FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Aravind, L Subramanian, G AF Aravind, L Subramanian, G TI Origin of multicellular eukaryotes - insights from proteome comparisons SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Article ID CAENORHABDITIS-ELEGANS; PROTEINS; DOMAIN; FAMILY; BINDING; DIVERGENCE; YEAST; MODEL; PLANT AB The complete genomes of the yeast Saccharomyces cerevisiae and the nematode worm Caenorhabditis elegans have recently become available allowing the comparison of the complete protein sets of a unicellular and multicellular eukaryote for the first time. These comparisons reveal some striking trends in terms of expansions or extensive shuffling of specific domains that are involved in regulatory functions and signaling. Similar comparisons with the available sequence data from the plant Arabidopsis thaliana produce consistent results. These observations have provided useful insights regarding the origin of multicellular organisms. C1 Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20894 USA. RP Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. EM aravind@ncbi.nlm.nih.gov; GSubrama@niaid.nih.gov NR 41 TC 38 Z9 40 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X EI 1879-0380 J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD DEC PY 1999 VL 9 IS 6 BP 688 EP 694 DI 10.1016/S0959-437X(99)00028-3 PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 266AF UT WOS:000084277900011 PM 10607613 ER PT J AU Blumberg, RS Saubermann, LJ Strober, W AF Blumberg, RS Saubermann, LJ Strober, W TI Animal models of mucosal inflammation and their relation to human inflammatory bowel disease SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID CD4(+) T-CELLS; COLITIC C3H/HEJBIR MICE; ALPHA MUTANT MICE; IL-2-DEFICIENT MICE; BACTERIAL-ANTIGENS; EPITHELIAL-CELL; TRANSGENIC MICE; GAMMA; EXPRESSION; ANTIBODY AB Animal models of inflammatory bowel disease (IBD) have been useful in the identification of those immune responses uniquely involved in IBD pathogenesis and in defining the important roles of environmental influences, such as normal luminal bacterial flora and the genetic composition of the host, in modifying IBD-associated inflammation. Recent studies have focused particular attention on CD4(+) T cells which produce excessive quantities either of Th1 cytokines (IFN-gamma and TNF) directed by IL-12 or of a Th2 cytokine (IL-4), relative to the production of suppressive cytokines such as IL-10 and transforming growth factor beta. Such insights will be extremely beneficial in the development of novel approaches to the control of is D-type inflammation, such as the use of anticytokine therapies and gene therapy and, finally, in the identification of the genetic abnormalities and the antigens driving the inflammation that underlies the human disease. C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Digest Dis Ctr, Boston, MA 02115 USA. NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. RP Blumberg, RS (reprint author), Brigham & Womens Hosp, Div Gastroenterol, 75 Francis St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK44319, DK51362, DK53056] NR 55 TC 343 Z9 353 U1 1 U2 16 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 DEC PY 1999 VL 11 IS 6 BP 648 EP 656 DI 10.1016/S0952-7915(99)00032-1 PG 9 WC Immunology SC Immunology GA 260CE UT WOS:000083930100010 PM 10631550 ER PT J AU Griffiths, MM Encinas, JA Remmers, EF Kuchroo, VK Wilder, RL AF Griffiths, MM Encinas, JA Remmers, EF Kuchroo, VK Wilder, RL TI Mapping autoimmunity genes SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SYSTEMIC LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; MULTIPLE-SCLEROSIS; TRANSGENIC MICE; LINKAGE; MODEL; GENETICS AB Rat and mouse models for the major human autoimmune/inflammatory diseases are under intense genetic scrutiny. Genome-wide linkage studies reveal that each model is regulated by multiple genetic loci, Many of these loci colocalize to homologous genomic regions associated with several different autoimmune diseases of mice, rats and humans. Candidate genes are being identified, Polymorphic alleles associated with these chromosomal segments may represent predisposing genetic elements common to a number of human diseases with very different clinical presentations. C1 Univ Utah, Sch Med, Dept Med, Vet Affairs Med Ctr,Res Serv, Salt Lake City, UT 84132 USA. Brigham & Womens Hosp, Dept Med, Ctr Neurol Dis, Boston, MA 02115 USA. Bayer Yakuhin Ltd, Res Ctr, Kyoto 6190216, Japan. NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Griffiths, MM (reprint author), Univ Utah, Sch Med, Dept Med, Vet Affairs Med Ctr,Res Serv, 50 N Med Dr, Salt Lake City, UT 84132 USA. NR 78 TC 65 Z9 65 U1 0 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 DEC PY 1999 VL 11 IS 6 BP 689 EP 700 DI 10.1016/S0952-7915(99)00038-2 PG 12 WC Immunology SC Immunology GA 260CE UT WOS:000083930100016 PM 10631556 ER PT J AU Englert, CR Petricoin, EF Krizman, DB Emmert-Buck, MR AF Englert, CR Petricoin, EF Krizman, DB Emmert-Buck, MR TI Molecular profiling of human cancer: New opportunities SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE genomics; Human Genome Project; microdissection; microarrays; molecular profiling; tissue proteomics ID LASER CAPTURE MICRODISSECTION; GENE-EXPRESSION PROFILES; HUMAN-GENOME; SERIAL ANALYSIS; SINGLE CELLS; TISSUE; MICROARRAYS; PROTEOMICS; PROJECT; BIOLOGY AB The Human Genome Project will be completed in the near future, providing new opportunities for researchers to better understand human biology. In order to maximize the value of the genetic data, high-throughput molecular analyses will become an essential experimental methodology, allowing global views of gene expression to be produced and examined. As an example, this approach will permit investigators studying cancer to comprehensively examine the genes and gene products whose alterations underlie tumor development and progression. This information will be essential in determining the fundamental causes of human neoplasms as well as having immediate practical value in the development of clinically useful diagnostic markers and therapeutic targets. C1 NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biolog & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Gaithersburg, MD 20877 USA. RP Englert, CR (reprint author), NIH, Howard Hughes Med Inst, Res Scholars Program, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Howard Hughes Medical Institute NR 39 TC 1 Z9 1 U1 0 U2 0 PU PHARMAPRESS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD DEC PY 1999 VL 1 IS 6 BP 712 EP 719 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 342HL UT WOS:000088639100007 PM 19629868 ER PT J AU Shenoy, S Sobel, M Harris, RB AF Shenoy, S Sobel, M Harris, RB TI Development of heparin antagonists with focused biological activity SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID ISOTHERMAL TITRATION CALORIMETRY; MOLECULAR-WEIGHT HEPARIN; VONWILLEBRAND-FACTOR; PROTAMINE REACTIONS; ANTITHROMBIN-III; BINDING; REVERSAL; ANTICOAGULATION; SULFATE; INHIBITION AB Heparin, a complex glycosaminoglycan, has long been used to temporarily render the blood incoagulable during extracorporeal circulation, cardiovascular surgery, and other arterial interventions. But bleeding complications are especially common when the arterial tree is violated, occurring in as many as 10-15% of cases. For cardiovascular surgery and many related interventions, protamine has long been the standard antagonist when acute and complete neutralization of heparin's anticoagulant effect is necessary. Protamine's efficacy is related in part to its total net cationic charge, but unfortunately so is its toxicity. For these reasons, there is renewed interest in developing heparin antagonists which will replace the use of protamine. At Commonwealth Biotechnologies, Inc., we have used a rationale design approach for the preparation of a family of low molecular weight helix peptides which bind heparin with high affinity. For each of the new compounds, we have assessed their ability to bind heparin using isothermal titration calorimetry and circular dichroism spectrometry and have examined potential complexes formed with the anticoagulant pentasaccharide unit of heparin using molecular modeling techniques. The biological potencies of these compounds were assessed in ex vivo experiments where their ability to compete with antithrombin for binding heparin was determined. The best of the compounds, designated HepArrest(TM), is highly effective in reversing heparin-mediated and HepArrest is a safer drug than protamine because of reduced adverse hemodynamic side effects compared with those associated with protamine. HepArrest binds low molecular weight heparins and causes reversal of anticoagulation by low molecular weight heparins, as determined by activated partial thromboplastin time, thrombin time, or factor Xa neutralization assays. These highly promising preclinical results indicate that HepArrest is a novel heparin neutralizing agent that may well fill a substantial unmet need for vascular surgeons and cardiac anesthesiologists who perform coronary artery bypass grafts and several other major vascular surgeries, as well as for cardiologists and interventional radiologists. C1 Commonwealth Biotechnol Inc, Richmond, VA 23235 USA. Syracuse VA Med Ctr, Surg Serv 112, Syracuse, NY 13210 USA. RP NCI, Frederick, MD 21701 USA. EM rharris@cbi-biotech.com NR 53 TC 18 Z9 18 U1 4 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 EI 1873-4286 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD DEC PY 1999 VL 5 IS 12 BP 965 EP 986 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 265NQ UT WOS:000084250600001 PM 10607857 ER PT J AU Liang, BT Swierkosz, TA Herrmann, HC Kimmel, S Jacobson, KA AF Liang, BT Swierkosz, TA Herrmann, HC Kimmel, S Jacobson, KA TI Adenosine and ischemic preconditioning SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID A(3) RECEPTOR; CORONARY ANGIOPLASTY; INFARCT SIZE; IN-VITRO; INTRACORONARY ADENOSINE; NONXANTHINE ANTAGONIST; MYOCARDIAL PROTECTION; VENTRICULAR-FUNCTION; RADIOLIGAND BINDING; ACTIVATION AB Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. C1 Univ Penn, Med Ctr, Dept Med, Div Cardiovasc, Philadelphia, PA 19104 USA. NIH, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Liang, BT (reprint author), Univ Penn, Med Ctr, Dept Med, Div Cardiovasc, 956 BRBII-III,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 83 TC 17 Z9 21 U1 0 U2 1 PU BENTHAM SCIENCE PUBL BV PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PD DEC PY 1999 VL 5 IS 12 BP 1029 EP 1041 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 265NQ UT WOS:000084250600004 PM 10607860 ER PT J AU Kobayashi, H Tagaya, Y Han, ES Kim, IS Le, N Paik, CH Pastan, I Nelson, DL Waldmann, TA Carrasquillo, JA AF Kobayashi, H Tagaya, Y Han, ES Kim, IS Le, N Paik, CH Pastan, I Nelson, DL Waldmann, TA Carrasquillo, JA TI Use of an antibody against the soluble interleukin 2 receptor alpha subunit can modulate the stability and biodistribution of interleukin 2 SO CYTOKINE LA English DT Article DE immunotherapy; interleukin-2; monoclonal antibody; soluble receptor ID HAIRY-CELL LEUKEMIA; MONOCLONAL-ANTIBODY; RECOMBINANT INTERLEUKIN-2; FV FRAGMENT; CYTOKINE RECEPTORS; ANTITUMOR-ACTIVITY; TAC ANTIGEN; BINDING; DISEASE; IL-2 AB The authors have previously reported that the soluble serum form of the alpha subunit of the IL-2 receptor (sIL-2R alpha), whose natural half-life is approximately 40 min, survived much longer in the circulation when bound by a specific antibody, In the present study, the authors evaluated the extent to which sIL-2R alpha protected IL-2 in freshly collected serum using biochemical analyses, and a functional CTLL-2 assay. In particular, sIL-2R alpha protected IL-2 from forming complexes with alpha(2)-macroglobulin and from inactivation in vitro. In addition, the authors demonstrated that the anti-IL-2R alpha monoclonal antibody 7G7/B6, which does not inhibit the binding of IL-2 to its binding site on sIL-2R alpha, protected IL-2 from degradation and inactivation in vivo in the presence of sIL-2R alpha. Both I-125-labelled and unlabelled IL-2 were injected into mice preinjected with humanized anti-Tac (hTac) or 7G7/B6 and sIL-2R alpha, or sIL-2R alpha alone. Using size-exclusion HPLC, ELISA, and CTLL-2 cell proliferation assays, we observed that the presence of 7G7/B6 led to formation of complexes with sIL-2R alpha and increased the serum levels of IL-2 more than 3- to 40-fold those of groups receiving IL-2 alone, sIL-2R alpha, or hTac, Taken as a whole, these results suggest that the complex of 7G7/B6 and sIL-2R alpha not only prolongs the survival of IL-2 in vivo, but also maintains the bioactivity of IL-2, The use of antibodies against endogenous soluble receptors could increase the in vivo survival of cytokines, protect their bioactivity and thereby facilitate their clinical use in the treatment of various malignancies and AIDS. (C) 1999 Academic Press. C1 NCI, Dept Nucl Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Diagnost & Intervent Radiol, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan. RI Carrasquillo, Jorge/E-7120-2010 NR 49 TC 7 Z9 8 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 1043-4666 J9 CYTOKINE JI Cytokine PD DEC PY 1999 VL 11 IS 12 BP 1065 EP 1075 DI 10.1006/cyto.1999.0509 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 274QC UT WOS:000084775700009 PM 10623432 ER PT J AU Telford, WG Cox, WG Stiner, D Singer, VL Doty, SB AF Telford, WG Cox, WG Stiner, D Singer, VL Doty, SB TI Detection of endogenous alkaline phosphatase activity in intact cells by flow cytometry using the fluorogenic ELF-97 phosphatase substrate SO CYTOMETRY LA English DT Article DE fluorescence; flow cytometry; alkaline phosphatase; ELF-97; fast red violet RB ID FAST RED; QUANTIFICATION; HYBRIDIZATION; ASSAY AB Background: The alkaline phosphatase (AP) substrate 2-(5'-chloro-2'-phosphoryloxyphenyl)-6-chloro-4-(3H)-azolinone (ELF(R)-97 for enzyme-labeled fluorescence) was been found useful for the histochemical detection of endogenous AP activity and AP-tagged proteins and oligonucleotide probes. In this study, we evaluated its effectiveness at detecting endogenous AP activity by flow cytometry. Methods: The ELF-97 phosphatase substrate was used to detect endogenous AP activity in UMR-106 rat osteosarcoma cells and primary cultures of chick chondrocytes. Cells were labeled with the ELF-97 reagent and analyzed by flow cytometry using an argon ultraviolet (UV) laser. For comparison purposes, cells were also assayed for AP using a Fast Red Violet LB azo dye assay previously described for use in detecting AP activity by flow cytometry. Results: The ELF-97 phosphatase substrate effectively detected endogenous AP activity in UMR-106 cells, with over 95% of the resulting fluorescent signal resulting from AP-specific activity (as determined by levamisole inhibition of AP activity). In contrast, less than 70% of the fluorescent signal from the Fast Red Violet LB (FRV) assay was AP-dependent, reflecting the high intrinsic fluorescence of the unreacted components. The ELF-97 phosphatase assay was also able to detect very low AP activity in chick chondrocytes that was undetectable by the azo dye method. Conclusions: The ELF-97 phosphatase assay was able to detect endogenous AP activity in fixed mammalian and avian cells by flow cytometry with superior sensitivity to previously described assays. This work also shows the applicability of ELF-97 to flow cytometry, supplementing its previously demonstrated histochemical applications. Cytometry 37:314-319, 1999. (C) 1999 Wiley-Liss, Inc. C1 Hosp Special Surg, Immunol & Inflammat Sect, New York, NY 10021 USA. Mol Probes Inc, Eugene, OR 97402 USA. Hosp Special Surg, Mineralized Tissue Sect, New York, NY 10021 USA. RP Telford, WG (reprint author), NCI, Med Branch, NIH, DCS, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 17 Z9 19 U1 4 U2 6 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 DEC 1 PY 1999 VL 37 IS 4 BP 314 EP 319 DI 10.1002/(SICI)1097-0320(19991201)37:4<314::AID-CYTO9>3.0.CO;2-X PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 260FH UT WOS:000083938500009 PM 10547617 ER PT J AU Supp, DM Brueckner, M Kuehn, MR Witte, DP Lowe, LA McGrath, J Corrales, J Potter, SS AF Supp, DM Brueckner, M Kuehn, MR Witte, DP Lowe, LA McGrath, J Corrales, J Potter, SS TI Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries SO DEVELOPMENT LA English DT Article DE left-right asymmetry; situs inversus; dynein; ATP; mouse ID LEFT-RIGHT AXIS; SITUS-INVERSUS; TRANSCRIPTION FACTORS; CHICK EMBRYOGENESIS; NODAL EXPRESSION; IMMOTILE CILIA; MOUSE; MUTATION; PITX2; MICE AB Vertebrates develop distinct asymmetries along the left-right axis, which are consistently aligned with the anteroposterior and dorsoventral axes. The mechanisms that direct this handed development of left-right asymmetries have been elusive, but recent studies of mutations that affect left-right development have shed light on the molecules involved. One molecule implicated in left-right specification is left-right dynein (LRD), a microtubule-based motor protein. In the LRD protein of the inversus viscerum (iv) mouse, there is a single amino acid difference at a conserved position, and the lrd gene is one of many genes deleted in the legless (Igl) mutation. Both iv and Igl mice display randomized left-right development. Here we extend the analysis of the lrd gene at the levels of sequence, expression and function, The complete coding sequence of the lrd gene confirms its classification as an axonemal, or ciliary, dynein, Expression of bd in the node at embryonic day 7.5 is shown to be symmetric, At embryonic day 8.0, however, a striking asymmetric expression pattern is observed in all three germ layers of the developing headfold, suggesting roles in both the establishment and maintenance of left-right asymmetries. At later times, expression of lrd is also observed in the developing floorplate, gut and limbs, These results suggest function for LRD protein in both cilitated and non-ciliated cells, despite its sequence classification as axonemal, In addition, a targeted mutation of lrd was generated that deletes the part of the protein required for ATP binding, and hence motor function. The resulting left-right phenotype, randomization of laterality, is identical to that of iv and Igl mutants. Gross defects in ciliary structure were not observed in lrd/lrd mutants. Strikingly, how-ever, the monocilia on mutant embryonic node cells were immotile, These results prove the identity of the iv and lrd genes. Further, they argue that LRD motor function, and resulting nodal monocilia movement, are required for normal left-right development. C1 Childrens Hosp Res Fdn, Div Mol Biol, Cincinnati, OH 45229 USA. Childrens Hosp Res Fdn, Div Dev Biol, Cincinnati, OH 45229 USA. Yale Sch Med, Dept Pediat Cardiol, New Haven, CT 06520 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Med Ctr, Dept Pathol, Cincinnati, OH 45229 USA. RP Potter, SS (reprint author), Childrens Hosp Res Fdn, Div Mol Biol, Cincinnati, OH 45229 USA. RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU NICHD NIH HHS [HD07200, HD24517, HD36439-01, R01 HD024517, T32 HD007200] NR 51 TC 162 Z9 163 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD DEC PY 1999 VL 126 IS 23 BP 5495 EP 5504 PG 10 WC Developmental Biology SC Developmental Biology GA 271PG UT WOS:000084602200028 PM 10556073 ER PT J AU Chang, WS Nunes, FD De Jesus-Escobar, JM Harland, R Wu, DK AF Chang, WS Nunes, FD De Jesus-Escobar, JM Harland, R Wu, DK TI Ectopic Noggin blocks sensory and nonsensory organ morphogenesis in the chicken inner ear SO DEVELOPMENTAL BIOLOGY LA English DT Article DE bone morphogenetic proteins; TUNEL; vestibule; Msx1; p75NGFR ID SEMICIRCULAR CANAL FORMATION; SPEMANN ORGANIZER; TOOTH DEVELOPMENT; XENOPUS EMBRYOS; MICE LACKING; EXPRESSION; MOUSE; PROTEINS; SOMITE; GENE AB Bone morphogenetic protein 4 (Bmp4) is expressed during multiple stages of development of the chicken inner ear. At the otocyst stage, Bmp4 is expressed in each presumptive sensory organ, as well as in the mesenchymal cells surrounding the region of the otocyst that is destined to form the semicircular canals. After the formation of the gross anatomy of the inner ear, Bmp4 expression persists in some sensory organs and restricted domains of the semicircular canals. To address the role of this gene in inner ear development, we blocked BMP4 function(s) by delivering one of its antagonists, Noggin, to the developing inner ear in ovo. Exogenous Noggin was delivered to the developing otocyst by using a replication-competent avian retrovirus encoding the Noggin cDNA (RCAS-N) or implanting beads coated with Noggin protein. Noggin treatment resulted in a variety of phenotypes involving both sensory and nonsensory components of the inner ear. Among the nonsensory structures, the semicircular canals were the most sensitive and the endolymphatic duct and sac most resistant to exogenous Noggin. Noggin affected the proliferation of the primordial canal outpouch, as well as the continual outgrowth of the canal after its formation. In addition, Noggin affected the structural patterning of the cristae, possibly via a decrease of Msx1 and p75NGFR expression. These results suggest that BMP4 and possibly other BMPs are required for multiple phases of inner ear development, (C) 1999 Academic Press. C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 USA. Univ Calif Berkeley, Dept Cell & Mol Biol, Div Biochem & Mol Biol, Berkeley, CA 94720 USA. RP Wu, DK (reprint author), Natl Inst Deafness & Other Commun Disorders, 5 Res Court,Room 2B34, Rockville, MD 20850 USA. RI Nunes, Fabio/B-4543-2011 OI Nunes, Fabio/0000-0002-7785-6785 NR 37 TC 78 Z9 86 U1 0 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 DEC 1 PY 1999 VL 216 IS 1 BP 369 EP 381 DI 10.1006/dbio.1999.9457 PG 13 WC Developmental Biology SC Developmental Biology GA 264GD UT WOS:000084171500028 PM 10588886 ER PT J AU Federici, M Giaccari, A Hribal, ML Giovannone, B Lauro, D Morviducci, L Pastore, L Tamburrano, G Lauro, R Sesti, G AF Federici, M Giaccari, A Hribal, ML Giovannone, B Lauro, D Morviducci, L Pastore, L Tamburrano, G Lauro, R Sesti, G TI Evidence for glucose/hexosamine in vivo regulation of insulin/IGF-I hybrid receptor assembly SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; SKELETAL-MUSCLE; DIABETIC RATS; HEXOSAMINE BIOSYNTHESIS; RELATIVE CONTRIBUTION; GLYCOGEN-SYNTHESIS; GLUCOSE-TRANSPORT; GENE-EXPRESSION; ALPHA-SUBUNIT; RESISTANCE AB Hybrid receptors composed of an insulin alpha beta-hemireceptor and a type 1 IGF alpha beta-hemireceptor are formed in tissues expressing both molecules. We recently reported an increased hybrid receptor expression in skeletal muscle of type 2 diabetic patients that is inversely correlated with in vivo insulin sensitivity. It is unclear whether these changes were due to primary abnormalities or to secondary derangements acting in vivo, such as hyperglycemia. To address this, we determined abundance of hybrids in skeletal muscle from three groups of rats: controls, diabetic (90% pancreatectomy), and diabetic treated with phlorizin to normalize plasma glucose levels. We found that the abundance of hybrid receptors was higher in diabetic rats compared with control and phlorizin-treated diabetic rats (percentage of I-125-insulin bound versus total added radioactivity [B/T] 1.8 +/- 0.11, 0.4 +/- 0.01 and 0.32 +/- 0.04, respectively; P < 0.0001). Fasting plasma glucose levels were positively correlated with hybrids abundance (r = 0.77, P < 0.002). Hybrid receptor protein content, assessed by immunoblotting, was 2.4-fold higher in diabetic rats as compared with control and phlorizin-treated diabetic rats. Because it has been shown that some of the regulatory effects of glucose may be mediated by the glucosamine pathway, we subsequently determined the effect of an in vivo glucosamine infusion on hybrid receptor formation. We found that abundance of hybrids was significantly higher in muscle from glucosamine-treated rats compared with control rats (B/T = 0.17 +/- 0.02 and 0.11 +/- 0.01, respectively; P < 0.009). Quantitation of hybrid content by immunoblotting revealed that their abundance was 1.9-fold higher in glucosamine-treated rats. The results demonstrate that I) elevated glucose levels in diabetic rats are associated with increased expression of hybrid receptors in muscle, 2) correction of hyperglycemia with phlorizin completely reverses increased expression of hybrids, and 3) glucosamine infused into control rats mimics the effects of hyperglycemia on hybrid receptor formation. Thus, the results support the hypothesis that glucose acting, at least in part, through the glucosamine pathway may play an important role in regulating hybrid receptor assembly in vivo. C1 Univ Roma Tor Vergata, Dipartimento Med Interna, Mol Med Lab, I-00173 Rome, Italy. Univ Roma La Sapienza, Div Endocrinol, Rome, Italy. Univ Cattolica Sacro Cuore, Inst Endocrinol, I-00168 Rome, Italy. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Sesti, G (reprint author), Univ Roma Tor Vergata, Dipartimento Med Interna, Mol Med Lab, Via Orazio Raimondo, I-00173 Rome, Italy. EM sesti@uniroma2.it RI Sesti, Giorgio/B-1509-2012; Federici, Massimo/G-9940-2012; Giaccari, Andrea/J-1889-2012; OI Federici, Massimo/0000-0003-4989-5194; Giaccari, Andrea/0000-0002-7462-7792; Lauro, Davide/0000-0002-8597-4415; Sesti, Giorgio/0000-0002-1618-7688 NR 39 TC 19 Z9 20 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1999 VL 48 IS 12 BP 2277 EP 2285 DI 10.2337/diabetes.48.12.2277 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259EE UT WOS:000083880900003 PM 10580414 ER PT J AU Zhou, J Wang, XL Pineyro, MA Egan, JM AF Zhou, J Wang, XL Pineyro, MA Egan, JM TI Glucagon-like peptide 1 and exendin-4 convert pancreatic AR42J cells into glucagon- and insulin-producing cells SO DIABETES LA English DT Article ID PROTEIN-KINASE-C; BETA-CELLS; TRANSCRIPTION FACTOR; GENE-TRANSCRIPTION; LINE AR42J; EXPRESSION; EXOCRINE; REGENERATION; GLUCOKINASE; SYSTEM AB In this article, we show that glucagon-like peptide 1 (GLP-1) can induce AR42J cells to differentiate into insulin, pancreatic polypeptide, and glucagon-positive cells. In their natural state, these cells, which are derived from a chemically induced pancreatic tumor, possess exocrine and neuroendocrine properties but are negative for islet hormones and their mRNAs, We found that when these cells were exposed to GLP-1 (1 or 10 nmol), a peptide normally released from the gut in response to food and a modulator of insulin release, intracellular cAMP levels mere increased, and proliferation of cells was increased for the first 24 h, followed by inhibition, Up to 50% of the cells became positive for islet hormones. The mRNAs for glucose transporter 2 and glucokinase were detected in the GLP-1-treated cells. Insulin was detected by radioimmunoassay (RIA) in the medium of GLP-1-treated cells, and the cells were capable of releasing insulin in a glucose-mediated fashion. Exendin-4, an analog of GLP-1, in some critical experiments performed in a similar manner to GLP-1, with the exception of it being 10-fold more potent. We therefore propose that GLP-1 and exendin-4 are capable of causing pancreatic precursor cells to differentiate into islet cells. C1 NIA, Diabet Sect, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Diabet Sect, Gerontol Res Ctr, NIH, Box 23,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 25 TC 253 Z9 270 U1 0 U2 10 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD DEC PY 1999 VL 48 IS 12 BP 2358 EP 2366 DI 10.2337/diabetes.48.12.2358 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259EE UT WOS:000083880900013 PM 10580424 ER PT J AU Lauro, D Kido, Y Hayashi, H Ebina, Y Accili, D AF Lauro, D Kido, Y Hayashi, H Ebina, Y Accili, D TI Expression of kinase-inactive mutant insulin receptors does not rescue insulin receptor-deficient mice from perinatal death SO DIABETOLOGIA LA English DT Letter ID MONOCLONAL-ANTIBODIES; TYROSINE KINASE C1 NIH, Bethesda, MD 20892 USA. RP Accili, D (reprint author), NIH, Bldg 10,Room 10D18, Bethesda, MD 20892 USA. OI Lauro, Davide/0000-0002-8597-4415 NR 8 TC 4 Z9 4 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD DEC PY 1999 VL 42 IS 12 BP 1441 EP 1442 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 266LE UT WOS:000084300800012 PM 10651265 ER PT J AU Dykman, DD Cuccherini, BA Fuss, IJ Blum, LW Woodward, JE Strober, W AF Dykman, DD Cuccherini, BA Fuss, IJ Blum, LW Woodward, JE Strober, W TI Whipple's disease in a father-daughter pair SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE interferon-gamma; interleukin-12; Tropheryma whippelii; Whipple's disease ID CENTRAL-NERVOUS-SYSTEM; TERM FOLLOW-UP; TRIMETHOPRIM-SULFAMETHOXAZOLE; RELAPSE C1 Anne Arundel Gastroenterol Associates PA, Glen Burnie, MD 21061 USA. NIAID, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs HQ, Med Res Serv 121E, Washington, DC USA. Anne Arundel Med Ctr, Dept Pathol, Annapolis, MD USA. RP Dykman, DD (reprint author), Anne Arundel Gastroenterol Associates PA, 200 Hosp Dr,Suite 502, Glen Burnie, MD 21061 USA. NR 18 TC 12 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 1999 VL 44 IS 12 BP 2542 EP 2544 DI 10.1023/A:1026607726745 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 270XX UT WOS:000084563400027 PM 10630510 ER PT J AU Fletcher, BW Battjes, RJ AF Fletcher, BW Battjes, RJ TI Introduction to the special issue: treatment process in DATOS SO DRUG AND ALCOHOL DEPENDENCE LA English DT Editorial Material DE DATOS; treatment process; cost-benefit model ID DRUG-ABUSE TREATMENT; FOLLOW-UP OUTCOMES; METHADONE-MAINTENANCE; TREATMENT RETENTION; COCAINE DEPENDENCE; TREATMENT SERVICES; TREATMENT CAREERS; CLIENT RETENTION; TIME SPENT; ADDICTION AB Several important findings from the drug abuse treatment outcome studies (DATOS) are presented in this issue of drug and alcohol dependence. These studies focus on the drug abuse treatment process in areas of engagement in treatment and participation in program activities, the effect of the patient's age and treatment history in predicting treatment retention and outcomes, and the impact of prior treatment experience on the level of treatment engagement and subsequent outcomes. A cost-benefit model for drug abuse treatment is developed. Significant contributions are made in the development of a comprehensive model of the treatment process, including the relationship of patient attributes, program factors, and outcomes. Findings on retention from the United Kingdom's national treatment outcome research study (NTORS), a study similar in design to DATOS, also are presented. (C) 1999 Elsevier Science Ireland Ltd. C1 NIDA, Serv Res Branch, Div Clin & Serv Res, NIH, Bethesda, MD 20892 USA. RP Fletcher, BW (reprint author), NIDA, Serv Res Branch, Div Clin & Serv Res, NIH, 6001 Execut Blvd,Room 4222, Bethesda, MD 20892 USA. NR 81 TC 13 Z9 13 U1 2 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD DEC 1 PY 1999 VL 57 IS 2 BP 81 EP 87 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 262GP UT WOS:000084057900001 PM 10617093 ER PT J AU Li, AH Ji, XD Kim, HS Melman, N Jacobson, KA AF Li, AH Ji, XD Kim, HS Melman, N Jacobson, KA TI Pyran template approach to the design of novel A(3) adenosine receptor antagonists SO DRUG DEVELOPMENT RESEARCH LA English DT Article DE G protein-coupled receptors; structure-activity relationships; template; radioligand binding; purines ID RAT-BRAIN; MAST-CELLS; DIHYDROPYRIDINE; DERIVATIVES; STIMULATION; ACTIVATION; LIGANDS AB A(3) adenosine receptor antagonists have potential as anti-inflammatory, anti-asthmatic, and anti-ischemic agents. We previously reported the preparation of chemical libraries of 1, 1-dihydropyridine (DHP) and pyridine derivatives and identification of members having high affinity at A(3) adenosine receptors. These derivatives were synthesized through standard three-component condensation/oxidation reactions, which permitted versatile ring substitution at five positions, i.e., the central ring served as a molecular scaffold for structurally diverse substituents. We extended this template approach from the DHP series to chemically stable pyran derivatives, in which the ring NH is replaced by O and which is similarly derived from a stepwise reaction of three components. Since the orientation of substituent groups may be conformationally similar to the 1,4-DH Ps, a direct comparison between the structure activity relationships of key derivatives in binding to adenosine receptors was carried out. Affinity at human Ag receptors expressed in CHO cells was determined vs, binding of [I-125]AB-MECA (N-6-(4-amino-3-iodobenzyl)-5'-N-methyl-carbamoyladenosine). There was no potency-enhancing effect, as was observed for DHPs, of 4-styryl, 4-phenylethynyl, or 6-phenyl substitutions. The most potent ligands in this group in binding to human A(3) receptors were 6-methyl and 6-phenyl analogs, 3a (MRS 1704) and 4a (MRS 1705), respectively, of 3,5-diethyl 2-methyl-4-phenyl-4H-pyran-3,5-dicarboxy which had K-i values of 381 and 583 nM, respectively. These two derivatives were selective for human A3 receptors vs. rat brain A(1) receptors by 57-fold and 24-fold, respectively. These derivatives were inactive in binding at rat brain A(2A) receptors, and at recombinant human A(2B) receptors displayed K-i values of 17.3 and 23.2 mu M, respectively. The selectivity, but not affinity of the pyran derivatives in binding to the A(3) receptor subtype was generally enhanced vs. the corresponding DHP derivatives. Drug Dev. Res. 48:171-177, 1999. Published 1999 Wiley-Liss, Inc.(+) C1 NIDDK, LBC, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, LBC, Mol Recognit Sect, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 33 TC 12 Z9 13 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0272-4391 J9 DRUG DEVELOP RES JI Drug Dev. Res. PD DEC PY 1999 VL 48 IS 4 BP 171 EP 177 DI 10.1002/(SICI)1098-2299(199912)48:4<171::AID-DDR4>3.0.CO;2-5 PG 7 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 285QN UT WOS:000085399900004 PM 27182099 ER PT J AU Lemkin, PF Myrick, JM Lakshmanan, Y Shue, MJ Patrick, JL Hornbeck, PV Thornwal, GC Partin, AW AF Lemkin, PF Myrick, JM Lakshmanan, Y Shue, MJ Patrick, JL Hornbeck, PV Thornwal, GC Partin, AW TI Exploratory data analysis groupware for qualitative and quantitative electrophoretic gel analysis over the Internet-WebGel SO ELECTROPHORESIS LA English DT Article DE Web; databases; two-dimensional electrophoresis; Internet; groupware; exploratory data analysis ID PROSTATE-CANCER; MATRIX; IMAGES; PATTERNS AB Many scientists use quantitative measurements to compare the presence and amount, of various proteins and nucleotides among series of one- and two-dimensional (1-D and 2-D) electrophoretic gels. These gels are often scanned into digital image files. Gel spots are then quantified using stand-alone analysis software. However, as more research collaborations take place over the Internet, it has become useful to share intermediate quantitative data between researchers. This allows research group members to investigate their data and share their work in progress. We developed a World Wide Web group-accessible software system, WebGel, for interactively exploring qualitative and quantitative differences between electrophoretic gels. Such Internet databases are useful for publishing quantitative data and allow other researchers to explore the data with respect to their own research. Because intermediate results of one user may be shared with their collaborators using WebGel, this form of active data-sharing constitutes a groupware method for enhancing collaborative research. Quantitative and image gel data from a stand-alone gel image processing system are copied to a database accessible on the WebGel Web server. These data are then available for analysis by the WebGel database program residing on that server. Visualization is critical for better understanding of the data. WebGel helps organize labeled gel images into montages of corresponding spots as seen in these different gels. Various views of multiple gel images, including sets of spots, normalization spots, labeled spots, segmented gels, etc, may also be displayed. These displays are active and may be used for performing database operations directly on individual protein spots by simply clicking on them. Corresponding regions between sets of gels may be visually analyzed using Flicker-comparison (Electrophoresis 1997, 18, 122-140) as one of the WebGel methods for qualitative analysis. Quantitative exploratory data analysis can be performed by comparing protein concentration values between corresponding spots for multiple samples run in separate gels. These data are then used to generate reports on statistical differences between sets of gels (e.g., between different disease states such as benign or metastatic cancers, etc.). Using combined visual and quantitative methods, WebGel can help bridge the analysis of dissimilar gels which are difficult to analyze with stand-alone systems and can serve as a collaborative Internet tool in a groupware setting. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Johns Hopkins Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43699 USA. PhosphoProt Databases, Baltimore, MD USA. Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Lemkin, PF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Bldg 469,Room 150, Frederick, MD 21702 USA. NR 19 TC 12 Z9 12 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD DEC PY 1999 VL 20 IS 18 BP 3492 EP 3507 DI 10.1002/(SICI)1522-2683(19991201)20:18<3492::AID-ELPS3492>3.3.CO;2-M PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 279LH UT WOS:000085044900003 PM 10612275 ER PT J AU Bulavin, DV Saito, S Hollander, MC Sakaguchi, K Anderson, CW Appella, E Fornace, AJ AF Bulavin, DV Saito, S Hollander, MC Sakaguchi, K Anderson, CW Appella, E Fornace, AJ TI Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation SO EMBO JOURNAL LA English DT Article DE apoptosis; DNA damage; p38; p53; phosphorylation ID DNA-DAMAGE; ULTRAVIOLET-RADIATION; GAMMA-RADIATION; ACTIVATES P53; GROWTH ARREST; IN-VIVO; PROTEIN; STRESS; ACETYLATION; STABILIZES AB Components of the ras signaling pathway contribute to activation of cellular p53, In MCF-7 cells, p38 kinase activated p53 more effectively than other members of the ras pathway. p53 and p38 kinase exist in the same physical complex, and co-expression of p38 stabilized p53 protein. In vitro, p38 kinase phosphorylated p53 at Ser33 and Ser46, a newly identified site, Mutation of these sites decreased p53-mediated and UV-induced apoptosis, and the reduction correlated with total abrogation of UV-induced phosphorylation on Ser37 and a significant decrease in Ser15 phosphorylation in mutant p53 containing alanine at Ser33 and Ser46, Inhibition of p38 activation after UV irradiation decreased phosphorylation of Ser33, Ser37 and Ser15, and also markedly reduced UV-induced apoptosis in a p53-dependent manner. These results suggest that p38 kinase plays a prominent role in an integrated regulation of N-terminal phosphorylation that regulates p53-mediated apoptosis after UV radiation. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Fornace, AJ (reprint author), NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NIGMS NIH HHS [GM52825] NR 35 TC 487 Z9 498 U1 4 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1999 VL 18 IS 23 BP 6845 EP 6854 DI 10.1093/emboj/18.23.6845 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 264JQ UT WOS:000084177700026 PM 10581258 ER PT J AU Ma, XM Aguilera, G AF Ma, XM Aguilera, G TI Differential regulation of corticotropin-releasing hormone and vasopressin transcription by glucocorticoids SO ENDOCRINOLOGY LA English DT Article ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; PARVOCELLULAR NEUROSECRETORY NEURONS; ARGININE-VASOPRESSIN; HETERONUCLEAR RNA; STRESS-RESPONSE; RAPID CHANGES; RECEPTOR; EXPRESSION; CRF AB CRH and vasopressin (VP), the main regulators of pituitary ACTH secretion, co-exist in parvocellular cells of the PVN, but their levels of expression are regulated differentially during manipulations of the hypothalamic pituitary adrenal (HPA) axis. The effects of glucocorticoids on this system was studied using in situ hybridization with intronic and exonic probes to measure changes in CRH and VP messenger RNA (mRNA) and heteronuclear (hn) RNA in 48-h adrenalectomized (ADX) rats receiving injections of corticosterone (2.8 mg/ 100 g, ip) or vehicle. We also determined the time course of changes in VP expression following the first 12 h of ADX Levels of VP heteronuclear Om) RNA and the number of parvocellular cells containing VP hnRNA remained very low in sham operated rats, whereas biphasic changes were observed after ADX. Grain density levels increased 11.5-fold over sham-operated controls by 6 h, declined to 2-fold by 18 h, to increase again to 10- and 20-fold by 48 and 72 h, respectively. In 48-h ADX rats, vehicle injection increased CRH hnRNA levels transiently (11-fold the basal by 15 and 30 min), returning to basal at 60 min, whereas VP hnRNA levels increased progressively up to 28-fold the basal by 2 h. Corticosterone injection had no significant effect on vehicle-induced increases in CRH hnRNA, in spite of marked elevations in circulating corticosterone. In contrast to CRH; VP hnRNA levels increased only transiently by 15 min, and then decreased below basal (near sham-ADX levels) by 2 h. The data show that in normal conditions the responsiveness of parvocellular neurons to stress is under marked inhibition by the low resting levels of glucocorticoids, and that the sensitivity of CRH and VP transcription to glucocorticoid feedback is markedly different. C1 NICHHD, Sect Endocrine Physiol, DEB, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, DEB, NIH, Bldg 10,Room 10N 262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM greti@helix.nih.gov NR 30 TC 60 Z9 61 U1 0 U2 4 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 DEC PY 1999 VL 140 IS 12 BP 5642 EP 5650 DI 10.1210/en.140.12.5642 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257QF UT WOS:000083792500021 PM 10579328 ER PT J AU Couse, JF Bunch, DO Lindzey, J Schomberg, DW Korach, KS AF Couse, JF Bunch, DO Lindzey, J Schomberg, DW Korach, KS TI Prevention of the polycystic ovarian phenotype and characterization of ovulatory capacity in the estrogen receptor-alpha knockout mouse SO ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; GONADOTROPIN-RELEASING-HORMONE; RAT GRANULOSA-CELLS; HUMAN CHORIONIC-GONADOTROPIN; MESSENGER-RIBONUCLEIC-ACID; LUTEINIZING-HORMONE; PROGESTERONE-RECEPTOR; TARGETED DISRUPTION; ER-ALPHA; CHROMOSOMAL LOCALIZATION AB Ovarian-derived estradiol plays a critical endocrine role in the regulation of gonadotropin synthesis and secretion from the hypothalamic-pituitary axis. In turn, several para/autocrine effects of estrogen within the ovary are known, including increased ovarian weight, stimulation of granulosa cell growth, augmentation of FSH action, and attenuation of apoptosis. The estrogen receptor-alpha (ER alpha) is present in all three components of the hypothalamic-pituitary-ovarian axis of the mouse. In contrast, estrogen receptor-beta (ER beta) is easily detectable in ovarian granulosa cells but is low to absent in the pituitary of the adult mouse. This distinct expression pattern for the two ERs suggests the presence of separate roles for each in the regulation of ovarian function. Herein, we definitively show that a lack of ER alpha in the hypothalamic-pituitary axis of the ER alpha-knockout (alpha ERKO) mouse results in chronic elevation of serum LH and is the primary cause of the ovarian phenotype of polycystic follicles and anovulation. Prolonged treatment with a GnRH antagonist reduced serum LH levels and prevented the alpha ERKO cystic ovarian phenotype. To investigate a direct role for ER alpha within the ovary, immature alpha ERKO females were stimulated to ovulate with exogenous gonadotropins. Ovulatory capacity in the immature alpha ERKO female was reduced compared with age-matched wild-type (14.5 +/- 2.9 vs. 40.6 +/- 2.6 oocytes/animal, respectively); however, oocytes collected from the alpha ERKO were able to undergo successful in vitro fertilization. A similar discrepancy in oocyte yield was observed after superovulation of peripubertal (42 days) wild-type and alpha ERKO females. In addition, ovaries from immature superovulated alpha ERKO females possessed several ovulatory but unruptured follicles. Investigations of the possible reasons for the reduced number of ovulations in the alpha ERKO included ribonuclease protection assays to assess the mRNA levels of several markers of follicular maturation and ovulation, including ER beta, LH-receptor, cyclin-D2, P450-side chain cleavage enzyme, prostaglandin synthase-a, and progesterone receptor. No marked differences in the expression pattern for these mRNAs during the superovulation regimen were observed in the immature alpha ERKO ovary compared with that of the wild-type. Serum progesterone levels just before ovulation were slightly lower in the alpha ERKO compared with wild-type. These studies indicate that treatment of alpha ERKO females with a GnRH antagonist decreased the serum LH levels to within the wild-type range and concurrently prevented development of the characteristic ovarian phenotype of cystic and hemorrhagic follicles. Furthermore, a lack of functional ER alpha within the ovary had no effect on the regulation of several genes required for follicular maturation and ovulation. However, the reduced numbers of ovulations following the administration of exogenous gonadotropins in the alpha ERKO suggests an intraovarian role for ER alpha in follicular development and ovulation. C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Cell Biol, Reprod Biol Lab, Chapel Hill, NC 27599 USA. Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 69 TC 83 Z9 83 U1 0 U2 4 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 DEC PY 1999 VL 140 IS 12 BP 5855 EP 5865 DI 10.1210/en.140.12.5855 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257QF UT WOS:000083792500044 PM 10579351 ER PT J AU Dabelea, D Pettitt, DJ Jones, KL Arslanian, SA AF Dabelea, D Pettitt, DJ Jones, KL Arslanian, SA TI Type 2 diabetes mellitus in minority children and adolescents - An emerging problem SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; RESTING ENERGY-EXPENDITURE; BLOOD-INSTITUTE GROWTH; PIMA INDIAN WOMEN; MEXICAN-AMERICANS; INSULIN-RESISTANCE; RISK-FACTORS; PHYSICAL-ACTIVITY; ACANTHOSIS NIGRICANS; BLACK-CHILDREN AB Type 2 diabetes mellitus is a disease of adults and has been considered rare in the pediatric population. Over the last decade, however, there has been a disturbing trend of increasing cases of type 2 diabetes in children, particularly adolescents, and with a greater proportion of minority children being affected. This article reviews the clinical characteristics of youth with type 2 diabetes, presents the risk factors associated with insulin resistance and type 2 diabetes, discusses treatment options, and projects future directions in research. The ultimate goal is to raise awareness of this challenging entity among healthcare professionals. C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. Sansum Med Res Inst, Santa Barbara, CA USA. Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Div Endocrinol & Diabet, La Jolla, CA 92093 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15260 USA. Childrens Hosp Pittsburgh, Div Pediat Endocrinol Metab & Diabet Mellitus, Pittsburgh, PA 15213 USA. RP Arslanian, SA (reprint author), Childrens Hosp Pittsburgh, Div Endocrinol, 3705 5th Ave, Pittsburgh, PA 15213 USA. FU NCRR NIH HHS [MO1 RR00084]; NICHD NIH HHS [HD27503] NR 109 TC 139 Z9 148 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 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD DEC PY 1999 VL 28 IS 4 BP 709 EP + DI 10.1016/S0889-8529(05)70098-0 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 262NX UT WOS:000084074300004 PM 10609116 ER PT J AU Lubin, JH AF Lubin, JH TI Estimating lung cancer risk with exposure to environmental tobacco smoke SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Environmental Tobacco Smoke Risl Assessment CY JUL 09-10, 1998 CL BALTMORE, MARYLAND DE epidemiology; lung cancer; meta-analysis; passive smoking; relative risk ID PASSIVE SMOKING; CIGARETTE-SMOKING; BRITISH DOCTORS; UNITED-STATES; REANALYSIS; WORKPLACE; MODELS AB Estimates of lung cancer in nonsmokers due to exposure to environmental tobacco smoke (ETS) in the workplace or in the home may be developed in several ways. Estimates may be based on a) models developed using the full range of data in smokers; b) models developed using data restricted to smokers with a low smoking rate, for example, less than or equal to 10 cigarettes per day: c) models developed using data from studies of residential exposure to ETS of nonsmokers, with exposures based on smoking rates of spouses; and d) models using data from studies of occupational exposure to ETS of nonsmokers. Methods a and b require an estimate of cigarette equivalent exposure for ETS as well as assumptions on the cigarette equivalent dose to target cells from ETS and on the comparability of lung cancer risk per unit dose from smokers and nonsmokers. Summary relative risks (RRs) and 95% confidence intervals (CI) from ETS studies of nonsmokers with exposures based on smoking patterns of spouses are 1.24 (1.1, 1.4) for females and 1.34 (1.0, 1.8) for males, whereas the RR estimate for occupational ETS exposure and its 95% CI is 1.39 (1.2, 1.7). Using RR estimates for ETS exposure, cigarette equivalents for ETS range from 0.1 to 1.0, based on a range of descriptive and biologically motivated models in active smokers; a cigarette equivalent is 0.2 based on a comparison of log-linear trends in RR with number of cigarettes smoked per day in active smokers and in spouses of nonsmokers. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-8042, Bethesda, MD 20892 USA. NR 34 TC 13 Z9 15 U1 0 U2 1 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 DEC PY 1999 VL 107 SU 6 BP 879 EP 883 DI 10.2307/3434569 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 271WA UT WOS:000084616000010 PM 10592146 ER PT J AU Tennant, R AF Tennant, R TI Tumor promoters: Tennant's response SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Tennant, R (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 DEC PY 1999 VL 107 IS 12 BP A599 EP A599 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 271DL UT WOS:000084578900006 ER PT J AU Samaraweera, P Donatien, PD Qazi, S Kobayashi, T Hearing, VJ Panthier, JJ Orlow, SJ AF Samaraweera, P Donatien, PD Qazi, S Kobayashi, T Hearing, VJ Panthier, JJ Orlow, SJ TI Identification and characterization of a melanocyte-specific novel 65-kDa peripheral membrane protein SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE albino; melanogenesis; melanocyte; mouse ID LINKED OCULAR ALBINISM; II OCULOCUTANEOUS ALBINISM; HERMANSKY-PUDLAK-SYNDROME; SILVER LOCUS PROTEIN; EYED DILUTION GENE; PALE EAR EP; DOPACHROME TAUTOMERASE; MONOCLONAL-ANTIBODIES; MAMMALIAN TYROSINASE; MOUSE AB In order to study proteins of the melanosome, we developed a panel of antisera against various protein fractions of melanosomes from B16 melanoma cells. An antiserum raised against a Triton X-100 insoluble fraction of melanosomes recognized a 65-kDa protein in melanocytes from mice homozygous for the buff mutation, but not in their wild type counterparts. Further studies were conducted using a specific, second generation antiserum raised against the purified protein. The protein was also detected in melanocytes cultured from albino mice, but absent in cultured mouse cell lines not of melanocyte origin. Density gradient centrifugation of subcellular organelles and indirect immunofluorescent cell staining, indicated that the protein was associated with melanosomes and vesicles. The protein on intact organelles could be made soluble using sodium carbonate, and digested with proteases in the absence of detergent suggesting that it was a peripheral membrane protein localized on the cytosolic face of organelle membranes. Metabolic labelling of cells and N-glycosidase F digestion of cell extracts indicated that the protein was not N-glycosylated. Based on its intracellular localization and biochemical defects in the buff mouse, a potential role has been suggested for the 65-kDa protein in intracellular membrane trafficking. C1 NYU, Sch Med, Dept Dermatol, New York, NY 10016 USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. ENVA, URA INRA Genet Mol, Maisons Alfort, France. RP Orlow, SJ (reprint author), NYU, Sch Med, Dept Dermatol, H-100,560 1st Ave, New York, NY 10016 USA. RI PANTHIER, Jean-Jacques/I-4366-2014 OI PANTHIER, Jean-Jacques/0000-0002-7966-0663 FU NIAMS NIH HHS [5T32AR07190, AR41880] NR 49 TC 6 Z9 6 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD DEC PY 1999 VL 266 IS 3 BP 924 EP 934 DI 10.1046/j.1432-1327.1999.00930.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 268UH UT WOS:000084433600025 PM 10583387 ER PT J AU Kelloff, GJ Sigman, CC Greenwald, P AF Kelloff, GJ Sigman, CC Greenwald, P TI Cancer chemoprevention: Progress and promise SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE chemoprevention; surrogate endpoints; risk evaluation; molecular carcinogenesis; intraepithelial neoplasia ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; BLADDER-CANCER; PROSTATE-CANCER; BREAST-CANCER; LESIONS; MODEL; CARCINOGENESIS; TAMOXIFEN; TUMORIGENESIS; PREVENTION AB Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. The focus of chemoprevention research in the next millennium will include defining the genotypic and phenotypic (functional and histological) changes during carcinogenesis, the cancer risk conferred by these changes, their modulation in preclinical experimentation and randomised clinical trials by chemopreventive drugs, dietary agents and regimens and treatments resulting from early detection. The key elements of this research effort will be basic and translational risk evaluation programmes; chemopreventive and dietary agent drug discovery and development; development of transgenic animal models; required safety and pharmacology studies; well-designed phase I, II and III chemoprevention studies; and much expanded early detection programmes. The large number of chemoprevention research programmes now ongoing ensures that the promise of chemoprevention will continue to be realised in the next decade. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. CCS Associates, Mt View, CA USA. RP Kelloff, GJ (reprint author), NCI, Div Canc Prevent, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 37 Z9 37 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 1999 VL 35 IS 13 BP 1755 EP 1762 DI 10.1016/S0959-8049(99)00164-1 PG 8 WC Oncology SC Oncology GA 254GD UT WOS:000083602800007 PM 10673988 ER PT J AU Schnur, J Nagy, P Sebestyen, A Schaff, Z Thorgeirsson, SS AF Schnur, J Nagy, P Sebestyen, A Schaff, Z Thorgeirsson, SS TI Chemical hepatocarcinogenesis in transgenic mice overexpressing mature TGF beta-1 in liver SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE thioacetamide; transforming growth factor beta; mice; transgenic; carcinogens; aflatoxin B1; 2-acetylaminofluorene ID GROWTH-FACTOR-BETA; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; RAT-LIVER; HEPATOCELLULAR-CARCINOMA; MESSENGER-RNA; EXPRESSION; TUMORS; MOUSE; CARCINOGENESIS AB The role of transforming growth factor beta I (TGF-beta 1) in carcinogenesis is a controversial issue. Certain results suggest a promoter role of this growth factor whilst in other experimental models TGF-beta 1 seems to inhibit the process of tumorigenesis. In an attempt to resolve this problem, we have performed chemical hepatocarcinogenesis experiments on transgenic mice expressing a high level of active TGF-beta 1 in their liver. Transgenic production of TGF-beta 1 did not result in spontaneous tumour formation during our observation period. However, two carcinogens, thioacetamide and N-OH acetylaminofluorene, were more potent in transgenic than in wild-type mice, whereas aflatoxin B1 was equally effective in both groups. Our observations suggest that an increased level of TGF-beta 1 in the liver does not provide protection against the effect of chemical carcinogens. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Semmelweis Univ Med, Inst Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Nagy, P (reprint author), Semmelweis Univ Med, Inst Pathol & Expt Canc Res 1, Ulloi Ut 26, H-1085 Budapest, Hungary. NR 30 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 1999 VL 35 IS 13 BP 1842 EP 1845 DI 10.1016/S0959-8049(99)00224-5 PG 4 WC Oncology SC Oncology GA 254GD UT WOS:000083602800022 PM 10674001 ER PT J AU Fisher, B AF Fisher, B TI From Halsted to prevention and beyond: Advances in the management of breast cancer during the twentieth century SO EUROPEAN JOURNAL OF CANCER LA English DT Article ID SURGICAL-ADJUVANT-BREAST; COMPARING RADICAL-MASTECTOMY; RECEPTOR-POSITIVE TUMORS; RAT MAMMARY-CARCINOMA; PREOPERATIVE CHEMOTHERAPY; COMBINATION CHEMOTHERAPY; FOLLOW-UP; TAMOXIFEN; TRIAL; THERAPY AB This commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the 'non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti-oestrogen tamoxifen benefited patients with all stages of the disease. Tamoxifen also reduced the incidence of contralateral breast cancer, as well as tumour in the ipsilateral breast following lumpectomy. The use of preoperative therapy was also found to enhance breast-conserving surgery in women with large tumours, although its value in other circumstances is still being defined. The observation that, as a result of tamoxifen administration, invasive and non-invasive breast cancers can be prevented in women who are at increased risk for such tumours, and the finding that pathological entities such as atypical hyperplasia, lobular carcinoma in situ (LCIS) and intraductal carcinoma (DCIS) can identify women who should be considered candidates for tamoxifen serve as a fitting capstone to the accomplishments of the twentieth century. Breast cancer prevention has now become a reality. Unfortunately, a variety of circumstances have arisen as the result of advances in the understanding and treatment of breast cancer over the last 30 years that threaten to nullify the progress that has been achieved. This distressing phenomenon may be reviewed as a 'paradox of accomplishment'. The numerous uncertainties, issues and questions that have arisen following the report of each advance in treatment, the surfeit of new information that has not yet been integrated into treatment strategies, the undesirable consequences of enhanced tumour detection, a reversion to Halstedianism and anecdotalism, and the uncertainty of therapeutic decision making resulting from the demonstration of small but statistically significant benefits, particularly in patients with good prognosis, need to be addressed. Inappropriate interpretation of those circumstances threatens to deny women with breast cancer and those at high risk for the disease the opportunity to benefit from treatments that have been proven to be of worth. Perhaps the most important accomplishment of the twentieth century relates to the change in the process of therapeutic decision making. The continued use of the scientific process to test scientifically based hypotheses in well-designed clinical trials must continue if future progress is to be made in the treatment of breast cancer. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Natl Surg Adjuvant Breast & Bowel Project, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. EM bemard.fisher@nsabp.org NR 64 TC 62 Z9 68 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 1999 VL 35 IS 14 SI SI BP 1963 EP 1973 DI 10.1016/S0959-8049(99)00217-8 PG 11 WC Oncology SC Oncology GA 270ZH UT WOS:000084566700012 PM 10711239 ER PT J AU Kelloff, GJ Sigman, CC Greenwald, P AF Kelloff, GJ Sigman, CC Greenwald, P TI Cancer chemoprevention: Progress and promise (Reprinted from Eur J Cancer, vol 35, pg 1755-1762, 1999) SO EUROPEAN JOURNAL OF CANCER LA English DT Reprint DE chemoprevention; surrogate endpoints; risk evaluation; molecular carcinogenesis; intraepithelial neoplasia ID NONSTEROIDAL ANTIINFLAMMATORY DRUG; BLADDER-CANCER; PROSTATE-CANCER; BREAST-CANCER; LESIONS; MODEL; CARCINOGENESIS; TAMOXIFEN; TUMORIGENESIS; PREVENTION AB Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. The focus of chemoprevention research in the next millennium will include defining the genotypic and phenotypic (functional and histological) changes during carcinogenesis, the cancer risk conferred by these changes, their modulation in preclinical experimentation and randomised clinical trials by chemopreventive drugs, dietary agents and regimens and treatments resulting from early detection. The key elements of this research effort will be basic and translational risk evaluation programmes; chemopreventive and dietary agent drug discovery and development; development of transgenic animal models; required safety and pharmacology studies; well-designed phase I, II and III chemoprevention studies; and much expanded early detection programmes. The large number of chemoprevention research programmes now ongoing ensures that the promise of chemoprevention will continue to be realised in the next decade. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. CCS Associates, Mt View, CA USA. RP Kelloff, GJ (reprint author), NCI, Div Canc Prevent, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 46 Z9 49 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD DEC PY 1999 VL 35 IS 14 SI SI BP 2031 EP 2038 DI 10.1016/S0959-8049(99)00299-3 PG 8 WC Oncology SC Oncology GA 270ZH UT WOS:000084566700017 PM 10711244 ER PT J AU Shalev, A AF Shalev, A TI Hope for insulin mimetic oral antidiabetic drugs SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Shalev, A (reprint author), NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. NR 9 TC 5 Z9 6 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD DEC PY 1999 VL 141 IS 6 BP 561 EP 562 DI 10.1530/eje.0.1410561 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 276EM UT WOS:000084862700002 PM 10601956 ER PT J AU Meunier, M Bachevalier, J Murray, EA Malkova, L Mishkin, M AF Meunier, M Bachevalier, J Murray, EA Malkova, L Mishkin, M TI Effects of aspiration versus neurotoxic lesions of the amygdala on emotional responses in monkeys SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE emotions; ibotenic acid lesions; medial temporal cortex; rhesus macaques; rhinal cortex ID ANTERIOR TEMPORAL CORTEX; KLUVER-BUCY SYNDROME; RHESUS-MONKEYS; SOCIAL-BEHAVIOR; IBOTENIC ACID; RECOGNITION; MEMORY; FEAR; REWARD; REINFORCEMENT AB All previous reports describing alterations in emotional reactivity after amygdala damage in monkeys were based on aspiration or radiofrequency lesions which likely disrupted fibres of passage coursing to and from adjacent ventral and medial temporal cortical areas. To determine whether this associated indirect damage was responsible for some or all of the changes described earlier, we compared the changes induced by aspiration of the amygdala with those induced by fibre-sparing neurotoxic lesions. Four different stimuli, two with and two without a social component, were used to evaluate the expression of defence, aggression, submission and approach responses. In unoperated controls, defence and approach behaviours were elicited by all four stimuli, 'social' and inanimate alike, whereas aggression and submission responses occurred only in the presence of the two 'social' stimuli. Furthermore, all defence reactions were reduced with an attractive inanimate item, while freezing was selectively increased with an aversive one. Relative to controls, monkeys with neurotoxic amygdala lesions showed the same array of behavioural changes as those with aspiration lesions, i.e. reduced fear and aggression, increased submission, and excessive manual and oral exploration. Even partial neurotoxic lesions involving less than two-thirds of the amygdala significantly altered fear and manual exploration. These findings convincingly demonstrate that the amygdala is crucial for the normal regulation of emotions in monkeys. Nevertheless, because some of the symptoms observed after neurotoxic lesions were less marked than those seen after aspiration lesions, the emotional disorders described earlier after amygdalectomy in monkeys were likely exacerbated by the attendant fibre damage. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. CNRS, Inst Cognit Sci, Bron, France. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Meunier, M (reprint author), NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA. RI MEUNIER, Martine/C-2611-2015; OI MEUNIER, Martine/0000-0002-9380-9372; Murray, Elisabeth/0000-0003-1450-1642 FU NICHD NIH HHS [HD35471]; PHS HHS [58846] NR 70 TC 121 Z9 121 U1 0 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 1999 VL 11 IS 12 BP 4403 EP 4418 DI 10.1046/j.1460-9568.1999.00854.x PG 16 WC Neurosciences SC Neurosciences & Neurology GA 274CV UT WOS:000084746900029 PM 10594668 ER PT J AU Gao, CY Rampalli, AM Cai, HC He, HY Zelenka, PS AF Gao, CY Rampalli, AM Cai, HC He, HY Zelenka, PS TI Changes in cyclin dependent kinase expression and activity accompanying lens fiber cell differentiation SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE cyclin dependent kinases (Cdk); differentiation; rat lens; development; p57(kip2) ID EMBRYONIC CHICKEN LENS; PROTEIN-KINASE; NEURONAL DIFFERENTIATION; TERMINAL DIFFERENTIATION; CATALYTIC SUBUNIT; S-PHASE; PHOSPHORYLATION; IDENTIFICATION; ACTIVATION; INHIBITION AB Previous studies from this laboratory have shown that differentiating lens fiber cells contain two active cyclin dependent kinases (Cdks), Cdk1 and Cdk5. The present study was undertaken to explore the expression and regulation of six additional members of the Cdk family (Cdk2, Cdk3, Cdk4, Cdk6, Cdk7 and Cdk8) during lens differentiation. Differentiating lens fiber cells were separated from lens epithelial cells by microdissection of developing rat lenses [embryonic day 16 (E16) to postnatal day 8 (ps)] and Cdk expression eras assessed by RT-PCR and immunoblotting. Two Cdks (Cdk3 and Cdk6) were not expressed in lens fiber cells or epithelial cells during this developmental period, in the lens epithelium, we detected proteins and mRNAs corresponding to all other Cdks examined (Cdk2, Cdk4, Cdk7, Cdk8) throughout this developmental period. Epithelial cells showed significant Cdk2 activity, which decreased with developmental age, but no significant activity was detected for Cdk4, Cdk7, or Cdk8. Fiber cells contained all four Cdk proteins and the corresponding Cdk mRNAs except for Cdk2 mRNA. None of the Cdks examined showed significant kinase activity in fiber cells. Immunoprecipitates of Cdk2 and Cdk4 from fiber cells contained p57(kip2), supporting the view that this Cdk inhibitor blocks the activity of these Cdks in lens fibers. In contrast, p57(kip2) did not co-immunoprecipitate with Cdk5 from lens fibers. These findings suggest that the differential affinity of p57(kip2) for members of the Cdk family may provide a mechanism for specific regulation of individual Cdks during fiber cell differentiation. (C) 1999 Academic Press. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Room 214,6 Ctr Dr MSC 2730, Bethesda, MD 20892 USA. NR 59 TC 26 Z9 26 U1 0 U2 2 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 DEC PY 1999 VL 69 IS 6 BP 695 EP 703 DI 10.1006/exer.1999.0749 PG 9 WC Ophthalmology SC Ophthalmology GA 273PR UT WOS:000084716500013 PM 10620399 ER PT J AU Djordjevic-Markovic, R Radic, O Jelic, V Radojcic, M Rapic-Otrin, V Ruzdijic, S Krstic-Demonacos, M Kanazir, S Kanazir, D AF Djordjevic-Markovic, R Radic, O Jelic, V Radojcic, M Rapic-Otrin, V Ruzdijic, S Krstic-Demonacos, M Kanazir, S Kanazir, D TI Glucocorticoid receptors in ageing rats SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE ageing; glucocorticoid receptor; TAT ID TYROSINE AMINOTRANSFERASE; LIVER; GENE; TRANSCRIPTION; HORMONES; BINDING AB The role of the glucocorticoid receptor (GR) in senescence was studied in rats of increasing age. Statistically significant changes in the number of GRs from rat liver were detected, whereas the affinity for the ligand triamcinolone acetonide (TA) did not change with increasing age, and was in the range of 1-2 nM. In all cases the number of receptors was lower in rats treated with hormone in vivo relative to untreated animals. In addition, we have found changes in GR activation, as measured by the binding to DNA cellulose in the mentioned age groups. Furthermore, expression of the glucocorticoid hormone (GH)-inducible gene, tyrosine amino transferase (TAT) also showed age-related alterations. We conclude that receptor function shows oscillatory changes during ageing. In addition, response to GH generally declines towards the older age. This. specific periodicity in functional characteristics of the GR may reconcile conflicting results about the receptor number and properties during the ageing process, and marks particular age at which individual organism shows the highest or the lowest sensitivity to the actions of GH. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Inst Nucl Sci Vinca, Lab Mol Biol & Endocrinol, YU-11001 Belgrade, Yugoslavia. NICHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Inst Biol Sci Sinisa Stankov, YU-11000 Belgrade, Yugoslavia. Univ Glasgow IBLS, Div Biochem & Mol Biol, Glasgow G12 8QQ, Lanark, Scotland. RP Krstic-Demonacos, M (reprint author), Inst Nucl Sci Vinca, Lab Mol Biol & Endocrinol, 090,POB 522, YU-11001 Belgrade, Yugoslavia. RI Kanazir, Selma/E-5495-2015 OI Kanazir, Selma/0000-0002-7229-5296 NR 25 TC 12 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD DEC PY 1999 VL 34 IS 8 BP 971 EP 982 DI 10.1016/S0531-5565(99)00067-4 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 265VV UT WOS:000084267400007 PM 10673150 ER PT J AU Keir, SD House, SB Li, J Xiao, X Gainer, H AF Keir, SD House, SB Li, J Xiao, X Gainer, H TI Gene transfer into hypothalamic organotypic cultures using an adeno-associated virus vector SO EXPERIMENTAL NEUROLOGY LA English DT Article DE AAV; viral vector; oxytocin; magnocellular neurons; hypothalamus ID VASOPRESSIN MAGNOCELLULAR NEURONS; ADENOASSOCIATED VIRUS; EFFICIENT TRANSDUCTION; EXPRESSION; OXYTOCIN; RECEPTOR; PROTEIN; TYPE-2; BRAIN; CELLS AB Organotypic cultures of rat hypothalamic slice cultures were successfully transduced using adenoassociated viral vectors. Using nuclear-targeted Lac-Z as the reporter gene, transduction was found to be very effective, occurring in as high as 89% of a specific cell type, the oxytocin neurons, present in the cultured explants. These transduction levels were not accompanied by any deleterious effects in the cultured cells 7 days after transduction. Such an in vitro approach should be valuable for the study of cell-specific gene expression in neurons in the central nervous system for which there are no homologous (surrogate) cell lines, (C) 1999 Academic Press. C1 NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Univ Glasgow, Dept Neurol, So Gen Hosp, Inst Neurol Sci, Glasgow G41 4TF, Lanark, Scotland. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Gene Therapy Ctr, Pittsburgh, PA 15261 USA. RP Keir, SD (reprint author), NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. NR 22 TC 14 Z9 14 U1 0 U2 1 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 DEC PY 1999 VL 160 IS 2 BP 313 EP 316 DI 10.1006/exnr.1999.7236 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 264WE UT WOS:000084205300001 PM 10619549 ER PT J AU Blum, M Weickert, C Carrasco, E AF Blum, M Weickert, C Carrasco, E TI The weaver GIRK2 mutation leads to decreased levels of serum thyroid hormone: Characterization of the effect on midbrain dopaminergic neuron survival SO EXPERIMENTAL NEUROLOGY LA English DT Article DE hypothyroidism; neurodegeneration; dopaminergic neuron; TGF-alpha ID GROWTH-FACTOR-ALPHA; RECTIFYING K+ CHANNELS; MUTANT MOUSE WEAVER; ADULT-RAT BRAIN; GRANULE CELL; INWARD RECTIFIER; CEREBELLAR CORTEX; MESSENGER-RNAS; DEVELOPMENTAL EXPRESSION; POSTNATAL-DEVELOPMENT AB The selective neurodegenerative changes occurring in the weaver mutant cerebellum and midbrain are Linked to a point mutation in an inward rectifying potassium channel (GIRK2). However, given that GIRK2 is widely expressed in the CNS, it is not understood why this mutation only leads to neuroanatomically selective and developmentally specific neuronal cell death. Here we show that the phenotype of the weaver mutant mouse includes hypothyroidism, which is associated with delays in somatic development and decreased expression of striatal transforming growth factor alpha (TGF-alpha). Since thyroid hormone has major effects on brain development, further studies were performed to address whether some of pathological changes detected the weaver mutant mouse are due to the reduced thyroid hormone levels. We observed that daily thyroid hormone replacement was able to stimulate somatic growth and restore TGF-alpha expression to wild-type levels, indicating that while these mice are responsive to thyroid hormone they possibly have a defect in the ability to regulate its release at the level of the hypothalamic pituitary axis. However when we assessed whether thyroid hormone replacement could rescue midbrain dopaminergic neurons we found that this treatment accelerated rather than attenuated neurodegeneration. We did not observe that thyroid hormone was able to directly regulate expression of GIRK2 mRNA levels in the midbrain and therefore, speculate that the mechanism by which thyroid hormone accelerates midbrain dopaminergic neurodegeneration is by enhancing the maturation of the striatonigral inputs. In summary, we detected reduced levels of serum thyroid hormone in the weaver mutant mouse, which appears to be responsible for delays in somatic growth and the onset of neurodegenerative changes in the midbrain. (C) 1999 Academic Press. C1 CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA. NIH, Bethesda, MD 20892 USA. CUNY Hunter Coll, Subprogram Biopsychol, New York, NY 10021 USA. RP Blum, M (reprint author), CUNY Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, 1 Gustave Levy Pl, New York, NY 10029 USA. RI Shannon Weickert, Cynthia/G-3171-2011 FU NIA NIH HHS [AG08538] NR 76 TC 7 Z9 7 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 DEC PY 1999 VL 160 IS 2 BP 413 EP 424 DI 10.1006/exnr.1999.7231 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 264WE UT WOS:000084205300010 PM 10619558 ER PT J AU Sanchez, GI Carucci, DJ Sacci, J Resau, JH Rogers, WO Kumar, N Hoffman, SL AF Sanchez, GI Carucci, DJ Sacci, J Resau, JH Rogers, WO Kumar, N Hoffman, SL TI Plasmodium yoelii: Cloning and characterization of the gene encoding for the mitochondrial heat shock protein 60 SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Plasmodium yoelii; Plasmodium falciparum; protozoa; malaria; heat shock protein; chaperonin 60; polymerase chain reaction; circumsporozoite protein; apical membrane antigen-1; Plasmodium; mitochondrial chaperonin ID MALARIA PARASITES; MOLECULAR CHARACTERIZATION; FALCIPARUM; EXPRESSION; FAMILY; STAGE; LOCALIZATION; CHAPERONES; BERGHEI; BIOLOGY AB Heat shock proteins are a highly conserved group of proteins required for the correct folding, transport, and degradation of other proteins in vivo. The Hsp70, Hsp90, and Hsp60 families are among the most widely studied families. Hsp60 is found in eubacteria, mitochondria, and chloroplasts, where, in cooperation with Hsp10, it participates in protein folding and translocation of proteins to the organelles. We have cloned and characterized the Hsp60 gene of Plasmodium yoelii (PyHsp60). PyHsp60 is a single-copy gene, located on chromosome 9, 10, or 11. The PyHsp60 cDNA sequence showed an open reading frame of 1737 nucleotides that codes for a polypeptide of 579 amino acids, with 93% amino acid identity to Plasmodium falciparum Hsp60 (PfHsp60). Cloning and sequencing of a genomic PCP clone showed the presence of a 201-bp intron, located 141 bp downstream of the ATG codon. A single, heat-inducible, 2.3-kb transcript was detected in Northern blots of RNA isolated from blood stage parasites. Mouse antisera raised against a DNA vaccine vector that expresses PyHsp60 recognized sporozoites and liver- and blood-stage parasites by indirect fluorescent antibody test (IFAT). By Western blot, these antisera reacted with the mycobacterial Hsp65 and recognized a protein of approximately 65 kDa in P. yoelii sporozoites and P. falciparum blood stages. These results show that PyHsp60 and PfHsp60 genes are homologous and that of the PyHsp60 gene encodes a heat-inducible, intracellular protein that is expressed in several of the developmental stages of P. yoelii. (C) 1999 Academic Press. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. USN, Med Res Ctr, Malaria Program, Rockville, MD 20852 USA. Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Sanchez, GI (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St, Baltimore, MD 21205 USA. OI Sanchez, Gloria Ines/0000-0001-5992-0475 FU NIAID NIH HHS [AI31589] NR 33 TC 14 Z9 17 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD DEC PY 1999 VL 93 IS 4 BP 181 EP 190 DI 10.1006/expr.1999.4455 PG 10 WC Parasitology SC Parasitology GA 262AE UT WOS:000084042900001 PM 10600443 ER PT J AU Hirschberg, K Lippincott-Schwartz, J AF Hirschberg, K Lippincott-Schwartz, J TI Secretory pathway kinetics and in vivo analysis of protein traffic from the Golgi complex to the cell surface SO FASEB JOURNAL LA English DT Article; Proceedings Paper CT Symposium on a Half-Century of Advances in Microscopy CY JUL 24-25, 1998 CL MARINE BIOL LAB, WOODS HOLE, MASSACHUSETTS SP Carl Zeiss Inc, Microscope Div, Federat Amer Soc Exptl Biol, Hamamatsu Photon Inc, JEOL/Japan Electron Opt Lab, Leica Inc, Microscopy & Sci Instruments Div, Marine Biol Lab, NASA, Natl Inst Gen Med Sci, NINCDS, Nikon Inc, Instrument Grp, Olympus Amer Inc, Porter Fdn, Universial Imaging Corp HO MARINE BIOL LAB ID GREEN FLUORESCENT PROTEIN; PLASMA-MEMBRANE PROTEINS; ENDOPLASMIC-RETICULUM; LIVING CELLS; TRANSPORT VESICLES; VISUALIZATION; EXPRESSION; MICROSCOPY; APPARATUS; DYNAMICS C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hirschberg, K (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Room 101,18 Lib Dr, Bethesda, MD 20892 USA. NR 33 TC 27 Z9 27 U1 0 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 DEC PY 1999 VL 13 SU 2 BP S251 EP S256 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 267ZY UT WOS:000084390200016 PM 10619138 ER PT J AU Leondires, MP Escalpes, M Segars, JH Scott, RT Miller, BT AF Leondires, MP Escalpes, M Segars, JH Scott, RT Miller, BT TI Microdose follicular phase gonadotropin-releasing hormone agonists (GnRH-a) compared with luteal phase GnRH-a for ovarian stimulation at in vitro fertilization SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting for the American-Society-for-Reproductive-Medicine CY OCT 18-23, 1997 CL CINCINNATI, OHIO SP Amer Soc Reprod Med DE microdose GnRH-a; in vitro fertilization; cost efficiency ID INVITRO FERTILIZATION; OVULATION INDUCTION; LEUPROLIDE ACETATE; OOCYTE RETRIEVAL; SUPPRESSION; PROTOCOL; FLARE; HYPERSTIMULATION; RESPONSIVENESS; FECUNDITY AB Objective: To compare an ovarian stimulation protocol using microdose follicular phase GnRH agonist (GnRH-a) and oral contraceptive (OC) pills to a luteal phase CnRH-a protocol. Design: Retrospective analysis. Setting: University affiliated IVF program. Patient(s): One hundred seventy patients who underwent IVF and ET in 1996. Intervention(s): Patients were assigned to either a midluteal start of leuprolide acetate (LA) 1 mg/d, reduced to 0.5 mg/d after addition of gonadotropins (LUT), or OC pills until cycle day 0 followed by 20 mu g of LA every 12 hours on cycle day 3 with addition of gonadotropins on cycle day 5 (MICRO). Main Outcome Measure(s): Number of FSH ampules, days of stimulation, peak E-2, and number of oocytes retrieved. Result(s): There were no statistically significant differences in the main outcome measures between the two groups using an age-matched ANOVA. Clinical pregnancy rate per cycle start was not statistically different (LUT = 54%, and MICRO = 37%). The cancellation rate was significantly higher in the MICRO group (22.5% vs. 8.2%). Conclusion(s): Given the higher cancellation rate in the microdose group, a randomized clinical trial is required to determine the possible benefit of a lower dose of GnRN-a in patients with normal ovarian function. ((C)1999 by American Society for Reproductive Medicine.). C1 USN, Dept Obstet & Gynecol, Natl Med Ctr, Gaithersburg, MD 20899 USA. Wayne State Univ, NICHHD, NIH, Detroit, MI USA. Reprod Med Associates New Jersey, Morristown, NJ USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Miller, BT (reprint author), USN, Dept Obstet & Gynecol, Natl Med Ctr, 8901 Wisconsin Ave, Gaithersburg, MD 20899 USA. NR 21 TC 41 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD DEC PY 1999 VL 72 IS 6 BP 1018 EP 1023 DI 10.1016/S0015-0282(99)00423-9 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 259QL UT WOS:000083904500012 PM 10593374 ER PT J AU Baumert, TF Vergalla, J Satoi, J Thomson, M Lechmann, M Herion, D Greenberg, HB Ito, S Liang, TJ AF Baumert, TF Vergalla, J Satoi, J Thomson, M Lechmann, M Herion, D Greenberg, HB Ito, S Liang, TJ TI Hepatitis C virus-like particles synthesized in insect cells as a potential vaccine candidate SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 07-12, 1997 CL CHICAGO, ILLINOIS SP Amer Assoc Study Liver Dis ID STRUCTURAL PROTEINS; IMMUNE-RESPONSE; NEUTRALIZING ANTIBODIES; GLYCOPROTEIN COMPLEXES; HYPERVARIABLE REGION-1; FLAVIVIRUS ENVELOPE; ENCEPHALITIS-VIRUS; IMMUNIZATION; PAPILLOMAVIRUS; INFECTIONS AB Background & Aims: Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. Successful vaccine development is crucial in controlling global HCV infection. We have previously described the generation of HCV-like particles (HCV-LPs) in insect cells using a recombinant baculovirus containing the complementary DNA of the HCV structural proteins. These HCV-LPs had similar morphological and biophysical properties as the putative virions. In this study, we analyzed the structural features, antigenic composition, seroreactivity, and immunogenicity of purified HCV-LPs. Methods: HCV-LPs were analyzed by electron microscopy and antibody immunolabeling and precipitation, An enzyme-linked immunosorbent assay (ELISA) using HCV-LPs was developed. The humoral response to HCV-LPs in mice was studies by core and envelope ELISAs, Western immunoblotting, and immunofluorescence. Results: Structural and antigenic compositions of HCV-LPs were shown to be similar to those of putative HCV virions. Using the HCV-LP ELISA, high-titer anti-HCV antibodies were detected in individuals infected with various HCV genotypes, In vivo, HCV-LPs elicited a humoral response broadly directed against HCV structural proteins, Conclusions: HCV-LPs resemble HCV virions and are capable of inducing a humoral response targeted against various regions of HCV structural proteins, suggesting that HCV-LPs may be promising as a potential vaccine candidate. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Div Gastroenterol, Palo Alto, CA 94304 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI95-012] NR 34 TC 83 Z9 87 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 1999 VL 117 IS 6 BP 1397 EP 1407 DI 10.1016/S0016-5085(99)70290-8 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 260LQ UT WOS:000083952500021 PM 10579981 ER PT J AU Auerbach, JD AF Auerbach, JD TI From the SWS president - Gender as proxy SO GENDER & SOCIETY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Auerbach, JD (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-2432 J9 GENDER SOC JI Gend. Soc. PD DEC PY 1999 VL 13 IS 6 BP 701 EP 704 DI 10.1177/089124399013006001 PG 4 WC Sociology; Women's Studies SC Sociology; Women's Studies GA 258DT UT WOS:000083823400001 ER PT J AU Hottiger, MO Dam, TN Nickoloff, BJ Johnson, TM Nabel, GJ AF Hottiger, MO Dam, TN Nickoloff, BJ Johnson, TM Nabel, GJ TI Liposome-mediated gene transfer into human basal cell carcinoma SO GENE THERAPY LA English DT Article DE antigen-presenting cells; basal cell carcinoma; cationic liposomes; gene therapy; interferon; lipoplexes ID INTRALESIONAL INTERFERON; IMMUNE-RESPONSE; NUDE-MICE; ALPHA; DNA; REGRESSION; EXPRESSION; THERAPY; COMPLEXES; MELANOMA AB Direct intralesional injection of DNA encoding interferon-alpha 2 (IFN-alpha 2) was used in an effort to sustain local protein delivery for the treatment of human basal cell carcinoma (BCC). A novel model to study this malignancy was established by transplantation of human BCC tissue on to immunodeficient mice with a relatively high rate of engraftment and stable phenotype for superficial BCC (20 of 25; 80%. Gene transfer was significantly increased by using DNA liposome complexes (lipoplexes). Recombinant gene expression was detected predominantly in the epidermis and, to a lesser extent, in the dermis. Gene transfer of IFN-alpha 2 using this method resulted in sustained production of IFN-alpha 2 protein and increased expression of a known IFN-inducible gene, the class II major histocompatibility (MHC) antigen, and induced BCC regression, presumably through a non-immune mechanism. Intralesional injection of DNA lipoplexes encoding IFN-alpha protein may therefore be applicable to the treatment of cutaneous BCC. C1 Univ Michigan, Med Ctr, Howard Hughes Med Inst, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Med Ctr, Howard Hughes Med Inst, Dept Biol Chem, Ann Arbor, MI USA. Univ Michigan, Med Ctr, Dept Dermatol Otorhinolaryngol & Surg, Ann Arbor, MI 48109 USA. Loyola Univ, Med Ctr, Dept Pathol, Skin Canc Res Labs,Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Nabel, GJ (reprint author), NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA. RI Hottiger, Michael/J-7747-2013 OI Hottiger, Michael/0000-0002-7323-2270 FU NCI NIH HHS [1P01CA59327] NR 33 TC 19 Z9 21 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD DEC PY 1999 VL 6 IS 12 BP 1929 EP 1935 DI 10.1038/sj.gt.3301036 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 269GU UT WOS:000084469000005 PM 10637444 ER PT J AU Kim, DR Dai, Y Mundy, CL Yang, W Oettinger, MA AF Kim, DR Dai, Y Mundy, CL Yang, W Oettinger, MA TI Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase SO GENES & DEVELOPMENT LA English DT Article DE RAG1; RAG2; V(D)J recombination; T-cell receptor; recombination signal sequence ID HIV-1 INTEGRASE; RESTRICTION ENDONUCLEASES; RETROVIRAL INTEGRASES; DIRECTED MUTAGENESIS; CATALYTIC DOMAIN; STRUCTURAL BASIS; DNA; CLEAVAGE; MECHANISM; PROTEIN AB The RAG1 and RAG2 proteins collaborate to initiate V(D)J recombination by binding recombination signal sequences (RSSs) and making a double-strand break between the RSS and adjacent coding DNA. Like the reactions of their biochemical cousins, the bacterial transposases and retroviral integrases, cleavage by the RAG proteins requires a divalent metal ion but does not involve a covalent protein/DNA intermediate. In the transposase/integrase family, a triplet of acidic residues, commonly called a DDE motif, is often found to coordinate the metal ion used for catalysis. We show here that mutations in each of three acidic residues in RAG1 result in mutant derivatives that can bind the RSS but whose ability to catalyze either of the two chemical steps of V(D)J cleavage (nicking and hairpin formation) is severely impaired. Because both chemical steps are affected by the same mutations, a single active site appears responsible for both reactions. Two independent lines of evidence demonstrate that at least two of these acidic residues are directly involved in coordinating a divalent metal ion: The substitution of Cys for Asp allows rescue of some catalytic function, whereas an alanine substitution is no longer subject to iron-induced hydroxyl radical cleavage. Our results support a model in which the RAG1 protein contains the active site of the V(D)J recombinase and are interpreted in light of predictions about the structure of RAG1. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU NIGMS NIH HHS [GM58026] NR 49 TC 144 Z9 149 U1 0 U2 1 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 DEC 1 PY 1999 VL 13 IS 23 BP 3070 EP 3080 DI 10.1101/gad.13.23.3070 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 266EP UT WOS:000084287900004 PM 10601033 ER PT J AU Waldman, AS Tran, H Goldsmith, EC Resnick, MA AF Waldman, AS Tran, H Goldsmith, EC Resnick, MA TI Long inverted repeats are an at-risk motif for recombination in mammalian cells SO GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; SITE-SPECIFIC ENDONUCLEASES; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; GENE CONVERSION; MOUSE CELLS; TRINUCLEOTIDE REPEATS; CHROMOSOMAL SEQUENCES; ESCHERICHIA-COLI; TRIPLET REPEATS AB Certain DNA sequence motifs and structures can promote genomic instability. We have explored instability induced in mouse cells by long inverted repeats (LIRs). A cassette was constructed containing a herpes simplex virus thymidine kinase (tk) gene into which was inserted an LIR composed of two inverted copies of a 1.1-kb yeast URA3 gene sequence separated by a 200-bp spacer sequence. The tk gene was introduced into the genome of mouse Ltk(-) fibroblasts either by itself or in conjunction with a closely linked tk gene that was disrupted by an 8-bp XhoI linker insertion; rates of intrachromosomal homologous recombination between the markers were determined. Recombination between the two tk alleles was stimulated 5-fold by the LIR, as compared to a long direct repeat (LDR) insert, resulting in nearly 10(-5) events per cell per generation. Of the tk(+) segregants recovered from LIR-containing cell lines, 14% arose from gene conversions that eliminated the LIR, as compared to 3% of the tk(+) segregants from LDR cell lines, corresponding to a >20-fold increase in deletions at the LIR hotspot. Thus, an LIR, which is a common motif in mammalian genomes, is at risk for the stimulation of homologous recombination and possibly other genetic rearrangements. C1 Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Waldman, AS (reprint author), Univ S Carolina, Dept Biol Sci, 700 Sumter St, Columbia, SC 29208 USA. FU NIGMS NIH HHS [GM47110] NR 56 TC 30 Z9 31 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD DEC PY 1999 VL 153 IS 4 BP 1873 EP 1883 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 262RB UT WOS:000084079300033 PM 10581292 ER PT J AU Murphy, WJ Sun, S Chen, ZQ Pecon-Slattery, J O'Brien, SJ AF Murphy, WJ Sun, S Chen, ZQ Pecon-Slattery, J O'Brien, SJ TI Extensive conservation of sex chromosome organization between cat and human revealed by parallel radiation hybrid mapping SO GENOME RESEARCH LA English DT Article ID HUMAN Y-CHROMOSOME; HUMAN GENOME; MOUSE; MAP; EVOLUTION; GENES; KARYOTYPE; PRIMATES; HOMOLOGS; REGIONS AB A radiation hybrid [RH]-derived physical map of 25 markers on the feline X chromosome (including 19 Type I coding loci and 6 Type II microsatellite markers) was compared to homologous marker order on the human and mouse X chromosome maps. Complete conservation of synteny and marker order was observed between feline and human X chromosomes, whereas the same markers identified a minimum of seven rearranged syntenic segments between mouse and cat/human X chromosome marker order. Within the blocks, the feline human, and mouse marker order was strongly conserved. Similarly, Y chromosome locus order was remarkably conserved between cat and human Y chromosomes, with only one marker (SMCY) position rearranged between the species. Tight linkage and a conserved gene order for a segment encoding three genes, DFFRY-DBY-UTY in human, mouse, and cat Y chromosomes, coupled with demonstrated deletion effects of these genes on reproductive impairment in both human and mouse, implicates the region as critical for Y-mediated sperm production. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. George Mason Univ, Grad Program Biol, Fairfax, VA 22030 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. EM murphywi@mail.ncifcrf.gov NR 42 TC 73 Z9 77 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD DEC PY 1999 VL 9 IS 12 BP 1223 EP 1230 DI 10.1101/gr.9.12.1223 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 270RU UT WOS:000084550600009 PM 10613845 ER PT J AU Caetano, AR Shiue, YL Lyons, LA O'Brien, SJ Laughlin, TF Bowling, AT Murray, JD AF Caetano, AR Shiue, YL Lyons, LA O'Brien, SJ Laughlin, TF Bowling, AT Murray, JD TI A comparative gene map of the horse (Equus caballus) SO GENOME RESEARCH LA English DT Article ID LINKAGE MAP; HUMAN GENOME; ZOO-FISH; MARKERS; CHROMOSOME; SYNTENY; MICROSATELLITES; VERTEBRATES; CATTLE; CATS AB A comparative gene map of the horse genome composed of 127 loci was assembled based on the new assignment of 68 equine type I loci and on data published previously. PCR primers based on consensus gene sequences conserved across mammalian species were used to amplify markers for assigning 68 equine type I loci to 27 horse synteny groups established previously with a horse-mouse somatic cell hybrid panel (SCHP, UC Davis). This increased the number of coding genes mapped to the horse genome by over 2-fold and allowed refinements of the comparative mapping data available For this species. In conjunction with 57 previous assignments of type I loci to the horse genome map, these data have allowed us to confirm the assignment of 24 equine synteny groups to their respective chromosomes, to provisionally assign nine synteny groups to chromosomes, and to further refine the genetic composition established with Zoo-FISH of two horse chromosomes. The equine type I markers developed in this study provide an important resource for the future development of the horse linkage and physical genome maps. C1 Univ Calif Davis, Dept Anim Sci, Livermore, CA 95616 USA. Univ Calif Davis, Vet Genet Lab, Livermore, CA 95616 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. E Tennessee State Univ, Dept Biol Sci, Johnson City, TN 37614 USA. Univ Calif Davis, Dept Populat Hlth & Reprod, Livermore, CA 95616 USA. RP Murray, JD (reprint author), Univ Calif Davis, Dept Anim Sci, Livermore, CA 95616 USA. RI Rodrigues Caetano, Alexandre/B-5227-2017 OI Rodrigues Caetano, Alexandre/0000-0002-3419-7337 NR 34 TC 47 Z9 48 U1 0 U2 6 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 DEC PY 1999 VL 9 IS 12 BP 1239 EP 1249 DI 10.1101/gr.9.12.1239 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 270RU UT WOS:000084550600011 PM 10613847 ER PT J AU Pietu, G Eveno, E Soury-Segurens, B Fayein, NA Mariage-Samson, R Matingou, C Leroy, E Dechesne, C Krieger, S Ansorge, W Reguigne-Arnould, I Cox, D Dehejia, A Polymeropoulos, MH Devignes, MD Auffray, C AF Pietu, G Eveno, E Soury-Segurens, B Fayein, NA Mariage-Samson, R Matingou, C Leroy, E Dechesne, C Krieger, S Ansorge, W Reguigne-Arnould, I Cox, D Dehejia, A Polymeropoulos, MH Devignes, MD Auffray, C TI The genexpress IMAGE knowledge base of the human muscle transcriptome: A resource of structural, functional, and positional candidate genes for muscle physiology and pathologies SO GENOME RESEARCH LA English DT Article ID HUMAN SKELETAL-MUSCLE; HUMAN ERYTHROCYTE ANKYRIN; EXPRESSED SEQUENCE TAGS; CYCLE CONTROL PROTEINS; RADIATION HYBRID MAP; RING FINGER GENE; HUMAN GENOME; RAT-LIVER; CDNA; HYBRIDIZATION AB Sequence, gene mapping, and expression data corresponding to 910 genes transcribed in human skeletal muscle have been integrated to Form the muscle module of the Genexpress IMAGE Knowledge Base. Based on cDNA array hybridization, a set of 14 transcripts preferentially or specifically expressed in muscle have been selected and characterized in more detail: Their pattern of expression was confirmed by Northern blot analysis; their structure was further characterized by Full-insert cDNA sequencing and cDNA extension; the map location of the corresponding genes was refined by radiation hybrid mapping. Five of the 14 selected genes appear as interesting positional and functional candidate genes to study in relation with muscle physiology and/or specific orphan muscular pathologies. One example is discussed in more detail. The expression profiling data and the associated Genexpress Index2 entries for the 910 genes and the detailed characterization of the 14 selected transcripts are available from a dedicated Web server at http://idefix.upr420.vjF.cnrs.f/IMAGE/Page_unique/ welcome_muscles.html. The database has been organized to provide the users with a working space where they can find curated, annotated, integrated data for their genes of interest. Different navigation routes to exploit the resource are discussed. C1 Genexpress, CNRS, F-94801 Villejuif, France. NIH, Natl Human Gerome Res Inst, Bethesda, MD 20892 USA. CNRS, UMR 6548, F-06108 Nice, France. European Mol Biol Lab, Heidelberg, Germany. Stanford Univ, Dept Genet, Stanford, CA 96305 USA. RP Pietu, G (reprint author), Genexpress, CNRS, ERS 1984, F-94801 Villejuif, France. OI Devignes, Marie-Dominique/0000-0002-0399-8713 NR 26 TC 18 Z9 18 U1 0 U2 0 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 DEC PY 1999 VL 9 IS 12 BP 1313 EP 1320 DI 10.1101/gr.9.12.1313 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 270RU UT WOS:000084550600018 PM 10613854 ER PT J AU Caterina, J Shi, J Krakora, S Bartlett, JD Engler, JA Kozak, CA Birkedal-Hansen, H AF Caterina, J Shi, J Krakora, S Bartlett, JD Engler, JA Kozak, CA Birkedal-Hansen, H TI Isolation, characterization, and chromosomal location of the mouse enamelysin gene SO GENOMICS LA English DT Article ID MATRIX; METALLOPROTEINASE; TOOTH AB Mouse enamelysin (Mmp20), a member of the matrix metalloproteinase (MMP) family of extracellular matrix degrading enzymes, shows a high degree of homology with other MMPs, particularly those of the stromelysin/collagenase subfamilies. It is expressed exclusively in ameloblasts and odontoblasts. The mouse enamelysin gene (Mmp20) is made up of 10 exons spanning approximately 65 kb within the MMP gene cluster at the centromeric end of chromosome 9. (C) 1999 Academic Press. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35294 USA. RP Caterina, J (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 30 Convent Dr,MSC 4380, Bethesda, MD 20892 USA. FU NIDCR NIH HHS [DE08228, DE12098, R29 DE012098, DE10631] NR 15 TC 12 Z9 13 U1 0 U2 0 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 DEC 1 PY 1999 VL 62 IS 2 BP 308 EP 311 DI 10.1006/geno.1999.5990 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 275MZ UT WOS:000084825100025 PM 10610728 ER PT J AU Ben-Yosef, T Francomano, CA AF Ben-Yosef, T Francomano, CA TI Characterization of the human Talin (TLN) gene: Genomic structure, chromosomal localization, and expression pattern SO GENOMICS LA English DT Article ID CARTILAGE HAIR HYPOPLASIA; CYTOSKELETAL PROTEIN; PLATELET FORMATION; VINCULIN; DOMAINS; RAT AB Talin is a high-molecular-weight cytoskeletal protein, localized at cell-extracellular matrix associations known as focal contacts. In these regions, talin is thought to link integrin receptors to the actin cytoskeleton. Talin plays a key role in the assembly of actin filaments and in spreading and migration of various cell types. Talin proteins are found in a wide variety of organisms, from slime molds to humans. The human Talin (HGMW-approved symbol TLN) gene was previously mapped to chromosome 9p, but little was known of its sequence and genomic structure. To characterize human TLN further, we have isolated a single bacterial artificial chromosome clone, harboring the entire gene. The gene extends over more than 23 kb and consists of 57 exons. We have localized TLN to human chromosome band 9p13 by both fluorescence in situ hybridization and radiation hybrid mapping. Northern blot analysis detected TLN expression in various human tissues, including leukocytes, lung, placenta, Liver, kidney, spleen, thymus, colon, skeletal muscle, and heart. Based on its chromosomal location, expression pattern, and protein function, we considered TLN as a candidate gene for cartilage-hair hypoplasia (CHH), an autosomal recessive metaphyseal chondrodysplasia, previously mapped to 9p13. We sequenced the entire TLN coding sequence in several CHH patients, but no functional mutations were detected. (C) 1999 Academic Press. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Francomano, CA (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 20 TC 10 Z9 12 U1 0 U2 2 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 DEC 1 PY 1999 VL 62 IS 2 BP 316 EP 319 DI 10.1006/geno.1999.6019 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 275MZ UT WOS:000084825100027 PM 10610730 ER PT J AU Rahman, MM Gu, XX Tsai, CM Kolli, VSK Carlson, RW AF Rahman, MM Gu, XX Tsai, CM Kolli, VSK Carlson, RW TI The structural heterogeneity of the lipooligosaccharide (LOS) expressed by pathogenic non-typeable Haemophilus influenzae strain NTHi 9274 SO GLYCOBIOLOGY LA English DT Article DE HTHi; lipooligosaccharide; characterization; otitis media ID HEMOPHILUS-INFLUENZAE; DETOXIFIED LIPOOLIGOSACCHARIDE; LIPOPOLYSACCHARIDE; OLIGOSACCHARIDE; DUCREYI; POLYSACCHARIDE; GLYCOFORMS; PROTEINS AB Nontypeable Haemophilus influenzae (NTHi) is an important pathogen responsible for otitis media in children and of pneumonitis in adults with depressed resistance. NTHi is acapsular and, therefore, capsular polysaccharide-based vaccines are ineffective for preventing infections by this pathogen, Recently it was found that a detoxified lipooligosaccharide (LOS) conjugate from NTHi 9274 induced bactericidal antibodies effective against a large number of NTHi isolates, and conferred protection against NTHi otitis media in chinchillas (X,-X,Gu et al, 1996, Infect, Immun., 64, 4047-4053; X.-X.Gu et al,, 1997,, Infect. Immun., 65, 4488-4493), In this paper we report the chemical characterization of the LOS from NTHi 9274 LOS, NTHi is capable of expressing a heterogenous population of LOS exhibited by multiple oligosaccharide (OS) epitopes, OSs released from the LOS of NTHi 9274 by mild acid hydrolysis were purified using Bio-Gel P4 gel permeation chromatography. The OSs were characterized by glycosyl composition analysis, glycosyl linkage analysis, nuclear magnetic resonance spectroscopy (NMR), fast atom bombardment mass spectrometry (FAB-MS), matrix-assisted laser desorption time of flight mass spectrometry (MALDITOF-MS), and tandem MS/MS. At least 17 different OS molecules were observed. These contained variable glycosyl residues, phosphate (P), and phosphoethanolamine (PEA) substituents, These molecules contained either three, four, or five hexoses, and all contained four heptosyl residues. The four heptosyl residues consisted of one D,D-Hep and three L,D-Hep, Dephosphorylation of the OSs with aqueous 48% hydrofluoric acid (HF) reduced the number of molecules to about to seven; Hex(1-7)Hep(4)Kdo(1). Of these seven, Hex(2)Hep(4)Kdo(1), Hex(3)Hep(4)Kdo(1), and Hex(4)Hep(4)Kdo(1) were the major constituents, Thus, this NTHi LOS preparation is very heterogeneous, and contains structures different from those previously published for Haemophilus influenzae. The tandem MS/MS analysis and glycosyl linkage data suggest that the LOS oligosaccharides have the following structures: [GRAPHICS] where Hex is either a Glc or Gal residue. C1 Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. Natl Inst Deafness & Other Commun Disorders, Immunol Lab, Rockville, MD 20850 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Carlson, RW (reprint author), Univ Georgia, Complex Carbohydrate Res Ctr, 220 Riverbend Rd, Athens, GA 30602 USA. NR 31 TC 41 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD DEC PY 1999 VL 9 IS 12 BP 1371 EP 1380 DI 10.1093/glycob/9.12.1371 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 262AU UT WOS:000084044200010 PM 10561462 ER PT J AU Lertsumitkul, S Whitcup, SM Nussenblatt, RB Chan, CC AF Lertsumitkul, S Whitcup, SM Nussenblatt, RB Chan, CC TI Subretinal fibrosis and choroidal neovascularization in Vogt-Koyanagi-Harada syndrome SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID OCULAR HISTOPLASMOSIS SYNDROME; UVEITIS SYNDROME; MULTIFOCAL CHOROIDITIS; MACULAR DEGENERATION; SURGICAL REMOVAL; PROLIFERATION; FIBROBLAST; MEMBRANES; FEATURES; DISEASE AB Background: To describe clinical findings of subretinal fibrosis and choroidal neovascularization in patients with Vogt-Koyanagi-Harada (VKH) syndrome. Methods. We retrospectively reviewed 75 medical records of patients with VKH seen at the National Eye Institute, Bethesda. Maryland between 1978 and 1996. Recorded data included age, gender, race, duration of disease, extraocular manifestations, best-corrected visual acuity, slit-lamp biomicroscopy, retinal examination, retinal photographs and fluorescens angiograms. We sought features that correlated with the visual outcome. Results: Thirty of 75 (40%) patients developed subretinal fibrosis. Eleven patients (14.7%) had choroidal neovascularization. Presence of subretinal fibrosis was associated with a longer duration of the disease (42.6 vs 19.1 months, P=0.07). Patients with subretinal fibrosis had worse visual acuity than those without subretinal fibrosis (26.2 vs 57.3 ETDRS letters read, P<0.001) after adjusting for duration of disease (P=0.021), degree of vitreous haze (P=0.074), and use of immunosuppressive therapy (P=0.008). Conclusions: Presence of subretinal fibrosis in patients with VKH is associated with a poor visual prognosis. The diagnosis of choroidal neovascularization and subretinal fibrosis presents a challenge in the management of this disease. C1 NEI, NIH, Bethesda, MD 20892 USA. Liverpool Hosp, Dept Ophthalmol, Liverpool, NSW 2170, Australia. RP Lertsumitkul, S (reprint author), NEI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 35 TC 21 Z9 24 U1 0 U2 0 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 DEC PY 1999 VL 237 IS 12 BP 1039 EP 1045 DI 10.1007/s004170050342 PG 7 WC Ophthalmology SC Ophthalmology GA 273JY UT WOS:000084705200016 PM 10654175 ER PT J AU Beck, KH Shattuck, T Haynie, D Crump, AD Simons-Morton, B AF Beck, KH Shattuck, T Haynie, D Crump, AD Simons-Morton, B TI Associations between parent awareness, monitoring, enforcement and adolescent involvement with alcohol SO HEALTH EDUCATION RESEARCH LA English DT Article ID TEENAGE DRINKING; ATTITUDES; PERCEPTIONS; BEHAVIORS AB In a statewide random telephone survey of 454 parents and their 14- to 19-year-old adolescents, we examined the associations between various parenting strategies and self-reported teen drinking. Less teen drinking was associated with parents' reports of checking to see if other parents would be present at teen parties, particularly among White parents. Parents' monitoring of teens' activities was associated with feelings of competence at doing so, There was, however, no difference in drinking between teens with parents who did or did not report restricting their teens due to teen misbehavior. These findings suggest that a proactive parental monitoring approach may be associated with less adolescent drinking. Prospective research is needed to clarify the causal relationship between parental monitoring, efficacy and teen alcohol-related behavior. C1 Univ Maryland, Dept Hlth Educ, College Pk, MD 20742 USA. NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. RP Beck, KH (reprint author), Univ Maryland, Dept Hlth Educ, College Pk, MD 20742 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 25 TC 49 Z9 49 U1 4 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1153 J9 HEALTH EDUC RES JI Health Educ. Res. PD DEC PY 1999 VL 14 IS 6 BP 765 EP 775 DI 10.1093/her/14.6.765 PG 11 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 266DH UT WOS:000084285000006 PM 10585384 ER PT J AU Carosi, M Heistermann, M Visalberghi, E AF Carosi, M Heistermann, M Visalberghi, E TI Display of preceptive behaviors in relation to urinary and fecal progestin levels over the ovarian cycle in female tufted capuchin monkeys SO HORMONES AND BEHAVIOR LA English DT Article DE tufted capuchin; urinary hormones; fecal hormones; proceptivity; attractivity ID CEBUS-APELLA; REPRODUCTIVE STATUS; SEXUAL-BEHAVIOR; CALLITHRIX-JACCHUS; MENSTRUAL-CYCLE; METABOLITES; PREGNANCY; EXCRETION; ENDOCRINE; PRIMATES AB In many primates species, female sexual attractivity is influenced by behavioral cues as well as by nonbehavioral cues (i.e., visual-morphological or chemical signals). Both kinds of cues are usually related to the ovarian cycle and female hormonal state. Female tufted capuchins (Cebus apella) lack any external morphological change in relation to the ovarian cycle and evidence of scent-marking behavior has never been reported. In addition, tufted capuchin males do not routinely investigate the female's body or urine. Instead, capuchin females are extremely active in sexually soliciting the male(s) and their courtship toward them involves a rich behavioral repertoire. In the present study we defined female tufted capuchin proceptivity and investigated its relationship with female reproductive state. ovarian hormones were measured in urine and fecal samples from four captive females in order to (a) assess their reliability for monitoring female ovarian function and (b) provide information on the timing of the component cycle phases and in particular the periovulatory phase. Measurements of urinary and fecal progestin metabolites provided the best: indicator of ovarian cyclicity and for timing of the periovulatory phase. Through a multivariate analysis of the behavioral data set we distinguished four behaviors (eyebrow raising with vocalization, touching-and-running, nuzzling and head cocking) which showed a marked cyclicity (21.3 days) that matched that of urinary progesterone (21.9 days). Data showed that each period of proceptive behaviors was 2.7 +/- 0.8 days long and the day of a defined luteal phase vise in urinary progesterone levels was markedly shifted toward the end of this period. Furthermore, the ejaculations observed always occurred within proceptive periods. The results clearly indicate that female behavior is a goad indicator of the periovulatory phase and can enhance female attractivity. (C) 1999 Academic Press. C1 Natl Res Council, Inst Psychol, Rome, Italy. German Primate Ctr, Dept Reprod Biol, Gottingen, Germany. RP Carosi, M (reprint author), NICHD, Comparat Ethol Lab, Anim Ctr, Bldg 112,Rm 205,POB 529, Poolesville, MD 20837 USA. RI Carosi, Monica/C-9683-2014; OI Visalberghi, Elisabetta/0000-0001-7407-5468 NR 62 TC 53 Z9 61 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD DEC PY 1999 VL 36 IS 3 BP 252 EP 265 DI 10.1006/hbeh.1999.1545 PG 14 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 274AA UT WOS:000084740500006 PM 10603289 ER PT J AU Nanni, L Ming, JE Bocian, M Steinhaus, K Bianchi, DW de Die-Smulders, C Giannotti, A Imaizumi, K Jones, KL Del Campo, M Martin, RA Meinecke, P Pierpont, MEM Robin, NH Young, ID Roessler, E Muenke, M AF Nanni, L Ming, JE Bocian, M Steinhaus, K Bianchi, DW de Die-Smulders, C Giannotti, A Imaizumi, K Jones, KL Del Campo, M Martin, RA Meinecke, P Pierpont, MEM Robin, NH Young, ID Roessler, E Muenke, M TI The mutational spectrum of the Sonic Hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly SO HUMAN MOLECULAR GENETICS LA English DT Article ID LEMLI-OPITZ-SYNDROME; RETINOIC ACID; AUTOPROCESSING DOMAIN; CRYSTAL-STRUCTURE; INDUCTION; DROSOPHILA; PROMOTER; PROTEINS; HOMOLOG; PRODUCT AB Holoprosencephaly (HPE) is a common developmental anomaly of the human forebrain and midface where the cerebral hemispheres fail to separate into distinct left and right halves. We have previously reported haploinsufficiency for Sonic Hedgehog (SHH) as a cause for HPE. We have now performed mutational analysis of the complete coding region and intron-exon junctions of the SHH gene in 344 unrelated affected individuals. Herein, we describe 13 additional unrelated affected individuals with SHH mutations, including nonsense and missense mutations, deletions and an insertion. These mutations occur throughout the extent of the gene. No specific genotype-phenotype association is evident based on the correlation of the type or position of the mutations. In conjunction with our previous studies, we have identified a total of 23 mutations in 344 unrelated cases of HPE, They account for 14 cases of familial HPE and nine cases of sporadic HPE. Mutations in SHH were detected in 10 of 27 (37%) families showing autosomal dominant transmission of the HPE spectrum, based on structural anomalies. Interestingly, three of the patients with an SHH mutation also had abnormalities in another gene that is expressed during forebrain development. We suggest that the interactions of multiple gene products and/or environmental elements may determine the final phenotypic outcome for a given individual and that variations among these factors: may cause the wide variability in the clinical features seen in HPE. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Genet, Philadelphia, PA 19104 USA. Univ Calif Irvine, Orange, CA 92668 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ Hosp Maastricht, Maastricht, Netherlands. Bambino Gesu Hosp, Rome, Italy. Kanagawa Childrens Med Ctr, Yokohama, Kanagawa, Japan. Univ Calif San Diego, San Diego, CA 92103 USA. St Christophers Hosp Children, Philadelphia, PA 19133 USA. Altonaer Kinder Krankenhaus, Hamburg, Germany. Univ Minnesota Hosp, Minneapolis, MN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. City Hosp Nottingham, Nottingham, England. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,10C101, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD29862, HD01218, HD28732] NR 37 TC 205 Z9 212 U1 0 U2 14 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 DEC PY 1999 VL 8 IS 13 BP 2479 EP 2488 DI 10.1093/hmg/8.13.2479 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 262GX UT WOS:000084059700016 PM 10556296 ER PT J AU Roth, MJ AF Roth, MJ TI Mucoid arteriosclerotic and nerve degenerative lesions in esophageal carcinoma - Reply SO HUMAN PATHOLOGY LA English DT Letter ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; CANCER INCIDENCE; LINXIAN; CHINA; SUPPLEMENTATION; VASCULOPATHY C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. RP Roth, MJ (reprint author), NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD DEC PY 1999 VL 30 IS 12 BP 1526 EP 1527 DI 10.1016/S0046-8177(99)90183-1 PG 2 WC Pathology SC Pathology GA 270YJ UT WOS:000084564500027 ER PT J AU Cassano, GB Frank, E Maser, JD Shear, MK Rotondo, A Mauri, M Dell'Osso, L AF Cassano, GB Frank, E Maser, JD Shear, MK Rotondo, A Mauri, M Dell'Osso, L TI The panic-agoraphobic spectrum SO HUMAN PSYCHOPHARMACOLOGY-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 2nd International Symposium on Generalised Anxiety Disorder Psychopharmacology, Cognition and Treatment CY MAR, 1998 CL LONDON, ENGLAND DE panic; agoraphobia; mental disorders ID BRIQUETS SYNDROME; DISORDER; ATTACKS; HYPOCHONDRIASIS; ILLNESS AB Categorical classifications of mental disorders do not take into account the subthreshold, atypical and often enduring symptoms that accompany the core manifestations of full-blown mental disorders. However, this often neglected spectrum of symptoms may be as distressing and debilitating as the full-blown disorder and may have unrecognized importance in treatment selection and response. To this end, a spectrum approach to mental disorders, such as bipolar, obsessive-compulsive, eating, and panic disorder has been developed, which has been extensively used and proven effective in clinical practice. The need for a systematic identification and assessment of a broad array of symptoms and behavioural features led, as a first step, to the conceptualization of the panic-agoraphobic spectrum model and to the development of a structured interview (SCI-PAS). This model has been constructed by identifying different psychopathological and clinical domains incorporating and extending Panic Disorder as described in DSM-IV. The rationale, clinical usefulness, and heuristic significance of the panic-agoraphobic spectrum model will be discussed. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA USA. NIMH, Integrat Neurosci Schizophrenia Mood & Other Brai, Rockville, MD 20857 USA. RP Cassano, GB (reprint author), Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. NR 21 TC 3 Z9 3 U1 6 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6222 J9 HUM PSYCHOPHARM CLIN JI Hum. Psychopharmacol.-Clin. Exp. PD DEC PY 1999 VL 14 SU 1 BP S38 EP S44 DI 10.1002/(SICI)1099-1077(199908)14:1+3.3.CO;2-Y PG 7 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry; Psychology GA 260RD UT WOS:000083962900007 ER PT J AU Yap, GS Sher, A AF Yap, GS Sher, A TI Cell-mediated immunity to Toxoplasma gondii: Initiation, regulation and effector function SO IMMUNOBIOLOGY LA English DT Article ID INDUCIBLE NITRIC-OXIDE; IFN-GAMMA; IN-VIVO; TNF-ALPHA; INTRACELLULAR PARASITES; DENDRITIC CELLS; HOST-RESISTANCE; ACUTE INFECTION; IL-12; MICE AB Cell-mediated immune responses are essential for host control of intracellular infections. Toxoplasma gondii is a protozoan parasite that infects multiple vertebrate species and invades multiple cell types. Upon initial encounter with the immune system, the parasite rapidly induces production of the type-1 promoting cytokine IL-12 most likely from a subpopulation of dendritic cells. NK and T cells are then activated and triggered to synthesize IFN-gamma, the major mediator of host resistance during the acute and chronic phases of infection. During the acute phase, a concomitant IL-10 response dampens the systemic type-1 cytokine production and prevents lethal immunopathology. Cytokine (IFN-gamma and TNF-alpha) rather than cytotoxicity-based effector functions are more critical for protective immunity both during the acute and chronic phases of T. gondii infection. Both hemopoietic and non-hemopoietic cellular elements act as IFN-gamma and TNF-dependent effecters of host resistance. Type II iNOS-derived nitric oxide (NO) is required mainly for hemopoietic cell-derived effector cell activity in the central nervous system (CNS) during the chronic phase of infection. Nevertheless, in both the acute and chronic stages, IFN-gamma-dependent bur iNOS-independent mechanism(s) play a major function in parasite control and their identification remains an important challenge for this field. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sher, A (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bldg 4,Room 126,4 Ctr Drv MSC 0425, Bethesda, MD 20892 USA. NR 28 TC 133 Z9 143 U1 3 U2 9 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD DEC PY 1999 VL 201 IS 2 BP 240 EP 247 PG 8 WC Immunology SC Immunology GA 267MD UT WOS:000084361000011 PM 10631573 ER PT J AU Yewdell, J Anton, LC Bacik, I Schubert, U Snyder, HL Bennink, JR AF Yewdell, J Anton, LC Bacik, I Schubert, U Snyder, HL Bennink, JR TI Generating MHC class I ligands from viral gene products SO IMMUNOLOGICAL REVIEWS LA English DT Review ID TOXIC LYMPHOCYTES-T; UBIQUITIN-ACTIVATING ENZYME; ENDOGENOUSLY SYNTHESIZED PEPTIDE; ANTIGEN-PROCESSING PATHWAY; ENDOPLASMIC-RETICULUM; PROTEASOME INHIBITORS; INFECTED-CELLS; INFLUENZA NUCLEOPROTEIN; PROTEIN; MOLECULES AB MHC class I molecules function to present peptides comprised of eight to 11 residues to CD8(+) T lymphocytes. Here we review the efforts of our laboratory to understand how cells generate such peptides from viral gene products. We particularly focus on the nature of substrates acted on by cytosolic proteases, the contribution of proteasomes and non-proteasomal proteases to peptide generation, the involvement of ubiquitination in peptide generation, the intracellular localization of proteasome generation of antigenic peptides, and the trimming of peptides in the endoplasmic reticulum. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, J (reprint author), NIAID, Viral Dis Lab, NIH, Room 209,Bldg 4,4 Ctr Dr,MSC 0440, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; Anton, Luis/C-4740-2013 OI Anton, Luis/0000-0001-9665-011X NR 76 TC 51 Z9 52 U1 0 U2 2 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 DEC PY 1999 VL 172 BP 97 EP 108 DI 10.1111/j.1600-065X.1999.tb01359.x PG 12 WC Immunology SC Immunology GA 268TY UT WOS:000084432700009 PM 10631940 ER PT J AU Cohen, MB Giannella, RA Losonsky, GA Lang, DR Parker, S Hawkins, JA Gunther, C Schiff, GA AF Cohen, MB Giannella, RA Losonsky, GA Lang, DR Parker, S Hawkins, JA Gunther, C Schiff, GA TI Validation and characterization of a human volunteer challenge model for cholera by using frozen bacteria of the new Vibrio cholerae epidemic serotype, O139 SO INFECTION AND IMMUNITY LA English DT Article ID NORTH-AMERICAN VOLUNTEERS; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; BLOOD-GROUP; VACCINE; SPECIFICITY; RELEVANCE; EFFICACY; BENGAL AB Until recently, all epidemic strains of Vibrio cholerae were of the O1 serotype. Current epidemics have also been caused by a new serotype, Vibrio cholerae O139. Although the pathogenesis and clinical features of O139 cholera are similar to those of O1 cholera, immunity to serotype O1 does not confer immunity to serotype O139, Therefore, prior to beginning vaccine efficacy studies, we sought to validate the use of a large standardized frozen inoculum of virulent V. cholerae O139 4260B for use in a human volunteer challenge model. Healthy volunteers (n = 25) were recruited for an Internal Review Board-approved inpatient dose-escalation challenge, Our goal was to identify a dose at which the cholera attack rate and the geometric mean purge were sufficient for determining vaccine efficacy against moderate and severe disease. At a dose of 10(5) CFU 8 of 10 volunteers experienced purging and had a positive stool culture far V. cholerae. However, at this dose, the geometric mean stool volume of 2,175 g was insufficient by study criteria, At a dose of 10(6) CFU, 14 of 15 volunteers experienced purging, with a geometric mean stool volume of 5,621 g, Disease severity was significantly greater in volunteers with blood group O than those with non-O blood types (10,353 g versus 3,555 g, P < 0.001), Following challenge, all volunteers demonstrated a significant rise in antitoxin antibodies but the serum vibriocidal titer nas attenuated compared to that seen after challenge dth an O1 strain. This model provides a reproducible illness of sufficient severity for testing the efficacies of new O139 or combined O1-O139 vaccines. C1 Univ Cincinnati, Div Pediat Gastroenterol & Nutr, Cincinnati, OH 45229 USA. Univ Cincinnati, Cincinnati, OH 45229 USA. Gamble Program Clin Studies, Div Infect Dis, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Cincinnati, Div Digest Dis, Cincinnati, OH 45267 USA. Univ Maryland, Ctr Vaccine Dev, Sch Med, Baltimore, MD 21201 USA. NIAID, Div Microbiol & Infect Dis, Rockville, MD 20892 USA. RP Cohen, MB (reprint author), Univ Cincinnati, Div Pediat Gastroenterol & Nutr, Cincinnati, OH 45229 USA. RI Gunther, Carolyn/N-3026-2013; OI Cohen, Mitchell/0000-0002-4412-350X FU NCRR NIH HHS [M01RR08084, M01 RR008084]; NIAID NIH HHS [N01AI45252] NR 17 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1999 VL 67 IS 12 BP 6346 EP 6349 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 257DW UT WOS:000083768000018 PM 10569748 ER PT J AU Levine, SJ AF Levine, SJ TI Diagnosing pulmonary infections in HIV-positive patients - part 2: Diagnostic approach SO INFECTIONS IN MEDICINE LA English DT Article DE pneumonia; infection, respiratory; immunosuppression; HIV; infection, opportunistic ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; OPEN-LUNG-BIOPSY; BRONCHOALVEOLAR LAVAGE FLUID; PROPHYLACTIC AEROSOLIZED PENTAMIDINE; TRANSTHORACIC NEEDLE-BIOPSY; INDUCED SPUTUM EXAMINATION; ENDOBRONCHIAL TUBERCULOSIS; VIRUS INFECTION; AIDS AB Pulmonary infections continue to be an important cause of morbidity and mortality in HIV-infected patients. In this second part of a two-part article, we present a general approach to the diagnosis of pulmonary disease in HIV-positive patients that requires individualization based on the patient's clinical status, risk factors for specific pathogens or noninfectious processes, radiographic findings, and associated illnesses. C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NIH, Dept Crit Care Med, Bldg 10, Bethesda, MD 20892 USA. NR 54 TC 0 Z9 0 U1 0 U2 0 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD DEC PY 1999 VL 16 IS 12 BP 802 EP + PG 8 WC Infectious Diseases SC Infectious Diseases GA 268DE UT WOS:000084398400011 ER PT J AU Rubin, KH Nelson, LJ Hastings, P Asendorpf, J AF Rubin, KH Nelson, LJ Hastings, P Asendorpf, J TI The transaction between parents' perceptions of their children's shyness and their parenting styles SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID MOTHER-INFANT RELATIONSHIP; EARLY-CHILDHOOD; INDIVIDUAL-DIFFERENCES; MIDDLE CHILDHOOD; SOCIAL BEHAVIORS; FOLLOW-UP; INHIBITION; PRESCHOOLERS; UNFAMILIAR; ASYMMETRY AB In recent years, researchers have examined factors that "determine" parenting beliefs, styles, and behaviours. One potential determinant of parenting is the child him/herself. Child characteristics, such as temperament, have been cited as evocative influences on parenting beliefs and behaviours. The primary purpose of this study was to investigate the longitudinal relations between children's social wariness/inhibition and parents' beliefs about how to best socialise their children. Questionnaire data on child temperament and parenting practices were collected from the parents (mothers and fathers) of sixty 2-year-olds; identical data were collected 2 years later. Observations of inhibited behaviour were taken at two years. Results indicated that few differences existed between mothers' and fathers' expressed parenting styles at ages 2 and 4 years. Second, parental perceptions of child shyness at age 2 were: (a) stable to age 4; and (b) predicted a lack of encouragement of independence at age 4. Third, parents' expressed lack of encouragement of independence, although stable from 2 to 4 years, failed to predict child shyness at age 4. The findings support the conjecture that young children's dispositional characteristics predict subsequent maternal and paternal behaviour. C1 Univ Maryland, Dept Human Dev, Ctr Children Relationships & Culture, College Pk, MD 20742 USA. NIMH, Bethesda, MD 20892 USA. Humboldt Univ, Berlin, Germany. RP Rubin, KH (reprint author), Univ Maryland, Dept Human Dev, Ctr Children Relationships & Culture, 3304 Benjamin Bldg, College Pk, MD 20742 USA. NR 66 TC 129 Z9 131 U1 4 U2 25 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD DEC PY 1999 VL 23 IS 4 BP 937 EP 957 PG 21 WC Psychology, Developmental SC Psychology GA 272YZ UT WOS:000084680200006 ER PT J AU Idriss, H Kawa, S Damuni, Z Thompson, EB Wilson, SH AF Idriss, H Kawa, S Damuni, Z Thompson, EB Wilson, SH TI HIV-1 reverse transcriptase is phosphorylated in vitro and in a cellular system SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE HIV; reverse transcriptase; phosphorylation; kinase; AIDS ID INACTIVATES PROTEIN PHOSPHATASE-2A; DNA POLYMERASE-ALPHA; KINASE-C; INVITRO; PURIFICATION; VIRUS; BETA; PHOSPHOPROTEIN; EXPRESSION; BINDING AB Phosphorylation modulates the activity of many proteins that interact with nucleic acids including DNA and RNA polymerases. The HIV-I reverse transcriptase (RT) is essential during the replicative cycle of the HIV-I virus. HIV-I RT has several potential sites for phosphorylation that could regulate its activities. In this work, the phosphorylation of HIV-I RT is examined in vitro and in vivo, to evaluate any role for this modification in regulating RT metabolism. Recombinant unphosphorylated HIV-1 RT heterodimer expressed in bacteria can be phosphorylated in vitro by several purified mammalian protein kinases. Seven kinases were tested, and five of these enzymes phosphorylated HIV-1 RT, Using an insect baculovirus expression system, the 66 kDa HIV-I RT was also phosphorylated in viva. However, HIV-1 RT immunoprecipitated from H9-lymphoma cells infected with HIV-I showed negligible phosphorylation. Our results indicate that purified HIV-1 RT can be phosphorylated by several mammalian protein kinases in vitro and during expression in baculovirus infected insect cells. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA. Penn State Univ, Milton S Hershey Med Ctr, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. EM hi@st-and.ac.uk FU NIDDK NIH HHS [DK41058] NR 38 TC 9 Z9 9 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 EI 1878-5875 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD DEC PY 1999 VL 31 IS 12 BP 1443 EP 1452 DI 10.1016/S1357-2725(99)00097-7 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 266AA UT WOS:000084277400010 PM 10641798 ER PT J AU Johnson, CC Gorell, JM Rybicki, BA Sanders, K Peterson, EL AF Johnson, CC Gorell, JM Rybicki, BA Sanders, K Peterson, EL TI Adult nutrient intake as a risk factor for Parkinson's disease SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carotenoids; case-control study; diet; Parkinson's disease; risk factors ID FOOD-FREQUENCY QUESTIONNAIRE; CIGARETTE-SMOKING; BETA-CAROTENE; VITAMIN-E; PLASMA; DESIGN; WOMEN; RATES; DIET; IRON AB Background This population-based case-control study evaluated nutrient intake as a risk factor for Parkinson's disease (PD) among people aged greater than or equal to 50 years in metropolitan Detroit. Methods Cases (n = 126) were diagnosed between 1991 and 1995 and neurologist-confirmed. Controls (n = 432) were frequency-matched for sex, age (+/-5 years) and race. Using a standardized food frequency questionnaire, subjects reported the foods they ate within the past year. Results Estimating the association between PD and risk of being in the highest versus the lowest intake quartile, there were elevated odds ratios for total fat (OR 1.94, 95% confidence interval [CI] : 1.05-3.58), cholesterol (OR 2.11, 95% CI : 1.14-3.90), lutein (OR 2.52, 95% CI : 1.32-4.84) and iron (OR 1.88, 95% CI : 1.05-3.38). Conclusions These results suggest an association of PD with high intake of total fat, saturated fats, cholesterol, lutein and iron. C1 Henry Ford Hlth Syst, Josephine Ford Canc Ctr, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. Henry Ford Hlth Syst, Dept Neurol, Detroit, MI 48202 USA. Wayne State Univ, NIEHS, Ctr Mol & Cellular Toxicol Human Applicat, Detroit, MI USA. RP Johnson, CC (reprint author), Henry Ford Hlth Syst, Josephine Ford Canc Ctr, Dept Biostat & Res Epidemiol, 1 Ford Pl,5C, Detroit, MI 48202 USA. OI Johnson, Christine Cole/0000-0002-6864-6604 FU NIEHS NIH HHS [ES06418] NR 45 TC 94 Z9 95 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1999 VL 28 IS 6 BP 1102 EP 1109 DI 10.1093/ije/28.6.1102 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 270FB UT WOS:000084523800013 PM 10661654 ER PT J AU Schrauwen, P Xia, J Walder, K Snitker, S Ravussin, E AF Schrauwen, P Xia, J Walder, K Snitker, S Ravussin, E TI A novel polymorphism in the proximal UCP3 promoter region: effect on skeletal muscle UCP3 mRNA expression and obesity in male nondiabetic Pima Indians SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE UCP3 promoter; obesity; genotype ID UNCOUPLING PROTEIN-2 GENE; ENERGY-METABOLISM; MARKERS AB OBJECTIVE: UCP2 and UCP3 are newly discovered uncoupling proteins, which are thought to underlie the variability in energy metabolism in humans. Mutations in the UCP2 and/or UCP3 gene have been associated with sleeping metabolic rate. Recently we reported that skeletal muscle UCP3 mRNA expression was positively correlated with sleeping metabolic rate in Pima Indians. To study whether genetic variation in the promoter region of UCP3 contributed to the variation in expression of UCP3, we screened part of the proximal promoter region for polymorphisms. METHODS: In the first part of the study, the proximal promoter region of UCP3 was screened by direct sequencing in 24 non-diabetic Pima Indians (range body mass index (BMI): 18- 47 kg/m(2)) (Schrauwen et al. Diabetes 1999; 48: 146-149) and skeletal muscle UCP3 mRNA expression was measured by RT-PCR. In the second part of the study, we typed the polymorphism found in the first part of the study in 67 Pima Indians (32 males, 35 females) from the upper and lower extremes of the BMI distribution. RESULTS: We identified a novel C to T substitution in the UCP3 promoter, 6bp upstream of the putative TATA signal, and 55bp upstream of the transcription starting site, Among 18 male subjects, skeletal muscle UCP3 mRNA expression was significantly higher in the C/T & T/T group compared to the C/C homozygotes (P < 0.02). However, in the group of 67 Pima Indians genotype frequencies were not different in the obese and lean groups. CONCLUSION: We identified a novel polymorphism in the proximal promoter region of UCP3, which was associated with increased skeletal muscle expression of UCP3 in male non-diabetic Pima Indians. Considering the suggested role of UCP3 in energy metabolism, this polymorphism might be of physiological importance in the regulation of energy balance. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Lilly Corp Ctr, Indianapolis, IN 46285 USA. Maastricht Univ, Dept Human Biol, Maastricht, Netherlands. RP Xia, J (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. NR 11 TC 86 Z9 90 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 1999 VL 23 IS 12 BP 1242 EP 1245 DI 10.1038/sj.ijo.0801057 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 261VJ UT WOS:000084030100004 PM 10643679 ER PT J AU Morozov, VE Fuller, BG AF Morozov, VE Fuller, BG TI 5 ' to 3 ' Single strand DNA exonuclease activity in a preparation of human Ku protein SO IUBMB LIFE LA English DT Article DE DNA-PK; double-strand DNA break; exonuclease activity; Ku protein ID NONHOMOLOGOUS RECOMBINATION; SACCHAROMYCES-CEREVISIAE; HOMOLOGOUS RECOMBINATION; V(D)J RECOMBINATION; DEPENDENT ATPASE; BREAK REPAIR; HELICASE-II; KINASE; AUTOANTIGEN; BINDING AB We describe a novel 5' to 3' single-strand exonuclease activity exhibited by a Ku preparation purified from a human cell line, The enzyme removes 5' single-strand extensions from duplex DNA molecules. The exonuclease and helicase activities respond reciprocally to changes in ATP concentrations: Nuclease activity is inhibited at the ATP concentrations that are optimal for the helicase. The exonuclease activity does not require divalent cations. The potential implications of the exonuclease activity findings for repair of double-strand breaks and recombination processes are discussed. C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Morozov, VE (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10,Room B3 B69, Bethesda, MD 20892 USA. NR 32 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD DEC PY 1999 VL 48 IS 6 BP 593 EP 599 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273QG UT WOS:000084717900005 PM 10683763 ER PT J AU Lenfant, C AF Lenfant, C TI Conquering cardiovascular disease - Progress and promise SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), NHLBI, NIH, Room 5A52,Bldg 31,MSC 2486, Bethesda, MD 20892 USA. NR 26 TC 12 Z9 12 U1 0 U2 0 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 DEC 1 PY 1999 VL 282 IS 21 BP 2068 EP 2070 DI 10.1001/jama.282.21.2068 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 259TB UT WOS:000083908700027 PM 10591390 ER PT J AU Jensen, PS Edelbrock, C AF Jensen, PS Edelbrock, C TI Subject and interview characteristics affecting reliability of the diagnostic interview schedule for children SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE DISC; psychopathology; assessment; reliability; diagnostic interviews ID BEHAVIOR PROBLEM SYNDROMES; PSYCHIATRIC DIAGNOSES; ALGORITHMS; AGREEMENT; PARENT AB Despite the well-known difficulties in obtaining reliable and valid assessments of child psychopathology, investigators generally have not examined the influence of factors such as subject characteristics or the specific assessment procedures themselves on the validity of the information obtained. To address these issues, this special section presents four studies of the Diagnostic Interview Schedule for Children, in which investigators examined the impact of a range of variables on the reliability of its symptom and diagnostic information. Factors studied include interview structural characteristics; question length, complexity, and placement within the interview; and interview subject characteristics. Overall findings suggest that interview and subject characteristics exert important influences on the data obtained, and that novel approaches, such as allowing subjects a greater role in the ordering of questions to be answered, may improve the precision and accuracy of such measures of children's psychopathology. C1 NIMH, Bethesda, MD 20892 USA. Penn State Univ, University Pk, PA 16802 USA. RP Jensen, PS (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Child Psychiat, Ctr Advancement Childrens Mental Hlth,Unit 78, 1051 Riverside Dr, New York, NY 10032 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 15 TC 5 Z9 5 U1 2 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD DEC PY 1999 VL 27 IS 6 BP 413 EP 415 DI 10.1023/A:1021971724048 PG 3 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 267KA UT WOS:000084356100001 PM 10821622 ER PT J AU Piacentini, J Roper, M Jensen, P Lucas, C Fisher, P Bird, H Bourdon, K Schwab-Stone, M Rubio-Stipec, M Davies, M Dulcan, M AF Piacentini, J Roper, M Jensen, P Lucas, C Fisher, P Bird, H Bourdon, K Schwab-Stone, M Rubio-Stipec, M Davies, M Dulcan, M TI Informant-based determinants of symptom attenuation in structured child psychiatric interviews SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE structured interviews; diagnosis; DISC; child; attenuation; reliability; informant ID ADOLESCENTS; RELIABILITY; SCHEDULE; IMPAIRMENT; VALIDITY AB Informant-related determinants of item attenuation, that is, the drop-off in symptom endorsement rates at retest, were examined in an enriched community subsample of 245 parent-child pairs drawn from the National Institute of Mental Health Methods for Epidemiology of Child and Adolescent Mental Disorders Study. Youngsters and their parents were interviewed with the Diagnostic Interview Schedule for Children (Version 2.3; DISC-2.3) on two occasions with a mean test-retest interval of 12 days. Item attenuation rates were high for both informants;with adults failing to confirm 42% and children 58% of baseline responses at retest. Stepwise regressions revealed that item attenuation at DISC-P retest was higher for adult informants who were younger, and who reported on older and less impaired children. On the DISC-C, attenuation was higher for children who were less impaired, rated as doing worse in school, and who had a longer test-retest interval. These results are broadly consistent with past studies examining the determinants of attenuation and test-retest reliability and have implications for the design and use of structured diagnostic instruments. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Sch Med, Div Child & Adolescent Psychiat, Los Angeles, CA 90024 USA. NIMH, Div Epidemiol & Serv Res, Rockville, MD 20857 USA. NIMH, Div Clin & Treatment Res, Rockville, MD 20857 USA. Columbia Univ, New York State Psychiat Inst, Div Child & Adolescent Psychiat, New York, NY USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. Childrens Mem Hosp, Dept Psychiat, Chicago, IL 60614 USA. RP Piacentini, J (reprint author), Univ Calif Los Angeles, Inst Neuropsychiat, Sch Med, Div Child & Adolescent Psychiat, 760 Westwood Plaza,Room 68-251A, Los Angeles, CA 90024 USA. RI Piacentini, John/C-4645-2011; OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [MH 278 89 0002, MH 36971, MH278 89 0001] NR 22 TC 24 Z9 24 U1 6 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD DEC PY 1999 VL 27 IS 6 BP 417 EP 428 DI 10.1023/A:1021923808118 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 267KA UT WOS:000084356100002 PM 10821623 ER PT J AU Lucas, CP Fisher, P Piacentini, J Zhang, HY Jensen, PS Shaffer, D Dulcan, M Schwab-Stone, M Regier, D Canino, G AF Lucas, CP Fisher, P Piacentini, J Zhang, HY Jensen, PS Shaffer, D Dulcan, M Schwab-Stone, M Regier, D Canino, G TI Features of interview questions associated with attenuation of symptom reports SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE attenuation; reliability; diagnosis; assessment; diagnostic interviews; DISC ID CHILDREN DISC-2.1; SCHEDULE; RELIABILITY; VALIDITY; EPIDEMIOLOGY; REFLECTIONS; POPULATION; DIAGNOSIS AB Previous studies have suggested that discrepant reporting in a test-retest reliability paradigm is not purely random measurement error, but partly a function of a systematic tendency to say "no" during retest to questions answered positively at initial testing ("attenuation"). To examine features of interview questions that may be associated with attenuation, three raters independently assessed the structural and content features of questions from the Diagnostic Interview Schedule for Children (version 2.3) and linked these to data from a test-retest reliability study of 223 community respondents (parent and child reports). Results indicated that for both parent and youth reports, item features most strongly associated with attenuation were (a) being a "stem" question (asked of all respondents, regardless of any skip structure); (b) question placement in the first half of the interview; (c) question length; (d) question complexity; or (e) requiring assessment of the timing, duration, or frequency of a symptom. Findings may be explained by participants' conscious efforts to avoid further questions or by their learning more about the nature and purpose of the interview as they gain more experience; alternatively, findings may represent a methodological artifact of structured interview design. C1 Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. NIMH, Off Director, Bethesda, MD 20892 USA. Childrens Mem Hosp, Div Child & Adolescent Psychiat, Chicago, IL 60614 USA. Yale Child Study Ctr, New Haven, CT USA. Behav Sci Res Inst, San Juan, PR USA. Mental Hlth & Anti Addict Serv Puerto Rico, San Juan, PR USA. RP Lucas, CP (reprint author), Columbia Univ, Dept Child Psychiat, 1051 Riverside Dr,Box 78, New York, NY 10032 USA. RI Piacentini, John/C-4645-2011; OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [U01 MH46717, U01 MH46725, U01 MH46718] NR 20 TC 28 Z9 28 U1 3 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD DEC PY 1999 VL 27 IS 6 BP 429 EP 437 DI 10.1023/A:1021975824957 PG 9 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 267KA UT WOS:000084356100003 PM 10821624 ER PT J AU Jensen, PS Watanabe, HK Richters, JE AF Jensen, PS Watanabe, HK Richters, JE TI Who's up first? Testing for order effects in structured interviews using a counterbalanced experimental design SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE DISC; reliability; diagnosis; assessment; diagnostic interviews ID TEST-RETEST RELIABILITY; CHILD PSYCHOPATHOLOGY; K-SADS; DIAGNOSES; SCHEDULE; VALIDITY; SCALES; CBCL AB A growing body of research suggests that, apart from the wording of specific questions, various aspects of the interview process itself may affect the reliability of information provided by research participants. To examine whether the order of presentation of specific diagnostic modules affects the likelihood of subjects' yes/no responses within the Diagnostic Interview Schedule for Children (DISC), the authors used a counterbalanced design, presenting two DISC diagnostic modules to children and their parents in standard or reversed order. Results indicate that the order of module administration exerts effects on the total numbers of symptoms endorsed, level of impairment, and the likelihood of meeting diagnostic criteria, regardless of whether the information is provided by parent or child respondents. Future child and adult assessment measures should take these difficulties fully into account through novel approaches to instrument design and interview procedures. C1 NIMH, Bethesda, MD 20892 USA. Univ Nevada, Dept Psychiat, Reno, NV 89557 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Jensen, PS (reprint author), Columbia Univ, New York State Psychiat Inst, Dept Child Psychiat, Ctr Advancement Childrens Mental Hlth,Unit 78, 1051 Riverside Dr, New York, NY 10032 USA. OI Richters, John/0000-0002-6780-1828; Jensen, Peter/0000-0003-2387-0650 NR 25 TC 30 Z9 30 U1 9 U2 10 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD DEC PY 1999 VL 27 IS 6 BP 439 EP 445 DI 10.1023/A:1021927909027 PG 7 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 267KA UT WOS:000084356100004 PM 10821625 ER PT J AU Alston, B Ellenberg, JH Standiford, HC Muth, K Martinez, A Greaves, W Kumi, J AF Alston, B Ellenberg, JH Standiford, HC Muth, K Martinez, A Greaves, W Kumi, J CA Division AIDS Treatment Res Initia TI A multicenter, randomized, controlled trial of three preparations of low-dose oral alpha-interferon in HIV-infected patients with CD4(+) counts between 50 and 350 cells/mm(3) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; acquired immunodeficiency syndrome; AIDS therapy; diarrhea; fever ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND AB To evaluate the effectiveness of low-dose oral alpha-interferon (alpha-IFN), 247 HIV-infected study subjects received placebo, Alferon LDO, Veldona, or Ferimmune in a randomized, double-blind trial. Subjects had CD4(+) counts between 50 and 350 cells/mm(3) and HIV-related symptoms at entry. Study subjects rated the severity of eight symptoms using a symptom burden index (SBI). Study endpoints included changes in SBI, weight, CD4(+) count, and Karnofsky score between baseline and the 24-week visit. The SBI outcome and weight were measured in 99 and 106 study subjects, respectively, at both the baseline and 24-week visits. Baseline SBI scores ranged from 5.4 to 7.9 in the four arms. No clinically important or statistically significant differences were found among the four arms with regard to SBI or weight change over the 24-week period. There were also no significant differences among the arms for CD4(+) cell count and Karnofsky score. Few adverse reactions were noted in any arm, and there were no significant differences between arms. Although the trial was designed to enroll 560 study subjects and was prematurely terminated because of slow accrual and discontinuations of participants, the small differences among the arms in the primary and secondary endpoints do not support claims of efficacy for the measures studied. C1 NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Westat, Rockville, MD USA. Univ Maryland, Inst Human Virol, Sch Med, Baltimore, MD 21201 USA. Vet Adm Med Ctr, Baltimore, MD 21218 USA. SPRI, Kenilworth, NJ USA. Mercy Specialty Ctr, Detroit, MI USA. RP Alston, B (reprint author), NIAID, Div Aids, NIH, 6700 B Rockledge Dr,MSC 7624,Room 5109, Bethesda, MD 20892 USA. FU PHS HHS [N01-A1-15123] NR 18 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD DEC 1 PY 1999 VL 22 IS 4 BP 348 EP 357 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 284MP UT WOS:000085336400005 PM 10634196 ER PT J AU Sher, L Rosenthal, NE Wehr, TA AF Sher, L Rosenthal, NE Wehr, TA TI Free thyroxine and thyroid-stimulating hormone levels in patients with seasonal affective disorder and matched controls SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE seasonal affective disorder; depression; free thyroxine; thyroid-stimulating hormone ID THYROTROPIN; HYPOTHYROIDISM; DEPRESSION; SECRETION; LIGHT; TSH; CORTISOL; SERUM AB Seasonal affective disorder (SAD) is characterized by recurrent episodes of depression in the fall and winter that alternate with nondepressed periods in the spring and summer. Because some symptoms of SAD, such as decreased energy and weight gain, also occur in hypothyroidism, it is possible that individuals with-SAD have a subtle decrease in thyroid function. To test this hypothesis, we studied blood levels of free thyroxine (T-4) and thyroid-stimulating hormone (TSH) in SAD patients and matched controls in the winter. We found that free T-4 blood levels were slightly but significantly lower in patients than in healthy volunteers. The difference between TSH levels in SAD patients and controls was not statistically significant. Future research will be needed to determine whether the difference in thyroid function between SAD patients and controls is an epiphenomenon or is related to the biological mechanisms that cause symptoms of SAD. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. RP Sher, L (reprint author), NIMH, Sect Biol Rhythms, 10 Ctr Dr,Bldg 10,Rm 3S-231, Bethesda, MD 20892 USA. NR 38 TC 21 Z9 24 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD DEC PY 1999 VL 56 IS 2-3 BP 195 EP 199 DI 10.1016/S0165-0327(99)00049-X PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 284CN UT WOS:000085313300013 PM 10701477 ER PT J AU Sarno, RJ Clark, WR Bank, MS Prexl, WS Behl, MJ Johnson, WE Franklin, WL AF Sarno, RJ Clark, WR Bank, MS Prexl, WS Behl, MJ Johnson, WE Franklin, WL TI Juvenile guanaco survival: management and conservation implications SO JOURNAL OF APPLIED ECOLOGY LA English DT Article DE Chile; Lama guanicoe; predation; Puma concolor; ungulate ID TAILED DEER FAWNS; DENSITY-DEPENDENCE; NATIONAL-PARK; MULE DEER; ROE DEER; MORTALITY; POPULATION; PREDATION; PATAGONIA; WOLF AB 1. The Chilean National Forestry and Park Service is striving to implement a guanaco management programme of sustained-yield use. To achieve this, the rate, variation and causes of juvenile guanaco mortality must be understood thoroughly. Therefore, we monitored the survival of 409 radio-collared juvenile guanacos in Torres del Paine National Park, Chile, from 1991 to 1996. 2. The Kaplan-Meier product limit estimator of survival for staggered entry was calculated, and survival rates between juvenile males and females and among years were compared using the lifetest procedure in SAS. The Cox proportional hazards model was used to relate mortality rate to explanatory variables such as juvenile sex, birth weight, adult female aggression towards researchers during the capture and tagging of newborns, population density, and mean monthly winter snowfall. 3. Mean juvenile survival rate (S) was 0.38, but varied between 0.31 and 0.55. Survival rates between the sexes were not significantly different, although male survival was lower than that of females. Mortality rate was highest during the first 14 days after birth. Most deaths occurred between birth and 7 months of age. 4. The risk of mortality increased by almost 6% with every 1 cm increase in winter snowfall, whereas the risk of mortality decreased by almost 24% as adult female aggression increased towards researchers. 5. Current management objectives are aimed at the implementation of a rational harvest of guanacos on the Chilean side of the island of Tierra del Fuego. Our results provide improved and updated estimates of juvenile guanaco survival and will aid in the modelling of harvest rates of guanacos in southern Chile. Future proposed harvests from wild populations in southern Chile need to consider the rate and variation of this critical life-history parameter. C1 NCI, FCRDC, Lab Genom Divers, Frederick, MD 21702 USA. Iowa State Univ, Dept Anim Ecol, Ames, IA 50011 USA. Univ Maine, Dept Wildlife Ecol, Orono, ME 04469 USA. RP Sarno, RJ (reprint author), NCI, FCRDC, Lab Genom Divers, Bldg 560,Room 11-84, Frederick, MD 21702 USA. RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 61 TC 34 Z9 36 U1 0 U2 13 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0021-8901 J9 J APPL ECOL JI J. Appl. Ecol. PD DEC PY 1999 VL 36 IS 6 BP 937 EP 945 DI 10.1046/j.1365-2664.1999.00449.x PG 9 WC Biodiversity Conservation; Ecology SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 271WR UT WOS:000084617900008 ER PT J AU Rywik, TM Blackman, MR Yataco, AR Vaitkevicius, PV Zink, RC Cottrell, EH Wright, JG Katzel, LI Fleg, JL AF Rywik, TM Blackman, MR Yataco, AR Vaitkevicius, PV Zink, RC Cottrell, EH Wright, JG Katzel, LI Fleg, JL TI Enhanced endothelial vasoreactivity in endurance-trained older men SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE endothelial function; exercise; training ID CORONARY-ARTERY DISEASE; EXERCISE-INDUCED VASODILATION; DEPENDENT DIABETES-MELLITUS; FOREARM BLOOD-FLOW; NITRIC-OXIDE; BRACHIAL-ARTERY; ESSENTIAL-HYPERTENSION; PHYSICAL-ACTIVITY; SYSTEMIC ARTERIES; MEDIATED DILATION AB Using external vascular ultrasound, we measured brachial artery diameter (Diam) at rest, after release of 4 min of limb ischemia, i.e., endothelium-dependent dilation (EDD), and after sublingual nitroglycerin, i.e., non-endothelium-dependent; dilation (NonEDD), in 35 healthy men aged 61-83 yr: 12 endurance athletes (A) and 23 controls (C). As anticipated, treadmill exercise maximal oxygen consumption ((V) over dot O-2max) was significantly higher in A than in C (40.2 +/- 6.6 vs. 27.9 +/- 3.8 ml.kg(-1).min(-1); respectively, P < 0.0001). With regard to arterial physiology, A had greater EDD (8.9 +/- 4.2 vs. 5.7 +/- 3.5%; P = 0.02) and a tendency for higher NonEDD (13.9 +/- 6.7 vs. 9.7 +/- 4.2%; P = 0.07) compared with C. By multiple linear regression analysis in the combined sample of older men, only baseline Diam (beta = -2.0, where beta is the regression coefficient; P = 0.005) and VO2max (beta = 0.23; P = 0.003) were independent predictors of EDD; similarly, only Diam (beta = -4.0; P = 0.0003) and (V) over dot O-2max (beta = 0.27; P = 0.01) predicted NonEDD. Thus endurance-trained older men demonstrate both augmented EDD and NonEDD, consistent with a generalized enhanced vasodilator responsiveness, compared with their sedentary age peers. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Inst Cardiol, Dept Vasc Heart Dis 2, Warsaw, Poland. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Vet Affairs Med Ctr, Baltimore, MD 21201 USA. RP Fleg, JL (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Bendinelli, Jason/B-3196-2012 FU NCRR NIH HHS [M01RR02719]; NIA NIH HHS [R01AG110002] NR 57 TC 52 Z9 53 U1 0 U2 3 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 DEC PY 1999 VL 87 IS 6 BP 2136 EP 2142 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 264KV UT WOS:000084182000020 PM 10601160 ER PT J AU Bristol-Power, MM Spinella, G AF Bristol-Power, MM Spinella, G TI Research on screening and diagnosis in autism: A work in progress SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE screening; diagnosis; autism ID DISORDERS; INFANTS AB In June 1998, the National Institutes of Health Autism Coordinating Committee (NIH/ACC) invited representatives of 13 major medical and other professional academies and associations and six national autism parent research organizations to review research data on screening and diagnosis of autism spectrum disorders. Ten review papers and more than 4,000 publications were consulted in this effort. This paper highlights some promising areas for research identified in this process. One of the highest priorities is the search for the ultimate diagnostic indicator, a biological marker(s), for example, genetic, metabolic, immunologic, neurologic, that will distinguish autism unequivocally from other developmental disabilities. In the interim, research on infant screening and diagnosis might lower the threshold age for diagnosis to 8-12 months. The role of sensory-motor disorders in early diagnosis needs further research. Earlier and better diagnosis of co-occurring, potentially treatable disorders, including epileptic and epileptiform disorders, has implications both for diagnosis and treatment. Pharmacogenetic and pharmacogenomic research strategies could help diagnose subtypes and responders versus nonresponders to potential treatments. Better endpoints and outcome measures are needed, including improved procedures for cognitive and neuropsychological testing, more knowledge about verbal and nonverbal communication milestones, and less invasive and more sensitive neuroimaging measures. Critical questions remain regarding regression after apparently normal development, and about possible environmental precipitants. Finally, field trials of the reliability and validity of screening and diagnosis using the newly developed practice guidelines are needed. C1 NICHHD, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Bristol-Power, MM (reprint author), NICHD, MRDD, CRMC, Room 4B09,6100 Execut Blvd MSC 7150, Bethesda, MD 20817 USA. NR 11 TC 32 Z9 35 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD DEC PY 1999 VL 29 IS 6 BP 435 EP 438 DI 10.1023/A:1021991718423 PG 4 WC Psychology, Developmental SC Psychology GA 268EV UT WOS:000084402100002 PM 10638458 ER PT J AU Thompson, J Ruvinov, SB Freedberg, DI Hall, BG AF Thompson, J Ruvinov, SB Freedberg, DI Hall, BG TI Cellobiose-6-phosphate hydrolase (CelF) of Escherichia coli: Characterization and assignment to the unusual family 4 of glycosylhydrolases SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; BETA-GLUCOSIDE UTILIZATION; BGL OPERON; GLYCOSYL HYDROLASES; CELLOBIOSE UTILIZATION; NUCLEOTIDE-SEQUENCE; AMINO-ACID; PHOSPHOTRANSFERASE SYSTEM; FUSOBACTERIUM-MORTIFERUM; STAPHYLOCOCCUS-AUREUS AB The gene celF of the cryptic cel operon of Escherichia coli has been cloned, and the encoded 6-phospho-beta-glucosidase (cellobiose-6-phosphate [6P] hydrolase; CelF [EC 3.2.1.86]) has been expressed and purified in a catalytically active state. Among phospho-beta-glycosidases, CelF exhibits unique requirements for a divalent metal ion and NAD(+) for activity and, by sequence alignment, is assigned to family 4 of the glycosylhydrolase superfamily. CelF hydrolyzed a variety of P-beta-glucosides, including cellobiose-6P, salicin-6P, arbutin-6P, gentiobiose-6P, methyl-beta-glucoside-6P, and the chromogenic analog, p-nitrophenyl-beta-D-glucopyranoside-6P. In the absence of a metal ion and NAD(+), purified CelF was rapidly and irreversibly inactivated. The functional roles of the cofactors have not been established, but NAD(+) appears not to be a reactant and there is no evidence for reduction of the nucleotide during substrate cleavage. In solution, native CelF exists as a homotetramer (M-w, similar to 200,000) composed of noncovalently linked subunits, and this oligomeric structure is maintained independently of the presence or absence of a metal ion. The molecular weight of the CelF monomer (M-r, similar to 50,000), estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is in agreement with that calculated from the amino acid sequence of the polypeptide (450 residues; M-r = 50,512). Comparative sequence alignments provide tentative identification of the NAD(+)-binding domain (residues 7 to 40) and catalytically important glutamyl residues (Glu(112) and Glu(356)) of CelF. C1 NIDCR, Oral Infect & Immun Branch, Microbial Biochem & Genet Unit, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20892 USA. Univ Rochester, Dept Biol, Rochester, NY 14627 USA. RP Thompson, J (reprint author), NIDCR, Oral Infect & Immun Branch, Microbial Biochem & Genet Unit, Bldg 30,Room 528,Covent Dr 4350, Bethesda, MD 20892 USA. NR 51 TC 42 Z9 47 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1999 VL 181 IS 23 BP 7339 EP 7345 PG 7 WC Microbiology SC Microbiology GA 259FV UT WOS:000083884600026 PM 10572139 ER PT J AU Gorbatyuk, VY Chen, YC Wu, YJ Youle, RJ Huang, TH AF Gorbatyuk, VY Chen, YC Wu, YJ Youle, RJ Huang, TH TI Sequence-specific H-1, C-13 and N-15 resonance assignments of recombinant onconase/P-30 protein SO JOURNAL OF BIOMOLECULAR NMR LA English DT Letter DE anti-tumor agent; cytotoxic protein; lectin; P-30 protein; ribonuclease ID CYTOTOXIC RIBONUCLEASE; P-30 PROTEIN C1 Acad Sinica, Inst Biomed Sci, Div Struct Biol, Taipei 115, Taiwan. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Huang, TH (reprint author), Acad Sinica, Inst Biomed Sci, Div Struct Biol, Taipei 115, Taiwan. NR 9 TC 2 Z9 2 U1 0 U2 0 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 DEC PY 1999 VL 15 IS 4 BP 343 EP 344 DI 10.1023/A:1008312325225 PG 2 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 269LP UT WOS:000084479100010 PM 10685344 ER PT J AU Wu, JC Shapiro, BA AF Wu, JC Shapiro, BA TI A Boltzmann filter improves the prediction of RNA folding pathways in a massively parallel genetic algorithm SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID SECONDARY STRUCTURE; COMPUTER-SIMULATION; MOLECULE AB RNA folding using the massively parallel genetic algorithm (GA) has been enhanced by the addition of a Boltzmann filter. The filter uses the Boltzmann probability distribution in conjunction with Metropolis' relaxation algorithm. The combination of these two concepts within the GA's massively parallel computational environment helps guide the genetic algorithm to more accurately reflect RNA folding pathways and thus final solution structures. Helical regions (base-paired stems) now form in the structures based upon the stochastic properties of the thermodynamic parameters that have been determined from experiments. Thus, structural changes occur based upon the relative energetic impact that the change causes rather than just geometric conflicts alone. As a result, when comparing the predictions to phylogenetically determined structures, over multiple runs, fewer false-positive stems (predicted incorrectly) and more true-positive stems (predicted correctly) are generated, and the total number of predicted stems representing a solution is diminished. In addition, the significance (rate of occurrence) of the true-positive stems is increased. Thus, the predicted results more accurately reflect phylogenetically determined structures. C1 NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, LECB, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Image Proc Sect, Lab Expt & Computat Biol,Div Basic Sci,NIH, Frederick, MD 21702 USA. RP Wu, JC (reprint author), NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, LECB, Frederick, MD 21702 USA. NR 29 TC 12 Z9 13 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 1999 VL 17 IS 3 BP 581 EP 595 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 280XC UT WOS:000085128200015 PM 10636092 ER PT J AU Buzard, GS Enomoto, T Anderson, LM Perantoni, AO Devor, DE Rice, JM AF Buzard, GS Enomoto, T Anderson, LM Perantoni, AO Devor, DE Rice, JM TI Activation of neu by missense point mutation in the transmembrane domain in schwannomas induced in C3H/HeNCr mice by transplacental exposure to N-nitrosoethylurea SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE neu; mouse; schwannoma; transplacental ID GROWTH-FACTOR RECEPTOR; NERVOUS-SYSTEM; CELL LINEAGE; ERBB-2 GENE; TUMORS; ONCOGENE; PROTOONCOGENE; INDUCTION; EXPRESSION; PROTEIN AB Transplacentally initiated schwannomas in mice and rats arise preferentially in the Gasserian ganglion of the trigeminal nerve and spinal root ganglia, while those of the Syrian golden hamster most commonly occur subcutaneously. Rat and hamster schwannomas almost invariably contain a mutationally activated neu oncogene. In rat schwannomas, the mutant allele predominates, while the relative abundance of mutant alleles is very low in hamster nerve tumors. We investigated whether neu is mutated in mouse schwannomas and whether the pattern and allelic ratio of the mutation resemble those for the hamster or the rat, Pregnant C3H/HeNCr mice received 0.4 mu mol N-nitrosoethylurea/g body weight on day 19 of gestation. Ten trigeminal and one peripheral nerve schwannomas developed in II of the 201 offspring. Missense T --> A transversion mutations were detected in the neu transmembrane domain in eight of ten schwannomas analyzed, as determined by MnlI digestion of polymerase chain reaction products. The mutant allele was pre dominantly detected in two tumors and was abundant in six others. Transfection of eight out of ten mouse tumor DNAs into hamster cells yielded transformed foci; seven out of eight contained mutant mouse neu. Mouse schwannomas closely resembled those of rats both in the preferred anatomical site and in the mutant/wild-type neu allele ratios. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Comparat Carcinogenesis, FCRDC, Frederick, MD 21702 USA. RP Buzard, GS (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 538, Frederick, MD 21702 USA. NR 38 TC 11 Z9 11 U1 0 U2 0 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 DEC PY 1999 VL 125 IS 12 BP 653 EP 659 DI 10.1007/s004320050330 PG 7 WC Oncology SC Oncology GA 259HZ UT WOS:000083889600001 PM 10592097 ER PT J AU Roden, DM Spooner, PM AF Roden, DM Spooner, PM TI Inherited long QT syndromes: A paradigm for understanding arrhythmogenesis SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE long QT syndrome; cardiac arrhythmias; genetic diseases; ion channels; sudden cardiac death ID TORSADE-DE-POINTES; RECTIFIER K+-CURRENT; ACTION-POTENTIAL PROLONGATION; POTASSIUM CHANNEL GENE; EPICARDIAL BORDER ZONE; CANINE MYOCARDIAL INFARCTS; TRANSIENT OUTWARD CURRENT; RAT VENTRICULAR MYOCYTES; III ANTIARRHYTHMIC AGENT; CARDIAC SODIUM-CHANNEL AB LQTS as a Paradigm. The inherited long QT syndrome (LQTS) is a familial disease characterized by QT interval changes that often are labile, syncope, and sudden death due to arrhythmias, predominantly in young people. Multiple mutations in five genes encoding structural subunits of cardiac ion channels now have been identified in families with LQTS, Correlations are being described between genotype and specific clinical features in LQTS, However, increasing screening of affected families and sporadic cases has identified incomplete penetrance with highly variable clinical manifestations, even among individuals carrying the same mutations. The identification of LQTS disease genes represents a crucial first step in developing an understanding of the molecular basis for normal cardiac repolarization, This information will be important not only for identifying new therapies in LQTS, but also in further understanding arrhythmias, and their potential therapies, in situations such as heart failure, cardiac hypertrophy, myocardial infarction, or sudden infant death syndrome, where abnormal repolarization has been linked to sudden death. LQTS thus presents a new paradigm to cardiac electrophysiology, in which new molecular information is being brought to bear both on clinical management of patients and on development of a new framework to study the fundamental causes of arrhythmias and new approaches to therapy. C1 NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Med & Pharmacol, Nashville, TN USA. RP Spooner, PM (reprint author), NHLBI, Div Heart & Vasc Dis, NIH, 2 Rockledge Ctr,Suite 9192,6701 Rockledge Dr,MSC, Bethesda, MD 20892 USA. NR 184 TC 106 Z9 116 U1 2 U2 3 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 1999 VL 10 IS 12 BP 1664 EP 1683 DI 10.1111/j.1540-8167.1999.tb00231.x PG 20 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 270AY UT WOS:000084514300012 PM 10636197 ER PT J AU Gough, NR Zweifel, ME Martinez-Augustin, O Aguilar, RC Bonifacino, JS Fambrough, DM AF Gough, NR Zweifel, ME Martinez-Augustin, O Aguilar, RC Bonifacino, JS Fambrough, DM TI Utilization of the indirect lysosome targeting pathway by lysosome-associated membrane proteins (LAMPs) is influenced largely by the C-terminal residue of their GYXX Phi targeting signals SO JOURNAL OF CELL SCIENCE LA English DT Article DE LAMP; lysosome associated membrane protein; lysosome; protein targeting; endocytosis; adaptor ID ADAPTER MEDIUM CHAINS; PLASMA-MEMBRANE; INTRACELLULAR TRAFFICKING; CYTOPLASMIC TAIL; SORTING SIGNALS; CELL-SURFACE; MDCK CELLS; GLYCOPROTEIN; CLATHRIN; TRANSPORT AB A systematic study was conducted on the requirements at the C-terminal position for the targeting of LAMPs to lysosomes, examining the hypothesis that a bulky hydrophobic residue is required. Mutations deleting or replacing the C-terminal valine with G, A, C, L, I, M, K, F, Y, or W were constructed in a reporter protein consisting of the lumenal/extracellular domain of avian LAMP-1 fused to the transmembrane and cytoplasmic domains of LAMP-2b. The steady-state distribution of each mutant form in mouse L-cells was assessed by quantitative antibody binding assays and immunofluorescence microscopy; efficiency of internalization from the plasma membrane and delivery to the lysosome were also estimated. It is found that (a) only C-terminal V, L, I, M, and F mediated efficient targeting to lysosomes, demonstrating the importance hydrophobicity and an optimal size of the C-terminal residue in targeting; (b) efficiency of lysosomal targeting generally correlated with efficiency of internalization; and (c) mutant forms that did not target well to lysosomes showed unique distributions in cells rather than simply default accumulation in the plasma membrane. Interactions of the targeting signals with adaptor subunits were measured using a yeast two-hybrid assay. The results are consistent with the hypothesis that trafficking of LAMP forms in cells through the indirect pathway is determined by the affinities of their targeting signals, predominantly for the mu 2 and mu 3 adaptors involved at plasma membrane and endosomal cellular sorting sites, respectively. C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Gough, NR (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RI Martinez Augustin, Olga/K-6720-2014 OI Martinez Augustin, Olga/0000-0001-8291-3468 FU NINDS NIH HHS [NS 23241] NR 40 TC 40 Z9 40 U1 0 U2 4 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 DEC PY 1999 VL 112 IS 23 BP 4257 EP 4269 PG 13 WC Cell Biology SC Cell Biology GA 290VN UT WOS:000085698700010 PM 10564644 ER PT J AU Zhou, J Montrose-Rafizadeh, C Janczewski, AM Pineyro, MA Sollott, SJ Wang, YH Egan, JM AF Zhou, J Montrose-Rafizadeh, C Janczewski, AM Pineyro, MA Sollott, SJ Wang, YH Egan, JM TI Glucagon-like peptide-1 does not mediate amylase release from AR42J cells SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID PANCREATIC ACINAR CELL; BETA-CELLS; TYROSINE PHOSPHORYLATION; GENE-TRANSCRIPTION; RECEPTOR; SECRETION; PROTEIN; CALCIUM; BINDING; SECRETAGOGUES AB In this study, AR42J pancreatic acinar cells were used to investigate if glucagon-like peptide-1 (GLP-1) or glucagon might influence amylase release and acinar cell function. We first confirmed the presence of GLP-1 receptors on AR42J cells by reverse trasncriptase-polymerase chain reaction (RT-PCR), Western blotting, and partial sequencing analysis. While cholecystokinin (CCK) increased amylase release from AR42J cells, GLP-1, alone or in the presence of CCK, had no effect on amylase release but both CCK and GLP-1 increased intracellular calcium. Similar to GLP-1, glucagon increased both cyclic adenosine monophosphate (cAMP) and intracellular calcium in AR42J cells but it actually decreased CCK-mediated amylase release (n = 20, P < 0.01). CCK stimulation resulted in an increase in tyrosine phosphorylation of several cellular proteins, unlike GLP-1 treatment, where no such increased phosphorylation was seen. Instead, GLP-1 decreased such protein phosphorylations. Genestein blocked CCK-induced phosphorylation events and amylase secretion while vanadate increased amylase secretion. These results provide evidence that tyrosine phosphorylation is necessary for amylase release and that signaling through GLP-1 receptors does not mediate amylase release in AR42J cells. Published 1999 Wiley-Liss, Inc. C1 NIA, Gerontol Res Ctr, Diabet Sect, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Egan, JM (reprint author), NIA, Gerontol Res Ctr, Diabet Sect, NIH, Box 23,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 36 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD DEC PY 1999 VL 181 IS 3 BP 470 EP 478 DI 10.1002/(SICI)1097-4652(199912)181:3<470::AID-JCP11>3.0.CO;2-P PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 252UT UT WOS:000083521200011 PM 10528233 ER PT J AU Chiang, YH Lin, SZ Borlongan, CV Hoffer, BJ Morales, M Wang, Y AF Chiang, YH Lin, SZ Borlongan, CV Hoffer, BJ Morales, M Wang, Y TI Transplantation of fetal kidney tissue reduces cerebral infarction induced by middle cerebral artery ligation SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ischemia; trophic factors; glial cell line-derived neurotrophic factor (GDNF); kidney ID MIDBRAIN DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR PROTECTS; KAINATE-INDUCED EXCITATION; FACTOR MESSENGER-RNA; MICE LACKING GDNF; ADULT-RATS; IN-VIVO; NERVOUS-SYSTEM; BRAIN INFARCTS; MORPHOGENETIC PROTEIN AB The authors, and others, have recently reported that intracerebral administration of glial cell line-derived neurotrophic factor (GDNF) or osteogenic protein-1 protects against ischemia-induced injury in the cerebral cortex of adult rats. Because these trophic factors are highly expressed in the fetal, but not adult, kidney cortex, the possibility that transplantation of fetal kidney tissue could serve as a cellular reservoir for such molecules and protect against ischemic injury in cerebral cortex was examined. Fetal kidneys obtained from rat embryos at gestational day 16, and adult kidney cortex, were dissected and cut into small pieces. Adult male Sprague-Dawley rats were anesthetized with chloral hydrate and placed in a stereotactic apparatus. Kidney tissues were transplanted into three cortical areas adjacent to the right middle cerebral artery (MCA). Thirty minutes after grafting, the right MCA was transiently ligated for 90 minutes. Twenty-four hours after the onset of reperfusion, animals were evaluated behaviorally. It was found that the stroke animals that received adult kidney transplantation developed motor imbalance. However, animals that received fetal kidney grafts showed significant behavioral improvement. Animals were later sacrificed and brains were removed for triphenyltetrazolium chloride staining, Pax-2 immunostaining, and GDNF mRNA expression. It was noted that transplantation of fetal kidney but not adult kidney tissue greatly reduced the volume of infarction in the cerebral cortex. Fetal kidney grafts showed Pax-2 immunoreactivity and GDNF mRNA in the host cerebral cortex. In contrast, GDNF mRNA expression was not found in the adult kidney grafts. Taken together, our data indicate that fetal kidney transplantation reduces ischemia/reperfusion-induced cortical infarction and behavioral deficits in adult rats, and that such tissue grafts could serve as an unique cellular reservoir for trophic factor application to the brain. C1 NIDA, Baltimore, MD 21224 USA. Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Neurosurg, Taipei, Taiwan. Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Pharmacol, Taipei, Taiwan. RP Wang, Y (reprint author), NIDA, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 50 TC 37 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 1999 VL 19 IS 12 BP 1329 EP 1335 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 276NL UT WOS:000084884200006 PM 10598937 ER PT J AU Wudarsky, M Nicolson, R Hamburger, SD Spechler, L Gochman, P Bedwell, J Lenane, MC Rapoport, JL AF Wudarsky, M Nicolson, R Hamburger, SD Spechler, L Gochman, P Bedwell, J Lenane, MC Rapoport, JL TI Elevated prolactin in pediatric patients on typical and atypical antipsychotics SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID CHILDHOOD-ONSET SCHIZOPHRENIA; CLOZAPINE; HALOPERIDOL; ADOLESCENTS; OLANZAPINE AB As part of systematic treatment trials of haloperidol, clozapine, and olanzapine with a total of 35 children and adolescents with early onset psychosis, prolactin was measured at baseline and week 6 of treatment. The National Institute of Mental Health patients-13 females, 22 males (mean age, 14.1 +/- 2.3 years; range, 9.1-19 years) with childhood onset schizophrenia (n = 32), or Psychotic Disorder not otherwise specified (NOS) (n = 3) with onset of psychosis before age 13-were recruited for open or double-blind trials of haloperidol, clozapine, or olanzapine. Baseline serum prolactin was measured after a 3-week washout period and after 6 weeks of treatment. Mean prolactin concentration after 6 weeks of treatment was significantly elevated on all three drugs; however, on clozapine, mean prolactin remained within the normal range. Prolactin was increased above the upper limit of normal for 100% of 10 patients on haloperidol, 70% of 10 patients on olanzapine, and 0% of 15 patients on clozapine (chi(2) analyses: H > C, p = 0.004; O > C, p = 0.001). Given the potential endocrine and possible cardiac correlates of hyperprolactinemia, these more robust prolactin elevations in pediatric patients after short-term exposure to olanzapine than those reported for adults justify longer observation intervals with bigger samples to establish treatment safety of atypical antipsychotics in adolescents. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Wudarsky, M (reprint author), NIMH, Child Psychiat Branch, NIH, 10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 23 TC 95 Z9 101 U1 2 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 1999 VL 9 IS 4 BP 239 EP 245 DI 10.1089/cap.1999.9.239 PG 7 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 267WF UT WOS:000084381700002 PM 10630453 ER PT J AU Jensen, PS AF Jensen, PS TI Links among theory, research, and practice: Cornerstones of clinical scientific progress SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article AB Discusses how explicit links among clinical theory, research, and practice are necessary if a clinical discipline is to survive in the managed care marketplace of today. Robust links among theory, research, and practice enable the elaboration of a systematic body of clinical knowledge that is practical in its deployment effective in its methods, and compelling in its rationale. Moreover, theoretical advances are increasingly necessary, in that they allow scientists to categorize and prioritize the growing amount of empirically derived information, determine how pieces of multilevel data fit together, identify, knowledge gaps, and set priorities for future studies. As shown by some of the articles in this special section, evolving theories of behavior have several characteristics in common; namely that they are developmental, transactional, contextual, adaptational, multilevel, and multidetermined. Concerns may be raised, however, as to whether current research methods are fully adequate to test these newer, more complex, multilevel theories or the clinical phenomena they seek to characterize. To address these difficulties, as well as to increase the pace of scientific advances that may result from propitious links among theory, research, and practice, I offer several recommendations to clinical psychology in general and to clinical child psychological research in particular. C1 NIMH, Rockville, MD 20857 USA. RP Jensen, PS (reprint author), New York State Psychiat Inst, Dept Child Psychiat, Unit 78,1051 Riverside Dr, New York, NY 10032 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 1 TC 9 Z9 9 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD DEC PY 1999 VL 28 IS 4 BP 553 EP 557 DI 10.1207/S15374424JCCP2804_17 PG 5 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 254YB UT WOS:000083640900017 PM 10587908 ER PT J AU Beitins, IZ AF Beitins, IZ TI Commentary - Opportunities and challenges in pediatric clinical research SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 NIH, Natl Ctr Res Resources, Gen Clin Res Ctr Program, Bethesda, MD 20892 USA. RP Beitins, IZ (reprint author), NIH, Natl Ctr Res Resources, Gen Clin Res Ctr Program, 1 Rockledge Ctr,Room 6030,6705 Rockledge Dr,MSC 7, Bethesda, MD 20892 USA. NR 14 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4302 EP 4306 DI 10.1210/jc.84.12.4302 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100001 PM 10599679 ER PT J AU Lafferty, AR Chrousos, GP AF Lafferty, AR Chrousos, GP TI Commentary - Pituitary tumors in children and adolescents SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CHILDHOOD CRANIOPHARYNGIOMA; OCTREOTIDE THERAPY; CUSHINGS-SYNDROME; FOLLOW-UP; ADENOMAS; ENDOCRINE; HORMONE; MULTICENTER; EXPERIENCE; DIAGNOSIS C1 NICHHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP NICHHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, 10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 36 TC 42 Z9 43 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4317 EP 4323 DI 10.1210/jc.84.12.4317 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100003 PM 10599681 ER PT J AU Le Roith, D Butler, AA AF Le Roith, D Butler, AA TI Commentary - Insulin-like growth factors pediatric health and disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID FACTOR-I RECEPTOR; DEPENDENT DIABETES-MELLITUS; GENE-EXPRESSION; WILMS-TUMOR; IGF-I; RETINAL NEOVASCULARIZATION; RIBONUCLEIC-ACID; POSTNATAL-GROWTH; BINDING-PROTEINS; DNA-SYNTHESIS C1 NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Le Roith, D (reprint author), NIDDKD, Clin Endocrinol Branch, Room 8D12,Bldg 10, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 43 TC 31 Z9 31 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4355 EP 4361 DI 10.1210/jc.84.12.4355 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100010 PM 10599688 ER PT J AU Taylor, SI Arioglu, E AF Taylor, SI Arioglu, E TI Commentary - Genetically defined forms of diabetes in children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID INSULIN-RECEPTOR GENE; CONGENITAL GENERALIZED LIPODYSTROPHY; POLYCYSTIC-OVARY-SYNDROME; TYROSINE KINASE-ACTIVITY; 2 MUTANT ALLELES; EXTRACELLULAR DOMAIN; MITOCHONDRIAL-DNA; HYBRID RECEPTORS; ALPHA-GENE; RESISTANCE C1 NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Taylor, SI (reprint author), NIDDKD, Diabet Branch, NIH, Bldg 10,Room 9S-213,10 Ctr Dr, Bethesda, MD 20892 USA. EM Simeon_Taylor@nih.gov NR 52 TC 15 Z9 15 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4390 EP 4396 DI 10.1210/jc.84.12.4390 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100016 PM 10599693 ER PT J AU Oddoux, C Guillen-Navarro, E Ditivoli, C Dicave, E Cilio, MR Clayton, CM Nelson, H Sarafoglou, K McCain, N Peretz, H Seligsohn, U Luzzatto, L Nafa, K Nardi, M Karpatkin, M Aksentijevich, I Kastner, D Axelrod, F Ostrer, H AF Oddoux, C Guillen-Navarro, E Ditivoli, C Dicave, E Cilio, MR Clayton, CM Nelson, H Sarafoglou, K McCain, N Peretz, H Seligsohn, U Luzzatto, L Nafa, K Nardi, M Karpatkin, M Aksentijevich, I Kastner, D Axelrod, F Ostrer, H TI Commentary - Mendelian diseases among Roman Jews: Implications for the origins of disease alleles SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID ASHKENAZI-JEWISH POPULATION; FAMILIAL MEDITERRANEAN FEVER; FACTOR-XI DEFICIENCY; CARRIER FREQUENCY; GAUCHER-DISEASE; CYSTIC-FIBROSIS; 21-HYDROXYLASE DEFICIENCY; CFTR GENE; NEW-YORK; MUTATIONS AB The Roman Jewish community has been historically continuous in Rome since pre-Christian times and may have been progenitor to the Ashkenazi Jewish community. Despite a history of endogamy over the past 2000 yr, the historical record suggests that there was admixture with Ashkenazi and Sephardic Jews during the Middle Ages. To determine whether Roman and Ashkenazi Jews shared common signature mutations, we tested a group of 107 Roman Jews, representing 176 haploid sets of chromosomes. No mutations were found for Bloom syndrome, BRCA1, BRCA2, Canavan disease, Fanconi anemia complementation group C, or Tay-Sachs disease. Two unrelated individuals were positive for the 3849 + 10C->T cystic fibrosis mutation; one carried the N370S Gaucher disease mutation, and one carried;he connexin 26 167delT mutation. Each of these was shown to be associated with the same haplotype of tightly linked microsatellite markers as that found among Ashkenazi Jews. In addition, 14 individuals had mutations in the familial Mediterranean fever gene and three unrelated individuals carried the factor XI type III mutation previously observed exclusively among Ashkenazi Jews. These findings suggest that the Gaucher, connexin 26, and familial Mediterranean fever mutations are over 2000 yr old, that the cystic fibrosis 3849 + 10kb C->T and factor XI type III mutations had a common origin in Ashkenazi and Roman Jews, and that other mutations prevalent among Ashkenazi Jews are of more recent origin. C1 NYU, Sch Med, Dept Pediat, Human Genet Program, New York, NY 10016 USA. Univ Roma La Sapienza, Rome, Italy. Osped Israelit, Rome, Italy. Bambino Gesu Pediat Hosp, Rome, Italy. Sourasky Med Ctr, Tel Aviv, Israel. Chaim Sheba Med Ctr, Dept Hematol, Inst Thrombosis & Hemostasis, IL-52621 Tel Hashomer, Israel. Mem Sloan Kettering Canc Ctr, Dept Human Genet, New York, NY 10021 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Ostrer, H (reprint author), NYU, Sch Med, Dept Pediat, Human Genet Program, 550 1St Ave,MSB 136, New York, NY 10016 USA. EM harry.ostrer@med.nyu.edu NR 37 TC 12 Z9 12 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4405 EP 4409 DI 10.1210/jc.84.12.4405 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100018 PM 10599695 ER PT J AU Chrousos, GP AF Chrousos, GP TI Editorial: A new "new" syndrome in the new world: Is multiple postreceptor steroid hormone resistance due to a coregulator defect? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID CREB-BINDING PROTEIN; GLUCOCORTICOID-RECEPTOR; NUCLEAR RECEPTOR; PHOSPHORYLATION; TRANSCRIPTION; COACTIVATION; ACETYLATION; MECHANISMS; SRC-1; P300 C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM chrousog@mail.nih.gov NR 25 TC 13 Z9 13 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1999 VL 84 IS 12 BP 4450 EP 4453 DI 10.1210/jc.84.12.4450 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 263PH UT WOS:000084134100024 PM 10599701 ER PT J AU Yano, K Kodama, K Shimizu, Y Chyou, PH Sharp, DS Tracy, RP Rodriguez, BL Curb, JD Kusumi, S AF Yano, K Kodama, K Shimizu, Y Chyou, PH Sharp, DS Tracy, RP Rodriguez, BL Curb, JD Kusumi, S TI Plasma fibrinogen and its correlates in elderly Japanese men living in Japan and Hawaii SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Asian-Americans; cross-sectional study; fibrinogen; smoking; white blood cell count ID ISCHEMIC-HEART-DISEASE; BLOOD-CELL COUNT; CARDIOVASCULAR RISK-FACTORS; MYOCARDIAL-INFARCTION; HEMOSTATIC FUNCTION; LEUKOCYTE COUNT; FACTOR-VII; ASSOCIATION; POPULATION; SPEEDWELL AB Plasma fibrinogen levels were determined using comparable methods for 329 Japanese men in Hiroshima Japan, and 3571 Japanese-American men in Honolulu Hawaii, aged 71-93 years. The age-adjusted mean fibrinogen level in Japanese-American men (307 mg/dl) was significantly higher (p < 0.0001) than in native Japanese men (270 mg/dl). In multiple linear regression models, the fibrinogen level was associated significantly and positively with white blood cell count (WBC) and total cholesterol, and inversely with HDL cholesterol and hematocrit in both study samples. The strongest association with fibrinogen was shown for WBC, and this association was not mediated through cigarette smoking. The observed difference in fibrinogen levels could not be fully explained by WBC, total and HDL cholesterol, triglyceride, hematocrit, body mass index, and diabetes. Some unmeasured environmental or lifestyle variables such as diet and physical activity may be partly responsible for the observed difference in fibrinogen levels between native Japanese men and Japanese-American men in Hawaii. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI 96813 USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Div Clin Epidemiol & Geriatr Med, Honolulu, HI 96822 USA. Marshfield Med Res Fdn, Marshfield, WI 54449 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Vermont, Burlington, VT 05405 USA. RP Yano, K (reprint author), Kuakini Med Ctr, Honolulu Heart Program, 846 S Hotel St,Suite 306, Honolulu, HI 96813 USA. FU NHLBI NIH HHS [N01-HC-05102, UO1HL56274] NR 32 TC 9 Z9 9 U1 0 U2 0 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 DEC PY 1999 VL 52 IS 12 BP 1201 EP 1206 DI 10.1016/S0895-4356(99)00095-5 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 258AZ UT WOS:000083817000010 PM 10580783 ER PT J AU Hakim, AA Curb, JD Burchfiel, CM Rodriguez, BL Sharp, DS Yano, K Abbott, RD AF Hakim, AA Curb, JD Burchfiel, CM Rodriguez, BL Sharp, DS Yano, K Abbott, RD TI Screening for coronary heart disease in elderly men based on current and past cholesterol levels SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE cholesterol; coronary heart disease; aging; screening ID DENSITY-LIPOPROTEIN CHOLESTEROL; RISK-FACTORS; SERUM-CHOLESTEROL; OLDER PERSONS; 7 COUNTRIES; LONGITUDINAL CHANGES; HDL CHOLESTEROL; FINNISH COHORTS; FOLLOW-UP; MORTALITY AB Efficient use of cholesterol measurements to screen for coronary heart disease in the elderly is not well defined. The purpose of this report is to examine such screening based on national guidelines in a sample of older men. Since relations between cholesterol and coronary heart disease are better established in those who are younger, screening in the elderly will also consider levels of cholesterol that existed earlier in life. Data are from a prospective study of 1,170 men enrolled in the Honolulu Heart Program who were followed over a 12-year period for coronary heart disease. Follow-up began from 1980 to 1982, when cholesterol levels were determined in men who were aged 61 to 81 years. Past cholesterol levels were measured 10 years earlier (1970-1972). During the course of follow-up, coronary heart disease developed in 117 of the men. Risk of disease rose significantly (P = 0.003) with increases in past cholesterol levels (1970-1972) but not with more recent levels (1980-1982). For men with current cholesterol levels that were desirable (<5.2 mmol/L [200 mg/dl], as defined by guidelines from the National Cholesterol Education Program), disease incidence continued to rise with increasing past cholesterol levels (P < 0.001). Accounting for high-density lipoprotein cholesterol and other screening factors did little to alter these findings. We conclude that desirable cholesterol levels in the elderly may not be a marker of a healthy risk profile if past cholesterol levels were high. Screening fur coronary heart disease in the elderly could be improved by considering past cholesterol levels, rather than just a single measurement in later life. (C) Elsevier Science Inc. C1 Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Kuakini Med Ctr, Honolulu Heart Program, Honolulu, HI 96822 USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. RP Abbott, RD (reprint author), Univ Virginia, Sch Med, Dept Hlth Evaluat Sci, Div Biostat & Epidemiol, Box 600, Charlottesville, VA 22908 USA. FU NCRR NIH HHS [P20 RR 11091]; NHLBI NIH HHS [N01-HC-05102] NR 35 TC 13 Z9 13 U1 0 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 DEC PY 1999 VL 52 IS 12 BP 1257 EP 1265 DI 10.1016/S0895-4356(99)00130-4 PG 9 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 258AZ UT WOS:000083817000017 PM 10580790 ER PT J AU Chen, L Adar, R Yang, X Monsonego, EO Li, CL Hauschka, PV Yayon, A Deng, CX AF Chen, L Adar, R Yang, X Monsonego, EO Li, CL Hauschka, PV Yayon, A Deng, CX TI Gly369Cys mutation in mouse FGFR3 causes achondroplasia by affecting both chondrogenesis and osteogenesis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR RECEPTOR-3; TRANSMEMBRANE DOMAIN; BONE-GROWTH; CONSTITUTIVE ACTIVATION; TARGETED DISRUPTION; CROUZON SYNDROME; INDIAN HEDGEHOG; IN-VIVO; FIBROBLAST; MICE AB Missense mutations in fibroblast growth factor receptor 3 (FGFR3) result in several human skeletal dysplasias, including the most common form of dwarfism, achondroplasia. Here we show that a glycine-to-cysteine substitution at position 375 (Gly375Cys) in human FGFR3 causes ligand-independent dimerization and phosphorylation of FGFR3 and that the equivalent substitution at position 369 (Gly369Cys) in mouse FGFR3 causes dwarfism with features mimicking human achondroplasia. Accordingly, homozygous mice were more severely affected than heterozygotes. The resulting mutant mice exhibited macrocephaly and shortened limbs due to retarded endochondral bone growth and premature closure of cranial base synchondroses. Compared with their wild-type littermates, mutant mice growth plates shared an expanded resting zone and narrowed proliferating and hypertrophic zones, which is correlated with the activation of Stat proteins and upregulation of cell-cycle inhibitors. Reduced bone density is accompanied by increased activity of osteoclasts and upregulation of genes that are related to osteoblast differentiation, including osteopontin, osteonectin, and osteocalcin. These data reveal an essential role for FGF/FGFR3 signals in both chondrogenesis and osteogenesis during endochondral ossification. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Oral Biol, Boston, MA 02115 USA. Childrens Hosp, Sch Dent Med, Boston, MA 02115 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 45 TC 165 Z9 179 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 11 BP 1517 EP 1525 DI 10.1172/JCI6690 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263FG UT WOS:000084114200009 PM 10587515 ER PT J AU Ohh, M Takagi, Y Aso, T Stebbins, CE Pavletich, NP Zbar, B Conaway, RC Conaway, JW Kaelin, WG AF Ohh, M Takagi, Y Aso, T Stebbins, CE Pavletich, NP Zbar, B Conaway, RC Conaway, JW Kaelin, WG TI Synthetic peptides define critical contacts between elongin C, elongin B, and the von Hippel-Lindau protein SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; GERMLINE MUTATIONS; CELLULAR PROTEINS; PRODUCT; DISEASE; VHL; BINDING; IDENTIFICATION; ELONGATION; CARCINOMA AB The von Hippel-Lindau tumor suppressor protein (pVHL) negatively regulates hypoxia-inducible mRNAs such as the mRNA encoding vascular endothelial growth factor (VEGF). This activity has been linked to its ability to form multimeric complexes that contain elongin C, elongin B, and Cul2. To understand this process in greater detail, we performed a series of in vitro binding assays using pVHL, elongin B, and elongin C variants as well as synthetic peptide competitors derived from pVHL or elongin C. A subdomain of elongin C (residues 17-50) was necessary and sufficient for detectable binding to elongin B. In contrast, elongin B residues required for binding to elongin C were not confined to a discrete colinear domain. We found that the pVHL (residues 157-171) is necessary and sufficient for binding to elongin C in vitro and is frequently mutated in families with VHL disease. These mutations preferentially involve residues that directly bind to elongin C and/or alter the conformation of pVHL such that binding to elongin C is at least partially diminished. These results are consistent with the view that diminished binding of pVHL to the elongins plays a causal role in VHL disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Oklahoma Med Res Fdn, Program Mol & Cell Biol, Oklahoma City, OK 73104 USA. Cornell Univ, Joan & Sanford I Weill Grad Sch Med Sci, Dept Biochem & Struct Biol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Conaway, Joan/0000-0002-2786-0663 NR 31 TC 69 Z9 72 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 1999 VL 104 IS 11 BP 1583 EP 1591 DI 10.1172/JCI8161 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 263FG UT WOS:000084114200016 PM 10587522 ER PT J AU Boman, J Gaydos, CA Quinn, TC AF Boman, J Gaydos, CA Quinn, TC TI Molecular diagnosis of Chlamydia pneumoniae infection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Review ID POLYMERASE-CHAIN-REACTION; REACTION-ENZYME-IMMUNOASSAY; NUCLEIC-ACID AMPLIFICATION; RESTRICTION-ENDONUCLEASE ANALYSIS; COMMUNITY-ACQUIRED PNEUMONIA; ACUTE RESPIRATORY-INFECTIONS; ABDOMINAL AORTIC-ANEURYSMS; CORONARY-ARTERY DISEASE; MEMBRANE PROTEIN GENE; PCR-BASED ASSAY AB Chlamydia pneumoniae is a common and important intracellular bacterium implicated in upper and lower respiratory tract infections in humans. Also, C. pneumoniae has been associated with chronic diseases such as atherosclerosis and asthma. Since C. pneumoniae can cause severe clinical disease, correct diagnosis and therapy are important issues. However, conventional assays for the detection of C. pneumoniae have limitations, and there is a need for more accurate diagnostic methods. Nucleic acid amplification (NAA) techniques have the potential to offer clinical laboratories a convenient means of detecting C. pneumoniae rapidly and reliably, ensuring optimal clinical decisions and patient care, including choice of appropriate antibiotic therapy. This minireview discusses the molecular biology-based amplification methods that are currently available for the detection of C. pneumoniae as well as potential new techniques. Topics that are discussed include specimen collection, preparation of nucleic acid from samples, choice of gene target and primer set selection, optimal amplification conditions, and detection of the amplification product. Also reviewed are methods for recognition and prevention of false-positive and false-negative results, evaluations of new and old tests, and clinical applications. C1 Umea Univ, Dept Virol, Umea, Sweden. Johns Hopkins Univ, Dept Med, Div Infect Dis, Baltimore, MD USA. NIAID, NIH, Bethesda, MD USA. RP Boman, J (reprint author), Umea Univ Hosp, Dept Clin Virol, Bldg 6G,Room 178, S-90185 Umea, Sweden. RI Gaydos, Charlotte/E-9937-2010 NR 94 TC 62 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1999 VL 37 IS 12 BP 3791 EP 3799 PG 9 WC Microbiology SC Microbiology GA 259CY UT WOS:000083877400001 PM 10565886 ER PT J AU Hsieh, SY Meng, XJ Wu, YH Liu, ST Tam, AW Lin, DY Liaw, YF AF Hsieh, SY Meng, XJ Wu, YH Liu, ST Tam, AW Lin, DY Liaw, YF TI Identity of a novel swine hepatitis E virus in Taiwan forming a monophyletic group with Taiwan isolates of human hepatitis E virus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID NON-B HEPATITIS; TRANSMITTED NON-A; UNITED-STATES TRAVELER; C VIRUS; EXPERIMENTAL-INFECTION; SYNTHETIC PEPTIDES; BLOOD-DONORS; ANTIBODY; GENOME; IDENTIFICATION AB Recently, we found that more than 10% of the cases of acute non-A, non-B, non-C hepatitis in Taiwan were caused by a novel strain of hepatitis E virus (HEV), Since none of these patients had a history of travel to areas where HEV is endemic, the source of transmission remains unclear. The recent discovery of a swine HEV in herd pigs in the United States has led us to speculate that HEV may also circulate in herd pigs in Taiwan and may serve as a reservoir for HEV in Taiwan, Of 275 herd pigs obtained from 10 pig farms in Taiwan, 102 (37%) were seropositive for serum anti-HEV immunoglobulin G (IgG), A 185-bp genomic sequence within the ORF-2 of the HEV genome was amplified and cloned from serum samples of an anti-HEV positive pig and subsequently from serum samples of a patient with acute hepatitis E. Sequence comparison revealed that the swine and human isolates of HEV share 97.3% identity. Phylogenetic analyses further showed that the Taiwan swine and human isolates of HEV form a distinct branch divergent from all other known strains of HEV, including the U.S, swine strain. To examine the potential risk of cross-species transmission of swine HEV to humans, the seroprevalences of anti-HEV IgG in 30 swine handlers, 20 pork dealers, and 50 control subjects were assessed and were found to be 26.7, 15, and 8%, respectively (for swine handlers versus controls, P = 0.048), Our findings may help provide an understanding of the modes of HEV transmission and may also raise potential public health concerns for HEV zoonosis. C1 Chang Gung Univ, Sch Med, Dept Microbiol & Immunol, Tao Yuan, Taiwan. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Genelabs Technol, Dept Mol Virol, Redwood City, CA 94063 USA. Chang Gung Mem Hosp, Liver Res Unit, Taoyuan, Taiwan. RP Hsieh, SY (reprint author), Chang Gung Mem Hosp, Liver Res Unit, 199 Tung Hwa N Rd, Taipei 115, Taiwan. RI Liaw, Yun-Fan /B-4305-2009; Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 NR 50 TC 181 Z9 194 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1999 VL 37 IS 12 BP 3828 EP 3834 PG 7 WC Microbiology SC Microbiology GA 259CY UT WOS:000083877400007 PM 10565892 ER PT J AU Liang, FT Steere, AC Marques, AR Johnson, BJB Miller, JN Philipp, MT AF Liang, FT Steere, AC Marques, AR Johnson, BJB Miller, JN Philipp, MT TI Sensitive and specific serodiagnosis of Lyme disease by enzyme-linked immunosorbent assay with a peptide based on an immunodominant conserved region of Borrelia burgdorferi VlsE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID OUTER-SURFACE PROTEIN; CROSS-REACTIVITY; ESCHERICHIA-COLI; RHESUS-MONKEY; ELISA TESTS; IN-VITRO; EXPRESSION; LIPOPROTEIN; ADSORPTION; INFECTION AB VlsE, the variable surface antigen of Borrelia burgdorferi, contains an immunodominant conserved region named IR,, In the present study, the diagnostic performance of a peptide enzyme-linked immunosorbent assay (ELISA) based on a 26-mer synthetic peptide (C-6) with the IR, sequence was explored, Sensitivity was assessed with serum samples (n = 210) collected from patients with clinically defined Lyme disease at the acute (early Localized or early disseminated disease), convalescent, or late disease phase, The sensitivities for acute-, convalescent-, and late-phase specimens were 74% (29 of 39), 85 to 90% (34 of 40 to 35 of 39), and 100% (59 of 59), respectively. Serum specimens from early neuroborreliosis patients were 95% positive (19 of 20), and those from an additional group of patients with posttreatment Lyme disease syndrome yielded a sensitivity of 62% (8 of 13), To assess the specificity of the peptide ELISA, 77 serum samples from patients with other spirochetal or chronic infections, autoimmune diseases, or neurologic diseases and 99 serum specimens from hospitalized patients in an area where Lyme disease is not endemic were examined. Only two potential false positives from the hospitalized patients were found, and the overall specificity was 99% (174 of 176), Precision, which was assessed with a panel of positive and negative serum specimens arranged in blinded duplicates, was 100%. Four serum samples with very high anti-OspA antibody titers obtained from four monkeys given the OspA vaccine did not react with the C-6 peptide. This simple, sensitive, specific, and precise ELISA may contribute to alleviate some of the remaining problems in Lyme disease serodiagnosis. Because of its synthetic peptide base, it will be inexpensive to manufacture. It also will be applicable to serum specimens from OspA-vaccinated subjects. C1 Tulane Univ, Med Ctr, Tulane Reg Primate Res Ctr, Dept Parasitol, Covington, LA 70433 USA. Tufts Univ, New England Med Ctr, Sch Med, Div Rheumatol, Boston, MA 02111 USA. NIAID, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Ft Collins, CO 80522 USA. Univ Calif Los Angeles, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA. RP Philipp, MT (reprint author), Tulane Univ, Med Ctr, Tulane Reg Primate Res Ctr, Dept Parasitol, 18703 3 Rivers Rd, Covington, LA 70433 USA. FU NCRR NIH HHS [P51 RR000164, RR00164]; NIAID NIH HHS [AI35027] NR 42 TC 192 Z9 197 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1999 VL 37 IS 12 BP 3990 EP 3996 PG 7 WC Microbiology SC Microbiology GA 259CY UT WOS:000083877400035 PM 10565920 ER PT J AU Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD AF Harris, NL Jaffe, ES Diebold, J Flandrin, G Muller-Hermelink, HK Vardiman, J Lister, TA Bloomfield, CD TI World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting - Airlie House, Virginia, November 1997 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AMERICAN AB Purpose: The European Association of Hematopathologists and the Society for Hematopathology have developed a new World Health Organization (WHO) classification of hematologic malignancies, including lymphoid, myeloid, histiocytic, and mast cell neoplasms, Design: Ten committees of pathologists developed lists and definitions of disease entities. A clinical advisory committee (CAC) of international hematologists and oncologists was formed to ensure that the classification would be useful to clinicians, The CAC met in November 1997 to discuss clinical issues related to the classification. Results: The WHO uses the Revised European-American Lymphoma (REAL) classification, published in 1994 by the International Lymphoma Study Group, to categorize lymphoid neoplasms. The REAL classification is based on the principle that a classification is a list of "real" disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one gold standard, The WHO classification applies the principles of the REAL classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. At the CAC meeting, which was organized around a series of clinical questions, participants reached a consensus on most of the questions posed. They concluded that clinical groupings of lymphoid neoplasms were neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors, such as the International Prognostic Index. Conclusion: The WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies, J Clin Oncol 17:3835-3849, (C) 1999 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Hotel Dieu, Paris, France. Hop Necker Enfants Malad, Paris, France. Univ Wurzburg, Wurzburg, Germany. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. St Bartholomews Hosp, Dept Med Oncol, London, England. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,Fruit St, Boston, MA 02114 USA. NR 4 TC 1896 Z9 1993 U1 1 U2 57 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1999 VL 17 IS 12 BP 3835 EP 3849 PG 15 WC Oncology SC Oncology GA 262AJ UT WOS:000084043300018 PM 10577857 ER PT J AU Huh, CG Hakansson, K Nathanson, CM Thorgeirsson, UP Jonsson, N Grubb, A Abrahamson, M Karlsson, S AF Huh, CG Hakansson, K Nathanson, CM Thorgeirsson, UP Jonsson, N Grubb, A Abrahamson, M Karlsson, S TI Decreased metastatic spread in mice homozygous for a null allele of the cystatin C protease inhibitor gene SO JOURNAL OF CLINICAL PATHOLOGY-MOLECULAR PATHOLOGY LA English DT Article DE cystatin C; cysteine protease inhibitor; knockout mouse; metastasis ID CYSTEINE-PROTEINASE-INHIBITOR; HERPES-SIMPLEX VIRUS; CATHEPSIN-B; AMYLOID ANGIOPATHY; BONE-RESORPTION; BIOLOGICAL-FLUIDS; GAMMA-TRACE; CELLS; EXPRESSION; MELANOMA AB Aims-Increased or altered activities of cysteine proteases have been implicated in serious human disorders such as cancer, rheumatoid arthritis, sepsis, and osteoporosis. To improve the current knowledge of the regulatory role of a major mammalian cysteine protease inhibitor, cystatin C, in such disease processes, a cystatin C deficient mouse was generated and characterised. Methods-The mouse cystatin C gene was inactivated by insertion of a bacterial neo gene through homologous recombination in 129/Sv embryonic stem cells. Embryonic stem cell clones were injected into C57BL/6J blastocysts followed by injection of the blastocysts into pseudopregnant female mice. F1 offspring with agouti coat colour after mating of chimaeric males with C57BL/6J females were examined by DNA analysis, and mice carrying the targeted mutation were intercrossed to obtain homozygous cystatin C deficient (CysC(-/-)) mice. To study the role of cysteine proteases and their inhibitors in metastasis, the spread of B16-F10 melanoma cells in CysC(-/-) and wild-type mice was compared. Analysis of the formation of remote metastases was carried out by intravenous injection of beta-galactosidase transfected B16-F10 cells and subseqent determination of cancer cell colonies in the lungs. Results-Cystatin C deficient mice were fertile and showed no gross pathological abnormality up to 6 months of age. Compared with wild-type mice, seven times fewer large metastatic colonies were counted by means of a dissecting microscope in CysC(-/-) mice two weeks after tail vein injection of B16-F10 cells. At all of eight time points from 15 minutes to two weeks after intravenous injection of tumour cells, the CysC(-/-) mice had significantly fewer lung metastases. The observed differences were smaller when beta-galactosidase transfected cells were used to allow counting of small colonies. Subcutanous and intracerebral tumour growth was not different in the CysC(-/-) mice. Conclusions-Cystatin C concentrations in vivo might influence metastasis in some tissues. The decreased metastatic spread of B16-F10 cells in CysC(-/-) mice is the result of both reduced seeding and reduced growth of tumour cells in their lungs. C1 Univ Lund, Dept Gene Therapy & Mol Med, S-22100 Lund, Sweden. NCI, Mol & Med Genet Sect, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tumor Biol & Carcinogenesis Sect, NIH, Bethesda, MD 20892 USA. Univ Lund, Dept Clin Chem, S-22185 Lund, Sweden. Univ Lund, Dept Pathol, Lund, Sweden. RP Karlsson, S (reprint author), Univ Lund, Dept Gene Therapy & Mol Med, S-22100 Lund, Sweden. NR 48 TC 75 Z9 75 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1366-8714 J9 J CLIN PATHOL-MOL PA JI J. Clin. Pathol.-Mol. Pathol. PD DEC PY 1999 VL 52 IS 6 BP 332 EP 340 PG 9 WC Pathology SC Pathology GA 267LU UT WOS:000084360100003 ER PT J AU Shibaki, A AF Shibaki, A TI Demonstration of the high affinity IgE receptor on Langerhans cells - Reply to B.M. Henz SO JOURNAL OF DERMATOLOGICAL SCIENCE LA English DT Letter C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. RP Shibaki, A (reprint author), NCI, Dermatol Branch, Bldg 10,Rm 12N250,10 Ctr Dr, Bethesda, MD 20892 USA. NR 0 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 0923-1811 J9 J DERMATOL SCI JI J. Dermatol. Sci. PD DEC PY 1999 VL 22 IS 1 BP 67 EP 67 PG 1 WC Dermatology SC Dermatology GA 275ZY UT WOS:000084852200011 ER PT J AU Kostic, TS Andric, SA Maric, D Stojilkovic, SS Kovacevic, R AF Kostic, TS Andric, SA Maric, D Stojilkovic, SS Kovacevic, R TI Involvement of inducible nitric oxide synthase in stress-impaired testicular steroidogenesis SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID LEYDIG-CELL STEROIDOGENESIS; SELECTIVE-INHIBITION; OPIOID ANTAGONIST; RAT; AMINOGUANIDINE; IMMOBILIZATION; ANDROGEN; TESTIS AB The immobilization stress induces an acute inhibition of testicular steroidogenesis that is mediated by the nitric oxide (NO) signaling pathway. Here we compared the effects of 2-h immobilization stress on in vivo and in vitro rat steroidogenesis at two time points, 0 h and 6 h after the end of the stress session. As expected, serum androgens and human chorionic gonadotropin (hCG)-stimulated progesterone and testosterone production by testicular tissue were inhibited at 0 h, and also at the 6-h time point. Both the acute and sustained inhibitions of in vitro steroidogenesis were accompanied by a significant increase in nitrite, a stable oxidation product of NO. To clarify which subtype of NO synthase (NOS) (constitutive (cNOS) or inducible (iNOS)) participates in down-regulation of testicular steroidogenesis, aminoguanidine hydrochloride (AG), a selective iNOS inhibitor, was employed. Intratesticular injection of AG prevented the sustained, but not the acute, stress-induced decrease in serum testosterone. When added in vitro, it also prevented the sustained decrease in steroid production and increase in nitrite production by testicular tissue, both in a dose-dependent manner and with EC50 of about 50 mu M. Furthermore, AG added in vivo and in vitro effectively blocked the sustained decrease in 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) and 17 alpha-hydroxylase/C17-20 lyase (P450c17) activities. In all concentrations employed, AG did not affect serum androgens and in vitro steroid and nitrite production in unstressed animals. These results indicate that the NO signaling pathway participates in acute and sustained stress-induced down-regulation of testicular steroidogenesis, presumably through its direct action on 3 beta HSD and P450c17. The acute NO production is controlled by cNOS and the sustained production of this messenger is controlled by iNOS. C1 Univ Novi Sad, Fac Sci, Inst Biol, YU-21000 Novi Sad, Serbia Monteneg. NICHHD, SCS, ERRB, Bethesda, MD 20892 USA. RP NICHHD, SCS, ERRB, Bldg 49,Room 6A 36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov NR 30 TC 26 Z9 29 U1 1 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD DEC PY 1999 VL 163 IS 3 BP 409 EP 416 DI 10.1677/joe.0.1630409 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 267ML UT WOS:000084361700005 PM 10588814 ER PT J AU Gulko, P Remmers, EF AF Gulko, P Remmers, EF TI Report on rat chromosome 9 SO JOURNAL OF EXPERIMENTAL ANIMAL SCIENCE LA English DT Article C1 Columbia Univ Coll Phys & Surg, Div Autoimmune & Mol Dis, New York, NY 10032 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Gulko, P (reprint author), Columbia Univ Coll Phys & Surg, Div Autoimmune & Mol Dis, 630 W 168th St, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0939-8600 J9 J EXP ANIM SCI JI J. Exp. Anim. Sci. PD DEC PY 1999 VL 40 IS 1-3 BP 77 EP 80 DI 10.1016/S0939-8600(99)80010-8 PG 4 WC Zoology SC Zoology GA 280RK UT WOS:000085115600010 ER PT J AU Remmers, EF Wilder, RL AF Remmers, EF Wilder, RL TI Report on rat chromosome 11 SO JOURNAL OF EXPERIMENTAL ANIMAL SCIENCE LA English DT Article C1 NIAMSD, Arthritis Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Remmers, EF (reprint author), NIAMSD, Arthritis Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0939-8600 J9 J EXP ANIM SCI JI J. Exp. Anim. Sci. PD DEC PY 1999 VL 40 IS 1-3 BP 93 EP 95 DI 10.1016/S0939-8600(99)80012-1 PG 3 WC Zoology SC Zoology GA 280RK UT WOS:000085115600012 ER PT J AU Dracheva, SV Remmers, EF AF Dracheva, SV Remmers, EF TI Report on rat chromosome 14 SO JOURNAL OF EXPERIMENTAL ANIMAL SCIENCE LA English DT Article C1 NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Dracheva, SV (reprint author), NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0939-8600 J9 J EXP ANIM SCI JI J. Exp. Anim. Sci. PD DEC PY 1999 VL 40 IS 1-3 BP 111 EP 115 DI 10.1016/S0939-8600(99)80015-7 PG 5 WC Zoology SC Zoology GA 280RK UT WOS:000085115600015 ER PT J AU Feerick, MM Haugaard, JJ AF Feerick, MM Haugaard, JJ TI Long-term effects of witnessing marital violence for women: The contribution of childhood physical and sexual abuse SO JOURNAL OF FAMILY VIOLENCE LA English DT Article DE marital violence; child abuse; effects on children; adjustment ID BEHAVIOR PROBLEMS; YOUNG-ADULTS; FAMILY VIOLENCE; BATTERED WOMEN; INTERGENERATIONAL TRANSMISSION; INTERPARENTAL VIOLENCE; RETROSPECTIVE REPORTS; UNINTENDED VICTIMS; DOMESTIC VIOLENCE; COLLEGE-STUDENTS AB A sample of 313 college women completed a questionnaire about experiences with violence in childhood and adulthood and adult adjustment and relationship functioning. Nine percent of the women reported having witnessed some type of physical conflict between their parents. Witnessing marital violence was associated with other family mental health risks, childhood physical and sexual abuse, and adult physical assaults by strangers. Women who witnessed marital violence reported more symptoms of posttraumatic stress disorder than other women, after family background and abuse variables were accounted for. Significant interactions between witnessing marital violence and childhood physical abuse were observed for measures of social avoidance and predictability in partner relationships, indicating that the effects of witnessing marital violence depended on the presence of childhood abuse. Implications of these results for research and interventions are discussed. C1 NICHHD, Child Dev & Behav Branch, Bethesda, MD 20892 USA. Cornell Univ, Dept Human Dev, Ithaca, NY USA. RP Feerick, MM (reprint author), NICHHD, Child Dev & Behav Branch, 6100 Executive Blvd,Room 4B05,MSC 7510, Bethesda, MD 20892 USA. NR 68 TC 28 Z9 28 U1 1 U2 6 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0885-7482 J9 J FAM VIOLENCE JI J. Fam. Violence PD DEC PY 1999 VL 14 IS 4 BP 377 EP 398 DI 10.1023/A:1022882131610 PG 22 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA 263RL UT WOS:000084139000003 ER PT J AU Hirschberg, K Presley, J Phair, R Lippincott-Schwartz, J AF Hirschberg, K Presley, J Phair, R Lippincott-Schwartz, J TI Analysis of secretory protein trafficking within living cells SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract C1 BioInforinat Serv, Rockville, MD 20854 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1999 VL 47 IS 12 MA 5 BP 1644 EP 1644 PG 1 WC Cell Biology SC Cell Biology GA 263RX UT WOS:000084140000021 ER PT J AU Weisz, A Ito, Y AF Weisz, A Ito, Y TI Standardization of biological dyes and stains through use of pH-zone-refining countercurrent chromatography SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Meeting Abstract C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NHLBI, NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1999 VL 47 IS 12 MA 12 BP 1645 EP 1645 PG 1 WC Cell Biology SC Cell Biology GA 263RX UT WOS:000084140000028 ER PT J AU Henderson, DK AF Henderson, DK TI Weighing the consequence of doing nothing versus those of doing something: post-exposure chemoprophylaxis for occupational exposures to HIV SO JOURNAL OF HOSPITAL INFECTION LA English DT Article; Proceedings Paper CT 4th International Conference of the Hospital-Infection-Society CY SEP 13-17, 1998 CL EDINBURGH, SCOTLAND SP Hosp Infect Soc ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEALTH-CARE WORKERS; SCID-HU MICE; ZIDOVUDINE TREATMENT; POSTEXPOSURE PROPHYLAXIS; INFECTED BLOOD; ACCIDENTAL EXPOSURE; RHESUS-MONKEYS; SIV INFECTION; HEPATITIS-B C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C 146, Bethesda, MD 20892 USA. NR 76 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-6701 J9 J HOSP INFECT JI J. Hosp. Infect. PD DEC PY 1999 VL 43 SU S BP S225 EP S233 DI 10.1016/S0195-6701(99)90091-9 PG 9 WC Infectious Diseases SC Infectious Diseases GA 275PP UT WOS:000084828800033 PM 10658784 ER PT J AU Heptonstall, J Turnbull, S Henderson, D Morgan, D Harling, K Scott, G AF Heptonstall, J Turnbull, S Henderson, D Morgan, D Harling, K Scott, G TI Sharps injury! A review of controversial areas in the management of sharps accidents SO JOURNAL OF HOSPITAL INFECTION LA English DT Article; Proceedings Paper CT 4th International Conference of the Hospital-Infection-Society CY SEP 13-17, 1998 CL EDINBURGH, SCOTLAND SP Hosp Infect Soc C1 UCL Hosp, London WC1E 6DB, England. Dept Hlth, London SE1 8UG, England. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. British Med Assoc, Dept Sci, London WC1H 9JP, England. RP Scott, G (reprint author), UCL Hosp, London WC1E 6DB, England. NR 7 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-6701 J9 J HOSP INFECT JI J. Hosp. Infect. PD DEC PY 1999 VL 43 SU S BP S219 EP S223 DI 10.1016/S0195-6701(99)90090-7 PG 5 WC Infectious Diseases SC Infectious Diseases GA 275PP UT WOS:000084828800032 PM 10658783 ER PT J AU Wang, JH Guan, EN Roderiquez, G Norcross, MA AF Wang, JH Guan, EN Roderiquez, G Norcross, MA TI Inhibition of CCR5 expression by IL-12 through induction of beta-chemokines in human T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL STIMULATORY FACTOR; INTERFERON-GAMMA PRODUCTION; MACROPHAGE-TROPIC HIV-1; MOLECULAR-CLONING; HUMAN MONOCYTES; IFN-GAMMA; IN-VITRO; RECEPTOR; INTERLEUKIN-12; MIP-1-ALPHA AB IL-12 induces initiation of the differentiation of naive CD4(+) T lymphocytes into Thl cells and is important for the control of cell-mediated immunity, beta-Chemokines serve to attract various types of blood leukocytes to sites of infection and inflammation. The specific receptor for the beta-chemokines (macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES), CCR5, also functions as the primary coreceptor for macrophage-tropic isolates of HIV-1, IL-12, but not IL-4, IL-10, or IL-13, now has been shown to down-modulate the surface expression of CCR5 induced by IL-2 on both CD4(+) and CD8(+) T lymphocytes, Decreased CCR5 surface expression was not secondary to transcriptional inhibition, given that CCR5 mRNA was enhanced in cells cultured in IL-12/IL-2 compared with those cultured in IL-2 only. The effect of IL-12 in down-modulation of CCR5 surface expression was shown to be mediated by soluble factors secreted from the T cells. Rapid and transient intracellular Ca2+ mobilization was induced in monocytes by IL-12-induced supernatants, which desensitized the response of monocytes to MIP-1 alpha, but not their response to stromal cell-derived factor-1 alpha. Neutralization with specific Abs identified these factors as MIP-1 alpha and MIP-1 beta from most donors. IL-4, IL-10, IFN-gamma, and IL-18 primarily inhibited MIP-1 beta secretion and also weakly suppressed MIP-1 alpha secretion. HIV-1 replication was inhibited in IL-2/IL-12-containing cultures that correlated with chemokine and chemokine-receptor levels. These data suggest that the effects of IL-12 on beta-chemokine production and chemokine-receptor expression may contribute to the immunomodulatory activities of IL-12 and may have potential therapeutic relevance in controlling HIV-1 replication. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cell & Viral Regulat, Div Therapeut Prot,NIH, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cell & Viral Regulat, Div Therapeut Prot,NIH, Bldg 29B,Room 4E12,HFM 525,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 43 TC 42 Z9 42 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 DEC 1 PY 1999 VL 163 IS 11 BP 5763 EP 5769 PG 7 WC Immunology SC Immunology GA 258MT UT WOS:000083843500003 PM 10570258 ER PT J AU Onda, M Kreitman, RJ Vasmatzis, G Lee, B Pastan, I AF Onda, M Kreitman, RJ Vasmatzis, G Lee, B Pastan, I TI Reduction of the nonspecific animal toxicity of anti-Tac(Fv)-PE38 by mutations in the framework regions of the Fv which lower the isoelectric point SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO BIODISTRIBUTION; HUMAN ENDOTHELIAL-CELLS; VASCULAR LEAK SYNDROME; PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; RECOMBINANT IMMUNOTOXIN; VARIABLE DOMAINS; CANCER-THERAPY; PROTEIN; CHAIN AB Anti-Tac(Fv)-PE38, also called LMB-2, is a very active recombinant immunotoxin that has produced eight responses, including a durable clinical complete remission in a recently completed phase I trial of leukemias and lymphomas, Dose escalation was limited by liver toxicity. We have noted that the Pv of anti-Tac has an isoelectric point (pI) of 10.2. We hypothesize that the overall positive charge on the Fv portion of anti-Tac(Fv)-PE38 contributes to nonspecific binding to liver cells and results in dose-limiting Liver toxicity. We have used a mouse model to investigate the basis of this toxicity and found that lowering the pi of the Fv of anti-Tac from. 10.2 to 6.82 by selective mutation of surface residues causes a 3-fold decrease in animal toxicity and hepatic necrosis, This change in pI did not significantly alter the CD25 binding affinity, the cytotoxic activity toward target cells, or antitumor activity, resulting in a 3-fold improvement in the therapeutic index. If this decreased toxicity occurs in humans, it should greatly increase the clinical utility of this immunotoxin. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP NCI, Mol Biol Lab, NIH, Bldg 37,Room 4E16,37 Convent MSC 4255, Bethesda, MD 20892 USA. EM pasta@helix.nih.gov NR 22 TC 43 Z9 43 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 6072 EP 6077 PG 6 WC Immunology SC Immunology GA 258MT UT WOS:000083843500041 PM 10570296 ER PT J AU Lee, KH Wang, E Nielsen, MB Wunderlich, J Migueles, S Connors, M Steinberg, SM Rosenberg, SA Marincola, FM AF Lee, KH Wang, E Nielsen, MB Wunderlich, J Migueles, S Connors, M Steinberg, SM Rosenberg, SA Marincola, FM TI Increased vaccine-specific T cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-MELANOMA; REPLICATIVE SENESCENCE; ELISPOT ASSAY; LYMPHOCYTES; ANTIGEN; INDUCTION; CTL; IDENTIFICATION; IMMUNIZATION; EXHAUSTION AB Although in vitro sensitization assays have shown increased melanoma Ag (MA)-specific CTL reactivity after vaccination with MA peptides, clinical responses have been uncommon, This paradox questions whether data obtained from the in vitro stimulation and expansion of T cells lead to an overestimation of the immune response to vaccines, Using HLA/peptide tetramer (tHLA), we enumerated MA-specific T cell precursor frequency (TCPF) directly in PBMC from 23 melanoma patients vaccinated with gp100:209-217(210M) (g209-2M) peptide, Vaccine-specific TCPF was higher in postvaccination PBMC from seven of seven patients treated with peptide alone and four of five patients treated with peptide plus IL-12 (range of postvaccination TCPF, 0.2-2.4% and 0.2-2.5%, respectively), The increased TCPF correlated with enhanced susceptibility to in vitro stimulation with the relevant epitope, Paradoxically, no increase in postvaccination TCPF was observed in most patients who had been concomitantly treated with IL-2 (1 of 11 patients; range of postvaccination TCPF, 0.02-1.0%), a combination associated with enhanced rates of tumor regression. The lack of increase in TCPF seen in these patients corresponded to inability to elicit expansion of vaccine-specific T cells in culture, This study shows that a peptide-based vaccine can effectively generate a quantifiable T cell-specific immune response in the PBMC of cancer patients, though such a response does not associate with a clinically evident regression of metastatic melanoma. C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Bldg 10,Room 2B42,10 Ctr Dr MSC 1502, Bethesda, MD 20892 USA. NR 39 TC 219 Z9 228 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1999 VL 163 IS 11 BP 6292 EP 6300 PG 9 WC Immunology SC Immunology GA 258MT UT WOS:000083843500068 PM 10570323 ER PT J AU Housseau, F Bright, RK Simonis, T Nishimura, MI Topalian, SL AF Housseau, F Bright, RK Simonis, T Nishimura, MI Topalian, SL TI Recognition of a shared human prostate cancer-associated antigen by nonclassical MHC-restricted CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; COLONY-STIMULATING FACTOR; HUMAN-MELANOMA ANTIGENS; NATURAL-KILLER-CELLS; T-CELLS; HLA-G; CLASS-I; EXPRESSION; CD94/NKG2A; RECEPTORS AB To identify prostate cancer-associated Ags, tumor-reactive T lymphocytes were generated using iterative stimulations of PBMC from a prostate cancer patient with an autologous IFN-gamma-treated carcinoma cell Line in the presence of IL-2, A CD8(+) T cell line and TCR alpha beta(+) T cell clone were isolated that secreted IFN-gamma and TNF-alpha in response to autologous prostate cancer cells but not to autologous fibroblasts or lymphoblastoid cells, However, these T cells recognized several normal and malignant prostate epithelial cell lines without evidence of shared classical HLA molecules, The T cell line and clone also recognized colon cancers, but not melanomas, sarcomas, or lymphomas, suggesting recognition of a shared epithelium-associated Ag presented by nonclassical MHC or MHC-like molecules, Although Ag recognition by T cells was inhibited by mAb against CDS and the TCR complex (anti-TCR alpha beta, CD3, V beta 12), it was not inhibited by mAb directed against MHC class Ia or MHC class II molecules, Neither target expression of CD1 molecules nor HLA-G correlated with T cell recognition,but beta(2)-microglobulin expression was essential. Ag expression was diminished by brefeldin A, lactacystin, and cycloheximide, but not by chloroquine, consistent with an endogenous/cytosolic Ag processed through the classical class I pathway. These results suggest that prostate cancer and colon cancer cells can process and present a shared peptidic Ag to TCR alpha beta(+) T cells via a nonclassical MHC I-like molecule yet to be defined. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Transfus Med, HLA Lab, Bethesda, MD 20892 USA. RP Topalian, SL (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B47, Bethesda, MD 20892 USA. NR 40 TC 11 Z9 11 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 DEC 1 PY 1999 VL 163 IS 11 BP 6330 EP 6337 PG 8 WC Immunology SC Immunology GA 258MT UT WOS:000083843500073 PM 10570328 ER PT J AU Murphy, EL Watanabe, K Nass, CC Ownby, H Williams, A Nemo, G AF Murphy, EL Watanabe, K Nass, CC Ownby, H Williams, A Nemo, G CA Retrovirus Epidemiology Donors Stu TI Evidence among blood donors for a 30-year-old epidemic of human T lymphotropic virus type II infection in the United States SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INTRAVENOUS-DRUG-USERS; HTLV-I; CELL LEUKEMIA; RISK-FACTORS; DEMOGRAPHIC DETERMINANTS; SEROPREVALENCE; TRANSMISSION; MYELOPATHY; ANTIBODY; LYMPHOMA AB The demographic and geographic determinants of human T lymphotropic virus types I and II (HTLV-I and -II) are not well defined in the United States. Antibodies to HTLV-I and -II were measured in 1.7 million donors at five US blood centers during 1991-1995, Among those tested, 156 (9.1/10(5)) were HTLV-I seropositive and 384 (22.3/10(5)) were HTLV-II seropositive, In contrast to monotonously increasing age-specific HTLV-I seroprevalence, HTLV-II prevalence rose until age 40-49 years and declined thereafter, suggesting a birth cohort effect. HTLV-II infection was independently associated with an age of 40-49 years (odds ratio [OR], 12.4; 95% confidence interval [CI], 8.8-18.9), female sex (OR, 3.3; 95% CI, 2.6-4.1), high school or lower education (OR, 1.7; 95% CI, 1.3-2.1), hepatitis C seropositivity (OR, 25.0; 95% CI, 17.5-35.8), and first-time blood donation (OR, 3.6; 95% CI, 2.8-4.7). HTLV-II seroprevalence was highest at the two West Coast blood centers. These data are consistent with a 30-year-old epidemic of HTLV-II in the United States due to injection drug use and secondary sexual transmission and with an apparent West Coast focus. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. Amer Red Cross, Blood Serv, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Blood Serv SE Michigan Reg, Detroit, MI USA. RP Murphy, EL (reprint author), Dept Lab Med, UCSF Box 0884, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HB-47114, HB-97077, HB-97078] NR 39 TC 35 Z9 36 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1999 VL 180 IS 6 BP 1777 EP 1783 DI 10.1086/315139 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600004 PM 10558931 ER PT J AU Engels, EA Rosenberg, PS Biggar, RJ AF Engels, EA Rosenberg, PS Biggar, RJ CA Dist Columbia Gay Cohort Study Multicenter Hemophilia Cohort TI Zoster incidence in human immunodeficiency virus-infected hemophiliacs and homosexual men, 1984-1997 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HERPES-ZOSTER; AIDS; PROGRESSION; ACYCLOVIR; THERAPY; COHORT; RISK AB Zoster is an important clinical problem for human immunodeficiency virus type 1 (HIV)-infected patients. Risk factors for tester and trends in incidence in HIV-infected hemophiliacs and homosexual men (n = 1218) were examined. From 1984 to 1997, 174 tester cases were identified (average yearly incidence, 2.5%). Prior tester episodes were associated with increased risk for a subsequent episode (relative risk [RR], 4.30; 95% confidence interval [CI], 3.11-5.95), Among hemophiliacs, children and adolescents had the highest tester risk, and tester risk declined with age (RR, 0.80 per decade; 95% CI, 0.68-0.93), These findings suggest that HIV-infected persons do not produce or maintain adequate booster responses after varicella tester virus exposure. Zoster risk was relatively constant when CD4 cell counts >200 cells/mm(3) but increased steeply below this level. During the 14 years of follow-up, tester incidence declined 9% per year. This trend occurred despite decreasing CD4 cell counts and was unexplained by zidovudine or acyclovir use. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20822 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20822 USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7248, Rockville, MD 20822 USA. NR 29 TC 34 Z9 35 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1999 VL 180 IS 6 BP 1784 EP 1789 DI 10.1086/315146 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600005 PM 10558932 ER PT J AU Greenough, TC Brettler, DB Kirchhoff, F Alexander, L Desrosiers, RC O'Brien, SJ Somasundaran, M Luzuriaga, K Sullivan, JL AF Greenough, TC Brettler, DB Kirchhoff, F Alexander, L Desrosiers, RC O'Brien, SJ Somasundaran, M Luzuriaga, K Sullivan, JL TI Long-term nonprogressive infection with human immunodeficiency virus type 1 in a hemophilia cohort SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th Conference on Retroviruses and Opportunistic Infections CY JAN 31-FEB 04, 1999 CL CHICAGO, ILLINOIS ID CYTOTOXIC T-LYMPHOCYTES; LOW VIRAL LOAD; DISEASE PROGRESSION; HIV-1 INFECTION; IN-VIVO; CELL RESPONSES; GENETIC RESTRICTION; CORECEPTOR USAGE; NEF SEQUENCES; AIDS AB Seven long-term nonprogressors (LTNPs) have been identified in a cohort of 128 human immunodeficiency virus (HIV)-1 infected individuals with hemophilia. Studies included quantitation of virus by polymerase chain reaction, characterization of primary virus isolates in vitro, analysis of lymphocyte surface markers, and measurement of virus-specific cytotoxic T lymphocytes (CTLs). Viruses of LTNPs exhibited slow growth in vivo and in vitro. LTNPs had expansion of CD8 T cells with increased expression of HLA-DR. Intermittent HIV-1-specific CTL effector activity was detected in freshly isolated peripheral blood mononuclear cells of most LTNPs. CTL precursor frequencies were higher in LTNPs than in patients with progressive disease. Virus antigen-specific lymphoproliferation was vigorous in some LTNPs. Thus, LTNPs in this cohort have maintained remarkably low virus burdens and vigorous HIV-l-specific cell-mediated immunity over a 15-year period. The presence of expanded, activated CD8 T cells with cytotoxic effector function in the peripheral blood suggests ongoing viral replication. C1 Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. Univ Massachusetts, New England Area Comprehens Hemophilia Ctr, Worcester, MA 01605 USA. Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-8520 Erlangen, Germany. New England Reg Primate Res Ctr, Southborough, MA 01772 USA. NCI, Lab Genomic Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Greenough, TC (reprint author), Univ Massachusetts, Sch Med, Program Mol Med, 373 Plantat St,Suite 318, Worcester, MA 01605 USA. FU NHLBI NIH HHS [HL-42257]; NIAID NIH HHS [AI-26507, AI-39400] NR 66 TC 47 Z9 47 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1999 VL 180 IS 6 BP 1790 EP 1802 DI 10.1086/315128 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600006 PM 10558933 ER PT J AU Biggar, RJ Janes, M Pilon, R Miotti, P Taha, TET Broadhead, R Mtimivalye, L Kumwenda, N Cassol, S AF Biggar, RJ Janes, M Pilon, R Miotti, P Taha, TET Broadhead, R Mtimivalye, L Kumwenda, N Cassol, S TI Virus levels in untreated African infants infected with human immunodeficiency virus type 1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID TO-CHILD TRANSMISSION; VIRAL LOAD; HIV-1 INFECTION; FILTER-PAPER; VERTICAL TRANSMISSION; RNA AMPLIFICATION; PLASMA; QUANTITATION; PROGRESSION; COUNT AB In developed areas, human immunodeficiency virus (HIV)-infected infants have high virus levels and rapidly progress to death. HIV levels were assessed in 1994-1997 in untreated infants in Malawi by analysis of dried blood spots tested by nucleic acid silica-bound amplification. Of 24 umbilical cord blood (CB)-positive samples, 83% had >10,000 copies/mL. The median virus level was 78,000 copies/mL. First positive sample median levels were 355,000 copies/mL among 52 perinatally infected infants and 130,000 copies/mL among 43 infants infected by breast-feeding. Virus levels were stable, and initial levels predicted Levels 1 year after infection (P = .005), at which time levels did not significantly differ among in utero, perinatally, or postnatally infected infants. Thus, neither age at infection nor route of infection significantly influenced HIV levels measured 1 year after infection, Most (87%) CB-positive infants were infected before labor onset, since virus levels greatly exceeded those expected in their mothers. C1 NIAID, Viral Epidemiol Branch, Bethesda, MD 20892 USA. NIAID, AIDS Program, Bethesda, MD 20892 USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. Ottawa Gen Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada. Univ Malawi, Queen Elizabeth Cent Hosp, Sch Med, Blantyre, Malawi. Johns Hopkins Minist Hlth Project, Blantyre, Malawi. RP Biggar, RJ (reprint author), 6130 Execut Blvd,EPN 434, Rockville, MD 20862 USA. NR 28 TC 26 Z9 28 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1999 VL 180 IS 6 BP 1838 EP 1843 DI 10.1086/315122 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600012 PM 10558939 ER PT J AU Ma, L Borio, L Masur, H Kovacs, JA AF Ma, L Borio, L Masur, H Kovacs, JA TI Pneumocystis carinii dihydropteroate synthase but not dihydrofolate reductase gene mutations correlate with prior trimethoprim sulfamethoxazole or dapsone use SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Joint Meeting of the Society-of-Protozoologists/6th International Workshop on Opportunistic Protists CY MAY 27-29, 1999 CL RALEIGH, NORTH CAROLINA SP Soc Protozoologists ID POLYMERASE CHAIN-REACTION; FOLIC-ACID SYNTHESIS; PLASMODIUM-FALCIPARUM; AIDS PATIENTS; HYDROXYMETHYLDIHYDROPTERIN PYROPHOSPHOKINASE; STREPTOCOCCUS-PNEUMONIAE; SULFONAMIDE RESISTANCE; DNA AMPLIFICATION; MALARIA; PYRIMETHAMINE AB Recent studies of the human Pneumocystis carinii dihydropteroate synthase (DHPS) gene suggest that P. carinii is developing resistance to sulfamethoxazole (SMX) and dapsone. To explore whether P. carinii is also developing resistance to trimethoprim (TMP), the human fl carinii dihydrofolate reductase (DHFR) gene was cloned, DHFR and DHPS genes in 37 P. carinii isolates from 35 patients were sequenced, and the relationship between TMP-SMX or dapsone use and gene mutations was analyzed. The DHFR gene sequences were identical in all isolates except 1 with a synonymous substitution. In contrast, the DHPS gene sequences showed mutations in 16 of the 37 isolates; prior sulfa/sulfone prophylaxis was associated with the presence of these mutations (P <.001). In addition to suggesting that there is less selective pressure on DHFR than on DHPS, this study reinforces the hypothesis that mutations in the DHPS gene are likely involved in the development of sulfa resistance in P. carinii. C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIH, Ctr Clin, Dept Crit Care Med, Bldg 10,Rm 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 39 TC 122 Z9 124 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1999 VL 180 IS 6 BP 1969 EP 1978 DI 10.1086/315148 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600027 PM 10558954 ER PT J AU Levesque, MC Hobbs, MR Anstey, NM Vaughn, TN Chancellor, JA Pole, A Perkins, DJ Misukonis, MA Chanock, SJ Granger, DL Weinberg, JB AF Levesque, MC Hobbs, MR Anstey, NM Vaughn, TN Chancellor, JA Pole, A Perkins, DJ Misukonis, MA Chanock, SJ Granger, DL Weinberg, JB TI Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY OCT, 1998 CL SAN JUAN, PUERTO RICO SP Amer Soc Trop Med & Hygiene ID CEREBRAL MALARIA; GENE; EXPRESSION; INDUCTION; CELLS AB Nitric oxide (NO) plays an important role in host resistance to infection with a variety of organisms. Two recent reports from Gabon and Gambia identified associations of malaria disease severity with the inducible NO synthase (NOS2) promoter G-954C and short allele (<11 repeats) pentanucleotide microsatellite polymorphisms, respectively. It was postulated that there would be a correlation of these polymorphisms with malaria disease severity and with measures of NO production in our cohort of Tanzanian children with malaria. In Tanzanian children, 15% were heterozygous or homozygous for the G-954C polymorphism, and 13% had the short-allele microsatellite polymorphism. There was no significant correlation of either polymorphism with disease severity or with measures of NO production and NOS2 expression. Black and white Americans differed significantly in the frequencies of these polymorphisms. The various association of these gene polymorphisms with malaria severity in different populations underscores the complexity of host resistance to malaria. C1 VA Med Ctr, Dept Med, Durham, NC 27705 USA. Duke Univ, Med Ctr, Durham, NC 27705 USA. Univ Utah, Med Ctr, Dept Med, Salt Lake City, UT 84132 USA. Menzies Sch Hlth Res, Dept Med, Darwin, NT, Australia. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Weinberg, JB (reprint author), VA Med Ctr, Dept Med, 508 Fulton St, Durham, NC 27705 USA. FU NIAID NIH HHS [R01 AI041764, AI-41764]; NIAMS NIH HHS [AR-39162, AR-01918] NR 23 TC 67 Z9 72 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC PY 1999 VL 180 IS 6 BP 1994 EP 2002 DI 10.1086/315140 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 263QW UT WOS:000084137600030 PM 10558957 ER PT J AU Quackenbush, EJ Kraemer, KH Gahl, WA Schirch, V Whiteman, DAH Levine, K Levy, HL AF Quackenbush, EJ Kraemer, KH Gahl, WA Schirch, V Whiteman, DAH Levine, K Levy, HL TI Hypoglycinaemia and psychomotor delay in a child with xeroderma pigmentosum SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID 3-PHOSPHOGLYCERATE DEHYDROGENASE-DEFICIENCY; SERINE HYDROXYMETHYLTRANSFERASE; DISORDERS; GLYCINE AB Glycine is a nonessential amino acid that serves as both an inhibitory and an excitatory neurotransmitter. Hyperglycinaemia occurs in nonketotic hyperglycinaemia, a primary defect in the glycine cleavage pathway, and as a secondary feature of several inborn errors of organic acid metabolism. However, specifically low levels of glycine have never been reported. Here we report a child with complementation group C xeroderma pigmentosum (XP) characterized by a splice donor mutation in the XPC gene, multiple skin cancers and specific and persistent hypoglycinaemia. He has cognitive delay, lack of speech, autistic features, hyperactivity and hypotonia, all unexplained by the diagnosis of XP group C, a non-neurological form of the disease. Treatment with oral glycine has improved his hyperactivity. Specific hypoglycinaemia could indicate a metabolic disorder producing neurological dysfunction. Whether it is related to or coincidental with the XP is unclear. C1 Childrens Hosp, Div Genet, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Richmond, VA USA. Maine Med Ctr, Portland, OR USA. RP Levy, HL (reprint author), Childrens Hosp, Div Genet & Metab, IC Smith Bldg,300 Longwood Ave, Boston, MA 02115 USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 23 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD DEC PY 1999 VL 22 IS 8 BP 915 EP 924 DI 10.1023/A:1005691424004 PG 10 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 256GA UT WOS:000083716500006 PM 10604143 ER PT J AU Kuhn, U Vogel, JC AF Kuhn, U Vogel, JC TI Transduction of human keratinocytes with a lentiviral vector. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Natl Inst Hlth, 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 DEC PY 1999 VL 113 IS 6 MA 085 BP 1136 EP 1136 PG 1 WC Dermatology SC Dermatology GA 268VE UT WOS:000084436600048 ER PT J AU Price, VH Moshell, AN Stenn, KS Duvic, M Goldsmith, LA Cork, MJ Happle, R Kalabokes, V AF Price, VH Moshell, AN Stenn, KS Duvic, M Goldsmith, LA Cork, MJ Happle, R Kalabokes, V TI Third International Research Workshop on Alopecia Areata - Introduction SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Editorial Material C1 Natl Alopecia Areata Fdn, San Rafael, CA 94915 USA. NIAMSD, Bethesda, MD 20892 USA. RP Price, VH (reprint author), Natl Alopecia Areata Fdn, San Rafael, CA 94915 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 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD DEC PY 1999 VL 4 IS 3 BP 199 EP 199 DI 10.1038/sj.jidsp.5640209 PG 1 WC Dermatology SC Dermatology GA 276AE UT WOS:000084852800001 ER PT J AU Stenn, KS Lichti, U Shapiro, J Whiting, DA AF Stenn, KS Lichti, U Shapiro, J Whiting, DA TI Third International Research Workshop on Alopecia Areata - Introduction SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Editorial Material C1 Johnson & Johnson Skin Biol TRC, Skillman, NJ 08558 USA. NCI, Lab Cell Carcinogenesis, Bethesda, MD 20892 USA. Univ British Columbia, Div Dermatol, Vancouver, BC V5Z 1M9, Canada. Baylor Hair Res Ctr, Dallas, TX USA. RP Stenn, KS (reprint author), Johnson & Johnson Skin Biol TRC, Skillman, NJ 08558 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 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD DEC PY 1999 VL 4 IS 3 BP 257 EP 257 DI 10.1038/sj.jidsp.5640224 PG 1 WC Dermatology SC Dermatology GA 276AE UT WOS:000084852800015 ER PT J AU London, RE AF London, RE TI Theoretical analysis of the inter-ligand overhauser effect: A new approach for mapping structural relationships of macromolecular ligands SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; TRANSFER-NOE EXPERIMENTS; CROSS-RELAXATION; NMR-SPECTROSCOPY; SPIN-DIFFUSION; PROTEINS; BINDING; SPECTRA; DEHYDROGENASE; CONFORMATION AB A theoretical framework has been developed for the evaluation of inter-ligand Overhauser effects (ILOE), predicted when pairs of ligands are observed in the presence of a macromolecular receptor which can form a ternary complex such that some of the protons on the two ligands are in close proximity with each other (generally less than similar to 5 Angstrom). Simulations for a pair of ligands with three spins each have been performed for a variety of geometric and rate parameters. Analogous to previously described calculations of TRNOE behavior, theoretical behavior of each of the nine cross peaks, A(v), in a NOESY experiment involving ligands which can exist in the free, binary, or ternary complex states can be calculated. However, for exchange which is sufficiently rapid on the relaxation and chemical shift time scales, use of a collapsed matrix, C, corresponding to sums of sets of nine elements, will often be appropriate and generally simplifies the analysis. In order to generate inter-ligand Overhauser effects, it is optimal for the fraction of receptor involved in the ternary complex to be reasonably large; i.e., concentrations of both ligands should be near saturation. Based on a model assuming random binding order of the ligands, the dependence of ILOE resonance intensities on kinetic rate constants roughly parallels the dependence of transferred NOE (TRNOE) intensities. For diffusion controlled binding, i.e., k(on) similar to 10(8) M-1 s(-1), the method is best suited for equilibrium dissociation constants in the micromolar-millimolar range (k(off) similar to 10(2)-10(5) s(-1)). Toward the slower dissociation rate constant end of this range, TRNOE and ILOE effects are still predicted, but the initial build-up curves become markedly nonlinear. For a kinetic binding scheme which assumes ordered binding of the ligands, the inherent asymmetry of the ligand binding process leads to more complex kinetics and alters the dependence of the ILOE on the kinetic parameters. In this case, the binding of the second ligand effectively reduces the exchange rate of the first ligand, reducing the transfer of NOE and ILOE information. The reduction in TRNOE and ILOE information which is prediced for the ordered ligand binding model is overcome at larger dissociation rate constants for either ligand 1 or ligand 2. In addition to the structural information available from ILOE data, the strong dependence of TRNOE and ILOE curves on ordered ligand binding suggests that such measurements could be useful for the characterization of ligand binding kinetics. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, MR-01,Box 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 37 Z9 37 U1 0 U2 6 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 DEC PY 1999 VL 141 IS 2 BP 301 EP 311 DI 10.1006/jmre.1999.1897 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 263RZ UT WOS:000084140200011 PM 10579953 ER PT J AU Furnia, A Lal, RN Maloney, E Wiktor, S Pate, E Rudolph, D Waters, D Blattner, W Manns, A AF Furnia, A Lal, RN Maloney, E Wiktor, S Pate, E Rudolph, D Waters, D Blattner, W Manns, A TI Estimating the time of HTLV-I infection following mother-to-child transmission in a breast-feeding population in Jamaica SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HTLV-I; vertical transmission; infants; seroconversion; immunoglobulins; polymerase chain reaction ID VIRUS TYPE-I; PERINATAL HIV-INFECTION; EARLY DIAGNOSIS; IGA ANTIBODIES; INFANTS; IMMUNOGLOBULIN; ASSAY AB Mother-to-child transmission of human T-cell lymphotropic virus type I (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the postnatal period. Most infant infections are not identifiable until 12 to 18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-l-seropositive children while IgM reactivity was assessed in 9 of the 16 children. Approximately three to five samples were tested for each child. IgG reactivity was observed in 100% of children at 24 months of age and 73% of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50% of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P = 0.72). PCR tests support a median time to infection that is similar to that estimated by whole virus Western blot. (C) 1999 Wiley-Liss, Inc. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. George Washington Univ, Sch Publ Hlth, Washington, DC USA. George Washington Univ, Hlth Serv, Washington, DC USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ W Indies, Dept Pediat, Kingston 7, Jamaica. SAIC, Frederick, MD USA. RP Manns, A (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NR 19 TC 11 Z9 11 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 1999 VL 59 IS 4 BP 541 EP 546 DI 10.1002/(SICI)1096-9071(199912)59:4<541::AID-JMV19>3.0.CO;2-S PG 6 WC Virology SC Virology GA 251JZ UT WOS:000083443700019 PM 10534739 ER PT J AU Jhee, KH Yoshimura, T Kurokawa, Y Esaki, N Soda, K AF Jhee, KH Yoshimura, T Kurokawa, Y Esaki, N Soda, K TI A stereochemical aspect of pyridoxal 5 '-phosphate dependent enzyme reactions and molecular evolution SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Review DE pyridoxal phosphate; aminotransferase; amino acid racemase; amino deoxychorismate lyase; stereochemistry; molecular evolution; stereobiochemistry ID AMINO-ACID AMINOTRANSFERASE; THERMOSTABLE ALANINE RACEMASE; BROAD SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; BACILLUS-STEAROTHERMOPHILUS; 3-DIMENSIONAL STRUCTURE; ASPARTATE-AMINOTRANSFERASE; SALMONELLA-TYPHIMURIUM; ACTIVE-SITE AB We have studied the stereospecificities of various pyridoxal 5'-phosphate (PLP) dependent enzymes for the hydrogen transfer between the C-4' of a bound coenzyme and the C-2 of a substrate in the transamination catalyzed by the enzymes. Stereospecificities reflect the structures of enzyme active-sites, in particular the geometrical relationship between the coenzyme-substrate Schiff base and the active site base participating in an alpha-hydrogen abstraction. The PLP enzymes studied so far catalyze only a si-face specific (pro-S) hydrogen transfer. This stereochemical finding suggests that the PLP enzymes have the same topological active-site structures, and that the PLP enzymes have evolved divergently from a common ancestral protein. However, we found that D-amino acid aminotransferase, branched chain L-amino acid aminotransferase, and 4-amino-4-deoxychorismate lyase, which have significant sequence homology with one another, catalyze a re-face specific (pro-R) hydrogen transfer. We also showed that PLP-dependent amino acid racemases, which have no sequence homology with any aminotransferases, catalyze a non-stereospecific hydrogen transfer: the hydrogen transfer occurs on both faces of the planar intermediate. Crystallographical studies have shown that the catalytic base is situated on the re-face of the C-4' of the bound coenzyme in D-amino acid aminotransferase and branched chain L-amino acid aminotransferase, whereas the catalytic base is situated on the si-face in other aminotransferases (such as L-aspartate aminotransferase) catalyzing the si-face hydrogen transfer. Thus, we have clarified the stereospecificities of PLP enzymes in relation with the primary structures and three-dimensional structures of the enzymes. The characteristic stereospecificities of these enzymes for the hydrogen transfer suggest the convergent evolution of PLP enzymes. C1 Kansai Univ, Fac Engn, Dept Biotechnol, Suita, Osaka 5648680, Japan. Kyoto Univ, Inst Chem Res, Lab Biofunct Mol, Kyoto 6110011, Japan. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Soda, K (reprint author), Kansai Univ, Fac Engn, Dept Biotechnol, Suita, Osaka 5648680, Japan. EM soda@ipcku.kansai-u.ac.jp NR 59 TC 5 Z9 5 U1 2 U2 6 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD DEC PY 1999 VL 9 IS 6 BP 695 EP 703 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 271CY UT WOS:000084577500001 ER PT J AU Collingwood, TN Urnov, FD Wolffe, AP AF Collingwood, TN Urnov, FD Wolffe, AP TI Nuclear receptors: coactivators, corepressors and chromatin remodeling in the control of transcription SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Review ID THYROID-HORMONE RECEPTOR; TUMOR VIRUS PROMOTER; RETINOIC ACID RECEPTOR; RNA-POLYMERASE-III; GLUCOCORTICOID RESPONSE ELEMENT; MAMMALIAN SWI/SNF COMPLEXES; NUCLEOSOME CORE PARTICLE; ACTIVATION FUNCTION AF-2; LINKING NUMBER CHANGE; LONG TERMINAL REPEAT AB A contemporary view of hormone action at the transcriptional level requires knowledge of the transcription factors including the hormone receptor that may bind to promoters or enhancers, together with the chromosomal context within which these regulatory proteins function. Nuclear receptors provide the best examples of transcriptional control through the targeted recruitment of large protein complexes that modify chromosomal components and reversibly stabilize or destabilize chromatin. Ligand-dependent recruitment of transcriptional coactivators destabilizes chromatin by mechanisms including histone acetylation and contacts with the basal transcriptional machinery. In contrast, the recruitment of corepressors in the absence of ligand or in the presence of hormone antagonists serves to stabilize chromatin by the targeting of histone deacetylases. Both activation and repression require the action of other chromatin remodeling engines of the switch 2/sucrose nonfermentable 2 (SWI2/SNF2) class. Here we summarize this information and integrate hormone action into a chromatin contest. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 173 TC 228 Z9 231 U1 1 U2 10 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 DEC PY 1999 VL 23 IS 3 BP 255 EP 275 DI 10.1677/jme.0.0230255 PG 21 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 271LW UT WOS:000084596300001 PM 10601972 ER PT J AU Singhania, NA Dyer, KD Zhang, JZ Deming, MS Bonville, CA Domachowske, JB Rosenberg, HF AF Singhania, NA Dyer, KD Zhang, JZ Deming, MS Bonville, CA Domachowske, JB Rosenberg, HF TI Rapid evolution of the ribonuclease A superfamily: Adaptive expansion of independent gene clusters in rats and mice SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE ribonucleases; host defense; eosinophils; evolution; rodents ID RESPIRATORY SYNCYTIAL VIRUS; EOSINOPHIL-DERIVED NEUROTOXIN; ANTIVIRAL ACTIVITY; CATIONIC PROTEIN; FAMILY; PURIFICATION; SEQUENCES AB The two eosinophil ribonucleases, eosinophil-derived neurotoxin (EDN/RNase 2) and eosinophil cationic protein (ECP/RNase 3), are among the most rapidly evolving coding sequences known among primates. The eight mouse genes identified as orthologs of EDN and ECP form a highly divergent, species-limited cluster. We present here the rat ribonuclease cluster, a group of eight distinct ribonuclease A superfamily genes that are more closely related to one another than they are to their murine counterparts. The existence of independent gene clusters suggests that numerous duplications and diversification events have occurred at these loci recently, sometime after the divergence of these two rodent species (similar to 10-15 million years ago). Nonsynonymous substitutions per site (d(N)) calculated for the 64 mouse/rat gene pairs indicate that these ribonucleases are incorporating nonsilent mutations at accelerated rates, and comparisons of nonsynonymous to synonymous substitution (d(N)/d(S)) suggest that diversity in the mouse ribonuclease cluster is promoted by positive (Darwinian) selection. Although the pressures promoting similar but clearly independent styles of rapid diversification among these primate and rodent genes remain uncertain, our recent findings regarding the function of human EDN suggest a role for these ribonucleases in antiviral host defense. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. SUNY Hlth Sci Ctr, Dept Pediat, Syracuse, NY 13210 USA. RP Rosenberg, HF (reprint author), NIAID, Host Def Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 35 Z9 38 U1 3 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD DEC PY 1999 VL 49 IS 6 BP 721 EP 728 DI 10.1007/PL00006594 PG 8 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 260WY UT WOS:000083977500003 PM 10594173 ER PT J AU Groweiss, A Newcomer, JJ O'Keefe, BR Blackman, A Boyd, MR AF Groweiss, A Newcomer, JJ O'Keefe, BR Blackman, A Boyd, MR TI Cytotoxic metabolites from an Australian collection of the sponge Jaspis species SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID AMINO-ACID DERIVATIVES; MARINE SPONGE; IN-VITRO; BENGAMIDES; STEREOCHEMISTRY; METAMORPHOSIS; TRITERPENES; STELLIFERA; INDUCERS AB Three new natural products, bengamide Y (1), bengamide Z (3), and bengazole Z (5), were isolated from the aqueous extract of an Australian collection of the sponge Jaspis sp. Their structures were solved by spectroanalytical methods and by comparison of their spectral data with known bengamides and bengazoles that were reported from the same genus. Bengamides Y (1) and Z (3) showed a striking differential cytotoxicity pattern against a panel of 10 human tumor cell lines, with closely related cell lines (e.g., SNB-19 and SNB-75) displaying significant differences in sensitivity. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diagno, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diagno, Bldg 1052,Room 102, Frederick, MD 21702 USA. NR 23 TC 45 Z9 45 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD DEC PY 1999 VL 62 IS 12 BP 1691 EP 1693 DI 10.1021/np9902688 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 270DE UT WOS:000084519500025 ER PT J AU Rall, JE AF Rall, JE TI Darwinism comes to America. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 1999 VL 187 IS 12 BP 761 EP 762 DI 10.1097/00005053-199912000-00011 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 271EE UT WOS:000084580600011 ER PT J AU Rall, JE AF Rall, JE TI Guns, germs, and steel: The fates of human societies. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 1999 VL 187 IS 12 BP 763 EP 765 DI 10.1097/00005053-199912000-00013 PG 3 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 271EE UT WOS:000084580600013 ER PT J AU Glazner, GW Boland, F Dresse, AE Brenneman, DE Gozes, I Mattson, MP AF Glazner, GW Boland, F Dresse, AE Brenneman, DE Gozes, I Mattson, MP TI Activity-dependent neurotrophic factor peptide (ADNF9) protects neurons against oxidative stress-induced death SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE activity-dependent neurotrophic factor; neurons; trophic factor withdrawal; reactive oxygen species; apoptosis ID AMYLOID BETA-PEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; SUPEROXIDE-DISMUTASE; HIPPOCAMPAL-NEURONS; CELL-DEATH; NITRIC-OXIDE; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; FREE-RADICALS; PEROXYNITRITE AB Activity-dependent neurotrophic factor (ADNF) and a 14-amino acid fragment of this peptide (sequence VLGGGSALLRSIPA) protect neurons from death associated with an array of toxic conditions, including amyloid beta-peptide, N-methyl-D-aspartate, tetrodotoxin, and the neurotoxic HIV envelope coat protein gp120. We report that an even smaller, nine-amino acid fragment (ADNFS) with the sequence SALLRSIPA potently protects cultured embryonic day 18 rat hippocampal neurons from oxidative injury and neuronal apoptosis induced by FeSO4 and trophic factor withdrawal. Among the characteristics of this protection are maintenance of mitochondrial function and a reduction in accumulation of intracellular reactive oxygen species. C1 Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. Univ Kentucky, Dept Anat & Neurobiol, Lexington, KY 40536 USA. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Liege, Inst Pathol, Liege, Belgium. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. RP Univ Kentucky, Sanders Brown Res Ctr Aging, 211 Sanders Brown Bldg, Lexington, KY 40536 USA. RI Mattson, Mark/F-6038-2012 FU NIA NIH HHS [AG605119]; NINDS NIH HHS [NS29001, NS35253] NR 48 TC 54 Z9 55 U1 0 U2 2 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1999 VL 73 IS 6 BP 2341 EP 2347 DI 10.1046/j.1471-4159.1999.0732341.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 256JX UT WOS:000083723100013 PM 10582592 ER PT J AU Jafarian-Tehrani, M Sternberg, EM AF Jafarian-Tehrani, M Sternberg, EM TI Animal models of neuroimmune interactions in inflammatory diseases SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; PITUITARY-ADRENAL AXIS; LONG-TERM POTENTIATION; TRANSGENIC EXPRESSION; AUTOIMMUNE-DISEASES; INDUCED ARTHRITIS; IMMUNOENDOCRINE COMMUNICATION; CEREBRAL OVEREXPRESSION; SUSCEPTIBILITY LOCI; ALZHEIMERS-DISEASE AB Animal models have been used successfully to study various aspects of neural-immune interactions. Although different approaches carry certain advantages and disadvantages, current high sensitivity screening and manipulation methods coupled with molecular and genetic approaches can be successfully used to tease out the neural pathways that regulate inflammatory disease and the effects of immune molecules, such as interleukins, on neuronal function and pathology. Newer methodologies that measure gene expression of thousands of genes will in the future add to the ability to evaluate complex systems interactions in whole animal models. This review addresses the advantages and disadvantages of some of these approaches in the context of application to neural-immune interactions. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Sect Neuroendocrine Immunol & Behav, CNE, NIH, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, CNE, NIH, Bldg 10,Rm 2D-46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. NR 78 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 1999 VL 100 IS 1-2 BP 13 EP 20 DI 10.1016/S0165-5728(99)00207-6 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 284XE UT WOS:000085357500003 PM 10695711 ER PT J AU Bielekova, B Muraro, PA Golestaneh, L Pascal, J McFarland, HF Martin, R AF Bielekova, B Muraro, PA Golestaneh, L Pascal, J McFarland, HF Martin, R TI Preferential expansion of autoreactive T lymphocytes from the memory T-cell pool by IL-7 SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; antigen-specific T cells; interleukin-7; primary proliferation ID MYELIN BASIC-PROTEIN; MULTIPLE-SCLEROSIS PATIENTS; PERIPHERAL-BLOOD; AUTOIMMUNE-DISEASES; HEALTHY-INDIVIDUALS; GROWTH-FACTOR; RECOGNITION; EXPRESSION; LINES; INTERLEUKIN-12 AB We have developed a new technique that allows us to quantify antigen-specific T cells, and to determine their functional phenotype and origin from naive versus memory populations. Using this methodology, we have characterized a total of 286 T-cell lines specific for myelin basic protein (MBP) and influenza hemagglutinin from 16 multiple sclerosis (MS) patients and nine healthy donors. Our data support the notion that MBP-specific T cells undergo in vivo activation in MS patients and indicate a presence of immune dysregulation that renders MS patients prone to develop autoimmunity. Our methodology offers a way to study antigen-specific T-cell characteristics as a surrogate marker in immunotherapy trials. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ G Annunzio, Dept Oncol & Neurosci, Sch Med, I-66013 Chieti, Italy. Multiple Peptide Syst, San Diego, CA 92121 USA. RP Martin, R (reprint author), NINDS, Cellular Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA. NR 37 TC 54 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC PY 1999 VL 100 IS 1-2 BP 115 EP 123 DI 10.1016/S0165-5728(99)00200-3 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 284XE UT WOS:000085357500014 PM 10695722 ER PT J AU Jia, M Li, MX Liu, XW Jiang, H Nelson, PG Guroff, G AF Jia, M Li, MX Liu, XW Jiang, H Nelson, PG Guroff, G TI Voltage-sensitive calcium currents are acutely increased by nerve growth factor in PC12 cells SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PROTEIN-KINASE-C; NEUROTROPHIC FACTORS; MESSENGER-RNA; K-252A; NEURONS; RELEASE; SURVIVAL; PHOSPHORYLATION; INHIBITOR; CULTURES AB Whole cell calcium currents were recorded from PC12 cells with the perforated patch technique. Currents were evoked by step depolarization from a holding potential of -90 mV. Nerve growth factor (NGF) increased calcium currents through L-type calcium channels by >75% within 3-5 min. This increase was inhibited by K-252a, by nifedipine, and by inhibition or down-regulation of kinase C. Brain-derived neurotrophic factor (BDNF) also increased calcium current, but to a smaller extent. Thus increases in calcium current can be linked to activation of either the high- or the low-affinity nerve growth factor receptor. Increases in presynaptic calcium uptake appear to be a crucial element in the short-term actions of the neurotrophins on neurotransmitter release leading to long-term potentiation. Also, the control of calcium uptake is likely to be an important factor in the long-term actions of the neurotrophins on neuronal survival and neuronal protection. The present data indicate that the PC12 cell may be a useful model for studying the effect of the neurotrophins on calcium uptake. C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Growth Factors Sect, NIH, Bethesda, MD 20892 USA. Henry Ford Hlth Sci Ctr, William T Gossett Neurol Labs, Detroit, MI 48202 USA. John D Dingell Vet Adm Med Ctr, Detroit, MI 48201 USA. RP Nelson, PG (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bldg 49,Rm 5A38,49 Convent Dr,MSC 4480, Bethesda, MD 20892 USA. NR 36 TC 25 Z9 25 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 DEC PY 1999 VL 82 IS 6 BP 2847 EP 2852 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 268NH UT WOS:000084422100001 PM 10601423 ER PT J AU Wiener, MC Richmond, BJ AF Wiener, MC Richmond, BJ TI Using response models to estimate channel capacity for neuronal classification of stationary visual stimuli using temporal coding SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TWO-DIMENSIONAL PATTERNS; SINGLE UNITS; 2-DIMENSIONAL PATTERNS; CORTICAL-NEURONS; STRIATE CORTEX; SPIKE TRAINS; INFORMATION; MONKEY; CAT; VARIABILITY AB Both spike count and temporal modulation are known to carry information about which of a set of stimuli elicited a response; but how much information temporal modulation adds remains a subject of debate. This question usually is addressed by examining the results of a particular experiment that depend on the specific stimuli used. Developing a response model allows us to ask how much more information is carried by the best use of response strength and temporal modulation together (that is, the channel capacity using a code incorporating both) than by the best use of spike count alone (the channel capacity using the spike count code). This replaces dependence on a particular data set with dependence on the accuracy of the model. The model is constructed by finding statistical. rules obeyed by all the observed responses and assuming that responses to stimuli not presented in our experiments obey the same rules. We assume that all responses within the observed dynamic range, even if not elicited by a stimulus in our experiment, could be elicited by some stimulus. The model used here is based on principal component analysis and includes both response strength and a coarse (+/-10 ms) representation of temporal modulation. Temporal modulation at finer time scales carries little information about the identity of stationary visual stimuli (although it may carry information about stimulus motion or change), and we present evidence that, given its variability, it should not be expected to do so. The model makes use of a linear relation between the logarithms of mean and variance of responses, similar to the widely seen relation between mean and variance of spike count. Responses are modeled using truncated Gaussian distributions. The amount of stimulus-related information carried by spike count in our data are 0.35 and 0.31 bits in primary visual and inferior temporal cortices, respectively, rising to 0.52 and 0.37 bits for the two-principal-component code. The response model estimates that the channel capacity is 1.1 and 1.4 bits, respectively, using the spike count only, rising to 2.0 and 2.2 bits using two principal components. Thus using this representation of temporal modulation is nearly equivalent to adding a second independent cell using the spike count code. This is much more than estimated using transmitted information but far less than would be expected if all degrees of freedom provided by the individual spike times carried independent information. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Richmond, BJ (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B-80, Bethesda, MD 20892 USA. NR 51 TC 27 Z9 27 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 DEC PY 1999 VL 82 IS 6 BP 2861 EP 2875 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 268NH UT WOS:000084422100003 PM 10601425 ER PT J AU Litvan, I McKee, A AF Litvan, I McKee, A TI Clinicopathologic case report SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID LEWY BODIES; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; PICKS-DISEASE; DIAGNOSIS; DEMENTIA; BODY; UBIQUITIN; CRITERIA C1 NINCDS, Neuropharmacol Unit, Def & Vet Head Injury Program, Henry M Jackson Fdn,NIH, Bethesda, MD 20892 USA. Vet Adm Med Ctr, GRECC, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. RP Litvan, I (reprint author), NINCDS, Neuropharmacol Unit, Def & Vet Head Injury Program, Henry M Jackson Fdn,NIH, Fed Bldg,Room 714,7550 Wisconsin Ave, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445 NR 30 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 1999 VL 11 IS 1 BP 107 EP 112 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 162PC UT WOS:000078354800018 PM 9990566 ER PT J AU Erickson, CA Desimone, R AF Erickson, CA Desimone, R TI Responses of macaque perirhinal neurons during and after visual stimulus association learning SO JOURNAL OF NEUROSCIENCE LA English DT Article DE single unit; electrophysiology; Macaca mulatta; perirhinal cortex; inferior temporal cortex; paired associates; association; learning; memory; primates; medial temporal lobe ID INFERIOR TEMPORAL CORTEX; LONG-TERM-MEMORY; INFEROTEMPORAL CORTEX; PARAHIPPOCAMPAL CORTICES; HIPPOCAMPAL-FORMATION; RHESUS-MONKEYS; SINGLE UNITS; RECOGNITION; LESIONS; IMPAIRMENT AB Recent lesion studies have implicated the perirhinal cortex in learning that two objects are associated, i.e., visual association learning. In this experiment we tested whether neuronal responses to associated stimuli in perirhinal cortex are altered over the course of learning. Neurons were recorded from monkeys during performance of a visual discrimination task in which a predictor stimulus was followed, after a delay, by a GO or NO-GO choice stimulus. Association learning had two major influences on neuronal responses. First, responses to frequently paired predictor-choice stimuli were more similar to one another than was the case with infrequently paired stimuli. Second, the magnitude of activity during the delay was correlated with the magnitude of responses to both the predictor and choice stimuli. Both of these learning effects were found only for stimulus pairs that had been associated on at least 2 d of training. Early in training, the delay activity was correlated only with the response to the predictor stimuli. Thus, with long-term training, perirhinal neurons tend to link the representations of temporally associated stimuli. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Desimone, R (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. NR 34 TC 147 Z9 148 U1 0 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 DEC 1 PY 1999 VL 19 IS 23 BP 10404 EP 10416 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 258YN UT WOS:000083867400023 PM 10575038 ER PT J AU Mankowski, JL Queen, SE Kirstein, LM Spelman, JP Laterra, J Simpson, IA Adams, RJ Clements, JE Zink, MC AF Mankowski, JL Queen, SE Kirstein, LM Spelman, JP Laterra, J Simpson, IA Adams, RJ Clements, JE Zink, MC TI Alterations in blood-brain barrier glucose transport in SIV-infected macaques SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE blood-brain barrier; GLUT1; endothelial cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTION; NEOCORTICAL DAMAGE; AIDS PATIENTS; RAT-BRAIN; EXPRESSION; DEMENTIA; LOCALIZATION; ENCEPHALITIS; PATHOLOGY AB The neurological manifestations of HIV infection may be in part due to alterations in the blood-brain barrier. These may be caused hy structural changes in the barrier or may consist of subtle metabolic or biochemical disturbances in barrier function. In the CNS, the family of glucose transporter proteins plays a key role in controlling movement of glucose across cell membranes. The 55 kDa isoform of glucose transporter 1 (GLUT1) regulates import of glucose from blood to brain across the endothelial cells of the blood-brain barrier (BBB), whereas the 45 kDa form of GLUT1 predominantly regulates nonvascular glial glucose uptake. In this study, expression of 55 and 45 kDa forms of GLUT1 in different regions of the brain from 18 SIV-infected macaques was measured by quantitative immunoblot and then compared with the severity of SIV encephalitis to determine whether neurologic disease is related to altered glucose metabolism at the BBB and in brain parenchyma. An inverse relationship was found between severity of SIV encephalitis and expression of the endothelial 55 kDa isoform of GLUT1 at the BBB in cortical grey matter, caudate nucleus, and cerebellum A similar relationship also was found for the glial 45 kDa GLUT1 isoform in cortical grey matter. In addition, a significant increase in 55 kDa GLUT1 expression was found in caudate nucleus during the early stages of infection. In the brains of macaques with moderate to severe encephalitis, 55 kDa GLUT1 expression had declined to pre-infection levels. These GLUT1 alterations at the BBB and in glial cells may reflect severe disturbances in the CNS microenvironment that contribute to CNS dysfunction. C1 Johns Hopkins Univ, Sch Med, Div Comparat Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Kennedy Krieger Inst, Baltimore, MD 21205 USA. NIDDKD, Expt Diabet Metab & Nutr Sect, Bethesda, MD 20892 USA. RP Zink, MC (reprint author), Johns Hopkins Univ, Sch Med, Retrovirus Lab, Traylor G-60,720 Rutland Ave, Baltimore, MD 21205 USA. FU NCRR NIH HHS [RR00116]; NINDS NIH HHS [NS35751, NS38008] NR 28 TC 25 Z9 26 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD DEC PY 1999 VL 5 IS 6 BP 695 EP 702 DI 10.3109/13550289909021298 PG 8 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 268ZN UT WOS:000084451300016 PM 10602410 ER PT J AU Buxton, DB AF Buxton, DB TI Glucose permeability in nonprimate erythrocytes SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 NHLBI, Bethesda, MD 20892 USA. RP Buxton, DB (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. OI Buxton, Denis/0000-0003-3077-6435 NR 5 TC 3 Z9 3 U1 0 U2 1 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 DEC PY 1999 VL 40 IS 12 BP 2125 EP 2126 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 269GP UT WOS:000084468600029 PM 10616896 ER PT J AU Shrader, JA AF Shrader, JA TI Nonsurgical management of the foot and ankle affected by rheumatoid arthritis SO JOURNAL OF ORTHOPAEDIC & SPORTS PHYSICAL THERAPY LA English DT Editorial Material DE arthritis education; exercise; footwear; gait; orthoses; rehabilitation; shoe modifications ID PATIENT EDUCATION; PAIN; DISABILITY; DEFORMITY; FOREFOOT; HINDFOOT; GAIT; DISORDERS; ORTHOSES; STRENGTH AB Rheumatoid arthritis frequently affects root and ankle function, leading to pain, difficulty with ambulation, and disability The purpose of this article is to describe common root and ankle deformities associated with rheumatoid arthritis and present state-of-the-art nonsurgical management strategies. Physical impairments thought to be commonly associated with limitations or function and practical interventions for alleviating those impairments or reducing the impact of the impairment on ambulation are identified. Examples of rehabilitation interventions discussed include prescription footwear, custom and premolded root orthoses, hindfoot orthoses, ankle-foot orthoses, shoe modifications, therapeutic exercises, and patient education. Early and aggressive attempts at prevention, delay or correction of foot and ankle pathomechanics related to rheumatoid arthritis may play a key role in helping patients maintain an active ambulatory lifestyle. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Phys Therapy Sect, Bethesda, MD 20892 USA. RP Shrader, JA (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Rehabil Med, Phys Therapy Sect, Bldg 10,Room 6S235,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. NR 82 TC 13 Z9 14 U1 0 U2 5 PU J O S P T, ALLIANCE GROUP COMMUNICATIONS PI LAWRENCE PA 810 EAST 10TH ST, PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0190-6011 J9 J ORTHOP SPORT PHYS JI J. Orthop. Sports Phys. Ther. PD DEC PY 1999 VL 29 IS 12 BP 703 EP 717 PG 15 WC Orthopedics; Rehabilitation; Sport Sciences SC Orthopedics; Rehabilitation; Sport Sciences GA 265VH UT WOS:000084266200003 PM 10612068 ER PT J AU Favre, A Briano, S Mazzola, C Brizzolara, A Torre, M Cilli, M Sanguineti, M Martucciello, G AF Favre, A Briano, S Mazzola, C Brizzolara, A Torre, M Cilli, M Sanguineti, M Martucciello, G TI Anorectal malformations associated with enteric dysganglionosis in Danforth's short tail (Sd) mice SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Sd mice; Danforth's short tail mice; aganglionosis; Hirschsprung's disease ID MEGACOLON; MUTATION AB Background: The spontaneous mutant Danforth's short tail (Sd) mouse has been studied over the last 60 years from the morphological, embryological, and genetic point of view. The Sd mutation affects a gene essential to notochordal development,and the Sd mouse phenotype represents an analogue of human caudal regression syndrome. The Sd/Sd mouse presents different types of anorectal malformations (ARM) and was suggested as a simple and cheap model of investigation of ARM morphology and embryology. In the current study, the Sd mouse enteric nervous system (ENS) was thoroughly investigated with specific immunohistochemical markers. Methods: Macroscopic analysis,normal histology, and immunohistochemical techniques for detecting neurofilaments (NF) and NOS1 were used to study ENS of 138 Sd mice and 25 controls. Results: The surprising results of this study showed that Sd mutation is associated with different degrees of hypoganglionosis and aganglionosis. In 41% of Sd/SD-affected mice, the rectal pouch was aganglionic and in the remaining 58% was severely hypoganglionic. In addition, 4.1% of heterozygous mice presented a distal aganglionosis and 8.3% hypoganglionosis. Conclusions: These results suggest that Sd mutation independently affects distinct cell lines during early organogenesis, as notochord cells, ventral hingut endoderm, and neuroblasts migrating from neural crest cells. Comparing the Sd murine model with human pathology, this study confirms that the association between ARM and intestinal dysganglionosis is not rare and underlines the importance of detecting in every ARM patient the innervation abnormalities of rectal pouch and fistulas. J Pediatr Surg 34:1818-1821. Copyright (C) 1999 by W.B. Saunders Company. C1 Univ Genoa, G Gaslini Inst, Dept Pediat Surg, I-16147 Genoa, Italy. Univ Genoa, G Gaslini Inst, Chair Pediat Surg, I-16147 Genoa, Italy. Adv Biotechnol Ctr, Natl Canc Inst, Genoa, Italy. RP Martucciello, G (reprint author), Univ Genoa, G Gaslini Inst, Dept Pediat Surg, Largo Gaslini 5, I-16147 Genoa, Italy. NR 14 TC 8 Z9 8 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD DEC PY 1999 VL 34 IS 12 BP 1818 EP 1821 DI 10.1016/S0022-3468(99)90320-2 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 266FA UT WOS:000084288900015 PM 10626862 ER PT J AU Wood, LV AF Wood, LV TI Highly active antiretroviral therapy: Progress and pitfalls SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHILDREN; DISEASE C1 NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Wood, LV (reprint author), NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD DEC PY 1999 VL 135 IS 6 BP 655 EP 657 DI 10.1016/S0022-3476(99)70078-8 PG 3 WC Pediatrics SC Pediatrics GA 265UG UT WOS:000084263700002 PM 10586162 ER PT J AU McCrae, RR AF McCrae, RR TI Mainstream personality psychology and the study of religion SO JOURNAL OF PERSONALITY LA English DT Article ID TRAITS AB In this commentary, I make some general observations about the study of personality and religion and some specific comments about individual articles from the perspective of contemporary personality psychology. Most of the authors represented here treat religion as a domain of human experience and behavior that can be understood in terms of familiar personality principles and processes. I therefore urge greater attention to the Five-Factor Model of personality traits, especially Openness to Experience, in understanding religious phenomena. Mainstream psychologists, including longitudinal researchers, behavior geneticists, and epidemiologists, should consider the inclusion of religious variables in their research designs. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 28 TC 17 Z9 17 U1 0 U2 4 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 DEC PY 1999 VL 67 IS 6 BP 1209 EP 1218 DI 10.1111/1467-6494.00088 PG 10 WC Psychology, Social SC Psychology GA 268DP UT WOS:000084399300013 PM 10637992 ER PT J AU Hamer, DH Greenberg, BD Sabol, SZ Murphy, DL AF Hamer, DH Greenberg, BD Sabol, SZ Murphy, DL TI Role of the serotonin transporter gene in temperament and character SO JOURNAL OF PERSONALITY DISORDERS LA English DT Article ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; UNIFIED BIOSOCIAL THEORY; ANXIETY-RELATED TRAITS; PROMOTER POLYMORPHISM; REGULATORY REGION; EUROPEAN-AMERICAN; AFRICAN-AMERICAN; HARM AVOIDANCE; MESSENGER-RNA; ASSOCIATION AB The biosocial model postulates that personality is comprised of two broad domains: temperament, which is largely due to inherited variations in specific monoamine neurotransmitter systems; and character, which arises from socioculturally learned differences in values, goals, and self-concepts and is the strongest predictor of personality disorders, The model also proposes that serotonin modulates the temperament trait of harm avoidance, We analyzed the association of temperament and character traits with the 5-HTTLPR, an inherited variation that modulates serotonin transporter gene expression, in 634 volunteer subjects. Contrary to theory, the 5-HTTLPR was most strongly associated with the character traits of cooperativeness and self-directedness, Associations with the temperament traits of reward dependence and harm avoidance were weaker and could be attributable largely to cross-correlations with the character traits and demographic variables. Psychometric analysis indicated that the serotonin transporter influences two broad areas of personality, negative affect and social disaffiliation, that are consistent across inventories but are more concisely described by the 5-factor model of personality than by the biosocial model, These results suggest that there is no fundamental mechanistic distinction between character and temperament in regard to the serotonin transporter gene, and that a single neurotransmitter can influence multiple personality traits C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Hamer, DH (reprint author), NCI, Biochem Lab, NIH, Bld 37,Rm 4A13,37 Convent Dr, Bethesda, MD 20892 USA. NR 37 TC 57 Z9 58 U1 0 U2 7 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0885-579X J9 J PERS DISORD JI J. Pers. Disord. PD WIN PY 1999 VL 13 IS 4 BP 312 EP 327 PG 16 WC Psychiatry SC Psychiatry GA 266WX UT WOS:000084324200002 PM 10633313 ER PT J AU Li, Q Wichems, C Heils, A Van de Kar, LD Lesch, KP Murphy, DL AF Li, Q Wichems, C Heils, A Van de Kar, LD Lesch, KP Murphy, DL TI Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT1A binding sites in 5-HT transporter knockout mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PITUITARY-ADRENOCORTICAL RESPONSE; GLUCOCORTICOID RECEPTOR FUNCTION; RAT-BRAIN; 8-OH-DPAT-INDUCED HYPOTHERMIA; SEROTONIN TRANSPORTER; G(O) PROTEINS; ANTIDEPRESSANT; FLUOXETINE; PAROXETINE; AGONIST AB The aim of the present study was to determine whether alterations in 5-hydroxytryptamine (5-HT)(1A) receptors would be found in knockout mice lacking the serotonin transporter (5-HTT). Hypothermic and neuroendocrine responses to the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) were used to examine the function of 5-HT1A receptors. Initial studies evaluated the dose-response and time course of 8-OH-DPAT-induced hypothermia and hormone secretion in normal CD-1 mice (the background strain of the 5-HTT knockout mice). 8-OH-DPAT dose-dependently produced hypothermic responses that peaked at 20 min postinjection. 8-OH-DPAT-induced hypothermia was blocked by the 5-HT1A antagonist WAY-100635.8-OH-DPAT dose-dependently increased the concentrations of plasma oxytocin, corticotropin, and corticosterone. In the 5-HTT knockout (-/-) mice, the hypothermic response to 8-OH-DPAT (0.1 mg/kg s.c.) was completely abolished. Furthermore, 5-HTT-/- mice had significantly attenuated plasma oxytocin and corticosterone responses to 8-OH-DPAT. No significant changes in the hypothermic or hormonal responses to 8-OH-DPAT were observed in heterozygous (5-HTT+/-) mice. [H-3]8-OH-DPAT- and [I-125]MPPI [4-(2'-methoxyphenyl)-1-[2'-[N-(2 "-pyridinyl)-iodobenzamido]ethyl]piperazine]-binding sites in the hypothalamus and [I-125]MPPI-binding sites in the dorsal raphe were significantly decreased in 5-HTT-/- mice. The results indicate that lack of the 5-HTT is associated with a functional desensitization of 5-HT1A receptor responses to 8-OH-DPAT, which may be a consequence, at least in part, of the decrease in density of 5-HT1A receptors in the hypothalamus and dorsal raphe of 5-HTT-/- mice. C1 NIMH, Clin Sci Lab, NIH, Ctr Clin, Bethesda, MD 20892 USA. Loyola Univ, Stritch Sch Med, Dept Pharmacol, Maywood, IL 60153 USA. Univ Wurzburg, Dept Psychiat, D-8700 Wurzburg, Germany. RP Li, Q (reprint author), NIMH, Clin Sci Lab, NIH, Ctr Clin, Room 3D41,10 Ctr Dr,MSC-1264, Bethesda, MD 20892 USA. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 41 TC 142 Z9 147 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1999 VL 291 IS 3 BP 999 EP 1007 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 256ZX UT WOS:000083757300011 PM 10565817 ER PT J AU Zhou, YY Song, LS Lakatta, EG Xiao, RP Cheng, HP AF Zhou, YY Song, LS Lakatta, EG Xiao, RP Cheng, HP TI Constitutive beta(2)-adrenergic signalling enhances sarcoplasmic reticulum Ca2+ cycling to augment contraction in mouse heart SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID BETA-ADRENERGIC STIMULATION; CARDIAC RYANODINE RECEPTORS; RAT VENTRICULAR MYOCYTES; TRANSGENIC MICE; CALCIUM-RELEASE; PHOSPHOLAMBAN PHOSPHORYLATION; LOCAL-CONTROL; CELLS; CHANNEL; PROTEIN AB 1. Transgenic overexpression of the beta(2)-adrenergic receptor (beta(2)AR) in mouse heart augments baseline cardiac function in a ligand-independent manner, due to the presence of spontaneously active beta(2)AR (beta(2)AR*). This study aims to elucidate the mechanism of beta(2)AR*-mediated modulation of cardiac excitation-contraction (EC) coupling. 2. Confocal imaging was used to analyse Ca2+ sparks and spatially resolve Ca2+ transients in single ventricular myocytes from transgenic (TG4) and non-transgenic (NTG) littermates. Whole-cell voltage- and current-clamp techniques were used to record L-type Ca2+ currents (I-Ca) and action potentials, respectively. 3. In the absence of any beta(2)AR ligand, TG4 myocytes had greater contraction amplitudes, larger Ca2+ transients and faster relaxation times than did NTG cells. 4. The action potentials of TG4 and NTG myocytes were similar, except for a prolonged end-stage repolarization in TG4 cells; the I-Ca density and kinetics were nearly identical. The relationship between peak Ca2+ and contraction, which reflects myofilament Ca2+ sensitivity, was similar. 5. In TG4 cells, the frequency of Ca2+ sparks (spontaneous or evoked at -40 mV) was 2-7 times greater, despite the absence of change in the resting Ca2+, sarcoplasmic reticulum (SR) Ca2+ content, and I-Ca. Individual sparks were brighter, broader and lasted longer, leading to a 2.3-fold greater signal mass. Thus, changes in both spark frequency and size underlie the greater Ca2+ transient in TG4 cells. 6. The inverse agonist ICI 118,551 (ICI, 5 x 10(-7) M), which blocks spontaneous beta(2)AR activation, reversed the aforementioned beta(2)AR* effects on cardiac EC coupling without affecting the sarcolemmal I-Ca. However, ICI failed to detect significant constitutive beta(2)AR activity in NTG cells. 7. We conclude that beta(2)AR*-mediated signalling enhances SR release channel activity and Ca2+-induced Ca2+ release in TG4 cardiac myocytes, and that beta(2)AR* enhances EC coupling by reinforcing SR Ca2+ cycling (release and reuptake), but bypassing the sarcolemmal I-Ca. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Cheng, HP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Song, Long-Sheng/D-5899-2012 NR 56 TC 52 Z9 54 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 1999 VL 521 IS 2 BP 351 EP 363 DI 10.1111/j.1469-7793.1999.00351.x PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 268PD UT WOS:000084424000004 PM 10581307 ER PT J AU Morton, SL Leighfield, TA Haynes, BL Petitpain, DL Busman, MA Moeller, PDR Bean, L Mcgowan, J Hurst, JW Van Dolah, FM AF Morton, SL Leighfield, TA Haynes, BL Petitpain, DL Busman, MA Moeller, PDR Bean, L Mcgowan, J Hurst, JW Van Dolah, FM TI Evidence of diarrhetic shellfish poisoning along the coast of Maine SO JOURNAL OF SHELLFISH RESEARCH LA English DT Article ID OKADAIC ACID; TOXIN AB Following the occurrence of several unexplained incidents of shellfish-related gastroenteritis, field studies were conducted to determine if diarrhetic shellfish poisoning (DSP) toxins are present in Maine coastal waters. A protein phosphatase inhibition assay for DSP toxins revealed the presence of low levels of okadaic acid-like activity in blue mussels (Mytilus edulis) at sampling sites in the Frenchman Bay-Eastern Bay region. All other sires along the Maine coast were negative. Phytoplankton populations from this area were dominated by Dinophysis norvegica, a known toxic species. Two additional known toxic species of Dinophysis were also found: Dinophysis acuminata and D. rotunda. However, all plankton samples were negative for okadaic acid-like activity. Examination of the epiphytic communities from areas where mussels showed okadaic acid-like activity revealed the presence of the toxic dinoflagellate Prorocentrum lima in association with the brown alga, Ectocarpus sp. Epiphytic samples rich in P. lima were active in the phosphatase inhibition assay; Subsequent analysis of these samples using LC-MS/MS identified the presence of dinophysis toxin-l (DTX-1). Empty P. lima thecae identified in the digestive tract of mussels from these areas indicate that P. lima is consumed by mussels. This is the first confirmation of P. lima in northern United States coastal waters and identifies DSP as a potential public health issue. C1 Natl Ocean Serv, Marine Biotoxins Program, Ctr Coastal Environm Hlth & Biomol Res, NOAA, Charleston, SC 29412 USA. Maine Dept Marine Resources, W Boothbay Harbor, ME 04575 USA. NIEHS, Marine & Freshwater Biomed Sci Ctr, Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Morton, SL (reprint author), Natl Ocean Serv, Marine Biotoxins Program, Ctr Coastal Environm Hlth & Biomol Res, NOAA, Charleston, SC 29412 USA. NR 17 TC 18 Z9 18 U1 1 U2 5 PU NATL SHELLFISHERIES ASSOC PI SOUTHAMPTON PA C/O DR. SANDRA E. SHUMWAY, NATURAL SCIENCE DIVISION, SOUTHAMPTON COLLEGE, SOUTHAMPTON, NY 11968 USA SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD DEC PY 1999 VL 18 IS 2 BP 681 EP 686 PG 6 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 276YM UT WOS:000084906000043 ER PT J AU Subramaniam, S Henderson, R AF Subramaniam, S Henderson, R TI Electron crystallography of bacteriorhodopsin with millisecond time resolution SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Electron Crystallography CY DEC, 1998 CL GRANLIBAKKEN, CALIFORNIA SP M E Muller Fdn DE electron diffraction; photocycle; high-resolution electron microscopy; intermediates; membrane protein; two-dimensional crystals ID STRUCTURAL-CHANGES; PHOTOCYCLE; CRYOMICROSCOPY; MEMBRANE; PUMP AB The goal of time-resolved crystallographic experiments is to capture dynamic "snapshots" of molecules at different stages of a reaction pathway In recent work, we have developed approaches to determine determined light-induced conformational changes in the proton pump bacteriorhodopsin by electron crystallographic analysis of two-dimensional protein crystals. For this purpose, crystals of bacteriorhodopsin were deposited on an electron microscopic grid and were plunge-frozen in liquid ethane at a variety of times after illumination. Electron diffraction patterns were recorded either from unilluminated crystals or from crystals frozen as early as 1 ms after illumination and used to construct projection difference Fourier maps at 3.5-Angstrom resolution to define light-driven changes in protein conformation. As demonstrated here, the data are of a sufficiently high quality that structure factors obtained from a single electron diffraction pattern of a plunge-frozen bacteriorhodopsin crystal are adequate to obtain an interpretable difference Fourier map. These difference maps report on the nature and extent of light-induced conformational changes in the photocycle and have provided incisive tools for understanding the molecular mechanism of proton transport by bacteriorhodopsin. C1 NCI, Biochem Lab, Bethesda, MD 20892 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RP Subramaniam, S (reprint author), NCI, Biochem Lab, Bethesda, MD 20892 USA. NR 19 TC 29 Z9 30 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD DEC 1 PY 1999 VL 128 IS 1 BP 19 EP 25 DI 10.1006/jsbi.1999.4178 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 268ZQ UT WOS:000084451600004 PM 10600554 ER PT J AU Conway, JF Steven, AC AF Conway, JF Steven, AC TI Methods for reconstructing density maps of "single" particles from cryoelectron micrographs to subnanometer resolution SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Electron Crystallography CY DEC, 1998 CL GRANLIBAKKEN, CALIFORNIA SP M E Muller Fdn DE high-resolution cryo-electron microscopy; image processing; contrast transfer function; macromolecular complexes ID ESCHERICHIA-COLI RIBOSOME; FROZEN-HYDRATED SPECIMENS; VIRUS CAPSID PROTEIN; ELECTRON-MICROSCOPY; 3-DIMENSIONAL RECONSTRUCTION; CONTRAST TRANSFER; ACETYLCHOLINE-RECEPTOR; SPHERICAL VIRUSES; C-TERMINUS; CRYSTALLOGRAPHY AB Recently the resolution attainable in density maps calculated from cryo-electron micrographs of freestanding virus capsids has advanced to resolutions below 1 nm. This represents a significant milestone in that resolutions of this order potentially allow direct visualization of individual elements of protein secondary structure (i.e., alpha-helices), in addition to the shapes and connectivity of subdomains. We describe here a computational strategy for structural analyses at this level of detail: its principal innovation is a procedure for correcting the contrast transfer function of the electron microscope. Also important is the practice of combining data from pairs of differently defocused micrographs to improve the signal-to-noise ratio of the images, thereby allowing more precise determinations of the particles' orientations and origins and contributing to higher resolution reconstructions. These procedures proved instrumental in our analysis of the capsid of hepatitis B virus at 9-Angstrom resolution (Conway ef al, 1997, Nature 386, 91-94). Finally, we discuss the prospects for achieving comparable resolutions for isolated macromolecular complexes with lower symmetry or no symmetry and for further extension of the resolution. C1 NIH, Struct Biol Lab, Natl Inst Arthritis Musculoskeletal & Skin Dis, Bethesda, MD 20892 USA. RP Conway, JF (reprint author), NIH, Struct Biol Lab, Natl Inst Arthritis Musculoskeletal & Skin Dis, Bldg 6,Room B2-34,6 Ctr Dr,MSC-2717,9000 Rockvill, Bethesda, MD 20892 USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 42 TC 134 Z9 134 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD DEC 1 PY 1999 VL 128 IS 1 BP 106 EP 118 DI 10.1006/jsbi.1999.4168 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 268ZQ UT WOS:000084451600015 PM 10600565 ER PT J AU Asbahr, FR Ramos, RT Negrao, AB Gentil, V AF Asbahr, FR Ramos, RT Negrao, AB Gentil, V TI Case series: Increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE Sydenham chorea; obsessive-compulsive symptoms; obsessive-compulsive disorder; group A beta-hemolytic streptococcal infections; pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections ID AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; STREPTOCOCCAL INFECTIONS; RHEUMATIC-FEVER AB The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions. Four children with 2 distinct SC episodes were evaluated to assess the course of OCS. All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder [OCD]), but not in their first episodes (2 developed OCS and met criteria for OCD). These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS. C1 Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Sao Paulo, Sch Med, Lab Med Invest, Sao Paulo, Brazil. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Asbahr, FR (reprint author), FMUSP, Dept Psiquiatria, Rua Dr Ovidio Pires Campos S-N,Caixa Postal 8091, BR-05403010 Sao Paulo, Brazil. RI Ramos, Renato/G-1566-2013; Negrao, Andre Brooking/C-9526-2014; Asbahr, Fernando/G-8469-2015 OI Negrao, Andre Brooking/0000-0002-8133-6723; NR 12 TC 21 Z9 21 U1 1 U2 2 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 DEC PY 1999 VL 38 IS 12 BP 1522 EP 1525 DI 10.1097/00004583-199912000-00013 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 260UF UT WOS:000083971300013 PM 10596252 ER PT J AU Usiskin, SI Nicolson, R Krasnewich, DM Yan, WL Lenane, M Wudarsky, M Hamburger, SD Rapoport, JL AF Usiskin, SI Nicolson, R Krasnewich, DM Yan, WL Lenane, M Wudarsky, M Hamburger, SD Rapoport, JL TI Velocardiofacial syndrome in childhood-onset schizophrenia SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE schizophrenia; genetics; 22q11 deletions; velocardioiacial syndrome; age of onset ID CARDIO-FACIAL SYNDROME; SEX-CHROMOSOME ANOMALIES; CORPUS-CALLOSUM; 22Q11; DISORDERS; TRANSLOCATION; DELETIONS; LANGUAGE; SPECTRUM; DISEASE AB Objectives: Deletion of chromosome 22q11 (velocardiofacial syndrome) is associated with early neurodevelopmental abnormalities and with schizophrenia in adults. The rate of 22q11 deletions was examined in a series of patients with childhood-onset schizophrenia (COS), in whom early premorbid developmental and cognitive impairments are more pronounced than in adult-onset cases. Method: Through extensive recruiting and screening, a cohort of 47 patients was enrolled in a comprehensive study of very-early-onset schizophrenia. All were tested with fluorescence in situ hybridization for deletions on chromosome 22q11. Results: Three (6.4%) of 47 patients were found to have a 22q11 deletion. All 3 COS patients with 22q11 deletions had premorbid impairments of language, motor, and social development, although their physical characteristics varied. Brain magnetic resonance imaging revealed increased midbody corpus callosum area and ventricular volume in relation both to healthy controls and to other COS patients. Conclusions: The rate of 22q11 deletions in COS is higher than in the general population (0.025%, p < .001) and may be higher than reported for adult-onset schizophrenia (2.0%, p = .09). These results suggest that 22q11 deletions may be associated with an earlier age of onset of schizophrenia, possibly mediated by a more salient neurodevelopmental disruption. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD USA. RP Nicolson, R (reprint author), Bldg 10,Room 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 49 TC 98 Z9 102 U1 8 U2 10 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 DEC PY 1999 VL 38 IS 12 BP 1536 EP 1543 DI 10.1097/00004583-199912000-00015 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 260UF UT WOS:000083971300015 PM 10596254 ER PT J AU Jensen, PS Rubio-Stipec, M Canino, G Bird, HR Dulcan, MK Schwab-Stone, ME Lahey, BB AF Jensen, PS Rubio-Stipec, M Canino, G Bird, HR Dulcan, MK Schwab-Stone, ME Lahey, BB TI Parent and child contributions to diagnosis of mental disorder: Are both informants always necessary? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE informants; child psychopathology; Diagnostic Interview Schedule for Children ID PSYCHOPATHOLOGY RATING-SCALES; PSYCHIATRIC-SYMPTOMS; INTERRATER AGREEMENT; DEPRESSIVE SYMPTOMS; CRITERION VALIDITY; INTERVIEW SCHEDULE; DISC-2.3; RISK AB Objective: To examine the unique cases contributed by parent and child informants to diagnostic classification, with the goal of identifying those diagnoses for which either or both informants are needed,Method: The authors examined survey data from the Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) Study. a 4-community epidemiology survey of 9- to 17-year-old children and their parents, Parent-child dyads (1,285 pairs) were independently interviewed by lay persons with the Diagnostic Interview Schedule for Children; a subset of these pairs (n = 247) were also interviewed by clinicians. Agreement between parents and children was examined with respect to levels of impairment, need for/use of services, and clinicians' diagnoses. Results: Parents and children rarely agreed on the presence of diagnostic conditions, regardless of diagnostic type. Nonetheless, most child-only- and parent-only-identified diagnoses were similarly related to impairment and clinical validation, with 2 exceptions: child-only-identified attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD), Conclusions: Overall findings suggest that most "discrepant' diagnoses (those reported by one but not the other informant) reflect meaningful clinical conditions. In some instances, however, diagnoses reported by one but not the other informant should be treated with caution, as they may not reflect the full diagnostic condition (e.g., possibly child-only-identified ADHD or ODD). Further research is needed to determine the salience of child-only- or parent-only-reported cases. C1 NIMH, Bethesda, MD 20892 USA. Univ Puerto Rico, Behav Sci Res Inst, San Juan, PR 00936 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Childrens Mem Hosp, Dept Child Psychiat, Chicago, IL 60614 USA. Northwestern Univ, Chicago, IL 60611 USA. Yale Univ, Ctr Child Study, Sch Med, New Haven, CT 06520 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. RP Rubio-Stipec, M (reprint author), Univ Puerto Rico, Behav Sci Res Inst, Med Sci Campus,POB 365067, San Juan, PR 00936 USA. OI Jensen, Peter/0000-0003-2387-0650 FU NIMH NIH HHS [UO1MH46717, UO1 MH46718, UO1 MH46725] NR 27 TC 353 Z9 357 U1 6 U2 17 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 DEC PY 1999 VL 38 IS 12 BP 1569 EP 1579 DI 10.1097/00004583-199912000-00019 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 260UF UT WOS:000083971300019 PM 10596258 ER PT J AU Block, G Mangels, AR Patterson, BH Levander, OA Norkus, EP Taylor, PR AF Block, G Mangels, AR Patterson, BH Levander, OA Norkus, EP Taylor, PR TI Body weight and prior depletion affect plasma ascorbate levels attained on identical vitamin C intake: A controlled-diet study SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE ascorbic acid; vitamin C; nutrient requirements; obesity ID STEADY-STATE TURNOVER; ACID METABOLISM; BLOOD-PRESSURE; DETERMINANTS; REQUIREMENT; INDEXES; HUMANS; WOMEN; MALES; POOL AB Purpose: To evaluate the role of factors that may affect the lever of plasma ascorbic acid (AA), including age, body weight, physical activity, minor illness and the impact of prior depletion and repletion. Methods: After one month of stabilization on 60 me vitamin C/day, subjects underwent two complete depletion-repletion cycles (one cycle=one month of vitamin C depletion with nine mg/day, followed by one month of repletion with 117 mg per day). Subjects (68 men, ages 30 to 59 years) did not smoke or drink alcohol during the study. All food was provided by the study. Results: There was extreme individual variability in the plasma AA level achieved on an identical repletion dose: after four weeks at 117 mg/day of vitamin C AA ranged from 26.5 mu mol/L to 85.8 mu mol/L. Body weight was inversely associated with plasma AA attained (p<0.0001). Regression analysis indicated that, compared to a 130-lb man, a 200-lb man reached 10 mu mol/L rower AA after the first repletion and 18 mu mol/L lower AA after the second repletion. One-third of the subjects did not reach a plasma plateau after the first repletion. Prier depletion and apparent repletion also had a major impact, and only 10% of subjects reached the same plasma AA on the second repletion as on the first repletion. Conclusions: Plasma AA attained on a given dose depends on body weight (or dose per kg of body weight) and an whether or not any prior depletions had been repleted adequately. The results have implications for nutrition recommendations and research design. C1 USDA, Agr Res Ctr, Beltsville, MD 20705 USA. NCI, Bethesda, MD 20892 USA. Our Lady Mercy Med Ctr, Bronx, NY USA. RP Block, G (reprint author), Univ Calif Berkeley, 426 Warren Hall, Berkeley, CA 94720 USA. RI Block, Gladys/E-3304-2010 NR 45 TC 23 Z9 24 U1 1 U2 2 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD DEC PY 1999 VL 18 IS 6 BP 628 EP 637 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 266VV UT WOS:000084321700010 PM 10613415 ER PT J AU Slavkin, HC AF Slavkin, HC TI Streptococcus mutans, early childhood caries and new opportunities SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID DENTAL-CARIES; CHILDREN; IMMUNIZATION; FAMILIES; STRAINS; REGION; AGE C1 Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Craniofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 25 TC 13 Z9 14 U1 0 U2 1 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 DEC PY 1999 VL 130 IS 12 BP 1787 EP 1792 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 261HB UT WOS:000084002800029 PM 10599184 ER PT J AU Zamboni, M Turcato, E Santana, H Maggi, S Harris, TB Pietrobelli, A Heymsfield, SB Micciolo, R Bosello, O AF Zamboni, M Turcato, E Santana, H Maggi, S Harris, TB Pietrobelli, A Heymsfield, SB Micciolo, R Bosello, O TI The relationship between body composition and physical performance in older women SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE obesity; aging; body composition; physical performance; strength ID SOFT-TISSUE COMPOSITION; SKELETAL-MUSCLE MASS; X-RAY ABSORPTIOMETRY; FAT-FREE MASS; MAINTAINING MOBILITY; VISCERAL FAT; LATE-LIFE; DISABILITY; AGE; RISK AB BACKGROUND: The relationship between age-associated change in body composition and physical disability is still unknown. Skeletal muscle mass declines with age in both sexes; however, since women have less muscle mass per unit of weight than men, these changes may be more debilitating in women. OBJECTIVE: To evaluate the relationship between body composition and physical performance. DESIGN: A cross-sectional study. PARTICIPANTS: 144 women aged 68 to 75 were selected randomly from the general population of Verona. MEASUREMENTS: Body composition was evaluated using dual energy X-ray absorptiometry and bioimpedance. Physical performance was evaluated using a modified version of the Activities of Daily Living scale. Distance walked in 6 minutes was calculated, and isometric knee strength was tested. RESULTS: Normal women had a significantly lower body mass index (BMI) and percent body fat. These women also had a higher ratio of body cell mass (BCM) and total fat free mass (FFM) than women with physical impairments. After adjusting for BMI, women in the lowest tertile of muscle strength had significantly lower BCM than those in the highest tertile. CONCLUSIONS: These cross-sectional data show that although muscle strength is related to fat-free mass, disability in older women is associated with heavier BMI and with a higher percentage of body fat. C1 Univ Verona, Cattedra Geriatr, I-37126 Verona, Italy. CNR, Program Aging, Padua, Italy. NIA, Off Geriatr Epidemiol, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10032 USA. Univ Trent, Inst Stat, Trent, Italy. RP Zamboni, M (reprint author), Univ Verona, Osped Maggiore, Cattedra Geriatr, Piazzale Stefani 1, I-37126 Verona, Italy. OI ZAMBONI, Mauro/0000-0001-6961-9483 NR 37 TC 67 Z9 70 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 1999 VL 47 IS 12 BP 1403 EP 1408 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 261KQ UT WOS:000084008700002 PM 10591232 ER PT J AU Schnermann, J AF Schnermann, J TI Micropuncture analysis of tubuloglomerular feedback regulation in transgenic mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR CAPILLARY-PRESSURE; NITRIC-OXIDE SYNTHASE; BLOOD-PRESSURE; GENE AB Micropuncture methods have been used widely as a means to define the function of single tubules and study the functional connection between tubules and afferent arterioles (so-called tubuloglomerular feedback [TGF]). Transgenic mouse strains have become a new research tool with the potential of shedding new light on the role of specific gene products in renal tubular and vascular function. The micropuncture approach has therefore been adapted to studies in the mouse kidney. Although the data presented here support the feasibility of using this technique in the mouse, technical improvements are desirable in the areas of anesthesia, ureteral urine collections, blood collections, volume replacement, and functional stability for extended time periods. During ketamine/inactin anesthesia, TGF responses could regularly be elicited in wild-type mice. In contrast, changes in loop flow did not alter stop-flow pressure in angiotensin II type 1A receptor and angiotensin-converting enzyme knockout mice. infusion of angiotensin Il in subpressor doses partially restored TGF responsiveness in angiotensin-converting enzyme knockout animals. Normal TGF responses compared to wild type were found in nitric oxide synthase I and thromboxane receptor knockout mice. Using free-flow micropuncture techniques, the proximal-distal single-nephron GFR difference was found to be augmented in aquaporin-1 and Na/H exchanger-3 knockout mice, suggesting TGF activation in these strains of mice. These results support an essential role of angiotensin II in TGF regulation mediated through the angiotensin LI type IA receptor. Chronic nitric oxide synthase I and thromboxane receptor deficiency did not change TGF responsiveness. Aquaporin-1 and Na/H exchanger-3 deficiency enhances TGF suppression of TGF probably by volume depletion-mediated TGF sensitization. The use of micropuncture methodology in transgenic mice combines old and new research tools in a way that promises to yield important new insights into single-nephron function in physiologic and pathophysiologic conditions. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bldg 10,Room 4D 51,10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK 40042, DK 37448, DK 39255] NR 24 TC 19 Z9 19 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 DEC PY 1999 VL 10 IS 12 BP 2614 EP 2619 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 259CH UT WOS:000083876000020 PM 10589702 ER PT J AU Balis, FM Adamson, PC AF Balis, FM Adamson, PC TI Application of pharmacogenetics to optimization of mercaptopurine dosing SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CHILDHOOD LYMPHOBLASTIC-LEUKEMIA; ACUTE LYMPHOCYTIC-LEUKEMIA; MAINTENANCE CHEMOTHERAPY; 6-MERCAPTOPURINE; METABOLISM; RISK; PHARMACOKINETICS; METHOTREXATE; POLYMORPHISM; CHILDREN C1 NIH, Pediat Oncol Branch, Div Clin Sci, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Div Clin Pharmacol & Therapeut, Philadelphia, PA USA. RP Balis, FM (reprint author), NIH, Pediat Oncol Branch, Div Clin Sci, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 18 TC 15 Z9 16 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 DEC 1 PY 1999 VL 91 IS 23 BP 1983 EP 1985 DI 10.1093/jnci/91.23.1983 PG 3 WC Oncology SC Oncology GA 266ER UT WOS:000084288100002 PM 10580012 ER PT J AU Weinberg, CR Sandler, DP AF Weinberg, CR Sandler, DP TI Gene-by-environment interaction for passive smoking and glutathione S-transferase M1? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LUNG-CANCER; TOBACCO-SMOKE; EXPOSURE C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. OI Sandler, Dale/0000-0002-6776-0018 NR 8 TC 8 Z9 8 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 DEC 1 PY 1999 VL 91 IS 23 BP 1985 EP 1986 DI 10.1093/jnci/91.23.1985 PG 2 WC Oncology SC Oncology GA 266ER UT WOS:000084288100003 PM 10580013 ER PT J AU Morris, JC AF Morris, JC TI Enzyme/prodrug-based tumor vaccination: All politics (and immunity) are local SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CYTOSINE DEAMINASE GENE; THYMIDINE KINASE GENE; SUICIDE GENE; COLORECTAL-CARCINOMA; BRAIN-TUMORS; PHASE-I; THERAPY; CELLS; 5-FLUOROCYTOSINE; EXPRESSION C1 NCI, Metab Branch, Div Clin Sci, Bethesda, MD 20892 USA. Natl Human Genome Res Inct, Clin Gene Therapy Branch, Bethesda, MD USA. RP Morris, JC (reprint author), NIH, Bldg 10,Rm 4N115, Bethesda, MD 20892 USA. NR 37 TC 5 Z9 5 U1 0 U2 1 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 DEC 1 PY 1999 VL 91 IS 23 BP 1986 EP 1989 DI 10.1093/jnci/91.23.1986 PG 4 WC Oncology SC Oncology GA 266ER UT WOS:000084288100004 PM 10580014 ER PT J AU Bennett, WP Alavanja, MCR Blomeke, B Vahakangas, KH Castren, K Welsh, JA Bowman, ED Khan, MA Flieder, DB Harris, CC AF Bennett, WP Alavanja, MCR Blomeke, B Vahakangas, KH Castren, K Welsh, JA Bowman, ED Khan, MA Flieder, DB Harris, CC TI Environmental tobacco smoke, genetic susceptibility, and risk of lung cancer in never-smoking women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID S-TRANSFERASE M1; LOS-ANGELES-COUNTY; NONSMOKING WOMEN; MOLECULAR EPIDEMIOLOGY; BLADDER-CANCER; UNITED-STATES; CARCINOGEN EXPOSURE; JAPANESE POPULATION; AFRICAN-AMERICANS; SUPERGENE FAMILY AB Background: Exposure to environmental tobacco smoke (ETS) is considered to be a major lung cancer risk factor for never smokers. We investigated the hypothesis that never-smoking women who are exposed to ETS and develop lung cancer are a genetically susceptible population Methods: Archival tumor tissues were analyzed from 106 never-smoking women enrolled in a case-control study of ETS land other personal and environmental factors) and lung cancer risk. We analyzed germline polymorphisms in genes that have been associated with cancer susceptibility and whose products activate (cytochrome P450 1A1 [CYP1A1]) and detoxify (glutathione S-transferases M1 [GSTM1] and T1 [GSTT1]) chemical carcinogens found in tobacco smoke. Results: When compared with never smokers who had no ETS exposure and developed lung cancer (n = 55), never smokers with exposure to ETS who developed lung cancer (n = 51) were more likely to be deficient in GSTM1 activity (i.e., were GSTM1 null) because of a genetic polymorphism in the GSTM1 gene (odds ratio = 2.6; 95% confidence interval = 1.1-6.1). A statistically significant rising trend in risk occurred with increasing ETS exposure (two-sided P = .02), reaching a more than sixfold excess risk in those exposed to 55 pack-years of ETS (ETS pack-year ETS produced by an active smoker, within a confined space such as a room, who smokes one pack of cigarettes a day for a year). No evidence was found of associations between GSTT1 deficiency or the CYP1A1 valine variant and lung cancer risk due to ETS exposure. Conclusions: A common genetic polymorphism divides the population of never smokers into two groups of approximately equal size, one (homozygous carriers of the GSTM1 null allele) that has a statistically significant greater risk of lung cancer from ETS than the other (heterozygous or homozygous carriers of the wild-type GSTM1 allele). C1 NIH, Human Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. NIH, Radiat Epidemiol Branch, Div Canc Epidemiol, Bethesda, MD 20892 USA. Oulu Univ, Dept Pharmacol & Toxicol, SF-90220 Oulu, Finland. Cornell Univ, Ctr Med, Dept Pathol, New York, NY USA. RP Harris, CC (reprint author), NIH, Human Carcinogenesis Lab, Div Basic Sci, Bldg 37,Rm 2C01, Bethesda, MD 20892 USA. NR 58 TC 120 Z9 121 U1 0 U2 9 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 DEC 1 PY 1999 VL 91 IS 23 BP 2009 EP 2014 DI 10.1093/jnci/91.23.2009 PG 6 WC Oncology SC Oncology GA 266ER UT WOS:000084288100011 PM 10580025 ER PT J AU Legler, JM Ries, LAG Smith, MA Warren, JL Heineman, EF Kaplan, RS Linet, MS AF Legler, JM Ries, LAG Smith, MA Warren, JL Heineman, EF Kaplan, RS Linet, MS TI Re: Brain and other central nervous system cancers: Recent trends in incidence and mortality - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Canc Surveillance Res Prog, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Div Canc Etiol, Bethesda, MD 20892 USA. RP Legler, JM (reprint author), NIH, Execut Pl N,Suite 313, Bethesda, MD 20892 USA. NR 6 TC 9 Z9 11 U1 0 U2 1 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 DEC 1 PY 1999 VL 91 IS 23 BP 2050 EP 2051 PG 2 WC Oncology SC Oncology GA 266ER UT WOS:000084288100023 ER PT J AU Fikree, FF Rahbar, MH Berendes, HW AF Fikree, FF Rahbar, MH Berendes, HW TI Role of intrauterine growth retardation on physical growth of Pakistani squatter children from birth to 2 years of age SO JOURNAL OF TROPICAL PEDIATRICS LA English DT Article ID FOR-GESTATIONAL-AGE; FOLLOW-UP; WEIGHT AB A birth cohort of 727 squatter children from Karachi was followed to study growth patterns by measuring anthropometric parameters at specific ages during the first 2 years of life, The mean weight and length of the intrauterine growth retarded and appropriate for gestational age children fell below the 10th percentile of the NCHS standards after 9 months and further deteriorated in the subsequent study period. However, the intrauterine growth retarded children showed slightly higher growth velocities compared to appropriate for gestational age children in the first few months for all four measurements, but subsequently these differences in growth velocities diminished. Our results suggest that nutrition intervention strategies should begin in early pregnancy. C1 Aga Khan Univ, Dept Community Hlth Sci, Karachi 74800, Pakistan. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Fikree, FF (reprint author), Aga Khan Univ, Dept Community Hlth, Stadium Rd,POB 3500, Karachi 74800, Pakistan. NR 23 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0142-6338 J9 J TROP PEDIATRICS JI J. Trop. Pediatr. PD DEC PY 1999 VL 45 IS 6 BP 338 EP 344 DI 10.1093/tropej/45.6.338 PG 7 WC Pediatrics; Tropical Medicine SC Pediatrics; Tropical Medicine GA 270JQ UT WOS:000084532500005 PM 10667002 ER PT J AU Whitehead, SS Hill, MG Firestone, CY St Claire, M Elkins, WR Murphy, BR Collins, PL AF Whitehead, SS Hill, MG Firestone, CY St Claire, M Elkins, WR Murphy, BR Collins, PL TI Replacement of the F and G proteins of respiratory syncytial virus (RSV) subgroup A with those of subgroup B generates chimeric live attenuated RSV subgroup B vaccine candidates SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANT; ANTIGENIC RELATEDNESS; FUSION GLYCOPROTEINS; GENE-EXPRESSION; DENGUE VIRUSES; CHIMPANZEES; CONSTRUCTION; MUTATIONS; IMMUNOGENICITY; SUBSTITUTION AB Human respiratory syncytial virus (RSV) exists as two antigenic subgroups, A and B, both of which should be represented in a vaccine. The F and G glycoproteins are the major neutralization and protective antigens, and the G protein in particular is highly divergent between the subgroups. The existing system for reverse genetics is based on the A2 strain of RSV subgroup A, and most efforts to develop a live attenuated RSV vaccine have focused on strain A2 or other subgroup A viruses. In the present study, the development of a live attenuated subgroup B component was expedited by the replacement of the F and G glycoproteins of recombinant A2 virus with their counterparts from the RSV subgroup B strain B1, This gene replacement was initially done for wild-type (,vt) recombinant A2 virus to create a wt AB chimeric virus and then for a series of A2 derivatives which contain various combinations of A2-derived attenuating mutations located in genes other than F and G, The wt AB virus replicated in cell culture with an efficiency which was comparable to that of the,ut A2 and B1 parents. AB viruses containing temperature-sensitive mutations in the A2 background exhibited levels of temperature sensitivity in vitro which were similar to those of A2 viruses bearing the same mutations. In chimpanzees, the replication of the wt AB chimera was intermediate between that of the A2 and B1 wt viruses and was accompanied by moderate rhinorrhea, as previously seen in this species, An AB chimeric virus, rABcp248/404/1030, which was constructed to contain a mixture of attenuating mutations derived from two different biologically attenuated A2 viruses, was highly attenuated in both the upper and lower respiratory tracts of chimpanzees, This attenuated AB chimeric virus was immunogenic and conferred a high level of resistance on chimpanzees to challenge with,ct AB virus. The rABcp248/404/1030 chimeric virus is a promising vaccine candidate for RSV subgroup B and will be evaluated next in humans, Furthermore, these results suggest that additional attenuating mutations derived from strain A2 can be inserted into the A2 background of the recombinant chimeric AB virus as necessary to modify the attenuation phenotype in a reasonably predictable manner to achieve an optimal balance between attenuation and immunogenicity in a virus bearing the subgroup B antigenic determinants. C1 NIAID, Resp Viruses Sect, Infect Dis Lab, Bethesda, MD 20892 USA. NIAID, Expt Primate Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Whitehead, SS (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, 7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 45 TC 34 Z9 37 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 9773 EP 9780 PG 8 WC Virology SC Virology GA 255ZD UT WOS:000083699300010 PM 10559287 ER PT J AU Santiago, F Clark, E Chong, SY Molina, C Mozafari, F Mahieux, R Fujii, M Azimi, N Kashanchi, F AF Santiago, F Clark, E Chong, SY Molina, C Mozafari, F Mahieux, R Fujii, M Azimi, N Kashanchi, F TI Transcriptional up-regulation of the cyclin D2 gene and acquisition of new cyclin-dependent kinase partners in human T-cell leukemia virus type 1-infected cells SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TAX PROTEIN; HUMAN-LYMPHOCYTES; COACTIVATOR CBP; IN-VITRO; EXPRESSION; TRANSACTIVATION; PHOSPHORYLATION; PROGRESSION; INHIBITION AB Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis. Tax(1) is a 40-kDa phosphoprotein, predominantly localized in the nucleus of the host cell, which functions to transactivate both viral and cellular promoters. It seems likely that HTLV-1, through expression of the viral regulatory protein Tax(1), provides some initial alteration in cell metabolism predisposing the development of ATL. Here, we demonstrate that HTLV-1 infection in T-cell lines and patient samples causes overexpression of an early G(1) cyclin, cyclin D2. The transcriptional up-regulation of the cyclin D2 gene is due to activation of Tax on the cyclin D2 gene. More important, we find that overexpression of cyclin D2 is accompanied by acquisition of new partners such as cyclin-dependent kinase 2 (cdk2), cdk4, and cdk6 in infected cells, This is in contrast to uninfected T cells, where cyclin D2 associates only with cdk6, Functional effects of these cyclin-cdk complexes in infected cells are shown by hyperphosphorylation of Rb and histone H1, indicators of active progression into S phase as well as changes in cellular chromatin and transcription machinery. These studies link HTLV-1 infection with changes of cellular cyclin gene expression, hence providing clues to development of T-cell leukemia. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07103 USA. Inst Pasteur, Dept Hepatitis & Retroviruses, Tehran, Iran. NCI, NIH, Bethesda, MD 20874 USA. Niigata Univ, Sch Med, Dept Virol, Niigata 9518510, Japan. RP Kashanchi, F (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, MSB E-635, Newark, NJ 07103 USA. FU NCRR NIH HHS [RR13969]; NIAID NIH HHS [AI42524, AI43894, R01 AI043894] NR 49 TC 68 Z9 68 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 9917 EP 9927 PG 11 WC Virology SC Virology GA 255ZD UT WOS:000083699300027 PM 10559304 ER PT J AU Taraporewala, Z Chen, DY Patton, JT AF Taraporewala, Z Chen, DY Patton, JT TI Multimers formed by the rotavirus nonstructural protein NSP2 bind to RNA and have nucleoside triphosphatase activity SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; DOUBLE-STRANDED-RNA; 3-DIMENSIONAL STRUCTURE; REPLICASE PARTICLE; BLUETONGUE VIRUS; MESSENGER-RNA; POLYMERASE; SA11; PHOSPHOPROTEIN; GENOME AB The nonstructural protein NSP2 is a component of rotavirus replication intermediates and accumulates in cytoplasmic inclusions (viroplasms), sites of genome RNA replication and the assembly of subviral particles. To better understand the structure and function of the protein, C-terminally His-tagged NSP2 was expressed in bacteria and purified to homogeneity. In its purified form, the protein did not exist as a monomer but rather was present as an 8S-10S homomultimer consisting of 6 +/- 2 subunits of recombinant NSP2 (rNSP2), As shown by gel mobility shift assays, the rNSP2 multimers hound to RNA in discrete cooperative steps to form higher-order RNA-protein complexes. The RNA-binding activity of the rNSP2 multimers was determined to be nonspecific and to have a strong preference for single-stranded RNA over double-stranded RNA for which it displayed little affinity. Enzymatic analysis revealed that rNSP2 possessed an associated nucleoside triphosphatase (NTPase) activity in vitro, which in the presence of Mg2+ catalyzed the hydrolysis of each of the four NTPs to NDPs with equal efficiency. Evidence indicating that the hydrolysis of NTP resulted in the covalent linkage of the gamma-phosphate to rNSP2 was obtained. Additional experiments showed that NSP2 expressed transiently in MA014 cells is phosphorylated. We propose that NSP2 functions as a molecular motor, catalyzing the packaging of viral mRNA into core-like replication intermediates through the energy derived from its NTPase activity. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, 7 Ctr Dr,MSC 0720,Room 117, Bethesda, MD 20892 USA. RI Patton, John/P-1390-2014 NR 42 TC 83 Z9 88 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 9934 EP 9943 PG 10 WC Virology SC Virology GA 255ZD UT WOS:000083699300029 PM 10559306 ER PT J AU Holmen, SL Salter, DW Payne, WS Dodgson, JB Hughes, SH Federspiel, MJ AF Holmen, SL Salter, DW Payne, WS Dodgson, JB Hughes, SH Federspiel, MJ TI Soluble forms of the subgroup A avian leukosis virus [ALV(A)] receptor Tva significantly inhibit ALV(A) infection in vitro and in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID DENSITY-LIPOPROTEIN RECEPTOR; ROUS-SARCOMA VIRUS; RETROVIRAL VECTORS; CELLULAR RECEPTOR; ENVELOPE GLYCOPROTEIN; NUCLEOTIDE-SEQUENCE; HIV-1 INFECTION; CHICKEN-EMBRYO; MESSENGER-RNA; GENE-TRANSFER AB The interactions between the subgroup A avian leukosis virus [ALV(A)] envelope glycoproteins and soluble forms of the ALV(A) receptor Tva were analyzed both in vitro and in vivo by quantitating the ability of the soluble Tva proteins to inhibit ALV(A) entry into susceptible cells. Two soluble Tva proteins were tested: the 83-amino-acid Tva extracellular region fused to two epitope tags (sTva) or fused to the constant region of the mouse immunoglobulin G heavy chain (sTva-mIgG). Replication-competent ALV-based retroviral vectors,,with subgroup B or C env were used to deliver and express the two soluble tv-a (sba) genes in avian cells. In vitro, chicken embryo fibroblasts or DF-1 cells expressing sTva or sTva-mIgG proteins were much more resistant to infection by ALV(A) (similar to 200-fold) than were control cells infected by only the vector. The antiviral effect was specific for ALV(A), which is consistent with a receptor interference mechanism. The antiviral effect of sTva-mIgG was positively correlated with the amount of sTva-mIgG protein. In vivo, the stva genes were delivered and expressed in line 0 chicken embryos by the ALV(B)-based vector RCASBP(B). Viremic chickens expressed relatively high levels of stva and stva-mIgG RNA in a broad range of tissues. High levels of sTva-mIgG protein were detected in the sera of chickens infected with RCASBP(B)stva-mIgG. Viremic chickens infected with RCASBP(B) alone, RCASBP(B)stva, or RCASBP(B)stva-mIgG were challenged separately with ALV(A) and ALV(C). Both sTva and sTva-mIgG significantly inhibited infection by ALV(A) (95 and 100% respectively) but had no measurable effect on ALV(C) infection. The results of this study indicate that a soluble receptor can effectively block infection of at least some retroviruses and demonstrates the utility of the ALV experimental system in characterizing the mechanism(s) of viral entry. C1 Mayo Clin & Mayo Fdn, Program Mol Med, Rochester, MN 55905 USA. Univ W Alabama, Dept Biol Sci, Livingston, AL 35470 USA. Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. NCI, ABL Basic Res Program, Fred Hutchinson Canc Res Ctr, Ft Detrick, MD 21702 USA. RP Federspiel, MJ (reprint author), Mayo Clin & Mayo Fdn, Program Mol Med, Guggenheim 1842,200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [T32CA75926, T32 CA075926] NR 50 TC 27 Z9 28 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10051 EP 10060 PG 10 WC Virology SC Virology GA 255ZD UT WOS:000083699300042 PM 10559319 ER PT J AU Crawford, JM Earl, PL Moss, B Reimann, KA Wyand, MS Manson, KH Bilska, M Zhou, JT Pauza, CD Parren, PWHI Burton, DR Sodroski, JG Letvin, NL Montefiori, DC AF Crawford, JM Earl, PL Moss, B Reimann, KA Wyand, MS Manson, KH Bilska, M Zhou, JT Pauza, CD Parren, PWHI Burton, DR Sodroski, JG Letvin, NL Montefiori, DC TI Characterization of primary isolate-like variants of simian-human immunodeficiency virus SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; N-LINKED OLIGOSACCHARIDE; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; PERSISTENT INFECTION; RHESUS MACAQUES; V3 LOOP; LYMPHOCYTE DEPLETION; SOLUBLE CD4; HIV TYPE-1 AB Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human immunodeficiency virus type 1 (HIV-1) are now available. One of the advantages of these chimeric viruses is their application to studies of HIV-1-specific neutralizing antibodies in preclinical AIDS vaccine studies in nonhuman primates. In this regard, an important consideration is the spectrum of antigenic properties exhibited by the different envelope glycoproteins used for SHIV construction. The antigenic properties of six SHIV variants were characterized here in neutralization assays with recombinant soluble CD4 (rsCD4), monoclonal antibodies, and serum samples from SHIV-infected macaques and HIV-1-infected individuals, Neutralization of SHIV variants HXBc2, KU2, 89.6, and 89.6P by autologous and heterologous sera from SHIV-infected macaques was restricted to an extent that these viruses may be considered heterologous to one another in their major neutralization determinants. Little or no variation was seen in the neutralization determinants on SHIV variants 89.6P, 89.6PD, and SHIV-KB9, Neutralization of SHIV HXBc2 by sera from HXBc2-infected macaques could be blocked with autologous V3-loop peptide; this was less true in the case of SHIV 89.6 and sera from SHIV 89.6-infected macaques, The poorly immunogenic but highly conserved epitope for monoclonal antibody 1gG1b12 was a target for neutralization on SHIV variants HXBc2, KU2, and 89.6 but not on 89.6P and KB9, The 2G12 epitope was a target for neutralization on all five SHIV variants. SHIV variants KU2, 89.6, 89.6P, 89.6PD, and KB9 exhibited antigenic properties characteristic of primary isolates by being relatively insensitive to neutralization in peripheral blood mononuclear cells with serum samples from HIV-1-infected individuals and 12 fold to 38-fold less sensitive to inhibition with recombinant soluble CD4 than TCLA strains of HIV-1. The utility of nonhuman primate models in AIDS vaccine development is strengthened by the availability of SHIV variants that are heterologous in their neutralization determinants and exhibit antigenic properties shared with primary isolates. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Primedica Corp, Worcester, MA 01608 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA. OI Parren, Paul/0000-0002-4365-3859 FU NIAID NIH HHS [R37 AI033292, AI-85345, AI36643, AI65303, R01 AI033292, R01 AI065303] NR 75 TC 65 Z9 65 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10199 EP 10207 PG 9 WC Virology SC Virology GA 255ZD UT WOS:000083699300059 PM 10559336 ER PT J AU Wallace, M Waterman, PM Mitchen, JL Djavani, M Brown, C Trivedi, P Horejsh, D Dykhuizen, M Kitabwalla, M Pauza, CD AF Wallace, M Waterman, PM Mitchen, JL Djavani, M Brown, C Trivedi, P Horejsh, D Dykhuizen, M Kitabwalla, M Pauza, CD TI Lymphocyte activation during acute simian/human immunodeficiency virus SHIV89.6PD infection in macaques SO JOURNAL OF VIROLOGY LA English DT Article ID PRIMARY HIV-INFECTION; PROGRAMMED CELL-DEATH; T-CELLS; TYPE-1 INFECTION; NATURAL-HISTORY; RHESUS MACAQUES; HOST RESPONSES; APOPTOSIS; AIDS; DISEASE AB Host-virus interactions control disease progression in human immunodeficiency virus-infected human beings and in nonhuman primates infected with simian or simian/human immunodeficiency viruses (SHIV). These interactions evolve rapidly during acute infection and are key to the mechanisms of viral persistence and AIDS. SHIV89.6PD infection in rhesus macaques can deplete CD4(+) T cells from the peripheral blood, spleen, and lymph nodes within 2 weeks after exposure and is a model for virulent, acute infection. Lymphocytes isolated from blood and tissues during the interval of acute SHIV89.6PD infection have lost the capacity to proliferate in response to phytohemagglutinin (PHA). T-cell unresponsiveness to mitogen occurred within 1 week after mucosal inoculation yet prior to massive CD4(+) T-cell depletion and extensive virus dissemination. The lack of mitogen response was due to apoptosis in vitro, and increased activation marker expression on circulating T cells in vivo coincided with the appearance of PHA-induced apoptosis in vitro. Inappropriately high immune stimulation associated with rapid loss of mature CD4(+) T cells suggested that activation-induced cell death is a mechanism for helper T-cell depletion in the brief period before widespread virus dissemination. Elevated levels of lymphocyte activation likely enhance SHIV89.6PD replication, thus increasing the loss of CD4(+) T cells and diminishing the levels of virus-specific immunity that remain after acute infection. The level of surviving immunity may dictate the capacity to control virus replication and disease progression. We describe this level of immune competence as the host set point to show its pivotal role in AIDS pathogenesis. C1 Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53705 USA. NIH, Immunodeficiency Viruses Sect, Infect Dis Lab, Rockville, MD 20852 USA. RP Pauza, CD (reprint author), Univ Wisconsin, Dept Pathol, 1300 Univ Ave, Madison, WI 53705 USA. FU NCI NIH HHS [T32 CA009075]; NCRR NIH HHS [RR00167, P51 RR000167]; NIAID NIH HHS [AIRR42534, AI38491] NR 34 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10236 EP 10244 PG 9 WC Virology SC Virology GA 255ZD UT WOS:000083699300063 PM 10559340 ER PT J AU Kostrikis, LG Neumann, AU Thomson, B Korber, BT McHardy, P Karanicolas, R Deutsch, L Huang, YX Lew, JF McIntosh, K Pollack, H Borkowsky, W Spiegel, HML Palumbo, P Oleske, J Bardeguez, A Luzuriaga, K Sullivan, J Wolinsky, SM Koup, RA Ho, DD Moore, JP AF Kostrikis, LG Neumann, AU Thomson, B Korber, BT McHardy, P Karanicolas, R Deutsch, L Huang, YX Lew, JF McIntosh, K Pollack, H Borkowsky, W Spiegel, HML Palumbo, P Oleske, J Bardeguez, A Luzuriaga, K Sullivan, J Wolinsky, SM Koup, RA Ho, DD Moore, JP TI A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 DISEASE PROGRESSION; MACROPHAGE-TROPIC HIV-1; ZIDOVUDINE TREATMENT; DELETION ALLELE; INFECTION; EXPRESSION; RESISTANCE; CCR5-DELTA-32; INDIVIDUALS; CXCR4 AB There are natural mutations in the coding and noncoding regions of the human immunodeficiency virus type I (HIV-1) CC-chemokine coreceptor 5 (CCR5) and in the related CCR2 protein (the CCR2-64I mutation). Individuals homozygous for the CCR5-Delta 32 allele, a which prevents CCR5 expression, strongly resist HIV-1 infection. Several genetic polymorphisms have been identified within the CCR5 5' regulatory region, same of which influence the rate of disease progression in adult AIDS study cohorts. We genotyped 1,442 infants (1,235 uninfected and 207 HIV-1 infected) for five CCR5 and CCR2 polymorphisms: CCR5-59353-T/C, CCR5-59356-C/T CCR5-59402-A/G, CCR5-Delta 32, and CCR2-64I. The clinical significance of each genotype was assessed by measuring whether it influenced the rate of perinatal HIV-1 transmission among 667 AZT-untreated mother-infant pairs (554 uninfected and 113 HIV-1 infected). We found that the mutant CCR5-59356-T allele is relatively common in African-Americans (20.6% allele frequency among 552 infants) and rare in Caucasians and Hispanics (3.4 and 5.6% of 174 and 458 infants, respectively; P < 0.001). There were 38 infants homozygous for CCR5-59356-T, of whom 35 were African-Americans. Among the African-American infants in the AZT-untreated group? there was a highly significant increase in HIV-1 transmission to infants with two mutant CCR5-59356-T alleles (47.6% of 21), compared to those with no or one mutant allele (13.4 to 14.1% of 187 and 71, respectively; P < 0.001). The increased relative risk was 5.9 (95% confidence interval, 2.3 to 15.3; P < 0.001). The frequency of the CCR5-59356-T mutation varies between population groups in the United States, a low frequency occurring in Caucasians and a higher frequency occurring in African-Americans. Homozygosity for CCR5-59356-T is strongly associated with an increased rate of perinatal HIV-1 transmission. C1 Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. NYU Med Ctr, New York, NY 10016 USA. Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. Clin Trials & Surveys Corp, Baltimore, MD USA. Univ Calif Los Alamos Natl Lab, Los Alamos, NM USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Med & Dent New Jersey, Sch Med, Dept Pediat, Newark, NJ 07103 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX USA. RP Kostrikis, LG (reprint author), Rockefeller Univ, Aaron Diamond AIDS Res Ctr, 455 1st Ave, New York, NY 10016 USA. RI Wolinsky, Steven/B-2893-2012; Kostrikis, Leondios/A-5330-2016; OI Kostrikis, Leondios/0000-0002-5340-7109; Wolinsky, Steven/0000-0002-9625-6697; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [N01AI85339, N01-AI85339, R01 AI041420, R01 AI41420, R01 AI43868, U01 AI034841, U01 AI034858] NR 42 TC 102 Z9 104 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10264 EP 10271 PG 8 WC Virology SC Virology GA 255ZD UT WOS:000083699300066 PM 10559343 ER PT J AU Guidotti, LG Eggers, CM Raney, AK Chi, SY Peters, JM Gonzalez, FJ McLachlan, A AF Guidotti, LG Eggers, CM Raney, AK Chi, SY Peters, JM Gonzalez, FJ McLachlan, A TI In vivo regulation of hepatitis B virus replication by peroxisome proliferators SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; HEPATOMA-CELL LINE; GENE-EXPRESSION; NUCLEOCAPSID PROMOTER; CORE PROMOTER; FATTY-ACIDS; HBV-DNA; TRANSCRIPTIONAL REGULATION; TRANSIENT EXPRESSION; BINDING-PROTEIN AB The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in regulating hepatitis B virus (HBV) transcription and replication in vivo was investigated in an HBV transgenic mouse model. Treatment of HBV transgenic mice with the peroxisome proliferators Wy-14,643 and clofibric acid resulted in a less than twofold increase in HBV transcription rates and steady-state levels of HBV RNAs in the livers of these mice. In male mice, this increase in transcription was associated with a 2- to 3-fold increase in replication intermediates, whereas in female mice it was associated with a 7- to 14-fold increase in replication intermediates. The observed increases in transcription and replication were dependent on PPARa. HBV transgenic mice lacking this nuclear hormone receptor showed similar levels of HBV transcripts and replication intermediates as untreated HBV transgenic mice expressing PPAR alpha but failed to demonstrate alterations in either RNA or DNA synthesis in response to peroxisome proliferators. Therefore, it appears that very modest alterations in transcription can, under certain circumstances, result in relatively large increases in HBV replication in HBV transgenic mice. C1 Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. RP McLachlan, A (reprint author), Scripps Res Inst, Dept Cell Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Peters, Jeffrey/D-8847-2011; OI Guidotti, Luca G./0000-0002-0205-2678; McLachlan, Alan/0000-0002-4168-2365 FU NIAID NIH HHS [AI40696, N01AI30070, R01 AI030070, R01 AI040696] NR 51 TC 34 Z9 37 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10377 EP 10386 PG 10 WC Virology SC Virology GA 255ZD UT WOS:000083699300079 PM 10559356 ER PT J AU Zink, MC Suryanarayana, K Mankowski, JL Shen, AD Piatak, M Spelman, JP Carter, DL Adams, RJ Lifson, JD Clements, JE AF Zink, MC Suryanarayana, K Mankowski, JL Shen, AD Piatak, M Spelman, JP Carter, DL Adams, RJ Lifson, JD Clements, JE TI High viral load in the cerebrospinal fluid and brain correlates with severity of simian immunodeficiency virus encephalitis SO JOURNAL OF VIROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; IMMUNE-RESPONSES; RHESUS MACAQUES; HIV-1 INFECTION; TYPE-1 RNA; DEMENTIA; SIV; PATHOGENESIS; VIREMIA; IMMUNIZATION AB AIDS dementia and encephalitis are complications of AIDS occurring most frequently in patients who are immunosuppressed, The simian immunodeficiency virus (SIV) model used in this study was designed to reproducibly induce,AIDS in macaques in order to examine the effects of a neurovirulent virus in this context. Pigtailed macaques (Macaca nemestrina) were coinoculated with an immunosuppressive virus (SIV/DeltaB670) and a neurovirulent molecularly cloned virus (SIV/17E-Fr), and more than 90% of the animals developed moderate to severe encephalitis within 6 months of inoculation. Viral load in plasma and cerebrospinal fluid (CSF) was examined longitudinally to onset of AIDS, and viral load was measured in brain tissue at necropsy to examine the relationship of systemic and central nervous system (CNS) viral replication to the development of encephalitis. In all animals, plasma viral load peaked at 10 to 14 days postinfection and remained high throughout infection with no correlation found between plasma viremia and SIV encephalitis. In contrast, persistent high levels of CSF viral RNA after the acute phase of infection correlated with the development of encephalitis. Although high levels of viral RNA were found in the CSF of all macaques (six of six) during the acute phase, this high level was maintained only in macaques developing SIV encephalitis (five of six). Furthermore, the level of both viral RNA and antigen in the brain correlated with the severity of the CNS lesions. The single animal in this group that did not have CNS lesions had no detectable viral RNA in any of the regions of the brain. The results substantiate the use of CSF viral load measurements in the postacute phase of SIV infection as a marker for encephalitis and CNS viral replication. C1 Johns Hopkins Univ, Sch Med, Retrovirus Lab, Div Comparat Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Retroviral Pathogenesis, SAIC Frederick, Frederick, MD 21702 USA. RP Zink, MC (reprint author), Johns Hopkins Univ, Sch Med, Retrovirus Lab, Div Comparat Med, Traylor G-60,720 Rutland Ave, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [HL53248]; NINDS NIH HHS [NS35344, NS36911] NR 36 TC 164 Z9 164 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10480 EP 10488 PG 9 WC Virology SC Virology GA 255ZD UT WOS:000083699300089 PM 10559366 ER PT J AU Tang, Y Winkler, U Freed, EO Torrey, TA Kim, W Li, H Goff, SP Morse, HC AF Tang, Y Winkler, U Freed, EO Torrey, TA Kim, W Li, H Goff, SP Morse, HC TI Cellular motor protein KIF-4 associates with retroviral Gag SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS; EXPRESSION AB Previously we demonstrated that murine retroviral Gag proteins associate with a cellular motor protein, I(KIF-4. Using the yeast two-hybrid assay, we also found an association of KIF-4 with Gag proteins of Mason-Pfizer monkey virus (MPMV). simian immunodeficiency virus (SIV), and human immunodeficiency virus type 1 (HIV-1), Studies performed with mammalian fell systems confirmed that the HIV-1 Gag protein associates with KIF-4. Soluble cytoplasmic proteins from cells infected with recombinant vaccinia virus expressing the entire Gag-Pol precursor protein of HIV-1 or transfected with HIV-1 molecular clone pNL4-3 were fractionated by sucrose gradient centrifugation and further separated by size-exclusion and anion-exchange chromatographies, KIF-4 and HIV-1 Gag cofractionated in both chromatographic separations, Immunoprecipitation assays have also verified the KIF-4-Gag association. KIF-4 binds mainly to the Gag precursor (Pr55 Gag) and a matrix-capsid processing intermediate (Pr42) but not to other processed Gag products. The binding of Gag is mediated hy a domain of KIF-4 proximal to the C terminus. These results, and our previous studies, raise the possibility that KIF-4 may play an important role in retrovirus Gag protein transport. C1 NIAID, LIP, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Ajou Univ, Sch Med, Inst Med Sci, Suwon 441749, South Korea. Columbia Univ, Coll Phys & Surg, Dept Biochem & Mol Biophys, New York, NY USA. RP Morse, HC (reprint author), NIAID, LIP, NIH, Bldg 7,Room 304,MSC 0760, Bethesda, MD 20892 USA. RI Goff, Stephen/K-6337-2014; OI Goff, Stephen/0000-0003-0693-5547; Morse, Herbert/0000-0002-9331-3705 NR 13 TC 76 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10508 EP 10513 PG 6 WC Virology SC Virology GA 255ZD UT WOS:000083699300092 PM 10559369 ER PT J AU Pevenstein, SR Williams, RK McChesney, D Mont, EK Smialek, JE Straus, SE AF Pevenstein, SR Williams, RK McChesney, D Mont, EK Smialek, JE Straus, SE TI Quantitation of latent varicella-zoster virus and herpes simplex virus genomes in human trigeminal ganglia SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPES; POLYMERASE CHAIN-REACTION; DORSAL-ROOT GANGLIA; INFECTED NEURONS; INSITU HYBRIDIZATION; MESSENGER-RNA; VIRAL-DNA; REACTIVATION; EXPRESSION; NUMBER AB Using rear-time fluorescence PCR, we quantitated the numbers of copies of latent varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) genomes in 15 human trigeminal ganglia. Eight (538) and 1 (7%) of 15 ganglia were PCR positive for HSV-1 or -2 glycoprotein G genes, with means of 2,902 +/- 1,082 (standard error of the mean) or 109 genomes/10(5) cells, respectively. Eleven of 14 (79%) to 13 of 15 (87%) of the ganglia were PCR positive for VZV gene 29, 31, or 62. Pooling of the results for the three VZV genes yielded a mean of 258 +/- 38 genomes/10(5) ganglion cells. These levels of latent viral genome loads have implications for virus distribution in and reactivation from human sensory ganglia. C1 NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Serv Anat Pathol, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, Med Virol Sect, NIH, Bldg 10,11N228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 36 TC 111 Z9 115 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1999 VL 73 IS 12 BP 10514 EP 10518 PG 5 WC Virology SC Virology GA 255ZD UT WOS:000083699300093 PM 10559370 ER PT J AU Fischbach, RL Hunt, M AF Fischbach, RL Hunt, M TI "Behind every problem lies an opportunity": Meeting the challenge of diversity in medical schools SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article AB The authors describe the historical evolution and present status of affirmative action in medical school admission policies. The demographic transformation of the medical student body between 1965 and 1998 from a homogeneous white and male group to one that includes a significant number of women and minority students is presented. Challenges to affirmative action are outlined. In addition, the authors note the increasing diversity of the general population and discuss the benefits of diversity to medical practice, research, and education. However, the upper ranks of professors and administrators remain white and male. The rationale for an innovative course on the history of bias in medicine and the benefits that diversity brings to the medical enterprise are presented. C1 Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Med Eth, Boston, MA 02115 USA. Natl Lib Med, Hist Med Div, Bethesda, MD 20209 USA. RP Fischbach, RL (reprint author), 5630 Wisconsin Ave 1502, Chevy Chase, MD 20815 USA. NR 29 TC 0 Z9 0 U1 2 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD DEC PY 1999 VL 8 IS 10 BP 1240 EP 1247 DI 10.1089/jwh.1.1999.8.1240 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 272EX UT WOS:000084638500006 PM 10643831 ER PT J AU Fischbach, RL Hunt, M AF Fischbach, RL Hunt, M TI Educating for diversity: A decade of experience (1989-1999) SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article AB In response to tensions created by a racial misunderstanding, the authors developed a course for first year medical students entitled Race and Gender in Medicine. The course, presented in a seminar format, enables the participants to discuss openly their concerns about diversity and its impact on their institution and the medical enterprise. Physician speakers describe their experiences with gender bias, racism, and other discriminatory practices and then present strategies they used to overcome these obstacles in their career path. Given the increasing heterogeneity of the population, the authors advocate integrating a course such as this one into the curriculum that will help prepare students to practice humane medicine in the multiracial, multiethnic, and multicultural society of the 21st century. C1 Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Med Eth, Boston, MA 02115 USA. Natl Lib Med, Hist Med Div, Bethesda, MD 20209 USA. RP Fischbach, RL (reprint author), 5630 Wisconsin Ave 1502, Chevy Chase, MD 20815 USA. NR 24 TC 3 Z9 3 U1 1 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD DEC PY 1999 VL 8 IS 10 BP 1249 EP 1256 DI 10.1089/jwh.1.1999.8.1249 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 272EX UT WOS:000084638500007 PM 10643832 ER PT J AU Culleton, BF Larson, MG Wilson, PWF Evans, JC Parfrey, PS Levy, D AF Culleton, BF Larson, MG Wilson, PWF Evans, JC Parfrey, PS Levy, D TI Cardiovascular disease and mortality in a community-based cohort with mild renal insufficiency SO KIDNEY INTERNATIONAL LA English DT Article DE serum creatinine; renal failure; Framingham Heart Study; mortality ID SERUM CREATININE ASSAYS; CORONARY HEART-DISEASE; RISK-FACTORS; INDEPENDENT PREDICTOR; FAILURE; STROKE AB Background. Little is known about the prevalence of cardiovascular disease (CVD) and associated risk factors in individuals with mild renal insufficiency (RI). Furthermore, the longterm outcomes associated with mild RI in the community have not been described. Methods. Serum creatinine (S-Cr) was measured in 6233 adult participants of the Framingham Heart Study (mean age 54 years, 54% women). Mild RI was defined as S-Cr 136 to 265 mu mol/liter (1.5 to 3.0 mg/dl) in men and 120 to 265 mu mol/liter (1.4 to 3.0 mg/dl) in women. The lower limits for mild RI were defined by the sex-specific 95th percentile S-Cr values in a healthy subgroup of our sample. The upper limit for mild RI was chosen to exclude those subjects with more advanced renal failure. Cox proportional hazards analyses were used to determine the relationship of baseline RI to CVD and all-cause mortality. Results. At baseline, 8.7% of men (N = 246) and 8.0% of women (N = 270) had mild RI. Nineteen percent of the subjects with mild RI had prevalent CVD. During 15 years of followup, there were 1000 CVD events and 1406 deaths. In women, mild RI was not associated with increased risk for CVD events [hazards ratio (HR) 1.04, 95% CI, 0.79 to 1.37] or all-cause mortality (HR 1.08, 95% CI, 0.87 to 1.34). In men, mild RI showed no significant associations with CVD events (HR 1.17, 95% CI, 0.85 to 1.57), but it was associated with all-cause mortality in age-adjusted (HR 1.42, 95% CI, 1.12 to 1.79) and multivariable adjusted (HR 1.31,95% CI, 1.02 to 1.67) analyses. Conclusion. Mild RI in the community is common and is associated with a high prevalence of CVD. The association of RI with risk for adverse outcomes is strongly related to coexisting CVD and CVD risk factors. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. Mem Univ Newfoundland, Div Nephrol, St Johns, NF, Canada. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 29 TC 584 Z9 616 U1 0 U2 7 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1999 VL 56 IS 6 BP 2214 EP 2219 DI 10.1046/j.1523-1755.1999.00773.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 263CK UT WOS:000084104900022 PM 10594797 ER PT J AU Swift, ME Kleinman, HK DiPietro, LA AF Swift, ME Kleinman, HK DiPietro, LA TI Impaired wound repair and delayed angiogenesis in aged mice SO LABORATORY INVESTIGATION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; EPIDERMAL-KERATINOCYTES; GENE-EXPRESSION; HEALING WOUNDS; OLD RATS; MACROPHAGES; COLLAGEN; FIBROBLASTS; MODEL; YOUNG AB Wound repair is a multistep process consisting of hemostasis, inflammatory cell infiltration, tissue regrowth, and remodeling. In aged individuals, this progression of events is altered, resulting in wounds that heal more slowly than wounds in the young. These studies were designed to examine the proliferative phase of repair in young and aged mice, with attention to the angiogenic process. Using a standardized excisional injury model, wound re-epithelialization, collagen accumulation, and angiogenesis were examined. Re-epithelialization and collagen synthesis were substantially delayed in aged mice as compared with young mice. Angiogenesis in wounds from aged mice was also delayed, with significantly more capillary growth in wounds from young mice than aged mice. In addition, wounds from aged mice contained significantly less of the angiogenic mediators fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) than wounds from young animals (p < 0.05). Because macrophages are a rich source of angiogenic factors in wounds, macrophage production of VEGF was examined. Macrophages from aged mice produced significantly less VEGF than cells from young mice. To examine the in vivo endothelial cell responsiveness, a defined amount of rFGF-2 was suspended in Matrigel and placed subcutaneously in either young or aged mice. In response to FGF-2, capillary growth into Matrigel was significantly less in aged than young mice. The results suggest that a decline in angiogenic growth factor production, as well as a decline in endothelial responsiveness to specific factors, may account for the delayed wound angiogenesis in aged mice. These results also indicate that age-related alterations in macrophage function might partially account for the overall delay in the wound repair process. C1 Loyola Univ, Med Ctr, Burn & Shock Trauma Inst, Dept Microbiol & Immunol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Surg, Maywood, IL 60153 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP DiPietro, LA (reprint author), Loyola Univ, Med Ctr, Burn & Shock Trauma Inst, Dept Microbiol & Immunol, 2160 S 1st Ave, Maywood, IL 60153 USA. FU NIGMS NIH HHS [GM55238, GM50875] NR 43 TC 191 Z9 202 U1 5 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1999 VL 79 IS 12 BP 1479 EP 1487 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 268YM UT WOS:000084448200006 PM 10616199 ER PT J AU Teruya-Feldstein, J Setsuda, J Yao, X Kingma, DW Straus, S Tosato, G Jaffe, ES AF Teruya-Feldstein, J Setsuda, J Yao, X Kingma, DW Straus, S Tosato, G Jaffe, ES TI MIP-1 alpha expression in tissues from patients with hemophagocytic syndrome SO LABORATORY INVESTIGATION LA English DT Article ID EPSTEIN-BARR-VIRUS; T-CELL LYMPHOMA; TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA; MALIGNANT HISTIOCYTOSIS; INDUCIBLE PROTEIN-10; HUMAN MONOCYTES; LYMPHOHISTIOCYTOSIS; HYPERCYTOKINEMIA; PATHOGENESIS AB Hemophagocytic syndrome (HPS) is a clinicopathologic syndrome that can be precipitated by a variety of causes and is characterized by a systemic activation of macrophages, which are induced to undergo phagocytosis. Chemokines play an important role in the inflammatory cell recruitment into tissues. We examined the expression of chemokines and cytokines in tissues exhibiting histologic evidence of HPS in a variety of settings: peripheral T-cell lymphoma, three patients; nasal T/NK cell lymphoma, one patient; subcutaneous panniculitis-like T-cell lymphoma, one patient; and chronic EBV infection, one patient. Compared with control tissues, we found elevated macrophage inflammatory protein-alpha (MIP-1 alpha) and interferon-gamma (IFN-gamma) expression, but not macrophage-derived chemotactic factor (MDC) or TNF-alpha, in tissues of patients with HPS irrespective of the cause or setting. MIP-1 alpha can promote macrophage chemotaxis and IFN-gamma promotes macrophage activation. Elevated expression of IP-10 and monokine induced by IFN-gamma (Mig) was also detected in tissues exhibiting features of HPS, providing an explanation for the occurrence of chemoattraction of T-cells and NK cells. Immunohistochemical analysis of tissues with evidence of phagocytic activity in that site showed MIP-1 alpha characteristically localized to endothelial cells of blood vessels and splenic sinuses, lymphocytes, and macrophages. These results provide evidence for MIP-1 alpha chemokine expression in tissues from patients with HPS and suggest that MIP-1 alpha may play an important role in the pathogenesis of the hemophagocytic syndrome. C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 36 TC 28 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 1999 VL 79 IS 12 BP 1583 EP 1590 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 268YM UT WOS:000084448200016 PM 10616208 ER PT J AU Baum, BJ AF Baum, BJ TI Crowning achievements in dentistry SO LANCET LA English DT Article C1 Natl Inst Dent & Cranofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Cranofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC PY 1999 VL 354 SU S BP 12 EP 12 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 267DT UT WOS:000084342100013 ER PT J AU Fee, E AF Fee, E TI The wages of sin SO LANCET LA English DT Article C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Fee, E (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 LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC PY 1999 VL 354 SU S BP 61 EP 61 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 267DT UT WOS:000084342100062 ER PT J AU Blagosklonny, MV AF Blagosklonny, MV TI Drug-resistance enables selective killing of resistant leukemia cells: exploiting of drug resistance instead of reversal SO LEUKEMIA LA English DT Article DE chemotherapy; cancer; leukemia; resistance; cytotoxicity ID MULTIDRUG-RESISTANCE; MYELOID-LEUKEMIA; EFFLUX PUMP; PROTEIN MRP; CANCER; EXPRESSION; APOPTOSIS; BCL-2 AB Drug resistance is a well recognized problem in cancer therapy. Despite the current dogma that drug resistance is always an obstacle for treatment, here I show that it provides opportunities for selective protection of non-resistant cells with killing of drug-resistant cancer cells. According to the proposed 'two-drug' strategy, the first drug should be ineffective against a target drug-resistant cell (ie the drug is a substrate of MRP or Pgp pumps). In addition, it must be cytostatic but not cytotoxic. The second drug, which is applied in sequence, must be a cycle-dependent apoptotic drug to which the target cell is not cross-resistant. Thus, low doses of adriamycin, etoposide and actinomycin D, used as the first drugs, were cytostatic to parental HL60 cells. Therefore, these drugs precluded Bcl-2/Raf-1 phosphorylation, PARP cleavage and cell death which are otherwise induced by paclitaxel, a mitosis selective apoptotic drug for HL60 cells. In contrast, HL60/ADR cells which express MRP, a transporter which pumps out the first drugs from a cell, were insensitive to the first drugs and therefore readily underwent apoptosis following the second drug. This strategy also allowed a selective killing of HL60/TX cells which express MDR-1, with the only difference being that the second drug, paclitaxel, was substituted for epothilones, non-Pgp substrates. Lack of protection by the first drug, a Pgp substrate, resulted in HL60/TX killing by the second drug, whereas parental HL-60 cells were fully protected. Therefore, drug resistant cells can be selectively killed by a combination of drugs not killing sensitive cells. Lack of toxicity against normal cells will be clinically translated in reduction of adverse side-effects of chemotherapy against drug-resistant malignancies. 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 18 TC 39 Z9 41 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 1999 VL 13 IS 12 BP 2031 EP 2035 DI 10.1038/sj.leu.2401623 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 263GH UT WOS:000084116700015 PM 10602425 ER PT J AU Thandla, S Alashari, M Green, DM Aplan, PD AF Thandla, S Alashari, M Green, DM Aplan, PD TI Therapy-related T cell lymphoblastic lymphoma with t(11;19)(q23;p13) and MLL gene rearrangement SO LEUKEMIA LA English DT Letter ID SECONDARY LEUKEMIAS C1 Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY 14263 USA. Childrens Hosp, Dept Pathol, Buffalo, NY 14222 USA. Childrens Hosp, Dept Pediat Hematol Oncol, Buffalo, NY 14222 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Pathol, Buffalo, NY 14260 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14260 USA. RP Aplan, PD (reprint author), Natl Canc Inst, Div Clin Sci, 8717 Grovemont Circle, Gaithersburg, MD 20877 USA. RI Aplan, Peter/K-9064-2016 FU NCI NIH HHS [CA 15606, CA 73773] NR 9 TC 10 Z9 10 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD DEC PY 1999 VL 13 IS 12 BP 2116 EP 2118 DI 10.1038/sj.leu.2401558 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 263GH UT WOS:000084116700029 PM 10602439 ER PT J AU Yongbi, MN Yang, YH Frank, JA Duyn, JH AF Yongbi, MN Yang, YH Frank, JA Duyn, JH TI Multislice perfusion imaging in human brain using the C-FOCI inversion pulse: Comparison with hyperbolic secant SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE FAIR; FOCI; hyperbolic secant; perfusion ID RECOVERY FAIR TECHNIQUE; CEREBRAL BLOOD-FLOW; MAGNETIC-RESONANCE; ARTERIAL WATER; SPIN INVERSION; FREQUENCY; IMPLEMENTATION; SPECTROSCOPY AB Perfusion studies based on pulsed arterial spin labeling have primarily applied hyperbolic secant (HS) pulses for spin inversion. To optimize perfusion sensitivity, it is highly desirable to implement the HS pulse with the same slice width as the width of the imaging purse. Unfortunately, this approach causes interactions between the slice profiles and manifests as residual signal from static tissue in the resultant perfusion image. This problem is currently overcome by increasing the selective HS width relative to the imaging slice width. However, this solution increases the time for the labeled blood to reach the imaging slice (transit time), causing loss of perfusion sensitivity as a result of T-1 relaxation effects. in this study, we demonstrate that the preceding problems can be largely overcome by use of the C-shaped frequency offset corrected inversion (FOCI) pulse [Ordidge et al., Magn Reson Med 1996;36:562]. The implementation of this pulse for multislice perfusion imaging on the cerebrum is presented, showing substantial improvement in slice definition in vivo compared with the HS pulse. The sharper FOCI profile is shown to reduce the physical gap (or "safety margin") between the inversion and imaging slabs, resulting in a significant increase in perfusion signal without residual contamination from static tissue. The mean +/- SE (n = 6) gray matter perfusion-weighted signal (Delta M/M-o) without the application of vascular signal suppression gradients were 1.19 +/- 0.10% (HS-flow-sensitive alternating inversion recovery [FAIR]), and 1.51 +/- 0.11% for the FOCI-FAIR sequence. The corresponding values with Vascular signal suppression were 0.64 +/- 0.14%, and 0.91 +/- 0.08% using the HS- and FOCI-FAIR sequences, respectively. Compared with the MS-based data, the FOCI-FAIR results correspond to an average increase in perfusion signal of up to between 26%-30%. (C) 1999 Wiley-Liss, Inc. C1 NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. Cornell Univ, Coll Med, Funct Neuroimaging Lab, Dept Psychiat, New York, NY 10021 USA. RP Duyn, JH (reprint author), NIH, Lab Diagnost Radiol Res, Bldg 10,Room B1N256,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Duyn, Jozef/F-2483-2010 NR 24 TC 50 Z9 51 U1 0 U2 2 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 DEC PY 1999 VL 42 IS 6 BP 1098 EP 1105 DI 10.1002/(SICI)1522-2594(199912)42:6<1098::AID-MRM14>3.0.CO;2-1 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 260PP UT WOS:000083959300014 PM 10571931 ER PT J AU Nelms, K O'Neill, TJ Li, SQ Hubbard, SR Gustafson, TA Paul, WE AF Nelms, K O'Neill, TJ Li, SQ Hubbard, SR Gustafson, TA Paul, WE TI Alternative splicing, gene localization, and binding of SH2-B to the insulin receptor kinase domain SO MAMMALIAN GENOME LA English DT Article ID SIGNAL-TRANSDUCTION PROTEIN; MULTIFACTORIAL MOUSE MODEL; IRS-1 PTB DOMAIN; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE KINASE; GLUT4 TRANSLOCATION; 2-HYBRID SYSTEM; I RECEPTOR; SUBSTRATE-1; GROWTH AB The SH2-B protein is an SH2-domain-containing molecule that interacts with a number of phosphorylated kinase and receptor molecules including the insulin receptor. Two isoforms of the SH2-B have been identified and have been proposed to arise through alternate splicing. Here we have identified a third isoform of the SH2-B protein, SH2-B gamma, that interacts specifically with the insulin receptor. This interaction required phosphorylation of residue Y1146 in the triple tyrosine motif within the activation loop of the IR kinase and is one of only two signaling molecules shown to interact directly with this residue of the insulin receptor kinase domain. The intron/exon structure of the SH2-B gene was determined. Alternate splice sites utilized to generate the different isoforms of the SH2-B protein were identified in the 3' end of the SH2-B gene immediately downstream of the exon encoding the core of the SH2 domain. Additionally, the chromosomal location of the SH2-B gene was determined to be the distal arm of mouse Chromosome (Chr) 7 in a region linked to obesity in mice. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. NYU, Med Ctr, Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Med Ctr, Dept Pharmacol, New York, NY 10016 USA. Metabolex Inc, Hayward, CA 94545 USA. RP Nelms, K (reprint author), Monsanto Searle, AA4C,700 Chesterfield Pkwy, St Louis, MO 63198 USA. FU NIDDK NIH HHS [DK52916, DK50602] NR 48 TC 56 Z9 59 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1999 VL 10 IS 12 BP 1160 EP 1167 DI 10.1007/s003359901183 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 259XZ UT WOS:000083920400008 PM 10594240 ER PT J AU Matsuo-Takasaki, M Lim, JH Sato, SM AF Matsuo-Takasaki, M Lim, JH Sato, SM TI The POU domain gene, XlPOU 2 is an essential downstream determinant of neural induction SO MECHANISMS OF DEVELOPMENT LA English DT Article DE neural induction; neural determination; POU; XIPOU 2 ID XENOPUS-LAEVIS; SPEMANN ORGANIZER; TRANSCRIPTION FACTOR; CELL-DIFFERENTIATION; VERTEBRATE EMBRYOS; EARLY RESPONSE; FACTOR BRN-2; EXPRESSION; MESODERM; HOMOLOG AB The POU domain gene, XIPOU 2, acts as a transcriptional activator during mid-gastrulation in Xenopus. Overexpression or misexpression of VP16-POU-GR, a fusion protein consisting of the strong activator domain of VP16 and the POU domain of XIPOU 2, results in ectopic expression of the neural-specific genes, nrp-1, en-2, and beta-tubulin. In contrast, overexpressing a dominant-inhibitory form of XIPOU 2 inhibits the chordin-induced neuralization of uncommitted ectoderm, and results in a loss of nrp-1 and en-2 expression in embryos. Furthermore, in uncommitted ectoderm, XIPOU 2 regulates the developmental neural program that includes a number of pre-pattern genes and at least one proneural gene, X-ngnr-1, thus playing a key:role during neural determination. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NIH, NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. RP Matsuo-Takasaki, M (reprint author), NIH, NICHHD, Mol Genet Lab, Bldg 6B,Room 412,MSC 2790,6 Ctr Dr, Bethesda, MD 20892 USA. NR 73 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 1999 VL 89 IS 1-2 BP 75 EP 85 DI 10.1016/S0925-4773(99)00204-X PG 11 WC Developmental Biology SC Developmental Biology GA 260DL UT WOS:000083934200008 PM 10559482 ER PT J AU Brown, ML Riley, GF Potosky, AL Etzioni, RD AF Brown, ML Riley, GF Potosky, AL Etzioni, RD TI Obtaining long-term disease specific costs of care - Application to Medicare enrollees diagnosed with colorectal cancer SO MEDICAL CARE LA English DT Article DE costs; cancer; colon; rectum; methods AB OBJECTIVES; This study develops estimates of long-term, cancer-related treatment cost using a modeling approach and data from the SEER-Medicare linked database. The method is demonstrated for colorectal cancer. METHODS. Data on Medicare payments were obtained for colorectal cancer patients for the years 1990 to 1994 from the SEER-Medicare linked database. Claims payment data for control subjects were obtained for Medicare enrollees without cancer residing in the same areas as patients. Estimates of long-term cost (less than or equal to 25 years following the date of diagnosis) were obtained by combining treatment/phase-specific cost estimates with estimates of longterm survival from SEER. Treatment phases were defined as initial care, terminal care, and continuing care. Cancer-related estimates for each phase were obtained by subtracting costs for control subjects from the observed costs for cancer patients, matching on age group, gender, and registry area. Estimates of long-term cost less than or equal to 11 years obtained by this method were compared with 11-year estimates obtained by application of the Kaplan-Meier sample average (KMSA) method. RESULTS. The mean initial-phase cancer-related cost was approximately $18,000 but was higher among patients with more advanced cancer. The mean continuing-phase cancer-related cost was $1,500 per year and declined with increasing age, but was higher on an annual basis among persons with later stages of cancer and shorter survival time. The mean terminal-phase cancer-related cost was $15,000 and declined with bath age at death and more advanced stage at diagnosis. After the phase-specific estimates were combined, the average long-term cancer-related cost was $33,700 ($31,300 at 3% discount rate) for colon cancer compared with $36,500 ($33,800 at 3% discount rate) for cancer of the rectum. This represented about half of the total long-term cost for Medicare enrollees diagnosed with this disease. Long-term cost was highest for Stage III cancer and lowest for in situ cancer. Eleven-year cancer-related costs estimated by the KMSA method were similar to estimates using the phase-based approach. CONCLUSIONS. This paper demonstrates that valid estimates of cancer-related long-term cost can be obtained from administrative claims data linked to incidence cancer registry data. C1 NCI, Appl Res Program, Bethesda, MD 20892 USA. US Hlth Care Financing Adm, Off Strateg Planning, Baltimore, MD 21207 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Brown, ML (reprint author), NCI, Appl Res Program, EPN Room 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 27 TC 126 Z9 126 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 1999 VL 37 IS 12 BP 1249 EP 1259 DI 10.1097/00005650-199912000-00008 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 261PQ UT WOS:000084017900008 PM 10599606 ER PT J AU Deuster, PA Zelazowska, EB Singh, A Sternberg, EM AF Deuster, PA Zelazowska, EB Singh, A Sternberg, EM TI Expression of lymphocyte subsets after exercise and dexamethasone in high and low stress responders SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE adhesion molecules; immunophenotyping; interleukin 6; lymphocyte subsets ID PITUITARY-ADRENAL AXIS; INTERCELLULAR-ADHESION MOLECULE-1; CELL-ADHESION; GLUCOCORTICOID SUPPRESSION; METABOLIC RESPONSES; LEUKOCYTE ADHESION; STRENUOUS EXERCISE; TREADMILL EXERCISE; MARKED DIFFERENCES; CIRCADIAN-RHYTHM AB Purpose: Recent work indicates that among the normal population, persons can be classified as low (LR) or high (HR) stress responders based on hypothalamic-pituitary-adrenal (HPA) axis responses to high-intensity exercise. We studied whether differential activation of the HPA axis affected cytokine production and expression of selected lymphocyte subsets in HR and LR in response to high-intensity exercise after placebo and dexamethasone (DEX; 4 mg). Methods: Healthy HR (N = 12) and LR (N = 10) underwent two exercise tests at 90% of VO2max 8 h after placebo or DEX. Expression of lymphocyte surface markers (CD3(+), CD4(+), CD8(+), CD56(+)), adhesion molecule markers (intercellular adhesion molecule-1/ICAM-1: CD54(+) and L-selectin: CD62L(+)), and concentrations of plasma interleukin 6 (IL-6) were examined before and after exercise. Results: Baseline percentages of CD8(+) and CD56(+) cells were significantly higher, and concentrations of IL-6 and percentages of CD4(+) cells were significantly lower in HR as compared with LR. The percentage of CD54(+) and CD62L(+) cells was not significantly different in HR and LR. DEX significantly reduced the percentage of CD3(+) and CD4(+) and increased the percentage of CDS' and CD56(+) subsets; the percent of cells expressing CD54(+) increased, whereas CD62L(+) decreased. Exercise-induced changes in the percentage of lymphocyte subsets were similar to those induced by DEX. Conclusion: In summary, HR and LR have different baseline patterns of IL-6 and lymphocyte subsets, which may reflect differential sensitivity to endogenous glucocorticoids. However, exogenous glucocorticoids induced similar patterns of lymphocyte expression in HR and LR. C1 Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. Walter Reed Army Ins Res, Dept Bacterial Dis, Washington, DC USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. RP Deuster, PA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. RI Deuster, Patricia/G-3838-2015 OI Deuster, Patricia/0000-0002-7895-0888 NR 42 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD DEC PY 1999 VL 31 IS 12 BP 1799 EP 1806 DI 10.1097/00005768-199912000-00016 PG 8 WC Sport Sciences SC Sport Sciences GA 265MC UT WOS:000084247100016 PM 10613431 ER PT J AU Wahl, SM AF Wahl, SM TI TGF-beta in the evolution and resolution of inflammatory and immune processes - Introduction SO MICROBES AND INFECTION LA English DT Editorial Material ID GROWTH-FACTOR-BETA; DEATH C1 NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), NIDCR, Oral Infect & Immun Branch, NIH, Bldg 30,Room 332,30 Convent Dr,MSC 4352, Bethesda, MD 20892 USA. NR 26 TC 28 Z9 31 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD DEC PY 1999 VL 1 IS 15 BP 1247 EP 1249 DI 10.1016/S1286-4579(99)00261-0 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 273GK UT WOS:000084699400001 PM 10611751 ER PT J AU Roberts, AB AF Roberts, AB TI TGF-beta signaling from receptors to the nucleus SO MICROBES AND INFECTION LA English DT Article DE TGF-beta; Smad; signal transduction ID GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR SMAD4; TRANSCRIPTIONAL ACTIVATION; HETERO-OLIGOMERIZATION; BINDING-PROTEIN; FAMILY MEMBERS; MOUSE EMBRYO; DNA-BINDING; GENE; PROMOTER AB In the past three years, a novel signal transduction pathway downstream of the transforming growth factor-beta (TGF-beta) superfamily receptor serine-threonine kinases has been shown to be mediated by a family of latent transcription factors called 'Smads'. These proteins mediate a short-circuited pathway in which a set of receptor-activated Smads are phosphorylated directly by the receptor kinase and then translocate to the nucleus complexed to the common mediator, Smad4, to participate in transcriptional complexes. Smads 2 and 3 mediate signals predominantly from the TGF-beta receptors. Of these, specific roles have been ascribed to Smad3 in control of chemotaxis of neutrophils and macrophages and the inhibition of Smad3 activity by the oncogene Evi-1 suggests that it may play a role in leukemogenesis. Other data, such as the induction by the inflammatory cytokine interferon-gamma of an inhibitory Smad, Smad7, which blocks the actions of Smad3, suggest that identification of the specific gene targets of Smad proteins in immune cells will provide new insight into the mechanisms of TGF-beta action on these cells. (C) 1999 Editions scientifiques et medicales Elsevier. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 64 TC 105 Z9 115 U1 0 U2 3 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD DEC PY 1999 VL 1 IS 15 BP 1265 EP 1273 DI 10.1016/S1286-4579(99)00258-0 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 273GK UT WOS:000084699400004 PM 10611754 ER PT J AU Ashcroft, GS AF Ashcroft, GS TI Bidirectional regulation of macrophage function by TGF-beta SO MICROBES AND INFECTION LA English DT Article DE TGF-beta; macrophage function; deactivation; reactivation; bidirectional regulation ID TRANSFORMING-GROWTH-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; FC-GAMMA-RIII; HUMAN-MONOCYTES; IN-VIVO; INFLAMMATORY RESPONSE; NEUTRALIZING ANTIBODY; ENDOTHELIAL-CELLS; HUMAN-PLATELETS; EXPRESSION AB The dual role of transforming growth factor-beta (TGF-beta) in modulating macrophage function is an important concept gaining increasing recognition. In addition to its role as a 'macrophage-deactivating' agent, TGF-beta functions as a monocyte activator, inducing cytokine production and mediating host defence. These functions are context-dependent, modulated by the differentiation state of the cell, the local cytokine environment, and the local levels of TGF-beta in itself. In general, during the initial stages of inflammation, TGF-beta locally acts as a proinflammatory agent by recruiting and activating resting monocytes. As these cells differentiate specific immunosuppressive actions of TGF-beta predominate, leading to resolution of the inflammatory response. Increasing our understanding of the bidirectional regulation of macrophage function will facilitate prediction of the ultimate outcome of modulating TGF-beta levels in vivo. (C) 1999 Editions scientifiques et medicales Elsevier SAS. C1 Natl Inst Craniofacial & Dent Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Ashcroft, GS (reprint author), Natl Inst Craniofacial & Dent Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 86 TC 123 Z9 127 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD DEC PY 1999 VL 1 IS 15 BP 1275 EP 1282 DI 10.1016/S1286-4579(99)00257-9 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 273GK UT WOS:000084699400005 PM 10611755 ER PT J AU Branton, MH Kopp, JB AF Branton, MH Kopp, JB TI TGF-beta and fibrosis SO MICROBES AND INFECTION LA English DT Review DE TGF-beta; glomerulosclerosis; diabetic nephropathy; renal interstitial fibrosis; extracellular matrix; matrix metalloproteinase; angiotensin ID GROWTH-FACTOR-BETA; PROXIMAL TUBULAR CELLS; GLOMERULAR MESANGIAL CELLS; MESSENGER-RNA EXPRESSION; PLASMA TRANSFORMING GROWTH-FACTOR-BETA-1; METALLOPROTEINASES-3 GENE-EXPRESSION; PLASMINOGEN-ACTIVATOR ACTIVITY; EOSINOPHILIA-MYALGIA-SYNDROME; MATRIX PROTEIN EXPRESSION; SYNOVIAL LINING CELLS AB Transforming growth factor-beta (TGF-beta) isoforms are multifunctional cytokines that play a central role in wound healing and in tissue repair. TGF-beta is found in all tissues, bm is particularly abundant in bone, lung, kidney and placental tissue. TGF-beta is produced by many but not all parenchymal cell types, and is also produced or released by infiltrating cells such as lymphocytes, monocytes/macrophages, and platelets. Following wounding or inflammation, all these cells are potential sources of TGF-beta. In general, the release and activation of TGF-beta stimulates the production of various extracellular matrix proteins and inhibits the degradation of these matrix proteins, although exceptions to these principles abound. These actions of TGF-beta contribute to tissue repair, which under ideal circumstances leads to the restoration of normal tissue architecture and may involve a component of tissue fibrosis. In many diseases, excessive TGF-beta contributes to a pathologic excess of tissue fibrosis that compromises normal organ function, a topic that has been the subject of numerous reviews [1-3]. In the following chapter, we will discuss the role of TGF-beta in tissue fibrosis, with particular emphasis on renal fibrosis. (C) 1999 Editions scientifiques et medicales Elsevier SAS. C1 NIDDK, Kidney Dis Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Branton, MH (reprint author), NIDDK, Kidney Dis Sect, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 228 TC 355 Z9 386 U1 1 U2 22 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD DEC PY 1999 VL 1 IS 15 BP 1349 EP 1365 DI 10.1016/S1286-4579(99)00250-6 PG 17 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 273GK UT WOS:000084699400012 PM 10611762 ER PT J AU Chen, WJ Wahl, SM AF Chen, WJ Wahl, SM TI Manipulation of TGF-beta to control autoimmune and chronic inflammatory diseases SO MICROBES AND INFECTION LA English DT Review DE TGF-beta; autoimmune disease; inflammation; oral tolerance; T lymphocyte; gene therapy; cytokine ID TRANSFORMING-GROWTH-FACTOR; MYELIN BASIC-PROTEIN; CD4(+) T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ACQUIRED THYMIC TOLERANCE; INDUCED ARTHRITIS MODEL; NONOBESE DIABETIC MICE; WALL-INDUCED ARTHRITIS; NECROSIS-FACTOR-ALPHA; IN-VIVO EXPRESSION AB Defining the mechanisms whereby transforming growth factor-beta (TGF-beta) controls physiologic inflammation and the immune response and how it contributes to pathology when it is dysregulated is critical to our ability to manipulate the levels and activity of this potent cytokine for therapeutic benefit. In keeping with its dichotomous nature, recent evidence suggests that overproduction and/or activation contribute to persistent inflammation and that antagonists of TGF-beta delivered locally can break the cycle of leukocyte recruitment and fibrotic sequelae. On the other hand, systemic routing of TGF-beta can also inhibit inflammatory pathogenesis by multiple mechanisms as exemplified by systemic injections of the protein and by recent gene transfer studies. In addition, enhanced levels of circulating endogenous TGF-beta appear to be an instrument of suppression during the development of oral tolerance, cyclosporin treatment, and following administration of retinoic acid. Although treatment of autoimmune and chronic inflammatory diseases is an important goal, the multiplicity of actions of TGF-beta and the nearly ubiquitous expression of TGF-beta and its receptors dictate a cautious approach to the use of this powerful cytokine as a therapeutic agent. (C) 1999 Editions scientifiques et medicales Elsevier. C1 Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. NR 116 TC 49 Z9 52 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD DEC PY 1999 VL 1 IS 15 BP 1367 EP 1380 DI 10.1016/S1286-4579(99)00249-X PG 14 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 273GK UT WOS:000084699400013 PM 10611763 ER PT J AU Wickner, RB Taylor, KL Edskes, HK Maddelein, ML Moriyama, H Roberts, BT AF Wickner, RB Taylor, KL Edskes, HK Maddelein, ML Moriyama, H Roberts, BT TI Prions in Saccharomyces and Podospora spp.: Protein-based inheritance SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID DE-NOVO APPEARANCE; CHAIN RELEASE FACTORS; YEAST SUP35 PROTEIN; VEGETATIVE INCOMPATIBILITY; PSI+ DETERMINANT; TRANSGENIC MICE; SCRAPIE PRION; RNA VIRUSES; IN-VITRO; CEREVISIAE AB Genetic evidence showed two non-Mendelian genetic elements of Saccharomyces cerevisiae, called [URE3] and [PSI] to be prions of Ure2p and Sup35p, respectively. [URE3] makes cells derepressed for nitrogen catabolism, while [PSI] elevates the efficiency of weak suppressor tRNAs. The same approach led to identification of the non-Mendelian element [Het-s] of the filamentous fungus Podospora anserina, as a prion of the het-s protein. The pr-ion form of the the het-s protein is required for heterokaryon incompatibility, a normal fungal function, suggesting that other normal cellular functions may be controlled by prions. [URE3] and [PSI] involve a self-propagating aggregation of Ure2p and Sup35p, respectively. In vitro, Ure2p and Sup35p form amyloid, a filamentous protein structure, high in beta-sheet with a characteristics green birefringent staining by the dye Congo Red. Amyloid deposits are a cardinal feature of Alzheimer's disease, non-insulin-dependent diabetes mellitus, the transmissible spongiform encephalopathies, and many other diseases. The pr-ion domain of Ure2p consists of Asn-rich residues 1 to 80, bur two nonoverlapping fragments of the molecule can, when overproduced, induce the de nova appearance of [URE3]. The prion domain of Sup35 consists of residues 1 to 114, also rich in Asn and Gin residues. While runs of Asn and Gin are important for [URE3] and [PSI] no such structures are found in PrP or the Het-s protein. Either elevated or depressed levels of the chaperone Hsp104 interfere with propagation of [PSI]. Both [URE3] and [PSI] are cured by growth of cells in millimolar guanidine HCL [URE3] Is also cured by overexpression of fragments of Ure2p or fusion proteins including parts of Ure2p. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. RI MADDELEIN, Marie-Lise/G-5395-2010; MORIYAMA, Hiromitsu/F-9256-2013 NR 111 TC 44 Z9 47 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD DEC PY 1999 VL 63 IS 4 BP 844 EP + PG 20 WC Microbiology SC Microbiology GA 263KC UT WOS:000084123000005 PM 10585968 ER PT J AU Lininger, RA Zhuang, ZP Man, YG Park, WS Emmert-Buck, M Tavassoli, FA AF Lininger, RA Zhuang, ZP Man, YG Park, WS Emmert-Buck, M Tavassoli, FA TI Loss of heterozygosity is detected at chromosomes 1p35-36 (NB), 3p25 (VHL), 16p13 (TSC2/PKD1), and 17p13 (TP53) in microdissected apocrine carcinomas of the breast SO MODERN PATHOLOGY LA English DT Article DE apocrine; breast; genetics; neoplasms ID HUMAN MAMMARY-CARCINOMA; HIPPEL-LINDAU DISEASE; ANDROGEN RECEPTORS; SOMATIC MUTATIONS; ALLELIC IMBALANCE; DUCTAL CARCINOMA; CANCER; GENE; EXPRESSION; DELETION AB Introduction: Apocrine carcinomas of the breast are an unusual special category of predominantly AR+, ER-, and PR- breast cancer, characterized by cells with abundant, eosinophilic cytoplasm and nuclei with often prominent nucleoli. To further investigate these lesions, loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci, including loci frequently mutated in breast cancer. Materials and Methods: Twenty-five intraductal apocrine carcinomas, 11 invasive apocrine carcinomas, and six apocrine hyperplasias were retrieved from the files of the Armed Forces Institute of Pathology (Washington, DC) and Fairfax Hospital (Fairfax, VA). Cells from lesional as well as normal tissues were microdissected. LOH was performed at a number of chromosomal loci, including loci commonly altered in breast cancer: 1p35-36 (NB), 3p25.5 (VHL), 8p12 (D8S136), 9p21 (p16), 11p13 (D11S904), 11q13 (INT-2 and PYGM), 16p13.3 (TSC1/PKD1 gene region), 17p13 (TP53), 17q13 (NM23), and 22q12 (D22S683). Results: Among informative in situ and invasive apocrine carcinomas, LOH was present in 33% of 15 cases for 17p13 (TP53), as well as 36% of 14 cases for 3p25 (VHL), 30% of 10 cases for 1p35-36 (NB), and 27% of 11 cases for 16p13.3 (TSC2/PKD1). A higher frequency of LOH was noted among invasive apocrine carcinomas (30 to 50%) compared with in situ apocrine carcinomas (23 to 33%) at these loci. LOH was present simultaneously for TP53 and either VHL or NE in five cases. Infrequent (less than or equal to 12%) or absent LOH was detected at the remaining loci, including several loci commonly mutated in breast cancer (i.e., INT2, PYGM, and NM23). LOH was not detected in any of the six apocrine hyperplasias. Conclusion: Am intermediate frequency of allelic loss was detected at multiple tumor suppressor gene loci, including 17p13 (TP53), as well as 1p35-336 (NB), 3p25 (VHL), and 16p13 (PKD1/TSC2), in apocrine carcinomas of the breast, with a higher overall frequency of LOH noted among invasive tumors compared with in situ tumors. Aside from LOH at p53, LOH was infrequent or absent at several other loci commonly mutated in breast cancer. This preliminary molecular evidence supports immunohistochemical data that apocrine carcinomas of the breast may possess unique mechanisms of carcinogenesis, compared with ordinary ductal carcinomas. However, further study is needed to support this assertion and to determine if the LOH detected is truly etiologic or if it is the result of genetic progression. C1 Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Lininger, RA (reprint author), Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Brinkhous Bullitt Bldg,CB 7525, Chapel Hill, NC 27599 USA. NR 40 TC 21 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 1999 VL 12 IS 12 BP 1083 EP 1089 PG 7 WC Pathology SC Pathology GA 270WA UT WOS:000084559100001 PM 10619258 ER PT J AU Veenstra, GJC Destree, OHJ Wolffe, AP AF Veenstra, GJC Destree, OHJ Wolffe, AP TI Translation of maternal TATA-binding protein mRNA potentiates basal but not activated transcription in Xenopus embryos at the midblastula transition SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; HISTONE H2B GENE; MAJOR DEVELOPMENTAL TRANSITION; PROGRAMMED CELL-DEATH; POU-DOMAIN; MESSENGER-RNA; IN-VIVO; CYTOPLASMIC POLYADENYLATION; IMMUNOGLOBULIN GENES; TEMPORAL REGULATION AB Early embryonic development in Xenopus laevis is characterized by transcriptional repression which is relieved at the midblastula stage (MBT). Here we show that the relative abundance of TATA-binding protein (TBP) increases robustly at the MBT and that the mechanism underlying this increase is translation of maternally stored TBP RNA. We show that TBP is rate-limiting in egg extract under conditions that titrate nucleosome assembly. Precocious translation of TBP mRNA in Xenopus embryos facilitates transcription before the MBT, without requiring TBP to be prebound to the promoter before injection. This effect is transient in the absence of chromatin titration and is sustained when chromatin is titrated. These data show that translational regulation of TBP RNA contributes to limitations on the transcriptional capacity before the MBT. Second, we examined the ability of trans-acting factors to contribute to promoter activity before the MBT. Deletion of cia-acting elements does not affect histone H2B transcription in egg extract, a finding indicative of limited trans-activation. Moreover, in the context of the intact promoter, neither the transcriptional activator Oct-1, nor TBP, nor TFIID enable transcriptional activation in vitro. HeLa cell extract, however, reconstitutes activated transcription in mixed extracts. These data suggest a deficiency in egg extract cofactors required far activated transcription. We show that the capacity for activated H2B transcription is gradually acquired at the early gastrula transition. This transition occurs well after the blastula stage when the basal transcription machinery can first be complemented with TBP. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. RI Veenstra, Gert Jan C./D-4963-2012 OI Veenstra, Gert Jan C./0000-0002-7787-4940 NR 63 TC 45 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 7972 EP 7982 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300008 PM 10567523 ER PT J AU Lee, WP Liao, Y Robinson, D Kung, HJ Liu, ET Hung, MC AF Lee, WP Liao, Y Robinson, D Kung, HJ Liu, ET Hung, MC TI Ax1-Gas6 interaction counteracts E1A-mediated cell growth suppression and proapoptotic activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID E1A GENE-PRODUCTS; RECEPTOR TYROSINE KINASES; ADENOVIRUS EARLY REGION-1A; PROTEINS INDUCE APOPTOSIS; ARREST-SPECIFIC GENE-6; OVARIAN-CANCER CELLS; HUMAN TUMOR-CELLS; C-HA-RAS; SURVIVAL ACTIVITIES; IN-VIVO AB The adenovirus type 5 early region 1A gene (E1A) has previously been known as an immortalization oncogene because E1A is required for transforming oncogenes, such as pas and E1B, to transform cells in primary cultures. However, E1A has also been shown to downregulate the overexpression of the Her-2/neu oncogene, resulting in suppression of transformation and tumorigenesis induced by that oncogene. In addition, E1A is able to promote apoptosis induced by anticancer drugs, irradiation, and serum deprivation. Many tyrosine kinases, such as the epidermal growth factor receptor, Her-2/Neu, Src, and Axl, are known to play a role in oncogenic signals in transformed cells. To study the mechanism underlying the E1A-mediated tumor-suppressing function, we exploited a modified tyrosine kinase profile assay (D. Robinson, F. Lee, T. Pretlow, and H.-J. Kung, Proc. Natl. Acad. Sci. USA 93:5958-5962, 1996) to identify potential tyrosine kinases regulated by E1A. Reverse transcription (RT)-PCR products were synthesized with two degenerate primers derived from the conserved motifs of various tyrosine kinases. A tyrosine kinase downregulated by E1A was identified by analyzing the AluI-digested RT-PCR products. We isolated the DNA fragment of interest and found that E1A negatively regulated the expression of the transforming receptor tyrosine kinase Axl at the transcriptional level. To study whether downregulation of the Axl receptor is involved in E1A-mediated growth suppression, we transfected axl cDNA into E1A-expressing cells (ipl-E1A) to establish cells that overexpressed Axl. The Axl ligand Gas6 triggered a greater mitogenic effect in these ip1-E1A-Axl cells than in ipl-E1A control cells and protected the Art-expressing cells from serum deprivation-induced apoptosis. These results indicate that downregulation of the Axl receptor by E1A is involved in E1A-mediated growth suppression and ELA-induced apoptosis and thereby contributes to E1A's antitumor activities. C1 Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Sect Mol Cell Biol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Breast Canc Res Program, Houston, TX 77030 USA. Univ Calif Davis, Sacramento, CA 95817 USA. NCI, Div Clin Sci, Bethesda, MD 20892 USA. RP Hung, MC (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Sect Mol Cell Biol, 1515 Holcombe Blvd,Box 108, Houston, TX 77030 USA. RI Liu, Edison/C-4141-2008; Kung, Hsing-Jien/C-7651-2013 FU NCI NIH HHS [R01CA58880, R01CA77858, R01 CA058880] NR 59 TC 47 Z9 51 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 8075 EP 8082 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300018 PM 10567533 ER PT J AU Jiang, H Lu, HX Schiltz, RL Pise-Masison, CA Ogryzko, VV Nakatani, Y Brady, JN AF Jiang, H Lu, HX Schiltz, RL Pise-Masison, CA Ogryzko, VV Nakatani, Y Brady, JN TI PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL LEUKEMIA-VIRUS; CREB-BINDING-PROTEIN; LONG TERMINAL REPEAT; I TRANSCRIPTIONAL ACTIVATOR; PRIMARY HUMAN-LYMPHOCYTES; 21-BASE-PAIR REPEATS; TYPE-1 TAX; NF-Y; P300/CBP-ASSOCIATED FACTOR; RESPONSIVE ELEMENT AB Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-I LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Tao independent PCAF RAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the RAT activity on the viral long terminal repeat. C1 NCI, Tumor Virus Biol Sect, Lab Receptor Biol & Gene Express, Div Basic Sci,NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. George Washington Univ, GWIBS, Grad Program Genet, Washington, DC 20037 USA. RP Brady, JN (reprint author), NCI, Tumor Virus Biol Sect, Lab Receptor Biol & Gene Express, Div Basic Sci,NIH, Bldg 41,Room B201, Bethesda, MD 20892 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 85 TC 118 Z9 118 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 8136 EP 8145 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300024 PM 10567539 ER PT J AU Sheldon, LA Smith, CL Bodwell, JE Munck, AU Hager, GL AF Sheldon, LA Smith, CL Bodwell, JE Munck, AU Hager, GL TI A ligand binding domain mutation in the mouse glucocorticoid receptor functionally links chromatin remodeling and transcription initiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TUMOR VIRUS PROMOTER; LONG TERMINAL REPEAT; THYROID-HORMONE RECEPTOR; HISTONE ACETYLTRANSFERASE; STEROID-RECEPTORS; GENE ACTIVATION; IN-VIVO; TRANSACTIVATION DOMAIN; ESTROGEN-RECEPTOR; NUCLEAR RECEPTORS AB We utilized the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) in vivo to understand how the interaction of the glucocorticoid receptor (GR) with a nucleosome-assembled promoter allows access of factors required for the transition from a repressed promoter to a derepressed, transcriptionally competent promoter. A mutation (C644G) in the ligand binding domain (LBD) of the mouse GR has provided information regarding the steps required in the derepression/activation process and in the functional significance of the two major transcriptional activation domains, AF1 and AF2. The mutant GR activates transcription from a transiently transfected promoter that has a disordered nucleosomal structure, though significantly less well than the wild-type GR With an integrated, replicated promoter, which is assembled in an ordered nucleosomal array, the mutant GR does not activate transcription, and it fails to induce chromatin remodeling of the MMTV LTR promoter, as indicated by nuclease accessibility assays. Together, these findings support a two-step model for the transition of a nucleosome-assembled, repressed promoter to its transcriptionally active, derepressed form. In addition, we find that the C-terminal GR mutation is dominant over the transcription activation function of the N-terminal GR activation domain. These findings suggest that the primary activation function of the C-terminal activation domain is different from the function of the N-terminal activation domain and that it is required for derepression of the chromatin-repressed MMTV promoter. C1 Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Sheldon, LA (reprint author), Dartmouth Med Sch, Dept Physiol, 750W Borwell,1 Med Ctr Dr, Lebanon, NH 03756 USA. FU NIDDK NIH HHS [DK45337, DK03535] NR 80 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 8146 EP 8157 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300025 PM 10567540 ER PT J AU Pasquet, JM Gross, B Quek, L Asazuma, N Zhang, WG Sommers, CL Schweighoffer, E Tybulewicz, V Judd, B Lee, JR Koretzky, G Love, PE Samelson, LE Watson, SP AF Pasquet, JM Gross, B Quek, L Asazuma, N Zhang, WG Sommers, CL Schweighoffer, E Tybulewicz, V Judd, B Lee, JR Koretzky, G Love, PE Samelson, LE Watson, SP TI LAT is required for tyrosine phosphorylation of phospholipase C gamma 2 and platelet activation by the collagen receptor GPVI SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID T-CELL RECEPTOR; GAMMA-CHAIN; KINASE SYK; 3-KINASE; INTEGRIN; PROTEINS; MEMBRANE; PLC-GAMMA-1; SUBSTRATE; PEPTIDES AB In the present study we have addressed the role of the linker for activation of T cells (LAT) in the regulation of phospholipase C gamma 2 (PLC gamma 2) by the platelet collagen receptor glycoprotein VI (GPVI). LAT is tyrosine phosphorylated in human platelets heavily in response to collagen, collagen-related peptide (CRP), and Fc gamma RIIA cross-linking but only weakly in response to the G-protein-receptor-coupled agonist thrombin. LAT tyrosine phosphorylation is abolished in CRP-stimulated Syk-deficient mouse platelets, whereas it is not altered in SLP-76-deficient mice or Btk-deficient X-linked agammaglobulinemia (XLA) human platelets. Using mice engineered to lack the adapter LAT, we showed that tyrosine phosphorylation of Syk and Btk in response to CRP was maintained in LAT-deficient platelets whereas phosphorylation of SLP-76 was slightly impaired. In contrast, tyrosine phosphorylation of PLC gamma 2 was substantially reduced in LAT-deficient platelets but was not completely inhibited. The reduction in phosphorylation of PLC gamma 2 was associated with marked inhibition of formation of phosphatidic acid, a metabolite of 1,2-diacylglycerol, phosphorylation of pleckstrin, a substrate of protein kinase C, and expression of P-selectin in response to CRP, whereas these parameters were not altered in response to thrombin. Activation of the fibrinogen receptor integrin alpha(IIb)beta(3) in response to CRP was also reduced in LAT-deficient platelets but was not completely inhibited. These results demonstrate that LAT tyrosine phosphorylation occurs downstream of Syk and is independent of the adapter SLP-76, and they establish a major role for LAT in the phosphorylation and activation of PLC gamma 2, leading to downstream responses such as alpha-granule secretion and activation of integrin alpha(IIb)beta(3). The results further demonstrate that the major pathway of tyrosine phosphorylation of SLP-76 is independent of LAT and that there is a minor, LAT-independent pathway of tyrosine phosphorylation of PLC gamma 2. We propose a model in which LAT and SLP-76 are required for PLC gamma 2 phosphorylation but are regulated through independent pathways downstream of Syk. C1 Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. Natl Inst Med Res, Div Cellular Immunol, London NW7 1AA, England. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. NIH, Sect Lymphocyte Signaling, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Pasquet, JM (reprint author), Univ Oxford, Dept Pharmacol, Mansfield Rd, Oxford OX1 3QT, England. RI Watson, Stephen/Q-6292-2016 OI Watson, Stephen/0000-0002-7846-7423 FU Wellcome Trust NR 43 TC 133 Z9 133 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 8326 EP 8334 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300042 PM 10567557 ER PT J AU Li, LW Lorenzo, PS Bogi, K Blumberg, PM Yuspa, SH AF Li, LW Lorenzo, PS Bogi, K Blumberg, PM Yuspa, SH TI Protein kinase C delta targets mitochondria, alters mitochondrial membrane potential, and induces apoptosis in normal and neoplastic keratinocytes when overexpressed by an adenoviral vector SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOUSE EPIDERMAL-CELLS; TYROSINE PHOSPHORYLATION; PROTEOLYTIC ACTIVATION; TUMOR PROMOTERS; HUMAN SKIN; DIFFERENTIATION; EXPRESSION; INDUCTION; ALPHA; GENE AB Inactivation of protein kinase C delta (PKC delta) is associated with resistance to terminal cell death in epidermal tumor cells, suggesting that activation of PKC delta in normal epidermis may be a component of a cell death pathway, To test this hypothesis, we constructed an adenovirus vector carrying an epitope-tagged PKC delta under a cytomegalovirus promoter to overexpress PKC delta in normal and neoplastic keratinocytes, While PKC delta overexpression was detected by immunoblotting in keratinocytes, the expression level of other PKC isozymes, including PKC alpha, PKC epsilon, PKC zeta, and PRC eta, did not change, Calcium-independent PKC-specific kinase activity increased after infection of keratinocytes with the PKC delta adenovirus, Activation of PKC delta by 12-O-tetradecanoylphorbol-13-acetate (TPA) at a nanomolar concentration was lethal to normal and neoplastic mouse and human keratinocytes overexpressing PKC delta. Lethality was inhibited by PKC selective inhibitors, GF109203X and Ro-32-0432, TPA-induced cell death was apoptotic as evidenced by morphological criteria, TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay, DNA fragmentation, and increased caspase activity. Subcellular fractionation indicated that PKC delta translocated to a mitochondrial enriched fraction after TPA activation, and this finding was confirmed by confocal microscopy of cells expressing a transfected PKC delta-green fluorescent protein fusion protein, Furthermore, activation of PKC delta in keratinocytes altered mitochondrial membrane potential, as indicated by rhodamine-123 fluorescence. Mitochondrial inhibitors, rotenone and antimycin A reduced TPA-induced cell death in PKC delta-overexpressing keratinocytes. These results indicate that PKC delta can initiate a death pathway in keratinocytes that involves direct interaction with mitochondria and alterations of mitochondrial function. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, Bldg 27,Rm 3B25,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 51 TC 236 Z9 239 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1999 VL 19 IS 12 BP 8547 EP 8558 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257KP UT WOS:000083781300064 PM 10567579 ER PT J AU Silberman, JD Clark, CG Diamond, LS Sogin, MS AF Silberman, JD Clark, CG Diamond, LS Sogin, MS TI Phylogeny of the genera Entamoeba and Endolimax as deduced from small-subunit ribosomal RNA sequences SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE Entamoebidae; Entamoeba; Endolimax; 16S-like; rDNA; phylogeny; evolution ID MOLECULAR SYSTEMATICS; EVOLUTION; MITOCHONDRIA; HISTOLYTICA; EUKARYOTES; LIKELIHOOD; TREE; PERSPECTIVE; POSITION; PROTOZOA AB We sequenced small-subunit ribosomal RNA genes (16S-like rDNAs) of 10 species belonging to the genera Entamoeba and Endolimax. This study was undertaken to (1) resolve the relationships among the major lineages of Entamoeba previously identified by riboprinting; (2) examine the validity of grouping the genera Entamoeba and Endolimax in the same family, the Entamoebidae; and (3) examine how different models of nucleotide evolution influence the position of Entamoeba in eukaryotic phylogenetic reconstructions. The results obtained with distance, parsimony, and maximum-likelihood analyses support monophyly of the genus Entamoeba and are largely in accord with riboprinting results. Species of Entamoeba producing cysts with the same number of nuclei form monophyletic groups. The most basal Entamoeba species are those that produce cysts with eight nuclei, while the group producing four-nucleated cysts is most derived. Most phylogenetic reconstructions support monophyly of the Entamoebidae. In maximum-likelihood and parsimony analyses, Endolimax is a sister taxon to Entamoeba, while in some distance analyses, it represents a separate lineage. The secondary loss of mitochondria and other organelles from these genera is confirmed by their relatively late divergence in eukaryotic 16S-like rDNA phylogenies. Finally, we show that the positions of some (fast-evolving) eukaryotic lineages are uncertain in trees constructed with models that make corrections for among-site rate variation. C1 Marine Biol Lab, Josephine Bay Paul Ctr Comp Mol Biol & Evolut, Woods Hole, MA 02543 USA. London Sch Hyg & Trop Med, Dept Infect & Trop Med, London WC1, England. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Sogin, MS (reprint author), Marine Biol Lab, Josephine Bay Paul Ctr Comp Mol Biol & Evolut, 7 MBL St, Woods Hole, MA 02543 USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 FU NIGMS NIH HHS [GM32964] NR 45 TC 68 Z9 73 U1 0 U2 2 PU SOC MOLECULAR BIOLOGY EVOLUTION PI LAWRENCE PA PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD DEC PY 1999 VL 16 IS 12 BP 1740 EP 1751 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 263WF UT WOS:000084147700009 PM 10605115 ER PT J AU Cabaniols, JP Ravichandran, V Roche, PA AF Cabaniols, JP Ravichandran, V Roche, PA TI Phosphorylation of SNAP-23 by the novel kinase SNAK regulates t-SNARE complex assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID APICAL PLASMA-MEMBRANE; EPITHELIAL-CELLS; FUSION; PROTEIN; TRAFFICKING; PALMITOYLATION; SYNTAXIN-4; MACHINERY; BINDING; PATHWAY AB The docking and fusion of cargo-containing vesicles with target membranes of eukaryotic cells is mediated by the interaction of SNARE proteins present on both vesicle;and target membranes. In many cases, the target membrane SNARE, or t-SNARE,exists as a complex of syntaxin with a member of the SNAP-25 family of palmitoylated proteins. We have identified a novel human kinase SNAK (SNARE kinase) that specifically phosphorylates the nonneuronal t-SNARE SNAP-23 in vivo. Interestingly, only SNAP-23 that:is not assembled into t-SNARE complexes is phosphorylated by SNAK, and phosphorylated SNAP-23 resides exclusively in the cytosol. Coexpression with SNAK significantly enhances-the stability of unassembled SNAP-23, and as a consequence, the assembly of newly synthesized SNAP-23 with syntaxin is augmented. These;data demonstrate that phosphorylation of SNAP-23 by,SNAK enhances the kinetics of t-SNARE assembly in vivo. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 35 TC 26 Z9 27 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1999 VL 10 IS 12 BP 4033 EP 4041 PG 9 WC Cell Biology SC Cell Biology GA 263VX UT WOS:000084146900004 PM 10588641 ER PT J AU Kingsley, DH Behbahani, A Rashtian, A Blissard, GW Zimmerberg, J AF Kingsley, DH Behbahani, A Rashtian, A Blissard, GW Zimmerberg, J TI A discrete stage of baculovirus GP64-mediated membrane fusion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID NUCLEAR POLYHEDROSIS-VIRUS; GP64 ENVELOPE GLYCOPROTEIN; LEUCINE-ZIPPER MOTIF; HEMAGGLUTININ SURFACE-DENSITY; PREDICTING COILED COILS; INFLUENZA HEMAGGLUTININ; CELL-FUSION; POTENT INHIBITORS; SYNTHETIC PEPTIDE; VIRAL FUSION AB Viral: fusion protein trimers can play a critical role in. limiting lipids in membrane fusion. Because the trimeric oligomer of many viral fusion proteins is often stabilized by hydrophobic 4-3 heptad repeats, higher-order oligomers might be stabilized by similar sequences. There is a hydrophobic;4-3 heptad repeat contiguous to a putative oligomerization domain of Autographa californica multicapsid nucleopolyhedrovirus envelope glycoprotein GP64. We performed mutagenesis and peptide inhibition studies to determine if this sequence might play a role in catalysis of membrane fusion. First, leucine-to-alanine mutants within and flanking the amino terminus of the hydrophobic 4-3 heptad repeat motif that oligomerize into trimers and traffic to insect Sf9 cell surfaces were identified. These mutants retained their wild-type conformation at neutral pH and changed conformation in acidic conditions, as judged by the reactivity of a conformationally sensitive mAb. These mutants, however, were defective for membrane fusion. Second, a peptide encoding the portion flanking the GP64 hydrophobic 4-3 heptad repeat was synthesized. Adding peptide led to inhibition of membrane fusion, which occurred only when the peptide was present during low pH application. The presence of peptide during low pH application did not prevent low pH-induced conformational changes, as determined by the loss of-a conformationally sensitive epitope. In control experiments, a peptide of identical composition but different sequence, or a peptide encoding a portion of the Ebola GP heptad motif,had no effect on GP64-mediated fusion. Furthermore, when the hemagglutinin (X31 strain) fusion protein of influenza was functionally expressed in Sf9 cells, no effect on hemagglutinin-mediated fusion was observed, suggesting that the: peptide does not exert nonspecific effects on other fusion proteins or cell membranes. Collectively, these studies suggest that the specific peptide sequences of GP64 that are adjacent to and: include portions of the hydrophobic 4-3 heptad repeat play a dynamic role in membrane fusion at a stage that is downstream of the initiation of protein conformational changes but upstream of lipid mixing. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RI Blissard, Gary/H-5544-2012; OI Blissard, Gary/0000-0001-9228-567X FU NIAID NIH HHS [R01 AI033657] NR 73 TC 41 Z9 44 U1 1 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1999 VL 10 IS 12 BP 4191 EP 4200 PG 10 WC Cell Biology SC Cell Biology GA 263VX UT WOS:000084146900015 PM 10588652 ER PT J AU Steinert, PM Marekov, LN AF Steinert, PM Marekov, LN TI Initiation of assembly of the cell envelope barrier structure of stratified squamous epithelia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PROLINE-RICH PROTEINS; KERATIN INTERMEDIATE FILAMENTS; HUMAN EPIDERMAL-KERATINOCYTES; CROSS-LINKED ENVELOPE; CORNIFIED ENVELOPE; DIFFERENTIAL EXPRESSION; HUMAN LORICRIN; INVOLUCRIN; LINKING; PRECURSOR AB The cell envelope (CE) is a specialized structure that is important for barrier function in terminally differentiated stratified squamous epithelia. The CE is formed inside the plasma membrane and becomes insoluble as a result of cross-linking of constituent proteins by isopeptide bonds formed by transglutaminases. To investigate the earliest:stages of assembly of the CE, we have studied human epidermal keratinocytes induced to terminally differentiate in submerged liquid culture as a model system for epithelia in general. CEs were harvested from 2-, 3-, 5-, or 7-d cultured cells and examined by 1) immunogold electron microscopy-using antibodies to known CE or other junctional proteins and 2) amino acid sequencing of cross-linked peptides derived by proteolysis of CEs. Our data document that CE assembly is initiated: along the plasma membrane between desmosomes by head-to-tail and head-to-head cross-linking of involucrin to itself and to envoplakin and perhaps periplakin. Essentially only one lysine and two glutamine residues of involucrin and two glutamines of envoplakin were used initially. In CEs of 3-d cultured cells, involucrin, envoplakin, and small proline-rich proteins were physically located at desmosomes and had become cross-linked to desmoplakin, and in 5-d CEs, these. three proteins had formed a continuous layer extending uniformly along the cell periphery. By this time >15 residues of involucrin were used for cross-linking. The CEs of 7-d cells contain significant amounts of the protein loricrin, typically expressed at a later stage of CE assembly. Together, these data stress the importance of juxtaposition of membranes, transglutaminases, and involucrin and envoplakin in the, initiation of CE assembly of stratified squamous epithelia. C1 NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMSD, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 59 TC 99 Z9 100 U1 0 U2 5 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1999 VL 10 IS 12 BP 4247 EP 4261 PG 15 WC Cell Biology SC Cell Biology GA 263VX UT WOS:000084146900019 PM 10588656 ER PT J AU Karas, M Zaks, TZ Liu, JL LeRoithe, D AF Karas, M Zaks, TZ Liu, JL LeRoithe, D TI T cell receptor-induced activation and apoptosis in cycling human T cells occur throughout the cell cycle SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; FAS-MEDIATED APOPTOSIS; (CD95)-MEDIATED APOPTOSIS; DIVISION CYCLE; LEUKEMIC-CELLS; S-PHASE; DEATH; ANTIGEN; LIGAND; P53 AB Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, most of the studies used potentially toxic pharmacological agents for cell cycle synchronization. A panel of human melanoma tumor-reactive T cell lines, a CD8 + HER-2/neu-reactive T cell clone, and the leukemic T cell line Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0-G1, S, and G2-M phases of:the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca2+ flux, cytolytic recognition of tumor targets, and induction of Fas Ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell-cycle. C1 NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Karas, M (reprint author), NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. NR 59 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD DEC PY 1999 VL 10 IS 12 BP 4441 EP 4450 PG 10 WC Cell Biology SC Cell Biology GA 263VX UT WOS:000084146900032 PM 10588669 ER PT J AU Eliceiri, BP Paul, R Schwartzberg, PL Hood, JD Leng, J Cheresh, DA AF Eliceiri, BP Paul, R Schwartzberg, PL Hood, JD Leng, J Cheresh, DA TI Selective requirement for Src kinases during VEGF-induced angiogenesis and vascular permeability SO MOLECULAR CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TYROSINE KINASES; C-SRC; INTEGRIN ALPHA(V)BETA(3); SIGNAL-TRANSDUCTION; NITRIC-OXIDE; MICE; CELLS; EXPRESSION; INHIBITION AB Src kinase activity was found to protect endothelial cells from apoptosis during vascular endothelial growth factor (VEGF)-, but not basic fibroblast growth factor (bFGF)-, mediated angiogenesis in chick embryos and mice. In fact, retroviral targeting of kinase-deleted Src to tumor-associated blood vessels suppressed angiogenesis and the growth of a VEGF-producing tumor. Although mice lacking individual Src family kinases (SFKs) showed normal angiogenesis, mice deficient in pp60(c-src) or pp62(c-yes) showed no VEGF-induced vascular permeability (VP), yet fyn(-/-) mice displayed normal VP. In contrast, inflammation-mediated VP appeared normal in Src-deficient mice. Therefore, VEGF-, but not bFGF-, mediated angiogenesis requires SFK activity in general, whereas the VP activity of VEGF specifically depends on the SFKs, Src, or Yes. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Vasc Biol, La Jolla, CA 92037 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Cheresh, DA (reprint author), Scripps Res Inst, Dept Immunol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. FU NCI NIH HHS [1T32CA75924, CA50286]; NHLBI NIH HHS [1F32HL09435] NR 41 TC 521 Z9 535 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1999 VL 4 IS 6 BP 915 EP 924 DI 10.1016/S1097-2765(00)80221-X PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 269PC UT WOS:000084485900004 PM 10635317 ER PT J AU Levkowitz, G Waterman, H Ettenberg, SA Katz, M Tsygankov, AY Alroy, I Lavi, S Iwai, K Reiss, Y Ciechanover, A Lipkowitz, S Yarden, Y AF Levkowitz, G Waterman, H Ettenberg, SA Katz, M Tsygankov, AY Alroy, I Lavi, S Iwai, K Reiss, Y Ciechanover, A Lipkowitz, S Yarden, Y TI Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1 SO MOLECULAR CELL LA English DT Article ID C-CBL PROTOONCOGENE; FACTOR-RECEPTOR; EGF RECEPTOR; IN-VITRO; KINASE; PATHWAY; DEGRADATION; REGULATOR; PROTEIN; IDENTIFICATION AB Receptor desensitization is accomplished by accelerated endocytosis and degradation of ligand-receptor complexes. An in vitro reconstituted system indicates that Cbl adaptor proteins directly control downregulation of the receptor for the epidermal growth factor (EGFR) by recruiting ubiquitin-activating and -conjugating enzymes. We infer a sequential process initiated by autophosphorylation of EGFR at a previously identified lysosome-targeting motif that subsequently recruits Cbl. This is followed by tyrosine phosphorylation of c-Cbl at a site flanking its RING finger, which enables receptor ubiquitination and degradation. Whereas ail three members of the Cbl family can enhance ubiquitination, two oncogenic Cbl variants, whose RING fingers are defective and phosphorylation sites are missing, are unable to desensitize EGFR. Our study identifies Cbl proteins as components of the ubiquitin ligation machinery and implies that they similarly suppress many other signaling pathways. C1 Weizmann Inst Sci, Dept Regulat Biol, IL-76100 Rehovot, Israel. Tel Aviv Univ, George S Wise Fac Life Sci, Dept Biochem, IL-69978 Ramat Aviv, Israel. Technion Israel Inst Technol, Bruce Rappaport Fac Med, Dept Biochem, IL-31096 Haifa, Israel. Kyoto Univ, Dept Immunol & Cell Biol, Sankyu Ku, Kyoto 6068501, Japan. Natl Canc Inst, Med Branch, Bethesda, MD 20889 USA. Uniformed Serv Univ Hlth Sci, Mol & Cel Biol Program, Bethesda, MD 20889 USA. Temple Univ, Sch Med, Dept Microbiol & Immunol, Philadelphia, PA 19140 USA. RP Yarden, Y (reprint author), Weizmann Inst Sci, Dept Regulat Biol, 1 Hertzel St, IL-76100 Rehovot, Israel. RI YARDEN, YOSEF/K-1467-2012; OI Levkowitz, Gil/0000-0002-3896-1881 FU NCI NIH HHS [CA72981, CA78499] NR 44 TC 686 Z9 703 U1 1 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD DEC PY 1999 VL 4 IS 6 BP 1029 EP 1040 DI 10.1016/S1097-2765(00)80231-2 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 269PC UT WOS:000084485900014 PM 10635327 ER PT J AU Johnson, WE Slattery, JP Eizirik, E Kim, JH Raymond, MM Bonacic, C Cambre, R Crawshaw, P Nunes, A Seuanez, HN Moreira, MAM Seymour, KL Simon, F Swanson, W O'Brien, SJ AF Johnson, WE Slattery, JP Eizirik, E Kim, JH Raymond, MM Bonacic, C Cambre, R Crawshaw, P Nunes, A Seuanez, HN Moreira, MAM Seymour, KL Simon, F Swanson, W O'Brien, SJ TI Disparate phylogeographic patterns of molecular genetic variation in four closely related South American small cat species SO MOLECULAR ECOLOGY LA English DT Article DE conservation genetics; evolution; microsatellites; mitochondrial DNA; phylogeography; South American felids ID MITOCHONDRIAL-DNA; PHYLOGENETIC RECONSTRUCTION; RIBOSOMAL-RNA; DOMESTIC CAT; FELIDAE; SEQUENCES; MICROSATELLITES; CHROMOSOME; EVOLUTION; RODENTS AB Tissue specimens from four species of Neotropical small cats (Oncifelis geoffroyi, N = 38; O. guigna, N = 6; Leopardus tigrinus, N = 32; Lynchailurus colocolo, N = 22) collected from throughout their distribution were examined for patterns of DNA sequence variation using three mitochondrial genes, 16S rRNA, ATP8, and NADH-5. Patterns between and among O. guigna and O. geoffroyi individuals were assessed further from size variation at 20 microsatellite loci. Phylogenetic analyses using mitochondrial DNA sequences revealed monophyletic clustering of the four species, plus evidence of natural hybridization between L. tigrinus and L. colocolo in areas of range overlap and discrete population subdivisions reflecting geographical isolation. Several commonly accepted subspecies partitions were affirmed for L. colocolo, but not for O. geoffroyi. The lack of geographical substructure in O. geoffroyi was recapitulated with the microsatellite data, as was the monophyletic clustering of O. guigna and O. geoffroyi individuals. L. tigrinus forms two phylogeographic clusters which correspond to L.t. oncilla (from Costa Rica) and L.t. guttula (from Brazil) and which have mitochondrial DNA (mtDNA) genetic distance estimates comparable to interspecific values between other ocelot lineage species. Using feline-specific calibration rates for mitochondrial DNA mutation rates, we estimated that extant lineages of O. guigna diverged 0.4 million years ago (Ma), compared with 1.7 Ma for L. colocolo, 2.0 Ma for O. geoffroyi, and 3.7 Ma for L. tigrinus. C1 NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. Univ Catolica, Dept Ingn Forestal, Santiago, Chile. Smithsonian Inst, Natl Zool Pk, Dept Anim Hlth, Washington, DC 20008 USA. CENAP, IBAMA, Sorocaba, Brazil. Zoo Municipal Sorocaba, Sorocaba, Brazil. Inst Nacl Canc, Serv Pesquisa Basica, Rio De Janeiro, Brazil. Royal Ontario Museum, Dept Palaeobiol, Toronto, ON M5S 2C6, Canada. Parque Zool Sao Paulo, Sao Paulo, Brazil. Cincinnati Zoo & Bot Garden, Cincinnati, OH 45267 USA. RP Johnson, WE (reprint author), NCI, Lab Genom Divers, Ft Detrick, MD 21702 USA. EM johnsonw@ncifcrf.gov RI Eizirik, Eduardo/K-8034-2012; Johnson, Warren/D-4149-2016 OI Eizirik, Eduardo/0000-0002-9658-0999; Johnson, Warren/0000-0002-5954-186X NR 52 TC 28 Z9 34 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1083 EI 1365-294X J9 MOL ECOL JI Mol. Ecol. PD DEC PY 1999 VL 8 IS 12 SU 1 BP S79 EP S94 DI 10.1046/j.1365-294X.1999.00796.x PG 16 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 291MB UT WOS:000085737800009 PM 10703553 ER PT J AU Nystrom, FH Chen, H Cong, LN Li, YH Quon, MJ AF Nystrom, FH Chen, H Cong, LN Li, YH Quon, MJ TI Caveolin-1 interacts with the insulin receptor and can differentially modulate insulin signaling in transfected Cos-7 cells and rat adipose cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ONCOGENICALLY TRANSFORMED-CELLS; NATURALLY-OCCURRING MUTATIONS; TYROSINE KINASE DOMAIN; EPITOPE-TAGGED GLUT4; PROTEIN-KINASE; STIMULATED TRANSLOCATION; CRYSTAL-STRUCTURE; PLASMA-MEMBRANE; UP-REGULATION; CANCER-CELLS AB Caveolae may function as microdomains for signaling that help to determine specific biological actions mediated by the insulin receptor (IR). Caveolin-1, a major component of caveolae, contains a scaffolding domain (SD) that binds to a caveolin-1 binding motif in the kinase domain of the in in vitro. To investigate the potential role of caveolin-1 in insulin signaling we overexpressed wild-type (Cav-WT) or mutant (Cav-Mut; F92A/V94A in SD) caveolin-1 in either Cos-7 cells cotransfected with in or rat adipose cells (low and high levels of endogenous caveolin-1, respectively). Cav-WT coimmunoprecipitated with the in to a much greater extent than Cav-Mut, suggesting that the SD is important for interactions between caveolin-1 and the in in intact cells. We also constructed several in mutants with a disrupted caveolin-1 binding motif and found that these mutants were poorly expressed and did not undergo autophosphorylation. Interestingly, overexpression of Cav-WT in Cos-7 cells significantly enhanced insulin-stimulated phosphorylation of Elk-l (a mitogen-activated protein kinase-dependent pathway) while overexpression of Cav-Mut was without effect. In contrast, in adipose cells, overexpression of either Cav-WT or Cav-Mut did not affect insulin-stimulated phosphorylation of a cotransfected ERK2 (but did significantly inhibit basal phosphorylation of ERK2). Furthermore, we also observed a small inhibition of insulin-stimulated translocation of GLUT4 when either Cav-WT or Cav-Mut was overexpressed in adipose cells. Thus, interaction of caveolin-1 with ins may differentially modulate insulin signaling to enhance insulin action in Cos-7 cells but inhibit insulin's effects in adipose cells. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NHLBI, Hypertens Endocrine Branch, NIH, Bldg 10,Room 8C-103,10 Ctr Dr MSC 1754, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Nystrom, Fredrik/0000-0002-1680-1000; Quon , Michael /0000-0002-5289-3707 NR 46 TC 123 Z9 126 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1999 VL 13 IS 12 BP 2013 EP 2024 DI 10.1210/me.13.12.2013 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 262XM UT WOS:000084093600004 PM 10598578 ER PT J AU Szapary, D Huang, Y Simons, SS AF Szapary, D Huang, Y Simons, SS TI Opposing effects of corepressor and coactivators in determining the dose-response curve of agonists, and residual agonist activity of antagonists, for glucocorticoid receptor-regulated gene expression SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID THYROID-HORMONE RECEPTOR; HUMAN PROGESTERONE-RECEPTOR; CARBOXYL-TERMINAL REGIONS; HUMAN ESTROGEN-RECEPTOR; STEROID-BINDING DOMAIN; TUMOR VIRUS TEMPLATES; NUCLEAR-RECEPTOR; TRANSCRIPTIONAL COACTIVATOR; N-COR; HISTONE ACETYLTRANSFERASE AB A distinguishing, but unexplained, characteristic of steroid hormone action is the dose-response curve for the regulation of gene expression. We have previously reported that the dose-response curve for glucocorticoid induction of a transfected reporter gene in CV-1 and HeLa cells is repositioned in the presence of increasing concentrations of glucocorticoid receptors (GRs). This behavior is now shown to be independent of the reporter, promoter, or enhancer, consistent with our proposal that a transacting factor(s) was being titrated by added receptors. Candidate factors have been identified by the observation that changes in glucocorticoid induction parameters in CV-1 cells could be reproduced by varying the cellular levels of coactivators [transcriptional intermediary factor 2 (TIF2), steroid receptor coactivator 1 (SRC-1), and amplified in breast cancer 1 (AIB1)], comodulator [CREB-binding protein (CBP)], or corepressor [silencing mediator for retinoid and thyroid-hormone receptors (SMRT)] without concomitant increases in on. Significantly, the effects of TIF2 and SMRT were mutually antagonistic. Similarly, additional SMRT could reverse the action of increased levels of GRs in HeLa cells, thus indicating that the effects of cofactors on transcription may be general for GR in a variety of cells. These data further indicate that GRs are yet an additional target of the corepressor SMRT. At the same time, these cofactors were found to be capable of regulating the level of residual agonist activity displayed by antiglucocorticoids. Finally, these observations suggest that a novel role for cofactors is to participate in processes that determine the dose-response curve, and partial agonist activity, of OR-steroid complexes. This new activity of cofactors is disconnected from their ability to increase or decrease GR transactivation. An equilibrium model is proposed in which the ratio of coactivator-corepressor bound to either receptor-agonist or -antagonist complexes regulates the final transcriptional properties. C1 NIDDKD, Steroid Hormones Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDKD, Steroid Hormones Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov NR 90 TC 103 Z9 103 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1999 VL 13 IS 12 BP 2108 EP 2121 DI 10.1210/me.13.12.2108 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 262XM UT WOS:000084093600011 PM 10598585 ER PT J AU Lavoie, TB Mohan, S Lipschultz, CA Grivel, JC Li, Y Mainhart, CR Kam-Morgan, LNW Drohan, WN Smith-Gill, SJ AF Lavoie, TB Mohan, S Lipschultz, CA Grivel, JC Li, Y Mainhart, CR Kam-Morgan, LNW Drohan, WN Smith-Gill, SJ TI Structural differences among monoclonal antibodies with distinct fine specificities and kinetic properties SO MOLECULAR IMMUNOLOGY LA English DT Article DE antigen binding; antigen-antibody interactions; antibodies; binding kinetics; affinity maturation ID SITE-DIRECTED MUTAGENESIS; SURFACE-PLASMON RESONANCE; IMMUNOGLOBULIN-VH GENES; IMMUNE-RESPONSE; SOMATIC MUTATION; VARIABLE REGION; B-CELLS; MOLECULAR CHARACTERIZATION; BINDING-AFFINITY; CHICKEN LYSOZYME AB The mAbs HyHEL-8, HyHEL-26 (HH8, and HH26, respectively) recognize epitopes on hen egg-white lysozyme (HEL) highly overlapping with the structurally defined HH10 epitope, while the structurally related XRPC-25 is specific for DNP and does not bind HEL. All four Abs appear to use the same V(k)23 germ line gene, and all but HH8 use the same V(H)36-60 germ line gene. Of the three anti-MEL Abs, the sequences of HH26 variable regions are closest to those encoded by the respective germ line sequences. HH8 utilizes a different member of the V(H)36-60 gene family. Thus, the same V-k and V-H genes, combined with somatically derived sequence differences, are used to recognize the unrelated Ags HEL and DNP. In contrast, different V(H)36-60 germ line genes are used to bind the same antigen (e.g. HH8 vs HM10 and HH26). While the affinities of HH10, HH8, and HH26 for HEL vary by less than 10-fold, their affinities for mutated Ag vary over several orders of magnitude. Analyses of Fab binding kinetics with natural species variants and site-directed mutants of lysozyme indicate that these cross-reactivity differences reflect the relative sensitivities of both the association and dissociation rates to antigenic mutation: HH8 has relatively mutation-insensitive association and dissociation rates, HH10 has a relatively mutation-sensitive association rate but more variable dissociation rates, and HH26 has variable association and dissociation rates. Only a few amino acid differences among the antibodies produce the observed differences in the robustness of the association and dissociation rates. Our results suggest that association and dissociation rates and mutation sensitivity of these rates may be independently modulated during antibody repertoire development. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD 21702 USA. Univ Maryland, Dept Zool, College Pk, MD 20742 USA. Lab Corp Amer, Dept Mol Oncol & Genet, Res Triangle Pk, NC 27709 USA. Amer Red Cross, Plasma Derivat Lab, Rockville, MD 20855 USA. RP Smith-Gill, SJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, POB B,Bldg 469,Room 206, Frederick, MD 21702 USA. EM smithgil@helix.nih.gov NR 80 TC 28 Z9 28 U1 0 U2 1 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 DEC PY 1999 VL 36 IS 17 BP 1189 EP 1205 DI 10.1016/S0161-5890(99)00130-3 PG 17 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 283VT UT WOS:000085297300007 PM 10698321 ER PT J AU Berger, O Gan, XH Gujuluva, C Burns, AR Sulur, G Stins, M Way, D Witte, M Weinand, M Said, J Kim, KS Taub, D Graves, MC Fiala, M AF Berger, O Gan, XH Gujuluva, C Burns, AR Sulur, G Stins, M Way, D Witte, M Weinand, M Said, J Kim, KS Taub, D Graves, MC Fiala, M TI CXC and CC chemokine receptors on coronary and brain endothelia SO MOLECULAR MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOW-DENSITY-LIPOPROTEIN; INFLAMMATORY CYTOKINES; HIV-1 INFECTION; CO-RECEPTORS; TNF-ALPHA; CELLS; EXPRESSION; CORECEPTORS; BETA AB Background: Chemokine receptors on leukocytes play a key role in inflammation and HIV-1 infection. Chemokine receptors on endothelia may serve an important role in HIV-1 tissue invasion and angiogenesis. Materials and Methods: The expression of chemokine receptors in human brain microvascular endothelial cells (BMVEC) and coronary artery endothelial cells (CAEC) in vitro and cryostat sections of the heart tissue was determined by light and confocal microscopy and now cytometry with monodonal antibodies. Chemotaxis of endothelia by CC chemokines was evaluated in a transmigration assay. Results: In BMVEC, the chemokine receptors CCR3 and CXCR4 showed the strongest expression. CXCR4 was localized by confocal microscopy to both the cytoplasm and the plasma membrane of BMVEC. In CAEC, CXCR4 demonstrated a strong expression with predominantly periplasmic localization. CCR5 expression was detected both in BMVEC and CAEC but at a lower level. Human strongly CXCR4 but only weakly CCR3 and CCRS5. Two additional CC chemokines, CCR2A and CCR4, were detected in BMVEC and CAEC by immunostaining. Immunocytochemistry of the heart tissues with monoclonal antibodies revealed a high expression of CXCR4 and CCR2A and a low expression of CCR3 and CCR5 on coronary vessel endothelia. Coronary endothelia showed in vitro a strong chemotactic response to the CC chemokines RANTEs, MIP-1 alpha, and MIP-1 beta. Conclusions: The endothelia isolated from the brain display strongly both the CCR3 and CXCR4 HIV-1 coreceptors, whereas the coronary endothelia express strongly only the CXCR4 coreceptor. CCR5 is expressed at a lower level in both endothelia. The differential display of CCR3 on the brain and coronary endothelia could be significant with respect to the differential susceptibility of the heart and the brain to HIV-1 invasion. In addition, CCR2A is strongly expressed in the heart endothelium. All of the above chemokine receptors could play a role in endothelial migration and repair. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. Baylor Coll Med, Dept Med, Sect Cardiovasc Sci & Leukocyte Biol, Houston, TX 77030 USA. Childrens Hosp Los Angeles, Div Infect Dis, Los Angeles, CA 90027 USA. Univ Arizona, Dept Surg, Tucson, AZ USA. NIA, Baltimore, MD 21224 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. RP Fiala, M (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NHLBI NIH HHS [HL 48493]; NIDA NIH HHS [DA10442]; NINDS NIH HHS [NS 26126] NR 45 TC 89 Z9 98 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD DEC PY 1999 VL 5 IS 12 BP 795 EP 805 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 280CF UT WOS:000085084100003 PM 10666479 ER PT J AU Nahum-Levy, R Fossom, LH Skolnick, P Benveniste, M AF Nahum-Levy, R Fossom, LH Skolnick, P Benveniste, M TI Putative partial agonist 1-aminocyclopropanecarboxylic acid acts concurrently as a glycine-site agonist and a glutamate-site antagonist at N-methyl-D-aspartate receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID KINETIC-ANALYSIS; XENOPUS OOCYTES; BINDING-SITES; CELL-DEATH; MOUSE; ACTIVATION; ISCHEMIA; NEURONS; RAT; DESENSITIZATION AB 1-Aminocyclopropanecarboxylic acid (ACPC) has been shown to protect against neuronal cell death after ischemic insult in vivo. Such results can be correlated with in vitro assays in which ACPC protected neurons against glutamate-induced neurotoxicity by reducing the activity of N-methyl-D-aspartate (NMDA) channel activation. Electrophysiological studies have determined that ACPC inhibits NMDA receptor activity by acting as a glycine-binding site partial agonist. In this study, rapid drug perfusion combined with whole-cell voltage-clamp was used to elicit and measure the effects of ACPC on NMDA receptor-mediated responses from cultured hippocampal neurons and cerebellar granule cells. The ACPC steady-state dose-response curve had both stimulatory and inhibitory phases. Half-maximal activation by ACPC as a glycine-site agonist was 0.7 to 0.9 mu M. Half-maximal inhibition by ACPC was dependent on NMDA concentration. Peak responses to a >100 mu M ACPC pulse in the presence of 1 mu M glutamate were similar to those of glycine but decayed to a steady-state amplitude below that of glycine. The removal of ACPC initially caused an increase in inward current followed by a subsequent decrease to baseline levels. This suggests that relief of low-affinity antagonism occurs before high-affinity agonist dissociation. Simulations of ACPC action by a two glutamate-binding site/two glycine-binding site model for NMDA channel activation in conjunction with the concurrent role of ACPC as a glycine-site full agonist and glutamate-site competitive antagonist were able to successfully approximate experimental results. C1 Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NIDDKD, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Benveniste, M (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. NR 37 TC 27 Z9 28 U1 0 U2 0 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 DEC PY 1999 VL 56 IS 6 BP 1207 EP 1218 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258MC UT WOS:000083842100013 PM 10570048 ER PT J AU Heidel, SM Holston, K Buters, JTM Gonzalez, FJ Jefcoate, CR Czupyrynski, CJ AF Heidel, SM Holston, K Buters, JTM Gonzalez, FJ Jefcoate, CR Czupyrynski, CJ TI Bone marrow stromal cell cytochrome P4501B1 is required for pre-B cell apoptosis induced by 7,12-dimethylbenz[a] anthracene SO MOLECULAR PHARMACOLOGY LA English DT Article ID AROMATIC HYDROCARBON RECEPTOR; THYMOCYTE APOPTOSIS; AH RECEPTOR; IMMUNOSUPPRESSION; GROWTH; MICE; ACTIVATION; EXPOSURE; BENZOPYRENE; LYMPHOPOIESIS AB We previously demonstrated that murine bone marrow stromal cells express high levels of cytochrome P4501B1 (CYP1B1) that metabolizes 7,12-dimethylbenza[a]anthracene (DMBA), and that DMBA activates the Ah receptor (AhR) in these cells in vitro. More recently, we reported that CYP1B1 is required for DMBA-induced lymphoblastoma formation in vivo. In this study, we addressed the hypothesis that bone marrow stromal cell CYP1B1, and not AhR activation, is required for DMBA-induced pre-B-cell apoptosis. Although DMBA did not directly cause apoptosis in pre-B cells, dose-dependent apoptosis of pre-B cells was observed when they were cocultured with a bone marrow stromal cell line. The DMBA 3,4-dihydrodiol metabolite was more potent in effecting pre-B-cell apoptosis than DMBA, whereas the potent AhR agonist 2,3,7,8-tetrachlorod-ibenzo-p-dioxin was inactive. Both pre-B cells and bone marrow stromal cells contained DMBA-diol-epoxide DNA adducts, indicating that reactive metabolites were transferred from stromal cells to pre-B cells. DMBA caused apoptosis when cocultured with primary bone marrow stromal cells isolated from AhR-null mice but not CYP1B1-null mice. When cocultured with AhR-null primary bone marrow stromal cells, DMBA induced approximately 50% of the pre-B-cell apoptosis seen with stromal cells from AhR-heterozygous mice. This reduced level of apoptosis parallels the decreased CYP1B1 expression in AhR-null mouse bone marrow stromal cells. These findings provide convincing evidence that bone marrow stromal cell CYP1B1 metabolism of DMBA, but not AhR activation, is required for DMBA-induced pre-B-cell apoptosis. C1 Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA. Tech Univ Munich, Inst Toxicol & Environm Hlth, D-8000 Munich, Germany. NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Univ Wisconsin, Ctr Environm Toxicol, Madison, WI 53706 USA. RP Czupyrynski, CJ (reprint author), Univ Wisconsin, Dept Pathobiol Sci, 2015 Linden Dr W, Madison, WI 53706 USA. RI Buters, Jeroen/G-5070-2011 FU NCI NIH HHS [CA16265]; NIEHS NIH HHS [ES07015]; PHS HHS [IF32E505827] NR 40 TC 33 Z9 36 U1 0 U2 1 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 DEC PY 1999 VL 56 IS 6 BP 1317 EP 1323 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258MC UT WOS:000083842100025 PM 10570060 ER PT J AU Glass, M Northup, JK AF Glass, M Northup, JK TI Agonist selective regulation of g proteins by cannabinoid CB1 and CB2 receptors SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT CEREBELLAR MEMBRANES; NEUROBLASTOMA-CELLS; GUANINE-NUCLEOTIDES; SIGNAL-TRANSDUCTION; ADENYLATE-CYCLASE; CALCIUM CURRENTS; INVERSE AGONIST; LIGAND-BINDING; MOUSE-BRAIN; INHIBITION AB We have examined the ligand regulation and G protein selectivity of the human cannabinoid CB1 and CB2 receptors by an in situ reconstitution technique directly measuring G protein activation. Membranes from Spodoptera frugiperda cells expressing CB1 and CB2 receptors were chaotrope extracted to denature endogenous GTP-binding proteins. The ability of the receptors to catalyze the GDP-GTP exchange of each G protein was then examined with purified bovine brain G(i) and G(o). Activation of CB1 receptors produced a high-affinity saturable interaction for both G(i) and G(o). Agonist stimulation of CB2 receptors also resulted in a high-affinity saturable interaction with G(i). In contrast, CB2 receptors did not interact efficiently with G(o). G protein activation was then examined with a diverse group of ligands. For the interaction of CB2 receptors with G(i), HU210 was the only compound tested that demonstrated maximal activation. In contrast, WIN55,212 (64%), anandamide (42%), and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) (44%) all initiated submaximal levels of G protein activation. For CB1 receptor-catalyzed activation of G(i), HU210, WIN55,212, and anandamide all elicited maximal activation, whereas Delta(9)-THC (56 +/- 6%) caused only partial G(i) activation. In contrast, only HU210 effected maximal CB1 stimulation of G(o), with anandamide, WIN55,212, and Delta(9)-THC all stimulating between 60 and 75% compared with HU210. These data demonstrate that different agonists induce different conformations of the CB1 receptor, which in turn can distinguish between different G proteins. Our data thus demonstrate agonist-selective G protein signaling by the CB1 receptor and suggest that therapeutic agents may be designed to regulate individual G protein-signaling pathways selectively. C1 NIDODS, Sect Signal Transduct, NIH, Rockville, MD 20850 USA. RP Northup, JK (reprint author), NIDODS, Sect Signal Transduct, NIH, 5 Res Court, Rockville, MD 20850 USA. OI Glass, Michelle/0000-0002-5997-6898 NR 36 TC 166 Z9 177 U1 1 U2 10 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 DEC PY 1999 VL 56 IS 6 BP 1362 EP 1369 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258MC UT WOS:000083842100031 PM 10570066 ER PT J AU Nuckolls, GH Slavkin, HC AF Nuckolls, GH Slavkin, HC TI Paths of glorious proteases SO NATURE GENETICS LA English DT News Item ID DIPEPTIDYL PEPTIDASE-I; UNITED-STATES; GRANZYME-B; EXPRESSION; ACTIVATION; GENERATION; DISEASE C1 NIAMSD, Craniofacial Dev Sect, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Nuckolls, GH (reprint author), NIAMSD, Craniofacial Dev Sect, Bethesda, MD 20892 USA. NR 15 TC 16 Z9 16 U1 0 U2 0 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 DEC PY 1999 VL 23 IS 4 BP 378 EP 380 DI 10.1038/70472 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 261RZ UT WOS:000084023900004 PM 10581013 ER PT J AU Velculescu, VE Madden, SL Zhang, L Lash, AE Yu, J Rago, C Lal, A Wang, CJ Beaudry, GA Ciriello, KM Cook, BP Dufault, MR Ferguson, AT Gao, YH He, TC Hermeking, H Hiraldo, SK Hwang, PM Lopez, MA Luderer, HF Mathews, B Petroziello, JM Polyak, K Zawel, L Zhang, W Zhang, XM Zhou, W Haluska, FG Jen, J Sukumar, S Landes, GM Riggins, GJ Vogelstein, B Kinzler, KW AF Velculescu, VE Madden, SL Zhang, L Lash, AE Yu, J Rago, C Lal, A Wang, CJ Beaudry, GA Ciriello, KM Cook, BP Dufault, MR Ferguson, AT Gao, YH He, TC Hermeking, H Hiraldo, SK Hwang, PM Lopez, MA Luderer, HF Mathews, B Petroziello, JM Polyak, K Zawel, L Zhang, W Zhang, XM Zhou, W Haluska, FG Jen, J Sukumar, S Landes, GM Riggins, GJ Vogelstein, B Kinzler, KW TI Analysis of human transcriptomes SO NATURE GENETICS LA English DT Letter ID GENE-EXPRESSION; SERIAL ANALYSIS; CANCER C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Otolaryngol, Baltimore, MD 21205 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Dept Pathol, Durham, NC 27706 USA. Massachusetts Gen Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Velculescu, VE (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA43460, CA57345, CA62924] NR 11 TC 552 Z9 583 U1 0 U2 7 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 DEC PY 1999 VL 23 IS 4 BP 387 EP 388 DI 10.1038/70487 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 261RZ UT WOS:000084023900009 PM 10581018 ER PT J AU McGuirt, WT Prasad, SD Griffith, AJ Kunst, HPM Green, GE Shpargel, KB Runge, C Huybrechts, C Mueller, RF Lynch, E King, MC Brunner, HG Cremers, CWRJ Takanosu, M Li, SW Arita, M Mayne, R Prockop, DJ Van Camp, G Smith, RJH AF McGuirt, WT Prasad, SD Griffith, AJ Kunst, HPM Green, GE Shpargel, KB Runge, C Huybrechts, C Mueller, RF Lynch, E King, MC Brunner, HG Cremers, CWRJ Takanosu, M Li, SW Arita, M Mayne, R Prockop, DJ Van Camp, G Smith, RJH TI Mutations in COL11A2 cause non-syndromic hearing loss (DFNA13) SO NATURE GENETICS LA English DT Article ID AUTOSOMAL-DOMINANT; STICKLER-SYNDROME; XI COLLAGEN; MOLECULAR HETEROGENEITY; TECTORIAL MEMBRANE; FIBRILLAR COLLAGEN; COCHLEAR PATHOLOGY; II COLLAGEN; GENE; IMPAIRMENT AB We report that mutation of COL11A2 causes deafness previously mapped to the DFNA13 locus on chromosome 6p. We found two families (one American and one Dutch) with autosomal dominant, non-syndromic hearing loss to have mutations in COL11A2 that are predicted to affect the triple-helix domain of the collagen protein. In both families, deafness is non-progressive and predominantly affects middle frequencies. Mice with a targeted disruption of Col11a2 also were shown to have hearing loss. Electron microscopy of the tectorial membrane of these mice revealed loss of organization of the collagen fibrils. Our findings revealed a unique ultrastructural malformation of inner-ear architecture associated with non-syndromic hearing loss, and suggest that tectorial membrane abnormalities may be one aetiology of sensorineural hearing loss primarily affecting the mid-frequencies. C1 Univ Iowa, Dept Otolaryngol Head & Neck Surg, Mol Otolayngol Res Labs, Iowa City, IA 52242 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. Univ Nijmegen Hosp, Dept Otorhinolaryngol, NL-6500 HB Nijmegen, Netherlands. Univ Antwerp, Dept Genet, Antwerp, Belgium. St James Hosp, Dept Clin Genet, Leeds LS9 7TF, W Yorkshire, England. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Med Coll Penn & Hahnemann Univ, Ctr Gene Therapy, Philadelphia, PA USA. RP Smith, RJH (reprint author), Univ Iowa, Dept Otolaryngol Head & Neck Surg, Mol Otolayngol Res Labs, Iowa City, IA 52242 USA. RI Kunst, Henricus/J-6456-2012; Van Camp, Guy/F-3386-2013; Brunner, Han/C-9928-2013; Cremers, C.W.R.J./L-4254-2015 OI Van Camp, Guy/0000-0001-5105-9000; FU NIDCD NIH HHS [5-T32-DC00040, R01-DC03544, Z01-DC00054-01] NR 38 TC 149 Z9 158 U1 1 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 DEC PY 1999 VL 23 IS 4 BP 413 EP 419 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 261RZ UT WOS:000084023900015 PM 10581026 ER PT J AU Hemmer, B Gran, B Zhao, YD Marques, A Pascal, J Tzou, A Kondo, T Cortese, I Bielekova, B Straus, SE McFarland, HF Houghten, R Simon, R Pinilla, C Martin, R AF Hemmer, B Gran, B Zhao, YD Marques, A Pascal, J Tzou, A Kondo, T Cortese, I Bielekova, B Straus, SE McFarland, HF Houghten, R Simon, R Pinilla, C Martin, R TI Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease SO NATURE MEDICINE LA English DT Article ID PEPTIDE COMBINATORIAL LIBRARIES; MYELIN BASIC-PROTEIN; BORRELIA-BURGDORFERI; TREATMENT-RESISTANT; ANTIGEN RECOGNITION; AMINOPEPTIDASE-A; CLONING; EXPRESSION; ARTHRITIS; RECEPTOR AB Elucidating the cellular immune response to infectious agents is a prerequisite for understanding disease pathogenesis and designing effective vaccines. In the identification of microbial T-cell epitopes, the availability of purified or recombinant bacterial proteins has been a chief limiting factor. In chronic infectious diseases such as Lyme disease, immune-mediated damage may add to the effects of direct infection by means of molecular mimicry to tissue autoantigens. Here, we describe a new method to effectively identify both microbial epitopes and candidate autoantigens. The approach combines data acquisition by positional scanning peptide combinatorial libraries and biometric data analysis by generation of scoring matrices. In a patient with chronic neuroborreliosis, we show that this strategy leads to the identification of potentially relevant T-cell targets derived from both Borrelia burgdorferi and the host. We also found that the antigen specificity of a single T-cell clone can be degenerate and yet the clone can preferentially recognize different peptides derived from the same organism, thus demonstrating that flexibility in T-cell recognition does not preclude specificity. This approach has potential applications in the identification of ligands in infectious diseases, tumors and autoimmune diseases. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Invest, NIH, Rockville, MD 20892 USA. Mixtures Sci, San Diego, CA 92121 USA. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. Univ Marburg, Dept Neurol, D-35039 Marburg, Germany. RP Pinilla, C (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr DR MSC 1400, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 56 TC 160 Z9 161 U1 2 U2 6 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 DEC PY 1999 VL 5 IS 12 BP 1375 EP 1382 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 262DE UT WOS:000084049700036 PM 10581079 ER PT J AU Romanski, LM Tian, B Fritz, J Mishkin, M Goldman-Rakic, PS Rauschecker, JP AF Romanski, LM Tian, B Fritz, J Mishkin, M Goldman-Rakic, PS Rauschecker, JP TI Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex SO NATURE NEUROSCIENCE LA English DT Article ID POSTERIOR PARIETAL CORTEX; SUPERIOR TEMPORAL SULCUS; RHESUS-MONKEY; MACAQUE MONKEYS; FRONTAL-CORTEX; TONOTOPIC ORGANIZATION; CORTICAL CONNECTIONS; FUNCTIONAL MRI; COMPLEX SOUNDS; MEMORY AB 'What' and 'where' visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory-prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. C1 Yale Univ, Sch Med, New Haven, CT 06510 USA. Georgetown Univ, Med Ctr, Georgetown Inst Cognit & Computat Sci, Washington, DC 20007 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Romanski, LM (reprint author), Yale Univ, Sch Med, B 413 SHM,333 Cedar St, New Haven, CT 06510 USA. RI Rauschecker, Josef/A-4120-2013 FU NIDCD NIH HHS [R01 DC004845, R01 DC004845-01]; NIMH NIH HHS [R01 MH038546-21] NR 50 TC 647 Z9 657 U1 4 U2 27 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 DEC PY 1999 VL 2 IS 12 BP 1131 EP 1136 DI 10.1038/16056 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 292TA UT WOS:000085810100019 PM 10570492 ER PT J AU Cayouette, M Smith, SB Becerra, SP Gravel, C AF Cayouette, M Smith, SB Becerra, SP Gravel, C TI Pigment epithelium-derived factor delays the death of photoreceptors in mouse models of inherited retinal degenerations SO NEUROBIOLOGY OF DISEASE LA English DT Article ID FIBROBLAST GROWTH-FACTOR; CEREBELLAR GRANULE CELLS; CILIARY NEUROTROPHIC FACTOR; FACTOR PEDF; RETINITIS-PIGMENTOSA; MUTANT MICE; RD MOUSE; CGMP-PHOSPHODIESTERASE; PROGENITOR CELLS; BINDING PROTEIN AB Pigment epithelium-derived factor (PEDF) is a member of the serine protease inhibitor superfamily produced by retinal pigment epithelial cells in the developing and adult retina. In vitro, it induces neuronal differentiation of retinoblastoma cells and promotes survival of cerebellar granule neurons. The pedf gene is closely linked to an autosomal-dominant locus for retinitis pigmentosa, suggesting that PEDF could be a survival factor for photoreceptors. We have investigated this possibility by injecting PEDF into the eyes of homozygous retinal degeneration (rd) and retinal degeneration slow (rds) mice, two mutants displaying apoptotic photoreceptor loss. This procedure resulted in a transient delay of photoreceptor loss in the rd mouse and a reduction in apoptotic photoreceptor profiles in the rds mouse. We conclude that PEDF can act as a survival-promoting factor for photoreceptors in vivo and could potentially be useful for the treatment of photoreceptor diseases. (C) 1999 Academic Press. C1 Ctr Rech Univ Laval Robert Giffard, Lab Transfert Genes, Beauport, PQ G1J 2G3, Canada. Med Coll Georgia, Dept Cellular Biol & Anat & Ophthalmol, Augusta, GA 30912 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Laval, Fac Med, Dept Psychiat, St Foy, PQ G1K 7P4, Canada. RP Gravel, C (reprint author), Ctr Rech Univ Laval Robert Giffard, Lab Transfert Genes, 2601 Canardiere, Beauport, PQ G1J 2G3, Canada. OI Cayouette, Michel/0000-0003-4655-9048 FU NEI NIH HHS [EY09682] NR 53 TC 146 Z9 155 U1 0 U2 4 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 DEC PY 1999 VL 6 IS 6 BP 523 EP 532 DI 10.1006/nbdi.1999.0263 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 271ED UT WOS:000084580500007 PM 10600408 ER PT J AU Dawson, DA Sugano, H McCarron, RM Hallenbeck, JM Spatz, M AF Dawson, DA Sugano, H McCarron, RM Hallenbeck, JM Spatz, M TI Endothelin receptor antagonist preserves microvascular perfusion and reduces ischemic brain damage following permanent focal ischemia SO NEUROCHEMICAL RESEARCH LA English DT Article DE endothelin-1; cerebral ischemia; microvascular perfusion; ET-1 receptor antagonist; spontaneously hypertensive rat ID CEREBRAL-ARTERY OCCLUSION; GLOBAL-ISCHEMIA; BLOOD-FLOW; IN-VITRO; RAT; VASOSPASM; HYPOPERFUSION; PHARMACOLOGY; INFARCTION; MODEL AB Synthesis and release of the potent vasoconstrictor peptide endothelin-1 (ET-1) increases following cerebral ischemia and has previously been shown to mediate the delayed hypoperfusion associated with transient global ischemia. In this study we assessed the impact of ET-1 on perfusion and infarct volume in a focal model of cerebral ischemia by use of the selective ETA receptor antagonist Ro 61-1790 (affinity for ETA receptor 1000 fold greater than ETB receptor). Control rats subjected to permanent middle cerebral artery occlusion (MCAO) showed extensive reductions in microvascular perfusion 4 h post-MCAO that were significantly attenuated by Ro 61-1790 pretreatment (10 mg/kg, i.v.). Ro 61-1790 concomitantly and significantly reduced the ischemic lesion volume in the same animals. This effect was maintained 24 h post-MCAO providing that the animals received additional i.v. injections of 5 mg/kg Ro 61-1790 at 5 h and 8 h after MCAO. These findings demonstrate that ETA receptor antagonism partially preserves tissue perfusion following focal ischemia and that this effect is associated with significant neuroprotection. The results also support the hypothesis that vasoactive mediators, and ET-1 in particular, are important contributors to the pathogenesis of cerebral ischemic injury. C1 NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. USN, Resuscitat Med Dept, Med Res Ctr, Gaithersburg, MD 20899 USA. RP Spatz, M (reprint author), NINDS, Stroke Branch, NIH, 36 Convent Dr,MSC 4128, Bethesda, MD 20892 USA. NR 33 TC 51 Z9 52 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD DEC PY 1999 VL 24 IS 12 BP 1499 EP 1505 DI 10.1023/A:1021139713026 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 258DH UT WOS:000083822500001 PM 10591398 ER PT J AU Klein, RC Galdzicki, Z Castellino, FJ AF Klein, RC Galdzicki, Z Castellino, FJ TI Inhibition of NMDA-induced currents by conantokin-G and conantokin-T in cultured embryonic murine hippocampal neurons SO NEUROPHARMACOLOGY LA English DT Article DE N-methyl-D-aspartate receptor; conantokins; electrophysiology; polyamines; hippocampal neurons ID METHYL-D-ASPARTATE; VOLTAGE-DEPENDENT BLOCK; SPINAL-CORD NEURONS; GAMMA-CARBOXYGLUTAMATE; ALZHEIMERS-DISEASE; BINDING PROPERTIES; CORTICAL-NEURONS; XENOPUS OOCYTES; RECEPTOR; GLYCINE AB Conantokin-G (con-G) and conantokin-T (con-T) are small (17 and 21 amino acids, respectively) gamma-carboxyglutamate (Gla) containing peptides derived from the venoms of marine cone snails that are potent and selective inhibitors of N-methyl-D-aspartate (NMDA) receptors. In this study, the effects of con-G and con-T on NMDA-evoked responses were evaluated in mouse primary hippocampal neuronal cultures using the whole-cell patch-clamp technique. Under equilibrium conditions, NMDA-induced currents were inhibited by con-G and con-T (10 nM-100 mu M) in a dose-dependent manner while maintaining a holding potential of -70 mV. In the presence of saturating amounts of NMDA (100 mu M) and glycine (1 mu M), the IC50 values obtained were 487 +/- 85 nM for con-G and 1030 +/- 130 nM for con-T. NMDA (10 mu M-1 mM) dose-response curves produced in the presence of con-G or con-T (1 or 3 mu M) resulted in a downward shift of the current response at saturation with NMDA, without affecting the EC,,. The maximum response obtainable in the absence of peptide could not be achieved by increasing concentrations of NMDA. The same effect was also observed for conantokin inhibition of spermine-potentiated responses. Association rate constants (k(on)) for the peptides were determined in the presence of NMDA and glycine, with and without the addition of spermine. Using a single binding site bimolecular model, k(on) values were 3.1 +/- 0.2 x 10(3) M-1 s(-1) for con-G and 3.2 +/- 0.1 x 103 M-1 s(-1) for con-T in the absence of spermine. The added presence of a saturating amount of spermine (300 mu M) resulted in an approximate 60% increase in the k(on) values for both con-G and con-T. These results demonstrate that con-T and con-G inhibit NMDA-evoked currents, as well as the potentiation by spermine, in what appears to be a noncompetitive manner, and that spermine increases the rate of conantokin inhibition. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Castellino, FJ (reprint author), Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. FU NHLBI NIH HHS [HL19982] NR 43 TC 18 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 1999 VL 38 IS 12 BP 1819 EP 1829 DI 10.1016/S0028-3908(99)00065-9 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 257PP UT WOS:000083790900002 PM 10608277 ER PT J AU Kriegler, S Sudweeks, S Yakel, JL AF Kriegler, S Sudweeks, S Yakel, JL TI MTSEA potentiates 5-HT3 receptors containing the nicotinic alpha 4 subunit SO NEUROPHARMACOLOGY LA English DT Article AB In order to study the subunit composition of 5-HT3 receptors (5-HT3R), we report that (2-aminoethyl)methanethiosulfonate (MTSEA) can enhance the function of both nicotinic ACh receptors (nAChRs) comprised of alpha 4/beta 2 subunits, and heteromeric channels assembled from serotonin 5-HT3R and alpha 4 nAChR subunits. MTSEA has no effect on homomeric 5-HT3 receptor channels. Published by Elsevier Science Ltd. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 1999 VL 38 IS 12 BP 1913 EP 1915 DI 10.1016/S0028-3908(99)00109-4 PG 3 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 257PP UT WOS:000083790900011 PM 10608286 ER PT J AU Siarey, RJ Carlson, EJ Epstein, CJ Balbo, A Rapoport, SI Galdzicki, Z AF Siarey, RJ Carlson, EJ Epstein, CJ Balbo, A Rapoport, SI Galdzicki, Z TI Increased synaptic depression in the Ts65Dn mouse, a model for mental retardation in Down syndrome SO NEUROPHARMACOLOGY LA English DT Article DE Down syndrome; Ts65Dn; long-term potentiation; long-term depression; hippocampus; mental retardation ID LONG-TERM POTENTIATION; HIPPOCAMPUS; DEFICITS; NEURONS AB Long-term potentiation (LTP) and depression (LTD) were investigated in hippocampus of a genetic model of Down syndrome, the segmental trisomy (Ts65Dn) mouse. Field excitatory postsynaptic potentials were recorded from hippocampal slices and LTP and LTD evoked sequentially. LTP decreased whereas LTD increased significantly in Ts65Dn compared with control hippocampus. (C) 1999 Published by Elsevier Science Ltd. All rights reserved. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Galdzicki, Z (reprint author), NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG 08938]; NICHD NIH HHS [HD 31498] NR 12 TC 130 Z9 131 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 1999 VL 38 IS 12 BP 1917 EP 1920 DI 10.1016/S0028-3908(99)00083-0 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 257PP UT WOS:000083790900012 PM 10608287 ER PT J AU Crozier, S Sirigu, A Lehericy, S van de Moortele, PF Pillon, B Grafman, J Agid, Y Dubois, B LeBihan, D AF Crozier, S Sirigu, A Lehericy, S van de Moortele, PF Pillon, B Grafman, J Agid, Y Dubois, B LeBihan, D TI Distinct prefrontal activations in processing sequence at the sentence and script level: An fMRI study SO NEUROPSYCHOLOGIA LA English DT Article DE neuropsychology; planning; temporal order; action sequence; frontal lobes ID POSITRON EMISSION TOMOGRAPHY; WORKING-MEMORY; HUMAN BRAIN; LANGUAGE; PERFORMANCE; LESIONS; CORTEX; DAMAGE; TASK AB Neuropsychological studies have shown that the prefrontal cortex is important in planning and monitoring everyday behaviour. In this study, using functional magnetic resonance imaging (fMRI), we investigated whether specific prefrontal regions are involved in processing a sequence of actions. Subjects were required to perform two different tasks: Script-event order and Sentence-word order. Script sequence and word sequence processing were found to activate partially overlapping areas which are known to be implicated in language processing. In addition, the Script-task activated a large area in the dorsolateral prefrontal cortex (Brodmann area 6 and 8, BA 6 and 8), in both the left and right hemispheres, as well as the left supplementary motor area and left angular gyrus (BA 39). Our results suggest that these prefrontal areas may be more specifically involved in the process of analysing sequential links in the action domain. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 CNRS, Inst Cognit Sci, Bron, France. Hop La Pitie Salpetriere, INSERM, U289, Paris, France. Serv Hosp Frederic Joliot, Orsa, France. Hop La Pitie Salpetriere, Serv Neuroradiol, Paris, France. NIH, CNS, Bethesda, MD 20892 USA. RP Sirigu, A (reprint author), CNRS, Inst Cognit Sci, Bron, France. RI Van de Moortele, Pierre-Francois/H-5087-2011; OI Van de Moortele, Pierre-Francois/0000-0002-6941-5947; Grafman, Jordan H./0000-0001-8645-4457 NR 25 TC 81 Z9 81 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD DEC PY 1999 VL 37 IS 13 BP 1469 EP 1476 DI 10.1016/S0028-3932(99)00054-8 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 260WH UT WOS:000083976100005 PM 10617267 ER PT J AU Purkerson, SL Baden, DG Fieber, LA AF Purkerson, SL Baden, DG Fieber, LA TI Brevetoxin modulates neuronal sodium channels in two cell lines derived from rat brain SO NEUROTOXICOLOGY LA English DT Article DE Na+ channel; brevetoxin; single channel; patch clamp; neurotoxic shellfish poisoning; cell lines ID CAT SENSORIMOTOR CORTEX; PTYCHODISCUS-BREVIS; NA+ CHANNEL; HIPPOCAMPAL-NEURONS; SENSORY NEURONS; MESSENGER-RNAS; DINOFLAGELLATE; SLICES; TOXINS; NERVE AB Single Na+ channel currents were recorded from cell-attached membrane patches from two neuronal cell lines derived from rat brain, B50 and B104, and compared before and after exposure of the cells to purified brevetoxin, PbTx-3. B50 and B104 Na+ channels usually exhibited fast activation and inactivation as is typical of TTX-sensitive Na+ channels. PbTx-3 modified channel gating in both cell lines. PbTx-3 caused (1) significant increases in the frequency of channel reopening, indicating a slowing of channel inactivation, (2) a change in the voltage dependence of the channels, promoting channel opening during steady-state voltage clamp of the membrane at voltages throughout the activation range of Na+ currents, but notably near the resting potential of these cells (-60 - -50 mV), and (3) a significant, 6.7 mV hyperpolarized shift in the threshold potential for channel opening. Na+ channel slope conductance did not change in PbTx-3-exposed 850 and B104 neurons. These effects of Pbx-3 may cause hyperexcitability as well as inhibitory effects in intact brain. (C) 1999 Intox Press, Inc. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS Marine & Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. RP Fieber, LA (reprint author), Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, NIEHS Marine & Freshwater Biomed Sci Ctr, 4600 Rickenbacker Cswy, Miami, FL 33149 USA. OI Fieber, Lynne/0000-0002-7717-2260 FU NIEHS NIH HHS [ES05785, ES05705, ES05853] NR 40 TC 30 Z9 33 U1 0 U2 3 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD DEC PY 1999 VL 20 IS 6 BP 909 EP 920 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 281FZ UT WOS:000085148400005 PM 10693972 ER PT J AU Glover, RE Koshkin, V Dunford, HB Mason, RP AF Glover, RE Koshkin, V Dunford, HB Mason, RP TI The reaction rates of NO with horseradish peroxidase compounds I and II SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE nitric oxide; nitrosonium; horseradish; peroxidase; reaction rates ID NITRIC-OXIDE; HYDROGEN-PEROXIDE; PULSE-RADIOLYSIS; PEROXYNITRITE; MECHANISM; OXIDATION; SUPEROXIDE; MYOGLOBIN; KINETICS; OXYGEN AB In this study the reactions between nitric oxide (NO) and horseradish peroxidase (HRP) compounds I and II were investigated. The reaction between compound I and NO has biphasic kinetics with a clearly dominant initial fast phase and an apparent second-order rate constant of (7.0 +/- 0.3) x 10(5) M(-1)s(-1) for the fast phase. The reaction of compound II and NO was found to have an apparent second order rate constant of k(app)= (1.3 +/- 0.1) x 10(6) M(-1)s(-1) or (7.4 +/- 0.7) x 10(5) M(-1)s(-1) when measured at 409 nm (the isosbestic point between HRP and HRP-NO) and 419 nm (lambda(max) of compound II and HRP-NO), respectively. Interestingly, the reaction of compound II with NO is unusually high relative to that of compound I, which is usually the much faster reaction. Since horseradish peroxidase is prototypical of mammalian peroxidases with respect to the oxidation of small substrates, these results may have important implications regarding the lifetime and biochemistry of NO in vivo after inflammation where both NO and H2O2 generation are increased several fold. (C) 1999 Academic Press. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada. RP Glover, RE (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 26 TC 46 Z9 48 U1 1 U2 4 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 DEC PY 1999 VL 3 IS 6 BP 439 EP 444 DI 10.1006/niox.1999.0256 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 277ET UT WOS:000084920300002 PM 10637121 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI DNA-binding proteins and evolution of transcription regulation in the archaea SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMPLETE GENOME SEQUENCE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; METHANOCOCCUS-JANNASCHII; 3-DIMENSIONAL STRUCTURE; DOMAIN SUPERFAMILY; RNA-POLYMERASES; CRO REPRESSOR; MCM PROTEINS; RECOGNITION AB Likely DNA-binding domains in archaeal proteins were analyzed using sequence profile methods and available structural information. It is shown that all archaea encode a large number of proteins containing the helix-turn-helix (HTH) DNA-binding domains whose sequences are much more similar to bacterial HTH domains than to eukaryotic ones, such as the PAIRED, POU and homeodomains, The predominant class of HTH domains in archaea is the winged-HTH domain. The number and diversity of HTH domains in archaea is comparable to that seen in bacteria, The HTH domain in archaea combines with a variety of other domains that include replication system components, such as MCM proteins, translation system components, such as the alpha-subunit of phenylalanyl-tRNA synthetase, and several metabolic enzymes. The majority of the archaeal HTH-containing proteins are predicted to be gene/operon-specific transcriptional regulators. This apparent bacterial-type mode of transcription regulation is in sharp contrast to the eukaryote-like layout of the core transcription machinery in the archaea, In addition to the predicted bacterial-type transcriptional regulators, the HTH domain is conserved in archaeal and eukaryotic core transcription factors, such as TFIIB, TFIIE-alpha and MBF1, MBF1 is the only highly conserved, classical HTH domain that is vertically inherited in all archaea and eukaryotes. In contrast, while eukaryotic TFIIB and TFIIE-alpha possess forms of the HTH domain that are divergent in sequence, their archaeal counterparts contain typical HTH domains. It is shown that, besides the HTH domain, archaea encode unexpectedly large numbers of two other predicted DNA-binding domains, namely the Arc/MetJ domain and the Zn-ribbon, The core transcription regulators in archaea and eukaryotes (TFIIB/TFB, TFIIE-alpha and MBF1) and in bacteria (the sigma factors) share no similarity beyond the presence of distinct HTH domains, Thus HTH domains might have been independently recruited for a role in transcription regulation in the bacterial and archaeal/eukaryotic lineages. During subsequent evolution, the similarity between archaeal and bacterial gene/operon transcriptional regulators might have been established and maintained through multiple horizontal gene transfer events. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 88 TC 182 Z9 187 U1 1 U2 11 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 DEC 1 PY 1999 VL 27 IS 23 BP 4658 EP 4670 DI 10.1093/nar/27.23.4658 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261WM UT WOS:000084033500018 PM 10556324 ER PT J AU Wysocki, AB AF Wysocki, AB TI Skin anatomy, physiology, and pathophysiology SO NURSING CLINICS OF NORTH AMERICA LA English DT Article ID CHRONIC WOUND FLUID; REPERFUSION INJURY; DECUBITUS ULCER; HISTOPATHOLOGY; FIBRONECTIN; CELL AB Human skin is the largest multifunctional organ of the body, and knowledge of its structure and function is essential to clinicians and researchers. The skin has two layers, the epidermis and dermis, separated by a basement membrane zone. Tt provides protection, sensation, thermoregulation, biochemical/metabolic, and immune functions. Key and emerging concepts important to understanding pathophysiological mechanisms for practicing clinicians are: knowledge of differences between acute and chronic wounds; ability to evaluate depth and extent of injury; understanding stages of healing versus zones of activity; and knowledge of ischemic-reperfusion injury, the skin immune system, cytokines, growth factors and other biomolecules, and matrix synthesis and degradation. These concepts are addressed in this article. C1 NINR, Wound Healing Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Wysocki, AB (reprint author), NINR, Wound Healing Lab, Div Intramural Res, NIH, 9 Ctr Dr,MSC 0967,Bldg 9,Room 1W125, Bethesda, MD 20892 USA. NR 28 TC 18 Z9 18 U1 0 U2 19 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD DEC PY 1999 VL 34 IS 4 BP 777 EP + PG 22 WC Nursing SC Nursing GA 255DV UT WOS:000083655000002 PM 10523436 ER PT J AU Sempos, CT Looker, AC AF Sempos, CT Looker, AC TI Iron status and the risk of coronary heart disease SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Review DE iron; ferritin; heart disease; coronary heart disease; epidemiology ID ACUTE MYOCARDIAL-INFARCTION; EASTERN FINNISH MEN; SERUM FERRITIN; ARTERY DISEASE; CAROTID ATHEROSCLEROSIS; LDL-OXIDATION; BLOOD DONATION; DIETARY IRON; CAUSE MORTALITY; NO ASSOCIATION C1 NIH, Off Res Minor Hlth, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Sempos, CT (reprint author), SUNY Buffalo, Dept Social & Prevent Med, 270 Farber Hall,3435 Main St,Bldg 26, Buffalo, NY 14214 USA. NR 100 TC 6 Z9 7 U1 1 U2 1 PU MEDIKAL PRESS S R L PI MILAN PA VIA LUIGI ZOJA, 30, 20153 MILAN, ITALY SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD DEC PY 1999 VL 9 IS 6 BP 294 EP 303 PG 10 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA 291HW UT WOS:000085729400005 PM 10765522 ER PT J AU Maiman, M Watts, DH Andersen, J Clax, P Merino, M Kendall, MA AF Maiman, M Watts, DH Andersen, J Clax, P Merino, M Kendall, MA TI Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: A randomized trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PAPILLOMAVIRUS-ASSOCIATED LESIONS; INTRAEPITHELIAL NEOPLASIA; SEROPOSITIVE WOMEN; ABNORMALITIES; PREVALENCE; RISK AB Objective: To compare the efficacy and toxicity of topical vaginal 5-fluorouracil (5-FU) maintenance therapy against the effects of observation after standard treatment for high-grade cervical. dysplasia in human immunodeficiency virus (HIV)-infected women and to evaluate the association between baseline CD4 count and time to recurrence. Methods: In a phase III unmasked, randomized, multicenter, outpatient clinical trial, 101 HIV-positive women either received 6 months of biweekly treatment with vaginal 5-FU cream (2 g) or underwent 6 months of observation after standard excisional or ablative cervical treatment for cervical intraepithelial neoplasia (CIN). Papanicolaou smears and colposcopy were scheduled at regular intervals during the ensuing 18 months, with the primary end point being the time at which CIN of any grade recurred. Results: Thirty-eight percent of women developed recurrence: 14 (28%) of 50 in the 5-FU therapy group and 24 (47%) of 51 in the observation group. Treatment with 5-FU was significantly associated with prolonged time to CIN development (P = .04). Observation subjects were more likely to have high-grade recurrences, with 31% developing CIN 2-3 compared with 8% in the 5-FU treatment arm (P = .014), and disease recurred more quickly in observation subjects as well. Baseline CD4 count was related significantly to time to recurrence (P = .04), with 46% of subjects with CD4 counts less than 200 cells/mm(3) developing recurrence compared with 33% of subjects with CD4 counts at least 200 cells/mm3. Disease recurred more slowly in subjects who had received antiretroviral therapy than in antiretroviral therapy-naive subjects. There were no instances of grade 3 or 4 toxicity, and compliance with 5-FU treatment was generally good. Conclusion: Adjunctive maintenance intravaginal 5-FU therapy after standard surgery for high-grade lesions safely and effectively reduced recurrence of cervical intraepithelial neoplasia in HIV-infected women. (Obstet Gynecol 1999;94:954-61. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 Staten Isl Univ Hosp, Dept Obstet & Gynecol, Staten Isl, NY 10305 USA. NIAID, Adult AIDS Clin Trials Grp, Div AIDS, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. RP Maiman, M (reprint author), Staten Isl Univ Hosp, Dept Obstet & Gynecol, 475 Seaview Ave, Staten Isl, NY 10305 USA. RI Kendall, Michelle/B-7665-2016 OI Kendall, Michelle/0000-0001-9160-4544 NR 20 TC 41 Z9 44 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1999 VL 94 IS 6 BP 954 EP 961 DI 10.1016/S0029-7844(99)00407-X PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 257QJ UT WOS:000083792800010 PM 10576182 ER PT J AU Cooper, GS Thorp, JM AF Cooper, GS Thorp, JM TI FSH levels in relation to hysterectomy and to unilateral oophorectomy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID OVARIAN-FUNCTION; SURGERY; WOMEN; RISK AB Objective: To examine the association between hysterectomy, unilateral oophorectomy, and ovarian status, measured by FSH concentrations, in women aged 35-49 years. Methods: From the National Health and Examination Survey III, 1716 women aged 35-49 years were studied. Information on menopausal status, surgical history (hysterectomy, single or bilateral oophorectomy), smoking, and other characteristics was collected in a structured interview, height and weight were measured, and one blood sample was collected. We used logistic regression to analyze FSH concentration in relation to hysterectomy and oophorectomy, controlling for age, ethnicity, body mass index, smoking, education, nulligravidity, and exercise. Results: Hysterectomy with unilateral oophorectomy was associated with an increased prevalence of elevated FSH (above 20 IU/L) (adjusted odds ratio [OR] 2.4, 95% confidence interval [CI] 1.3, 4.6) compared with women who had not had hysterectomies or oophorectomies. Among women with two ovaries, hysterectomy was associated with increased prevalence of elevated FSH (adjusted OR 1.5, 95% CI 1.0, 2.5). As a comparison of the effect size, the observed association between hysterectomy and elevated FSH was smaller than the association between FSH and current smoking (OR 2.0), a factor associated with a 1-2 year decrease in mean age at natural menopause. Conclusion: Although the differences in FSH levels were small, there was evidence of elevated FSH in women who have had hysterectomies, even if at least,one ovary remained, (Obstet Gynecol 1999;94:969-72. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 NIEHS, Epidemiol Branch MD A3 05, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch MD A3 05, POB 12233, Res Triangle Pk, NC 27709 USA. NR 15 TC 58 Z9 60 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1999 VL 94 IS 6 BP 969 EP 972 DI 10.1016/S0029-7844(99)00429-9 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 257QJ UT WOS:000083792800012 PM 10576184 ER PT J AU Burns, DN Minkoff, H AF Burns, DN Minkoff, H TI Hepatitis C: Screening in pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS-INFECTION; CRYSTAL-STRUCTURE; NATURAL-HISTORY; BLOOD-DONORS; TRANSMISSION; INTERFERON-ALPHA-2B; COMBINATION; RIBAVIRIN; VIREMIA; ROUTES AB Hepatitis C virus infection, which is far more prevalent than human immunodeficiency virus (HIV)-1, can lead to cirrhosis, hepatocellular carcinoma, hepatic failure, and death. Like HIV-1, hepatitis C is transmitted parenterally, sexually, and from mother to infant. The American Academy of Pediatrics and the Centers for Disease Control and Prevention (CDC) recently recommended that all children born to women who are infected with hepatitis C virus or have risk factors for infection be screened for hepatitis C. Most infected women are asymptomatic and unaware of their infection, so routine prenatal testing is needed to fully meet that goat We do not believe that current data justify universal testing, but we believe it is time for all obstetricians to test selectively based on risk factors. (Obstet Gynecol 1999;94: 1044-8. (C) 1999 by The American College of Obstetricians and Gynecologists.). C1 Maimonides Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. RP Minkoff, H (reprint author), Maimonides Med Ctr, Dept Obstet & Gynecol, 967 48th St, Brooklyn, NY 11219 USA. NR 24 TC 5 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 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 1999 VL 94 IS 6 BP 1044 EP 1048 DI 10.1016/S0029-7844(99)00488-3 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 257QJ UT WOS:000083792800027 PM 10576199 ER PT J AU Maberley, DAL Yannuzzi, LA Gitter, K Singerman, L Chew, E Freund, KB Noguiera, F Sallas, D Willson, R Tillocco, K AF Maberley, DAL Yannuzzi, LA Gitter, K Singerman, L Chew, E Freund, KB Noguiera, F Sallas, D Willson, R Tillocco, K TI Radiation exposure - A new risk factor for idiopathic perifoveal telangiectasis SO OPHTHALMOLOGY LA English DT Article ID JUXTAFOVEOLAR RETINAL TELANGIECTASIS; PARAFOVEAL AB Objective: To examine the association between previous radiation exposure and idiopathic perifoveal telangiectasis (IPT). Design: A multicentered, individually matched, case-control study design was used. Participants/Controls: Sixty-five case subjects were matched with 175 control subjects. Individuals with unequivocal evidence of angiographically confirmed IPT were included as cases. Control subjects were matched for center, age, and gender. Main Outcome Measure: The main exposures of interest were a history of therapeutic head or neck irradiation and environmental radiation exposure. Methods: A standardized questionnaire was administered to case and control subjects. Data were collected for the main exposures of interest as well as pertinent covariates. Conditional logistic regression was used to evaluate therapeutic and environmental radiation as risks for IPT. Results: On univariate analysis, head or neck irradiation was associated with IPT (odds ratios [OR] = 4.15, 95% confidence interval [CI] = 1.30 -13.24). While controlling for diabetes and family history of diabetes, IPT was found to be associated with both head or neck irradiation (OR = 4,06, 95% CI = 1.20-13.76) and with environmental irradiation (OR = 6.73, 95% CI = 1.06-42.74). Conclusions: This study presents a previously unreported association between prior radiation exposure and IPT. C1 Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. E Jefferson Hosp, Touro Infirm, New Orleans, LA USA. Mt Sinai Hosp, Cleveland, OH USA. Lakewood Hosp, Cleveland, OH USA. Hillcrest Hosp, Cleveland, OH USA. NEI, NIH, Div Biometry & Epidemiol, Washington, DC USA. RP Maberley, DAL (reprint author), Univ British Columbia, Vancouver Gen Hosp, Eye Care Ctr, 2550 Willow St, Vancouver, BC V5Z 3N9, Canada. FU Intramural NIH HHS [Z99 EY999999] NR 11 TC 9 Z9 9 U1 0 U2 0 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 DEC PY 1999 VL 106 IS 12 BP 2248 EP 2252 DI 10.1016/S0161-6420(99)90523-7 PG 5 WC Ophthalmology SC Ophthalmology GA 261BC UT WOS:000083987100017 PM 10599653 ER PT J AU Hubbard, LD Brothers, RJ King, WN Clegg, LX Klein, R Cooper, LS Sharrett, AR Davis, MD Cai, JW AF Hubbard, LD Brothers, RJ King, WN Clegg, LX Klein, R Cooper, LS Sharrett, AR Davis, MD Cai, JW CA Atherosclerosis Risk Communities TI Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities study SO OPHTHALMOLOGY LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; RETINOPATHY; PREVALENCE; POPULATION; AGE AB Objective: To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. Design: Population-based, cross-sectional study. Participants: Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. Methods: One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (AAI ratio) was calculated. Main Outcome Measures Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). Results: Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower Values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0,10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher brood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1,34), and retinopathy had an OR of 1,25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. Conclusion: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors. C1 Univ Wisconsin, Dept Ophthalmol & Visual Sci, ARIC Retinal Reading Ctr, Madison, WI 53705 USA. NCI, NIH, Bethesda, MD 20892 USA. NHLBI, ARIC Project Off, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, ARIC Coordinating Ctr, Chapel Hill, NC USA. RP Hubbard, LD (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, ARIC Retinal Reading Ctr, 610 N Walnut St,WARF Bldg,Rm 438, Madison, WI 53705 USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-35125, N01-HC-35126] NR 27 TC 635 Z9 648 U1 3 U2 28 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 DEC PY 1999 VL 106 IS 12 BP 2269 EP 2280 DI 10.1016/S0161-6420(99)90525-0 PG 12 WC Ophthalmology SC Ophthalmology GA 261BC UT WOS:000083987100022 PM 10599656 ER PT J AU Miller, MA Wenger, J Rosenstein, N Perkins, B AF Miller, MA Wenger, J Rosenstein, N Perkins, B TI Evaluation of meningococcal meningitis vaccination strategies for the meningitis belt in Africa SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE meningococcal meningitis; vaccine; prevention; Africa; cost effectiveness ID MASS VACCINATION; EPIDEMIC; AGE AB Background. Although the meningococcal polysaccharide vaccine has contributed to the control of Group A meningitis in the "meningitis belt" of Africa, recurrent large outbreaks have led to questions regarding vaccination strategy, We evaluated current and hypothetical vaccination strategies for the region, Methods. ih model was formulated to analyze the effectiveness and costs of vaccine campaigns in response to outbreaks based on 7 years of weekly incidence data from Burkina Faso, Additional models analyzed the potential impact and costs of either a 1- or 4-dose routine scheduled delivery of meningococcal polysaccharide vaccine-based on data reported to the World Health Organization from 16 countries during 1948 through 1996, Vaccine efficacy, vaccination coverage and economic data from literature reviews provided model assumptions, Results. For Burkina Faso neither 1- nor 4-dose vaccination schedules would prevent >30% of meningitis cases compared with the 42% prevented through an outbreak response program of vaccinating districts, which reach an incidence of 15 per 100 000 persons for 2 weeks. For the entire meningitis belt, routine coverage with the 1- or 4-dose schedule meningococcal vaccine would require 4.9 and 19.6 million doses annually, respectively, for an annual net cost of $4.4 to $12.3 million and prevent an average 10 300 to 12 600 cases (23 to 28%), assuming a long term vaccine efficacy of 50%, In addition an initial "catch-up" campaign costing up to $72 million to vaccinate the population from 1 to 30 years of age would be required before achieving that level of effectiveness, Conclusion. Given the relatively poor routine vaccination coverage in this region, current strategies of vaccination campaigns that achieve higher coverage would generally be more effective and less costly than the modeled routine scheduled programs, assuming that campaigns can be rapidly implemented. Until a better vaccine is available, countries in this region would be more efficient in improving the response times to outbreaks, perhaps through improved surveillance, and in bolstering existing vaccination infrastructures rather than embarking on strategies of questionable effectiveness. C1 Childrens Vaccine Initiat, Geneva, Switzerland. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Miller, MA (reprint author), NIH, Fogarty Int Ctr, Bldg 31,Room B2CO2, Bethesda, MD 20892 USA. NR 31 TC 37 Z9 37 U1 3 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 DEC PY 1999 VL 18 IS 12 BP 1051 EP 1059 DI 10.1097/00006454-199912000-00005 PG 9 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 263TR UT WOS:000084141800004 PM 10608623 ER PT J AU Hay, WW Lucas, A Heird, WC Ziegler, E Levin, E Grave, GD Catz, CS Yaffe, SJ AF Hay, WW Lucas, A Heird, WC Ziegler, E Levin, E Grave, GD Catz, CS Yaffe, SJ TI Workshop summary: Nutrition of the extremely low birth weight infant SO PEDIATRICS LA English DT Review ID CHRONIC LUNG-DISEASE; EPIDERMAL GROWTH-FACTOR; FED HUMAN-MILK; PRETERM INFANTS; PARENTERAL-NUTRITION; PREMATURE-INFANTS; AMINO-ACID; GLUCOSE-PRODUCTION; FETAL GROWTH; FATTY-ACIDS C1 Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. UCL, Inst Child Hlth, MRC, Childhood Nutr Res Ctr, London, England. Baylor Coll Med, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. NICHHD, Ctr Res Mothers & Children, Bethesda, MD USA. RP Hay, WW (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pediat, 4200 E 9th Ave,Box B 195, Denver, CO 80262 USA. EM bill.hay@uchsc.edu NR 114 TC 50 Z9 56 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD DEC PY 1999 VL 104 IS 6 BP 1360 EP 1368 DI 10.1542/peds.104.6.1360 PG 9 WC Pediatrics SC Pediatrics GA 262LP UT WOS:000084069000018 PM 10585989 ER PT J AU Seashore, MR Wappner, R Cho, SC de la Cruz, F AF Seashore, MR Wappner, R Cho, SC de la Cruz, F TI Development of guidelines for treatment of children with phenylketonuria: Report of a meeting at the National Institute of Child Health and Human Development held August 15, 1995, National Institutes of Health, Bethesda, Maryland SO PEDIATRICS LA English DT Article DE phenylketonuria; treatment; guidelines; American Academy of Pediatrics ID EARLY-TREATED PHENYLKETONURIA AB Objective. To convene a small group of experts in diagnosis and management of PKU to discuss the following issues: the Subject Review of PKU management being performed by the American Academy of Pediatrics (AAP) Committee on Genetics (COG), the published British guidelines on PKU management, and the feasibility, suitability, and mechanism of developing PKU management guidelines for the United States. Methods. A 1-day meeting was held at the National Institutes of Health under the auspices of National Institute of Child Health and Human Development, convening experts in PKU diagnosis and management and members of the AAP/COG. Results. The group reviewed the published reports of outcomes of treatment of PKU and the British guidelines that were developed based on those data. It also reviewed the results of surveys of directors of clinics that manage PKU, parents of children with PKU, and young adults with PKU. Conclusion. The group supported the efforts of the AAP/COG to perform this review of PKU management. The group concluded that significant issues need to be resolved to provide sufficient information to establish US guidelines for PKU management. The establishment of such guidelines is an important next step in PKU management in the United States. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. James Whitcomb Riley Hosp Children, Sect Pediat Metab Genet, Indianapolis, IN 46202 USA. Wesley Med Ctr, Wichita, KS USA. NICHHD, Mental Retardat Program, NIH, Bethesda, MD USA. RP Seashore, MR (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA. NR 16 TC 5 Z9 5 U1 1 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 DEC PY 1999 VL 104 IS 6 AR e67 DI 10.1542/peds.104.6.e67 PG 3 WC Pediatrics SC Pediatrics GA 262LP UT WOS:000084069000039 PM 10586001 ER PT J AU Goodman, CB Heyliger, S Emilien, B Partilla, JS Yang, HYT Lee, CH Cadet, JL Rothman, RB AF Goodman, CB Heyliger, S Emilien, B Partilla, JS Yang, HYT Lee, CH Cadet, JL Rothman, RB TI Chronic exposure to antibodies directed against anti-opiate peptides alter delta-opioid receptor levels SO PEPTIDES LA English DT Article DE NPFF; dynorphin; alpha-melanocyte stimulating hormone (alpha-MSH); delta-opioid receptor; receptor autoradiography ID MELANOCYTE-STIMULATING HORMONE; THYROTROPIN RELEASING HORMONE; MORPHINE-INDUCED ANALGESIA; NEUROPEPTIDE-FF RECEPTORS; BETA-ENDORPHIN ANALGESIA; DYNORPHIN-A 1-17; RAT-BRAIN; BINDING-SITES; CHOLECYSTOKININ OCTAPEPTIDE; ANTAGONIST L-365,260 AB The development of addictive states in response to chronic opioid use may be regulated partially by the release of endogenous peptides. These anti-opiate peptides (AOP) are secreted or released into the CNS and produce diverse actions that counterbalance the effects of prolonged opiate exposure. Though the mechanism(s) by which these peptides exert their physiological properties remain largely unknown, then is some indication that AOP's modulate opioid receptor levels. In this study, we investigated the effects of chronically infused alpha-melanocyte stimulating hormone (alpha-MSH), dynorphin(1-8) (DYN1-8), dynorphin A (DYNA), and NPFF antibodies on delta-opioid receptor expression in rat blains. Quantitative autoradiographic experiments revealed that antibodies directed against alpha-MSH and DYNA produced significant increases in delta receptor levels in the caudate, claustrum, and cingulate cortex of the rat brain. Conversely, NPFF monoclonal antibodies caused significant decreases in the caudate, nucleus accumbens, olfactory tubercle, and cingulate cortex. These results suggest that the density of delta-opioid receptors is affected by changes in the levels of the anti-opioid peptides in the extracelluar fluid in the rat brain. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32303 USA. Hampton Univ, Sch Pharm, Dept Pharmaceut Sci, Hampton, VA 23668 USA. NIDA, Mol Neuropsychiat Sect, Div Intramural Res, NIH, Baltimore, MD 21224 USA. NIDA, Clin Psychopharmacol Sect, Div Intramural Res, NIH, Baltimore, MD 21224 USA. St Elizabeth Hosp, Ctr Neurosci, NIMH, Lab Biochem Genet, Washington, DC 20032 USA. RP Goodman, CB (reprint author), Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32303 USA. NR 78 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 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 1999 VL 20 IS 12 BP 1419 EP 1424 DI 10.1016/S0196-9781(99)00151-5 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 283FH UT WOS:000085265100004 PM 10698116 ER PT J AU Martinez, A Elsasser, TH Bhathena, SJ Pio, R Buchanan, TA Macri, CJ Cuttitta, F AF Martinez, A Elsasser, TH Bhathena, SJ Pio, R Buchanan, TA Macri, CJ Cuttitta, F TI Is adrenomedullin a causal agent in some cases of type 2 diabetes? SO PEPTIDES LA English DT Article DE adrenomedullin; gastational diabetes; radioimmunoassay; glucose tolerance; glycemia regulation; diabetic rat model ID INSULIN-SECRETION; PLASMA ADRENOMEDULLIN; GLUCOSE-TOLERANCE; HYPOTENSIVE PEPTIDE; CAMP ACCUMULATION; EXPRESSION; MELLITUS; RAT; COMPLICATIONS; HYPERTENSION AB The study of two populations with a recent onset of type 2 diabetes showed that a subset of the patients had higher levels of adrenomedullin (AM) than the rest of the diabetics. In this subset, physiological elevations of AM might have triggered the disease in predisposed individuals. Diabetics showed higher levels of AM than healthy controls. In addition, glycemia was measured in diabetic rats after injection of saline, AM, or antiAM antibody. AM elevated glycemia, whereas the antibody reduced circulating glucose to normal. These results suggest that manipulation of AM levels could represent a new approach in the management of diabetes for the appropriate individuals. Published by Elsevier Science Inc. C1 NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. ARS, USDA, Beltsville, MD 20705 USA. Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Martinez, A (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci,NIH, Bldg 10,Room 13N262, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 NR 49 TC 41 Z9 45 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 1999 VL 20 IS 12 BP 1471 EP 1478 DI 10.1016/S0196-9781(99)00158-8 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 283FH UT WOS:000085265100011 PM 10698123 ER PT J AU Bagby, RM Costa, PT McCrae, RR Livesley, WJ Kennedy, SH Levitan, RD Levitt, AJ Joffe, RT Young, LT AF Bagby, RM Costa, PT McCrae, RR Livesley, WJ Kennedy, SH Levitan, RD Levitt, AJ Joffe, RT Young, LT TI Replicating the five factor model of personality in a psychiatric sample SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article ID 5-FACTOR MODEL AB In this study we examined whether the factor structure and. traits of the five-factor model of personality (FFM), derived from non-clinical samples, could be replicated in a sample of psychiatric patients. The revised NEO Personality Inventory (NEO PI-R) was administered to a study group of psychiatric patients (n = 176). The test scores from these patients were intercorrelated, factor analyzed and the obtained factor structure was then compared to the factor structure of the normative data from the NEO PI-R. The factor structure from the psychiatric study group and that from the normative sample were virtually identical, with all five factors showing significant congruence. These results argue favorably for the clinical applicability of the FFM with psychiatric patients. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Toronto, Ctr Addict & Mental Hlth, Clarke Div, Toronto, ON M5T 1R8, Canada. NIA, Baltimore, MD 21224 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Toronto, Sunnybrooke Med Ctr, Toronto, ON M4N 3M5, Canada. McMaster Univ, Med Ctr, Hamilton, ON, Canada. RP Bagby, RM (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Clarke Div, 250 Coll St, Toronto, ON M5T 1R8, Canada. OI Costa, Paul/0000-0003-4375-1712 NR 11 TC 52 Z9 54 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD DEC PY 1999 VL 27 IS 6 BP 1135 EP 1139 DI 10.1016/S0191-8869(99)00055-0 PG 5 WC Psychology, Social SC Psychology GA 235RZ UT WOS:000082557500011 ER PT J AU Preusch, PC AF Preusch, PC TI News from the National Institute of General Medical Sciences (NIGMS) small business research grants update SO PHARMACEUTICAL RESEARCH LA English DT News Item C1 Natl Inst Gen Med Sci, Pharmacol Physiol & Biol Chem Div, NIH, Bethesda, MD 20892 USA. RP Preusch, PC (reprint author), Natl Inst Gen Med Sci, Pharmacol Physiol & Biol Chem Div, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD DEC PY 1999 VL 16 IS 12 BP 1791 EP 1792 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 272XB UT WOS:000084675300001 ER PT J AU Noble, F Wank, SA Crawley, JN Bradwejn, J Seroogy, KB Hamon, M Roques, BP AF Noble, F Wank, SA Crawley, JN Bradwejn, J Seroogy, KB Hamon, M Roques, BP TI International union of pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors SO PHARMACOLOGICAL REVIEWS LA English DT Review ID CCK-B RECEPTOR; PANCREATIC ACINAR-CELLS; GASTRIC PARIETAL-CELLS; GUINEA-PIG BRAIN; MESSENGER-RNA LEVELS; H-3 PBC 264; GENERALIZED ANXIETY DISORDER; MUSCLE MYENTERIC PLEXUS; DECREASES FOOD-INTAKE; INDUCED PANIC ATTACKS C1 Univ Paris 05, CNRS, UMR 8600, INSERM,U266, F-75270 Paris 06, France. Univ Ottawa, Royal Ottawa Hosp, Ottawa, ON, Canada. NIMH, Sect Behav Neuropharmacol, Expt Therapeut Branch, Bethesda, MD 20892 USA. Univ Kentucky, Albert B Chandler Med Ctr, Dept Anat & Neurobiol, Lexington, KY 40536 USA. Fac Med Pitie Salpetriere, INSERM, U288, Paris, France. RP Roques, BP (reprint author), Univ Paris 05, CNRS, UMR 8600, INSERM,U266, 4 Ave Observ, F-75270 Paris 06, France. NR 416 TC 304 Z9 317 U1 1 U2 15 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 1999 VL 51 IS 4 BP 745 EP 781 PG 37 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 260RB UT WOS:000083962700005 PM 10581329 ER PT J AU Pandeya, SN Ponnilavarasan, I Pandey, A Lakhan, R Stables, JP AF Pandeya, SN Ponnilavarasan, I Pandey, A Lakhan, R Stables, JP TI Evaluation of p-nitrophenyl substituted semicarbazones for anticonvulsant properties SO PHARMAZIE LA English DT Article AB A series of p-nitrophenyl substituted semicarbazones has been synthesised and their anticonvulsant activity was screened against MES, scPTZ and scSTY. 4(4'-Nitrophenyl)-o-nitrobenzaldehyde semicarbazone has been found to be the most active in all these tests. The studies revealed that a primary amino function is not essential for anticonvulsant activity in the semicarbazone series of compounds. Presumably these compounds could further act on glycine receptors. C1 Banaras Hindu Univ, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. Banaras Hindu Univ, Inst Technol, Dept Chem, Varanasi 221005, Uttar Pradesh, India. NINDS, NIH, Bethesda, MD USA. RP Pandeya, SN (reprint author), Banaras Hindu Univ, Dept Pharmaceut, Varanasi 221005, Uttar Pradesh, India. NR 3 TC 38 Z9 41 U1 0 U2 2 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD DEC PY 1999 VL 54 IS 12 BP 923 EP 925 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 273UL UT WOS:000084725900013 PM 10631757 ER PT J AU Yeh, SY AF Yeh, SY TI Comparative anorectic effects of metaraminol and phenylephrine in rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE anorexia; body weight; metaraminol; 2-amino-1-(m-hydroxyphenyl)1-propanol; phenylephrine; 2-methylamino-1-(m-hydroxyphenyl)-1-ethanolamine; locomotor activity AB Structure-anorectic activity relationship of two substituted amphetamines has been investigated in this study. Literature reports showed conflicting results in their anorectic activities in spite of the similarity in chemical structures of metaraminol and phenylephrine. Hence, the effects of alpha-carbon atom substitution and primary (metaraminol) and secondary amine (phenylephrine) moieties of these substituted amphetamines on the anorexia of rats were investigated in this study in nonfood- and food-deprived rats. Food intake at 1, 3, 14, and 24 h intervals, water intake at a 24-h interval, and body weight alteration for 10 days were monitored after daily drug administration for 3 consecutive days. Both metaraminol and phenylephrine were found to be potent anorectic. The relative anorectic potencies of phenylephrine were 0.54 and 0.81 of that of metaraminol at 1- and 3-h intervals, respectively. Body weight of rats treated with metaraminol (5.0 mg/kg) and phenylephrine (10 mg/kg) decreased significantly from Days 1 to 9. Published by Elsevier Science Inc. C1 NIH, NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Yeh, SY (reprint author), NIH, NIDA, Intramural Res Program, POB 5180, Baltimore, MD 21224 USA. NR 16 TC 6 Z9 6 U1 0 U2 1 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 DEC 1 PY 1999 VL 68 IS 1-2 BP 227 EP 234 DI 10.1016/S0031-9384(99)00180-8 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 267FJ UT WOS:000084346800031 PM 10627085 ER PT J AU Cantrell, CL Rajab, MS Franzblau, SG Fronczek, FR Fischer, NH AF Cantrell, CL Rajab, MS Franzblau, SG Fronczek, FR Fischer, NH TI Antimycobacterial ergosterol-5,8-endoperoxide from Ajuga remota SO PLANTA MEDICA LA English DT Article DE Ajuga remota; Labiatae; ergosterol-5,8-endoperoxide; Mycobacterium tuberculosis; antituberculosis; clerodin; ajugarin-I; ajugarin-II ID TUBERCULOSIS; CRYSTAL AB In a bioassay-guided search for antimycobacterial natural products from higher plants, we have chemically investigated the methanol extract of aerial parts of Ajuga remote Benth. (Labiatae) for its active constituent(s). Bioactive chromatographic fractions of the crude extract provided the known triterpene ergosterol-5,8-endoperoxide plus the diterpenes clerodin, ajugarin-I, and ajugarin-II, which had been previously isolated from A. remote. This is the first report on the isolation of ergosterol-5,8-endoperoxide from this plant. The above compounds were tested in a radiorespirometric bioassay for activity against Mycobacterium tuberculosis. Ergosterol-5,8-endoperoxide showed a minimum inhibitory concentration (MIC) of 1 mu g/ml, while ergosterol-5,8-endoperoxide acetate, ergosterol, and ergosta-5,7,9(11),22-tetraen-3 beta-ol gave MICs of 8 mu g/ ml, >128 mu g/ml, and 128 mu g/ml, respectively. Clerodin, ajugarin-I, and ajugarin-II were inactive with MICs of >128 mu g/ml. C1 Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA. Moi Univ, Dept Chem, Eldoret, Kenya. GWL Hansens Dis Ctr, Baton Rouge, LA USA. RP Cantrell, CL (reprint author), NCI, FCRDC, Drug Discovery Res & Dev Lab, Bldg 560,Rm 32-60, Ft Detrick, MD 21702 USA. OI Franzblau, Scott/0000-0002-8698-0243 FU NIAID NIH HHS [Y1-AI-5016] NR 16 TC 46 Z9 49 U1 0 U2 5 PU GEORG THIEME VERLAG PI STUTTGART PA P O BOX 30 11 20, D-70451 STUTTGART, GERMANY SN 0032-0943 J9 PLANTA MED JI Planta Med. PD DEC PY 1999 VL 65 IS 8 BP 732 EP 734 DI 10.1055/s-1999-14053 PG 3 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 269LL UT WOS:000084478700014 PM 10630115 ER PT J AU Ebrahim, SH Anderson, AL Floyd, RL AF Ebrahim, SH Anderson, AL Floyd, RL TI Alcohol consumption by reproductive-aged women in the USA: an update on assessment, burden and prevention in the 1990s SO PRENATAL AND NEONATAL MEDICINE LA English DT Review DE alcohol; women; USA; 1990s; update ID RANDOMIZED CONTROLLED TRIAL; PREGNANT-WOMEN; CAFFEINE CONSUMPTION; SPONTANEOUS-ABORTION; CIGARETTE-SMOKING; NEWBORN-INFANTS; UNITED-STATES; BREAST-CANCER; RISK-DRINKING; FOLLOW-UP AB Because of alcohol's effects on maternal, fetal and child health, the public health implications of alcohol abuse by women are potentially greater than those of alcohol abuse by men. This report provides a summary of developments in the field of alcohol use and women's health in the 1990s. During the 1990s, the prevalence of alcohol consumption, including binge drinking, appears to have increased among pregnant women, whereas there was little change among non-pregnant women of childbearing age. The prevalence of alcohol use among women under 21 years of age, for whom alcohol should be inaccessible, is equal to or greater than that in older age groups. Adverse effects have been detected among pregnant women who consume more than three drinks per week on average. Alcohol may impair fertility and increase the risk for breast cancer. The national burden from all effects of alcohol on women's health has not been assessed. The available brief screening instruments to detect alcohol use do not detect moderate alcohol consumption or binge drinking by pregnant women. Brief primary care clinic-based behavioral interventions and some medications have been shown to decrease alcohol use and subsequent problems among women who are problem drinkers. To prevent alcohol-exposed pregnancies, researchers need to study the feasibility of these interventions for pregnant women including moderate drinkers, as well as interventions that enhance the use of contraception among women who misuse alcohol and are at risk for pregnancy. Attempts to reduce alcohol-exposed pregnancies should begin prior to conception. Primary care providers for women, including obstetricians, general practitioners, family planning advisers and school health-care providers can play an important role in the prevention of all adverse effects of alcohol consumption by women. C1 Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. Natl Inst Drug Abuse, Bethesda, MD USA. RP Ebrahim, SH (reprint author), Ctr Dis Control & Prevent, MS-K55,4770 Buford Hway NE, Atlanta, GA 30341 USA. NR 79 TC 7 Z9 7 U1 3 U2 3 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1359-8635 J9 PRENAT NEONAT MED JI Prenat. Neonatal Med. PD DEC PY 1999 VL 4 IS 6 BP 419 EP 430 PG 12 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 286WQ UT WOS:000085472200001 ER PT J AU Peschka, B Leygraaf, J Hansmann, D Hansmann, M Schrock, E Ried, T Engels, H Schwanitz, G Schubert, R AF Peschka, B Leygraaf, J Hansmann, D Hansmann, M Schrock, E Ried, T Engels, H Schwanitz, G Schubert, R TI Analysis of a de novo complex chromosome rearrangement involving chromosomes 4, 11, 12 and 13 and eight breakpoints by conventional cytogenetic, fluorescence in situ hybridization and spectral karyotyping SO PRENATAL DIAGNOSIS LA English DT Article DE complex chromosome rearrangement (CCR); prenatal diagnosis; fluorescence in situ hybridization (FISH); spectral karyotyping (SKY) ID PRENATAL-DIAGNOSIS; MOLECULAR ANALYSIS; ALPHA-THALASSEMIA; TRANSLOCATION; FOLLOW AB A complex chromosome rearrangement (CCR) with:eight breakpoints resulting in four derivative chromosomes (4, 11, 12 and 13) was detected prenatally in a male fetus of a twin pregnancy. The karyotype of the female second fetus was normal. The apparently balanced de novo CCR was identified by classical cytogenetic methods and fluorescence in situ hybridization (FISH). We compared these findings with results from spectral karyotyping (SKY). Copyright 1999 John Wiley & Sons, Ltd. C1 Univ Bonn, Inst Human Genet, D-53111 Bonn, Germany. Lab Hansmann Weiss, Meckenheim, Germany. Univ Bonn, Dept Obstet & Gynecol, D-5300 Bonn, Germany. NHGRI, NIH, Bethesda, MD USA. RP Peschka, B (reprint author), Univ Bonn, Inst Human Genet, Wilhelmstr 31, D-53111 Bonn, Germany. NR 25 TC 18 Z9 19 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD DEC PY 1999 VL 19 IS 12 BP 1143 EP 1149 PG 7 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 266CD UT WOS:000084282300010 PM 10590433 ER PT J AU Zambrana, RE Breen, N Fox, SA Gutierrez-Mohamed, ML AF Zambrana, RE Breen, N Fox, SA Gutierrez-Mohamed, ML TI Use of cancer screening practices by Hispanic women: Analyses by subgroup SO PREVENTIVE MEDICINE LA English DT Article DE cancer screening; women's health; Latina; ethnicity ID MEXICAN-AMERICAN WOMEN; BREAST-CANCER; MAMMOGRAPHY USE; UNITED-STATES; ETHNIC-GROUPS; OLDER WOMEN; HEALTH-CARE; PAP SMEAR; ACCULTURATION; PHYSICIAN AB Objectives. This study compares the use of three cancer screening practices (Pap smear, mammogram, and clinical breast examination) 3 years prior to interview among five subgroups of Hispanic women, and examines whether sociodemographic; access; health behavior, perception, and knowledge; and acculturation factors predict screening practices for any subgroup. Methods. Descriptive and multiple logistic regression analyses were conducted with data pooled from the 1990 and 1992 National Health Interview Surveys on women who reported that they were Hispanic. The study sample includes 2,391 respondents: 668 Mexican-American, 537 Mexican, 332 Puerto Rican, 143 Cuban, and 711 other Hispanic women. Results. Subgroup profiles reveal differences in education, health insurance, use of English language, and screening use. Mexican women were the least likely to be screened with any procedure. Logistic regression results for each screening practice show that having a usual source of care was a positive predictor for obtaining each of the three screening practices within the last 3 years. Being married, being more than 50 years of age, and having knowledge of breast self-examination were all predictors of having a Pap smear. Having health insurance and ever having had a clinical breast examination and Pap smear were predictors of having a mammography, while age, knowledge of breast self-examination, ever having had a Pap smear and mammogram, and being a nonsmoker all predicted having a clinical breast examination. Conclusions. We conclude that access factors and prior screening are more strongly associated with current screening than are language and ethnic factors. Our data confirm that a disproportionate percentage of Hispanic women are low income and at risk of being underscreened. Our findings from a nationally representative sample of Hispanics have implications for provider practices, ethnic-specific community interventions, and future development of measures and data collection approaches, (C) 1999 American Health Foundation and Academic Press. C1 George Mason Univ, Social Work Program, Fairfax, VA 22030 USA. NIH, Appl Res Program, Div Canc Control & Populat Sci, NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA 90407 USA. Jackson State Univ, Jackson Heart Study, Jackson, MS 39216 USA. RP Zambrana, RE (reprint author), Univ Maryland, Dept Womens Studies, 2101 Woods Hall, College Pk, MD 20742 USA. NR 77 TC 145 Z9 146 U1 2 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD DEC PY 1999 VL 29 IS 6 BP 466 EP 477 DI 10.1006/pmed.1999.0566 PN 1 PG 12 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 268CU UT WOS:000084397400006 PM 10600427 ER PT J AU Eastman, RC Garfield, SA AF Eastman, RC Garfield, SA TI Prevention and treatment of microvascular and neuropathic complications of diabetes SO PRIMARY CARE LA English DT Article ID GLYCEMIC CONTROL; MELLITUS; INTERVENTION; RETINOPATHY; PROGRESSION; DIAGNOSIS; BENEFITS; TRIAL; MODEL; NIDDM AB The most important factors that influence development of the eye, kidney, and nerve complications of diabetes are the duration and degree of exposure to hyperglycemia. Hypertension is also very important. The risk of complications appears to be similar for all patients with diabetes; differences in complication rates between patients with type 1 and type 2 diabetes are largely due to differences in duration of diabetes and glycemic control. The benefits of lowering blood sugar are also similar for patients with diabetes, regardless of the type. Significant reductions in complications san be seen with relatively short-term treatment of hyperglycemia. C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Eastman, RC (reprint author), NIDDK, NIH, Bldg 31,Room 9A16,31 Ctr Dr MSC 2560, Bethesda, MD 20892 USA. NR 33 TC 6 Z9 6 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 0095-4543 J9 PRIMARY CARE JI Primary Care PD DEC PY 1999 VL 26 IS 4 BP 791 EP + DI 10.1016/S0095-4543(05)70131-7 PG 18 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 253YR UT WOS:000083585200004 PM 10523460 ER PT J AU Lagomasino, I Daly, R Stoudemire, A AF Lagomasino, I Daly, R Stoudemire, A TI Medical assessment of patients presenting with psychiatric symptoms in the emergency setting SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID LEWY BODY DISEASE; PANIC DISORDER; CHEST PAIN; INTRAVENOUS HALOPERIDOL; ORGANIC PSYCHOSIS; DOUBLE-BLIND; PREVALENCE; DELIRIUM; MANIA; PHENOMENOLOGY AB Psychiatrists in the emergency department (ED) are often asked to evaluate patients with disturbances of affect, behavior, and cognition. The first and most crucial step in the evaluation process is to eliminate possible medical causes for a patient presenting psychiatric symptoms. Failure to detect and diagnose underlying medical disorders may result in significant and unnecessary morbidity and mortality. C1 NIMH, Behav Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Ctr Hlth Serv Res, Los Angeles, CA USA. Emory Univ, Sch Med, Dept Psychiat, Atlanta, GA 30322 USA. RP Daly, R (reprint author), NIMH, Behav Endocrinol Branch, NIH, Bldg 10,Room 3N242,10 Ctr Dr, Bethesda, MD 20892 USA. NR 58 TC 13 Z9 13 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD DEC PY 1999 VL 22 IS 4 BP 819 EP + DI 10.1016/S0193-953X(05)70128-3 PG 34 WC Psychiatry SC Psychiatry GA 266FK UT WOS:000084289800008 PM 10623973 ER PT J AU Osuch, EA Noll, JG Putnam, FW AF Osuch, EA Noll, JG Putnam, FW TI The motivations for self-injury in psychiatric inpatients SO PSYCHIATRY-INTERPERSONAL AND BIOLOGICAL PROCESSES LA English DT Article ID BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ABUSE; BEHAVIORAL TREATMENT; MUTILATION; PHENOMENOLOGY; NALTREXONE; CHILDHOOD; CONTAGION; SYMPTOMS AB NONSUICIDAL self-injurious behavior (SIB) occurs in both culturally appropriate and culturally inappropriate forms. It is one of the diagnostic criteria for borderline personality disorder, but it occurs in several psychiatric and neurological populations. The personal intent of SIB in psychiatric populations is incompletely understood. A self-report scale (Self-Injury Motivation Scale; SIMS) to assess motivation for self-injury was developed. Relationships among motivation for SIB, characteristics of SIB, and psychopathology were explored. A semistructured interview and the SIMS, Dissociative Experiences Scale, Beck Depression Inventory, Davidson Trauma Scale, and Millon Clinical Multiaxial Inventory-II were given to 99 consecutively admitted inpatients. The SIMS had good reliability and validity. A high SIMS score suggested distinct psychopathology. Several factors on the SIMS differentiated motivations for SIB. Patients with different SIMS factor profiles had different psychopathology. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. USC, Sch Social Work, Washington, DC USA. Childrens Hosp, Med Ctr, Mayerson Ctr Safe & Healthy Children, Cincinnati, OH 45229 USA. RP Osuch, EA (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,Room 3N 212,MSC 1272, Bethesda, MD 20892 USA. RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 43 TC 45 Z9 46 U1 0 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0033-2747 J9 PSYCHIATRY JI Psychiatry-Interpers. Biol. Process. PD WIN PY 1999 VL 62 IS 4 BP 334 EP 346 PG 13 WC Psychiatry SC Psychiatry GA 284DG UT WOS:000085315000008 PM 10693230 ER PT J AU Duckworth, EA Koutouzis, TK Borlongan, CV Gordon, MN Willing, AE Cahill, DW Sanberg, PR AF Duckworth, EA Koutouzis, TK Borlongan, CV Gordon, MN Willing, AE Cahill, DW Sanberg, PR TI Rats receiving systemic 3-nitropropionic acid demonstrate impairment of memory in Morris water maze SO PSYCHOBIOLOGY LA English DT Article ID BLOOD-BRAIN-BARRIER; HUNTINGTONS-DISEASE; EXCITOTOXIC LESIONS; DYSFUNCTION; STRIATUM; SYMPTOMS; DEFICITS; CARRIERS; TOXIN; DEATH AB A recent hypothesis for the etiology of Huntington's disease (HD) postulates that impaired mitochondrial energy production and/or the presence of reactive free radical species may lead to slow excitotoxic neuronal death. Consistent with this hypothesis, systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in rats produces selective striatal neuropathology mimicking that seen in HD. Such injections of 3-NP additionally produce motor changes thought to model HD, but possible cognitive changes have not been well described. The present study explores this issue. Sixteen rats underwent acquisition training and subsequent memory assessment in a Morris water maze apparatus. Training over 5 consecutive days consisted of trials during which each rat could escape swimming by finding a permanently located submerged platform. Following training, the rats were divided into two groups and received daily intraperitoneal injections of either 3-NP (15 mg/kg) or saline vehicle for 7 days. On Day 8, a retention trial was conducted, in which the platform was removed and the rats were allowed to swim for 2 min. Swimming patterns were tracked and recorded. The rats receiving 3-NP had impaired memory of the platform location, as represented by decreased time swimming over the platform area, fewer entries into the area, and longer latency to entering the area. These results suggest that the 3-NP rat model produces cognitive dysfunctions that parallel HD dementia. C1 Univ S Florida, Coll Med, Dept Neurosurg, Tampa, FL 33612 USA. NIDA, NIH, Baltimore, MD USA. RP Sanberg, PR (reprint author), Univ S Florida, Coll Med, Dept Neurosurg, MDC Box 16,12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. RI Gordon, Marcia N./K-2420-2012; Willing, Alison/I-4946-2012; OI Gordon, Marcia N./0000-0002-4051-9283; Borlongan, Cesar/0000-0002-2966-9782 NR 30 TC 12 Z9 12 U1 2 U2 2 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0889-6313 J9 PSYCHOBIOLOGY JI Psychobiology PD DEC PY 1999 VL 27 IS 4 BP 561 EP 566 PG 6 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 285VN UT WOS:000085409100016 ER PT J AU Jiang, Y Greenwood, PM Parasuraman, R AF Jiang, Y Greenwood, PM Parasuraman, R TI Age-related reduction in 3-D visual motion priming SO PSYCHOLOGY AND AGING LA English DT Article ID IMPLICIT MEMORY; OPTIC FLOW; STEREOPSIS; SENSITIVITY; PERCEPTION; OCCLUSION; DEPTH AB In 3 experiments, younger and older adults judged the perceived motion of three-dimensional (3-D) figures that rotated in depth either unambiguously or ambiguously. Both groups were found to be equivalent in judging the direction of single rotations of the simulated 3-D objects (Experiment I). In Experiments 2 and 3, a single unambiguous rotation (prime) was followed 0-3200 ms later by an ambiguous rotation (target). Motion priming was indicated by the disambiguation of the second rotation by the first rotation. 3-D motion priming was initially found to be similar in young and old, but it rapidly reduced in the older participants compared to the younger ones. Using a nonluminance depth cue-occlusion-to induce 3-D motion, diminished contrast sensitivity in the elderly was ruled out as a cause of the reduced priming. The results' show that 3-D motion priming exhibits robust age-related decline. An age-related decrease in temporal persistence may account for the reduction in 3-D motion priming in older adults. C1 Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. RP Jiang, Y (reprint author), NIMH, Lab Brain & Cognit, Bldg 10,Room 4C104,MSC 1366, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG07569, AG12387] NR 30 TC 9 Z9 10 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 1999 VL 14 IS 4 BP 619 EP 626 DI 10.1037/0882-7974.14.4.619 PG 8 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 273EF UT WOS:000084694400007 PM 10632149 ER PT J AU Hillman, BJ Gatsonis, C Sullivan, DC AF Hillman, BJ Gatsonis, C Sullivan, DC TI American College of Radiology Imaging Network: New National Cooperative Group for Conducting Clinical Trials of Medical Imaging Technologies SO RADIOLOGY LA English DT Article DE radiology and radiologists, outcome studies; radiology and radiologists, research C1 Univ Virginia, Hlth Sci Ctr, Dept Radiol, Charlottesville, VA 22908 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. NCI, Diagnost Imaging Program, Bethesda, MD 20892 USA. RP Hillman, BJ (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Radiol, Box 170, Charlottesville, VA 22908 USA. NR 4 TC 17 Z9 17 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1999 VL 213 IS 3 BP 641 EP 645 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258EM UT WOS:000083825200003 PM 10580934 ER PT J AU Walter, BL Nguyen, JHC Ehrenfeld, E Semler, BL AF Walter, BL Nguyen, JHC Ehrenfeld, E Semler, BL TI Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE 5 ' noncoding region; cap-independent translation; coxsackievirus; encephalomyocarditis virus; foot-and-mouth disease virus; human rhinovirus; poliovirus; RNA binding proteins ID INTERNAL RIBOSOMAL ENTRY; ENCEPHALOMYOCARDITIS VIRUS-RNA; 5' NONTRANSLATED REGION; CELLULAR 57-KILODALTON PROTEIN; CAP-INDEPENDENT TRANSLATION; MOUTH-DISEASE VIRUS; POLIOVIRUS RNA; INITIATION-FACTOR; IN-VITRO; 5'-NONCODING REGION AB The translation of picornavirus genomic RNAs occurs by a cap-independent mechanism that requires the formation of specific ribonucleoprotein complexes involving host cell factors and highly structured regions of picornavirus 5' noncoding regions known as internal ribosome entry sites (IRES), Although a number of cellular proteins have been shown to be involved in picornavirus RNA translation, the precise role of these factors in picornavirus internal ribosome entry is not understood, In this report, we provide evidence for the existence of distinct mechanisms for the internal initiation of translation between type I and type II picornavirus IRES elements, In vitro translation reactions were conducted in HeLa cell cytoplasmic translation extracts that were depleted of the cellular protein, poly(rC) binding protein 2 (PCBP2). Upon depletion of PCBP2, these extracts possessed a significantly diminished capacity to translate reporter RNAs containing the type I IRES elements of poliovirus, coxsackievirus, or human rhinovirus linked to luciferase; however, the addition of recombinant PCBP2 could reconstitute translation, Furthermore, RNA electrophoretic mobility-shift analysis demonstrated specific interactions between PCBP2 and both type I and type II picornavirus IRES elements; however, the translation of reporter RNAs containing the type II IRES elements of encephalomyocarditis virus and foot-and-mouth disease virus was not PCBP2 dependent. These data demonstrate that PCBP2 is essential for the internal initiation of translation on picornavirus type I IRES elements but is dispensable for translation directed by the structurally distinct type II elements. C1 Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. RP Semler, BL (reprint author), Univ Calif Irvine, Coll Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. FU NIAID NIH HHS [AI 12387, AI 26765] NR 68 TC 98 Z9 101 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD DEC PY 1999 VL 5 IS 12 BP 1570 EP 1585 DI 10.1017/S1355838299991483 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 263JR UT WOS:000084122000006 PM 10606268 ER PT J AU Blair, A Rothman, N Zahm, SH AF Blair, A Rothman, N Zahm, SH TI Occupational cancer epidemiology in the coming decades SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE cohort; gene-exposure interactions; methods; minorities; nested case-control; prospective designs; women ID BLADDER-CANCER; CHILDHOOD-CANCER; EXPOSED WORKERS; LUNG-CANCER; EXPOSURES; WOMEN; CARCINOGENESIS; PESTICIDES; MORTALITY; HEALTH AB Occupational studies have identified many of the established chemical carcinogens. Studies in the next millennium will be needed to identify the hazardous agents in occupations known to have high cancer rates, to assess human risks from animal carcinogens that have not been well evaluated epidemiologically, to provide information on women and minorities, to evaluate interactions with genetic factors and other risk factors, to contribute to our understanding of risks from the spread of chemicals from the workplace to the general environment, and to identify mechanisms of cancer. The traditional retrospective cohort design will be insufficient to meet these needs. Population-based case-control, nested case-control, prospective cohorts, and cross-sectional designs will assume more important roles because of the need to collect information on nonoccupational risk factors and biological tissues. Improvement in the assessment of quantitative exposures is needed for the efficient evaluation of interactions between occupational exposures, genetic factors, and nonoccupational exposures. C1 NCI, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Execut Plaza S,Room 8118, Bethesda, MD 20892 USA. RI Zahm, Shelia/B-5025-2015 NR 55 TC 7 Z9 7 U1 1 U2 1 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 DEC PY 1999 VL 25 IS 6 SI SI BP 491 EP 497 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 270UB UT WOS:000084553700004 PM 10884144 ER PT J AU Stewart, P AF Stewart, P TI Challenges to retrospective exposure assessment SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE epidemiology; occupation ID SEMICONDUCTOR HEALTH; OCCUPATIONAL EXPOSURE; CANCER; WORKERS; COHORT AB Retrospective exposure assessment has become a crucial component in the interpretation of occupational epidemiologic results. Many advances have been made over the last 2 decades, but substantial progress is still necessary to reduce the misclassification of exposure. The efforts needed include evaluating the validity and reliability of assessment methods, better documentation of the methods, use of exposure determinants to estimate exposure levels more accurately and reliably, and an increase in the understanding of industrial hygiene and biological measurement data and questionnaires, their limitations, and how to use them best. In addition, better characterization of exposures is necessary. This need includes evaluating dermal and ingestion hazards, incorporating nonoccupational sources of exposures, particularly hobbies, evaluating the effect of multiple chemicals, and exploring different exposure metrics. C1 NCI, Occupat Epidemiol Branch, Rockville, MD 20892 USA. RP Stewart, P (reprint author), NCI, Occupat Epidemiol Branch, EPS 8102,6120 Execut Blvd, Rockville, MD 20892 USA. NR 30 TC 36 Z9 39 U1 0 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 DEC PY 1999 VL 25 IS 6 SI SI BP 505 EP 510 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 270UB UT WOS:000084553700006 PM 10884146 ER PT J AU Collins, FS Jegalian, KG AF Collins, FS Jegalian, KG TI Deciphering the code of life SO SCIENTIFIC AMERICAN LA English DT Article C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Collins, FS (reprint author), NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 3 TC 14 Z9 14 U1 0 U2 1 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 0036-8733 J9 SCI AM JI Sci.Am. PD DEC PY 1999 VL 281 IS 6 BP 86 EP 91 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 258TU UT WOS:000083855900026 PM 10614070 ER PT J AU Schlom, J Tsang, KY Kantor, JA Abrams, SI Zaremba, S Greiner, J Hodge, JW AF Schlom, J Tsang, KY Kantor, JA Abrams, SI Zaremba, S Greiner, J Hodge, JW TI Strategies in the development of recombinant vaccines for colon cancer SO SEMINARS IN ONCOLOGY LA English DT Review ID HUMAN CARCINOEMBRYONIC ANTIGEN; T-CELL-RECEPTOR; B7-2 COSTIMULATORY MOLECULES; MHC CLASS-II; TUMOR-CELLS; WILD-TYPE; IMMUNE-RESPONSES; LYMPHOCYTES-T; GENE FAMILY; OVERLAPPING EPITOPES C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 8B07, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 92 TC 17 Z9 18 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 DEC PY 1999 VL 26 IS 6 BP 672 EP 682 PG 11 WC Oncology SC Oncology GA 266GR UT WOS:000084292700010 PM 10606260 ER PT J AU Klabunde, CN Springer, BC Butler, B White, MS Atkins, J AF Klabunde, CN Springer, BC Butler, B White, MS Atkins, J TI Factors influencing enrollment in clinical trials for cancer treatment SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID MANAGED CARE; COVERAGE; PHYSICIANS AB Background. Recruitment of cancer patients to clinical trials is an ongoing challenge. In this study, we assess factors that may influence enrollment in clinical trials for cancer treatment. Methods, Between June 1997 and January 1998, data were collected on all adult cancer patients evaluated for enrollment in National Cancer Institute-sponsored clinical trials at 15 medical facilities in the southeastern United States. Results. More than 2,300 cancer patients were evaluated; 7% were enrolled. Neither patient sex nor race predicted enrollment. Patients with fee-for-service coverage were more than twice as likely to be enrolled compared with patients with other types of coverage, including managed care. Patient refusal accounted for the nonenrollment of nearly 40% of those clinically eligible. Conclusions. Although multiple factors influence enrollment in clinical trials for cancer treatment, results suggest that insurance coverage plays a role. Patient refusal, a substantial reason for nonenrollment, points to the need for continued efforts to educate physicians and the public in the value of clinical trials. C1 NCI, Appl Res Branch, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. SE Canc Control Consortium, Winston Salem, NC USA. Advisory Comm Canc Coordinat & Control, Raleigh, NC USA. RP Klabunde, CN (reprint author), NCI, Appl Res Branch, Execut Plaza N,Room 313,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 20 TC 60 Z9 60 U1 1 U2 1 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD DEC PY 1999 VL 92 IS 12 BP 1189 EP 1193 DI 10.1097/00007611-199912000-00011 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 268PR UT WOS:000084425200011 PM 10624912 ER PT J AU Egan, CA Florell, SR Zone, JJ AF Egan, CA Florell, SR Zone, JJ TI Localized bullous pemphigoid in a patient with B-cell lymphoma SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID ANTIGEN; AUTOANTIBODIES; DISEASE AB Bullous pemphigoid (BP) is an immunobullous disease characterized by circulating IgG antibodies directed towards cutaneous basement zone antigens, We report the case of a patient who had BP localized to a stoma site. At initial examination, a nodule was noted on the temple, which proved to be a large cell lymphoma, B-cell phenotype, On Western immunoblot, the patient's serum showed circulating IgG antibodies reactive with the 230 kDa BP antigen and the 97 kDa linear IgA bullous dermatosis antigen. The co-incident onset of the two diseases suggest that this may represent a case of paraneoplastic BP. C1 Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT USA. Vet Affairs Med Ctr, Med Serv, Dermatol Sect, Salt Lake City, UT 84148 USA. RP Egan, CA (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK50678-01A1] NR 15 TC 11 Z9 12 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD DEC PY 1999 VL 92 IS 12 BP 1220 EP 1222 DI 10.1097/00007611-199912000-00019 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 268PR UT WOS:000084425200019 PM 10624920 ER PT J AU Shevach, EM Chang, JT Segal, BM AF Shevach, EM Chang, JT Segal, BM TI The critical role of IL-12 and the IL-12R beta 2 subunit in the generation of pathogenic autoreactive Th1 cells SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; INTERFERON-GAMMA-PRODUCTION; COLLAGEN-INDUCED ARTHRITIS; IFN-GAMMA; T-CELLS; ANTIGEN RECOGNITION; MULTIPLE-SCLEROSIS; IMMUNE DEVIATION AB Experimental Allergic Encephalomyelitis (EAE) is a demyelinating disease of the central nervous system which is an animal model for the human autoimmune disease, multiple sclerosis. EAE is mediated by CD4(+) T cells and the T cells responsible for disease induction produce Th1 cytokines. IL-12 produced by monocytes and dendritic cells is the most critical factor which influences the development and differentiation of pathogenic autoreactive Th1 cells. Here, we review our recent studies on the critical contributions of IL-12 and the IL-12R beta 2 subunit to the generation of autoreactive effector cells which mediate EAE. In addition, we discuss the potential contribution of IL-18 to the upregulation of the IL-12/IL-12R beta 2 pathway and the contribution of the suppressor cytokines, IL-4 and IL-10, in downregulating this pathway. Collectively, our studies demonstrate that the IL-12/IL-12R beta 2 pathway is a critical intermediary in the process of Th1 differentiation which can be both positively or negatively regulated. This pathway remains an attractive immunotherapeutic target for blockade of function with inhibitory reagents or downregulation by Th2 cytokines. C1 NIH, Immunol Lab, NIAID, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIH, Immunol Lab, NIAID, Bldg 10,RM11N315, Bethesda, MD 20892 USA. NR 50 TC 51 Z9 52 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PD DEC PY 1999 VL 21 IS 3 BP 249 EP 262 DI 10.1007/BF00812256 PG 14 WC Immunology; Pathology SC Immunology; Pathology GA 273FA UT WOS:000084696200004 PM 10666772 ER PT J AU Simon, R AF Simon, R TI The role of statisticians in intervention trials SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Review AB The planning, conduct, analysis and reporting of randomized trials to reliably evaluate an intervention create a complex intellectual and logistical endeavour. Success generally requires active collaboration of a well-trained, experienced and committed statistician. A good intervention trial asks an important question, gets a reliable answer and is honestly reported. Many trials fail on one of these components and some of these failures could have been avoided with better statistical involvement. Many subject matter investigators do not understand how to effectively collaborate with statisticians. The objective here is to outline some of the important responsibilities of the statistician in intervention trials. C1 NCI, Bethesda, MD 20892 USA. RP Simon, R (reprint author), Natl Inst Hlth, EPN-Room 739, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 4 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD DEC PY 1999 VL 8 IS 4 BP 281 EP 286 DI 10.1191/096228099673618608 PG 6 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 291UD UT WOS:000085753900002 PM 10730334 ER PT J AU Leppala, JM Virtamo, J Fogelholm, R Albanes, D Heinonen, OP AF Leppala, JM Virtamo, J Fogelholm, R Albanes, D Heinonen, OP TI Different risk factors for different stroke subtypes - Association of blood pressure, cholesterol, and antioxidants SO STROKE LA English DT Article DE antioxidants; blood pressure; cerebral infarction; cholesterol; intracerebral hemorrhage; subarachnoid hemorrhage ID CIGARETTE-SMOKING; SUBARACHNOID HEMORRHAGE; INTRACEREBRAL HEMORRHAGE; CARDIOVASCULAR-DISEASE; SERUM-CHOLESTEROL; PLATELET-FUNCTION; BRAIN INFARCTION; BETA-CAROTENE; VITAMIN-E; DIETARY AB Background and Purpose-Blood pressure is an important risk factor for stroke, but the roles of serum total and HDL cholesterol, alpha-tocopherol, and beta-carotene are poorly established. We studied these factors in relation to stroke subtypes, Methods-Male smokers (n=28 519) aged 50 to 69 years without a history of stroke participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, a controlled trial to test the effect of alpha-tocopherol and beta-carotene supplementation on cancer. From 1985 to 1993, a total of 1057 men suffered from primary stroke: 85 had subarachnoid hemorrhage; 112, intracerebral hemorrhage; 807, cerebral infarction; and 53, unspecified stroke. Results-Systolic blood pressure greater than or equal to 160 mm Hg increased the risk of all stroke subtypes 2.5 to 4-fold. Serum total cholesterol was inversely associated with the risk of intracerebral hemorrhage, whereas the risk of cerebral infarction was raised at concentrations greater than or equal to 7.0 mmol/L, The risks of subarachnoid hemorrhage and cerebral infarction were lowered with serum HDL cholesterol levels greater than or equal to 0.85 mmol/L. Pretrial high serum alpha-tocopherol decreased the risk of intracerebral hemorrhage by half and cerebral infarction by one third, whereas high serum beta-carotene doubled the risk of subarachnoid hemorrhage and decreased that of cerebral infarction by one fifth. Conclusions-The risk factor profiles of stroke subtypes differ, reflecting different etiopathology, Because reducing atherosclerotic diseases, including ischemic stroke, by lowering high serum cholesterol is one of the main targets in public health care, further studies are needed to distinguish subjects with risk of hemorrhagic stroke. The performance of antioxidants needs confirmation from clinical trials. C1 Univ Helsinki, Dept Publ Hlth, FIN-00014 Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Clin Neurosci, Helsinki, Finland. Natl Publ Hlth Inst, Helsinki, Finland. Natl Canc Inst, Bethesda, MD USA. RP Leppala, JM (reprint author), Univ Helsinki, Dept Publ Hlth, POB 41,Mannerheimintie 172, FIN-00014 Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 41 TC 152 Z9 164 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1999 VL 30 IS 12 BP 2535 EP 2540 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 259JL UT WOS:000083890700005 PM 10582974 ER PT J AU Nadareishvili, ZG Choudary, Z Joyner, C Brodie, D Norris, JW AF Nadareishvili, ZG Choudary, Z Joyner, C Brodie, D Norris, JW TI Cerebral microembolism in acute myocardial infarction SO STROKE LA English DT Article; Proceedings Paper CT 34th Meeting of Canadian Congress of Neurological Sciences CY JUN 15-19, 1999 CL EDMONTON, CANADA DE embolism; myocardial infarction; ultrasonography, Doppler, transcranial ID LEFT-VENTRICULAR THROMBUS; PROSTHETIC CARDIAC VALVES; CORONARY-ARTERY DISEASE; ATRIAL-FIBRILLATION; STROKE; SIGNALS; RISK; DYSFUNCTION; PREVALENCE; STENOSIS AB Background and Purpose-This study was undertaken to determine the frequency of cerebral microemboli (high-intensity transient signals; HITS) detected by transcranial Doppler (TCD) in patients with acute myocardial infarction (AMI) and to relate them to the various putative risk factors and clinical embolic events. Methods-We investigated 112 consecutive patients within 72 hours of admission to an acute coronary care unit using TCD to monitor for cerebral microemboli, Twelve patients were excluded because of failure of ultrasound insonation. All patients had 2-dimensional echocardiograms within the study period. Results-HITS were detected in 17% of patients, with significantly higher frequency in patients with reduced (<65%) left ventricular (LV) ejection fraction (P=0.019), akinetic LV segments (P=0.002), and LV thrombus (P=0.015), A marginally significant (P=0.059) increase of HITS was found in patients with anterior AMI, Stroke was significantly more frequent in patients with cerebral microemboli (P=0.01). Conclusions-HITS were detected in 17% of patients in spite of adequate antithrombotic therapy and were increased in patients with reduced LV function, akinetic myocardial segments, and LV thrombus, They were present in all 3 patients with stroke and may represent a predictor of clinical embolic events. C1 Univ Toronto, Sunnybrook & Woments Coll Hth Sci Ctr, Stroke Res Unit, Toronto, ON, Canada. Univ Toronto, Sunnybrook & Woments Coll Hth Sci Ctr, Div Cardiol, Toronto, ON, Canada. RP Nadareishvili, ZG (reprint author), NINDS, NIH, Stroke Branch, Bldg 36,Room 4A03,36 Convent Dr, Bethesda, MD 20892 USA. NR 35 TC 22 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 1999 VL 30 IS 12 BP 2679 EP 2682 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 259JL UT WOS:000083890700027 PM 10582996 ER PT J AU Feldman, AL Sharaf, RN Skarulis, MC Bartlett, DL Libutti, SK Weinstein, LS Marx, SJ Norton, JA Fraker, DL Alexander, HR AF Feldman, AL Sharaf, RN Skarulis, MC Bartlett, DL Libutti, SK Weinstein, LS Marx, SJ Norton, JA Fraker, DL Alexander, HR TI Results of heterotopic parathyroid autotransplantation: A 13-year experience SO SURGERY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Association-of-Endocrine Surgeons CY MAY 02-04, 1999 CL NEW HAVEN, CONNECTICUT SP Amer Assoc Endocrine Surgeons ID PRIMARY HYPERPARATHYROIDISM; AUTO-TRANSPLANTATION; CRYOPRESERVED TISSUE; SURGERY; HYPERPLASIA AB Background. The reported success of heterotopic parathyroid autotransplantation (HPA) in Intients With primary hyperparathyroidism varies from 20 % to 60 %. The purpose of this study was to evaluate our results with HPA to help define its role in this patient group Methods. Between July 1985 and June 1998, 44 patients underwent 51 HPA procedures at our institution. Twenty to 25 fragments of parathyroid tissue measuring 1 to 3 mm(3) each were placed into the forearm musculature. HPA results were scored as nonfunctional (requiring calcium and vitamin D), partially functional (normocalcemia on calcium alone), fully functional (normocalcemia without supplementation), or hyperfunctional (hypercalcemia without supplementation). Results, Follow-up data were available for 39 patients who underwent 46 autografts (20 immediate and 26 cryopreserved). With a median follow-up of 35 months, 19 autografts (41 %) were nonfunctional; 9 autografts (20 %) were partially functional; 15 autografts (33 %) were fully functional, and 3 autografts (7 %) were hyperfunctional. Full function was observed in 35 % of immediate and 31 % of delayed autografts. Conclusions. One third parathyroid autografts develop full function, and an additional one fifth develop partial function. Recurrent hyperparathyroidism is uncommon. No benefit was observed from immediate versus delayed HPA, and the modest success rate of HPA, suggests that improvements in technique are warranted. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012; Weinstein, Lee/I-5575-2015; OI Weinstein, Lee/0000-0002-1899-5152 NR 16 TC 44 Z9 45 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1999 VL 126 IS 6 BP 1042 EP 1048 DI 10.1067/msy.2099.101580 PG 7 WC Surgery SC Surgery GA 262JV UT WOS:000084064500016 PM 10598186 ER PT J AU Libutti, SK Alexander, HR Bartlett, DL Sampson, ML Ruddel, ME Skarulis, M Marx, SJ Spiegel, AM Simmonds, W Remaley, AT AF Libutti, SK Alexander, HR Bartlett, DL Sampson, ML Ruddel, ME Skarulis, M Marx, SJ Spiegel, AM Simmonds, W Remaley, AT TI Kinetic analysis of the rapid intraoperative parathyroid hormone assay in patients during operation for hyperparathyroidism SO SURGERY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the American-Association-of-Endocrine Surgeons CY MAY 02-04, 1999 CL NEW HAVEN, CONNECTICUT SP Amer Assoc Endocrine Surgeons ID SURGERY AB Background, Rapid intraoperative parathyroid hormone (RI-PTH) assay is used to guide adequacy of resection during operation for hyperparathyroidism. We compared the RI-PTH assay (15 minutes) with a standard PTH assay, determined whether the PTH half-life varied between patients, and constructed a kinetic analysis of the RI-PTH data. Methods. Forty-five patients with hyperparathyroidism had blood sampled at baseline and at times after parathyroid resection. Intact PTH was determined using RI-PTH and a standard assay. Values were fitted to an exponential decay curve using the baseline and the follow-up time points. PTH half-life and the new postexcision baseline value were calculated from the decay curve. Results, The RI-PTH assay and the standard PTH assay correlated well. Average PTH half-life was 1.68 +/- 0.94 minutes (0.42 to 3.81 minutes). A kinetic analysis yielded a formula for the generation of a PTH decay curve. Using a 50% reduction in RI-PTH at 5 minutes as the criterion for adequate resection, 2 patients were incorrectly classified as not being cured. These patients were correctly classified using the kinetic analysis. Conclusions. PTH half-life can vary substantially. A kinetic analysis may be more accurate in assessing adequacy of resection. This method allows the surgeon to interpret RI-PTH data independent of the timing of samples. C1 NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NIH, Ctr Clin, Dept Clin Pathol, Bldg 10-2C-431, Bethesda, MD 20892 USA. NR 12 TC 94 Z9 96 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD DEC PY 1999 VL 126 IS 6 BP 1145 EP 1150 DI 10.1067/msy.2099.101835 PG 6 WC Surgery SC Surgery GA 262JV UT WOS:000084064500044 PM 10598200 ER PT J AU Lammers, CH D'Souza, U Qin, ZH Lee, SH Yajima, S Mouradian, MM AF Lammers, CH D'Souza, U Qin, ZH Lee, SH Yajima, S Mouradian, MM TI Regulation of striatal dopamine receptors by estrogen SO SYNAPSE LA English DT Article DE dopamine receptors; estrogen; caudate-putamen; nucleus accumbens; promoter ID RAT-BRAIN; DIFFERENTIAL DISTRIBUTION; TREATMENT INCREASES; ANTERIOR-PITUITARY; NERVOUS-SYSTEM; MESSENGER-RNA; FEMALE RATS; ESTRADIOL; EXPRESSION; RELEASE AB The ability of estrogen to modulate the expression of ventral and dorsal striatal dopamine receptors D-1, D-2, and D-3 was examined in vivo using semi-quantitative in situ hybridization and ligand binding autoradiography. Two-week treatment with subcutaneous pellets of 17 beta-estradiol (25 mg) downregulated D-2 dopamine receptor mRNA in both dorsal and ventral striatum (shell and core regions of nucleus accumbens). No significant changes in D-1 or D-3 mRNA expression were detected. Ligand binding autoradiography did not reveal changes in D-1, D-2, or D-3 receptor protein expression. We also assessed the ability of 17 beta-estradiol to regulate D-2 gene promoter activity in NB41A3 neuroblastoma cells that express this gene endogenously using co-transfections with an estrogen receptor expression vector. While a small fragment of the D-2 promoter could be activated 2.5-fold by estrogen, a larger portion of the D-2 gene was not regulated by this treatment. Estrogens do not appear to have a net effect on striatal dopamine receptor expression. The observed downregulation of D-2 receptor mRNA in the dorsal and ventral striatum in vivo could be secondary to the increased striatal dopamine release induced by estrogen. Synapse 34:222-227, 1999. Published 1999 Wiley-Liss, Inc.dagger. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Pharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, 10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 52 TC 69 Z9 78 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC PY 1999 VL 34 IS 3 BP 222 EP 227 DI 10.1002/(SICI)1098-2396(19991201)34:3<222::AID-SYN6>3.0.CO;2-J PG 6 WC Neurosciences SC Neurosciences & Neurology GA 250RF UT WOS:000083401200006 PM 10523759 ER PT J AU Chen, JJ Hollenbach, JA Trachtenberg, EA Just, JJ Carrington, M Ronningen, KS Begovich, A King, MC McWeeney, S Mack, SJ Erlich, HA Thomson, G AF Chen, JJ Hollenbach, JA Trachtenberg, EA Just, JJ Carrington, M Ronningen, KS Begovich, A King, MC McWeeney, S Mack, SJ Erlich, HA Thomson, G TI Hardy-Weinberg testing for HLA class II (DRB1, DQA1, DQB1, AND DPB1) loci in 26 human ethnic groups SO TISSUE ANTIGENS LA English DT Article DE exact test; Hardy-Weinberg proportions; HLA; individual test; population genetics ID DEPENDENT DIABETES-MELLITUS; HISTOCOMPATIBILITY COMPLEX LOCI; BALANCING SELECTION; EXPEDICION-HUMANA; ALLELES; POLYMORPHISM; HAPLOTYPES; FAMILIES; POPULATIONS; EVOLUTION AB Testing the fit of population data to Hardy-Weinberg proportions is crucial in the validation of many current approaches in population genetic studies. In this paper, we tested fit to Hardy-Weinberg proportions using exact approaches for both the overall and individual heterozygote genotype data of four HLA Class II loci: DRB1, DQA1, DQB1, and DPB1, from 26 human populations. Eighty of 99 overall tests fit the Hardy-Weinberg expectation (73% for DRB1, 89% for DQA1, 81% for DQB1 and 81% for DPB1). Deviations from Hardy-Weinberg proportions were both locus and group specific. Although we could not rule out other mechanisms at work, the individual test results indicated that the departure was possibly partly due to recent admixture. Evidence for selection and other sources of deviation are also discussed. C1 St Louis Univ, Sch Publ Hlth, St Louis, MO 63108 USA. Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Millenium Pharmaceut, Dept Human Genet, Cambridge, MA USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. Natl Inst Publ Hlth, Epidemiol Sect, Oslo, Norway. Roche Mol Syst, Dept Human Genet, Alameda, CA USA. Univ Washington, Dept Genet, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Chen, JJ (reprint author), St Louis Univ, Sch Publ Hlth, 3663 Lindell Blvd, St Louis, MO 63108 USA. OI Mack, Steven/0000-0001-9820-9547 FU NIAID NIH HHS [AI-29042]; NIGMS NIH HHS [GMHD 25792, GM 35326] NR 24 TC 19 Z9 19 U1 1 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD DEC PY 1999 VL 54 IS 6 BP 533 EP 542 DI 10.1034/j.1399-0039.1999.540601.x PG 10 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 278HA UT WOS:000084982200001 PM 10674966 ER PT J AU Fant, RV Henningfield, JE Nelson, RA Pickworth, WB AF Fant, RV Henningfield, JE Nelson, RA Pickworth, WB TI Pharmacokinetics and pharmacodynamics of moist snuff in humans SO TOBACCO CONTROL LA English DT Article DE snuff; nicotine absorption; cardiovascular effects ID TOBACCO; NICOTINE; ABSORPTION; DEPENDENCE; USERS; GUM AB Objective-To examine the effects of four brands of commercially available moist snuff and non-tobacco mint "snuff" on plasma nicotine concentration, heart rate, blood pressure, and subjective measures. Intervention-Four brands of moist snuff and a non-tobacco mint snuff were tested. Subjects reported to the laboratory for five experimental sessions. After baseline measurement of dependent variables, each subject placed 2 g of one of the brands of snuff (or one Skoal Bandits pouch) between the cheek and gum for 30 minutes. The subjects remained in the experimental laboratory for an additional 60 minutes. Subjects-Ten volunteers who were daily users of smokeless tobacco. Main outcome measures-Plasma nicotine concentration, cardiovascular effects, and subjective effects. Results-Large amounts of nicotine were delivered rapidly to the bloodstream. The amount of nicotine absorbed and the rate of absorption were related to the pH of the snuff product in aqueous suspension. Cardiovascular and subjective effects were related to me amount of nicotine absorbed. Conclusions-Snuff products are capable of rapidly delivering high doses of nicotine, which can lead to dependence. Long-term use of snuff can lead to a number of adverse health effects including oral cancers, cardiovascular diseases, and gingival diseases. For these reasons, it is important that the public health community considers oral snuff use as a burden on public health in the same way that cigarette smoking is recognised. C1 NIDA, Div Intramural Res, Baltimore, MD USA. RP Fant, RV (reprint author), Pinney Associates, 4800 Montgomery Lane,Suite 1000, Bethesda, MD 20814 USA. NR 17 TC 71 Z9 71 U1 1 U2 7 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0964-4563 J9 TOB CONTROL JI Tob. Control PD WIN PY 1999 VL 8 IS 4 BP 387 EP 392 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 273TJ UT WOS:000084723300015 PM 10629244 ER PT J AU Lane, MA Ingram, DK Roth, GS AF Lane, MA Ingram, DK Roth, GS TI Calorie restriction in nonhuman primates: Effects on diabetes and cardiovascular disease risk SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Society-of-Toxicology Symposium on Contemporary Concepts in Toxicology CY OCT 26-28, 1998 CL RESTON, VIRGINIA SP Soc Toxicol DE rhesus monkeys; aging; biomarkers; sulfated dehydroepiandrosterone (DHEAS) ID MONKEYS MACACA-MULATTA; TERM DIETARY RESTRICTION; MALE RHESUS-MONKEYS; DEHYDROEPIANDROSTERONE-SULFATE; INSULIN-RESISTANCE; AGING RATS; GLUCOSE; METABOLISM; MELLITUS; MODEL AB The effects of calorie restriction (CR) on life span, disease, and aging in physiological systems have been documented extensively in rodent models, However, whether CR has similar effects in longer-lived species more closely related to humans remains unknown, Studies of CR and aging using nonhuman primates (rhesus monkeys) have been ongoing for several years at the National Institute on Aging and the University of Wisconsin-Madison, The majority of data published from these studies are consistent with the extensive findings reported in rodents. For example, monkeys on CR weigh less and have less body fat. Monkeys on CR also exhibit lower body temperature, fasting blood glucose and insulin, and serum lipids. In addition, insulin sensitivity is increased in monkeys on CR, Recent efforts in the NIA study have focused on the effect of this intervention on risk factors for various age-related diseases, in particular for diabetes and cardiovascular disease, We have shown that monkeys on CR have lower blood pressure, reduced body fat, and a reduced trunk:leg fat ratio. Also, monkeys on CR have reduced triglycerides and cholesterol and have increased levels of HDL2(B). Low levels of this HDL subfraction have been associated with increased cardiovascular disease in humans. In short-term studies, older (>18 years) monkeys on CR exhibit reductions in insulin and triglycerides before changes in body composition and fat distribution became evident. These and other findings have suggested that CR might have beneficial effects on certain disease risk factors independent of reductions in body weight or prevention of obesity. C1 NIA, Intramural Res Program, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Intramural Res Program, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 42 TC 97 Z9 101 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 1999 VL 52 IS 2 SU S BP 41 EP 48 DI 10.1093/toxsci/52.suppl_1.41 PG 8 WC Toxicology SC Toxicology GA 268VX UT WOS:000084438400007 PM 10630589 ER PT J AU Waalkes, MP Anver, M Diwan, BA AF Waalkes, MP Anver, M Diwan, BA TI Carcinogenic effects of cadmium in the noble (NBL/Cr) rat: Induction of pituitary, testicular, and injection site tumors and intraepithelial proliferative lesions of the dorsolateral prostate SO TOXICOLOGICAL SCIENCES LA English DT Article DE cadmium; prostate; proliferative lesions; rat; carcinogenesis ID LEYDIG-CELL TUMORS; METALLOTHIONEIN MESSENGER-RNA; DIETARY ZINC-DEFICIENCY; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; VENTRAL PROSTATE; CANCER; MECHANISM; TESTES; GENE AB Cadmium is a known human carcinogen based on findings of lung cancer in exposed populations. A more controversial target site for cadmium is the human prostate gland, for which some studies indicate a link between cadmium exposure and cancer. Our work in various strains of Wistar rats has shown that cadmium can induce tumors in the ventral lobe of the prostate. The relevance of this type of lesion to human prostate cancer has been questioned because the ventral lobe of the rat prostate, unlike the dorsolateral lobe, has no embryological homolog in the human gland. In this study we investigated the chronic toxic and carcinogenic effects of cadmium in the Noble (NBL/Cr) rat, with particular attention to lesions of the prostate. Cadmium chloride (CdCl2) was given as a single sc injection (0, 1, 2, 4, 8, 16, or 32 mu mol/kg) to groups (initially n = 30) of 10-week-old rats, Rats were observed for up to 72 weeks following exposure. In rats that were injected with the lower doses of cadmium (less than or equal to 4 mu mol/kg), a clear dose-related increase in proliferative lesions of the dorsolateral prostate occurred (0 mu mol/kg = 36% incidence, 1 mu mol/kg = 62%, 2 mu mol/kg = 65%; 4 mu mol/kg = 79%; trend p < 0.003). Lesions were described as intraepithelial hyperplasia with occasional areas of atypical epithelial cells, without stromal invasion. At higher doses (greater than or equal to 8 mu mol/kg) the proliferative-lesion response in the dorsolateral prostate gradually declined to near control levels (8 mu mol/kg = 63%; 16 mu mol/kg = 60%; 32 mu mol/kg = 52%). The loss of prostatic response at the higher doses of cadmium was probably due to loss of testicular function secondary to cadmium treatment. This was reflected in a very high incidence (>90%) of lesions, indicative of testicular hypofunction, including tubular degeneration, mineralization, and interstitial (Leydig) cell tumors, at doses in excess of 16 mu mol/kg. Malignant injection-site sarcomas occurred at the two highest doses of cadmium, while pituitary adenomas were elevated by cadmium exposure at the highest dose. These results show that cadmium induces proliferative lesions in the dorsolateral prostate of the Noble rat, a model having a presumed relevance to human prostate cancers. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. NCI, IRSP, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, POB 12233, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [N01-CO-56000] NR 42 TC 54 Z9 57 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 1999 VL 52 IS 2 BP 154 EP 161 DI 10.1093/toxsci/52.2.154 PG 8 WC Toxicology SC Toxicology GA 267YV UT WOS:000084387600004 PM 10630567 ER PT J AU Witschi, H Espiritu, I Pinkerton, KE Murphy, K Maronpot, RR AF Witschi, H Espiritu, I Pinkerton, KE Murphy, K Maronpot, RR TI Ozone carcinogenesis revisited SO TOXICOLOGICAL SCIENCES LA English DT Article DE ozone; carcinogen; lung tumor; strain A/J mice ID NITROGEN-DIOXIDE; TOBACCO-SMOKE; MICE; EXPOSURE; CANCER; STRAINS; INJURY; RAT AB The question was asked whether ozone would act as a lung carcinogen in mice. To test the hypothesis, female strain A/J mice were exposed for 6 h/day, 5 days/week to 0.12 ppm, 0.5 ppm, or 1.0 ppm of ozone; control animals were kept in filtered air. No ozone-related deaths were observed at any time during the experiment, After 5 months, one-third of the animals were killed. The remaining animals were split into two groups: exposure to ozone continued for one group, whereas the other group was transferred into filtered air. Four months later, these animals were killed. No significant increase in lung tumor multiplicity (average number of tumors per lung) or lung tumor incidence (percentage of tumor-bearing animals) was found in the animals exposed to ozone when compared to animals kept in filtered air, regardless of ozone concentration. Morphometric analysis of lungs of animals exposed to the highest ozone concentration (1.0 ppm) showed a small, statistically not significant increase in centriacinar lesions. It was concluded that ozone is not a lung carcinogen in strain A/J mice at those exposure levels. Moreover, this mouse strain appears to be particularly resistant towards chronic ozone toxicity. C1 Univ Calif Davis, Inst Toxicol & Environm Hlth, Sch Vet Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Mol Biosci, Sch Vet Med, Davis, CA 95616 USA. Univ Calif Davis, Dept Anat Physiol & Cell Biol, Sch Vet Med, Davis, CA 95616 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Witschi, H (reprint author), Univ Calif Davis, Inst Toxicol & Environm Hlth, Sch Vet Med, 1 Shields Ave, Davis, CA 95616 USA. FU NIEHS NIH HHS [ES05707, ES00628] NR 23 TC 10 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 1999 VL 52 IS 2 BP 162 EP 167 DI 10.1093/toxsci/52.2.162 PG 6 WC Toxicology SC Toxicology GA 267YV UT WOS:000084387600005 PM 10630568 ER PT J AU Webster, JC Cidlowski, JA AF Webster, JC Cidlowski, JA TI Mechanisms of glucocorticoid-receptor-mediated repression of gene expression SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID DOWN-REGULATION; BETA-ISOFORM; RESPONSE ELEMENT; POMC GENE; NGFI-B; TRANSCRIPTION; HORMONE; BINDING; CDNA; LOCALIZATION AB It is hoped that this review will give the reader a taste, of some of the mechanisms used by the glucocorticoid receptor to repress gene function. These mechanisms include direct binding to DNA, antagonism of other transcription factor families and sequestration of necessary cofactors. Each of these mechanisms, and others, are discussed. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Webster, JC (reprint author), NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NR 41 TC 101 Z9 103 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 1999 VL 10 IS 10 BP 396 EP 402 DI 10.1016/S1043-2760(99)00186-1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259PY UT WOS:000083903300003 ER PT J AU Jones, S Sudweeks, S Yakel, JL AF Jones, S Sudweeks, S Yakel, JL TI Nicotinic receptors in the brain: correlating physiology with function SO TRENDS IN NEUROSCIENCES LA English DT Review ID VENTRAL TEGMENTAL AREA; CENTRAL-NERVOUS-SYSTEM; RAT HIPPOCAMPAL INTERNEURONS; MIDBRAIN DOPAMINE NEURONS; DEVELOPING VISUAL-CORTEX; LONG-TERM POTENTIATION; SUBUNIT MESSENGER-RNAS; KITTEN STRIATE CORTEX; FRONTAL-LOBE EPILEPSY; ACETYLCHOLINE-RECEPTORS AB Nicotinic ACh receptors (nAChRs) have been implicated in a variety of brain functions, including neuronal development, learning and memory formation, and reward. Although there are substantial data indicating that nAChR subunits are found in many brain regions, the precise cellular roles of these subunits in neuronal functions have remained elusive. Until recently, nAChRs were thought primarily to serve a modulatory role in the brain by regulating neurotransmitter release from nerve:terminals. However, new evidence has revealed that nAChRs also function in a postsynaptic role by mediating fast ACh-mediated synaptic transmission in the hippocampus and in the sensory cortex, and are found at somatodendritic as well as nerve terminal sites in the reward system. It is possible that presynaptic and postsynaptic nAChRs mediate changes in the efficacy of synaptic transmission in these brain regions. These changes could underlie the proposed functions of nAChRs in cognitive functions of the hippocampus and cerebral cortex, in neuronal development in the sensory cortex, and in reward. C1 Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Jones, S (reprint author), Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. NR 93 TC 334 Z9 343 U1 1 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD DEC PY 1999 VL 22 IS 12 BP 555 EP 561 DI 10.1016/S0166-2236(99)01471-X PG 7 WC Neurosciences SC Neurosciences & Neurology GA 253EG UT WOS:000083543200010 PM 10542436 ER PT J AU Khazaeli, MB Rodenburg, CM Mayo, MS Schlom, J AF Khazaeli, MB Rodenburg, CM Mayo, MS Schlom, J TI Characterization of V-region immunogenicity of CC49 monoclonal antibody in patients SO TUMOR TARGETING LA English DT Article DE HAMA; monoclonal antibody; V-region immunogenicity; preparative electrophoresis; heavy and light chain; TCEP center dot HC1 ID PHASE-I TRIAL; METASTATIC COLON-CANCER; HUMAN IMMUNE-RESPONSE; PHARMACOKINETICS; THERAPY; 17-1A AB The characterization of immunogenic epitopes in murine V-regions is vital to the understanding of molecular mechanisms responsible for patient antibody response to genetically engineered molecules. We have prepared a purified light and heavy chains of mouse and mouse/human chimeric CC49 in an attempt to characterize the human immune response of this reagent. Intact antibody was reduced with Tris-(2-carboxyethyl)-phosphine hydrochloride (TCEP . HC1) and purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoreils (SDS-PAGE) using BIO-RAD's Model 491 Prep Cell. All final preparations were analyzed by Western blot, SDS-PAGE and were used in competitive inhibition assays to characterize Immunogenicity, The final products proved to be stable for several months. The light and heavy chains of mouse and chimeric CC49 inhibited human anti-mouse antibody (HAMA) response in human serum equally in most cases but did not demonstrate an additive effect. All 15 patients, Infused with mCC49, had an immune response to mCC49 by day 14 with 13/15 patients having Immune response to the V-region of mCC49. V-region immunogenicity varied from patient to patient and during the course of response in each individual patient. The light and heavy chain of mouse and chimeric CC49 inhibited equally. The epitope specificity study of the human V-region immune response indicated that almost all of V-region immuno-genicity resides in the CDR epitopes. C1 Univ Alabama, Ctr Comprehens Canc, Dept Med, Wallace Tumor Inst 263, Birmingham, AL 35294 USA. Kansas Canc Inst, Kansas City, KS USA. NCI, Bethesda, MD 20892 USA. RP Khazaeli, MB (reprint author), Univ Alabama, Ctr Comprehens Canc, Dept Med, Wallace Tumor Inst 263, 1824 6th Ave S, Birmingham, AL 35294 USA. RI Mayo, Matthew/E-3774-2015 NR 28 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1351-8488 J9 TUMOR TARGET JI Tumor Target. PD DEC PY 1999 VL 4 IS 4 BP 257 EP 265 PG 9 WC Materials Science, Multidisciplinary; Medicine, Research & Experimental SC Materials Science; Research & Experimental Medicine GA 324AP UT WOS:000087598400007 ER PT J AU Otsuki, T Kajigaya, S Ozawa, E Liu, JM AF Otsuki, T Kajigaya, S Ozawa, E Liu, JM TI SNX5, a new member of the sorting nexin family, binds to the Fanconi anemia complementation group A protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Fanconi anemia; yeast two-hybrid; sorting nexin; immunoprecipitation ID SACCHAROMYCES-CEREVISIAE; ALKYLATING-AGENTS; MEMBRANE-PROTEINS; LATE-GOLGI; FAA; LOCALIZATION; RECEPTORS; COMPLEX; GENES AB The function of the Fanconi anemia complementation group A (FANCA) protein remains unclear. To investigate possible protein-protein interactions, we performed yeast two-hybrid screening using a FANCA fragment as bait. Sorting nexin 5 (SNX5), a new member of the human SNX family, was identified as a putative FANCA-binding protein. The interaction between FANCA and SNX5 was confirmed by immunoprecipitation studies. All members of the SNX family have a characteristic amino acid region termed the phox homology (PX) domain. Deletion mutant analysis indicated that the PX domain is not required for binding to FANCA. The SNX proteins are thought to play an important role in receptor trafficking between organelles. We found that overexpression of SNX5 increased FANCA protein levels. Northern blot analysis of SNX5 showed the presence of alternatively spliced transcripts and different expression patterns in various human cancer cell lines and normal tissues. Further studies are needed to elucidate the functional significance of FANCA and SNX5 binding; however, we speculate that FANCA may affect SNX5 traffic with cell surface receptors. (C) 1999 Academic Press. C1 Jichi Med Sch, Dept Hematol, Minami Kawachi, Tochigi 3290498, Japan. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Otsuki, T (reprint author), Jichi Med Sch, Dept Hematol, Yakushiji 3311-1, Minami Kawachi, Tochigi 3290498, Japan. NR 24 TC 45 Z9 45 U1 0 U2 0 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 NOV 30 PY 1999 VL 265 IS 3 BP 630 EP 635 DI 10.1006/bbrc.1999.1731 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 261FH UT WOS:000083998500004 PM 10600472 ER PT J AU Gidon-Jeangirard, C Solito, E Hofmann, A Russo-Marie, F Freyssinet, JM Martinez, MC AF Gidon-Jeangirard, C Solito, E Hofmann, A Russo-Marie, F Freyssinet, JM Martinez, MC TI Annexin V counteracts apoptosis while inducing Ca2+ influx in human lymphocytic T cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE apoptosis; signal transduction; T lymphocytes ID PHOSPHATIDYLSERINE EXPOSURE; EXTRACELLULAR CALCIUM; N-TERMINUS; MEMBRANES; VESICLES; INHIBITION; PROTEIN; BINDING; DEATH; SELECTIVITY AB We have previously shown that when annexin V is present during the execution of a cell death program, apoptosis is delayed. This is reflected by the inhibition of DNA cleavage and of the release of apoptotic membrane particles, and by reduction of the proteolytic processing of caspase-3. Here, we have studied the mechanism(s) through which annexin V counteracts apoptosis in the human CEM. T cell line. The degree of apoptosis inhibition was associated with an increase of intracellular Ca2+ concentration ([Ca2+](i)). Reduction of the extracellular Ca2+ concentration by EG;TA abolished the anti-apoptotic effect, suggesting that annexin V favors Ca2+ influx and that Ca2+ acts as an inhibitor rather than an activator of apoptosis in CEM: T cells. The effects on apoptosis and [Ca2+](i) of several modified annexins with different electrophysiological properties indicate that the N-terminal domain of annexin V is necessary for the Ca2+-dependent anti-apoptotic action of annexin V. These results suggest that annexin V regulates membrane Ca2+ permeability and is protective against apoptosis by increasing [Ca2+](i) in CEM T cells. (C) 1999 Academic Press. C1 Univ Strasbourg 1, Fac Med, Inst Hematol & Immunol, F-67085 Strasbourg, France. Hop Bicetre, INSERM, U143, F-94275 Le Kremlin Bicetre, France. Inst Cochin Genet Mol, INSERM, U332, F-75014 Paris, France. Frederick Canc Res & Dev Ctr, Frederick, MD USA. RP Martinez, MC (reprint author), Univ Strasbourg 1, Fac Med, Inst Hematol & Immunol, 4 Rue Kirschleger, F-67085 Strasbourg, France. RI Freyssinet, Jean-Marie/G-2719-2013; Hofmann, Andreas/B-9515-2008 OI Hofmann, Andreas/0000-0003-4408-5467 NR 41 TC 20 Z9 21 U1 0 U2 0 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 NOV 30 PY 1999 VL 265 IS 3 BP 709 EP 715 DI 10.1006/bbrc.1999.1752 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 261FH UT WOS:000083998500017 PM 10600485 ER PT J AU Lii, JH Ma, BY Allinger, NL AF Lii, JH Ma, BY Allinger, NL TI Importance of selecting proper basis set in quantum mechanical studies of potential energy surfaces of carbohydrates SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE ab initio; diffuse function; basis set superposition error; molecular mechanics; water dimer; hydrogen bonding; carbohydrates; aldohexose; ketohexose ID MM3 FORCE-FIELD; WATER DIMER; MOLECULAR MECHANICS; AQUEOUS-SOLUTION; D-GLUCOSE; HYDROCARBONS; ABINITIO; (NH3)2; ERRORS AB An extensive quantum mechanical study of a water dimer suggests that the introduction of a diffuse function into the basis set, which significantly reduces the basis set superposition error (BSSE) in the hydrogen bonding energy calculation, is the key to better calculations of the potential energy surfaces of carbohydrates. This article examines the potential energy surfaces of selected D-aldo- and D-ketohexoses (a total of 82 conformers) by quantum mechanics (QM) and molecular mechanics (MM) methods. Ln contrast to the results with a smaller basis set (B3LYP/6-31G** 5d), we found at the higher level calculation (B3LYP/6-311++G(2d,2p)//B3LYP/6-31G** 5d) that, in most cases, the furanose forms are less stable than the pyranose forms. These discrepancies are mainly due to the fact that intramolecular hydrogen bonding energies are overestimated in the lower level calculations. The higher level QM calculations of the potential energy surfaces of D-aldo- and D-ketohexoses now are more comparable to the MM3 results. (C) 1999 John Wiley & Sons, Inc. C1 Univ Georgia, Comp Ctr Mol Struct & Design, Dept Chem, Athens, GA 30602 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Comp Biol, Frederick, MD 21702 USA. RP Allinger, NL (reprint author), Univ Georgia, Comp Ctr Mol Struct & Design, Dept Chem, Athens, GA 30602 USA. EM allinger@sunchem.chem.uga.edu RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X NR 37 TC 124 Z9 124 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0192-8651 EI 1096-987X J9 J COMPUT CHEM JI J. Comput. Chem. PD NOV 30 PY 1999 VL 20 IS 15 BP 1593 EP 1603 DI 10.1002/(SICI)1096-987X(19991130)20:15<1593::AID-JCC1>3.0.CO;2-A PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 250YW UT WOS:000083418700001 ER PT J AU Saavedra, JM AF Saavedra, JM TI Emerging features of brain angiotensin receptors SO REGULATORY PEPTIDES LA English DT Review DE angiotensin receptor subtypes; stress; brain hypoxia; hippocampus; hypothalamus; neuropeptides ID MESSENGER-RNA EXPRESSION; I-125 CGP-42112 BINDING; II TYPE-1 RECEPTOR; UNILATERAL CAROTID LIGATION; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; MOLECULAR-CLONING; GENE-EXPRESSION; AUTORADIOGRAPHIC LOCALIZATION; PARAVENTRICULAR NUCLEUS AB In mammalian brain, angiotensin II AT(1) and AT(2) receptor subtypes are apparently expressed only in neurons and not in glia. AT(1) and AT(2) receptor subtypes are sometimes closely associated, but apparently expressed in different neurons. Brain AT(1)/AT(2) interactions may occur in selective cases as inter-neuron cross talk. There are two AT(1) isoforms in rodents, AT(1A), which predominates, and AT(1B). There are also important inter-species differences in receptor expression. Relative lack of amino acid conservation in the gerbil gAT(1A), receptor substantially decreases affinity for the AT(1) antagonists. AT(1) receptors are expressed in brain areas regulating autonomic and hormonal responses. AT(1A) receptors are heterogeneously regulated in a number of experimental conditions. In specific areas. AT(1A) receptors are not normally expressed, but are induced under influence of reproductive hormones in dopaminergic neurons. There are AT(1) and AT(2) receptors also in areas related to limbic, sensory and motor functions and their expression is developmentally regulated. A picture is emerging of widespread, neuronally localized, heterogeneously regulated, closely associated brain angiotensin receptor subtypes, modulating multiple functions including neuroendocrine and autonomic responses, stress, cerebrovascular flow, and perhaps brain maturation, neuronal plasticity, memory and behavior. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Bldg 10,Rm 2D57,MSC 1514,10 Ctr Dr, Bethesda, MD 20892 USA. NR 72 TC 67 Z9 69 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD NOV 30 PY 1999 VL 85 IS 1 BP 31 EP 45 DI 10.1016/S0167-0115(99)00081-6 PG 15 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 257VF UT WOS:000083802300004 PM 10588448 ER PT J AU Bilker, WB Berlin, JA Gail, MH Strom, BL AF Bilker, WB Berlin, JA Gail, MH Strom, BL TI An efficient design for verifying disease outcome status in large cohorts with rare exposures and low disease rates SO STATISTICS IN MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MISCLASSIFICATION AB Cohort studies require the use of large samples when the risk of the event is very low. Databases that are large and population-based, such as Medicaid files, are frequently used for cohort studies, since they provide access to the large samples required for adequate statistical power at a relatively affordable cost. Epidemiologic studies using these databases typically require verification of reported diagnoses, however, because of the potential for errors in disease reporting. When exposure prevalence is also low, as in many pharmacoepidemiologic investigations of drug toxicity, there are few exposed cases compared to the number of unexposed cases. Verification of all unexposed presumptive cases through medical records is costly. We investigate the statistical efficiency of a design in which all exposed cases but only a subsample of the unexposed cases are verified. We show that good efficiency can usually be achieved with a small subsample of unexposed cases. Published in 1999 by John Wiley & Sons, Ltd. This is a US Government work and is in the public domain in the United States. C1 Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. RP Bilker, WB (reprint author), Univ Penn, Dept Biostat & Epidemiol, Blockley Hall,Room 601,423 Guardian Dr, Philadelphia, PA 19104 USA. NR 9 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 30 PY 1999 VL 18 IS 22 BP 3021 EP 3036 DI 10.1002/(SICI)1097-0258(19991130)18:22<3021::AID-SIM242>3.3.CO;2-K PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 256FH UT WOS:000083714900003 PM 10544304 ER PT J AU Cross, HR Steenbergen, C Lefkowitz, RJ Koch, WJ Murhy, E AF Cross, HR Steenbergen, C Lefkowitz, RJ Koch, WJ Murhy, E TI Overexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (beta ARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury SO CIRCULATION RESEARCH LA English DT Article DE adrenergic signaling; energetics; G proteins; ischemia; NMR spectroscopy ID NUCLEAR-MAGNETIC-RESONANCE; G-PROTEIN; PERTUSSIS-TOXIN; TRANSGENIC MICE; RAT-HEART; ATPASE ACTIVITY; GAMMA-SUBUNITS; PHOSPHORYLATION; DESENSITIZATION; INVOLVEMENT AB Cardiac beta(2)-adrenergic receptor (beta(2)AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing beta(2)ARs (TG4s) with no adverse effects under normal conditions. To assess the consequences of beta(2)AR overexpression during ischemia, perfused hearts from TG4 and wild-type mice were subjected to 20-minute ischemia and 40-minute reperfusion. During ischemia, ATP and pH fell lower in TG4 hearts than wild type. Ischemic injury was greater in TG4 hearts, as indicated by lower postischemic recoveries of contractile function, ATP, and phosphocreatine. Because beta(2)ARs, unlike beta(1)ARs, couple to G(i) as well as G(s), we pretreated mice with the G(i) inhibitor pertussis toxin (PTX). PTX treatment increased basal contractility in TG4 hearts and abolished the contractile resistance to isoproterenol. During ischemia, ATP fell lower in TG4 +PTX than in TG4 hearts. Recoveries of contractile function and ATP were lower in TG4+PTX than in TG4 hearts. We also studied mice that overexpressed either beta ARK1 (TG beta ARK1) or a beta ARK1 inhibitor (TG beta ARKct). Recoveries of function. ATP, and phosphocreatine were higher in TG beta ARK1 hearts than in wild-typehearts. Despite basal contractility being elevated in TG beta ARKct hearts to the same level as that of TG4s, ischemic injury was not increased. In summary, beta(2)AR overexpression increased ischemic injury, whereas beta ARK1 overexpression was protective. Ischemic injury in the beta(2)AR overexpressors was exacerbated by PTX treatment, implying that it was G(s) not G(i) activity that enhanced injury. Unlike beta(2)AR overexpression, basal contractility was increased by beta ARK1 inhibitor expression without increasing ischemic injury, thus implicating a safer potential therapy for heart failure. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Cross, HR (reprint author), NIEHS, Mail Drop D2-03,Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NHLBI NIH HHS [R01 HL039752] NR 36 TC 49 Z9 50 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 29 PY 1999 VL 85 IS 11 BP 1077 EP 1084 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 260BV UT WOS:000083929200014 PM 10571539 ER PT J AU Xiao, RP Cheng, HP Zhou, YY Kuschel, M Lakatta, EG AF Xiao, RP Cheng, HP Zhou, YY Kuschel, M Lakatta, EG TI Recent advances in cardiac beta(2)-adrenergic signal transduction SO CIRCULATION RESEARCH LA English DT Review DE beta-adrenergic receptor subtype; G protein; cAMP compartmentalization; heart failure ID BETA-ADRENERGIC-RECEPTOR; PROTEIN-COUPLED RECEPTOR; RAT VENTRICULAR MYOCYTES; HEART-FAILURE; TRANSGENIC MICE; PERTUSSIS-TOXIN; PHOSPHOLAMBAN PHOSPHORYLATION; BETA-2-ADRENERGIC RECEPTORS; PHOSPHATASE INHIBITOR-1; CONFORMATIONAL-CHANGES AB Recent studies have added complexities to the conceptual framework of cardiac beta-adrenergic receptor (beta-AR) signal transduction. Whereas the classical linear G(s)-adenylyl cyclase-cAMP-protein kinase A (PKA) signaling cascade has been corroborated for beta(1)-AR stimulation, the beta(2)-AR signaling pathway bifurcates at the very first postreceptor step, the G protein level. Ln addition to G(s), beta(2)-AR couples to pertussis toxin-sensitive G(i) proteins, G(i2) and G(i3). The coupling of beta(2)-AR to G(i) proteins mediates, to a large extent, the differential actions of the beta-AR subtypes on cardiac Ca2+ handling, contractility, cAMP accumulation, and PKA-mediated protein phosphorylation. The extent of G(i) coupling in ventricular myocytes appears to be the basis of the substantial species-to-species diversity in beta(2)-AR-mediated cardiac responses. There is an apparent dissociation of beta(2)-AR-induced augmentations of the intracellular Ca2+ (Ca-i) transient and contractility from cAMP production and PKA-dependent cytoplasmic protein phosphorylation. This can be largely explained by G(i)-dependent functional compartmentalization of the beta(2)-AR-directed cAMP/PKA signaling to the sarcolemmal microdomain. This compartmentalization allows the common second messenger, cAMP, to perform selective functions during P\beta-AR subtype stimulation. Emerging evidence also points to distinctly different roles of these beta-AR subtypes in modulating noncontractile cellular processes. These recent findings not only reveal the diversity and specificity of beta-AR and G protein interactions but also provide new insights for understanding the differential regulation and functionality of beta-AR subtypes in healthy and diseased hearts. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Xiao, RP (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 99 TC 177 Z9 185 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 29 PY 1999 VL 85 IS 11 BP 1092 EP 1100 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 260BV UT WOS:000083929200016 PM 10571541 ER PT J AU Sullivan, T Escalante-Alcalde, D Bhatt, H Anver, M Bhat, N Nagashima, K Stewart, CL Burke, B AF Sullivan, T Escalante-Alcalde, D Bhatt, H Anver, M Bhat, N Nagashima, K Stewart, CL Burke, B TI Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy SO JOURNAL OF CELL BIOLOGY LA English DT Article DE emerin; muscular dystrophy; nuclear envelope; lamins ID INTERMEDIATE FILAMENTS; MEMBRANE-PROTEINS; STEM-CELLS; MOUSE; EMERIN; PHOSPHORYLATION; ORGANIZATION; MITOSIS; BINDING; DISEASE AB The nuclear lamina is a protein meshwork lining the nucleoplasmic face of the inner nuclear membrane and represents an important determinant of interphase nuclear architecture. Its major components are the A- and B-type lamins. Whereas B-type lamins are found in all mammalian cells, A-type lamin expression is developmentally regulated, In the mouse, A-type lamins do not appear until midway through embryonic development, suggesting that these proteins may be involved in the regulation of terminal differentiation. Here we show that mice lacking A-type lamins develop to term with no overt abnormalities. However, their postnatal growth is severely retarded and is characterized by the appearance of muscular dystrophy. This phenotype is associated with ultrastructural perturbations to the nuclear envelope. These include the mislocalization of emerin, an inner nuclear membrane protein, defects in which are implicated in Emery-Dreifuss muscular dystrophy (EDMD), one of the three major X-linked dystrophies. Mice lacking the A-type lamins exhibit tissue-specific alterations to their nuclear envelope integrity and emerin distribution. In skeletal and cardiac muscles, this is manifest as a dystrophic condition related to EDMD. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Lab Canc & Dev Biol, Frederick, MD 21702 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Univ Calgary, Fac Med, Dept Cell Biol & Anat, Calgary, AB T2N 4N1, Canada. RP Stewart, CL (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Lab Canc & Dev Biol, POB B, Frederick, MD 21702 USA. FU PHS HHS [N01-C0-56000] NR 32 TC 729 Z9 750 U1 1 U2 17 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 29 PY 1999 VL 147 IS 5 BP 913 EP 919 DI 10.1083/jcb.147.5.913 PG 7 WC Cell Biology SC Cell Biology GA 261EK UT WOS:000083995800005 PM 10579712 ER PT J AU Tatsumoto, T Xie, XZ Blumenthal, R Okamoto, I Miki, T AF Tatsumoto, T Xie, XZ Blumenthal, R Okamoto, I Miki, T TI Human ECT2 is an exchange factor for Rho GTPases, phosphorylated in G2/M phases, and involved in cytokinesis SO JOURNAL OF CELL BIOLOGY LA English DT Article DE cell division; phosphorylation; nucleotide exchange; oncogene; microinjection ID GUANINE-NUCLEOTIDE EXCHANGE; GTP-BINDING PROTEINS; DNA-REPLICATION; CHECKPOINT; ONCOGENE; KINASE; CLONING; CLB5 AB Animal cells divide into two daughter cells by the formation of an actomyosin-based contractile ring through a process called cytokinesis. Although many of the structural elements of cytokinesis have been identified, little is known about the signaling pathways and molecular mechanisms underlying this process. Here we show that the human ECT2 is involved in the regulation of cytokinesis. ECT2 catalyzes guanine nucleotide exchange on the small GTPases, RhoA, Rad, and Cdc42. ECT2 is phosphorylated during G2 and M phases, and phosphorylation is required for its exchange activity. Unlike other known guanine nucleotide exchange factors for Rho GTPases, ECT2 exhibits nuclear localization in interphase, spreads through-out the cytoplasm in prometaphase, and is condensed in the midbody during cytokinesis. Expression of an ECT2 derivative, containing the NH2-terminal domain required for the midbody localization but lacking the COOH-terminal catalytic domain, strongly inhibits cytokinesis, Moreover, microinjection of affinity-purified anti-ECT2 antibody into interphase cells also inhibits cytokinesis, These results suggest that ECT2 is an important link between the cell cycle machinery and Rho signaling pathways involved in the regulation of cell division. C1 NCI, Basic Res Lab, Mol Tumor Biol Sect, Bethesda, MD 20892 USA. RP Miki, T (reprint author), NCI, Basic Res Lab, Mol Tumor Biol Sect, Bldg 37,Room 1E24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 24 TC 260 Z9 262 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD NOV 29 PY 1999 VL 147 IS 5 BP 921 EP 927 DI 10.1083/jcb.147.5.921 PG 7 WC Cell Biology SC Cell Biology GA 261EK UT WOS:000083995800006 PM 10579713 ER PT J AU Khromov-Borisov, NN Rogozin, IB Henriques, JAP de Serres, FJ AF Khromov-Borisov, NN Rogozin, IB Henriques, JAP de Serres, FJ TI Similarity pattern analysis in mutational distributions SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE mutational spectra; mutational distributions; SPAN; similarity pattern analysis; contingency table collapsing; Kastenbaum-Hirotsu squared distance; Escherichia coli; lacl gene; Neurospora crassa; ad-3 forward mutation assay; spontaneous mutations; chemical mutagens; non-ionizing radiation; ionizing radiation ID 2-WAY CONTINGENCY-TABLES; AD-3 REGION; NEUROSPORA-CRASSA; LOCUS MUTATION; TRANSGENIC RODENTS; SPECTRA; DATABASES; HETEROKARYON-12; ASSOCIATION; SOFTWARE AB The validity and applicability of the statistical procedure - similarity pattern analysis (SPAN) - to the study of mutational distributions (MDs) was demonstrated with two sets of data. The first was mutational spectra (MS) for 697 GC to AT transitions produced with eight alkylating agents (AAs) in the loci gene of Escherichia coli. The second was a recently summarized data on the distributions of 11562 spontaneous, radiation- and chemical-induced forward mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. They were analyzed as large two-way contingency tables (CTs) where two kinds of profiles were compared: site (or genotypic class) profiles and origin (or mutagen) profiles. To measure similarity (homogeneity) between any pair of profiles, the relevant sufficient statistics, Kastenbaum-Hirotsu squared distance (KHi(2)), was used. Collapsing the similar profiles into distinct internally homogeneous clusters named 'collapsets' revealed their similarity pattern. To facilitate the procedure, the computer program, COLLAPSE, was elaborated. The results of SPAN for the lacI spectra were found comparable with the results of their previous analysis with two multivariate statistical methods, the factor and cluster analyses. In the ad-3 data set, five collapsets were revealed among origin profiles (OPs): (I) ENU = 4NQO = 4HAQO = FANFT = SQ18506; (II) AF-2 = EI = MMS = DEP; (III) ETO = UV; (IV) AHA = PROCARB; and (V) He ions = protons. Moreover, the previous observation that MDs are dose-dependent was confirmed for X-ray-induced MDs. Profiles induced with the low doses of X-rays are similar to that induced with Sr-85, and profiles induced with the medium X-ray doses to those induced with protons and He ions. Evaluated similarities appear to be rather reasonable: mutagens with similar mode of action induce similar MDs. Similarity pattern revealed among genotypic class profiles (GCPs) seems to be also interpretable. When supplemented with descriptive cluster analysis, SPAN appears to be a fruitful methodology in MS analysis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Fed Rio Grande Sul, Ctr Biotecnol, Lab Genotoxicidade, GENOTOX, BR-91501970 Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Dept Biofis, BR-91501970 Porto Alegre, RS, Brazil. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk, Russia. NIEHS, Environm Toxicol Program, Toxicol Lab, Syst Toxicol Branch, Res Triangle Pk, NC 27709 USA. RP Khromov-Borisov, NN (reprint author), Univ Fed Rio Grande Sul, Ctr Biotecnol, Lab Genotoxicidade, GENOTOX, Bloco IV,Predio 43-421,Caixa Postal 15-005, BR-91501970 Porto Alegre, RS, Brazil. NR 59 TC 22 Z9 22 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD NOV 29 PY 1999 VL 430 IS 1 BP 55 EP 74 DI 10.1016/S0027-5107(99)00148-7 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 267BM UT WOS:000084334800006 PM 10592318 ER PT J AU Padberg, F Zwanzger, P Thoma, H Kathmann, N Haag, C Greenberg, BD Hampel, H Moller, HJ AF Padberg, F Zwanzger, P Thoma, H Kathmann, N Haag, C Greenberg, BD Hampel, H Moller, HJ TI Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMSI SO PSYCHIATRY RESEARCH LA English DT Article; Proceedings Paper CT International Symposium on Transcranial Magnetic Simulation CY SEP 30-OCT 04, 1998 CL GOTTINGEN, GERMANY DE affective disorders; treatment; prefrontal cortex; verbal memory; reaction time ID CORTEX; MOOD; TMS AB In previous studies, fast repetitive transcranial magnetic stimulation (rTMS) with a frequency >1 Hz demonstrated substantial antidepressant effects compared to sham rTMS. However, it is not clear whether fast rTMS is superior to slow rTMS (frequency less than or equal to 1 Hz) which is safe at therapeutically promising higher intensities. The aim of this double-blind study was to compare the action of fast, slow and sham rTMS. Eighteen patients with pharmacotherapy-resistant major depression were randomized to receive fast (10 Hz), slow (0.3 Hz) or sham rTMS with 250 stimuli/day for 5 successive days. rTMS was applied at 90% motor threshold intensity to the left dorsolateral prefrontal cortex. Scores on the Hamilton Depression Rating Scale (HDRS), but not on the Montgomery-Asberg Depression Rating Scale (MADRS), showed a statistically significant time x group interaction with a reduction of 19% after slow rTMS. However, the effect was clinically marginal and not reflected by self-rating scores. Verbal memory and reaction performance were not impaired after rTMS, and there was even a statistically significant time x group interaction with improvement of verbal memory performance after fast rTMS. In conclusion, this study further supported the safety of rTMS but does not show any clinically meaningful antidepressant efficacy of rTMS at 250 daily stimuli over 5 days in pharmacotherapy-refractory major depression. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Munich, Dept Psychiat, D-80336 Munich, Germany. NIMH, NIH, Bethesda, MD 20892 USA. RP Padberg, F (reprint author), Univ Munich, Dept Psychiat, Nussbaumstr 7, D-80336 Munich, Germany. NR 36 TC 179 Z9 186 U1 2 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 29 PY 1999 VL 88 IS 3 BP 163 EP 171 DI 10.1016/S0165-1781(99)00092-X PG 9 WC Psychiatry SC Psychiatry GA 263YG UT WOS:000084152400001 PM 10622338 ER PT J AU Hahm, SH Eiden, LE AF Hahm, SH Eiden, LE TI Distinct members of the AP-1 family regulate cell-specific and inducible transcription of the VIP gene SO BRAIN RESEARCH LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 27 PY 1999 VL 848 IS 1-2 MA P211 BP A26 EP A26 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 268MN UT WOS:000084420300057 ER PT J AU Hahm, SH Lee, HW Eiden, LE AF Hahm, SH Lee, HW Eiden, LE TI Combinatorial regulation of neuropeptide gene transcription by calcium SO BRAIN RESEARCH LA English DT Meeting Abstract C1 NIMH, Mol Neurosci Sect, LCMR, IRP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 27 PY 1999 VL 848 IS 1-2 MA P27 BP A25 EP A25 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 268MN UT WOS:000084420300053 ER PT J AU Offen, D Melamed, E Fridkin, M Brenneman, DE Gozes, I AF Offen, D Melamed, E Fridkin, M Brenneman, DE Gozes, I TI VIP protects from dopamine toxicity: relevance for Parkinson's disease SO BRAIN RESEARCH LA English DT Meeting Abstract C1 Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NICHD, NIH, Bethesda, MD USA. Weizmann Inst Sci, IL-76100 Rehovot, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 27 PY 1999 VL 848 IS 1-2 MA P46 BP A36 EP A36 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 268MN UT WOS:000084420300106 ER PT J AU Sudakov, SK Terebilina, NN Medvedeva, OF Rusakova, IV Goldberg, SR AF Sudakov, SK Terebilina, NN Medvedeva, OF Rusakova, IV Goldberg, SR TI Genetic predisposition to high anxiety in rats may be determined by a low level of substance P in the brain SO BRAIN RESEARCH LA English DT Meeting Abstract C1 Res Inst Addict, Moscow, Russia. NIDA, Preclin Pharmacol Lab, NIH, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 27 PY 1999 VL 848 IS 1-2 MA P327 BP A34 EP A34 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 268MN UT WOS:000084420300094 ER PT J AU Weihe, E Bette, M Rohrenbeck, A Schafer, MKH Eiden, LE Dietzschold, B AF Weihe, E Bette, M Rohrenbeck, A Schafer, MKH Eiden, LE Dietzschold, B TI Virus-induced regulation of neuropeptide expression in rat cerebrocortical neurons: Differential influence of immunosuppression and immune tolerance SO BRAIN RESEARCH LA English DT Meeting Abstract C1 Univ Marburg, Inst Anat & Cell Biol, D-35033 Marburg, Germany. NIH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Ctr Neurovirol, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 27 PY 1999 VL 848 IS 1-2 MA 065 BP A20 EP A20 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 268MN UT WOS:000084420300030 ER PT J AU Chuman, Y Bergman, AC Ueno, T Saito, S Sakaguchi, K Alaiya, AA Franzen, B Bergman, T Arnott, D Auer, G Appella, E Jornvall, H Linder, S AF Chuman, Y Bergman, AC Ueno, T Saito, S Sakaguchi, K Alaiya, AA Franzen, B Bergman, T Arnott, D Auer, G Appella, E Jornvall, H Linder, S TI Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas SO FEBS LETTERS LA English DT Article DE lung adenocarcinoma; aspartic protease; tumor diagnosis; mass spectrometry AB A pair of 35 kDa polypeptides (TAO1/TAO2) are expressed in more than 90% of all primary lung adenocarcinomas but not in other major malignancies. Mass spectrometry of tryptic peptides showed that TAO1/TAO2 is identical to napsin A, a recently described member of the aspartic proteinase family. The site of processing of pronapsin A to the mature form was located, Napsin expression was detected in human lung adenocarcinoma tumors, compatible with the marker nature of TAO1/TAO2 in the diagnosis of primary lung adenocarcinoma. This is important since identification of markers which can distinguish primary lung adenocarcinomas from distant metastases is desirable. Northern blot analysis showed expression of napsin also in normal lung and kidney tissue, and in situ hybridization showed expression in type II alveolar cells of the lung. This protease is concluded to have a specific functional role in the normal alveolar epithelium and is a candidate protease for the proteolytic processing of surfactant precursors. (C) 1999 Federation of European Biochemical Societies. C1 Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Radiumhemmets Res Lab, Stockholm, Sweden. Karolinska Hosp, Unit Tumor Pathol, Canc Ctr Karolinska, Dept Pathol & Oncol, S-17176 Stockholm, Sweden. Genentech Inc, Dept Prot Chem, S San Francisco, CA 94080 USA. RP Jornvall, H (reprint author), Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden. NR 16 TC 77 Z9 80 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 26 PY 1999 VL 462 IS 1-2 BP 129 EP 134 DI 10.1016/S0014-5793(99)01493-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 260HK UT WOS:000083943300025 PM 10580105 ER PT J AU Lopez-Carrillo, L Lopez-Cervantes, M Ward, MH Bravo-Alvarado, J Ramirez-Espitia, A AF Lopez-Carrillo, L Lopez-Cervantes, M Ward, MH Bravo-Alvarado, J Ramirez-Espitia, A TI Nutrient intake and gastric cancer in Mexico SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID STOMACH; RISK AB In contrast to the decreasing trends observed in most countries, gastric-cancer mortality has remained at about the same level in Mexico throughout the last 40 years. As part of a study carried out in the metropolitan area of Mexico City, an assessment of nutrient intake and gastric cancer is presented here. The study population comprised 220 cases of gastric cancer and 752 population-based controls. Our results showed 70 to 80% reduction in the risk of developing this tumor, associated with the intake of polyunsaturated fat, fiber and vitamin E; and this effect was independent of the histological type of the tumor (i.e., intestinal or diffuse). On the other hand, an increased risk of gastric cancer was related to the consumption of saturated fat (ORQ4vs.Q1 = 4.37, 95% Cl 1.89-10.12) and, cholesterol (ORQ4vs.Q1 = 2.39, 95% Cl 1.23-4.64), but such effects were restricted to the intestinal type of gastric cancer. In the whole study population, monounsaturated fat intake increased the risk for gastric cancer, and a marginally significant increasing trend was observed for protein consumption. The findings from this study add information about the role of specific nutrients in the etiology of gastric cancer. (C) 1999 Wiley-Liss, Inc. C1 Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. RP Lopez-Carrillo, L (reprint author), Av Univ 655,Col Sta Ma Ahuacatitlan, Cuernavaca 62508, Morelos, Mexico. NR 20 TC 62 Z9 63 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 26 PY 1999 VL 83 IS 5 BP 601 EP 605 DI 10.1002/(SICI)1097-0215(19991126)83:5<601::AID-IJC5>3.0.CO;2-6 PG 5 WC Oncology SC Oncology GA 249YH UT WOS:000083360500005 PM 10521793 ER PT J AU You, WC Li, JY Blot, WJ Chang, YS Jin, ML Gail, MH Zhang, L Liu, WD Ma, JL Hu, YR Mark, SD Correa, P Fraumeni, JF Xu, GW AF You, WC Li, JY Blot, WJ Chang, YS Jin, ML Gail, MH Zhang, L Liu, WD Ma, JL Hu, YR Mark, SD Correa, P Fraumeni, JF Xu, GW TI Evolution of precancerous lesions in a rural Chinese population at high risk of gastric cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID METAPLASIA TYPE-III; STOMACH-CANCER; FOLLOW-UP; DYSPLASIA; COHORT AB The pathogenesis of gastric cancer (GC), particularly of the intestinal type, is thought to involve a multistep and multifactorial process. Our objective was to determine the rates of transition from early to advanced gastric lesions in a population in Linqu County, China, where the GC rates are among the highest in the world. An endoscopic screening survey was launched in 1989-1990 among 3,399 residents aged 34-64 years with precancerous lesions diagnosed from biopsies taken from 7 standard locations in the stomach and from any suspicious sites. The cohort was subsequently followed, with endoscopic and histopathologic examinations conducted in 1994. Logistic regression analysis was used to estimate odds ratios (ORs) of progression to advanced lesions of various levels of severity as a function of age, sex and baseline pathology. The rates of progression were higher among older subjects, among men and among subjects with more extensive gastric lesions. 34 incident GCs were identified during the follow-up period. The Ops of GC, adjusted for age and sex, varied from 17.1 for those with baseline diagnoses of superficial intestinal metaplasia (IM), to 29.3, for those with deep IM or mild dysplasia (DYS) or IM with glandular atrophy and neck hyperplasia, to 104.2, for those with moderate or severe DYS, as compared with subjects with superficial gastritis (SG) or chronic atrophic gastritis (CAG) at baseline. Our prospective study of a high-risk population revealed sharp increases in the risk of GC and advanced precursor lesions according to the severity of lesions diagnosed at the start of follow-up. (dagger) Published 1999 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Beijing Med Univ, Beijing Inst Canc Res, Beijing 100083, Peoples R China. Beijing Med Univ, Sch Oncol, Beijing 100083, Peoples R China. Int Epidemiol Inst, Rockville, MD USA. Linqu Publ Hlth Bur, Shandong, Peoples R China. Westat Inc, Rockville, MD USA. Louisiana State Univ, Med Ctr, New Orleans, LA USA. RP You, WC (reprint author), NCI, Div Canc Epidemiol & Genet, EPS Room 8030,6120 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CP-05631, N01-CP-15620, N01-CP-95660] NR 21 TC 94 Z9 100 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 26 PY 1999 VL 83 IS 5 BP 615 EP 619 DI 10.1002/(SICI)1097-0215(19991126)83:5<615::AID-IJC8>3.0.CO;2-L PG 5 WC Oncology SC Oncology GA 249YH UT WOS:000083360500008 PM 10521796 ER PT J AU Bennett, MC Bishop, JF Leng, Y Chock, PB Chase, TN Mouradian, MM AF Bennett, MC Bishop, JF Leng, Y Chock, PB Chase, TN Mouradian, MM TI Degradation of alpha-synuclein by proteasome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PARKINSONS-DISEASE; LEWY BODIES; PROTEIN-DEGRADATION; DEMENTIA; AGGREGATION; UBIQUITIN; MUTATION AB Mutations in alpha-synuclein are known to be associated with Parkinson's disease (PD), The coexistence of this neuronal protein with ubiquitin and proteasome subunits in Lewy bodies in sporadic disease suggests that alterations of alpha-synuclein catabolism may contribute to the pathogenesis of PD. The degradation pathway of alpha-synuclein has not been identified nor has the kinetics of this process been described. We investigated the degradation kinetics of both wild-type and A53T mutant 6XHis-tagged alpha-synuclein in transiently transfected SH-SY5Y cells. Degradation of both isoforms followed first-order kinetics over 24 h as monitored by the pulse-chase method. However, the t(1/2) of mutant alpha-synuclein was 50% longer than that of the wild-type protein (p < 0.01). The degradation of both recombinant proteins and endogenous alpha-synuclein in these cells was blocked by the selective proteasome inhibitor beta-lactone (40 mu M), indicating that both wild-type and A53T mutant alpha-synuclein are degraded by the ubiquitin-proteasome pathway. The slower degradation of mutant alpha-synuclein provides a kinetic basis for its intracellular accumulation, thus favoring its aggregation. C1 NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Expt Therapeut Branch, NIH, 10 Ctr Dr,MSC 1046,Bldg 10,Rm 5C-116, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 23 TC 285 Z9 292 U1 2 U2 10 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 NOV 26 PY 1999 VL 274 IS 48 BP 33855 EP 33858 DI 10.1074/jbc.274.48.33855 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 258UL UT WOS:000083857500008 PM 10567343 ER PT J AU Razin, E Zhang, ZC Nechushtan, H Frenkel, S Lee, YN Arudehandran, R Rivera, J AF Razin, E Zhang, ZC Nechushtan, H Frenkel, S Lee, YN Arudehandran, R Rivera, J TI Suppression of microphthalmia transcriptional activity by its association with protein kinase C-interacting protein 1 in mast cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEIN; SECRETORY GRANULE PROTEASES; SERINE PROTEASES; GENE-EXPRESSION; MUTANT MICE; LOCUS; TFE3; POPULATIONS; ACTIVATION; FAMILY AB Microphthalmia (mi) is a transcription factor that plays a major role in the regulation of growth and function in mast cells and melanocytes. Association of mi with other proteins is a critical step in the regulation of mi-mediated transcriptional activation We found protein kinase C-interacting protein 1 (PKCI) specifically associated with mi in yeast two-hybrid screening. Immunoprecipitation of mi from quiescent rat basophilic leukemic cells or mouse melanocytes resulted in the specific co-immunoprecipitation of PKCI. This association was significantly reduced on engagement of the surface Fc epsilon RI of mast cells or engagement of the Kit receptor on melanocytes. Hence, cell activation caused disengagement of mi from PKCI. Microphthalmia was previously shown to activate the mouse mast cell protease 6 (mMCP-6) promoter. Cotransfection of mi with PKCI in NIH 3T3 fibroblasts containing an mMCP-6 promoter-luciferase reporter demonstrated an up to 94% inhibition of mi-mediated transcriptional activation PKCI by itself, although localized in the cytosol and nucleus of the cells, has no known physiological function and did not demonstrate transcriptional activity. Its ability to suppres mi transcriptional activity in the transient transfected fibroblast system suggests that it can function in vivo as a negative regulator of mi-induced transcriptional activation. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. NIAMS, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Razin, E (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, POB 12272, IL-91120 Jerusalem, Israel. OI Frenkel, Shahar/0000-0002-3688-8676 NR 26 TC 74 Z9 77 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 NOV 26 PY 1999 VL 274 IS 48 BP 34272 EP 34276 DI 10.1074/jbc.274.48.34272 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 258UL UT WOS:000083857500067 PM 10567402 ER PT J AU Lee, SK Anzick, SL Choi, JE Bubendorf, L Guan, XY Jung, YK Kallioniemi, OP Kononen, J Trent, JM Azorsa, D Jhun, BH Cheong, JH Lee, YC Meltzer, PS Lee, JW AF Lee, SK Anzick, SL Choi, JE Bubendorf, L Guan, XY Jung, YK Kallioniemi, OP Kononen, J Trent, JM Azorsa, D Jhun, BH Cheong, JH Lee, YC Meltzer, PS Lee, JW TI A nuclear factor, ASC-2, as a cancer-amplified transcriptional coactivator essential for ligand-dependent transactivation by nuclear receptors in vivo SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID THYROID-HORMONE RECEPTOR; ACTIVATION FUNCTION AF-2; HUMAN BREAST-CANCER; ESTROGEN-RECEPTOR; HISTONE ACETYLTRANSFERASE; MEDIATED TRANSACTIVATIONS; CRYSTAL-STRUCTURE; BINDING DOMAIN; RETINOIC-ACID; CO-REPRESSOR AB Many transcription coactivators interact with nuclear receptors in a ligand- and C-terminal transactivation function (AF2)-dependent manner. We isolated a nuclear factor (designated ASC-2) with such properties by using the ligand-binding domain of retinoid X receptor as a bait in a yeast two-hybrid screening. ASC-2 also interacted with other nuclear receptors, including retinoic acid receptor, thyroid hormone receptor, estrogen receptor alpha, and glucocorticoid receptor, basal factors TFIIA and TBP, and transcription integrators CBP/p300 and SRC-1. In transient cotransfections, ASC-2, either alone or in conjunction with CBP/p300 and SRC-1, stimulated ligand dependent transactivation by wild type nuclear receptors but not mutant receptors lacking the AF2 domain. Consistent with an idea that ASC-2 is essential for the nuclear receptor function in vivo, microinjection of anti-ASC-2 antibody abrogated the ligand-dependent transactivation of retinoic acid receptor, and this repression was fully relieved by coinjection of ASC-2-expression vector. Surprisingly, ASC-2 was identical to a gene previously identified during a search for genes amplified and overexpressed in breast and other human cancers. From these results, we concluded that ASC-2 is a bona fide transcription coactivator molecule of nuclear receptors, and its altered expression may contribute to the development of cancers. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea. Kwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500303, South Korea. Chonnam Natl Univ, Ctr Ligand & Transcript, Kwangju 500757, South Korea. Chonnam Natl Univ, Hormone Res Ctr, Kwangju 500757, South Korea. RP Lee, JW (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RI Guan, Xin-Yuan/A-3639-2009; Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011; Kallioniemi, Olli/H-4738-2012; OI Guan, Xin-Yuan/0000-0002-4485-6017; Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Jung, Yong-Keun/0000-0002-9686-3120 NR 76 TC 159 Z9 170 U1 0 U2 3 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 NOV 26 PY 1999 VL 274 IS 48 BP 34283 EP 34293 DI 10.1074/jbc.274.48.34283 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 258UL UT WOS:000083857500069 PM 10567404 ER PT J AU Groll, AH Mickiene, D Werner, K Piscitelli, SC Walsh, TJ AF Groll, AH Mickiene, D Werner, K Piscitelli, SC Walsh, TJ TI High-performance liquid chromatographic determination of liposomal nystatin in plasma and tissues for pharmacokinetic and tissue distribution studies SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE nystatin ID ENCAPSULATED NYSTATIN; AMPHOTERICIN-B; MICE; VALIDATION; TOXICITY AB A reliable reversed-phase high-performance liquid chromatographic method was developed for the determination of liposomal nystatin in plasma. Nystatin is extracted by 1:2 (v/v) liquid-liquid extraction with methanol. separation is achieved by HPLC after direct injection on a mu Bondapak(TM) C-18 analytical column with a mobile phase composed of 10 mM sodium phosphate, 1 mM EDTA, 30% methanol and 30% acetonitrile adjusted to pH 6. Detection is by ultraviolet absorbance at 305 nm. Quantitation is based on the sum of the peak area concentration of the two major isomers of nystatin, which elute at 7.5-8.5 and 9.5-10.5 min. The assay was linear over the concentration range of 0.05 to 50 mu g/ml. The lower limit of quantitation was 0.05 mu g/ml, sufficient for investigating the plasma pharmacokinetics of liposomal nystatin in preclinical studies. Accuracies and intra- and inter-day precision showed good reproducibility. With minor modifications, this method also was used for assaying nystatin in various non-plasma body fluids and tissues. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Pharmacokinet Res Lab, Dept Pharm, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 19 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD NOV 26 PY 1999 VL 735 IS 1 BP 51 EP 62 DI 10.1016/S0378-4347(99)00396-5 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 267WN UT WOS:000084382400007 PM 10630890 ER PT J AU Borlongan, CV Stahl, CE Redei, E Wang, Y AF Borlongan, CV Stahl, CE Redei, E Wang, Y TI Prepro-thyrotropin-releasing hormone 178-199 exerts partial protection against cerebral ischemia in adult rats SO NEUROREPORT LA English DT Article DE corticosterone; corticotrophin release-inhibiting factor; infarction; locomotor activity; stress; stroke ID INHIBITING FACTOR; STRESS; BRAIN; INFARCTION; STROKE; INJURY; DAMAGE AB WE examined in the present study the effects of the centrally administered prepro-thyrotropin-releasing-hormone 178-199 (prepro-TRH 178-199) on cerebral ischemia induced by ligation of the middle cerebral artery (MCA) in adult Sprague-Dawley rats. Animals were intracerebrally injected with prepro-TRH 178-199 (6 mu g/kg or 200 mu g/kg) or saline 1-2 h before ligation of MCA. Ischemic animals that received prepro-TRH 178-199, regardless of dosage, displayed some amelioration (20%) of motor asymmetry associated with MCA ligation, while ischemic animals that received saline continued to exhibit significant asymmetrical behaviors, Interestingly, triphenyltetrazolium chloride staining (a marker for tissue metabolic activity) revealed that four of five ischemic animals that received 200 mu g/kg prepro-TRH 178-199 showed a marked reduction (90-100%) in the infarction of the frontal cortex, although the posterior sections of the cortex remained infarcted, In contrast, ischemic animals that received 6 mu g/kg prepro-TRH 178-199 demonstrated infarction that did not differ in size and extent from those that received saline. Post hoc examination revealed that ischemic animals treated with 200 mu g/kg prepro-TRH 178-199 had significantly lower corticosterone (CORT) levels (115 +/- 23 ng/ml) than ischemic animals treated with 6 mu g/kg prepro-TRH 178-199 or saline (288 +/- 51 ng/ml). The present observation provides the first evidence that prepro-TRH 178-199 can promote neuroprotection against cerebral ischemia. (C) 1999 Lippincott Williams & Wilkins. C1 Natl Inst Drug Abuse, NIH, Intramural Res Program, Baltimore, MD 21224 USA. William Beaumont Army Med Ctr, Dept Internal Med, El Paso, TX 79920 USA. Northwestern Univ, Sch Med, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. Natl Def Med Ctr, Taipei 100, Taiwan. RP Borlongan, CV (reprint author), Natl Inst Drug Abuse, NIH, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Borlongan, Cesar/0000-0002-2966-9782 NR 27 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 26 PY 1999 VL 10 IS 17 BP 3501 EP 3505 DI 10.1097/00001756-199911260-00007 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 260DJ UT WOS:000083934000008 PM 10619633 ER PT J AU Desmoucelles, C Vaudry, H Eiden, LE Anouar, Y AF Desmoucelles, C Vaudry, H Eiden, LE Anouar, Y TI Synergistic action of upstream elements and a promoter-proximal CRE is required for neuroendocrine cell-specific expression and second-messenger regulation of the gene encoding the human secretory protein secretogranin II SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE secretogranin II; promoter; gene expression; second messengers; cyclic AMP response element; human ID GONADOTROPIN-RELEASING-HORMONE; CAMP RESPONSE ELEMENT; CHROMOGRANIN-A; TRANSCRIPTIONAL ACTIVITY; BINDING PROTEIN; CYCLIC-AMP; PITUITARY; PEPTIDE; FAMILY; ACID AB Secretogranin II (SgII) is a secretory polypeptide stored in large dense core vesicles of neuroendocrine and neuronal cells. In order to characterize the molecular mechanisms underlying the tissue-specific expression of the SgII gene and its regulation by second-messenger pathways in endocrine and neuronal cells, we have cloned and characterized the human SgII gene. Sequence analysis revealed the existence of numerous putative cis regulatory elements in the SgII gene promoter, including a consensus cyclic AMP-responsive element (CRE). Constructs containing different portions of the human SgII promoter fused to the luciferase reporter were transfected in AtT-20, SH-SY5Y, LLC-PK1 or COS-7 cells. Northern blot analysis showed that the endogenous SgII gene is more highly expressed in AtT-20 cells than in SH-SY5Y cells, and not expressed at all in LLC-PK1 cells. Treatment by forskolin or 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a 1.5- and 10-fold increase, respectively, in SgII mRNA levels in SH-SY5Y cells but not in AtT-20 cells. Transfection experiments revealed that 4 kb of the human SgII promoter is sufficient to impart cell-specific expression of the reporter gene in the four cell lines studied. Specifically, in AtT-20 cells, a positive element located between - 1.38 and - 4 kb, in addition to the CRE, is responsible for the high expression of the SgII gene. In SH-SY5Y cells, a negative element located between - 0.66 and - 1.4 kb represses the activating effect of the CRE leading to an overall lower activity of fusion genes in these cells compared to the activity in AtT-20 cells. Finally, the promoter activity was very low in LLC-PK1 and COS-7 cells. Forskolin and TPA stimulated the activity of a SgII-luciferase fusion gene in SH-SY5Y but not in AtT-20 cells. Disruption of the CRE abolished the stimulatory effect of forskolin and TPA. These data suggest that the basal activity of the human SgII gene relies on cell-specific trans-acting factors in addition to factors that bind to the CRE and show that the regulation of this gene by second messengers is cell-specific and requires an intact CRE. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Rouen, European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol,IFRMP 23, INSERM U413,UA CNRS, F-76821 Mt St Aignan, France. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Vaudry, H (reprint author), Univ Rouen, European Inst Peptide Res, Lab Cellular & Mol Neuroendocrinol,IFRMP 23, INSERM U413,UA CNRS, F-76821 Mt St Aignan, France. OI Eiden, Lee/0000-0001-7524-944X NR 41 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD NOV 25 PY 1999 VL 157 IS 1-2 BP 55 EP 66 DI 10.1016/S0303-7207(99)00158-6 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 259GH UT WOS:000083885800006 PM 10619397 ER PT J AU O'Brien, SJ Stanyon, R AF O'Brien, SJ Stanyon, R TI Phylogenomics - Ancestral primate viewed SO NATURE LA English DT Article ID CHROMOSOMES C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. OI Stanyon, Roscoe/0000-0002-7229-1092 NR 14 TC 44 Z9 47 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 25 PY 1999 VL 402 IS 6760 BP 365 EP 366 DI 10.1038/46450 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259VA UT WOS:000083913600036 PM 10586870 ER PT J AU Klebanoff, MA Levine, RJ DerSimonian, R Clemens, JD Wilkins, DG AF Klebanoff, MA Levine, RJ DerSimonian, R Clemens, JD Wilkins, DG TI Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PREGNANCY; CONSUMPTION; BEVERAGES; COFFEE AB Background: Whether the consumption of caffeine during pregnancy increases the risk of spontaneous abortion is controversial. Prior studies have determined caffeine consumption by questionnaire. We used a biologic marker, serum paraxanthine, a metabolite of caffeine, to measure the dose of caffeine. Methods: In a nested case-control study, we measured serum paraxanthine in 591 women who had spontaneous abortions at less than 140 days' gestation and in 2558 matched women from the same clinic who gave birth to live infants at 28 weeks' gestation or later and who had serum drawn on the same day of gestation as the women who had abortions. The women were enrolled in the Collaborative Perinatal Project during the period from 1959 to 1966, and serum paraxanthine was measured over 30 years later. Results: A total of 487 women who had spontaneous abortions (82 percent) and 2087 controls (82 percent) had quantifiable serum paraxanthine concentrations. However, the mean serum paraxanthine concentration was higher in the women who had spontaneous abortions than in the controls (752 vs. 583 ng per milliliter, P<0.001). The odds ratio for spontaneous abortion was not significantly elevated in the women who had serum paraxanthine concentrations of 1845 ng per milliliter or lower, corresponding to the 95th percentile of the matched women. However, the adjusted odds ratio for spontaneous abortion among women with serum paraxanthine concentrations higher than 1845 ng per milliliter, as compared with women who had concentrations below 50 ng per milliliter, was 1.9 (95 percent confidence interval, 1.2 to 2.8). Conclusions: Only extremely high serum paraxanthine concentrations are associated with spontaneous abortion. This suggests that moderate consumption of caffeine is unlikely to increase the risk of spontaneous abortion. (N Engl J Med 1999;341:1639-44.) (C) 1999, Massachusetts Medical Society. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Univ Utah, Ctr Human Toxicol, Salt Lake City, UT USA. RP Klebanoff, MA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Bldg,Rm 7B03,MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-7-3262] NR 20 TC 76 Z9 79 U1 1 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 1999 VL 341 IS 22 BP 1639 EP 1644 DI 10.1056/NEJM199911253412202 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 258PL UT WOS:000083847500002 PM 10572151 ER PT J AU Garcia, PM Moye, J Lew, JF AF Garcia, PM Moye, J Lew, JF TI Maternal viral load and the risk of perinatal transmission of HIV-1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1 C1 Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NICHHD, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL 32610 USA. RP Garcia, PM (reprint author), Northwestern Univ, Sch Med, Chicago, IL 60611 USA. NR 7 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 1999 VL 341 IS 22 BP 1699 EP 1700 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 258PL UT WOS:000083847500019 ER PT J AU Mofenson, LM Lambert, JS Stiehm, ER AF Mofenson, LM Lambert, JS Stiehm, ER TI Maternal viral load and the risk of perinatal transmission of HIV-1 - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NICHHD, Rockville, MD 20852 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Mofenson, LM (reprint author), NICHHD, Rockville, MD 20852 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 25 PY 1999 VL 341 IS 22 BP 1699 EP 1699 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 258PL UT WOS:000083847500018 ER PT J AU Sabri, F Tresoldi, E Di Stefano, M Polo, S Monaco, MC Verani, A Fiore, JR Lusso, P Major, E Chiodi, F Scarlatti, G AF Sabri, F Tresoldi, E Di Stefano, M Polo, S Monaco, MC Verani, A Fiore, JR Lusso, P Major, E Chiodi, F Scarlatti, G TI Nonproductive human immunodeficiency virus type 1 infection of human fetal astrocytes: Independence from CD4 and major chemokine receptors SO VIROLOGY LA English DT Article DE HIV-1; astrocytes; chemokine receptors; biological phenotype; latency ID CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; HIV-1 INFECTION; GLIAL-CELLS; T-CELLS; FUNCTIONAL EXPRESSION; CELLULAR-LOCALIZATION; CORECEPTOR USAGE; ENVELOPE PROTEIN; CO-RECEPTORS AB Human immunodeficiency virus type 1 (HIV-1) infection of the brain is associated with neurological manifestations both in adults and in children. The primary target for HIV-1 infection in the brain is the microglia, but astrocytes can also be infected. We tested 26 primary HIV-1 isolates for their capacity to infect human fetal astrocytes in culture. Eight of these isolates, independent of their biological phenotype and chemokine receptor usage, were able to infect astrocytes. Although no sustained viral replication could be demonstrated, the virus was recovered by coculture with receptive cells such as macrophages or on stimulation with interleukin-1 beta. To gain knowledge into the molecular events that regulate attachment and penetration of HIV-1 in astrocytes, we investigated the expression of several chemokine receptors. Fluorocytometry and calcium-mobilization assay did not provide evidence of expression of any of the major HIV-1 coreceptors, including CXCR4, CCR5, CCR3, and CCR2b, as well as the CD4 molecule on the cell surface of human fetal astrocytes. However, mRNA transcripts for CXCR4, CCR5, Bonzo/STRL33/TYMSTR, and APJ were detected by RT-PCR. Furthermore, infection of astrocytes by HIV-I isolates with different chemokine receptor usage was not inhibited by the chemokines SDF-1 beta, RANTES, MIP-1 beta, or MCP-1 or by antibodies directed against the third variable region or the CD4 binding site of gp120. These data show that astrocytes can be infected by primary HIV-I isolates via a mechanism independent of CD4 or major chemokine receptors. Furthermore, astrocytes are potential carriers of latent HIV-1 and on activation may be implicated in spreading the infection to other neighbouring cells, such as microglia or macrophages. (C) 1999 Academic Press. C1 Karolinska Inst, Microbiol & Tumorbiol Ctr, S-17177 Stockholm, Sweden. San Raffaele Sci Inst, DIBIT, Unit Immunobiol HIV, I-20132 Milan, Italy. San Raffaele Sci Inst, DIBIT, Unit Human Virol, I-20132 Milan, Italy. San Raffaele Sci Inst, DIBIT, Mol Immunoregulat Unit, I-20132 Milan, Italy. Univ Bari, Clin Infect Dis, I-70124 Bari, Italy. NINDS, Lab Mol Med & Neurosci, Bethesda, MD 20892 USA. RP Scarlatti, G (reprint author), Karolinska Inst, Microbiol & Tumorbiol Ctr, Doktorsringen 13, S-17177 Stockholm, Sweden. RI Polo, Simona/P-3509-2014; OI fiore, jose ramon/0000-0002-3079-5866 NR 69 TC 82 Z9 83 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 1999 VL 264 IS 2 BP 370 EP 384 DI 10.1006/viro.1999.9998 PG 15 WC Virology SC Virology GA 259RQ UT WOS:000083907200011 PM 10562499 ER PT J AU Qiu, JM Brown, KE AF Qiu, JM Brown, KE TI Integrin alpha V beta 5 is not involved in adeno-associated virus type 2 (AAV2) infection SO VIROLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; MOUTH-DISEASE VIRUS; CELLULAR ENTRY; RGD SEQUENCE; CELLS; BINDING; VITRONECTIN; EXPRESSION; PROTEIN; ADENOVIRUS-2 AB alpha V beta 5 integrin was recently proposed as a coreceptor for adeno-associated virus type 2 (AAV2) infection (Summerford et al., 1999, Nat Med. 5, 78-82), based mainly on the direct binding of AAV2 to denatured beta 5 by virus overlay assay. In studies using purified natural or recombinant human integrin alpha V beta 5 we were unable to demonstrate AAV2 binding, either by virus overlay or by liquid binding assay. Furthermore, neither purified integrin alpha V beta 5, nor RGD peptides, nor functional blocking monoclonal antibody blocked rAAV2 transduction. These data strongly suggest that integrin alpha V beta 5 is not involved in AAV2 infection. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Qiu, JM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C218,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 30 Z9 30 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 1999 VL 264 IS 2 BP 436 EP 440 DI 10.1006/viro.1999.0010 PG 5 WC Virology SC Virology GA 259RQ UT WOS:000083907200017 PM 10562505 ER PT J AU Bird, AP Wolffe, AP AF Bird, AP Wolffe, AP TI Methylation-induced repression - Belts, braces, and chromatin SO CELL LA English DT Review ID CPG METHYLATION; DNA METHYLATION C1 Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Bird, AP (reprint author), Univ Edinburgh, Inst Cell & Mol Biol, Kings Bldg, Edinburgh EH9 3JR, Midlothian, Scotland. NR 21 TC 1205 Z9 1253 U1 8 U2 63 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 24 PY 1999 VL 99 IS 5 BP 451 EP 454 DI 10.1016/S0092-8674(00)81532-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 261AU UT WOS:000083986300003 PM 10589672 ER PT J CA CDC TI Safer and healthier foods - 1900-1999 (Reprinted from MMWR, vol 48, pg 905, 1999) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID UNITED-STATES; INFECTIONS; OUTBREAK; PELLAGRA; EPIDEMIC; OBESITY C1 US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. USDA, Washington, DC USA. US EPA, Washington, DC 20460 USA. NIH, Div Nutr Res Coordinat, Bethesda, MD USA. CDC, Natl Ctr Hlth Stat, Atlanta, GA 30333 USA. CDC, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. CDC, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. CDC, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. RP US EPA, Washington, DC 20460 USA. NR 34 TC 0 Z9 0 U1 0 U2 0 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 NOV 24 PY 1999 VL 282 IS 20 BP 1909 EP 1912 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 257BZ UT WOS:000083763400010 ER PT J AU Ellis, GB AF Ellis, GB TI Keeping research subjects out of harm's way SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Off Protect Res Risks, Off Director, NIH, Rockville, MD 20892 USA. RP Ellis, GB (reprint author), Off Protect Res Risks, Off Director, NIH, Suite 3B01,6100 Execut Blvd, Rockville, MD 20892 USA. NR 10 TC 16 Z9 16 U1 0 U2 0 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 NOV 24 PY 1999 VL 282 IS 20 BP 1963 EP 1965 DI 10.1001/jama.282.20.1963 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 257BZ UT WOS:000083763400034 PM 10580465 ER PT J AU Zhu, PP Szczepanowski, RH Nosworthy, NJ Ginsburg, A Peterkofsky, A AF Zhu, PP Szczepanowski, RH Nosworthy, NJ Ginsburg, A Peterkofsky, A TI Reconstitution studies using the helical and carboxy-terminal domains of enzyme I of the phosphoenolpyruvate : sugar phosphotransferase system SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI PHOSPHOENOLPYRUVATE; CONTAINING PHOSPHOCARRIER PROTEIN; PYRUVATE PHOSPHATE DIKINASE; MYCOPLASMA-CAPRICOLUM; BACTERIAL PHOSPHOENOLPYRUVATE; CRYSTAL-STRUCTURE; BINDING SURFACE; HPR; IDENTIFICATION; PURIFICATION AB Enzyme I of the bacterial phosphoenolpyruvate:sugar phosphotransferase system can be phosphorylated by PEP on an active-site histidine residue, localized to a cleft between an ex-helical domain and an alpha/beta domain on the amino terminal half of the protein. Tho phosphoryl group on the active-site histidine can be passed to an active-site histidine residue of HPr. It has been proposed that the major interaction between enzyme I and HPr occurs via the a-helical domain of enzyme I. The isolated recombinant or-helical domain (residues 25-145) with similar to 80% a-helices as well as enzyme I deficient in that domain [EI(Delta HD)] with similar to 50% alpha-helix content from RI. capricolum were used to further elucidate the nature of the enzyme I-HPr complex. Isothermal titration calorimetry demonstrated that HPr binds to the a-helical domain and intact enzyme I with K'(A) = 5 x 10(4) and 1.4 x 10(5) M-1 at pH 7.5 and 25 degrees C, respectively, but not to EI(Delta HD), which contains the active-site histidine of enzyme I and can be autophosphorylated by PEP, In vitro reconstitution experiments with proteins from both RI. capricolum and E, coli showed that EI(Delta HD) can donate its bound phosphoryl group to HPr in the presence of the isolated a-helical domain. Furthermore, M. capricolum recombinant C-terminal domain of enzyme I (EIC) was shown to reconstitute phosphotransfer activity with recombinant N-terminal domain (EIN) approximately 5% as efficiently as the HD-EI(Delta HD) pair. Recombinant EIC strongly self-associates (K'(A) approximate to 10(10) M-1) in comparison to dimerization constants of 10(5)-10(7) M-1 measured for EI and EI(Delta HD). C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Peterkofsky, A (reprint author), NHLBI, Lab Biochem Genet, NIH, Bldg 36,Room 4C-11, Bethesda, MD 20892 USA. NR 32 TC 23 Z9 23 U1 2 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 23 PY 1999 VL 38 IS 47 BP 15470 EP 15479 DI 10.1021/bi991680p PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 261PD UT WOS:000084016800007 PM 10569929 ER PT J AU Srivastava, M Atwater, I Glasman, M Leighton, X Goping, G Caohuy, H Miller, G Pichel, J Westphal, H Mears, D Rojas, E Pollard, HB AF Srivastava, M Atwater, I Glasman, M Leighton, X Goping, G Caohuy, H Miller, G Pichel, J Westphal, H Mears, D Rojas, E Pollard, HB TI Defects in inositol 1,4,5-trisphosphate receptor expression, Ca2+ signaling, and insulin secretion in the anx7(+/-) knockout mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SYNEXIN ANNEXIN-VII; CHROMAFFIN GRANULES; ISLETS; GLUCOSE; GENE; CELLS; LOCALIZATION; MOBILIZATION; SUBTYPE-3; SEQUENCE AB The mammalian anx7 gene codes for a Ca2+-activated GTPase, which supports Ca2+/CTP-dependent secretion events and Ca2+ channel activities in vitro and in vivo, To test whether anx7 might be involved in Ca2+ signaling in secreting pancreatic beta cells, we knocked out the anx7 gene in the mouse and tested the insulin-secretory properties of the beta cells. The nullizygous anx7 (-/-) phenotype is lethal at embryonic day 10 because of cerebral hemorrhage. However, the heterozygous anx7 (+/-) mouse, although expressing only low levels of ANX7 protein, is Viable and fertile. The anx7 (+/-) phenotype is associated with a substantial defect in insulin secretion, although the insulin content of the islets, is 8- to 10-fold higher in the mutants than in the normal littermate control. We infer from etectrophysiological studies that both glucose-stimulated secretion and voltage-dependent Ca2+ channel functions are normal. However, electrooptical recordings indicate that the (+/-) mutation has caused a change in the ability of inositol 1,4,5-trisphosphate (IP3)-generating agonists to release intracellular calcium. The principle molecular consequence of lower anx7 expression is a profound reduction in IP3 receptor expression and function in pancreatic islets. The profound increase in islets, beta cell number, and size may be a means of compensating for less efficient insulin secretion by individual defective pancreatic beta cells. This is a direct demonstration of a connection between glucose-activated insulin secretion and Ca2+ signaling through IP3-sensitive Ca2+ stores. C1 Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Sch Med, Inst Mol Med, Bethesda, MD 20814 USA. NIDDKD, Cell Biol & Genet Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NIH, Vet Resources Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Pollard, HB (reprint author), Uniformed Serv Univ Hlth Sci, Sch Med, Dept Anat & Cell Biol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 30 TC 89 Z9 93 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 13783 EP 13788 DI 10.1073/pnas.96.24.13783 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900036 PM 10570150 ER PT J AU Drake, JW Holland, JJ AF Drake, JW Holland, JJ TI Mutation rates among RNA viruses SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VESICULAR STOMATITIS-VIRUS; HIGH-FREQUENCY; CHEMICAL MUTAGENESIS; HUMAN RHINOVIRUS-16; CLONAL POOLS; POLIOVIRUS; MUTANT; SITES; REVERSION; SEQUENCE AB The rate of spontaneous mutation is a key parameter in modeling the genetic structure and evolution of populations. The impact of the accumulated load of mutations and the consequences of increasing the mutation rate are important in assessing the genetic health of populations. Mutation frequencies are among the more directly measurable population parameters, although the information needed to convert them into mutation rates is often racking. A previous analysis of mutation rates in RNA viruses (specifically in riboviruses rather than retroviruses) was constrained by the quality and quantity of available measurements and by the lack of a specific theoretical framework for converting mutation frequencies into mutation rates in this group of organisms. Here, we describe a simple relation between ribovirus mutation frequencies and mutation rates, apply it to the best (albeit far from satisfactory) available data, and observe a central value for the mutation rate per genome per replication of mu(g) approximate to 0.76.(The rate per round of cell infection is twice this value or about 1.5.)This value is so large, and ribovirus genomes are so informationally dense, that even a modest increase extinguishes the population. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Calif San Diego, Inst Genet Mol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 36 TC 615 Z9 631 U1 5 U2 37 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 13910 EP 13913 DI 10.1073/pnas.96.24.13910 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900058 PM 10570172 ER PT J AU Yoshimoto, T Tsutsui, H Tominaga, K Hoshino, K Okamura, H Akira, S Paul, WE Nakanishi, K AF Yoshimoto, T Tsutsui, H Tominaga, K Hoshino, K Okamura, H Akira, S Paul, WE Nakanishi, K TI IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAMMA-INDUCING FACTOR; NON-T CELLS; MAST-CELLS; BONE-MARROW; B-CELLS; INTERLEUKIN-18 RECEPTOR; PRODUCE INTERLEUKIN-13; TH2 CELLS; IGE; LIGAND AB IL-18 is a proinflammatory cytokine that plays an important role in natural killer cell activation and T helper 1 (Th1) cell responses. Mast cells and basophils are major inducers and effecters of allergic inflammation. Here we show that basophils and mast cells derived by culture of bone marrow cells with IL-3 for 10 days express IL-18R alpha chain and that basophils produce large amounts of IL-4 and IL-13 in response to stimulation with IL-3 and IL-18. Injection of IL-12 and IL-18 inhibits IgE production in helminth-infected wildtype mice and abolishes the capacity of their basophils to produce IL-4 and IL-13 in response to stimulation either with IL-3 and IL-18 or with Fc is an element of R cross-linkage, By contrast, this combination of cytokines actually increases IgE levels in helminth-infected IFN-gamma(-/-)mice and enhances IL-4 and IL-13 production by their basophils. Furthermore, injection of IL-18 alone enhances basophil production of IL-4 and histamine both in wild-type and IFN-gamma(-/-) mice. Thus, IL-18 has the potential to stimulate basophils but, when given with IL-12, exhibits an antiallergic action in vivo. C1 Hyogo Coll Med, Dept Immunol & Med Zool, Nishinomiya, Hyogo 6638501, Japan. Hyogo Coll Med, Inst Adv Med Sci, Host Def Lab, Nishinomiya, Hyogo 6638501, Japan. Hyogo Coll Med, Dept Internal Med 3, Nishinomiya, Hyogo 6638501, Japan. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Nakanishi, K (reprint author), Hyogo Coll Med, Dept Immunol & Med Zool, 1-1 Mukogawa, Nishinomiya, Hyogo 6638501, Japan. RI Akira, Shizuo/C-3134-2009; Hoshino, Katsuaki/L-9162-2014; OI Hoshino, Katsuaki/0000-0003-0493-4815; Tsutsui, Hiroko/0000-0001-7928-4875 NR 31 TC 295 Z9 310 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 13962 EP 13966 DI 10.1073/pnas.96.24.13962 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900067 PM 10570181 ER PT J AU Cmarik, JL Min, HZ Hegamyer, G Zhan, SN Kulesz-Martin, M Yoshinaga, H Matsuhashi, S Colburn, NH AF Cmarik, JL Min, HZ Hegamyer, G Zhan, SN Kulesz-Martin, M Yoshinaga, H Matsuhashi, S Colburn, NH TI Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE EPIDERMAL-CELLS; ANCHORAGE-INDEPENDENT GROWTH; SENSITIVE JB6 CELLS; GENE-EXPRESSION; TOPOISOMERASE INHIBITORS; MOLECULAR-CLONING; RESISTANT; AP-1; RNA; KERATINOCYTES AB An mRNA differential display comparison of mouse JB6 promotion-sensitive (P+) and -resistant (P-) cells identified a novel gene product that inhibits neoplastic: transformation. The JB6 P+ and P- cells are genetic variants that differ in their transformation response to tumor promoters; P+ cells form anchorage-independent colonies that are tumorigenic, and P- cells do not. A differentially displayed fragment, A7-1. was preferentially expressed in P- cells at levels greater than or equal to 10-fold those in P+ cells, making its mRNA a candidate inhibitor of neoplastic transformation. An A7-1 cDNA was isolated that was identical to murine Pdcd4 gene cDNAs. also known as MA-3 or TIS,and analogous to human H731 and 197/15a. Until now, the function of the Pdcd4 protein has been unknown. Paralleling the mRNA levels, Pdcd4 protein levels were greater in P- than in P+ cells. Pdcd4 mRNA was also expressed at greater levels in the less progressed keratinocytes of another mouse skin neoplastic progression series. To test the hypothesis that Pdcd4 inhibits tumor promoter-induced transformation, stable cell lines expressing antisense Pdcd4 were generated from parental P- cells. The reduction of Pdcd4 proteins in antisense lines was accompanied by acquisition of a transformation-sensitive (Pf) phenotype. The antisense-transfected cells were reverted to their initial P-phenotype by overexpression of a Pdcd4 sense fragment. These observations demonstrate that the Pdcd4 protein inhibits neoplastic transformation. C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Programs, SAIC, Frederick, MD 21702 USA. Roswell Pk Canc Inst, Grace Canc Drug Ctr, Buffalo, NY 14263 USA. Saga Med Sch, Dept Biochem, Saga 849, Japan. RP Cmarik, JL (reprint author), NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, Bldg 560,Rm 21-4, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 34 TC 192 Z9 203 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 14037 EP 14042 DI 10.1073/pnas.96.24.14037 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900080 PM 10570194 ER PT J AU Igarashi, T Endo, Y Englund, G Sadjadpour, R Matano, T Buckler, C Buckler-White, A Plishka, R Theodore, T Shibata, R Martin, M AF Igarashi, T Endo, Y Englund, G Sadjadpour, R Matano, T Buckler, C Buckler-White, A Plishka, R Theodore, T Shibata, R Martin, M TI Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID T-LYMPHOCYTE; ENVELOPE GLYCOPROTEIN; HIV-1 INFECTION; TYPE-1; RESPONSES; MONKEYS; DISEASE; DETERMINANTS; CHIMERA; STRAIN AB Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus loads measured in SHIVDH12-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previously reported that the administration of anti-human CD8 mAb to rhesus macaques at the time of primary SHIVDH12 infection resulted in marked elevations of virus loads. One of the treated animals experienced rapid and profound depletions of circulating CD4+ T lymphocytes. Although the CD4(+) T cell number partially recovered, this monkey subsequently suffered significant weight loss and was euthanized. A tissue culture Virus stock derived from this animal, designated SHIVDH12R, induced marked and rapid CD4(+) cell loss after i.v, inoculation of rhesus monkeys. Retrospective analyses of clinical specimens, collected during the emergence of SHIVDH12R indicated: (i) the input cloned SHIV remained the predominant Virus during the first 5-7 months of infection; (ii) Variants bearing only a few of the SHIVDH12R consensus changes first appeared 7 months after the administration of anti-CD8 mAb;(iii) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (iv) no neutralizing antibody against SHIVDH12R ever developed. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Mol Virol & Immunol, Washington, DC 20057 USA. RP Martin, M (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 61 Z9 61 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 14049 EP 14054 DI 10.1073/pnas.96.24.14049 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900082 PM 10570196 ER PT J AU Vinetz, JM Dave, SK Specht, CA Brameld, KA Xu, B Hayward, R Fidock, DA AF Vinetz, JM Dave, SK Specht, CA Brameld, KA Xu, B Hayward, R Fidock, DA TI The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSMISSION-BLOCKING VACCINES; VECTOR ANOPHELES-GAMBIAE; YELLOW-FEVER MOSQUITO; AEDES-AEGYPTI; PERITROPHIC MEMBRANE; GALLINACEUM; SEQUENCE; CLONING; PROTEIN; GENE AB Within hours after the ingestion of a blood meal, the mosquito midgut epithelium synthesizes a chitinous sac, the peritrophic matrix. Plasmodium ookinetes traverse the peritrophic matrix while escaping the mosquito midgut. Chitinases (EC 3.2.1.14) are critical for parasite invasion of the midgut: the presence of the chitinase inhibitor, allosamidin, in an infectious blood meal prevents oocyst development. A chitinase gene, PgCHT1, recently has been identified in the avian malaria parasite P, gallinaceum. We used the sequence of PgCHT1 to identify a P. falciparum chitinase gene, PfCHT1, in the P. falciparum genome database. PfCHT1 differs from PgCHT1 in that the P. falciparum gene lacks proenzyme and chitin-binding domains. PfCHT1 was expressed as an active recombinant enzyme in Escherichia coli. PfCHT1 shares with PgCHT1 a substrate preference unique to Plasmodium chitinases: the enzymes cleave tri- and tetramers of GlcNAc from penta- and hexameric oligomers and are unable to cleave smaller native chitin oligosaccharides. The pH activity profile of PfCHT1 and its IC50 (40 nM) to allosamidin are distinct from endochitinase activities secreted by P. gallinaceum ookinetes. Homology modeling predicts that PgCHT1 has a novel pocket in the catalytic active site that PfCHT1 lacks, which may explain the differential sensitivity of PfCHT1 and PgCHT1 to allosamidin. PfCHT1 may be the ortholog of a second, as yet unidentified, chitinase gene of P, gallinaceum. These results may allow us to develop novel strategies of blocking human malaria transmission based on interfering with P. falciparum chitinase. C1 Univ Texas, Med Branch, WHO, Ctr Trop Dis, Galveston, TX 77555 USA. Boston Univ, Dept Mol & Cell Biol, Goldman Sch Dent Med, Boston, MA 02118 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Vinetz, JM (reprint author), Univ Texas, Med Branch, WHO, Ctr Trop Dis, Keiller 2-138,301 Univ Blvd, Galveston, TX 77555 USA. OI Fidock, David/0000-0001-6753-8938; Vinetz, Joseph/0000-0001-8344-2004; Brameld, Ken/0000-0001-8643-3218 FU NIAID NIH HHS [F32 AI-10416, F32 AI010416]; NIEHS NIH HHS [P30 ES006676]; NIGMS NIH HHS [GM31318, R01 GM031318, GM54380] NR 34 TC 81 Z9 82 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 14061 EP 14066 DI 10.1073/pnas.96.24.14061 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900084 PM 10570198 ER PT J AU Jarai, Z Wagner, JA Varga, K Lake, KD Compton, DR Martin, BR Zimmer, AM Bonner, TI Buckley, NE Mezey, E Razdan, RK Zimmer, A Kunos, G AF Jarai, Z Wagner, JA Varga, K Lake, KD Compton, DR Martin, BR Zimmer, AM Bonner, TI Buckley, NE Mezey, E Razdan, RK Zimmer, A Kunos, G TI Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HYPOTENSIVE ACTION; ANANDAMIDE; RAT; ANTAGONIST; ARTERY; PHARMACOLOGY; RELAXATIONS; INHIBITION; SR141716A; CELLS AB Cannabinoids, including the endogenous ligand arachidonyl ethanolamide (anandamide), elicit not only neurobehavioral but also cardiovascular effects. Two cannabinoid receptors, CBI and CBZ, have been cloned, and studies with the selective CB1 receptor antagonist SR141716A have implicated peripherally located CBI receptors in the hypotensive action of cannabinoids. In rat mesenteric arteries, anandamide-induced vasodilation is inhibited by SR141716A, but other potent CBI receptor agonists, such as HU210, do not cause vasodilation, which implicates an as-yet-unidentified receptor in this effect. Here we show that "abnormal cannabidiol" (Abn-cbd) is a neurobehaviorally inactive cannabinoid that does not bind to CBI receptors, yet causes SR141716A-sensitive hypotension and mesenteric vasodilation in wild-type mice and in mice lacking CBI receptors or both CB1 and CBZ receptors. Hypotension by Abn-cbd is also inhibited by cannabidiol (20 mu g/g), which does not influence anandamide- or HU-210-induced hypotension. In the rat mesenteric arterial bed, Abn-cbd-induced vasodilation is unaffected by blockade of endothelial NO synthase, cyclooxygenase. or capsaicin receptors, but it is abolished by endothelial denudation. Mesenteric vasodilation by Abn-cbd, but not by acetylcholine, sodium nitroprusside, or capsaicine, is blocked by SR141716A (1 mu M) or by cannabidiol (10 mu M). Abn-cbd-induced vasodilation is also blocked in the presence of charybdotoxin (100 nM) plus apamin (100 nM), a combination of Kf-channel toxins reported to block the release of an endothelium-derived hyperpolarizing factor (EDHF). These findings suggest that Abn-cbd and cannabidiol are a selective agonist and antagonist, respectively, of an as-yet-unidentified endothelial receptor for anandamide, activation of which elicits NO-independent mesenteric vasodilation. possibly by means of the release of EDHF. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIMH, Genet Lab, Bethesda, MD 20892 USA. Organix Inc, Woburn, MA 01801 USA. RP Kunos, G (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. RI Zimmer, Andreas/B-8357-2009 NR 44 TC 438 Z9 450 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 23 PY 1999 VL 96 IS 24 BP 14136 EP 14141 DI 10.1073/pnas.96.24.14136 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 259AY UT WOS:000083872900097 PM 10570211 ER PT J AU Huff, J AF Huff, J TI GM foods: Two views SO SCIENTIST LA English DT Letter C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD NOV 22 PY 1999 VL 13 IS 23 BP 11 EP 11 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 265AK UT WOS:000084216000008 ER PT J AU Baum, BJ Berkman, ME Marmary, Y Goldsmith, CM Baccaglini, L Wang, SL Wellner, RB Hoque, ATMS Atkinson, JC Yamagishi, H Kagami, H Parlow, AF Chao, JL AF Baum, BJ Berkman, ME Marmary, Y Goldsmith, CM Baccaglini, L Wang, SL Wellner, RB Hoque, ATMS Atkinson, JC Yamagishi, H Kagami, H Parlow, AF Chao, JL TI Polarized secretion of transgene products from salivary glands in vivo SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; HUMAN GROWTH-HORMONE; RAT SUBMANDIBULAR GLANDS; PROLINE-RICH PROTEIN; EPITHELIAL-CELLS; TISSUE KALLIKREIN; PLASMA-MEMBRANE; SYSTEMIC DELIVERY; FLUID MOVEMENT; ATT-20 CELLS AB Previously (Kagami et al, Hum. Gene Ther, 1996;7:2177-2184) we have shown that salivary glands are able to secrete a transgene-encoded protein into serum as well as saliva. This result and other published data suggest that salivary glands may be a useful target site for vectors encoding therapeutic proteins for systemic delivery. The aim of the present study was to assess in vivo if transgene-encoded secretory proteins follow distinct, polarized sorting pathways as has been shown to occur "classically" in cell biological studies in vitro. Four first-generation, E1(-), type 5 recombinant adenoviruses were used to deliver different transgenes to a rat submandibular cell line in vitro or to rat submandibular glands in vivo. Subsequently, the secretary distribution of the encoded proteins was determined. Luciferase, which has no signal peptide, served as a cell-associated, negative control and was used to correct for any nonspecific secretory protein release from cells. The three remaining transgene products tested, human tissue kallikrein (hK1), human growth hormone (hGH), and human alpha(1)-antitrypsin (h alpha 1AT), were predominantly secreted (>96%) in vitro, Most importantly, in vivo, after a parasympathomimetic secretory stimulus, both hK1 and hGH mere secreted primarily in an exocrine manner into saliva, Conversely, h alpha 1AT was predominantly secreted into the bloodstream, i.e., in an endocrine manner. The aggregate results are consistent with the recognition of signals encoded within the transgenes that result in specific patterns of polarized protein secretion from rat submandibular gland cells in vivo. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Harbor UCLA Med Ctr, Natl Hormone & Pituitary Program, Torrance, CA 90509 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Rm 1N113,MSC 1190, Bethesda, MD 20892 USA. NR 65 TC 47 Z9 47 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 20 PY 1999 VL 10 IS 17 BP 2789 EP 2797 DI 10.1089/10430349950016528 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 257ZJ UT WOS:000083813100006 PM 10584925 ER PT J AU Pfutzner, W Hengge, UR Joari, MA Foster, RA Vogel, JC AF Pfutzner, W Hengge, UR Joari, MA Foster, RA Vogel, JC TI Selection of keratinocytes transduced with the multidrug resistance gene in an in vitro skin model presents a strategy for enhancing gene expression in vivo SO HUMAN GENE THERAPY LA English DT Article ID BONE-MARROW CELLS; PRODUCT P-GLYCOPROTEIN; LONG-TERM EXPRESSION; HUMAN MDR1 GENE; TRANSGENIC MICE; RETROVIRAL VECTORS; EPIDERMAL-KERATINOCYTES; IN-VIVO; THERAPY; TRANSPLANTATION AB In gene therapy studies, achieving prolonged, high-level gene expression in a significant percentage of cells has been difficult. One solution to enhance expression would be to select for cells expressing both the desired gene and a linked selectable marker gene in a bicistronic vector. As a potential target tissue, the skin is easily accessible for safe topical application of a selecting agent that could lead to significant gene expression in a high percentage of keratinocytes. To test the feasibility of such an approach, a skin raft culture model was developed. Human keratinocytes were transduced with the multidrug resistance (MDR) gene, which confers resistance to a variety of cytostatic and antimitotic compounds, such as colchicine. While growing on acellular dermis, transduced keratinocytes were treated with various doses of colchicine (10-50 ng/ml). Colchicine treatment increased the percentage of keratinocytes expressing MDR to almost 100% in raft cultures, Significantly, keratinocytes in colchicine-treated, MDR-transduced raft cultures were able to proliferate normally and form a stratified, differentiated epidermis. This model suggests that topical selection for MDR-expressing keratinocytes in vivo should be feasible without hampering the biologic integrity of skin. Thus, topical selection leading to enhanced expression of a desired gene, linked to a resistance gene, holds future promise for skin gene therapy. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Univ Essen Gesamthsch, Dept Dermatol, Essen, Germany. RP Vogel, JC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 66 TC 30 Z9 30 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV 20 PY 1999 VL 10 IS 17 BP 2811 EP 2821 DI 10.1089/10430349950016546 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 257ZJ UT WOS:000083813100008 PM 10584927 ER PT J AU Lacbawan, FL White, BJ Anguiano, A Rigdon, DT Ball, KD Bromage, GB Yang, XJ DiFazio, MP Levin, SW AF Lacbawan, FL White, BJ Anguiano, A Rigdon, DT Ball, KD Bromage, GB Yang, XJ DiFazio, MP Levin, SW TI Rare interstitial deletion (2)(p11.2p13) in a child with pericentric inversion (2)(p11.2q13) of paternal origin SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE chromosome 2; pericentric inversion; interstitial deletion 2p12; unequal crossingover ID PARACENTRIC INVERSION; CHROMOSOME 2; DUPLICATION; ASSOCIATION; CARRIERS AB An unbalanced 46,XY,der(2)del(2) (p11.2p13) inv(2)(p11.2q13) karyotype was found in a phenotypically abnormal child with a de novo interstitial deletion of band 2p12 associated with an inv(2)(p11.2q13) inherited from the father. The inv(a) is generally considered a benign familial variant without significant reproductive consequences. However, our findings led us to consider a previously proposed mechanism of unequal meiotic crossing over at the base of a parental inversion loop, which could lead to either a deletion or duplication of a segment adjacent to the inverted region in the offspring. This phenomenon has been reported in other inversions of chromosomes 1, 7, 13, 15, and 17 and may explain the origin of the deletion in our patient. Although repetitive sequences might be present around such inversions, which could predispose to de novo deletions independently of the inversion, current evidence including this case favors a proposed causal relationship between the parental inversion and the deletion in the child. Our review and results suggest there could be a small risk for a related imbalance to couples with an inv(2)(p11.2q13). For del(2)(p11.2p13), which is rare, a more distinct phenotype has been proposed herein. Our patient shared several findings with the three previously published cases, namely the broad nasal bridge, abnormal ears, high-arched palate, psychomotor retardation, and micrognathia, However, our patient also had sensorineural hearing loss and significant hypotonia, which have not been previously reported, thereby expanding our understanding of this rare deletion. Published 1999 Wiley-Liss, Inc.(dagger) C1 Walter Reed Army Med Ctr, Dept Pediat, Genet Sect, Washington, DC 20307 USA. Walter Reed Army Med Ctr, Dept Neurol, Washington, DC 20307 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Nichols Inst, Quest Diagnost, Dept Cytogenet, San Juan Capistrano, CA USA. USAF, Ctr Med Genet, Kessler AFB, MS USA. RP Levin, SW (reprint author), Walter Reed Army Med Ctr, Dept Pediat, Genet Sect, Bldg 38, Washington, DC 20307 USA. NR 17 TC 16 Z9 16 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD NOV 19 PY 1999 VL 87 IS 2 BP 139 EP 142 DI 10.1002/(SICI)1096-8628(19991119)87:2<139::AID-AJMG5>3.0.CO;2-J PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 253LV UT WOS:000083558800005 PM 10533028 ER PT J AU Fromm, SJ Fromm, HJ AF Fromm, SJ Fromm, HJ TI A two-step computer-assisted method for deriving steady-state rate equations SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PROGRAM; ENZYME AB A number of computer-assisted methods have been described for the derivation of enzyme-catalyzed steady-state rate equations [K. R. Runyan and R. B. Gunn (1989) Methods Enzymol. 171, 164-190; R. Varon, F. Garcia-Seville, M. Garvia-Moreno, F. Garcia-Canovas, R. Peyro, and R. G. Duggleby (1997) Comput. Appl. Biosci. 13, 159-167]; however, the required programs are either not readily available or require special software. We present here a two-step computer-assisted procedure for deriving steady-state rate equations using the widely available program Mathematica. In the first step, the differential equations for a particular kinetic mechanism that describe changes in enzyme concentration as a function of time are set equal to zero and entered into Mathematica in matrix form. In the second step, a single command allows for the computation of the distribution equations for the free enzyme and each enzyme-ligand complex. (C) 1999 Academic Press. C1 Consad Res Corp, Pittsburgh, PA 15206 USA. Iowa State Univ, Dept Biochem Biophys & Mol Biol, Ames, IA 50011 USA. RP Fromm, SJ (reprint author), NIDCH, NIH, Bldg 10,Room 3C716, Bethesda, MD 20892 USA. FU NINDS NIH HHS [NS 10546] NR 8 TC 12 Z9 12 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 19 PY 1999 VL 265 IS 2 BP 448 EP 452 DI 10.1006/bbrc.1999.1679 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 259NC UT WOS:000083899100032 PM 10558887 ER PT J AU Seo, MS Kim, JK Lim, Y Kang, SW Cho, YJ Lee, WK Kim, HJ Cho, KK Lee, KH Rhee, SG AF Seo, MS Kim, JK Lim, Y Kang, SW Cho, YJ Lee, WK Kim, HJ Cho, KK Lee, KH Rhee, SG TI Rapid degradation of PrxI and PrxII induced by silica in Rat2 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID THIOL-SPECIFIC ANTIOXIDANT; KAPPA-B ACTIVATION; MAMMALIAN PEROXIREDOXIN; GLUTATHIONE-PEROXIDASE; ALVEOLAR MACROPHAGES; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; IN-VITRO; MECHANISM; ALPHA AB Peroxidases of the peroxiredoxin (Prx) family catalyze the reduction of H2O2 and lipid peroxides, The effects of H2O2, 12-O-tetradecanoylphorbol 13-acetate (TPA), and silica on the abundance of two cytosolic isoforms of Prx (PrxI. and PrxII) were examined in Rata cells. TPA induces the production of reactive oxygen species (ROS) in various mammalian cell types, and silica induces the production of ROS in Rata cells. Whereas H2O2 and TPA did not affect the concentration of PrxI or Prx II, silica triggered a rapid degradation of both Prx enzymes. Silica also induced degradation of the NF-KB inhibitor I kappa B-alpha. N-Acetylcysteine and diphenyleneiodonium, both of which inhibit the accumulation of intracellular ROS, each blocked silica-induced degradation of I kappa B-alpha but had no effect on that of the Prx enzymes, suggesting that ROS do not contribute to Prx proteolysis, The silica-induced degradation of Prx enzymes was also insensitive to the proteasome inhibitors MG132 and lactacystin, whereas I kappa B-alpha proteolysis was completely blocked by these inhibitors. Experiments with the Ca2+ ionophore A23187 indicated that a Ca2+-dependent protease such as calpain might contribute substantially to silica-induced degradation of PrxII, but only moderately to that of PrxI, These results indicate that silica increases cellular oxidative stress not only by inducing ROS production, but also by triggering the degradation of Prx enzymes that are responsible for elimination of cellular ROS, Such aggravated oxidative stress might be important in the initial pathogenesis of silica-associated pulmonary diseases. (C) 1999 Academic Press. C1 Catholic Univ Korea, Dept Pharmacol, Catholic Neurosci Ctr, Coll Med,Seocho Gu, Seoul 137701, South Korea. Catholic Univ Korea, Coll Med, Catholic Neurosci Ctr, Seoul 137701, South Korea. Catholic Univ Korea, Coll Med, Dept Ind Med, Seoul 137701, South Korea. Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Lee, KH (reprint author), Catholic Univ Korea, Dept Pharmacol, Catholic Neurosci Ctr, Coll Med,Seocho Gu, 505 Banpo Dong, Seoul 137701, South Korea. NR 33 TC 13 Z9 14 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 NOV 19 PY 1999 VL 265 IS 2 BP 541 EP 544 DI 10.1006/bbrc.1999.1709 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 259NC UT WOS:000083899100050 PM 10558905 ER PT J AU Wang, SB Wang, WH Wesley, RA Danner, RL AF Wang, SB Wang, WH Wesley, RA Danner, RL TI A Sp1 binding site of the tumor necrosis factor alpha promoter functions as a nitric oxide response element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article; Proceedings Paper CT Experimental Biology 98 Meeting CY APR 18-22, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Exper Biol ID TRANSCRIPTION FACTOR SP1; HUMAN MONOCYTIC CELLS; SMOOTH-MUSCLE CELLS; GENE-TRANSCRIPTION; ENDOTHELIAL-CELLS; HUMAN NEUTROPHILS; PROTEIN-KINASE; CYCLIC-AMP; U937 CELLS; EXPRESSION AB Regulation of gene transcription is an incompletely understood function of nitric oxide (NO). Human leukocytes produce increased amounts of tumor necrosis factor alpha (TNF-alpha) in response to NO. This effect is associated with decreases in intracellular cAMP, suggesting that NO might regulate gene transcription through promoter sequences sensitive to cAMP such as cAMP response elements (CRE) and Sp1 binding sites. Here we report that a Sp1 binding site in the TNF-alpha promoter conveys NO responsiveness. Human U937 cells were differentiated for TNF-alpha production with phorbol 12-myristate 13-acetate. NO donors and H89, an inhibitor of cAMP-dependent protein kinase increased, while dibutyryl cAMP (Bt(2)cAMP) decreased TNF-alpha promoter activity. Deletion or mutation of the proximal Sp1 site, but not the CRE site, abolished the activating effects of NO donors and H89. Further, NO- and H89-mediated increases in TNF-alpha promoter activity were associated with decreased Sp1 binding. The insertion of Sp1 sites into a minimal cytomegalovirus promoter conferred NO responsiveness, an effect blocked by Bt(2)cAMP, Mutation of these inserted Sp1 sites prevented this heterologous promoter from responding to NO, H89 and Bt(2)cAMP. These results identify the Sp1 binding site as a promoter motif that allows NO to control gene transcription. 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, Bethesda, MD 20892 USA. NR 32 TC 64 Z9 67 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 NOV 19 PY 1999 VL 274 IS 47 BP 33190 EP 33193 DI 10.1074/jbc.274.47.33190 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200004 PM 10559188 ER PT J AU Choi, CY Kim, YH Kwon, HJ Kim, Y AF Choi, CY Kim, YH Kwon, HJ Kim, Y TI The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOMEOBOX GENES; N-COR; COREPRESSOR; DOMAIN; CHROMATIN; REGULATOR; MSIN3A; FAMILY; HAIRY; ACTS AB Transcriptional repression by sequence-specific DNA binding factors is mediated by the recruitment of a corepressor complex to the promoter region. The NK-3 homeodomain protein is a transcriptional repressor that recruits the nuclear protein kinase, homeodomain interacting protein kinase 2 (HIPK2). Here we show that HIPK2 is a component of a corepressor complex containing Groucho and a histone deacetylase complex. Groucho, like HIPK2, acts as a corepressor for NK-3 and binds to NK-3 and HlPK2. Moreover, HIPK2 appears to regulate the corepressor activity of Groucho. Transcriptional repression by NK-3 and Groucho is relieved by the histone deacetylase inhibitor trichostatin A, and both NK-3 and Groucho directly interact with the histone deacetylase HDAC1 that is associated with mSin3A in vivo. Recruitment of the histone deacetylase complex by NK-3 decreases the acetylated histones that are associated with the target gene promoter. These results indicate that NK-3 represses transcription by recruiting a complex containing Groucho and a histone deacetylase complex that leads to histone modification on chromatin and suggest that HIPK2 may play a regulatory role in the corepressor complex formation. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Radiat Med, Washington, DC 20007 USA. RP Kim, Y (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N228, Bethesda, MD 20892 USA. NR 23 TC 129 Z9 131 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 NOV 19 PY 1999 VL 274 IS 47 BP 33194 EP 33197 DI 10.1074/jbc.274.47.33194 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200005 PM 10559189 ER PT J AU Tassi, E Biesova, Z Di Fiore, PP Gutkind, JS Wong, WT AF Tassi, E Biesova, Z Di Fiore, PP Gutkind, JS Wong, WT TI Human JIK, a novel member of the STE20 kinase family that inhibits JNK and is negatively regulated by epidermal growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAY; N-TERMINAL KINASE; MAP KINASE; C-JUN; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; COUPLED RECEPTORS; PROTEIN-KINASE-1 BMK1; CELLULAR STRESSES AB Mammalian members related to Saccharomyces cerevisiae serine/threonine kinase STE20 can be divided into two subfamilies based on their structure and function. The PAK subfamily is characterized by an N-terminal p21-binding domain (also known as CRIB domain), a C-terminal kinase domain, and is regulated by the small GTP-binding proteins Rad and Cdc42Hs. The second group is represented by the GCK-like members, which contain an N-terminal catalytic domain and lack the p21-binding domain. Some of them have been demonstrated to induce c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) cascade, while others have been shown to be activated by a subset of stress conditions or apoptotic agents, although little is known about their specific function. Here, we have identified a novel human STE20-related serine/threonine kinase, belonging to the GCK-like subfamily. This kinase does not induce the JNK/SAPK pathway, but, instead, inhibits the basal activity of JNK/SAPK, and diminishes its activation in response to human epidermal growth factor (EGF). Therefore, we designated this molecule JIK for JNK/SAPK-inhibitory kinase. The inhibition of JNK/SAPK signaling pathway by JIK was found to occur between the EGF receptor and the small GTP-binding proteins Rad and Cdc42Hs. In contrast, JIK does not activate nor does it inhibit ERK2, ERK6, p38, or ERK5. Furthermore, JIK kinase activity is not modulated by any exogenous stimuli, but, interestingly it is dramatically decreased upon EGF receptor activation. Thus, JIK might represent the first member of the STE20 kinase family whose activity can be negatively regulated by tyrosine kinase receptors, and whose downstream targets inhibit, rather than enhance, JNK/SAPK activation. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Inst Virol, Bratislava 84246, Slovakia. European Inst Oncol, Dept Expt Oncol, I-20140 Milan, Italy. GenoQuest Inc, Germantown, MD 20874 USA. RP NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM wwong@genoquest.com RI Gutkind, J. Silvio/A-1053-2009; Di Fiore, Pier Paolo/K-2130-2012; Tassi, Enrico/K-3958-2015 OI Di Fiore, Pier Paolo/0000-0002-2252-0950; NR 91 TC 41 Z9 42 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 19 PY 1999 VL 274 IS 47 BP 33287 EP 33295 DI 10.1074/jbc.274.47.33287 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200020 PM 10559204 ER PT J AU Pritchard, JB Sweet, DH Miller, DS Walden, R AF Pritchard, JB Sweet, DH Miller, DS Walden, R TI Mechanism of organic anion transport across the apical membrane of choroid plexus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOLATERAL MEMBRANE; RAT-KIDNEY; P-AMINOHIPPURATE; BRUSH-BORDER; VESICLES; EXCHANGE; ACID; ACCUMULATION; LOCALIZATION; SECRETION AB The mechanism and membrane localization of choroid plexus (CP) organic anion transport were determined in apical (or brush border) membrane vesicles isolated from bovine choroid plexus and in intact CP tissue from cow and rat. Brush border membrane vesicles were enriched in Na+,K+-ATPase (20-fold; an apical marker in CP) and demonstrated specific, sodium-coupled transport of proline, glucose, and glutarate. Vesicular uptake of the anionic herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) was markedly stimulated by an inward sodium gradient but only in the presence of glutarate, indicating the presence of apical dicarboxylate/organic anion exchange. Consistent with this interpretation, an imposed outward glutarate gradient stimulated 2,4-D uptake in the absence of sodium. Under both conditions, uptake was dramatically slowed and overshoot was abolished by probenecid. Likewise, apical accumulation of 2,4-D by intact bovine choroid plexus tissue in vitro was stimulated by external glutarate in the presence of sodium. Glutarate stimulation was abolished by 5 mM LiCl. Identical findings were obtained using rat CP tissue, which showed both sodium/glutarate-stimulated 2,4-D (tissue/medium (T/M) similar to 8) and p-aminohippurate (T/M = 2) transport. Finally, since the renal exchanger (rROAT1) has been cloned in rat kidney, a rROAT1-green fluorescent protein construct was used to analyze exchanger distribution directly in transiently transfected rat CP. As predicted by the functional studies, the fluorescently tagged transporter was seen in apical but not basolateral membranes of the CP. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Pritchard, JB (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F1-3, Res Triangle Pk, NC 27709 USA. RI Sweet, Douglas/H-7914-2013 OI Sweet, Douglas/0000-0002-8911-9184 NR 34 TC 61 Z9 62 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 NOV 19 PY 1999 VL 274 IS 47 BP 33382 EP 33387 DI 10.1074/jbc.274.47.33382 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200033 PM 10559217 ER PT J AU Grimaldi, M Favit, A Alkon, DL AF Grimaldi, M Favit, A Alkon, DL TI cAMP-induced cytoskeleton rearrangement increases calcium transients through the enhancement of capacitative calcium entry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CORTICAL ASTROCYTES; CELLS; RECEPTOR; CULTURE; STORES; BRADYKININ AB In this report we investigated the correlation between cell morphology and regulation of cytosolic calcium homeostasis. Type I astrocytes were differentiated to stellate process-bearing cells by a 100-min exposure to cAMP, Differentiation of cortical astrocytes increased the magnitude and duration of calcium transients elicited by phospholipase C-activating agents as measured by single cell Fura-a-based imaging. Calcium imaging showed differences in the spatial pattern of the response. In both differentiated and the control cells, the response originated in the periphery and gradually extended into the center of the cell. However, the elevation of cytosolic calcium concentration ([Ca2+](i)) was particularly evident within the processes and adjacent to the inner cell membrane of the differentiated astrocytes, In addition, differentiation significantly prolonged the duration of the [Ca2+](i) elevation. Potentiation of the calcium transients was mimicked by forskolin-induced differentiation and abolished by a specific protein kinase-A blocker. Conversely, the enhancement of the calcium transients was not mimicked by brief exposure to cAMP not causing morphological differentiation, and in PC12 cells that did not undergo morphological changes after 100 min of cAMP treatment. Impairing cAMP-induced cytoskeleton re-organization, by means of cytochalasin D and nocodazole, prevented the potentiation of the calcium transients in cAMP-treated astrocytes. Phospholipase C activity and sensitivity to inositol (1,4,5)-trisphosphate were not involved in the enhancement of the calcium responses. Also, potentiation of the calcium transients was dependent on extracellular calcium. Calcium storage and thapsigargin-depletable intracellular calcium reservoirs were analogously not increased in differentiated astrocytes, Rearrangement of the cell shape also caused a condensation of the endoplasmic reticulum and altered the spatial relationship between the endoplasmic reticulum and the cell membrane. In conclusion, morphological rearrangements of type I astrocytes increase the magnitude and the duration of agonist-induced calcium transients via enhancement of capacitative calcium entry and is associated with a spatial reorganization of the relationship between cell membrane and the endoplasmic reticulum structures. C1 NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20817 USA. RP Grimaldi, M (reprint author), NINDS, Lab Adapt Syst, NIH, 36 Convent Dr,Bldg 36,Rm 4A22, Bethesda, MD 20817 USA. OI Grimaldi, Maurizio/0000-0002-7331-7055 NR 25 TC 50 Z9 50 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 NOV 19 PY 1999 VL 274 IS 47 BP 33557 EP 33564 DI 10.1074/jbc.274.47.33557 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200058 PM 10559242 ER PT J AU Bour, S Perrin, C Strebel, K AF Bour, S Perrin, C Strebel, K TI Cell surface CD4 inhibits HTV-1 particle release by interfering with Vpu activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; ENDOPLASMIC-RETICULUM; TRANSMEMBRANE DOMAIN; CYTOPLASMIC DOMAIN; HIV-1 VPU; T-CELL; SUPERINFECTION INTERFERENCE; PERIPHERAL-BLOOD; PLASMA-MEMBRANE AB One of the hallmarks of human immunodeficiency virus type I (HIV-1) infection is the rapid removal of the viral receptor CD4 from the cell surface. This remarkably efficient receptor interference requires the activity of three separate viral proteins: Env, Vpu, and Nef. We have investigated whether this unusually tight interference on cell surface CD4 expression had a more essential function during the viral life cycle than simply preventing superinfection. We now report that the removal of cell surface CD4 is required for optimal virus production by HIV-1, Indeed, maintenance of CD4 surface expression in infected cells lead to a 3-5-fold decrease in viral particle production. This effect was not due to the formation of intracellular complexes between CD4 and the gp160 viral envelope precursor but instead required the presence of CD4 at the cell surface and was specifically mediated by CD4 but not closely related plasma membrane receptors. The finding that CD4 had no significant effect on particle release by a Vpu-deficient variant indicates that CD4 acts by inhibiting the particle release-promoting activity of Vpu. Co-immunoprecipitation experiments further showed that CD4 and Vpu physically interact at the cell surface, suggesting that CD4 might inhibit Vpu activity by disrupting its oligomeric structure. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Bour, S (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 312,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 52 TC 56 Z9 56 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 NOV 19 PY 1999 VL 274 IS 47 BP 33800 EP 33806 DI 10.1074/jbc.274.47.33800 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 256UQ UT WOS:000083745200091 PM 10559275 ER PT J AU White, O Eisen, JA Heidelberg, JF Hickey, EK Peterson, JD Dodson, RJ Haft, DH Gwinn, ML Nelson, WC Richardson, DL Moffat, KS Qin, HY Jiang, LX Pamphile, W Crosby, M Shen, M Vamathevan, JJ Lam, P McDonald, L Utterback, T Zalewski, C Makarova, KS Aravind, L Daly, MJ Minton, KW Fleischmann, RD Ketchum, KA Nelson, KE Salzberg, S Smith, HO Venter, JC Fraser, CM AF White, O Eisen, JA Heidelberg, JF Hickey, EK Peterson, JD Dodson, RJ Haft, DH Gwinn, ML Nelson, WC Richardson, DL Moffat, KS Qin, HY Jiang, LX Pamphile, W Crosby, M Shen, M Vamathevan, JJ Lam, P McDonald, L Utterback, T Zalewski, C Makarova, KS Aravind, L Daly, MJ Minton, KW Fleischmann, RD Ketchum, KA Nelson, KE Salzberg, S Smith, HO Venter, JC Fraser, CM TI Genome sequence of the radioresistant bacterium Deinococcus radiodurans R1 SO SCIENCE LA English DT Article ID MICROCOCCUS-RADIODURANS; ESCHERICHIA-COLI; RADIATION-RESISTANT; IONIZING-RADIATION; GENUS DEINOCOCCUS; DNA-REPAIR; PROTEIN; IDENTIFICATION; MUTATION; THERMUS AB The complete genome sequence of the radiation-resistant bacterium Deinococcus radiodurans R1 is composed of two chromosomes (2,648,638 and 412,348 base pairs), a megaplasmid (172,466 base pairs), and a small plasmid (45,704 base pairs), yielding a total genome of 3,284,156 base pairs. Multiple components distributed on the chromosomes and megaplasmid that contribute to the ability of D. radiodurans to survive under conditions of starvation, oxidative stress, and high amounts of DNA damage were identified. Deinococcus radiodurans represents an organism in which all systems for DNA repair, DNA damage export, desiccation and starvation recovery, and genetic redundancy are present in one cell. C1 Inst Genome Res, Rockville, MD 20850 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. RP Fraser, CM (reprint author), Inst Genome Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. RI Nelson, William/E-9263-2016; Salzberg, Steven/F-6162-2011; OI Nelson, William/0000-0002-1873-3929; Salzberg, Steven/0000-0002-8859-7432; Fraser, Claire/0000-0003-1462-2428 FU NCI NIH HHS [R01 CA077712] NR 41 TC 638 Z9 1200 U1 9 U2 59 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 19 PY 1999 VL 286 IS 5444 BP 1571 EP 1577 DI 10.1126/science.286.5444.1571 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 257DZ UT WOS:000083768300062 PM 10567266 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI The fukutin protein family - predicted enzymes modifying cell-surface molecules SO CURRENT BIOLOGY LA English DT Letter ID CONGENITAL MUSCULAR-DYSTROPHY; GANGLIOSIDES; DATABASE C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 13 TC 84 Z9 85 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 18 PY 1999 VL 9 IS 22 BP R836 EP R837 DI 10.1016/S0960-9822(00)80039-1 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 257EX UT WOS:000083770500005 PM 10574772 ER PT J AU Seder, RA Gurunathan, S AF Seder, RA Gurunathan, S TI DNA vaccines. Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIAID, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 18 PY 1999 VL 341 IS 21 BP 1623 EP 1624 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 256GF UT WOS:000083717000032 ER PT J AU Potosky, AL Warren, JL AF Potosky, AL Warren, JL TI Radical prostatectomy: Does higher volume lead to better quality? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID MAJOR CANCER-SURGERY; HOSPITAL VOLUME; MANAGEMENT C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD 20892 USA. RP Potosky, AL (reprint author), NIH, Execut Plaza N,Rm 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. NR 20 TC 13 Z9 13 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 NOV 17 PY 1999 VL 91 IS 22 BP 1906 EP 1907 DI 10.1093/jnci/91.22.1906 PG 2 WC Oncology SC Oncology GA 256QJ UT WOS:000083736500001 PM 10564667 ER PT J AU Brawley, OW Freeman, HP AF Brawley, OW Freeman, HP TI Race and outcomes: Is this the end of the beginning for minority health research? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID NIH-REVITALIZATION-ACT; CELL LUNG-CANCER; CLINICAL-TRIALS; ADJUVANT THERAPY; PROSTATE-CANCER; COLON-CANCER; CARCINOMA; SURVIVAL; WOMEN; FLUOROURACIL C1 NCI, Off Special Populat Res, Off Director, Bethesda, MD 20892 USA. N Gen Hosp, New York, NY USA. RP Brawley, OW (reprint author), NIH, Execut Plaza S,Rm 320, Bethesda, MD 20892 USA. NR 32 TC 57 Z9 57 U1 3 U2 5 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 NOV 17 PY 1999 VL 91 IS 22 BP 1908 EP 1909 DI 10.1093/jnci/91.22.1908 PG 2 WC Oncology SC Oncology GA 256QJ UT WOS:000083736500002 PM 10564668 ER PT J AU Ali, IU Schriml, LM Dean, M AF Ali, IU Schriml, LM Dean, M TI Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID RILEY-RUVALCABA-SYNDROME; GERMLINE PTEN MUTATION; BANNAYAN-ZONANA-SYNDROME; COWDEN-DISEASE; JUVENILE POLYPOSIS; ENDOMETRIAL CANCERS; PROSTATE-CANCER; MICROSATELLITE INSTABILITY; GLIOMA-CELLS; GLIOBLASTOMA-MULTIFORME AB PTEN/MMAC1 (phosphatase, tensin homologue/mutated in multiple advanced cancers) is a tumor suppressor protein that has sequence homology with dual-specificity phosphatases, which ave capable of dephosphorylating both tyrosine phosphate and serine/threonine phosphate residues on proteins, The in vivo function of PTEN/MMAC1 appears to be dephosphorylation of phosphotidylinositol 3,4,5-triphosphate, The PTEN/MMAC1. gene is mutated in the germline! of patients with rare autosomal dominant cancer syndromes and in subsets of specific cancers. Here we review the mutational spectra of the PTEN/MMAC1 gene in tumors from various tissues, especially endometrium, brain, prostate, and ovary, in which the gene is inactivated very frequently, Germline and somatic mutations in the PTEN/MMAC1 gene occur mostly in the protein coding region and involve the phosphatase domain and poly(A)(6) stretches. Compared with germline alterations found in the PTEN/MMAC1 gene, there is a substantially increased frequency of frameshift mutations in tumors. Glioblastomas and endometrial carcinomas appear to have, distinct mutational spectra, probably reflecting differences in the underlying mechanisms of inactivation of the PTEN/MMAC1 gene in the two tissue types. Also, depending on the tissue type, the gene appears to be involved in the initiation or the progression of cancers. Further understanding of PTEN/MMAC1 gene mutations in different tumors and the physiologic consequences of these mutations is likely to open up new therapeutic opportunities for targeting this critical gene. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Lab Genom Divers, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Ali, IU (reprint author), NIH, Execut Plaza N,Rm 201, Bethesda, MD 20892 USA. RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; Schriml, Lynn/0000-0001-8910-9851 NR 120 TC 364 Z9 398 U1 3 U2 11 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 NOV 17 PY 1999 VL 91 IS 22 BP 1922 EP 1932 DI 10.1093/jnci/91.22.1922 PG 11 WC Oncology SC Oncology GA 256QJ UT WOS:000083736500008 PM 10564676 ER PT J AU Dignam, JJ Colangelo, L Tian, W Jones, J Smith, L Wickerham, DL Wolmark, N AF Dignam, JJ Colangelo, L Tian, W Jones, J Smith, L Wickerham, DL Wolmark, N TI Outcomes among African-Americans and Caucasians in colon cancer adjuvant therapy trials: Findings from the National Surgical Adjuvant Breast and Bowel Project SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID COLORECTAL-CANCER; SOCIOECONOMIC-FACTORS; CARCINOMA PATIENTS; MEDICAL SYSTEM; SURVIVAL; BLACKS; WHITES; RACE; FLUOROURACIL; POPULATION AB Background: African-Americans generally have lower survival rates from colon cancer than Caucasian Americans. This disparity has been attributed to many sources, including diagnosis at later disease stage and other unfavorable disease features, inadequate treatment, and socioeconomic factors. The randomized clinical trial setting ensures similarity in disease stage and a uniform treatment plan between blacks and whites. In this study, we evaluated survival and related end points for African-American and Caucasian patients with colon cancer participating in randomized clinical trials of the National Surgical Adjuvant Breast and Bowel Project (NSABP) to determine whether outcomes were less favorable for African-Americans. Methods: The study included African-American (n = 663) or Caucasian (n = 5969) patients from five serially conducted, randomized clinical trials of the NSABP, We compared recurrence-free survival, disease-free survival (recurrence, new primary cancer, or death), and survival (death from any cause) between blacks and whites by using statistical modeling to account for differences in patient and disease characteristics between the groups. Statistical tests were two-sided. Results: Dukes' stage and number of positive lymph nodes were remarkably similar between African-American and Caucasian patients in each trial. Over all trials combined, an 8% (95% confidence interval [CI] = -6% to 25%; P =.27) excess risk of colon cancer recurrence that was not statistically significant was observed for blacks. A greater disparity in survival was seen, with blacks experiencing a statistically significant 21% (95% CI = 6%-37%; P =.004) greater risk of death. Treatment efficacy appeared similar between the groups. Conclusions: While the overall survival prognosis was less favorable for African-Americans compared with Caucasians in these trials, other outcomes measured were considerably more similar than those seen in the population at large, suggesting that earlier detection and adjuvant therapy could appreciably improve colon cancer prognosis for African-Americans, Continued investigations into causes of the deficits noted are warranted. C1 Univ Pittsburgh, Pittsburgh, PA 15213 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Dignam, JJ (reprint author), Univ Pittsburgh, 230 McKee Pl,Suite 403, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [U10CA12027, U10CA69651] NR 45 TC 94 Z9 95 U1 0 U2 1 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 NOV 17 PY 1999 VL 91 IS 22 BP 1933 EP 1940 DI 10.1093/jnci/91.22.1933 PG 8 WC Oncology SC Oncology GA 256QJ UT WOS:000083736500009 PM 10564677 ER PT J AU Kelland, LR Sharp, SY Rogers, PM Myers, TG Workman, P AF Kelland, LR Sharp, SY Rogers, PM Myers, TG Workman, P TI DT-diaphorase expression and tumor cell sensitivity to 17-allylamino,17-demethoxygeldanamycin, an inhibitor of heat shock protein 90 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID IMPORTANT BIOLOGIC ACTIVITIES; ANTITUMOR AGENT; MUTANT P53; GELDANAMYCIN DERIVATIVES; MOLECULAR CHAPERONE; BIOREDUCTIVE DRUGS; HSP90; LINES; COMPLEX; RESISTANCE AB Background: To our knowledge, 17-allylamino,17-demethoxygeldanamycin (17AAG) is the first inhibitor of heat shock protein 90 (Hsp90) to enter a phase I clinical trial in cancer, Inhibition of Hsp90, a chaperone protein (a protein that helps other proteins avoid misfolding pathways that produce inactive or aggregated states), leads to depletion of important oncogenic proteins, including Raf-1 and mutant p53 (also known as TP53), Given its ansamycin benzoquinone structure, we questioned whether the antitumor activity of 17AAG was affected by expression of the NQO1 gene, which encodes the quinone-metabolizing enzyme DT-diaphorase. Methods: The antitumor activity of 17AAG and other Hsp90 inhibitors was determined by use of a sulforhodamine B-based cell growth inhibition assay in culture and by the arrest of xenograft tumor growth in nude mice. DT-diaphorase activity was determined by use of a spectrophotometric assay, and protein expression was determined by means of western immunoblotting. Results: In two independent in vitro human tumor cell panels, we observed a positive relationship between DT-diaphorase expression level and growth inhibition by 17AAG. Stable, high-level expression of the active NQO1 gene transfected, into the DT-diaphorase-deficient (by NQO1 mutation) BE human colon carcinoma cell line resulted in a 32-fold increase in 17AAG growth-inhibition activity. Increased sensitivity to 17AAG in the transfected cell line was also confirmed in xenografts. The extent of depletion of Raf-1 and mutant p53 protein confirmed that the Hsp90 inhibition mechanism was maintained in cells with high and low levels of DT-diaphorase. 17AAG was shown to be a substrate for purified human DT-diaphorase. Conclusion: These results suggest that the antitumor activity and possibly the toxicologic properties of 17AAG in humans may be influenced by the expression of DT-diaphorase. Careful monitoring for NQO1 polymorphism and the level of tumor DT-diaphorase activity is therefore recommended in clinical trials with 17AAG. C1 Inst Canc Res, Canc Res Campaign, Ctr Canc Therapeut, Sutton SM2 5NG, Surrey, England. NCI, Dev Therapeut Program, Informat Technol Branch, Bethesda, MD 20892 USA. RP Workman, P (reprint author), Inst Canc Res, Canc Res Campaign, Ctr Canc Therapeut, 15 Cotswold Rd, Sutton SM2 5NG, Surrey, England. NR 41 TC 288 Z9 298 U1 0 U2 3 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 NOV 17 PY 1999 VL 91 IS 22 BP 1940 EP 1949 DI 10.1093/jnci/91.22.1940 PG 10 WC Oncology SC Oncology GA 256QJ UT WOS:000083736500010 PM 10564678 ER PT J AU Garcia-Closas, M Kelsey, KT Hankinson, SE Spigelman, D Springer, K Willett, WC Speizer, FE Hunter, DJ AF Garcia-Closas, M Kelsey, KT Hankinson, SE Spigelman, D Springer, K Willett, WC Speizer, FE Hunter, DJ TI Glutathione S-transferase mu and theta polymorphisms and breast cancer susceptibility SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GENETIC POLYMORPHISMS; CYTOGENETIC DAMAGE; UNITED-STATES; GSTM1; RISK; LYMPHOCYTES; GSTT1; DICHLOROMETHANE; EPIDEMIOLOGY; ASSOCIATION AB Background: The enzymes encoded by the glutathione S-transferase mu 1 (GSTM1) and theta 1 (GSTT1) genes are involved in the metabolism (mainly inactivation, but activation is possible) of a wide range of carcinogens that are ubiquitous in the environment; the enzyme encoded by the GSTT1 gene may also be active in endogenous mutagenic processes. Homozygous deletions of the GSTM1 and GSTT1 genes are commonly found in the population and result in a lack of enzyme activity. This study was undertaken to evaluate the association between GSTM1 and GSTT1 gene polymorphisms and breast cancer risk. Methods: Our study included 466 women with incident cases of breast cancer occurring from May 1989 through May 1994 and 466 matched control subjects. These individuals were part of a prospective cohort of U.S. women (i.e., the Nurses' Health Study). Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression models were used to estimate the association between genetic polymorphisms and breast cancer risk. Results: The GSTM1 and GSTT1 null genotypes were not associated with an increased risk of breast cancer (OR = 1.05 [95% CI = 0.80-1.37] for GSTM1 null; OR = 0.86 [95% CI = 0.61-1.21] for GSTT1 null). On the contrary, a suggestion of a decreased risk of breast cancer associated with the GSTT1 null genotype was observed among premenopausal women. When considered together, no combination of the GSTM1 and GSTT1 genotypes was associated with an increased risk of breast cancer. The relationship between GSTM1 and GSTT1 gene deletions and breast cancer risk was not substantially modified by cigarette smoking. Conclusions: Our data provide evidence against a substantially increased risk of breast cancer associated with GSTM1 and/or GSTT1 homozygous gene deletions. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Hunter, DJ (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014; Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 FU NCI NIH HHS [CA40356, CA49449, CA67262] NR 25 TC 70 Z9 71 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 NOV 17 PY 1999 VL 91 IS 22 BP 1960 EP 1964 DI 10.1093/jnci/91.22.1960 PG 5 WC Oncology SC Oncology GA 256QJ UT WOS:000083736500013 PM 10564681 ER PT J AU Koo, MM Vande Woude, GF AF Koo, MM Vande Woude, GF TI The ras oncogene mediated sensitization of human cells to topoisomerase II inhibitor-induced apoptosis SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Adv Biosci Labs Inc, Basic Res Program, Frederick, MD USA. NCI, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Koo, MM (reprint author), Van Andel Res Inst, 201 Monroe Ave NW,Suite 400, Grand Rapids, MI 49503 USA. NR 3 TC 0 Z9 0 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 NOV 17 PY 1999 VL 91 IS 22 BP 1969 EP 1969 PG 1 WC Oncology SC Oncology GA 256QJ UT WOS:000083736500015 ER PT J AU Guardiola, J Xiol, X Sallie, R Nolla, JM Roig-Escofet, D Jaurrieta, E Casais, L AF Guardiola, J Xiol, X Sallie, R Nolla, JM Roig-Escofet, D Jaurrieta, E Casais, L TI Influence of the vitamin D receptor gene polymorphism on bone loss in men after liver transplantation SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID MINERAL DENSITY; RHEUMATOID-ARTHRITIS; WOMEN; ALLELES; CALCIUM; GENOTYPE; DISEASE; RATES; LOCUS AB Background: Bone loss is a frequent complication after liver transplantation. Objective: To investigate whether vitamin D receptor gene polymorphism influences bone loss in men after liver transplantation. Design: Prospective cohort study. Setting: University hospital. Patients: 55 male candidates for liver transplantation. Measurements: Lumbar spine bone mineral density was measured before and 3, 6, 12, and 24 months after liver transplantation. Vitamin D receptor genotype was determined by restriction endonuclease Bsml. Results: Vitamin D receptor genotypes were significantly associated with post-transplantation changes in bone mineral density (P = 0.028). Within 3 months after transplantation, patients with the genotypes Bb or BE showed a vertebral bone loss substantially greater than that in patients with the bb genotype (between-group difference in the percentage change with respect to baseline bone mineral density, 3.7% [95% CI, 0.6% to 6.9%]). In 3 to 24 months after transplantation, bone mineral density increased steadily in the three allelic groups. Conclusions: Vitamin D receptor gene polymorphism influences bone loss after liver transplantation. Patients with the bb genotype are, to some extent, protected against post-transplantation bone loss. C1 Ciudad Sanitaria & Univ Bellvitge, Hosp Princeps Espanya, Dept Gastroenterol, Barcelona 08907, Spain. Ciudad Sanitaria & Univ Bellvitge, Hosp Princeps Espanya, Dept Rheumatol, Barcelona 08907, Spain. Ciudad Sanitaria & Univ Bellvitge, Hosp Princeps Espanya, Dept Gen Surg, Barcelona 08907, Spain. NIDDKD, Liver Unit, NIH, Bethesda, MD 20892 USA. RP Guardiola, J (reprint author), Hosp Comarcal LAlt Penedes, Gastroenterol Unit, Espriall S-N, Barcelona 08720, Spain. OI Guardiola, Jordi/0000-0002-0464-241X NR 20 TC 16 Z9 16 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 16 PY 1999 VL 131 IS 10 BP 752 EP 755 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 255QC UT WOS:000083680100005 PM 10577298 ER PT J AU Burden, LM Rao, VD Murray, D Ghirlando, R Doughman, SD Anderson, RA Hurley, JH AF Burden, LM Rao, VD Murray, D Ghirlando, R Doughman, SD Anderson, RA Hurley, JH TI The flattened face of type II beta phosphatidylinositol phosphate kinase binds acidic phospholipid membranes SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; ANNEXIN-V; 5-KINASE; DOMAIN; ASSOCIATION; PROTEINS; VESICLES; RESIDUES; LIPIDS; FAMILY AB Type II beta phosphatidylinositol phosphate kinase is a representative phosphatidylinositol phosphate kinase that is active against membrane-bound substrates, The structure of the enzyme contains a flattened basic face that spans the crystallographic dimer interface and is adjacent to the active site. Analytical ultracentrifugation shows that phosphatidylinositol phosphate kinase is a dimer in solution. Modeling suggested that the flattened face binds to acidic phospholipids by electrostatic interactions. The enzyme binds to acidic vesicles containing phosphatidylserine, phosphatidic acid, or phosphoinositides mixed with phosphatidylcholine, but not to neutral phosphatidylcholine vesicles, Binding to acidic vesicles is abolished in the presence of 1.0 M NaCl, consistent with an essential electrostatic contribution to the free energy of binding. The +14 charge on the flattened face of the dimer was reduced to +2 in the triple mutant Lys72Glu/Lys76Glu/Lys78Glu. The mutation has no effect on dimerization, but reduces the apparent K-A for 25% phosphatidylserine/75% phosphatidylcholine mixed vesicles by 16-fold. The reduction in the level of binding can be ascribed to a loss of electrostatic interactions based on the finite difference solution to the Poisson-Boltzmann equation. The mutant reduces catalytic activity toward phosphatidylinositol 5-phosphate by similar to 50-fold. The wild-type enzyme binds half-maximally to phosphatidylinositol 4,5-bisphosphate-containing vesicles at a mole fraction of 0.3% in a phosphatidylcholine background, as compared to a 22% mole fraction in phosphatidylserine. The binding to phosphatidylinositol 3,5-bisphosphate-containing membranes is less sensitive to salt and to the triple mutation than binding to phosphatidylserine-containing membranes, suggesting that at least part of phosphatidylinositol 4,5-bisphosphate's interaction with the enzyme is independent of the flattened face. It is concluded that the flattened face of type II beta phosphatidylinositol phosphate kinase binds to membranes through nonspecific interactions, and that this interaction is essential for efficient catalysis. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RI Ghirlando, Rodolfo/A-8880-2009 FU NIGMS NIH HHS [GM51968, GM57549] NR 52 TC 27 Z9 27 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 16 PY 1999 VL 38 IS 46 BP 15141 EP 15149 DI 10.1021/bi991571a PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 259NF UT WOS:000083899400009 PM 10563796 ER PT J AU Inbaraj, JJ Krishna, MC Gandhidasan, R Murugesan, R AF Inbaraj, JJ Krishna, MC Gandhidasan, R Murugesan, R TI Cytotoxicity, redox cycling and photodynamic action of two naturally occurring quinones SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article; Proceedings Paper CT 5th International Workshop on ESR Imaging and in Vivo ESR Spectroscopy CY OCT 12-16, 1997 CL YAMAGATA, JAPAN SP ESR DE spin trapping; redox cycling; nitroxide; 5,5-dimethyl-1-pyrroline-N-oxide; superoxide; singlet oxygen ID OXYGEN; SUPEROXIDE; SEMIQUINONE; GENERATION; RESONANCE; AGENTS AB Two naturally occurring anthraquinones, barleriaquinone-I (BQ-I) and barleriaquinone-II (BQ-II), extracted from Barleria buxifolia, are tested for their cytotoxic action by aerobic incubation with human breast adenocarcinoma cells (MCF7). Cytotoxicities, measured as LD50 (50% inhibition of colony formation) values, show BQ-II to be more active than BQ-I. Electron paramagnetic resonance studies confirm that BQ-II is reductively activated by NADH:cytochrome c reductase to superoxide anion radical. Cyclic voltammetric studies show one quasi-reversible redox couple for both BQ-I and BQ-II. Also, aerobic solutions of both BQ-I and BQ-II on visible illumination generate reactive oxygen species. Formation of O-2(-.) is studied by both EPR spin trapping and SOD-inhibitable cytochrome c reduction techniques. BQ-I generates more singlet oxygen as evidenced from the photobleaching of N,N-dimethyl-4-nitrosoaniline. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Madurai Kamaraj Univ, Sch Chem, Madurai 625021, Tamil Nadu, India. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Murugesan, R (reprint author), Madurai Kamaraj Univ, Sch Chem, Madurai 625021, Tamil Nadu, India. NR 27 TC 27 Z9 27 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD NOV 16 PY 1999 VL 1472 IS 3 BP 462 EP 470 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 258QJ UT WOS:000083849600005 ER PT J AU Guidry, UC Evans, JC Larson, MG Wilson, PWF Murabito, JM Levy, D AF Guidry, UC Evans, JC Larson, MG Wilson, PWF Murabito, JM Levy, D TI Temporal trends in event rates after Q-wave myocardial infarction - The framingham heart study SO CIRCULATION LA English DT Article DE myocardial infarction; morbidity; mortality; heart failure; epidemiology ID LONG-TERM SURVIVAL; DISEASE MORTALITY; PROGNOSIS; DECLINE AB Background-Short-term (<30 day) mortality after Q-wave myocardial infarction (MI) has declined over the decades, but it is unclear if rates of long-term sequelae after Q-wave MI have improved. Methods and Results-In 546 Framingham Heart Study subjects (388 men with a mean age of 60 years; 158 women with a mean age of 69 years) with an initial recognized Q-wave MI from 1950 through 1989, we investigated time trends in risk for coronary heart disease (CHD) death (n=199), all-cause mortality (n=287), reinfarction (n=108), and congestive heart failure (CHF; n=121). With 1950 through 1969 as the reference period, hazards ratios (HRs) for these outcomes were determined for the 1970s and 1980s. Trend analyses across the 3 time periods were performed for each outcome. Compared with the 1950 through 1969 reference period, the HRs for CHD death were lower in subsequent decades (1970 through 1979. HR, 0.69; 95% CI, 0.49 to 0.98; 1980 through 1989: HR, 0.48; 95% CI, 0.33 to 0.72). All-cause mortality also declined (1970 through 1979, HR, 0.70; 95% CI, 0.0.52 to 0.94; 1980 through 1989: HR, 0.59; 95% CI, 0.43 to 0.81). There were no significant temporal changes in the risks for recurrent MI or CHF. Conclusions-Substantial reductions in risk of CHD death and all-cause mortality occurred over these 4 decades, coincident with improvements in post-MI therapies. The absence of a decline in CHF incidence may be due to improved post-MI survival of individuals with depressed left ventricular systolic function who are at high risk for CHF. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Cardiol, Beth Israel Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Clin Epidemiol, Beth Israel Hosp, Boston, MA 02115 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038, U01-HL-53941] NR 28 TC 72 Z9 75 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 16 PY 1999 VL 100 IS 20 BP 2054 EP 2059 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 260JC UT WOS:000083944900006 PM 10562260 ER PT J AU Dobs, AS Nieto, FJ Szklo, M Barnes, R Sharrett, AR Ko, WJ AF Dobs, AS Nieto, FJ Szklo, M Barnes, R Sharrett, AR Ko, WJ CA ARIC Study Grp TI Risk factors for popliteal and carotid wall thicknesses in the Atherosclerosis Risk in Communities (ARIC) Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE atherosclerosis; carotid arteries; peripheral vascular diseases; popliteal artery; ultrasonography ID PERIPHERAL VASCULAR-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; IMPROVED LIPOLYTIC EFFICIENCY; CORONARY HEART-DISEASE; INTIMA-MEDIA THICKNESS; B-MODE ULTRASOUND; INTERMITTENT CLAUDICATION; ARTERIAL-DISEASE; BLOOD COLLECTION; CEREBROVASCULAR-DISEASE AB The authors evaluated risk factors potentially associated with the development of popliteal artery atherosclerosis in a population-based study and compared them with factors linked to carotid wall intimal-medial thickness. The Atherosclerosis Risk in Communities (ARIC) Study is a longitudinal investigation of cardiovascular disease in 15,800 individuals. The present analyses are based on the baseline popliteal and carotid ultrasonography examination in 10,002 subjects conducted in 1987-1989. After adjustment for covariates, both carotid and popliteal intimal-medial thicknesses were strongly associated with male sex and age (p < 0.01), having a graded relation with increasing quartiles of plasma total cholesterol and low density lipoprotein cholesterol and with plasma triglycerides (women only for popliteal) (p < 0.01). An inverse correlation was noted between plasma high density lipoprotein cholesterol and carotid (p < 0.01) and popliteal (women only) (p < 0.05) intimal-medial thicknesses. Cigarette use (p < 0.01), a history of diabetes mellitus (p < 0.01), alcohol use, elevated systolic pressures (p < 0.01), and fibrinogen levels (p < 0.01) were directly associated with both popliteal and carotid intimal-medial thicknesses. Although menopause was associated with thickened carotid (p < 0.01) and popliteal (p < 0.05) intimal-medial thicknesses, hormone replacement therapy was associated with thinner carotid walls only (p < 0.05). Although there were some differences, many of the classical risk factors associated with cardiovascular disease were also related to early thickening of both the popliteal and the carotid artery walls. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. ARIC Ultrasound Reading Ctr, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC USA. NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, ARIC Data Coordinating Ctr, Chapel Hill, NC 27515 USA. RP Dobs, AS (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. FU NHLBI NIH HHS [N01-HC 55018, N01-HC-55015, N01-HC-55016] NR 67 TC 41 Z9 42 U1 1 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 1999 VL 150 IS 10 BP 1055 EP 1067 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 255ZU UT WOS:000083700700006 PM 10568620 ER PT J AU Struble, K Piscitelli, SC AF Struble, K Piscitelli, SC TI Syndromes of abnormal fat redistribution and metabolic complications in HIV-infected patients SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article C1 NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Piscitelli, SC (reprint author), NIH, Ctr Clin, Dept Pharm, Clin Pharmacokinet Res Lab, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. NR 36 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 15 PY 1999 VL 56 IS 22 BP 2343 EP 2348 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 259LM UT WOS:000083895400023 PM 10582831 ER PT J AU Williams, RC Shah, C Sackett, D AF Williams, RC Shah, C Sackett, D TI Separation of tubulin isoforms by isoelectric focusing in immobilized pH gradient gels SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID 2-DIMENSIONAL ELECTROPHORESIS; BRAIN; PROTEINS; NEURONS C1 Vanderbilt Univ, Dept Mol Biol, Nashville, TN 37235 USA. NICHD, Lab Integrat & Med Biophy, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Williams, RC (reprint author), Vanderbilt Univ, Dept Mol Biol, Nashville, TN 37235 USA. FU NIGMS NIH HHS [GM25638] NR 20 TC 22 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 1999 VL 275 IS 2 BP 265 EP 267 DI 10.1006/abio.1999.4326 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 259MF UT WOS:000083897100021 PM 10552916 ER PT J AU Ketter, TA Kimbrell, TA George, MS Willis, MW Benson, BE Danielson, A Frye, MA Herscovitch, P Post, RM AF Ketter, TA Kimbrell, TA George, MS Willis, MW Benson, BE Danielson, A Frye, MA Herscovitch, P Post, RM TI Baseline cerebral hypermetabolism associated with carbamazepine response, and hypometabolism with nimodipine response in mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 148th Annual Meeting of the American-Psychiatric-Association CY MAY 20-26, 1995 CL MIAMI BEACH, FLORIDA SP Amer Psychiat Assoc DE PET; cerebral; metabolism; carbamazepine; nimodipine; mood disorders ID PET IMAGES; SOMATOSTATIN; INHIBITION; CELLS; LINE AB Background: Positron emission tomography (PET) studies have reported baseline (medication free) differences between mood disorder patients and healthy control subjects, but relatively little is known about relationships between baseline PET scans and treatment responses. Carbamazepine (CBZ) and to a more limited extent nimodipine (NIMO) seem useful in mood disorders. We explored whether baseline regional cerebral glucose metabolism (rCMRglu) could discriminate CBZ and NIMO responders from nonresponders and healthy control subjects. Methods: In refractory mood disorder patients, we examined relationships between responses to these drugs, assessed by Clinical Global Impression-Improvement scores, and baseline rCMRglu, determined with fluorine-18 deoxyglucose and PET. Results: CBZ responders had baseline left insular hypermetabolism compared to healthy control subjects and nonresponders, whereas nonresponders had widespread (including left insular) hypometabolism. Degree of CBZ response correlated with baseline paralimbic (including insula) and prefrontal hypermetabolism, In responders but not nonresponders, CBZ decreased widespread metabolism, with the degree of decrease in left insula correlating with response. In contrast, NIMO responders but not nonresponders had baseline widespread (including left insular) hypometabolism, Left prefrontal and left insular baseline hypometabolism but not metabolic changes with treatment correlated with degree of NIMO response. Conclusions: These data suggest that baseline anterior paralimbic and prefrontal hypermetabolism may be associated with CBZ response, and hypometabolism with NIMO response. Based an these preliminary data, further exploration of relationships between baseline PET scans and treatment responses is indicated. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Stanford, CA USA. Med Univ S Carolina, Charleston, SC USA. NIH, Ctr Clin, Bethesda, MD USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, Bldg 10,Rm 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 25 TC 57 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1999 VL 46 IS 10 BP 1364 EP 1374 DI 10.1016/S0006-3223(99)00210-3 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256VE UT WOS:000083746500004 PM 10578451 ER PT J AU Nicolson, R Rapoport, JL AF Nicolson, R Rapoport, JL TI Childhood-onset schizophrenia: Rare but worth studying SO BIOLOGICAL PSYCHIATRY LA English DT Review DE schizophrenia; genetics; family studies ID OBSTETRIC COMPLICATIONS; ROSCOMMON FAMILY; BIRTH COHORT; FOLLOW-UP; DSM-III; RELATIVES; AGE; RISK; PREGNANCY; DIAGNOSIS AB Childhood-onset schizophrenia (defined by an onset of psychosis by age 12) is a rare and severe form of the disorder that is clinically and neurobiologically continuous with the adult-onset disorder. There is growing evidence for more salient risk or etiologic factors, particularly familial, in this possibly more homogenous patient population. For the 49 patients with very early onset schizophrenia studied to date at the National institute of Mental Health, there were more severe premorbid neurodevelopmental abnormalities a higher rate of cytogenetic anomalies, and a seemingly higher rate of familial schizophrenia and spectrum disorders than later onset cases, There was no evidence far increased obstetric complications or environmental stress. These data, while preliminary, suggest that a very early age of onset of schizophrenia may be secondary to greater familial vulnerability. Consequently, genetic studies of these patients may be particular ly informative and may provide important etiologic information. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Nicolson, R (reprint author), Bldg 10,Room 3N202,10 Ctr Dr MSC 1600, Bethesda, MD 20892 USA. RI Nicolson, Robert/E-4797-2011 NR 95 TC 130 Z9 131 U1 8 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 1999 VL 46 IS 10 BP 1418 EP 1428 DI 10.1016/S0006-3223(99)00231-0 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 256VE UT WOS:000083746500009 PM 10578456 ER PT J AU Rivera, CE Heath, AP AF Rivera, CE Heath, AP TI Identification of a new mutation in erythroid-specific delta-aminolevulinate synthase in a patient with congenital sideroblastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NIH, Warren Grant Magnuson Clin Ctr, Hematol Serv, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3230 BP 19B EP 19B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700074 ER PT J AU Likousi, KS Zoi, K Noguchi, CT Schechter, AN Loukopoulos, D AF Likousi, KS Zoi, K Noguchi, CT Schechter, AN Loukopoulos, D TI Modulation of gammaa globin mRNA stability in K562 erythroleukemic cells induced by hydroxyurea. SO BLOOD LA English DT Meeting Abstract C1 Univ Athens, Dept Med 1, Athens, Greece. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3297 BP 33B EP 33B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700141 ER PT J AU Akin, C Jaffe, ES Semere, T Daley, T Metcalfe, DD AF Akin, C Jaffe, ES Semere, T Daley, T Metcalfe, DD TI Demonstration of stem cell factor associated with mast cells in the bone marrow of patients with systemic indolent mastocytosis. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3311 BP 37B EP 37B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700155 ER PT J AU Chang, AC Magner, WJ Coligan, JE AF Chang, AC Magner, WJ Coligan, JE TI Aberrant development of thymocytes in mice lacking laminin-2. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NIAID, Mol Struct Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 164 BP 40A EP 40A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300213 ER PT J AU Hinds, KA Watt, SM Kirby, MR Sellers, SE Magnusson, MK Dunbar, CE AF Hinds, KA Watt, SM Kirby, MR Sellers, SE Magnusson, MK Dunbar, CE TI Expression of cell adhesion molecules on marrow and PBCD34+cells over time following filgrastim administration. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. IMM, MRC, Mol Hematol Unit, Oxford, England. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 183 BP 44A EP 44A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300232 ER PT J AU Darnay, BG Wang, C Aggarwal, BB Melenhorst, JJ Barrett, AJ Rath, P Singh, S Hernandez, C Molldrem, JJ AF Darnay, BG Wang, C Aggarwal, BB Melenhorst, JJ Barrett, AJ Rath, P Singh, S Hernandez, C Molldrem, JJ TI Survival of T-LGL leukemia cells is associated with expression and constitutive activation of the anti-apoptosis receptor rank and rank ligand on T-LGL cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NHLBI, Bethesda, MD 20892 USA. Imgenex, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 187 BP 45A EP 45A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300236 ER PT J AU Stroncek, DF Carter, L Procter, JL Dale, JK Straus, SE AF Stroncek, DF Carter, L Procter, JL Dale, JK Straus, SE TI Granulocyte antibodies in autoimmune lymphoproliferative syndrome. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3351 BP 45B EP 45B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700195 ER PT J AU Goldman, F Hollenback, C Loew, T Puck, J Jackson, C Cook, R AF Goldman, F Hollenback, C Loew, T Puck, J Jackson, C Cook, R TI Aberrant T cell antigen receptor signaling in CD3+4-/8-double negative Fas defective T cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Pathol, Iowa City, IA 52242 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3388 BP 53B EP 53B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700232 ER PT J AU Mohammad, SF Iacobucci, ML Welniak, LA Murphy, WJ Koh, CY Bos, LS Junge, GR Kadereit, S Miller, RE Stewart, CC Sramkoski, RM Jacobberger, J Laughlin, MJ AF Mohammad, SF Iacobucci, ML Welniak, LA Murphy, WJ Koh, CY Bos, LS Junge, GR Kadereit, S Miller, RE Stewart, CC Sramkoski, RM Jacobberger, J Laughlin, MJ TI Novel generation of cytokine induced killer cells (CIK) from human umbilical cord blood (UCB) expanded ex vivo with IL-15. SO BLOOD LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NCI, IRSP, Frederick, MD 21701 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3397 BP 55B EP 55B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700241 ER PT J AU Ponka, P Rouault, T AF Ponka, P Rouault, T TI Targeted disruption of iron regulatory protein 2 in mice leans to neuronal iron overload and progressive neurodegeneration SO BLOOD LA English DT Meeting Abstract C1 McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Montreal, PQ H3T 1E2, Canada. NICHHD, Bethesda, MD 20892 USA. RI Ponka, Prem/A-4123-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 BP 56 EP 56 PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300018 ER PT J AU van Rhee, F Szamania, S Arthur, A Clave, E Hensel, N Lamb, L Madrigal, A Barrett, AJ Henslee-Downey, PJ AF van Rhee, F Szamania, S Arthur, A Clave, E Hensel, N Lamb, L Madrigal, A Barrett, AJ Henslee-Downey, PJ TI Dendritic cells (DC's) cultured in autologous plasma for clinical use are highly efficient in inducing immune responses. SO BLOOD LA English DT Meeting Abstract C1 Palmetto Richland Mem Hosp, Div Transplantat Med, Columbia, SC USA. NIH, BMT Unit, Bethesda, MD 20892 USA. Anthony Nolan Res Ctr, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3423 BP 60B EP 60B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700267 ER PT J AU Shami, PJ Saavedra, JE Wang, LY Davies, KM Booth, MN Citro, ML Keefer, LK AF Shami, PJ Saavedra, JE Wang, LY Davies, KM Booth, MN Citro, ML Keefer, LK TI Esterase-sensitive nitric oxide donors of the diazeniumdiolate family. In vitro antileukemic activity. SO BLOOD LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT USA. Salt Lake City VA Med Ctr, Salt Lake City, UT USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 260 BP 61A EP 61A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300309 ER PT J AU Waxman, S Zelent, A Melnick, A Licht, JD Monks, A Sausville, E Jing, YK AF Waxman, S Zelent, A Melnick, A Licht, JD Monks, A Sausville, E Jing, YK TI Development of novel agents targeted to overcome site-specific transcriptional repression of leukemia. SO BLOOD LA English DT Meeting Abstract C1 Mt Sinai Sch Med, New York, NY USA. Inst Canc Res, Leukaemia Res Fund Ctr, London SW3 6JB, England. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 262 BP 61A EP 61A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300311 ER PT J AU Licht, T von Schilling, C Lubbert, M AF Licht, T von Schilling, C Lubbert, M TI Tumor necrosis factor-alpha and interleukin-6 induce multidrug resistance in PXF1118L pleural mesothelioma cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 3, D-8000 Munich, Germany. Univ Freiburg, Dept Internal Med 1, D-7800 Freiburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 276 BP 64A EP 64A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300325 ER PT J AU Dover, G Chanock, S AF Dover, G Chanock, S TI Genetic modifiers of severity of chronic granulomatous disease SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Hosp, Baltimore, MD 21287 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 BP 67 EP 68 PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790300034 ER PT J AU Tamm, I Kornblau, SM Segall, H Kitada, S Scudiero, DA Tudor, G Qui, YH Monks, A Sausville, E Andreeff, M Reed, JC AF Tamm, I Kornblau, SM Segall, H Kitada, S Scudiero, DA Tudor, G Qui, YH Monks, A Sausville, E Andreeff, M Reed, JC TI Expression and prognostic significance of IAP-family genes in human cancers and leukemias. SO BLOOD LA English DT Meeting Abstract C1 Burnham Inst, La Jolla, CA 92037 USA. Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 298 BP 69A EP 69A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300347 ER PT J AU Saunthararajah, Y Wang, JX Wolk, A Redner, RL Liu, JM AF Saunthararajah, Y Wang, JX Wolk, A Redner, RL Liu, JM TI Phenylbutyrate and trichostatin-A induce differentiation of AML1-ETO leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. CAMS, Inst Hematol, Tianjin, Peoples R China. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 347 BP 80A EP 80A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300396 ER PT J AU Davis, TA Grillo-Lopez, AJ White, CA McLaughlin, P Czuczman, MS Link, BK Maloney, DG Weaver, RL Rosenberg, J Levy, R AF Davis, TA Grillo-Lopez, AJ White, CA McLaughlin, P Czuczman, MS Link, BK Maloney, DG Weaver, RL Rosenberg, J Levy, R TI Final report on the safety and efficacy of retreatment with rituximab for patients with non-Hodgkin's lymphoma. SO BLOOD LA English DT Meeting Abstract C1 NCI, CTEP, Rockville, MD USA. Idec Pharmaceut Corp, San Diego, CA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Roswell Pk Canc Ctr, Buffalo, NY USA. Univ Iowa, Iowa City, IA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. NR 0 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 385 BP 88A EP 88A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300434 ER PT J AU Heestand, G Robbins, DH Onda, M Pastan, I Kreitman, RJ AF Heestand, G Robbins, DH Onda, M Pastan, I Kreitman, RJ TI Recombinant toxins containing pseudomonas exotoxin directly injure hepatocytes in the absence of kupffer cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 408 BP 93A EP 93A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300457 ER PT J AU Tuscano, JM DeNardo, G Wun, T Tedder, TF Kehrl, JH AF Tuscano, JM DeNardo, G Wun, T Tedder, TF Kehrl, JH TI Manipulation of CD22 signal transduction for the treatment of lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Duke Univ, Durham, NC USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 405 BP 93A EP 93A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300454 ER PT J AU Kreitman, RJ Wilson, WH Margulies, I Stetler-Stevenson, M Raggio, M FitzGerald, DJ Waldmann, TA Pastan, I AF Kreitman, RJ Wilson, WH Margulies, I Stetler-Stevenson, M Raggio, M FitzGerald, DJ Waldmann, TA Pastan, I TI Patients with chemotherapy-refractory hairy cell leukemia achieve major responses to recombinant immunotoxins containing truncated pseudomonas exotoxin and targeting either CD25 or CD22. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD USA. NCI, Med Branch, NIH, Bethesda, MD USA. NCI, Clin Pathol Lab, NIH, Bethesda, MD USA. NCI, Metab Branch, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 421 BP 96A EP 96A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300470 ER PT J AU Saunthararajah, Y Molldrem, J Rivera, M Young, NS Barrett, JA AF Saunthararajah, Y Molldrem, J Rivera, M Young, NS Barrett, JA TI Coincidence of T-LGL with myelodysplastic syndrome is associated with a poor response of cytopenia to therapy with cyclosporine. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Hematol Branch, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 429 BP 98A EP 98A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300478 ER PT J AU Deng, M Jena, N Tamura, T Ozato, K Daley, GQ AF Deng, M Jena, N Tamura, T Ozato, K Daley, GQ TI ICSBP expression abrogates BCR/ABL-induced leukemia in immunocompetent mice. SO BLOOD LA English DT Meeting Abstract C1 Whitehead Inst, Cambridge, MA 02142 USA. NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 455 BP 104A EP 104A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300504 ER PT J AU Davis, BR Yannariello-Brown, J Prokopishyn, NL Luo, Z Smith, MR Wang, J Carsrud, NDV Brown, DB AF Davis, BR Yannariello-Brown, J Prokopishyn, NL Luo, Z Smith, MR Wang, J Carsrud, NDV Brown, DB TI A novel methodology for experimental stem cell studies - Microinjection mediated delivery of macromolecules and transgenes. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Sealy Ctr Oncol & Hematol, Galveston, TX 77550 USA. Gene Cell Inc, Houston, TX USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3725 BP 126B EP 126B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700569 ER PT J AU Wong, E Oblitas, J Tisdale, J Walsh, T Young, NS Leitman, SF AF Wong, E Oblitas, J Tisdale, J Walsh, T Young, NS Leitman, SF TI Efficacy of G-CSF/dexamethasone-mobilized granulocyte transfusions in the treatment of life-threatening infections in patients with severe aplastic anemia (SAA). SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 554 BP 126A EP 126A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300603 ER PT J AU Janik, JE Gause, BL Curti, B Longo, DL AF Janik, JE Gause, BL Curti, B Longo, DL TI A phase II trial of deoxycoformycin (2-dCF) in patients with large granular lymphocyte (LGL) leukemia. SO BLOOD LA English DT Meeting Abstract C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. Milton S Hershey Med Ctr, Dept Med, Hershey, PA 17033 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 560 BP 127A EP 127A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300609 ER PT J AU Bartelmez, S Storey, C Sitnicka, E Ruscetti, F AF Bartelmez, S Storey, C Sitnicka, E Ruscetti, F TI Endogenous transforming growth factor beta-1 is a potent regulator of the engraftment kinetics of long term repopulating hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 Seattle Biomed Res Inst, Seattle, WA 98109 USA. NCI, Lab Leukocyte Biol, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 565 BP 128A EP 128A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300614 ER PT J AU Han, JY Kim, IH Park, JI Je, GH Rodgers, GP AF Han, JY Kim, IH Park, JI Je, GH Rodgers, GP TI Enrichment and detection of fetal erythroid cells from the maternal peripheral blood using a two-phase liquid culture with molecular genetic analysis. SO BLOOD LA English DT Meeting Abstract C1 Dong A Univ, Coll Med, Pusan, South Korea. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3734 BP 128B EP 128B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700578 ER PT J AU Mackall, CL Long, LM Dagher, R Bernstein, D Fleisher, TA Brown, MR Carter, C Read, EJ Wong, E Berzofsky, JA Helman, LJ AF Mackall, CL Long, LM Dagher, R Bernstein, D Fleisher, TA Brown, MR Carter, C Read, EJ Wong, E Berzofsky, JA Helman, LJ TI Combined immune reconstitution/tumor vaccination to induce anti-tumor immune responses in the setting of minimal residual neoplastic disease. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, CC, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, CC, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 586 BP 133A EP 133A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300635 ER PT J AU Bahceci, E Epperson, D Patibandla, A Childs, R Melenhorst, J Phang, S Greene, A Mayo, V Barrett, AJ AF Bahceci, E Epperson, D Patibandla, A Childs, R Melenhorst, J Phang, S Greene, A Mayo, V Barrett, AJ TI Rapid reconstitution of T-cell compartment after myeloablative allogeneic stem cell transplantation (NMAT). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bone Marrow Transplant Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 590 BP 134A EP 134A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300639 ER PT J AU Read, EJ Van Epps, DE Butz, RE Carter, CS Horwitz, ME Malech, HL Dunbar, C Gress, R Barrett, J AF Read, EJ Van Epps, DE Butz, RE Carter, CS Horwitz, ME Malech, HL Dunbar, C Gress, R Barrett, J TI Automated T cell depletion of G-CSF mobilized normal donor peripheral blood progenitor cells by CD34-positive or combined positive/negative immuno-magnetic selection using the Isolex 300i system. SO BLOOD LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Nexell Inc, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 616 BP 141A EP 141A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300665 ER PT J AU Yam, A Flyun, T Baserga, R Cairo, MS Li, WQ AF Yam, A Flyun, T Baserga, R Cairo, MS Li, WQ TI Activation of Shc/Ras/MAPK cascade is required for IL-4-induced mitogenesis in myeloid progenitor cells overexpressing IGF-I receptor. SO BLOOD LA English DT Meeting Abstract C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3852 BP 152B EP 152B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700696 ER PT J AU Pavletic, S Tarantolo, S Lynch, J Oria, N Ketcham, M Brand, R Armitage, J Kessinger, A Bishop, M AF Pavletic, S Tarantolo, S Lynch, J Oria, N Ketcham, M Brand, R Armitage, J Kessinger, A Bishop, M TI Acute graft-versus-host disease after allogeneic blood stem cell transplantation: Factors determining treatment failure and survival. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 669 BP 153A EP 153A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300718 ER PT J AU Clave, E Jin, SWA Bradstock, K Hensel, N van Rhee, F Melenhorst, J Barrett, J AF Clave, E Jin, SWA Bradstock, K Hensel, N van Rhee, F Melenhorst, J Barrett, J TI Use of a CMV pp65-specific HLA tetramer to select and expand CMV-specific CD8+CTL. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bone Marrow Transplant Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. Westmead Hosp, Dept Hematol, Sydney, NSW, Australia. Univ S Carolina, Bone Marrow Tranplant Program, Columbia, SC 29208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 679 BP 155A EP 155A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300728 ER PT J AU Chute, JP Clark, WB Saini, AA Smoot, D Wells, MR Harlan, DM AF Chute, JP Clark, WB Saini, AA Smoot, D Wells, MR Harlan, DM TI Characterization of human brain endothelial cells (HUBEC): Primary cells which support the expansion of CD34+CD38-hematopoietic progenitor cells. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Stem Cell Biol lab, Navy Transplantat & Autoimmunity Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3903 BP 163B EP 163B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700747 ER PT J AU Bahceci, E Read, EJ Leitman, S Carter, C Childs, R Dunbar, C Young, N Barrett, AJ AF Bahceci, E Read, EJ Leitman, S Carter, C Childs, R Dunbar, C Young, N Barrett, AJ TI Treatment of chronic myelogenous leukemia (CML) with T-cell depleted hematopoietic stem cell transplantation (TCD-SCT) followed by delayed T-cell add-back. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 726 BP 166A EP 166A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300775 ER PT J AU Schwartz, GN Kammula, U Warren, MK Park, MK Yan, X Marincola, FM Gress, RE AF Schwartz, GN Kammula, U Warren, MK Park, MK Yan, X Marincola, FM Gress, RE TI Modulatory effects of GM-CSF and patient chemotherapy on thrombopoietin and chemokine mRNA expression in marrow stromal layers. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med & Surg Branch, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3924 BP 167B EP 167B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700768 ER PT J AU Roesler, J Bukovsky, AA Theobald-Whiting, N Dull, T Kelly, M Ayengar, VJ Stull, M Yang, Y Civin, CI Malech, HL AF Roesler, J Bukovsky, AA Theobald-Whiting, N Dull, T Kelly, M Ayengar, VJ Stull, M Yang, Y Civin, CI Malech, HL TI 3rd generation self-inactivating gp91phox lentivector corrects the oxidase defect in CD34+cells from patients with X-linked chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Cell Genesys Inc, Foster City, CA USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 764 BP 175A EP 175A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300813 ER PT J AU Seidel, NE Sabatino, DE Cline, AP Gallagher, PG Papayannopoulou, T Bodine, DM AF Seidel, NE Sabatino, DE Cline, AP Gallagher, PG Papayannopoulou, T Bodine, DM TI Retrovirus vectors containing the ankyrin promoter fused to a human A-gamma globin gene are stable when transduced into mouse hematopoietic stem cells and express gamma globin mRNA at levels which are approximately 2-6% of total mouse alpha globin mRNA. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, GMBB, NIH, Bethesda, MD USA. Yale Univ, New Haven, CT 06520 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 767 BP 176A EP 176A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300816 ER PT J AU Emery, DW Yannaki, E Bell, A Felsenfeld, G Stamatoyannopoulos, G AF Emery, DW Yannaki, E Bell, A Felsenfeld, G Stamatoyannopoulos, G TI Core elements from Drosophila gypsy and chicken beta-globin HS4 do not insulate retrovirus vectors from position effects. SO BLOOD LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 770 BP 177A EP 177A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300819 ER PT J AU Chinnasamy, N Chinnasamy, D Toso, J Lapointe, R Candotti, F Morgan, RA Hwu, P AF Chinnasamy, N Chinnasamy, D Toso, J Lapointe, R Candotti, F Morgan, RA Hwu, P TI Efficient gene transfer to peripheral blood monocyte derived human dendritic cells by lentiviral vectors. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 775 BP 178A EP 178A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300824 ER PT J AU Bloom, ML Ware, JA Wolk, AG Graf, MM Pohl, LR AF Bloom, ML Ware, JA Wolk, AG Graf, MM Pohl, LR TI Immunochemical detection of diclofenac protein adducts in erythrocytes membrane skeleton: Possible role in diclofenac-induced hemolytic anemia in the mouse. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 820 BP 188A EP 188A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300869 ER PT J AU Kontny, HU Hammerle, K Shayan, P Mackall, CL Niemeyer, M AF Kontny, HU Hammerle, K Shayan, P Mackall, CL Niemeyer, M TI Sensitivity to trail-mediated apoptosis in Ewing's sarcoma. SO BLOOD LA English DT Meeting Abstract C1 Univ Freiburg, Childrens Hosp, Freiburg, Germany. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4050 BP 193B EP 193B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700894 ER PT J AU Miller, JL Gubin, AN Njoroge, JM Lee, YT Mitchell, LB AF Miller, JL Gubin, AN Njoroge, JM Lee, YT Mitchell, LB TI Human erythroid cell genomics. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 848 BP 194A EP 194A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300897 ER PT J AU Asakura, T Lian, L Ollinger, FK Chen, Q Li, X Cao, B Wick, TM Brugnara, C Evans, G AF Asakura, T Lian, L Ollinger, FK Chen, Q Li, X Cao, B Wick, TM Brugnara, C Evans, G TI Screening of antisickling agents by the new systematic multi-level analysis protocol developed at the sickle cell disease reference laboratory. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Georgia Inst Technol, Atlanta, GA 30332 USA. Childrens Hosp, Boston, MA 02115 USA. NHLBI, Sickle Cell Dis Sci Res Grp, NIH, Bethesda, MD 20892 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 872 BP 199A EP 199A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300921 ER PT J AU Dang, NH Melenhorst, J Barrett, AJ Molldrem, JJ AF Dang, NH Melenhorst, J Barrett, AJ Molldrem, JJ TI CD26 as a marker for clinically aggressive T-LGL leukemia. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4094 BP 201B EP 201B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790700938 ER PT J AU Gladwin, MT Ognibene, FP Shelhamer, JH Pannell, LK Nichols, JS Pease-Fye, ME Schechter, AN AF Gladwin, MT Ognibene, FP Shelhamer, JH Pannell, LK Nichols, JS Pease-Fye, ME Schechter, AN TI The role of hemoglobin in the transport and metabolism of nitric oxide in normal individuals. SO BLOOD LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 882 BP 201A EP 201A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300931 ER PT J AU Gladwin, MT Ognibene, FP Shelhamer, JH Hrinczenko, BW Pannell, LK Nichols, JS Pease-Fye, ME Noguchi, CT Rodgers, GP Schechter, AN AF Gladwin, MT Ognibene, FP Shelhamer, JH Hrinczenko, BW Pannell, LK Nichols, JS Pease-Fye, ME Noguchi, CT Rodgers, GP Schechter, AN TI Nitric oxide (NO) inhalation augments nitrosyl(heme)hemoglobin and SNO-Hemoglobin formation in SS patients without changing oxygen affinity. SO BLOOD LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 879 BP 201A EP 201A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300928 ER PT J AU Oonishi, T Hrinczenko, B AF Oonishi, T Hrinczenko, B TI Nitric oxide release from human erythrocytes. SO BLOOD LA English DT Meeting Abstract C1 Kanto Teishin Hosp, NTT, Inst Med Res, Tokyo, Japan. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 883 BP 202A EP 202A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300932 ER PT J AU Ikonomi, P Smith, RD Rivera, E Riordan, M Schechter, AN AF Ikonomi, P Smith, RD Rivera, E Riordan, M Schechter, AN TI Purification of stage specific primary erythroid cells and their use for studying the pharmacologic modulation of globin gene expression. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, Bethesda, MD USA. NIH, Dept Clin Pathol, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 906 BP 206A EP 207A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790300955 ER PT J AU Smith, RD Noguchi, CT Schechter, AN AF Smith, RD Noguchi, CT Schechter, AN TI Analysis of globin gene expression in single erythroid cells by real time, quantitative PCR. SO BLOOD LA English DT Meeting Abstract C1 NIH, Biol Chem Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 905 BP 206A EP 206A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300954 ER PT J AU Lavigne, MC de Mendez, I Leto, TL AF Lavigne, MC de Mendez, I Leto, TL TI Formyl-methionyl-leucyl-phenylalanine-induced activation of NADPH oxidase in FPR-transfected K562 cells: A model for receptor-mediated activation of the respiratory burst. SO BLOOD LA English DT Meeting Abstract C1 NIH, Host Def Lab, Bethesda, MD 20892 USA. Parke Davis, Inst Rech Jouveinal, Fresnes, France. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 908 BP 207A EP 207A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300957 ER PT J AU Anderson-Cohen, M Roesler, J Holland, SM Fleisher, TA Malech, HL AF Anderson-Cohen, M Roesler, J Holland, SM Fleisher, TA Malech, HL TI Severe phenotype of chronic granulomatous disease (CGD) presenting in a female with a spontaneous mutation in gp91phox and non-random X-chromosome inactivation. SO BLOOD LA English DT Meeting Abstract C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. NIH, Clin Pathol, CC, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 916 BP 208A EP 209A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790300965 ER PT J AU Altarescu, G Schiffmann, R O'Brady, R Barton, NW AF Altarescu, G Schiffmann, R O'Brady, R Barton, NW TI Dose effect on enzyme replacement therapy (ERT) in type I gaucher disease. SO BLOOD LA English DT Meeting Abstract C1 NINDS, DMNB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 919 BP 209A EP 209A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300968 ER PT J AU Choi, E Lehrnbecher, T Zhu, S Foster, CB Heller, S Goldin, L Leitman, SF Chanock, SJ AF Choi, E Lehrnbecher, T Zhu, S Foster, CB Heller, S Goldin, L Leitman, SF Chanock, SJ TI Distribution of variant genotypes of the nadph-oxidase components, p22-phox and p67-phox in two healthy populations. SO BLOOD LA English DT Meeting Abstract C1 NCI, DCEG, Bethesda, MD 20892 USA. NCI, POB, Bethesda, MD 20892 USA. NIH, DTM, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 923 BP 210A EP 210A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300972 ER PT J AU Zhu, S Lehnrbecher, T Foster, CB Leitman, SF Curnutte, J Aerts, MFG Chanock, SJ AF Zhu, S Lehnrbecher, T Foster, CB Leitman, SF Curnutte, J Aerts, MFG Chanock, SJ TI Distribution of variant genotypes of chitotriosidase in two healthy populations and lack of association between variant genotypes and complications of chronic granulomatous disease. SO BLOOD LA English DT Meeting Abstract C1 Univ Wurzburg, Kinderklin, D-8700 Wurzburg, Germany. Genentech Inc, S San Francisco, CA 94080 USA. NIH, DTM, CC, S San Francisco, CA USA. NCI, POB, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Dept Biochem, NL-1066 CX Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 931 BP 212A EP 212A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790300980 ER PT J AU Frankel, AE Hall, PD Kreitman, RJ AF Frankel, AE Hall, PD Kreitman, RJ TI Steroid prophylaxis prevents systemic inflammatory response syndrome (SIRS) in AML patients treated with diphtheria fusion protein. SO BLOOD LA English DT Meeting Abstract C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4228 BP 229B EP 229B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701072 ER PT J AU Farrell, DH Moaddel, M AF Farrell, DH Moaddel, M TI Acceleration of factor XIII activation by gamma a/gamma' fibrinogen. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Expt Diabet Metab & Nutr Sect, Bethesda, MD USA. Oregon Hlth Sci Univ, Dept Oral Mol Biol, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1022 BP 231A EP 231A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301071 ER PT J AU Lyons, SE Xu, BX Oates, A Zon, LI Thisse, B Liu, PP AF Lyons, SE Xu, BX Oates, A Zon, LI Thisse, B Liu, PP TI A unique myeloid-specific C/EBP transcription factor is present in zebrafish. SO BLOOD LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Childrens Hosp, Dept Pediat Hematol & Oncol, HHMI, Boston, MA 02115 USA. Univ Louis Pasteur Strasbourg 1, CNRS, INSERM, Strasbourg, France. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1135 BP 256A EP 256A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301184 ER PT J AU Linnekin, D DeBerry, C Wallander, M Chian, R Longo, D Mou, S AF Linnekin, D DeBerry, C Wallander, M Chian, R Longo, D Mou, S TI C-kit associates with the beta common subunit of the GM-CSF receptor and enhances GM-CSF-induced proliferation. SO BLOOD LA English DT Meeting Abstract C1 NCI, DBS, Basic Res Lab, Frederick, MD 21701 USA. NIA, Baltimore, MD 21224 USA. NCI, FCRF, SAIC, IRSP, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1169 BP 263A EP 263A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301218 ER PT J AU Alexander, RL McCubrey, JA Kucera, GL Miller, MS Hogge, D Kreitman, RJ Delatte, S Ramage, J Kiser, M Hall, PD Tagge, EP Beran, M Frankel, AE AF Alexander, RL McCubrey, JA Kucera, GL Miller, MS Hogge, D Kreitman, RJ Delatte, S Ramage, J Kiser, M Hall, PD Tagge, EP Beran, M Frankel, AE TI Diphtheria toxin fused to human IL3 is toxic to blasts from patients with acute phase CML. SO BLOOD LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. E Carolina Univ, Sch Med, Dept Microbiol, Greenville, NC USA. Terry Fox Lab, Vancouver, BC, Canada. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Pharmaceut Sci & Surg, Charleston, SC 29425 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4434 BP 273B EP 273B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701278 ER PT J AU Kantarjian, HM Talpaz, M Cortes, J Rios, MB Giles, FJ Mallard, S Bramble, D Murgo, A Cheson, B Kornblau, S Keating, M O'Brien, S AF Kantarjian, HM Talpaz, M Cortes, J Rios, MB Giles, FJ Mallard, S Bramble, D Murgo, A Cheson, B Kornblau, S Keating, M O'Brien, S TI Homoharringtonine and low-dose cytosine (LDara-C) in late chronic prase chronic myelogenous leukemia (CML). SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4439 BP 274B EP 275B PN 2 PG 2 WC Hematology SC Hematology GA 257PM UT WOS:000083790701283 ER PT J AU Kantarjian, HM Talpaz, M Cortes, J Rios, MB Giles, FJ Thomas, D Andreeff, M Mallard, S Lim, J Murgo, A Cheson, B Keating, M O'Brien, S AF Kantarjian, HM Talpaz, M Cortes, J Rios, MB Giles, FJ Thomas, D Andreeff, M Mallard, S Lim, J Murgo, A Cheson, B Keating, M O'Brien, S TI Triple combination therapy with interferon-alpha (IFN-alpha),low-dose cytarabine (LDara-c) and homoharringtonine (HHT) in philadelphia chromosome (PH)-positive chronic myelogenous leukemia (CML) ln early chronic phase. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4440 BP 275B EP 275B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701284 ER PT J AU Wang, J Jani-Sait, SN Escalon, EA Carroll, AJ de Jong, PJ Kirsch, IR Aplan, PD AF Wang, J Jani-Sait, SN Escalon, EA Carroll, AJ de Jong, PJ Kirsch, IR Aplan, PD TI The t(14;21)(q11.2;q22) chromosomal translocation associated with T-cell acute lymphoblastic leukemia activates the BHLHB1 gene. SO BLOOD LA English DT Meeting Abstract C1 Roswell Pk Canc Inst, Dept Canc Genet Biochem Clin Cytogenet & Pediatr, Buffalo, NY 14263 USA. Miami Childrens Hosp, Div Hematol Oncol, Miami, FL USA. Univ Alabama, Dept Human Genet, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1226 BP 275A EP 275A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301275 ER PT J AU Wood, JD Nucifora, FC Duan, K Wang, J Kim, Y Schilling, G Sacchi, N Liu, JM Ross, CA AF Wood, JD Nucifora, FC Duan, K Wang, J Kim, Y Schilling, G Sacchi, N Liu, JM Ross, CA TI The ETO/MTG8 oncoprotein interacts with atrophin-1, the DRPLA gene product, in the nuclear matrix. SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Div Neurobiol, Baltimore, MD 21205 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Univ Milan, Dept Biol, Milan, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1232 BP 276A EP 276A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301281 ER PT J AU Castilla, LH Garrett, L Wolff, L Liu, PP AF Castilla, LH Garrett, L Wolff, L Liu, PP TI Identification of genes cooperationg with Cbfb-MYH11 in leukemogenesis. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1237 BP 277A EP 277A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301286 ER PT J AU Wang, J Wang, M Saunthararajah, Y Liu, JM AF Wang, J Wang, M Saunthararajah, Y Liu, JM TI Two separate domains of the human nuclear receptor co-repressor contact the ETO oncoprotein: Model of interaction. SO BLOOD LA English DT Meeting Abstract C1 CAMS, Inst Hematol, Tianjin, Peoples R China. NHLBI, Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1234 BP 277A EP 277A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301283 ER PT J AU Onda, M Kreitman, RJ Vasmatzis, G Lee, B Pastan, I AF Onda, M Kreitman, RJ Vasmatzis, G Lee, B Pastan, I TI Reduction of the nonspecific toxicity of immunotoxin anti-Tac(Fv)-PE38 (LMB-2) by mutations in the Fv which lower the isoelectric point. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1246 BP 279A EP 279A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301295 ER PT J AU Selleri, C Maciejewski, JP Ricci, P Varriale, G Risitano, AM Luciano, L Picardi, H Califano, C Della Cioppa, P Bruno, R AF Selleri, C Maciejewski, JP Ricci, P Varriale, G Risitano, AM Luciano, L Picardi, H Califano, C Della Cioppa, P Bruno, R TI Interferon-alpha may modulate the balance between FAS-receptor and FAS-ligand expression on bone marrow chronic myeloid leukemia cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Naples Federico II, Div Hematol, Naples, Italy. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4460 BP 279B EP 279B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701304 ER PT J AU Rao, VK Litman, T Eriksen, J Fojo, T Dean, M Skovsgaard, T AF Rao, VK Litman, T Eriksen, J Fojo, T Dean, M Skovsgaard, T TI Molecular cytogenetic evaluation of MXR overexpression in drug resistant leukemia cell lines. SO BLOOD LA English DT Meeting Abstract C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Herlev Univ Hosp, Dept Oncol, DK-2730 Herlev, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1262 BP 282A EP 282A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301311 ER PT J AU Molldrem, JJ Rivera, M Stetler-Stevenson, M Saborro, L Barrett, AJ AF Molldrem, JJ Rivera, M Stetler-Stevenson, M Saborro, L Barrett, AJ TI Treatment with low-dose cyclosporine induces sustained recovery from cytopenia in patients with T-LGL leukemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1326 BP 297A EP 297A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301375 ER PT J AU Sakai, A Marti, GE Caporaso, N Pittaluga, S Touchman, JW Fend, F Raffeld, M AF Sakai, A Marti, GE Caporaso, N Pittaluga, S Touchman, JW Fend, F Raffeld, M TI Analysis of expressed immunoglobulin heavy chain genes in familial B-CLL. SO BLOOD LA English DT Meeting Abstract C1 NCI, Hematopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Flow & Image Cytometry Sect, Lab Med & Mol Genet, Div Cell & Gene Therapies, Bethesda, MD 20014 USA. NCI, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, NIH, Intramural Sequencing Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4586 BP 304B EP 304B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701430 ER PT J AU Trivedi, C Al-Katib, A Murgo, A Mohammad, R Eilender, D Hulburd, K Rodriguez, D Pemberton, P Lagrone, F Manica, B Spadoni, V Varterasian, M AF Trivedi, C Al-Katib, A Murgo, A Mohammad, R Eilender, D Hulburd, K Rodriguez, D Pemberton, P Lagrone, F Manica, B Spadoni, V Varterasian, M TI Phase II clinical evaluation of bryostatin-1 in patients with relapsed Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract C1 Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4635 BP 315B EP 315B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701479 ER PT J AU Vaishampayan, UN Wall, NR Varterasian, ML Murgo, A Sorice, P Dan, M Shurafa, M Mohammad, RM Al-Katib, AM AF Vaishampayan, UN Wall, NR Varterasian, ML Murgo, A Sorice, P Dan, M Shurafa, M Mohammad, RM Al-Katib, AM TI Differentiation therapy of chronic lymphocytic leukemia (CLL) cells by bryostatin-1 (bryo) in vivo: Validity of preclinical model. SO BLOOD LA English DT Meeting Abstract C1 Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. NCI, Bethesda, MD 20892 USA. Henry Ford Hosp, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4636 BP 315B EP 315B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701480 ER PT J AU Fry, TJ Christensen, BL Mackall, CL AF Fry, TJ Christensen, BL Mackall, CL TI Increased susceptibility to tolerance induction in T cell depleted hosts during immune reconstitution SO BLOOD LA English DT Meeting Abstract C1 NCI, NIH, Pediat Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1430 BP 320A EP 320A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303208 ER PT J AU Shaaban, AF Kim, HB Milner, R Hayashi, S Fichter, C Flake, AW AF Shaaban, AF Kim, HB Milner, R Hayashi, S Fichter, C Flake, AW TI Agonistic cd40 antibodies inhibit murine renal cell carcinoma cells in vitro, provide anti-tumor effects in resting mice, but result in significant toxicity after syngeneic bone marrow transplantation: Potential therapeutic considerations. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN USA. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1441 BP 322A EP 322A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301489 ER PT J AU Epperson, DE Margolis, DA McOlash, L Janczak, T Barrett, AJ AF Epperson, DE Margolis, DA McOlash, L Janczak, T Barrett, AJ TI In vitro T cell receptor V beta repertoire analysis can identify which T cells mediate graft vs. leukemia (GVL) and graft vs. host (GVH) responses after HLA-matched sibling bone marrow transplantation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, BMT Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1453 BP 325A EP 325A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301501 ER PT J AU van Rhee, F Szmania, S Arthur, A Clave, E Hensel, N Lamb, L Madrigal, A Barrett, AJ Henslee-Downey, PJ AF van Rhee, F Szmania, S Arthur, A Clave, E Hensel, N Lamb, L Madrigal, A Barrett, AJ Henslee-Downey, PJ TI Cytomegalovirus (CMV) pp65 pulsed dendritic cells (DC'S) cultured in autologous plasma can stimulate CMV specific autologous cytotoxic T-lymphocyte (CTL) responses. SO BLOOD LA English DT Meeting Abstract C1 Univ S Carolina, Palmetto Richland Mem Hosp, Div Transplantat Med, Columbia, SC 29208 USA. NIH, Bone Marrow Transplant Unit, Bethesda, MD 20892 USA. Anthony Nolan Res Ctr, London, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4708 BP 332B EP 332B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701552 ER PT J AU Carabasi, MH Khazaeli, MB Tilden, AB Brezovich, IA Schlom, J Salzman, DE Vaughan, WP LoBuglio, AF Meredith, RF AF Carabasi, MH Khazaeli, MB Tilden, AB Brezovich, IA Schlom, J Salzman, DE Vaughan, WP LoBuglio, AF Meredith, RF TI Autologous stem cell transplantation for breast and prostate cancer after combined modality therapy with radioimmunotherapy plus external beam radiation. SO BLOOD LA English DT Meeting Abstract C1 Univ Alabama, Stem Cell Transplant Program, Birmingham, AL USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1487 BP 333A EP 333A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301535 ER PT J AU Hensel, N Almeida, K Bahceci, E Childs, R Barrett, J AF Hensel, N Almeida, K Bahceci, E Childs, R Barrett, J TI Factors affecting incidence and timing of cytomegalovirus (CMV) reactivation after allogeneic peripheral blood stem cell transplants (PBSCT). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bone Marrow Transplant Unit, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1506 BP 337A EP 337A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301554 ER PT J AU Hensel, N Clave, E Bradstock, K Barrett, J Barret, A AF Hensel, N Clave, E Bradstock, K Barrett, J Barret, A TI Variations in cytomegalovirus (CMV) antigen-specific T-cell frequency in CMV seropositive and seronegative stem cell donors. SO BLOOD LA English DT Meeting Abstract C1 Westmead Hosp, Sydney, NSW 2145, Australia. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1520 BP 340A EP 340A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301568 ER PT J AU Saif, MW Leitman, SF Horne, M Freifeld, A Cusack, G Cowan, KH Zujewski, J AF Saif, MW Leitman, SF Horne, M Freifeld, A Cusack, G Cowan, KH Zujewski, J TI Pulmonary embolism following removal of apheresis catheters in patients with malignancy. SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4751 BP 341B EP 341B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701595 ER PT J AU Bos, LS Mohammad, SF Haynesworth, SE Sramkoski, RM Jacobberger, J Welniak, LA Murphy, WJ Koh, CY Szekely, E Junge, GR Kadereit, S Miller, RE Laughlin, MJ AF Bos, LS Mohammad, SF Haynesworth, SE Sramkoski, RM Jacobberger, J Welniak, LA Murphy, WJ Koh, CY Szekely, E Junge, GR Kadereit, S Miller, RE Laughlin, MJ TI Mesenchymal stem cell (MSC)-based umbilical cord blood ex vivo expansion. SO BLOOD LA English DT Meeting Abstract C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NCI, IRSP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4769 BP 345B EP 345B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701613 ER PT J AU Aviles-Mendoza, G Simon-Stoos, K Seidel, NE Cline, AP Anderson, SM Candotti, F Malech, HL Puck, JM Bodine, DM AF Aviles-Mendoza, G Simon-Stoos, K Seidel, NE Cline, AP Anderson, SM Candotti, F Malech, HL Puck, JM Bodine, DM TI Direct comparison of LTR and vector backbones demonstrates that retrovirus vectors with internal splicing signals express the highest levels of interleukin-2 receptor common chain mrna in primary murine lymphocytes and supports their development for human gene therapy XSCID. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, GMBB, NIH, Bethesda, MD USA. NHGRI, Immunol Genet Sect, GMBB, NIH, Bethesda, MD USA. NHGRI, CGTB, NIH, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1584 BP 356A EP 356A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301633 ER PT J AU Wu, T Tisdale, JF Bloom, ML Meade, KE Sellers, SE Donahue, RE Dunbar, CE AF Wu, T Tisdale, JF Bloom, ML Meade, KE Sellers, SE Donahue, RE Dunbar, CE TI Improved retroviral transduction efficiency of murine and primates hematopoietic repopulating cells by abrogation of TGF-beta activity with a neutralizing antibody. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1589 BP 357A EP 357A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301638 ER PT J AU Martelli, MP Samelson, LE Bierer, BE AF Martelli, MP Samelson, LE Bierer, BE TI CD2 recruits alternative pathways of human T cell activation defined by the requirement for Zap70/Syk kinases and LAT phosphorylation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RI Martelli, Maria Paola/I-5618-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1646 BP 370A EP 370A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301695 ER PT J AU Miller, JD Stacy, T Liu, PP Speck, NA AF Miller, JD Stacy, T Liu, PP Speck, NA TI The CBF beta-SMMHC protein generated by the INV(16) preferentially inhibits the differentiation of myeloid lineage cells. SO BLOOD LA English DT Meeting Abstract C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Biochem, Hanover, NH 03756 USA. Natl Humane Genome Res Inst, Lab Gene Transfer, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1688 BP 380A EP 380A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301737 ER PT J AU Kim, HJ Tisdale, JF Wu, T Takatoku, M Sellers, SE Donahue, RE Brown, KE Dunbar, CE AF Kim, HJ Tisdale, JF Wu, T Takatoku, M Sellers, SE Donahue, RE Brown, KE Dunbar, CE TI Many multi-potential gene-marked progenitors contribute to hematopoiesis in non-human primates. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. Chonnam Med Univ, Kwangju, South Korea. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1730 BP 390A EP 390A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301779 ER PT J AU Salcedo, R Howard, OMZ Oppenheim, JJ Welniak, LA Blazar, BR Murphy, WJ AF Salcedo, R Howard, OMZ Oppenheim, JJ Welniak, LA Blazar, BR Murphy, WJ TI Inhibition of graft-versus-host disease by a distamycin analogue that interferes with chemokine receptor function. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Univ Minnesota, Dept Pediat, Ctr Canc, Minneapolis, MN 55455 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1738 BP 392A EP 392A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301787 ER PT J AU Childs, R Contentin, N Clave, E Bahceci, E Hensel, N Boland, C Pomper, G Read, EJ Leitman, S Dunbar, C Young, NS Barrett, AJ AF Childs, R Contentin, N Clave, E Bahceci, E Hensel, N Boland, C Pomper, G Read, EJ Leitman, S Dunbar, C Young, NS Barrett, AJ TI Reduced toxicity and transplant related mortality (TRM) following nonmyeloablative allogeneic peripheral blood stem cell transplantation for malignant diseases. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 0 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1743 BP 393A EP 393A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301792 ER PT J AU Giri, N Kang, EM Wu, T Sellers, S Kirby, M Hanazano, Y Tisdale, JF Dunbar, C AF Giri, N Kang, EM Wu, T Sellers, S Kirby, M Hanazano, Y Tisdale, JF Dunbar, C TI In vivo persistence of genetically-modified murine hematopoietic progenitors is not limited by the expression of the neo or GFP gene after full or minimal myeloablation. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1764 BP 398A EP 398A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301813 ER PT J AU Njoroge, JM Mitchell, LB Centola, M Kastner, D Raffeld, M Miller, JL AF Njoroge, JM Mitchell, LB Centola, M Kastner, D Raffeld, M Miller, JL TI Non-adherent macrophages among liquid cultured peripheral blood cells inhibit erythropoiesis. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, Bethesda, MD USA. NIAMS, Arthrit & Rheumatism Branch, Bethesda, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1775 BP 401A EP 401A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301824 ER PT J AU Pavletic, S O'Dell, J Ursick, M Haire, C Maher, K Bishop, M Reed, E Armitage, J Kessinger, A Klassen, L AF Pavletic, S O'Dell, J Ursick, M Haire, C Maher, K Bishop, M Reed, E Armitage, J Kessinger, A Klassen, L TI Autologous blood stem cell transplantation can overcome and modulate therapeutic resistance in severe rheumatoid arthritis. SO BLOOD LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5035 BP 404B EP 404B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701879 ER PT J AU Tisdale, JF Dunn, DE Rosenfeld, SE Nunez, O Sloand, E Barrett, AJ Dunbar, CE Young, NS AF Tisdale, JF Dunn, DE Rosenfeld, SE Nunez, O Sloand, E Barrett, AJ Dunbar, CE Young, NS TI Report on a randomized trial comparing cyclophosphamide and cyclosporine vs antithymocyte globulin and cyclosporine as initial treatment for severe aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. Univ Utah, Div Hematol, Salt Lake City, UT USA. NIH, Ctr Clin, Bethesda, MD USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1804 BP 407A EP 407A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301853 ER PT J AU Berger, F Soligo, D Schwarz, K Bossolasco, P Schrezenmeier, H Kubanek, B Lambertenghi-Deliliers, G Licht, T AF Berger, F Soligo, D Schwarz, K Bossolasco, P Schrezenmeier, H Kubanek, B Lambertenghi-Deliliers, G Licht, T TI Efficient retroviral transduction into hematopoietic stem cells facilitated by a FLT-3 ligand containing cytokine combination preserving a primitive stem cell phenotype. SO BLOOD LA English DT Meeting Abstract C1 Fdn Matarelli, Milan, Italy. Osped Maggiore, IRCCS, I-20122 Milan, Italy. Tech Univ Munich, D-8000 Munich, Germany. Univ Ulm, D-89069 Ulm, Germany. NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5051 BP 408B EP 408B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701895 ER PT J AU Kang, EM Giri, N Rivera, M Tisdale, JF Young, NS Dunbar, CE AF Kang, EM Giri, N Rivera, M Tisdale, JF Young, NS Dunbar, CE TI Treatment of refractory Diamond-Blackfan Anemia with anti-thymocyte globulin (ATG) and cyclosporine (CysA). SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Cellular Hematol Branch, Bethesda, MD USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1807 BP 408A EP 408A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301856 ER PT J AU Freimark, BD Goel, AS Szalay, P Malech, HL Van Epps, DE AF Freimark, BD Goel, AS Szalay, P Malech, HL Van Epps, DE TI Comparison of retroviral transduction efficiencies of human CD34 cells in closed culture systems. SO BLOOD LA English DT Meeting Abstract C1 Nexell Therapeut Inc, Irvine, CA USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5059 BP 410B EP 410B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701903 ER PT J AU Guerrera, MF Lacbawan, FL Tifft, CJ Amaya, M Pennybacker, M Weinstien, S Wong, LC Luban, NLC AF Guerrera, MF Lacbawan, FL Tifft, CJ Amaya, M Pennybacker, M Weinstien, S Wong, LC Luban, NLC TI Macrocytic anemia as the initial presentation of a novel 4.4kb mtDNA deletion. SO BLOOD LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NHGRI, NIH, Bethesda, MD USA. Georgetown Univ, Inst Mol & Human Genet, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1822 BP 411A EP 411A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301871 ER PT J AU Licht, T Hafkemeyer, P Pastan, I Gottesman, MM Kreitman, RJ AF Licht, T Hafkemeyer, P Pastan, I Gottesman, MM Kreitman, RJ TI Chemoprotection of hematopoietic cells by a mutant P-glycoprotein resistant to trans(E)flupentixol, a potent chemosensitizer of multidrug resistant cancers. SO BLOOD LA English DT Meeting Abstract C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5076 BP 414B EP 414B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701920 ER PT J AU Giri, N Kang, EM Tisdale, JF Follman, D Rivera, M Kim, S Rick, M Schwartz, GN Young, NS Dunbar, CE AF Giri, N Kang, EM Tisdale, JF Follman, D Rivera, M Kim, S Rick, M Schwartz, GN Young, NS Dunbar, CE TI Clinical and laboratory evidence for a trilineage hematopoietic defect in patients with refractory Diamond-Blackfan anemia. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, MCHB, Bethesda, MD USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NIH, Hematol Serv, CC, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1839 BP 415A EP 415A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301888 ER PT J AU Chinnasamy, D Chimasamy, N Puck, JM O'Shea, JJ Morgan, RA Candotti, F Lozier, JN AF Chinnasamy, D Chimasamy, N Puck, JM O'Shea, JJ Morgan, RA Candotti, F Lozier, JN TI Lentiviral-mediate gene correction of severe combined immunodeficiencies. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5096 BP 418B EP 418B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701940 ER PT J AU Lozier, JN Donahue, RE Donahue, BA Metzger, ME McGehee, J Synder, RO Powell, S Winters, P Morgan, RA AF Lozier, JN Donahue, RE Donahue, BA Metzger, ME McGehee, J Synder, RO Powell, S Winters, P Morgan, RA TI Portal vein infusion of a human factor IX-containing raav vector to rhesus macaques results in minimal affects on liver function and no perturbation of coagulation measures. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Cell Genesys Inc, Foster City, CA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5100 BP 418B EP 419B PN 2 PG 2 WC Hematology SC Hematology GA 257PM UT WOS:000083790701944 ER PT J AU Lian, LR Ollinger, F Li, X Shah, SP Emanuele, M Evans, G Asakura, T AF Lian, LR Ollinger, F Li, X Shah, SP Emanuele, M Evans, G Asakura, T TI Prevention of hypoxia-induced acute chest syndrome in transgenic sickle cell mice by FLOCOR SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. CytRex Corp, Norcross, GA USA. NHLBI, Sickle Cell Dis Sci Res Grp, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1863 BP 420A EP 420A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301912 ER PT J AU Baltus, B Buitenhuis, M van Dijk, T Vinson, C Raaijmakers, J Lammers, JW Koenderman, L de Groot, RP AF Baltus, B Buitenhuis, M van Dijk, T Vinson, C Raaijmakers, J Lammers, JW Koenderman, L de Groot, RP TI C/EBP regulates the promoter of the eosinophil derived neurotoxin/RNS2 gene in human eosinophilic cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Univ Utrecht, Ctr Med, Utrecht, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1911 BP 430A EP 430A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301960 ER PT J AU Kissel, K Santoso, S Hofmann, C Stroncek, D Bux, J AF Kissel, K Santoso, S Hofmann, C Stroncek, D Bux, J TI Elucidation of the primary structure of the neutrophil antigen HNA-2a (NB1): Evidence for a new glycoprotein. SO BLOOD LA English DT Meeting Abstract C1 Univ Giessen, Inst Clin Immunol & Transfus Med, D-35390 Giessen, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1910 BP 430A EP 430A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301959 ER PT J AU Aoki, Y Yarchoan, R Chang, Y Iwamoto, A Okamoto, S Tosato, G AF Aoki, Y Yarchoan, R Chang, Y Iwamoto, A Okamoto, S Tosato, G TI Detection of viral interleukin-6 in Kaposi's sarcoma-associated herpesvirus-linked diseases. SO BLOOD LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NCI, NIH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Univ Tokyo, Tokyo, Japan. Keio Univ, Tokyo, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1915 BP 431A EP 431A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301964 ER PT J AU Lehrnbecher, T Foster, CB Zhu, S Venzon, D Steinberg, S Wyvill, K Metcalf, JA Cohen, S Kovacs, J Yarchoan, R Blauvelt, A Chanock, SJ AF Lehrnbecher, T Foster, CB Zhu, S Venzon, D Steinberg, S Wyvill, K Metcalf, JA Cohen, S Kovacs, J Yarchoan, R Blauvelt, A Chanock, SJ TI Variant genotypes of Fc gamma RIIIa influence the development of Kaposi's sarcoma in HIV-infected men. SO BLOOD LA English DT Meeting Abstract C1 Univ Wurzburg, Kinderklin, D-8700 Wurzburg, Germany. NCI, POB, NIH, Bethesda, MD 20892 USA. NCI, BDMS, NIH, Bethesda, MD 20892 USA. NCI, HAMB, NIH, Bethesda, MD 20892 USA. NIAID, LI, NIH, Bethesda, MD 20892 USA. NCI, DB, NIH, Bethesda, MD 20892 USA. NIH, CC, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1916 BP 431A EP 431A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301965 ER PT J AU Foster, CB Lehrnbecher, T Stein, S Samuels, S Mol, F Steinberg, SM Venzon, DJ Kovacs, J Blauvelt, A Yarchoan, R Chanock, SJ AF Foster, CB Lehrnbecher, T Stein, S Samuels, S Mol, F Steinberg, SM Venzon, DJ Kovacs, J Blauvelt, A Yarchoan, R Chanock, SJ TI A study of proinflammatory cytokine polymorphisms demonstrates that an IL-6 promoter polymorphism (-174) is associated with development of Kaposi's sarcoma in HIV infected SO BLOOD LA English DT Meeting Abstract C1 NCI, POB, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Kinderklin, Wurzburg, Germany. NCI, BDMS, NIH, Bethesda, MD 20892 USA. NIH, CC, Bethesda, MD 20892 USA. NCI, DB, NIH, Bethesda, MD 20892 USA. NCI, HAMB, NIH, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1917 BP 432A EP 432A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301966 ER PT J AU Fry, TJ Wood, LV Liewehr, DJ Steinberg, SM Mackall, CL AF Fry, TJ Wood, LV Liewehr, DJ Steinberg, SM Mackall, CL TI A potential role for IL-7 in T cell homeostasis in HIV infected patients. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, BDMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1919 BP 432A EP 432A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301968 ER PT J AU Levine, AM Berhane, K Masri-Lavine, L Sanchez, ML Greenblatt, RM Anastos, K Young, M Augenbraun, M Cohen, M Gange, S Burns, D AF Levine, AM Berhane, K Masri-Lavine, L Sanchez, ML Greenblatt, RM Anastos, K Young, M Augenbraun, M Cohen, M Gange, S Burns, D TI Prevalence of, and risk factors for anemia among a large cohort of HIV infected women: Women's interagency HIV study (WIHS). SO BLOOD LA English DT Meeting Abstract C1 Univ So Calif, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Catholic Med Ctr, Jamaica, NY USA. Cook Cty Hosp, Chicago, IL 60612 USA. Georgetown Univ, Washington, DC USA. Maimonides Med Ctr, Brooklyn, NY 11219 USA. Johns Hopkins, Baltimore, MD USA. NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1920 BP 432A EP 432A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301969 ER PT J AU Christensen, BL Jankelevich, S Duan, ZJ Noel, NL Mackall, CL AF Christensen, BL Jankelevich, S Duan, ZJ Noel, NL Mackall, CL TI Semi-quantitative analysis of T cell receptor repertoire diversity. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1932 BP 435A EP 435A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301981 ER PT J AU Baskar, S Kwak, LW AF Baskar, S Kwak, LW TI Identification of lymphoma idiotype (Id)-derived CDR2 and CDR3 peptides as tumor antigens by T cells from vaccinated patients. SO BLOOD LA English DT Meeting Abstract C1 NCI, Dept Expt Transplantat & Immunol, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. SAIC, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1941 BP 437A EP 437A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301990 ER PT J AU Woei-A-Jin, S Clave, E Melenhorst, J Barrett, J AF Woei-A-Jin, S Clave, E Melenhorst, J Barrett, J TI HLA class I tetramers identify CD8+T cell responses to alleles of the myeloid-restricted protein proteinase-3 SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1940 BP 437A EP 437A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301989 ER PT J AU Fukazawa, M Telford, WG Gress, RE Schwartz, GN AF Fukazawa, M Telford, WG Gress, RE Schwartz, GN TI Modulatory effects of monokine induced by IFN-gamma (Mig) on insulin-like growth factor II- (IGF-II) and stem cell growth factor- (SCF) enhanced proliferation of marrow and mobilized CD34+cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Dept Exp Transplantat & Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2069 BP 464A EP 464A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302118 ER PT J AU Ruscetti, FW Walz, T Sitnicka, E Letterio, JJ Bartelmez, SH AF Ruscetti, FW Walz, T Sitnicka, E Letterio, JJ Bartelmez, SH TI Endogenous transforming growth factor beta 1 is a direct regulator of the survival of long-term repopulating murine stem cells in vitro. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, Frederick, MD USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2076 BP 466A EP 466A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302125 ER PT J AU Blake, TB Adya, N Zon, LI Weinstein, B Liu, PP AF Blake, TB Adya, N Zon, LI Weinstein, B Liu, PP TI The relationship of zebrafish CBFB to SCL and GATA-1 in hematopoiesis. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Childrens Hosp, Boston, MA 02115 USA. NICHD, NIH, Bethesda, MD USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2083 BP 467A EP 467A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302132 ER PT J AU Curtis, DJ Hilton, DJ Jane, SM Bodine, DM Begley, CG AF Curtis, DJ Hilton, DJ Jane, SM Bodine, DM Begley, CG TI Cloning and characterisation of a murine homologue of human SKAP55R, a myeloid expressed src-kinase substrate (Mess) that inhibits growth of myeloid cells. SO BLOOD LA English DT Meeting Abstract C1 Walter & Eliza Hall Inst Med Res, Canc & Haematol Div, Melbourne, Vic 3050, Australia. Royal Melbourne Hosp, Rotary Bone Marrow Res Lab, Melbourne, Vic, Australia. NHGRI, Hematopoeisis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. RI Jane, Stephen/D-6659-2011; Hilton, Douglas/C-7250-2013 OI Hilton, Douglas/0000-0002-7698-2392 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2116 BP 474A EP 474A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302165 ER PT J AU Weiniak, LA Ruscetti, FW Farrar, WL Kirken, RA Blazar, BR Murphy, WJ AF Weiniak, LA Ruscetti, FW Farrar, WL Kirken, RA Blazar, BR Murphy, WJ TI Assessment of JAK3 knockout mice: Increased myelopoiesis in vivo and in vitro. SO BLOOD LA English DT Meeting Abstract C1 NCI, LLB, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, LMI, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Univ Houston, Houston, TX USA. Univ Minnesota, Dept Pediat, Ctr Canc, Minneapolis, MN 55455 USA. SAIC Frederick, IRSP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2113 BP 474A EP 474A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302162 ER PT J AU Linnekin, D Ashman, L Ferrao, P Chian, R Keller, J AF Linnekin, D Ashman, L Ferrao, P Chian, R Keller, J TI Signaling mechanisms of an oncogenic form of c-Kit in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Basic Res Lab, DBS, Frederick, MD USA. Inst Med & Vet Sci, Adelaide, SA 5000, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2128 BP 476A EP 477A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790302177 ER PT J AU Li, WQ Zhang, IC Flechner, L Hyun, T Yarn, A Franke, TF Pierce, JH AF Li, WQ Zhang, IC Flechner, L Hyun, T Yarn, A Franke, TF Pierce, JH TI Protein kinase C-alpha overexpression stimulates Akt activity and suppresses apoptosis induced by interleukin 3 withdrawal. SO BLOOD LA English DT Meeting Abstract C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2154 BP 482A EP 482A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302203 ER PT J AU Cortes, JE Wright, J Giles, FJ Thomas, D Andreeff, M O'Brien, S Estey, E Kantarjian, HM AF Cortes, JE Wright, J Giles, FJ Thomas, D Andreeff, M O'Brien, S Estey, E Kantarjian, HM TI Phase I study of dolastatin-10 in refractory or relapsed acute leukemia. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Investigat Drug Branch, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2274 BP 508A EP 508A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302323 ER PT J AU Fassone, L Cingolani, A Martini, M Oreste, P Gutierrez, M Migliaretti, G Capello, D Vivenza, D Saglio, G Bhatia, K Antinori, A Larocca, M Gaidano, G AF Fassone, L Cingolani, A Martini, M Oreste, P Gutierrez, M Migliaretti, G Capello, D Vivenza, D Saglio, G Bhatia, K Antinori, A Larocca, M Gaidano, G TI Molecular characterization of Epstein-Barr virus in AIDS-related primary central nervous system lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Amedeo Avogadro Univ Eastern Piedmont, Novara, Italy. Univ Cattolica Sacro Cuore, I-00168 Rome, Italy. Niguarda Ca Grande Hosp, Milan, Italy. NCI, Lymphoma Biol Sect, NIH, Bethesda, MD 20892 USA. Univ Turin, Orbassano, TO, Italy. INRCCS Spallanzani, Rome, Italy. RI Capello, Daniela/J-4110-2012 OI Capello, Daniela/0000-0001-9157-8753 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2324 BP 519A EP 519A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302373 ER PT J AU Jain, N Carter, P Washington, GC Abassi, F Caporaso, N Marti, GE Rick, M AF Jain, N Carter, P Washington, GC Abassi, F Caporaso, N Marti, GE Rick, M TI B cell monoclonal lymphocytosis (BCML): A marker for early detection of BCLL. SO BLOOD LA English DT Meeting Abstract C1 NCI, POB, NIH, Bethesda, MD 20892 USA. US FDA, LMMG, CBER, Bethesda, MD 20014 USA. NCI, GEB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2401 BP 537A EP 537A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302450 ER PT J AU Shou, Y Martelli, ML Gabrea, A Qi, Y Brents, LA Roschke, A Dewald, G Kirsch, IR Bergsagel, PL Kuehl, M Monahan, B AF Shou, Y Martelli, ML Gabrea, A Qi, Y Brents, LA Roschke, A Dewald, G Kirsch, IR Bergsagel, PL Kuehl, M Monahan, B TI Complex karyotypic abnormalities are associated with c-myc dysregulation and tumor progression in multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2417 BP 541A EP 541A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302466 ER PT J AU Martelli, ML Gabrea, A Qi, Y Shou, Y Shaughnessy, JD Sawyer, JR Barlogie, B Bergsagel, PL Kuehl, MW Monahan, B AF Martelli, ML Gabrea, A Qi, Y Shou, Y Shaughnessy, JD Sawyer, JR Barlogie, B Bergsagel, PL Kuehl, MW Monahan, B TI Immunoglobulin translocations in multiple myeloma: Present in all cell lines but not all primary tumors. SO BLOOD LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Little Rock, AR USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2431 BP 544A EP 544A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302480 ER PT J AU Drobyski, WR Agostini, T Burns, WH Morse, H Sandford, G AF Drobyski, WR Agostini, T Burns, WH Morse, H Sandford, G TI Mitigation of murine graft versus host disease (GVHD) without compromise of alloengraftment using transgenic donor T cells expressing a thymidine kinase (TK) suicide gene. SO BLOOD LA English DT Meeting Abstract C1 Med Coll Wisconsin, Bone Marrow Transplant Program, Milwaukee, WI 53226 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2461 BP 550A EP 550A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302510 ER PT J AU Welniak, LA Blazar, BR Henry, M Wiltrout, RH Murphy, WJ AF Welniak, LA Blazar, BR Henry, M Wiltrout, RH Murphy, WJ TI Differential effects of endogenous IL-12 (p35/p30 heterodimer) and p40 homodimer on the acceleration of acute lethal GVHD. SO BLOOD LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, LLB, Frederick, MD USA. Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN USA. NCI, Frederick Canc Res & Dev Ctr, LEI, Frederick, MD USA. SAIC, IRSP, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2460 BP 550A EP 550A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302509 ER PT J AU Persons, DA Allay, E Kelly, P Sabatino, DE Bodine, DM Nienhuis, AW AF Persons, DA Allay, E Kelly, P Sabatino, DE Bodine, DM Nienhuis, AW TI Characterization of the proportion of corrected cells and level of gamma globin transgene expression required for phenotypic improvement of murine beta-thalassemia. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Div Expt Hematol, Memphis, TN 38105 USA. NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2595 BP 582A EP 582A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302644 ER PT J AU Handa, A Nagafuji, K Young, NS Dickstein, BM Brown, KE AF Handa, A Nagafuji, K Young, NS Dickstein, BM Brown, KE TI Very high prevalence of TTV in American blood donors and presence of TTV DNA and RNA in hematopoietic cells. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2632 BP 591A EP 591A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302681 ER PT J AU Jaffe, ES Puck, JM Jackson, CE Dale, JK Sneller, MC Fischer, RE Hsu, AP Hallahan, CW Lenardo, MJ Straus, SE AF Jaffe, ES Puck, JM Jackson, CE Dale, JK Sneller, MC Fischer, RE Hsu, AP Hallahan, CW Lenardo, MJ Straus, SE TI Increased risk for diverse lymphomas in autoimmune lymphoproliferative syndrome (ALPS), an inherited disorder due to defective lymphocyte apoptosis. SO BLOOD LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2660 BP 597A EP 597A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302709 ER PT J AU Wilson, WH Gutierrez, M Raffeld, M Raggio, M Jaffe, ES AF Wilson, WH Gutierrez, M Raffeld, M Raggio, M Jaffe, ES TI Lymphomatoid granulomatosis: Phase II study of dose-adjusted interferon-alpha or EPOCH chemotherapy. SO BLOOD LA English DT Meeting Abstract C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2668 BP 599A EP 599A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302717 ER PT J AU Panoskaltsis-Mortari, A Taylor, PA Rubin, JS Farrell, CL Lacey, DL Blazar, BR AF Panoskaltsis-Mortari, A Taylor, PA Rubin, JS Farrell, CL Lacey, DL Blazar, BR TI Keratinocyte growth factor (KGF) facilitates alloengraftment and ameliorates GVHD by a mechanism independent of repair of conditioning-induced tissue injury. SO BLOOD LA English DT Meeting Abstract C1 Univ Minnesota, Ctr Canc, Minneapolis, MN USA. NIH, Bethesda, MD 20892 USA. Amgen, Thousand Oaks, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2689 BP 604A EP 604A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302738 ER PT J AU Bennett, M Koh, CY Blazar, BR Murphy, WJ AF Bennett, M Koh, CY Blazar, BR Murphy, WJ TI Blockade of inhibitory receptors as a means to augment anti-leukemia effects of NK cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX USA. Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN USA. NCI, SAIC, Frederick, MD USA. RI Koh, Crystal/D-9986-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2692 BP 605A EP 605A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302741 ER PT J AU Futaki, M Igarashi, T Watanabe, S Kajigaya, S Liu, JM AF Futaki, M Igarashi, T Watanabe, S Kajigaya, S Liu, JM TI FANCG, the Fanconi Anemia group G gene product, interacts with cytochrome P450 2E1: Pathophysiologic implications. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2727 BP 613A EP 613A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302776 ER PT J AU Melenhorst, JJ Bummendorf, TH Kim, S Kirby, M Sloand, E Bahceci, E Sorbara, L Molldrem, JJ Lansdorp, PM Barrett, J AF Melenhorst, JJ Bummendorf, TH Kim, S Kirby, M Sloand, E Bahceci, E Sorbara, L Molldrem, JJ Lansdorp, PM Barrett, J TI Large granular T cell lymphocytosis (LGL) is an unresolved CD8+immune response. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. British Columbia Canc Res Ctr, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NCI, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Bone Marrow Transplant Program, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2799 BP 630A EP 630A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302848 ER PT J AU Weissinger, EM Melenhorst, JJ Kirby, M Barrett, JA AF Weissinger, EM Melenhorst, JJ Kirby, M Barrett, JA TI T cell receptor analysis reveals oligoclonal expansion of CD4 and CD8 positive cells in patients with large granular lymphoproliferative disorder (T-LGL). SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2800 BP 630A EP 630A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302849 ER PT J AU Takenaka, T Murray, GJ Qin, G Quirk, JM Ohshima, T Qasba, P Tei, C Brady, RO Kulkarni, AB Medin, JA AF Takenaka, T Murray, GJ Qin, G Quirk, JM Ohshima, T Qasba, P Tei, C Brady, RO Kulkarni, AB Medin, JA TI Long-term lipid reduction and enzyme correction in multiple organs of alpha-galactosidase a deficient mice receiving transduced bone marrow cells. SO BLOOD LA English DT Meeting Abstract C1 NINDS, DMNB, NIH, Bethesda, MD 20892 USA. Univ Illinois, Sect Hem Onc, Chicago, IL USA. NIDCR, NIH, Bethesda, MD USA. Kagoshima Univ, Dept Internal Med 1, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2853 BP 642A EP 642A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302902 ER PT J AU Kang, KM Hanazano, Y Vanin, EF Metzger, M Donahue, R Liu, J Tisdale, JF AF Kang, KM Hanazano, Y Vanin, EF Metzger, M Donahue, R Liu, J Tisdale, JF TI Persistent low level marking following non-myeloablative transplantation of rhesus PBSCS transduced with a retroviral vector carrying the Fanconi anemia C gene. SO BLOOD LA English DT Meeting Abstract C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. Jichi Med Sch, Minami Kawachi, Tochigi, Japan. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Div Exp Hematol, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2854 BP 643A EP 643A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302903 ER PT J AU Nakamura, R Huhn, RD Read, EJ Rick, M Leitman, SF Greene, A Gratwohl, A Young, NS Barrett, AJ Dunbar, CE AF Nakamura, R Huhn, RD Read, EJ Rick, M Leitman, SF Greene, A Gratwohl, A Young, NS Barrett, AJ Dunbar, CE TI Intensive immunosuppression with high-dose cyclophosphamide and autologous CD34+selected hematopoietic cell support for chronic refractory autoimmune thrombocytopenia (AITP): Interim report. SO BLOOD LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. GD Searle & Co, Clin Res Oncol, Skokie, IL 60077 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. Univ Basel, Basel, Switzerland. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2869 BP 646A EP 646A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302918 ER PT J AU Tamura, T Kuwata, T Nagamura-Inoue, T Contursi, C Ozato, K AF Tamura, T Kuwata, T Nagamura-Inoue, T Contursi, C Ozato, K TI Macrophage differentiation by a transcription factor interferon consensus sequence binding protein (ICSBP). SO BLOOD LA English DT Meeting Abstract C1 NIH, Lab Mol Growth Regulat, NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2894 BP 652A EP 652A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302943 ER PT J AU Barrette, S Douglas, J Seidel, NE Miller, AD Bodine, DM AF Barrette, S Douglas, J Seidel, NE Miller, AD Bodine, DM TI Comparative transduction of mouse HSC with lentivirus or murine Moloney leukemia virus (MMLV)vectors pseudotyped with VSV-G, amphotropic or 10A1 envelope reveals superior transduction with 10A1 pseudotyped vectors and identical transduction frequencies with MMLV and lentivirus vectors. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, GMBB, NIH, Bethesda, MD USA. Systemix Inc, Palo Alto, CA USA. FHCRC, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2971 BP 670A EP 670A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303020 ER PT J AU Schmidt, M Zickler, P Glimm, H Wu, T Tisdale, J Kim, HJ Dunbar, CE von Kalle, C AF Schmidt, M Zickler, P Glimm, H Wu, T Tisdale, J Kim, HJ Dunbar, CE von Kalle, C TI Peripheral blood integration site analysis in a rhesus macaque model of highly efficient retroviral ex vivo transduction of hematopoietic repopulating cells. SO BLOOD LA English DT Meeting Abstract C1 Univ Freiburg, Freiburg, Germany. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIDDK, MCHB, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2974 BP 671A EP 671A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303023 ER PT J AU Sabatino, DE Gallagher, PG Garrett, LJ Cline, AP Bodine, DM AF Sabatino, DE Gallagher, PG Garrett, LJ Cline, AP Bodine, DM TI An ankyrin promoter linked to a human gamma globin gene demonstrates erythroid specific expression in a copy number dependent manner with minimal position or enhancer dependence in transgenic mice. SO BLOOD LA English DT Meeting Abstract C1 NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, Bethesda, MD USA. Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2980 BP 672A EP 672A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303029 ER PT J AU Brummendorf, TH Maciejewski, JP Mak, J Young, NS Lansdorp, PM AF Brummendorf, TH Maciejewski, JP Mak, J Young, NS Lansdorp, PM TI Telomere length in blood cells of bone marrow failure patients. SO BLOOD LA English DT Meeting Abstract C1 British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2984 BP 673A EP 673A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303033 ER PT J AU Gallagher, PG Sabatino, DE Boulanger, L Garbarz, M Dhermy, D Forget, BG Bodine, DM AF Gallagher, PG Sabatino, DE Boulanger, L Garbarz, M Dhermy, D Forget, BG Bodine, DM TI Promoter and enhancer elements are required for expression of the human alpha-spectrin gene in vivo. SO BLOOD LA English DT Meeting Abstract C1 Yale Univ, Sch Med, New Haven, CT USA. NIH, NHGRI, Bethesda, MD 20892 USA. INSERM U409, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2982 BP 673A EP 673A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303031 ER PT J AU Kearns, WG Liu, J Aridgides, L Stacey, MW Osgood, C Byrd, RL Saunthararajah, Y Maciejewski, JP Saunthararajah, Y Young, NS AF Kearns, WG Liu, J Aridgides, L Stacey, MW Osgood, C Byrd, RL Saunthararajah, Y Maciejewski, JP Saunthararajah, Y Young, NS TI Genomic instability in bone marrow failure syndromes: High frequency of aneuploidy by fluorescence in situ hybridization and identification of a spindle checkpoint gene mutation. SO BLOOD LA English DT Meeting Abstract C1 Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA 23501 USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2986 BP 674A EP 674A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303035 ER PT J AU Stacey, MW Mcaninch, T Santi, L Clarey, MC Osgood, C Byrd, RL Liu, JM Young, NS Kearns, WG AF Stacey, MW Mcaninch, T Santi, L Clarey, MC Osgood, C Byrd, RL Liu, JM Young, NS Kearns, WG TI Glutathione-S transferase (GSTT1 and GSTM1) null genotypes in patients with aplastic anemia and myelodysplastic syndromes. SO BLOOD LA English DT Meeting Abstract C1 Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA 23501 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2990 BP 675A EP 675A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303039 ER PT J AU Foster, CB Choi, EH Zhu, S Lehrnbecher, T Imbach, P Kuhne, T Chanock, SJ AF Foster, CB Choi, EH Zhu, S Lehrnbecher, T Imbach, P Kuhne, T Chanock, SJ TI Polymorphisms within inflammatory cytokines and Fc gamma receptors are associated with chronic immune thrombocytopenia purpura. SO BLOOD LA English DT Meeting Abstract C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Basel, Childrens Hosp, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3009 BP 679A EP 679A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303058 ER PT J AU Cline, AP Orlic, D Seidel, NE Anderson, SM Garrett, LJ Bodine, DM AF Cline, AP Orlic, D Seidel, NE Anderson, SM Garrett, LJ Bodine, DM TI The mRNA encoding HMG-4, a chromatin binding protein, is specifically expressed in hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract C1 NIH, GMBB, NHGRI, Bethesda, MD 20892 USA. NIH, GDRB, NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3020 BP 682A EP 682A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303069 ER EF