. C1 NIDA, NIH, Baltimore, MD 21224 USA. Tri Serv Gen Hosp, Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan. RP Sarabi, A (reprint author), NIDA, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 21 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD AUG PY 2001 VL 170 IS 2 BP 283 EP 289 DI 10.1006/exnr.2001.7714 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 464BA UT WOS:000170511600006 PM 11476594 ER PT J AU Groll, AH Walsh, TJ AF Groll, AH Walsh, TJ TI Caspofungin: pharmacology, safety and therapeutic potential in superficial and invasive fungal infections SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE animal models; antifungal agents; aspergillosis; candidiasis; caspofungin; clinical studies; echinocandins; in vitro susceptibility; mycoses; pharmacokinetics; safety ID IN-VITRO ACTIVITY; ANTIFUNGAL MK-0991 L-743,872; CRYPTOCOCCUS-NEOFORMANS; ECHINOCANDIN ANTIFUNGAL; AMPHOTERICIN-B; DISSEMINATED ASPERGILLOSIS; PNEUMOCANDIN L-743,872; PNEUMOCYSTIS-CARINII; MK-991 L-743,872; GLUCAN SYNTHASE AB Invasive fungal infections are important causes of morbidity and mortality in hospitalised patients. Current therapy with amphotericin B and antifungal triazoles has overlapping targets and is limited by toxicity and resistance. The echinocandin lipopeptide caspofungin is the first of a new class of antifungal compounds that inhibit the synthesis of 1,3-beta -D-glucan. This homopolysaccharide is a major component of the cell wall of many pathogenic fungi and yet is absent in mammalian cells. It provides osmotic stability and is important for cell growth and cell division. In vitro, caspofungin has broad-spectrum antifungal activity against Candida and Aspergillus spp. without cross-resistance to existing agents. The compound exerts prolonged post-antifungal effects and fungicidal activity against Candida species and causes severe damage of Aspergillus fumigatus at the sites of hyphal growth. Animal models have demonstrated efficacy against disseminated candidiasis and disseminated and pulmonary aspergillosis, both in normal and in immunocompromised animals. Caspofungin possesses favourable pharmacokinetic properties and is not metabolised through the CYP450 enzyme system. It showed highly promising antifungal efficacy in Phase II and III clinical trials in immunocompromised patients with oesophageal candidiasis. Caspofungin was effective in patients with invasive aspergillosis intolerant or refractory to standard therapies. Based on its documented antifungal efficacy and an excellent safety profile, caspofungin has been approved recently by the US Food and Drug Administration for the treatment of invasive aspergillosis in patients who are refractory to or intolerant of other therapies (i.e., amphotericin B, lipid formulations of amphotericin B, and/or itraconazole). Phase III clinical trials in patients with candidaemia and in persistently febrile neutropenic patients requiring empirical antifungal therapy are ongoing. This paper reviews the preclinical and clinical pharmacology of caspofungin and its potential role for treatment of invasive and superficial fungal infections in patients. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Groll, AH (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13 N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 66 TC 93 Z9 100 U1 1 U2 9 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD AUG PY 2001 VL 10 IS 8 BP 1545 EP 1558 DI 10.1517/13543784.10.8.1545 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 472ZB UT WOS:000171013900011 PM 11772269 ER PT J AU Jayanthi, S Deng, XL Bordelon, M McCoy, MT Cadet, JL AF Jayanthi, S Deng, XL Bordelon, M McCoy, MT Cadet, JL TI Methamphetamine causes differential regulation of pro-death and anti-death Bcl-2 genes in the mouse neocortex SO FASEB JOURNAL LA English DT Article DE neurotoxicity; apoptosis; bcl-2 gene family; cDNA array ID DISMUTASE TRANSGENIC MICE; CYTOCHROME-C; CELL-DEATH; BRAIN DOPAMINE; PERMEABILITY TRANSITION; ENDOPLASMIC-RETICULUM; LIPID-PEROXIDATION; PREFRONTAL CORTEX; INDUCED APOPTOSIS; RELEASE AB Bcl-2, an inner mitochondrial membrane protein, inhibits apoptotic neuronal cell death. Expression of Bcl-2 inhibits cell death by decreasing the net cellular generation of reactive oxygen species. Studies by different investigators have provided unimpeachable evidence of a role for oxygen-based free radicals in methamphetamine (METH)-induced neurotoxicity. In addition, studies from our laboratory have shown that immortalized rat neuronal cells that overexpress Bcl-2 are protected against METH-induced apoptosis in vitro. Moreover, the amphetamines can cause differential changes in the expression of Bcl-X splice variants in primary cortical cell cultures. These observations suggested that METH might also cause perturbations of Bcl-2-related genes when administered to rodents. Thus, the present study was conducted to determine whether the use of METH might indeed be associated with transcriptional and translational changes in the expression of Bcl-2-related genes in the mouse brain. Here we report that a toxic regimen of METH did cause significant increases in the pro-death Bcl-2 family genes BAD, BAX, and BID. Concomitantly, there were significant decreases in the anti-death genes Bcl-2 and Bcl-X-L. These results thus support the notion that injections of toxic doses of METH trigger the activation of the programmed death pathway in the mammalian brain. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM JCADET@intra.nida.nih.gov NR 62 TC 91 Z9 106 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD AUG PY 2001 VL 15 IS 10 BP 1745 EP 1752 DI 10.1096/fj.01-0025com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 469JC UT WOS:000170809900010 PM 11481222 ER PT J AU Bose-Basu, B DeRose, EF Chen, YR Mason, RP London, RE AF Bose-Basu, B DeRose, EF Chen, YR Mason, RP London, RE TI Protein NMR spin trapping with [methyl-C-13(3)]-MNP: Application to the tyrosyl radical of equine myoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE myoglobin; tyrosyl radical; spin trapping; MNP; NMR; free radicals ID HYDROGEN-PEROXIDE; SPECTRA; METMYOGLOBIN AB Direct spin trapping studies of protein radical adducts are limited as a consequence of the long rotational correlation times and consequent broadening of the ESR resonances. It can be difficult to determine both the nature and number of adduct species present. NMR detection of reduced spin adducts represents an alternate approach which, however, is subject to the limitations of lower sensitivity and a limited capability for isolating the resonances arising from the reduced adduct from other chemistry involving the spin trap. In the present study, we have utilized [methy1-C-13(3)]-MNP for the detection and analysis of tyrosyl spin adducts formed as a result of exposure of equine myoglobin to hydrogen peroxide. The methyl-C-13 label allows high detection sensitivity in two dimensions, narrow line widths and most significantly, removal by dialysis of unreacted spin trap as well as any nonprotein derivatives that may form. For equine myoglobin, it is found that adduct formation involves a single residue-Tyr-103 and further that adduct formation occurs at the C-3 carbon of the amino acid. HMQC-NOESY experiments further revealed the proximity of the labeled methyl groups to both the three aromatic tyrosyl protons as well as the aromatic protons of the nearby Phe-106 residue. (C) 2001 Elsevier Science Inc. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Box 12233,MR-01, Res Triangle Pk, NC 27709 USA. NR 17 TC 9 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2001 VL 31 IS 3 BP 383 EP 390 DI 10.1016/S0891-5849(01)00599-8 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 460AP UT WOS:000170283900012 PM 11461776 ER PT J AU Choi, EH Zimmerman, PA Foster, CB Zhu, S Kumaraswami, V Nutman, TB Chanock, SJ AF Choi, EH Zimmerman, PA Foster, CB Zhu, S Kumaraswami, V Nutman, TB Chanock, SJ TI Genetic polymorphisms in molecules of innate immunity and susceptibility to infection with Wuchereria bancrofti in South India SO GENES AND IMMUNITY LA English DT Article DE filariasis; polymorphism; chitotriosidase; mannose-binding lectin; innate immunity ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CHRONIC GRANULOMATOUS-DISEASE; MANNOSE-BINDING LECTIN; SCHISTOSOMA-MANSONI; LYMPHATIC FILARIASIS; HOST-DEFENSE; HLA; CHITINASE; ANTIGEN; IDENTIFICATION AB A pilot study was conducted to determine if host genetic factors influence susceptibility and outcomes in human filariasis. Using the candidate gene approach, a well-characterized population in South India was studied using common polymorphisms in six genes (CHIT1, MPO, NRAMP, CYBA, NCF2, and MBL2). A total of 216 individuals from South India were genotyped, 67 normal (N), 63 asymptomatic microfilaria positive (MF+), 50 with chronic lymphatic dysfunction/elephantiasis (CP), and 36 tropical pulmonary eosinophilia (TPE). An association was observed between the HH variant CHIT1 genotype, which correlates with decreased activity and levels of chitotriosidase and susceptibility to filarial infection (MF+ and CP; P = 0.013). The heterozygosity of CHIT1 gene was over-represented in the normal individuals (P = 0.034). The XX genotype of the promoter region in MBL2 was associated with susceptibility to filariasis (P = 0.0093). Since analysis for MBL-sufficient vs insufficient haplotypes was not informative, it is possible the MBL2 promoter association results from linkage disequilibrium, with neighboring loci. We have identified two polymorphisms, CHIT1 and MBL2 that are associated with susceptibility to human filarial infection, findings that merit further follow-up in a larger study. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, Helminth Immunol Sect, NIH, Bethesda, MD 20892 USA. TB Res Ctr, Chennai, India. RP Chanock, SJ (reprint author), NCI, Ctr Adv Technol, Pediat Oncol Grp, Immunocompromised Host Sect, 8717 Grovement Circle, Gaithersburg, MD 20877 USA. RI Choi, Eun Hwa/J-5691-2012 NR 50 TC 95 Z9 100 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD AUG PY 2001 VL 2 IS 5 BP 248 EP 253 DI 10.1038/sj.gene.6363767 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 465UA UT WOS:000170607300002 PM 11528516 ER PT J AU Chen, CS Brabham, WW Stultz, BG Frierson, HF Barrett, JC Sawyers, CL Isaacs, JT Dong, JT AF Chen, CS Brabham, WW Stultz, BG Frierson, HF Barrett, JC Sawyers, CL Isaacs, JT Dong, JT TI Defining a common region of deletion at 13q21 in human cancers SO GENES CHROMOSOMES & CANCER LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN PROSTATE-CANCER; GENETIC ALTERATIONS; CELL-LINES; DNA-SEQUENCES; TUMOR; CARCINOMA; REVEALS; LOSSES; MAP AB Previous molecular genetic analyses identified a region of deletion at 13q21 in a variety of human cancers, suggesting the existence of a tumor suppressor gene(s) at this locus. In our earlier study on prostate cancer, the region of deletion was confined to a 3.1 cM interval between D13S152 and D13S162. At present, however, no known gene located in this interval has been firmly implicated in cancer, and the region remains too large for gene identification. To fine-map the area of interest, we established a contig of bacterial artificial chromosome (BAC) clones, narrowed the region of deletion by loss of heterozygosity (LOH) and homozygosity-mapping-of-deletion (HOMOD) analyses in different types of cancers, and tested a candidate gene from the region for mutation and alteration of expression in prostate cancers. The contig consisted of 75 overlapping BAC clones. In addition to the generation of 47 new sequence-tagged-site (STS) markers from the ends of BAC inserts, 76 known STS and expressed sequence tag markers were mapped to the contig (25 kb per marker on average). The minimal region of deletion was further defined to be about 700 kb between markers D 13S791 and D13S166 by LOH analysis of 42 cases of prostate cancer, and by HOMOD analysis of eight prostate cancer cell lines/xenografts and 49 cell lines from cancers of the breast, ovary, endometrium, and cervix, using 18 microsatellite markers encompassing the deletion region. A gene that is homologous to the WTI tumor suppressor gene, AP-2rep (KLF12), was mapped in this region and was analyzed for its expression and generic mutation. In addition to low levels of expression in both normal and neoplastic cells of the prostate, this gene did not have any mutations in a group of aggressive prostate cancers and cell lines/xenografts, as assessed by the methods of polymerase chain reaction-single strand conformational polymorphism analysis and direct sequencing. These studies suggest that a 700 kb interval at 13q21 harbors a tumor suppressor gene(s) that seems to be involved in multiple types of cancer, and that the AP-2rep gene is unlikely to be an important tumor suppressor gene in prostate cancer. The BAC contig and high-resolution physical map of the defined region of deletion should facilitate the cloning of a tumor suppressor gene(s) at 13q21. (C) 2001 Wiley-Liss. Inc. C1 Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. Johns Hopkins Univ, Johns Hopkins Oncol Ctr, Baltimore, MD USA. RP Dong, JT (reprint author), Univ Virginia, Dept Pathol, POB 800214, Charlottesville, VA 22908 USA. RI Sawyers, Charles/G-5327-2016 FU NCI NIH HHS [CA87904, CA87921] NR 36 TC 25 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 2001 VL 31 IS 4 BP 333 EP 344 DI 10.1002/gcc.1152 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 450BR UT WOS:000169722100004 PM 11433524 ER PT J AU Li, G Hu, N Goldstein, AM Tang, ZZ Roth, MJ Wang, QH Dawsey, SM Han, XY Ding, T Huang, J Giffen, C Taylor, PR Emmert-Buck, MR AF Li, G Hu, N Goldstein, AM Tang, ZZ Roth, MJ Wang, QH Dawsey, SM Han, XY Ding, T Huang, J Giffen, C Taylor, PR Emmert-Buck, MR TI Allelic loss on chromosome bands 13q1 1-q13 in esophageal squamous cell carcinoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID LASER CAPTURE MICRODISSECTION; TUMOR-SUPPRESSOR GENES; SUSCEPTIBILITY GENE; HETEROZYGOSITY; CANCER; IDENTIFICATION; NEOPLASIA; CLONING; REGIONS AB Allelic loss on chromosome 13 occurs frequently in esophageal squamous cell carcinoma. However, studies of the two known tumor suppressor genes located on 13q, RBI and BRCA2, have shown few mutations, suggesting that other genes are likely to be involved in the development of this tumor type. To identify a minimal deletion interval, we first analyzed 42 microsatellite markers spanning chromosome bands 13q11-q13 in 56 esophageal squamous cell carcinoma patients, including 34 with a family history of upper gastrointestinal cancer and 22 without a family history of cancer. Lifestyle risk factors and clinical/pathologic characteristics were also collected. Two commonly deleted regions were identified: one was located on band 13q12.11, between markers D13S787 and D13S221; the other was located on bands 13q12.3-q13.1 from markers D13S267 to D13S219. We observed higher allelic loss frequencies for eight of the microsatellite markers in those patients with a family history of upper gastrointestinal cancer compared to patients without such a history. This study suggests that one or more unidentified tumor suppressor genes are located on chromosome arm 13q that play a role in the development of esophageal squamous cell carcinoma. (C) 2001 Wiley-Liss, Inc. C1 Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China. NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100037, Peoples R China. Informat Management Serv Inc, Silver Spring, MD USA. RP Taylor, PR (reprint author), NCI, Canc Prevent Studies Branch, 6006 Execut Plaza,Rm 321, Bethesda, MD 20892 USA. NR 24 TC 26 Z9 31 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD AUG PY 2001 VL 31 IS 4 BP 390 EP 397 DI 10.1002/gcc.1158 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 450BR UT WOS:000169722100010 PM 11433530 ER PT J AU Fernandez, AM Kim, JK Yakar, S Dupont, J Hernandez-Sanchez, C Castle, AL Filmore, J Shulman, GI Le Roith, D AF Fernandez, AM Kim, JK Yakar, S Dupont, J Hernandez-Sanchez, C Castle, AL Filmore, J Shulman, GI Le Roith, D TI Functional inactivation, of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes SO GENES & DEVELOPMENT LA English DT Article DE IGF-I receptors; type 2 diabetes; insulin receptor; skeletal muscle; dominant-negative; transgenic ID GROWTH-FACTOR-I; ADIPOSE-TISSUE; HYBRID RECEPTORS; TARGETED DISRUPTION; GLUCOSE-TOLERANCE; TRANSGENIC MICE; EXPRESSION; RESISTANCE; DEFICIENT; KNOCKOUT AB Peripheral insulin resistance and impaired insulin action are the primary characteristics of type 2 diabetes. The first observable defect in this major disorder occurs in muscle, where glucose disposal in response to insulin is impaired. We have developed a transgenic mouse with a dominant-negative insulin-like growth factor-I receptor (KR-IGF-IR) specifically targeted to the skeletal muscle. Expression of KR-IGE-IR resulted in the formation of hybrid receptors between the mutant and the endogenous IGF-I and insulin receptors, thereby abrogating the normal function of these receptors and leading to insulin resistance. Pancreatic P-cell dysfunction developed at a relative early age, resulting in diabetes. These mice provide an excellent model to study the molecular mechanisms underlying the development of human type 2 diabetes. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. RP Le Roith, D (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RI Hernandez Sanchez, Catalina/N-1737-2014 OI Hernandez Sanchez, Catalina/0000-0002-0846-5019 FU NIDDK NIH HHS [R01 DK040936, R01 DK080756] NR 31 TC 217 Z9 231 U1 3 U2 10 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 1 PY 2001 VL 15 IS 15 BP 1926 EP 1934 DI 10.1101/gad.908001 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 460ZP UT WOS:000170340700006 PM 11485987 ER PT J AU Pouliot, JJ Robertson, CA Nash, HA AF Pouliot, JJ Robertson, CA Nash, HA TI Pathways for repair of topoisomerase I covalent complexes in Saccharomyces cerevisiae SO GENES TO CELLS LA English DT Article ID DOUBLE-STRAND BREAKS; CELL-CYCLE ARREST; DNA-DAMAGE; BUDDING YEAST; RAD9 GENE; CAMPTOTHECIN; CHECKPOINT; REPLICATION; DRUGS; SENSITIVITY AB Background: The covalent linkage between DNA and the active site tyrosine of topoisomerase I can be stabilized by chemotherapeutic agents, adjacent DNA lesions, or mutational defects in the topoisomerase itself. Following collision with a replication fork, the covalent complex can be converted to a double-strand break. Tdp1, an enzyme that can hydrolyse the bond between topoisomerase I and DNA, is thought to be involved in the repair of these lesions, but little is known about how such repair is accomplished. Results: Reaction kinetics with model substrates reveal that the catalytic efficiency of Saccharomyces cerevisiae Tdp1 is relatively poor when the scissile bond is located in the middle of a duplex, but much better when it is located at the end of a structure. Survival of yeast after induction of a toxic topoisomerase is substantially reduced by inactivation of the TDP1 gene. Comparison of survival of single and double mutants places TDP1 and RAD52 in the same epistasis group but TDP1 and RAD9 in different epistasis groups. In the absence of RAD9, inactivation of MPI has a significant effect on the survival of cells following exposure to camptothecin but is without consequence for the survival of agents that do not target topoisomerase 1. Conclusions: Tdp1 acts as a specific repair enzyme for topoisomerase I lesions. Rather than working at their earliest occurrence, the enzyme acts after covalent complexes have been converted to DSBs. A second repair pathway also exists that functions independently of Tdp1 but requires RAD9 function to efficiently repair topoisomerase I-linked DSBs. The efficiency of these pathways differs for complexes induced with the chemotherapeutic agent camptothecin vs. those accumulated by mutant forms of topoisomerase 1. C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP NIMH, Mol Biol Lab, Bldg 36,Room 1B08, Bethesda, MD 20892 USA. EM nash@codon.nih.gov NR 37 TC 112 Z9 112 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1356-9597 EI 1365-2443 J9 GENES CELLS JI Genes Cells PD AUG PY 2001 VL 6 IS 8 BP 677 EP 687 DI 10.1046/j.1365-2443.2001.00452.x PG 11 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 469BY UT WOS:000170793900003 PM 11532027 ER PT J AU Scacheri, PC Crabtree, JS Novotny, EA Garrett-Beal, L Chen, A Edgemon, KA Marx, SJ Spiegel, AM Chandrasekharappa, SC Collins, FS AF Scacheri, PC Crabtree, JS Novotny, EA Garrett-Beal, L Chen, A Edgemon, KA Marx, SJ Spiegel, AM Chandrasekharappa, SC Collins, FS TI Bidirectional transcriptional activity of PGK-neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice SO GENESIS LA English DT Article ID MEN1 GENE; EXPRESSION; LOCUS AB In an effort to create a conventional knockout mouse model for multiple endocrine neoplasia type 1 (MEN1), we targeted disruption of the mouse Men I gene through homologous recombination in ES cells. Men1 exons 2-4 were replaced by a PGK-neomycin cassette inserted in the opposite direction of Men1 transcription (Men1(MSK/+)). Unexpectedly, the Men1 conventional knockout was lethal in heterozygous, chimeric animals. Analysis of embryos revealed late gestational lethality with some embryos showing omphalocele. This was a very surprising phenotype, given that humans and mice that are heterozygotes for loss of function mutations in MEN1 are phenotypically normal except for a risk of endocrine tumors. Northern analysis of Men1(MSK/+) embryonic stem cell RNA revealed the presence of an abundant, novel transcript of 2.1 kb, in addition to the expected wild-type transcripts of 2.7 kb and 3.1 kb. RT-PCR analysis identified this aberrant transcript as arising from the antisense strand of the PGK promoter. We hypothesize that this transcript is producing either a toxic effect at the RNA level, or a dominant negative effect through the production of an amino-terminal truncated protein product. This example serves as a cautionary reminder that mouse knockouts using PGK-neo may sometimes display phenotypes that reflect more than just the loss of function of the targeted gene. Published 2001 Wiley-Liss, Inc.(dagger) C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIDDKD, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bldg 31,Room 4B09,31 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 54 Z9 55 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD AUG PY 2001 VL 30 IS 4 BP 259 EP 263 DI 10.1002/gene.1072 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 469NX UT WOS:000170822700007 PM 11536432 ER PT J AU Knezevic, V Mackem, S AF Knezevic, V Mackem, S TI Activation of epiblast gene expression by the hypoblast layer in the prestreak chick embryo SO GENESIS LA English DT Article DE hypoblast; visceral endoderm; inductive interaction; Gnot-1 and Gnot-2 regulation; retinoic acid; primitive streak extension ID RETINOIC ACID; HOMEOBOX GENE; PRIMITIVE STREAK; MOUSE EMBRYO; INDUCTION; AXIS; GASTRULATION; NOTOCHORD; ACTIVIN; ASYMMETRY AB Axis formation is a highly regulated process in vertebrate embryos. In mammals, inductive interactions between an extra-embryonic, layer, the visceral endoderm, and the embryonic layer before gastrulation are critical both for anterior neural patterning and normal primitive streak formation. The role(s) of the equivalent extra-embryonic endodermal layer in the chick, the hypoblast, is still less clear, and dramatic effects of hypoblast on embryonic gene expression have yet to be demonstrated. We present evidence that two genes later associated with the gastrula organizer (Gnot-1 and Gnot-2) are induced by hypoblast signals in prestreak embryos. The significance of this induction by hypoblast Is discussed in terms of possible hypoblast functions and the regulation of axis formation in the early embryo. Several factors known to be expressed in hypoblast, and retinotic acid, synergistically induce Gnot-1 and Gnot-2 expression in blastoderm cell culture. The presence of retinoic acid in prestreak embryos has not yet been directly demonstrated, but exogenous retinoic acid appears to mimic the effects of hypoblast rotation on primitive streak extension, raising the possibility that retinoid signaling plays some role in the pregastrula embryo. (C) 2001 Wiley-Liss, Inc. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Mackem, S (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 44 TC 12 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1526-954X J9 GENESIS JI Genesis PD AUG PY 2001 VL 30 IS 4 BP 264 EP 273 DI 10.1002/gene.1073 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 469NX UT WOS:000170822700008 PM 11536433 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI Prokaryotic homologs of the eukaryotic DNA-end-binding protein Ku, novel domains in the Ku protein and prediction of a prokaryotic double-strand break repair system SO GENOME RESEARCH LA English DT Article ID TRANSCRIPTION TERMINATION FACTOR; INTERACTION REGIONS; CRYSTAL-STRUCTURE; IDENTIFICATION; RECOGNITION; FOLD; ARCHITECTURE; EVOLUTION; CHROMATIN; TELOMERE AB Homologs of the eukaryotic DNA-end-binding protein Ku were identified in several bacterial and one archeal genome using iterative database searches with sequence profiles. Identification of prokaryotic Ku homologs allowed the dissection of the Ku protein sequences into three distinct domains, the Ku core that is conserved in eukaryotes and prokaryotes, a derived von Willebrand A domain that is fused to the amino terminus of the core in eukaryotic Ku proteins, and the newly recognized helix-extension-helix (HEH) domain that is fused to the carboxyl terminus of the core in eukaryotes and in one of the Ku homologs from the Actinomycete Streptomyces coelicolor. The version of the HEH domain present in eukaryotic Ku proteins represents the previously described DNA-binding domain called SAP. The Ku homolog from S. coelicolor contains a distinct version of the HEH domain that belongs to a previously unnoticed family of nucleic-acid-binding domains, which also includes HEH domains from the bacterial transcription termination factor Rho, bacterial and eukaryotic lysyl-tRNA synthetases, bacteriophage T4 endonuclease VII, and several uncharacterized proteins. The distribution of the Ku homologs in bacteria coincides with that of the archeal-eukaryotic-type DNA primase and genes for prokaryotic Ku homologs form predicted operons with genes coding for an ATP-dependent DNA li.-ase and/or archeal-eukaryotic-type DNA primase. Some of these operons additionally encode an Uncharacterized protein that may function as nuclease or an SIxlp-like predicted nuclease containing a URI domain. A hypothesis is proposed that the Ku homolog, together with the associated gene products, comprise a previously unrecognized prokaryotic system for repair of double-strand breaks in DNA. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 50 TC 154 Z9 160 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD AUG PY 2001 VL 11 IS 8 BP 1365 EP 1374 DI 10.1101/gr.181001 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 459RC UT WOS:000170263900008 PM 11483577 ER PT J AU Mumm, S Herrera, L Waeltz, PW Scardovi, A Nagaraja, R Esposito, T Schlessinger, D Rocchi, M Forabosco, A AF Mumm, S Herrera, L Waeltz, PW Scardovi, A Nagaraja, R Esposito, T Schlessinger, D Rocchi, M Forabosco, A TI X/autosomal translocations in the Xq critical region associated with premature ovarian failure fall within and outside genes SO GENOMICS LA English DT Article DE X chromosome; translocation; premature ovarian failure ID TURNER SYNDROME; STS RESOLUTION; SEX-CHROMOSOME; HUMAN HOMOLOG; MAP; CHOROIDEREMIA; BREAKPOINTS; DYSGENESIS; OOGENESIS; PATIENT AB Premature ovarian failure curtails female reproductive life and is often linked to balanced Xq/autosomal translocations in a critical region. We mapped regions around translocations at the edges of this zone (one in Xq13.3, two in Xq26) in large-insert clones and analyzed their sequence. One Xq26 region is extensively transcribed and, in agreement with a recent independent analysis, the breakpoint interrupts a gene that encodes a widely expressed peptidase. In contrast 430 kb around the second Xq26 breakpoint has no putative or detected gene content. In 260 kb around the Xq13 translocation, the breakpoint falls among a duster of repetitive elements at least 59 kb from the only detected gene (a rarely expressed T-box family transcription factor). We discuss our results in relation to models that ascribe premature ovarian failure to interruption of ovarian genes or to a failure of interactions involving DNA of the critical region during follicle development. C1 Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO 63110 USA. Barnes Jewish Hosp, St Louis, MO 63110 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. Univ Modena, Chair Med Genet, Dept Morphol & Legal Med Sci, I-41100 Modena, Italy. Ist Genet, I-70126 Bari, Italy. RP Forabosco, A (reprint author), Washington Univ, Sch Med, Div Bone & Mineral Dis, St Louis, MO 63110 USA. RI Rocchi, Mariano/B-8451-2011; OI Esposito, Teresa/0000-0002-7879-8441 NR 40 TC 31 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD AUG PY 2001 VL 76 IS 1-3 BP 30 EP 36 DI 10.1006/geno.2001.6611 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 461VP UT WOS:000170384400007 PM 11560122 ER PT J AU Stuart, M Weinrich, M AF Stuart, M Weinrich, M TI Home- and community-based long-term care: Lessons from Denmark SO GERONTOLOGIST LA English DT Article DE long-term care; Medicaid; Medicare ID MEDICAID; PEOPLE; POLICY AB purpose: Denmark is cited as a model in the development of home- and community-based systems for the frail elderly population. We examined the results of this natural experiment and considered implications for U.S. policy. Design and Methods: We used international comparative policy analysis, including site visits and semistructured interviews with Danish leadership in conjunction with a review of published literature, reports, and administrative data from Denmark and the United States. Results: After 12 years of implementing integrated systems for home- and community-based services in 275 municipalities, growth in Danish long-term care expenditures has leveled off; expenditures appear to be decreasing for the over-80 population and have dropped as a percentage of the gross domestic product. Access to and quality of long-term care services appear to remain generally satisfactory. During this period, comparable expenditures in the United States have increased, and deficits in access and quality persist. Implications: These Findings should be of interest to state and federal policy makers considering strategies to reduce the rate of growth in Medicaid and Medicare expenditures for elders and to expand home- and community-based services. C1 Univ Maryland, Dept Sociol & Anthropol, Baltimore, MD 21250 USA. NICHHD, Natl Ctr Med Rehabil Res, Bethesda, MD 20892 USA. RP Stuart, M (reprint author), Univ Maryland, Dept Sociol & Anthropol, 1000 Hilltop Circle, Baltimore, MD 21250 USA. NR 42 TC 25 Z9 25 U1 1 U2 7 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 2001 VL 41 IS 4 BP 474 EP 480 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 459JY UT WOS:000170248300005 PM 11490045 ER PT J AU Burgio, L Corcoran, M Lichstein, KL Nichols, L Czaja, S Gallagher-Thompson, D Bourgeois, M Stevens, A Ory, M Schulz, R AF Burgio, L Corcoran, M Lichstein, KL Nichols, L Czaja, S Gallagher-Thompson, D Bourgeois, M Stevens, A Ory, M Schulz, R CA REACH Investigators TI Judging outcomes in psychosocial interventions for dementia caregivers: The problem of treatment implementation SO GERONTOLOGIST LA English DT Article DE treatment implementation; Alzheimer's caregiving; interventions ID MULTISYSTEMIC THERAPY; ALZHEIMERS-DISEASE; TREATMENT FIDELITY; FAMILY AB Purpose: In published dementia caregiver intervention research, there is widespread failure to measure the level at which treatment was implemented as intended, thereby introducing threats to internal and external validity. The purpose of this article is to discuss the importance of inducing and assessing treatment implementation (TI) strategies in caregiving trials and to propose Lichstein's TI model as a potential guide. Design and Methods: The efforts of a large cooperative research study of caregiving interventions, Resources for Enhancing Alzheimer's Caregiver Health (REACH), illustrates induction and assessment of the three components of TI: delivery, receipt, and enactment. Results: The approaches taken in REACH vary with the intervention protocols and include using treatment manuals, training and certification of interventionists, and continuous monitoring of actual implementation. Implications: Investigation and description of treatment process variables allows researchers to understand which aspects of the intervention are responsible for therapeutic change, potentially resulting in development of more efficacious and efficient interventions. C1 Univ Alabama, Appl Gerontol Program, Tuscaloosa, AL 35487 USA. George Washington Univ, Dept Hlth Care Serv, Washington, DC USA. Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. Vet Affairs Med Ctr, Memphis, TN USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Univ Miami, Ctr Adult Dev & Aging, Miami, FL 33152 USA. Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. Florida State Univ, Dept Commun Disorders, Tallahassee, FL 32306 USA. NIA, Behav & Social Sci Program, NIH, Washington, DC USA. Univ Pittsburgh, Ctr Social & Urban Res, Pittsburgh, PA USA. RP Burgio, L (reprint author), Univ Alabama, Appl Gerontol Program, 210 Osband Hall,Box 870315, Tuscaloosa, AL 35487 USA. RI Bourgeois, Michelle/F-9397-2015 OI Bourgeois, Michelle/0000-0003-1458-6842 FU NIA NIH HHS [U01 AG013289, AG13255, AG13265, AG13289, AG13297, AG13305, AG13313, U01 AG013265, U01 AG013305, U01 AG013313]; NINR NIH HHS [NR04261, U01 NR004261, U01 NR004261-07] NR 23 TC 65 Z9 66 U1 2 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD AUG PY 2001 VL 41 IS 4 BP 481 EP 489 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 459JY UT WOS:000170248300006 PM 11490046 ER PT J AU Becker, MD Crespo, T Martin, TM Planck, SR Naramura, M Rosenbaum, JT AF Becker, MD Crespo, T Martin, TM Planck, SR Naramura, M Rosenbaum, JT TI Intraocular in vivo imaging of activated T-lymphocytes expressing green-fluorescent protein after stimulation with endotoxin SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID INDUCED UVEITIS; LEUKOCYTE MIGRATION; RECEPTOR HOMOLOG; MICE; MODEL AB Background: Intravital microscopy allows imaging of specific cell populations in vivo. The value of this technique is well established, but would be enhanced if one could distinguish functional states of cells in vivo. Interleukin-2 (IL-2) is expressed upon stimulation of T-cells and is a commonly used marker for T-cell activation. This study tests the use of enhanced green fluorescent protein (GFP) as a reporter gene for interleukin-2 (IL-2) expression in vivo. Methods: Characterization of mice that have the GFP gene under the control of IL-2 regulatory sequences has previously been published. Uveitis was induced by injection of E. coli endotoxin into the vitreous of these IL-2/GFP(ki) transgenic mice. Four hours later, 3 mug of recombinant mouse IL-2 was injected into the anterior chambers of one group of mice. In vivo imaging of infiltrating cells in the iris stroma was performed with fluorescence microscopy at 6, 24, 48, and 72 h after endotoxin injection. The absolute number of fluorescent cells per mm(2) was evaluated. Results: Eyes with endotoxin-induced uveitis had cells that expressed GFP and were identifiable by intravital microscopy. The fluorescent cells were exclusively seen in the subset of cells that had infiltrated the iris stroma or arrested along the vascular endothelium. The number of GFP-positive infiltrating cells in the iris increased from undetectable at baseline to 0.5 cells/mm(2) at 6 h and 1.3 cells/mm(2) at 72 h. The animals that received endotoxin as well as IL-2 tended to have more GFP-positive cells at the 48-h and 72-h time points, but these differences were not statistically significant Conclusions: GFP is commonly used as a reporter gene for in vitro expression assays. The results presented here document that transgenic mice with GFP under the control of IL-2 regulatory elements can be used with intravital microscopy for in vivo expression assays that allow detection of activated T-cells at multiple time points within the same animal. This provides a novel method for temporal and spatial studies on the state of cell activation in inflammatory responses. C1 Univ Heidelberg, Augenklin, D-69120 Heidelberg, Germany. Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. NIH, Bethesda, MD 20892 USA. RP Becker, MD (reprint author), Univ Heidelberg, Augenklin, Neuenheimer Feld 400, D-69120 Heidelberg, Germany. RI Becker, Matthias/A-8733-2014 OI Becker, Matthias/0000-0003-4933-7010 FU NEI NIH HHS [EY10572, EY06477, EY13093] NR 11 TC 11 Z9 11 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD AUG PY 2001 VL 239 IS 8 BP 609 EP 612 DI 10.1007/s004170100320 PG 4 WC Ophthalmology SC Ophthalmology GA 470TV UT WOS:000170888000010 PM 11585318 ER PT J AU Kadakia, R Arraztoa, JA Bondy, C Zhou, J AF Kadakia, R Arraztoa, JA Bondy, C Zhou, J TI Granulosa cell proliferation is impaired in the Igf1 null ovary SO GROWTH HORMONE & IGF RESEARCH LA English DT Article DE oestrogen; IGF1; granulosa cell; proliferation; apoptosis ID GROWTH-FACTOR-I; GENE-EXPRESSION; FOLLICULAR DEVELOPMENT; FOLLICLES; SYSTEM; CYCLE AB Insulin-like growth factor-I (IGF-I) expression is highly correlated with ovarian follicular growth and granulosa cell proliferation in both pre-pubertal and mature murine ovaries. Igf1 gene deleted mice are infertile, with ovarian follicles arrested at an early stage of development. To elucidate the cause of follicular dysfunction in IgfI null mice, this study compared granulosa cell proliferation at baseline and in response to exogenous oestradiol (E2) in prepubertal Igf1 null and wild-type (WT) littermate mice. The basal granulosa cell mitotic index was 3.8 +/- 0.48 in WT and 1.3 +/- 0.7 in Igf1 null mice (P = 0.03). After E2 treatment, WT granulosa mitotic index was 12.7 +/- 0.0 vs 5.5 +/- 0.8 for Igf1 null mice (P < 0.001). Granulosal BRDU incorporation was also significantly reduced as were cyclin D2 and B1 immunoreactivities in Igf1 null compared with WT mice. The incidence of apoptosis was not increased in Igf1 null follicles, although BAX immunostaining was increased. These data suggest that IGF1 is essential for normal basal and oestrogen-induced granulosa cell proliferation and follicular growth. (C) 2001 Harcourt Publishers Ltd. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kadakia, R (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 19 TC 40 Z9 40 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1096-6374 J9 GROWTH HORM IGF RES JI Growth Horm. IGF Res. PD AUG PY 2001 VL 11 IS 4 BP 220 EP 224 DI 10.1054/ghir.2001.0201 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 492WU UT WOS:000172191200003 PM 11735237 ER PT J AU Hahm, KB Im, YH Parks, TW Park, SH Markowitz, S Jung, HY Green, J Kim, SJ AF Hahm, KB Im, YH Parks, TW Park, SH Markowitz, S Jung, HY Green, J Kim, SJ TI Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease SO GUT LA English DT Article DE inflammatory bowel disease; transforming growth factor beta; matrix metalloproteinases; intestinal trefoil factor; mouse ID ULCERATIVE-COLITIS; FACTOR-ALPHA; EXPRESSION; MICE; RECEPTOR; GENE; COLLAGENASE; MOUSE; INDUCTION; MUTATION AB Background - Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract caused by an abnormal and uncontrolled immune response to one or more normally occurring gut constituents. Aim-Given the effects of transforming growth factor beta (TGF-beta1) on both the immune system and extracellular matrix, we postulated that alterations in TGF-beta signalling in intestinal epithelial cells may play an important role in the development of IBD. Methods - TGF-beta signalling was inactivated in mouse intestine by expressing a dominant negative mutant form of the TGF-beta type II receptor under the control of the mouse intestinal trefoil peptide (ITF)/TFF3 promoter. Transgenic mice (ITF-dnRII) developed spontaneous colitis presenting with diarrhoea, haematochezia, and anal prolapse when not maintained under specific pathogen free (SPF) conditions. Under SPF conditions we induced colitis by mixing dextran sodium sulphate (DSS) in drinking water to examine the significance of loss of TGF-beta signalling in the pathogenesis of IBD. Results - Transgenic mice showed increased susceptibility to DSS induced IBD, and elicited increased expression of major histocompatibility complex class II, generation of autoantibodies against intestinal goblet cells, and increased activity of matrix metalloproteinase in intestinal epithelial cells compared with wild-type littermates challenged with DSS. Conclusions - Deficiency of TGF-beta signalling specifically in the intestine contributes to the development of IBD. Maintenance of TGF-beta signalling may be important in regulating immune homeostasis in the intestine. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Ireland Canc Ctr, Dept Med, Cleveland, OH 44124 USA. Univ Hosp Cleveland, Cleveland, OH 44124 USA. Howard Hughes Med Inst, Cleveland, OH 44124 USA. Ajou Univ, Sch Med, Dept Gastroenterol, Seoul, South Korea. Univ Ulsan, Sch Med, Dept Gastroenterol, Seoul, South Korea. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room B1106,Lib Dr, Bethesda, MD 20892 USA. NR 35 TC 115 Z9 129 U1 0 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD AUG PY 2001 VL 49 IS 2 BP 190 EP 198 DI 10.1136/gut.49.2.190 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 454GN UT WOS:000169965000009 PM 11454793 ER PT J AU Miyazaki, M Lin, YW Okada, M Hamahata, K Kubota, M AF Miyazaki, M Lin, YW Okada, M Hamahata, K Kubota, M TI Childhood cutaneous natural killer/T-cell lymphoma successfully treated with only one course of chemotherapy and incomplete tumor resection SO HAEMATOLOGICA LA English DT Letter DE NK lymphoma; childhood; L-Asp; thiotepa ID FEATURES; CD56 C1 Kyoto Univ, Grad Sch Med, Dept Pediat, Kyoto, Japan. Kobe Gen Hosp, Dept Pediat, Kobe, Hyogo, Japan. RP Lin, YW (reprint author), NCI, Ctr Adv Technol, NIH, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD AUG PY 2001 VL 86 IS 8 BP 883 EP 884 PG 2 WC Hematology SC Hematology GA 470HL UT WOS:000170865100020 PM 11524256 ER PT J AU Bernstein, ML Reaman, GH Hirschfeld, S AF Bernstein, ML Reaman, GH Hirschfeld, S TI Developmental therapeutics in childhood cancer - A perspective from the Children's Oncology Group and the US Food and Drug Administration SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID PHASE-I TRIAL; REFRACTORY SOLID TUMORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; EVERY 3 WEEKS; PEDIATRIC-ONCOLOGY; ANTITUMOR-ACTIVITY; CONTINUOUS-INFUSION; SYSTEMIC EXPOSURE; PHARMACOKINETIC PK; MYELOID-LEUKEMIA AB New agents are required for the treatment of childhood cancer. Current therapies fail to cure approximately 30% of children with malignancies. The toxicity is high, with serious short-term and long-term side effects. The number of children with cancer is small, with only approximately I child in 315 affected by age 20 years. Approximately 12,500 new cases are diagnosed in the United States each year.(66) A variety of histologic subtypes, mostly different from adult cancers, are represented. The pharmacokinetics of drugs in children often are different from those in adults, with children frequently eliminating drug more rapidly. The pharmacodynamics also may be different. Children less than age 10 years are more susceptible to pseudotumor cerebri induced by retinoids than are older children or adults,(81) As a consequence, specific studies of pharmacokinetics; and pharmacodynamics are needed in children. Because the number of children affected is small, most studies are multicentric, to enable a sufficiently large group to be accrued. This is especially true of new agent studies. This article briefly reviews the strategy for selecting promising agents for study, including efforts by the U.S. Food and Drug Administration (FDA) to increase the availability of agents in early development. Study design and recent and planned developmental therapeutics studies are described, with an emphasis on Children's Oncology Group (COG) studies of cytotoxic agents. For an additional review of the general issues involved in phase I trials in children with cancer, see Smith et al.(80) C1 Hop St Justine, Div Hematol Oncol, Serv Hematol Oncol, Montreal, PQ H3T 1C5, Canada. Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA. Childrens Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA. Childrens Oncol Grp, Arcadia, CA USA. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. NCI, Bethesda, MD 20892 USA. RP Bernstein, ML (reprint author), Hop St Justine, Div Hematol Oncol, Serv Hematol Oncol, 3175 Cote St Catherine,2nd Floor,Block 4, Montreal, PQ H3T 1C5, Canada. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 99 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2001 VL 15 IS 4 BP 631 EP + DI 10.1016/S0889-8588(05)70240-9 PG 26 WC Oncology; Hematology SC Oncology; Hematology GA 482BR UT WOS:000171555400004 PM 11676277 ER PT J AU Cripe, TP Mackall, CL AF Cripe, TP Mackall, CL TI Exploiting genetic alterations to design novel therapies for cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID CYTOTOXIC T-CELLS; WILD-TYPE P53; SELECTIVELY-REPLICATING ADENOVIRUS; ALVEOLAR RHABDOMYOSARCOMA CELLS; DISEASE VIRUS THERAPY; TUMOR-CELLS; IN-VITRO; NECK-CANCER; ATTENUATED ADENOVIRUS; ANTITUMORAL EFFICACY AB Cancer is a genetic disease, arising as a result of genetic mutations that endow the cell with many specific functional capabilities.(43) Individual mutations may accumulate over time that summarily lead to all of the capabilities (84) likely accounting for the increased incidence of cancer with age. Alternatively the cancerous phenotype may result from only one or a few seminal genetic events that have multifunctional consequences, such as mutation of transcription factor genes, a theme common among childhood cancers.(41, 61, 72) The latter mechanism may give rise to cancers that occur in childhood because decades are not required to accumulate the requisite cadre of mutations. Therapies aimed at such pivotal events similarly might have multifactorial effects. To contemplate exploiting genetic mutations for therapy, it is imperative to understand molecular details of cancer-associated gene mutations. A categorization of the various mechanisms of gene mutations uncovered in pediatric cancers is summarized in Table 1. Interventions based on these mutations fall into three broad areas: gene manipulation, viral oncolysis, and immunotherapy. These fields are relatively new and speculative by nature. Consideration of early successes in vitro and in animal models combined with the broad range of strategies being explored warrants optimism that at least some of these efforts will be fruitful. C1 Univ Cincinnati, Childrens Hosp, Med Ctr, Dept Pediat,Div Hematol Oncol, Cincinnati, OH USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Cripe, TP (reprint author), Div Hematol Oncol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 92 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2001 VL 15 IS 4 BP 657 EP + DI 10.1016/S0889-8588(05)70241-0 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 482BR UT WOS:000171555400005 PM 11676278 ER PT J AU Chiaramonte, MG Cheever, AW Malley, JD Donaldson, DD Wynn, TA AF Chiaramonte, MG Cheever, AW Malley, JD Donaldson, DD Wynn, TA TI Studies of murine schistosomiasis reveal interleukin-13 blockade as a treatment for established and progressive liver fibrosis SO HEPATOLOGY LA English DT Article ID INHIBITS COLLAGEN-SYNTHESIS; GRANULOMA-FORMATION; HEPATIC-FIBROSIS; GAMMA-INTERFERON; CYTOKINE RESPONSES; LUNG FIBROSIS; TH2 RESPONSES; MANSONI EGGS; IN-VIVO; NON-T AB in several allergic, autoimmune, and infectious diseases, fibrosis is a major cause of morbidity and mortality. Here, using a model of infection-induced liver fibrosis, we show that interleukin (IL)-13 is required at all stages of Schistosomiasis mansoni infection to induce fibrosis. IL-4 production was preserved in IL-13-deficient mice, yet failed to significantly contribute to the fibrotic response in either acute or chronic infection. Significant fibrosis develops in all infected mice, although the magnitude of the response varies widely in inbred mice. C3H/HeN, BALB/c, and C57BL/6 mice develop high, intermediate, and low levels of fibrosis, respectively. Despite these differences, IL-13 antagonism resulted in a marked amelioration of fibrosis in all strains. The fibrotic mechanism in the high- and low-responder strains was unrelated to their tissue eosinophil or mast cell responses, but did correlate with their patterns of IL-13, IL-10, and interferon gamma (IFN-gamma) mRNA expression. Indeed, severe fibrosis correlated with a high IL-13 and low IFN-gamma /IL-10 mRNA response. Because fibrotic diseases are typically progressive disorders, an important issue was to determine whether IL-13 inactivation might be used to treat an established and ongoing fibrotic disease. Here, IL-13 antagonism was highly efficacious, even after fibrosis and the Th2 cytokine response were firmly established. These studies demonstrate the central role played by IL-13 in fibrogenesis and suggest that therapeutic approaches aimed at disrupting the IL-13 pathway will be highly effective at preventing fibrotic disease caused by chronic Th2-mediated inflammatory reactions. C1 NIAID, Schistosomiasis Immunol & Pathol Unit, Immunobiol Sect, Parasit Dis Lab,NIH, Bethesda, MD USA. NIAID, Ctr Informat Technol, NIH, Bethesda, MD USA. Inst Biomed Res, Rockville, MD USA. Wyeth Genet Inst, Cambridge, MA USA. RP Wynn, TA (reprint author), 9000 Rockville Pike,NIH Bldg 4-126, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 60 TC 94 Z9 105 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2001 VL 34 IS 2 BP 273 EP 282 DI 10.1053/jhep.2001.26376 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 457VH UT WOS:000170157200009 PM 11481612 ER PT J AU Lechmann, M Murata, K Satoi, J Vergalla, J Baumert, TF Liang, TJ AF Lechmann, M Murata, K Satoi, J Vergalla, J Baumert, TF Liang, TJ TI Hepatitis C virus-like particles induce virus-specific humoral and cellular immune responses in mice SO HEPATOLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSE; VACCINE DEVELOPMENT; NONSTRUCTURAL PROTEIN-3; NEUTRALIZING ANTIBODIES; STRUCTURAL PROTEINS; VIRAL CLEARANCE; INSECT CELLS; INFECTION; PROTECTION; PAPILLOMAVIRUS AB We have recently described the production of hepatitis C virus-like particles (HCV-LPs) in insect cells that resemble the putative virions. Here we evaluate the Immoral and cellular immunogenicity of the virus-like particles with or without viral p7 protein, a small viral polypeptide that resides between the structural and nonstructural regions of the HCV polyprotein and whose function has not been defined. Immunized BALB/c mice developed high titers of anti-E2 antibodies and virus-specific cellular immune responses including cytotoxic T lymphocytes and T helper responses with gamma interferon production. The virus-like particles without p7 generated a higher cellular immune response with a more T(H)1 profile than the particles with p7. Immunization of heat-denatured particles resulted in substantially lower humoral and cellular responses, suggesting that the immunogenicity is strongly dependent on particle formation. Administration of CpG oligonucleotide or cationic lipid 3 beta-[N-(N ' ,N ' -dimethylaminoethane)carbamoyl]-cholesterol (DC-Chol), two potent adjuvants, did not significantly enhance the immunogenicity of HCV-LPs. Our results indicate that HCV-LPs can induce humoral and cellular immune responses and offer a promising approach to vaccine development. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Rm 9B16, Bethesda, MD 20892 USA. NR 46 TC 69 Z9 71 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2001 VL 34 IS 2 BP 417 EP 423 DI 10.1053/jhep.2001.26523 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 457VH UT WOS:000170157200025 PM 11481628 ER PT J AU Lin, HJ Seeff, LB Barbosa, L Hollinger, FB AF Lin, HJ Seeff, LB Barbosa, L Hollinger, FB TI Occurrence of identical hypervariable region 1 sequences of hepatitis C virus in transfusion recipients and their respective blood donors: Divergence over time SO HEPATOLOGY LA English DT Article ID HUMORAL IMMUNE-RESPONSE; GENETIC GROUPS; PERSISTENT HEPATITIS; ANTIBODY-RESPONSE; VIRAL GENOME; INFECTION; GENOTYPES; VARIANTS; IDENTIFICATION; TRANSMISSION AB A total of 240 stored serum specimens from 30 transfusion recipients and 120 blood donors from the Transfusion-Transmitted Viruses Study (TTVS) were evaluated with the objective of establishing transmission of hepatitis C virus (HCV) by specific blood donors. Phylogenetic analysis of hypervariable region 1 (HVR1) and HCV genotyping were performed on the genomic region encoding amino acids 329 to 410. Amino acid distances between HVR1 sequences were calculated by the Kimura formula. Bootstrap analysis of HVR1 sequences provided support for linking recipients to specific donors. Linear regression analysis showed no differences between donor and recipient HVR1 sequences 7.9 weeks posttransfusion, but donor and recipient sequences diverged thereafter (r = 0.690). The initial lag phase in the evolution of HVR1 in the infected recipient was attributed to the time required to mount host immunologic defenses against the virus. Within-recipient divergence in HVR1 was determined from analyses of serial specimens collected within 2 weeks after the alanine transaminase peak, at the end of the original study (1974-1979), and in the follow-up study (1987-present). HVR1 remained invariant over a period of 6.7 to 9.5 days (95% CI) during acute infection. Within-patient divergence in HVR1 increased over a period of 11 to 15 years (r = 0.771), reaching the degree of divergence observed between unlinked subjects. In cases in which transfusion involved more than one HCV subtype, only one of the HCV subtypes established infection in the recipient. Subtype-specific differences in HVR1 were shown. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Hollinger, FB (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza,BCM-385, Houston, TX 77030 USA. FU NHLBI NIH HHS [N01-HB-37093] NR 41 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 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2001 VL 34 IS 2 BP 424 EP 429 DI 10.1053/jhep.2001.26635 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 457VH UT WOS:000170157200026 PM 11481629 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, J TI The secretory membrane system studied in real-time SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article; Proceedings Paper CT 43rd Symposium of the Society-for-Histochemistry CY SEP 27-28, 2001 CL VIENNA, AUSTRIA SP Soc Histochem DE green fluorescent protein; endoplasmic reticulum; Golgi apparatus; pre-Golgi intermediates; membrane traffic; protein mobility; membrane cycling ID GREEN FLUORESCENT PROTEIN; TO-GOLGI TRANSPORT; LIVING CELLS; ENDOPLASMIC-RETICULUM; PLASMA-MEMBRANE; LIVE CELLS; INTERMEDIATE COMPARTMENT; EXIT SITES; ER; DYNAMICS AB The discovery and development of green fluorescent protein (GFP) from the jellyfish, Aequorea victoria, has revolutionized studies on protein localization and dynamics by allowing direct observation of a protein's life history and pathway in living cells, previously only deduced from genetic, biochemical, or immunolabeling studies. Applied to the secretory membrane system, which regulates delivery of newly synthesized proteins and lipids to the cell surface, GFP-based studies are providing important new insights into the maintenance and biogenesis of organelles, as well as the origin, pathway, and fate of secretory transport intermediates. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 68 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0948-6143 J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD AUG PY 2001 VL 116 IS 2 BP 97 EP 107 PG 11 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA 475FY UT WOS:000171152700001 PM 11685538 ER PT J AU Agarwala, R Schaffer, AA Tomlin, JF AF Agarwala, R Schaffer, AA Tomlin, JF TI Towards a complete North American Anabaptist genealogy II. Analysis of inbreeding SO HUMAN BIOLOGY LA English DT Article DE Amish; Mennonite; genealogy; inbreeding coefficient; kinship coefficient; isolated populations ID OLD ORDER AMISH; MCKUSICK-KAUFMAN-SYNDROME; PREREPRODUCTIVE MORTALITY; EPIDEMIOLOGY; PEDIGREES; MUTATION AB We describe a large genealogy data base, which can be searched by computer, of 295,095 Amish and Mennonite individuals. The data base was constructed by merging our existing Anabaptist Genealogy Database 2.0 containing approximately 85,000 individuals with a genealogy file containing approximately 242,000 individuals, kindly provided by Mr. James Hostetler. The merging process corrected thousands of inconsistencies and eliminated hundreds of duplicate individuals. Geneticists have long been interested in Anabaptist populations because they are closed and have detailed written genealogies. The creation of an enlarged and unified data base affords the opportunity to examine inbreeding trends and correlates in these populations. We show the following results. The frequency of consanguineous marriages shows steady increase over time and reached approximately 85% for individuals born in 1940-1959. Among consanguineous marriages, the median kinship coefficient stayed stable in the 19th century, but rose from 0.0115 to 0.0151 in the 20th century. There are statistically significant associations (p < 0.0001) between inbreeding and family size and interbirth intervals in the 20th century. There is an association (p < 0.0005) between inbreeding and early death for individuals born in 1920-1959. However, this association reverses dramatically (p < 0.0005 in the opposite direction) for individuals born in 1960-1979, We tested for an association between inbreeding and being the mother of twins, but found none. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, Informat Engn Branch, NIH, Bethesda, MD 20894 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20894 USA. Ctr Informat Technol, Computat Biosci & Engn Lab, NIH, Bethesda, MD USA. RP Agarwala, R (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Informat Engn Branch, NIH, Bethesda, MD 20894 USA. RI Schaffer, Alejandro/F-2902-2012 NR 25 TC 36 Z9 36 U1 0 U2 2 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0018-7143 J9 HUM BIOL JI Hum. Biol. PD AUG PY 2001 VL 73 IS 4 BP 533 EP 545 DI 10.1353/hub.2001.0045 PG 13 WC Biology; Genetics & Heredity SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 461VD UT WOS:000170383400004 PM 11512680 ER PT J AU Yan, B Raben, N Lu, N Plotz, PH AF Yan, B Raben, N Lu, N Plotz, PH TI Identification and characterization of a tissue-specific silencer element in the first intron of the human acid maltase gene SO HUMAN GENETICS LA English DT Article ID GLYCOGENOSIS TYPE-II; ALPHA-GLUCOSIDASE; TRANSCRIPTIONAL REGULATION; ONSET; EXPRESSION; MUTATION AB Deficiency of acid maltase (acid alpha -glucosidase), a lysosomal enzyme that degrades glycogen, results in glycogenosis type II, an autosomal recessive disease whose manifestations and severity largely depend on the level of residual enzyme activity. Previous studies have established that there are transcriptional control elements in the first intron; in particular a silencer responsive to Hes-1 and YY1 has been identified in the human hepatoma line, HepG2. This region functions as an enhancer in human fibroblasts. Here we have localized a silencer active in fibroblasts to a nearby 25-bp element in intron 1. This element repressed thymidine kinase promoter activity by about 50% in both orientations in human fibroblasts. This silencer, as with the previous one, is tissue specific since constructs containing this region are inactive in HepG2 cells. Electrophoretic mobility shift assay revealed three proteins specifically binding to the element in fibroblasts, and site-directed mutagenesis analysis indicated that all the three proteins binding to the element contribute to the silencer function. The data may be helpful for designing therapy to increase the level of enzyme, particularly when, as in most adults with the disease, there is reduced production of structurally normal enzyme. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Plotz, PH (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 20 TC 6 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 2001 VL 109 IS 2 BP 186 EP 190 DI 10.1007/s004390100562 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 470TX UT WOS:000170888200009 PM 11511924 ER PT J AU Anantharaman, V Koonin, EV Aravind, L AF Anantharaman, V Koonin, EV Aravind, L TI Peptide-N-glycanases and DNA repair proteins, Xp-C/Rad4, are, respectively, active and inactivated enzymes sharing a common transglutaminase fold SO HUMAN MOLECULAR GENETICS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; PIGMENTOSUM GROUP-C; XERODERMA-PIGMENTOSUM; DAMAGED DNA; PSI-BLAST; YEAST; RAD23; DATABASE; DOMAINS; COMPLEX AB Yeast RAD4, its human ortholog Xp-C and their orthologs in other eukaryotes are DNA repair proteins which participate in nucleotide excision repair through a ubiquitin-dependent process. However, no conserved globular domains that might have shed light on their origin or functions have been reported for these proteins. By using sequence profile analysis, we show that RAD4/Xp-C proteins contain the ancient transglutaminase fold and are specifically related to the recently characterized peptide-N-glycanases (PNGases) which remove glycans from glycoproteins during their degradation. The PNGases retain the catalytic triad that is typical of this fold and are predicted to have a reaction mechanism similar to that involved in transglutamination. In contrast, the RAD4/Xp-C proteins are predicted to be inactive and are likely to only possess the protein interaction function in DNA repair. These proteins also contain a long, low-complexity insert in the globular transglutaminase domain. The RAD4/Xp-C proteins, along with other inactive transglutaminase-fold proteins, represent a case of functional re-assignment of an ancient domain following the loss of the ancestral enzymatic activity. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. OI Anantharaman, Vivek/0000-0001-8395-0009 NR 29 TC 32 Z9 33 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD AUG 1 PY 2001 VL 10 IS 16 BP 1627 EP 1630 DI 10.1093/hmg/10.16.1627 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 463BH UT WOS:000170456600002 PM 11487565 ER PT J AU Saha, PK Udupa, JK Conant, EF Chakraborty, DP Sullivan, D AF Saha, PK Udupa, JK Conant, EF Chakraborty, DP Sullivan, D TI Breast tissue density quantification via digitized mammograms SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE fuzzy connectedness; glandular tissue; image analysis; image segmentation; mammograms ID PARENCHYMAL PATTERNS; IMAGE SEGMENTATION; MULTIPLE-SCLEROSIS; FUZZY-CONNECTEDNESS; CANCER RISK; SYSTEM; CLASSIFICATION; ALGORITHMS; VOLUME; INDEX AB Studies reported in the literature indicate that breast cancer risk is associated with mammographic densities. An objective, repeatable, and a quantitative measure of risk derived from mammographic densities will be of considerable use in recommending alternative screening paradigms and/or preventive measures. However, image processing efforts toward this goal seem to be sparse in the literature, and automatic and efficient methods do not seem to exist. In this paper, we describe and validate an automatic and reproducible method to segment dense tissue regions from fat within breasts from digitized mammograms using scale-based fuzzy connectivity methods. Different measures for characterizing mammographic density are computed from the segmented regions and their robustness in terms of their linear correlation across two different projections-cranio-caudal and medio-lateral-oblique-are studied. The accuracy of the method is studied by computing the area of mismatch of segmented dense regions using the proposed method and using manual outlining. A comparison between the mammographic density parameter taking into account the original intensities and that just considering the segmented area indicates that the former may have some advantages over the latter. C1 Univ Penn, Dept Radiol, Med Image Proc Grp, Philadelphia, PA 19104 USA. NCI, Rockville, MD 20852 USA. RP Udupa, JK (reprint author), Univ Penn, Dept Radiol, Med Image Proc Grp, 4th Floor,Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. RI Saha, Punam /F-8833-2011 FU NINDS NIH HHS [NS 37172] NR 32 TC 68 Z9 71 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD AUG PY 2001 VL 20 IS 8 BP 792 EP 803 DI 10.1109/42.938247 PG 12 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 460QM UT WOS:000170320100011 PM 11513030 ER PT J AU Vaquero, JJ Desco, M Pascau, J Santos, A Lee, I Seidel, J Green, MV AF Vaquero, JJ Desco, M Pascau, J Santos, A Lee, I Seidel, J Green, MV TI PET, CT, and MR image registration of the rat brain and skull SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE image reconstruction; positron emission tomography (PET); small animal imaging ID SMALL ANIMALS; RESOLUTION; SYSTEM; ALGORITHM; CAMERA; SPECT AB Spatially registered positron emission tomography (PET), computed tomography (CT), and magnetic resonance (MR) images of the same small animal offer potential advantages over PET alone: CT images should allow accurate, nearly noise-free correction of the PET image data for attenuation; the CT or MR images should permit more certain identification of structures evident in the PET images; and CT images provide a priori anatomical information that may be of use with resolution-improving image-reconstruction algorithms that model the PET imaging process. However, image registration algorithms effective in human studies have not been characterized in the small-animal setting. Accordingly, we evaluated the ability of the automated image registration (AIR) and mutual information (MI) algorithms to register PET images of the rat skull and brain to CT or MR images of the same animal. External fiducial marks visible in all three modalities were used to estimate residual errors after registration. The AIR algorithm registered PET bone-to-CT bone images with a maximum error of less than 1.0 mm. The registration errors for PET brain-to-CT brain images, however, were greater, and considerable user intervention was required prior to registration. The AIR algorithm either failed or required excessive user intervention to register PET and MR brain images. In contrast, the MI algorithm yielded smaller registration errors in all scenarios with little user intervention. The MI algorithm thus appears to be a more robust method for registering PET, CT, and MR images of the rat head. C1 NIH, Bethesda, MD 20892 USA. Univ Madrid, Hosp Gen Gregorio Maranon, Madrid 3, Spain. Univ Politecn Madrid, Madrid, Spain. RP Vaquero, JJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM juanjo@nih.gov; desco@mce.hggm.es; andres@die.upm.es RI Vaquero, Juan Jose/D-3033-2009; Pascau, Javier/B-5734-2013; Santos, Andres/C-4012-2009; Desco, Manuel/D-2822-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X; Pascau, Javier/0000-0003-1484-731X; Santos, Andres/0000-0001-7423-9135; Desco, Manuel/0000-0003-0989-3231 NR 19 TC 30 Z9 30 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD AUG PY 2001 VL 48 IS 4 BP 1440 EP 1445 DI 10.1109/23.958376 PN 2 PG 6 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 483XG UT WOS:000171660700017 ER PT J AU Tenney, CR Tornai, MP Smith, MF Turkington, TG Jaszczak, RJ AF Tenney, CR Tornai, MP Smith, MF Turkington, TG Jaszczak, RJ TI Uranium pinhole collimators for 511-keV photon SPECT imaging of small volumes SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE depleted uranium; pinhole collimator; small animal biomedical imaging; single photon emission computed tomography ID ULTRA-HIGH-RESOLUTION; EMISSION COMPUTED-TOMOGRAPHY; PET SCANNER; SMALL ANIMALS; PERFORMANCE; DESIGN; SYSTEM; PENETRATION; SENSITIVITY; MICROPET AB Depleted uranium (DU) pinhole collimators are evaluated for small-volume SPECT imaging of 511-keV gammas, with a view toward small-animal imaging. Tungsten (W) pinholes are examined for comparison. Line source measurements show planar full-width at half-maximum (FWHM) as low as 6.5 mm for a 1-mm DU pinhole, with SPECT system FWHM of 5.0 mm at 43-mm ROR and 6.7 mm at 69-mm ROR. Planar FWHM is smaller for DU than for W pinholes but is insensitive to aperture size for pinholes of 1-3 rum diameter at this energy for the collimators studied. These trends indicate penetration at pinhole edges, as confirmed by LSF shape and full-width at tenth-maximum trends. In SPECT scans of rod phantoms at 71-mm ROR, DU pinholes were only barely able to resolve cold rods as large as 4.7 mm (center-to-center spacing = 2 x diameter). For both F-18 alone and F-18 imaged along with Tc-99m, 3.9-mm hot rods were resolved. Te-99m scans resolved 2.3-mm rods with F-18 present and 1.5-mm rods without F-18. DU pinhole SPECT at 511 keV does not currently match the spatial resolution of high-resolution positron emission tomography (PET) but is open to improvement and, unlike PET, is capable of simultaneous multiple-isotope acquisitions. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. NIH, Bethesda, MD 20892 USA. RP Tenney, CR (reprint author), Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 29 TC 8 Z9 8 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD AUG PY 2001 VL 48 IS 4 BP 1483 EP 1489 DI 10.1109/23.958384 PN 2 PG 7 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 483XG UT WOS:000171660700023 ER PT J AU Morroll, S Goodchild, M Salmon, N Copeland, NG Gilbert, DJ Jenkins, NA Bumstead, N Boyd, Y AF Morroll, S Goodchild, M Salmon, N Copeland, NG Gilbert, DJ Jenkins, NA Bumstead, N Boyd, Y TI The genes encoding E-selectin (SELE) and lymphotactin (SCYC1) lie on separate chicken chromosomes although they are closely linked in human and mouse SO IMMUNOGENETICS LA English DT Article DE selectin; lymphotactin; paired related homeobox 1; chicken comparative mapping; COM0185 ID GENOMIC ORGANIZATION; GALLUS-DOMESTICUS; LINKAGE MAP; LOCALIZATION; CHEMOKINE; CLONING AB Three differentially expressed selectin genes (SELE, SELP, and SELL), important in the initial stages of leukocyte extravasation, have been reported in mammals. All three genes map close to the chemokine SCYC1 (small inducible cytokine subfamily C, member 1) in a large conserved chromosomal segment that extends from RXRG (retinoic acid receptor, gamma) to TNNT2 (troponin T2) on Chromosome (Chr) I in both human and mouse. In the mouse, we demonstrate that Sele is flanked by Prrx1 (paired-related homeobox gene 1) and Scyc1 and define the order of, and distances between, loci as centromere-Prrx1-(0.7 +/- 0.7 cM)-Sele-(1.2 +/- 0.9 cM)-Scyc1-telomere. In the chicken, we isolated BAC clones containing PRRX1, SELE, and SCYC1 and positioned them by fluorescent in situ hybridization. SELE and PRRX1 mapped to the short arm of chicken Chr 8 and SCYC1 mapped to the region equivalent to 1q11-1q13 on the long arm of chicken Chr 1. The location of SELE on chicken Chr 8 was independently established by linkage analysis of COM0185, an (AT)(16) microsatellite locus identified in a BAC clone that contained SELE. COM0185 was linked to several loci that mapped to one end of chicken Chr 8, with the order of loci, and genetic distances (in cM) between them defined as MSU0435, MSU0325-(7.8 +/- 3.7)-COM0185-(5.8 +/- 3.2)-ROS0338-(9.6 +/- 4.0)-ABR0322-(3.8 +/- 2.6)-GLUL. We have therefore positioned an evolutionary breakpoint in mammals and chickens between SELE and SCYC1. Furthermore, comparative mapping analysis of the RXRG-TNNT2 chromosomal segment that is conserved on human and mouse Chr 1 indicates that it is divided into four segments in the chicken, each of which maps to a different chromosome. C1 Inst Anim Hlth, Div Mol Biol, Newbury RG20 7NN, Berks, England. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Boyd, Y (reprint author), Inst Anim Hlth, Div Mol Biol, Newbury RG20 7NN, Berks, England. NR 27 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD AUG PY 2001 VL 53 IS 6 BP 477 EP 482 DI 10.1007/s002510100350 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 478BG UT WOS:000171322600006 PM 11685458 ER PT J AU Shevach, EM McHugh, RS Piccirillo, CA Thornton, AM AF Shevach, EM McHugh, RS Piccirillo, CA Thornton, AM TI Control of T-cell activation by CD4(+) CD25(+) suppressor T cells SO IMMUNOLOGICAL REVIEWS LA English DT Review ID THYMECTOMY AUTOIMMUNE GASTRITIS; IMMUNOLOGICAL SELF-TOLERANCE; LYMPHOCYTE-ASSOCIATED ANTIGEN-4; INTESTINAL INFLAMMATION; EFFECTOR FUNCTION; PARIETAL-CELLS; DISEASES; INHIBIT; MICE; COSTIMULATION AB Depletion of the minor (similar to 10%) subpopulation of CD4(+) T cells that co-expresses CD25 (interleukin (IL)-2 receptor alpha -chain) by thymectomy of neonates on the third day of life or by treatment of adult CD4(+) T cells with anti-CD25 a-nd complement results in the development of organ-specific autoimmunity, Autoimmune disease can be prevented by reconstitution of the animals with CD4(+) CD25 (+) cells. CD4(+) CD25(+)mediated protection of autoimmune gastritis does not require die suppressor cytokines IL-4, IL-10, or transforming growth factor (TGF)-beta. Mice that express a transgenic T-cell receptor (TCR) derived from a thymectomized newborn that recognizes the gastric parietal cell antigen H/ K ATPase all develop severe autoimmune gastritis very early in life. CD4(+) CD25(+) T cells are also powerful suppressors of the activation of both CD4(+) and CD8(+) T cells in vitro. Suppression is mediated by a cell contactdependent, cytokine-independent T-T interaction. Activation of CD4(+) CD25(+) via their TCR generates suppressor effector cells that are capable of non-specifically suppressing the activation of any CD4(+) or CDS+ T cell. Activation of suppressor effector function is independent of co-stimulation mediated by CD28/CTLA-4 interactions with CD80/CD86. We propose that CD4(+) CD25(+) T cells recognize organ-specific antigens, are recruited to sites of autoimmune damage where they are activated by their target antigen, and then physically interact with autoreactive CD4(+) or CD8(+) effector cells to suppress the development of autoimmune disease. C1 NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Cellular Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. NR 35 TC 387 Z9 428 U1 0 U2 8 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2001 VL 182 BP 58 EP 67 DI 10.1034/j.1600-065X.2001.1820104.x PG 10 WC Immunology SC Immunology GA 495FP UT WOS:000172329800004 PM 11722623 ER PT J AU Zipp, F Windemuth, C Dichgans, J Wienker, T Martin, R Muller, C AF Zipp, F Windemuth, C Dichgans, J Wienker, T Martin, R Muller, C TI Peripheral blood cell bulk cultures are not suitable for the analysis of the genetic control of T-cell cytokine function SO IMMUNOLOGY LETTERS LA English DT Article DE TNF; T lymphocytes; multiple sclerosis ID MYELIN BASIC-PROTEIN; NECROSIS-FACTOR-ALPHA; MULTIPLE-SCLEROSIS; HEALTHY-INDIVIDUALS; SUBSET ACTIVATION; CRYSTAL-STRUCTURE; MHC CONTROL; PEPTIDE; COMPLEX; HLA AB Recently evidence has been provided for a genetic control of T-cell dependent cytokine production by HLA-class II. Candidate genes in multiple sclerosis, a T-cell mediated autoimmune disease, are the disease-associated DR2, DQ6, Dw2 haplotype. Previous observations by us and others imply a HLA-DR2 dependent propensity of antigen-specific T-cell lines to produce increased amounts of TNF-alpha/beta. Here, we tested a possible association between HLA or disease status with cytokine production employing the simple and widely used method of bulk cultures. Peripheral blood cells of 48 patients and 68 healthy individuals were analyzed. We observed no significant differences of the cytokine production in relation to disease status or any HLA polymorphism. Our data indicate that, in contrast to monoclonal T-cell cultures, bulk cultures are not suitable to detect immunogenetic control of T-cell function. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Hosp Charite, Div Neuroimmunol, Dept Neurol, D-13353 Berlin, Germany. Univ Bonn, Dept Med Stat, D-5300 Bonn, Germany. Univ Tubingen, Dept Neurol, D-7400 Tubingen, Germany. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Dept Internal Med, Div Transplantationimmunol, D-7400 Tubingen, Germany. RP Zipp, F (reprint author), Univ Hosp Charite, Div Neuroimmunol, Dept Neurol, Campus Virchow,Forschungshaus,2-OG,R-535,Augusten, D-13353 Berlin, Germany. RI Zipp, Frauke/C-9968-2015 OI Zipp, Frauke/0000-0002-1231-1928 NR 29 TC 0 Z9 0 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 AUG PY 2001 VL 78 IS 1 BP 21 EP 27 DI 10.1016/S0165-2478(01)00227-9 PG 7 WC Immunology SC Immunology GA 461UV UT WOS:000170382600004 PM 11470147 ER PT J AU Derby, E Reddy, V Kopp, W Nelson, E Baseler, M Sayers, T Malyguine, A AF Derby, E Reddy, V Kopp, W Nelson, E Baseler, M Sayers, T Malyguine, A TI Three-color flow cytometric assay for the study of the mechanisms of cell-mediated cytotoxicity SO IMMUNOLOGY LETTERS LA English DT Article DE flow cytometry; cell-mediated cytotoxicity; CTL; NK ID ANNEXIN-V; CYTO-TOXICITY; APOPTOSIS AB Cytotoxic lymphocytes kill tumor or virus-infected target cells utilizing two mechanisms (1) release of lytic granules (containing perform and granzymes) and (2) Fas ligand (FasL)/Fas or TNF initiated apoptosis. We have examined mechanisms of target cell lysis using a new Flow Cytometric Cytotoxicity Assay (FC Assay). Target cells were labeled with PKH 67 dye. Cell death was estimated by 7-amino-actinomycin (7-AAD) inclusion and annexin V-PE binding. A strong direct correlation has been found between the percentage of dead target cells in the FC Assay and the results of Cr-51 release assay when human LAK and CTL were used as a model system. We have shown that both NK and CTL kill tumor cells mostly by granule-mediated mechanisms, as lysis was blocked by a perforin inhibitor Concanamycin A (Folimycin) but was significantly less sensitive to zVAD-FMK caspase inhibition. The FC assay allows accurate measurement of cell-mediated cytotoxicity as individual target cell death is detected directly. (C) 2001 Elsevier Science BN. All rights reserved. C1 Univ Calif Irvine, Irvine, CA 92697 USA. NCI, SAIC, Frederick, MD 20878 USA. RP Malyguine, A (reprint author), NCI, SAIC, POB B, Frederick, MD 21702 USA. RI Sayers, Thomas/G-4859-2015 FU PHS HHS [N01-C0-56000] NR 15 TC 52 Z9 54 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD AUG PY 2001 VL 78 IS 1 BP 35 EP 39 DI 10.1016/S0165-2478(01)00226-7 PG 5 WC Immunology SC Immunology GA 461UV UT WOS:000170382600006 PM 11470149 ER PT J AU Fatma, S Mushinski, JF Bansal, SK AF Fatma, S Mushinski, JF Bansal, SK TI Multiple isoforms of protein kinase C in lymphocytes and airway smooth muscle of guinea pig SO INDIAN JOURNAL OF BIOCHEMISTRY & BIOPHYSICS LA English DT Article ID SIGNAL-TRANSDUCTION; EXPRESSION; ISOENZYMES; CELLS; LUNG; ACTIVATION; MEMBER; FAMILY AB The isoenzyme pattern of protein kinase C (PKC) in lymphocytes and airway smooth muscles (ASM) was examined by Western blot using commercially available monoclonal antibodies. The results showed the presence of PKC alpha, beta, gamma, epsilon, eta, mu, xi and in lymphocytes and PKC alpha, gamma, epsilon, eta and xi in ASM. The unexpected feature was the presence of PKC gamma in both lymphocytes and ASM of guinea pigs. Expression of this PKC isoform is usually restricted to tissues in the central nervous system or spinal cord. Expression of PKC delta, theta, lambda and tau was not detected in either lymphocytes or ASM. C1 Univ Delhi, Dept Biochem, Vallabhbhai Patel Chest Inst, Delhi 110007, India. NCI, Genet Lab, NIH, Bethesda, MD 20892 USA. RP Bansal, SK (reprint author), Univ Delhi, Dept Biochem, Vallabhbhai Patel Chest Inst, Delhi 110007, India. NR 24 TC 1 Z9 1 U1 0 U2 0 PU NATL INST SCIENCE COMMUNICATION PI NEW DELHI PA DR K S KRISHNAN MARG, NEW DELHI 110 012, INDIA SN 0301-1208 J9 INDIAN J BIOCHEM BIO JI Indian J. Biochem. Biophys. PD AUG PY 2001 VL 38 IS 4 BP 280 EP 284 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 468QJ UT WOS:000170769400013 PM 11811627 ER PT J AU Letterio, JJ Lehrnbecher, T Pollack, G Walsh, TJ Chanock, SJ AF Letterio, JJ Lehrnbecher, T Pollack, G Walsh, TJ Chanock, SJ TI Invasive candidiasis stimulates hepatocyte and monocyte production of active transforming growth factor beta SO INFECTION AND IMMUNITY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; MURINE PERITONEAL-MACROPHAGES; INTERFERON-GAMMA PRODUCTION; T-CELL RESPONSES; TGF-BETA; HEPATOSPLENIC CANDIDIASIS; TARGETED DISRUPTION; IFN-GAMMA; MYCOBACTERIUM-TUBERCULOSIS; INTERLEUKIN-10 AB Candida albicans is an opportunistic fungal pathogen and a major cause of morbidity and mortality in patients with compromised immune function. The cytokine response to tissue invasion by C. albicans can influence the differentiation and function of lymphocytes and other mononuclear cells that are critical components of the host response. While the production of transforming growth factor beta (TGF-beta) has been documented in mice infected with C. albicans and is known to suppress phagocyte function, the cellular source and role of this cytokine in the pathogenesis of systemic candidiasis are not well understood. We have investigated the source of production of TGF-beta by immunohistochemical studies in tissue samples from patients with an uncommon complication of lymphoreticular malignancy, chronic disseminated candidiasis (CDC), and from a neutropenic-rabbit model of CDC. Liver biopsy specimens from patients with documented CDC demonstrated intense staining for extracellular matrix-associated TGF-beta1 within inflammatory granulomas, as well as staining for TGF-beta1 and TGF-beta3 within adjacent hepatocytes. These results correlate with the immunolocalization of TGF-beta3 observed in livers of infected neutropenic rabbits, using a neutralizing antibody that recognizes the mature TGF-beta protein. Human peripheral blood monocytes incubated with C. albicans in vitro release large amounts of biologically active TGF-beta1. The data demonstrate that local production of active TGF-betas by hepatocytes and by infected mononuclear cells is a component of the response to C. albicans infection that most probably contributes to disease progression in the immunocompromised host. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Gaithersburg, MD 20877 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Gaithersburg, MD 20877 USA. NCI, Ctr Adv Technol, NIH, Gaithersburg, MD 20877 USA. RP Chanock, SJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. NR 60 TC 17 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2001 VL 69 IS 8 BP 5115 EP 5120 DI 10.1128/IAI.69.8.5115-5120.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 456UP UT WOS:000170100900053 PM 11447193 ER PT J AU Morgan, DL Ward, SM Wilson, RE Price, HC O'Connor, RW Seely, JC Cunningham, ML AF Morgan, DL Ward, SM Wilson, RE Price, HC O'Connor, RW Seely, JC Cunningham, ML TI Inhalation toxicity studies of the alpha,beta-unsaturated ketones: Ethyl vinyl ketone SO INHALATION TOXICOLOGY LA English DT Article ID DOSE LEVELS; IDENTIFICATION; VOLATILES; ACROLEIN; RATS; MICE AB The National Toxicology Program is conducting a chemical class study to investigate the structure-activity relationships for the toxicity of alpha,beta -unsaturated ketones. Ethyl vinyl ketone (EVK) was selected for study because it is a representative straight-chain aliphatic alpha,beta -unsaturated ketone with extensive use and widespread exposure. Short-term inhalation studies of EVK were conducted to provide toxicity data for comparison with the related alpha,beta -unsaturated ketones 2-cyclohexene-1-one (CHX) and methyl vinyl ketone (MVK). These data will be used in designing chronic toxicity and carcinogenicity studies of these ketones. Male and female F344 rats and B6C3F1 mice were exposed to 0, 2, 4, or 8 ppm EVK 6 h/day, 5 days/wk for 13 wk. The nasal cavity was the major target organ of EVK in both rats and mice. Pathologic findings in both the olfactory and respiratory epithelium were observed. Lesions consisted primarily of olfactory epithelial necrosis, atrophy and regeneration, and/or hyperplasia and squamous metaplasia of the respiratory epithelium. Squamous metaplasia of the respiratory epithelium was present in all rats and mice exposed to 4 and 8 ppm EVK, and these lesions were more severe in rats than in mice. Few systemic effects were observed in rats and mice exposed to EVK. A transient decrease in total leukocytes due to decrements in lymphocyte and monocyte populations was present in male rats after exposure to 8 ppm for 3 and 21 days; however, this effect was not present after exposure for 13 wk. There were no chemical-related effects on micronucleus formation in mice, or on sperm motility and vaginal cytology in either species. EVK, like other alpha,beta -unsaturated ketones, is a reactive, direct-acting gaseous irritant with toxicity limited primarily to the upper respiratory tract. C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. ManTech Environm Technol Inc, Res Triangle Pk, NC 27709 USA. PATHCO Inc, Res Triangle Pk, NC USA. RP Morgan, DL (reprint author), NIEHS, Natl Toxicol Program, Mail Stop IF-00,POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD AUG PY 2001 VL 13 IS 8 BP 633 EP 658 DI 10.1080/08958370152409883 PG 26 WC Toxicology SC Toxicology GA 456XX UT WOS:000170109000001 PM 11498798 ER PT J AU Hiroi, N Ichijo, T Shimojo, M Ueshiba, H Tsuboi, K Miyachi, Y AF Hiroi, N Ichijo, T Shimojo, M Ueshiba, H Tsuboi, K Miyachi, Y TI Pituitary apoplexy caused by luteinizing hormone-releasing hormone in prolactin-producing adenoma SO INTERNAL MEDICINE LA English DT Article DE LH-RH test; pituitary adenoma; prolactinoma; FSH-producing pituitary adenoma ID ANTERIOR-PITUITARY; STIMULATION TESTS; MANAGEMENT; HEMORRHAGE; CLOMIPHENE; HEADACHE; PATIENT AB We report a case in which pituitary apoplexy developed shortly after an intravenous (i.v.) injection of luteinizing hormone-releasing hormone (LH-RH). A 56-year-old man with prolactin-producing pituitary tumor complained of severe headache, visual field loss and facial nerve palsy shortly after LH-RH test. Magnetic resonance image (MRI) revealed a hemorrhage in the pituitary adenoma. He showed dramatic improvement in his symptoms after decompression surgery. These findings suggest a causal relationship between the Lv. injection of LH-RH and pituitary apoplexy. Possible pituitary apoplexy should be kept in mind during pituitary testing. C1 Toho Univ, Sch Med, Dept Internal Med 1, Tokyo, Japan. RP Hiroi, N (reprint author), Nichhd, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D24,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. NR 29 TC 2 Z9 2 U1 0 U2 2 PU JAPAN SOC INTERNAL MEDICINE PI TOKYO PA 34-3 3-CHOME HONGO BUNKYO-KU, TOKYO, 113, JAPAN SN 0918-2918 J9 INTERNAL MED JI Intern. Med. PD AUG PY 2001 VL 40 IS 8 BP 747 EP 750 DI 10.2169/internalmedicine.40.747 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 461UL UT WOS:000170381800017 PM 11518116 ER PT J AU Fishelson, Z Hochman, I Greene, LE Eisenberg, E AF Fishelson, Z Hochman, I Greene, LE Eisenberg, E TI Contribution of heat shock proteins to cell protection from complement-mediated lysis SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE azetidine; complement resistance; deoxyspergualin; extracellular; hsp70; protection ID MEMBRANE ATTACK COMPLEX; HUMAN TUMOR-CELLS; GENE-TRANSCRIPTION; IMMUNOSUPPRESSANT 15-DEOXYSPERGUALIN; ERYTHROLEUKEMIA-CELLS; PLASMA-MEMBRANE; COGNATE PROTEIN; TRANSGENIC MICE; HSC70 GENE; HSP70 AB The possible participation of hsc70 and hsp70 in cellular protection from complement damage was studied. Human erythroleukemia K562 cells were pretreated with reagents affecting hsc70 or hsp70, and cell sensitivity to lysis by antibody and human complement was examined. Treatment with deoxyspergualin, an hsc70 inhibitor, sensitized K562 cells to complement lysis, whereas treatment with ethanol, butanol or hemin, inducers of hsc70 synthesis, protected the cells from complement-mediated lysis. Incubation of K562 at either 42 degreesC or with the amino acid analogue L-azetidine-2-carboxylic acid induced synthesis of hsp70, but not of hsc70. The latter treatment also conferred elevated resistance to complement lysis on K562 cells. Pretreatment of K562 cells with sub-lethal doses of complement desensitizes them to lethal complement doses. No effect of sublytic complement on synthesis of hsc70 and hsp70 was found. However, the results demonstrated that complement stress causes translocation of hsc70 from the cytoplasm to the K562 cell surface. Two monoclonal and two polyclonal antibodies identified hsc70 on the surface of intact, viable complement-stressed cells, while antibodies directed to hsp70 did not bind to these cells. Altogether, the results suggest that the heat shock proteins hsc70 and hsp70 play a role in cell defense against complement. C1 Tel Aviv Univ, Sackler Sch Med, Dept Cell Biol & Histol, IL-69978 Tel Aviv, Israel. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Fishelson, Z (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Cell Biol & Histol, IL-69978 Tel Aviv, Israel. NR 61 TC 24 Z9 27 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD AUG PY 2001 VL 13 IS 8 BP 983 EP 991 DI 10.1093/intimm/13.8.983 PG 9 WC Immunology SC Immunology GA 463MY UT WOS:000170481000002 PM 11470768 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI Hypoxia-inducible factor: Achilles' heel of antiangiogenic cancer therapy (Review) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE hypoxia; antiangiogenic therapy ID ENDOTHELIAL GROWTH-FACTOR; HUMAN PROSTATE-CANCER; TUMOR-SUPPRESSOR PROTEIN; FACTOR 1-ALPHA; DRUG-RESISTANCE; SIGNAL-TRANSDUCTION; SOLID TUMORS; ANGIOGENESIS; CELLS; EXPRESSION AB Could a rational, hypothesis-driven and well-tolerated therapy drive tumor progression? This scenario can be foreseen for antiangiogenic therapy, despite it is one of the most elegant anticancer strategies. Antiangiogenic agents inhibit growth of endothelial cells resulting in tumor hypoxia and starvation which in turn inhibit tumor growth. On the other hand, it is known that hypoxia selects for a highly aggressive and metastatic cancer and is associated with unfavorable prognosis. This review attempts to reconcile these opposite notions and to revisit the thesis that antiangiogenic therapy is 'resistant to resistance'. The latter logical paradigm is based on the notion that endothelial cells cannot become drug resistant. Although endothelial cells may not acquire drug-resistance, cancer cells can acquire hypoxia-resistance which is also associated with the resistance to growth arrest and apoptosis as well as high metastatic potentials. Hypoxia-inducible factor (HIF-1) renders cells capable of surviving hypoxia and stimulating endothelial growth. Disruption of the HIF-1 pathway inhibits tumor growth, indicating HIF-1 as a potential anticancer target. Furthermore, inhibition of HIF-1 is a mechanism-based antiangiogenic strategy because it is the HIF-mediated response that drives tumor angiogenesis. Pharmacological approaches to HIF-1 inhibition are discussed. C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Blagosklonny, MV (reprint author), NCI, Med Branch, NIH, Bldg 10,R 12N226, Bethesda, MD 20892 USA. NR 82 TC 70 Z9 71 U1 1 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD AUG PY 2001 VL 19 IS 2 BP 257 EP 262 PG 6 WC Oncology SC Oncology GA 452RQ UT WOS:000169872900004 PM 11445836 ER PT J AU Shen, DF Matteson, DM Tuaillon, N Suedekum, BK Buggage, RR Chan, CC AF Shen, DF Matteson, DM Tuaillon, N Suedekum, BK Buggage, RR Chan, CC TI Involvement of apoptosis and interferon-gamma in murine toxoplasmosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INDUCED UVEITIS EMIU; CD8+ LYMPHOCYTES-T; OCULAR TOXOPLASMOSIS; NITRIC-OXIDE; IFN-GAMMA; TNF-ALPHA; MACROPHAGE ACTIVATION; IMMUNE PRIVILEGE; PROTECTIVE ROLE; CELL-DEATH AB PURPOSE. A murine toxoplasmosis model has been developed that results in central nervous system (CNS) and ocular inflammation characterized by encephalitis with numerous brain tissue cysts and milder inflammation with rare tissue cysts in the eye after 4 weeks of Toxoplasma gondii infection. In this model IFN gamma and inducible nitric oxide (iNO) are protective against T. gondii infection. In this study, the role of apoptosis in the pathogenesis of toxoplasmosis was investigated. METHODS. C57BL/6 (wild-type mice), B6MRL/lpr, and B6MRL/gld (defective Fas or FasL expression, respectively) mice were infected intraperitoneally with 20 to 30 tissue cysts of the ME-49 strain of T. gondii. Mice were killed at days 0, 14, or 28 after infection. The eyes and brains were harvested for histologic, immunohistochemical, and molecular studies. Analysis included immunostaining for Fas, FasL, Bcl-2, and Bax; in situ apoptosis detection (TUNEL assay); RT-PCR amplification for IFN gamma; and measurement of ocular nitrite levels. The control mice were naive mice of each strain that received no inoculation or injection. RESULTS. Wild-type mice appeared to constitutively express apoptotic molecules at higher levels in the eye than in the brain. Consequently, during T. gondii infection, apoptosis was greater in the eyes than in the brain. Untreated naive lpr and gld mice showed no expression of Fas and FasL, respectively. After infection, a slightly higher number of tissue cysts (lpr, 11.8 +/- 2.4; gld, 10.3 +/- 3.4) were found in the brains of the mutants than in the control animals (8.8 +/- 2.9). However, no significant differences between the number of apoptotic cells, inflammatory scores, or number of tissue cysts were noted in the eyes. IFN gamma mRNA in control mice was detected at day 28 after infection, whereas in both mutants, mRNA production occurred earlier, at day 14. Ocular nitrite levels were higher in lpr and gld mice than in wild-type mice. CONCLUSIONS. No significant difference in the degree of ocular inflammation and apoptosis was detected between the wildtype and Fas or FasL mutant mice. However, there was an earlier and subjectively greater expression of IFN gamma in the brain and eye and a higher level of nitrite in the ocular tissue of mutant strains than in the wild type. Multiple factors are likely to be involved in the pathogenesis of ocular toxoplasmosis. C1 NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. NR 47 TC 20 Z9 25 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2001 VL 42 IS 9 BP 2031 EP 2036 PG 6 WC Ophthalmology SC Ophthalmology GA 462XL UT WOS:000170445000013 PM 11481268 ER PT J AU Strunnikova, N Baffi, J Gonzalez, A Silk, W Cousins, SW Csaky, KG AF Strunnikova, N Baffi, J Gonzalez, A Silk, W Cousins, SW Csaky, KG TI Regulated heat shock protein 27 expression in human retinal pigment epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 05, 2000 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID INDUCED CELL-DEATH; AGE-RELATED MACULOPATHY; GREEN FLUORESCENT PROTEIN; ALPHA-B-CRYSTALLIN; PLASMA-MEMBRANE; GENE-TRANSFER; TNF-ALPHA; MACULAR DEGENERATION; MAMMALIAN-CELLS; STRESS PROTEINS AB PURPOSE. To examine the expression and regulation of an injury-related protein, heat shock protein (Hsp) 27, in retinal pigment epithelium (RPE), since RPE injury may be an important feature of age-related macular degeneration (ARMD). METHODS. Retinal cross sections from eyes of Lewis rats were examined for Hsp27 in vivo by immunohistochemistry, and in vitro expression of Hsp27 in human ARPE-19 cells was determined by Northern and Western blot analysis. Oxidant-mediated injury was performed by exposing ARPE-19 cells to myeloperoxidase and hydrogen peroxide. Cell lines stably expressing green fluorescent protein (GFP) targeted to the cell membrane were used to study injury-induced membrane blebbing, and XTT conversion was used to detect cell viability. RESULTS. High level of Hsp27 expression was detected in vivo in ganglion cells, RPE, and photoreceptor outer segments of rat retina. ARPE-19 cells also expressed high levels of Hsp27 in vitro. Oxidative injury in ARPE-19 cells resulted in transcriptional and translational activation of Hsp27 and induced extensive membrane blebbing. A high level of Hsp 27 protein was detected within membrane blebs. Increased expression of Hsp27 was also observed in differentiated ARPE-19 cells when compared with dividing cells. Higher Hsp27 levels in differentiated RPE cells correlated with increased viability and phenotypically different blebbing after exposure to the injury stimulus. In addition, sublethal injury doses caused a moderate amount of membrane blebbing, which was well tolerated by differentiated ARPE-19 cells. CONCLUSIONS. These results indicate that Hsp27 may be an important component of the RPE injury response and may contribute to injury-induced membrane blebbing in differentiated RPE cells. It is hypothesized that Hsp27 levels may play a role in disease states in the retina, such as ARMD. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Miami, Dept Ophthalmol, Miami, FL USA. RP Csaky, KG (reprint author), NEI, Immunol Lab, NIH, Bldg 10-10N119, Bethesda, MD 20892 USA. NR 77 TC 39 Z9 40 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2001 VL 42 IS 9 BP 2130 EP 2138 PG 9 WC Ophthalmology SC Ophthalmology GA 462XL UT WOS:000170445000027 PM 11481282 ER PT J AU Pras, E Pras, E Bakhan, T Levy-Nissenbaum, E Lahat, H Assia, EI Garzozi, HJ Kastner, DL Goldman, B Frydman, M AF Pras, E Pras, E Bakhan, T Levy-Nissenbaum, E Lahat, H Assia, EI Garzozi, HJ Kastner, DL Goldman, B Frydman, M TI A gene causing autosomal recessive cataract maps to the short arm of chromosome 3 SO ISRAEL MEDICAL ASSOCIATION JOURNAL LA English DT Article DE recessive; cataract; mapping; linkage; single nucleotide polymorphism ID DOMINANT CONGENITAL CATARACT; ALPHA-B-CRYSTALLIN; MISSENSE MUTATION; LINKAGE; CLEARER; LOCUS; CRYAA AB Background: Fourteen loci have been associated with autosomal dominant cataract, but only one with the recessive form of the disease. Objectives: To find the chromosomal location of a gene causing autosomal recessive cataract in three inbred Arab families. Methods: A single nucleotide polymorphism-based genome-wide search, with the Effymetrix GeneChip HuSNP genotyping array, was performed on a pooled DNA sample from six affected family members in a search for regions showing homozygosity. Using conventional microsatellite markers, regions of homozygosity were further analyzed in all the families. Results: A region on chromosome 3p spanning 43 megabases showed homozygosity with 13 consecutive SNPs. Three microsatellite markers from this region yielded lod scores >3.00. A maximal two-point lod of 4.83 was obtained with the marker D3S1298 at 0=0.004. Haplotype analysis placed the disease gene in a 20 Mb interval between D3S1768 and D3S2409. Conclusions: A gene causing autosomal recessive cataract maps to the short arm of chromosome 3. C1 Chaim Sheba Med Ctr, Danek Gertner Inst Human Genet, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. HaEmek Med Ctr, Dept Ophthalmol, Afula, Israel. Natl Inst Arthrit & Musculoskeletal & Skin Dis, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. Sapir Med Ctr, Dept Ophthalmol, Kefar Sava, Israel. RP Pras, E (reprint author), Chaim Sheba Med Ctr, Danek Gertner Inst Human Genet, IL-52621 Tel Hashomer, Israel. EM epras@post.tau.ac.il NR 23 TC 34 Z9 34 U1 0 U2 1 PU ISRAEL MEDICAL ASSOC JOURNAL PI RAMAT GAN PA 2 TWIN TOWERS, 11TH FL, 35 JABOTINSKY ST, PO BOX 3604, RAMAT GAN 52136, ISRAEL SN 1565-1088 J9 ISR MED ASSOC J JI Isr. Med. Assoc. J. PD AUG PY 2001 VL 3 IS 8 BP 559 EP 562 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 478GF UT WOS:000171334800001 PM 11519376 ER PT J AU Pezzolo, A Prigione, I Facchetti, P Castellano, E Viale, M Gimelli, G Pistoia, V AF Pezzolo, A Prigione, I Facchetti, P Castellano, E Viale, M Gimelli, G Pistoia, V TI T-cell apoptosis in ICF syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID DNA METHYLTRANSFERASE GENE; IMMUNODEFICIENCY SYNDROME; INSTABILITY C1 Ist Giannina Gaslini, Lab Oncol, I-16148 Genoa, Italy. Ist Giannina Gaslini, Lab Cytogenet, I-16148 Genoa, Italy. Ist Giannina Gaslini, Div Pediat 3, I-16148 Genoa, Italy. Natl Canc Inst, Pharmacol Lab, Genoa, Italy. RP Pezzolo, A (reprint author), Ist Giannina Gaslini, Lab Oncol, Largo G Gaslini 5, I-16148 Genoa, Italy. NR 7 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2001 VL 108 IS 2 BP 310 EP 312 DI 10.1067/mai.2001.116863 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 465HY UT WOS:000170584600028 PM 11496256 ER PT J AU Wootton, JC Sparber, A AF Wootton, JC Sparber, A TI Surveys of complementary and alternative medicine: Part III. Use of alternative and complementary therapies for HIV/AIDS SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; AIDS AB A series of 16 independent studies of the human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) community and their use of alternative and complementary therapies over the past 10 years helps document the changes that have occurred. The earlier studies are characterized by political activism, lack of confidence in conventional therapies, and widespread use of alternative pharmacological therapies and unapproved drug use. The improvement of conventional treatment since the mid-1990s has been accompanied by a greater emphasis on complementary therapies used in conjunction with conventional drug therapy. Mind-body or psycho-spiritual therapies that help the patient cope with stress and adjust to life-threatening illness are the most popular. C1 Alternat Med Fdn Inc, Bethesda, MD 20814 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wootton, JC (reprint author), Alternat Med Fdn Inc, 5411 W Cedar Lane,205A, Bethesda, MD 20814 USA. NR 17 TC 28 Z9 28 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD AUG PY 2001 VL 7 IS 4 BP 371 EP 377 DI 10.1089/107555301750463251 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 469WM UT WOS:000170839100011 PM 11558780 ER PT J AU Ryan, AS Muller, DC Elahi, D AF Ryan, AS Muller, DC Elahi, D TI Sequential hyperglycemic-euglycemic clamp to assess beta-cell and peripheral tissue: studies in female athletes SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE glucose kinetics; maximal oxygen uptake; insulin secretion ID BODY-FAT DISTRIBUTION; INSULIN ACTION; GLUCOSE-TOLERANCE; POSTMENOPAUSAL WOMEN; DIABETES-MELLITUS; EXERCISE; MEN; SECRETION; HUMANS; SENSITIVITY AB Insulin secretion and rate of utilization (Rd) of glucose were tested during a newly developed sequential clamp in 42 highly trained female athletes (A; 18-69 yr old) and 14 sedentary control women (C; 18-50 yr old; body mass index <25 kg/m(2)). The A women were categorized into four age groups: 18-29, 30-39, 40-49, and 50-69 yr old. The C women were also grouped by age (18-29 and 40-50 yr old). During the three-step clamp (hyperglycemia, return to euglycemia, and hyperinsulinemia), glucose turnover was assessed with [3-H-3] glucose. Among the A, the youngest group had the largest first- and second-phase insulin response, which was significantly different from the oldest A (P < 0.05). Among the two C groups, first- phase response of both groups and second-phase response of the older group was higher than respective age-matched A (P, 0.05). During the hyperglycemic period, glucose Rd was similar among A groups and between A and C. Despite similar levels of insulin between groups during the hyperinsulinemic period (similar to 400 pmol/l), A utilized 36% more glucose than C (P < 0.001). Glucose Rd was not different across the age groups of A. This newly developed sequential clamp procedure allows assessment of both -cell sensitivity to glucose and peripheral tissue sensitivity to insulin in a single session. We have shown that physical activity improves beta -cell efficiency across the age span in women and ameliorates the effect of age on the decline of peripheral tissue sensitivity to insulin. C1 Vet Affairs Med Ctr, GRECC 18, Geriatr Serv, Div Gerontol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. NIA, Lab Clin Physiol, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Ryan, AS (reprint author), Vet Affairs Med Ctr, GRECC 18, Geriatr Serv, Div Gerontol, Baltimore, MD 21201 USA. FU NIA NIH HHS [1T32-AG-00219, AG-00599, P6O-AG-12583, KO1-AG-00747] NR 38 TC 12 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD AUG PY 2001 VL 91 IS 2 BP 872 EP 881 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 454AU UT WOS:000169950900043 PM 11457805 ER PT J AU Zheng, M Wang, X Templeton, LJ Smulski, DR LaRossa, RA Storz, G AF Zheng, M Wang, X Templeton, LJ Smulski, DR LaRossa, RA Storz, G TI DNA microarray-mediated transcriptional profiling of the Escherichia coli response to hydrogen peroxide SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; OXIDATIVE STRESS; SALMONELLA-TYPHIMURIUM; EXPRESSION ANALYSIS; RNA; REGULON; GENE; OXYR; K-12; ISCS AB The genome-wide transcription profile of Escherichia coli cells treated with hydrogen peroxide was examined with a DNA microarray composed of 4,169 E. coli open reading frames. By measuring gene expression in isogenic wild-type and oxyR deletion strains, we confirmed that the peroxide response regulator OxyR activates most of the highly hydrogen peroxide-inducible genes. The DNA microarray measurements allowed the identification of several new OxyR-activated genes, including the hemH heme biosynthetic gene; the six-gene suf operon, which may participate in Fe-S cluster assembly or repair; and four genes of unknown function, We also identified several genes, including uxuA, encoding mannonate hydrolase, whose expression might be repressed by OxyR, since their expression was elevated in the Delta oxyR mutant strain. In addition, the induction of some genes was found to be OxyR independent, indicating the existence of other peroxide sensors and regulators in E, coli, For example, the ise operon, which specifies Fe-S cluster formation and repair activities, was induced by hydrogen peroxide in strains lacking either OxyR or the superoxide response regulators SoxRS. These results expand our understanding of the oxidative stress response and raise interesting questions regarding the nature of other regulators that modulate gene expression in response to hydrogen peroxide. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Dupont Co, Cent Res & Dev, Biochem Sci & Engn, Wilmington, DE 19880 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 41 TC 516 Z9 540 U1 3 U2 35 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2001 VL 183 IS 15 BP 4562 EP 4570 DI 10.1128/JB.183.15.4562-4570.2001 PG 9 WC Microbiology SC Microbiology GA 451VX UT WOS:000169824000019 PM 11443091 ER PT J AU Zheng, M Wang, XD Doan, B Lewis, KA Schneider, TD Storz, G AF Zheng, M Wang, XD Doan, B Lewis, KA Schneider, TD Storz, G TI Computation-directed identification of OxyR DNA binding sites in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DISULFIDE BOND FORMATION; OXIDATIVE STRESS; IN-VIVO; PROTEIN; DSBG; SEQUENCE; OXIDOREDUCTASE; TRANSCRIPTION; ACTIVATION; REGULON AB A computational search was carried out to identify additional targets for the Escherichia coli OxyR transcription factor, This approach predicted OxyR binding sites upstream of dsbG, encoding a periplasmic disulfide bond chaperone-isomerase; upstream of fhuF, encoding a protein required for iron uptake; and within yfdI, DNase I footprinting assays confirmed that oxidized OxyR bound to the predicted site centered 54 bp upstream of the dsbG gene and 238 bp upstream of a known OxyR binding site in the promoter region of the divergently transcribed ahpC gene. Although the new binding site was near dsbG, Northern blotting and primer extension assays showed that OxyR binding to the dsbG-proximal site led to the induction of a second ahpCF transcript, while OxyR binding to the ahpCF-proximal site leads to the induction of both dsbG and ahpC transcripts. Oxidized OxyR binding to the predicted site centered 40 bp upstream of the fhuF gene was confirmed by DNase I footprinting, but these assays further revealed a second higher-affinity site in the fhuF promoter, Interestingly, the two OxyR sites in the fhuF promoter overlapped with two regions bound by the Fur repressor. Expression analysis revealed that fhuF was repressed by hydrogen peroxide in an OxyR-dependent manner, Finally, DNase I footprinting experiments showed OxyR binding to the site predicted to be within the coding sequence of yfdI, These results demonstrate the versatile modes of regulation by OxyR and illustrate the need to learn more about the ensembles of binding sites and transcripts in the E, call genome. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Exptl & Computat Biol, Frederick, MD 21702 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr,MSC 5430, Bethesda, MD 20892 USA. OI Schneider, Thomas/0000-0002-9841-1531; Storz, Gisela/0000-0001-6698-1241 NR 24 TC 88 Z9 94 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2001 VL 183 IS 15 BP 4571 EP 4579 DI 10.1128/JB.183.15.4571-4579.2001 PG 9 WC Microbiology SC Microbiology GA 451VX UT WOS:000169824000020 PM 11443092 ER PT J AU Srikantha, T Tsai, L Daniels, K Klar, AJS Soll, DR AF Srikantha, T Tsai, L Daniels, K Klar, AJS Soll, DR TI The histone deacetylase genes HDA1 and RPD3 play distinct roles in regulation of high-frequency phenotypic switching in Candida albicans SO JOURNAL OF BACTERIOLOGY LA English DT Article ID WHITE-OPAQUE TRANSITION; TRANSCRIPTIONAL REPRESSION; SACCHAROMYCES-CEREVISIAE; ASPARTYL PROTEINASES; RIBOSOMAL DNA; WH11 GENE; YEAST; PHASE; STRAINS; SIR2 AB Five histone deacetylase genes (HDA1, RPD3, HOS1, HOS2, and HOS3) have been cloned from Candida albicans and characterized. Sequence analysis and comparison with 17 additional deacetylases resulted in a phylogenetic tree composed of three major groups. Transcription of the deacetylases HDA1 and RPD3 is downregulated in the opaque phase of the white-opaque transition in strain WO-1, HOS3 is selectively transcribed as a 2.5-kb transcript in the white phase and as a less-abundant 2.3-kb transcript in the opaque phase, HD:II and RPD3 were independently deleted in strain WO-1, and both switching between the white and opaque phases and the downstream regulation of phase-specific genes were analyzed. Deletion of HDA1 resulted in an increase in the frequency of switching from the white phase to the opaque phase, but had no effect on the frequency of switching from the opaque phase to the white phase. Deletion of RPD3 resulted in an increase in the frequency of switching in both directions. Deletion of HDAI resulted in reduced white-phase-specific expression of the EFG1 3.2-kb transcript, but had no significant effect on white-phase-specific expression of WH11 or opaque-phase-specific expression of OP4, SAP1, and SAP3. Deletion of RPD3 resulted in reduced opaque-phase-specific expression of OP4 SAP1, and SAP3 and a slight reduction of white-phase-specific expression of WH11 and 3.2-kb EFG1. Deletion of neither HDAI nor RPD3 affected the high level of white-phase expression and the low level of opaque-phase expression of the MADS box protein gene MCM1, which has been implicated in the regulation of opaque-phase-specific gene expression. In addition, there was no effect on the phase-regulated levels of expression of the other deacetylase genes. These results demonstrate that the two, deacetylase genes HDA1 and RPD3 play distinct roles in the suppression of switching, that the two play distinct and selective roles in the regulation of phase-specific genes, and that the deacetylases are in turn regulated by switching. C1 Univ Iowa, Dept Sci Biol, Iowa City, IA 52242 USA. NCI, Frederick Canc Res & Dev Ctr, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Soll, DR (reprint author), Univ Iowa, Dept Sci Biol, Iowa City, IA 52242 USA. EM david-soll@uiowa.edu FU NIAID NIH HHS [AI2392] NR 65 TC 79 Z9 97 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2001 VL 183 IS 15 BP 4614 EP 4625 DI 10.1128/JB.183.15.4614-4625.2001 PG 12 WC Microbiology SC Microbiology GA 451VX UT WOS:000169824000025 PM 11443097 ER PT J AU Eggers, CH Kimmel, BJ Bono, JL Elias, AF Rosa, P Samuels, DS AF Eggers, CH Kimmel, BJ Bono, JL Elias, AF Rosa, P Samuels, DS TI Transduction by phi BB-1, a bacteriophage of Borrelia burgdorferi SO JOURNAL OF BACTERIOLOGY LA English DT Article ID 32-KILOBASE CIRCULAR PLASMIDS; LIPOPROTEIN GENE FAMILY; LYME-DISEASE SPIROCHETE; OUTER SURFACE-PROTEINS; UPSTREAM HOMOLOGY BOX; SUPERCOILED PLASMIDS; EXPRESSION; AGENT; OSPE; HYODYSENTERIAE AB We previously described a bacteriophage of the Lyme disease agent Borrelia burgdorferi designated phi BB-1. This phage packages the host complement of the 32-kb circular plasmids (cp32s), a group of homologous molecules found throughout the genus Borrelia. To demonstrate the ability of phi BB-1 to package and transduce DNA, a kanamycin resistance cassette was inserted into a cloned fragment of phage DNA, and the resulting construct was transformed into B. burgdorferi CA-11.2A cells. The kan cassette recombined into a resident cp32 and was stably maintained. The cp32 containing the kan cassette was packaged by phi BB-1 released from this B. burgdorferi strain. phi BB-1 has been used to transduce this antibiotic resistance marker into naive CA-11.2A cells, as well as two other strains of B. burgdorferi. This is the first direct evidence of a mechanism for lateral gene transfer in B. burgdorferi. C1 Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Samuels, DS (reprint author), Univ Montana, Div Biol Sci, 32 Campus Dr 4824, Missoula, MT 59812 USA. EM samuels@selway.umt.edu RI Samuels, D Scott/B-7549-2012 OI Samuels, D Scott/0000-0001-8352-7593 FU NIAID NIH HHS [AI41559] NR 42 TC 51 Z9 53 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2001 VL 183 IS 16 BP 4771 EP 4778 DI 10.1128/JB.183.16.4771-4778.2001 PG 8 WC Microbiology SC Microbiology GA 457CB UT WOS:000170118600012 PM 11466280 ER PT J AU Nolling, J Breton, G Omelchenko, MV Makarova, KS Zeng, QD Gibson, R Lee, HM Dubois, J Qiu, DY Hitti, J Wolf, YI Tatusov, RL Sabathe, F Doucette-Stamm, L Soucaille, P Daly, MJ Bennett, GN Koonin, EV Smith, DR AF Nolling, J Breton, G Omelchenko, MV Makarova, KS Zeng, QD Gibson, R Lee, HM Dubois, J Qiu, DY Hitti, J Wolf, YI Tatusov, RL Sabathe, F Doucette-Stamm, L Soucaille, P Daly, MJ Bennett, GN Koonin, EV Smith, DR CA GTC Sequencing Ctr Prod Finishing TI Genome sequence and comparative analysis of the solvent-producing bacterium Clostridium acetobutylicum SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ACETONE-BUTANOL FERMENTATION; BACILLUS-SUBTILIS; PSI-BLAST; SCAFFOLDING PROTEIN; GENES; ATCC-824; IDENTIFICATION; SPORULATION; CELLULOSOME; TOOL AB The genome sequence of the solvent-producing bacterium Clostridium acetobutylicum ATCC 824 has been determined by the shotgun approach. The genome consists of a 3.94-Mb chromosome and a 192-kb megaplasmid that contains the majority of genes responsible for solvent production. Comparison of C. acetobutylicum to Bacillus subtilis reveals significant local conservation of gene order, which has not been seen in comparisons of other genomes with similar, or, in some cases closer, phylogenetic proximity. This conservation allows the prediction of many previously undetected operons in both bacteria. However, the C. acetobutylicum genome also contains a significant number of predicted operons that are shared with distantly related bacteria and archaea but not with B. subtilis. Phylogenetic analysis is compatible with the dissemination of such operons by horizontal transfer. The enzymes of the solventogenesis pathway and of the cellulosome of C. acetobutylicum comprise a new set of metabolic capacities not previously represented in the collection of complete genomes. These enzymes show a complex pattern of evolutionary affinities, emphasizing the role of lateral gene exchange in the evolution of the unique metabolic profile of the bacterium. Many of the sporulation genes identified in B. subtilis are missing in C. acetobutylicum, which suggests major differences in the sporulation process. Thus, comparative analysis reveals both significant conservation of the genome organization and pronounced differences in many systems that reflect unique adaptive strategies of the two gram-positive bacteria. C1 Genome Therapeut Corp, GTC Sequencing Ctr, Waltham, MA 02453 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20814 USA. Inst Natl Sci Appl, Dept Genie Biochim, F-31077 Toulouse, France. Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA. RP Smith, DR (reprint author), Genome Therapeut Corp, GTC Sequencing Ctr, 100 Beaver St, Waltham, MA 02453 USA. NR 88 TC 497 Z9 670 U1 8 U2 80 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD AUG PY 2001 VL 183 IS 16 BP 4823 EP 4838 DI 10.1128/JB.183.16.4823-4838.2001 PG 16 WC Microbiology SC Microbiology GA 457CB UT WOS:000170118600018 PM 11466286 ER PT J AU Wehr, TA AF Wehr, TA TI Photoperiodism in humans and other primates: Evidence and implications SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Review DE melatonin; light; seasons; reproduction; depression ID SEASONAL AFFECTIVE-DISORDER; MALE RHESUS-MONKEYS; HUMAN SUPRACHIASMATIC NUCLEUS; HUMAN MELATONIN SECRETION; CIRCADIAN TIMING SYSTEM; GOMBE NATIONAL-PARK; HUMAN-REPRODUCTION; WINTER DEPRESSION; SERUM MELATONIN; LIGHT TREATMENT AB Most of the anatomical and molecular substrates of the system that encodes changes in photoperiod in the duration of melatonin secretion, and the receptor molecules that read this signal, have been shown to be conserved in monkeys and humans, and the functions of this system appear to be intact from the level of the retina to the level of the melatonin-duration signal of change of season. While photoperiodic seasonal breeding has been shown to occur in monkeys, it remains unclear whether photoperiod and mediation of photoperiod's effects by melatonin influence human reproduction. Epidemiological evidence suggests that inhibition of fertility by heat in men in summer contributes to seasonal variation in human reproduction at lower latitudes and that stimulation of fertility by lengthening of the photoperiod in spring contributes to the variation at higher latitudes. Parallels between the seasonality of human reproduction and seasonal affective disorder suggest that they may be governed by common biological processes. Historical and experimental evidence indicates that human responses to seasonal changes in the natural photoperiod may have been more robust prior to the Industrial Revolution and that subsequently they have been increasingly suppressed by alterations of the physical environment. C1 NIMH, Sect Biol Rhythms, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Wehr, TA (reprint author), NIMH, Sect Biol Rhythms, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 123 TC 127 Z9 135 U1 4 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD AUG PY 2001 VL 16 IS 4 BP 348 EP 364 DI 10.1177/074873001129002060 PG 17 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 482WJ UT WOS:000171600000006 PM 11506380 ER PT J AU Zweckstetter, M Bax, A AF Zweckstetter, M Bax, A TI Characterization of molecular alignment in aqueous suspensions of Pf1 bacteriophage SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE alignment; diamagnetic susceptibility; dipolar coupling; liquid crystal; nematic; paranematic; Pf1 phage; virial theory ID LIQUID-CRYSTALLINE MEDIUM; PROTEIN-STRUCTURE DETERMINATION; IMMUNOGLOBULIN-BINDING DOMAIN; DIPOLAR COUPLING INTERACTIONS; NEMATIC PHASE-TRANSITION; FILAMENTOUS BACTERIOPHAGE; COLLOIDAL SUSPENSION; BIOLOGICAL MACROMOLECULES; RODLIKE PARTICLES; POLY-ELECTROLYTES AB The phase diagram of Pf1 solutions has been studied indirectly by observation of H-2 quadrupole splittings of the solvent signal and measurement of dipolar couplings in solute macromolecules. At low volume fractions of Pf1 and at high ionic strength, alignment of both the phage and the solute depends strongly on the strength of the magnetic field. Both the theoretical and experimentally determined phase diagram of Pf1 show that at low concentrations and high ionic strengths the solution becomes isotropic. However, just below the nematic phase boundary the behavior of the system is paranematic, with cooperative alignment which depends on the strength of the applied magnetic field. Above 16 mg/ml Pf1 is fully nematic up to 600 mM NaCl. Alignment of proteins with a significant electric dipole moment, which tends to be strong in Pf1, can be reduced by either high ionic strength or low phage concentration. Because ionic strength modulates both the orientation and magnitude of the alignment tensor in Pf1 medium, measurement at two ionic strengths can yield linearly independent alignment tensors. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Zweckstetter, M (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 61 TC 83 Z9 85 U1 1 U2 9 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD AUG PY 2001 VL 20 IS 4 BP 365 EP 377 DI 10.1023/A:1011263920003 PG 13 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 462GX UT WOS:000170413300006 PM 11563559 ER PT J AU Qin, LX Tang, ZY Ye, SL Liu, YK Ma, ZC Zhou, XD Wu, ZQ Lin, ZY Sun, FX Tian, J Guan, XY Pack, SD Zhuang, ZP AF Qin, LX Tang, ZY Ye, SL Liu, YK Ma, ZC Zhou, XD Wu, ZQ Lin, ZY Sun, FX Tian, J Guan, XY Pack, SD Zhuang, ZP TI Chromosome 8p deletion is associated with metastasis of human hepatocellular carcinoma when high and low metastatic models are compared SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE hepatocellular carcinoma (HCC); metastasis; chromosome; comparative genomic hybridization (CGH) ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; URINARY-BLADDER CANCER; SHORT ARM; LOCALIZATION; STAGE; PROGRESSION; INSTABILITY; IMBALANCES; INTERVAL AB Recently, we found that chromosome 8p deletion might be associated with hepatocellular carcinoma (HCC) metastasis by analyzing the differences in chromosomal alterations between primary tumors and their matched metastatic lesions of HCC with comparative genomic hybridization (CGH) (Qin et al. 1999). To further confirm this interesting finding, the genomic changes of two models bearing human HCC with different metastatic potentials (LCI-D20 and LCI-D35), and the new human HCC cell line with high metastatic potential (MHCC97) were analyzed by CGH. Gains on 1q, 6q, 7p, and 8q, and losses on 13p, 14p. 19p, 21, and 22 were detected in both LCI-D20 and LCI-D35 models. However, high copy number amplification of a minimum region at 1q12-q22 and 12q, and deletions on 1p32-pter, 3p21-pter, 8p, 9p, 10q, 14q, and 15p were detected only in the LCI-D20 model. Gains on 1p21-p32, 2pI3-p21, 6p12-pter, 9p, 15q, and 16q11-q21, and losses on 2p23-pter, 4q24-qter, 7q31-qter, 12q, 17p, and 18 were detected only in the LCI-D35 model. The chromosomal aberration patterns in the MHCC97 cell line were similar to its parent LCI-D20 model, except that gains on 19q and losses on 4, 5, 10q, and 13q were found only in the cell line. These results provide some indirect clues to the metastasis-related chromosomal aberrations of HCC and further support the finding that 8p deletion is associated with HCC metastasis. 1q12-22 and 12q might harbor a novel oncogene(s) that contributes to the development and progression of HCC. Amplification on 8q and deletions on 4q and 17p may be not necessary for HCC metastasis. C1 Fudan Univ, Med Ctr, Liver Canc Inst, Shanghai 200032, Peoples R China. Fudan Univ, Med Ctr, Zhongshan Hosp, Shanghai 200032, Peoples R China. Univ Hong Kong, Queen Mary Hosp, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China. NINDS, SNB, Mol Pathogenesis Unit, NIH, Bethesda, MD 20892 USA. RP Tang, ZY (reprint author), Fudan Univ, Med Ctr, Liver Canc Inst, 136 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China. RI Guan, Xin-Yuan/A-3639-2009; Pack, Svetlana/C-2020-2014 OI Guan, Xin-Yuan/0000-0002-4485-6017; NR 33 TC 30 Z9 36 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD AUG PY 2001 VL 127 IS 8 BP 482 EP 488 DI 10.1007/s004320100236 PG 7 WC Oncology SC Oncology GA 457DA UT WOS:000170120800004 PM 11501747 ER PT J AU Wassarman, DA Sauer, F AF Wassarman, DA Sauer, F TI TAF(II)250: a transcription toolbox SO JOURNAL OF CELL SCIENCE LA English DT Article DE TAF(II)250; TFIID; histone acetyltransferase; kinase; ubiquitination; chromatin; transcription ID RNA-POLYMERASE-II; TATA-BINDING PROTEIN; TEMPERATURE-SENSITIVE MUTANTS; CELL-CYCLE PROGRESSION; LARGE T-ANTIGEN; IN-VIVO; GENE-EXPRESSION; KINASE-ACTIVITY; DNA-BINDING; BOX-BINDING AB Activation of RNA-polymerase-II-dependent transcription involves conversion of signals provided by gene-specific activator proteins into the synthesis of messenger RNA. This conversion requires dynamic structural changes in chromatin and assembly of general transcription factors (GTFs) and RNA polymerase II at core promoter sequence elements surrounding the transcription start site of genes. One hallmark of transcriptional activation is the interaction of DNA-bound activators with coactivators such as the TATA-box binding protein (TBP)-associated factors (TAF(II)s) within the GTF TFIID. TAF(II)250 possesses a variety of activities that are likely to contribute to the initial steps of RNA polymerase II transcription. TAF(II)250 is a scaffold for assembly of other TAF(II)s and TBP into TFIID, TAF(II)250 binds activators to recruit TFIID to particular promoters, TAF(II)250 regulates binding of TBP to DNA, TAF(II)250 binds core promoter initiator elements, TAF(II)250 binds acetylated lysine residues in core histones, and TAF(II)250 possesses protein kinase, ubiquitin-activating/conjugating and acetylase activities that modify histones and GTFs. We speculate that these activities achieve two goals - (1) they aid in positioning and stabilizing TFIID at particular promoters, and (2) they alter chromatin structure at the promoter to allow assembly of GTFs - and we propose a model for how TAF(II)250 converts activation signals into active transcription. C1 Univ Heidelberg, Zentrum Mol Biol, D-69120 Heidelberg, Germany. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Sauer, F (reprint author), Univ Heidelberg, Zentrum Mol Biol, Neuenheimer Feld 282, D-69120 Heidelberg, Germany. NR 84 TC 62 Z9 62 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG PY 2001 VL 114 IS 16 BP 2895 EP 2902 PG 8 WC Cell Biology SC Cell Biology GA 468KT UT WOS:000170757400002 PM 11686293 ER PT J AU Munzer, T Harman, SM Hees, P Shapiro, E Christmas, C Bellantoni, MF Stevens, TE O'Connor, KG Pabst, KM St Clair, C Sorkin, JD Blackman, MR AF Munzer, T Harman, SM Hees, P Shapiro, E Christmas, C Bellantoni, MF Stevens, TE O'Connor, KG Pabst, KM St Clair, C Sorkin, JD Blackman, MR TI Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN GROWTH-HORMONE; ADIPOSE-TISSUE DISTRIBUTION; BODY-COMPOSITION; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; MAGNETIC-RESONANCE; DEFICIENT ADULTS; CARDIOVASCULAR-DISEASE; OLDER MEN; TESTOSTERONE TREATMENT AB Aging is associated with reduced GH, IGF-I, and sex steroid axis activity and with increased abdominal fat. We employed a randomized, double-masked, placebo-controlled, noncrossover design to study the effects of 6 months of administration of GH alone (20 mug/kg BW), sex hormone alone (hormone replacement therapy in women, testosterone enanthate in men), or GH + sex hormone on total abdominal area, abdominal se fat, and visceral fat in 110 healthy women (n = 46) and men (n = 64), 65-88 yr old (mean, 72 yr). GH administration increased IGF-I levels in women (P = 0.05) and men (P = 0.0001), with the increment in IGF-I levels being higher in men (P = 0.05). Sex steroid administration increased levels of estrogen and testosterone in women and men, respectively (P = 0.05). In women, neither GH, hormone replacement therapy, nor GH + hormone replacement therapy altered total abdominal area, se fat, or visceral fat significantly. In contrast, in men, administration of GH and GH + testosterone enanthate decreased total abdominal area by 3.9% and 3.8%, respectively, within group and vs. placebo (P = 0.05). Within-group comparisons revealed that se fat decreased by 10% (P = 0.01) after GH, and by 14% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, sc fat decreased by 14% (P = 0.05) after GH, by 7% (P = 0.05) after testosterone enanthate, and by 16% (P = 0.0005) after GH + testosterone enanthate. Compared with placebo, visceral fat did not decrease significantly after administration of GH, testosterone enanthate, or GH + testosterone enanthate. These data suggest that in healthy older individuals, GH and/or sex hormone administration elicits a sexually dimorphic response on se abdominal fat. The generally proportionate reductions we observed in sc and visceral fat, after 6 months of GH administration in healthy aged men, contrast with the disproportionate reduction of visceral fat reported after a similar period of GH treatment of nonelderly GH deficient men and women. Whether longer term administration of GH or testosterone enanthate, alone or in combination, will reduce abdominal fat distribution-related cardiovascular risk in healthy older men remains to be elucidated. C1 NIA, Endocrine Sect, Clin Invest Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NIA, Metab Sect, Clin Invest Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Div Cardiol, Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Div Endocrinol & Metab, Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. RP Blackman, MR (reprint author), NIH, Natl Ctr Complementary & Alternat Med, 8 W Dr,Quarters 15B-1, Bethesda, MD 20892 USA. EM blackman@mail.nih.gov OI Bellantoni, Michele/0000-0001-8525-2247 FU NCRR NIH HHS [MO-1-RR-02719]; NIA NIH HHS [R0-1-AG11005] NR 49 TC 103 Z9 107 U1 0 U2 3 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 AUG PY 2001 VL 86 IS 8 BP 3604 EP 3610 DI 10.1210/jc.86.8.3604 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200021 PM 11502785 ER PT J AU Gallagher, JC Fowler, SE Detter, JR Sherman, SS AF Gallagher, JC Fowler, SE Detter, JR Sherman, SS TI Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VITAMIN-D METABOLITES; INTESTINAL CALCIUM-ABSORPTION; POST-MENOPAUSAL OSTEOPOROSIS; CONTROLLED CLINICAL-TRIAL; POSTMENOPAUSAL OSTEOPOROSIS; ELDERLY WOMEN; VERTEBRAL FRACTURES; D SUPPLEMENTATION; MINERAL DENSITY; RISK AB Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol, are important factors in the pathogenesis of age-related bone loss. The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women. Four hundred eighty-nine elderly women with normal bone density for their age, aged 65-77 yr, were entered into a randomized double blind, placebo-controlled trial. Women were randomized to one of four groups: conjugated estrogens (0.625 mg, daily) to women without a uterus (estrogen replacement therapy) plus medroxyprogesterone acetate (2.5 mg, daily) to women with a uterus (hormone replacement therapy), calcitriol (0.25 mug twice daily), a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol, or placebos for 3 yr. The primary outcome was the change in bone mineral density of the femoral neck and spine. In the intent to treat analysis, hormone therapy (hormone replacement therapy/estrogen replacement therapy) produced a mean (+/- 1 SD) increase in bone mineral density of 2.98% (+/-5.45%) at the femoral neck (P < 0.0001) and 4.36% (+/-6.42%) at the spine (P < 0.0001). There were parallel increases in total hip and trochanter bone mineral density. Calcitriol increased bone mineral density 0.10% (+/- 4.27%) at the femoral neck (P = 0.57) and 1.65% (+/- 4.83%) at the spine (P < 0.0124). The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80% (+/-4.95%) at the femoral neck (P < 0.001), 4.91% (+/-6.0%) at the spine (P < 0.0001), and parallel changes at the total hip and trochanter. All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck, spine, total hip and trochanter. There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis. In a secondary analysis of the effect in women who were adherent to treatment, calcitriol had a more significant effect on spine (P = 0.003) and total hip (P = 0.004). The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups. Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter (P = 0.007) and total hip bone mineral density (P = 0.0017). In summary, hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinically relevant sites in a group of elderly women, with normal bone density for their age. Calcitriol was effective in increasing spine bone mineral density. In the adherent women, combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone. C1 Creighton Univ, Med Ctr, Hop St Joseph, Omaha, NE 68131 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Gallagher, JC (reprint author), Creighton Univ, Med Ctr, Hop St Joseph, Suite 6718,601 N 30th St, Omaha, NE 68131 USA. EM jcg@creighton.edu FU NIA NIH HHS [R01-AG10373, UO1-AG10373] NR 48 TC 126 Z9 127 U1 0 U2 5 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 AUG PY 2001 VL 86 IS 8 BP 3618 EP 3628 DI 10.1210/jc.86.8.3618 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200023 PM 11502787 ER PT J AU Pacak, K Goldstein, DS Doppman, JL Shulkin, BL Udelsman, R Eisenhofer, G AF Pacak, K Goldstein, DS Doppman, JL Shulkin, BL Udelsman, R Eisenhofer, G TI A "Pheo" lurks: Novel approaches for locating occult pheochromocytoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLASMA METANEPHRINES; MIBG SCINTIGRAPHY; DIAGNOSIS; METAIODOBENZYLGUANIDINE; CATECHOLAMINES; LOCALIZATION; METABOLISM; MEDICINE; TUMORS C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Div Endocrine & Oncol Surg, Baltimore, MD 21218 USA. RP Pacak, K (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 9D42,10 Ctr Dr,MSC 1583, Bethesda, MD 20892 USA. EM karel@mail.nih.gov NR 27 TC 46 Z9 49 U1 0 U2 2 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 AUG PY 2001 VL 86 IS 8 BP 3641 EP 3646 DI 10.1210/jc.86.8.3641 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200026 PM 11502790 ER PT J AU Kung, AWC Lau, KS Kohn, LD AF Kung, AWC Lau, KS Kohn, LD TI Epitope mapping of TSH receptor-blocking antibodies in Graves' disease that appear during pregnancy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID THYROID-STIMULATING ANTIBODIES; HUMAN THYROTROPIN RECEPTOR; CHORIONIC-GONADOTROPIN RECEPTOR; ANTITHYROID DRUG-TREATMENT; EXTRACELLULAR DOMAIN; IDIOPATHIC MYXEDEMA; WILD-TYPE; HYPOTHYROIDISM; AUTOANTIBODIES; BINDING AB Spontaneous remission of Graves' disease during pregnancy is thought to be due to a reduction of thyroid-stimulating antibody activity. We suspected, however, that a broader change in TSH receptor antibody characteristics might play an important role in modulating disease activity during pregnancy. We measured TSH binding inhibitory Ig, thyroid-stimulating antibody, and thyroid stimulating-blocking antibody activities in 13 pregnant Graves' disease patients at first, second, and third trimesters and 4 months postpartum. To measure and epitope-map thyroid-stimulating antibody and thyroid stimulating-blocking antibody activities, we used CHO cells transfected with wild-type human TSH receptor or with several TSH receptor-LH/hCG receptor chimeras: Mc1+2, Mc2, and Mc4. These chimeric cells have their respective TSH receptor residues 9-165, 90-165, and 261-370 substituted with equivalent residues of the LH/hCG receptor. Overall thyroid-stimulating antibody decreased, whereas thyroid stimulating-blocking antibody increased progressively during pregnancy. TSH binding inhibitory Ig fluctuated in individual patients, but overall the activities remained statistically un-changed. Thyroid stimulating-blocking antibody appeared in subjects who were either negative for thyroid-stimulating antibody or whose thyroid-stimulating antibody activity increased or decreased during pregnancy. Epitope mapping showed that the thyroid-stimulating antibodies were mainly directed against residues 9-165 of the N-terminus of the TSH receptor extracellular domain. All thyroid stimulating-blocking antibodies had blocking activities against residues 261-370 of the C-terminus of the ectodomain. However, the majority of the thyroid stimulating-blocking antibodies had a hybrid conformational epitope directed against N-terminal residues 9-89 or 90-165 as well. Despite a change in the activity level, we did not observe any change in the epitope of either the stimulatory or blocking Abs as pregnancy advanced. In conclusion, a change in the specificity of TSH receptor antibody from stimulatory to blocking activity was observed during pregnancy, and the appearance of thyroid stimulating-blocking antibody may contribute to the remission of Graves' disease during pregnancy. C1 Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. NIDDKD, Cell Regulat Sect, Metab Dis Branch, Bethesda, MD 20892 USA. RP Kung, AWC (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Med, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China. EM awckung@hkucc.hku.hk RI Kung, Annie/C-4294-2009 NR 31 TC 25 Z9 26 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 AUG PY 2001 VL 86 IS 8 BP 3647 EP 3653 DI 10.1210/jc.86.8.3647 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200027 PM 11502791 ER PT J AU Bucci, A Shore-Freedman, E Gierlowski, T Mihailescu, D Ron, E Schneider, AB AF Bucci, A Shore-Freedman, E Gierlowski, T Mihailescu, D Ron, E Schneider, AB TI Behavior of small thyroid cancers found by screening radiation-exposed individuals SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHERNOBYL; MICROCARCINOMA; CARCINOMA; PAPILLARY; CHILDREN; BYELARUS; ACCIDENT; THERAPY; HEAD; NECK AB Thyroid cancers detected by screening irradiated individuals are often small and of uncertain clinical significance. We retrospectively analyzed the effect of screening in a cohort of 4296 individuals exposed to radiation as children in the 1940s and 1950s and followed by us from 1974 until the present. We compared the thyroid cancers diagnosed before 1974 (122 cases, routine care) with the cancers found in subjects screened by us after 1974 (172 cases, screened), using cancer recurrence as the end point. Screening included a thyroid scan or, more recently, thyroid ultrasound. As expected, many of the cancers found by screening were very small (52% were < 10 mm), but the range of tumor sizes overlapped those found by routine care. The recurrence rate was significantly lower in the cases found by screening, but when the comparison was limited to cancers 10 mm or larger, no difference in the recurrence rates was seen. This would suggest that the lower recurrence rate observed for small thyroid cancers detected at screening was due to earlier diagnosis rather than more effective treatment. By univariate analysis, four factors were associated with an increased risk of recurrence of small (< 10 mm) thyroid cancers: short latency (i.e. a shorter time interval between the radiation exposure and the first thyroid surgery), lymph node metastases present at diagnosis, multifocal cancers, and higher radiation dose. In a multivariate analysis combining the four risk factors, only short latency was significant. As thyroid cancers that escape detection by routine means should be diagnosed at screening, and both large and small thyroid cancers have the potential to recur, screening may be of value, but only if groups with a sufficiently high prevalence of thyroid cancer can be identified to offset the adverse effects of unnecessary treatment due to false positive results. C1 Univ Illinois, Sect Endocrinol & Metab, Coll Med, Chicago, IL 60612 USA. Michael Reese Hosp & Med Ctr, Chicago, IL 60616 USA. NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Schneider, AB (reprint author), Univ Illinois, Sect Endocrinol & Metab, Coll Med, 1819 W Polk St,MC 640, Chicago, IL 60612 USA. EM abschnei@uic.edu OI Shore-Freedman, Eileen/0000-0001-6194-1814 FU NCI NIH HHS [R01-CA-21518] NR 22 TC 17 Z9 18 U1 0 U2 2 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 AUG PY 2001 VL 86 IS 8 BP 3711 EP 3716 DI 10.1210/jc.86.8.3711 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200036 PM 11502800 ER PT J AU Vgontzas, AN Bixler, EO Lin, HM Prolo, P Mastorakos, G Vela-Bueno, A Kales, A Chrousos, GP AF Vgontzas, AN Bixler, EO Lin, HM Prolo, P Mastorakos, G Vela-Bueno, A Kales, A Chrousos, GP TI Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: Clinical implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; TIME-SERIES; CORTISOL SECRETION; SLEEP-DEPRIVATION; STRESS SYSTEM; DSM-III; DISORDERS; TRIAL; TEMPERATURE; MELATONIN AB Although insomnia is, by far, the most commonly encountered sleep disorder in medical practice, our knowledge in regard to its neurobiology and medical significance is limited. Activation of the hypothalamic-pituitary-adrenal axis leads to arousal and sleeplessness in animals and humans; however, there is a paucity of data regarding the activity of the hypothalamic-pituitary-adrenal axis in insomniacs. We hypothesized that chronic insomnia is associated with increased plasma levels of ACTH and cortisol. Eleven young insomniacs (6 men and 5 women) and 13 healthy controls (9 men and 4 women) without sleep disturbances, matched for age and body mass index, were monitored in the sleep laboratory for 4 consecutive nights, whereas serial 24-h plasma measures of ACTH and cortisol were obtained during the fourth day. Insomniacs, compared with controls, slept poorly (significantly higher sleep latency and wake during baseline nights). The 24-hACTH and cortisol secretions were significantly higher in insomniacs, compared with normal controls (4.2 +/- 0.3 vs. 3.3 +/- 0.3 pm, P = 0.04; and 218.0 +/- 11.0 vs. 190.4 +/- 8.3 um, P = 0.07). Within the 24-h period, the greatest elevations were observed in the evening and first half of the night. Also, insomniacs with a high degree of objective sleep disturbance (% sleep time < 70), compared with those with a low degree of sleep disturbance, secreted a higher amount of cortisol. Pulsatile analysis revealed a significantly higher number of peaks per 24 h in insomniacs than in controls (P < 0.05), whereas cosinor analysis showed no differences in the temporal pattern of ACTH or cortisol secretion between insomniacs and controls. We conclude that insomnia is associated with an overall increase of ACTH and cortisol secretion, which, however, retains a normal circadian pattern. These findings are consistent with a disorder of central nervous system hyperarousal rather than one of sleep loss' which is usually associated with no change or decrease in cortisol secretion or a circadian disturbance. Chronic activation of the hypothalamic-pituitary-adrenal axis in insomnia suggests that insomniacs are at risk not only for mental disorders, i.e. chronic anxiety and depression, but also for significant medical morbidity associated with such activation. The therapeutic goal in insomnia should be to decrease the overall level of physiologic and emotional arousal, and not just to improve the nighttime sleep. C1 Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Athens, Evgenidion Hosp, Endocrine Unit, Athens 10674, Greece. Autonomous Univ Madrid, Dept Psychiat, Madrid 28003, Spain. Nichhd, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept Psychiat, Sleep Res & Treatment Ctr, 500 Univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu NR 42 TC 330 Z9 338 U1 2 U2 36 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 AUG PY 2001 VL 86 IS 8 BP 3787 EP 3794 DI 10.1210/jc.86.8.3787 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200048 PM 11502812 ER PT J AU Glasow, A Horn, LC Taymans, SE Stratakis, CA Kelly, PA Kohler, U Gillespie, J Vonderhaar, BK Bornstein, SR AF Glasow, A Horn, LC Taymans, SE Stratakis, CA Kelly, PA Kohler, U Gillespie, J Vonderhaar, BK Bornstein, SR TI Mutational analysis of the PRL receptor gene in human breast tumors with differential PRL receptor protein expression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LASER CAPTURE MICRODISSECTION; HUMAN PROLACTIN RECEPTORS; GROWTH-HORMONE RECEPTOR; PROGESTERONE RECEPTORS; CLINICAL IMPLICATIONS; MONOCLONAL-ANTIBODY; ESTROGEN-RECEPTOR; POOR-PROGNOSIS; CANCER CELLS; MAMMARY AB PRL is a major growth and differentiating hormone in the human breast, with activation of the PRL-PRL receptor complex increasingly recognized as an important mechanism in the induction and progression of mammary tumors. Although constitutive activation of various hormone and growth factor receptors is newly recognized as a common cause of tumor development, the PRL receptor gene has not been analyzed for similar aberrations in breast and other tumors. Therefore, using bacterial artificial chromosomes containing the PRL receptor gene and intron-spanning PCR, we determined the exon-surrounding intron sequences providing primers for the first analysis of the entire coding region of the human PRL receptor gene. We examined the presence of PRL receptor in 41 breast tumors by immunohistochemistry and attempted a correlation of its expression to pathological grading of the disease. Then tumor cells were isolated by laser capture microdissection to examine DNA from 30 patients for PRL receptor mutations. The PRL receptor immunoreactive score did not correlate to the tumor size, histopathological grading, age, or family history of patients. PRL receptor immunoreactivity was predominantly found in steroid hormone receptor-positive tumors, but without overall correlation of immunoreactive score. In both PRL receptor-positive and PRL receptor-negative breast cancer cells, direct sequencing of the coding sequence of the PRL receptor gene did not detect any somatic or hereditary gene aberrations. In conclusion, PRL receptor mutations do not appear to be common in human breast cancer, suggesting that constitutive activation of the PRL receptor can be excluded as a major cause of mammary tumor genesis. The molecular structure of the PILL receptor seems to remain intact in tumor tissue, and systemic and local production of PRL may participate in tumor cell growth and proliferation through functional receptors. C1 Univ Dusseldorf, Dept Endocrinol, D-40225 Dusseldorf, Germany. NCI, Tumor Immunol & Biol Lab, Mol & Cellular Endocrinol Sect, NIH, Bethesda, MD 20892 USA. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Fac Med Necker Enfants Malad, INSERM, U344, F-75730 Paris, France. St George Hosp, D-04129 Leipzig, Germany. Univ Leipzig, Inst Pathol, D-04103 Leipzig, Germany. Univ Leipzig, Childrens Hosp, D-04317 Leipzig, Germany. RP Glasow, A (reprint author), Inst Canc Res, Chester Beatty Labs, Leukaemia Res Fund Ctr, 237 Fulham Rd, London SW3 6JB, England. EM aglasow@icr.ac.uk RI Kelly, Paul/A-7951-2008 NR 68 TC 21 Z9 21 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 AUG PY 2001 VL 86 IS 8 BP 3826 EP 3832 DI 10.1210/jc.86.8.3826 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200055 PM 11502819 ER PT J AU Phillips, JL AF Phillips, JL TI Author's response: Distinguishing unilateral aldosteronoma from bilateral disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Phillips, JL (reprint author), NCI, Urol Oncol Branch, Bldg 10,Room 2B47, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 AUG PY 2001 VL 86 IS 8 BP 4005 EP 4005 DI 10.1210/jc.86.8.4005 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 462QA UT WOS:000170430200090 ER PT J AU Weiderpass, E Gridley, G Nyren, O Pennello, G Landstrom, AS Ekbom, A AF Weiderpass, E Gridley, G Nyren, O Pennello, G Landstrom, AS Ekbom, A TI Cause-specific mortality in a cohort of patients with diabetes mellitus: A population-based study in Sweden SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE diabetes mellitus; standardised mortality ratio; cohort study; Sweden; epidemiology; cause-specific mortality ID HEART-DISEASE MORTALITY; FOLLOW-UP; RISK; HYPERGLYCEMIA; DEATH AB A cohort of patients with diabetes mellitus hospitalised in Sweden from 1965 to 1983 was followed up until 1989, by linkages of population-based registers. Standardised mortality ratios (SMR), adjusted for confounding variables, and 95% confidence intervals (CIs) were calculated. After exclusion of the first year of follow-up (to reduce the effect of selection bias), the cohort consisted of 144,427 patients, of whom 92,248 patients died during follow-up. The SMR for all causes of death combined was 2.62 (95% CI 2.58- 2.67) among men and 3.23 (95% CI 3.18-3.28) among women. The excess mortality was still evident 20 years after first hospitalisation. but became less marked with longer follow-up time. Patients with presumably insulin-dependent diabetes mellitus (IDDM) had the highest SMRs (10.2: CI 9.5-11.0); however, there was a significant (34%) improvement over time in their mortality risk. We conclude that excess mortality persisted throughout all calendar periods and at all ages, indicating the need for health care prevention measures. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Int Agcy Res Canc, F-69372 Lyon 08, France. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Hosp, Dept Internal Med, Uppsala, Sweden. RP Weiderpass, E (reprint author), Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. RI Weiderpass, Elisabete/M-4029-2016 OI Weiderpass, Elisabete/0000-0003-2237-0128 FU NCI NIH HHS [N01CP60538] NR 31 TC 34 Z9 34 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD AUG PY 2001 VL 54 IS 8 BP 802 EP 809 DI 10.1016/S0895-4356(01)00342-0 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 455GV UT WOS:000170019900007 PM 11470389 ER PT J AU Chackerian, B Lowy, DR Schiller, JT AF Chackerian, B Lowy, DR Schiller, JT TI Conjugation of a self-antigen to papillomavirus-like particles allows for efficient induction of protective autoantibodies SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; ONGOING ADJUVANT ARTHRITIS; VIRUS-LIKE PARTICLES; B-LYMPHOCYTES; TNF-ALPHA; BOVINE PAPILLOMAVIRUS; RHEUMATOID-ARTHRITIS; ANTIBODY-RESPONSES; VACCINATION; RESOLUTION AB High avidity and long-lasting autoantibodies to a self-polypeptide (TNF-alpha) were generated after parenteral vaccination of mice with low doses of virus-like particle-based (VLP-based) vaccines that were constructed by linking mouse TNF-alpha peptides to the surface of papillomavirus VLPs. High-titer autoantibodies were induced with or without coadministration of potent conventional adjuvants, but were enhanced by coadministration of CFA. Compared with immunization with the fusion protein alone, attachment to VLPs increased autoantibody titers 1,000-fold. A comparison of Ab responses against the self (TNF-alpha) and foreign components of the fusion protein showed that VLP conjugation abrogated the ability of the humoral immune system to distinguish between self and foreign. Similar levels of IgM were detected to self and foreign epitopes regardless of the assembly state of the antigen, suggesting that conjugation of self-peptides to VLPs promotes survival or expansion of mature autoreactive B cells. In a mouse model, vaccination with conjugated particles inhibited development of type II collagen-induced arthritis. Together, these results suggest a potentially flexible method to efficiently generate autoantibodies against specific self-proteins that mediate arthritis and other diseases. C1 NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NIH, Cellular Oncol Lab, Bldg 36,Room 1D-32, Bethesda, MD 20892 USA. NR 44 TC 132 Z9 136 U1 2 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2001 VL 108 IS 3 BP 415 EP 423 DI 10.1172/JCI11849 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 460PT UT WOS:000170318300013 PM 11489935 ER PT J AU Takatoku, M Sellers, S Agricola, BA Metzger, ME Kato, I Donahue, RE Dunbar, CE AF Takatoku, M Sellers, S Agricola, BA Metzger, ME Kato, I Donahue, RE Dunbar, CE TI Avoidance of stimulation improves engraftment of cultured and retrovirally transduced hematopoietic cells in primates SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID EX-VIVO EXPANSION; BLOOD CD34(+) CELLS; GREEN FLUORESCENT PROTEIN; LONG-TERM ENGRAFTMENT; GROWTH-FACTOR-BETA; BONE-MARROW CELLS; STEM-CELLS; PERIPHERAL-BLOOD; PROGENITOR CELLS; GENE-TRANSFER AB Recent reports suggest that cells in active cell cycle have an engraftment defect compared with quiescent cells. We used nonhuman primates to investigate this finding, which has direct implications for clinical transplantation and gene therapy applications. Transfer of rhesus CD34(+) cells to culture in stem cell factor (SCF) on the CH-296 fibronectin fragment (FN) after 4 days of culture in stimulatory cytokines maintained cell viability but decreased cycling. Using retroviral marking with two different gene transfer vectors, we compared the engraftment potential of cytokine-stimulated cells versus those transferred to nonstimulatory conditions (SCF on FN alone) before reinfusion. In vivo competitive repopulation studies showed that the level of marking originating from the cells continued in culture for 2 days with SCF on FN following a 4-day stimulatory transduction was significantly higher than the level of marking coming from cells transduced for 4 days and reinfused without the 2-day culture under nonstimulatory conditions. We observed stable in vivo overall gene marking levels of up to 29%. This approach may allow more efficient engraftment of transduced or ex vivo expanded cells by avoiding active cell cycling at the time of reinfusion. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Takara Shuzo Co, Biotechnol Res Labs, Otsu, Shiga, Japan. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 48 TC 83 Z9 83 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2001 VL 108 IS 3 BP 447 EP 455 DI 10.1172/JCI200112593 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 460PT UT WOS:000170318300016 PM 11489938 ER PT J AU Phan, GQ Attia, P Steinberg, SM White, DE Rosenberg, SA AF Phan, GQ Attia, P Steinberg, SM White, DE Rosenberg, SA TI Factors associated with response to high-dose interleukin-2 in patients with metastatic melanoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; BOLUS INTERLEUKIN-2; THYROID-DYSFUNCTION; MALIGNANT-MELANOMA; ADVANCED CANCER; VITILIGO; CARCINOMA; INFUSION AB Purpose: The present study attempted to identify characteristics that correlated with clinical response to interleukin (IL)-2 therapy in patients with metastatic melanoma. Patients and Methods: We retrospectively evaluated laboratory and clinical characteristics of 374 consecutive patients with metastatic melanoma treated with high-dose intravenous bolus IL-2 (720,000 IU/kg) from July 1, 1988, to December 31, 1999, at the Surgery Branch of the National Cancer Institute. Results: The overall objective response rate was 15.5%. Pretreatment parameters such as patient demographics, laboratory values, and prior therapy did not correlate with response; however, 53.6% of patients with only subcutaneous and/or cutaneous metastases responded, compared with 12.4% of patients with disease at other sites (P-2 = .000001). During therapy, patients who were responders tended to have received more doses during course 1 (16.2 +/- 0.3 doses v 14.5 +/- 0.2 doses; P-2 = .0095); however, when limited to patients who were able to complete both cycles of course 1, there was no statistically significant difference (P-2 = .27). Responders had a higher maximum lymphocyte count immediately after therapy compared with nonresponders (P-2 = .0026). The development of abnormal thyroid function tests and vitiligo after therapy was associated with response (thyroid-stimulating hormone, P-2 = .01; free T4, P-2 = .0049; vitiligo, P-2 < 10(-6)), although thyroid dysfunction may have been related more to the length of IL-2 therapy than to response. Conclusion: The presence of metastases only to subcutaneous and/or cutaneous sites, lymphocytosis immediately after treatment, and long-term immunologic side effects, especially vitiligo, were associated with antitumor response to IL-2 therapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B42,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 29 TC 209 Z9 213 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2001 VL 19 IS 15 BP 3477 EP 3482 PG 6 WC Oncology SC Oncology GA 459AV UT WOS:000170228400006 PM 11481353 ER PT J AU James, LP Farrar, HC Sullivan, JE Givens, TG Kearns, GL Wasserman, GS Walson, PD Hinson, JA Pumford, NR AF James, LP Farrar, HC Sullivan, JE Givens, TG Kearns, GL Wasserman, GS Walson, PD Hinson, JA Pumford, NR CA Pediat Pharmacology Res Unit Netwo TI Measurement of acetaminophen-protein adducts in children and adolescents with acetaminophen overdoses SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Society-of-Clinical-Pharmacology-and-Therapeutics CY MAR 18-20, 1999 CL SAN ANTONIO, TEXAS SP Amer Soc Clin Pharmacol & Therapeut ID 3-(CYSTEIN-S-YL)ACETAMINOPHEN ADDUCTS; COVALENT BINDING; TREATED MICE; HEPATOTOXICITY; SERUM; DEHYDROGENASE; TOXICITY; ASSAY AB Acetaminophen-protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen-induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen-protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time of routine blood sampling for clinical monitoring. Six subjects developed "severe" hepatotoxicity (transaminase elevation > 1000 IU/L), and 6 subjects had transaminase elevation of 100 to 1000 IU/L. Acetaminophen-protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6000 IU/L) and high risk for the development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen-protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury. (C) 2001 the American College of Clinical Pharmacology. C1 Arkansas Childrens Hosp, Sect Clin Pharmacol & Toxicol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pediat, Sect Clin Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Louisville, Dept Pediat, Louisville, KY 40292 USA. Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Kosair Childrens Hosp, Louisville, KY 40292 USA. Univ Missouri, Dept Pediat, Kansas City, MO USA. Univ Missouri, Dept Pharmacol, Kansas City, MO USA. Childrens Mercy Hosp, Div Pediat Pharmacol & Toxicol, Kansas City, MO 64108 USA. Ohio State Univ, Sch Med, Dept Pediat, Columbus, OH 43210 USA. Childrens Hosp, Columbus, OH 43205 USA. Univ Arkansas Med Sci, Dept Toxicol, Little Rock, AR 72205 USA. Natl Inst Child Hlth & Dev, Bethesda, MD USA. RP James, LP (reprint author), Arkansas Childrens Hosp, Sect Clin Pharmacol & Toxicol, 800 Marshall St, Little Rock, AR 72202 USA. FU NICHD NIH HHS [1 U10 HD31324-04]; NIGMS NIH HHS [GM58884] NR 24 TC 23 Z9 24 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD AUG PY 2001 VL 41 IS 8 BP 846 EP 851 DI 10.1177/00912700122010744 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 457ED UT WOS:000170123400005 PM 11504272 ER PT J AU Preston, KL Umbricht, A Wong, CJ Epstein, DH AF Preston, KL Umbricht, A Wong, CJ Epstein, DH TI Shaping cocaine abstinence by successive approximation SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID METHADONE-MAINTENANCE PATIENTS; CARBON-MONOXIDE LEVELS; HUMAN BEHAVIORAL MOMENTUM; CONTINGENT REINFORCEMENT; DRUG-USE; INCENTIVES; REDUCTION; DELIVERY; SCHEDULE; THERAPY AB Cocaine-using methadone-maintenance patients were randomized to standard contingency management (abstinence group, n = 49) or to a contingency designed to increase contact with reinforcers (shaping group, n = 46). For 8 weeks, both groups earned escalating-value vouchers based on thrice-weekly urinalyses: The abstinence group earned vouchers for cocaine-negative urines only; the shaping group earned vouchers for each urine specimen with a 25% or more decrease in cocaine metabolite (first 3 weeks) and then for negative urines only (last 5 weeks). Cocaine use was lower in the shaping group, but only in the last 5 weeks, when the response requirement was identical. Thus, the shaping contingency appeared to better prepare patients for abstinence. A 2nd phase of the study showed that abstinence induced by escalating-value vouchers can be maintained by a nonescalating schedule, suggesting that contingency management, can be practical as a maintenance treatment. C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Preston, KL (reprint author), Natl Inst Drug Abuse, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 41 TC 44 Z9 44 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD AUG PY 2001 VL 69 IS 4 BP 643 EP 654 DI 10.1037//0022-006X.69.4.643 PG 12 WC Psychology, Clinical SC Psychology GA 468UJ UT WOS:000170776300006 PM 11550730 ER PT J AU Yoshimura, K Tsukamoto, K Okazaki, M Virador, VM Lei, TC Suzuki, Y Uchida, G Kitano, Y Harii, K AF Yoshimura, K Tsukamoto, K Okazaki, M Virador, VM Lei, TC Suzuki, Y Uchida, G Kitano, Y Harii, K TI Effects of all-trans retinoic acid on melanogenesis in pigmented skin equivalents and monolayer culture of melanocytes SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Article DE all-trans retinoic acid; melanogenesis; pigmented skin equivalents; melanocytes ID TOPICAL TRETINOIN; GROWTH-FACTOR; HUMAN KERATINOCYTES; MELANOMA-CELLS; DIFFERENTIATION; MODULATION; EXPRESSION; PROTOCOL; INVITRO; MELASMA AB The effects of all-trans retinoic acid (RA) on melanogenesis and the mechanism of its action in topical treatment have not been elucidated. The purpose of this study was to determine the effects or RA oil melanogenesis in the pigmented skin equivalent as well as in monolayer Culture of melanocytes, and to determine whether RA, hydroquinone (HQ), and hydrocortisone (HC) show synergistic depigmenting effects in combined treatments of each other. The suppressing effect of RA on melanogenesis was not observed in pigmented skin equivalents and monolayer culture of murine and human melanocytes, although HQ showed strong inhibition of melanogenesis. The synergistic effects between RA, HQ, and HC were not particularly seen. The results suggested that RA neither has direct inhibitory effects on melanogenesis of melanocytes, nor influences the cell cell interactions between melanocytes, keratinocytes and fibroblasts, such as paracrine actions with regard to melanin production. The role of RA in bleaching treatments appears to be in other specific actions. such as promotion of keratinocytes proliferation and acceleration of epidermal turnover. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Tokyo, Grad Sch med, Dept Plast & Reconstruct Surg, Bunkyo Ku, Tokyo 1138655, Japan. Yamanashi Prefectural Cent Hosp, Dept Dermatol, Yamanashi, Japan. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Yoshimura, K (reprint author), Univ Tokyo, Grad Sch med, Dept Plast & Reconstruct Surg, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. RI Yoshimura, Kotaro/C-8524-2009 NR 41 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD AUG PY 2001 VL 27 SU 1 BP S68 EP S75 PG 8 WC Dermatology SC Dermatology GA 473JQ UT WOS:000171038200010 PM 11514127 ER PT J AU Blank, PS Vogel, SS Malley, JD Zimmerberg, J AF Blank, PS Vogel, SS Malley, JD Zimmerberg, J TI A kinetic analysis of calcium-triggered exocytosis SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE cytoplasmic vesicles; membrane fusion; sea urchins; secretion; neurosecretion ID SEA-URCHIN EGG; BOVINE CHROMAFFIN CELLS; SQUID GIANT SYNAPSE; INDIVIDUAL SECRETORY VESICLES; READILY RELEASABLE POOL; TRANSMITTER RELEASE; PRESYNAPTIC CALCIUM; SUBMAXIMAL RESPONSES; NEUROENDOCRINE CELLS; HIPPOCAMPAL SYNAPSES AB Although the relationship between exocytosis and calcium is fundamental both to synaptic and nonneuronal secretory function, analysis is problematic because of the temporal and spatial properties of calcium, and the fact that vesicle transport, priming, retrieval, and recycling are coupled. By analyzing the kinetics of sea urchin egg secretory vesicle exocytosis in vitro, the final steps of exocytosis are resolved. These steps are modeled as a three-state system: activated, committed, and fused, where interstate transitions are given by the probabilities that an active fusion complex commits (alpha) and that a committed fusion complex results in fusion, p. The number of committed complexes per vesicle docking site is Poisson distributed with mean (n) over bar. Experimentally, p and (n) over bar increase with increasing calcium, whereas alpha and the p/(n) over bar ratio remain constant, reducing the kinetic description to only one calcium-dependent, controlling variable, n. On average, the calcium dependence of the maximum rate (R-max) and the time to reach R-max (T-peak) are described by the calcium dependence of (n) over bar. Thus, the nonlinear relationship between the free calcium concentration and the rate of exocytosis can be explained solely by the calcium dependence of the distribution of fusion complexes at vesicle docking sites. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Blank, PS (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bldg 10,Room 10D14,10 Ctr Dr,MSC 1855, Bethesda, MD 20892 USA. RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 FU NINDS NIH HHS [NS41055, R01 NS041055] NR 56 TC 16 Z9 17 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 2001 VL 118 IS 2 BP 145 EP 155 DI 10.1085/jgp.118.2.145 PG 11 WC Physiology SC Physiology GA 461DN UT WOS:000170349800002 PM 11479342 ER PT J AU Erokhina, TN Vitushkina, MV Zinovkin, RA Lesemann, DE Jelkmann, W Koonin, EV Agranovsky, AA AF Erokhina, TN Vitushkina, MV Zinovkin, RA Lesemann, DE Jelkmann, W Koonin, EV Agranovsky, AA TI Ultrastructural localization and epitope mapping of the methyltransferase-like and helicase-like proteins of Beet yellows virus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TO-CELL MOVEMENT; NICOTIANA-BENTHAMIANA PROTOPLASTS; STRAND RNA VIRUSES; GENOME STRUCTURE; CLOSTEROVIRUS; REPLICATION; EVOLUTION; ORGANIZATION; IDENTIFICATION; EXPRESSION AB Monoclonal antibodies (MAbs) specific to the methyltransferase (MT) and helicase (MEL) domains of the closterovirus Beet yellows virus (BYV) were used for immunogold labelling of ultrathin sections of virus-infected Tetragonia expansa plants, MAbs 4A2 and 4A5 from the MT panel, and 1C4 from the HEL panel, specifically labelled distinct closterovirus-induced membranous structures, the 'BYV-type vesicles', thus suggesting that the closterovirus MT-like and MEL-like proteins co-localize in these structures. Probing of the MT and HEL MAbs with synthetic octapeptides spanning the sequences of the recombinant MT and HEL fragments that had been used as immunogens showed that 4A5 and 4A2 recognized a single epitope, SRLLENET (aa 686-692 in the BW la protein), and 1C4 reacted with the DDPF epitope (aa 2493-2496). These epitopes apparently reside on the exposed parts of the membrane-associated molecules of the closterovirus MT-like and MEL-like proteins. Two other epitopes determined for the MT MAbs that were nonreactive in the immunogold labelling, namely TMVTPGEL (aa 750-757; MAbs 3C5, 4B4 and 4C5) and SREQLVEA (aa 806-813; MAb 2A4), are possibly buried in the MT domain fold or shielded by membranes or other proteins involved in the viral replicative complex. C1 Moscow State Univ, Dept Virol, Moscow 119899, Russia. Moscow State Univ, Belozersky Inst Phys Chem Biol, Moscow 119899, Russia. Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow 117871, Russia. Fed Biol Res Ctr Agr & Forestry, Dept Plant Virol Microbiol & Biosafety, D-38104 Braunschweig, Germany. Inst Plant Protect Fruit Crops, D-69221 Dossenheim, Germany. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Agranovsky, AA (reprint author), Moscow State Univ, Dept Virol, Moscow 119899, Russia. RI Zinovkin, Roman/J-2500-2013 OI Zinovkin, Roman/0000-0001-5337-4346 NR 45 TC 20 Z9 21 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD AUG PY 2001 VL 82 BP 1983 EP 1994 PN 8 PG 12 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 454FW UT WOS:000169962900022 PM 11458006 ER PT J AU Tamm, ER Russell, P AF Tamm, ER Russell, P TI The role of myocilin/TIGR in glaucoma: Results of the Glaucoma Research Foundation Catalyst Meeting in Berkeley, California, March 2000 SO JOURNAL OF GLAUCOMA LA English DT Review ID OPEN-ANGLE GLAUCOMA; HUMAN TRABECULAR MESHWORK; GLUCOCORTICOID RESPONSE PROTEIN; UPSTREAM STIMULATORY FACTOR; TRANSCRIPTION FACTOR USF; IN-SITU HYBRIDIZATION; MYOC GENE-EXPRESSION; ALPHA-B-CRYSTALLIN; HEAVY-CHAIN GENE; MOLECULAR-CLONING AB Approximately 3 years ago, the first major (biochemical, molecular biologic, and biologic) insight into primary open-angle glaucoma was the finding that mutations in the myocilin (MYOC/TIGR) gene were related to certain forms of juvenile onset of this disease. Since then, a great deal of work has been done to determine the possible mechanisms by which MYOC/TIGR might cause not only juvenile but also adult-onset primary open-angle glaucoma. To assess the current knowledge and those areas in which more research is necessary, a meeting of scientists was held by the Glaucoma Research Foundation of San Francisco, California in the spring of 2000. This meeting attempted to concentrate on the MYOC/TIGR protein rather than the genetics of this gene. Possible functions and roles of this protein intracellularly and extracellularly were critically examined and discussed. Normal transcriptional and translational events and the effect of mutations on these events were explored. The discussions yielded insight not only in those areas in which important information is known but also in vital areas in which little is currently understood. This review attempts to summarize the current knowledge regarding MYOC/TIGR and to elucidate the points that the people attending the meeting thought needed further study. C1 Univ Erlangen Nurnberg, Dept Anat Mol Anat & Embyrol, D-91054 Erlangen, Germany. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Tamm, ER (reprint author), Univ Erlangen Nurnberg, Dept Anat, Univ Str 19, D-91054 Erlangen, Germany. NR 105 TC 11 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD AUG PY 2001 VL 10 IS 4 BP 329 EP 339 DI 10.1097/00061198-200108000-00014 PG 11 WC Ophthalmology SC Ophthalmology GA 466RH UT WOS:000170658500014 PM 11558819 ER PT J AU Telford, WG Moss, MW Morseman, JP Allnutt, FCT AF Telford, WG Moss, MW Morseman, JP Allnutt, FCT TI Cyanobacterial stabilized phycobilisomes as fluorochromes for extracellular antigen detection by flow cytometry SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE cyanobacteria; phycobiliprotein; phycobilisome; flow cytometry ID EXCITATION-ENERGY TRANSFER; FLUORESCENT; ALLOPHYCOCYANIN; ORIENTATION AB Phycobilisomes are cyanobacterial photosynthetic energy transfer complexes partly composed of phycobiliproteins, proteins that are widely used as conjugable fluorochromes for flow cytometry. The brightness and photostability of phycobiliproteins suggest that intact phycobilisomes could constitute even brighter probes for fluorescence-based detection systems. Stabilized phycobilisomes have been isolated and the red-excited, far red-emitting Spirulina platensis-derived complex PBXL-3 was accessed as a fluorochrome for flow cytometric immunodetection of surface antigens on immune cells. Although the large size of intact phycobilisomes initially precluded efficient cell surface labeling, the addition of a PEG spacer arm between PBXL-3 and its conjugated avidin molecule (designated PBXL-3L) reduced the steric hindrance associated with the high molecular weight PBXL complex. PBXL-3L increased the surface labeling surface-to-noise ratio and subsequent sensitivity by several-fold over commonly used red-excited fluorochromes such as APC. Interestingly, low power laser sources (including helium-neon and red diode) were particularly efficient at exciting PBXL-3. PBXL-3 was also compatible in with other fluorochromes for multicolor flow cytometry applications. In summary, PBXL-3 was found to possess superior sensitivity and efficiency for flow cytometric immunodetection, particularly with low power laser sources. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NCI, Dept Expt Transplantat & Immunol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. Martek Biosci Corp, Columbia, MD USA. RP Telford, WG (reprint author), NCI, Dept Expt Transplantat & Immunol, Med Branch, Div Clin Sci,NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 24 TC 20 Z9 21 U1 1 U2 11 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 AUG 1 PY 2001 VL 254 IS 1-2 BP 13 EP 30 DI 10.1016/S0022-1759(01)00367-2 PG 18 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 449ZQ UT WOS:000169717400002 PM 11406150 ER PT J AU Piccirillo, CA Shevach, EM AF Piccirillo, CA Shevach, EM TI Cutting edge: Control of CD8(+) T cell activation by CD4(+)CD25(+) immunoregulatory cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; AUTOIMMUNE-DISEASES; MOUSE; DIFFERENTIATION; PROLIFERATION; COSTIMULATION; HOMEOSTASIS; MECHANISM; BREAKDOWN; PATHWAYS AB CD4(+)CD25(+) regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4(+)CD25(-) T cells and are potent suppressors of CD4(+)CD25(-) T cell activation in vitro. We demonstrate that CD4(+)CD25(+) T cells also suppress both proliferation and IFN-gamma production by CD8(+) T cells induced either by polyclonal or Ag-specific stimuli. CD4(+)CD25(+) T cells inhibit the activation of CD8(+) responders by inhibiting both IL-2 production and up-regulation of IL-2R alpha -chain (CD25) expression. Suppression is mediated via a T-T interaction as activated CD4(+)CD25(+) T cells suppress the responses of TCR-transgenic CD8(+) T cells stimulated with soluble peptide-MHC class I tetramers in the complete absence of APC. These results broaden the immunoregulatory role played by CD4(+)CD25(+) T cells in the prevention of autoimmune diseases, but also raise the possibility that they may hinder the induction of effector CD8(+) T cells to tumor or foreign Ags. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr, Bethesda, MD 20892 USA. NR 23 TC 535 Z9 573 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1137 EP 1140 PG 4 WC Immunology SC Immunology GA 471VM UT WOS:000170949400001 PM 11466326 ER PT J AU Wang, B Norbury, CC Greenwood, R Bennink, JR Yewdell, JW Frelinger, JA AF Wang, B Norbury, CC Greenwood, R Bennink, JR Yewdell, JW Frelinger, JA TI Multiple paths for activation of naive CD8(+) T cells: CD4-independent help SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELLS; TOXIC LYMPHOCYTE-T; DENDRITIC CELLS; IN-VIVO; CD4-DEFICIENT MICE; GAMMA-HERPESVIRUS; EXOGENOUS ANTIGEN; EFFECTOR FUNCTION; VIRUS-INFECTION; DNA VACCINATION AB CD8(+) CTLs play a pivotal role in immune responses against many viruses and tumors. Two models have been proposed. The "three-cell" model focuses on the role of CD4(+) T cells, proposing that help is only provided to CTLs by CD4(+) T cells that recognize Ag on the same APC. The sequential "two-cell" model proposes that CD4(+) T cells can first interact with APCs, which in turn activate naive CTLs. Although these models provide a general framework for the role of CD4(+) T cells in mediating help for CTLs, a number of issues are unresolved. We have investigated the induction of CTL responses using dendritic cells (DCs) to immunize mice against defined peptide Ags. We find that help is required for activation of naive CTLs when DCs are used as APCs, regardless of the origin or MHC class I restriction of the peptides we studied in this system. However, CD8(+) T cells can provide self-help if they are present at a sufficiently high precursor frequency. The important variable is the total number of T cells responding, because class II-knockout DCs pulsed with two noncompeting peptides are effective in priming. C1 Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. NIAID, Viral Dis Lab, Bethesda, MD 20235 USA. RP Frelinger, JA (reprint author), Univ N Carolina, Dept Microbiol & Immunol, Campus Box 7290,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 FU NIAID NIH HHS [AI 20288] NR 56 TC 65 Z9 70 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1283 EP 1289 PG 7 WC Immunology SC Immunology GA 471VM UT WOS:000170949400019 PM 11466344 ER PT J AU Huang, LY Sousa, CR Itoh, Y Inman, J Scott, DE AF Huang, LY Sousa, CR Itoh, Y Inman, J Scott, DE TI IL-12 induction by a Th1-inducing adjuvant in vivo: Dendritic cell subsets and regulation by IL-10 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4+ T-CELLS; INTERLEUKIN-10 PROTECTS MICE; IMMUNITY IN-VIVO; BRUCELLA-ABORTUS; IFN-GAMMA; INTRACELLULAR INFECTION; TOXOPLASMA-GONDII; LIPOPOLYSACCHARIDE; MACROPHAGES; EXPRESSION AB IL-12 induction is critical for immune responses against many viruses and intracellular bacterial pathogens. Recent studies suggest that IL-12-secreting dendritic cells (DC) are potent Th1-inducing APC. However, controversy exists concerning the function of DC subsets. Murine studies have suggested that CD8(+) DC preferentially induce Th1 responses, whereas CD8(-) DC induce Th2 development; in this model, different DC subsets prime different responses. Alternatively, the propensity of DC subsets to prime a Th1 response could depend upon the type of initial stimulus. We used a prototypic Th1-inducing adjuvant, heat-killed Brucella abortus (HKBA) to assess stimulation of DC subsets, relationship between Ag burden and IL-12 production, and down-regulation of DC subset IL-12 production by IL-10. In this study, we show that DC were sole producers of IL-12, although most HKBA uptake was by splenic macrophages and granulocytes. More CD8(-) than CD8(+) DC produced IL-12 after HKBA challenge, whereas only CD8(+) DC produced IL-12 after injection of another Th1-promoting microbial substance, soluble Toxoplasma gondii Ags. Studies in IL-10-deficient mice revealed that IL-10 down-regulates frequency and duration of IL-12 production by both DC subsets. In the absence of IL-10, IL-12 expression is enabled in CD11c(low) cells, but not in macrophages or granulocytes. These findings support the concept of DC as the major IL-12 producers in spleens, but challenge the notion that CD8(+) and CD8(-) DC are destined to selectively induce Th1 or Th2 responses, respectively. Thus, the nature of the stimulating substance is important in determining which DC subsets are activated to produce IL-12. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bethesda, MD 20892 USA. Imperial Canc Res Fund, Immunobiol Lab, London WC2A 3PX, England. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Scott, DE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Plasma Derivat, Bldg 29,Room 232,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 47 TC 84 Z9 88 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1423 EP 1430 PG 8 WC Immunology SC Immunology GA 471VM UT WOS:000170949400036 PM 11466361 ER PT J AU Hu, RQ Bekisz, J Schmeisser, H McPhie, P Zoon, K AF Hu, RQ Bekisz, J Schmeisser, H McPhie, P Zoon, K TI Human IFN-alpha protein engineering: The amino acid residues at positions 86 and 90 are important for antiproliferative activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOBLASTOID INTERFERON-ALPHA; 3-DIMENSIONAL CRYSTAL-STRUCTURE; I INTERFERONS; EVOLUTIONARY IMPLICATIONS; CASSETTE MUTAGENESIS; RECEPTOR-BINDING; BETA RECEPTOR; CELLS; CLONING; SITES AB Human IFN-alpha is a family of structurally related proteins that exhibit a wide range of antiproliferative activities. To understand the structural basis for these different antiproliferative activities, eight recombinant human IFN-alpha hybrids (HY) of alpha 21a/alpha 2c (HY-4, HY-5) and mutants (site-directed mutagenesis (SDM)-1, 2 and cassette mutagenesis (CM)-1, 2, 3, and 4) have been expressed, purified, and characterized. The data showed that the amino acid region 81-95 is important for antiproliferative activity. Site-directed mutagenesis and cassette mutagenesis studies showed that if serine (S) 86 and asparagine (N) 90 were replaced by tyrosine (Y), the antiproliferative activity was increased. We have also observed that if Y86 was replaced by isoleucine (I), the antiproliferative activity was comparable. However, if Y86 was replaced by aspartic acid (D), lysine (K), or alanine (A), the antiproliferative activity was substantially decreased. Our results indicate that Y and/or I at position 86 and Y at position 90 are very important in antiproliferative activity of human IFN-alpha. Circular dichroism spectra showed that the amino acid replacements at position 86 did not change the secondary structure. Thus the biological activity changes among those mutants do not appear to be due to conformational changes. The results also suggest that hydrophobic residue(s) at position 86 may be important for the interaction of the molecule with its receptor. The competitive binding data correlated with the antiproliferative activity. The N-terminal region of the molecule and the hydrophobic residues (including Y and I) on the C-helix region at positions 86 and/or 90 are important for binding and antiproliferative activities of human ifn-alphas.. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hu, RQ (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NR 38 TC 19 Z9 22 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1482 EP 1489 PG 8 WC Immunology SC Immunology GA 471VM UT WOS:000170949400043 PM 11466368 ER PT J AU Horner, AA Datta, SK Takabayashi, K Belyakov, IM Hayashi, T Cinman, N Nguyen, MD Van Uden, JH Berzofsky, JA Richman, DD Raz, E AF Horner, AA Datta, SK Takabayashi, K Belyakov, IM Hayashi, T Cinman, N Nguyen, MD Van Uden, JH Berzofsky, JA Richman, DD Raz, E TI Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL RESPONSES; B SURFACE-ANTIGEN; CPG-DNA; BACTERIAL-DNA; INNATE IMMUNITY; CLASS-I; SYNTHETIC OLIGONUCLEOTIDES; INTERFERON-GAMMA; POTENT ENHANCER AB Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathogen-associated molecular patterns that are potent stimulators of innate immunity. We tested the ability of ISS to act as an immunostimulatory pathogen-associated molecular pattern in a model HIV vaccine using gp120 envelope protein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate, developed gp120-specific immune responses which included: 1) Ab production; 2) a Th1-biased cytokine response; 3) the secretion of beta -chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL activity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immunization holds promise for the development of an effective preventive and therapeutic HIV vaccine. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, Bethesda, MD 20892 USA. RP Raz, E (reprint author), Univ Calif San Diego, Dept Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. OI Datta, Sandip/0000-0003-0243-7815 FU NIAID NIH HHS [AI01490, AI07036-22, AI29164, AI36214, AI38858, AI40682, AI47078] NR 63 TC 65 Z9 70 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1584 EP 1591 PG 8 WC Immunology SC Immunology GA 471VM UT WOS:000170949400055 PM 11466380 ER PT J AU Hundley, TR Prasad, AR Beaven, MA AF Hundley, TR Prasad, AR Beaven, MA TI Elevated levels of cyclooxygenase-2 in antigen-stimulated mast cells is associated with minimal activation of p38 mitogen-activated protein kinase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); BASOPHILIC LEUKEMIA-CELLS; NECROSIS-FACTOR-ALPHA; FC-EPSILON-RI; ARACHIDONIC-ACID; MESSENGER-RNA; RBL-2H3 CELLS; PROSTAGLANDIN SYNTHASE-1; CROSS-LINKING; IGE RECEPTORS AB We have investigated possible factors that underlie changes in the production of eicosanoids after prolonged exposure of mast cells to Ag. Ag stimulation of cultured RBL-2H3 mast cells resulted in increased expression of cyclooxygenase (COX-2) protein and message. Other eicosanoid-related enzymes, namely COX-1, 5-lipoxygenase, and cytosolic phospholipase A(2) were not induced. Activation of extracellular signal-regulated kinase, e-Jun N-terminal kinase, and p38 mitogen-activated protein (MAP) kinase preceded the induction of COX-2, whereas phosphatidylinositol 3' kinase and its substrate, Akt, were constitutively activated in RBL-2H3 cells. Studies with pharmacologic inhibitors indicated that of these kinases, only p38 MAP kinase regulated expression of COX-2. The induction of COX-2 was blocked by the p38 MAP kinase inhibitor SB202190, even when added 12-16 h after stimulation with Ag when p38 MAP kinase activity had returned to near basal, but still minimally elevated, levels. Interestingly, expression of COX-2 as well as cytosolic phospholipase A(2) and 5-lipoxygenase were markedly reduced by SB202190 in unstimulated cells. Collectively, the results imply that p38 MAP kinase regulates expression of eicosanoid-related enzymes, passively or actively, at very low levels of activity in RBL-2H3 cells. Also, comparison with published data suggest that different MAP kinases regulate induction of COX-2 in inflammatory cells of different and even similar phenotype and suggest caution in extrapolating results from one type of cell to another. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Room 8N109,Bldg 10, Bethesda, MD 20892 USA. NR 50 TC 29 Z9 29 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1629 EP 1636 PG 8 WC Immunology SC Immunology GA 471VM UT WOS:000170949400061 PM 11466386 ER PT J AU Rosati, M Valentin, A Patenaude, DJ Pavlakis, GN AF Rosati, M Valentin, A Patenaude, DJ Pavlakis, GN TI CCAAT-enhancer-binding protein beta (C/EBP beta) activates CCR5 promoter: Increased C/EBP beta and CCR5 in T lymphocytes from HIV-1-infected individuals SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; NF-KAPPA-B; HIV-1 DISEASE PROGRESSION; LONG TERMINAL REPEAT; CHEMOKINE RECEPTOR-5 CCR5; TRANSCRIPTION FACTORS; EXPRESSION NF-IL6; FUSION COFACTOR; NUCLEAR FACTOR; GENE AB C/EBP beta is a member of a family of leucine zipper transcription factors that are involved in regulating the expression of several cytokines, including IL-1, IL-6, IL-8, TNF, and macrophage-inflammatory protein-1 alpha. We identified multiple C/EBP beta binding sites within the gene for CCR5, suggesting that C/EBP beta may be involved in its regulation. Transient transfection experiments in both myeloid and lymphoid cells showed an increase in CCR5 promoter-driven green fluorescent protein production in the presence of C/EBP beta. Deletion analysis identified two C/EBP beta -responsive regions in the CCR5 gene, one in the promoter region and one at the 3' part of the intron. We provide evidence that, in myeloid cells (U937), C/EBP beta independently activates CCR5 expression through sites located either in the promoter region or in the intron of the CCR5 gene. In contrast, in lymphoid cells (jurkat) the presence of the intronic cis-regulatory regions is required for C/EBP beta -mediated activation. In agreement with the functional data, EMSA demonstrated that in both myeloid and lymphoid cells C/EBP beta binds specifically to sites present in the intron, whereas interaction with the sites located in the promoter was cell type specific and was detected only in myeloid cells. Analysis of C/EBP beta in primary PBMCs obtained from HIV-1-infected individuals revealed a significant increase in C/EBP beta expression. The enhanced C/EBP beta activity correlated with a higher frequency of circulating CCR5(+) lymphocytes in AIDS patients and with a decline in CD4 lymphocyte numbers. Taken together, these results suggest that C/FBP beta is an important regulator of CCR5 expression and may play a relevant role in the pathogenesis of HIV disease. C1 NCI, Human Retrovirus Sect, Basic Res Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Pavlakis, GN (reprint author), NCI, Human Retrovirus Sect, Basic Res Lab, Frederick Canc Res & Dev Ctr, Bldg 535,Room 210, Frederick, MD 21702 USA. NR 65 TC 23 Z9 25 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1654 EP 1662 PG 9 WC Immunology SC Immunology GA 471VM UT WOS:000170949400064 PM 11466389 ER PT J AU Ohnmacht, GA Wang, E Mocellin, S Abati, A Filie, A Fetsch, P Riker, AI Kammula, US Rosenberg, SA Marincola, FM AF Ohnmacht, GA Wang, E Mocellin, S Abati, A Filie, A Fetsch, P Riker, AI Kammula, US Rosenberg, SA Marincola, FM TI Short-term kinetics of tumor antigen expression in response to vaccination SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MELANOMA-ASSOCIATED ANTIGENS; MHC CLASS-I; METASTATIC MELANOMA; T-LYMPHOCYTES; GENE-EXPRESSION; HETEROGENEOUS EXPRESSION; MONOCLONAL-ANTIBODIES; PEPTIDE VACCINATION; CELL-LINES; LESIONS AB The melanoma patient's immune response to tumor has been extensively studied. Yet, the frequently observed coexistence of tumor-associated Ag (TAA)-specific T cells with their target cells in vivo remains unexplained. Loss of TAA expression might contribute to this paradox. We studied TAA expression in metastases by obtaining fine-needle aspirations from 52 tumor lesions in 30 patients with melanoma before and soon after immunotherapy. Limitations due to low amounts of starting material were overcome with a high fidelity antisense RNA amplification method. TAA expression was measured by quantitative real-time PCR of anti-sense RNA. Decrease in gp100/Pmel-17 TAA preceded tumor disappearance in several instances and could be best explained by immune selection because most patients had received gp100/Pmel-17-specific vaccination. Conversely, immune selection was absent in nonregressing lesions. These observations suggest that vaccination, when successful, triggers a broad inflammatory reaction that can lead to tumor destruction despite immune selection. Additionally, lack of clinical response might be attributed to lack of this initiating event rather than immune escape. This study provides an insight into the natural history of tumors and defines a strategy for the characterization of gene expression in tumors during therapy. C1 NCI, Ctr Clin, Dept Transfus Med, Surg Branch,NIH, Bethesda, MD 20892 USA. NCI, Dept Cytopathol, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Ctr Clin, Dept Transfus Med, Surg Branch,NIH, Bldg 10,Room 2B42,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. RI Riker, Adam/A-6065-2011 NR 41 TC 70 Z9 73 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2001 VL 167 IS 3 BP 1809 EP 1820 PG 12 WC Immunology SC Immunology GA 471VM UT WOS:000170949400082 PM 11466407 ER PT J AU Engels, EA Rosenberg, PS Katki, H Goedert, JJ Biggar, RJ AF Engels, EA Rosenberg, PS Katki, H Goedert, JJ Biggar, RJ CA Multicenter Hemophilia Cohort Stud TI Trends in human immunodeficiency virus type 1 (HIV-1) load among HIV-1-infected children with hemophilia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 7th Conference on Retroviruses and Opportunistic Infections CY JAN 29-FEB 03, 2000 CL SAN FRANCISCO, CALIFORNIA ID RNA LEVELS; VIRAL LOAD; INFECTION; SEROCONVERSION; INFANTS; COHORT; AIDS AB In human immunodeficiency virus type 1 (HIV-1)-infected persons, virus load (serum/plasma level of HIV) predicts outcome. Virus load trends have been characterized in adults and infants but not in children. Virus load trends in 22 male children with hemophilia who acquired HIV-1 postnatally (age 0.7-5.2 years at seroconversion) were studied. The mean HIV-1 load 2 years after seroconversion was 4.40 log(10) copies/mL, and the mean change over time (slope) was 0.03 log(10) copies/(mL . year). Significant among-children variation was apparent: a random effects model predicted that 95% of children had early virus loads 3.75-5.04 log(10) copies/mL and slopes -0.07 to 0.12 log(10) copies/(mL . year). Higher early virus loads and higher slopes were each associated with increased mortality ( and, respectively). In P = .006 P = .03 conclusion, those subjects had virus load trends similar to those in adults. Early virus loads were lower than those in vertically infected infants, which suggests that factors changing soon after birth affect viral replication. C1 NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Rockville, MD 20852 USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, 6120 Execut Blvd,Rm 8005, Rockville, MD 20852 USA. RI Katki, Hormuzd/B-4003-2015 NR 15 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2001 VL 184 IS 3 BP 364 EP 368 DI 10.1086/322022 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 454FK UT WOS:000169961600017 PM 11443565 ER PT J AU Preas, HL Nylen, ES Snider, RH Becker, KL White, JC Agosti, JM Suffredini, AF AF Preas, HL Nylen, ES Snider, RH Becker, KL White, JC Agosti, JM Suffredini, AF TI Effects of anti-inflammatory agents on serum levels of calcitonin precursors during human experimental endotoxemia SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 39th Interdisciplinary Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 26-29, 1999 CL SAN FRANCISCO, CALIFORNIA ID SYSTEMIC INFLAMMATION; PROCALCITONIN; SEPSIS; RESPONSES; RECEPTOR AB Calcitonin precursor (CTpr) levels are both markers and mediators of inflammation. The duration of their elevation after intravenous endotoxin challenge and the effects of anti-inflammatory therapies were studied in 52 subjects. CTpr levels maximized at 24 h in all subjects. At 7 days (n = 4), after levels of acute-phase cytokines and C-reactive protein had normalized, CTpr levels remained 2-4-fold above baseline levels. The elimination half-life of CTpr levels ranged from 26.9 to 45.7 h. At 24 h, endotoxin and ibuprofen (compared with endotoxin alone) increased CTpr levels similar to2-fold (P = .03), whereas soluble tumor necrosis factor receptor blunted the increase in CTpr levels by 2-3-fold (P = .0015). However, soluble interleukin-1 receptor failed to alter the increase in CTpr levels. Thus, the fact that anti-inflammatory agents may alter CTpr levels resulting from a single stimulus must be considered when CTpr is used as a clinical marker. Of importance, this study reveals that anti-inflammatory agents may modulate the CTpr level, which is a potential toxic mediator of inflammation. C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. Vet Affairs Med Ctr, Dept Med, Washington, DC 20422 USA. Vet Affairs Med Ctr, Dept Surg, Washington, DC 20422 USA. Immunex Corp, Seattle, WA USA. RP Suffredini, AF (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Rm 7D-43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 16 TC 42 Z9 45 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2001 VL 184 IS 3 BP 373 EP 376 DI 10.1086/322031 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 454FK UT WOS:000169961600019 PM 11443567 ER PT J AU Jackson, SH Miller, GF Segal, BH Mardiney, M Domachowske, JB Gallin, JI Holland, SM AF Jackson, SH Miller, GF Segal, BH Mardiney, M Domachowske, JB Gallin, JI Holland, SM TI IFN-gamma is effective in reducing infections in the mouse model of chronic granulomatous disease (CGD) SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID PHAGOCYTE SUPEROXIDE PRODUCTION; RECOMBINANT INTERFERON-GAMMA; RESPIRATORY BURST; NITRIC-OXIDE; MACROPHAGES; EXPRESSION; NEUTROPHILS; DEFICIENCY; RESPONSES; MICE AB Chronic granulomatous disease (CGD) is a genetic disorder characterized by recurrent bacterial and fungal infections and tissue granuloma formation. CGD phagocytes are unable to generate superoxide because of mutations in any of four proteins of the phagocyte NADPH oxidase. Prophylactic recombinant human interferon-gamma (IFN-gamma) has been shown to reduce the frequency and severity of infections in CGD patients, but its mechanism(s) remains undefined, and its benefit has been questioned. We investigated the prophylactic effect of IFN-gamma in the mouse model of the major autosomal recessive (p47(phox)) form of CGD. In a prospective, randomized, placebo-controlled study, we compared IFN-gamma, 20,000 U administered subcutaneously (s.c.) three times weekly, to placebo in 118 p47(phox-/-) mice. By 6 weeks of study, there were 3 infections in the IFN-gamma group compared with 13 infections in the placebo group (77% reduction in infections, p < 0.01). By 18 months of study, there were 7 infections in the IFN-gamma group compared with 18 infections in the placebo group (39% reduction in infections, p < 0.01). Two animals receiving IFN-gamma had seizures after 7 months in the study. No other toxicities were observed. Peripheral blood phagocytes from IFN-gamma treated p47(phox-/-) mice produced no superoxide, excluding restoration of the oxidative burst as a mechanism for the IFN-gamma effect. There were no differences in either peritoneal macrophage nitrate production or thioglycollate-induced peritoneal exudate between treatment groups. This animal model demonstrates a prophylactic benefit of IFN-gamma similar to that seen in humans and provides an opportunity to investigate the mechanism(s) of action for IFN-gamma in CGD. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCRR, Vet Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), Bldg 10,11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 28 TC 29 Z9 30 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2001 VL 21 IS 8 BP 567 EP 573 DI 10.1089/10799900152547821 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 469KT UT WOS:000170813600002 PM 11559434 ER PT J AU Sprecher, E Chavanas, S DiGiovanna, JJ Amin, S Nielsen, K Prendiville, JS Silverman, R Esterly, NB Spraker, MK Guelig, E de Luna, ML Williams, ML Buehler, B Siegfried, EC Van Maldergem, L Pfendner, E Bale, SJ Uitto, J Hovnanian, A Richard, G AF Sprecher, E Chavanas, S DiGiovanna, JJ Amin, S Nielsen, K Prendiville, JS Silverman, R Esterly, NB Spraker, MK Guelig, E de Luna, ML Williams, ML Buehler, B Siegfried, EC Van Maldergem, L Pfendner, E Bale, SJ Uitto, J Hovnanian, A Richard, G TI The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: Implications for mutation detection and first case of prenatal diagnosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE atopic dermatitis; congenital recessive ichthyosis; hair abnormalities; linkage analysis; serine proteinase inhibitors ID PROTEIN PROTEINASE-INHIBITORS; LANCEOLATE HAIR LAH; INFANTILE ERYTHRODERMAS; LINKAGE ANALYSIS; DENATURING HPLC; CATHEPSIN-C; SKIN; GENE; DIFFERENTIATION; DESQUAMATION AB The Comel-Netherton syndrome is an autosomal recessive multisystemic disorder characterized by localized or generalized congenital ichthyosis, hair shaft abnormalities, immune deficiency, and markedly elevated IgE levels. Life-threatening complications during infancy include temperature and electrolyte imbalance, recurrent infections, and failure to thrive. To study the clinical presentations of the Comel-Netherton syndrome and its molecular cause, we ascertained 19 unrelated families of various ethnic backgrounds. Results of initial linkage studies mapped the Comel-Netherton syndrome in 12 multiplex families to a 12 cM interval on 5q32, thus confirming genetic homogeneity of Comel-Netherton syndrome across families of different origins. The Comel-Netherton syndrome region harbors the SPINK5 gene, which encodes a multidomain serine protease inhibitor (LEKTI) predominantly expressed in epithelial and lymphoid tissues. Recently, recessive mutations in SPINK5 were identified in several Comel-Netherton syndrome patients from consanguineous families. We used heteroduplex analysis followed by direct DNA sequencing to screen all 33 exons and flanking intronic. sequences of SPINK5 in the affected individuals of our cohort. Mutation analysis revealed 17 distinct mutations, 15 of which were novel, segregating in 14 Comel-Netherton syndrome families. The nucleotide changes included four non-sense mutations, eight small deletions or insertions leading to frameshift, and five splice site defects, all of which are expected to result in premature terminated or altered translation of SPINK5. Almost half of the mutations clustered between exons 2 and 8, including two recurrent mutations. Genotype-phenotype correlations suggested that homozygous nucleotide changes resulting in early truncation of LEKT1 are associated with a severe phenotype. For the first time, we used molecular data to perform prenatal testing, thus demonstrating the feasibility of molecular diagnosis in the Comel-Netherton syndrome. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Jefferson Inst Mol Med, Philadelphia, PA 19107 USA. Univ Oxford, Welcome Trust Ctr Human Genet, Oxford, England. Brown Univ, Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA. NCI, NIH, Providence, RI USA. British Columbia Childrens Hosp, Dept Pediat, Vancouver, BC V6H 3V4, Canada. Georgetown Univ, Dept Dermatol, Washington, DC USA. Choldrens Hosp Milwaukee, Dept Pediat, Milwaukee, WI USA. Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. Wellsboro Family Praxis, Wellsboro, PA USA. Hosp JM Ramos Majia, Dept Pediat, Buenos Aires, DF, Argentina. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Nebraska, Med Ctr, Dept Clin Genet, Omaha, NE USA. NIAMS, NIH, Bethesda, MD USA. GeneDx Rockville, Rockville, MD USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63104 USA. Ctr Genet Med, Inst Pathol & Genet, Gerpinnes, Belgium. RP Richard, G (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Dermatol & Cutaneous Biol, 233 S 10th St,BLSB Suite 409, Philadelphia, PA 19107 USA. RI Chavanas, stephane/K-1183-2014 FU NIAMS NIH HHS [AR02141, AR47157] NR 42 TC 93 Z9 100 U1 1 U2 4 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 BP 179 EP 187 DI 10.1046/j.1523-1747.2001.01389.x PG 9 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300002 PM 11511292 ER PT J AU Gozukara, EM Khan, SG Metin, A Emmert, S Busch, DB Shahlavi, T Coleman, DM Miller, M Chinsomboon, N Stefanini, M Kraemer, KH AF Gozukara, EM Khan, SG Metin, A Emmert, S Busch, DB Shahlavi, T Coleman, DM Miller, M Chinsomboon, N Stefanini, M Kraemer, KH TI A stop codon in xeroderma pigmentosum group C families in Turkey and Italy: Molecular genetic evidence for a common ancestor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE DNA repair; microsatellite markers; skin cancer; SNP; UV radiation ID DNA-REPAIR; SKIN-CANCER; MUTATIONS; CELLS; EXPRESSION; SUNLIGHT; PROTEIN; CLONING AB Xeroderma pigmentosum family G from Van, Turkey had two severely affected children: a son with multiple skin cancers who died at age 10 (XP67TMA), and an 8 y old daughter who began developing skin cancer before 3 y of age (XP68TMA). XP67TMA and XP68TMA cells were hypersensitive to killing by ultraviolet and the post-ultraviolet DNA repair level was 12-16% of normal. Host cell reactivation of an ultraviolet-treated reporter plasmid cotransfected with a vector expressing wild-type XPC cDNA assigned XP67TMA to xeroderma pigmentosum complementation group C. The XPC mRNA level was markedly reduced. Sequencing of the 3.5 kb XPC cDNA from XP67TMA showed a C-T mutation in XPC exon 8 at base pair 1840. This mutation converts the CGA codon of arginine at amino acid 579 to a UGA stop codon resulting in marked truncation of the 940 amino acid xeroderma pigmentosum C protein. Restriction fragment length polymorphism analysis of XPC exon 8 DNA in XP67TMA and XP68TMA showed that both affected children had a homozygous mutation and that both parents had heterozygous normal and mutated sequences at the same position consistent with a history of consanguinity in the family. The mutated allele also contained two XPC single nucleotide polymorphisms. The same mutated XPC allele was reported in an Italian family. Studies of 19 microsatellite markers flanking the XPC gene on chromosome 3 suggest that the XPC allele passed between Italy and Turkey approximately 300-500 y ago. This XPC allele containing a nonsense mutation is associated with severe clinical disease with multiple skin cancers and early death. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Inonu Univ, Sch Med, Dept Biochem, Malatya, Turkey. Yuzuncu YI Univ, Sch Med, Dept Dermatol, Van, Turkey. Armed Forces Inst Pathol, Washington, DC 20306 USA. Siriraj Med Fac, Dept Pharmacol, Bangkok, Thailand. Inst Genet Biochem & Evoluzionist, Pavia, Italy. RP Kraemer, KH (reprint author), NCI, Basic Res Lab, Bldg 37,Room 3E24, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 30 TC 33 Z9 34 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 BP 197 EP 204 DI 10.1046/j.1523-1747.2001.01424.x PG 8 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300004 PM 11511294 ER PT J AU Yang, JM Ahn, KS Cho, MO Yoneda, K Lee, CH Lee, JH Lee, ES Candi, E Melino, G Ahvazi, B Steinert, PM AF Yang, JM Ahn, KS Cho, MO Yoneda, K Lee, CH Lee, JH Lee, ES Candi, E Melino, G Ahvazi, B Steinert, PM TI Novel mutations of the transglutaminase 1 gene in lamellar ichthyosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE lamellar ichthyosis; mutations; transglutaminase gene ID CONGENITAL RECESSIVE ICHTHYOSIS; KERATINOCYTE TRANSGLUTAMINASE; IDENTIFICATION; HETEROGENEITY; DOMAINS; PROGRAM; CELLS AB Lamellar ichthyosis, one form of congenital autosomal recessive ichthyosis, is caused by mutations in the gene (TGM1) encoding the transglutaminase 1 enzyme. Mutations, deletions, or insertion of TGM1 have been reported so far. Here we report that three novel mutations of TGM1, D101V, N288T, and R306W, cause lamellar ichthyosis in two different families. The patient in family LI-KD has N288T and R306W mutations, and the patient in family LI-LK has D101V and R306W mutations. The activity of the transglutaminase 1 enzyme of the patient in family LI-LK was only about 15% of normal. Also, three-dimensional structural prediction analyses revealed that the N288T and R306W mutations, and possibly the D101V mutation, cause misfolding in the central catalytic core domain of the transglutaminase 1 enzyme that would probably result in reduced enzyme activity. Our data suggest that the greatly reduced transglutaminase 1 activities are due to disruptions of the native folding of transglutaminase 1, and that these mutations may play a critical role in the pathology of lamellar ichthyosis. C1 Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Dermatol, Seoul 135710, South Korea. Samsung Biomed Res Inst, Clin Res Ctr, Seoul, South Korea. Akita Univ, Sch Med, Dept Dermatol, Akita 010, Japan. Univ Roma Tor Vergata, Dept Expt Med & Biochem Sci, I-00173 Rome, Italy. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. RP Yang, JM (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Dermatol, 50 Ilwon Dong, Seoul 135710, South Korea. EM jmyang@smc.samsung.co.kr FU Telethon [417/BI] NR 29 TC 14 Z9 15 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 BP 214 EP 218 DI 10.1046/j.0022-202x.2001.01429.x PG 5 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300006 PM 11511296 ER PT J AU Uutani, A Nomizu, M Matsuura, H Kato, K Kobayashi, T Aaota, S Nielsen, P Sinkai, H AF Uutani, A Nomizu, M Matsuura, H Kato, K Kobayashi, T Aaota, S Nielsen, P Sinkai, H TI A specific sequence of G4 domain of laminin alpha 3 chain supports cell adhesion through syndecans and cooperative involvement of integrin beta 1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Chiba Univ, Chiba, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 060, Japan. Biomol Engn Res Inst, Suita, Osaka, Japan. NIH, Mol Biol Sect, Bethesda, MD 20892 USA. NIDCR, Bethesda, MD USA. CDBRB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 034 BP 395 EP 395 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300069 ER PT J AU Albert, M Foster, R Vogel, J AF Albert, M Foster, R Vogel, J TI Murine epidermal label-retaining cells isolated by flow cytometry do not express CD34, Sca-1 or Flk-1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 075 BP 402 EP 402 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300108 ER PT J AU Huber, A Yancey, K AF Huber, A Yancey, K TI Genes encoding hemidesmosome proteins are not coordinately regulated by TNF-alpha or IFN-gamma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 096 BP 405 EP 405 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300130 ER PT J AU Idler, W Steinert, P Kee, S AF Idler, W Steinert, P Kee, S TI Cdc42, a member of RhoA GTPases family, is associated with microtubules in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 101 BP 406 EP 406 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300133 ER PT J AU Kee, S Steinert, P AF Kee, S Steinert, P TI Activation of RhoA and actin polymerization are not required for cell-cell adhesion induced by microtubule disruption in keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 102 BP 406 EP 406 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300136 ER PT J AU Jang, S Steinert, P Kee, S AF Jang, S Steinert, P Kee, S TI Multi-step model of cell-cell adhesion induced by microtubule disruptions in normal human epidermal keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 103 BP 407 EP 407 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300137 ER PT J AU Park, G Denning, M Morasso, M AF Park, G Denning, M Morasso, M TI Role of PKC phosphorylation on Dlx3 homeoprotein function SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, NIAMS, Skin Biol Lab, Bethesda, MD USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 117 BP 409 EP 409 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300150 ER PT J AU Marekov, L Sprecher, E Steinert, P Neldner, K Richard, G AF Marekov, L Sprecher, E Steinert, P Neldner, K Richard, G TI Mass-spectroscopic identification of a mutant keratin 1 protein assosiated with ichtyosis hystrix Curth-Mackin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Thomas Jefferson Univ, Jefferson Inst Mol Med, Dept Dermatol & Cutaneous Biol, Philadelphia, PA 19107 USA. Texas Tech Univ, Dept Dermatol, Lubbock, TX 79409 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 136 BP 412 EP 412 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300170 ER PT J AU Steinert, P Marekov, L Parry, D AF Steinert, P Marekov, L Parry, D TI Evidence for protofibrils in keratin intermediate filaments SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Massey Univ, Inst Fundamental Sci, Palmerston North, New Zealand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 137 BP 412 EP 412 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300168 ER PT J AU Ahvazi, B Kim, H Idler, W Steinert, P AF Ahvazi, B Kim, H Idler, W Steinert, P TI Three-dimensional structures of human transglutaminase 3, from zymogen to active form SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 146 BP 414 EP 414 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300181 ER PT J AU Kalinin, A Idler, W Steinert, P AF Kalinin, A Idler, W Steinert, P TI Mechanism of cornified cell envelope scaffold formation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 147 BP 414 EP 414 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300179 ER PT J AU Blauvelt, A Kawamura, T AF Blauvelt, A Kawamura, T TI Chemically modified RANTES analogues block CCR5-mediated HIV infection of Langerhans cells within epithelial tissue explants: Implications for blocking sexual transmission of HIV SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 277 BP 436 EP 436 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300310 ER PT J AU Kawamura, T Blauvelt, A AF Kawamura, T Blauvelt, A TI HIV envelope glycoprotein gp120 secreted by HIV-infected dendritic cells impairs T cell proliferation and IL-2 production: Implications for HAART-treated patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 278 BP 436 EP 436 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300313 ER PT J AU Lenczowski, J Wilson, M Udey, M AF Lenczowski, J Wilson, M Udey, M TI Increased expression of Stat4 mRNA and protein by activated murine skin dendritic cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 330 BP 444 EP 444 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300362 ER PT J AU Wu, M Saeki, H Hwang, S AF Wu, M Saeki, H Hwang, S TI Subcutaneously (SC)-injected, CXCR5-transduced bone marrow-derived dendritic cells (BMDC) traffic to B cells zones of lymph nodes (LN) and modify antigen-specific immune responses SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Univ Tokyo, Dept Dermatol, Tokyo 113, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 350 BP 448 EP 448 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300384 ER PT J AU Shibagaki, N Udey, M AF Shibagaki, N Udey, M TI Dendritic cells (DC) treated with TAT protein transduction domain (PTD)-containing recombinant tumor antigens efficiently induce cytotoxic lymphocytes (CTL) and tumor immunity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 360 BP 449 EP 449 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300392 ER PT J AU Lenz, P Day, P Pang, Y Lowy, D Schiller, J AF Lenz, P Day, P Pang, Y Lowy, D Schiller, J TI Papillomavirus-like particles cause dendritic cell maturation and induce a potent in vitro primary immune response SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 364 BP 450 EP 450 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300397 ER PT J AU Olasz, E Katz, S AF Olasz, E Katz, S TI Mouse bone marrow-derived dendritic cells do not effectively cross-present haptens and soluble proteins on MHC class II molecules SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 365 BP 450 EP 450 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300395 ER PT J AU Yamada, N Tagaya, Y Shimada, S Katz, S AF Yamada, N Tagaya, Y Shimada, S Katz, S TI Fetal skin-derived cultured mast cells (FSMC); A novel model to study cutaneous mast cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Yamanashi Med Univ, Yamanashi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 379 BP 453 EP 453 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300411 ER PT J AU Maki, W Fitzhugh, D Caughman, S Naik, S Hwang, S AF Maki, W Fitzhugh, D Caughman, S Naik, S Hwang, S TI A critical role for CCR6 in the arrest of CLA(+) memory T cells on microvascular endothelia under physiologic flow conditions in vitro SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 395 BP 455 EP 455 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300425 ER PT J AU Roh, J Yee, C Vogel, J Yancey, K AF Roh, J Yee, C Vogel, J Yancey, K TI A transgenic approach for model immune responses against bullous pemphigoid antigen 2 (BPAG2) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 427 BP 461 EP 461 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300459 ER PT J AU Shibaki, A Sato, A Katz, S AF Shibaki, A Sato, A Katz, S TI Induction of autoimmune skin disease by passively transferred T cell? @ receptor transgenic T cells into keratin 14-ovalbumin transgenic mouse SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 459 BP 466 EP 466 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300490 ER PT J AU Seiter, S Monsurro, V Wunderlich, J Rosenberg, S Marincola, F AF Seiter, S Monsurro, V Wunderlich, J Rosenberg, S Marincola, F TI MART-1/MelanA and gp100/PMel17 immunodominance revisited: Direct enumeration of frequency of melanoma differentiation antigen (MDA)-specific T-cells in tumor metastases TIL cultures SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, DTM, Bethesda, MD USA. NIH, NCI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 471 BP 468 EP 468 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300502 ER PT J AU Lee, S Kim, S Steinert, P AF Lee, S Kim, S Steinert, P TI Regulation of transglutaminase 2 by transforming growth factor-beta 1 in dermal fibroblasts SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, NIAMS, LSB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 479 BP 469 EP 469 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300509 ER PT J AU Verrecchia, F Vindevoghel, L Lechleider, R Roberts, A Uitto, J Mauviel, A AF Verrecchia, F Vindevoghel, L Lechleider, R Roberts, A Uitto, J Mauviel, A TI Smad3/AP-1 interactions control transcriptional responses to TGF-beta in a promoter-specific manner SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 INSERM, Skin Res Inst, U532, Paris, France. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 484 BP 470 EP 470 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300516 ER PT J AU Gerdes, M Levy, M Michael, L Moitra, J Glick, A Vinson, C Yuspa, S AF Gerdes, M Levy, M Michael, L Moitra, J Glick, A Vinson, C Yuspa, S TI Development of a transgenic model for conditional regulation of AP-1 transcription factors in epidermis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Div Basic Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 489 BP 471 EP 471 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300519 ER PT J AU Sampat, K Yuspa, S Li, L AF Sampat, K Yuspa, S Li, L TI Negative regulation of the Akt cell survival pathway by the protein kinase C signal transduction pathway SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 508 BP 474 EP 474 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300540 ER PT J AU Bhogte, E Marko, R Glick, A AF Bhogte, E Marko, R Glick, A TI Inhibition of TGF beta signaling in keratinocytes activates ERK through a Smad and MEK independent pathway SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 514 BP 475 EP 475 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300546 ER PT J AU Vijayachandra, K Glick, A AF Vijayachandra, K Glick, A TI A role for Smad3 in the senescence response of mouse keratinocytes to oncogenic Ras SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 524 BP 477 EP 477 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300557 ER PT J AU Liu, X Alexander, V Marko, R Glick, A AF Liu, X Alexander, V Marko, R Glick, A TI Rapid and sustained induction of Smad7 in the epidermis and hair follicles of transgenic mice conditionally expressing active TGF beta 1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 533 BP 478 EP 478 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300561 ER PT J AU Gonzalez, E Wiley, H Hwang, S AF Gonzalez, E Wiley, H Hwang, S TI CC chemokine receptor 7 (CCR7)-Transduced B16 melanoma cells show enhanced early metastases to regional lymph nodes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 561 BP 483 EP 483 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300590 ER PT J AU Maeda, T Hanna, A Sim, A Chua, P Chong, M Nikaido, O Fornace, A Tron, V AF Maeda, T Hanna, A Sim, A Chua, P Chong, M Nikaido, O Fornace, A Tron, V TI Gadd45 regulates the G2/M checkpoint via cdc2 kinase, DNA repair and cell death in mouse keratinocytes after UV exposure SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Alberta, Edmonton, AB, Canada. Kanazawa Univ, Kanazawa, Ishikawa 920, Japan. NIH, NCI, Div Basic Sci, Gene Response Sect, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 584 BP 487 EP 487 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300616 ER PT J AU Athar, M Morel, K An, K Kim, A Kepelovich, L Bickers, D AF Athar, M Morel, K An, K Kim, A Kepelovich, L Bickers, D TI Chemopreventive effect of the cyclooxygenase inhibitor sulindac against UVB-induced expression of surrogate markers of skin cancer SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. NCI, Div Canc Prevent, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 589 BP 488 EP 488 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300619 ER PT J AU Hwang, S Fitzhugh, D AF Hwang, S Fitzhugh, D TI Up-regulated L-selectin and diminished integrin expression in Sezary cells: Functional consequences under physiologic shear stress conditions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 599 BP 489 EP 489 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300627 ER PT J AU Beaty, M Toro, J Sobara, L Stern, J Wilson, W Jaffe, E AF Beaty, M Toro, J Sobara, L Stern, J Wilson, W Jaffe, E TI Cutaneous lymphomatoid granulomatosis: A clinical, microscopic and molecular study SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 603 BP 490 EP 490 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300632 ER PT J AU Nguyen, J Wang, J Vortmeyer, A Turner, M Marx, S Zhuang, Z Darling, T AF Nguyen, J Wang, J Vortmeyer, A Turner, M Marx, S Zhuang, Z Darling, T TI Genetic and immunohistochemical studies of angiofibromas and collagenomas in multiple endocrine neoplasia type 1 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. NIH, NINDS, Bethesda, MD 20814 USA. NIH, Bethesda, MD 20814 USA. NIH, NIDDK, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 610 BP 491 EP 491 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300641 ER PT J AU Sodhi, A Montaner, S Gutkind, J AF Sodhi, A Montaner, S Gutkind, J TI The Kaposi's Sarcoma Associated Herpesvirus G protein-coupled receptor up-regulates VEGF and promotes endothelial cell survival SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 614 BP 492 EP 492 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300646 ER PT J AU Noonan, F Recio, J Anvers, M De Fabo, E Merlino, G AF Noonan, F Recio, J Anvers, M De Fabo, E Merlino, G TI A mouse model for UV-induced junctional melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 George Washington Univ, Med Ctr, Washington, DC 20037 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. N Carolina FCRDC, SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 620 BP 493 EP 493 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300652 ER PT J AU Tadokoro, T Kobayashi, N Beer, J Zmudzka, B Hearing, V Korossy, K Ito, S Wakamatsu, K AF Tadokoro, T Kobayashi, N Beer, J Zmudzka, B Hearing, V Korossy, K Ito, S Wakamatsu, K TI DNA damage and melanin production induced by ultraviolet radiation in human skin within various racial/ethnic groups SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, CDRH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 650 BP 498 EP 498 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300682 ER PT J AU Pinnell, S DeBuys, H Omar, M Walker, L Monteiro-Riviere, N Dawson, T Waalkes, M AF Pinnell, S DeBuys, H Omar, M Walker, L Monteiro-Riviere, N Dawson, T Waalkes, M TI Topical zinc sulphate - An antioxidant for skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Duke Univ, Durham, NC USA. Phytoceut, Elmwood Pk, NJ USA. N Carolina State Univ, Raleigh, NC 27695 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 699 BP 506 EP 506 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300728 ER PT J AU Lei, T Virador, V Vieira, W Toyofuku, K Hearing, V AF Lei, T Virador, V Vieira, W Toyofuku, K Hearing, V TI Involvement of MITF and the PKA signal pathway in regulation of melanoblast differentiation induced by 8-methoxypsoralen SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 710 BP 508 EP 508 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300742 ER PT J AU Kushimoto, T Basrur, V Matsunaga, J Vieira, W Muller, J Appella, E Hearing, V AF Kushimoto, T Basrur, V Matsunaga, J Vieira, W Muller, J Appella, E Hearing, V TI Melanosome mapping by purification of early stage melanosomes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 715 BP 509 EP 509 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300745 ER PT J AU Rouzaud, F Julien, R Leveziel, H Gallet, P Oulmouden, A AF Rouzaud, F Julien, R Leveziel, H Gallet, P Oulmouden, A TI The role of extension gene in bovine coat color determination. Non-black phenotypes are associated with transcripts spliced in the 3 ' UT region SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, NCI, Cell Biol Lab, Bethesda, MD 20892 USA. INRA, Unite Genet Mol Anim, Limoges, France. Univ Limoges, Limoges, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 718 BP 509 EP 509 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300749 ER PT J AU Boissy, R Huizing, M Zhao, Y Sarangarajan, R Gahl, W AF Boissy, R Huizing, M Zhao, Y Sarangarajan, R Gahl, W TI Melanocyte dysfunction in Hermansky-Puklak Syndromes (HPS-1 & 2) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Cincinnati, Coll Med, Cincinnati, OH USA. NIH, NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 725 BP 510 EP 510 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300753 ER PT J AU Khan, S Shahlavi, T Muniz-Medina, V Baker, C Schneider, T Kraemer, K AF Khan, S Shahlavi, T Muniz-Medina, V Baker, C Schneider, T Kraemer, K TI Influence of a single nucleotide polymorphism in an XPC splice acceptor site on alternative splicing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 756 BP 515 EP 515 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300786 ER PT J AU Ueda, T Khan, S Emmett, S Shahlavi, T Busch, D Schneider, T Kraemer, K AF Ueda, T Khan, S Emmett, S Shahlavi, T Busch, D Schneider, T Kraemer, K TI A G to A change at the splice donor site of intron 2 in the Xeroderma pigmentosum group C (XPC) gene alters the efficiency of PremRNA splicing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Environm & Toxicol Pathol, Washington, DC 20306 USA. NCI, Lab Expt & Computat Biol, Frederick, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 755 BP 515 EP 515 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300783 ER PT J AU Sprecher, E Ishida-Yamamoto, A Becker, O Marekov, L Neldner, K Steinert, P Miller, C Richard, G AF Sprecher, E Ishida-Yamamoto, A Becker, O Marekov, L Neldner, K Steinert, P Miller, C Richard, G TI Evidence for novel functions of the keratin tail emerging from a mutation causing ichthyosis hystrix SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Rambam Med Ctr, Dept Dermatol, Haifa, Israel. Asahikawa Med Coll, Asahikawa, Hokkaido 078, Japan. Tel Aviv Univ, Sch Chem, IL-69978 Tel Aviv, Israel. Niams, Skin Biol Lab, Bethesda, MD USA. Texas Tech Univ, Lubbock, TX 79409 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 763 BP 517 EP 517 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300793 ER PT J AU Kim, S Jeong, E Steinert, P Jang, S AF Kim, S Jeong, E Steinert, P Jang, S TI Increase of transglutaminase 1 expression by interferon-gamma is directly mediated by STATs in keratinocytes and muscle cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 769 BP 518 EP 518 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300799 ER PT J AU Bale, S Toro, J Gahl, W AF Bale, S Toro, J Gahl, W TI A new locus for Hermansky-Pudlak Syndrome in Puerto Rico SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 783 BP 520 EP 520 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300812 ER PT J AU Zbar, B Toro, J Turner, M Glenn, G Duray, P Choyke, P Linehan, M AF Zbar, B Toro, J Turner, M Glenn, G Duray, P Choyke, P Linehan, M TI Birt-Hogg-Dube syndrome has an increase risk for renal neoplasms and spontaneous pneumothrorax SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 787 BP 521 EP 521 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300817 ER PT J AU Jang, GLI Steinert, SP AF Jang, GLI Steinert, SP TI An AP2 site in the mouse trichohyalin gene promoter may confer tissue specific expression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, NIAMSD, Skin Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 796 BP 522 EP 522 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300827 ER PT J AU Dallinger, G Puttaraju, M Mitchell, L Yancey, K Klausegger, A Hintner, H Bauer, J AF Dallinger, G Puttaraju, M Mitchell, L Yancey, K Klausegger, A Hintner, H Bauer, J TI SMaRT repair of collagen 17A1 mRNA: Semi-quandtytive PCR analysis of cis- vs. trans-splicing SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Gen Hosp, Salzburg, Austria. NIH, Dermatol Branch, Bethesda, MD USA. Intronn, LLC, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 805 BP 524 EP 524 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300835 ER PT J AU Pfutzner, W Kolodka, T Foster, R Snead, E Taichman, L Vogel, J AF Pfutzner, W Kolodka, T Foster, R Snead, E Taichman, L Vogel, J TI Topical selection of keratinocytes transduced with the multidrug resistance (MDR) gene results in sustained high-level transgene expression in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Johnson & Johnson, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 836 BP 529 EP 529 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300868 ER PT J AU Egan, C Brown, M White, J Yancey, K AF Egan, C Brown, M White, J Yancey, K TI Treatment of epidermolysis bullosa acquisita with the humanized anti-Tac mAb Daclizumab SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH, NCI, Dermatol Branch, DCS, Bethesda, MD USA. NIH, DLM, CC, Bethesda, MD USA. NIH, Off Canc Complementary & Alternat Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 915 BP 542 EP 542 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300944 ER PT J AU Kimball, A Kawamura, T Turner, M Blauvelt, A AF Kimball, A Kawamura, T Turner, M Blauvelt, A TI Randomized double-blind placebo-controlled trial using interleukin-10 for psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 937 BP 546 EP 546 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668300967 ER PT J AU Nguyen, D Turner, J Biesecker, L Darling, T AF Nguyen, D Turner, J Biesecker, L Darling, T TI Skin findings in Proteus syndrome SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. NIH, Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2001 VL 117 IS 2 MA 973 BP 552 EP 552 PG 1 WC Dermatology SC Dermatology GA 466WC UT WOS:000170668301003 ER PT J AU Pawlosky, RJ Hibbeln, JR Novotny, JA Salem, N AF Pawlosky, RJ Hibbeln, JR Novotny, JA Salem, N TI Physiological compartmental analysis of alpha-linolenic acid metabolism in adult humans SO JOURNAL OF LIPID RESEARCH LA English DT Article DE fatty acid metabolism; omega-3 fatty acids; compartmental model; kinetics; docosahexaenoic acid; isotope tracer ID POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; TERM INFANTS; ARACHIDONIC-ACID; VISUAL-ACUITY; GUINEA-PIG; IN-VIVO; DIETARY; PLASMA; BRAIN AB A physiological compartmental model of a-linolenic acid metabolism was derived from the plasma concentration-time curves for d5-18:3n-3, d5-20:5n-3, d5-22:5n-3, and d5-22:6n-3 in eight healthy subjects. Subjects received a I-g oral dose of an isotope tracer of a-linolenate (d5-18:3n-3 ethyl ester) while subsisting on a rigorously controlled beef-based diet. By utilizing the Windows Simulation and Analysis Modeling program, kinetic parameters were determined for each subject. Half-lives and mean transit times of the n-3 fatty acids in the plasma were also determined. The model predicted plasma values for the n-3 fatty acids in good accordance with the measured steady state concentrations and also predicted dietary linolenic acid intake for each subject in accordance with values determined by lipid analysis of the diet. Only about 0.2% of the plasma 18:3n-3 was destined for synthesis of 20:5n-3, approximately 63% of the plasma 20:5n-3 was accessible for production of 22:5n-3, and 37% of 22:5n-3 was available for synthesis of 22:6n-3.ie The inefficiency of the conversion of 18:3n-3 to 20:5n-3 indicates that the biosynthesis of long-chain n-3 PUFA from a-linolenic acidis limited in healthy individuals. In contrast, the much greater rate of transfer of mass from the plasma 20:5n-3 compartment to 22:5n-3 suggests that dietary eicosapentaenoic acid may be well utilized in the biosynthesis of 22:6n-3 in humans. C1 Food Composit Lab, Beltsville, MD 20705 USA. USDA ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Pawlosky, RJ (reprint author), Food Composit Lab, Beltsville, MD 20705 USA. NR 39 TC 335 Z9 352 U1 0 U2 29 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2001 VL 42 IS 8 BP 1257 EP 1265 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 459VV UT WOS:000170272900011 PM 11483627 ER PT J AU Wu, ZR Bax, A AF Wu, ZR Bax, A TI Measurement of homonuclear proton couplings based on cross-peak nulling in CT-COSY SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; LIQUID-CRYSTALLINE MEDIUM; QUANTITATIVE J-CORRELATION; TWO-DIMENSIONAL NMR; SPIN SYSTEMS; 2D NMR; CONSTANTS; PROTEINS; MACROMOLECULES; SPECTRA AB A method in which H-1-H-1 scalar and dipolar couplings are obtained from the cross-peak nulling condition in a series of constant-time (CT) COSY spectra, as a function of the duration of the CT period, is described. The method is best suited for measurement of H-1-H-1 couplings in the range 5-20 Hz. It is shown, however, that results can be sensitive to cross-correlated relaxation effects. Also, artifactual resonances, resulting from strong coupling, can be quite pronounced in CT-COSY spectra, even when \J(AB) /(delta (A)- delta (B))\ < 0.1. The experiments are demonstrated for the DNA dodecamer d(CGCGAATTCGCG)(2), both in isotropic solution and in a liquid crystalline phase. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Wu, ZR (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 48 TC 20 Z9 20 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD AUG PY 2001 VL 151 IS 2 BP 242 EP 252 DI 10.1006/jmre.2001.2358 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 463ZV UT WOS:000170508200004 PM 11531346 ER PT J AU Martinez, A Hodge, DL Garayoa, M Young, HA Cuttitta, F AF Martinez, A Hodge, DL Garayoa, M Young, HA Cuttitta, F TI Alternative splicing of the proadrenomedullin gene results in differential expression of gene products SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID TUMOR-CELL LINES; MESSENGER-RNA; ADRENOMEDULLIN EXPRESSION; GENOMIC STRUCTURE; INTRON RETENTION; GROWTH-FACTOR; PEPTIDE GENE; HUMAN TISSUE; PROTEIN; RECEPTOR AB The adrenomedullin (AM) gene codifies for two bioactive peptides, AIM and proAM N-terminal 20 peptide (PAMP). We have found two forms of the AXI mRNA. Form A is devoid of introns and results in a prohormone containing both peptides. Form B retains the third intron, which introduces a premature stop codon, producing a shorter prohormone with only PAMP. Tissues with a higher B/A ratio were more immunoreactive for PAMP than for ANI. The form B message was found in the cytoplasmic compartment, thus excluding that the longer message was a result of contaminating nuclear mRNA. Form B was found in cells that express PAMP but not AM. mRNA expression in a variety of cell lines was investigated by ribonuclease protection assay and form B was found in significant amounts in two of them. Treatments that modify AM expression, such as exposure to hypoxia, were shown to change the B/A ratio and the relative secretion of AM and PAMP, indicating that the splicing mechanism for AM can be modulated and is physiologically relevant. Analysis of the sequence of the third intron and the fourth exon of the AM gene found motifs compatible with a highly regulated alternative splicing mechanism. C1 NCI, Dept Cell & Canc Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Expt Immunol Lab, Frederick, MD 21702 USA. RP Martinez, A (reprint author), NCI, Dept Cell & Canc Biol, Ctr Canc Res, NIH, Bldg 10,Room 13N262, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 47 TC 36 Z9 40 U1 1 U2 2 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD AUG PY 2001 VL 27 IS 1 BP 31 EP 41 DI 10.1677/jme.0.0270031 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 464UD UT WOS:000170549400003 PM 11463574 ER PT J AU Culmsee, C Monnig, J Kemp, BE Mattson, MP AF Culmsee, C Monnig, J Kemp, BE Mattson, MP TI AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE AICAR; Alzheimer; AMPK; amyloid; antisense; apoptosis; glutamate; hippocampus; ischemia ID CELL-PERMEABLE ACTIVATOR; ACETYL-COA CARBOXYLASE; HUMAN CORTICAL-NEURONS; HIPPOCAMPAL-NEURONS; FATTY-ACID; CALCIUM HOMEOSTASIS; SKELETAL-MUSCLE; 5-AMINOIMIDAZOLE-4-CARBOXAMIDE RIBONUCLEOSIDE; INDUCED APOPTOSIS; ATP DEPLETION AB Adenosine monophosphate-activated protein kinase (AMPK) is a member of metabolite-sensing kinase family that plays important roles in responses of muscle cells to metabolic stress. AMPK is a heterotrimer of a catalytic a subunit (alpha1 or alpha2), and beta(beta1 or beta2) and gamma(gamma1 or gamma2) subunits. Because the brain has a high metabolic rate and is sensitive to changes in the supply of glucose and oxygen, we investigated the expression of AMPK in rat embryonic and adult brain and its role in modifying neuronal survival under conditions of cellular stress. We report that catalytic (alpha1 and alpha2) and noncatalytic (beta2 and gamma1) subunits of AMPK are present at high levels in embryonic hippocampal neurons in vivo and in cell culture. In the adult rat brain, the catalytic subunits al and alpha2 are present in neurons throughout the brain. The AMPK-activating agent AICAR protected hippocampal neurons against death induced by glucose deprivation, chemical hypoxia, and exposure to glutamate and amyloid beta -peptide. Suppression of levels of the AMPK alpha1 and alpha2 subunits using antisense technology resulted in enhanced neuronal death following glucose deprivation, and abolished the neuroprotective effect of AICAR. These findings suggest that AMPK can protect neurons against metabolic and excitotoxic insults relevant to the pathogenesis of several different neurodegenerative conditions. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Marburg, Inst Pharmakol & Toxikol, D-35037 Marburg, Germany. Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. St Vincents Hosp, St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Kemp, Bruce/L-2633-2014 OI Kemp, Bruce/0000-0001-6735-5082 NR 59 TC 215 Z9 221 U1 0 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD AUG PY 2001 VL 17 IS 1 BP 45 EP 58 DI 10.1385/JMN:17:1:45 PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 478AT UT WOS:000171321300005 PM 11665862 ER PT J AU Chen, YW Yu, P Lu, D Tagle, DA Cai, T AF Chen, YW Yu, P Lu, D Tagle, DA Cai, T TI A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies and interacts with neurofibromatosis type 2 gene product schwannomin SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE beta-spectrin; beta SpII Sigma 2; Purkinje-cell bodies; cerebellum; schwannomin; neurofibromatosis type 2; human chromosome 2p13-21 ID GIRDLE MUSCULAR-DYSTROPHY; AXON INITIAL SEGMENTS; IN-VITRO; BRAIN; IDENTIFICATION; EXPRESSION; DOMAINS; DIFFERENTIATION; STATISTICS; ANKYRIN(G) AB We report the identification of a full-length novel beta -spectrin II gene (beta SpII Sigma2) in human brain. The beta SpII Sigma2 gene has 32 exons encoding an actin-binding domain, followed by 17-spectrin repeats, and a short COOH-terminal regulatory region that lacks the Pleckstrin homology (PH) domain. Pair-wise sequence analysis showed an additional 36 and 28 amino acids located at the NH2 and COOH-terminal regions of beta SpII Sigma2, respectively. Northern-blot analysis showed an abundant expression of beta SpII Sigma2 transcripts in brain, lung, and kidney. Western-blot analysis confirmed the predicted similar to 225 kD molecular size of beta SpII Sigma2 protein in these same tissues. In brain, immunofluorescent staining revealed that beta SPII Sigma2 was enriched in cerebellar neurons, with specific enrichment in Purkinje cell bodies, but not in dendrites. Of considerable interest, neurofibromatosis type 2 (NF2) gene product schwannomin was found to co-immunoprecipitate with beta SpII Sigma2 in cultured Purkinje cells. These results suggest that beta SpII Sigma2 may play an important role in the assembly of the specialized plasma membrane domain of Purkinje neurons and that schwannomin may be involved in actin-cytoskeleton organization by interacting with beta SpII Sigma2. C1 Georgetown Univ, Dept Physiol, Med Ctr, Washington, DC 20016 USA. Fujing Med Univ, Fujian, Peoples R China. NCI, Struct Biophys Lab, Frederick, MD 21702 USA. Vet Affairs Med Ctr, Washington, DC 20016 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Expt Med Sect, OIIB, NIH, Bethesda, MD 20892 USA. RP Chen, YW (reprint author), Georgetown Univ, Dept Physiol, Med Ctr, Washington, DC 20016 USA. NR 41 TC 10 Z9 11 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD AUG PY 2001 VL 17 IS 1 BP 59 EP 70 DI 10.1385/JMN:17:1:59 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 478AT UT WOS:000171321300006 PM 11665863 ER PT J AU Haughey, NJ Nath, A Mattson, MP Slevin, JT Geiger, JD AF Haughey, NJ Nath, A Mattson, MP Slevin, JT Geiger, JD TI HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AIDS dementia; glutamate; HIV-1; NMDA; phosphorylation; Tat ID PROTEIN-KINASE-C; IMMUNODEFICIENCY-VIRUS TYPE-1; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; AMINO-ACID RECEPTORS; HIPPOCAMPAL-NEURONS; PC12 CELLS; OXIDATIVE STRESS; ZINC INHIBITION; NR1 SUBUNIT; TNF-ALPHA AB Toxic effects of HIV-1 proteins contribute to altered function and decreased survival of select populations of neurons in HIV-1-infected brain. One such HIV-1 protein, Tat, can activate calcium release from IP3-sensitive intracellular pools, induce calcium influx in neural cells, and, as a result, can increase neuronal cell death. Here, we provide evidence that Tat potentiates excitatory amino acid (glutamate and NMDA) triggered calcium flux, as well as glutamate- and staurosporine-mediated neurotoxicity. Calcium flux in cultured rat hippocampal neurons triggered by the transient application of glutamate or NMDA was facilitated by pre-exposure to Tat. Facilitation of glutamate-triggered calcium flux by Tat was prevented by inhibitors of ADP-ribosylation of G(i)/G(o) proteins (pertussis toxin), protein kinase C (H7 and bisindolymide), and IP3-mediated calcium release (xestospongin C), but was not prevented by an activator of G(s) (cholera toxin) or an inhibitor of protein kinase A (H89). Facilitation of NMDA-triggered calcium flux by Tat was reversed by inhibitors of tyrosine kinase (genestein and herbimycin A) and by an inhibitor of NMDA receptor function (zinc). Tat increased P-32 incorporation into NMDA receptor subunits NR2A and NR2B and this effect was blocked by genestein. Subtoxic concentrations of Tat combined with subtoxic concentrations of glutamate or staurosporine increased neuronal cell death significantly. Together, these findings suggest that NMDA receptors play an important role in Tat neurotoxicity and the mechanisms identified may provide additional therapeutic targets for the treatment of HIV-1 associated dementia. C1 Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB R3E 0T6, Canada. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. VAMC, Lexington, KY USA. RP Geiger, JD (reprint author), Univ Manitoba, Dept Pharmacol & Therapeut, Winnipeg, MB R3E 0T6, Canada. RI Mattson, Mark/F-6038-2012 FU NINDS NIH HHS [NS/MH39253, NS39184] NR 63 TC 151 Z9 155 U1 1 U2 4 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2001 VL 78 IS 3 BP 457 EP 467 DI 10.1046/j.1471-4159.2001.00396.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 460TZ UT WOS:000170325800005 PM 11483648 ER PT J AU Lu, CB Chan, SL Haughey, N Lee, WT Mattson, MP AF Lu, CB Chan, SL Haughey, N Lee, WT Mattson, MP TI Selective and biphasic effect of the membrane lipid peroxidation product 4-hydroxy-2,3-nonenal on N-methyl-D-aspartate channels SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; amyloid precursor protein; calcium; excitotoxicity; mitochondrial depolarization; synaptic plasticity ID AMYLOID PRECURSOR PROTEIN; LONG-TERM POTENTIATION; CENTRAL-NERVOUS-SYSTEM; ISCHEMIC BRAIN INJURY; NEURONAL CELL-DEATH; HIPPOCAMPAL-NEURONS; BETA-PEPTIDE; RECEPTOR SUBUNITS; OXIDATIVE STRESS; KAPPA-B AB Increased oxyradical production and membrane lipid peroxidation occur in neurons under physiological conditions and in neurodegenerative disorders. Lipid peroxidation can alter synaptic plasticity and may increase the vulnerability of neurons to excitotoxicity, but the underlying mechanisms are unknown. We report that 4-hydroxy-2,3-nonenal (4HN), an aldehyde product of lipid peroxidation, exerts a biphasic effect on NMDA-induced current in cultured rat hippocampal neurons with current being increased during the first 2 h and decreased after 6 h. Similarly, 4HN causes an early increase and a delayed decrease in NMDA-induced elevation of intracellular Ca2+ levels. In contrast, 4HN affects neither the ion current nor the Ca2+ response to alpha -amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). The initial enhancement of NMDA-induced current is associated with increased phosphorylation of the NR1 receptor subunit, whereas the delayed suppression of current is associated with cellular ATP depletion and mitochondrial membrane depolarization. Cell death induced by 4HN is attenuated by an NMDA receptor antagonist, but not by an AMPA receptor antagonist. A secreted form of amyloid precursor protein, previously shown to protect neurons against oxidative and excitotoxic insults, prevented each of the effects of 4HN including the early and late changes in NMDA current, delayed ATP depletion, and cell death. These findings show that the membrane lipid peroxidation product 4HN can modulate NMDA channel activity, suggesting a role for this aldehyde in physiological and pathophysiological responses of neurons to oxidative stress. C1 NIA, Neurosci Lab, Gerontol Res Ctr 4F01, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr 4F01, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 79 TC 29 Z9 33 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2001 VL 78 IS 3 BP 577 EP 589 DI 10.1046/j.1471-4159.2001.00431.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 460TZ UT WOS:000170325800018 PM 11483661 ER PT J AU Grinevich, V Ma, XM Herman, JP Jezova, D Akmayev, I Aguilera, G AF Grinevich, V Ma, XM Herman, JP Jezova, D Akmayev, I Aguilera, G TI Effect of repeated lipopolysaccharide administration on tissue cytokine expression and hypothalamic-pituitary-adrenal axis activity in rats SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE corticotropin releasing hormone; vasopressin; glucocorticoid receptors; cytokines; lipopolysaccharide ID CORTICOTROPIN-RELEASING HORMONE; ADJUVANT-INDUCED ARTHRITIS; MESSENGER-RIBONUCLEIC-ACID; REPEATED ENDOTOXIN TREATMENT; HYPERTONIC SALINE INJECTION; GENE-EXPRESSION; DIFFERENTIAL REGULATION; INTERLEUKIN-1 RECEPTOR; ARGININE-VASOPRESSIN; ANTERIOR-PITUITARY AB The effects of chronic immune challenge on cytokine expression and hypothalamic-pituitary-adrenal axis (HPA) axis responses to stress were studied in Wistar rats after administration of increasing doses of lipopolysaccharide (LPS). Repeated LPS (R-LPS) decreased body weight and increased adrenal weight and pituitary pro-opiomelanocortin mRNA levels. LPS injection increased plasma adrenocorticotropic hormone (ACTH) and corticosterone but the effect was attenuated in R-LPS. Plasma corticosterone but not ACTH responses to restraint were also reduced in R-LPS. Basal and restraint-stimulated corticotropin releasing hormone (CRH) mRNA levels were lower in R-LPS, but responses to a new LPS injection were similar to controls. In contrast, type 1 CRH receptor (CRH-R1) mRNA responses to both LPS and restraint were blunted in R-LPS. Vasopressin mRNA levels in parvocellular neurones were higher in R-LPS, and increased further after restraint but not after a new LPS injection. Glucocorticoid receptor (GR) levels in the paraventricular nucleus (PVN) increased after a single LPS or R-LPS (24 h after the last injection) but declined after a new injection in R-LPS. Interleukin (IL)-1 beta and IL-6 mRNAs increased in the pituitary, spleen and circumventricular organs after single or R-LPS, suggesting that cytokines may contribute to the activation of the HPA axis though pathways from the circumventricular organs as well as paracrine effects in the pituitary. The data show that (i) adaptation of the HPA axis during repeated LPS injection involves increases in vasopressin: CRH expression ratios in parvocellular neurones; (ii) that hypothalamic CRH and vasopressin responses to acute stimulation are independent of CRH-R1 expression in the PVN; and (iii) there is a dissociation between pituitary and adrenal responses to acute stress suggesting a decrease of adrenal sensitivity to ACTH. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45221 USA. Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia. Russian Acad Med Sci, Natl Endocrinol Res Ctr, Moscow, Russia. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, DEB, NIH, Bldg 10 Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. RI Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 FU NIMH NIH HHS [MH49698] NR 57 TC 77 Z9 83 U1 1 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD AUG PY 2001 VL 13 IS 8 BP 711 EP 723 PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 462NQ UT WOS:000170426500007 PM 11489088 ER PT J AU Edelman, JA Goldberg, ME AF Edelman, JA Goldberg, ME TI Dependence of saccade-related activity in the primate superior colliculus on visual target presence SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL INTRAPARIETAL AREA; FRONTAL EYE FIELD; NEURONAL-ACTIVITY; SINGLE NEURONS; BEHAVIORAL-CHARACTERISTICS; FUNCTIONAL-PROPERTIES; COGNITIVE ACTIVATION; EXPRESS SACCADES; AUDITORY TARGETS; PARIETAL CORTEX AB Neurons in the intermediate layers of the superior colliculus respond to visual targets and/or discharge immediately before and during saccades. These visual and motor responses have generally been considered independent, with the visual response dependent on the nature of the stimulus, and the saccade-related activity related to the attributes of the saccade, but not to how the saccade was elicited. In these experiments we asked whether saccade-related discharge in the superior colliculus depended on whether the saccade was directed to a visual target. We recorded extracellular activity of neurons in the intermediate layers of the superior colliculus of three rhesus monkeys during saccades in tasks in which we varied the presence or absence of a visual target and the temporal delays between the appearance and disappearance of a target and saccade initiation. Across our sample of neurons (n = 64), discharge was highest when a saccade was made to a still-present visual target, regardless of whether the target had recently appeared or had been present for several hundred milliseconds. Discharge was intermediate when the target had recently disappeared and lowest when the target had never appeared during that trial. These results are consistent with the hypothesis that saccade-related discharge decreases as the time between the target disappearance and saccade initiation increases. Saccade velocity was also higher for saccades to visual targets, and correlated on a trial-by-trial basis with perisaccadic discharge for many neurons. However, discharge of many neurons was dependent on task but independent of saccade velocity, and across our sample of neurons, saccade velocity was higher for saccades made immediately after target appearance than would be predicted by discharge level. A tighter relationship was found between saccade precision and perisaccadic discharge. These findings suggest that just as the purpose of the saccadic system in primates is to drive the fovea to a visual target, presaccadic motor activity in the superior colliculus is most intense when such a target is actually present. This enhanced activity may, itself, contribute to the enhanced performance of the saccade system when the saccade is made to a real visual target. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Edelman, JA (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,7th Floor, Cambridge, MA 02138 USA. NR 68 TC 39 Z9 40 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2001 VL 86 IS 2 BP 676 EP 691 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 460RH UT WOS:000170322000014 PM 11495942 ER PT J AU Gusev, PA Alkon, DL AF Gusev, PA Alkon, DL TI Intracellular correlates of spatial memory acquisition in hippocampal slices: Long-term disinhibition of CA1 pyramidal cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INHIBITORY POSTSYNAPTIC POTENTIALS; ACTIVITY-DEPENDENT DISINHIBITION; RAT HIPPOCAMPUS; SYNAPTIC PLASTICITY; THETA-RHYTHM; RECEPTOR ANTAGONISM; GABA(A) RECEPTORS; IN-VITRO; NEURONS; EXCITABILITY AB Despite many advances in our understanding of synaptic models of memory such as long-term potentiation and depression, cellular mechanisms that correlate with and may underlie behavioral learning and memory have not yet been conclusively determined. We used multiple intracellular recordings to study learning-specific modifications of intrinsic membrane and synaptic responses of the CA1 pyramidal cells (PCs) in slices of the rat dorsal hippocampus prepared at different stages of the Morris water maze (WM) task acquisition. Schaffer collateral stimulation evoked complex postsynaptic potentials (PSP) consisting of the excitatory and inhibitory postsynaptic potentials (EPSP and IPSP, respectively). After rats had learned the WM task, our major learning-specific findings included reduction of the mean peak amplitude of the IPSPs, delays in the mean peak latencies of the EPSPs and IPSPs, and correlation of the depolarizing-shifted IPSP reversal potentials and reduced IPSP-evoked membrane conductance. In addition, detailed isochronal analyses revealed that amplitudes of both early and late IPSP phases were reduced in a subset of the CA1 PCs after WM training was completed. These reduced IPSPs were significantly correlated with decreased IPSP conductance and with depolarizing-shifted IPSP reversal potentials. Input-output relations and initial rising slopes of the EPSP phase did not indicate learning-related facilitation as compared with the swim and naive controls. Another subset of WM-trained CA1 PCs had enhanced amplitudes of action potentials but no learning-specific synaptic changes. There were no WM training-specific modifications of other intrinsic membrane properties. These data suggest that long-term disinhibition in a subset of CA1 PCs may facilitate cell discharges that represent and record the spatial location of a hidden platform in a Morris WM. C1 NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RP Gusev, PA (reprint author), Blanchette Rockefeller Neurosci Inst, 9601 Med Ctr Dr,Acad & Res Bldg,3D Floor, Rockville, MD 20850 USA. NR 79 TC 19 Z9 19 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2001 VL 86 IS 2 BP 881 EP 899 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 460RH UT WOS:000170322000030 PM 11495958 ER PT J AU Chalazonitis, AN Pham, TD Rothman, TP DiStefano, PS Bothwell, M Blair-Flynn, J Tessarollo, L Gershon, MD AF Chalazonitis, AN Pham, TD Rothman, TP DiStefano, PS Bothwell, M Blair-Flynn, J Tessarollo, L Gershon, MD TI Neurotrophin-3 is required for the survival-differentiation of subsets of developing enteric neurons SO JOURNAL OF NEUROSCIENCE LA English DT Review DE neurotrophins; Trk C; neural crest; apoptosis; retrograde transport; transgenic mice; gastrointestinal tract; autonomic nervous system ID PIG SMALL-INTESTINE; CREST-DERIVED CELLS; DEVELOPING NERVOUS-SYSTEM; MICE LACKING GDNF; CATECHOLAMINERGIC TC CELLS; PRIMARY AFFERENT NEURONS; NITRIC-OXIDE SYNTHASE; FETAL-RAT GUT; NEURAL CREST; MYENTERIC PLEXUS AB Neurotrophin-3 (NT-3) promotes enteric neuronal development in vitro; nevertheless, an enteric nervous system (ENS) is present in mice lacking NT-3 or TrkC. We thus analyzed the physiological significance of NT-3 in ENS development. Subsets of neurons developing in vitro in response to NT-3 became NT-3 dependent; NT-3 withdrawal led to apoptosis, selectively in TrkC-expressing neurons. Antibodies to NT-3, which blocked the developmental response of enteric crest-derived cells to exogenous NT-3, did not inhibit neuronal development in cultures of isolated crest-derived cells but did so in mixed cultures of crest- and non-neural crest- derived cells; therefore, the endogenous NT-3 that supports enteric neuronal development is probably obtained from noncrest-derived mesenchymal cells. In mature animals, retrograde transport of I-125-NT-3, injected into the mucosa, labeled neurons in ganglia of the submucosal but not myenteric plexus; injections of I-125-NT-3 into myenteric ganglia, the tertiary plexus, and muscle, labeled neurons in underlying submucosal and distant myenteric ganglia. The labeling pattern suggests that NT-3-dependent submucosal neurons may be intrinsic primary afferent and/or secretomotor, whereas NT-3-dependent myenteric neurons innervate other myenteric ganglia and/or the longitudinal muscle. Myenteric neurons were increased in number and size in transgenic mice that overexpress NT-3 directed to myenteric ganglia by the promoter for dopamine beta -hydroxylase. The numbers of neurons were regionally reduced in both plexuses in mice lacking NT-3 or TrkC. A neuropoietic cytokine (CNTF) interacted with NT-3 in vitro, and if applied sequentially, compensated for NT-3 withdrawal. These observations indicate that NT-3 is required for the normal development of the ENS. C1 Columbia Univ, Dept Anat & Cell Biol, New York, NY 10032 USA. Milennium Pharmaceut Inc, Cambridge, MA 02139 USA. Univ Washington, Dept Physiol & Biophys SJ40, Seattle, WA 98195 USA. NCI, Neural Dev Grp, Frederick, MD 21702 USA. RP Chalazonitis, AN (reprint author), Columbia Univ, Dept Anat & Cell Biol, 630 W 168th St, New York, NY 10032 USA. FU NICHD NIH HHS [HD21032]; NINDS NIH HHS [NS15547] NR 104 TC 59 Z9 60 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2001 VL 21 IS 15 BP 5620 EP 5636 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 456XW UT WOS:000170108900027 PM 11466433 ER PT J AU Liu, Y Ford, B Mann, MA Fischbach, GD AF Liu, Y Ford, B Mann, MA Fischbach, GD TI Neuregulins increase alpha 7 nicotinic acetylcholine receptors and enhance excitatory synaptic transmission in GABAergic interneurons of the hippocampus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuregulin; nicotinic acetylcholine receptors; hippocampus; alpha-bungarotoxin; GABAergic interneurons; synaptic transmission ID NEU DIFFERENTIATION FACTOR; BUNGAROTOXIN BINDING-SITES; NEUROMUSCULAR-JUNCTION; GROWTH-FACTOR; PYRAMIDAL CELLS; RAT HIPPOCAMPUS; MULTIPLE FORMS; NERVOUS-SYSTEM; ACH RECEPTORS; CNS SYNAPSES AB Neuregulins are highly expressed in the CNS, especially in cholinergic neurons. We have examined the effect of neuregulin on nicotinic acetylcholine receptors (nAChRs) in neurons dissociated from the rat hippocampus. Rapid application of acetylcholine (ACh) induced a rapidly rising and decaying inward current in some of the neurons, which was completely blocked by methyllycaconitine, a specific antagonist of the alpha7 subunit of the nAChR. When the cells were treated with 5 nM neuregulin (NRG1-beta1) for 2-4 d, a twofold increase in amplitude of the peak ACh-induced current was observed, and there was a comparable increase in I-125-alpha -bungarotoxin binding. The fast ACh-induced peak current was prominent in large neurons that also contained GABA immunoreactivity. These presumptive GABAergic neurons constituted similar to 10% of neurons present in 7- to 9-d-old cultures. In addition to the large inward peak current, ACh also evoked transmitter release from presynaptic nerve terminals. Pharmacologic experiments indicated that the shower of PSCs was mediated by glutamate, with a small minority caused by the action of GABA. Chronic exposure to NRG1-beta1 increased the amplitude of ACh-evoked PSCs but not the minimum "quantal" PSC. NRG1-beta1 also increased the percentage of neurons that exhibited ACh-evoked PSCs. C1 NIMH, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Liu, Y (reprint author), NIMH, Sect Dev Neurobiol, NIH, 36 Convent Dr,Bldg 36-1A31, Bethesda, MD 20892 USA. NR 55 TC 116 Z9 118 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2001 VL 21 IS 15 BP 5660 EP 5669 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 456XW UT WOS:000170108900031 PM 11466437 ER PT J AU Ranaldi, R Wise, RA AF Ranaldi, R Wise, RA TI Blockade of D1 dopamine receptors in the ventral tegmental area decreases cocaine reward: Possible role for dendritically released dopamine SO JOURNAL OF NEUROSCIENCE LA English DT Article DE drug abuse; reinforcement; dendritic release; motivation; operant learning; progressive ratio schedule ID PROGRESSIVE RATIO SCHEDULES; MEDIAL PREFRONTAL CORTEX; METHYL-D-ASPARTATE; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; BASAL GANGLIA; EXTRACELLULAR DOPAMINE; INTRAVENOUS COCAINE; SELF-STIMULATION; 5-HT2 RECEPTORS AB This study was designed to assess the involvement of D1 dopamine actions in the ventral tegmental area (VTA) on intravenous cocaine self-administration. Rats were trained to self-administer intravenous injections of cocaine (1.0 mg/kg per injection) on a fixed-ratio 1 (FR-1) schedule or a progressive ratio (PR) schedule of reinforcement and then were tested under the influence of bilateral VTA injections of the D1 dopamine receptor antagonist SCH 23390 or the 5-HT2 receptor antagonist ketanserin. SCH 23390 increased cocaine self-administration on the FR-1 schedule but decreased it on the PR schedule. Injections of ketanserin were ineffective, as were injections of SCH 23390 in a site 1 mm dorsal or 1 mm rostral to the effective VTA site. These data suggest a role for dendritically released dopamine, presumably acting through D1 receptors located on the axons of GABAergic or glutamatergic inputs to the VTA, in the effectiveness of cocaine reward. C1 CUNY Queens Coll, Dept Psychol, Flushing, NY 11367 USA. NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ranaldi, R (reprint author), CUNY Queens Coll, Dept Psychol, 65-30 Kissena Blvd, Flushing, NY 11367 USA. RI Wise, Roy/A-6465-2012 FU NIDA NIH HHS [DA1720] NR 70 TC 61 Z9 61 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 1 PY 2001 VL 21 IS 15 BP 5841 EP 5846 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 456XW UT WOS:000170108900050 PM 11466456 ER PT J AU Jensen, PN Major, EO AF Jensen, PN Major, EO TI A classification scheme for human polyomavirus JCV variants based on the nucleotide sequence of the noncoding regulatory region SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE JCV; regulatory region; nucleotide sequence; classification scheme; pathogenesis; progressive multifocal leukoencephalopathy (PML) ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; VIRUS-DNA SEQUENCE; GLIAL-CELLS; T-ANTIGEN; TRANSCRIPTIONAL ACTIVATION; CEREBROSPINAL-FLUID; HUMAN BRAIN; HOST RANGE; KAPPA-B; EXPRESSION AB The human polyomavirus JCV is responsible for the central nervous system (CNS) demyelination observed in cases of progressive multifocal leukoencephalopathy (PML). Lytic infection of oligodendrocytes, the cells that constitute the basis of myelin in the CNS, is established by JCV in conjunction with immunosuppressive conditions. Beyond this, however, many questions related to JCV pathogenesis remain unanswered. The JCV regulatory region is a hypervariable noncoding sequence positioned between the early and late protein-coding regions. The particular nucleotide sequence of a JCV regulatory region affects levels of viral transcription and replication. Modifications to this promoter/enhancer structure can alter the cellular host range and may be responsible for switching JCV between states of lytic and latent infection. The regulatory region structure has, therefore, been used to distinguish JCV variants. Nucleotide sequencing studies have uncovered numerous variations of regulatory region structure. Until now, however, no inclusive nomenclature existed that linked variants by regulatory region structure and/or activity We have arranged all known variant JCV regulatory regions into quadrants according to the integration of particular sequence sections and repetition of sequence section groups. This arrangement of regulatory regions results in an updated nomenclature that is well-suited for describing the relationships between JCV variants. Four distinct structural forms (I-S, I-R, II-S, and II-R) are defined along with tissue tropisms. This design provides logical connections between the variant regulatory regions and may be useful for elucidating crucial steps in JCV pathogenesis. C1 NINCDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Major, EO (reprint author), NINCDS, Lab Mol Med & Neurosci, NIH, Bldg 36,Room 5W21, Bethesda, MD 20892 USA. NR 40 TC 73 Z9 77 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 2001 VL 7 IS 4 BP 280 EP 287 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 475BG UT WOS:000171141300002 PM 11517403 ER PT J AU Cubitt, CL Cui, XH Agostini, HT Nerurkar, VR Scheirich, I Yanagihara, R Ryschkewitsch, CF Stoner, GL AF Cubitt, CL Cui, XH Agostini, HT Nerurkar, VR Scheirich, I Yanagihara, R Ryschkewitsch, CF Stoner, GL TI Predicted amino acid sequences for 100 JCV strains SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE amino acid sequence; genotype; JC virus; polyomavirus ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; VIRUS; AUTOPSY; AIDS AB DNA sequence variation between JCV genotypes is confined largely to noncoding intergenic regions and introns. Nevertheless, evidence suggests that the amino acid sequence variations among the 8 genotypes of JCV can influence the potential for neurovirulence of the virus. In the current study, the amino acid sequences for 100 JCV genomes were translated and grouped into genotype families. Subtype consensus sequences were determined and the type-specific amino acid sequence variants were identified. C1 NINCDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Dept Ophthalmol, Freiburg, Germany. Univ Hawaii Manoa, Pacific Biomed Res Ctr, Retrovirol Res Lab, Honolulu, HI 96822 USA. RP Stoner, GL (reprint author), NINCDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-27,MSC-426,36 Convent Dr, Bethesda, MD 20892 USA. NR 14 TC 22 Z9 22 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 2001 VL 7 IS 4 BP 339 EP 344 PG 6 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 475BG UT WOS:000171141300012 PM 11517413 ER PT J AU Levy, RM Major, E Ali, MJ Cohen, B Groothius, D AF Levy, RM Major, E Ali, MJ Cohen, B Groothius, D TI Convection-enhanced intraparenchymal delivery (CEID) of cytosine arabinoside (AraC) for the treatment of HIV-related progressive multifocal leukoencephalopathy (PML) SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE acquired immunodeficiency syndrome; convection-enhanced delivery; cytosine arabinoside; JC virus; progressive multifocal leukoencephalopathy ID BRAIN; CYTARABINE; INFUSION; EFFICACY AB AIDS-related PML continues to be a relatively common and rapidly fatal infection in patients with AIDS, and no effective therapy has been established to alleviate the effects of this disease. Through the years, isolated reports and small case studies have shown somewhat encouraging results using cytosine arabinoside (AraC) in the treatment of PML. The optimism behind the use AraC for this disease began to fade with ACTG trial 243, which suggested that AraC had no benefit in patients with HIV-related PML. In this article, we provide evidence that suggests that the failure of AraC in the ACTG trial may have been due to insufficient delivery of the drug through traditional intravenous and intrathecal routes. Furthermore, we provide evidence that convection-enhanced intraparenchymal delivery of AraC may prove to be a safe and effective means of treating this infection, and we outline a clinical trial that we have recently undertaken to test this hypothesis. C1 Northwestern Univ, Sch Med, Dept Neurosurg, Chicago, IL USA. NINCDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. Northwestern Univ, Sch Med, Dept Neurol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Evanston NW Healthcare, Dept Neurol, Evanston, IL USA. RP Levy, RM (reprint author), Dept Neurol Surg, 233 E Erie St,Suite 614, Chicago, IL 60611 USA. NR 13 TC 28 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 2001 VL 7 IS 4 BP 382 EP 385 PG 4 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 475BG UT WOS:000171141300020 PM 11517421 ER PT J AU Mariani, G Moresco, L Viale, G Villa, G Bagnasco, M Canavese, G Buscombe, J Strauss, HW Paganelli, G AF Mariani, G Moresco, L Viale, G Villa, G Bagnasco, M Canavese, G Buscombe, J Strauss, HW Paganelli, G TI Radioguided sentinel lymph node biopsy in breast cancer surgery SO JOURNAL OF NUCLEAR MEDICINE LA English DT Review DE sentinel lymph node; breast cancer; radiocolloid; interstitial administration; lymphoscintigraphy; intraoperative gamma-probe guidance ID INTRAOPERATIVE GAMMA-PROBE; INTERNAL MAMMARY NODES; POLYMERASE CHAIN-REACTION; AXILLARY DISSECTION; BLUE-DYE; NEOADJUVANT CHEMOTHERAPY; RADIATION PROTECTION; RANDOMIZED-TRIAL; T1 CARCINOMA; LYMPHOSCINTIGRAPHY AB The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way through the lymphatic system, from the first to upper levels. Therefore, the first lymph node met (the sentinel node) will most likely be the first to be affected by metastasis, and a negative sentinel node makes it highly unlikely that other nodes are affected. Because axillary node dissection does not improve prognosis of patients with breast cancer (being important only to stage the axilla), sentinel lymph node biopsy might replace complete axillary dissection to stage the axilla in clinically NO patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that, after surgery, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Furthermore, histologic sampling errors can be reduced if a single (sentinel) node is assessed extensively rather than few histologic sections in a high number of lymph nodes per patient. Although the pattern of lymph drainage from breast cancer can be variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Therefore, considering that tumor lymphatics are disorganized and relatively ineffective, subdermal and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100- to 200-nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy because images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than that of background (at least 10:1 intraoperatively). After removal of the sentinel node, the axilla must be reexamined to ensure that all radioactive sites are identified and removed for analysis. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when needed, immune staining with anticytokeratin antibody. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94%-97% in institutions where a high number of procedures are performed and approaches 99% when combined with the vital blue dye technique. At present, there is no definite evidence that negative sentinel lymph node biopsy is invariably correlated with negative axillary status, except perhaps for T1a-b breast cancers, with a size of less than or equal to1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection on patients with a negative sentinel lymph node on the long-term clinical outcome of patients. C1 Univ Genoa, Sch Med, Dept Internal Med & Med Specialties, Nucl Med Serv, Genoa, Italy. Univ Genoa, Dept Oncol Biol & Genet, Div Surg Oncol, Genoa, Italy. Natl Canc Inst, Div Surg Oncol, Genoa, Italy. European Inst Oncol, Dept Pathol, Milan, Italy. European Inst Oncol, Div Nucl Med, Milan, Italy. Univ London Royal Free Hosp, Dept Nucl Med, London, England. Stanford Univ, Sch Med, Dept Radiol, Div Nucl Med, Stanford, CA 94305 USA. RP Mariani, G (reprint author), Univ Pisa, Sch Med, Reg Ctr Nucl Med, Via Roma 67, I-56126 Pisa, Italy. NR 151 TC 188 Z9 198 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 2001 VL 42 IS 8 BP 1198 EP 1215 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 460ML UT WOS:000170311300014 PM 11483681 ER PT J AU Lovqvist, A Humm, JL Sheikh, A Finn, RD Koziorowski, J Ruan, S Pentlow, KS Jungbluth, A Welt, S Lee, FT Brechbiel, MW Larson, SM AF Lovqvist, A Humm, JL Sheikh, A Finn, RD Koziorowski, J Ruan, S Pentlow, KS Jungbluth, A Welt, S Lee, FT Brechbiel, MW Larson, SM TI PET imaging of (86)Y-labeled anti-Lewis Y monoclonal antibodies in a nude mouse model: Comparison between (86)Y and (111)In radiolabels SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE (86)Y; PET imaging; radioimmunotherapy; Lewis Y; 3S193 antibody ID BREAST-CANCER; BREMSSTRAHLUNG; THERAPY; RADIOPHARMACEUTICALS; PHARMACOKINETICS; BIODISTRIBUTION; DOSIMETRY; DISEASE; 3S193 AB Absorbed doses in (90)Y radioimmunotherapy are usually estimated by extrapolating from (111)In imaging data. PET using (86)Y (beta (+) 33%; half-life, 14.7 h) as a surrogate radiolabel could be a more accurate alternative. The aim of this study was to evaluate an (86)Y-labeled monoclonal antibody (mAb) as a PET imaging agent and to compare the biodistribution of (86)Y- and (111)In-labeled mAb. Methods The humanized anti-Lewis Y mAb hu3S193 was labeled with (111)In or 86Y through CHX-A"-diethylenetriaminepentaacetic acid chelation. In vitro cell binding and cellular retention of radiolabeled hu3S193 were evaluated using HCT-15 colon carcinoma cells, a cell line expressing Lewis Y. Nude mice bearing HCT-15 xenografts were injected with (86)Y-hu3S193 or (111)In-hu3S193. The biodistribution was studied by measurements of dissected tissues as well as by PET and planar imaging. Results: The overall radiochemical yield in hu3S193 labeling and purification was 42 +/-2% (n = 2) and 76%+/-3% (n = 6) for (86)Y and (111)In, respectively. Both radioimmunoconjugates specifically bound to HCT-15 cells. When cellular retention of hu3S193 was studied using (111)In-hu3S193, 80% of initially cell-bound (111)In activity was released into the medium as high-molecular-weight compounds within 8 h. When coadministered, in vivo tumor uptake of (86)Y-hu3S193 and (111)In-hu3S193 reached maximum values of 30 +/-6 and 29 +/-6 percentage injected dose per gram and tumor sites were easily identifiable by PET and planar imaging, respectively. Conclusion: At 2 d after injection of (111)In-hu3S193 and (86)Y-hu3S193 radioimmunoconjugates, the uptake of (111)In and (86)Y activity was generally similar in most tissues. After 4 d, however, the concentration of (86)Y activity was significantly higher in several tissues, including tumor and bone tissue. Accordingly, the quantitative information offered by PET, combined with the presumably identical biodistribution of (86)Y and (90)Y radiolabels, should enable more accurate absorbed dose estimates in (90)Y radioimmunotherapy. C1 Mem Sloan Kettering Canc Ctr, Dept Med Phys, Nucl Med Serv, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Radiol, Nucl Med Serv, New York, NY 10021 USA. Ludwig Inst Canc Res, New York, NY USA. Austin & Repatriat Med Ctr, Ludwig Inst Canc Res, Heidelberg, Vic, Australia. NCI, Div Clin Sci, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. RP Humm, JL (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med Phys, Nucl Med Serv, 1275 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [1R24CA83084, R01 CA78642] NR 20 TC 62 Z9 64 U1 1 U2 11 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD AUG PY 2001 VL 42 IS 8 BP 1281 EP 1287 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 460ML UT WOS:000170311300025 PM 11483692 ER PT J AU Shopland, DR Gerlach, KK Burns, DM Hartman, AM Gibson, JT AF Shopland, DR Gerlach, KK Burns, DM Hartman, AM Gibson, JT TI State-specific trends in smoke-free workplace policy coverage: The Current Population Survey Tobacco Use Supplement, 1993 to 1999 SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID EXPOSURE AB We examined trends in smoke-free workplace policies among all indoor workers in the United States using the National Cancer Institute's Tobacco Use Supplement to the Census Bureau's Current,free was defined as Population Survey (total n = 270,063). Smoke-free was defined as not permitted in public or common areas or in work areas of a worksite. Nationally, we found that nearly 70% of the US workforce worked under a smoke-free policy in 1999. At the state level, a greater than 30-percentage-point differential existed in the proportion of workers with such policies. Although significant progress has been made to reduce worker exposure to environmental tobacco smoke on the job, we predict further progress may be difficult unless comprehensive regulations to protect all workers are implemented at the national, state, or loral level. C1 Robert Wood Johnson Fdn, Princeton, NJ 08543 USA. NCI, Smoking & Tobacco Control Program, Bethesda, MD 20892 USA. NCI, Risk Factor Monitoring & Methods Branch, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Gerlach, KK (reprint author), Robert Wood Johnson Fdn, Route 1 & Coll Rd E, Princeton, NJ 08543 USA. NR 27 TC 57 Z9 57 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD AUG PY 2001 VL 43 IS 8 BP 680 EP 686 DI 10.1097/00043764-200108000-00005 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 463BT UT WOS:000170457500004 PM 11515250 ER PT J AU Kador, PF Sun, GP Rait, VK Rodriguez, L Ma, Y Sugiyama, K AF Kador, PF Sun, GP Rait, VK Rodriguez, L Ma, Y Sugiyama, K TI Intrinsic inhibition of aldose reductase SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID GALACTOSE-FED DOGS; DIABETIC COMPLICATIONS; RETINOPATHY; PREVENTION; CATARACTS; M79175; RATS AB The development of aldose reductase inhibitors for the treatment of diabetic complications, such as cataract and retinopathy, has been of intense interest in the pharmaceutical community for the last 20 years. To date, aldose reductase inhibitors have been synthetically developed from leads obtained from in vitro screening studies. Recently, we have observed that mammalian tissues contain intrinsic inhibitors of aldose reductase, which may be used as potential drugs for treating diabetic complications with potentially less side effects than synthetic aldose reductase inhibitors. Intrinsic inhibitor(s) of aldose reductase have been observed in the methanolic extracts from rat and human kidneys and bovine lenses that were subjected to a number of chromatographic techniques, including counter current chromatography, flash chromatography, gel filtration and high pressure liquid chromatography. This inhibition results from a direct interaction between the inhibitor and enzyme. The intrinsic inhibitor, present in the lipophilic fraction of human kidney and bovine lens extracts, can easily penetrate into the lens to inhibit sugar alcohol formation. Intraperitoneal injection of partially purified bovine lens extract inhibited lens polyol formation in young rats fed 50% galactose diet. C1 NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Kador, PF (reprint author), NEI, Lab Ocular Therapeut, NIH, 10 Ctr Dr MSC 1850,Bldg 10,Room 10B11, Bethesda, MD 20892 USA. NR 22 TC 3 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD AUG PY 2001 VL 17 IS 4 BP 373 EP 381 DI 10.1089/108076801753162780 PG 9 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA 472YG UT WOS:000171012100007 PM 11572468 ER PT J AU Smith, MA Anderson, B AF Smith, MA Anderson, B TI Phase II window studies: 10 years of experience and counting SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Editorial Material ID PEDIATRIC-ONCOLOGY-GROUP; PROSPECTIVE RANDOMIZED TRIAL; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; METASTATIC BREAST-CANCER; TRANS-RETINOIC ACID; LUNG METASTASES; CARBOPLATIN; CHILDREN; CHEMOTHERAPY C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 37 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG-SEP PY 2001 VL 23 IS 6 BP 334 EP 337 DI 10.1097/00043426-200108000-00002 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 470RE UT WOS:000170884300003 PM 11563765 ER PT J AU Alter, BP AF Alter, BP TI Modern review of congenital hypoplastic anemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article ID DIAMOND-BLACKFAN-ANEMIA C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Room 7020,6120 Execut Blvd, Rockville, MD 20852 USA. NR 14 TC 0 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD AUG-SEP PY 2001 VL 23 IS 6 BP 383 EP 384 DI 10.1097/00043426-200108000-00016 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 470RE UT WOS:000170884300016 PM 11563776 ER PT J AU Li, P Xu, JC AF Li, P Xu, JC TI The development of highly efficient onium-type peptide coupling reagents based upon rational molecular design SO JOURNAL OF PEPTIDE RESEARCH LA English DT Review DE coupling reagent; molecular design; peptide; racemization; reactivity ID CHLORIDE BOP-CL; METHYLATED AMINO-ACIDS; TETRAMETHYLFLUOROFORMAMIDINIUM HEXAFLUOROPHOSPHATE; PRODUCT; RACEMIZATION; MECHANISM; PYBROP; PYBOP; BOMI AB Novel and highly efficient immonium-, pyridinium- and thiazolium-type peptide coupling reagents, such as BOMI, BDMP, BPMP, BEP, FEP, BEPH, FEPH and BEMT, were developed by rational modifying of the molecular structures of commonly used uronium-type reagents. The high efficiency of these onium salts has been evaluated and proven by model reaction tests and the successful synthesis of various oligopeptides and biologically active peptides, both in solution and in the solid-phase, for example Leu-enkephalin, the pentapeptide moiety of Dolastatin 15 and the immunosuppressive undecapeptide cyclosporin O. Based upon these results, the relationship between the molecular structure and the capability of onium-type peptide coupling reagents was studied. A preliminary guideline for the molecular design of onium-type coupling reagents was developed. C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. Chinese Acad Sci, Shanghai Inst Organ Chem, Beijing 100864, Peoples R China. RP Li, P (reprint author), NCI, Med Chem Lab, NIH, 376 Boyles St, Frederick, MD 21702 USA. NR 35 TC 18 Z9 18 U1 0 U2 11 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD AUG PY 2001 VL 58 IS 2 BP 129 EP 139 DI 10.1034/j.1399-3011.2001.00867.x PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 463HU UT WOS:000170471700004 PM 11532072 ER PT J AU McCrae, RR Jang, KL Livesley, WJ Riemann, R Angleitner, A AF McCrae, RR Jang, KL Livesley, WJ Riemann, R Angleitner, A TI Sources of structure: Genetic, environmental, and artifactual influences on the covariation of personality traits SO JOURNAL OF PERSONALITY LA English DT Article ID 5-FACTOR MODEL; TWIN; HERITABILITY; PSYCHOPATHOLOGY; POLYMORPHISM; ASSOCIATION; VALIDATION; INVENTORY; ROTATION; DISORDER AB The phenotypic structure of personality traits has been well described, but it has not yet been explained causally. Behavior genetic covariance analyses can identify the underlying causes of phenotypic structure; previous behavior genetic research has suggested that the effects from both genetic and nonshared environmental influences mirror the phenotype. However, nonshared environmental effects are usually estimated as a residual term that may also include systematic bias, such as that introduced by implicit personality theory. To reduce that bias, we supplemented data from Canadian and German twin studies with cross-observer correlations on the Revised NEO Personality Inventory. The hypothesized five-factor structure was found in both the phenotypic and genetic/familial covariances. When the residual covariance was decomposed into true nonshared environmental influences and method bias, only the latter showed the five-factor structure. True nonshared environmental influences are not structured as genetic influences are, although there was some suggestion that they do affect two personality dimensions, Conscientiousness and Love. These data reaffirm the value of behavior genetic analyses for research on the underlying causes of personality traits. C1 NIA, Personal Stress & Coping Sect, Ctr Gerontol Res, Baltimore, MD 21224 USA. Univ British Columbia, Dept Psychiat, Vancouver, BC, Canada. Univ Bielefeld, Dept Psychol, D-4800 Bielefeld, Germany. RP McCrae, RR (reprint author), NIA, Personal Stress & Coping Sect, Ctr Gerontol Res, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 62 TC 89 Z9 90 U1 6 U2 11 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0022-3506 J9 J PERS JI J. Pers. PD AUG PY 2001 VL 69 IS 4 BP 511 EP 535 PG 25 WC Psychology, Social SC Psychology GA 454NC UT WOS:000169977800001 PM 11497029 ER PT J AU Jang, KL Hu, S Livesley, WJ Angleitner, A Riemann, R Ando, J Ono, Y Vernon, PA Hamer, DH AF Jang, KL Hu, S Livesley, WJ Angleitner, A Riemann, R Ando, J Ono, Y Vernon, PA Hamer, DH TI Covariance structure of neuroticism and agreeableness: A twin and molecular genetic analysis of the role of the serotonin transporter gene SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article ID ANXIETY-RELATED TRAITS; FACET-LEVEL TRAITS; PERSONALITY-TRAITS; PROMOTER POLYMORPHISM; READING DEFICITS; TEMPERAMENT; ASSOCIATION; CHARACTER; INVENTORY; REGION AB The Revised,NEO Personality Inventory domains of Neuroticism and Agreeableness are considered factorially distinct despite several intercorrelations between these. domains. The genetic correlation, an index of the degree to which these intercorrelations are caused by genetic influences, was estimated using data from 913 monozygotic and 562 dizygotic volunteer twin pairs from Canada, Germany, and Japan. The serotonin transporter gene, 5-HTTLPR, was assayed in a sample of 388 nontwin sibling pairs from the United States to determine the contribution of the serotonin transporter locus to the covariation between the Neuroticism and Agreeableness scales. In all four samples, genetic influences contributed to the covariance of Neuroticism and Agreeableness, with the serotonin transporter gene accounting for 10% of the relationship between these domains. C1 Univ British Columbia, Dept Psychiat, Div Behav Sci, Vancouver, BC V6T 2A1, Canada. NCI, NIH, Bethesda, MD 20892 USA. Univ Bielefeld, Dept Psychol, D-4800 Bielefeld, Germany. Univ Jena, Dept Psychol, D-6900 Jena, Germany. Keio Univ, Fac Letters, Dept Educ, Tokyo, Japan. Keio Univ, Sch Med, Dept Psychiat, Tokyo, Japan. Univ Western Ontario, Dept Psychol, London, ON, Canada. RP Jang, KL (reprint author), Univ British Columbia, Dept Psychiat, Div Behav Sci, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada. NR 54 TC 46 Z9 47 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD AUG PY 2001 VL 81 IS 2 BP 295 EP 304 DI 10.1037//0022-3514.81.2.295 PG 10 WC Psychology, Social SC Psychology GA 469PJ UT WOS:000170823800009 PM 11519933 ER PT J AU Costa, PT Terracciano, A McCrae, RR AF Costa, PT Terracciano, A McCrae, RR TI Gender differences in personality traits across cultures: Robust and surprising findings SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 2nd Annual Meeting of the Society-for-Personality-and-Social-Psychology CY FEB, 2001 CL SAN ANTONIO, TEXAS SP Soc Personal & Social Psychol ID CONGENITAL ADRENAL-HYPERPLASIA; SEX-DIFFERENCES; METAANALYSIS; ADOLESCENTS; INTERESTS; INTENSITY; CHILDREN; ADULTS AB Secondary analyses of Revised NEO Personality Inventory data from 26 cultures (N = 23,031) suggest that gender differences are small relative to individual variation within genders; differences are replicated across cultures for both college-age and adult samples, and differences are broadly consistent with gender stereotypes: Women reported themselves to be higher in Neuroticism, Agreeableness, Warmth, and Openness to Feelings, whereas men were higher in Assertiveness and Openness to Ideas. Contrary to predictions from evolutionary theory, the magnitude of gender differences varied across cultures. Contrary to predictions from the social role model, gender differences were most pronounced in European and American cultures in which traditional sex roles are minimized. Possible explanations for this surprising finding are discussed, including the attribution of masculine and feminine, behaviors to roles rather than traits in traditional cultures. C1 NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Costa, PT (reprint author), NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI terracciano, antonio/B-1884-2008; OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS [Z99 AG999999, ZIA AG000180-25, ZIA AG000180-26] NR 61 TC 820 Z9 832 U1 23 U2 204 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD AUG PY 2001 VL 81 IS 2 BP 322 EP 331 DI 10.1037/0022-3514.81.2.322 PG 10 WC Psychology, Social SC Psychology GA 469PJ UT WOS:000170823800011 PM 11519935 ER PT J AU Vitiello, B AF Vitiello, B TI Valproic acid and risperidone - Commentary SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 NIMH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Bethesda, MD 20892 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2001 VL 40 IS 8 BP 867 EP 867 DI 10.1097/S0890-8567(09)60329-4 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 454RP UT WOS:000169985800004 ER PT J AU Biederman, J Birmaher, B Carlson, GA Chang, KD Fenton, WS Geller, B Hoagwood, KE Hyman, SE Kendler, KS Koretz, DS Kowatch, RA Kupfer, DJ Leibenluft, E Nakamura, RK Nottelmann, ED Stover, E Vitiello, B Weiblinger, G Weller, E AF Biederman, J Birmaher, B Carlson, GA Chang, KD Fenton, WS Geller, B Hoagwood, KE Hyman, SE Kendler, KS Koretz, DS Kowatch, RA Kupfer, DJ Leibenluft, E Nakamura, RK Nottelmann, ED Stover, E Vitiello, B Weiblinger, G Weller, E TI National Institute of Mental Health research roundtable on prepubertal bipolar disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bipolar disorder; prepubertal; assessment; diagnosis ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC SYNDROMES CHIPS; EARLY ADOLESCENT BIPOLARITY; CHILDRENS INTERVIEW; CONCURRENT VALIDITY; MANIC SYMPTOMS; MAJOR DEPRESSION; FAMILIAL SUBTYPE; YOUNG-CHILDREN; DOUBLE-BLIND AB Objective: A research roundtable meeting was convened at the National Institute of Mental Health on April 27, 2000, to discuss the existing controversial areas in the diagnosis of bipolar disorder in prepubertal children. Method: Invited clinicians and researchers with expertise on bipolar disorder in children were asked to share and discuss their perspectives on diagnostic issues for bipolar disorder in prepubertal children. Results: The group reached agreement that diagnosis of bipolar disorder in prepubertal children is possible with currently available psychiatric assessment instruments. In addition to phenotypes that fit DSM-IV criteria for bipolar I and bipolar II, participants agreed on the existence of other phenotypic possibilities that do not meet diagnostic criteria. Bipolar not otherwise specified (NOS) was recommended as a "working diagnosis" for the non-DSM-IV phenotype. Conclusions: Bipolar disorder exists and can be diagnosed in prepubertal children. In children who present with both the DSM-IV and non-DSM-IV phenotypes (i.e., those given a diagnosis of bipolar-NOS), assessment should include careful evaluation of all behaviors that are impairing. Moreover, these children should be monitored systematically to explore stability and change over time in diagnosis and impairment. C1 NIMH, Dev Psychopathol & Prevent Res Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. SUNY Stony Brook, Dept Psychiat & Behav Sci, Stony Brook, NY 11794 USA. Stanford Univ, Sch Med, Div Child & Adolescent Psychiat, Stanford, CA 94305 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. Univ Cincinnati, Med Ctr, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Nottelmann, ED (reprint author), NIMH, Dev Psychopathol & Prevent Res Branch, 6001 Execut Blvd,Room 6200,MSC9617, Bethesda, MD 20892 USA. NR 87 TC 11 Z9 15 U1 8 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD AUG PY 2001 VL 40 IS 8 BP 871 EP 878 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 454RP UT WOS:000169985800008 ER PT J AU Chang, E Alexander, HR Libutti, SK Hurst, R Zhai, SP Figg, WD Bartlett, DL AF Chang, E Alexander, HR Libutti, SK Hurst, R Zhai, SP Figg, WD Bartlett, DL TI Laparoscopic continuous hyperthermic peritoneal perfusion SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID GASTRIC-CANCER; MITOMYCIN-C; CISPLATIN; CHEMOTHERAPY; MESOTHELIOMA; CELLS C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B17,10 Ctr Dr, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 16 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD AUG PY 2001 VL 193 IS 2 BP 225 EP 229 DI 10.1016/S1072-7515(01)00980-2 PG 5 WC Surgery SC Surgery GA 457LR UT WOS:000170139200016 PM 11491455 ER PT J AU Alfano, MC Coulter, ID Gerety, MB Hart, TC Imrey, PB LeResche, L Levy, J Luepker, RV Lurie, AG Page, RC Rye, LA Smith, L Walker, CB AF Alfano, MC Coulter, ID Gerety, MB Hart, TC Imrey, PB LeResche, L Levy, J Luepker, RV Lurie, AG Page, RC Rye, LA Smith, L Walker, CB CA Natl Inst Hlth Consensus Dev Panel TI National Institutes of Health Consensus Development Conference statement - Diagnosis and management of dental caries throughout life, March 26-28, 2001 SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB Objective. To provide health care providers, patients and the general public with a responsible assessment of currently available data regarding the diagnosis and management of dental caries throughout life. Participants. A nonfederal, nonadvocate, 13-member panel representing the fields of dentistry, epidemiology, genetics, medicine, oral biology, oral radiology, pathology, periodontics, public health, statistics and surgery, as well as a public representative. In addition, 31 experts in these same fields presented data to the panel and to a conference audience of approximately 700. Evidence. Presentations by experts; a systematic review of the dental research literature provided by the Agency for Healthcare Research and Quality; and an extensive bibliography of dental caries research articles, prepared by the National Library of Medicine. Scientific evidence was given precedence over clinical anecdotal experience. Consensus Process. Answering predefined questions, the panel drafted a statement based on the scientific evidence presented in open forum and the scientific literature. The draft statement was read in its entirety on the final day of the conference and circulated to the experts and the audience for comment. The panel then met in executive session to consider these comments and released a revised statement at the end of the conference. The statement was made available on the World Wide Web at "consensus.nih.gov" immediately after the conference. This statement is an independent report of the panel and is not a policy statement of the National Institutes or the federal government. C1 NIH, Off Dis Prevent, Bethesda, MD 20892 USA. NYU, Coll Dent, New York, NY USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA 15260 USA. Univ Illinois, Urbana, IL 61801 USA. Univ Illinois, Coll Dent, Chicago, IL USA. Univ Washington, Seattle, WA 98195 USA. Columbia Univ, New York, NY USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Univ Connecticut, Sch Dent Med, Farmington, CT 06032 USA. Voices Detroit Initiat, Detroit, MI USA. Univ Florida, Gainesville, FL USA. RP Alfano, MC (reprint author), NIH, Off Dis Prevent, 31 Ctr Dr,Room 1B03, Bethesda, MD 20892 USA. NR 0 TC 30 Z9 31 U1 2 U2 3 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD AUG PY 2001 VL 132 IS 8 BP 1153 EP 1161 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 464AT UT WOS:000170510700024 ER PT J AU Waterer, GW Wan, JY Kritchevsky, SB Wunderink, RG Satterfield, S Bauer, DC Newman, AB Taaffe, DR Jensen, RL Crapo, RO AF Waterer, GW Wan, JY Kritchevsky, SB Wunderink, RG Satterfield, S Bauer, DC Newman, AB Taaffe, DR Jensen, RL Crapo, RO CA Hlth ABC Study TI Airflow limitation is underrecognized in well-functioning older people SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE airflow limitation; older; cross-sectional studies ID OBSTRUCTIVE PULMONARY-DISEASE; RESPIRATORY SYMPTOMS; LUNG-FUNCTION; VENTILATORY IMPAIRMENT; FLOW LIMITATION; RISK-FACTORS; ASTHMA; POPULATION; MORTALITY; ADULTS AB OBJECTIVES: Dyspnea is a common symptom in older people. A reduced forced expiratory volume in I second (FEV1) is associated with a higher mortality rate from cardiovascular and respiratory disease, and increased admissions to hospitals. Underrecognized or undertreated airflow limitation may exacerbate the problem. The purpose of this study was to assess the prevalence and treatment of airflow limitation in a cohort of well-functioning older people. DESIGN: Cross-sectional study. SETTING: Baseline of a clinical-epidemiological study of incident functional limitation. PARTICIPANTS: Participants attended the baseline examination of the Health, Aging, and Body Composition study, a prospective cohort study of 3,075 well-functioning subjects age 70 to 79. MEASUREMENTS: Demographic and clinical data were collected by interview. Spirometry was performed unless contraindicated and repeated until three acceptable sets of flow-volume loops were obtained. Patients on bronchodilator medications had spirometry performed posttherapy. Blinded readers assessed the flow-volume loops, and inadequate tests were omitted from analysis. Airflow limitation was defined as a reduced forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) as determined by age-, sex-, and race-normalized values. Severity of airflow limitation was defined by American Thoracic Society criteria. RESULTS: Two thousand four hundred eighty-five subjects (80.8%) had assessable spirometry and data on treatment and diagnosis (1,265 men, 1,220 women). The mean age was 73.6 years. Two hundred sixty-two subjects (10.5%) had airflow limitation; 43 (16.4%) of these never smoked. Only 37.4% of participants with airflow limitation and 55.6% of participants with severe airflow limitation reported a diagnosis of lung disease. Only 20.5% of subjects with at least moderate airflow limitation had used a bronchodilator in the previous 2 weeks. CONCLUSION: Despite their good functional status, airflow limitation was present, and underrecognized, in a considerable proportion of our older population. The low bronchodilator use suggests a significant reservoir of untreated disease. Physicians caring for older people need to be more vigilant for both the presence, and the need for treatment, of airflow limitation. C1 Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Methodist Lebonheur Healthcare Fdn, Memphis, TN USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Pittsburgh, Div Geriatr Med, Dept Epidemiol, Pittsburgh, PA USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. LSD Hosp, Div Pulm, Salt Lake City, UT USA. Univ Utah, Salt Lake City, UT USA. RP Kritchevsky, SB (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Wunderink, Richard/0000-0002-8527-4195 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 33 TC 33 Z9 33 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD AUG PY 2001 VL 49 IS 8 BP 1032 EP 1038 DI 10.1046/j.1532-5415.2001.49205.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 466QR UT WOS:000170656700003 PM 11555063 ER PT J AU Vallon, V Traynor, T Barajas, L Huang, YG Briggs, JP Schnermann, J AF Vallon, V Traynor, T Barajas, L Huang, YG Briggs, JP Schnermann, J TI Feedback control of glomerular vascular tone in neuronal nitric oxide synthase knockout mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID THICK ASCENDING LIMB; TUBULOGLOMERULAR FEEDBACK; JUXTAGLOMERULAR APPARATUS; CAPILLARY-PRESSURE; PROXIMAL TUBULE; REABSORPTION; GENE; AUTOREGULATION; EXPRESSION; INHIBITION AB For further elucidation of the role of neuronal nitric oxide synthase (nNOS) in macula densa (MD) cells, experiments were performed in anesthetized nNOS knockout mice (nNOS -/-). At comparable levels of arterial BP, renal blood flow was not significantly different between nNOS+/+ and nNOS-/- (1.7 +/- 0.2 versus 1.4 +/- 0.1 ml/min), and autoregulation of renal blood flow was maintained to a pressure level of approximately 85 mmHg in both groups of mice (n = 6 in each group). The fall in proximal tubular stop-flow pressure in response to an increase in loop of Henle perfusion rate from 0 to 30 nl/min was comparable in nNOS+/+ and -/- mice (40.7 +/- 1.6 to 32 +/- 2 mmHg versus 40.6 +/- 1.6 to 31.6 +/- 2 mmHg; not significant; n = 13 versus 18 nephrons). Luminal application of the nonselective NOS inhibitor nitro-L-arginine (10(-3) and 10(-2) M) enhanced the perfusion-dependent fall in stop-flow pressure in nNOS +/+ (7 +/- 1 to 13 +/- 2 mmHg; P < 0.05) but not in nNOS-/- (7 +/- 1 to 8 +/- 1 mmHg; not significant) mice, nNOS-/- mice exhibited a lower nephron filtration rate, compared with nNOS+/+, during free-flow collections from early distal tubules (influence of MD intact, 7 +/- 0.7 versus 10.9 +/- 1 nl/min; P = 0.002) but not from late proximal tubule (influence of MD minimized, 10.1 +/- 1 versus 11.7 +/- 1 nl/min; not significant; n = 16 nephrons). Distal Cl concentration and fractional absorption of fluid or chloride up to the early distal tubule was not different between nNOS -/- and +/+ mice. The data indicate that nNOS in MD tonically attenuates the GFR-lowering influence of ambient luminal NaCl, which may serve to increase the fluid and electrolyte load to the distal tubule, consistent with a role of MD nNOS in tubuloglomerular feedback resetting. C1 NIDDKD, Bethesda, MD 20892 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Dept Pathol, Torrance, CA 90509 USA. RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Room 4D51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NIDDK NIH HHS [DK 35124] NR 33 TC 61 Z9 61 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD AUG PY 2001 VL 12 IS 8 BP 1599 EP 1606 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 455GL UT WOS:000170019100002 PM 11461931 ER PT J AU Hoover, RN Troisi, RJ AF Hoover, RN Troisi, RJ TI Understanding mechanisms of breast cancer prevention SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PREGNANCY; RISK C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Hoover, RN (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. NR 6 TC 9 Z9 9 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 1 PY 2001 VL 93 IS 15 BP 1119 EP 1120 DI 10.1093/jnci/93.15.1119 PG 2 WC Oncology SC Oncology GA 457QE UT WOS:000170147600001 PM 11481374 ER PT J AU Gardner, GJ Birrer, MJ AF Gardner, GJ Birrer, MJ TI Ovarian tumors of low malignant potential: Can molecular biology solve this enigma? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BORDERLINE TUMORS; P53 C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Birrer, MJ (reprint author), Key W Res Ctr, 9610 Med Ctr Dr,Bldg C,Rm 300, Rockville, MD 20850 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 1 PY 2001 VL 93 IS 15 BP 1122 EP 1123 DI 10.1093/jnci/93.15.1122 PG 2 WC Oncology SC Oncology GA 457QE UT WOS:000170147600003 PM 11481376 ER PT J AU Horikawa, I Barrett, JC AF Horikawa, I Barrett, JC TI cis-Activation of the human telomerase gene (hTERT) by the hepatitis B virus genome SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID REVERSE-TRANSCRIPTASE GENE; CATALYTIC SUBUNIT; PROMOTER REGION; CANCER; AMPLIFICATION; EXPRESSION; CELLS C1 NCI, Lab Biosyst & Canc, Canc & Aging Sect, Div Basic Sci,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Horikawa, I (reprint author), NCI, Lab Biosyst & Canc, Canc & Aging Sect, Div Basic Sci,Ctr Canc Res,NIH, Bldg 40,Rm 2609,MSC-3020, Bethesda, MD 20892 USA. NR 15 TC 58 Z9 70 U1 0 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD AUG 1 PY 2001 VL 93 IS 15 BP 1171 EP 1173 DI 10.1093/jnci/93.15.1171 PG 3 WC Oncology SC Oncology GA 457QE UT WOS:000170147600015 PM 11481390 ER PT J AU Sugai, J Eiden, M Anderson, MM Van Hoeven, N Meiering, CD Overbaugh, J AF Sugai, J Eiden, M Anderson, MM Van Hoeven, N Meiering, CD Overbaugh, J TI Identification of envelope determinants of feline leukemia virus subgroup B that permit infection and gene transfer to cells expressing human Pit1 or Pit2 SO JOURNAL OF VIROLOGY LA English DT Article ID RECEPTOR-BINDING DOMAIN; HOST-RANGE; RETROVIRUS RECEPTOR; VIRAL INTERFERENCE; HAMSTER-CELLS; MURINE; GLYCOPROTEIN; PROTEIN; SEQUENCES; RECOGNITION AB The retroviral vector systems that are in common use for gene therapy are designed to infect cells expressing either of two widely expressed phosphate transporter proteins, Pit1 or Pit2. Subgroup B feline leukemia viruses (FeLV-Bs) use the gibbon ape leukemia virus receptor, Pit1, as a receptor for entry. Our previous studies showed that some chimeric envelope proteins encoding portions of FeLV-B could also enter cells by using a related receptor protein, Pit2, which serves as the amphotropic murine leukemia virus receptor (S. Boomer, M. Eiden, C. C. Burns, and J. Overbaugh, J. Virol. 71:8116-8123, 1997). Here we show that an arginine at position 73 within variable region A (VRA) of the FeLV-B envelope surface unit (SU) is necessary for viral entry into cells via the human Pit2 receptor. However, C-terminal SU sequences have a dominant effect in determining human Pit2 entry, even though this portion of the protein is outside known receptor binding domains. This suggests that a combination of specific VRA sequences and C-terminal sequences may influence interactions between FeLV-B SU and the human Pit2 receptor. Binding studies suggest that the C-terminal sequences may affect a postbinding step in viral entry via the Pit2 receptor, although in all cases, binding of FeLV-B SU to human Pit2 was weak. In contrast, neither the arginine 73 nor specific C-terminal sequences are required for efficient binding or infection with Pit1.Taken together, these data suggest that different residues in SU may interact with these two receptors. The specific FeLV-Bs described here, which can enter cells using either human Pit receptor, may be useful as envelope pseudotypes for viruses used in gene therapy. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Univ Washington, Program Mol & Cellular Biol, Seattle, WA 98109 USA. Univ Washington, Dept Microbiol, Seattle, WA 98109 USA. NIMH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Overbaugh, J (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave N,C3-168, Seattle, WA 98109 USA. FU NCI NIH HHS [R01 CA051080, CA51080] NR 39 TC 32 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2001 VL 75 IS 15 BP 6841 EP 6849 DI 10.1128/JVI.75.15.6841-6849.2001 PG 9 WC Virology SC Virology GA 452QR UT WOS:000169870700012 PM 11435563 ER PT J AU Kaludov, N Brown, KE Walters, RW Zabner, J Chiorini, JA AF Kaludov, N Brown, KE Walters, RW Zabner, J Chiorini, JA TI Adeno-associated virus serotype 4 (AAV4) and AAV5 both require sialic acid binding for hemagglutination and efficient transduction but differ in sialic acid linkage specificity SO JOURNAL OF VIROLOGY LA English DT Article ID HEPARAN-SULFATE; PARVOVIRUS; VECTORS; TYPE-2; CELL; ERYTHROCYTES; GENERATION; SIALIDASES; PARTICLES; RECEPTOR AB Adeno-associated virus serotype 4 (AAV4) and AAV5 have different tropisms compared to AAV2 and to each other. We recently reported that alpha2-3 sialic acid is required for AAV5 binding and transduction. In this study, we characterized AAV4 binding and transduction and found it also binds sialic acid, but the specificity is significantly different from AAV5. AAV4 can hemagglutinate red blood cells from several species, whereas AAV5 hemagglutinates only rhesus monkey red blood cells. Treatment of red blood cells with trypsin inhibited hemagglutination for both AAV4 and AAV5, suggesting that the agglutinin is a protein. Treatment of Cos and red blood cells with neuraminidases also indicated that AAV4 bound alpha2-3 sialic acid. However, resialylation experiments with neuraminidase-treated red blood cells demonstrated that AAV4 binding required alpha2-3 O-linked sialic acid, whereas AAV5 required N-linked sialic acid. Similarly, resialylation of sialic acid-deficient CHO cells supported this same conclusion. The difference in linkage specificity for AAV4 and AAV5 was confirmed by binding and transduction experiments with cells incubated with either N-linked or O-linked inhibitors of glycosylation. Furthermore, AAV4 transduction was only blocked with soluble alpha2-3 sialic acid, whereas AAV5 could be blocked with either alpha2-3 or alpha2-6 sialic acid. These results suggest that AAV4 and AAV5 require different sialic acid-containing glycoproteins for binding and transduction of target cells and they further explain the different tropism of AAV4 and AAV5. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20902 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA. RP Chiorini, JA (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, 10-IN113,10 Ctr Dr,MSC 1190, Bethesda, MD 20902 USA. NR 37 TC 242 Z9 250 U1 1 U2 3 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 AUG PY 2001 VL 75 IS 15 BP 6884 EP 6893 DI 10.1128/JVI.75.15.6884-6893.2001 PG 10 WC Virology SC Virology GA 452QR UT WOS:000169870700017 PM 11435568 ER PT J AU Khan, MA Aberham, C Kao, S Akari, H Gorelick, R Bour, S Strebel, K AF Khan, MA Aberham, C Kao, S Akari, H Gorelick, R Bour, S Strebel, K TI Human immunodeficiency virus type I Vif protein is packaged into the nucleoprotein complex through an interaction with viral genomic RNA SO JOURNAL OF VIROLOGY LA English DT Article ID CELL-DEPENDENT REQUIREMENT; BLOOD MONONUCLEAR-CELLS; NUCLEOCAPSID PROTEIN; REVERSE TRANSCRIPTION; VIRION INCORPORATION; DNA-SYNTHESIS; ZINC-FINGER; NONPERMISSIVE CELLS; RESTRICTIVE CELLS; HIV-1 PARTICLES AB The human immunodeficiency virus type 1 (HIV-1) Vif protein plays a critical role in the production of infectious virions. Previous studies have demonstrated the presence of small amounts of Vif in virus particles. However, Vif packaging was assumed to be nonspecific, and its functional significance has been questioned. We now report that packaging of Vif is dependent on the packaging of viral genomic RNA in both permissive and restrictive HIV-1 target cells. Mutations in the nucleocapsid zinc finger domains that abrogate packaging of viral genomic RNA abolished packaging of Vif. Additionally, an RNA packaging-defective virus exhibited significantly reduced packaging of Vif. Finally, deletion of a putative RNA-interacting domain in Vif abolished packaging of Vif into virions. Virion-associated Vif was resistant to detergent extraction and copurified with components of the viral nucleoprotein complex and functional reverse transcription complexes. Thus, Vif is specifically packaged into virions as a component of the viral nucleoprotein complex. Our data suggest that the specific association of Vif with the viral nucleoprotein complex might be functionally significant and could be a critical requirement for infectivity of viruses produced from restrictive host cells. C1 NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21701 USA. RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, 4-312,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 72 TC 107 Z9 113 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2001 VL 75 IS 16 BP 7252 EP 7265 DI 10.1128/JVI.75.16.7252-7265.2001 PG 14 WC Virology SC Virology GA 456QD UT WOS:000170093000004 PM 11461998 ER PT J AU Crotty, S Miller, CJ Lohman, BL Neagu, MR Compton, L Lu, D Lu, FXS Fritts, L Lifson, JD Andino, R AF Crotty, S Miller, CJ Lohman, BL Neagu, MR Compton, L Lu, D Lu, FXS Fritts, L Lifson, JD Andino, R TI Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors SO JOURNAL OF VIROLOGY LA English DT Article ID COMBINATION IMMUNIZATION REGIMEN; MUCOSAL IMMUNE-RESPONSES; CYTOTOXIC T-LYMPHOCYTES; SIVMNE GP160 VACCINES; RHESUS MACAQUES; EFFECTIVE INDUCTION; GENETIC STABILITY; NEUTRALIZING ANTIBODIES; NUCLEOTIDE-SEQUENCE; INFECTION AB Here we provide the first report of protection against a vaginal challenge with a highly virulent simian immunodeficiency virus (SIV) by using a vaccine vector. New poliovirus vectors based on Sabin I and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragments. Two cocktails of 20 transgenic polioviruses (SabRV1-SIV and SabRV2-SIV were inoculated into seven cynomolgus macaques. All monkeys produced substantial anti-SIV serum and mucosal antibody responses. SIV-specific cytotoxic T-lymphocyte responses were detected in three of seven monkeys after vaccination. All 7 vaccinated macaques, as well as 12 control macaques, were challenged vaginally with pathogenic SIVmac251. Strikingly, four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge. All 12 control monkeys became SIV positive. In two of the seven SabRV-SIV-vaccinated monkeys we found no virological evidence of infection following challenge, indicating that these two monkeys were completely protected. Two additional SabRV-SIV-vaccinated monkeys exhibited a pronounced reduction in postacute viremia to < 10(3) copies/ml, suggesting that the vaccine elicited an effective cellular immune response. Three of six control animals developed clinical AIDS by 48 weeks postchallenge. In contrast, all seven vaccinated monkeys remained healthy as judged by all clinical parameters. These results demonstrate the efficacy of SabRV as a potential human vaccine vector, and they show that the use of a vaccine vector cocktail expressing an array of defined antigenic sequences can be an effective vaccination strategy in an outbred population. C1 Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif Davis, Sch Med, Calif Reg Primate Res Ctr, Dept Pathol, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program,Retroviral Pathogenesis Lab, Frederick, MD 21702 USA. RP Andino, R (reprint author), Univ Calif San Francisco, Dept Microbiol & Immunol, Box 0414,513 Parnassus Ave, San Francisco, CA 94143 USA. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [R21 AI036178, AI33434, AI36178, R56 AI036178, R01 AI036178] NR 83 TC 80 Z9 85 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2001 VL 75 IS 16 BP 7435 EP 7452 DI 10.1128/JVI.75.16.7435-7452.2001 PG 18 WC Virology SC Virology GA 456QD UT WOS:000170093000022 PM 11462016 ER PT J AU Husain, M Moss, B AF Husain, M Moss, B TI Vaccinia virus F13L protein with a conserved phospholipase catalytic motif induces colocalization of the B5R envelope glycoprotein in post-Golgi vesicles SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIN-CONTAINING MICROVILLI; PERIPHERAL MEMBRANE-PROTEIN; TO-CELL SPREAD; EXTRACELLULAR VIRUS; OUTER ENVELOPE; TAIL FORMATION; BREFELDIN-A; ENDOPLASMIC-RETICULUM; FUNCTIONAL-ANALYSIS; A33R GENE AB The wrapping of intracellular mature vaccinia virions by modified trans-Golgi or endosomal cisternae to form intracellular enveloped virions is dependent on at least two viral proteins encoded by the B5R and F13L open reading frames. B5R is a type I integral membrane glycoprotein, whereas F13L is an unglycosylated, palmitylated protein with a motif that is conserved in a superfamily of phospholipid-metabolizing enzymes. Microscopic visualization of the F13L protein was achieved by fusing it to the enhanced green fluorescent protein (GFP). F13L-GFP was functional when expressed by a recombinant vaccinia virus in which it replaced the wild-type F13L gene or by transfection of uninfected cells with a plasmid vector followed by infection with an F13L deletion mutant. In uninfected or infected cells, F13L-GFP was associated with Golgi cisternae and post-Golgi vesicles containing the LAMP 2 late endosomal-lysosomal marker. Association of F13L-GFP with vesicles was dependent on an intact phospholipase catalytic motif and sites of palmitylation. The B5R protein was also associated with LAMP2-containing vesicles when F13L-GFP was coexpressed, but was largely restricted to Golgi cisternae in the absence of F13L-GFP or when the F13L moiety was mutated. We suggest that the F13L protein, like its human phospholipase D homolog, regulates vesicle formation and that this process is involved in intracellular enveloped virion membrane formation. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. NR 72 TC 30 Z9 30 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2001 VL 75 IS 16 BP 7528 EP 7542 DI 10.1128/JVI.75.16.7528-7542.2001 PG 15 WC Virology SC Virology GA 456QD UT WOS:000170093000031 PM 11462025 ER PT J AU Lisziewicz, J Gabrilovich, DI Varga, G Xu, JQ Greenberg, PD Arya, SK Bosch, M Behr, JP Lori, F AF Lisziewicz, J Gabrilovich, DI Varga, G Xu, JQ Greenberg, PD Arya, SK Bosch, M Behr, JP Lori, F TI Induction of potent human immunodeficiency virus type 1-specific T-cell-restricted immunity by genetically modified dendritic cells SO JOURNAL OF VIROLOGY LA English DT Article ID IN-VIVO; ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; LYMPHOID ORGANS; GENE-TRANSFER; LYMPHOCYTES; ANTIGEN; RESPONSES; VECTOR; EXPRESSION AB A novel technology combining replication- and integration-defective human immunodeficiency virus type I (HIV-1) vectors with genetically modified dendritic cells was developed in order to induce T-cell immunity. We introduced the vector into dendritic cells as a plasmid DNA using polyethylenimine as the gene delivery system, thereby circumventing the problem of obtaining viral vector expression in the absence of integration. Genetically modified dendritic cells (GMDC) presented viral epitopes efficiently, secreted interleukin 12, and primed both CD4(+) and CD8(+) HIV-specific T cells capable of producing gamma interferon and exerting potent HIV-1-specific cytotoxicity in vitro. In nonhuman primates, subcutaneously injected GMDC migrated into the draining lymph node at an unprecedentedly high rate and expressed the plasmid DNA. The animals presented a vigorous HIV-specific effector cytotoxic-T-lymphocyte (CTL) response as early as 3 weeks after a single immunization, which later developed into a memory CTL response. Interestingly, antibodies did not accompany these CTL responses, indicating that GMDC can induce a pure Th1 type of immune response. Successful induction of a broad and long-lasting HIV-specific cellular immunity is expected to control virus replication in infected individuals. C1 Res Inst Genet & Human Therapy, Washington, DC 20007 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33612 USA. Univ Washington, Seattle, WA 98195 USA. NCI, NIH, Bethesda, MD 20892 USA. Fac Pharm, Lab Chim Genet, F-67401 Illkirch Graffenstaden, France. RP Lisziewicz, J (reprint author), Res Inst Genet & Human Therapy, 2233 Wisconsin Ave NW,Suite 503, Washington, DC 20007 USA. NR 48 TC 43 Z9 43 U1 0 U2 5 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 AUG PY 2001 VL 75 IS 16 BP 7621 EP 7628 DI 10.1128/JVI.75.16.7621-7628.2001 PG 8 WC Virology SC Virology GA 456QD UT WOS:000170093000040 PM 11462034 ER PT J AU Bartke, A Coshigano, K Kopchick, J Chandrashekar, V Mattison, J Kinney, B Hauck, S AF Bartke, A Coshigano, K Kopchick, J Chandrashekar, V Mattison, J Kinney, B Hauck, S TI Genes that prolong life: Relationships of growth hormone and growth to aging and life span SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Review ID HEALTHY OLDER MEN; AMES DWARF MICE; TRANSGENIC MICE; FACTOR-I; CAENORHABDITIS-ELEGANS; CALORIC RESTRICTION; OXIDATIVE STRESS; SACCHAROMYCES-CEREVISIAE; SUPEROXIDE-DISMUTASE; TESTICULAR FUNCTION AB Mutant mice with a combined deficiency of growth hormone (GH), prolactin, and thyrotropin, and knockout mice with GH resistance, live longer than their normal siblings. The extension of life span in these animals is very large (up to 65%) reproducible, and not limited to any particular genetic background or husbandry conditions. In addition to demonstrating that genes control aging in mammals, these findings suggest that GH actions, growth, and body size may have important roles in the determination of life span. We describe the key phenotypic characteristics of long-living mutant and knockout mice, with an emphasis on those characteristics that may be related to delayed aging in these animals. We also address the broader topic of the relationship between GH, growth, maturation, body size, and aging, and we attempt to reconcile the well-publicized antiaging action of GH with the evidence that suppression of GH release or action can prolong life. C1 So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. Ohio Univ, Coll Osteopath Med, Athens, OH 45701 USA. NIA, NIH, Anim Ctr, Poolesville, MD USA. RP Bartke, A (reprint author), So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. EM abartke@siumed.edu RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X NR 106 TC 138 Z9 138 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD AUG PY 2001 VL 56 IS 8 BP B340 EP B349 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 459KB UT WOS:000170248600004 PM 11487592 ER PT J AU Sazawal, S Gurbuxani, S Bhatia, K Khattar, A Raina, V Arya, LS Vats, T Magrath, I Bhargava, M AF Sazawal, S Gurbuxani, S Bhatia, K Khattar, A Raina, V Arya, LS Vats, T Magrath, I Bhargava, M TI Incidence, clinical characteristics and early treatment outcome in Indian patients of childhood acute lymphoblastic leukemia with ALL-1 gene rearrangement SO LEUKEMIA RESEARCH LA English DT Article DE ALL-1 gene rearrangement; acute lymphoblastic leukemia; Southern blot; Indian patients ID BIOLOGIC FEATURES PREDICT; POOR-PROGNOSIS; MLL-GENE; TRANSLOCATION; 11Q23; T(4-11)(Q21-Q23); INFANTS; CANCER; AGE AB In a series of 185 patients (median age 7 years) of acute lymphoblastic leukaemia (ALL) from India, the overall incidence of ALL-1 gene rearrangement using the Southern blot technique was 11.4% (21/185). The incidence amongst the infants (age 1 year, 70%) was significantly higher when compared to patients > 1- less than or equal to 10 years (7.4%, P = 0.00001) as well as > 10 years old (9.3%, P=0.0001). ALL-1 gene rearrangement was associated with significantly higher WBC count (P=0.01) and CD10 negativity (P=0.00000001). Complete remission (CR) and relapse rates in 98 patients evaluable for response to therapy on a uniform therapy protocol was independent of ALL-1 gene status. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 All India Inst Med Sci, Dept Haematol, New Delhi 110029, India. All India Inst Med Sci, Dept Paediat, New Delhi 110029, India. All India Inst Med Sci, Dept Med Oncol, New Delhi 110029, India. NCI, Lymphoma Biol Sect, Paediat Branch, NIH, Bethesda, MD 20892 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Paediat, Amarillo, TX USA. RP Bhargava, M (reprint author), All India Inst Med Sci, Dept Haematol, IRCH Bldg,1st Floor,Ansari Nagar, New Delhi 110029, India. OI Bhargava, Manorama/0000-0003-2135-7298 NR 29 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD AUG PY 2001 VL 25 IS 8 BP 693 EP 698 DI 10.1016/S0145-2126(01)00007-8 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 457UL UT WOS:000170155200009 PM 11397475 ER PT J AU Melenhorst, JJ Brummendorf, TH Kirby, M Lansdorp, PM Barrett, AJ AF Melenhorst, JJ Brummendorf, TH Kirby, M Lansdorp, PM Barrett, AJ TI CD8+T cells in large granular lymphocyte leukemia are not defective in activation- and replication-related apoptosis SO LEUKEMIA RESEARCH LA English DT Article DE LGL; apoptosis; telomere; flow-FISH; homeostasis; Fas ID TUMOR-NECROSIS-FACTOR; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; T-CELL; FAS LIGAND; TELOMERE LENGTH; RECEPTOR SIGNALS; CYCLOSPORINE-A; DEATH; EXPRESSION; MUTATIONS AB Persistent lymphocytosis in large granular lymphocyte leukemia (LGL) may result from defects in activation- or Fas crosslinking-induced cell death. Here we show that Fas crosslinking and CD3 activation causes apoptosis of in vitro activated CD8 T cells, but not of freshly isolated CD8 T cells. Death was partially blocked by a neutralizing antibody to FasL. Inhibition of metalloproteinase-mediated FasL solubilization significantly potentiated induction of cell death. Further-more, CD3 plus CD28 stimulation resulted in telomeric erosion in LGL cells, and ultimately proliferation ceased. Together, these data indicate that activation- and proliferation-related cell death mechanisms are functional in LGL cells. Published by Elsevier Science Ltd. C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. RP Melenhorst, JJ (reprint author), NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI29524]; NIGMS NIH HHS [GM56162] NR 47 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD AUG PY 2001 VL 25 IS 8 BP 699 EP 708 DI 10.1016/S0145-2126(01)00010-8 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 457UL UT WOS:000170155200010 PM 11397476 ER PT J AU Morse, HC Qi, CF Chattopadhyay, SK Hori, M Taddesse-Heath, L Ozato, K Hartley, JW Taylor, BA Ward, JM Jenkins, NA Copeland, NG Fredrickson, TN AF Morse, HC Qi, CF Chattopadhyay, SK Hori, M Taddesse-Heath, L Ozato, K Hartley, JW Taylor, BA Ward, JM Jenkins, NA Copeland, NG Fredrickson, TN TI Combined histiologic and molecular features reveal previously unappreciated subsets of lymphoma in AKXD recombinant inbred mice SO LEUKEMIA RESEARCH LA English DT Article DE diffuse large cell lymphoma; mouse B-cell lymphoma; oncogene; proviral insertional mutagenesis; splenic marginal zone lymphoma ID B-CELL LYMPHOMAS; HEALTH-ORGANIZATION CLASSIFICATION; TRUE HISTIOCYTIC LYMPHOMA; MURINE LEUKEMIA VIRUSES; T-CELL; MALIGNANT HISTIOCYTOSIS; NEOPLASTIC DISEASES; VIRAL INTEGRATION; MOUSE STRAINS; EXPRESSION AB Hematopoietic neoplasms developing in AKXD recombinant inbred, NFS.V+ and ICSBP knockout mice were assessed using morphologic, cytologic and molecular criteria that relate these disorders to human lymphoma, and leukemia. Lymphoma types included precursor T-cell and B-cell lymphoblastic, small lymphocytic, splenic marginal zone, follicular, and diffuse large cell (DLCL). In addition to previously defined subtypes of DLCL composed of centroblasts or immunoblasts, two additional subtypes are defined here: lymphoblastic lymphoma like (LL) and lymphoma characterized by a histiocytic reaction (HS). DLCL(HS) were distinguished from true histiocytic lymphomas by the presence of clonal Ig gene rearrangements. Published by Elsevier Science Ltd. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. NCI, Vet & Tumor Pathol Sect, NIH, Frederick, MD 21702 USA. NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Morse, HC (reprint author), NIAID, Immunopathol Lab, NIH, Room 7-304,7 Ctr Dr, Bethesda, MD 20892 USA. OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [CA33093] NR 58 TC 21 Z9 22 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD AUG PY 2001 VL 25 IS 8 BP 719 EP 733 DI 10.1016/S0145-2126(01)00022-4 PG 15 WC Oncology; Hematology SC Oncology; Hematology GA 457UL UT WOS:000170155200013 PM 11397479 ER PT J AU Kiss, A Schnur, J Szabo, Z Nagy, P AF Kiss, A Schnur, J Szabo, Z Nagy, P TI Immunohistochemical analysis of atypical ductular reaction in the human liver, with special emphasis on the presence of growth factors and their receptors SO LIVER LA English DT Article DE HGF; SCF; TGF alpha; TGF beta; UPA ID STEM-CELL FACTOR; FOCAL NODULAR HYPERPLASIA; BILIARY EPITHELIAL-CELLS; PROGENITOR CELLS; FACTOR-ALPHA; OVAL CELLS; RAT-LIVER; C-KIT; ADULT-RAT; HEPATOCELLULAR-CARCINOMA AB Aims/Background: The objective of this study was to characterize the expression of transforming growth factor-alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met, transforming growth factor-beta/Type I-II transforming growth factor-beta receptors, stem cell factor, urokinase plasminogen activator, smooth muscle actin, CD34 and alpha-fetoprotein in human liver samples with (sub)massive necrosis of different etiology containing atypical ductular reaction. Methods: Their presence was studied by immunohistochemistry on paraffin-embedded tissue sections. Results: Transforming growth factor-alpha and -beta, hepatocyte growth factor and their receptors were demonstrated in the ductules; additionally stem cell factor and urokinase plasminogen activator were also expressed. The atypical ductules were surrounded by smooth muscle actin-positive activated stellate cells. Conclusion: These phenotypic similarities confirm that the atypical ductules in the human liver may be equivalent of oval cells in the rat liver, which are regarded as the progeny of stem cells. That is, the atypical ductular proliferation may correspond to a stem cell-fed regenerative process. C1 Semmelweis Univ, Sch Med, Inst Pathol & Expt Canc Res, H-1085 Budapest, Hungary. St Laszlo Gen Hosp, Dept Pathol, Budapest, Hungary. NCI, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Nagy, P (reprint author), Semmelweis Univ, Sch Med, Inst Pathol & Expt Canc Res, Ulloi Ut 26, H-1085 Budapest, Hungary. NR 54 TC 29 Z9 35 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0106-9543 J9 LIVER JI Liver PD AUG PY 2001 VL 21 IS 4 BP 237 EP 246 DI 10.1034/j.1600-0676.2001.021004237.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 457UU UT WOS:000170155900003 PM 11454186 ER PT J AU Ory, S Jurdic, P AF Ory, S Jurdic, P TI Microtubules, cell compartments and Rho GTPases: a "menage a trois" for efficient migration SO M S-MEDECINE SCIENCES LA French DT Article ID ACTIN STRESS FIBERS; BINDING PROTEIN-RHO; PLASMA-MEMBRANE; FOCAL ADHESIONS; CDC42; RAC; CYTOSKELETON; ARF6; POLARITY; COMPLEX AB Dynamic cytoskeleton and membrane plasticity allow higher eucaryotic cells to actively migrate. To move, cells need to correctly integrate both extra and intracellular signals in order to completely reorganize their actin cytoskeleton and corresponding adhesion structures. It is well established that RhoGTPases are pivotal regulators of actin organization making them. key players in the Control of cell migration. Actin organisation between the leading and the rear edges of migrating cells is different, implying the existence of polarized activation and antagonistic activities. of the RhoGTPases within the e cell. Recent data suggest that both microtubules and subcellular compartments influence the local distribution and polarized activity of RhoGTPases in migrating cells. C1 NCI, FCRF, RCGL, Frederick, MD 21702 USA. RP Ory, S (reprint author), NCI, FCRF, RCGL, Bldg 560,Rm 22-31,POB B, Frederick, MD 21702 USA. RI Ory, Stephane/E-9947-2010 OI Ory, Stephane/0000-0003-4359-1157 NR 53 TC 1 Z9 1 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD AUG-SEP PY 2001 VL 17 IS 8-9 BP 878 EP 885 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 479CB UT WOS:000171385400007 ER PT J AU Barnett, A AF Barnett, A TI Comments on "Gradient-induced acoustic and magnetic field fluctuations in a 4T whole-body MR imager" SO MAGNETIC RESONANCE IN MEDICINE LA English DT Letter DE MRI; acoustic noise; magnetic field fluctuations; time stationary linear system AB The results published in the article Gradient-induced Acoustic and Magnetic Field Fluctuations in a 4T Whole-Body MR Imager by Wu et al. (Magn Reson Med 2000;44:532-536) appear to be consistent with the response of a time-stationary linear system. Since a linear system is more simply described than a nonlinear system, the authors are urged to reanalyze their data to test the linear-system hypothesis. Published 2001 Wiley-Liss, Inc. C1 NIH, Bethesda, MD 20892 USA. RP Barnett, A (reprint author), NIH, Bldg 10,Rm 4D20, Bethesda, MD 20892 USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD AUG PY 2001 VL 46 IS 2 BP 207 EP 207 DI 10.1002/mrm.1179 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 457AC UT WOS:000170114100001 PM 11477621 ER PT J AU Guttman, MA McVeigh, ER AF Guttman, MA McVeigh, ER TI Techniques for fast stereoscopic MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE stereoscopy; real-time; interventional; 3D; angiography ID CATHETER-TRACKING; INFORMATION; SENSITIVITY; ANGIOGRAMS AB Stereoscopic MRI can impart 3D perception with only two image acquisitions. This economy over standard multiplanar 3D volume renderings allows faster frame rates, which are needed for real-time imaging applications. Real-time 3D perception may enhance the appreciation of complex anatomical structures, and may improve hand-eye coordination while manipulating a medical device during an image-guided interventional procedure. To this goal, a system is being developed to acquire and display stereoscopic MR images in real-time. A clinically used, fast gradient-recalled echo-train sequence has been modified to produce stereo image pairs. Features have been added for depth cueing, view sharing, and bulk signal suppression. A workstation was attached to a clinical MR scanner for fast data extraction, image reconstruction and stereoscopic image display. Published 2001 Wiley-Liss, Inc.(dagger) C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Guttman, MA (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004608-08] NR 26 TC 16 Z9 16 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD AUG PY 2001 VL 46 IS 2 BP 317 EP 323 DI 10.1002/mrm.1194 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 457AC UT WOS:000170114100016 PM 11477636 ER PT J AU Kellman, P McVeigh, ER AF Kellman, P McVeigh, ER TI Ghost artifact cancellation using phased array processing SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE SENSE; artifact; ghost; EPI; phased array; FISP ID ECHO; REDUCTION AB In this article, a method for phased array combining is formulated which may be used to cancel ghosts caused by a variety of distortion mechanisms, including space variant distortions such as local flow or off-resonance. This method is based on a constrained optimization, which optimizes SNR subject to the constraint of nulling ghost artifacts at known locations. The resultant technique is similar to the method known as sensitivity encoding (SENSE) used for accelerated imaging; however, in this formulation it is applied to full field-of-view (FOV) images. The method is applied to multishot EPI with noninterleaved phase encode acquisition. A number of benefits, as compared to the conventional interleaved approach, are reduced distortion due to off-resonance, in-plane flow, and EPI delay misalignment, as well as eliminating the need for echo-shifting. Experimental results demonstrate the cancellation for both phantom as well as cardiac imaging examples. Published 2001 Wiley-Liss, Inc.(dagger) C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 HL004608-08] NR 16 TC 32 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD AUG PY 2001 VL 46 IS 2 BP 335 EP 343 DI 10.1002/mrm.1196 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 457AC UT WOS:000170114100018 PM 11477638 ER PT J AU Moldin, SO Farmer, ME Chin, HR Battey, JF AF Moldin, SO Farmer, ME Chin, HR Battey, JF TI Trans-NIH neuroscience initiatives on mouse phenotyping and mutagenesis SO MAMMALIAN GENOME LA English DT Review ID CIRCADIAN CLOCK GENE; EMBRYONIC STEM-CELLS; FUNCTIONAL-ANALYSIS; ENU MUTAGENESIS; HUMAN-DISEASE; MUTANT MICE; GENOME-WIDE; SEQUENCE; BEHAVIOR; SCREENS AB In the post-genomic era, the laboratory mouse will excel as a premier mammalian system to study normal and disordered biological processes, in part because of low cost, but largely because of the rich opportunities that exist for exploiting genetic tools and technologies in the mouse to systematically determine mammalian gene function. Many robust models of human disease may therefore be developed, and these in turn will provide critical clues to understanding gene function. The full potential of the mouse for understanding many of the neural and behavioral phenotypes of relevance to neuroscientists has yet to be realized. With the full anatomy of the mouse genome at hand, researchers for the first time will be able to move beyond traditional gene-by-gene approaches and take a global view of gene expression patterns crucial for neurobiological processes. In response to an action plan for mouse genomics developed on the basis of recommendations from the scientific community, seven institutes of the National Institutes of Health (NIH) initiated in 1999 a mouse genetics research program that specifically focused on neurobiology and complex behavior. The specific goals of these neuroscience initiatives are to develop high-throughput phenotyping assays and to initiate genome-wide mutagenesis projects to identify hundreds of mutant strains with heritable abnormalities of high relevance to neuroscientists. Assays and mutants generated in these efforts will be made widely available to the scientific community, and such resources will provide neuroscientists unprecedented opportunities to elucidate the molecular mechanisms of neural function and complex behavior. Such research tools ultimately will permit the manipulation and analysis of the mouse genome, as a means of gaining insight into the genetic bases of the mammalian nervous system and its complex disorders. C1 NIMH, Genet Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA. RP Moldin, SO (reprint author), NIMH, Genet Res Branch, Div Neurosci & Basic Behav Sci, NIH, 6001 Execut Blvd,Room 7189,MSC 9643, Bethesda, MD 20892 USA. EM smoldin@mail.nih.gov NR 40 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD AUG PY 2001 VL 12 IS 8 BP 575 EP 581 DI 10.1007/s00335-001-4005-7 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 455JN UT WOS:000170023900001 PM 11471049 ER PT J AU Rosner, K Winter, DB Skovgaard, GL Oshima, J Gearhart, PJ Bohr, VA AF Rosner, K Winter, DB Skovgaard, GL Oshima, J Gearhart, PJ Bohr, VA TI Analysis of microsatellite instability and hypermutation of immunoglobulin variable genes in Werner syndrome SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE Werner syndrome; microsatellite instability; hypermutation; immunoglobulin variable gene ID DNA MISMATCH REPAIR; PERIPHERAL-BLOOD LYMPHOCYTES; SYNDROME CELL-LINES; SYNDROME PROTEIN; MUTATOR PHENOTYPE; MICE DEFICIENT; B-LYMPHOCYTES; INTERACTS; DIVERSITY; LOCUS AB Werner syndrome (WS) is a human premature aging syndrome, which is associated with high frequencies of neoplasia and genetic instability. We have examined the occurrence of microsatellite instability, which may result from defective mismatch repair, in lymphoblastoid cell lines derived from nine WS patients. Instability was measured at the D2S123 locus by gel analysis of PCR products. Three WS cell lines had 4-13% altered alleles, compared with 0% in the other six lines. The increased frequency of microsatellite instability could not readily be associated with overt cancer or any other known clinical condition in the three patients. To examine whether the WS defect affected the humoral immune system, we measured the hypermutation of immunoglobulin variable genes in peripheral blood cells from the WS patient who donated the cell line with the highest frequency of microsatellite instability. The frequency and pattern of mutation was similar to that from normal individuals, suggesting that the Werner protein is not involved in generating hypermutation. Published by Elsevier Science Ireland Ltd. C1 NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. Rigshosp, Lab Mol Gerontol & Dermatol, DK-2100 Copenhagen, Denmark. Bispebjerg Hosp, Dept Dermatol, DK-2400 Copenhagen, Denmark. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Bohr, VA (reprint author), NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD AUG PY 2001 VL 122 IS 11 BP 1121 EP 1133 DI 10.1016/S0047-6374(01)00256-1 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 444YA UT WOS:000169426600003 PM 11389928 ER PT J AU Schaffner, AE Ghesquiere, A AF Schaffner, AE Ghesquiere, A TI The effect of type I astrocytes on neuronal complexity: A fractal analysis SO METHODS LA English DT Article ID ACTIVITY-DEPENDENT DEVELOPMENT; RAT HIPPOCAMPAL-NEURONS; SPINAL-CORD; NEURITE OUTGROWTH; CELLS; GLIA; DIFFERENTIATION; VITRO; MORPHOLOGY; MODULATION AB Embryonic, ventral spinal cord neurons were grown on ploy(D-lysine) (PDL) or on a monolayer of type I astrocytes. At various times from 6 h to 2 weeks postplating, cells were fluorescently labeled and fixed with 4% paraformaldehyde. The cell surface immunoreaction allowed visualization of neurons in their entirety, namely, cell bodies and various membranous extensions that included lamellipodia, growth cones, axons, and dendrites. Outlines were drawn for individual neurons and their fractal dimension (D) was calculated. Neurons on poly(D-lysine) reached a peak D at 3 days in vitro, 1 day later than neurons on astrocytes (2 days in vitro). The maximum D was greater for cells on poly(D-lysine) when compared with neurons on astrocytes. In a second experiment the maximum D was similar for neurons on both surfaces but neurons on PDL maintained a higher D for a much longer period than neurons on astrocytes. An examination of fluorescent images revealed that neurons on poly(D-lysine) exhibited lamellipodia and large growth cones for several days and these structures were likely responsible for the high D seen in these cells. These structures were rarely observed in neurons plated on astrocytes. Interestingly, D on both surfaces decreased to a similar value at between :1 and 2 weeks in vitro. The trend for D in these cultures, an initial increase to a peak value followed by a decrease to a stable value, is discussed in light of the chemical nature of the two surfaces and synapse formation and stabilization. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Schaffner, AE (reprint author), Ctr Sci Review, 6701 Rockledge Dr,Room 5214 MSC 7850, Bethesda, MD 20892 USA. NR 49 TC 4 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD AUG PY 2001 VL 24 IS 4 BP 323 EP 329 DI 10.1006/meth.2001.1202 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 458ZX UT WOS:000170226300003 PM 11465997 ER PT J AU Behar, TN AF Behar, TN TI Analysis of fractal dimension of 02A glial cells differentiating in vitro SO METHODS LA English DT Article ID RAT OPTIC-NERVE; OLIGODENDROCYTE DEVELOPMENT; ASTROCYTE LINEAGES; PROGENITOR-CELL; GROWTH-FACTOR; PROLIFERATION; EXPRESSION; INVITRO; CULTURE; PATHWAY AB Fractal dimension is a quantitative measure of morphological complexity. Glial cells of the oligodendrocyte-type 2 astrocyte (O2A) lineage exhibit increasing morphological complexity as they differentiate in vitro. Enriched populations of O2A progenitor cells isolated from neonatal rat cerebral hemispheres or optic nerves were allowed to differentiate in vitro, and their fractal dimensions were measured over time. The fractal dimensions of the maturing cells correlated with perceived complexity; cells with elaborate process branching had larger fractal dimensions than cells with a simpler morphology. An analysis of changes in fractal dimension revealed distinct rates of growth for both oligodendrocytes and type 2 astrocytes. The fractal dimension remained constant over a 10-fold range in optical magnification, demonstrating that cultured O2A glial cells exhibit self-similarity, a defining characteristic of fractal objects. These results illustrate that fractal dimension analysis of maturing cell populations is a useful method for quantitatively describing the process of cell differentiation. C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Behar, TN (reprint author), Bldg 36,Room 2C02,36 Convent Dr, Bethesda, MD 20892 USA. NR 24 TC 20 Z9 21 U1 2 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD AUG PY 2001 VL 24 IS 4 BP 331 EP 339 DI 10.1006/meth.2001.1203 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 458ZX UT WOS:000170226300004 PM 11465998 ER PT J AU Petter, R Kang, BS Boekhout, T Davis, BJ Kwon-Chung, KJ AF Petter, R Kang, BS Boekhout, T Davis, BJ Kwon-Chung, KJ TI A survey of heterobasidiomycetous yeasts for the presence of the genes homologous to virulence factors of Filobasidiella neoformans, CNLAC1 and CAP59 SO MICROBIOLOGY-SGM LA English DT Article DE Cryptococcus neoformans; virulence gene homologues; basidiomycetous yeasts ID CAPSULE-ASSOCIATED GENE; CRYPTOCOCCUS-NEOFORMANS; LACCASE GENE; BASIDIOMYCETOUS YEASTS; SEROTYPE-A; POLYSACCHARIDES; IDENTIFICATION; PHENOLOXIDASE; SEQUENCES; CLONING AB Among species of the heterobasidiomycetous yeasts, Filobasidiella neoformans is the only serious pathogen that causes fatal infections in both immunocompromised as well as immunocompetent patients. Three phenotypic characteristics, including growth at 37 degreesC, extracellullar polysaccharide capsule and laccase activity, of F. neoformans are known to play major roles in the pathogenicity of the fungus. Several CAP genes involved in polysaccharide capsule formation, as well as the CNLAC1 gene encoding a laccase, have previously been cloned and characterized. To analyse the presence of these Cryptococcus neoformans virulence factors in other heterobasidiomycetous yeasts, numerous species of heterobasidiomycetous yeasts were screened for the presence of laccase activity and a polysaccharide capsule. Species exhibiting laccase activity and possessing a glucuronoxylomannan (GXM) capsule were screened for homologues of both the CAP59 gene and the CNLAC1 gene of F. neoformans. Southern blots of genomic DNA from GXM capsule-producing species exhibited no discernible hybridization to the CAP59 DNA sequence except for the two varieties of F. neoformans and Cryptococcus podzolicus. Although discernible, the hybridization band observed with the DNA of C. podzolicus was faint. Oligonucleotide primers constructed using the CAP59 gene sequence also failed to yield PCR products from DNAs of these yeasts except for the two varieties of F. neoformans. These results, coupled with the absence of a CAP59 homologue in the database, suggested the CAP59 gene to be unique to F. neoformans. C. podzolicus was the only species besides F. neoformans that possessed a capsule and expressed strong laccase activity on various media containing phenolic compounds. A CNLAC1 homologue was isolated from C. podzolicus while it was not detected in the species producing beige to faint tan colonies on media with phenolic compounds. Compared to the CNLAC1 sequence of four serotypes of F. neoformans, the CNLAC1 homologue of C. podzolicus showed the highest homology to that of serotype B/C strains and the lowest homology to that of serotype A strains. C1 NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Cent Bur Schimmelcultures, Utrecht, Netherlands. RP Kwon-Chung, KJ (reprint author), NIAID, Mol Microbiol Sect, Clin Invest Lab, NIH, Bldg 10,11C304, Bethesda, MD 20892 USA. RI Boekhout, Teun/F-1552-2010 OI Boekhout, Teun/0000-0002-0476-3609 NR 35 TC 35 Z9 36 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD AUG PY 2001 VL 147 BP 2029 EP 2036 PN 8 PG 8 WC Microbiology SC Microbiology GA 464PN UT WOS:000170541100005 PM 11495981 ER PT J AU Chandrasekaran, K Liu, LI Hatanpaa, K Shetty, U Mehrabian, Z Murray, PD Fiskum, G Rapoport, SI AF Chandrasekaran, K Liu, LI Hatanpaa, K Shetty, U Mehrabian, Z Murray, PD Fiskum, G Rapoport, SI TI Chronic exposure of neural cells to elevated intracellular sodium decreases mitochondrial mRNA expression SO MITOCHONDRION LA English DT Article DE neural cells; mitochondrial mRNA; intracellular sodium ID NERVE GROWTH-FACTOR; CYTOCHROME-OXIDASE; NEURONAL-ACTIVITY; MESSENGER-RNA; ENERGY-METABOLISM; ALZHEIMER-DISEASE; GENE-EXPRESSION; BINDING PROTEIN; PC12 CELLS; ATP AB Regulation of expression of mitochondrial DNA- (mtDNA-) encoded genes of oxidative phosphorylation can occur rapidly in neural cells subjected to a variety of physiological and pathological conditions. However, the intracellular signal(s) involved in regulating these processes remain unknown. Using mtDNA-encoded cytochrome oxidase subunit III (COX III), we show that its mRNA expression in a differentiated rat pheochromocytoma cell line PC12S is decreased by chronic exposure to agents that increase intracellular sodium. Treatment of differentiated PC12S cells either with ouabain, an inhibitor of Na/K-ATPase, or with monensin, a sodium ionophore, decreased the steady-state levels of COX III mRNA by 50%, 3-4 h after addition of the drugs. No significant reduction in mtDNA-encoded 12S rRNA or nuclear DNA-encoded beta-actin mRNA were observed. Removal of the drugs restored the normal levels of COX III mRNA. Determination of half-lives of COX III mRNA, 12S rRNA, and beta-actin mRNA revealed a selective decrease in the half-life of COX III mRNA from 3.3 h in control cells to 1.6 h in ouabain-treated cells, and to 1 h in monensin-treated cells. These results suggest the existence of a mechanism of posttranscriptional regulation of mitochondrial gene expression that is independent of the energetic status of the cell and may operate under pathological conditions. (C) 2001 Elsevier Science B.V. and Mitochondria Research Society. All rights reserved. C1 Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. RP Chandrasekaran, K (reprint author), Univ Maryland, Sch Med, Dept Anesthesiol, MSTF 5-34,685 W Baltimore St, Baltimore, MD 21201 USA. NR 31 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD AUG PY 2001 VL 1 IS 2 BP 141 EP 150 DI 10.1016/S1567-7249(01)00010-1 PG 10 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 519BW UT WOS:000173705900003 PM 16120274 ER PT J AU Searfoss, A Dever, TE Wickner, R AF Searfoss, A Dever, TE Wickner, R TI Linking the 3 ' poly(A) tail to the subunit joining step of translation initiation: Relations of Pab1p, eukaryotic translation initiation factor 5B (Fun12p), and Ski2p-Slh1p SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; BINDING-PROTEIN; DEPENDENT TRANSLATION; ANTIVIRAL SYSTEM; YEAST; HOMOLOG; GENE; IDENTIFICATION; EXPRESSION AB The 3 ' poly(A) structure improves translation of a eukaryotic mRNA by 50-fold in vivo. This enhancement has been suggested to be due to an interaction of the poly(A) binding protein, Pab1p, with eukaryotic translation initiation factor 4G (eIF4G), However, we find that mutation of eIF4G eliminating its interaction with Pab1p does not diminish the preference for poly(A)(+) mRNA in vivo, indicating another role for poly(A). We show that either the absence of Fun12p (eIF5B), or a defect in eIF5, proteins involved in 60S ribosomal subunit joining, specifically reduces the translation of poly(A)(+) mRNA, suggesting that poly(A) may have a role in promoting the joining step. Deletion of two nonessential putative RNA helicases (genes SKI2 and SLH1) makes poly(A) dispensable for translation. However, in the absence of Fun12p, eliminating Ski2p and Slh1p shows little enhancement of expression of non-poly(A) mRNA. This suggests that Ski2p and Slh1p block translation of non-poly(A) mRNA by an effect on Fun12p, possibly by affecting 60S subunit joining. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. RP NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov NR 42 TC 57 Z9 60 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2001 VL 21 IS 15 BP 4900 EP 4908 DI 10.1128/MCB.21.15.4900-4908.2001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451YF UT WOS:000169829800006 PM 11438647 ER PT J AU Krishnamoorthy, T Pavitt, GD Zhang, F Dever, TE Hinnebusch, AG AF Krishnamoorthy, T Pavitt, GD Zhang, F Dever, TE Hinnebusch, AG TI Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2 alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PROTEIN-SYNTHESIS; KINASE GCN2; YEAST; EXPRESSION; MUTATIONS; EIF-2; IDENTIFICATION; EIF-2-ALPHA; OVERCOME AB Translation initiation factor 2 (eIF2) is a heterotrimeric protein that transfers methionyl-initiator tRNA(Met) to the small ribosomal subunit in a ternary complex with GTP. The eIF2 phosphorylated on serine 51 of its alpha subunit [eIF2(alphaP)] acts as competitive inhibitor of its guanine nucleotide exchange factor, eIF2B, impairing formation of the ternary complex and thereby inhibiting translation initiation. eIF2B is comprised of catalytic and regulatory subcomplexes harboring independent eIF2 binding sites; however, it was unknown whether the ct subunit of eIF2 directly contacts any eIF2B subunits or whether this interaction is modulated by phosphorylation. We found that recombinant eIF2 alpha (glutathione S-transferase [GST]-SUI2) bound to the eIF2B reguiatorg subcomplex in vitro, in a manner stimulated by Ser-51 phosphorylation. Genetic data suggest that this direct interaction also occurred in vivo, allowing overexpressed SUI2 to compete with eIF2(alphaP) holoprotein for binding to the eIF2B regulatory subcomplex. Mutations in SUI2 and in the eIF2B regulatory subunit GCD7 that eliminated inhibition of eIF2B by eIF2(alphaP) also impaired binding of phosphorylated GST-SUI2 to the eIF2B regulatory subunits. These findings provide strong evidence that tight binding of phosphorylated SUI2 to the eIF2B regulatory subcomplex is crucial for the inhibition of eIF2B and attendant downregulation of protein synthesis exerted by eIF2(alphaP). We propose that this regulatory interaction prevents association of the eIF2B catalytic subcomplex with the beta and gamma subunits of eIF2 in the manner required for GDP-CTP exchange. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Univ Manchester, Dept Biomol Sci, Manchester M60 1QD, Lancs, England. RP NICHHD, Lab Eukaryot Gene Regulat, NIH, 6 Ctr Dr,Bldg 6A,Rm B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov RI Pavitt, Graham/A-1363-2010 OI Pavitt, Graham/0000-0002-8593-2418 NR 29 TC 147 Z9 149 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2001 VL 21 IS 15 BP 5018 EP 5030 DI 10.1128/MCB.21.15.5018-5030.2001 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451YF UT WOS:000169829800017 PM 11438658 ER PT J AU Einstein, M Monga, SPS Liu, Y Brodie, SG Tang, Y Li, CL Mishra, L Deng, CX AF Einstein, M Monga, SPS Liu, Y Brodie, SG Tang, Y Li, CL Mishra, L Deng, CX TI Smad proteins and hepatocyte growth factor control parallel regulatory pathways that converge on beta 1-integrin to promote normal liver development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TGF-BETA; TARGETED DISRUPTION; TRANSCRIPTIONAL CONTROL; DEPENDENT DEGRADATION; KNOCKOUT MICE; CELL; EXPRESSION; DIFFERENTIATION; INTEGRINS; RECEPTOR AB Smads serve as intracellular mediators of transforming growth factor beta (TGF-beta) signaling. After phosphorylation by activated type I TGF-beta receptors, Smad proteins translocate to the nucleus, where they serve as transcription factors and increase or decrease expression of TGF-beta target genes, Mice lacking one copy each of Smad2 and Smad3 suffered midgestation lethality due to liver hypoplasia and anemia, suggesting essential dosage requirements of TGF-beta signal components. This is likely due to abnormal adhesive properties of the mutant hepatocytes, which may result from a decrease in the level of the beta1-integrin and abnormal processing and localization of E-cadherin. Culture of mutant livers in vitro revealed the existence of a parallel developmental pathway mediated by hepatocyte growth factor (HGF), which could rescue the mutant phenotype independent of Smad activation. These pathways merge at the beta1-integrin, the level of which was increased by HGF in the cultured mutant livers. HGF treatment reversed the defects in cell proliferation and hepatic architecture in the Smad2(+/-); Smad3(+/-) livers. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20878 USA. Ohio State Univ, Dept Mol Genet, Columbus, OH 43210 USA. Ohio State Univ, Mol Cellular & Dev Biol Program, Columbus, OH 43210 USA. Temple Univ, Fels Canc Inst, Lab Gastrointestinal Dev Mol Biol, Philadelphia, PA 19140 USA. Dept Vet Affairs, Washington, DC 20422 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bldg 10,Room 9N105, Bethesda, MD 20878 USA. NR 38 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2001 VL 21 IS 15 BP 5122 EP 5131 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451YF UT WOS:000169829800026 ER PT J AU Prymakowska-Bosak, M Misteli, T Herrera, JE Shirakawa, H Birger, Y Garfield, S Bustin, M AF Prymakowska-Bosak, M Misteli, T Herrera, JE Shirakawa, H Birger, Y Garfield, S Bustin, M TI Mitotic phosphorylation prevents the binding of HMGN proteins to chromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROUP CHROMOSOMAL-PROTEINS; MOBILITY-GROUP PROTEINS; NUCLEOSOME CORE PARTICLE; HISTONE H3; IN-VIVO; HMG-14; CONDENSATION; ACETYLATION; DOMAIN; DNA AB Condensation of the chromatin fiber and transcriptional inhibition during mitosis is associated,vith the redistribution of many DNA- and chromatin-binding proteins, including members of the high-mobility-group N (HMGN) family. Here we study the mechanism governing the organization of HMGN proteins in mitosis. Using site-specific antibodies and quantitative gel analysis with proteins extracted from synchronized HeLa cells, we demonstrate that, during mitosis, the conserved serine residues in the nucleosomal binding domain (NBD) of this protein family are highly and specifically phosphorylated. Nucleosome mobility shift assays with both in vitro-phosphorylated proteins and with point mutants bearing negative charges in the NBD demonstrate that the negative charge abolishes the ability of the proteins to bind to nucleosomes. Fluorescence loss of photobleaching demonstrates that, in living cells, the negative charge in the NBD increases the intranuclear mobility of the protein and significantly decreases the relative time that it is bound to chromatin. Expression of wild-type and mutant proteins in HmgN1(-/-) cells indicates that the negatively charged protein is not bound to chromosomes. We conclude that during mitosis the NBD of HMGN proteins is highly phosphorylated and that this modification regulates the interaction of the proteins with chromatin. C1 NCI, DBS, NIH, Prot Sect,Lab Metab, Bethesda, MD 20892 USA. NCI, DBS, NIH, Cell Biol & Gene Express Grp,Lab Receptor Biol &, Bethesda, MD 20892 USA. NCI, DBS, NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Prymakowska-Bosak, M (reprint author), NCI, DBS, NIH, Prot Sect,Lab Metab, Bldg 37,Rm 3D-12, Bethesda, MD 20892 USA. RI Shirakawa, Hitoshi/D-1406-2009; Bustin, Michael/G-6155-2015 NR 62 TC 54 Z9 54 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2001 VL 21 IS 15 BP 5169 EP 5178 DI 10.1128/MCB.21.15.5169-5178.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 451YF UT WOS:000169829800030 PM 11438671 ER PT J AU Bennett, CB Snipe, JR Westmoreland, JW Resnick, MA AF Bennett, CB Snipe, JR Westmoreland, JW Resnick, MA TI SIR functions are required for the toleration of an unrepaired double-strand break in a dispensable yeast chromosome SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE CHECKPOINTS; SACCHAROMYCES-CEREVISIAE; MATING-TYPE; DNA-DAMAGE; ILLEGITIMATE RECOMBINATION; MEIOTIC RECOMBINATION; ESSENTIAL GENE; BUDDING YEAST; REPAIR; REPLICATION AB Unrepaired DNA double-strand breaks (DSBs) typically result in G(2) arrest. Cell cycle progression can resume following repair of the DSBs or through adaptation to the checkpoint, even if the damage remains unrepaired. We developed a screen for factors in the yeast Saccharomyces cerevisiae that affect checkpoint control and/or viability in response to a single, unrepairable DSB that is induced by HO endonuclease in a dispensable yeast artificial chromosome containing human DNA. SIR2, -3, or -4 mutants exhibit a prolonged, RAD9-dependent G(2) arrest in response to the unrepairable DSB followed by a slow adaptation to the persistent break, leading to division and rearrest in the next G(2). There are a small number of additional cycles before permanent arrest as microcolonies. Thus, SIR genes, which repress silent mating type gene expression, are required for the adaptation and the prevention of indirect lethality resulting from an unrepairable DSB in nonessential DNA. Rapid adaptation to the G(2) checkpoint and high viability were restored in sir(-) strains containing additional deletions of the silent mating type loci HML and HMR, suggesting that genes under mating type control can reduce the toleration of a single DSB. However, coexpression of MATa1 and MAT alpha2 in Sir(+) haploid cells did not lead to lethality from the HO-induced DSB, suggesting that toleration of an unrepaired DSB requires more than one Sir(+) function. C1 NIEHS, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), NIEHS, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 89 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2001 VL 21 IS 16 BP 5359 EP 5373 DI 10.1128/MCB.21.16.5359-5373.2001 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 456UG UT WOS:000170100200008 PM 11463819 ER PT J AU Bhattacharjee, RN Banks, GC Trotter, KW Lee, HL Archer, TK AF Bhattacharjee, RN Banks, GC Trotter, KW Lee, HL Archer, TK TI Histone H1 phosphorylation by cdk2 selectively modulates mouse mammary tumor virus transcription through chromatin remodeling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID IN-VIVO; MMTV PROMOTER; ACETYLTRANSFERASE ACTIVITY; RETINOBLASTOMA PROTEIN; DEPENDENT KINASES; HORMONE RECEPTOR; GENE-EXPRESSION; LINKER HISTONES; CELL-CYCLE; ACTIVATION AB Transcriptional activation of the mouse mammary tumor virus (MMTV) promoter by ligand-bound glucocorticoid receptor (GR) is transient. Previously, we demonstrated that prolonged hormone exposure results in displacement of the transcription factor nuclear factor 1 (NF1) and the basal transcription complex from the promoter, the dephosphorylation of histone H1, and the establishment of a repressive chromatin structure. We have explored the mechanistic link between histone H1 dephosphorylation and silencing of the MMTV promoter by describing the putative kinase responsible for H1 phosphorylation. Both in vitro kinase assays and in vivo protein expression studies suggest that in hormone-treated cells the ability of cdk2 to phosphorylate histone H1 is decreased and the cdk2 inhibitory p21 protein level is increased. To address the role of cdk2 and histone H1 dephosphorylation in the silencing of the MMTV promoter, we used potent cdk2 inhibitors, Roscovitine and CVT-313, to generate an MMTV promoter which is associated predominantly with the dephosphorylated form of histone H1. Both Roscovitine and CVT-313 block phosphorylation of histone H1 and, under these conditions, the GR is unable to remodel chromatin, recruit transcription factors to the promoter, or stimulate MMTV mRNA accumulation. These results suggest a model where cdk2-directed histone H1 phosphorylation is a necessary condition to permit GR-mediated chromatin remodeling and activation of the MMTV promoter in vivo. C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Western Ontario, Dept Biochem, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Obstet & Gynaecol, London, ON N6A 4L6, Canada. RP Archer, TK (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, MD E4-06, Res Triangle Pk, NC 27709 USA. NR 47 TC 86 Z9 89 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2001 VL 21 IS 16 BP 5417 EP 5425 DI 10.1128/MCB.21.16.5417-5425.2001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 456UG UT WOS:000170100200013 PM 11463824 ER PT J AU Topalian, SL Kaneko, S Gonzales, MI Bond, GL Ward, Y Manley, JL AF Topalian, SL Kaneko, S Gonzales, MI Bond, GL Ward, Y Manley, JL TI Identification and functional characterization of neo-poly(A) polymerase, an RNA processing enzyme overexpressed in human tumors SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MAMMALIAN POLY(A) POLYMERASE; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; SPECIFICITY FACTOR; CARBOXYL-TERMINUS; MULTIPLE FORMS; POLYADENYLATION; CELLS; EXPRESSION; CLEAVAGE AB Poly(A) polymerase (PAP) plays an essential role in polyadenylation of mRNA precursors, and it has long been thought that mammalian cells contain only a single PAP gene. We describe here the unexpected existence of a human PAP, which we call neo-PAP, encoded by a previously uncharacterized gene. cDNA was isolated from a tumor-derived cDNA library encoding an 82.8-kDa protein bearing 71% overall similarity to human PAP. Strikingly, the organization of the two PAP genes is nearly identical, indicating that they arose from a common ancestor. Neo-PAP and PAP were indistinguishable in in vitro assays of both specific and nonspecific polyadenylation and also endonucleolytic cleavage. Neo-PAP produced by transfection was exclusively nuclear, as demonstrated by immunofluorescence microscopy. However, notable sequence divergence between the C-terminal domains of neo-PAP and PAP suggested that the two enzymes might be differentially regulated. While PAP is phosphorylated throughout the cell cycle and hyperphosphorylated during M phase, neo-PAP did not show evidence of phosphorylation on Western blot analysis, which was unexpected in the context of a conserved cyclin recognition motif and multiple potential cyclin-dependent kinase (cdk) phosphorylation sites. Intriguingly, Northern blot analysis demonstrated that each PAP displayed distinct mRNA splice variants, and both PAIR mRNAs were significantly overexpressed in human cancer cells compared to expression in normal or virally transformed cells. Neo-PAP may therefore be an important RNA processing enzyme that is regulated by a mechanism distinct from that utilized by PAP. C1 NCI, Surg Branch, NIH 10 2B47, Bethesda, MD 20892 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RP Topalian, SL (reprint author), NCI, Surg Branch, NIH 10 2B47, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM28983, R01 GM028983] NR 44 TC 90 Z9 91 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD AUG PY 2001 VL 21 IS 16 BP 5614 EP 5623 DI 10.1128/MCB.21.16.5614-5623.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 456UG UT WOS:000170100200031 PM 11463842 ER PT J AU Kim, C Jun, K Lee, T Kim, SS McEnery, MW Chin, H Kim, HL Park, JM Kim, DK Jung, SJ Kim, J Shin, HS AF Kim, C Jun, K Lee, T Kim, SS McEnery, MW Chin, H Kim, HL Park, JM Kim, DK Jung, SJ Kim, J Shin, HS TI Altered nociceptive response in mice deficient in the alpha(1B) subunit of the voltage-dependent calcium channel SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID ROOT GANGLION NEURONS; RAT SENSORY NEURONS; N-TYPE; OMEGA-CONOTOXIN; FORMALIN TEST; SPINAL-CORD; CA2+ CHANNEL; SUBCUTANEOUS FORMALIN; SYNAPTIC TRANSMISSION; NEUROPATHIC PAIN AB Calcium influx through N-type calcium channels mediates synaptic transmission at numerous central synapses and transduces nociceptive information in the spinal dorsal hom. However, the precise role of N-type calcium channels in pain perception is not fully elucidated. To address this issue, we generated and analyzed knockout mice for a,,, the pore-forming subunit of the N-type calcium channel. Homozygous mutants are viable, fertile, and show normal motor coordination. In small-diameter dorsal root ganglion neurons from mutants the density of calcium channel currents is significantly reduced, which can be accounted for by the abolition of N-type currents. We performed several pain-related behavioral tests using the mutant mice. alpha (1B)-Deficient mice show reduced response to mechanical stimuli in the von Frey test and increased tail flick latency in response to radiant heat, indicating altered spinal reflexes. However, pain response in the hot plate test is normal. In the formalin paw test, the mutant mice exhibit significantly attenuated response in Phase 2, but normal pain behaviors in Phase 1. The response to visceral inflammatory pain caused by acetic acid is also reduced in alpha (1B) knockout mice. These results suggest that the alpha (1B) subunit of N-type calcium channel plays a major role in pain perception by acting at the spinal level, but not at the supraspinal level. C1 Pohang Univ Sci & Technol, Natl CRI Ctr Calcium & Learning, Pohang 790784, South Korea. Pohang Univ Sci & Technol, Dept Life Sci, Div Mol & Life Sci, Pohang 790784, South Korea. Pochon CHA Univ, CHA Gen Hosp, Coll Med, Seoul, South Korea. Case Western Reserve Univ, Dept Physiol & Biophys & Neurosci, Cleveland, OH 44106 USA. NIH, Genet Res Branch, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Med, Dept Biochem, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Physiol & Biophys, Seoul, South Korea. Dankook Univ, Coll Med, Dept Physiol, Chunan, South Korea. RP Shin, HS (reprint author), Korea Inst Sci & Technol, POB 131, Seoul 130650, South Korea. NR 59 TC 113 Z9 121 U1 2 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD AUG PY 2001 VL 18 IS 2 BP 235 EP 245 DI 10.1006/mcne.2001.1013 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 470XH UT WOS:000170896600009 PM 11520183 ER PT J AU Wolford, JK Thameem, F Bogardus, C Prochazka, M AF Wolford, JK Thameem, F Bogardus, C Prochazka, M TI Polymorphism screening of the insulin receptor-related receptor gene (INSRR) on 1q in Pima Indians SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE insulin receptor-related receptor gene; 1q21-q23; DNA variants; association analysis; type-2 diabetes; Pima Indians ID DIABETES-SUSCEPTIBILITY GENES; MELLITUS; SEARCH AB INSRR coding for the insulin receptor-related receptor (IRR) is located within the 1q21-q23 region linked with type-2 diabetes mellitus in Pima Indians and Caucasians. Although the ligand and biological function of this receptor are not yet known, its tyrosine kinase phosphorylates proteins involved in insulin signaling, and IRR may also play a role in the control of the insulin producing beta -cell mass. Therefore, defects in INSRR could contribute to susceptibility to type-2 diabetes. By screening the 22 exons, 5' and 3' flanking sequences, and most introns in 20 Pima Indians and one Caucasian control, we detected nine diallelic variants, including eight single nucleotide polymorphisms (SNPs), and a length polymorphism involving a 26-nt motif. In this study sample, four of the identified SNPs were rare, while the remaining five common variants located within 4.5 kb from the 3' end of the gene were in linkage disequilibrium. When analysed in selected diabetic and non-diabetic Pimas, none of the markers was associated with the disease. We conclude that INSRR has no detectable mutations contributing to diabetes in the Pima Indians. However, information on the novel markers may prove useful for association studies of this candidate gene in other populations. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, Phoenix, AZ 85016 USA. RP Prochazka, M (reprint author), NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. NR 16 TC 5 Z9 5 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD AUG PY 2001 VL 15 IS 4 BP 223 EP 227 DI 10.1006/mcpr.2001.0361 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 452EQ UT WOS:000169844800006 PM 11513557 ER PT J AU Henderson, TA Nilles, AF Valjavec-Gratian, M Hill, TM AF Henderson, TA Nilles, AF Valjavec-Gratian, M Hill, TM TI Site-directed mutagenesis and phylogenetic comparisons of the Escherichia coli Tus protein: DNA-protein interactions alone can not account for Tus activity SO MOLECULAR GENETICS AND GENOMICS LA English DT Article DE Escherichia coli; DNA replication; replication arrest; Tus; site-directed mutagenesis ID REPLICATION-TERMINATOR PROTEIN; BACILLUS-SUBTILIS; ARREST PROTEIN; TER COMPLEX; SEQUENCE; HELICASES; FORKS; IMPEDES; INVITRO; REGION AB The Tus protein of Escherichia coli is capable of arresting DNA replication in an orientation-dependent manner when bound to specific sequences in the bacterial chromosome called Ter sites. Arrest of DNA replication has been postulated to occur either by a barrier mechanism, where Tus acts as a physical block to replication fork progression, or through protein-protein interactions between Tus and some component of the replication fork. A previous mutational analysis of Tus suggested that the amino acids in the Ll loop might play a role in replication arrest. Site-directed mutagenesis of amino acids in the Ll loop and other amino acid residues on the "non-permissive" face of Tus was performed to identify residues that affected Tus function. One mutant, E47Q, gave results that are inconsistent with the barrier model, showing a greater affinity for the Ter site (with a t(1/2) of 348 min versus 150 min for wild-type Tus) but a reduced ability to arrest DNA replication in vivo. In addition to the site-directed mutagenesis studies, the tus genes of Salmonella, Klebsiella, and Yersinia were sequenced and the proteins expressed in E. coli to assess their ability to arrest DNA replication. The results presented here support a role for protein-protein interactions in Tus function, and suggest that residues E47 and E49 participate in replication fork arrest. C1 Univ N Dakota, Sch Med & Hlth Sci, Dept Microbiol & Immunol, Grand Forks, ND 58202 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Hill, TM (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Microbiol & Immunol, Grand Forks, ND 58202 USA. NR 30 TC 16 Z9 19 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1617-4615 J9 MOL GENET GENOMICS JI Mol. Genet. Genomics PD AUG PY 2001 VL 265 IS 6 BP 941 EP 953 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 463RQ UT WOS:000170491400001 PM 11523786 ER PT J AU Tayebi, N Callahan, M Madike, V Stubblefield, BK Orvisky, E Krasnewich, D Fillano, JJ Sidransky, E AF Tayebi, N Callahan, M Madike, V Stubblefield, BK Orvisky, E Krasnewich, D Fillano, JJ Sidransky, E TI Gaucher disease and parkinsonism: A phenotypic and genotypic characterization SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Gaucher disease; parkinsonism; metaxin gene; glucocerebrosidase gene; gene duplication; genotype/phenotype correlation; pseudogene; recombination ID SIMPLE MENDELIAN DISORDERS; GLUCOCEREBROSIDASE LOCUS; REPLACEMENT THERAPY; COMPLEX TRAITS; FUSION GENE; MUTATIONS; METAXIN; TYPE-1; DEFICIENCY; PSEUDOGENE AB Among the many phenotypes associated with Gaucher disease, the inherited deficiency of glucocerebrosidase, are reports of patients with parkinsonian symptoms. The basis for this association is unknown, but could be due to alterations in the gene or gene region. The human glucocerebrosidase gene, located on chromosome 1q21, has a nearby pseudogene that shares 96% identity. Immediately adjacent to the glucocerebrosidase pseudogene is a convergently transcribed gene, metaxin, which has a pseudogene that is located just downstream to the glucocerebrosidase gene. We describe a patient with mild Gaucher disease but impaired horizontal saccadic eye movements who developed a tremor at age 42, followed by rapid deterioration of her gait. A pallidotomy at age 47 was unsuccessful. Her motor and cognitive deterioration progressed despite enzyme replacement therapy. Sequencing of the glucocerebrosidase gene identified mutations L444P and D409H. Southern blot analysis using the enzyme SspI showed that the maternal allele had an additional 17-kb band. PCR amplifications and sequencing of this fragment demonstrated a duplication which included the glucocerebrosidase pseudogene, metaxin gene, and a pseudometaxin/metaxin fusion. Gene alterations associated with this novel rearrangement, resulting from a crossover between the gene for metaxin and its pseudogene, could contribute to the atypical phenotype encountered in this patient. (C) 2001 Academic Press. C1 NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. Childrens Hosp Dartmouth, Dept Pediat, Lebanon, NH 03756 USA. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, 49 Convent Dr MSC405,49 B1EE16, Bethesda, MD 20892 USA. NR 45 TC 112 Z9 115 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD AUG PY 2001 VL 73 IS 4 BP 313 EP 321 DI 10.1006/mgme.2001.3201 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 468CK UT WOS:000170740400004 PM 11509013 ER PT J AU Leclerc, D Wu, Q Ellis, JR Goodyer, P Rozen, R AF Leclerc, D Wu, Q Ellis, JR Goodyer, P Rozen, R TI Is the SLC7A10 gene on chromosome 19 a candidate locus for cystinuria? SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE amino acid; transport; inherited disorder; genetics; kidney; stone; mutation ID AMINO-ACID-TRANSPORT; 4F2 HEAVY-CHAIN; III CYSTINURIA; KIDNEY CDNA; INFORMATION; MUTATIONS; CLONING; IDENTIFICATION; SEQUENCES; AFFINITY AB One of the genes (SLC7A9) that causes cystinuria, an inborn error of amino acid transport, is localized to 19q13. Close examination of human genomic DNA sequences has identified a similar gene (SLC7A10) that also maps to the 19q13.1 region and is highly expressed in kidney. The homologies between SLC7A9 and SLC7A10 are likely the result of gene duplication. SLC7A10 is known to encode a protein with a function similar to that of the SLC7A9 gene product. To determine if mutations in the SLC7A10 gene could also cause cystinuria, we characterized the primary genomic structure and sequenced the 11 exons and surrounding sequences from 10 unrelated patients with cystinuria. We identified one missense mutation which may account for cystinuria in one family. We also observed one intronic change, as well as one silent mutation, that were seen only in cystinuria patients. We therefore suggest that the SLC7A10 gene warrants further investigation as another candidate gene for cystinuria. (C) 2001 Academic Press. C1 McGill Univ, Dept Human Genet, Ctr Hlth, Montreal, PQ, Canada. McGill Univ, Dept Pediat, Ctr Hlth, Montreal, PQ, Canada. NIH, ORS, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Montreal Childrens Hosp, Res Inst, 4060 Ste Catherine St W,Room 200, Montreal, PQ H3Z 2Z3, Canada. EM rrozen@po-box.mcgill.ca RI Leclerc, Daniel/B-6375-2012 NR 23 TC 13 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD AUG PY 2001 VL 73 IS 4 BP 333 EP 339 DI 10.1006/mgme.2001.3209 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 468CK UT WOS:000170740400006 PM 11509015 ER PT J AU Anderson, J Shea-Donahue, T Rehring, S Fleming, S Tsokos, G Basta, M AF Anderson, J Shea-Donahue, T Rehring, S Fleming, S Tsokos, G Basta, M TI IVIG protects against mesenteric ischemia-reperfusion injury in rats by site-specific scavenging of C3 SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract C1 Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD USA. NIH, Bethesda, MD 20892 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 2001 VL 38 IS 2-3 MA 3 BP 78 EP 78 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 470MG UT WOS:000170875300005 ER PT J AU Steward, M Cox, V Oldroyd, R Gallagher, S Kareclas, P Ragnauth, C Bright, J Miller, L Holder, A Ogun, S Ross, T Smith, R AF Steward, M Cox, V Oldroyd, R Gallagher, S Kareclas, P Ragnauth, C Bright, J Miller, L Holder, A Ogun, S Ross, T Smith, R TI Towards a human C3d-based vaccine for malaria SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract C1 Adprotech Ltd, Saffron Walden CB10 1XL, Essex, England. NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Parasitol, London NW7 1AA, England. E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. RI Holder, Anthony/A-7554-2013 OI Holder, Anthony/0000-0002-8490-6058 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 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 2001 VL 38 IS 2-3 MA 118 BP 123 EP 123 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 470MG UT WOS:000170875300118 ER PT J AU Bera, TK Lee, S Salvatore, G Lee, B Pastan, I AF Bera, TK Lee, S Salvatore, G Lee, B Pastan, I TI MRP8, a new member of ABC transporter superfamily, identified by EST database mining and gene prediction program, is highly expressed in breast cancer SO MOLECULAR MEDICINE LA English DT Article ID MULTIDRUG-RESISTANCE; PROSTATE; FAMILY; DISCOVERY; PROTEINS; CELLS; LOCUS AB Background: With the completion of the human draft genome sequence, efforts are now devoted to identifying new genes. We have developed a computer-based strategy that utilizes the EST database to identify new genes that could be targets for the immunotherapy of cancer or could be involved in the multistep process of cancer. Materials and Methods: Utilizing our computer-based screening strategy, we identified a cluster of expressed sequence tags (ESTs) that are highly expressed in breast cancer. Northern blot and reverse transcriptase polymerase chain reaction (RT-PCR) analyses demonstrated the tissue specificity of the computer-generated cluster and comparison with the human genome sequence assisted in isolating a full-length cDNA clone. Results: We identified a new gene that is highly expressed in breast cancer. This gene is expressed at moderate levels in normal breast and testis and at very low levels in liver, brain, and placenta. The gene has two major transcripts of 4.5 kb and 4.1 kb. The 4.5-kb transcript is very abundant in breast cancer, and has an open reading frame of 1382 amino acids. The predicted protein sequence of the 4.5-kb transcript reveals that it has high homology with MRP5, a member of multidrug resistant-associated protein family (MRP). There are seven reported members in the MRP family; we designate this gene as MRP8 (ABCC11). The 4.5-kb MRP8 transcript consists of 31 exons and is located in a genomic region of over 80.4 kb on chromosome 16q12.1. The smaller 4.1-kb transcript of MRP8 is found in testis and may initiate within intron 6 of the gene. Conclusion: The selective expression of MRP8 (ABCC11), a new member of ATP-binding cassette transporter superfamily could be a molecular target for the treatment of breast cancer. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Dept Chem, Seoul 120750, South Korea. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 15 TC 134 Z9 142 U1 0 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD AUG PY 2001 VL 7 IS 8 BP 509 EP 516 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 477DJ UT WOS:000171267600001 PM 11591886 ER PT J AU Eidelman, O Srivastava, M Zhang, J Leighton, X Murtie, J Jozwik, C Jacobson, K Weinstein, DL Metcalf, EL Pollard, HB AF Eidelman, O Srivastava, M Zhang, J Leighton, X Murtie, J Jozwik, C Jacobson, K Weinstein, DL Metcalf, EL Pollard, HB TI Control of the proinflammatory state in cystic fibrosis lung epithelial cells by genes from the TNF-alpha R/NF kappa B pathway SO MOLECULAR MEDICINE LA English DT Article ID TRANSMEMBRANE CONDUCTANCE REGULATOR; PROTEIN-KINASE-A; PSEUDOMONAS-AERUGINOSA; EXPRESSION; CFTR; INTERLEUKIN-8; IDENTIFICATION; ACTIVATION; APOPTOSIS; EZRIN AB Background: Cystic fibrosis (CF) is the most common, lethal autosomal recessive disease affecting children in the United States and Europe. Extensive work is being performed to develop both gene and drug therapies. The principal mutation causing CF is in the CFTR gene ([Delta F508]CFTR). This mutation causes the mutant protein to traffic poorly to the plasma membrane, and degrades CFTR chloride channel activity. CPX, a candidate drug for CF, binds to mutant CFTR and corrects the trafficking deficit. CPX also activates mutant CFTR chloride channel activity. CF airways are phenotypically inundated by inflammatory signals, primarily contributed by sustained secretion of the proinflammatory cytokine interleukin 8 (IL-8) from mutant CFTR airway epithelial cells. IL-8 production is controlled by genes from the TNF-alphaR/NF kappaB pathway, and it is possible that the CF phenotype is due to dysfunction of genes from this pathway. In addition, because drug therapy with CPX and gene therapy with CFTR have the same common endpoint of raising the levels of CFTR, we have hypothesized that either approach should have a common genomic endpoint. Materials and Methods: To test this hypothesis, we studied IL-8 secretion and global gene expression in IB-3 CF lung epithelial cells. The cells were treated by either gene therapy with wild-type CFTR, or by pharmacotherapy with the CFTR-surrogate drug CPX. CF cells, treated with either CFTR or CPX, were also exposed to Pseudomonas aeruginosa, a common chronic pathogen in CF patients. cDNA microarrays were used to assess global gene expression under the different conditions. A novel bioinformatic algorithm (GENESAVER) was developed to identify genes whose expression paralleled secretion of IL-8. Results: We report here that IB3 CF cells secrete massive levels of IL-8. However, both gene therapy with CFTR and drug therapy with CPX substantially suppress IL-8 secretion. Nonetheless, both gene and drug therapy allow the CF cells to respond with physiologic secretion of IL-8 when the cells are exposed to P. aeruginosa. Thus, neither CFTR nor CPX acts as a nonspecific suppressor of IL-8 secretion from CF cells. Consistently, pharmacogenomic analysis indicates that CF cells treated with CPX greatly resemble CF cells treated with CFTR by gene therapy. Additionally, the same result obtains in the presence of P. aeruginosa. Classical hierarchical cluster analysis, based on similarity of global gene expression, also supports this conclusion. The GENESAVER algorithm, using the IL-8 secretion level as a physiologic variable, identifies a subset of genes from the TNF-alphaR/NF kappaB pathway that is expressed in phase with IL-8 secretion from CF epithelial cells. Certain other genes, previously known to be positively associated with CF also fall into this category. Identified genes known to code for known inhibitors are expressed inversely, out of phase with IL-8 secretion. Conclusions: Wild-type CFTR and CPX both suppress proinflammatory IL-8 secretion from CF epithelial cells. The mechanism, as defined by pharmacogenomic analysis, involves identified genes from the TNF-alphaR/NF kappaB pathway. The close relationship between IL-8 secretion and genes from the TNF-alphaR/NF kappaB pathway suggests that molecular or pharmaceutical targeting of these novel genes may have strategic use in the development of new therapies for CF. From the perspective of global gene expression, both gene and drug therapy have similar genomic consequences. This is the first example showing equivalence of gene and drug therapy in CF, and suggests that a gene therapy-defined endpoint may prove to be a powerful paradigm for CF drug discovery. Finally, because the GENESAVER algorithm is capable of isolating disease-relevant genes in a hypothesis-driven manner without recourse to any a priori knowledge about the system, this new algorithm may also prove useful in applications to other genetic diseases. C1 Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Physiol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Genet, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Inst Mol Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NIDDK, Mol Recognit Sect, Chem Lab, NIH, Bethesda, MD 20892 USA. RP Pollard, HB (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NIAID NIH HHS [R01-AI48151]; NIDDK NIH HHS [R01-DK53051] NR 37 TC 68 Z9 71 U1 0 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD AUG PY 2001 VL 7 IS 8 BP 523 EP 534 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 477DJ UT WOS:000171267600003 PM 11591888 ER PT J AU Liu, J Chen, H Miller, DS Saavedra, JE Keefer, LK Johnson, DR Klaassen, CD Waalkes, MP AF Liu, J Chen, H Miller, DS Saavedra, JE Keefer, LK Johnson, DR Klaassen, CD Waalkes, MP TI Overexpression of glutathione S-transferase II and multidrug resistance transport proteins is associated with acquired tolerance to inorganic arsenic SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACUTE PROMYELOCYTIC LEUKEMIA; HAMSTER OVARY CELLS; BILIARY-EXCRETION; CARCINOMA-CELLS; GENE-EXPRESSION; TUMOR-CELLS; MRP; CISPLATIN; TRIOXIDE; SYSTEM AB Recent work shows that long-term exposure to low levels of arsenite induces malignant transformation in a rat liver epithelial cell line. Importantly, these chronic arsenic-exposed (CASE) cells also develop self-tolerance to acute arsenic exposure. Tolerance is accompanied by reduced cellular arsenic accumulation, suggesting a mechanistic basis for reduced arsenic sensitivity. The present study examined the role of xenobiotic export pumps in acquired arsenic tolerance. Microarray analysis of CAsE cells showed increased expression of the genes encoding for glutathione S-transferase Pi (GST-Pi), multidrug resistance-associated protein genes (MRP1/MRP2, which encode for the efflux transporter Mrp1/Mrp2) and the multidrug resistance gene (MDR1, which encodes for the efflux transporter P-glycoprotein). These findings were confirmed at the transcription level by reverse transcription-polymerase chain reaction and at the translation level by Western-blot analysis. Acquired arsenic tolerance was abolished when cells were exposed to ethacrynic acid (an inhibitor of GST-Pi), buthionine sulfoximine (a glutathione synthesis inhibitor), MK571 (a specific inhibitor for Mrps), and PSC833 (a specific inhibitor for P-glycoprotein) in dose-dependent fashions. MK571, PSC833, and buthionine sulfoximine markedly increased cellular arsenic accumulation. Consistent with a role for multidrug resistance efflux pumps in arsenic resistance, CASE cells were found to be cross-resistant to cytotoxicity of several anticancer drugs, such as vinblastine, doxorubicin, actinomycin-D, and cisplatin, that are also substrates for Mrps and P-glycoprotein. Thus, acquired tolerance to arsenic is associated with increased expression GST-H, Mrp1/Mrp2 and P-glycoprotein, which function together to reduce cellular arsenic accumulation. C1 NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21701 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Waalkes, MP (reprint author), NIEHS, Comparat Carcinogenesis Lab, NCI, Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000]; NIEHS NIH HHS [ES09716]; PHS HHS [07079] NR 39 TC 164 Z9 173 U1 1 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 2001 VL 60 IS 2 BP 302 EP 309 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 458DW UT WOS:000170178800009 PM 11455017 ER PT J AU Yang, BC Graham, L Dikalov, S Mason, RP Falck, JR Liao, JK Zeldin, DC AF Yang, BC Graham, L Dikalov, S Mason, RP Falck, JR Liao, JK Zeldin, DC TI Overexpression of cytochrome P450CYP2J2 protects against hypoxia-reoxygenation injury in cultured bovine aortic endothelial cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID NITRIC-OXIDE SYNTHASE; POTENTIAL FUNCTIONAL-SIGNIFICANCE; ARACHIDONIC-ACID; 8-EPI-PROSTAGLANDIN F2-ALPHA; DIHYDROXYEICOSATRIENOIC ACIDS; EPOXYEICOSATRIENOIC ACIDS; DEPENDENT RELAXATION; LIPID-PEROXIDATION; CORONARY-ARTERIES; BIOLOGICAL-FLUIDS AB CYP2J2 is abundant in human heart and its arachidonic acid metabolites, the epoxyeicosatrienoic acids (EETs), have potent vasodilatory, antiinflammatory and cardioprotective properties. This study was designed to examine the role of CYP2J2 in hypoxia-reoxygenation-induced injury in cultured bovine aortic endothelial cells (BAECs). Early passage BAECs were exposed to 24-h hypoxia followed by 4-h reoxygenation (HR). HR resulted in cell injury, as indicated by significant increases in lactate dehydrogenase (LDH) release and trypan blue stained cells (p < 0.01) and was associated with a decrease in CYP2J2 protein expression. Transfection of BAECs with the CYP2J2 cDNA resulted in increased CYP2J2 expression and arachidonic acid epoxygenase activity, compared with cells transfected with an irrelevant green fluorescent protein (GFP) cDNA. HR induced significant injury in GFP-transfected BAECs, as indicated by increases in LDH release and trypan blue-stained cells (p < 0.01); however, the HR-induced injury was markedly attenuated in CYP2J2-transfected cells (p < 0.01). HR increased cellular 8-iso-prostaglandin F-2 (P < 0.05), and decreased eNOS expression, L-arginine uptake and conversion, and nitrite production (p < 0.01) in GFP-transfected BAECs. CYP2J2 transfection attenuated the HR-induced increase in 8-iso-prostaglandin F-2 alpha (P < 0.05) and decreased the amount of extracellular superoxide detected by cytochrome c reduction under normoxic conditions (p < 0.05) but did not significantly affect HR-induced decreases in eNOS expression, L-arginine uptake and conversion, and nitrite production. Treatment of BAECs with synthetic EETs and/or epoxide hydrolase inhibitors also showed protective effects against FIR injury (p < 0.05). These observations suggest: (1) HR results in endothelial injury and decreased CYP2J2 expression; (2) transfection with the CYP2J2 cDNA protects against HR injury; and (3) the cytoprotective effects of CYP2J2 may be mediated, at least in part, by antioxidant effects. C1 NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75235 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, 111 TW Alexander Dr,Bldg 101,Room D236, Res Triangle Pk, NC 27709 USA. OI Falck, John/0000-0002-9219-7845 FU NHLBI NIH HHS [HL52233]; NIGMS NIH HHS [GM31278] NR 70 TC 112 Z9 123 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 2001 VL 60 IS 2 BP 310 EP 320 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 458DW UT WOS:000170178800010 PM 11455018 ER PT J AU Puttaraju, M DiPasquale, J Baker, CC Mitchell, LG Garcia-Blanco, MA AF Puttaraju, M DiPasquale, J Baker, CC Mitchell, LG Garcia-Blanco, MA TI Messenger RNA repair and restoration of protein function by spliceosome-mediated RNA trans-splicing SO MOLECULAR THERAPY LA English DT Article DE trans-splicing; RNA repair; genetic disease; gene therapy ID SICKLE-CELL-ANEMIA; FETAL HEMOGLOBIN; MAMMALIAN-CELLS; GENE-THERAPY; RIBOZYMES; EFFICIENCY AB The functional repertoire of the human genome is amplified by the differential assortment of exons. Spliceosome-mediated RNA trans-splicing can mobilize these packets of genetic information to reprogram mRNAs. In principle, this process could repair defective transcripts in loss-of-function genetic disorders in humans. We developed a tractable lacZ repair system to serve as a model for these genetic disorders. Targeted pre-trans-splicing RNA molecules efficiently and specifically repaired mutated lacZ transcripts and restored enzymatic activity in human cells. The development of this model confirms the potential for spliceosome-mediated RNA trans-splicing in genetic repairs and provides a powerful tool for rational design and in vitro evolution of pre-trans-splicing molecules. C1 Intronn LLC, Raleigh, NC 27606 USA. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Garcia-Blanco, MA (reprint author), Intronn LLC, 840 Main Campus Dr, Raleigh, NC 27606 USA. FU BHP HRSA HHS [I R43 DH56526-01] NR 24 TC 50 Z9 52 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD AUG PY 2001 VL 4 IS 2 BP 105 EP 114 DI 10.1006/mthe.2001.0426 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 461NV UT WOS:000170371100005 PM 11482981 ER PT J AU Chen, M Gran, B Costello, K Johnson, K Martin, R Dhib-Jalbut, S AF Chen, M Gran, B Costello, K Johnson, K Martin, R Dhib-Jalbut, S TI Glatiramer acetate induces a Th2-biased response and crossreactivity with myelin basic protein in patients with MS SO MULTIPLE SCLEROSIS LA English DT Article DE multiple sclerosis; glatiramer acetate; Copaxone((R)); Copolymer-1; immune deviation ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; T-CELL LINES; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; REMITTING MULTIPLE-SCLEROSIS; ANTIGEN-PRESENTING CELLS; SYNTHETIC COPOLYMER-1; BYSTANDER SUPPRESSION; IMMUNE-DEVIATION; LARGE NUMBERS; RELAPSE RATE AB Glatiramer acetate (GA) is an approved treatment for multiple sclerosis (MS). The proposed mechanism of action is the induction of GA-specific T cells characterized by protective anti-inflammatory Th2 response. We tested this hypothesis in II MS patients treated with GA from 1 - 19 months. Interferon-gamma and IL-5 (markers of Th1 and Th2 responses respectively) were assayed by ELISA in GA-specific T-cell lines (TCL) supernatants. Th1/Th2 bias was defined based on the ratio of IFN-gamma /IL-5 secretion. Fifty-eight pre-treatment and 75 on-treatment GA-specific TCL were generated. On-treatment mean IL-5 levels in GA-TCL increased significantly, whereas those for IFN-gamma were markedly reduced. Consequently, the ratio of IFN gamma /IL-5 also shifted in favor of a Th2 response. The percentage of GA-TCL classified as Th I was decreased, whereas those classified as TH increased on-treatment as compared to pre-treatment. Some GA-specific TC (approximately 25%) generated during treatment secreted predominantly IL-5 in response to MBP and the immunodominant MBP peptide 83-99, indicating that these crossreactive antigens can act as partial agonists for GA-reactive TCL. These results strongly suggest that the mechanism of action of GA in MS involves the induction of crossreactive GA-specific T cells with a predominant Th2 cytokine profile. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Baltimore VA Med Ctr, Baltimore, MD 21201 USA. RP Dhib-Jalbut, S (reprint author), Univ Maryland Hosp, Dept Neurol, Rm N4W46,22 S Greene St, Baltimore, MD 21201 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 FU NINDS NIH HHS [K-24 NS02082] NR 37 TC 65 Z9 69 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD AUG PY 2001 VL 7 IS 4 BP 209 EP 219 DI 10.1191/135245801680209303 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 465QD UT WOS:000170600700001 PM 11548979 ER PT J AU Molloy, FM Floeter, MK Syed, NA Sandbrink, F Culcea, E Steinberg, SM Dahut, W Pluda, J Kruger, EA Reed, E Figg, WD AF Molloy, FM Floeter, MK Syed, NA Sandbrink, F Culcea, E Steinberg, SM Dahut, W Pluda, J Kruger, EA Reed, E Figg, WD TI Thalidomide neuropathy in patients treated for metastatic prostate cancer SO MUSCLE & NERVE LA English DT Article DE electromyography; nerve conduction studies; neuropathy; thalidomide; toxicity ID TOXIC NEUROPATHY; NERVE-CONDUCTION; CLINICAL-TRIALS; POLYNEUROPATHY; NEUROTOXICITY AB We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection. (C) 2001 John Wiley & Sons, Inc. C1 NINDS, EMG Sect, Bethesda, MD 20892 USA. NCI, Div Clin Sci, Med Branch, Bethesda, MD USA. NCI, Div Clin Sci, Biostat & Data Management Sect, Bethesda, MD USA. NCI, Canc Treatment & Evaluat Program, Bethesda, MD USA. RP Floeter, MK (reprint author), NINDS, EMG Sect, 10 Ctr Dr,MSC 1404, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012; Figg Sr, William/M-2411-2016 OI Ain, Kenneth/0000-0002-2668-934X; NR 29 TC 56 Z9 58 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD AUG PY 2001 VL 24 IS 8 BP 1050 EP 1057 DI 10.1002/mus.1109 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 453ZD UT WOS:000169947300008 PM 11439380 ER PT J AU Storici, F Lewis, LK Resnick, MA AF Storici, F Lewis, LK Resnick, MA TI In vivo site-directed mutagenesis using oligonucleotides SO NATURE BIOTECHNOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SYNTHETIC OLIGONUCLEOTIDES; ARTIFICIAL CHROMOSOMES; DNA-REPAIR; YEAST; RECOMBINATION; GENE; TRANSFORMATION; REPLACEMENT; DISRUPTION AB Functional characterization of the genes of higher eukaryotes has been aided by their expression in model organisms and by analyzing site-specific changes in homologous genes in model systems such as the yeast Saccharomyces cerevisiae(1), Modifying sequences in yeast or other organisms such that no heterologous material is retained requires in vitro mutagenesis together with subcloning(2,3). PCR-based procedures that do not involve cloning are inefficient or require multistep reactions that increase the risk of additional mutations(4,5). An alternative approach, demonstrated in yeast, relies on transformation with an oligonucleotide(6), but the method is restricted to the generation of mutants with a selectable phenotype. Oligonucleoticles, when combined with gap repair, have also been used to modify plasmids in yeast(7); however, this approach is limited by restriction-site availability. We have developed a mutagenesis approach in yeast based on transformation by unpurified oligonucleotides that allows the rapid creation of site-specific DNA mutations in vivo. A two-step, cloning-free process, referred to as delitto perfetto, generates products having only the desired mutation, such as a single or multiple base change, an insertion, a small or a large deletion, or even random mutations. The system provides for multiple rounds of mutation in a window up to 200 base pairs. The process is RAD52 dependent, is not constrained by the distribution of naturally occurring restriction sites, and requires minimal DNA sequencing. Because yeast is commonly used for random and selective cloning of genomic DNA from higher eukaryotes(8) such as yeast artificial chromosomes, the delitto perfetto strategy also provides an efficient way to create precise changes in mammalian or other DNA sequences. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), NIEHS, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 22 TC 202 Z9 209 U1 1 U2 24 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD AUG PY 2001 VL 19 IS 8 BP 773 EP 776 DI 10.1038/90837 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 458HH UT WOS:000170188600031 PM 11479573 ER PT J AU Dai, RM Li, CCH AF Dai, RM Li, CCH TI Valosin-containing protein is a multiubiquitin chain targeting factor required in ubiquitin-proteasome degradation SO NATURE CELL BIOLOGY LA English DT Article ID AAA-ATPASE; CYCLIN-E; PATHWAY; BINDING; SUBUNIT; INVOLVEMENT; ACTIVATION; HOMOLOG AB The ubiquitin-proteasome (Ub-Pr) degradation pathway regulates many cellular activities(1,2), but how ubiquitinated substrates are targeted to the proteasome is not understood. We have shown previously that valosin-containing protein (VCP) physically and functionally targets the ubiquitinated nuclear factor kappaB inhibitor, I kappaB alpha, to the proteasome for degradation(3). VCP is an abundant and a highly conserved member of the AAA (ATPases associated with a variety of cellular activities) family(5-7). Besides acting as a chaperone in membrane fusions, VCP has been shown to have a role in a number of seemingly unrelated cellular activities. Here we report that loss of VCP function results in an inhibition of Ub-Pr-mediated degradation and an accumulation of ubiquitinated proteins. VCP associates with ubiquitinated proteins through the direct binding of its amino-terminal domain to the multi-ubiquitin chains of substrates. Furthermore, its N-terminal domain is required in Ub-Pr-mediated degradation. We conclude that VCP is a multi-ubiquitin chain-targeting factor that is required in the degradation of many Ub-Pr pathway substrates, and provide a common mechanism that underlies many of the functions of VCP. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Li, CCH (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NR 30 TC 313 Z9 314 U1 2 U2 15 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD AUG PY 2001 VL 3 IS 8 BP 740 EP 744 DI 10.1038/35087056 PG 5 WC Cell Biology SC Cell Biology GA 461ZF UT WOS:000170393200019 PM 11483959 ER PT J AU Rouault, TA AF Rouault, TA TI Iron on the brain SO NATURE GENETICS LA English DT Editorial Material AB Accumulations of iron are often detected in the brains of people suffering from neurodegenerative diseases. But it is often not known whether such accumulations contribute directly to disease progression. The identification of the genes mutated in two such disorders suggests that errors in iron metabolism do indeed have a key role. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. NR 9 TC 78 Z9 88 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2001 VL 28 IS 4 BP 299 EP 300 DI 10.1038/91036 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 458CC UT WOS:000170174800002 PM 11479580 ER PT J AU Filippova, GN Thienes, CP Penn, BH Cho, DH Hu, YJ Moore, JM Klesert, T Lobanenkov, VV Tapscott, SJ AF Filippova, GN Thienes, CP Penn, BH Cho, DH Hu, YJ Moore, JM Klesert, T Lobanenkov, VV Tapscott, SJ TI CTCF-binding sites flank CTG/CAG repeats and form a methylation-sensitive insulator at the DM1 locus SO NATURE GENETICS LA English DT Article ID C-MYC GENE; ENHANCER-BLOCKING ACTIVITY; MYOTONIC-DYSTROPHY GENE; CTG REPEAT; MESSENGER-RNA; TRANSCRIPTIONAL ACTIVATION; REDUCES EXPRESSION; TRIPLET REPEATS; DNA-SEQUENCE; PROTEIN CTCF AB An expansion of a CTG repeat at the DM1 locus causes myotonic dystrophy (DM) by altering the expression of the two adjacent genes, DMPK and SIX5, and through a toxic effect of the repeat-containing RNA. Here we identify two CTCF-binding sites that flank the CTG repeat and form an insulator element between DMPK and SIX5. Methylation of these sites prevents binding of CTCF, indicating that the DM1 locus methylation in congenital DM would disrupt insulator function. Furthermore, CTCF-binding sites are associated with CTG/CAG repeats at several other loci. We suggest a general role for CTG/CAG repeats as components of insulator elements at multiple sites in the human genome. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98109 USA. NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98109 USA. RP Lobanenkov, VV (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. FU NCI NIH HHS [R01-CA68360]; NIAMS NIH HHS [R01-AR45203] NR 45 TC 185 Z9 191 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2001 VL 28 IS 4 BP 335 EP 343 DI 10.1038/ng570 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 458CC UT WOS:000170174800013 PM 11479593 ER PT J AU Douglas, JA Boehnke, M Gillanders, E Trent, JA Gruber, SB AF Douglas, JA Boehnke, M Gillanders, E Trent, JA Gruber, SB TI Experimentally-derived haplotypes substantially increase the efficiency of linkage disequilibrium studies SO NATURE GENETICS LA English DT Article ID FREQUENCIES; LOCUS; INDIVIDUALS; PHENOTYPES; MUTATIONS AB The study of complex genetic traits in humans is limited by the expense and difficulty of ascertaining populations of sufficient sample size to detect subtle genetic contributions to disease. Here we introduce an application of a somatic cell hybrid construction strategy called conversion(1-4) that maximizes the genotypic information from each sampled individual. The approach permits direct observation of individual haplotypes, thereby eliminating the need for collecting and genotyping DNA from family members for haplotype-based analyses. We describe experimental data that validate the use of conversion as a whole-genome haplotyping too[ and evaluate the theoretical efficiency of using conversion-derived haplotypes instead of conventional genotypes in the context of haplotype-frequency estimation. We show that, particularly when phenotyping is expensive, conversion-based haplotyping can be more efficient and cost-effective than standard genotyping. C1 Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. NHGRI, Bethesda, MD 20892 USA. RP Boehnke, M (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [R01 CA81488]; NHGRI NIH HHS [R01-HG00376] NR 17 TC 119 Z9 125 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2001 VL 28 IS 4 BP 361 EP 364 DI 10.1038/ng582 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 458CC UT WOS:000170174800017 PM 11443299 ER PT J AU Anikster, Y Huizing, M White, J Shevchenko, YO Fitzpatrick, DL Touchman, JW Compton, JG Bale, SJ Swank, RT Gahl, WA Toro, JR AF Anikster, Y Huizing, M White, J Shevchenko, YO Fitzpatrick, DL Touchman, JW Compton, JG Bale, SJ Swank, RT Gahl, WA Toro, JR TI Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico SO NATURE GENETICS LA English DT Article ID LOCUS HETEROGENEITY; VESICLE FORMATION; AP-3 ADAPTER; PROTEINS; DUPLICATION; ALBINISM; SUBUNIT; COMPLEX; MODELS; MOUSE AB Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies(1-3). Lysosomal ceroid lipofuscinosis, pulmonary fibrosis and granulomatous colitis are occasional manifestations of the disease(4). HPS occurs witha frequency of one in 1800 in northwest Puerto Rico(5) due to a founder effect(6). Several non-Puerto Rican patients also have mutations in HPS1(7,8), which produces a protein of unknown function(9). Another gene, ADTB3A, causes HPS in the pearl mouse(10) and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a coat protein involved in vesicle formation(3,13), implicating HPS as a disorder of membrane trafficking. We sought to identify other HPS-causing genes(7,8,14). Using homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24. The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells. The homozygous, disease-causing mutation is a large deletion and represents the secon example of a founder mutation causing HPS on the small island of Puerto Rico. We also present an allele-specific assay for diagnosing individuals heterozygous or homozygous for this mutation. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. Natl Inst Hlth Intramural Sequencing Ctr, NIH, Gaithersburg, MD USA. NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA. RP Gahl, WA (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA16506]; NHLBI NIH HHS [HL31698] NR 30 TC 115 Z9 116 U1 0 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD AUG PY 2001 VL 28 IS 4 BP 376 EP 380 DI 10.1038/ng576 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 458CC UT WOS:000170174800020 PM 11455388 ER PT J AU Andre, P Biassoni, R Colonna, M Cosman, D Lanier, LL Long, EO Lopez-Botet, M Moretta, A Moretta, L Parham, P Trowsdale, J Vivier, E Wagtmann, N Wilson, MJ AF Andre, P Biassoni, R Colonna, M Cosman, D Lanier, LL Long, EO Lopez-Botet, M Moretta, A Moretta, L Parham, P Trowsdale, J Vivier, E Wagtmann, N Wilson, MJ TI New nomenclature for MHC receptors SO NATURE IMMUNOLOGY LA English DT Letter ID HUMAN NATURAL-KILLER; CLASS-I MOLECULES; CELLS C1 Innate Pharma, Marseille, France. Ist Nazl Ric Canc, I-16132 Genoa, Italy. Basel Inst Immunol, Basel, Switzerland. Immunex Corp, Seattle, WA USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Canc Res, San Francisco, CA 94143 USA. NIAID, Immunogenet Lab, NIH, Rockville, MA USA. Univ Pompeu Fabra, CEXS Immunol, Barcelona, Spain. Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy. Ist Giannina Gaslini, I-16148 Genoa, Italy. Stanford Univ, Sch Med, Dept Cell Biol, Stanford, CA 94305 USA. Univ Cambridge, Dept Pathol, Div Immunol, Cambridge, England. Univ Mediterranee, CNRS, INSERM, Ctr Immunol Marseille Luminy, Marseille, France. Novo Nordisk AS, Dept Mol Genet, DK-2880 Bagsvaerd, Denmark. GlaxoSmithKline, Stevenage, Herts, England. RP Andre, P (reprint author), Innate Pharma, Marseille, France. RI Long, Eric/G-5475-2011; Lopez-Botet, Miguel/I-5434-2014 OI Long, Eric/0000-0002-7793-3728; Lopez-Botet, Miguel/0000-0003-4882-065X NR 8 TC 71 Z9 73 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2001 VL 2 IS 8 BP 661 EP 661 DI 10.1038/90589 PG 1 WC Immunology SC Immunology GA 459BN UT WOS:000170230100002 PM 11477395 ER PT J AU Tripp, RA Jones, LP Haynes, LM Zheng, HQ Murphy, PM Anderson, LJ AF Tripp, RA Jones, LP Haynes, LM Zheng, HQ Murphy, PM Anderson, LJ TI CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein SO NATURE IMMUNOLOGY LA English DT Article ID MESSENGER-RNA EXPRESSION; BALB/C MICE; F-PROTEIN; CHEMOTACTIC RECEPTOR; VIRAL REPLICATION; TRACT DISEASE; RSV CHALLENGE; SUBGROUP-B; IN-VITRO; INFECTION AB Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C. Chemokines have roles in immunity and inflammation that affect cell trafficking and activation of T cells as well as cells of the innate immune system. We report here CX3C chemokine mimicry for the G glycoprotein of respiratory syncytial virus (RSV) and show binding to CX3CRI-the specific receptor for the CX3C chemokine fractalkine-and induction of leukocyte chemotaxis. We also show that CX3CRI facilitates RSV infection of cells. Thus, G glycoprotein interaction with CX3CRI probably plays a key role in the biology of RSV infection. C1 Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Resp & Enter Virus Branch, Atlanta, GA USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Tripp, RA (reprint author), Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Resp & Enter Virus Branch, Mailstop G-09,1600 Clifton Rd, Atlanta, GA USA. OI Tripp, Ralph/0000-0002-2924-9956 NR 46 TC 223 Z9 235 U1 1 U2 10 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD AUG PY 2001 VL 2 IS 8 BP 732 EP 738 DI 10.1038/90675 PG 7 WC Immunology SC Immunology GA 459BN UT WOS:000170230100016 PM 11477410 ER PT J AU Yung, E Sorin, M Pal, A Craig, E Morozov, A Delattre, O Kappes, J Oti, D Kalpana, GV AF Yung, E Sorin, M Pal, A Craig, E Morozov, A Delattre, O Kappes, J Oti, D Kalpana, GV TI Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1 SO NATURE MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FINGER-LIKE DOMAIN; TYPE-1 INTEGRASE; VIRAL REPLICATION; MUTATIONS; DNA; COMPLEX; BINDING; PROTEIN; CELLS AB Integase Interactor 1(INI), also known as hSNF5, is a protein that interacts with HIV-1 integrase. We report here that a cytoplasmically localized fragment of INI (S6; aa183-294) containing the minimal integrase-interaction domain potently inhibits HIV-1 particle production and replication. Mutations in 56 or integrase that disrupt integrase-INI1 interaction abrogated the inhibitory effect. An integrase-deficient HIV-1 transcomplemented with integrase fused to Vpr was not affected by S6. INI1 was specifically incorporated into virions and was required for efficient HIV-1 particle production. These results indicate that INI1 is required for late events in the viral life cycle, and that ectopic expression of S6 inhibits HIV-1 replication in a transdominant manner via its specific interaction with integrase within the context of Gag-Pol, providing a novel strategy to control HIV-1 replication. C1 Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. Inst Curie, Lab Pathol Mol Canc, Paris, France. RP Kalpana, GV (reprint author), Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. EM kalpana@aecom.yu.edu OI Yung, Eric/0000-0002-7328-7204 FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [AI/GM 399951, T32-AI07501] NR 33 TC 100 Z9 105 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD AUG PY 2001 VL 7 IS 8 BP 920 EP 926 DI 10.1038/90959 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 485EK UT WOS:000171740400029 PM 11479624 ER PT J AU Yamauchi, T Kamon, J Waki, H Terauchi, Y Kubota, N Hara, K Mori, Y Ide, T Murakami, K Tsuboyama-Kasaoka, N Ezaki, O Akanuma, Y Gavrilova, O Vinson, C Reitman, ML Kagechika, H Shudo, K Yoda, M Nakano, Y Tobe, K Nagai, R Kimura, S Tomita, M Froguel, P Kadowaki, T AF Yamauchi, T Kamon, J Waki, H Terauchi, Y Kubota, N Hara, K Mori, Y Ide, T Murakami, K Tsuboyama-Kasaoka, N Ezaki, O Akanuma, Y Gavrilova, O Vinson, C Reitman, ML Kagechika, H Shudo, K Yoda, M Nakano, Y Tobe, K Nagai, R Kimura, S Tomita, M Froguel, P Kadowaki, T TI The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity SO NATURE MEDICINE LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; PPAR-GAMMA; DIABETES-MELLITUS; ADIPOSE-TISSUE; PROTEIN; MICE; EXPRESSION; GENE; SENSITIVITY; METABOLISM AB Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes. C1 Univ Tokyo, Grad Sch Med, Dept Internal Med, Tokyo, Japan. Pasteur Inst Lille, CNRS, Inst Biol, Lille, France. Natl Inst Hlth & Nutr, Div Clin Nutr, Tokyo 162, Japan. Asahi Life Fdn, Inst Diabet Care & Res, Tokyo, Japan. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Tokyo, Japan. RP Kadowaki, T (reprint author), Univ Tokyo, Grad Sch Med, Dept Internal Med, Tokyo, Japan. RI sheng, jian/E-9474-2012; Reitman, Marc/B-4448-2013; Kubota, Naoto/N-7892-2015 OI Reitman, Marc/0000-0002-0426-9475; NR 37 TC 2884 Z9 3101 U1 33 U2 270 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2001 VL 7 IS 8 BP 941 EP 946 DI 10.1038/90984 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 485EK UT WOS:000171740400032 PM 11479627 ER PT J AU Takebayashi, Y Pourquier, P Zimonjic, DB Nakayama, K Emmert, S Ueda, T Urasaki, Y Kanzaki, A Akiyama, S Popescu, N Kraemer, KH Pommier, Y AF Takebayashi, Y Pourquier, P Zimonjic, DB Nakayama, K Emmert, S Ueda, T Urasaki, Y Kanzaki, A Akiyama, S Popescu, N Kraemer, KH Pommier, Y TI Antiproliferative activity of ecteinascidin 743 is dependent upon transcription-coupled nucleotide-excision repair SO NATURE MEDICINE LA English DT Article ID DNA TOPOISOMERASE-I; MINOR-GROOVE; CARIBBEAN TUNICATE; MECHANISM; ACTIVATION; DAMAGE; CANCER; DRUG AB While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a region that included the gene implicated in the hereditary disease xeroderma pigmentosum (XPG, also known as Ercc5). Complementation with wild-type XPG restored the drug sensitivity. Xeroderma pigmentosum cells deficient in the NER genes XPG, XPA, XPD or XPF were resistant to Et743, and sensitivity was restored by complementation with wildtype genes. Moreover, studies of cells deficient in XPC or in the genes implicated in Cockayne syndrome (CSA and CSS) indicated that the drug sensitivity is specifically dependent on the transcription-coupled pathway of NER. We found that Et743 interacts with the transcription-coupled NER machinery to induce lethal DNA strand breaks. C1 NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Tohoku Univ, Inst Dev Aging & Canc, Dept Pathol, Sendai, Miyagi 980, Japan. Kagoshima Univ, Fac Med, Canc Res Inst, Dept Canc Chemotherapy, Kagoshima 890, Japan. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 36 TC 248 Z9 258 U1 0 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD AUG PY 2001 VL 7 IS 8 BP 961 EP 966 DI 10.1038/91008 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 485EK UT WOS:000171740400035 PM 11479630 ER PT J AU Roche, KW Standley, S McCallum, J Ly, CD Ehlers, MD Wenthold, RJ AF Roche, KW Standley, S McCallum, J Ly, CD Ehlers, MD Wenthold, RJ TI Molecular determinants of NMDA receptor internalization SO NATURE NEUROSCIENCE LA English DT Article ID DENSITY PROTEIN PSD-95; GLUTAMATE RECEPTORS; AMPA RECEPTORS; SYNAPTIC TRANSMISSION; HIPPOCAMPAL SYNAPSES; SORTING SIGNALS; SILENT SYNAPSES; K+ CHANNELS; RAT-BRAIN; SUBUNIT AB Although synaptic AMPA receptors have been shown to rapidly internalize, synaptic NMDA receptors are reported to be static. It is not certain whether NMDA receptor stability at synaptic sites is an inherent property of the receptor, or is due to stabilization by scaffolding proteins. In this study, we demonstrate that NMDA receptors are internalized in both heterologous cells and neurons, and we define an internalization motif, YEKL, on the distal C-terminus of NR2B. In addition, we show that the synaptic protein PSD-95 inhibits NR2B-mediated internalization, and that deletion of the PDZ-binding domain of NR2B increases internalization in neurons. This suggests an involvement for PSD-95 in NMDA receptor regulation and an explanation for NMDA receptor stability at synaptic sites. C1 Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. RP Roche, KW (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bldg 36,Room 5B25, Bethesda, MD 20892 USA. OI Roche, Katherine/0000-0001-7282-6539 FU NINDS NIH HHS [R01-NS39402] NR 50 TC 339 Z9 355 U1 0 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD AUG PY 2001 VL 4 IS 8 BP 794 EP 802 DI 10.1038/90498 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 457KY UT WOS:000170137300012 PM 11477425 ER PT J AU Green, ED AF Green, ED TI Strategies for the systematic sequencing of complex genomes SO NATURE REVIEWS GENETICS LA English DT Review ID YEAST ARTIFICIAL CHROMOSOMES; YAC CONTIG MAP; DNA-SEQUENCE; PHYSICAL MAP; DROSOPHILA-MELANOGASTER; ARABIDOPSIS-THALIANA; NUCLEOTIDE-SEQUENCE; DRAFT SEQUENCE; LARGE-SCALE; SHOTGUN AB Recent spectacular advances in the technologies and strategies for DNA sequencing have profoundly accelerated the detailed analysis of genomes from myriad organisms. The past few years alone have seen the publication of near-complete or draft versions of the genome sequence of several well-studied, multicellular organisms - most notably, the human. As well as providing data of fundamental biological significance, these landmark accomplishments have yielded important strategic insights that are guiding current and future genome-sequencing projects. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD 20892 USA. RP NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM egreen@nhgri.nih.gov NR 102 TC 82 Z9 89 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 EI 1471-0064 J9 NAT REV GENET JI Nat. Rev. Genet. PD AUG PY 2001 VL 2 IS 8 BP 573 EP 583 DI 10.1038/35084503 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 460WT UT WOS:000170332000010 PM 11483982 ER PT J AU Trankle, C Kostenis, E Mohr, K AF Trankle, C Kostenis, E Mohr, K TI Muscarinic allosteric modulation: M-2/M-3 subtype selectivity of gallamine is independent of G-protein coupling specificity SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE muscarinic M-2 receptor; muscarinic M-3 receptor; gallamine; allosteric modulation; G protein coupling ID SITE-DIRECTED MUTAGENESIS; M-2 RECEPTOR-BINDING; ACETYLCHOLINE-RECEPTORS; ANTAGONIST BINDING; MAMMALIAN-CELLS; IDENTIFICATION; LIGANDS; RADIOLIGAND; ALCURONIUM; MODES AB Among the five subtypes of muscarinic acetylcholine receptors, the sensitivity towards allosteric modulation is generally higher in M-2 and M-4 receptors that preferentially couple to inhibitory G-proteins of the G(i/o) type than in M-1, M-3, and M-5 that preferentially couple to stimulatory G-proteins such as G(q/11). We aimed to check whether the high allosteric sensitivity of the M-2 receptor compared to M-3 is related to the differential G-protein coupling preference. As the third intracellular loop (i3) is known to be the major determinant in receptor G-protein coupling specificity, we used wild-type M-2 and M-3 receptors and the related chimeric constructs with exchanged i3-loops, i.e., M-2 containing M-3-i3 (M-2/M-3-i3) and M-3 containing M-2-i3 (M-3/M-2-i3). The allosteric effect of the archetypal modulator gallamine on the dissociation and the equilibrium binding of [H-3]N-methylscopolamine ([H-3]NMS) was measured in membranes of mouse A9L cells stably expressing the wild-type and the chimeric receptors (4 mM Na2HPO4, 1 mM KH2PO4, pH 7.4, 23 degreesC). The dissociation of [3H]NMS was monophasic under all conditions studied. Control values of t(1/2), were (means SEM, n=4-7): M-2: 3.8 +/-0.2 min, M-2/M-3-i3: 4.8 +/-0.3 min. M-3: 43.3 +/-4.2 min. M-3/M-2-i3: 41.1 +/-3.6 min. At M-2 receptors, 0.2 muM gallamine allosterically reduced the apparent rate constant of dissociation k(-1) to 51 +/-5% of the control value (n=5). At M2/M-3-i3 the allosteric potency of gallamine was not significantly changed (0.2 muM gallamine --> k-1=61 +/-4%, n=7). At M-3, a 20-fold higher concentration was required for an equieffective allosteric action (10 muM gallamine ---> k-1=51 5%, n=5). The potency of gallamine at M-3/M-2-i3 was not increased compared with M3 receptors (10 muM gallamine -> k(-1)=73 +/-2%, n=4) but even significantly diminished. [H-3]NMS equilibrium binding experiments revealed that neither the binding constants of gallamine at free receptor subtypes (pK(A,M2): 7.57 +/-0.04, n=4; pK(A,M3): 5.56 +/-0.13, n=3) nor the factors of negative cooperativity with [H-3]NMS (alpha (M2)=31 +/-1, alpha (M3)=3 +/-0.4) were affected by the exchanged i3-loops (PKA,M2/M3-i3: 7.65 +/-0.03, PKA.M3/(M2-i2): 5.35 +/-0.24, alpha (M2/M3-i3)= 30 +/-2, alpha (M3/M2-i2)=3 +/-0.7). In conclusion, the different sensitivities Of M2 and M3 receptors towards allosteric modulation by gallamine are not related to the G-protein coupling specificity of the receptors. C1 Univ Bonn, Inst Pharm, Dept Pharmacol & Toxicol, D-53121 Bonn, Germany. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Trankle, C (reprint author), Univ Bonn, Inst Pharm, Dept Pharmacol & Toxicol, Immenburg 4, D-53121 Bonn, Germany. NR 43 TC 10 Z9 12 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD AUG PY 2001 VL 364 IS 2 BP 172 EP 178 DI 10.1007/s002100100441 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 461ZK UT WOS:000170393600011 PM 11534857 ER PT J AU Hertle, RW Dell'Osso, LF FitzGibbon, EJ Caruso, RC Butman, JA Yang, DS Mellow, SD AF Hertle, RW Dell'Osso, LF FitzGibbon, EJ Caruso, RC Butman, JA Yang, DS Mellow, SD TI Clinical, radiographic, and electrophysiologic findings in patients with achiasma or hypochiasma SO NEURO-OPHTHALMOLOGY LA English DT Article DE achiasma; hypochiasma; see-saw nystagmus ID SEE-SAW NYSTAGMUS; EVOKED POTENTIAL EVIDENCE; CONGENITAL NYSTAGMUS; BELGIAN SHEEPDOGS; LATENT; DOGS AB Objective: To report the clinical, electrophysiologic, and radiographic analysis of four patients presenting with nystagmus and diagnosed with achiasma or hypochiasma and summarize all 11 patients reported with this syndrome. Methods: Each patient underwent complete ophthalmologic examination, fundus photography, ocular motor recordings (OMR), visual evoked potentials (VEP), visual field testing (VFT), and magnetic resonance imaging (MRI) of the optic pathways. Results: Reduced vision, strabismus, optic nerve dysplasia, congenital nystagmus (CN), and see-saw nystagmus were present in all patients. One of these four patients had congenital hydrocephalus and three of the four patients had amblyopia. Monocular VFT was full in the older patients tested. OMR showed dysconjugate vertical, multiplanar ocular oscillations with CN slow phases, well-developed foveation periods, and occasional spontaneous uniocular saccades. VEPs showed crossed asymmetry and increased latency consistent with uncrossed optic pathways and optic nerve dysplasia. Specific MRI studies showed no chiasm in three patients and a hypoplastic chiasm in one. Conclusions: These patients further elucidate the spectrum of human achiasma/hypochiasma. Careful intraocular and ocular motor evaluation found optic nerve anomalies and seesaw nystagmus in all patients. Patients with congenital optic nerve hypoplasia/dysplasia with or without other midline neurologic defects should be carefully evaluated for the clinical presence of see-saw nystagmus (SSN). The occurrence of the conditions CN, SSN, and optic nerve anomaly strongly suggests achiasma/hypochiasma. Electrophysiologic and radiographic evaluations should be considered in these patients. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Clin Serv Branch, Bethesda, MD 20892 USA. NIH, Diagnost Radiol Dept, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Neurol, Cleveland, OH 44106 USA. Vet Affairs Med Ctr, Cleveland, OH USA. RP Hertle, RW (reprint author), Columbus Childrens Hosp, 555 S 18th St,Suite 4C, Columbus, OH 43205 USA. RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 40 TC 3 Z9 3 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0165-8107 J9 NEURO-OPHTHALMOLOGY JI Neuro-Ophthalmol. PD AUG PY 2001 VL 26 IS 1 BP 43 EP 57 DI 10.1076/noph.26.1.43.8055 PG 15 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 599WK UT WOS:000178358000006 ER PT J AU Borlongan, CV Zhou, FC Hayashi, T Su, TP Hoffer, BJ Wang, Y AF Borlongan, CV Zhou, FC Hayashi, T Su, TP Hoffer, BJ Wang, Y TI Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Parkinson's disease; neural transplantation; dopamine; glial cell line-derived neurotrophic factor; substantia nigra; striatum; motor asymmetry ID MIDBRAIN DOPAMINERGIC-NEURONS; VENTRAL MESENCEPHALIC GRAFTS; NEUROTROPHIC FACTOR GDNF; FUNCTIONAL RECOVERY; ROTATIONAL BEHAVIOR; SUBSTANTIA-NIGRA; 6-HYDROXYDOPAMINE-INDUCED HEMIPARKINSONISM; STRIATAL DOPAMINE; FIBER OUTGROWTH; NERVOUS-SYSTEM AB Exogenous application of transforming growth factors-beta (TGF beta) family proteins, including glial cell line-derived neurotrophic factor (GDNF), neurturin, activin, and bone morphogenetic proteins, has been shown to protect neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effects for treatment of neurodegenerative diseases. Because fetal kidneys express many TGF beta trophic factors, we transplanted these tissues directly into the substantial nigra after a unilateral 6-hydroxydopamine lesion. We found that animals that received fetal kidney tissue grafts exhibited (1) significantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near normal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatum, (3) a preservation of K+-induced dopamine release in the lesioned striatum, and (4) high levels of GDNF protein within the grafts. In contrast, lesioned animals that received grafts of adult kidney tissues displayed significant behavioral deficits, dopaminergic depletion, reduced K+-mediated striatal dopamine release, and low levels of GDNF protein within the grafts. The present study suggests that fetal kidney tissue grafts can protect the nigrostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotrophic factors. (C) 2001 Academic Press. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Indiana Univ, Sch Med, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA. RP Borlongan, CV (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008; OI Borlongan, Cesar/0000-0002-2966-9782 NR 63 TC 23 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD AUG PY 2001 VL 8 IS 4 BP 636 EP 646 DI 10.1006/nbdi.2001.0410 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 463EF UT WOS:000170463300009 PM 11493028 ER PT J AU Beauchamp, MS Petit, L Ellmore, TM Ingeholm, J Haxby, JV AF Beauchamp, MS Petit, L Ellmore, TM Ingeholm, J Haxby, JV TI A parametric fMRI study of overt and covert shifts of visuospatial attention SO NEUROIMAGE LA English DT Article ID SACCADIC EYE-MOVEMENTS; HUMAN VISUAL-CORTEX; POSITRON EMISSION TOMOGRAPHY; SURFACE-BASED ANALYSIS; FUNCTIONAL-ANATOMY; MEDIAL WALL; HUMAN BRAIN; ACTIVATION; PURSUIT; SYSTEM AB It has recently been demonstrated that a cortical network of visuospatial and oculomotor control areas is active for covert shifts of spatial attention (shifts of attention without eye movements) as well as for overt shifts of spatial attention (shifts of attention with saccadic eye movements). Studies examining activity in this visuospatial network during attentional shifts at a single rate have given conflicting reports about how the activity differs for overt and covert shifts. To better understand how the network subserves attentional shifts, we performed a parametric study in which subjects made either overt attentional shifts or covert attentional shifts at three different rates (0.2, 1.0, and 2.0 Hz). At every shift rate, both overt and covert shifts of visuospatial attention induced activations in the precentral sulcus, intraparietal sulcus, and lateral occipital cortex that were of greater amplitude for overt than during covert shifting. As the rate of attentional shifts increased, responses in the visuospatial network increased in both overt and covert conditions but this parametric increase was greater during overt shifts. These results confirm that overt and covert attentional shifts are subserved by the same network of areas. Overt shifts of attention elicit more neural activity than do covert shifts, reflecting additional activity associated with saccade execution. An additional finding concerns the anatomical organization of the visuospatial network. Two distinct activation foci were observed within the precentral sulcus for both overt and covert attentional shifts, corresponding to specific anatomical landmarks. We therefore reappraise the correspondence of these two precentral areas with the frontal eye fields. (C) 2001 Academic Press. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Caen, Univ Paris 05, CNRS,CEA,UMR 6095, Grp Imagerie Neurofonct, F-14032 Caen, France. RP Beauchamp, MS (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RI GINSPAN, All/B-8714-2008; Petit, Laurent/D-6583-2011; OI Petit, Laurent/0000-0003-2499-5367; Beauchamp, Michael/0000-0002-7599-9934; Ellmore, Timothy/0000-0001-6125-0044 NR 50 TC 192 Z9 195 U1 1 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG PY 2001 VL 14 IS 2 BP 310 EP 321 DI 10.1006/nimg.2001.0788 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 459MG UT WOS:000170253700006 PM 11467905 ER PT J AU Goebel, HH Halbig, LE Goldfarb, L Schober, R Albani, M Neuen-Jacob, E Voit, T AF Goebel, HH Halbig, LE Goldfarb, L Schober, R Albani, M Neuen-Jacob, E Voit, T TI Reducing body myopathy with cytoplasmic bodies and rigid spine syndrome: A mixed congenital myopathy SO NEUROPEDIATRICS LA English DT Article DE congenital myopathy; reducing body myopathy; cytoplasmic bodies; desmin; rigid spine; mixed myopathy ID RYANODINE RECEPTOR; SKELETAL-MUSCLE; DISTAL MYOPATHY; DESMIN STORAGE; GENE; MUTATION; CORES; RODS; FORM AB At the age of five years a male child started to develop a progressive rigid spine, torsion scoliosis. and flexion contractures of his elbows, knees, hips, and ankles owing to severe proximal and distal muscle weakness. He had three muscle biopsies from three different muscles at ages 7, 11, and 14 years, respectively. Myopathologically, these muscle tissues contained numerous inclusions which, at the ultrastructural level, turned out to be reducing bodies and cytoplasmic bodies, often in close spatial proximity. Similar histological inclusions, although not further identified by histochemistry and electron microscopy, were seen in his maternal grandmother's biopsied muscle tissue who had developed weakness of the legs and hands after the age of 50 years. The patient's parents were healthy, but the mother's quadriceps muscle showed an increased spectrum of muscle fibre diameters. Our patient, thus. had a neuromuscular disorder, perhaps familial, presenting as a mixed congenital myopathy, i.e., reducing body myopathy with cytoplasmic bodies, of which the morphological lesions could be consistently documented over several years in his different limb muscles. While other mixed congenital myopathies had shown cores and rods, both related to sarcomeres and thus possibly morphogenetically related, cytoplasmic bodies thought to be related to Z-bands and reducing bodies dissimilar to any muscle fibre constituent do not share any common denominator. Therefore, we suggest that this neuromuscular disorder may be a unique mixed congenital myopathy, either sporadic or genetic. In the latter case, the transmission pattern suggested X-linked recessive inheritance, but an autosomal-dominant transmission with variable penetrance could not be ruled out. C1 Univ Mainz, Med Ctr, Dept Neuropathol, D-55131 Mainz, Germany. NIH, Bethesda, MD 20892 USA. Univ Leipzig, Dept Neuropathol, D-7010 Leipzig, Germany. Univ Hamburg, Hamburg, Germany. Univ Dusseldorf, Dept Neuropathol, D-4000 Dusseldorf, Germany. Univ Essen Gesamthsch, Dept Pediat, Essen, Germany. RP Goebel, HH (reprint author), Univ Mainz, Med Ctr, Dept Neuropathol, Langenbeckstr 1, D-55131 Mainz, Germany. NR 39 TC 20 Z9 20 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0174-304X J9 NEUROPEDIATRICS JI Neuropediatrics PD AUG PY 2001 VL 32 IS 4 BP 196 EP 205 DI 10.1055/s-2001-17374 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 477WY UT WOS:000171308300005 PM 11571700 ER PT J AU Crespo, JA Manzanares, J Oliva, JM Corchero, J Palomo, T Ambrosio, E AF Crespo, JA Manzanares, J Oliva, JM Corchero, J Palomo, T Ambrosio, E TI Extinction of cocaine self-administration produces a differential time-related regulation of proenkephalin gene expression in rat brain SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE extinction; cocaine self-administration; proenkephalin mRNA; gene expression; withdrawal ID PREPROENKEPHALIN MESSENGER-RNA; AMYGDALA DOPAMINE LEVELS; NUCLEUS-ACCUMBENS; OPIOID RECEPTORS; BASAL FOREBRAIN; RHESUS-MONKEYS; BINGE COCAINE; REWARD; PREPRODYNORPHIN; AMPHETAMINE AB The purpose of this study was to examine the time course effects of extinction of cocaine self-administration behavior on proenkephalin (PENK) gene expression in caudate-putamen nucleus (ST), nucleus accumbens (Acc), olfactory tubercle (Tu), piriform cortex (Pir), ventromedial hypothalamic nucleus (VMN), and central amygdala (Ce) as measured by in situ hybridization histochemistry. Seventy-two littermate male Lewis rats were randomly assigned in triads to one of three conditions: (1) contingent intravenous self-administration of 1 mg/kg/injection of cocaine (CONT), (2) noncontingent injections of either I mg/kg/injection of cocaine (NONCONT); or (3) saline yoked (SALINE) to the intake of the self-administering subject. The self-administering rats were trained to self-administer cocaine under a FR5 schedule of reinforcement for a minimum of 3 weeks. After stable baseline levels of drug intake had been reached, saline was substituted for drug. Following this first extinction period, cocaine self administration was reinstated for an additional period of 2 weeks. Immediately after cessation of the last session of cocaine self-administration (day 0) and 1-, 5-, and 10-day after the second extinction period, animal brains in each triad were removed to be processed for in situ hybridization, PENK mRNA levels were significantly higher in the cocaine groups when compared with SALINE group in the ST, Acc, Pir, and Tu regions on days 0, 1, 5, and 10 of the extinction and lower in the Ce region of CONT group when compared to NONCONT and SALINE groups on days 1, 5, and 10 of the extinction period. In the VMN nucleus, PENK mRNA content in CONT group versus NONCONT and SALINE groups was also lower, but there were statistically significant differences only on day 5. These results suggest that changes in PENK gene expression after contingent cocaine administration might be involved in cocaine withdrawal states. [Neuropsychopharmacology 25:185-194,2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Hosp Doce de Octubre, Serv Psiquiatria, Madrid 28041, Spain. Univ Nacl Educ Distancia, Fac Psicol, Dept Psicobiol, E-28040 Madrid, Spain. NCI, Div Basic Sci, Bethesda, MD 20892 USA. RP Manzanares, J (reprint author), Hosp Doce de Octubre, Serv Psiquiatria, Av Cordoba S-N, Madrid 28041, Spain. NR 64 TC 38 Z9 41 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 2001 VL 25 IS 2 BP 185 EP 194 DI 10.1016/S0893-133X(01)00221-4 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 466PK UT WOS:000170653800004 PM 11425502 ER PT J AU Park, KW Eglitis, MA Mouradian, MM AF Park, KW Eglitis, MA Mouradian, MM TI Protection of nigral neurons by GDNF-engineered marrow cell transplantation SO NEUROSCIENCE RESEARCH LA English DT Article DE Parkinson; MPTP; GDNF; transplantation; gene therapy; bone marrow; tyrosine hydroxylase ID NEUROTROPHIC FACTOR PROTECTS; BLOOD-BRAIN-BARRIER; BONE-MARROW; STROMAL CELLS; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; IN-VIVO; C57BL/6 MICE; GENE-THERAPY; ADULT MICE AB Marrow stromal cells, which have many characteristics of stem cells, populate various non-hematopoietic tissues including the brain. In the present study, the cDNA for the dopaminergic neurotrophic factor Glial Cell Line-Derived Neurotrophic Factor (GDNF) was delivered using marrow cells in the mouse 1-Methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) model of Parkinson's disease. Following cross-sex intravenous bone marrow transplantation with mate donor cells that had been transduced with GDNF (GDNF-BMT) or with non-manipulated marrow (Control-BMT), female recipient mice were subjected to systemic MPTP injections. Eight weeks after neurotoxin exposure, more tyrosine hydroxylase immunoreactive nigral neurons and striatal terminal density were observed in the GDNF-BMT mice compared with the Control-BMT group. In addition. following the expected initial behavioral hyperactivity in both groups, a significant difference in motor activity was detected between the two groups. GDNF immunoreactive mate donor marrow derived cells were detected in the brains of GDNF-BMT mice but not in controls. These data indicate that marrow derived cells that seed the brain can express biologically active gene products and, therefore, can function as effective vehicles for therapeutic gene transfer to the brain. (C) 2001 Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Park, KW (reprint author), Korea Univ, Dept Neurol, Coll Med, Seoul 136701, South Korea. OI Mouradian, M. Maral/0000-0002-9937-412X NR 35 TC 59 Z9 83 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0168-0102 J9 NEUROSCI RES JI Neurosci. Res. PD AUG PY 2001 VL 40 IS 4 BP 315 EP 323 DI 10.1016/S0168-0102(01)00242-5 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 463EM UT WOS:000170463900003 PM 11463477 ER PT J AU Keefer, LK Flippen-Anderson, JL George, C Shanklin, AP Dunams, TA Christodoulou, D Saavedra, JE Sagan, ES Bohle, DS AF Keefer, LK Flippen-Anderson, JL George, C Shanklin, AP Dunams, TA Christodoulou, D Saavedra, JE Sagan, ES Bohle, DS TI Chemistry of the diazeniumdiolates - 1. Structural and spectral characteristics of the [N(O)NO](-) functional group SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE nitric oxide; X-ray crystallography; infrared; ultraviolet spectroscopy; density functional; theory calculations; nitrogen-15 ID NITRIC-OXIDE DONOR; MOLECULAR-ORBITAL METHODS; RAY CRYSTAL-STRUCTURE; PULMONARY-HYPERTENSION; AQUEOUS-SOLUTION; SODIUM TRIOXODINITRATE(II); CEREBRAL VASOSPASM; NO RELEASE; AB-INITIO; IN-VITRO AB Ions of structure X[N(O)NO](-), examples of which have seen increasing use as probes for studying the biology of nitric oxide (NO) over the past decade, have a varied chemical history spanning nearly two centuries. Nevertheless, they have not been widely appreciated for their physicochemical similarities. Here we begin a series of systematic inquiries into the fundamental chemistry of such compounds aimed at identifying both the characteristics that justify considering them as a group and the factors that contribute to observed differences in their physicochemical properties. In the present paper, X-ray structures in which X is SO3- (1), O- (2), Ph (3), and Et2N (5), as well as that of the gem-disubstituted carbon derivative CH2[N(O)NO](2)(2-) (4), are compared. All their O-N-N-O systems are essentially planar, with cis oxygens and an N-N linkage exhibiting considerable double-bond character. The ultraviolet spectrum of the isolated chromophore consists of a relatively intense (similar to6-10 mM(-1) cm(-1) per [N(O)NO](-) group) absorption at 248-250 nm (for 2 and 5) that is red shifted by through-space Stark interactions (e.g., by similar to 10 nm in 1 and 4) as well as by conjugative interaction with X (lambda (max) = 284 run for 3). Infrared and Raman spectra for the widely used pharmacological probe 5 were determined, with analysis of vibrational modes being aided by comparison with the spectra of the [N-15(O)(NO)-N-15](-) isotopomer and density functional theory calculations at the B3LYP/6-311++G** level. To address confusion that has arisen in the literature resulting from rather widespread use of differing trivial designations for this class of compounds, a unifying nomenclature system is recommended in which compounds containing the [N(O)NO](-) moiety are named as diazeniumdiolates. It is hoped that these and other efforts to understand and predict the physicochemical similarities and differences among different members of the diazeniumdiolate class will aid in reaping their full potential in the area of rational drug design. C1 NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. Univ Wyoming, Dept Chem, Laramie, WY 82071 USA. RP Keefer, LK (reprint author), NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-56000]; NIGMS NIH HHS [GM-53828] NR 89 TC 62 Z9 63 U1 1 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD AUG PY 2001 VL 5 IS 4 BP 377 EP 394 DI 10.1006/niox.2001.0359 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 461ZB UT WOS:000170392800010 PM 11485376 ER PT J AU Dadachova, E Park, C Eberly, N Ma, D Paik, CH Brechbiel, MW AF Dadachova, E Park, C Eberly, N Ma, D Paik, CH Brechbiel, MW TI In vitro and in vivo characterization of Ga-67(3+) complexes with cis,cis-1,3,5-triamino-cyclohexane-N,N ',N ''-triacetic acid derivatives SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE Ga-67; cis,cis-1,3,5-triaminocyclohexane-N,N ',N ''-triacetic acid (tachta) ID LIGANDS; BIODISTRIBUTION; GALLIUM; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; RADIOPHARMACEUTICALS; INDIUM AB The aim of this study was to investigate the in vitro and in vivo performance of a Ga-67 complex with cis,cis-1,3,5-triaminocyclohexane-N,N,N"-triacetic acid (tachta) as a potential ligand for use as a Ga(III) radiopharmaceutical for PET imaging. The radiolabeling procedure, electrophoretic properties. lipophilicity. acid stability, human serum stability and biodistribution in mice of Ga-67(tachta) were investigated. The Ga-67(tachta) complex forms at 10(-3) M tachta concentration at 40 degreesC in 100% yield; it is neutral, non-lipophilic, 90% stable at pH = 4 and 5 and 100% stable at pH = 6, for at least 8 d. Serum stability experiments demonstrated that at 5 hr Ga-67(tachta) exists in serum as a free complex. At 24 hr, 30% of Ga-67(tachta) is reversibly bound to transferrin-albumin fraction of serum, and that this percentage remains unchanged for a period of 4 d. Biodistribution in mice showed that Ga-67(tachta) rapidly clears via the kidneys from the body with less than 10% of injected activity left in the body at 3 hours and only 6% remaining after 24 hr, The complex also cleared rapidly from all of the major organs, with bone showing some slightly increased (1. 15% ID/g) 24 hr accumulation, in comparison with the 3 hr time point. Based upon these data, Ga-67(tachta) may be considered as a candidate for developing new Ga(III) radiopharmaceuticals for PET, (C) 2001 Elsevier Science Inc. All rights reserved. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Dadachova, Ekaterina/I-7838-2013 NR 26 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD AUG PY 2001 VL 28 IS 6 BP 695 EP 701 DI 10.1016/S0969-8051(01)00227-X PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 465LU UT WOS:000170591100010 PM 11518651 ER PT J AU Soe, K Dianov, G Nasheuer, HP Bohr, VA Grosse, F Stevnsner, T AF Soe, K Dianov, G Nasheuer, HP Bohr, VA Grosse, F Stevnsner, T TI A human topoisomerase I cleavage complex is recognized by an additional human topisomerase I molecule in vitro SO NUCLEIC ACIDS RESEARCH LA English DT Article ID BIPARTITE DNA INTERACTION; DOUBLE-STRAND BREAKS; MEDIATED CLEAVAGE; ILLEGITIMATE RECOMBINATION; MAMMALIAN-CELLS; REPLICATING DNA; CAMPTOTHECIN; DAMAGE; INDUCTION; SEQUENCE AB Several recent studies have shown that human topoisomerase I (htopol) can recognize various DNA lesions and thereby form a covalent topolsomerase I-DNA complex, which is known to be detrimental to cells. We have investigated whether htopol recognizes another htopol that is covalently trapped on a DNA substrate. For this purpose we created an artificial DNA substrate containing a specific topoisomerase I binding sequence, where the enzyme was trapped in the covalently bound form. We demonstrate that, in vitro, free htopol stimulates the formation of an additional cleavage complex immediately upstream of the covalently bound topolsomerase I. The predominant distance between the two cleavage sites is 13 nt. In addition we find that these two enzymes may form direct protein-protein contacts and we propose that these may be mediated through the formation of a dimer by domain swapping involving the C-terminal and the core domains. Finally, we discuss the possibility that the double cleavage reaction may be the initial step for the removal of the recognized cleavage complex. C1 Inst Mol Biotechnol, Dept Biochem, D-07745 Jena, Germany. Natl Inst Aging, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Aarhus Univ, Dept Mol & Struct Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus, Denmark. RP Grosse, F (reprint author), Inst Mol Biotechnol, Dept Biochem, Beutenbergstr 11, D-07745 Jena, Germany. RI Nasheuer, Heinz/B-9025-2008; OI Soe, Kent/0000-0001-7402-314X NR 38 TC 22 Z9 23 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 1 PY 2001 VL 29 IS 15 BP 3195 EP 3203 DI 10.1093/nar/29.15.3195 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 460PC UT WOS:000170316800009 PM 11470877 ER PT J AU Banerjee-Basu, S Baxevanis, AD AF Banerjee-Basu, S Baxevanis, AD TI Molecular evolution of the homeodomain family of transcription factors SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CONGENITAL HEART-DISEASE; FOOT-GENITAL SYNDROME; MURINE HOMEOBOX GENE; DNA-BINDING; CRYSTAL-STRUCTURE; HUMAN GENOME; ANTENNAPEDIA HOMEODOMAIN; ENGRAILED HOMEODOMAIN; VND/NK-2 HOMEODOMAIN; STRUCTURAL BASIS AB The homeodomain family of transcription factors plays a fundamental role in a diverse set of functions that include body plan specification, pattern formation and cell fate determination during metazoan development. Members of this family are characterized by a helix-turn-helix DNA-binding motif known as the homeodomain. Homeodomain proteins regulate various cellular processes by specifically binding to the transcriptional control region of a target gene. These proteins have been conserved across a diverse range of species, from yeast to human. A number of inherited human disorders are caused by mutations in homeodomain-containing proteins. In this study, we present an evolutionary classification of 129 human homeodomain proteins. Phylogenetic analysis of these proteins, whose sequences were aligned based on the three-dimensional structure of the homeodomain, was performed using a distance matrix approach. The homeodomain proteins segregate into six distinct classes, and this classification is consistent with the known functional and structural characteristics of these proteins. An ancestral sequence signature that accurately describes the unique sequence characteristics of each of these classes has been derived. The phylogenetic analysis, coupled with the chromosomal localization of these genes, provides powerful clues as to how each of these classes arose from the ancestral homeodomain. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Baxevanis, AD (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM andy@nhgri.nih.gov NR 85 TC 88 Z9 93 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 1 PY 2001 VL 29 IS 15 BP 3258 EP 3269 DI 10.1093/nar/29.15.3258 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 460PC UT WOS:000170316800016 PM 11470884 ER PT J AU Chen, HX Gore-Langton, RE Cheson, BD AF Chen, HX Gore-Langton, RE Cheson, BD TI Current clinical trials of the anti-VEGF monoclonal antibody bevacizumab SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS; CANCER; INHIBITION; THERAPY C1 NCI, Bethesda, MD 20892 USA. RP Chen, HX (reprint author), NCI, Bethesda, MD 20892 USA. NR 19 TC 33 Z9 35 U1 0 U2 6 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD AUG PY 2001 VL 15 IS 8 BP 1017 EP + PG 6 WC Oncology SC Oncology GA 467JJ UT WOS:000170698400013 PM 11548974 ER PT J AU Kousvelari, E AF Kousvelari, E TI Biomaterials, biomimetics and tissue engineering programs at the National Institute of Dental and Craniofacial Research/National Institutes of Health SO OPERATIVE DENTISTRY LA English DT Article; Proceedings Paper CT International Symposium on Management Alternatives of the Carious Lesion CY SEP 15-17, 2000 CL CHARLESTON, SOUTH CAROLINA SP Dentsply Int, ESPE, Procter & Gamble, Heraneus Kulzer, 3M, BISCO, GC, Ivoclar, Kerr Corp, Shofu, Ultradent ID IN-VITRO; SILICA; VIVO C1 Natl Inst Dent & Craniofacial Res, Biomat Biomimet & Tissue Engn Branch, Div Extramural Res, NIH, Bethesda, MD 20892 USA. RP Kousvelari, E (reprint author), Natl Inst Dent & Craniofacial Res, Biomat Biomimet & Tissue Engn Branch, Div Extramural Res, NIH, Natcher Bldg,Room 4AN 18A, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU OPERATIVE DENTISTRY INC PI INDIANAPOLIS PA INDIANA UNIV SCHOOL DENTISTRY, ROOM S411, 1121 WEST MICHIGAN ST, INDIANAPOLIS, IN 46202-5186 USA SN 0361-7734 J9 OPER DENT JI Oper. Dent. PD AUG PY 2001 SU 6 BP 61 EP 66 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 467VP UT WOS:000170724700007 ER PT J AU Sperduto, RD Milton, RC Lindblad, AS Klein, BEK Ferris, FL Clemons, TE AF Sperduto, RD Milton, RC Lindblad, AS Klein, BEK Ferris, FL Clemons, TE CA Age Related Eye Dis Res Grp TI Risk factors associated with age-related nuclear and cortical cataract - A case-control study in the age-related eye disease study, AREDS Report No. 5 SO OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; POSTERIOR SUBCAPSULAR CATARACTS; ULTRAVIOLET-LIGHT EXPOSURE; CAUSE-SPECIFIC PREVALENCE; BLUE MOUNTAINS EYE; BODY-MASS INDEX; LENS OPACITIES; CIGARETTE-SMOKING; VISUAL IMPAIRMENT; MACULAR DEGENERATION AB Objective: To investigate possible risk factors for age-related nuclear and cortical cataracts in participants in the Age-Related Eye Disease Study (AREDS). Design: Case-control study. Participants: Of the 4757 persons enrolled in AREDS, 4477 age 60 to 80 years are included in the study. Main Outcome Measures. Slit-lamp lens photographs were used to classify participants into one of three nuclear opacity groups (moderate nuclear, mild nuclear, and controls), ignoring cortical opacities. Retroillumination lens photographs were used to classify participants into one of three cortical opacity groups (moderate cortical, mild cortical, and controls), ignoring nuclear opacities. Results. Persons with moderate nuclear opacities were more likely to be female, nonwhite, and smokers and to have large drusen. Moderate nuclear opacities were less common in persons with higher educational status, a history of diabetes, and among those taking nonsteroidal antiinflammatory drugs. Moderate cortical opacities were associated with dark iris color, large drusen, weight change, and, at a borderline level of significance, higher levels of sunlight exposure and use of thyroid hormones. Moderate cortical opacities were less common in persons with higher educational status. Conclusion: Consistent findings have now been reported across many studies for gender, educational status, sunlight exposure, and smoking. Our findings that use of nonsteroidal antiinflammatory drugs is inversely associated with nuclear cataract and that dark iris color and use of thyroid hormones may increase cortical cataract risk are less well substantiated and require further investigation. Ophthalmology 2001;108:1400-1408 (C) 2001 by the American Academy of Ophthalmology. C1 EMMES Corp, AREDS Coordinating Ctr, Rockville, MD 20850 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Ophthalmol & Vis Sci, Fundus Photograph Reading Ctr, Madison, WI USA. RP Sperduto, RD (reprint author), EMMES Corp, AREDS Coordinating Ctr, 401 N Washington St,Suite 700, Rockville, MD 20850 USA. NR 57 TC 78 Z9 79 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 2001 VL 108 IS 8 BP 1400 EP 1408 PG 9 WC Ophthalmology SC Ophthalmology GA 457JV UT WOS:000170134500026 ER PT J AU Seltzer, Z Wu, TX Max, MB Diehl, SR AF Seltzer, Z Wu, TX Max, MB Diehl, SR TI Mapping a gene for neuropathic pain-related behavior following peripheral neurectomy in the mouse SO PAIN LA English DT Article DE pain; autotomy; genetics; mouse model; gene mapping ID BENZODIAZEPINE RECEPTORS; STRAIN DIFFERENCES; INBRED MOUSE; AUTOTOMY; RATS; MICE; INJURY; DEAFFERENTATION; HERITABILITY; RESPONSES AB Total hindpaw denervation in rodents elicits an abnormal behavior of licking, scratching and self-injury of the anesthetic limb ('autotomy'). Since the same denervation produces phantom limb pain and anesthesia dolorosa in humans, autotomy has been used as a model of human neuropathic pain. Autotomy is an inherited trait in rodents, attributable to a few genes of major effect. Here we used recombinant inbred (RI) mouse lines of the AXB-BXA RI set to map a gene for autotomy. Autotomy levels following unilateral sciatic and saphenous nerve section were scored daily for 36 days, using a standardized scale, in all 23 RI lines available for this set. We used a genetic map of 395 marker loci and a permutation-based statistical method for categorical data to assess the statistical significance of mapping results. We identified a marker on chromosome 15 with statistical support (P = 0.0003) in the range considered significant for genome-wide scans in the mouse. Several genes located in this chromosomal region encode for neural functions related to neuropathic pain and may indicate targets for development of novel analgesics. (C) 2001 Elsevier Science B.V. Published by Elsevier Science B.V. All rights reserved. C1 NIDCR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Fac Med, Dept Physiol, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Fac Med Dent, IL-91120 Jerusalem, Israel. NIDCR, Craniofacial Epidemiol & Genet Branch, NIH, Bethesda, MD 20892 USA. RP Diehl, SR (reprint author), NIDCR, Pain & Neurosensory Mechanisms Branch, NIH, 45 Ctr Dr,Room 4As-43G, Bethesda, MD 20892 USA. NR 31 TC 43 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD AUG PY 2001 VL 93 IS 2 BP 101 EP 106 DI 10.1016/S0304-3959(01)00295-0 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 451LY UT WOS:000169804600002 PM 11427320 ER PT J AU Yanovski, JA AF Yanovski, JA TI Intensive therapies for pediatric obesity SO PEDIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CONGENITAL LEPTIN DEFICIENCY; DEPENDENT DIABETES-MELLITUS; FAMILY-BASED TREATMENT; LONG-TERM TREATMENT; MORBID-OBESITY; WEIGHT-LOSS; HYPOTHALAMIC OBESITY; RECOMBINANT LEPTIN; CHILDHOOD OBESITY; GASTRIC BYPASS AB Three intensive treatment approaches, namely restriction of energy intake below 1000 kcal (42000 kj)/d, pharmacotherapy, and bariatric surgery, have been proposed for children and adolescents with obesity who have not been able to control their weight with programs of moderate caloric restriction, behavior modification, and increased activity. This article reviews the limited date available regarding these intensive treatment regimens for childhood obesity. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 10N262,MSC 1862, Bethesda, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 65 TC 50 Z9 50 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0031-3955 J9 PEDIATR CLIN N AM JI Pediatr. Clin. N. Am. PD AUG PY 2001 VL 48 IS 4 BP 1041 EP + DI 10.1016/S0031-3955(05)70356-4 PG 14 WC Pediatrics SC Pediatrics GA 457CF UT WOS:000170119000014 PM 11494637 ER PT J AU Capparelli, EV Sullivan, JL Mofenson, L Smith, E Graham, B Britto, P Becker, MI Holland, D Connor, JD Luzuriaga, K AF Capparelli, EV Sullivan, JL Mofenson, L Smith, E Graham, B Britto, P Becker, MI Holland, D Connor, JD Luzuriaga, K CA Pediat ACTG 356 Investigators TI Pharmacokinetics of nelfinavir in human immunodeficiency virus-infected infants SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE nelfinavir; human immunodeficiency virus; pharmacokinetics ID PROTEASE INHIBITOR NELFINAVIR; HIV-INFECTION; THERAPY; PLASMA; MESYLATE; ABSORPTION; INDINAVIR; CHILDREN; TRIAL; SIZE AB Background. Nelfinavir dosed at similar to 20 to 30 mg/kg three times a day (TID) in older children provides exposure similar to 750 mg TID in adults. However, the pharmacokinetics (PK) of nelfinavir in infants who are <2 years of age is not well-described. The objective of this study was to determine the pharmacokinetics of nelfinavir in infants <2 years of age. Methods. Nelfinavir concentrations were evaluated in 22 HIIV-infected infants between 15 days and 2 years of age receiving nelfinavir as part of Pediatric ACTG Study 356. Nelfinavir therapy was initiated at similar to 25 mg/kg TID (n = 18) or similar to 55 mg/kg twice a day (n = 4) and given in combination with nevirapine, stavudine and lamivudine. PK samples were obtained predose and 1.5 and 4 h postdose at similar to6-month intervals. Eight infants (all less than or equal to3 months of age) also had intensive PK samples collected at Week 1. Results. The median apparent clearance in the infants with intensive pharmacokinetic sampling was 2.7 liters/h/kg (range, 1.8 to greater than or equal to 10) and was similar between twice a day and TID dosing cohorts. Overall nelfinavir concentrations at all collection times were lower in these infants than previously reported in older pediatric patients. Conclusions. Nelfinavir concentrations in infants are highly variable and lower than those seen in adult or older pediatric populations receiving labeled dosing. Therefore it is necessary to further evaluate nelfinavir safety, effectiveness and pharmacokinetics at higher doses than used among other pediatric populations. C1 Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pharm 2, La Jolla, CA 92093 USA. Univ Massachusetts, Dept Pediat, Worcester, MA 01605 USA. Univ Massachusetts, Dept Mol Med, Worcester, MA 01605 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Harvard Sch Publ Hlth, Stat Dat Anal Ctr, Boston, MA USA. Agouron Pharmaceut Inc, La Jolla, CA USA. RP Capparelli, EV (reprint author), Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI 32907, AI 41089, AI 42845] NR 21 TC 31 Z9 31 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD AUG PY 2001 VL 20 IS 8 BP 746 EP 751 DI 10.1097/00006454-200108000-00006 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 462TT UT WOS:000170436400006 PM 11734735 ER PT J AU Rouault, TA AF Rouault, TA TI Systemic iron metabolism: A review and implications for brain iron metabolism SO PEDIATRIC NEUROLOGY LA English DT Article; Proceedings Paper CT 1st Scientific Workshop on Hallervorden-Spatz Syndrome CY MAY 19-20, 2000 CL TOKYO, JAPAN ID CULTURED RAT ASTROCYTES; ELEMENT-BINDING-PROTEIN; TRANSFERRIN-BOUND IRON; CENTRAL-NERVOUS-SYSTEM; HEREDITARY HEMOCHROMATOSIS; REGULATORY PROTEIN-2; CEREBROSPINAL-FLUID; GENE-EXPRESSION; SULFUR CLUSTERS; MESSENGER-RNAS AB Mammalian cells and organisms coordinate to regulate expression of numerous proteins involved in the uptake, sequestration, and export of iron. When cells in the systemic circulation are depleted of iron, they increase synthesis of the transferrin receptor and decrease synthesis of the iron sequestration protein, ferritin. In iron-depleted animals, expression of duodenal iron transporters markedly increases and intestinal iron uptake increases accordingly. The major proteins of iron metabolism in the systemic circulation are also expressed in the central nervous system. However, the mechanisms by which iron is transported and distributed throughout the central nervous system are not well understood. Iron accumulation in specific regions of the brain is observed in several neurodegenerative diseases. It is likely that misregulation of iron metabolism is important in the pathophysiology of several human neurodegenerative diseases. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 NICHHD, Cell Biol & Metab Branch, Sect Human Iron Metab, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, Sect Human Iron Metab, Bethesda, MD 20892 USA. NR 94 TC 53 Z9 57 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD AUG PY 2001 VL 25 IS 2 BP 130 EP 137 DI 10.1016/S0887-8994(01)00260-0 PG 8 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 474AG UT WOS:000171081700005 PM 11551743 ER PT J AU Chiueh, CC AF Chiueh, CC TI Iron overload, oxidative stress, and axonal dystrophy in brain disorders SO PEDIATRIC NEUROLOGY LA English DT Article; Proceedings Paper CT 1st Scientific Workshop on Hallervorden-Spatz Syndrome CY MAY 19-20, 2000 CL TOKYO, JAPAN ID HALLERVORDEN-SPATZ-DISEASE; LIPID-PEROXIDATION; NITRIC-OXIDE; S-NITROSOGLUTATHIONE; IN-VIVO; SUPEROXIDE-DISMUTASE; TRANSFERRIN RECEPTOR; ALZHEIMERS-DISEASE; RAT-BRAIN; SUBARACHNOID HEMORRHAGE AB Hallervorden-Spatz syndrome is an autosomal-recessive brain disorder with signs of extrapyramidal dysfunction and mental deterioration, which associate with iron accumulation in globus pallidus and substantia nigra pars reticulata. Studies of oxidant stress in parkinsonian animal models suggest a linkage of iron overload to axonal dystrophy. Redox cycling of iron complexes (i.e., ferrous citrate and hemoglobin) increases hydroxyl radicals, lipid peroxidation, axonal dystrophy, and necrotic or apoptotic cell death. An increase of oxidative stress in the basal ganglia because of redox cycling of iron complexes leads to dopamine overflow and psychomotor dysfunction. Iron overload-induced axonal dystrophy has been demonstrated consistently using in vitro and in vivo models with a prominent feature of lipid peroxidation. This iron-induced oxidative stress is often accentuated by ascorbate and oxidized glutathione, although it is suppressed by the following antioxidants: S-nitrosoglutathione or nitric oxide, MnSOD mimics, manganese, U-78517F, Trolox, and deferoxamine. Preconditioning induction of stress proteins (i.e., hemeoxygenase-1 and neuronal nitric oxide synthase) and hypothermia therapy suppress the generation of toxic reactive oxygen, lipid, and thiol species evoked by bioactive iron complexes in the brain. Finally, combined antioxidative therapeutics and gene induction procedures may prove to be useful for slowing progressive neurodegeneration caused by iron overload in the brain. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 NIMH, LCS, NIH, Unit Neurodegenerat & Neuroprotect, Bethesda, MD 20892 USA. RP Chiueh, CC (reprint author), NIMH, LCS, NIH, Unit Neurodegenerat & Neuroprotect, 10-3D-41, Bethesda, MD 20892 USA. NR 80 TC 44 Z9 46 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD AUG PY 2001 VL 25 IS 2 BP 138 EP 147 DI 10.1016/S0887-8994(01)00266-1 PG 10 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 474AG UT WOS:000171081700006 PM 11551744 ER PT J AU Auestad, N Halter, R Hall, RT Blatter, M Bogle, ML Burks, W Erickson, JR Fitzgerald, KM Dobson, V Innis, SM Singer, LT Montalto, MB Jacobs, JR Qiu, WZ Bornstein, MH AF Auestad, N Halter, R Hall, RT Blatter, M Bogle, ML Burks, W Erickson, JR Fitzgerald, KM Dobson, V Innis, SM Singer, LT Montalto, MB Jacobs, JR Qiu, WZ Bornstein, MH TI Growth and development in term infants fed long-chain polyunsaturated fatty acids: A double-masked, randomized, parallel, prospective, multivariate study SO PEDIATRICS LA English DT Article DE infant development; breast feeding; infant formula; long-chain polyunsaturated fatty acids; docosahexaenoic acid ID MARINE-OIL SUPPLEMENTATION; ACUITY CARD PROCEDURE; BIRTH-WEIGHT INFANTS; FED HUMAN-MILK; VISUAL-ACUITY; COGNITIVE-DEVELOPMENT; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; PRETERM INFANTS; GESTATION INFANTS AB Objective. To evaluate the effects of dietary intake of the long-chain polyunsaturated fatty acids, arachidonic acid (AA), and docosahexaenoic acid (DHA) on multiple indices of infant growth and development. Design. A double-masked, randomized, parallel trial was conducted with term infants fed formulas with or without AA+DHA for 1 year (N = 239). Reference groups of breastfed infants (N = 165) weaned to formulas with and without AA+DHA were also studied. Infants in the formula groups were randomized at less than or equal to9 days of age to a control formula with no AA or DHA (n = 77) or 1 of 2 otherwise identical formulas containing AA+DHA (AA, 0.46% and DHA, 0.14% of total fatty acids) from either egg-derived triglyceride (egg-DTG [n=80]) or fish oil and fungal oil (fish/fungal [n = 82]) at levels similar to the average in breast milk samples as measured in the reference group. All formulas contained 50% of energy from fat with the essential dietary fatty acids, linoleic acid (20% fatty acids) and alpha -linolenic acid (2% fatty acids). The main study outcomes were AA and DHA levels in plasma and red blood cells, and multiple measures of infant development at multiple ages from birth to 14 months: growth, visual acuity, information processing, general development, language, and temperament. Results. AA and DHA levels in plasma and red cells were higher in AA+DHA-supplemented groups than in the control formula group and comparable to those in reference groups. No developmental test results distinguished these groups. Expected differences in family demographics associated with breastfeeding were found, but no advantages to breastfeeding on any of the developmental outcome demonstrated. Conclusions. These findings do not support adding AA+DHA to formulas containing 10% energy as linoleic acid and 1% energy as alpha -linolenic acid to enhance growth, visual acuity, information processing, general development, language, or temperament in healthy, term infants during the first 14 months after birth. C1 Abbott Labs, Ross Prod Div, Columbus, OH 43215 USA. Univ Missouri, Kansas City, MO 64110 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. Pittsburgh Pediat Res, Pittsburgh, PA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Arizona, Tucson, AZ USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Nichhd, NIH, Bethesda, MD USA. RP Auestad, N (reprint author), Abbott Labs, Ross Prod Div, 625 Cleveland Ave, Columbus, OH 43215 USA. NR 51 TC 133 Z9 141 U1 1 U2 17 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2001 VL 108 IS 2 BP 372 EP 381 DI 10.1542/peds.108.2.372 PG 10 WC Pediatrics SC Pediatrics GA 458TZ UT WOS:000170211800042 PM 11483802 ER PT J AU Kombo, LA Gerber, MA Pickering, LK Atreya, CD Breiman, RF AF Kombo, LA Gerber, MA Pickering, LK Atreya, CD Breiman, RF TI Intussusception, infection, and immunization Summary of a workshop on rotavirus SO PEDIATRICS LA English DT Article DE rotavirus; intussusception; rhesus rotavirus vaccine tetravalent; workshop ID CHILDREN; LIPOPOLYSACCHARIDE; MICE AB This article summarizes the proceedings of a workshop sponsored by the National Institutes of Health and the National Vaccine Program Office, and held in Bethesda, Maryland, on January 21, 2000. The objective of the meeting was to focus research toward an understanding of the basis for the possible association between intussusception and the reassortant rhesus-human rotavirus vaccine tetravalent (RRV-TV). After numerous reports of intussusception after administration of RRV-TV, the manufacturers of this vaccine voluntarily withdrew it from the United States market. The American Academy of Pediatrics, the Advisory Committee on Immunization Practices, and the American Academy of Family Physicians also withdrew their original recommendations for administration of RRV-TV to children at 2, 4, and 6 months of age. These actions will have global implications for the prevention of morbidity and mortality attributable to rotavirus infection. Benefit-cost ratios for the use of RRV-TV will be substantially different in developing countries compared with developed countries. Therefore, extensive research is needed in both of these settings, to further our understanding of the epidemiology, pathogenesis, and pathology of both rotavirus disease and intussusception to enable optimal prevention. The workshop reviewed the current understanding of the possible association between RRV-TV and intussusception, as well as the possible association between a variety of viral infections and intussusception. The workshop also identified critical areas of research regarding this possible association. This research will be essential not only for the development of safe and effective rotavirus vaccines, but for the development of other oral vaccines as well. C1 Natl Vaccine Program Off, Atlanta, GA 30333 USA. NIAID, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. RP Kombo, LA (reprint author), Natl Vaccine Program Off, 1600 Clifton Rd NE,MS D-66, Atlanta, GA 30333 USA. NR 29 TC 12 Z9 12 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2001 VL 108 IS 2 AR e37 DI 10.1542/peds.108.2.e37 PG 7 WC Pediatrics SC Pediatrics GA 458TZ UT WOS:000170211800018 PM 11483847 ER PT J AU Luce, BR Zangwill, KM Palmer, CS Mendelman, PM Yan, LH Wolff, MC Cho, IS Marcy, SM Iacuzio, D Belshe, RB AF Luce, BR Zangwill, KM Palmer, CS Mendelman, PM Yan, LH Wolff, MC Cho, IS Marcy, SM Iacuzio, D Belshe, RB TI Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children SO PEDIATRICS LA English DT Article DE cost-effectiveness; influenza; vaccine; children ID ECONOMIC-IMPACT; HEPATITIS-B; HAEMOPHILUS-INFLUENZAE; CONJUGATE VACCINATION; RESPIRATORY-DISEASE; VIRUS-INFECTIONS; YOUNG-CHILDREN; EFFICACY; LIVE; IMMUNIZATION AB Objective. Intranasal influenza vaccine has proven clinical efficacy and may be better tolerated by young children and their families than an injectable vaccine. This study determined the potential cost-effectiveness (CE) of an intranasal influenza vaccine among healthy children. Methods. We conducted a CE analysis of data collected between 1996 and 1998 during a prospective 2-year efficacy trial of intranasal influenza vaccine, supplemented with data from the literature. The CE analysis included both direct and indirect costs. We enrolled 1602 healthy children aged 15 to 71 months in year 1, 1358 of whom were enrolled in year 2. One or 2 doses of intranasal influenza vaccine or placebo were administered to measure the cost per febrile influenza-like illness (ILI) day avoided. Results. During the 2-year study period, vaccinated children had an average of 1.2 fewer ILI fever days/child than unvaccinated children. In an individual-based vaccine delivery scenario with vaccine given twice in the first year and once each year thereafter at an assumed base case total cost of $20 for the vaccine and its administration (ie, per dose), CE was approximately $30/febrile ILI day avoided. CE ranged from $10 to $69/febrile ILI day avoided at $10 to $40/dose, respectively. In a group-based delivery scenario, vaccination was cost saving compared with placebo and remained so if vaccine cost was <$28 (the break-even price per dose). In the individual-based scenario, vaccination was cost saving if vaccine cost was <$5. In this scenario, nearly half of lost productivity in the vaccine group was attributable to vaccine visits, which overshadowed the relatively modest savings in ILI-associated costs averted. Conclusions. Routine use of intranasal influenza vaccine among healthy children may be cost-effective and may be maximized by using group-based vaccination approaches. C1 MEDTAP Int, Bethesda, MD 20814 USA. Univ Calif Los Angeles, Ctr Vaccine Res, Torrance, CA USA. Aviron, Mt View, CA USA. EMMES Corp, Potomac, MD USA. So Calif Kaiser Permanente Hlth Care Program, Panorama City, CA USA. NIAID, NIH, Bethesda, MD 20892 USA. St Louis Univ, Hlth Sci Ctr, St Louis, MO 63103 USA. RP Luce, BR (reprint author), MEDTAP Int, 7101 Wisconsin Ave,Ste 600, Bethesda, MD 20814 USA. FU NIAID NIH HHS [N01-AI45249] NR 50 TC 60 Z9 65 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 2001 VL 108 IS 2 AR e24 DI 10.1542/peds.108.2.e24 PG 8 WC Pediatrics SC Pediatrics GA 458TZ UT WOS:000170211800005 PM 11483834 ER PT J AU Tashima, Y Kohda, Y Nonoguchi, H Ikebe, M Machida, K Star, RA Tomita, K AF Tashima, Y Kohda, Y Nonoguchi, H Ikebe, M Machida, K Star, RA Tomita, K TI Intranephron localization and regulation of the V1a vasopressin receptor during chronic metabolic acidosis and dehydration in rats SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE RT-competitive PCR; vasopressin; acid-base balance ID ENDOTHELIN-CONVERTING ENZYME-1; CORTICAL COLLECTING DUCT; ARGININE-VASOPRESSIN; V2 RECEPTOR; MESSENGER-RNA; RENAL-FAILURE; NEPHRON; URINARY; KIDNEY; EXPRESSION AB The intrarenal localization and role of the V1a vasopressin receptor in body fluid homeostasis are unclear. We investigated the intranephron localization of Via receptor mRNA and protein using reverse transcription (RT)-competitive polymerase chain reaction (PCR) and immunohistochemistry with a specific polyclonal antibody. To determine whether the Via receptor is involved in the regulation of acid-base balance, we also examined the effects of acute and chronic metabolic acidosis and dehydration on V1a receptor expression. V1a mRNA was expressed most abundantly in the cortical collecting ducts (CCD) and decreased in the deeper CD. Expression in the glomeruli and thick ascending limbs was low. The immunohistochemical study revealed the presence of the V1a receptor in the glomeruli, the thick ascending limbs and the CD. Dehydration decreased Via mRNA expression in the CD. Chronic metabolic acidosis increased V1a receptor mRNA expression in the CD but decreased V2 receptor mRNA expression. Western blot analysis revealed up-regulation of the V1a receptor protein in chronic metabolic acidosis. Incubation of microdissected CCD or outer medullary CD (OMCD) in a low-pH (or or low-HCO3-) medium increased the levels of V1a receptor mRNA but decreased V2 receptor mRNA expression. Incubating OMCD with arginine vasopressin (AVP) and the V1a receptor antagonist (OPC21268) increased V2 receptor mRNA expression compared with incubation with AVP alone. These data suggest that V1a receptors are present primarily in the principal and intercalated cells in the CD and that these receptors are involved in the regulation of water and acid-base balance. C1 Kumamoto Univ, Sch Med, Dept Internal Med 3, Kumamoto 8608556, Japan. Univ Texas, SW Med Ctr, Div Nephrol, Dept Med, Dallas, TX 75235 USA. NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Nonoguchi, H (reprint author), Kumamoto Univ, Sch Med, Dept Internal Med 3, 1-1-1 Honjo, Kumamoto 8608556, Japan. NR 29 TC 37 Z9 38 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD AUG PY 2001 VL 442 IS 5 BP 652 EP 661 DI 10.1007/s004240100590 PG 10 WC Physiology SC Physiology GA 468HQ UT WOS:000170752400003 PM 11512020 ER PT J AU Groll, AH Piscitelli, SC Walsh, TJ AF Groll, AH Piscitelli, SC Walsh, TJ TI Antifungal pharmacodynamics: Concentration-effect relationships in vitro and in vivo SO PHARMACOTHERAPY LA English DT Review ID B LIPID COMPLEX; EXPERIMENTAL DISSEMINATED CANDIDIASIS; EXPERIMENTAL PULMONARY ASPERGILLOSIS; PERSISTENTLY NEUTROPENIC RABBITS; MULTILAMELLAR LIPOSOMAL NYSTATIN; TIME-KILL METHODOLOGY; IN-VITRO; AMPHOTERICIN-B; CRYPTOCOCCUS-NEOFORMANS; FILAMENTOUS FUNGI AB The pharmaco dynamics of antifungal compounds involve relationships among drug concentrations, time, and antimicrobial effects in vitro and in vivo. Beyond better understanding of a drug's mode of action, characterization of these relationships has important implications for setting susceptibility breakpoints, establishing rational dosing regimens, and facilitating drug development. Important advances have been made in the experimental investigation of pharmacokinetics and pharmaco dynamics of antifungal drugs; however, much remains to be learned about specific pathogens and specific sites of infection. Increased incorporation of pharmacokinetic and pharmacodynamic principles in experimental and clinical studies with antifungal agents is an important objective that will benefit the treatment and prophylaxis of life-threatening invasive fungal infections in immunocompromised patients. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Pharmacokinet Res Lab, Bethesda, MD 20892 USA. RP Groll, AH (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,Room 13N-240, Bethesda, MD 20892 USA. NR 131 TC 29 Z9 30 U1 1 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2001 VL 21 IS 8 SU S BP 133S EP 148S DI 10.1592/phco.21.12.133S.34507 PN 2 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 470ZM UT WOS:000170902400004 PM 11501987 ER PT J AU Hansen, PL Podgornik, R Parsegian, VA AF Hansen, PL Podgornik, R Parsegian, VA TI Osmotic properties of DNA: Critical evaluation of counterion condensation theory SO PHYSICAL REVIEW E LA English DT Article ID POLY-ELECTROLYTE; HYDRATION FORCES; CELL MODEL; POLYELECTROLYTES; SALT AB The Osmotic coefficient of B-DNA in water may, in dilute solutions, deviate by as much as 100% from predictions based on a simple line-charge "counterion condensation" theory. In contrast, a cell model description of the ionic atmosphere near a cylindrical polyelectrolyte predicts osmotic properties that are in surprisingly good harmony with all available experimental findings over a wide range of DNA concentrations. We argue that the neglect of molecular features, such as finite radius, makes line-charge condensation theory inapplicable at all but impractically low polyelectrolyte concentrations. C1 NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. Univ Ljubljana, Dept Phys, Fac Math & Phys, Ljubljana 61000, Slovenia. J Stefan Inst, Dept Theoret Phys, Ljubljana, Slovenia. RP Hansen, PL (reprint author), NICHHD, NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 28 TC 52 Z9 52 U1 1 U2 13 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD AUG PY 2001 VL 64 IS 2 AR 021907 DI 10.1103/PhysRevE.64.021907 PN 1 PG 4 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 463TF UT WOS:000170492800075 PM 11497620 ER PT J AU Paylor, R Zhao, YG Libbey, M Westphal, H Crawley, JN AF Paylor, R Zhao, YG Libbey, M Westphal, H Crawley, JN TI Learning impairments and motor dysfunctions in adult Lhx5-deficient mice displaying hippocampal disorganization SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE homeobox; development; gene; Lhx5; mice; hippocampus; neuroanatomy; learning; memory; motor; Barnes maze; fear conditioning; spontaneous alternation; activity; coordination ID CONTEXTUAL FEAR; PREPULSE INHIBITION; SPONTANEOUS-ALTERNATION; RETROGRADE-AMNESIA; DORSAL HIPPOCAMPUS; MEMORY DEFICITS; SPATIAL MEMORY; MOUSE STRAINS; KNOCKOUT MICE; LESIONS AB Lhx5 is a member of the LIM homeobox gene family that regulates development of the nervous system. Adult mice generated with a mutation in Lhx5 were found to display absent or disorganized hippocampal neuroanatomy. The pyramidal cell layer in Ammon's hom. and the granule cell layer in the dentate gyrus were absent or poorly defined in the hippocampus. of adult Lhx5 knockout mice. Behavioral phenotyping of Lhx5 null mutants detected deficits on learning and memory tasks, including the Barnes maze spatial learning task, spontaneous alternation recognition memory, and contextual and cued fear conditioning. General health, neurological reflexes, and sensory abilities appeared to be normal in Lhx5 knockout mice. Motor tests showed impaired performance on some measures of motor activity, coordination, balance, and gait. These results reveal functional outcomes of Lhx5 gene deletion on the integrity of hippocampal neuroanatomy and behavior in the adult mouse. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes Dev, NIH, Bethesda, MD 20892 USA. RP Crawley, JN (reprint author), NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bldg 10,Room 4D11, Bethesda, MD 20892 USA. NR 53 TC 48 Z9 48 U1 4 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD AUG PY 2001 VL 73 IS 5 SI SI BP 781 EP 792 DI 10.1016/S0031-9384(01)00515-7 PG 12 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 474AJ UT WOS:000171081900011 PM 11566211 ER PT J AU Virador, V Matsunaga, N Matsunaga, J Valencia, J Oldham, RJ Kameyama, K Peck, GL Ferrans, VJ Vieira, WD Abdel-Malek, ZA Hearing, VJ AF Virador, V Matsunaga, N Matsunaga, J Valencia, J Oldham, RJ Kameyama, K Peck, GL Ferrans, VJ Vieira, WD Abdel-Malek, ZA Hearing, VJ TI Production of melanocyte-specific antibodies to human melanosomal proteins: Expression patterns in normal human skin and in cutaneous pigmented lesions SO PIGMENT CELL RESEARCH LA English DT Article DE tyrosinase; pigmentation; melanogenesis; melanosome ID TYROSINASE; CELLS; DIFFERENTIATION; MARKERS; COMPLEX AB Multiple factors affect skin pigmentation, including those that regulate melanocyte and/or keratinocyte function. Such factors, particularly those that operate at the level of the melanosome, are relatively well characterized in mice, but the expression and function of structural and enzymatic proteins in melanocytes in human skin are not as well known. Some years ago, we generated peptide-specific antibodies to murine melanosomal proteins that proved to be instrumental in elucidating melanocyte development and differentiation in mice, but cross-reactivity of those antibodies with the corresponding human proteins often was weak or absent. In an effort to characterize the roles of melanosomal proteins in human skin pigmentation, and to understand the underlying mechanism(s) of abnormal skin pigmentation, we have now generated polyclonal antibodies against the human melanocyte-specific markers, tyrosinase, tyrosinase-related protein 1 (TYRP1), Dopachrome tautomerase (DCT) and PmeIl7 (SILV, also known as GP100). We used these antibodies to determine the distribution and function of melanosomal proteins in normal human skin (adult and newborn) and in various cutaneous pigmented lesions, such as intradermal nevi, lentigo simplex, solar lentigines and malignant melanomas. We also examined cytokeratin expression in these same samples to assess keratinocyte distribution and function. Immunohistochemical staining reveals distinct patterns of melanocyte distribution and function in normal skin and in various types of cutaneous pigmented lesions. Those differences in the expression patterns of melanocyte markers provide important clues to the roles of melanocytes in normal and in disrupted skin pigmentation. C1 NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Cosmet & Reconstruct Plast Surg Ctr, Bethesda, MD USA. Aoyama Dermatol Clin, Minato Ku, Tokyo 1070062, Japan. Washington Hosp Ctr, Washington Inst Canc, Melanoma Ctr, Washington, DC 20010 USA. Univ Cincinnati, Dept Dermatol, Cincinnati, OH 45221 USA. RP Hearing, VJ (reprint author), NCI, Pigment Cell Biol Sect, Cell Biol Lab, NIH, Bldg 37 Room 1B25, Bethesda, MD 20892 USA. NR 27 TC 43 Z9 43 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD AUG PY 2001 VL 14 IS 4 BP 289 EP 297 DI 10.1034/j.1600-0749.2001.140410.x PG 9 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 468PK UT WOS:000170765700009 PM 11549113 ER PT J AU Giese, SY Bulan, EJ Commons, GW Spear, SL Yanovski, JA AF Giese, SY Bulan, EJ Commons, GW Spear, SL Yanovski, JA TI Improvements in cardiovascular risk profile with large-volume liposuction: A pilot study SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Aesthetic-Plastic-Surgery CY MAY 06-16, 2000 CL ORLANDO, FLORIDA SP Amer Soc Aesthet Plast Surg ID ULTRASOUND-ASSISTED LIPOPLASTY; X-RAY ABSORPTIOMETRY; 250 CONSECUTIVE PATIENTS; INSULIN-RESISTANCE; BODY-COMPOSITION; ENERGY-EXPENDITURE; GLUCOSE-TOLERANCE; DIABETES-MELLITUS; HEART-DISEASE; YOUNG-ADULTS AB In this study, the authors investigated the physiologic effects of the altered body composition that results from surgical removal of large amounts of subcutaneous adipose tissue. Fourteen women with body mass indexes of greater than > 27 kg/m(2) underwent measurements of fasting plasma insulin, triglycerides, cholesterol, body composition by dual-energy x-ray absorptiometry (DXA), resting energy expenditure, and blood pressure before and after undergoing large-volume ultrasound-assisted liposuction. There were no significant intraoperative complications. Body weight had decreased by 5.1 kg (p < 0.0001) by 6 weeks after liposuction, with an additional 1.3-kg weight loss (p < 0.05) observed between 6 weeks and 4 months after surgery, for a total weight loss of 6.5 kg (p < 0.00006). Body mass index decreased from (mean +/- SEM) 28.8 +/- 2.3 to 26.8 +/- 1.5 kg/m(2) (p < 0.0001). This change in body weight was primarily the result of decreases in body fat mass: as assessed by DXA, lean body mass did not change (43.8 +/- 3.1 kg to 43.4 +/- 3.6 kg, p = 0.80.), whereas DXA total body fat mass decreased from 35.7 +/- 6.3 to 30.1 +/- 6.5 kg (P < 0.0001). There were significant decreases in fasting plasma insulin levels (14.9 +/- 6.5 mIU/ml before liposuction versus 7.2 +/- 3.2 mIU/ml 4 months after liposuction, P < 0.007), and systolic blood pressure (132.1 +/- 7.2 versus 120.5 +/- 7.8 mmHg, p < 0.0002). Total cholesterol, high-density lipoprotein cholesterol, plasma triglycerides, and resting energy expenditure values were not significantly altered after liposuction. In conclusion, over a 4-month period, large-volume liposuction decreased weight, body fat mass, systolic blood detrimental effects on sure, and fasting insulin levels without det lean body mass, bone mass, resting energy expenditure, or lipid profiles. Should these improvements be maintained over time, liposuction may prove to be a valuable tool for reducing the comorbid conditions associated with obesity. C1 Georgetown Univ, Washington, DC 20057 USA. NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD USA. RP Giese, SY (reprint author), 105 E 73rd St, New York, NY 10021 USA. NR 55 TC 62 Z9 67 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD AUG PY 2001 VL 108 IS 2 BP 510 EP 519 DI 10.1097/00006534-200108000-00035 PG 10 WC Surgery SC Surgery GA 456RW UT WOS:000170096900035 PM 11496197 ER PT J AU Oriji, GK AF Oriji, GK TI Angiotensin II stimulates PGF(2 alpha) release in cultured neonatal rat ventricular myocytes via L-type calcium channels SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID PIGLET PARIETAL CORTEX; MYOCARDIAL-CELLS; PROSTANOIDS; MUSCLE; HYPERTROPHY; EXPRESSION; INCREASES; PATHWAY; GROWTH; PKC AB Angiotensin II (Ang II) has been shown to cause Prostaglandin F-2 alpha (PGF(2 alpha)) release in neonatal rat ventricular myocytes and smooth muscle cells. In these cells, Ang II has also been shown to regulate growth. We used neonatal rat ventricular myocytes to investigate the role of calcium in maintenance of Ang II-induced PGF(2 alpha) release. The amount of PGF(2 alpha) produced was determined by radioimmunoassay. Ang II-induced PGF(2 alpha) release. Pretreatment of neonatal rat ventricular myocytes with different doses (10(-8) M, 10(-7) M, 10(-6) M and 10(-5) M) of diltiazm (voltage-sensitive L-type calcium channel blocker) produced significant inhibition in Ang II-induced PGF(2 alpha) release. Inhibition was first noted at 10(-8) M and was complete at 10(-6) M. Conversely, pretreatment of neonatal rat ventricular myocytes with different doses (10(-8) M, 10(-7) M, 10(-6) M and 10(-5) M) of calcium channel blockers (conotoxin; voltage-sensitive N-type calcium channel blocker or thapsigargin; intracellular calcium channel blocker) produced no changes in Ang II-induced PGF(2 alpha) release. These results strongly suggest that Ang II-induced PGF(2 alpha) release in neonatal rat ventricular myocytes is maintained, at least in part, via increase in extracellular calcium influx. (C) 2001 Harcourt Publishers Ltd. C1 William Paterson Univ, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Oriji, GK (reprint author), William Paterson Univ, Coll Sci & Hlth, Dept Biol, Wayne, NJ 07470 USA. NR 26 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD AUG PY 2001 VL 65 IS 2 BP 73 EP 77 DI 10.1054/plef.2001.0291 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 473NF UT WOS:000171049900003 PM 11545622 ER PT J AU Horwitz, SM Hoagwood, K Stiffman, AR Summerfeld, T Weisz, JR Costello, EJ Rost, K Bean, DL Cottler, L Leaf, PJ Roper, M Norquist, G AF Horwitz, SM Hoagwood, K Stiffman, AR Summerfeld, T Weisz, JR Costello, EJ Rost, K Bean, DL Cottler, L Leaf, PJ Roper, M Norquist, G TI Reliability of the services assessment for children and adolescents SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH-SERVICES; GREAT SMOKY MOUNTAINS; PSYCHIATRIC-DISORDERS; HELP-SEEKING; PREVALENCE; CARE; DEMAND; PATTERNS; EPISODES; PSYCHOTHERAPY AB Objective: This study examined the test-retest reliability of a new instrument, the Services Assessment for Children and Adolescents (SACA), for children's use of mental health services. Methods: A cross-sectional survey was undertaken at two sites. The St. Louis site used a volunteer sample recruited from mental health clinics and local schools. The Ventura County, California, site used a double-blind, community-based sample seeded with cases of service-using children. Participating families completed the SACA and were retested within four to 14 days. The reliability of service use items was calculated with use of the kappa statistic. Results: The SACA-Parent Version had excellent test-retest reliability for both lifetime service use and previous 12-month use. The SACA also had good to excellent reliability when administered to children aged 11 and older for lifetime and 12-month use. Reliability figures for children aged nine and ten years were considerably lower for lifetime and 12-month use. The younger children's responses suggested that they were confused about some questions. Conclusions: This study demonstrates that parents and older children can reliably report use of mental health services by using the SACA. The SACA can be used to collect currently unavailable information about use of mental health services. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. Yale Univ, Inst Social & Policy, New Haven, CT 06520 USA. NIMH, Child & Adolescent Mental Hlth Serv, Rockville, MD 20857 USA. Washington Univ, George Warren Brown Sch Social Work, St Louis, MO 63130 USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Chapel Hill, NC USA. Univ Colorado, Dept Family Med, Denver, CO 80202 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Johns Hopkins Univ, Dept Mental Hyg, Baltimore, MD USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Horwitz, SM (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St,Rm 310, New Haven, CT 06520 USA. NR 53 TC 111 Z9 112 U1 5 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD AUG PY 2001 VL 52 IS 8 BP 1088 EP 1094 DI 10.1176/appi.ps.52.8.1088 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 458CH UT WOS:000170175300017 PM 11474056 ER PT J AU Daly, RC Schmidt, PJ Davis, CL Danaceau, MA Rubinow, DR AF Daly, RC Schmidt, PJ Davis, CL Danaceau, MA Rubinow, DR TI Effects of gonadal steroids on peripheral benzodiazepine receptor density in women with PMS and controls SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE PMS; peripheral benzodiazepine receptor; gonadal steroids ID PREMENSTRUAL-SYNDROME; OVARIAN-STEROIDS; LUTEAL-PHASE; DOUBLE-BLIND; DISORDER; BINDING; STRESS; PROGESTERONE; LYMPHOCYTES; ALPRAZOLAM AB Background: GABA receptor-modifying neurosteroids may play a role in premenstrual syndrome (PMS). The peripheral benzodiazepine receptor (PBR) both regulates: the formation of neurosteroids and is, in animals, regulated by ovarian steroids. Alterations in PER density have been observed in association with several psychiatric disorders. Methods: We examined the effects of gonadal steroids on lymphocytic PBR density in nine women with prospectively confirmed PMS and nine controls. PER densities were measured during three pharmacologically controlled conditions: gonadotropin releasing hormone agonist (Lupron)-induced hypogonadism. Lupron plus estradiol, and Lupron plus progesterone replacement. Blood samples were obtained after six weeks of Lupron alone and after 3-4 weeks of estradiol and progesterone replacement. Results: No significant hormone state-related changes: in PBR density were observed (ANOVA-R: phase-F-2.32=1.5. P=0.2). Despite mood symptom development in the subjects with PMS, PER density did not differ in women with PMS compared to controls across hormonal states (ANOVA-R: F-1.16=0.6, P=0.4). Conclusions: PER densities are not altered in women with PMS and art: not changed significantly by selective gonadal steroid administration. Changes in PER density would not appear to underlie the differential sensitivity to the mood destabilizing effects of ovarian steroids in PMS. Published by Elsevier Science Ltd. C1 NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Daly, RC (reprint author), NIMH, Behav Endocrinol Branch, Bldg 10,Room 3N238,10 Ctr Dr MSC 1276, Bethesda, MD 20892 USA. NR 36 TC 7 Z9 7 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD AUG PY 2001 VL 26 IS 6 BP 539 EP 549 DI 10.1016/S0306-4530(01)00005-1 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 454PU UT WOS:000169981600001 PM 11403976 ER PT J AU Roth, BL Ernsberger, P Steinberg, S Rao, S Rauser, L Savage, J Hufeisen, S Berridge, MS Muzic, RF AF Roth, BL Ernsberger, P Steinberg, S Rao, S Rauser, L Savage, J Hufeisen, S Berridge, MS Muzic, RF TI The in vitro pharmacology of the beta-adrenergic receptor pet ligand (s)-fluorocarazolol reveals high affinity for cloned beta-adrenergic receptors and moderate affinity for the human 5-HT1A receptor SO PSYCHOPHARMACOLOGY LA English DT Article DE positron emission tomography; beta-adrenergic; 5-HT1A ID MEMORY STORAGE; HUMAN-BRAIN; INVOLVEMENT; BINDING; AMYGDALA; STRESS AB Rationale: s-Fluorocarazolol [(S)-FCZ] is the major positron emission tomography (PET) ligand currently used to visualize central P-adrenergic receptors in vivo, although its pharmacology is incompletely known. Objective: Our objective was to comprehensively characterize the in vitro pharmacology of (S)- and (R)-FCZ to determine its suitability for study of central and peripheral P-]l.beta -adrenergic receptors. Methods: We characterized the in vitro pharmacology of (S)-FCZ at 42 biogenic amine receptors and transporters in vitro using the resources of the National Institute of Mental Health Psychoactive Drug Screening Program. Results: As expected (R)- and (S)-FCZ had high affinities for beta -adrenergic receptors (Ki values=0.08-0.45 nM) and negligible affinities (Ki values > 100 nM) for nearly all other tested receptors and transporters with the exception of the h5-HT1A receptor for which (S)-FCZ had high affinity (Ki=34 nM). Interestingly, (R)-FCZ had low affinity for the h5-HT1A receptor (Ki=342 nM). Conclusion: The high affinity of (S)-FCZ for the h5-HT1A receptor is not likely to interfere with studies of peripheral beta -adrenergic receptors, since 5-HT1A receptors are expressed at very low levels outside the central nervous system. Indeed, computer simulations predict that even at low ligand concentrations, 5-HT1A binding in brain regions like hippocampus are likely to be substantial. Thus, (S)-FCZ may not be a suitable PET ligand for studies of central nervous system beta -adrenergic receptors unless the contribution by 5-HT1A sites can be shown to be negligible. C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, NIMH, Psychoact Drug Screening Program, Dept Biochem Psychiat & Neurosci,Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Nutr, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Dept Radiol & Chem, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Dept Radiol & Biomed Engn, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, Rm W438,10900 Euclid Ave, Cleveland, OH 44106 USA. RI Roth, Bryan/F-3928-2010; Ernsberger, Paul/O-2702-2014 OI Ernsberger, Paul/0000-0003-2372-2500 FU NHLBI NIH HHS [R01HL62399-02]; NIMH NIH HHS [N02MH80002, KO2MH01366] NR 14 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD AUG PY 2001 VL 157 IS 1 BP 111 EP 114 DI 10.1007/s002130100844 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 469QD UT WOS:000170825600015 PM 11512051 ER PT J AU Travis, LB Land, CE Andersson, M Nyberg, U Goldman, MB Gaul, LK Berger, E Storm, HH Hall, P Auvinen, A Janower, ML Holm, LE Monson, RR Schottenfeld, D Boice, JD AF Travis, LB Land, CE Andersson, M Nyberg, U Goldman, MB Gaul, LK Berger, E Storm, HH Hall, P Auvinen, A Janower, ML Holm, LE Monson, RR Schottenfeld, D Boice, JD TI Mortality after cerebral angiography with or without radioactive thorotrast: An international cohort of 3,143 two-year survivors SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; HUMAN BONE-MARROW; HEPATIC ANGIOSARCOMA; CANCER INCIDENCE; EXPOSED PATIENTS; DANISH; RADIATION; MUTATIONS; THORIUM; CELLS AB There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%. (C) 2001 by Radiation Research Society. C1 NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Rigshosp, Dept Oncol 5073, DK-2100 Copenhagen, Denmark. Danish Canc Soc, DK-2100 Copenhagen, Denmark. Karolinska Univ Hosp, Radiumhemmet, Stockholm, Sweden. New England Res Inst, Watertown, MA 02172 USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX USA. Informat Management Serv Inc, Rockville, MD USA. Karolinska Inst, Dept Med Epidemiol, Stockholm, Sweden. Radiat & Nucl Safety Author, Helsinki, Finland. Worcester Med Ctr, Worcester, MA USA. Swedish Radiat Protect Inst, Stockholm, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Int Epidemiol Inst, Rockville, MD 20852 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. RP Travis, LB (reprint author), NCI, Radiat Epidemiol Branch, Execut Plaza S,Suite 7086, Bethesda, MD 20892 USA. OI Auvinen, Anssi/0000-0003-1125-4818 NR 52 TC 13 Z9 13 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD AUG PY 2001 VL 156 IS 2 BP 136 EP 150 DI 10.1667/0033-7587(2001)156[0136:MACAWO]2.0.CO;2 PG 15 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 458DP UT WOS:000170178200002 PM 11448234 ER PT J AU Panyutin, IV Luu, AN Panyutin, IG Neumann, RD AF Panyutin, IV Luu, AN Panyutin, IG Neumann, RD TI Strand breaks in whole plasmid DNA produced by the decay of I-125 in a triplex-forming oligonucleotide SO RADIATION RESEARCH LA English DT Article ID ELECTRON-EMITTING I-125; SYNTHETIC OLIGODEOXYNUCLEOTIDE; MAMMALIAN-CELLS; LABELED OLIGONUCLEOTIDES; QUANTITATIVE-ANALYSIS; POSITIONAL CHANGES; AUGER; RADIOTOXICITY; I125; RADIATION AB DNA strand breaks produced by the decay of I-125 positioned against a specific site in plasmid DNA via a triplex-forming oligonucleotide were studied both in the immediate vicinity of the site of the decay with a single nucleotide resolution and in the whole plasmid by measuring the percentages of supercoiled, open-circular and linear forms. The localized breaks are distributed within 10 bp in each direction from the decay site with maxima in both strands just opposite the I-125-dC residue in the triplex-forming oligonucleotide. The distributions of breaks in the two DNA strands are almost symmetrical, in agreement with the geometry of the pyrimidine motif triplex. We found that about 25% of the double-strand breaks were located outside the 90-bp fragment containing the triplex-forming oligonucleotide binding sequence. The ratio of single-to double-strand breaks in the whole plasmid was 11 for bound triplex-forming oligonucleotide compared to 26 when the triplex-forming oligonucleotide was free in solution. The number of double-strand breaks per decay of I-125 was 0.46 for bound triplex-forming oligonucleotide and 0.17 for free triplex-forming oligonucleotide. Comparing the data on the localized damage and those for the whole plasmid, we concluded that, in addition to DNA breaks that are confined to a helical turn around the I-125 atom, the decay can produce breaks hundreds of base pairs away in the plasmid molecule. This linear plasmid molecule containing radiation-induced damage at a specific DNA site should be useful in studies of the molecular mechanisms of DNA repair. (C) 2001 by Radiation Research Society. C1 NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20854 USA. RP Panyutin, IV (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bld 10,Room 4D43,10 Cent Dr, Bethesda, MD 20854 USA. NR 29 TC 24 Z9 25 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD AUG PY 2001 VL 156 IS 2 BP 158 EP 166 DI 10.1667/0033-7587(2001)156[0158:SBIWPD]2.0.CO;2 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 458DP UT WOS:000170178200004 PM 11448236 ER PT J AU Elci, OC Dosemeci, M Blair, A AF Elci, OC Dosemeci, M Blair, A TI Occupation and the risk of laryngeal cancer in Turkey SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE cancer; case-control study; case-referent study; larynx; occupational epidemiology ID ORAL CAVITY; EXPOSURE; ALCOHOL; SMOKING; WORKERS; CARCINOMA; ACID AB Objectives A hospital-based case-referent study was conducted in Turkey to provide further information on occupational risk factors and laryngeal cancer. Methods Among 7631 cancer cases seen at an oncology treatment center between 1979 and 1984, 958 laryngeal cancer cases were identified among men. Occupational history, tobacco and alcohol use, and demographic data were obtained from patients with a standardized questionnaire. Special 7-digit standard occupational and industrial codes were created to classify the job and industrial titles of the subjects. After exclusions, 940 laryngeal cancer cases and 1519 referents were available for study. Age-, smoking- and alcohol-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. Results Excess laryngeal cancer occurred among guards (OR 1.5, 95% CI 1.1-2.1), production supervisors (OR 1.8, 95% CI 1.1-3.1), textile workers (OR 1.9, 95% CI 1.2-3.3), drivers (OR 1.7, 95% CI 1.1-2.4), construction workers (OR 1.7, 95% CI 1.2-2.6), and workers in grain mills (OR 3.1, 95% CI: 1.3-7.6), trade unions (OR 3.6, 95% CI: 1.1-11.7) and local government services (OR 4.7, 95% CI 1.7-12.5). Supraglottic cancer was excessive among the textile workers, construction workers, and local government laborers, all with potential dust exposure. The risks of the general managers, electricians, and workers from industries such as pharmaceutical production, industrial machinery production, electric utilities, and retail services were lower than expected. Conclusions The risk of laryngeal cancer was associated with several occupations, and supraglottic larynx cancer appears to be more common among workers in dusty occupations and industries. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Elci, OC (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8111,MSC 7240, Rockville, MD 20852 USA. NR 42 TC 15 Z9 16 U1 1 U2 2 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD AUG PY 2001 VL 27 IS 4 BP 233 EP 239 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 470VN UT WOS:000170892000004 PM 11560337 ER PT J AU Bakke, B Ulvestad, B Stewart, P Lund, MB Eduard, W AF Bakke, B Ulvestad, B Stewart, P Lund, MB Eduard, W TI Effects of blasting fumes on exposure and short-term lung function changes in tunnel construction workers SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE alpha-quartz; explosives; diesel exhaust; nitrogen dioxide ID PULMONARY-FUNCTION; NITROGEN-DIOXIDE; HEALTH; FORMALDEHYDE; INFLAMMATION; HUMANS; ANTIOXIDANT; PARTICULATE; RESPONSES; INDUSTRY AB Objectives This study attempts to determine the effects of exposure to blasting fumes and its influence on the lung function of tunnel workers. Methods Two groups of tunnel workers, one using ammonium nitrate fuel oil (ANFO) as the explosive and the other using size-sensitized emulsion (SSE), with 24 workers per group, were compared with a reference group (N=34) with low exposure. Spirometry was used to determine lung function. Personal exposure to total and respirable dust, alpha-quartz, volatile organic compounds, oil mist and vapors, formaldehyde, nitrogen dioxide, and carbon monoxide was measured. Results The ANFO workers were more exposed to all the agents than the reference group and more exposed than the SSE workers to all the agents except total dust and carbon monoxide. The SSE workers were significantly more exposed to total dust and alpha-quartz than the reference group. High peak exposures to nitrogen dioxide (up to 20 ppm) occurred for the ANFO workers in contrast to the SSE workers, whose exposure did not exceed 2 ppm. The lung function of the ANFO workers significantly decreased by 3% for forced vital capacity, 7% for forced expiratory volume in 1 second, and 8% for forced expiratory flow rate from 25% to 75% of the forced vital capacity over the 11-day period. The changes were reversible. There were no significant changes among the SSE workers and the outdoor workers. The ANFO workers had a significant decrease in FEV1.0 when compared with both the SSE and outdoor workers. Conclusions Tunnel workers using ANFO explosive show a temporary reduction in lung function, whereas those using SSE do not. The most likely explanation for the observed changes is peak exposures to nitrogen dioxide. C1 Natl Inst Occupat Hlth, N-0033 Oslo, Norway. Selmer ASA, Oslo, Norway. Univ Oslo, Natl Hosp, Dept Thorac Med, N-0316 Oslo, Norway. NCI, Rockville, MD USA. RP Bakke, B (reprint author), Natl Inst Occupat Hlth, POB 8149 Dep, N-0033 Oslo, Norway. NR 38 TC 10 Z9 10 U1 1 U2 4 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD AUG PY 2001 VL 27 IS 4 BP 250 EP 257 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 470VN UT WOS:000170892000006 PM 11560339 ER PT J AU Wyatt, RJ Henter, I AF Wyatt, RJ Henter, I TI Rationale for the study of early intervention SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; early intervention; duration of untreated psychosis ID FIRST-EPISODE SCHIZOPHRENIA; LONG-TERM MORBIDITY; QUALITY-OF-LIFE; UNTREATED PSYCHOSIS; 1ST ADMISSIONS; TREATMENT RESPONSE; GENDER DIFFERENCES; DURATION; DECLINE; DISORDER AB Consistent but relatively weak evidence exists that treating patients with schizophrenia early in the course of their illness can decrease long-term morbidity. Relatedly, it is possible that treating individuals even earlier might produce better results. The findings presented set the stage for early and even earlier formal intervention studies, where the potential benefits are thought to outweigh the potential risks. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIMH, Neuropsychiat Branch, NIH, Bethesda, MD 20892 USA. RP Wyatt, RJ (reprint author), NIMH, Neuropsychiat Branch, NIH, 5415 W Cedar Lane,MSC 2610,Suite 106B, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 MH999999] NR 77 TC 59 Z9 60 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD AUG 1 PY 2001 VL 51 IS 1 SI SI BP 69 EP 76 DI 10.1016/S0920-9964(01)00242-0 PG 8 WC Psychiatry SC Psychiatry GA 459BR UT WOS:000170230400009 PM 11479068 ER PT J AU Figg, WD Arlen, P Gulley, J Fernandez, P Noone, M Fedenko, K Hamilton, M Parker, C Kruger, EA Pluda, J Dahut, WL AF Figg, WD Arlen, P Gulley, J Fernandez, P Noone, M Fedenko, K Hamilton, M Parker, C Kruger, EA Pluda, J Dahut, WL TI A randomized phase II trial of docetaxel (taxotere) plus thalidomide in androgen-independent prostate cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID TUMOR ANGIOGENESIS; PATHOLOGICAL STAGE; HORMONAL-THERAPY; CARCINOMA; METASTASIS; RESISTANT; MYELOMA; DENSITY; GRADE C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), NCI, Med Branch, Div Clin Sci, NIH, 10 Ctr Dr,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 40 TC 88 Z9 92 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2001 VL 28 IS 4 SU 15 BP 62 EP 66 DI 10.1016/S0093-7754(01)90157-5 PG 5 WC Oncology SC Oncology GA 480VM UT WOS:000171483500011 PM 11685731 ER PT J AU Paik, S Park, C AF Paik, S Park, C TI HER-2 and choice of adjuvant chemotherapy in breast cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID INTRINSIC CHEMORESISTANCE; C-ERBB-2 EXPRESSION; GENE-EXPRESSION; CELL-LINES; THERAPY; DOXORUBICIN; MUTATIONS; ERBB-2; ALPHA; WOMEN C1 Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA 15212 USA. RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, 4 Allegheny Ctr,5th Floor,E Commons Profess Bldg, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-12027, U10-CA-373777, U10-CA-69651, U10-CA-69974] NR 20 TC 15 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2001 VL 28 IS 4 BP 332 EP 335 DI 10.1016/S0093-7754(01)90127-7 PG 4 WC Oncology SC Oncology GA 461WQ UT WOS:000170387200003 PM 11498827 ER PT J AU Zwiebel, JA AF Zwiebel, JA TI Cancer gene and oncolytic virus therapy SO SEMINARS IN ONCOLOGY LA English DT Review ID AUTOLOGOUS BONE-MARROW; BREAST-CANCER; ADENOVIRAL VECTORS; PROSTATE-CANCER; IN-VITRO; PHASE-I; ATTENUATED ADENOVIRUS; TRANSGENE EXPRESSION; COMPLETE REGRESSION; MALIGNANT GLIOMA C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Zwiebel, JA (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 67 TC 27 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2001 VL 28 IS 4 BP 336 EP 343 DI 10.1053/sonc.2001.26145 PG 8 WC Oncology SC Oncology GA 461WQ UT WOS:000170387200004 PM 11498828 ER PT J AU Tan, AR Swain, SM AF Tan, AR Swain, SM TI Adjuvant chemotherapy for breast cancer: An update SO SEMINARS IN ONCOLOGY LA English DT Review ID HIGH-DOSE CHEMOTHERAPY; RANDOMIZED TRIAL; PREMENOPAUSAL WOMEN; STAGE-II; DOXORUBICIN-CYCLOPHOSPHAMIDE; FLUOROURACIL CHEMOTHERAPY; C-ERBB-2 EXPRESSION; PROTEIN-C; BONE LOSS; THERAPY C1 NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), NCI, Med Branch, Div Clin Sci, 10 Ctr Dr,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 100 TC 16 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2001 VL 28 IS 4 BP 359 EP 376 DI 10.1053/sonc.2001.26147 PG 18 WC Oncology SC Oncology GA 461WQ UT WOS:000170387200006 PM 11498830 ER PT J AU Mamounas, EP Fisher, B AF Mamounas, EP Fisher, B TI Preoperative (neoadjuvant) chemotherapy in patients with breast cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID SURGICAL ADJUVANT BREAST; RADIATION-THERAPY; RANDOMIZED TRIAL; PRIMARY TUMOR; CHEMOENDOCRINE THERAPY; MASTECTOMY; KINETICS; GROWTH; DOXORUBICIN; DISEASE C1 Aultman Canc Ctr, Canton, OH 44710 USA. Case Western Reserve Univ, Dept Surg, Canton, OH USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Mamounas, EP (reprint author), Aultman Canc Ctr, 2600 6th St SW, Canton, OH 44710 USA. NR 39 TC 40 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2001 VL 28 IS 4 BP 389 EP 399 DI 10.1053/sonc.2001.26150 PG 11 WC Oncology SC Oncology GA 461WQ UT WOS:000170387200008 PM 11498832 ER PT J AU Fisher, B Land, S Mamounas, E Dignam, J Fisher, ER Wolmark, N AF Fisher, B Land, S Mamounas, E Dignam, J Fisher, ER Wolmark, N TI Prevention of invasive breast cancer in women with ductal carcinoma in situ: An update of the national surgical adjuvant breast and bowel project experience SO SEMINARS IN ONCOLOGY LA English DT Review ID RECEPTOR-POSITIVE TUMORS; IN-SITU; INTRADUCTAL CARCINOMA; PATHOLOGICAL FINDINGS; RADIATION-THERAPY; TAMOXIFEN THERAPY; PROGNOSTIC INDEX; PROTOCOL B-17; FOLLOW-UP; ESTROGEN C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Aultman Hosp, Ctr Canc, Canton, OH USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), NSABP, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. FU NCI NIH HHS [U10-CA-12027, U10-CA-37377, U10-CA-69651, U10-CA-69974] NR 48 TC 306 Z9 323 U1 0 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD AUG PY 2001 VL 28 IS 4 BP 400 EP 418 DI 10.1053/sonc.2001.26151 PG 19 WC Oncology SC Oncology GA 461WQ UT WOS:000170387200009 PM 11498833 ER PT J AU Rompalo, AM Lawlor, J Seaman, P Quinn, TC Zenilman, JM Hook, EW AF Rompalo, AM Lawlor, J Seaman, P Quinn, TC Zenilman, JM Hook, EW TI Modification of syphilitic genital ulcer manifestations by coexistent HIV infection SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED DISEASES; TREPONEMA-PALLIDUM; HAEMOPHILUS-DUCREYI; WOMEN; AIDS; CLINICS; TYPE-2; DIAGNOSIS; ETIOLOGY AB Background. Conflicting data exist regarding whether HIV infection leads to changes in the clinical manifestations and severity of genital ulcer disease (GUD). Goal. To determine the impact of HIV on the etiology and clinical severity of GUD. Study Design: From July 1990 to July 1992, consecutive patients presenting to the two Baltimore City Health Department (BCHD) Sexually Transmitted Diseases clinics were approached as candidates for enrollment in a prospective study to determine factors associated with the transmission and acquisition of sexually transmitted diseases (STDs). Results: Of the 1368 patients who presented to the BCHD, 214 (16%) had genital ulcerations: 160 (21%) of 757 men and 54 (9%) of 611 women. Among the patients with GUD who had undergone HIV testing, 28 (14%) of 204 were infected with HIV: 25 (17%) of 151 men and 3 (6%) of 53 women. Although both groups-those infected with HIV and those not infected with HIV-presented with GUD of similar duration (10 versus 11 days; P = 0.17), multiple lesions were found more frequently in men with HIV infection than in uninfected men: 87% versus 62% (P = 0.02). Although not statistically significant, GUD in men with HIV infection more often were deep (64% versus 44%, respectively) rather than superficial (36% versus 57%, respectively; P = 0.08), and larger (505 mm(2) versus 109 mm(2); P = 0.06). Primary syphilis caused more GUD among men with HIV infection than among uninfected men: 9 (36%) of 25 versus 24 (19%) of 126, respectively (P < 0.01). Secondary syphilis was diagnosed with concomitant GUD more frequently among men with HIV infection than among uninfected men: 3 (13%) of 25 versus 3 (2%) of 123, respectively (P < 0.01). Conclusions: In this study, patients who presented with GUD were more likely to be infected with HIV. A higher proportion of men with HIV infection had multiple lesions, and the lesions were more likely to be caused by syphilis. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21287 USA. Baltimore City Dept Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. RP Rompalo, AM (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 1830 E Monument St,Room 435A, Baltimore, MD 21287 USA. FU NIAID NIH HHS [5 RO1 AI27727] NR 37 TC 50 Z9 54 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD AUG PY 2001 VL 28 IS 8 BP 448 EP 454 DI 10.1097/00007435-200108000-00004 PG 7 WC Infectious Diseases SC Infectious Diseases GA 459GF UT WOS:000170242100004 PM 11473216 ER PT J AU Brey, RL Abbott, RD Curb, JD Sharp, DS Ross, GW Stallworth, CL Kittner, SJ AF Brey, RL Abbott, RD Curb, JD Sharp, DS Ross, GW Stallworth, CL Kittner, SJ TI beta(2)-glycoprotein 1-dependent anticardiolipin antibodies and risk of ischemic stroke and myocardial infarction - The Honolulu Heart Program SO STROKE LA English DT Article DE antibodies, anticardiolipin; case-control studies; cerebrovascular disorders; myocardial infarction; prospective studies; risk factors ID SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTIPHOSPHOLIPID ANTIBODIES; CEREBRAL-ISCHEMIA; JAPANESE MEN; DISEASE; THROMBOSIS; ANTICOAGULANT; POPULATION; YOUNG; CARDIOLIPIN AB Background-It has been hypothesized that immunoreactivity to beta (2)-glycoprotein 1 (beta 2GP1)-dependent anticardiolipin antibody (aCL), but not beta 2GP1 -independent aCL, is associated with increased risk of ischemic stroke and myocardial infarction (MI). Methods-We performed a nested case-control study examining aCL as a risk factor for ischernic stroke and MI by using stored frozen sera obtained from subjects enrolled in the Honolulu Heart Program and followed for up for 20 years. We measured beta 2GP1-dependent and beta 2GP1-independent aCL and anti-beta 2GP1 immunoreactivity in 259 men who developed an ischemic stroke, in 374 men who developed an MI. and in a control group of 1360 men who remained free of both conditions. Results-Only beta 2GP1-dependent aCL of the IgG class was significantly associated with both incident ischemic stroke and MI. This association was attenuated in the last 5 years of the 20-year follow-up. For stroke, the risk factor-adjusted relative odds for men with a positive versus a negative beta 2GP1-dependent aCL of the IgG class were 2.2 (95% CI 1.5 to 3.4) at 15 years and 1.5 (95% CI 1.0 to 2.3) at 20 years. For MI, the adjusted relative odds were 1.8 (95% CI 1.2 to 2.6) at 15 years and 1.5 (95% CI 1.1 to 2.1) at 20 years. Conclusions-These data suggest that aCL IgG, particularly the beta 2GP1 -dependent variety, is an important predictor of future stroke and MI in men. C1 Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. Univ Texas, Hlth Sci Ctr, Div Neurol, San Antonio, TX USA. Univ Virginia, Sch Med, Div Biostat, Charlottesville, VA USA. Univ Hawaii, John A Burns Sch Med, Honolulu Heart Progra, Dept Med, Honolulu, HI 96822 USA. Kuakini Med Ctr, Honolulu, HI USA. Honolulu Dept Vet Affairs, Honolulu, HI USA. NHLBI, Bethesda, MD 20892 USA. Baltimore Dept Vet Affairs Med Ctr, Dept Epidemiol & Prevent Med, Baltimore, MD USA. Baltimore Dept Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD USA. RP Kittner, SJ (reprint author), Univ Maryland, Sch Med, Dept Neurol, Box 175,22 S Greene st, Baltimore, MD 21201 USA. FU NCRR NIH HHS [5MO1 RR-01346]; NINDS NIH HHS [R01 NS-33910] NR 40 TC 145 Z9 151 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD AUG PY 2001 VL 32 IS 8 BP 1701 EP 1706 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 461WT UT WOS:000170387400002 PM 11486093 ER PT J AU Nicolson, DH Arculus, D AF Nicolson, DH Arculus, D TI Candidates for neotypification of Blanco's names of Philippine plants: specimens in the US National Herbarium SO TAXON LA English DT Article DE Blanco; Merrill; Philippine plants; US National Herbarium AB Evidence suggests that of the widely distributed sets of E. D. Merrill's "illustrative specimens" for F. M. Blanco's names of Philippine plants, the first, most complete, and best labelled extant set is the one at the U.S. National Herbarium. Workers considering neotypification of Blanco's plant names should give special consideration to the materials at US. C1 Smithsonian Inst, Natl Museum Nat Hist, Dept Bot, Washington, DC 20560 USA. Natl Lib Med, Bethesda, MD 20894 USA. RP Nicolson, DH (reprint author), Smithsonian Inst, Natl Museum Nat Hist, Dept Bot, Washington, DC 20560 USA. NR 12 TC 7 Z9 8 U1 0 U2 0 PU INT ASSOC PLANT TAXONOMY PI BERLIN PA BOTANISCHER GARTEN BOTANISCHES MUSEUM BERLIN-DAHLEM, KONIGIN-LUISE-STRABE 6-8, D-14191 BERLIN, GERMANY SN 0040-0262 J9 TAXON JI Taxon PD AUG PY 2001 VL 50 IS 3 BP 947 EP 954 PG 8 WC Plant Sciences; Evolutionary Biology SC Plant Sciences; Evolutionary Biology GA 475FU UT WOS:000171152300024 ER PT J AU Smallridge, RC Castro, MR Morris, JC Young, PR Reynolds, JC Merino, MJ Sarlis, NJ AF Smallridge, RC Castro, MR Morris, JC Young, PR Reynolds, JC Merino, MJ Sarlis, NJ TI Renal metastases from thyroid papillary carcinoma: Study of sodium iodide symporter expression SO THYROID LA English DT Article; Proceedings Paper CT 72nd Annual Meeting of the American-Thyroid-Association CY SEP 29-OCT 03, 1999 CL PALM BEACH, FLORIDA SP Amer Thyroid Assoc ID WHOLE-BODY SCANS; DISTANT METASTASES; SODIUM/IODIDE SYMPORTER; MONOCLONAL-ANTIBODIES; CLINICAL UTILITY; GENE-EXPRESSION; I-131 THERAPY; P53 PROTEIN; CANCER; THYROGLOBULIN AB Kidney metastases from thyroid cancer are rare. We report two such patients and demonstrate that the in vivo I-131 uptake by the kidney metastasis is associated with high levels of sodium iodide (Na+/I-) symporter (NIS) expression in the first case. Case 1: A 61-year-old woman with papillary thyroid carcinoma-follicular variant (PTC-FV) presented with scapular metastasis. After thyroidectomy and scapulectomy, a I-131 posttherapy scan showed left upper quadrant uptake. A 3.0-cm metastatic PTC-FV deposit was removed by partial nephrectomy. Case 2: A 53-year-old woman presented with back pain. A computed tomography (CT) scan showed a 3.5-cm renal mass, a multinodular goiter, and lung metastases thought secondary to a renal cell carcinoma. A unilateral nephrectomy revealed metastatic PTC-FV. After thyroidectomy, a I-131 posttherapy scan showed lung and skeletal metastases. NIS immunoreactivity in tumoral tissue was strongly positive in the primary tumor, shoulder, and kidney metastasis in case 1, as well as in the primary tumor in case 2. Spotty, low-level NIS expression was observed in the kidney metastasis in case 2. In conclusion, kidney metastases of PTC-FV may occasionally retain adequate levels of NIS expression, enabling their detection during life. Thus, intense uptake in the abdomen during I-131 imaging should not be assumed to be physiological gastrointestinal tract residual radionuclide activity. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Dept Med, Div Endocrinol, Jacksonville, FL 32224 USA. Mayo Clin, Dept Med, Div Endocrinol, Rochester, MN USA. Mayo Clin, Dept Surg, Div Urol, Jacksonville, FL 32224 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,Room 8D12C,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. NR 58 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD AUG PY 2001 VL 11 IS 8 BP 795 EP 804 DI 10.1089/10507250152484664 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 463MQ UT WOS:000170480300014 PM 11525275 ER PT J AU Aframian, DJ Zheng, C Goldsmith, CM Nikolovski, J Cukierman, E Yamada, KM Mooney, DJ Birkedal-Hansen, H Baum, BJ AF Aframian, DJ Zheng, C Goldsmith, CM Nikolovski, J Cukierman, E Yamada, KM Mooney, DJ Birkedal-Hansen, H Baum, BJ TI Using HSV-thymidine kinase for safety in an allogeneic salivary graft cell line SO TISSUE ENGINEERING LA English DT Article ID SUICIDE GENE-THERAPY; RETROVIRAL VECTOR; ADENOVIRAL VECTOR; NECK-CANCER; IN-VIVO; EXPRESSION; GLAND; PROTEIN; MATRIX; GROWTH AB Extreme salivary hypofunction is a result of tissue damage caused by irradiation therapy for cancer in the head and neck region. Unfortunately, there is no currently satisfactory treatment for this condition that affects up to 40,000 people in the United States every year. As a novel approach to managing this problem, we are attempting to develop an orally implantable, fluid-secreting device (an artificial salivary gland). We are using the well-studied HSG salivary cell line as a potential allogeneic graft cell for this device. One drawback of using a cell line is the potential for malignant transformation. If such an untoward response occurred, the device could be removed. However, in the event that any HSG cells escaped, we wished to provide additional patient protection. Accordingly, we have engineered HSG cells with a hybrid adeno-retroviral vector, AdLTR. CMV-tk, to express the herpes simplex virus thymidine kinase (HSV-tk) suicide gene as a novel safety factor. Cells were grown on plastic plates or on poly-L-lactic acid disks and then transduced with different multiplicities of infection (MOIs) of the hybrid vector. Thereafter, various concentrations of ganciclovir (GCV) were added, and cell viability was tested. Transduced HSG cells expressed HSV-tk and were sensitive to GCV treatment. Maximal effects were seen at a MOI of 10 with 50 muM of GCV, achieving 95% cell killing on the poly-L-lactic acid substrate. These results suggest that engineering the expression of a suicide gene in an allogeneic graft cell may provide additional safety for use in an artificial salivary gland device. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Matrix Met Prot Unit, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, Bldg 10,Rm 1N113,MSC-1190, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 34 TC 13 Z9 13 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD AUG PY 2001 VL 7 IS 4 BP 405 EP 413 DI 10.1089/10763270152436463 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 459EL UT WOS:000170238000005 PM 11506730 ER PT J AU Moser, VC Barone, S Smialowicz, RJ Harris, MW Davis, BJ Overstreet, D Mauney, M Chapin, RE AF Moser, VC Barone, S Smialowicz, RJ Harris, MW Davis, BJ Overstreet, D Mauney, M Chapin, RE TI The effects of perinatal tebuconazole exposure on adult neurological, immunological, and reproductive function in rats SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Society-for-Toxicology CY MAR 14-18, 1999 CL NEW ORLEANS, LOUISIANA SP Soc Toxicol DE tebuconazole; developmental neurotoxicity; immunotoxicity; reproductive toxicity; rats ID OBSERVATIONAL BATTERY; MICE; NEUROTOXICITY; TRIADIMEFON; FUNGICIDES; EXPRESSION; IMMUNE; SYSTEM; FETAL AB Studies are under way to address concerns of potential persistent immunotoxic, reproductive, and neurotoxic effects of perinatal exposure to several pesticides. Tebuconazole, a triazole fungicide, was evaluated as part of this project. Sprague-Dawley dams were administered tebuconazole (0, 6, 20, or 60 mg/kg) by oral gavage daily from gestational day 14 to postnatal day (PND)7; the pups were then dosed daily at the same levels from PND7-42. Separate groups of rats were used for testing of immunological parameters, neurobehavioral testing using a screening battery of functional tests, and cognitive evaluations. Other groups of rats were evaluated for reproductive development and function, while yet others were sacrificed at the end of the dosing period for histological analyses of major organs systems, including neuropathological assessments. Pup viability and body weight were decreased in the highest dose group. There were no differences in the fertility indices in the exposed rats mated as adults. In the sheep RBC-immunized high-dose rats, spleen weights and cellularity were increased, and the ratio of cell types was altered compared to controls. There were, however, no biologically significant changes in the immune function of these rats. At necropsy on PND46 or 152, kidney, liver, and spleen weights were altered by tebuconazole treatment, but a dose-response relationship was not clear for most organs; only decreased kidney and increased liver weights were consistent in both sexes. Histological analyses were generally unremarkable outside of the brain. One month after the end of dosing, acquisition of learning the platform location in a water tank (i.e., Morris water maze) was impaired in the high-dose group; there were no differences in neuromuscular ability, motor activity, or swim speed to account for this finding. Furthermore, there was no effect on recall of the position during a free-swim trial. Neuropathological evaluations revealed pyknotic cells across hippocampal cell fields in animals of all tebuconazole, treatment groups, with the highest incidence in the 20 and 60 mg/kg/day dose groups, coincident with cell loss within pyramidal cell layer of CA3-4 cell fields of the hippocampus and layer V of the neocortex. Thus, perinatal exposure to tebuconazole produced neurobehavioral deficits and neuropathology in rats, but did not alter immunological or reproductive function. C1 US EPA, Div Neurotoxicol, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. US EPA, Div Environm Toxicol, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. NIEHS, Natl Toxicol Program, Reprod Toxicol Grp, Res Triangle Pk, NC 27709 USA. ASI Inc, Durham, NC USA. RP Moser, VC (reprint author), US EPA, NTD, MD-74B, Res Triangle Pk, NC 27711 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES-55385] NR 42 TC 27 Z9 28 U1 3 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2001 VL 62 IS 2 BP 339 EP 352 DI 10.1093/toxsci/62.2.339 PG 14 WC Toxicology SC Toxicology GA 457NP UT WOS:000170143900019 PM 11452147 ER EF