FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Neumann, E McCloskey, MS Felio, AC AF Neumann, E McCloskey, MS Felio, AC TI Cross-language positive priming disappears, negative priming does not: Evidence for two sources of selective inhibition SO MEMORY & COGNITION LA English DT Article; Proceedings Paper CT 3rd Practical Aspects of Memory Conference CY JUL 31-AUG 05, 1994 CL UNIV MARYLAND, COLLEGE PK, MARYLAND HO UNIV MARYLAND ID LEXICAL DECISION TASK; ATTENTION; MECHANISMS; BILINGUALS; REPETITION; ACTIVATION; RETRIEVAL; MEMORY; PERSISTENCE; DEPENDS AB The authors used a unilingual and bilingual primed lexical decision task to investigate priming effects produced by attended and ignored words. In the unilingual experiment, accelerated lexical decisions to probe target words resulted when the word matched the preceding target word, whereas slowed lexical decisions to probe target words resulted when the word matched the preceding ignored nontarget word. In the bilingual (English-Spanish) experiment, between-language, rather than within-language, priming manipulations were used. Although the ignored repetition negative priming effect replicated across languages, cross-language attended repetition positive priming did not. This dissociation of priming effects in the inter versus intralanguage priming conditions contradicts episodic retrieval accounts of negative priming that deny the existence of selective inhibitory processes. On the other hand, these results support an extension of inhibition-based accounts of negative priming, because they indicate that inhibition can operate at two levels of abstraction-local word and global language-simultaneously. C1 NIMH, Bethesda, MD 20892 USA. Univ So Mississippi, Hattiesburg, MS 39406 USA. Tufts Univ, Medford, MA 02155 USA. RP Neumann, E (reprint author), Univ Canterbury, Dept Psychol, Private Bag 4800, Christchurch 1, New Zealand. NR 61 TC 15 Z9 15 U1 6 U2 13 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0090-502X J9 MEM COGNITION JI Mem. Cogn. PD NOV PY 1999 VL 27 IS 6 BP 1051 EP 1063 DI 10.3758/BF03201234 PG 13 WC Psychology, Experimental SC Psychology GA 256VL UT WOS:000083747100011 PM 10586580 ER PT J AU O'Connor, KG Harman, SM Stevens, TE Jayme, JJ Bellantoni, MF Busby-Whitehead, MJ Christmas, C Munzer, T Tobin, JD Roy, TA Cottrell, E St Clair, C Pabst, KM Blackman, MR AF O'Connor, KG Harman, SM Stevens, TE Jayme, JJ Bellantoni, MF Busby-Whitehead, MJ Christmas, C Munzer, T Tobin, JD Roy, TA Cottrell, E St Clair, C Pabst, KM Blackman, MR TI Interrelationships of spontaneous growth hormone axis activity, body fat, and serum lipids in healthy elderly women and men SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY HEART-DISEASE; FACTOR-I; DEFICIENT ADULTS; INSULIN SENSITIVITY; RISK-FACTORS; PLASMA; AGE; METABOLISM; MORTALITY AB Aging is associated with decreased growth hormone (GH) secretion and plasma Insulin-like growth factor-I (IGF-I) levels, increased total and abdominal fat, total and low-density lipoprotein (LDL) cholesterol, and triglycerides, and reduced high-density lipoprotein (HDL) cholesterol. Similar changes in lipids and body composition occur in nonelderly GH-deficient adults and are reversed with GH administration. To examine whether GH/IGF-I axis function in the elderly is related to the lipid profile independently of body fat,we evaluated GH secretion, serum IGF-I and IGF binding protein-3 (IGFBP-3) levers, adiposity via the body mass index (BMI), waist to hip ratio (WHR), dual-energy x-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI), and circulating lipids in 101 healthy subjects older than 65 years. Integrated nocturnal GH secretion (log IAUPGH) was inversely related (P < .005) to DEXA total and abdominal fat and MRI visceral fat in both genders. Log IAUPGH was inversely related to visceral fat in women (P < .005) and men (P < .0001), hut was not significantly related to total far in either gender. In women, log IAUPGH was related inversely to total and LDL cholesterol and positively to HDL cholesterol (P < .008). In men, log IAUPGH was inversely related to total cholesterol and triglycerides (P < .005). In women, HDL cholesterol was inversely related to the WHR (P < .005). In men, triglycerides were positively related (P < .001) to the WHR and DEXA abdominal and MRI visceral fat. Multivariate regression revealed log IAUPGH, but not DEXA total body fat, to be an independent determinant of total (P < .001 for women and P = .01 for men) and LDL (P < .007 and P = .05) cholesterol in both sexes and of HDL cholesterol (P <.005) and triglycerides (P < .03) in women. Log IAUPGH, but not: DEXA abdominal fat, was related to total (P < .005 and P < .03) and LDL (P < .03 and P = .05) cholesterol in both genders and to HDL in women (P < .05). Log IAUPGH, bat not MRI visceral fat, was related to total cholesterol (P < .03 and P = .05) in women and men. Age, IGF-I, and IGFBP-3 were not significantly related to any body fat or lipid measures, except for a positive correlation of IGF-I with triglycerides in men. Thus, endogenous nocturnal GH secretion predicts total, LDL, and HDL cholesterol levels independently of total or abdominal fat, suggesting that his an independent cardiometabolic risk factor in healthy elderly people. Copyright (C) 1999 by W.B. Saunders Company. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIA, Gerontol Res Ctr, Endocrine Sect, NIH, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Appl Phys Sect, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Med, Div Geriatr Med, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Med, Div Gerontol, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Med, Div Metab, Baltimore, MD 21224 USA. RP Blackman, MR (reprint author), Johns Hopkins Bayview Med Ctr, Dept Med, Div Geriatr Med, Baltimore, MD 21224 USA. OI Bellantoni, Michele/0000-0001-8525-2247 FU NCRR NIH HHS [MO-1-RR02719]; NIA NIH HHS [R0-1-AG11005] NR 39 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1999 VL 48 IS 11 BP 1424 EP 1431 DI 10.1016/S0026-0495(99)90154-3 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 256VM UT WOS:000083747200016 PM 10582552 ER PT J AU Baumann, CT Reyes, JC AF Baumann, CT Reyes, JC TI Tracking components of the transcription apparatus in living cells SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; NUCLEAR-LOCALIZATION SIGNALS; MOUSE SATELLITE DNA; C-TERMINAL DOMAIN; IN-VIVO; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID RECEPTOR; PROGESTERONE-RECEPTOR; MEMBRANE-PROTEIN; GENE-EXPRESSION AB Transcription regulatory proteins are an integral component of the cell nucleus and a great deal of work has been done to characterize the subnuclear distribution of these proteins. Much of the early work on this subject was done with immunofluorescence. The development of the green fluorescent protein (GFP) as a marker for intracellular protein localization has allowed for the real time study of protein localization and dynamics in living cells. In this review, an overview of the way in which GFP can be utilized to study protein localization is presented. (C) 1999 Academic Press. C1 Ctr Invest Cient, Inst Bioquim Vegetal & Fotosintesis, Seville 41092, Spain. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Reyes, JC (reprint author), Ctr Invest Cient, Inst Bioquim Vegetal & Fotosintesis, Seville 41092, Spain. RI Reyes, Jose/K-3699-2014 OI Reyes, Jose/0000-0002-8042-5142 NR 68 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 1999 VL 19 IS 3 BP 353 EP 361 DI 10.1006/meth.1999.0871 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264EU UT WOS:000084168300002 PM 10579930 ER PT J AU Ellenberg, J Lippincott-Schwartz, J AF Ellenberg, J Lippincott-Schwartz, J TI Dynamics and mobility of nuclear envelope proteins in interphase and mitotic cells revealed by green fluorescent protein chimeras SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID LAMIN-B-RECEPTOR; INTEGRAL MEMBRANE-PROTEIN; LIVING CELLS; MITOSIS; CHROMATIN; BINDING; PHOSPHORYLATION; ORGANELLES; TRANSPORT; VESICLES AB Understanding how membrane proteins are targeted to and retained within the nuclear envelope (NE) and the fate of these proteins during NE disassembly/reassembly in mitosis is central for insight into the function of the NE in nuclear organization and dynamics. To address these issues we have attached green fluorescent protein (GFP) to a well-characterized protein of the inner nuclear membrane, lamin B receptor, believed to be one of the major chromatin docking protein in the NE. We have used this construct in a variety of applications, including dual-color GFP time-lapse imaging, to investigate the mechanisms underlying protein targeting to the NE and NE breakdown and reassembly during mitosis. In this review, we present a summary of the results from such studies and discuss the photobleaching and imaging methodology on which they were derived. (C) 1999 Academic Press. C1 European Mol Biol Lab, Gene Express & Cell Biol Programme, D-69117 Heidelberg, Germany. European Mol Biol Lab, Biophys Programme, D-69117 Heidelberg, Germany. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lippincott-Schwartz, J (reprint author), European Mol Biol Lab, Gene Express & Cell Biol Programme, Menehofstr 1, D-69117 Heidelberg, Germany. RI Ellenberg, Jan/I-4688-2014 OI Ellenberg, Jan/0000-0001-5909-701X NR 43 TC 44 Z9 44 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 1999 VL 19 IS 3 BP 362 EP 372 DI 10.1006/meth.1999.0872 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264EU UT WOS:000084168300003 PM 10579931 ER PT J AU McNally, JG Karpova, T Cooper, J Conchello, JA AF McNally, JG Karpova, T Cooper, J Conchello, JA TI Three-dimensional imaging by deconvolution microscopy SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID OPTICAL-SECTIONING MICROSCOPY; EXPECTATION-MAXIMIZATION ALGORITHM; MAXIMUM; IMAGES; RECONSTRUCTION; CELLS AB Deconvolution is a computational method used to reduce out-of-focus fluorescence in three-dimensional (3D) microscope images. It can be applied in principle to any type of microscope image but has most often been used to improve images from conventional fluorescence microscopes. Compared to other forms of 3D light microscopy, like confocal microscopy, the advantage of deconvolution microscopy is that it can be accomplished at very low light levels, thus enabling multiple focal-plane imaging of light-sensitive living specimens over long time periods. Here we discuss the principles of deconvolution microscopy, describe different computational approaches for deconvolution, and discuss interpretation of deconvolved images with a particular emphasis on:what artifacts may arise. (C) 1999 Academic Press. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. Washington Univ, Inst Biomed Comp, St Louis, MO 63110 USA. Washington Univ, Dept Cell Biol, St Louis, MO 63110 USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RI Cooper, John/E-9389-2012 NR 27 TC 222 Z9 232 U1 7 U2 42 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 1999 VL 19 IS 3 BP 373 EP 385 DI 10.1006/meth.1999.0873 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264EU UT WOS:000084168300004 PM 10579932 ER PT J AU Walker, D Htun, H Hager, GL AF Walker, D Htun, H Hager, GL TI Using inducible vectors to study intracellular trafficking of GFP-tagged steroid/nuclear receptors in living cells SO METHODS-A COMPANION TO METHODS IN ENZYMOLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; GENE-EXPRESSION; CHIMERA; TRANSLOCATION; TEMPLATES AB Intracellular trafficking and localization of proteins can now be efficiently visualized by fusion of a polypeptide to the green fluorescent protein (GFP). Many spectral variants of this reagent are now available, providing powerful tools for studies in living cells, This approach is particularly useful for members of the steroid/nuclear receptor superfamily, since these molecules frequently undergo rapid subcellular redistribution on ligand activation. A major roadblock in the application of this technology concerns problems associated with transient transfections. This technique produces cell populations that are highly heterogeneous with respect to the newly introduced protein and usually contain the protein in a highly overexpressed state. In addition, long-term studies related to cell cycle and cellular differentiation are essentially impossible with this approach, These problems can be overcome by introduction of the GFP fusion into cells under appropriate induction control, We describe application of the tetracycline regulatory system to inducible control of a glucocorticoid receptor (GR)/GFP chimera, Intracellular concentrations of GFP-GR can be very effectively controlled in this system, providing an ideal environment in which to study subcellular trafficking of the receptor and interactions with a variety of intracellular targets. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), Univ Calif Los Angeles, Sch Med, Dept Obstet & Gynecol, 27-139 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 20 TC 68 Z9 70 U1 2 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD NOV PY 1999 VL 19 IS 3 BP 386 EP 393 DI 10.1006/meth.1999.0874 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264EU UT WOS:000084168300005 PM 10579933 ER PT J AU Safi, J DiPaula, AF Riccioni, T Kajstura, J Ambrosio, G Becker, LC Anversa, P Capogrossi, MC AF Safi, J DiPaula, AF Riccioni, T Kajstura, J Ambrosio, G Becker, LC Anversa, P Capogrossi, MC TI Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart SO MICROVASCULAR RESEARCH LA English DT Article DE adenovirus; aFGF; angiogenesis; collateral circulation; gene therapy ID MYOCARDIAL BLOOD-FLOW; IN-VIVO; REPLICATION-DEFICIENT; COLLATERAL FLOW; PORCINE HEART; INFARCT SIZE; VECTORS; PROSTACYCLIN; DYSFUNCTION; PERFUSION AB Most patients with severe coronary artery disease have normal baseline myocardial blood now. Therefore, interventions aimed at inducing therapeutic angiogenesis in these patients should cause new blood vessel growth in the heart in the absence of chronic ischemia. It was examined whether adenovirus-mediated gene transfer of recombinant, secreted acidic fibroblast growth factor (sp+aFGF(1-154)), next to a major epicardial artery, may induce neovascularization and reduce the risk region for myocardial infarction upon coronary ligation near the injection site. Fifteen days prior to coronary artery occlusion, rabbits were treated with intramyocardial injections of AdCMV.sp + aFGF(1-154), the control vector AdCMV.NLS beta gal (1 x 10(9) plaque-forming units), or saline. Messenger RNA transcripts for aFGF(1-154) were present up to 12 days after injection in the tissues exposed to AdCMV.aFGF(1-154). Following coronary artery occlusion rabbits treated with AdCMV.sp+aFGF(1-154) showed a 50% reduction of the risk region for myocardial infarction (P < 0.01 vs control). Histologic analysis showed a twofold increase in length density of intramural coronary arterioles (P < 0.01 vs control) and a 17% increase in length density of the capillary network (P < 0.001) in the myocardium exposed to AdCMV.sp+aFGF(1-154). Thus, gene therapy with AdCMV.sp+aFGF(1-154) can induce angiogenesis in the absence of chronic ischemia. The newly formed collateral blood vessels provide an anatomical basis for the reduction in the risk region for myocardial infarction upon subsequent occlusion of the coronary artery in proximity of the site where angiogenesis was induced. (C) 1999 Academic Press. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Gene Therapy Unit,NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Div Cardiol, Baltimore, MD 21287 USA. New York Med Coll, Cardiovasc Res Inst, Valhalla, NY 10595 USA. Ist Ricovero & Cura Carattere Sci, Ist Dermopat Immacolata, Lab Patol Vascolare, Rome, Italy. Univ Perugia, Div Cardiol, I-06100 Perugia, Italy. RP Safi, J (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Gene Therapy Unit,NIH, Baltimore, MD 21224 USA. NR 28 TC 46 Z9 54 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 1999 VL 58 IS 3 BP 238 EP 249 DI 10.1006/mvre.1999.2165 PG 12 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 255AV UT WOS:000083648100004 PM 10527767 ER PT J AU Wang, C Youssef, J Saran, B Rothberg, PG Cunningham, ML Molteni, A Badr, M AF Wang, C Youssef, J Saran, B Rothberg, PG Cunningham, ML Molteni, A Badr, M TI Diminished energy metabolism and enhanced apoptosis in livers of B6C3F1 mice treated with the antihepatocarcinogen rotenone SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE rotenone; apoptosis; oncogenes; liver cancer ID C-MYC ONCOGENE; RAT-LIVER; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; EXPRESSION; P53; CARCINOGENESIS; MECHANISM; CELLS; PHOSPHORYLATION; PROLIFERATION AB Rotenone decreases the incidence of hepatocellular carcinoma and lowers rates of hepatocellular proliferation. In an effort to delineate mechanisms involved, the in vivo effect of rotenone on liver mitochondrial metabolism, apoptotic machinery as well as elements of the hepatic signal transduction pathways were investigated. Mitochondria from livers of male B6C3F1 mice fed a standard diet containing 600 ppm rotenone for 7 days were uncoupled or inhibited when succinate or glutamate plus malate were used as the substrate, respectively. These livers also showed a significant increase in apoptosis compared with control livers. Furthermore, rotenone increased the expression of c-myc mRNA to 5-fold of control values within 3 days, an effect which was still observed (3-fold) after 7 days. Levels of p53 mRNA were also increased 3-fold after 1 day, but declined to control levels by 7 days. Rotenone also caused a transient, yet marked increase in liver particulate glyceraldehyde phosphate dehydrogenase (GAPDH) protein expression, while it did not alter the expression of the cytosolic form of the enzyme. Conversely, mRNA of the proto-oncogene H-ras showed a decline of 35% after 3 days of rotenone treatment, and remained diminished for the duration of the experiment. These data suggest that rotenone may act as an anticancer agent by diminishing mitochondrial bioenergetics which prevents basal hepatocyte proliferation and lowers the threshold for liver cells with DNA damage to undergo apoptosis. C1 Univ Missouri, Kansas City, MO 64108 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Badr, M (reprint author), Univ Missouri, 2411 Holmes St, Kansas City, MO 64108 USA. FU NCI NIH HHS [CA/OD 74384] NR 38 TC 5 Z9 5 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 1999 VL 201 IS 1-2 BP 25 EP 32 DI 10.1023/A:1007024905046 PG 8 WC Cell Biology SC Cell Biology GA 256GJ UT WOS:000083717300004 PM 10630619 ER PT J AU McDowell, JC Dean, A AF McDowell, JC Dean, A TI Structural and functional cross-talk between a distant enhancer and the epsilon-globin gene promoter shows interdependence of the two elements in chromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LOCUS-CONTROL REGION; TRANSCRIPTION FACTOR GATA-1; HUMAN ALPHA-GLOBIN; RNA-POLYMERASE-II; BINDING PROTEIN; IN-VIVO; HYPERSENSITIVE SITE; ACTIVATION DOMAIN; TRANSGENIC MICE; NUCLEOSOMAL DNA AB We investigated the requirements for enhancer-promoter communication by using the human P-globin locus control region (LCR) DNase I-hypersensitive site 2 (HS2) enhancer and the E-globin gene in chromatinized minichromosomes in erythroid cells. Activation of globin genes during development is accompanied by localized alterations of chromatin structure, and CACCC binding factors and GATA-1, which interact with both globin promoters and the LCR, are believed to be critical for globin gene transcription activation. We found that an HS2 element mutated in its GATA motif failed to remodel the E-globin promoter or activate transcription yet HS2 nuclcase accessibility did not change. Accessibility and transcription were reduced at promoters with mutated GATA-1 or CACCC sites. Strikingly, these mutations also resulted in reduced accessibility at HS2. In the absence of a globin gene, HS2 is similarly resistant to nuclease digestion. In contrast to observations in Saccharomyces cerevisiae, HS2-dependent promoter remodeling was diminished when we mutated the TATA box, crippling transcription, This mutation also reduced HS2 accessibility. The results indicate that the epsilon-globin promoter and HS2 interact both structurally and functionally and that both upstream activators and the basal transcription apparatus contribute to the interaction. Further, at least in this instance, transcription activation and promoter remodeling by a distant enhancer are not separable. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Dean, A (reprint author), Bldg 6,Room B1-08,6 Ctr Dr,MSC 2715, Bethesda, MD 20892 USA. NR 64 TC 20 Z9 20 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 NOV PY 1999 VL 19 IS 11 BP 7600 EP 7609 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 247CM UT WOS:000083203100031 PM 10523648 ER PT J AU Ptitsyn, OB Finkelstein, AV Dobson, CM AF Ptitsyn, OB Finkelstein, AV Dobson, CM TI Protein folding: A bridge between physics and biology SO MOLECULAR BIOLOGY LA English DT Article DE protein folding; protein structure; amino acid sequence; physical processes; evolutionary selection ID SEQUENCES; MOLECULES; CHAINS; MODEL AB Protein folding represents a bridge between the laws of physics and the results of the evolutionary pressure under which the character of biology has developed. Biological evolution selects only those sequences that fold into well-defined three-dimensional structures. The selected sequences appear to meet the requirement of forming stable three-dimensional structures simultaneously with the requirement of folding quickly. This review presents the modern view of folding across a broad compass of physical and biological phenomena. C1 Russian Acad Sci, Inst Prot Res, Pushchino 142292, Moscow Region, Russia. NCI, Lab Expt & Computat Biol, Mol Struct Sect, Bethesda, MD 20892 USA. Univ Oxford, New Chem Lab, Oxford Ctr Mol Sci, Oxford OX1 3QT, England. RI Finkelstein, Alexey/M-1440-2015 OI Finkelstein, Alexey/0000-0002-2138-4803 NR 25 TC 3 Z9 3 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA CONSULTANTS BUREAU, 233 SPRING ST, NEW YORK, NY 10013 USA SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD NOV-DEC PY 1999 VL 33 IS 6 BP 893 EP 896 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264CT UT WOS:000084163300007 ER PT J AU Pankov, R Cukierman, E Katz, BZ Matsumoto, K Lin, DC Lin, S Hahn, C Yamada, KM AF Pankov, R Cukierman, E Katz, BZ Matsumoto, K Lin, DC Lin, S Hahn, C Yamada, KM TI Integrin dynamics and matrix assembly: Actin- and tensin-induced translocation of alpha(5)beta, integrins drives early fibronectin fibrillogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 19 BP 4A EP 4A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500021 ER PT J AU Zhang, P Hinshaw, JE AF Zhang, P Hinshaw, JE TI Structural studies of dynamin tubular crystals by cryo-electron microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 26 BP 5A EP 5A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500025 ER PT J AU Jung, G Wu, X Hammer, JA AF Jung, G Wu, X Hammer, JA TI Myosin I, Arp2/3, CapZ and a 116 kDa leucine-rich repeat (LRR) protein are present in a complex critical for the formation of actin-rich extensions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 29 BP 6A EP 6A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500032 ER PT J AU Steinert, PM Wu, KC Parry, DAD Morasso, MI Bryan, JT AF Steinert, PM Wu, KC Parry, DAD Morasso, MI Bryan, JT TI A conserved set of ionic residues is required for intermediate filament assembly. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 68 BP 12A EP 12A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500069 ER PT J AU Herrmann, H Strelkov, S Feja, B Rogers, KR Brettel, M Lustig, A Haner, M Parry, DAD Steinert, PM Burkhard, P Aebi, U AF Herrmann, H Strelkov, S Feja, B Rogers, KR Brettel, M Lustig, A Haner, M Parry, DAD Steinert, PM Burkhard, P Aebi, U TI The intermediate filament protein consensus motif of helix 2B: Atomic structure and contribution to assembly. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 German Canc Res Ctr, D-69120 Heidelberg, Germany. Univ Basel, Biozentrum, CH-4003 Basel, Switzerland. Massey Univ, Palmerston North, New Zealand. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 69 BP 13A EP 13A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500070 ER PT J AU Strelkov, SV Herrmann, H Geisler, N Steinert, PM Aebi, U Burkhard, P AF Strelkov, SV Herrmann, H Geisler, N Steinert, PM Aebi, U Burkhard, P TI Toward an atomic model of intermediate filament (IF) architecture. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Basel, Biozentrum, ME Mueller Inst, CH-4003 Basel, Switzerland. Max Planck Inst Biophys Chem, Gottingen, Germany. NIH, Bethesda, MD 20892 USA. Biozentrum, ME Mueller Inst, CH-4056 Basel, Switzerland. RI Strelkov, Sergei/G-7425-2014 NR 0 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 71 BP 13A EP 13A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500071 ER PT J AU Resau, JH Dambach, M Jones, A Sathyanarayana, BK Alstock, R Tsarfaty, H AF Resau, JH Dambach, M Jones, A Sathyanarayana, BK Alstock, R Tsarfaty, H TI Method for the invitro quantification of scattering SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Van Andel Inst, Grand Rapids, MI 49503 USA. NCI, Frederick Canc Res & Dev Ctr, ABL, Bethesda, MD 20892 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 175 BP 30A EP 30A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500176 ER PT J AU Shu, S Liu, X Korn, ED AF Shu, S Liu, X Korn, ED TI Effect of substitution of the Acanthamoeba myosin II rod for the Dictyostelium myosin II rod SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 191 BP 33A EP 33A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500193 ER PT J AU Takeda, K Yu, ZX Qian, SJ Chin, TK Adelstein, RS Ferrans, VJ AF Takeda, K Yu, ZX Qian, SJ Chin, TK Adelstein, RS Ferrans, VJ TI Localization of nonmuscle myosin II-B in the Z-line, of cardiac and skeletal muscle cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. E Tennessee State Univ, Johnson City, TN 37614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 189 BP 33A EP 33A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500192 ER PT J AU Wei, Q Adelstein, RS AF Wei, Q Adelstein, RS TI Nonmuscle myosin II-A is involved in the maintenance of cell morphology. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 190 BP 33A EP 33A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500190 ER PT J AU McKee, ML Fitzgerald, DJ AF McKee, ML Fitzgerald, DJ TI Interaction of pseudomonas exotoxin a with epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 209 BP 36A EP 36A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500211 ER PT J AU Sieczkiewicz, GJ Sachs, Z Wakefield, LM Roberts, AB Herman, IM AF Sieczkiewicz, GJ Sachs, Z Wakefield, LM Roberts, AB Herman, IM TI TGF-beta 1 signaling controls pericyte contractile phenotype SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 217 BP 38A EP 38A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500218 ER PT J AU Zhou, YX Xu, X Chen, L Li, C Deng, CX AF Zhou, YX Xu, X Chen, L Li, C Deng, CX TI A proline to arginine substitution at codon 252 (pro252arg) in fibroblast growth factor receptor 1 (FGFRI) promoter premature intramembranous ossification and results in Pfeiffer syndrome. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 230 BP 40A EP 40A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500230 ER PT J AU Yu, C Wang, F Kan, M Jin, C Jones, RB Weinstein, M Deng, CX McKeehan, WL AF Yu, C Wang, F Kan, M Jin, C Jones, RB Weinstein, M Deng, CX McKeehan, WL TI Elevation of cholesterol and bile acid metabolism in mice larking membrane tyrosine kinase receptor FGFR4 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 239 BP 41A EP 41A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500240 ER PT J AU Chen, L Xu, X Yang, X Li, C Deng, C AF Chen, L Xu, X Yang, X Li, C Deng, C TI Ser365Cys mutation in mouse fibroblast growth factor receptor (FGFR)-3, which corresponds to human thanatophoric dysplasia I mutation, causes severe dwarfism SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 241 BP 42A EP 42A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500244 ER PT J AU Rabinovitz, M AF Rabinovitz, M TI Inhibition of phosphofructokinase by uncharged trna of amino acid deficiency: A unifying theory encompassing metabolic and cell cycle control SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 251 BP 43A EP 43A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500252 ER PT J AU Tan, SH Azuma, Y Cavenagh, M Saitoh, H Dasso, M AF Tan, SH Azuma, Y Cavenagh, M Saitoh, H Dasso, M TI Characterization of the vertebrate SUMO-1 AcTIVATING enzyme. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Picower Inst Med Res, Manhasset, NY 11030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 266 BP 46A EP 46A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500266 ER PT J AU Carter, CD Liu, ET AF Carter, CD Liu, ET TI The non-receptor tyrosine kinase, Rak, is located at the centrosome in a variety of epithelial cell liner. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Gaithersburg, MD 20877 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 304 BP 52A EP 52A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500305 ER PT J AU Metzger, H Torigoe, C AF Metzger, H Torigoe, C TI Size of receptor aggregates, the cytoskeleton and signal transduction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 303 BP 52A EP 52A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500302 ER PT J AU Kim, SY Park, GT Steinert, PM AF Kim, SY Park, GT Steinert, PM TI Transglutaminases are involved in the cen attachment by association with adhesion molecules in NIH3T3 fibroblasts. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 373 BP 64A EP 64A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500374 ER PT J AU Park, GT Kim, SY Steinert, PM AF Park, GT Kim, SY Steinert, PM TI Antisense probes of transglutaminase 1 and 2 reduce adhesion and spreading of NIH3T3 fibroblasts. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 372 BP 64A EP 64A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500371 ER PT J AU George, MD Roberts, JD Akiyama, SK Olden, K AF George, MD Roberts, JD Akiyama, SK Olden, K TI Alterations in cytoskeleton and morphology of human breast carcinoma cells in response to arachidonic acid SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 1999 VL 10 SU S MA 376 BP 65A EP 65A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500376 ER PT J AU Engbring, JA Kleinman, HK AF Engbring, JA Kleinman, HK TI Homologous peptides from the five laminin a chains vary in their biological effects on B16-F10 melanoma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 399 BP 69A EP 69A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500399 ER PT J AU Nielsen, PK Gho, YS Kleinman, HK Yamada, Y AF Nielsen, PK Gho, YS Kleinman, HK Yamada, Y TI Identification of cell and heparin binding domains in the laminin alpha 5 chain SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 401 BP 69A EP 69A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500400 ER PT J AU Damjanovski, S Shi, YB AF Damjanovski, S Shi, YB TI Contrasting expression profiles for collagenase-3,-4, and stromelysin-3 implicates distinct functions during Xenopus development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI Damjanovski, Sashko/N-8728-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 422 BP 73A EP 73A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500422 ER PT J AU Kim, SG Khiem, D Nelson, PG AF Kim, SG Khiem, D Nelson, PG TI Carbachol activates protein kinase C-alpha in primary mouse myotubes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, LDN, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 443 BP 76A EP 76A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500444 ER PT J AU Weng, BY Thompson, WC Kim, HJ Levine, RL Moss, J AF Weng, BY Thompson, WC Kim, HJ Levine, RL Moss, J TI Modification of the ADP-ribosyltransferase and NAD glycohydrolase activities of a mammalian transferase (ARTS) by auto-ADP-ribosylation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 469 BP 81A EP 81A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500469 ER PT J AU Greener, T Grant, B Greene, LE Hirsh, D Eisenberg, E AF Greener, T Grant, B Greene, LE Hirsh, D Eisenberg, E TI C-elegans auxilin is an essential protein required for the uncoating of clathrin-coated vesicles in vitro and clathrin-mediated endocytosis in vivo. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, LCB, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 473 BP 82A EP 82A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500476 ER PT J AU Kaushal, S Rajapandi, T Greener, T Eisenberg, E Greene, L AF Kaushal, S Rajapandi, T Greener, T Eisenberg, E Greene, L TI The DnaJ homolog auxilin induces two Hsp70 mutants with very low ATPase activity to bind to clathrin baskets SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 475 BP 82A EP 82A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500477 ER PT J AU Ma, YC Greener, T Eisenberg, E Greene, LE AF Ma, YC Greener, T Eisenberg, E Greene, LE TI A chimera constructed from the AP180 clathrin binding domain and the auxilin DNAJ domain supports clathrin uncoating by Hsc70 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, LCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 474 BP 82A EP 82A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500474 ER PT J AU Brown, FD Balla, T Donaldson, JG AF Brown, FD Balla, T Donaldson, JG TI Phosphatidylinositol-4,5-bisphosphate, is present on a subset of the Arf6-regulated plasma membrane recycling pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 484 BP 84A EP 84A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500487 ER PT J AU Miki, K Eddy, EM AF Miki, K Eddy, EM TI Consensus sequence on A-kinase anchoring proteins that determiner isozyme-specific binding for protein kinase A. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 516 BP 89A EP 89A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500517 ER PT J AU Ghedin, E Debrabant, A Engel, J Dwyer, D AF Ghedin, E Debrabant, A Engel, J Dwyer, D TI Trafficking of a GFP chimera in Leishmania is differentially regulated by a GPI-anchored carbohydrate SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, CBER, Rockville, MD 20857 USA. UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 517 BP 90A EP 90A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500518 ER PT J AU Tang, JR Manganiello, VC AF Tang, JR Manganiello, VC TI Identification of promoter regions in the 5'-Flanking region of the mouse adipocyte phosphodiesterase 3B (MPDE3B) gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 530 BP 92A EP 92A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500530 ER PT J AU Yu, S Ragano-Caracciolo, M Lubas, WA Hanover, JA AF Yu, S Ragano-Caracciolo, M Lubas, WA Hanover, JA TI Mapping of the mouse gene encoding O-linked GlcNAc transferase (OCT) SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 535 BP 93A EP 93A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500538 ER PT J AU Baumann, CT Lim, C Hager, G AF Baumann, CT Lim, C Hager, G TI PML colocalizes with GRIPI and functions in glucocorticold receptor-dependent transcription. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 544 BP 94A EP 94A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500543 ER PT J AU Choi, CY Kim, YH Kim, YS AF Choi, CY Kim, YH Kim, YS TI The homeodomain transcription factor NK-3 recruits the Groucho corepressor and histone deacetylase complex to repress transcription. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 546 BP 95A EP 95A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500547 ER PT J AU Chung, MC Kim, HK Kawamoto, S AF Chung, MC Kim, HK Kawamoto, S TI The E-box binding factors TFEC, TFE3 and USF activate transcription of the nonmuscle myosin II heavy chain (MHC)-A gene. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 552 BP 96A EP 96A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500553 ER PT J AU Jang, SI Morasso, MI Rossi, A Steinert, PM AF Jang, SI Morasso, MI Rossi, A Steinert, PM TI The transcriptional control of human loricrin gene SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD USA. Univ Roma Tor Vergata, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 566 BP 98A EP 98A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500566 ER PT J AU Yan, B Raben, N Nagaraju, K Nichols, R Plotz, PH AF Yan, B Raben, N Nagaraju, K Nichols, R Plotz, PH TI Hes-l binds to an E box within intron l of the human acid alpha-glucosidase gene and acts as a transcriptional repressor SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. Dartmouth Med Sch, Hanover, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 567 BP 98A EP 98A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500569 ER PT J AU Yu, X Chin, K Noguchi, CT AF Yu, X Chin, K Noguchi, CT TI Production and processing of erythropoietin receptor transcripts in brain SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 1999 VL 10 SU S MA 576 BP 100A EP 100A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500577 ER PT J AU Corsi, AK Kostas, S Jorgensen, E Fire, A Krause, M AF Corsi, AK Kostas, S Jorgensen, E Fire, A Krause, M TI CeTwist mutants have defective non-striated muscle development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Carnegie Inst Washington, Washington, DC 20005 USA. Univ Utah, Salt Lake City, UT 84112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 588 BP 102A EP 102A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500591 ER PT J AU Rouse, NM Sachs, LM Shi, YB AF Rouse, NM Sachs, LM Shi, YB TI Nuclear receptor co-repressor (N-CoR) in thyroid hormone receptor function during amphibian development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 595 BP 103A EP 103A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500595 ER PT J AU Sachs, LM Amano, T Shi, YB AF Sachs, LM Amano, T Shi, YB TI Roles of histone deacetylase in thyroid hormone receptor function during amphibian metamorphosis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 597 BP 103A EP 103A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500596 ER PT J AU Huizing, M Boissy, RE Gahl, WA AF Huizing, M Boissy, RE Gahl, WA TI Immunofluorescent screening for defects in vesicular trafficking in different cell types of patients with Hermansky-Pudlak syndrome. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Dermatol, Cincinnati, OH 45267 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 639 BP 111A EP 111A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500642 ER PT J AU Barr, VA Haft, CR Phillips, SA Sierra, L Taylor, SL AF Barr, VA Haft, CR Phillips, SA Sierra, L Taylor, SL TI Overexpression of SNX15 disrupts endosomal compartment identity. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 651 BP 113A EP 113A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500654 ER PT J AU Phillips, SA Barr, VA Taylor, SI Haft, CR AF Phillips, SA Barr, VA Taylor, SI Haft, CR TI Identification and characterization of SNX15, a novel PX domain containing protein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 655 BP 113A EP 113A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500656 ER PT J AU Haft, CR Sierra, L Barr, VA Bafford, R Taylor, SI AF Haft, CR Sierra, L Barr, VA Bafford, R Taylor, SI TI Sorting nexins (SNX) 1 and 2: Interaction domains involved in self-association and associations with human retromer proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Tulane Univ, Sch Med, New Orleans, LA 70118 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 656 BP 114A EP 114A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500657 ER PT J AU Kenworthy, AK Lippincott-Schwartz, J AF Kenworthy, AK Lippincott-Schwartz, J TI Protein and lipid diffusional mobility in the secretory pathway: Measurements in Golgi membranes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 660 BP 114A EP 114A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500659 ER PT J AU Morrison, DK Cacace, AM McGill, C AF Morrison, DK Cacace, AM McGill, C TI Brain-specific KSR1 promotes sustained MAPK activation and neuronal differentiation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 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 NOV PY 1999 VL 10 SU S MA 681 BP 118A EP 118A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500683 ER PT J AU Szczepanowska, J Kirby, M Young, R Korn, ED Brzeska, HZ AF Szczepanowska, J Kirby, M Young, R Korn, ED Brzeska, HZ TI Transfection of HeLa and NIH 3T3 cells by the catalytic domain of Acanthamoeba myosin I heavy chain kinase (MIHCK) affects focal adhesion complexes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 762 BP 132A EP 132A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500765 ER PT J AU Basciano, PA Deacon, S Sellers, JR King-Smith, C AF Basciano, PA Deacon, S Sellers, JR King-Smith, C TI Actin-dependent pigment granule motility and retrograde movement of surface-attached microspheres in isolated retinal pigment epithelial cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 St Josephs Univ, Philadelphia, PA 19131 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 797 BP 138A EP 138A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500800 ER PT J AU Galbraith, JA Reese, TS Schlief, ML Gallant, PE AF Galbraith, JA Reese, TS Schlief, ML Gallant, PE TI Slow axonal transport of polymerized and unpolymerized cytoskeletal proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 805 BP 139A EP 139A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500807 ER PT J AU LaVail, JH Schlief, ML Breakefield, XO Reese, TS Bearer, EL AF LaVail, JH Schlief, ML Breakefield, XO Reese, TS Bearer, EL TI Retrograde axonal transport of Herpes simplex virus in squid axoplasm SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NINDS, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brown Univ, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 806 BP 139A EP 139A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500805 ER PT J AU Zambito, AM Wolff, J AF Zambito, AM Wolff, J TI Plasma membrane localization of palmitoylated tubulin. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 817 BP 141A EP 141A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500816 ER PT J AU Williams, R Shah, C Sackett, D AF Williams, R Shah, C Sackett, D TI Separation of tubulin isoforms by isoelectric focusing in immobilized pH gradient (IPG) gels. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN 37235 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 820 BP 142A EP 142A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500823 ER PT J AU Cukierman, E Pankov, R Stevens, D Katz, BZ Yamada, KM AF Cukierman, E Pankov, R Stevens, D Katz, BZ Yamada, KM TI Cell-matrix adhesions on artificial 2D substrates differ in structure and function from those on natural 3D matrices SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 4 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 NOV PY 1999 VL 10 SU S MA 840 BP 145A EP 145A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500839 ER PT J AU Jacob, K Kleinman, H AF Jacob, K Kleinman, H TI Osteonectin and prostate cancer metastasis to bone SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 844 BP 146A EP 146A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500844 ER PT J AU Ponce, L Nomizu, M Yamada, Y Kleinman, HK AF Ponce, L Nomizu, M Yamada, Y Kleinman, HK TI A laminin gamma 1 site promotes angiogenesis through the alpha 5 beta 1 and alpha V beta 3 integrins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Hokkaido Univ, Sapporo, Hokkaido 060, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 848 BP 147A EP 147A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500849 ER PT J AU Whittard, JD Akiyama, SK AF Whittard, JD Akiyama, SK TI Induction of cell-cell adhesion by integrin activation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 862 BP 149A EP 149A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500862 ER PT J AU Xu, SG Gu, J Yu, LC Lucaveche, C Reedy, M Gutierrez, G Wang, K AF Xu, SG Gu, J Yu, LC Lucaveche, C Reedy, M Gutierrez, G Wang, K TI Structure of a 1.2 mu m wide Z band of the sonic muscle of type1 male midshipman fish SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Duke Univ, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 904 BP 156A EP 156A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500906 ER PT J AU Brzeska, HZ Liu, X Deresso, G Kom, ED May, GS Yamashita, R AF Brzeska, HZ Liu, X Deresso, G Kom, ED May, GS Yamashita, R TI The essential role of aspergillus myosin I may not require actin-dependent MgATPase activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 933 BP 161A EP 161A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500935 ER PT J AU Osherov, N Yamashita, RA Mathew, J May, GS AF Osherov, N Yamashita, RA Mathew, J May, GS TI Characterization of myosin I mutants in Aspergillus nidulans. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Natl Heart & Lung Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 932 BP 161A EP 161A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500932 ER PT J AU Brzeska, HZ Young, R Kom, ED AF Brzeska, HZ Young, R Kom, ED TI Localization of the regulatory regions of Acanthamoeba myosin I heavy chain kinase (MIHCK), a PAK family member SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 936 BP 162A EP 162A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500937 ER PT J AU Veigel, C Wang, F Bartoo, ML Hammer, JA Sellers, JR Molloy, JE AF Veigel, C Wang, F Bartoo, ML Hammer, JA Sellers, JR Molloy, JE TI Optical trapping of recombinant myosin v fragments. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ York, York YO1 5DD, N Yorkshire, England. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 946 BP 163A EP 163A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500945 ER PT J AU Chen, LF Wang, F Meng, HP Corey, DP Sellers, JR AF Chen, LF Wang, F Meng, HP Corey, DP Sellers, JR TI Baculovirus-mediated expression of myosin X. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 952 BP 164A EP 164A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500951 ER PT J AU Moncman, CL Wang, K AF Moncman, CL Wang, K TI Architecture of the thin filament-Z-line junction SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Texas, Austin, TX 78712 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 970 BP 167A EP 167A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500969 ER PT J AU Sanger, JW Ayoob, JC Yeh, C Wei, Q Adelstein, RS Sanger, JM AF Sanger, JW Ayoob, JC Yeh, C Wei, Q Adelstein, RS Sanger, JM TI Study of cultured avian muscle cells transfected with a GFP plasmid encoding non muscle myosin heavy chain IIB. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. NHLBI, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 974 BP 168A EP 168A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500974 ER PT J AU Carroll, SL Horowits, R AF Carroll, SL Horowits, R TI Expression of N-RAP, a nebulin-related LIM protein, during myofibrillogenesis in cultured chick cardiomyocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 979 BP 169A EP 169A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500982 ER PT J AU Zhang, JQ Elzey, B Law, DJ Horowits, R AF Zhang, JQ Elzey, B Law, DJ Horowits, R TI Ultrastructural and biochemical localization of N-RAP at the interface between myofibrils and intercalated disks in the mouse heart SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Univ Missouri, Kansas City, MO 64110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 978 BP 169A EP 169A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500979 ER PT J AU Torgan, CE Daniels, MP AF Torgan, CE Daniels, MP TI Calcineurin effects on myosin heavy chain expression in developing cultures of primary rat skeletal muscle. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 994 BP 171A EP 171A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500995 ER PT J AU Neuhuber, B Torgan, CE Huang, DI Daniels, MP AF Neuhuber, B Torgan, CE Huang, DI Daniels, MP TI Improved transfection of primary skeletal muscle cells with non-viral transfection reagents. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1009 BP 174A EP 174A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501011 ER PT J AU Tomarev, SI Mertts, M Tanemoto, K Zinovieva, R Ahmed, F Ford, A Garfield, S Andreazzoli, E Rebbert, M AF Tomarev, SI Mertts, M Tanemoto, K Zinovieva, R Ahmed, F Ford, A Garfield, S Andreazzoli, E Rebbert, M TI Analysis of the promoter activity of the MYOC/TIGR gene and properties of the encoded protein. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1008 BP 174A EP 174A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501009 ER PT J AU Zieler, H Dvorak, JA AF Zieler, H Dvorak, JA TI Invasion of mosquito midgut cells by the malaria parasite: live observations by video microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1044 BP 180A EP 180A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501044 ER PT J AU Hackstadt, T Scidmore-Carlson, M Dooley, C AF Hackstadt, T Scidmore-Carlson, M Dooley, C TI A Chlamydia trachomatis inclusion membrane protein required for intracellular development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, NIH, Hamilton, MT 59840 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1055 BP 182A EP 182A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501057 ER PT J AU Yamage, M Bates, P Rogers, M Dwyer, D Shakarian, A AF Yamage, M Bates, P Rogers, M Dwyer, D Shakarian, A TI Molecular cloning and characterization of a gene encoding the Leishmania mexicana chitinase SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1059 BP 183A EP 183A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501062 ER PT J AU Saxinger, C Ifon, E Robert, Z AF Saxinger, C Ifon, E Robert, Z TI Identification of new peptide targets for intervention at the cytokine and HIV receptor levels SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1063 BP 184A EP 184A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501064 ER PT J AU Trinh, DP Brown, KM Jeang, KT AF Trinh, DP Brown, KM Jeang, KT TI HIV-1 and HIV-2 Tat proteins bind epithelin/granulin growth factors: Possible cofactors for extracellular Tat function. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 George Washington Univ, Washington, DC 20052 USA. NIAID, NIH, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1064 BP 184A EP 184A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501067 ER PT J AU Wallace, W Luo, JJ Wallace, M Hawver, D Kusiak, J AF Wallace, W Luo, JJ Wallace, M Hawver, D Kusiak, J TI A truncated form of secreted amyloid precursor protein induces apoptosis of neurons. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1084 BP 187A EP 187A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501086 ER PT J AU Derby, MA Tse, R Berzofsky, JA AF Derby, MA Tse, R Berzofsky, JA TI Antigen-induced cell death in CD8+ CTL: A tandem TCR/TNFR2 signal initiates catastrophic apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1101 BP 190A EP 190A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501101 ER PT J AU Du, YB Liao, XB Morse, HC AF Du, YB Liao, XB Morse, HC TI Domains of Evi5 when expressed alone co-localized with annulate lamellae and the centrosome SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1119 BP 193A EP 193A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501121 ER PT J AU Ainsztein, AM Dasso, M AF Ainsztein, AM Dasso, M TI RanBP1 blocks the cell cycle in M-phase. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1125 BP 194A EP 194A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501127 ER PT J AU Fields, DD Fields, MC Fields, RD AF Fields, DD Fields, MC Fields, RD TI Variation in the thigmomorphogenic response among sorghum, allium, and arabidopsis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Sidwell Friends Sch, Washington, DC 20016 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 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 NOV PY 1999 VL 10 SU S MA 1173 BP 202A EP 202A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501172 ER PT J AU Shum, L Nonaka, K Dashner, R Price, J Takahashi, K Ikura, T Slavkin, HC Nuckolls, GH AF Shum, L Nonaka, K Dashner, R Price, J Takahashi, K Ikura, T Slavkin, HC Nuckolls, GH TI The mouse Dach gene participates in the morphogenesis of multiple organs SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1203 BP 207A EP 207A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501204 ER PT J AU Messam, CA Hou, J Major, EO AF Messam, CA Hou, J Major, EO TI Expression of nestin in neural and glial cells in the developing human CNS defined by a human specific anti-nestin antibody SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1205 BP 208A EP 208A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501208 ER PT J AU Roberts, TH Hammond, AT Glick, BS Lippincott-Schwartz, J AF Roberts, TH Hammond, AT Glick, BS Lippincott-Schwartz, J TI Membrane sorting and recycling in the early secretory pathway. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD, NIH, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. RI Ward, Theresa/E-9650-2013 OI Ward, Theresa/0000-0002-9881-8649 NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1229 BP 212A EP 212A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501229 ER PT J AU Coorssen, JR Blank, PS Kolosova, I Backlund, P Zimmerberg, J AF Coorssen, JR Blank, PS Kolosova, I Backlund, P Zimmerberg, J TI Are SNARE proteins necessary and sufficient for membrane fusion? SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1269 BP 219A EP 219A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501270 ER PT J AU Holowka, D Field, KA Apgar, J Siraganian, R Baird, B AF Holowka, D Field, KA Apgar, J Siraganian, R Baird, B TI Mutant RBL mast cells that lack ganglioside and GPI-protein expression are defective in Fc epsilon RI signaling downstream of tyrosine phosphorylation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Cornell Univ, Baker Lab, Ithaca, NY 14853 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Scripps Clin & Res Fdn, La Jolla, CA USA. NIDR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1273 BP 219A EP 219A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501272 ER PT J AU Aguilar, RC Boehm, M Ohno, H Dell'Angelica, EC Gough, NR Fambrough, DM Bonifacino, JS AF Aguilar, RC Boehm, M Ohno, H Dell'Angelica, EC Gough, NR Fambrough, DM Bonifacino, JS TI Specificity of the interaction of the mu 4 subunit of the AP-4 adaptor complex with tyrosine-based sorting signals. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, CBMBNICHD, Bethesda, MD 20892 USA. Kanazawa Univ, Canc Res Inst, Kanazawa, Ishikawa 920, Japan. Johns Hopkins Univ, Baltimore, MD 21218 USA. RI Ohno, Hiroshi/L-7899-2014 OI Ohno, Hiroshi/0000-0001-8776-9661 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1295 BP 223A EP 223A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501297 ER PT J AU Caplan, S Dell'Angelica, EC Gahl, WA Bonifacino, JS AF Caplan, S Dell'Angelica, EC Gahl, WA Bonifacino, JS TI MHC class II/invariant chain sorting in AP-3-deficient B lymphoblasts SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1296 BP 223A EP 223A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501295 ER PT J AU Dell'Angelica, EC Mullins, C Boehm, M Bonifacino, JS AF Dell'Angelica, EC Mullins, C Boehm, M Bonifacino, JS TI Identification of AP-4, a novel protein complex related to clathrin adaptors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, NICHD, CBMB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1294 BP 223A EP 223A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501294 ER PT J AU Mullins, C Hartnell, LM Wassarman, DA Bonifacino, JS AF Mullins, C Hartnell, LM Wassarman, DA Bonifacino, JS TI Mutations in subunits of the AP-3 adaptor complex result in defective pigment granule biogenesis in Drosophila melanogaster. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1297 BP 223A EP 223A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501298 ER PT J AU Cawley, NX Tam, WH Loh, YP AF Cawley, NX Tam, WH Loh, YP TI Mutant carboxypeptidase E targets proinsulin to the regulated secretory pathway in a beta-cell line derived from Cpe(fat)/Cpe(fat) mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1304 BP 225A EP 225A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501305 ER PT J AU Dhanvantari, S Loh, YP AF Dhanvantari, S Loh, YP TI Lipid raft association of carboxypeptidase E, a regulated secretory pathway sorting receptor. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Dhanvantari, Savita/B-5362-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1305 BP 225A EP 225A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501308 ER PT J AU Clay, JR Kuzirian, A AF Clay, JR Kuzirian, A TI Lozalization of K+ channels in squid giant axons. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1312 BP 226A EP 226A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501314 ER PT J AU Shen, DW Goldenberg, S Pastan, I Gottesman, MM AF Shen, DW Goldenberg, S Pastan, I Gottesman, MM TI Cisplatin resistance in human cancer cells: Is active efflux or defective uptake responsible for the resistance? SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1326 BP 228A EP 228A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501327 ER PT J AU Shumaker, DK Craigie, R Wilson, KL AF Shumaker, DK Craigie, R Wilson, KL TI Mutagenesis defines two distinct functional domains in the conserved n-terminal region of LAP2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1372 BP 237A EP 237A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501372 ER PT J AU Sullivan, T Escalente-Alcalde, D Bhatt, H Anver, M Bhat, N Nagashima, K Stewart, CL Burke, B AF Sullivan, T Escalente-Alcalde, D Bhatt, H Anver, M Bhat, N Nagashima, K Stewart, CL Burke, B TI Loss of A-type lamin expression compromises nuclear integrity leading to muscular dystrophy. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, ABL Basic Res Program, Frederick, MD 21702 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. NCI, SAIC, Frederick, MD 21702 USA. Univ Calgary, Calgary, AB T2N 4N1, Canada. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1373 BP 237A EP 237A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501375 ER PT J AU Tyler, JK Adams, CR Chen, SR Kobayashi, R Kamakaka, R Kadonaga, JT AF Tyler, JK Adams, CR Chen, SR Kobayashi, R Kamakaka, R Kadonaga, JT TI RCAF, a novel factor that mediates chromatin assembly during DNA replication and repair SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif San Diego, La Jolla, CA 92093 USA. NIH, Bethesda, MD 20892 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1380 BP 238A EP 238A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501381 ER PT J AU Soyal, SM Amleh, A Dean, J AF Soyal, SM Amleh, A Dean, J TI Mice lacking FIG alpha, a germline specific bHLH transcription factor, do not form primordial follicles and are infertile SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1387 BP 240A EP 240A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501388 ER PT J AU Kalab, P Dasso, M AF Kalab, P Dasso, M TI Stabilization of microtubules by RCC1-generated RanGTP gradient. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1484 BP 256A EP 256A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501485 ER PT J AU Roos, MD Lubas, WA Hanover, JA AF Roos, MD Lubas, WA Hanover, JA TI Structural and mutational analysis of O-GlcNAc transferase. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1554 BP 268A EP 268A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501555 ER PT J AU Topol, LZ Bardot, B Zhang, QY Marx, M Resau, JH Allen, RH Calothy, G Blair, DG AF Topol, LZ Bardot, B Zhang, QY Marx, M Resau, JH Allen, RH Calothy, G Blair, DG TI Biosynthesis, distinct post-translational modification, and functional characterization of DRM, a member of DAN/Cerberus family. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 SAIC Frederick, Frederick, MD 21702 USA. Inst Curie, F-75231 Paris, France. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1572 BP 272A EP 272A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501573 ER PT J AU Tsutsui, T Kumakura, S Tamura, Y Barrett, JC AF Tsutsui, T Kumakura, S Tamura, Y Barrett, JC TI Minisatellite instability in immortal cell lines derived from a Li-Fraumeni syndrome patient SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Nippon Dent Univ, Sch Dent, Chiyoda Ku, Tokyo 1028159, Japan. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1578 BP 273A EP 273A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501579 ER PT J AU Li, CL Shalizi, A Weinberg, W Deng, CX AF Li, CL Shalizi, A Weinberg, W Deng, CX TI Functional analysis of fibroblast growth factor (FGF) receptor 1 and receptor 2 during murine organogenesis and limb development by tetraploid rescue and chimeric animal formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1593 BP 275A EP 275A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501592 ER PT J AU Mahato, D Goulding, EH Korach, KS Eddy, EM AF Mahato, D Goulding, EH Korach, KS Eddy, EM TI Estrogen regulates spermatogenesis indirectly through somatic cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1615 BP 279A EP 279A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501615 ER PT J AU Fletcher, TM Ryu, BW Xiao, NQ Mautino, G Warren, B Hager, G AF Fletcher, TM Ryu, BW Xiao, NQ Mautino, G Warren, B Hager, G TI MMTV chromatin remodeling by the glucocorticoid receptor is localized to the nucleosome B and C region in reconstituted nucleosomal arrays SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1627 BP 281A EP 281A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501627 ER PT J AU Redon, C Boon, C Johnson, K Bonner, WM Rogakou, EP AF Redon, C Boon, C Johnson, K Bonner, WM Rogakou, EP TI Megabase chromatin domains involved in DNA double-strand breaks in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 1 U2 6 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 NOV PY 1999 VL 10 SU S MA 1634 BP 282A EP 282A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501636 ER PT J AU Dang, VD Balasundaram, D Levin, HL AF Dang, VD Balasundaram, D Levin, HL TI Nuclear Import of the retrotransposon Tfl is governed by a unique nuclear localization signal that requires the FXFG-nucleoporin Nup124p. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1641 BP 283A EP 283A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501642 ER PT J AU Morasso, MI Bryan, JT AF Morasso, MI Bryan, JT TI Bipartite NLS is essential for Dlx3 homeobox protein function. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Indiana Univ, Bloomington, IN 47405 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1654 BP 286A EP 286A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501655 ER PT J AU Dundr, M Misteli, T Olson, MO AF Dundr, M Misteli, T Olson, MO TI The dynamics of postmitotic reassembly of the nucleolus SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1673 BP 289A EP 289A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501673 ER PT J AU Misteli, T AF Misteli, T TI Rapid trafficking of nuclear proteins in living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1674 BP 289A EP 289A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501676 ER PT J AU DasGupta, SF Rapoport, SI Fiskum, G Chandrasekaran, K AF DasGupta, SF Rapoport, SI Fiskum, G Chandrasekaran, K TI The effect ADP, ATP and respiration an in organello synthesis or RNA transcripts in isolated rat liver mitochondria. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1716 BP 296A EP 296A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501717 ER PT J AU Timmers, KI Tahara, M Chen, HC Zimmerberg, J AF Timmers, KI Tahara, M Chen, HC Zimmerberg, J TI An 18kDa protein is associated with SNARE proteins in sea urchin egg cortical vesicles. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1726 BP 298A EP 298A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501726 ER PT J AU Markovic, I Leikina, E Chernomordik, LV AF Markovic, I Leikina, E Chernomordik, LV TI Mechanism of influenza virus hemagglutinin activation and/or inactivation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1732 BP 299A EP 299A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501731 ER PT J AU Hug, P Lin, HMJ Korte, T Xiao, X Dimitrov, D Wang, JM Puri, A Blumenthal, R AF Hug, P Lin, HMJ Korte, T Xiao, X Dimitrov, D Wang, JM Puri, A Blumenthal, R TI Glycosphingolipids promote entry of a broad range of human immunodeficiency virus type 1 isolates into cell lines expressing CD4, CXCR4 and/or CCR5 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Master Chem Corp, Perrysburg, OH 43551 USA. NCI, Frederick Canc Res & Dev Ctr, DBS, LECB, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, DBS, LMI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1737 BP 300A EP 300A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501739 ER PT J AU Lin, HMJ Puri, A Hug, P Mikovits, JA Mazout, A Ruscetti, F Blumenthal, R AF Lin, HMJ Puri, A Hug, P Mikovits, JA Mazout, A Ruscetti, F Blumenthal, R TI Involvement of a glycosphingolipid, other than globotriaosylceramide (Gb3), in HIV-1 cell-cell fusion and infectivity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, DBS, LECB, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, DBS, LLB, Frederick, MD 21702 USA. SAIC, LADM, Frederick, MD USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1736 BP 300A EP 300A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501736 ER PT J AU Hirschberg, K Phair, RD Lippincott-Schwartz, J AF Hirschberg, K Phair, RD Lippincott-Schwartz, J TI Characterization of Golgi organization and dynamics using kinetic analysis of protein traffic & dual-color live cell imaging. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. BioInformat Serv, Rockville, MD 20854 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1744 BP 301A EP 301A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501745 ER PT J AU Nichols, B Kenworthy, A Lippincott-Schwartz, J AF Nichols, B Kenworthy, A Lippincott-Schwartz, J TI Membrane traffic between the TGN and cell surface SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1743 BP 301A EP 301A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501743 ER PT J AU Kenworthy, AK Petranova, N Hubbard, AL Edidin, M AF Kenworthy, AK Petranova, N Hubbard, AL Edidin, M TI Membrane organization of GPI-anchored proteins in hepatocyte plasma membranes probed by imaging FRET. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1758 BP 304A EP 304A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501761 ER PT J AU Miura, Y Jones, TLZ AF Miura, Y Jones, TLZ TI The role of lipid rafts on signaling by heterotrimeric g proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 1999 VL 10 SU S MA 1772 BP 306A EP 306A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501774 ER PT J AU Cremona, O Di Paolo, G Wenk, MR Luthi, A Kim, WT Takei, K Daniell, L Nemoto, Y Shears, SB Flavell, RA McCormick, DA De Camilli, P AF Cremona, O Di Paolo, G Wenk, MR Luthi, A Kim, WT Takei, K Daniell, L Nemoto, Y Shears, SB Flavell, RA McCormick, DA De Camilli, P TI Essential role of the polyphosphoinositide phosphatase synaptojanin 1 in synaptic vesicle recycling. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT 06520 USA. NIH, Bethesda, MD 20892 USA. RI Kobelt, Liza/F-5926-2011; Wenk, Markus/D-1441-2014 NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1786 BP 309A EP 309A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501787 ER PT J AU Hunyady, L Gaborik, Z Mihalik, B Clark, AJL Catt, KJ AF Hunyady, L Gaborik, Z Mihalik, B Clark, AJL Catt, KJ TI Dynamin-dependent mechanism of internalization of the AT(1a). angiotensin receptor. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Semmelweis Univ Med, H-1088 Budapest, Hungary. St Bartholomews Hosp, London, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1829 BP 316A EP 316A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501831 ER PT J AU Xi, D Battey, JF Northup, JK AF Xi, D Battey, JF Northup, JK TI Functional characterization of the n-terminal domain of metabotropic glutamate receptor subtype 1a SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1828 BP 316A EP 316A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501828 ER PT J AU Engleka, KA Lewis, EW Rudo, TJ St John, MAR Heinze, AW Howard, BH AF Engleka, KA Lewis, EW Rudo, TJ St John, MAR Heinze, AW Howard, BH TI Endothelial cell DNA transfer and expression using petri dish electroporation and the nonreplicating vaccinia virus/T7 RNA polymerase hybrid system. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1852 BP 320A EP 320A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501852 ER PT J AU Prufer, K Racz, A Lin, GC Barsony, J AF Prufer, K Racz, A Lin, GC Barsony, J TI Vitamin D receptors are brought into the nucleus by heterodimerizing retinoid X receptors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 1882 BP 325A EP 325A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501883 ER PT J AU Teng, C Beard, C Gladwell, W AF Teng, C Beard, C Gladwell, W TI Characterization of rabbit antisera to mouse lactoferrin that cross-react with rat lactoferrin specifically SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1878 BP 325A EP 325A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501881 ER PT J AU McNally, JG Mueller, WG Walker, D Wolford, R Hager, GL AF McNally, JG Mueller, WG Walker, D Wolford, R Hager, GL TI The glucocorticoid receptor undergoes rapid exchange with regulatory sites in living cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 1999 VL 10 SU S MA 1887 BP 326A EP 326A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501886 ER PT J AU Basanez, G Zhang, J Chan, N Hardwick, JM Zimmerberg, J AF Basanez, G Zhang, J Chan, N Hardwick, JM Zimmerberg, J TI Caspase cleavage promotes Bcl-x(L)-dependent pore formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1911 BP 330A EP 330A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501912 ER PT J AU Liu, W Northup, JK AF Liu, W Northup, JK TI The helical domains of G protein a subunits determine selective interaction of members of G protein alpha(1) subfamily with a phospholipase C enzyme SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Natl Inst Deafness & Other Commun Disorder, Lab Cellular Biol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1918 BP 332A EP 332A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501919 ER PT J AU Li, BS Veranna, V Amin, ND Pant, HC AF Li, BS Veranna, V Amin, ND Pant, HC TI Integrin-mediated human NF-H tail domain phosphorylation through activation of cyclin-dependent kinase 5 activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 1943 BP 336A EP 336A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501946 ER PT J AU Han, J Nam, SW de la Pena, M Le, P Wrathall, LS Sobel, ME AF Han, J Nam, SW de la Pena, M Le, P Wrathall, LS Sobel, ME TI Targeted disruption of the 37LRP/p40 gene by antisense decreases properties associated with the metastatic phenotype in human melanoma cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2025 BP 350A EP 350A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502028 ER PT J AU Schneider, D Shahabuddin, M AF Schneider, D Shahabuddin, M TI Drosophila, a model host for malaria parasites SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Whitehead Inst, Cambridge Ctr 9, Cambridge, MA 02142 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2055 BP 355A EP 355A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502056 ER PT J AU Chang, W Nunes, FD De Jesus-Escobar, JM Harland, R Wu, DK AF Chang, W Nunes, FD De Jesus-Escobar, JM Harland, R Wu, DK TI Ectopic Noggin blocks morphogenesis of sensory and non-sensory organs during chicken inner ear development. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCD, NIH, Rockville, MD 20850 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2095 BP 362A EP 362A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502096 ER PT J AU Takasaki, N Mclsaac, R Rankin, T Dean, J AF Takasaki, N Mclsaac, R Rankin, T Dean, J TI Novel homeobox gene expressed in the mouse gonad at the time of sex-determination SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDDK, LCDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2094 BP 362A EP 362A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502093 ER PT J AU Shakes, DC Sadler, PL Wille, L Holt, G Wallenfang, M Seydoux, G Hamill, DR Bowerman, B Golden, A AF Shakes, DC Sadler, PL Wille, L Holt, G Wallenfang, M Seydoux, G Hamill, DR Bowerman, B Golden, A TI Getting to anaphase in C-elegans: Genes required for both mitosis and meiosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Coll William & Mary, Williamsburg, VA 23187 USA. Univ Houston, Houston, TX 77004 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. Univ Oregon, Eugene, OR 97403 USA. NCI, FCRDC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2256 BP 390A EP 390A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502258 ER PT J AU Low, SH Roche, PA Valdez, A Mostov, KE Weimbs, T AF Low, SH Roche, PA Valdez, A Mostov, KE Weimbs, T TI Plasma membrane t-SNAREs localize to intracellular apical and basolateral cognate compartments in non-polarized MDCK cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. NCI, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2287 BP 395A EP 395A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502288 ER PT J AU Debrabant, A Lee, N Dwyer, D Nakhasi, H AF Debrabant, A Lee, N Dwyer, D Nakhasi, H TI Overexpression of the endoplasmic reticulum chaperone calreticulin in Leishmania donovani results in altered release of secretory proteins. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2392 BP 413A EP 413A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502393 ER PT J AU Guo, GG Bourdi, M Ndubuisi, MI Fried, VA Pohl, LR Etlinger, JD Sehgal, PB AF Guo, GG Bourdi, M Ndubuisi, MI Fried, VA Pohl, LR Etlinger, JD Sehgal, PB TI Lactacystin inhibits GRP58/ER-60/ERp57 protease SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 New York Med Coll, Valhalla, NY 10595 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2403 BP 415A EP 415A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502402 ER PT J AU Al-Awar, OS Donaldson, JG AF Al-Awar, OS Donaldson, JG TI Two-hybrid screen for ARF6 interacting proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2411 BP 417A EP 417A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502414 ER PT J AU Ogasawara, M Kim, SC Adamik, R Takeda, K Kirby, M Togawa, A Ferrans, VJ Moss, J Vaughan, M AF Ogasawara, M Kim, SC Adamik, R Takeda, K Kirby, M Togawa, A Ferrans, VJ Moss, J Vaughan, M TI Similarities in function and gene structure of cytohesin-4 and cytohesin-1, guanine nucleotide-exchange proteins for ADP-ribosylation factors. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2410 BP 417A EP 417A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502411 ER PT J AU Donohue, PJ Sainz, E Akeson, M Kroog, GS Mantey, SA Battey, JF Jensen, RT Northup, JK AF Donohue, PJ Sainz, E Akeson, M Kroog, GS Mantey, SA Battey, JF Jensen, RT Northup, JK TI An aspartate residue in transmembrane domain II (TMII) and an arginine residue in transmembrane domain VII (TMVII) of the gastrin-releasing peptide receptor (GRP-R) interact to facilitate heterotrimeric G protein coupling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Amer Red Cross, Washington, DC 20006 USA. NIDCD, NIH, Rockville, MD 20850 USA. Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2416 BP 418A EP 418A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502417 ER PT J AU Dmitrieva, N Kultz, D Michea, L Ferraris, JD Burg, M AF Dmitrieva, N Kultz, D Michea, L Ferraris, JD Burg, M TI Hypertonicity increases transcriptional activity of p53 in renal inner medullary cells (mIMCD3). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, LKEM, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL 32611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2490 BP 430A EP 430A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502489 ER PT J AU Giannakakou, P Sackett, DL Ward, Y Blagosklonny, M Fojo, T AF Giannakakou, P Sackett, DL Ward, Y Blagosklonny, M Fojo, T TI P53 is associated with cytoplasmic and spindle microtubules and requires functional microtubules for nuclear accumulation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2489 BP 430A EP 430A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502491 ER PT J AU Brodie, SG Xu, XL Yang, X Im, YH Parks, WT Chen, L Zhou, YX Xie, JW Kim, SJ Deng, CX AF Brodie, SG Xu, XL Yang, X Im, YH Parks, WT Chen, L Zhou, YX Xie, JW Kim, SJ Deng, CX TI Haploinsufficiency of the tumor suppressor Smad4/Dpc4 initiates gastrointestinal polyposis and cancer. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2495 BP 431A EP 431A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502497 ER PT J AU Fang, SY Jensen, JP Ludwig, RL Vousden, KH Weissman, AM AF Fang, SY Jensen, JP Ludwig, RL Vousden, KH Weissman, AM TI The RING finger of Mdm2 is specifically required for p53 ubiquitination SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, LICB, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2492 BP 431A EP 431A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502493 ER PT J AU Xu, XL Linke, SP Harris, CC Deng, CX AF Xu, XL Linke, SP Harris, CC Deng, CX TI Haploidinsufficiency of p53 rescues cellular deficiency and promotes mammary gland tumor formation in Brca1 exon 11-isoform knockout mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. RI deng, chuxia/N-6713-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2494 BP 431A EP 431A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502494 ER PT J AU Gao, CY Negash, S Wang, HS Zelenka, PS AF Gao, CY Negash, S Wang, HS Zelenka, PS TI Heat shock transiently activates CDK5 in U373 glioma cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NEI, NIH, Bethesda, MD 20892 USA. Natl Yang Ming Univ, Natl Yang Ming Med Coll, Dept Anat, Taipei 112, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2506 BP 433A EP 433A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502506 ER PT J AU Ghiani, CA Tang, XM Cambi, F Gallo, V AF Ghiani, CA Tang, XM Cambi, F Gallo, V TI Expression and regulation of cyclin dependent kinase 5 in the oligodendrocyte lineage. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NICHD, Lab Cell Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2505 BP 433A EP 433A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502508 ER PT J AU Segura, M Craigie, R Wilson, KL AF Segura, M Craigie, R Wilson, KL TI Characterization of the nuclear function of barrier-to-autointegration factor (Baf) through site-directed mutagenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Baltimore, MD 21218 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2521 BP 436A EP 436A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502522 ER PT J AU Love, DC Wu, W Hanover, JA AF Love, DC Wu, W Hanover, JA TI Characterization of O-linked N-acetylglucosamine and nuclear transport SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2547 BP 440A EP 440A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502547 ER PT J AU Wu, W Lubas, WA Hanover, JA AF Wu, W Lubas, WA Hanover, JA TI Purification and characterization of enzymatically active recombinant human OGT SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2548 BP 440A EP 440A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502549 ER PT J AU Holaska, JM Leszyk, J Love, DC Hanover, JA Paschal, BM AF Holaska, JM Leszyk, J Love, DC Hanover, JA Paschal, BM TI Purification of a cytosolic factor that mediates nuclear export of protein kinase inhibitor (PKI) and rev. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. Worcester Fdn Biomed Res, Worcester, MA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2549 BP 441A EP 441A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502550 ER PT J AU Choi, YC Steinert, PM Kim, SY AF Choi, YC Steinert, PM Kim, SY TI TNF-alpha induces expression of transglutaminase 2 in the normal human small intestinal epithelial cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2596 BP 449A EP 449A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502597 ER PT J AU Longenecker, G Thyagarajan, T Nagineni, CN Flanders, K Factor, V Miller, G Ward, JM Nalca, A Rangnekar, V Thorgeirsson, S Kulkarni, AB AF Longenecker, G Thyagarajan, T Nagineni, CN Flanders, K Factor, V Miller, G Ward, JM Nalca, A Rangnekar, V Thorgeirsson, S Kulkarni, AB TI Therapeutic potential of active TGF-beta 1 to ameliorate lethal phenotype of TGF-beta 1 null mice SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH, Off Director, Bethesda, MD 20892 USA. Univ Kentucky, Lexington, KY 40536 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2598 BP 449A EP 449A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502598 ER PT J AU Vann, LR Twitty, S Spiegel, S Milstien, S AF Vann, LR Twitty, S Spiegel, S Milstien, S TI TNF-alpha regulates nitric oxide and tetrahydrobiopterin biosynthesis by ceramide-dependent and independent pathways SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIMH, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2608 BP 451A EP 451A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502609 ER PT J AU Hoffman, MP Jung, DW Hecht, D O'Connell, BC Kleinman, HK AF Hoffman, MP Jung, DW Hecht, D O'Connell, BC Kleinman, HK TI PKC and MAP kinase pathways regulate amylase promoter activity in salivary cell differentiation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2638 BP 456A EP 456A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502639 ER PT J AU Pendrak, ML Yan, SH Roberts, DD AF Pendrak, ML Yan, SH Roberts, DD TI Signal processing pathways leading to hemoglobin-induced extracellular matrix binding in candida albicans are unrelated to filamentous growth SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 10 SU S MA 2641 BP 456A EP 456A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502642 ER PT J AU Li, ZQ Roberts, DD AF Li, ZQ Roberts, DD TI Thrombospondin-1 inducer expression of cyclin-dependent kinase (CDK) inhibitors p21(CIP1/WAF1) and p27(KIP1) and inhibits cell proliferation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NCI, DCS, NIH, Bethesda, MD 20892 USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 10 SU S MA 2643 BP 457A EP 457A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502646 ER PT J AU Brosh, RM Balajee, AS Selzer, RR Sunesen, M De Santis, LP Bohr, VA AF Brosh, RM Balajee, AS Selzer, RR Sunesen, M De Santis, LP Bohr, VA TI The ATPase domain but not the acidic region of cockayne syndrome group B gene product is essential for DNA repair SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID RNA-POLYMERASE-II; TRANSCRIPTION-COUPLED REPAIR; CSB ERCC6 GENE; XERODERMA-PIGMENTOSUM; ESCHERICHIA-COLI; EXCISION-REPAIR; ACTIVE GENES; 4-HYDROXYAMINOQUINOLINE 1-OXIDE; 4-NITROQUINOLINE 1-OXIDE; ELONGATION COMPLEXES AB Cockayne syndrome (CS) is a human genetic disorder characterized by UV sensitivity, developmental abnormalities, and premature aging. Two of the genes involved, CSA and CSB, are required for transcription-coupled repair (TCR), a subpathway of nucleotide excision repair that removes certain lesions rapidly and efficiently from the transcribed strand of active genes. CS proteins have also been implicated in the recovery of transcription after certain types of DNA damage such as those lesions induced by UV light. In this study, site-directed mutations have been introduced to the human CSB gene to investigate the functional significance of the conserved ATPase domain and of a highly acidic region of the protein. The CSB mutant alleles were tested for genetic complementation of UV-sensitive phenotypes in the human CS-B homologue of hamster UV61. In addition, the CSB mutant alleles were tested for their ability to complement the sensitivity of UV61 cells to the carcinogen 4-nitroquinoline-1-oxide (4-NQO), which introduces bulky DNA adducts repaired by global genome repair. Point mutation of a highly conserved glutamic acid residue in ATPase motif II abolished the ability of CSB protein to complement the UV-sensitive phenotypes of survival, RNA synthesis recovery, and gene-specific repair. These data indicate that the integrity of the ATPase domain is critical for CSB function in vivo. Likewise, the CSB ATPase point mutant failed to confer cellular resistance to 4-NQO, suggesting that ATP hydrolysis is required for CSB function in a TCR-independent pathway. On the contrary, a large deletion of the acidic region of CSB protein did not impair the genetic function in the processing of either UV- or 4-NQO-induced DNA damage. Thus the acidic region of CSB is likely to be dispensable for DNA repair, whereas the ATPase domain is essential for CSB function in both TCR-dependent and -independent pathways. C1 NIA, Ctr Mol Genet, NIH, Baltimore, MD 21224 USA. Aarhus Univ, Dept Biol Mol & Struct, DK-8000 Aarhus C, Denmark. Univ Tuscia, Dipartimento Agrobiol & Agrochim, I-01100 Viterbo, Italy. RP NIA, Ctr Mol Genet, NIH, Baltimore, MD 21224 USA. EM vbohr@nih.gov NR 62 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 IS 11 BP 3583 EP 3594 PG 12 WC Cell Biology SC Cell Biology GA 255AL UT WOS:000083647300006 PM 10564257 ER PT J AU Caughey, B Raymond, GJ Priola, SA Kocisko, DA Race, RE Bessen, RA Lansbury, PT Chesebro, B AF Caughey, B Raymond, GJ Priola, SA Kocisko, DA Race, RE Bessen, RA Lansbury, PT Chesebro, B TI Methods for studying prion protein (PrP) metabolism and the formation of protease-resistant PrP in cell culture and cell-free systems - An update SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE prion protein; PrP; scrapie; transmissible spongiform encephalopathy ID CREUTZFELDT-JAKOB DISEASE; NEURO-BLASTOMA CELLS; SCRAPIE-INFECTED HAMSTERS; CONGO RED; NEUROBLASTOMA-CELLS; INCUBATION PERIOD; AGENT REPLICATION; DEXTRAN SULFATE; MOUSE-BRAIN; CONVERSION AB Transmissible spongiform encephalopathies (TSE) or prion diseases result in aberrant metabolism of prion protein (PrP) and the accumulation of a protease-resistant, insoluble, and possibly infectious form of PrP, PrP-res. Studies of PrP biosynthesis, intracellular trafficking? and degradation has been studied in a variety of tissue culture cells. Pulse-chase metabolic labeling studies in scrapie-infected cells indicated that PrP-res is made posttranslationally from an apparently normal protease-sensitive precursor, PrP-sen, after the latter reaches the cell surface. Cell-free reactions have provided evidence that PrP-res itself can induce the conversion of PrP-sen to PrP-res in a highly species- and strain-specific manner. These studies have shed light on the mechanism of PrP-res formation and suggest molecular bases for TSE species barrier effects and agent strain propagation. C1 NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. EM byron_caughey@nih.gov NR 65 TC 24 Z9 25 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD NOV PY 1999 VL 13 IS 1 BP 45 EP 55 DI 10.1385/MB:13:1:45 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 280TY UT WOS:000085120900005 PM 10934521 ER PT J AU Bennett, LM AF Bennett, LM TI Breast cancer: Genetic predisposition and exposure to radiation SO MOLECULAR CARCINOGENESIS LA English DT Article DE breast cancer; (genetic) susceptibility; radiation; BRCA1; BRCA2 ID ATAXIA-TELANGIECTASIA HETEROZYGOTES; MULTIPLE INTESTINAL NEOPLASIA; APC GENE; MOUSE CHROMOSOME-11; IONIZING-RADIATION; CELLULAR-RESPONSE; BRCA2 GENES; DNA-DAMAGE; MUTATIONS; ATM AB The identification of breast cancer susceptibility genes, such as BRCA1, BRCA2, ATM, and p53, has been accompanied by the examination of the effects of radiation in combination with genetic mutations at these loci. Women at high risk for developing breast cancer may respond differently than the general population to low- and high-dose radiation exposures associated with screening and treatment. Epidemiologic studies are being performed to investigate the effects of radiation on subsequent breast cancer development in genetically predisposed individuals. Mouse strains with specific genetic modifications are being created to study the consequence of both inherited mutations and radiation on mammary gland carcinogenesis. Finally, studies investigating DNA damage-response pathways after radiation exposure are being performed. Recent work on the effects of several known or suspected breast cancer susceptibility genes, alone or in combination with radiation, is presented here, and directions for future research are considered. (C) 1999 Wiley-Liss, Inc. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Bennett, LM (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 68 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD NOV PY 1999 VL 26 IS 3 BP 143 EP 149 DI 10.1002/(SICI)1098-2744(199911)26:3<143::AID-MC2>3.0.CO;2-S PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 253LL UT WOS:000083558000001 PM 10559788 ER PT J AU Sartorelli, V Puri, PL Hamamori, Y Ogryzko, V Chung, G Nakatani, Y Wang, JYJ Kedes, L AF Sartorelli, V Puri, PL Hamamori, Y Ogryzko, V Chung, G Nakatani, Y Wang, JYJ Kedes, L TI Acetylation of MyoD directed by PCAF is necessary for the execution of the muscle program SO MOLECULAR CELL LA English DT Article ID LOOP-HELIX PROTEINS; RNA-POLYMERASE-II; CELL-CYCLE ARREST; HISTONE ACETYLTRANSFERASE; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; SKELETAL-MUSCLE; REPRESS TRANSCRIPTION; CHROMATIN STRUCTURE; CRYSTAL-STRUCTURE AB p300/CBP and PCAF coactivators have acetyltransferase activites and regulate transcription, cell cycle progression, and differentiation. They are both required for MyoD activity and muscle differentiation. Nevertheless, their roles must be different since the acetyltransferase activity of PCAF but not of p300 is involved in controlling myogenic transcription and differentiation. Here, we provide a molecular explanation of this phenomenon and report that MyoD is directly acetylated by PCAF at evolutionarily conserved lysines. Acetylated MyoD displays an increased affinity for its DNA target. Importantly, conservative substitutions of acetylated lysines with nonacetylatable arginines impair the ability of MyoD to stimulate transcription and to induce muscle conversion indicating that acetylation of MyoD is functionally critical. C1 Univ So Calif, Inst Med Genet, Los Angeles, CA 90033 USA. Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90033 USA. Univ Calif San Diego, Ctr Mol Genet, Dept Biol, La Jolla, CA 92093 USA. NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. Univ Rome La Sapienza, Policlin Umberto I, Ist Clin Med 1, Fdn Andrea Cesalpino, I-00161 Rome, Italy. RP Sartorelli, V (reprint author), Univ So Calif, Inst Med Genet, Los Angeles, CA 90033 USA. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 FU NCI NIH HHS [CA58320, R01 CA058320]; Telethon [1072] NR 53 TC 265 Z9 270 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 NOV PY 1999 VL 4 IS 5 BP 725 EP 734 DI 10.1016/S1097-2765(00)80383-4 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 259GD UT WOS:000083885400007 PM 10619020 ER PT J AU Phillips, AC Ernst, MK Bates, S Rice, NR Vousden, KH AF Phillips, AC Ernst, MK Bates, S Rice, NR Vousden, KH TI E2F-1 potentiates cell death by blocking antiapoptotic signaling pathways SO MOLECULAR CELL LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; BCL-X-L; INDUCED APOPTOSIS; CYTOCHROME-C; RETINOBLASTOMA PROTEIN; CASPASE-8 ACTIVATION; MEDIATED APOPTOSIS; DNA-BINDING; RECEPTOR AB The E2F family of transcription factors plays an essential role in promoting cell cycle progression, and one member of the family, E2F-1, is also capable of inducing apoptosis. We show here that E2F-1 can induce apoptosis by a death receptor-dependent mechanism, by downregulating TRAF2 protein levels and inhibiting activation of antiapoptotic signals including NF-kappa B. In this way, E2F-1 expression can lead to the sensitization of cells to apoptosis by a number of agents independently of p53. Deregulation of E2F-1 activity occurs in the majority of human tumors, and the ability of E2F-1 to inhibit antiapoptotic signaling may contribute to the enhanced sensitivity of transformed cells to chemotherapeutic agents. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. SmithKline Beecham Pharmaceut, Harlow CM19 5AD, Essex, England. RP Vousden, KH (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, W 7th St, Frederick, MD 21702 USA. NR 59 TC 201 Z9 205 U1 0 U2 2 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 NOV PY 1999 VL 4 IS 5 BP 771 EP 781 DI 10.1016/S1097-2765(00)80387-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 259GD UT WOS:000083885400011 PM 10619024 ER PT J AU Wood, TI Griffith, KL Fawcett, WP Jair, KW Schneider, TD Wolf, RE AF Wood, TI Griffith, KL Fawcett, WP Jair, KW Schneider, TD Wolf, RE TI Interdependence of the position and orientation of SoxS binding sites in the transcriptional activation of the class I subset of Escherichia coli superoxide-inducible promoters SO MOLECULAR MICROBIOLOGY LA English DT Article ID MULTIPLE ANTIBIOTIC-RESISTANCE; CAP-DEPENDENT PROMOTERS; OXIDATIVE STRESS REGULON; RESPONSE REGULON; RNA-POLYMERASE; DNA-BINDING; INFORMATION-CONTENT; RECEPTOR PROTEIN; DUAL REGULATION; SEQUENCE LOGOS AB SoxS is the direct transcriptional activator of the member genes of the Escherichia coli superoxide regulon. At class I SoxS-dependent promoters, e.g. zwf and fpr, whose SoxS binding sites ('soxbox') lie upstream of the -35 region of the promoter, activation requires the C-terminal domain of the RNA polymerase alpha-subunit, while at class II SoxS-dependent promoters, e.g. fumC and micF, whose binding sites overlap the -35 region, activation is independent of the alpha-CTD. To determine whether SoxS activation of its class I promoters shows the same helical phase-dependent spacing requirement as class I promoters activated by catabolite gene activator protein, we increased the 7 bp distance between the 20 bp zwf soxbox and the zwf -35 promoter hexamer by 5 bp and 11 bp, and we decreased the 15 bp distance between the 20 bp fpr soxbox and the fpr -35 promoter hexamer by the same amounts, In both cases, displacement of the binding site by a half or full turn of the DNA helix prevented transcriptional activation, With constructs containing the binding site of one gene fused to the promoter of the other, we demonstrated that the positional requirements are a function of the specific binding site, not the promoter, Supposing that opposite orientation of the SoxS binding site at the two promoters might account for the positional requirements, we placed the zwf and fpr soxboxes in the reverse orientation at the various positions upstream of the promoters and determined the effect of orientation on transcription activation. We found that reversing the orientation of the zwf binding site converts its positional requirement to that of the fpr binding site in its normal orientation, and vice versa, Analysis by molecular information theory of DNA sequences known to bind SoxS in vitro is consistent with the opposite orientation of the zwf and fpr soxboxes. C1 Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, Frederick, MD 21702 USA. RP Wolf, RE (reprint author), Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA. EM wolf@umbc.edu OI Schneider, Thomas/0000-0002-9841-1531 FU NIGMS NIH HHS [GM27113] NR 69 TC 43 Z9 43 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1999 VL 34 IS 3 BP 414 EP 430 DI 10.1046/j.1365-2958.1999.01598.x PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 255QG UT WOS:000083680500002 PM 10564484 ER PT J AU Martin, RG Gillette, WK Rhee, S Rosner, JL AF Martin, RG Gillette, WK Rhee, S Rosner, JL TI Structural requirements for marbox function in transcriptional activation of mar/sox/rob regulon promoters in Escherichia coli: sequence, orientation and spatial relationship to the core promoter SO MOLECULAR MICROBIOLOGY LA English DT Article ID MULTIPLE ANTIBIOTIC-RESISTANCE; SUPEROXIDE-INDUCIBLE GENES; DNA-BINDING; DUAL REGULATION; PROTEIN; SOXS; MARA; OPERON; ROB; PURIFICATION AB The promoters of the mar/sox/rob regulon of Escherichia coli: contain a binding site (marbox) for the homologous transcriptional activators MarA, SoxS and Rob. In spite of data from footprinting studies, the marbox has not been precisely defined because of its degeneracy and asymmetry and seemingly variable location with respect to the -10 and -35 hexamers for RNA polymerase (RNP) binding. Here, we use DNA retardation studies and hybrid promoters to identify optimally binding 20 bp minimal marboxes from a number of promoters. This has yielded a more defined marbox consensus sequence (AYnG-CACnnWnnRYYAAAYn) and has led to the demonstration that some marboxes are inverted relative to others. Using transcriptional fusions to lacZ, we have found that only one marbox orientation is functional ata given location, Moreover, the functional orientation is determined by marbox location: marboxes that are 15 or more basepairs upstream of the -35 hexamer are oriented opposite those closer to the -35 hexamer. Marbox orientation and the spacing between marbox and signals for RNP binding are critical for transcriptional activation, presumably to align MarA with RNP. C1 NINCDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, RG (reprint author), NINCDS, Mol Biol Lab, NIH, Bldg 5,Rm 333, Bethesda, MD 20892 USA. NR 42 TC 114 Z9 116 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1999 VL 34 IS 3 BP 431 EP 441 DI 10.1046/j.1365-2958.1999.01599.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 255QG UT WOS:000083680500003 PM 10564485 ER PT J AU Zhou, Y Gottesman, MM Pastan, I AF Zhou, Y Gottesman, MM Pastan, I TI Domain exchangeability between the multidrug transporter (MDR1) and phosphatidylcholine flippase (MDR2) SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN P-GLYCOPROTEIN; TRANSIENT-EXPRESSION SYSTEM; CATALYTIC TRANSITION-STATE; STIMULATED ATPASE ACTIVITY; VACCINIA VIRUS; DRUG-BINDING; TRANSMEMBRANE SEGMENT-6; LABELING SITES; GENE; AZIDOPINE AB Multidrug resistance (MDR) mediated by P-glycoprotein (MDR1) is clinically significant. Understanding how MDR1 substrate specificity is determined will help to overcome MDR to improve cancer treatment. One potential approach to achieve this goal is to study chimeras of MDR1 and its homolog MDR2 (also called MDR3), which has been identified as a phosphatidylcholine flippase. With an approach involving exchanging homologous segments of MDR1 and MDR2 and site-directed mutagenesis, we previously demonstrated MDR1 residues Q330, V331, and L332 in transmembrane domain 6 (TM6) are essential for multidrug transport activity; substituting these residues allows the N-terminal transmembrane region of MDR2 to support MDR1 activity. To further determine the exchangeability between MDR1 and MDR2, we constructed additional MDR1/MDR2 chimeras. We found that the N-terminal half of MDR1 and MDR2 was mostly exchangeable except for a few residues in TM6. However, this degree of exchangeability was not found in the C-terminal half of MDR1 and MDR2. In addition, with substitution of MDR1 residues 318-332 (TM6) and 937-994 (TM11-12), MDR2 had relatively normal affinity for MDR1 substrates, but it did not have multidrug transporter activity. These results suggest that the inability of MDR2 to transport most MDR1 drugs efficiently may be due to failure of those drugs to stimulate ATPase and activate transport as well as to decreased drug binding. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Rm 4E16, Bethesda, MD 20892 USA. NR 36 TC 19 Z9 19 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 NOV PY 1999 VL 56 IS 5 BP 997 EP 1004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 247VG UT WOS:000083241200020 PM 10531406 ER PT J AU Murphy, WJ Thomerson, JE Collier, GE AF Murphy, WJ Thomerson, JE Collier, GE TI Phylogeny of the neotropical killifish family Rivulidae (Cyprinodontiformes, Aplocheiloidei) inferred from mitochondrial DNA sequences SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article ID CYTOCHROME-B; DEVELOPMENTAL BIOLOGY; ANNUAL FISHES; MAXIMUM-LIKELIHOOD; EVOLUTION; TREES; PROTEIN; REGIONS; EGGS AB Phylogenetic relationships of 70 taxa representing 68 species of the Neotropical killifish family Rivulidae were derived from analysis of 1516 nucleotides sampled from four different segments of the mitochondrial genome: 12S rRNA, 16S rRNA, cytochrome oxidase I, and cytochrome b. The basal bifurcation of Cynolebiatinae and Rivulinae (Costa, 1990a,b) is supported; however, Terranatos, Maratecoara, and Plesiolebias are rivulins, not cynolebiatins. These three genera, along with the other recognized annual rivulin genera, form a monophyletic clade. Austrofundulus,Rachovia, Renova, Terranatos, and 3 species of the genus Pterolebias, all from northeastern South America, form a monophyletic clade excluding other species of Pterolebias. Pterolebias as presently understood is clearly polyphyletic. Trigonectes and Moema are supported as sister groups but do not form a monophyletic group with the genera Neofundulus and Renova as previously proposed. The suite of adaptations necessary for an annual life history has clearly been lost several times in the course of rivulid evolution. Also revealed is a considerable increase in substitution rate in most annual lineages relative to the nonannual Rivulus species. The widespread and speciose genus Rivulus is paraphyletic, representing both basal and terminal clades within the Rivulidae. Previous hypotheses, regarding the vicariant origin of Greater Antillean Rivulus species are supported. Most rivulid clades show considerable endemism; thus, detailed analysis of rivulid phylogeny and distribution will contribute robust hypotheses to the clarification of Neotropical biogeography. (C) 1999 Academic Press. C1 Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA. So Illinois Univ, Dept Biol Sci, Edwardsville, IL 62026 USA. RP Murphy, WJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Genom Divers, Frederick, MD 21702 USA. RI Langerhans, R./A-7205-2009 NR 53 TC 79 Z9 86 U1 3 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD NOV PY 1999 VL 13 IS 2 BP 289 EP 301 DI 10.1006/mpev.1999.0656 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 257MW UT WOS:000083786500006 PM 10603257 ER PT J AU Wenning, GK Ebersbach, G Verny, M Chaudhuri, KR Jellinger, K McKee, A Poewe, W Litvan, I AF Wenning, GK Ebersbach, G Verny, M Chaudhuri, KR Jellinger, K McKee, A Poewe, W Litvan, I TI Progression of falls in postmortem-confirmed parkinsonian disorders SO MOVEMENT DISORDERS LA English DT Article DE gait disturbance; falls; Parkinson's disease; progressive supranuclear palsy; atypical parkinsonism ID MULTIPLE SYSTEM ATROPHY; RICHARDSON-OLSZEWSKI-SYNDROME; CORTICOBASAL DEGENERATION; SUPRANUCLEAR PALSY; INTERNATIONAL WORKSHOP; CLINICAL-FEATURES; NATURAL-HISTORY; LEWY BODIES; DISEASE; DIAGNOSIS AB Although falls are known to occur in several parkinsonian disorders, such as Parkinson's disease (PD), multiple system atrophy (MSA), dementia with Lewy bodies (DLB), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), differences in the evolution of this feature have not been studied systematically in pathologically confirmed cases. Seventy-seven cases with pathologically confirmed parkinsonian disorders (PD: n = 11, MSA: n = 15, DLB: n = 14, CBD: n = 13, PSP: n = 24), collected up to 1994, formed the basis for a multicenter clinicopathologic study organized by the National Institute of Neurological Disorders and Stroke to improve differential diagnosis of parkinsonian disorders. In the present study, we determined the time course, that is, the duration from first symptom to onset (latency) and duration from onset to death, of recurrent falls. Furthermore, we analyzed the diagnostic validity of a predefined latency to onset of recurrent falls within 1 year of symptom onset. Significant group differences for latency, but not duration, of recurrent falls were observed. Latencies to onset of falls were short in PSP patients, intermediate in MSA, DLB, and CBD, and long in PD. Recurrent falls occurring within the first year after disease onset predicted PSP in 68% of the patients. Our study demonstrates for the first time that latency to onset, but not duration, of recurrent falls differentiates PD from other parkinsonian disorders. Whereas early falls are important for the diagnosis of PSP, the addition of other features increases its diagnostic predictive value. C1 Henry M Jackson Fdn, Def & Vet Head Injury Program, Cognit Neuropharmacol Unit, Bethesda, MD 20892 USA. Univ Innsbruck Hosp, Dept Neurol, A-6020 Innsbruck, Austria. Hop La Pitie Salpetriere, Raymond Escourolle Neuropathol Lab, INSERM, U360, Paris, France. Univ London Kings Coll Hosp, Inst Psychiat, London, England. Lainz Hosp, Ludwig Boltzmann Inst Clin Neurobiol, A-1130 Vienna, Austria. 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. NINDS, Med Neurol Branch, NIH, Bethesda, MD USA. RP Litvan, I (reprint author), Henry M Jackson Fdn, Def & Vet Head Injury Program, Cognit Neuropharmacol Unit, Fed Bldg,Rm 714, Bethesda, MD 20892 USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 24 TC 82 Z9 86 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 1999 VL 14 IS 6 BP 947 EP 950 DI 10.1002/1531-8257(199911)14:6<947::AID-MDS1006>3.0.CO;2-O PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 255QM UT WOS:000083681100006 PM 10584668 ER PT J AU Dalakas, MC AF Dalakas, MC TI Intravenous immunoglobulin in the treatment of autoimmune neuromuscular diseases: Present status and practical therapeutic guidelines SO MUSCLE & NERVE LA English DT Review DE intravenous immunoglobulin; autoimmune demyelinating neuropathies; inflammatory myopathies; myasthenia gravis; immunomodulation; adverse reactions ID GUILLAIN-BARRE-SYNDROME; INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY; INCLUSION-BODY MYOSITIS; HUMAN IMMUNE GLOBULIN; GAMMA-GLOBULIN; MYASTHENIA-GRAVIS; DOUBLE-BLIND; POSSIBLE MECHANISM; PLASMA-EXCHANGE; DERMATOMYOSITIS AB This review summarizes the current status of intravenous immunoglobulin (IVIg) in the treatment of autoimmune neuromuscular disorders and the possible mechanisms of action of the drug based on work in vivo, in vitro, and in animal models. Supply of idiotypic antibodies, suppression of antibody production, or acceleration of catabolism of immunoglobulin G (IgG) are relevant in explaining the efficacy of IVIg in myasthenia gravis (MG), Lambert-Eaton myasthenic syndrome (LEMS), and antibody-mediated neuropathies, Suppression of pathogenic cytokines has putative relevance in inflammatory myopathies and demyelinating neuropathies, Inhibition of complement binding and prevention of membranolytic attack complex (MAC) formation are relevant in dermatomyositis (DM), Guillain-Barre syndrome (GBS), and MG. Modulation of Fc receptors or T-cell function is relevant in chronic inflammatory demyelinating polyneuropathy (CIDP), GBS, and inflammatory myopathies. The clinical efficacy of IVIg, based on controlled clinical trials conducted in patients with GBS, CIDP, multifocal motor neuropathy (MMN), DM, MG, LEMS, paraproteinemic IgM anti-myelin-associated glycoprotein (anti-MAG) demyelinating polyneuropathies, and inclusion body myositis is summarized and practical issues related to each disorder are addressed. The present role of IVIg therapy in other disorders based on small controlled or uncontrolled trials is also summarized. Finally, safety issues, risk factors, adverse reactions, spurious results or serological tests, and practical guidelines associated with the administration of IVIg in the treatment of neuromuscular disorders are presented. (C) 1999 John Wiley & Sons, Inc. C1 NINCDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINCDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 54 TC 115 Z9 118 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD NOV PY 1999 VL 22 IS 11 BP 1479 EP 1497 DI 10.1002/(SICI)1097-4598(199911)22:11<1479::AID-MUS3>3.0.CO;2-B PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 248ZE UT WOS:000083306000003 PM 10514226 ER PT J AU Hennighausen, L Furth, PA AF Hennighausen, L Furth, PA TI The right time and place for molecular scissors SO NATURE BIOTECHNOLOGY LA English DT News Item ID TETRACYCLINE-RESPONSIVE PROMOTER; TRANSGENIC MICE; TEMPORAL CONTROL; GENE-EXPRESSION; MAMMALIAN-CELLS C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Phys, Baltimore, MD 21201 USA. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, Bldg 8,Rm 101, Bethesda, MD 20892 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 1999 VL 17 IS 11 BP 1062 EP 1063 DI 10.1038/15046 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 251CX UT WOS:000083428000018 PM 10545907 ER PT J AU Weijer, C Goldsand, G Emanuel, EJ AF Weijer, C Goldsand, G Emanuel, EJ TI Protecting communities in research: current guidelines and limits of extrapolation SO NATURE GENETICS LA English DT Editorial Material ID ETHICS AB As genetic research increasingly focuses on communities, there have been calls for extending research protections to them. We critically examine guidelines developed to protect aboriginal communities and consider their applicability to other communities. These guidelines are based on a model of researcher-community partnership and span the phases of a research project, from protocol development to publication. The complete list of 23 protections may apply to those few non-aboriginal communities, such as the Amish, that are highly cohesive. Although some protections may be applicable to less-cohesive communities, such as Ashkenazi Jews, analysis suggests substantial problems in extending these guidelines in tote beyond the aboriginal communities for which they were developed. C1 Dalhousie Univ, Dept Bioeth, Halifax, NS, Canada. Univ Toronto, Joint Ctr Bioeth, Toronto, ON, Canada. NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Weijer, C (reprint author), Dalhousie Univ, Dept Bioeth, Halifax, NS, Canada. NR 32 TC 92 Z9 92 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1999 VL 23 IS 3 BP 275 EP 280 DI 10.1038/15455 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 257QC UT WOS:000083792200014 PM 10545946 ER PT J AU Marcelino, J Carpten, JD Suwairi, WM Gutierrez, OM Schwartz, S Robbins, C Sood, R Makalowska, I Baxevanis, A Johnstone, B Laxer, RM Zemel, L Kim, CA Herd, JK Ihle, J Williams, C Johnson, M Raman, V Alonso, LG Brunoni, D Gerstein, A Papadopoulos, N Bahabri, SA Trent, JM Warman, ML AF Marcelino, J Carpten, JD Suwairi, WM Gutierrez, OM Schwartz, S Robbins, C Sood, R Makalowska, I Baxevanis, A Johnstone, B Laxer, RM Zemel, L Kim, CA Herd, JK Ihle, J Williams, C Johnson, M Raman, V Alonso, LG Brunoni, D Gerstein, A Papadopoulos, N Bahabri, SA Trent, JM Warman, ML TI CACP, encoding a secreted proteoglycan, is mutated in camptodactyly-arthropathy-coxa vara-pericarditis syndrome SO NATURE GENETICS LA English DT Article ID ADENOMATOUS POLYPOSIS; FAMILIAL ARTHROPATHY; RHEUMATOID-ARTHRITIS; CONTRACTURES; SYNOVIOCYTES; PATHOLOGY; SYNOVITIS; FEATURES; FINGERS C1 Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ctr Human Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. King Faisal Specialist Hosp & Res Ctr, Riyadh Armed Forces Hosp, Dept Pediat, Riyadh, Saudi Arabia. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh, Saudi Arabia. Case Western Reserve Univ, Dept Orthopaed, Cleveland, OH 44106 USA. Hosp Sick Children, Div Rheumatol, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. Newington Childrens Hosp, Div Rheumatol, Hartford, CT USA. Univ Sao Paulo, Dept Genet, Sao Paulo, Brazil. E Tennessee State Univ, James H Quillen Coll Med, Dept Pediat, Johnson City, TN 37614 USA. Univ Tubingen, Childrens Hosp, Div Rheumatol, Tubingen, Germany. Washington Univ, Dept Pediat, St Louis, MO 63130 USA. St Louis Childrens Hosp, St Louis, MO 63178 USA. Univ Fed Sao Paulo, Paulista Sch Med, Inst Med Genet, Sao Paulo, Brazil. Columbia Univ, Dept Pathol, Inst Canc Genet, New York, NY USA. RP Warman, ML (reprint author), Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. EM mlw14@po.cwru.edu RI Papadopoulos, Nickolas/K-7272-2012; Brunoni, Decio/K-3155-2012; Alonso, Luis/I-2841-2013 OI Alonso, Luis/0000-0002-1704-6676 FU NIAMS NIH HHS [AR43827] NR 31 TC 169 Z9 174 U1 1 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1999 VL 23 IS 3 BP 319 EP 322 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 257QC UT WOS:000083792200021 PM 10545950 ER PT J AU Li, JY Shen, H Himmel, KL Dupuy, AJ Largaespada, DA Nakamura, T Shaughnessy, JD Jenkins, NA Copeland, NG AF Li, JY Shen, H Himmel, KL Dupuy, AJ Largaespada, DA Nakamura, T Shaughnessy, JD Jenkins, NA Copeland, NG TI Leukaemia disease genes: large-scale cloning and pathway predictions SO NATURE GENETICS LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA; LEUKEMIAS; PROTEIN; MICE; TRISTETRAPROLIN; ACTIVATION; NEOPLASMS; FRAGMENTS; LYMPHOMAS C1 NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Univ Minnesota, Ctr Canc, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. JST, PRESTO, Tokyo, Japan. Japanese Fdn Canc Res, Tokyo, Japan. Univ Arkansas Med Sci, Dept Med, Little Rock, AR 72205 USA. RP Copeland, NG (reprint author), NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RI Largaespada, David/C-9832-2014 NR 30 TC 182 Z9 184 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 1999 VL 23 IS 3 BP 348 EP 353 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 257QC UT WOS:000083792200027 PM 10610183 ER PT J AU Arikawa-Hirasawa, E Watanabe, H Takami, H Hassell, JR Yamada, Y AF Arikawa-Hirasawa, E Watanabe, H Takami, H Hassell, JR Yamada, Y TI Perlecan is essential for cartilage and cephalic development SO NATURE GENETICS LA English DT Article ID FIBROBLAST GROWTH-FACTOR; HEPARAN-SULFATE PROTEOGLYCAN; FACTOR RECEPTOR 3; DYSPLASIA TYPE-I; THANATOPHORIC DYSPLASIA; EXPRESSION; ACTIVATION; MUTATIONS; SKELETAL; MEMBRANE C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Shriners Hosp Crippled Children, Tampa, FL 33612 USA. RP Yamada, Y (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. EM yoshi.yamada@nih.gov NR 30 TC 333 Z9 341 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD NOV PY 1999 VL 23 IS 3 BP 354 EP 358 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 257QC UT WOS:000083792200028 PM 10545953 ER PT J AU Strandberg, J AF Strandberg, J TI NIH plans for chimps SO NATURE MEDICINE LA English DT Letter C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Strandberg, J (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 1999 VL 5 IS 11 BP 1217 EP 1217 DI 10.1038/15147 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 305PZ UT WOS:000086550600003 PM 10545960 ER PT J AU Gallucci, S Lolkema, M Matzinger, P AF Gallucci, S Lolkema, M Matzinger, P TI Natural adjuvants: Endogenous activators of dendritic cells SO NATURE MEDICINE LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; MHC CLASS-II; APOPTOTIC CELLS; T-CELLS; EFFICIENT PRESENTATION; ADHESION MOLECULE-1; HOST-DEFENSE; IN-VITRO; ANTIGEN AB Dendritic cells, the most potent antigen-presenting cells, need to be activated before they can function to initiate an immune response. We report here that, in the absence of any foreign substances, dendritic cells can be activated by endogenous signals received from cells that are stressed, virally infected or killed necrotically, but not by healthy cells or those dying apoptotically. Injected in vivo with an antigen, the endogenous activating substances can function as natural adjuvants to stimulate a primary immune response, and they may represent the natural initiators of transplant rejection, spontaneous tumor rejection, and some forms of autoimmunity. C1 NIAID, Ghost Lab, T Cell Tolerance & Memory Sect, Lab Cellular & Mol Immunol,NIH, Bethesda, MD 20892 USA. RP Gallucci, S (reprint author), NIAID, Ghost Lab, T Cell Tolerance & Memory Sect, Lab Cellular & Mol Immunol,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 1180 Z9 1212 U1 2 U2 21 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 NOV PY 1999 VL 5 IS 11 BP 1249 EP 1255 DI 10.1038/15200 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 305PZ UT WOS:000086550600034 PM 10545990 ER PT J AU Mateo, V Lagneaux, L Bron, D Biron, G Armant, M Delespesse, G Sarfati, M AF Mateo, V Lagneaux, L Bron, D Biron, G Armant, M Delespesse, G Sarfati, M TI CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia SO NATURE MEDICINE LA English DT Article ID INTEGRIN-ASSOCIATED PROTEIN; MARROW STROMAL CELLS; B-CELL; INDUCED APOPTOSIS; T-LYMPHOCYTES; IN-VITRO; MONOCLONAL-ANTIBODIES; CROSS-LINKING; TUMOR-CELLS; BCL-2 AB Thrombospondin forms a 'molecular bridge' between phagocytic and apoptotic cells through interaction with alpha v beta 3/CD36. We report here that engagement of CD47, a newly described thrombospondin receptor, by immobilized monoclonal antibody against CD47 or by thrombospondin induced in all B-cell chronic lymphocytic leukemia clones the cytoplasmic features of apoptosis (cell shrinkage, decrease in mitochondrial transmembrane potential and phosphatidylserine externalization) without the nuclear features (chromatin condensation, appearance of single-stranded DNA, DNA fragmentation and cleavage of poly ADP-ribose polymerase). These cytoplasmic events of apoptosis were not prevented by the addition of caspase inhibitor z-VAD-fmk, or by the presence of survival factors (such as interleukin-4 and gamma interferon) or cell activation. Morphological studies confirmed the integrity of the nucleus and showed swelling of the mitochondria. This caspase-independent death pathway may be relevant to the development of alternate therapeutic strategies in chronic lymphocytic leukemia, which remains an incurable disease. C1 Univ Montreal, Hop Notre Dame, Ctr Hosp, Ctr Rech,Lab Allergie, Montreal, PQ H2L 4M1, Canada. Univ Montreal, Hop Notre Dame, Ctr Hosp, Dept Hematol, Montreal, PQ H3C 3J7, Canada. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sarfati, M (reprint author), Univ Montreal, Hop Notre Dame, Ctr Hosp, Ctr Rech,Lab Allergie, 1560 Rue Sherbrooke Est, Montreal, PQ H2L 4M1, Canada. NR 55 TC 149 Z9 151 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 NOV PY 1999 VL 5 IS 11 BP 1277 EP 1284 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 305PZ UT WOS:000086550600038 PM 10545994 ER PT J AU Usdin, TB Hoare, SRJ Wang, T Mezey, E Kowalak, JA AF Usdin, TB Hoare, SRJ Wang, T Mezey, E Kowalak, JA TI TIP39: a new neuropeptide and PTH2-receptor agonist from hypothalamus SO NATURE NEUROSCIENCE LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; RENIN-RELEASING FACTOR; RAT SENSORY NEURONS; PARATHYROID-HORMONE; PTH2 RECEPTOR C1 NIMH, Cell Biol Unit, Genet Lab, Bethesda, MD 20892 USA. NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Cell Biol Unit, Genet Lab, Bldg 36,Room 3D06,36 Convent Dr MSC4094, Bethesda, MD 20892 USA. NR 15 TC 126 Z9 129 U1 1 U2 2 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 NOV PY 1999 VL 2 IS 11 BP 941 EP 943 DI 10.1038/14724 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 259FF UT WOS:000083883300008 PM 10526330 ER PT J AU Rapoport, SI AF Rapoport, SI TI In vivo fatty acid incorporation into brain phospholipids in relation to signal transduction and membrane remodeling SO NEUROCHEMICAL RESEARCH LA English DT Article DE brain; fatty acids; neuroplasticity; signaling; turnover; phospholipids; imaging; lithium ID NUCLEUS BASALIS MAGNOCELLULARIS; ACYL-COA CONCENTRATIONS; PLASMA C-14 PALMITATE; ARACHIDONIC-ACID; RAT-BRAIN; IN-VIVO; DOCOSAHEXAENOIC ACID; ALZHEIMERS-DISEASE; BETA-OXIDATION; AWAKE RATS AB A method and model are described to quantify in vivo turnover rates and half-lives of fatty acids within brain phospholipids. These "kinetic" parameters can be calculated by operational equations from measured rates of incorporation of intravenously injected fatty acid radiotracers into brain phospholipids. To do this, it is necessary to determine a "dilution factor" lambda, which estimates the contribution to the brain precursor acyl-CoA pool of fatty acids released from phospholipids through the action of PLA(1) or PLA(2). Some calculated fatty acid half-lives are minutes to hours, consistent with active participation of phospholipids in brain function and structure. The fatty acid method can be used to identify enzyme targets of drugs acting on phospholipid metabolism. For example, a reduced brain turnover of arachidonate by chronic lithium, demonstrated in rats by the fatty acid method, suggests that this agent, which is used to treat bipolar disorder, has for its target an arachidonate-specific PLA(2). In another context, when combined with in vivo imaging by quantitative autoradiography in rodents or positron emission tomography in macaques or humans, the fatty acid method can localize and quantify normal and modified PLA(2)-mediated signal transduction in brain. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Rapoport, SI (reprint author), NIA, Neurosci Lab, NIH, Bldg 10,Rm 6C-103, Bethesda, MD 20892 USA. NR 86 TC 45 Z9 53 U1 0 U2 0 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 NOV PY 1999 VL 24 IS 11 BP 1403 EP 1415 DI 10.1023/A:1022584707352 PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 250NJ UT WOS:000083394200013 PM 10555781 ER PT J AU Chesebro, B AF Chesebro, B TI Prion protein and the transmissible spongiform encephalopathy diseases SO NEURON LA English DT Review ID SCRAPIE; AGENT; BSE C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. NR 16 TC 69 Z9 69 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1999 VL 24 IS 3 BP 503 EP 506 DI 10.1016/S0896-6273(00)81105-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 259UU UT WOS:000083913000006 PM 10595502 ER PT J AU Schulte, D Furukawa, T Peters, MA Kozak, CA Cepko, CL AF Schulte, D Furukawa, T Peters, MA Kozak, CA Cepko, CL TI Misexpression of the Emx-related homeobox genes cVax and mVax2 ventralizes the retina and perturbs the retinotectal map SO NEURON LA English DT Article ID RECEPTOR TYROSINE KINASES; VISUAL-SYSTEM; CHICK-EMBRYO; TRANSCRIPTION FACTORS; COMMISSURAL AXONS; PROJECTION MAP; EPH RECEPTORS; EYE ANLAGE; IN-VITRO; T-BOX AB The mechanisms that establish the dorsal-ventral (D-V) axis of the eye are poorly understood. We isolated two homeobox genes from mouse and chicken, mVax2 and cVax, whose expression during early eye development is restricted to the ventral retina. In chick, ectopic expression of either Var leads to ventralization of the early retina, as assayed by expression of the transcription factors Pax2 and Tbx5, and the Eph family members EphB2, EphB3, ephrinB1, and ephrinB2, all of which are normally dorsally or ventrally restricted. Moreover, the projections of dorsal but not ventral ganglion cell axons onto the optic tectum showed profound targeting errors following cVax mis-expression, mVax2/cVax thus specify positional identity along the D-V axis of the retina and influence retinotectal mapping. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Cepko, CL (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. OI Schulte, Dorothea/0000-0002-7243-6319 FU NEI NIH HHS [T32 EYO 7110] NR 55 TC 133 Z9 136 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 1999 VL 24 IS 3 BP 541 EP 553 DI 10.1016/S0896-6273(00)81111-3 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 259UU UT WOS:000083913000012 PM 10595508 ER PT J AU Cohen, RM Nordahl, TE Semple, WE Pickar, D AF Cohen, RM Nordahl, TE Semple, WE Pickar, D TI The brain metabolic patterns of clozapine- and fluphenazine-treated female patients with schizophrenia: Evidence of a sex effect SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE striatum; cingulate; deoxyglucose; cerebral metabolic rates; positron emission tomography; neuroleptics ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL GLUCOSE-METABOLISM; DOPAMINE-RECEPTOR BINDING; GENDER DIFFERENCES; SUSTAINED ATTENTION; TREATMENT RESPONSE; CINGULATE CORTEX; BASAL GANGLIA; ABNORMALITIES; NEUROLEPTICS AB The regional cerebral glucose metabolic rates of clozapine-treated and fluphenazine-treated women with schizophrenia and normal controls were obtained by positron emission tomography (PET) using [F-18]-2-fluro-2-deoxy-D-glucose (FDG) as the tracer. The regional metabolic patterns were compared to each other and to the changes previously observed in men. In women, as in men, both clopazine- and fluphenazine-treatment were associated with lower metabolism in the superior prefrontal cortex and higher metabolism in the medial temporal lobe. In both men and women, clozapine treatment led to a greater lowering of inferior prefrontal cortex activity than fluphenazine, which was statistically significant in the larger male cohort. Fluphenazine led to higher metabolic rates in the lateral temporal lobe than clozapine did, but the differences between the two neuroleptics were not statistically significant in either group. The greatest differences in the female as compared to the male responses to fluphenazine and clozapine were in the cingulate and striatum. As compared to controls, the cingulate metabolic rates of women were reduced by 9.1% and 11.4% on clozapine and fluphenazine, respectively; whereas, men have a statistically nonsignificant reduction of 0.1% with clozapine and a 3.2% increase with fluphenazine. In men, fluphenazine was associated with a much greater elevation in basal ganglia metabolic rates than was clozapine, 23.5% as compared to 3.75%; whereas, in women, basal ganglia metabolic rates are nearly equally increased by fluphenazine (21.6%) and clozapine (15.1%). [Neuropsychopharmacology 21:632-640, 1999] Published by Elsevier Science Inc. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Univ Calif Davis, Med Ctr, Davis, CA 95616 USA. Napa State Hosp, Napa, CA USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. VAMC, Cleveland, OH USA. RP Cohen, RM (reprint author), NIH, Clin Brain Imaging Sect, LCM, Bldg 36,Room 1A05,36 Convent Dr,MSC 4030, Bethesda, MD 20892 USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 52 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 1999 VL 21 IS 5 BP 632 EP 640 DI 10.1016/S0893-133X(99)00065-2 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 240CJ UT WOS:000082807900004 PM 10516959 ER PT J AU Ashur-Fabian, O Sigalov, E Brenneman, DE Gozes, I AF Ashur-Fabian, O Sigalov, E Brenneman, DE Gozes, I TI NAP, a superactive neuroprotective peptide increases NO production in neuro-glial cells SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 NICHD, Sect Mol & Dev Pharmacol, LDN, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Dept Clin Biochem, Sackler Fac Med, IL-69978 Tel Aviv, Israel. 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S3 EP S3 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300013 ER PT J AU Blank, PS Coorssen, JR Epstein, J Harari, E Meiri, H Rahamimoff, R Raveh, A Zimmerberg, J AF Blank, PS Coorssen, JR Epstein, J Harari, E Meiri, H Rahamimoff, R Raveh, A Zimmerberg, J TI FLUO-4 fluorescence dynamics in docked secretory vesicles of sea urchin eggs SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Bernard Katz Minerva Ctr Cell Biophys, Dept Physiol, IL-91010 Jerusalem, Israel. 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S9 EP S10 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300039 ER PT J AU Furman, S Perl, O Bassan, M Rubinraut, S Fridkin, M Brenneman, DE Gozes, I AF Furman, S Perl, O Bassan, M Rubinraut, S Fridkin, M Brenneman, DE Gozes, I TI The novel VIP analogue, stearyl-KKYL-NH2 protects neurons against beta-amyloid toxicity independently of glial cells SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. NICHD, LDN, Sect Dev & Mol Pharmacol, NIH, Bethesda, MD 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S17 EP S17 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300072 ER PT J AU Gershon, E Wu, TX Shir, Y Vatine, JJ Brautbar, H Zeltser, R Dokkens, C Israel, S Azaria, M Max, M Johnson, E Diehl, SR Seltzer, Z AF Gershon, E Wu, TX Shir, Y Vatine, JJ Brautbar, H Zeltser, R Dokkens, C Israel, S Azaria, M Max, M Johnson, E Diehl, SR Seltzer, Z TI Phantom limb pain in Israeli Jewish veteran amputees may be associated with a locus on chromosome 6P21 SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Hebrew Univ Jerusalem, Fac Med Dent, IL-91120 Jerusalem, Israel. NIDCR, NIH, Bethesda, MD USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Ctr Med Genet, Marshfield, WI USA. Chaim Sheba Med Ctr, Tel Hashomer, Israel. Barrow Neurol Inst, Phoenix, AZ 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S17 EP S17 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300075 ER PT J AU Gozes, I Zamostiano, R Pinhasov, A Bassan, M Giladi, E Steingart, RA Brenneman, DE AF Gozes, I Zamostiano, R Pinhasov, A Bassan, M Giladi, E Steingart, RA Brenneman, DE TI A novel VIP-responsive, gene: Activity-dependent neuroprotective protein (ADNP) SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NICHD, LDN, Sect Mol & Dev Pharmacol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S18 EP S18 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300079 ER PT J AU Kronfeld, I Appel, E Lorenzo, PS Blumberg, PM Brodie, C AF Kronfeld, I Appel, E Lorenzo, PS Blumberg, PM Brodie, C TI Phosphorylation of PKC delta on specific tyrosine residues exerts selective effects on glial cell proliferation and differentiation. SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Bar Ilan Univ, Dept Life Sci, IL-52900 Ramat Gan, Israel. NCI, LCCTP, Mol Mechanisms Tumor Promot Sect, NIH, 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S25 EP S26 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300109 ER PT J AU Leker, RR Teichner, A Grigoriadis, N Brenneman, DE Gozes, I AF Leker, RR Teichner, A Grigoriadis, N Brenneman, DE Gozes, I TI The octapeptide NAP exerts neuroprotection in a model of focal cerebral ischemia by reducing apoptosis. SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Neurol, IL-91010 Jerusalem, Israel. NICHD, Sect Dev & Mol Pharmacol, LDN, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S26 EP S26 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300111 ER PT J AU Royak, Y Mandel, S Bick, T Green, J Jacobson, KA Youdim, MBH AF Royak, Y Mandel, S Bick, T Green, J Jacobson, KA Youdim, MBH TI Adenosine receptor A(2A) antagonists as neuroprotective agents: Possible involvement of calcium SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Technion Israel Inst Technol, Fac Med, US Natl Parkinson Fdn, Ctr Neurodegenerat Dis, Haifa, Israel. NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA. Technion Israel Inst Technol, Fac Med, Eve Topf Ctr Neurodegenerat Dis, Haifa, Israel. 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S35 EP S35 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300151 ER PT J AU Sigalov, E Steingart, RA Fridkin, M Brenneman, DE Gozes, I AF Sigalov, E Steingart, RA Fridkin, M Brenneman, DE Gozes, I TI Protection by neuropeptides against ischemic/hypoxic injury SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Tel Aviv Univ, Sackler Fac Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. NICHD, Sect Dev & Mol Pharmacol, LDN, NIH, Bethesda, MD 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S38 EP S38 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300165 ER PT J AU Steingart, RA Solomon, B Brenneman, DE Fridkin, M Gozes, I AF Steingart, RA Solomon, B Brenneman, DE Fridkin, M Gozes, I TI VIP and activity-dependent neurotrophic factor protect against oxidative stress in PC12 cell culture. SO NEUROSCIENCE LETTERS LA English DT Meeting Abstract C1 Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Dept Mol Microbiol Biotechnol, IL-69978 Tel Aviv, Israel. NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD USA. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. 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 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV PY 1999 SU 54 BP S39 EP S39 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 263AK UT WOS:000084100300169 ER PT J AU Dadachova, E Chappell, LL Brechbiel, MW AF Dadachova, E Chappell, LL Brechbiel, MW TI Spectrophotometric method for determination of bifunctional macrocyclic ligands in macrocyclic ligand-protein conjugates SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE polyazamacrocycles; antibodies; spectrophotometry; radioimmunotherapy; radiolabeling; conjugates ID MONOCLONAL-ANTIBODIES; TUMOR; STABILITY; COMPLEXES; RADIOIMMUNOTHERAPY; RADIOMETALS; DIAGNOSIS; CHELATE; THERAPY; AGENTS AB A simple spectrophotometric assay for determination of bifunctional polyazacarboxylate-macrocyclic ligands of different sizes that are conjugated to proteins has been developed for: 12-membered macrocycle DOTA (2[4 nitrobenzyl]-1, 4, 7, 10-tetraazacyclododecane-N, N',N", N"'-tetraacetic acid) and analogs, the 15-membered PEPA macrocycle (2-[4-nitrobenzyl]-1,4,7,10,13-pentaazacyclopentadecane-N,N',N",N''',N""-pentaacetic acid), and the large 18 membered macrocycle HEHA (1,4,7,10,13,16-hexaazacyclooctadecane-N,N',N",N"',N"",N""'-pentaacetic acid). The method is based on titration of the blue-colored 1:1 Pb(II)-Arsenazo III (AAIII) complex with the polyazacarboxylate macrocyclic ligand in the concentration range of 0-2.5 mu M, wherein color change occurring upon transchelation of the Pb(II) from the AAIII to the polyazamacrocyclic ligand is monitored at 656 nm. The assay is performed at ambient temperature within 20 min without any interfering interaction between the protein and Pb(II)-AA(III) complex. Thus, this method also provides a ligand-to-protein ratio (VP ratio) that reflects the effective number of ligands per protein molecule available to radiolabeling. The method is not suitable for 14-membered TETA macrocycle 2-[4-nitrobenzyl]-1, 4, 8, 11-tetraazacyclotetradecane N,N',N",N"'-tetraacetic acid) because of low stability constant of Pb(II)-TETA complex. The method is rapid, simple and may be customized for other polyazacarboxylate macrocyclic ligands. Published by Elsevier Science Inc. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Dadachova, E (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. RI Dadachova, Ekaterina/I-7838-2013 NR 22 TC 41 Z9 42 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 1999 VL 26 IS 8 BP 977 EP 982 DI 10.1016/S0969-8051(99)00054-2 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 275YP UT WOS:000084848200016 PM 10708314 ER PT J AU Mezhevaya, K Winters, TA Neumann, RD AF Mezhevaya, K Winters, TA Neumann, RD TI Gene targeted DNA double-strand break induction by I-125-labeled tripler-forming oligonucleotides is highly mutagenic following repair in human cells SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MULTIPLY DAMAGED SITES; COLI ENDONUCLEASE-III; GROUP NO 6; MAMMALIAN-CELLS; HELIX FORMATION; ILLEGITIMATE RECOMBINATION; BIOLOGICAL CONSEQUENCES; ABASIC SITES; BASE-PAIRS; I-125 AB A parallel binding motif 16mer tripler-forming oligonucleotide (TFO) complementary to a polypurine-polypyrimidine target region near the 3'-end of the SupF gene of plasmid pSP189 was labeled with [5-I-125]dCMP at position 15. Following tripler formation and decay accumulation, radiation-induced site-specific double-strand breaks (DSBs) were produced in the pSP189 SupF gene, Bulk damaged DNA and the isolated site-specific DSB-containing DNA were separately transfected into human WI38VA13 cells and allowed to repair prior to recovery and analysis of mutants. Bulk damaged DNA had a relatively low mutation frequency of 2.7 x 10(-3), In contrast, the isolated linear DNA containing site-specific DSBs had an unusually high mutation frequency of 7.9 x 10(-1), This was nearly 300-fold greater than that observed for the bulk damaged DNA mixture, and >1.5 x 10(4)-fold greater than background, The mutation spectra displayed a high proportion of deletion mutants targeted to the I-125 binding position within the SupF gene for both bulk damaged DNA and isolated linear DNA, Both spectra were characterized by complex mutations with mixtures of changes, However, mutations recovered from the linear site-specific DSB-containing DNA presented a much higher proportion of complex deletion mutations. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. RP Winters, TA (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bldg 10, Bethesda, MD 20892 USA. NR 61 TC 20 Z9 20 U1 1 U2 1 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 NOV 1 PY 1999 VL 27 IS 21 BP 4282 EP 4290 DI 10.1093/nar/27.21.4282 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 253BB UT WOS:000083535800022 PM 10518622 ER PT J AU Cocco, P Ward, MH Dosemeci, M AF Cocco, P Ward, MH Dosemeci, M TI Risk of stomach cancer associated with 12 workplace hazards: analysis of death certificates from 24 states of the United States with the aid of job exposure matrices SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE stomach; neoplasms; occupational exposure ID GASTRIC-CANCER; MONTREAL; DUSTS AB Objective-To investigate the risk of gastric cancer associated with 12 workplace exposures suspected or discussed as aetiological agents in previous reports. Methods-A case-control study was conducted based on the death certificates of several million deaths in 24 states of the United States in 1984-96. Overall, the data base included 41 957 deaths from stomach cancer among subjects aged greater than or equal to 25 years. These were 20 878 white men, 14 125 white women, 4215 African American men, and 2739 African American women. Two controls for each case were selected from among subjects who died from nonmalignant diseases, frequency matched to cases by geographic region, race, sex and 5 year age group. Each three digit occupation and industry code listed in the 1980 United States census was classified for probability and intensity of exposure to asbestos, inorganic dust, metals, lead, polycyclic aromatic hydrocarbons (PAHs), nitrogen oxides, nitrosamines, sulphuric acid, fertilisers, herbicides, other pesticides (including insecticides and fungicides), and wood dust. These job exposure matrices were subsequently applied to the occupation-industry combinations in the death certificates off study subjects, separately by sex and race. Results-Risk of stomach cancer showed a modest association with occupational exposure to inorganic dust (odds ratio (OR)=1.06; 95% confidence interval (95% CI) 1.03 to 1.11) with significant increasing trends by probability and intensity of exposure overall and by cross classification of the two exposure metrices. Workplace exposure to nitrosamines also showed a modest association (OR=1.06; 95% CI 1.01 to 1.11), but the excess risk was even smaller after adjusting for inorganic dust exposure. Risk of gastric cancer was not associated with any of the other workplace exposures considered in this study. Conclusions-Non-differential misclassification of exposure may have caused negative findings in this study, and inorganic dust may be a partial surrogate for exposure to other unknown risk factors. Alternatively, our results suggest that occupational factors contribute little to the aetiology of gastric cancer. Inorganic dust might act through non-specific mechanisms, similar to those proposed for salt, aspirin, and heat by other authors. C1 Univ Cagliari, Ist Med Lavoro, I-09124 Cagliari, Italy. NCI, Div Canc Epidemiol & Genet, Occupat Epidemiol Branch, NIH, Bethesda, MD USA. RP Cocco, P (reprint author), Univ Cagliari, Ist Med Lavoro, Via San Giorgio 12, I-09124 Cagliari, Italy. NR 20 TC 14 Z9 16 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD NOV PY 1999 VL 56 IS 11 BP 781 EP 787 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 248CC UT WOS:000083256900012 PM 10658565 ER PT J AU Sheikh, MS Fornace, AJ AF Sheikh, MS Fornace, AJ TI Regulation of translation initiation following stress SO ONCOGENE LA English DT Review DE translation initiation; eIF2; eIF3; eIF5; eIF1(A121/SU11); translation checkpoints ID ACTIVATED PROTEIN-KINASE; DAMAGE-INDUCIBLE TRANSCRIPTS; HERPES-SIMPLEX VIRUS; BJA-B CELLS; DNA-DAMAGE; INDUCED APOPTOSIS; PREMATURE SHUTOFF; GROWTH ARREST; ALPHA-SUBUNIT; RNA AB Recent studies suggest that genotoxic and non-genotoxic stresses appear to invoke translational checkpoints in order,to inhibit protein synthesis. Depending on the stress and/or cell type, this downregulation of protein synthesis may either (i) protect against the deleterious effects of noxious agents and ensure the conservation of resources that are needed to survive under adverse conditions or (ii) activate apoptosis, In this article, we have reviewed several lines of evidence which support the notion that regulation of translation initiation is an important component of the cellular stress response. While the stress-induced post-translational regulation of translation initiation factors (eIFs) has been well documented, stress-induced regulation of eIFs at the mRNA levels, as review ed here, is only beginning to be elucidated. Thus, the stress-mediated regulation of eIFs occurs at multiple different levels involving, transcriptional, post-transcriptional and post-translational controls. C1 NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Sheikh, MS (reprint author), NCI, Div Basic Sci, NIH, Bldg 37,Room 5CO9, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 57 TC 78 Z9 78 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 1 PY 1999 VL 18 IS 45 SI SI BP 6121 EP 6128 DI 10.1038/sj.onc.1203131 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 251LL UT WOS:000083447100006 PM 10557103 ER PT J AU Kupfer, C AF Kupfer, C TI The Low Vision Education Program: Improving quality of life SO OPTOMETRY AND VISION SCIENCE LA English DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Kupfer, C (reprint author), NEI, NIH, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD NOV PY 1999 VL 76 IS 11 BP 729 EP 730 DI 10.1097/00006324-199911000-00001 PG 2 WC Ophthalmology SC Ophthalmology GA 255ZP UT WOS:000083700300001 PM 10566856 ER PT J AU Eliav, E Herzberg, U Ruda, MA Bennett, GJ AF Eliav, E Herzberg, U Ruda, MA Bennett, GJ TI Neuropathic pain from an experimental neuritis of the rat sciatic nerve SO PAIN LA English DT Article DE carrageenan; complete Freund's adjuvant; neuropathic pain; sciatic nerve ID NECROSIS-FACTOR-ALPHA; PRIMARY AFFERENT-FIBERS; PERIPHERAL NEUROPATHY; THERMAL HYPERALGESIA; INFLAMMATORY HYPERALGESIA; BEHAVIORAL EVIDENCE; VASCULAR PATHOLOGY; CCI NEUROPATHY; SENSATION LIKE; MODEL AB Painful peripheral neuropathies involve both axonal damage and an inflammation of the nerve. The role of the latter by itself was investigated by producing an experimental neuritis in the rat. The sciatic nerves were exposed at mid-thigh level and wrapped loosely in hemostatic oxidized cellulose (Oxycel(TM)) that on one side was saturated with an inflammatory stimulus, carrageenan (CARRA) or complete Found's adjuvant (CFA), and on the other side saturated with saline. In other rats, a myositis was created by implanting Oxycel saturated with CFA into a pocket made in the biceps femoris at a position adjacent to where the nerve was treated. Pain-evoked responses from the plantar hind paws were tested before treatment and daily thereafter. Statistically significant heat- and mechano-hyperalgesia, and mechano- and cold-allodynia were present on the side of the inflamed nerve (CARRA or CFA) for 1-5 days after which responses returned to normal. There were no abnormal pain responses on the side of the saline-treated nerve, and none in the rats with the experimental myositis. The abnormal pain responses were inhibited by N-methyl-D-aspartate receptor blockade with MK-801, but were relatively resistant to the dose of morphine tested (10 mg/kg). Light microscopic examination of CARRA-treated nerves, harvested at the time of peak symptom severity, revealed that the treated region was mildly edematous and that there was an obvious endoneurial infiltration of immune cells (granulocytes and lymphocytes). There was either a complete absence of degeneration, or the degeneration of no more than a few tens of axons. Immunocytochemical staining for CD4 and CD8 T-lymphocyte markers revealed that both cell types were present in the epineurial and endoneurial compartments. The endoneurial T-cells appeared to derive from the endoneurial vasculature, rather than from migration across the nerve sheath. We conclude that a focal inflammation of the sciatic nerve produces neuropathic pain sensations in a distant region (the ipsilateral hind paw) and that this is not due to axonal damage. The neuropathic pain is specific to inflammation of the nerve because it was absent in animals with the experimental myositis and in those receiving sham-treatment. These results suggest that an acute episode of neuritis-evoked neuropathic pain may contribute to the genesis of chronically painful peripheral neuropathies, and that a chronic (or chronically recurrent) focal neuritis might produce neuropathic pain in the absence of significant (or clinically detectable) structural damage to the nerve. The model that we describe is likely to be useful in the study of the neuroimmune factors that contribute to painful peripheral neuropathies. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Med Coll Penn & Hahnemann Univ, Dept Neurol, Philadelphia, PA 19102 USA. NIDR, Neurobiol & Anesthesiol Branch, Bethesda, MD 20892 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Bennett, GJ (reprint author), Med Coll Penn & Hahnemann Univ, Dept Neurol, Philadelphia, PA 19102 USA. NR 61 TC 157 Z9 162 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 1999 VL 83 IS 2 BP 169 EP 182 DI 10.1016/S0304-3959(99)00102-5 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 253JY UT WOS:000083554500007 PM 10534588 ER PT J AU Gear, RW Miaskowski, C Gordon, NC Paul, SM Heller, PH Levine, JD AF Gear, RW Miaskowski, C Gordon, NC Paul, SM Heller, PH Levine, JD TI The kappa opioid nalbuphine produces gender- and dose-dependent analgesia and antianalgesia in patients with postoperative pain SO PAIN LA English DT Article DE opioids; dose response; placebo; men; women; third molars ID MORPHINE-TOLERANT RATS; PLACEBO ANALGESIA; RECEPTOR; DYNORPHIN; EFFICACY; AGONIST; PHARMACOKINETICS; ANTAGONISM; MECHANISM; NALOXONE AB Nalbuphine, pentazocine, and butorphanol, mixed agonist/antagonist opioids that induce analgesia by acting predominantly at kappa opioid receptors, have recently been shown in single-dose studies to have greater analgesic efficacy in women than in men. In the current experiments, the first placebo controlled dose response study of opioid analgesic efficacy that examines for gender differences, nalbuphine (5, 10, or 20 mg) and placebo were evaluated in 62 men and 69 women for the treatment of moderate to severe postoperative pain following extraction of impacted wisdom teeth. In a randomized, open injection, double blind experimental design, pain intensity was recorded on a 10 cm visual analog scale (VAS) immediately prior to drug administration (baseline) and at 20 min intervals thereafter. Although responses to placebo were similar in men and women, for all doses of nalbuphine women exhibited significantly greater analgesic response than men, compatible with our previous results. Unexpectedly, men receiving the 5 mg dose of nalbuphine experienced significantly greater pain than those receiving placebo; only the 20 mg dose of nalbuphine in men produced significant analgesia compared to placebo. While a similar antianalgesic effect was not observed in women, only the 10 mg dose of nalbuphine produced significant analgesia compared to placebo. These results suggest that the optimal analgesic dose of nalbuphine for women is lower than the highest dose that can be safely administered. In contrast, the antianalgesic effect of nalbuphine suggests avoidance of its routine use for postoperative analgesia in men until further studies clarify this issue. Because gender differences in other mixed kappa agonists/antagonists (i.e. pentazocine and butorphanol) have previously been shown, these results may generally apply to this class of opioid analgesics. (C) 1999 International Association for the Study of Pain. Published by Elsevier Science B.V. C1 Univ Calif San Francisco, Ctr Orofacial Pain, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Grad Program Neurosci, San Francisco, CA 94143 USA. Kaiser Fdn Hosp, Hayward, CA USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Levine Res Unit, Box 0440,521 Parnassus Ave,Room C-522, San Francisco, CA 94143 USA. FU NINR NIH HHS [NR03923] NR 28 TC 152 Z9 159 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 1999 VL 83 IS 2 BP 339 EP 345 DI 10.1016/S0304-3959(99)00119-0 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 253JY UT WOS:000083554500026 PM 10534607 ER PT J AU Bendon, RW Faye-Petersen, O Pavlova, Z Qureshi, F Mercer, B Miodovnik, M Das, AF Meis, PJ Moawad, AH Iams, JD McNellis, D AF Bendon, RW Faye-Petersen, O Pavlova, Z Qureshi, F Mercer, B Miodovnik, M Das, AF Meis, PJ Moawad, AH Iams, JD McNellis, D CA Natl Inst Child Hlth Human Dev Maternal TI Fetal membrane histology in preterm premature rupture of membranes: Comparison to controls, and between antibiotic and placebo treatment SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE placenta; histology; premature rupture of membranes AB The objectives of this study were to test the hypotheses that antibiotic therapy will alter the histologic appearance of fetal membranes in preterm premature rupture of membranes (pPROM), and that the membrane histology will demonstrate distinct differences between term and preterm rupture of membranes. We also wished to test interobserver variability of pathologists. Placental membranes were sampled from 268 women participating in a randomized placebo-controlled trial of antibiotic therapy for pPROM at 24-32 weeks of gestation (cases) and from 4 control groups who were not in the randomized trial: (1) preterm labor without pPROM (n = 21), (2) term labor (n = 65), (3) term FROM (n = 21), and (4) term cesarean section (n = 27). The cases and controls were scored for 40 histologic features by pathologists blinded to the identity of each sample (case or control). pPROM histology of samples from patients receiving antibiotics and those receiving placebo was compared using a chi-squared test and with control groups using logistic regression. There were no histological differences between pPROM cases treated with antibiotic and those receiving placebo, nor with respect to duration of membrane rupture greater or less than 48 h. Concordance among pathologists was low for features other than acute inflammation. Logistic regression analysis controlled for race and pathologist, and demonstrated that all of the control groups had significantly fewer common markers of acute inflammation when compared with the pPROM. cases. This study suggests that histopathologic evidence of infection is seen more frequently with pPROM than in preterm or term controls. The histologic features used in this study cannot be used to determine the effectiveness of antibiotic therapy. C1 Kosair Childrens Hosp, Dept Pathol, Louisville, KY 40232 USA. Univ Alabama, Birmingham, AL USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Wayne State Univ, Detroit, MI USA. Univ Tennessee, Memphis, TN USA. Univ Cincinnati, Cincinnati, OH USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Ohio State Univ, Columbus, OH 43210 USA. NICHHD, Bethesda, MD 20892 USA. RP Bendon, RW (reprint author), Kosair Childrens Hosp, Dept Pathol, 213 E Chestnut St, Louisville, KY 40232 USA. FU NICHD NIH HHS [HD21410, HD21414, HD21434] NR 7 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD NOV-DEC PY 1999 VL 2 IS 6 BP 552 EP 558 PG 7 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 244FV UT WOS:000083041900007 PM 10508879 ER PT J AU Liow, K Spanaki, MV Boyer, RS Greenlee, JE Bale, JF AF Liow, K Spanaki, MV Boyer, RS Greenlee, JE Bale, JF TI Bilateral hippocampal encephalitis caused by enteroviral infection SO PEDIATRIC NEUROLOGY LA English DT Article ID RAPID RECOVERY AB Nonpolio enteroviral encephalitis usually presents as a diffuse, generalized encephalitis. Focal cerebral involvement by nonpolioviruses is uncommon, and neuroradiologic studies in these cases are usually normal. The authors present a case of a 5-year-old male with an acute encephalitic illness and bilateral lesions of the hippocampi on magnetic resonance imaging. Enteroviral nucleic acids were detected in the cerebrospinal fluid by the reverse transcription polymerase chain reaction. The findings suggest that enteroviral infection should be considered in the differential diagnosis of acute bilateral hippocampal encephalitis in patients in whom polymerase chain reaction fails to demonstrate the presence of herpes simplex virus. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Utah, Sch Med, Dept Pediat Med Imaging, Salt Lake City, UT USA. Univ Utah, Sch Med, Vet Affairs Med Ctr, Neurol Serv, Salt Lake City, UT USA. Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT USA. RP Liow, K (reprint author), NINDS, NIH, Bldg 10-5N250,10 Ctr Dr,MSC 1402, Bethesda, MD 20892 USA. NR 7 TC 10 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD NOV PY 1999 VL 21 IS 5 BP 836 EP 838 DI 10.1016/S0887-8994(99)00083-1 PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 257YM UT WOS:000083810400012 PM 10593677 ER PT J AU Baker, SS Flores, CA Georgieff, MK Jacobson, MS Jaksic, T Krebs, NF AF Baker, SS Flores, CA Georgieff, MK Jacobson, MS Jaksic, T Krebs, NF CA Comm Nutr TI Calcium requirements of infants, children, and adolescents SO PEDIATRICS LA English DT Article ID BONE-MINERAL DENSITY; DIETARY CALCIUM; SKELETAL MASS; SUPPLEMENTATION; GIRLS; RATES; ABSORPTION; RICKETS; GROWTH; OSTEOPOROSIS AB This statement is intended to provide pediatric caregivers with advice about the nutritional needs of calcium of infants, children, and adolescents. It will review the physiology of calcium metabolism and provide a review of the data about the relationship between calcium intake and bone growth and metabolism. In particular, it will focus on the large number of recent studies that have identified a relationship between childhood calcium intake and bone mineralization and the potential relationship of these data to fractures in adolescents and the development of osteoporosis in adulthood. The specific needs of children and adolescents with eating disorders are not considered. C1 USDA, Washington, DC 20250 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NICHHD, Bethesda, MD 20205 USA. NIDDKD, Bethesda, MD 20205 USA. US FDA, Rockville, MD 20857 USA. NR 43 TC 89 Z9 95 U1 0 U2 4 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 NOV PY 1999 VL 104 IS 5 BP 1152 EP 1157 PG 6 WC Pediatrics SC Pediatrics GA 251LW UT WOS:000083448000021 PM 10545566 ER PT J AU Stoll, BJ Temprosa, M Tyson, JE Papile, LA Wright, LL Bauer, CR Donovan, EF Korones, SB Lemons, JA Fanaroff, AA Stevenson, DK Oh, W Ehrenkranz, RA Shankaran, S Verter, J AF Stoll, BJ Temprosa, M Tyson, JE Papile, LA Wright, LL Bauer, CR Donovan, EF Korones, SB Lemons, JA Fanaroff, AA Stevenson, DK Oh, W Ehrenkranz, RA Shankaran, S Verter, J TI Dexamethasone therapy increases infection in very low birth weight infants SO PEDIATRICS LA English DT Article; Proceedings Paper CT 1998 Annual Meeting of the Pediatric-Academic-Societies CY MAY 01-05, 1998 CL NEW ORLEANS, LOUISIANA SP Pediat Acad Soc DE very low birth weight; dexamethasone; nosocomial infection ID CHRONIC LUNG-DISEASE; RESPIRATORY-DISTRESS SYNDROME; BRONCHOPULMONARY DYSPLASIA; CONTROLLED TRIAL; PRETERM INFANTS; FOLLOW-UP; DEPENDENT INFANTS; PREMATURE-INFANTS; COLONIZATION; MULTICENTER AB Background. Infection is a major complication of preterm infants, resulting in increased morbidity and mortality. We recently reported the results of a multicenter trial of dexamethasone initiated at 14 or 28 days in very low birth weight (VLBW) infants who were at risk for chronic lung disease; the results showed an increase in nosocomial bacteremia in the group receiving dexamethasone. This study is an in-depth analysis of bacteremia/sepsis and meningitis among infants enrolled in the trial. Methods. Data on cultures performed and antibiotic therapy were collected prospectively. Infections were classified as definite or possible/clinical. Results. A total of 371 infants were enrolled in the trial. There were no baseline differences in risk factors for infection. For the first 14 days of study, infants received either dexamethasone (group I, 182) or placebo (group II, 189). During this period, infants in group I were significantly more likely than those in group II to have a positive blood culture result (48% vs 30%) and definite bacteremia/sepsis/meningitis (22% vs 14%). Over the 6-week study period, 47% of those cultured had at least one positive blood culture result (53% in group I vs 41% in group II) and 25% of the infants had at least one episode of definite bacteremia/sepsis/meningitis (29% in group I vs 21% in group II). Among infants with definite infections, 46.8% were attributable to Gram-positive organisms, 26.6% to Gram-negative organisms and 26.6% to fungi. The factors present at randomization were evaluated for their association with infection. Group I assignment and H-2 blocker therapy (before study entry) were associated with increased risk of definite infection, whereas cesarean section delivery and increasing birth weight were associated with decreased risk. Conclusions. Infants who received a 14-day course of dexamethasone initiated at 2 weeks of age were more likely to develop a bloodstream or cerebrospinal fluid infection while on dexamethasone therapy than were those who received placebo. Physicians must consider this increased risk of infection when deciding whether to treat VLBW infants with dexamethasone. C1 Emory Univ, Atlanta, GA 30322 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ New Mexico, Albuquerque, NM 87131 USA. NICHHD, Bethesda, MD 20892 USA. Univ Miami, Miami, FL 33152 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Tennessee, Memphis, TN USA. Indiana Univ, Indianapolis, IN 46204 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Stanford Univ, Stanford, CA 94305 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Yale Univ, New Haven, CT USA. Wayne State Univ, Detroit, MI USA. RP Stoll, BJ (reprint author), Emory Univ, Sch Med, Grady Mem Hosp, 80 Butler St SE,Box 26015, Atlanta, GA 30335 USA. FU NICHD NIH HHS [U10 HD27851, U01 HD19897, U01 HD21373] NR 29 TC 44 Z9 45 U1 0 U2 0 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 NOV PY 1999 VL 104 IS 5 AR e63 DI 10.1542/peds.104.5.e63 PG 7 WC Pediatrics SC Pediatrics GA 251LW UT WOS:000083448000043 PM 10545589 ER PT J AU Bekersky, I Boswell, GW Hiles, R Fielding, RM Buell, D Walsh, TJ AF Bekersky, I Boswell, GW Hiles, R Fielding, RM Buell, D Walsh, TJ TI Safety and toxicokinetics of intravenous liposomal amphotericin B (AmBisome (R)) in beagle dogs SO PHARMACEUTICAL RESEARCH LA English DT Article DE amphotericin B; liposomes; pharmacokinetics; tissue distribution; toxicity; toxicokinetics ID FUNGAL-INFECTIONS; LIPID COMPLEX; FORMULATION; PHARMACOKINETICS; CRYPTOCOCCOSIS; EFFICACY; CANCER; MICE AB Purpose. Amphotericin B (AmB) in small, unilamellar liposomes (AmBisome(R)) has an improved therapeutic index, and altered pharmacokinetics. The repeat-dose safety and toxicokinetic profiles of AmBisome were studied at clinically relevant doses. Methods. Beagle dogs (5/sex/group) received intravenous AmBisome (0.25, 1, 4, 8, and 16 mg/kg/day), empty liposomes or vehicle for 30 days. AmB was determined in plasma on days 1, 14, and 30, and in tissues on day 31. Safety parameters included body weight, clinical chemistry, hematology and microscopic pathology. Results. Seventeen of twenty animals receiving 8 and 16 mg/kg were sacrificed early due to weight loss caused by reduced food intake. Dose-dependent renal tubular nephrosis, and other effects characteristic of conventional AmB occurred at 1 mg/kg/day or higher. Although empty liposomes and AmBisome increased plasma cholesterol, no toxicities unique to AmBisome were revealed. Plasma ultrafiltrates contained no AmB. AmBisome achieved plasma levels 100-fold higher than other AmB formulations. AmBisome kinetics were non-linear, with clearance and distribution volumes decreasing with increasing dose. This, and nonlinear tissue uptake, suggest AmBisome disposition was saturable. Conclusions. AmBisome has the same toxic effects as conventional AmB, but they appear at much higher plasma exposures. AmBisome's non-linear pharmacokinetics are not associated with increased risk, as toxicity increases linearly with dosage. Dogs tolerated AmBisome with minimal to moderate changes in renal function at doses (4 mg/kg/day) producing peak plasma concentrations of 18-94 mu g/mL. C1 Fujisawa Healthcare Inc, Deerfield, IL 60015 USA. MDS Harris Labs, Lincoln, NE USA. Amylin Pharmaceut Inc, San Diego, CA USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Bekersky, I (reprint author), Fujisawa Healthcare Inc, 3 Pkwy N, Deerfield, IL 60015 USA. NR 24 TC 41 Z9 42 U1 1 U2 4 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 NOV PY 1999 VL 16 IS 11 BP 1694 EP 1701 DI 10.1023/A:1018997730462 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 254BE UT WOS:000083591000005 PM 10571274 ER PT J AU Linden, P Lee, L Walsh, TJ AF Linden, P Lee, L Walsh, TJ TI Retrospective analysis of the dosage of amphotericin B lipid complex for the treatment of invasive fungal infections SO PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Focus on Fungal Infection 7 CY MAR 13-15, 1997 CL SAN ANTONIO, TEXAS ID CANDIDA INFECTIONS AB Study Objective. To understand the relationship between dosage and therapeutic response of amphotericin B lipid complex (ABLC) by analyzing underlying diseases, types of infections, and therapeutic outcomes with different dosages as second-line antifungal therapy. Design. Retrospective analysis of low-dose (initial dose less than or equal to 3 mg/kg) ABLC from three open-label, clinical, second-line treatment studies. Setting. Centers in the United States (204), Canada (3), Australia (I), Mexico (1), and The Netherlands (I). Patients. Five hundred fifty-one patients (5 enrolled twice) with invasive fungal infections, of whom 289 failed and 267 were intolerant to conventional antifungal therapy. Interventions. Patients were to receive the recommended dosage of ABLC 5 mg/kg/day, with dosage reduction for markedly increased serum creatinine. The duration of treatment was 4 weeks; therapy could be extended if the investigator considered additional treatment necessary. Measurements and Main Results. Seventy-three patients (13%) received ABLC 3 mg/kg/day (low dosage) instead of the protocol-recommended 5 mg/kg/day. Response was 65% and 56%, respectively. Logistic regression analysis revealed that the following patients are most likely to start therapy at the lower dosage: those with candidiasis and other yeast infections, patients with nephrotoxicity due to prior amphotericin B, and those with underlying conditions other than hematologic malignancy. Conclusion. These results suggest that ABLC 3 mg/kg/day may be effective in treating patients with candidiasis who do not have hematologic malignancy. C1 Univ Pittsburgh, Med Ctr, Div Crit Care Med, Pittsburgh, PA 15213 USA. Liposome Co Inc, Princeton, NJ USA. NCI, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Linden, P (reprint author), Univ Pittsburgh, Med Ctr, Div Crit Care Med, Scaife Hall,Room 638,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 13 TC 20 Z9 21 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 1999 VL 19 IS 11 BP 1261 EP 1268 DI 10.1592/phco.19.16.1261.30870 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 251RH UT WOS:000083458300005 PM 10555932 ER PT J AU Tomasic, J Spoljar, B Ljevakovic, D Glaudemans, CPJ AF Tomasic, J Spoljar, B Ljevakovic, D Glaudemans, CPJ TI Preparation of novel conjugates involving immunomodulating peptidoglycan monomer SO PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY LA English DT Article ID BUILT-IN ADJUVANTICITY; GROUP-C POLYSACCHARIDE; INFLUENZAE TYPE-B; CRYPTOCOCCUS-NEOFORMANS; BREVIBACTERIUM-DIVARICATUM; AQUEOUS-SOLUTION; BETA-GLYCOSIDES; IMMUNOGENICITY; VACCINE; ANALOG AB Peptidoglycan monomer, the disaccharide pentapeptide beta-D-Glcp-N-Ac-(1-->4)-D-Murp-N-Ac-L-Ala-D-mesoA(2)pm- (epsilon N H(2))-D-Ala-D-Ala (PGM) is an immunomodulator. PGM and/or its derivative N-tert-butyloxycarbonyl-L-tyrosyl peptidoglycan monomer (Boc-Tyr-PGM) were coupled to two polysaccharides: the glucuronoxylomannan (GXM) from Cryptococcus neoformans, type B, solubilized by ultrasonic irradiation (MW 12-400 kDa) and to the dextran FP 70 (MW 70 kDa). Both polysaccharides were activated by CNBr. Initially, unprotected PGM was coupled via its amino group to GXM. The reactions yielded 42%-52% of the conjugate, containing only 0.18%-0.31% of PGM. In another approach Boc-Tyr-PGM (having its amino group blocked) was reacted via its free carboxyl group. Both CNBr-activated polysaccharides were first coupled to adipic acid dihydrazide (ADH) and then subsequently coupled to Boc-Tyr-PGM. The dextran conjugate (similar to 80% yield) contained 6.3% of Boc-Tyr-PGM. The isolation of GXM conjugate required several modifications and it was obtained in lower yield (similar to 30%) but contained 13.7% of Boc-Tyr-PGM. Both conjugates were water soluble and apyrogenic and suitable for further testing of biological activity. C1 Inst Immunol Inc, HR-10000 Zagreb, Croatia. NIH, Bethesda, MD 20892 USA. RP Tomasic, J (reprint author), Inst Immunol Inc, Rockefellerova 2, HR-10000 Zagreb, Croatia. OI Halassy, Beata/0000-0001-7370-0997 NR 25 TC 2 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6068 J9 PREP BIOCHEM BIOTECH JI Prep. Biochem. Biotechnol. PD NOV PY 1999 VL 29 IS 4 BP 385 EP 401 DI 10.1080/10826069908544936 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 253NC UT WOS:000083561800005 PM 10548254 ER PT J AU Fthenakis, VM Morris, SC Moskowitz, PD Morgan, DL AF Fthenakis, VM Morris, SC Moskowitz, PD Morgan, DL TI Toxicity of Cadmium Telluride, Copper Indium Diselenide, and Copper Gallium Diselenide SO PROGRESS IN PHOTOVOLTAICS LA English DT Article ID PULMONARY TOXICITY; RATS AB This paper reviews recently derived toxicity data for Copper Indium Diselenide (CIS), Cadmium Gallium Diselenide (CGS) and Cadmium Telluride (CT), promising new materials on which a new generation of thin-film photovoltaic cells for generating electricity may be based The new data deal with systemic and reproductive toxicity, acute pulmonary toxicity, and comparative pulmonary absorption, distribution and toxicity of these materials in laboratory rats. CT is shown to have higher lung toxicity than CIS, with the CGS toxicity being the lowest in the group. These data are extended to human exposure levels and exposure limits for CT are derived. The implications of these findings to the photovoltaic industry are also discussed. Published in 1999 by John Wiley & Sons, Ltd. This article is a U.S. Government Work and is in the public domain in the United States. C1 Brookhaven Natl Lab, Upton, NY 11973 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Fthenakis, VM (reprint author), Brookhaven Natl Lab, Bldg 830, Upton, NY 11973 USA. NR 14 TC 30 Z9 32 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1062-7995 J9 PROG PHOTOVOLTAICS JI Prog. Photovoltaics PD NOV-DEC PY 1999 VL 7 IS 6 BP 489 EP 497 DI 10.1002/(SICI)1099-159X(199911/12)7:6<489::AID-PIP287>3.3.CO;2-E PG 9 WC Energy & Fuels; Materials Science, Multidisciplinary; Physics, Applied SC Energy & Fuels; Materials Science; Physics GA 274NC UT WOS:000084771100008 ER PT J AU Sreenath, T Orosz, A Fujita, K Bieberich, CJ AF Sreenath, T Orosz, A Fujita, K Bieberich, CJ TI Androgen-independent expression of hoxb-13 in the mouse prostate SO PROSTATE LA English DT Article DE homeobox gene; gene expression; castration; cancer ID HOMEOBOX GENE; HOX GENES; MORPHOGENESIS; PATTERN; CANCER; NKX3.1; REGION; CELLS AB BACKGROUND. Hox genes encode transcriptional regulatory proteins that are largely responsible for establishing the body plan of all metazoan organisms. A subset of Hox genes is expressed during the period of organogenesis and into adulthood. hoxb-13 is a recently-described member of the Hox gene family that is expressed in the spinal cord, hindgut, and urogenital sinus during embryogenesis. METHODS. Northern blot and in situ hybridization analyses of hoxb-13 expression in adult mouse tissues were performed. RESULTS. hoxb-13 mRNA is restricted to the prostate gland and distal colon in adult animals. In situ hybridization of mouse prostate tissue demonstrated that hoxb-13 is expressed in the epithelial cells of the ventral, dorsal, lateral, and anterior prostate lobes. Accumulation of hoxb-13 mRNA is not diminished following castration. CONCLUSIONS. These data demonstrate that hoxb-13 expression is androgen-independent in mouse prostate glands. The identification of hoxb-13 as an androgen-independent gene expressed in adult mouse prostate epithelial cells provides a new potential target for developing therapeutics to treat advanced prostate cancer. (C) 1999 Wiley-Liss, Inc. C1 Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA. NIDCR, Funct Genom Unit, NIH, Bethesda, MD USA. Niigata Univ, Sch Med, Dept Obstet & Gynecol, Asahimachi, Japan. RP Bieberich, CJ (reprint author), Univ Maryland Baltimore Cty, Dept Biol Sci, 1000 Hilltop Circle, Baltimore, MD 21250 USA. NR 24 TC 44 Z9 45 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 0270-4137 J9 PROSTATE JI Prostate PD NOV 1 PY 1999 VL 41 IS 3 BP 203 EP 207 DI 10.1002/(SICI)1097-0045(19991101)41:3<203::AID-PROS8>3.0.CO;2-J PG 5 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 250QV UT WOS:000083400000008 PM 10517879 ER PT J AU Xie, D Suvorov, L Erickson, JW Gulnik, S AF Xie, D Suvorov, L Erickson, JW Gulnik, S TI Real-time measurements of dark substrate catalysis SO PROTEIN SCIENCE LA English DT Article DE continuous assay; kinetic constants; substrate competition; unmodified peptide cleavage ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL PROTEASES; KINETIC CHARACTERIZATION; DRUG-RESISTANCE; MUTATIONS; SPECIFICITY; INCREASE; MUTANTS; ASSAYS AB We have developed a novel procedure to monitor the real-time cleavage of natural unmodified peptides (dark substrates). Tn the competition-based assay, the initial cleavage rate of a fluorogenic peptide substrate is measured in the presence of a second substrate that is not required to exhibit any optical property change upon cleavage. Using a unique experimental design and steady-state enzyme kinetics for a two-substrate system, we were able to determine both K-m and k(cat) values for cleavage of the dark substrate. The method was applied to HIV-1 protease and to the V82F/I84V drug resistant mutant enzyme. Using two different substrates, we showed that the kinetic parameters derived from the competition assay are in good agreement with those determined independently using standard direct assay. This method can be applied to other enzyme systems as long as they have one substrate for which catalysis can be conveniently monitored in real time. C1 NCI, Struct Biochem Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Gulnik, S (reprint author), NCI, Struct Biochem Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 20 TC 9 Z9 9 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 1999 VL 8 IS 11 BP 2460 EP 2464 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254RP UT WOS:000083626200026 PM 10595550 ER PT J AU Makarova, KS Grishin, NV AF Makarova, KS Grishin, NV TI Thermolysin and mitochondrial processing peptidase: How far structure-functional convergence goes SO PROTEIN SCIENCE LA English DT Article DE core I protein; cytochrome bc(1) complex; metalloenzymes; mitochondrial processing peptidase; molecular evolution; thermolysin ID CYTOCHROME BC(1) COMPLEX; CRYSTAL-STRUCTURE; PROTEIN; DEFORMYLASE; EVOLUTION; FAMILIES AB The structure-functional convergence between two Zn-dependent proteases, namely thermolysin and mitochondrial processing peptidase (MPP), is described. These two families of nonhomologous enzymes show not only functional convergence of several active site residues as in chymotrypsin and subtilisin, but also structural convergence of overall molecular architectures including the P-sheet arrangement and packing of the surrounding alpha-helices. The major functionally important structural elements are present in both enzymes with different topological connections and often in reverse main-chain orientation, but display similar packing. The structural comparison helps to rationalize sequence "inversion" of the HEXXH thermolysin consensus present as HXXEH in MPP. The described structural convergence may be due to a limited number of alternatives to build a Zn-protease that utilizes hydrogen bonding between a substrate main chain and the enzyme beta-sheet for substrate binding. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Uniformed Serv Univ Hlth Sci, FE Hebert Sch Med, Dept Pathol, Bethesda, MD 20814 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Grishin, NV (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. NR 35 TC 19 Z9 19 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 1999 VL 8 IS 11 BP 2537 EP 2540 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 254RP UT WOS:000083626200038 PM 10595562 ER PT J AU Rick, SW Abashkin, YG Hilderbrandt, RL Burt, SK AF Rick, SW Abashkin, YG Hilderbrandt, RL Burt, SK TI Computational studies of the domain movement and the catalytic mechanism of thymidine phosphorylase SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE catalytic mechanism; conformational change; domain movement; molecular dynamics; thymidine phosphorylase ID PURINE NUCLEOSIDE PHOSPHORYLASE; TRANSITION-STATE ANALYSIS; CELL GROWTH-FACTOR; DENSITY-FUNCTIONAL THEORY; MOLECULAR-DYNAMICS; PHOSPHOGLYCERATE KINASE; 3-DIMENSIONAL STRUCTURE; AMP NUCLEOSIDASE; ESCHERICHIA-COLI; SIMULATIONS AB Thymidine phosphorylase (TP) is a dual substrate enzyme with two domains. Each domain binds a substrate. In the crystal structure of Escherichia coli TP, the two domains are arranged so that the two substrate binding sites are too far away for the two substrates to directly react. Molecular dynamics simulations reveal a different structure of the enzyme in which the two domains have moved to place the two substrates in close contact. This structure has a root-mean-square deviation from the crystal structure of 4.1 Angstrom. Quantum mechanical calculations-using this structure find that the reaction can proceed by a direct nucleophilic attack with a low barrier. This mechanism is not feasible in the crystal structure environment and is consistent with the mechanism observed for other N-glycosidic enzymes, Important catalytic roles are found for the three highly conserved residues His 85, Arg 171, and Lys 190. Proteins 1999;37:242-252. (C) 1999 Wiley-Liss, Inc. C1 NCI, Adv Biomed Comp Ctr, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. Natl Sci Fdn, Div Chem, Arlington, VA 22230 USA. RP Rick, SW (reprint author), NCI, Adv Biomed Comp Ctr, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. FU NCI NIH HHS [N0I-CO-56000] NR 50 TC 22 Z9 23 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 1 PY 1999 VL 37 IS 2 BP 242 EP 252 DI 10.1002/(SICI)1097-0134(19991101)37:2<242::AID-PROT9>3.0.CO;2-5 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 250GD UT WOS:000083379900009 PM 10584069 ER PT J AU Rocha, BA AF Rocha, BA TI Methodology for analyzing the parallel between cocaine psychomotor stimulant and reinforcing effects in mice SO PSYCHOPHARMACOLOGY LA English DT Article ID DOPAMINE-TRANSPORTER; LACKING C1 Natl Inst Drug Abuse, Intramural Res Program, Behav Neurosci Branch, Baltimore, MD 21224 USA. RP Rocha, BA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Behav Neurosci Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 11 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1999 VL 147 IS 1 BP 27 EP 29 DI 10.1007/s002130051136 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 258QN UT WOS:000083850000011 PM 10591863 ER PT J AU Shippenberg, TS He, M Chefer, V AF Shippenberg, TS He, M Chefer, V TI The use of microdialysis in the mouse: conventional versus quantitative techniques SO PSYCHOPHARMACOLOGY LA English DT Article C1 NIDA, NIH, Intramural Res Program, Integrat Neurosci Unit, Baltimore, MD 21224 USA. RP Shippenberg, TS (reprint author), NIDA, NIH, Intramural Res Program, Integrat Neurosci Unit, Baltimore, MD 21224 USA. NR 5 TC 10 Z9 11 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1999 VL 147 IS 1 BP 33 EP 34 DI 10.1007/s002130051138 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 258QN UT WOS:000083850000013 PM 10591865 ER PT J AU McCann, UD Eligulashvili, V Mertl, M Murphy, DL Ricaurte, GA AF McCann, UD Eligulashvili, V Mertl, M Murphy, DL Ricaurte, GA TI Altered neuroendocrine and behavioral responses to m-chlorophenylpiperazine in 3,4-methylenedioxymethamphetamine (MDMA) users SO PSYCHOPHARMACOLOGY LA English DT Article DE serotonin; neurotoxicity; mood; anxiety; cortisol; prolactin ID OBSESSIVE-COMPULSIVE DISORDER; CENTRAL SEROTONERGIC NEURONS; TRYPTOPHAN-HYDROXYLASE ACTIVITY; (+/-)3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; META-CHLOROPHENYLPIPERAZINE; NONHUMAN-PRIMATES; 5-HT2C RECEPTORS; RAT-BRAIN; ECSTASY; NEUROTOXICITY AB Rationale: (+/-) 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a popular drug of abuse and a brain serotonin neurotoxin in animals. Growing evidence indicates that humans are also susceptible to MDMA's neurotoxic effects, although few functional consequences of MDMA-induced 5-HT damage have been identified. Objective: The present study sought to determine whether possible differences between MDMA users and control subjects could be unmasked by utilizing a pharmacological challenge with the mixed 5-HT agonist, meta-chlorophenylpiperazine (m-CPP), It was postulated that 5-HT neurotoxicity in MDMA users would be associated with altered 5-HT responsivity, exemplified by altered physiological and behavioral responses to m-CPP, Methods: Twenty-five MDMA users who had not taken MDMA for at least 3 weeks and 25 controls received intravenous placebo (normal saline) and m-CPP (0.08 mg/kg) in a fixed order, single blind design. Repeated measures of mood, physical symptoms, and blood samples for neuroendocrine analyses were collected during the 90 min after each infusion. Results: MDMA users reported more positive and fewer negative emotions and physical symptoms following m-CPP than controls, and were significantly less likely to report an m-CPP-induced panic attack. Male MDMA users had diminished cortisol and prolactin responses to m-CPP. Conclusions: The present data indicate that MDMA users have alterations in 5-HT neuronal function, possibly as a consequence of MDMA-induced brain serotonin neural injury. C1 NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Psychiat, Baltimore, MD USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD USA. RP McCann, UD (reprint author), NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. FU NIDA NIH HHS [DA05938, DA05707, DA00206] NR 54 TC 59 Z9 59 U1 2 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1999 VL 147 IS 1 BP 56 EP 65 DI 10.1007/s002130051142 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 258QN UT WOS:000083850000017 PM 10591869 ER PT J AU Fernandez-Ruiz, J Doudet, D Aigner, TG AF Fernandez-Ruiz, J Doudet, D Aigner, TG TI Spatial memory improvement by levodopa in parkinsonian MPTP-treated monkeys SO PSYCHOPHARMACOLOGY LA English DT Article DE MPTP; levodopa; Parkinson's disease; memory; dopamine ID COGNITIVE DEFICITS; RHESUS-MONKEYS; DOPAMINE; DISEASE; DYSFUNCTION; PERFORMANCE; EXPOSURE; SYSTEM AB Rationale: The ameliorative effects of levodopa (L-3,4-dihydroxy-phenylalanine) on the motor impairment in Parkinson's disease patients is well established, but characterization of its effects on the associated cognitive deficits is still incomplete. Objective: The present study determined the effect of different doses of levodopa on performance on a test of working memory in MPTP-treated rhesus monkeys, an animal model of Parkinson's disease. Methods: Four MPTP-treated monkeys and their age-matched controls with the same experimental history as the MPTP-treated monkeys were tested on a spatial delay response task. Each daily session consisted of five trials at each of seven randomly presented delays (0, 10, 20, 30, 40, 50 and 60 s), Training was continued for 5 days in each of five different conditions. In the first condition, control and MPTP-treated animals performed the task without levodopa. In the second condition, both groups were tested with a dose of 100 mg of levodopa, In the third and fourth conditions, in which the doses of levodopa were increased to 250 and 500 mbo, respectively, only the MPTP-treated animals were tested. In the final condition, the MPTP-treated animals where retested without levodopa, Results: Significant improvement was observed at all doses tested (range 100-500 mg). Conclusions: Levodopa can ameliorate memory impairments in this parkinsonian model. C1 Univ Nacl Autonoma Mexico, Dept Fisiol, Fac Med, Mexico City 04510, DF, Mexico. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ British Columbia, Dept Med, Div Neurol, Vancouver, BC V67 2B5, Canada. RP Fernandez-Ruiz, J (reprint author), Univ Nacl Autonoma Mexico, Dept Fisiol, Fac Med, Apartado Postal 70-250, Mexico City 04510, DF, Mexico. EM jfr@ln.nimh.nih.gov RI Fernandez-Ruiz, Juan/B-6154-2012 OI Fernandez-Ruiz, Juan/0000-0002-4038-0904 NR 19 TC 24 Z9 24 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1999 VL 147 IS 1 BP 104 EP 107 DI 10.1007/s002130051148 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 258QN UT WOS:000083850000023 PM 10591875 ER PT J AU Vivian, JA Liang, YJ Higley, JD Linnoila, M Woods, JH AF Vivian, JA Liang, YJ Higley, JD Linnoila, M Woods, JH TI Oral self-administration of ethanol, phencyclidine, methadone, pentobarbital and quinine in rhesus monkeys SO PSYCHOPHARMACOLOGY LA English DT Article DE barbiturates; ethanol; individual differences; NMDA; opiates; preferences; quinine; self-administration ID NONHUMAN PRIMATE MODEL; DRUG-USE; ALCOHOL-CONSUMPTION; POLYDRUG USE; SACCHARIN; COCAINE; RATS; REINFORCER; CIGARETTE; DRINKING AB Rationale. Simultaneous and sequential drug use among clinical populations is the norm, whereas the pattern of self-administration of multiple drugs among non-human primate populations has not been thoroughly explored, Objectives: To determine the relationship between the preferences and intakes of a large group of rhesus monkeys exposed to various orally available solutions. Methods: Thirteen male and eleven female young adult rhesus monkeys (Macaca mulatta) were exposed to orally available drug solutions using a concurrent choice (drug and water) procedure, where fluid delivery was made contingent upon single spout contacts (fixed ratio one). Results: Ethanol (0.25-16% w:v) produced biphasic effects on the number of fluid deliveries obtained, with peak ethanol preferences over water demonstrated at the 1-2% w:v concentrations. No preferences for the N-methyl-D-aspartate receptor antagonist phencyclidine or water were demonstrated at lower concentrations (0.0078125-0.125 mg/ml) and, at higher concentrations (0.25, 0.5 mg/ml), a preference for water was demonstrated. The mu opioid receptor agonist methadone (0.001-0.3 mg/ml) and the prototypic bitter sub stance quinine (0.001-0.3 mg/ml) failed to produce preferences for drug or water. A large preference for water over the barbiturate pentobarbital (0.01-3 mg/ml) was also demonstrated. After rank-ordering the subjects based on their drug preferences or intakes, modest to no correlations across drugs were demonstrated. Conclusions: These results reveal that a robust ethanol preference is not predictive of a preference for drugs of abuse from other classes and suggests that fluid intakes were correlated, irrespective of the presence or absence of drug in the solution. C1 Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. NIAAA, Clin Studies Lab, Primate Unit, DICBR,NIH, Poolesville, MD USA. Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. RP Vivian, JA (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Med Ctr Blvd, Winston Salem, NC 27157 USA. FU NIDA NIH HHS [DA00254, DA05773] NR 30 TC 7 Z9 7 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 1999 VL 147 IS 2 BP 113 EP 124 DI 10.1007/s002130051151 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 261PB UT WOS:000084016600001 PM 10591878 ER PT J AU Coryell, W Turvey, C Leon, A Maser, JD Solomon, D Endicott, J Mueller, T Keller, M AF Coryell, W Turvey, C Leon, A Maser, JD Solomon, D Endicott, J Mueller, T Keller, M TI Persistence of depressive symptoms and cardiovascular death among patients with affective disorder SO PSYCHOSOMATIC MEDICINE LA English DT Article DE affective disorder; cardiovascular mortality; follow-up ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; FOLLOW-UP; MAJOR DEPRESSION; MORTALITY; RISK; SCHIZOPHRENIA; PREVALENCE; SUICIDE AB Objective: Studies of both community and clinical samples have associated depressive symptoms with risks for subsequent cardiovascular morbidity and mortality. Because the physiological mechanisms thought to underlie this link would be cumulative in their effects, the following analyses tested the prediction that risks for cardiovascular death would increase in proportion to the persistence of depressive symptoms in a long-term follow-up. Methods: Baseline assessment was performed as patients sought treatment for major depressive disorder, mania, or schizoaffective disorder. Follow-up evaluations occurred semiannually for the next 5 years and annually thereafter. The 903 patients described, observed for a mean of 11.0 years (SD 5.2 years), were divided into thirds according to the proportion of follow-up weeks in episodes of major depressive disorder, schizoaffective disorder, or intermittent depressive disorder. The resulting groups were then compared by cumulative risks of cardiovascular death. Results: Patients whose depressive symptoms were the most persistent were no more likely to die of cardiovascular causes than were those with the fewest weeks ill. A regression analysis showed that older age and the presence of cardiovascular disease at baseline, but not the subsequent chronicity of depressive symptoms, predicted cardiovascular death. Conclusions: The physiological concomitants of depressive illness apparently do not promote cardiovascular mortality in a cumulative manner. Efforts should be directed toward identification of risk factors common to both lifetime depressive symptoms and cardiovascular morbidity. C1 Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. Cornell Univ Med Coll, Dept Psychol, Ithaca, NY USA. NIMH, Bethesda, MD 20892 USA. Rhode Isl Hosp, Providence, RI USA. New York State Psychiat Inst, Dept Res Assessment & Training, New York, NY 10032 USA. Butler Hosp, Providence, RI 02906 USA. RP Coryell, W (reprint author), Univ Iowa, Coll Med, Psychiat Res MEB, Iowa City, IA 52242 USA. FU NIMH NIH HHS [R01 MH025478] NR 34 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 1999 VL 61 IS 6 BP 755 EP 761 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 259EN UT WOS:000083881700006 PM 10593626 ER PT J AU Sommer, B Avis, N Meyer, P Ory, M Madden, T Kagawa-Singer, M Mouton, C Rasor, MO Adler, S AF Sommer, B Avis, N Meyer, P Ory, M Madden, T Kagawa-Singer, M Mouton, C Rasor, MO Adler, S TI Attitudes toward menopause and aging across ethnic/racial groups SO PSYCHOSOMATIC MEDICINE LA English DT Article DE aging; attitudes; ethnicity; menopause; women ID HORMONE REPLACEMENT THERAPY; WOMENS ATTITUDES; AFRICAN-AMERICAN; CULTURAL-CONTEXT; SYMPTOMS; PERCEPTIONS; EXPERIENCE; SCALE AB Objective: Attitudes have a potential role to play in the experience of menopause. The objective of this study was to examine the degree to which attitudes toward menopause and aging vary across ethnic groups and menopausal status (ie, premenopausal through postmenopausal). Methods: More than 16,000 women were interviewed by telephone as part of the Study of Women's Health Across the Nation. They represented live ethnic/racial groups (African American, white, Chinese American, Japanese American. and Hispanic) from seven geographical sites (Boston, MA; Pittsburgh, PA; Chicago, IL; Michigan; New Jersey; and northern and southern California). Results: African American women were significantly more positive in attitude. The least positive groups were the less acculturated Chinese American and Japanese American women. Menopausal status was not a consistent predictor of attitude across ethnic groups. Conclusions: In general, women's attitudes toward menopause range from neutral to positive. Ethnic groups within the United States vary slightly, but reliably, in their attitudes toward menopause and aging. Factors other than those directly associated with menopausal status seem to play a role in attitude. C1 Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. Univ Calif Davis, Dept Epidemiol Prevent Med, Davis, CA 95616 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. New England Res Inst, Boston, MA USA. NIA, Behav & Social Res Program, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Asian Amer Studies, Los Angeles, CA 90024 USA. Univ Texas, Ctr Hlth, Dept Family Practice, San Antonio, TX 78285 USA. Univ Calif San Francisco, Dept Med Anthropol, San Francisco, CA 94143 USA. RP Sommer, B (reprint author), Univ Calif Davis, Dept Psychol, 1 Shields Ave, Davis, CA 95616 USA. NR 44 TC 83 Z9 86 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 1999 VL 61 IS 6 BP 868 EP 875 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 259EN UT WOS:000083881700020 PM 10593640 ER PT J AU Staab, EV Brady, TJ AF Staab, EV Brady, TJ TI Revitalizing the radiology research enterprise SO RADIOGRAPHICS LA English DT Article DE radiological society of North America; radiology and radiologists C1 NCI, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Staab, EV (reprint author), NCI, 6130 Execut Blvd,Rm 800, Rockville, MD 20852 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 1999 VL 19 IS 6 BP 1405 EP 1405 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 252YL UT WOS:000083529800001 ER PT J AU Staab, EV Brady, TJ AF Staab, EV Brady, TJ TI Revitalizing the radiology research enterprise SO RADIOLOGY LA English DT Editorial Material DE Radiological Society of North America; radiology and radiologists C1 NCI, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Staab, EV (reprint author), NCI, 6130 Execut Blvd,Rm 800, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 213 IS 2 BP 316 EP 316 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 249AE UT WOS:000083308900002 ER PT J AU Herskovits, EH Megalooikonomou, V Davatzikos, C Chen, A Bryan, RN Gerring, JP AF Herskovits, EH Megalooikonomou, V Davatzikos, C Chen, A Bryan, RN Gerring, JP TI Is the spatial distribution of brain lesions associated with closed-head injury predictive of subsequent development of attention-deficit/hyperactivity disorder? Analysis with brain-image database? SO RADIOLOGY LA English DT Article DE attention-deficit/hyperactivity disorder; brain, injuries; brain, MR; children, central nervous system; images, analysis; images, display ID BEHAVIOR; SCALE; ADHD AB PURPOSE: To determine whether there is an association between the spatial distribution of lesions detected at magnetic resonance (MR) imaging of the brain in children after closed-head injury and the development of secondary attention-deficit/hyperactivity disorder (ADHD). MATERIALS AND METHODS: Data obtained from 76 children without prior history of ADHD were analyzed. MR images were obtained 3 months after closed-head injury. After manual delineation of lesions, images were registered to the Talairach coordinate system. For each subject, registered images and secondary ADHD status were integrated into a brain-image database, which contains depiction (visualization) and statistical analysis software. Using this database, we assessed visually the spatial distributions of lesions and performed statistical analysis of image and clinical variables. RESULTS: Of the 76 children, 15 developed secondary ADHD. Depiction of the data suggested that children who developed secondary ADHD had more lesions in the right putamen than children who did not develop secondary ADHD; this impression was confirmed statistically. After Bonferroni correction, we could not demonstrate significant differences between secondary ADHD status and lesion burdens for the right caudate nucleus or the right globus pallidus. CONCLUSION: Closed-head injury-induced lesions in the right putamen in children are associated with subsequent development of secondary ADHD. Depiction software is useful in guiding statistical analysis of image data. C1 Johns Hopkins Med Inst, Div Neuroradiol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Bayview Med Ctr, Dept Psychiat, Baltimore, MD 21287 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Herskovits, EH (reprint author), Johns Hopkins Med Inst, Div Neuroradiol, 600 N Wolfe St, Baltimore, MD 21287 USA. RI Bryan, R. Nick/P-1661-2014 FU NIA NIH HHS [R01 AG13743-03] NR 19 TC 64 Z9 65 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1999 VL 213 IS 2 BP 389 EP 394 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 249AE UT WOS:000083308900013 PM 10551217 ER PT J AU Makarova, KS Wolf, YI White, O Minton, K Daly, MJ AF Makarova, KS Wolf, YI White, O Minton, K Daly, MJ TI Short repeats and IS elements in the extremely radiation-resistant bacterium Deinococcus radiodurans and comparison to other bacterial species SO RESEARCH IN MICROBIOLOGY LA English DT Article DE Deinococcus radiodurans; repeated sequences; genome analysis ID COMPLETE GENOME SEQUENCE; MYCOBACTERIUM-TUBERCULOSIS; INSERTION-SEQUENCE; DNA; IDENTIFICATION; REGIONS; SITE AB Computer analysis of the complete genome of Deinococcus radiodurans R1 has shown that the number of insertion sequences (ISs) and small noncoding repeats (SNRs) it contains is very high, and comparable with those of Escherichia coli. IS elements and several families of SNRs are described, together with their possible function in the D. radiodurans genome. (C) 1999 Editions scientifiques et medicales Elsevier SAS. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. Inst Genomic Res, Rockville, MD 20850 USA. RP Daly, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd,Rm B3153, Bethesda, MD 20814 USA. FU NIGMS NIH HHS [5R01-GM39933-09] NR 31 TC 16 Z9 19 U1 1 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD NOV-DEC PY 1999 VL 150 IS 9-10 BP 711 EP 724 DI 10.1016/S0923-2508(99)00121-7 PG 14 WC Microbiology SC Microbiology GA 275LN UT WOS:000084821800013 PM 10673009 ER PT J AU Goldstein, SR Pohida, T Smith, PD Peterson, JI Wellner, E Malekafzali, A Suarez-Quian, CA Bonner, RF AF Goldstein, SR Pohida, T Smith, PD Peterson, JI Wellner, E Malekafzali, A Suarez-Quian, CA Bonner, RF TI An instrument for performing laser capture microdissection of single cells SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID MOLECULAR ANALYSIS AB We have developed a new form of laser capture microdissection (LCM) optimized for isolating and concentrating single cells from a tissue slide for subsequent molecular analysis. In LCM an infrared laser diode is used together with a microscope to locally melt a thin film of ethylene vinyl acetate (EVA) placed in contact or close proximity to microscopically targeted cells. Since the desired cells adhere to the film where it has been melted, they are extracted from their adjacent tissue in the specimen when the film is separated from the slide. In our system the EVA is bonded to a cylindrical substrate resulting in a very small area of contact between the EVA and the slide which minimizes contamination to levels consistent with analyzing a few cells of a selected cell type. By collecting cells at different portions about the cylinder periphery, the novel geometry also allows the concentration of cells from different slides onto a single substrate, enabling very sensitive molecular analysis to be performed on collections of rare cells. A computer controlled mechanism gently lowers the cylinder to either contact the slide with a small preload force, or provide a minute gap between the cylinder and the tissue. In the latter noncontact mode, the possibility of stray contamination is further reduced since EVA/tissue contact is only made at the location of the laser beam at a minute spot. The mechanism also can rotate the cylinder to provide fresh EVA capture surface after it has raised the cylinder off the slide. A method of fabricating the required precision cylinders of EVA capture surface is described which uses a precision mold cavity and a reusable substrate made of polycarbonate and stainless steel. Results are presented for the preload and noncontact modes which demonstrate the capabilities of the system to capture and concentrate targeted single cells from a complex tissue. [S0034-6748(99)00911-9]. C1 NIH, Instrumentat Res & Dev Resource Bioengn & Phys Sc, Off Res Serv, Bethesda, MD 20892 USA. NIH, Signal Proc & Control Syst Grp, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. NICHHD, Sect Med Biophys, Lab Integrated & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Goldstein, SR (reprint author), NIH, Instrumentat Res & Dev Resource Bioengn & Phys Sc, Off Res Serv, Bldg 10, Bethesda, MD 20892 USA. RI Bonner, Robert/C-6783-2015 NR 9 TC 5 Z9 5 U1 0 U2 2 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD NOV PY 1999 VL 70 IS 11 BP 4377 EP 4385 DI 10.1063/1.1150043 PG 9 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 251NQ UT WOS:000083452100043 ER PT J AU Meehan, MP Sewankambo, NK Wawer, MJ McNairn, D Quinn, TC Lutalo, T Kalibbala, S Li, CJ Serwadda, D Wabwire-Mangen, F Gray, RH AF Meehan, MP Sewankambo, NK Wawer, MJ McNairn, D Quinn, TC Lutalo, T Kalibbala, S Li, CJ Serwadda, D Wabwire-Mangen, F Gray, RH CA Rakai Project Team TI Sensitivity and specificity of HIV-1 testing of urine compared with serum specimens: Rakai, Uganda SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIBODY AB Background and Objectives: To evaluate a urine HIV-1 test. Study Design: Paired urine and blood samples from a sample of 222 subjects were assayed for HIV-1 using Calypte HIV-1 Urine enzyme immunoassay (EIA) with Western blot (WB) confirmation, and sera were tested by EIA and WB. Masked assays were done on stored, refrigerated urine at Johns Hopkins University (JH), and on fresh specimens at the Rakai Project, Entebbe (RP), We assessed the sensitivity and specificity of the urine relative to serum assays. Results: Compliance with provision of urine samples (95.0%) was higher than provision of serum (90.5%). Ninety-six sera were HIV-positive; 92 were HIV-positive on stored mine at JH (sensitivity 95.8%, CI 91.8-99.8%); and 94 (100%) were positive on fresh samples at the RP laboratory (sensitivity = 100.0%). Among serum HIV-negative subjects, all frozen urine mere negative at JH and 97.7% of fresh samples were negative at RP. Conclusions: The Calypte urine HIV-1 EIA with WB is sensitive and specific. In this population, provision of urine was more acceptable than provision of blood samples. C1 Columbia Univ, Sch Publ Hlth, Ctr Populat & Family Hlth, New York, NY USA. Makerere Univ, Fac Med, Kampala, Uganda. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. NIAID, Bethesda, MD 20892 USA. Uganda Virus Res Inst, Entebbe, Uganda. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD 21205 USA. Rakai Project Team, Entebbe, Uganda. RP Gray, RH (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Room 4014,615 N Wolfe St, Baltimore, MD 21205 USA. OI Sewankambo, Nelson/0000-0001-9362-053X FU NICHD NIH HHS [5P30HD06826]; PHS HHS [R01 A134826, R01 A134826S] NR 11 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD NOV PY 1999 VL 26 IS 10 BP 590 EP 592 DI 10.1097/00007435-199911000-00009 PG 3 WC Infectious Diseases SC Infectious Diseases GA 252HP UT WOS:000083496300009 PM 10560724 ER PT J AU Gillette, MU Roth, T Kiley, JP AF Gillette, MU Roth, T Kiley, JP TI NIH funding of sleep research: A prospective and retrospective view SO SLEEP LA English DT Article C1 Univ Illinois, Neurosci Program, Dept Cell & Struct Biol, Urbana, IL 61801 USA. NHLBI, Sleep Disorders Res Advisory Board, Urbana, IL USA. Henry Ford Sleep Disorders Ctr, Detroit, MI 48202 USA. NHLBI, Natl Ctr Sleep Disorders Res, Bethesda, MD 20892 USA. RP Gillette, MU (reprint author), Univ Illinois, Neurosci Program, Dept Cell & Struct Biol, MC-123,B107 CLSL,601 S Goodwin Ave, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SLEEP DISORDERS ASSOC PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 1999 VL 22 IS 7 BP 956 EP 958 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 253PZ UT WOS:000083566100014 PM 10566914 ER PT J AU Backlund, E Sorlie, PD Johnson, NJ AF Backlund, E Sorlie, PD Johnson, NJ TI A comparison of the relationships of education and income with mortality: the national longitudinal mortality study SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE educational status; income; mortality; United States ID CORONARY HEART-DISEASE; SOCIAL-CLASS; SOCIOECONOMIC-STATUS; UNITED-STATES; RISK-FACTORS; DEATH-INDEX; ADULT MORTALITY; HEALTH; DIFFERENTIALS; INEQUALITIES AB A sample of over 400.000 men and women, ages 25-64, from the National Longitudinal Mortality Study (NLMS), a cohort study representative of the noninstitutionalized US population, was followed for mortality between the years of 1979 and 1989 in order to compare and contrast the functional forms of the relationships of education and income with mortality. Results from the study suggest that functional forms for both variables are nonlinear. Education is described significantly better by a trichotomy (represented by less than a high school diplomat a high school diploma or greater but no college diploma, or a college diploma or greater) than by a simple linear function for both men (p < 0.0001 for lack of fit) and women (p = 0.006 for lack of fit). For describing the association between income and mortality, a two-sloped function, where the decrease in mortality associated with a US$1000 increase in income is much greater at incomes below US$22,500 than at incomes above US$22,500, fits significantly better than a linear function for both men (p < 0.0001 for lack of fit) and women (p = 0.0005 for lack of fit). The different shapes for the two functional forms imply that differences in mortality may primarily be a function of income at the low end of the socioeconomic continuum, but primarily a function of education at the high end. Published by Elsevier Science Ltd. C1 US Bur Census, Washington, DC 20233 USA. NHLBI, Epidemiol & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Backlund, E (reprint author), US Bur Census, Washington, DC 20233 USA. NR 51 TC 114 Z9 117 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 1999 VL 49 IS 10 BP 1373 EP 1384 DI 10.1016/S0277-9536(99)00209-9 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 236CD UT WOS:000082579900008 PM 10509827 ER PT J AU Hollowell, GP Kuykendall, LD Gillette, WK Hashem, FM Hou, LH Tatem, HE Dutta, SK AF Hollowell, GP Kuykendall, LD Gillette, WK Hashem, FM Hou, LH Tatem, HE Dutta, SK TI Genetic transfer and expression of plasmid RP4 :: TOL in Sinorhizabium meliloti, Bradyrhizobium japonicum and B-elkanii SO SOIL BIOLOGY & BIOCHEMISTRY LA English DT Article DE exconjugant; plasmid RP4 :: TOL; Sinorhizobium sp; BTEX; bioremediation ID RHIZOBIUM-JAPONICUM; PSEUDOMONAS-PUTIDA; TOL PLASMID; NITROGEN-FIXATION; R FACTORS; STRAIN; RECOMBINANTS; RESISTANCE; AERUGINOSA; MT-2 AB Sinorhizobium species generally obviate the need for nitrogen fertilizer since they supply their legume hosts with biological fixed nitrogen, Our working hypothesis is that Sinorhizobium species can perhaps be genetically modified to perform rhizosphere-stimulated bioremediation, Plasmid RP4::TOL has gene clusters encoding the metabolic pathways for benzene, toluene and xylene degradation. Originally from Pseudomonas, this plasmid, in Escherichia coli C600, was successfully transferred to symbiotically elite strains of alfalfa-nodulating Sinorhizobium meliloti USDA 1936. Reciprocal crosses with E, coli RR28, followed by analysis of DNA by restriction enzymes verified S, meliloti USDA 1936 (RP4::TOL) exconjugant, Reciprocal crosses involving B, japonicum USDA I-110 (RP4::TOL) exconjugant and B. elkanii USDA 61 (RP4,,TOL) exconjugant as donors with E. coli RR28 as a recipient produced exconjugant bearing derivative plasmids having a major part of the TOL region deleted, Therefore, soybean-nodulating, B, japonicum USDA I-110 and B, elkanii USDA 61, were not suitable hosts for stable maintenance of this plasmid, Colony size of S, meliloti (RP4::TOL) exconjugant and B, elkanii (RP4,,TOL) exconjugant were enhanced by the addition of 1.0 mM meta-toluic acid in minimal salts media. Although in untreated sterile soil, S, meliloti USDA 1936 (RP4,:TOL) exconjugant formed more nodules per plant than S, meliloti USDA 1936, it was determined to be symbiotically a competent in nitrogen fixation, based on plant dry weight and acetylene reduction. In liquid culture 77% reduction in toluate was recorded in 10 d by this exconjugant compared with only 15% reduction by the parent culture, Alfalfa plant tin situ) studies revealed almost 100% reduction in the concentration of 1.0 mM m-toluate by S, meliloti USDA 1936 (RP4:,TOL) exconjugant when tested after 8 weeks compared with 92% by the parent culture. Thus, a symbiotic combination of genetically-modified S. meliloti and the alfalfa plants were shown to have potential usefulness in the bioremediation of toxic hydrocarbons in soil. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Howard Univ, Dept Biol, Washington, DC 20059 USA. ARS, Mol Plant Pathol Lab, Inst Plant Sci, USDA, Beltsville, MD 20705 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. ARS, Soybean & Alfalfa Res Lab, USDA, Beltsville, MD 20705 USA. USA, Corps Engineers, Waterways Expt Stn, Vicksburg, MS 39180 USA. RP Dutta, SK (reprint author), Howard Univ, Dept Biol, Washington, DC 20059 USA. NR 33 TC 4 Z9 5 U1 4 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0038-0717 J9 SOIL BIOL BIOCHEM JI Soil Biol. Biochem. PD NOV PY 1999 VL 31 IS 13 BP 1811 EP 1819 DI 10.1016/S0038-0717(99)00100-5 PG 9 WC Soil Science SC Agriculture GA 245HT UT WOS:000083101700007 ER PT J AU Linfante, I Llinas, RH Caplan, LR Warach, S AF Linfante, I Llinas, RH Caplan, LR Warach, S TI MRI features of intracerebral hemorrhage within 2 hours from symptom onset SO STROKE LA English DT Article DE hemoglobins; intracerebral hemorrhage; magnetic resonance imaging; stroke; tissue plasminogen activator ID APPEARANCE; BRAIN; BLOOD AB Background and Purpose-MRI has been increasingly used in the evaluation of acute stroke patients. However, MRI must be able to detect early hemorrhage to be the only imaging screen used before treatment such as thrombolysis, Susceptibility-weighted imaging, an echo-planar T2* sequence, can show intracerebral hemorrhage (ICH) in patients imaged between 2.5 and 5 hours from symptom onset. It is unknown whether MRI can detect ICH earlier than 2.5 hours. We describe 5 patients with ICH who had MRI between 23 and 120 minutes from symptom onset and propose diagnostic patterns of evolution of hyperacute ICH on MRI. Methods-As part of our acute imaging protocol, all patients with acute stroke within 24 hours from symptom onset were imaged with a set of sequences that included susceptibility-weighted imaging, diffusion- and perfusion-weighted imaging, T1- and T2-weighted imaging, fluid-attenuated inversion recovery (FLAIR), and MR angiography using echo-planar techniques. Five patients with ICH had MRI between 23 and 120 minutes from the onset of symptoms. Results-ICH was identified in all patients. Distinctive patterns of hyperacute ICH and absence of signs of ischemic stroke were the hallmark features of this diagnosis. The hyperacute hematoma appears to be composed of 3 distinct areas: (1) center: isointense to hyperintense heterogeneous signal on susceptibility-weighted and T2-weighted imaging; (2) periphery: hypointense (susceptibility effect) on susceptibility-weighted and T2-weighted imaging; and (3) rim: hypointense on T1-weighted imaging and hyperintense on T2-weighted imaging, representing vasogenic edema encasing the hematoma. Conclusions-MRI is able to detect hyperacute ICH and show a pattern of evolution of the hematoma within 2 hours from the onset of symptoms. C1 Harvard Univ, Div Cerebrovasc Dis, Sch Med, Beth Israel Deaconess Med Ctr,Dept Neurol, Boston, MA 02215 USA. NINDS, Sect Stroke Diagnost & Therapeut, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Linfante, I (reprint author), Harvard Univ, Div Cerebrovasc Dis, Sch Med, Beth Israel Deaconess Med Ctr,Dept Neurol, E Campus DA 779,330 Brookline Ave, Boston, MA 02215 USA. NR 12 TC 163 Z9 178 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1999 VL 30 IS 11 BP 2263 EP 2267 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 251FN UT WOS:000083434100001 PM 10548654 ER PT J AU Lyden, P Lu, M Jackson, C Marler, J Kothari, R Brott, T Zivin, J AF Lyden, P Lu, M Jackson, C Marler, J Kothari, R Brott, T Zivin, J CA NINDS tPA Stroke Trial Investigato TI Underlying structure of the National Institutes of Health Stroke Scale - Results of a factor analysis SO STROKE LA English DT Article DE cerebrovascular disorders; clinimetrics; factor analysis, statistical; neuropsychological tests ID ACUTE CEREBRAL INFARCTION; ISCHEMIC STROKE; RELIABILITY; PROGNOSIS; TRIAL; SIZE AB Background and Purpose-No stroke scale has been validated as an outcome measure using data from a clinical trial demonstrating a positive therapeutic effect. Therefore, we proposed to use data from the National Institute of Neurological Disorders and Stroke (NINDS) tPA Stroke Trial to determine whether the National Institutes of Health Stroke Scale (NIHSS) was valid in patients treated with tissue plasminogen activator (tPA) and to explore the underlying clinimetric structure of the NIHSS. Methods-We performed an exploratory factor analysis of NIHSS data from Part 1 (n=291) of the NINDS tPA Stroke Trial to derive a hypothesized underlying factor structure. We then performed a confirmatory factor analysis of this structure using NIHSS data from Part 2 of the same trial (n=333). We then tested whether this final factor structure could be found in tPA- and placebo-treated patients serially over time after stroke treatment. Using 3-month outcome data, we tested for an association between the NIHSS and other measures of stroke outcome. Results-The exploratory analysis suggested that there were 2 factors underlying the NIHSS, representing left and right brain function, confirming the content validity of the scale. An alternative structure composed of 4 factors could be derived, with a better goodness of fit: the first 2 factors could represent left brain cortical and motor function, respectively, and the second 2 factors could represent right brain cortical and motor function, respectively. The same factor structures were then found in tPA and placebo patient groups studied serially over time, confirming the exploratory analysis. All 3-month clinical outcomes were associated with each other at subsequent time points, confirming predictive validity. Conclusions-This is the first study of the validity of a stroke scale in patients treated with effective stroke therapy. The NIHSS appeared to be valid in patients with acute stroke and for finding treatment-related differences. The scale was valid when used serially over time after stroke, up to 3 months, and showed good agreement with other measures of outcome. C1 Vet Adm Med Ctr, Dept Neurol, San Diego, CA 92161 USA. Univ Calif San Diego, Sch Med, Dept Neurosci, San Diego, CA 92103 USA. Henry Ford Hlth Sci Ctr, Dept Biostat & Res Epidemiol, Detroit, MI USA. NINDS, Bethesda, MD 20892 USA. Univ Cincinnati, Med Ctr, Dept Emergency Med, Cincinnati, OH 45221 USA. Univ Cincinnati, Med Ctr, Dept Neurol, Cincinnati, OH 45221 USA. RP Lyden, P (reprint author), Stroke Ctr 8466, 3rd Floor,OPC,Suite 3,200 W Arbor Dr, San Diego, CA 92103 USA. FU NINDS NIH HHS [N01-NS02374, N01-NS02377, N01-NS02382] NR 36 TC 158 Z9 163 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1999 VL 30 IS 11 BP 2347 EP 2354 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 251FN UT WOS:000083434100016 PM 10548669 ER PT J AU Woo, D Broderick, JP Kothari, RU Lu, M Brott, T Lyden, PD Marler, JR Grotta, JC AF Woo, D Broderick, JP Kothari, RU Lu, M Brott, T Lyden, PD Marler, JR Grotta, JC CA NINDS t-PA Stroke Study Grp TI Does the National Institutes of Health Stroke Scale favor left hemisphere strokes? SO STROKE LA English DT Article DE dominance, cerebral; cerebral infarction; tomography, x-ray computed; infarction volume ID ACUTE CEREBRAL INFARCTION AB Background and Purpose-The National Institutes of Health Stroke Scale (NIHSS) is a valid, reproducible scale that measures neurological deficit. Of 42 possible points, 7 points are directly related to measurement of language compared with only 2 points related to neglect. Methods-We examined the placebo arm of the NINDS t-PA stroke trial to test the hypothesis that the total volume of cerebral infarction in patients with right hemisphere strokes would be greater than the volume of cerebral infarction in patients with left hemisphere strokes who have similar NIHSS scores. The volume of stroke was determined by computerized image analysis of CT films and CT images Stored on computer tape and optical disks. Cube-root transformation of lesion volume was performed for each CT, Transformed lesion volume was analyzed in a logistic regression model to predict volume of stroke by NIHSS score for each hemisphere. Spearman rank correlation was used to determine the relation between the NIHSS score and lesion volume. Results-The volume for right hemisphere stroke was statistically greater than the volume for left hemisphere strokes, adjusting for the baseline NIHSS (P<0.001). For each 5-point category of the NIHSS score <20, the median volume of right hemisphere strokes was approximately double the median volume of left hemisphere strokes. For example, for patients with a left hemisphere stroke and a 24-hour NIHSS score of 16 to 20, the median volume of cerebral infarction was 48 mt (interquartile range 14 to 111 mL) as compared with 133 mt (interquartile range 81 to 208 mLfor patients with a right hemisphere stroke (P<0.001). The median volume of a right hemisphere stroke was roughly equal to the median volume of a left hemisphere stroke in the next highest 5-point category of the NIHSS, The Spearman rank correlation between the 24-hour NIHSS score and 3-month lesion volume was 0.72 for patients with left hemisphere stroke and 0.71 for patients with right hemisphere stroke. Conclusions-For a given NIHSS score, the median volume of right hemisphere strokes is consistently larger than the median volume of left hemisphere strokes. The clinical implications of our finding need further exploration. C1 Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH 45200 USA. Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH 45200 USA. Henry Ford Hlth Syst, Biostat & Res Epidemiol, Detroit, MI USA. Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. Univ Calif San Diego, Dept Neurol, San Diego, CA 92103 USA. NINDS, Div Stroke & Trauma, Bethesda, MD 20892 USA. Univ Texas, Sch Med, Dept Neurol, Houston, TX USA. RP Woo, D (reprint author), Univ Cincinnati, Coll Med, Dept Neurol, 231 Bethesda Ave,ML 0525, Cincinnati, OH 45200 USA. FU NINDS NIH HHS [U10 NS077311, N-01-NS-02382, N01-NS-02374, N01-NS-02377] NR 17 TC 103 Z9 103 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 1999 VL 30 IS 11 BP 2355 EP 2359 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 251FN UT WOS:000083434100017 PM 10548670 ER PT J AU Mayo, DJ Cullinane, AM Merryman, PK Horne, MK AF Mayo, DJ Cullinane, AM Merryman, PK Horne, MK TI Serologic evidence of heparin sensitization in cancer patients receiving heparin flushes of venous access devices SO SUPPORTIVE CARE IN CANCER LA English DT Article DE heparin; venous access devices; thrombocytopenia ID MOLECULAR-WEIGHT HEPARIN; INDUCED THROMBOCYTOPENIA; UNFRACTIONATED HEPARIN; ANTIBODIES; COMPLEXES AB Cancer patients with venous access devices (VADs) often receive daily flushes of heparin. Even this relatively small heparin exposure has been reported to induce immune-mediated thrombocytopenia. To estimate how frequently this occurs we tested for heparin-related antibodies in 49 patients receiving daily heparin flushes of their VADs. Although one-third of the patients showed evidence of heparin sensitization on at least one occasion during their surveillance, their antibody titers were generally low and typical of those found in other cohorts of patients who become sensitized to heparin but do not develop secondary thrombocytopenia. However, one patient developed a positive serotonin release assay indicative of a more significant sensitization, but without thrombocytopenia. Therefore, our observations suggest that heparin-induced thrombocytopenia (HIT) related to heparin flushes of VADs is uncommon but still an important diagnosis to entertain. C1 NIH, Hematol Serv, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Hematol Serv, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Room 2C306,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD NOV PY 1999 VL 7 IS 6 BP 425 EP 427 DI 10.1007/s005200050303 PG 3 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 249FQ UT WOS:000083322700011 PM 10541985 ER PT J AU Scheinman, M Ascher, E Kallakuri, S Hingorani, A Gade, P Sherman, M Seth, P Jacob, T AF Scheinman, M Ascher, E Kallakuri, S Hingorani, A Gade, P Sherman, M Seth, P Jacob, T TI P53 gene transfer to the injured rat carotid artery promotes apoptosis SO SURGERY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the Eastern-Vascular-Society CY MAY 01-03, 1998 CL NEWPORT, RHODE ISLAND SP Eastern Vasc Soc ID SMOOTH-MUSCLE CELLS; WILD-TYPE P53; DEPENDENT KINASE INHIBITOR; ATHEROSCLEROTIC PLAQUES; CYCLE ARREST; IN-VIVO; PROLIFERATION; EXPRESSION; VECTOR; MODEL AB Background, In a previous study we have demonstrated significant reduction of intimal hyperplasia after adenovirus-mediated gene transfer of p53 protein to the injured rat carotid artery. The purpose of this study was to elucidate whether apoptosis is one of the mechanisms responsible for this reduction. Apoptosis, a physiologic cell death process that stabilizes cell numbers in tissues, can be independently induced by p53. Methods. In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus encoding for wild-type p53 protein (AdWTp53) was applied at 8 x 10(10) plaque-forming units/mL. Control rats received either adenovirus null at the same concentration or balloon injury alone. Arteries were harvested at 24 and 48 hours after the procedure. Apoptosis was detected in tissue sections by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. Specimens were graded either negative or positive less than 10%, 10% to 20%, 20% to 30%, or greater than 30% according to the number of apoptotic cells in the medial or intimal layer per high powerfield. Specimens were also subjected to DNA agarose gel electrophoresis and transmission, electron microscopy. Results. With the TUNEL, assay no apoptosis was visualized at 24 and 48 hours in the controls (n = 5 in each group), whereas in the AdWTp53 groups (n = 5 in each) all specimens presented apoptosis (P < .05, AdWTp53 vs controls). The average grade of apoptotic cells detected in the medial layer in the AdWTp53 groups was less than 10% to 20% at 24 hours and 20% to 30% at 48 hours. The DNA agarose gel electrophoresis failed to detect a DNA laddering pattern, characteristic of apoptosis. Electron microscopy revealed morphologic changes typical of apoptosis in the treated group, whereas specimens from control group did not reveal any apoptotic features. Conclusions. Ar 48 hours after balloon injury alone, no apoptosis was observed in the vessel wall. However; when p53 gene was transferred apoptosis was visualized in all specimens with greater intensity at 48 hours after injury. Promotion of apoptosis may play a hey role in the mechanism by which p53 gene decreases intimal hyperplasia. C1 Maimonides Med Ctr, Div Vasc Surg, Dept Surg, Brooklyn, NY 11219 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Ascher, E (reprint author), Maimonides Med Ctr, Div Vasc Surg, Dept Surg, 4802 10th Ave, Brooklyn, NY 11219 USA. NR 25 TC 22 Z9 22 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 NOV PY 1999 VL 126 IS 5 BP 863 EP 868 DI 10.1016/S0039-6060(99)70027-9 PG 6 WC Surgery SC Surgery GA 252XU UT WOS:000083528200009 PM 10568186 ER PT J AU Gnant, MFX Noll, LA Terrill, RE Wu, PC Berger, AC Nguyen, HQ Lans, TE Flynn, BM Libutti, SK Bartlett, DL Alexander, HR AF Gnant, MFX Noll, LA Terrill, RE Wu, PC Berger, AC Nguyen, HQ Lans, TE Flynn, BM Libutti, SK Bartlett, DL Alexander, HR TI Isolated hepatic perfusion for lapine liver metastases: Impact of hyperthermia on permeability of tumor neovasculature SO SURGERY LA English DT Article ID NECROSIS-FACTOR; CANINE LIVER; PORTAL-VEIN; MITOMYCIN-C; ARTERY; RABBIT; CANCER; IMPLANTATION; INFUSION; SURVIVAL AB Background. Hyperthermic isolated hepatic perfusion (IHP) has been shown to cause significant regression of advanced unresectable liver metastases in patients. Although there are different agents and treatment modalities used in IHF: the contribution of perfusion hyperthermia is unknown. Purpose. A large animal model of unresectable liver metastases and a technical standard for IHP in this model were established. This model was used to assess the effects of hyperthermia on vascular permeability of tumors and normal liver tissue during IHP. Methods. Sixty-five New Zealand White rabbits were used in a series of experiments. Disseminated liver tumors were established by direct injection of 1 x 10(6) VX-2 cells into the portal vein by laparotomy, in anesthetized animals. Several surgical perfusion techniques were explored to determine a reliable and reproducible IHP model. Vascular permeability in tumor versus liver was then assessed with Evan's Blue labeled bovine albumin under normothermic (tissue temperature 36.5 degrees C +/- 0.5 degrees C), moderate hyperthermic (39 degrees C +/- 0.5 degrees C), or severe hyperthermic (41 degrees C +/- 0.5 degrees C) conditions. Results. Tumor model and perfusion techniques were successfully established with inflow through the portal vein and outflow through an isolated segment of the inferior vena cava. A gravity driven perfusion circuit with stable perfusion parameters and complete vascular isolation was used. Vascular permeability tons higher in tumor than in normal tissues (P = .03) at all time points during IHP. Hyperthermia resulted in a significant (up to 5-fold) increase in. permeability of neovasculature; when severe hyperthermia was used, tumor vascular permeability was increased even more than normal liver permeability (P = .01). Conclusions, The VX-2/New Zealand White rabbit system can be used as a reproducible large-animal model for IHP of unresectable liver metastases. It can be used to characterize the contribution and mechanism of action of different treatment parameters used in IHP. Hyperthermia preferentially increases vascular permeability in tumors compared with liver tissue in a dose-dependent fashion, thus providing a mechanism for its presumed benefit during isolated organ perfusion. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Anim Med Sect, Anim Sci Branch, NIH, Bethesda, MD 20892 USA. Univ Vienna, Dept Surg, A-1010 Vienna, Austria. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Gnant, Michael/0000-0003-1002-2118 NR 31 TC 24 Z9 27 U1 0 U2 2 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 NOV PY 1999 VL 126 IS 5 BP 890 EP 899 DI 10.1067/msy.2099.100668 PG 10 WC Surgery SC Surgery GA 252XU UT WOS:000083528200012 PM 10568189 ER PT J AU Romero, DV Partilla, JS Zheng, QX Heyliger, SO Ni, Q Rice, KC Lai, J Rothman, RB AF Romero, DV Partilla, JS Zheng, QX Heyliger, SO Ni, Q Rice, KC Lai, J Rothman, RB TI Opioid peptide receptor studies. 12. Buprenorphine is a potent and selective mu/kappa antagonist in the [S-35]-GTP-gamma-S functional binding assay SO SYNAPSE LA English DT Article DE buprenorphine; methadone; opioid dependence; opioid receptors ID GUINEA-PIG BRAIN; RAT-BRAIN; STEREOCHEMICAL REQUIREMENTS; SIGNAL-TRANSDUCTION; G-PROTEINS; MU; CLONING; AGONIST; EXPRESSION; SUBTYPES AB We utilized the [S-35]-GTP-gamma-S functional binding assay to determine the selectivity of opioid receptor agonists in guinea pig caudate membranes. The study focused on two opioid agonists used for treating opioid-dependent patients: methadone and buprenorphine. Selective antagonists were used to generate agonist-selective conditions: TIPP + nor-BNI to measure mu receptors, CTAP + nor-BNI to measure gamma receptors and TIPP + CTAP to measure kappa receptors. The assay was first validated with opioid agonists of known subtype specificity (DAMGO for mu, SNC80 for delta, and U69,593 for kappa receptors). Methadone-stimulated [S-35]-GTP-gamma-S binding was mu-specific and less potent and efficacious than etorphine (K-d = 1,537 nM vs. K-d = 7.8 nM). Buprenorphine failed to stimulate [S-35]-GTP-gamma-S binding but inhibited agonist-stimulated [S-35]-GTP-gamma-S binding. The antagonist-K-i values (nM) of buprenorphine at mu, delta, and kappa receptors were 0.088 nM, 1.15 nM, and 0.072 nM, respectively. The antagonist-K-i values (nM) of naloxone at mu, delta, and kappa receptors were 1.39 nM, 25.0 nM, and 11.4 nM, respectively. Autoradiographic studies showed that buprenorphine failed to stimulate [S-35]-GTP-gamma-S binding in caudate-level rat brain sections but blocked DAMGO-stimulated [S-35]-GTP-gamma-S binding. In cells expressing the cloned rat mu receptor, buprenorphine was a partial agonist and potent mu antagonist. Administration of buprenorphine to rats produced a long-lasting (>24 h) decrease in mu and kappa 2 receptor binding and attenuated mu-stimulated [S-35]-GTP-gamma-S binding. Viewed collectively, these data indicate that, in this assay system, buprenorphine is a potent mu and gamma receptor antagonist. The clinical implications remain to be elucidated. Published 1999 Wiley-Liss, Inc.(dagger). C1 NIDA, CPS, DIR, NIH, Baltimore, MD 21224 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. RP Rothman, RB (reprint author), NIDA, CPS, DIR, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 44 TC 32 Z9 32 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 1999 VL 34 IS 2 BP 83 EP 94 DI 10.1002/(SICI)1098-2396(199911)34:2<83::AID-SYN1>3.0.CO;2-S PG 12 WC Neurosciences SC Neurosciences & Neurology GA 242CT UT WOS:000082921200001 PM 10502307 ER PT J AU Mills, JL AF Mills, JL TI Folate and oral clefts: Where do we go from here? New directions in oral clefts research SO TERATOLOGY LA English DT Editorial Material ID NEURAL-TUBE DEFECTS; HOMOCYSTEINE METABOLISM C1 NICHD, Pediat Epidemiol Sect, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), NICHD, Pediat Epidemiol Sect, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. NR 10 TC 4 Z9 4 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 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 1999 VL 60 IS 5 BP 251 EP 252 DI 10.1002/(SICI)1096-9926(199911)60:5<251::AID-TERA3>3.0.CO;2-# PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 250ZW UT WOS:000083421000003 PM 10525200 ER PT J AU Zhu, XG Kaneshige, M Parlow, AF Chen, E Hunziker, RD McDonald, MP Cheng, SY AF Zhu, XG Kaneshige, M Parlow, AF Chen, E Hunziker, RD McDonald, MP Cheng, SY TI Expression of the mutant thyroid hormone receptor PV in the pituitary of transgenic mice leads to weight reduction SO THYROID LA English DT Article ID LIGAND-BINDING DOMAIN; GENERALIZED RESISTANCE; BETA GENE; 3,5,3'-TRIIODOTHYRONINE; HYPERACTIVITY; BEARING; GLAND; ERBA AB Resistance to thyroid hormone (RTH) is a genetic disease caused by mutations of the thyroid hormone receptor beta gene (TR beta). One of the symptoms in some affected individuals is growth retardation. To understand the molecular basis of growth retardation in these patients with RTH, a transgenic mouse was prepared in which the expression of the TR beta 1 mutant PV was targeted to the pituitary using the promoter of the glycoprotein hormone alpha-subunit. The PV mutant was originally identified in a patient with severe growth impairment. The PV mutation is a C-insertion at codon 448 of the TR beta gene and leads to a frame-shift of the carboxyl-terminal 14 amino acids of TR beta 1, resulting in total loss of triiodothyronine (T-3) binding and transcriptional activation. PV was selectively expressed in the pituitary of the transgenic mouse and not in other tissues examined. The transgenic mice showed a significant impairment in weight gain. However, no changes in the serum level of thyroid-stimulating hormone were seen, and no elevation of thyroid hormones was detected in the transgenic mice. The circulating levels of growth hormone and insulin-like growth factor I were not affected in the transgenic mice, suggesting that the growth impairment in RTH is complex and is mediated by pathways that are yet to be elucidated. C1 NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Transgen Mouse Facil, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Pharmacol, Torrance, CA USA. Harbor UCLA Med Ctr, Res & Educ Inst, Natl Hormone & Pituitary Program, Torrance, CA 90509 USA. RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bldg 37,Room 2D24,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 25 TC 11 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 1999 VL 9 IS 11 BP 1137 EP 1145 DI 10.1089/thy.1999.9.1137 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259WJ UT WOS:000083916700015 PM 10595466 ER PT J AU Santostefano, MJ Richardson, VM Walker, NJ Blanton, J Lindros, KO Lucier, GW Alcasey, SK Birnbaum, LS AF Santostefano, MJ Richardson, VM Walker, NJ Blanton, J Lindros, KO Lucier, GW Alcasey, SK Birnbaum, LS TI Dose-dependent localization of TCDD in isolated centrilobular and periportal hepatocytes SO TOXICOLOGICAL SCIENCES LA English DT Article DE 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD); hepatocyte; cytochromes P450 ID ARYL-HYDROCARBON RECEPTOR; MULTICOMPARTMENT GEOMETRIC MODEL; RAT-LIVER; RESPONSE RELATIONSHIPS; TISSUE DISTRIBUTION; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; GENE-EXPRESSION; HEPATIC-UPTAKE; PERIVENOUS HEPATOCYTES; TRANSCRIPTION FACTORS AB Dose-response relationships for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suggest a differential sensitivity of liver cell types to the induction of cytochrome P450 gene expression, and that the induction of hepatic protein CYP1A2 causes sequestration of TCDD, In addition, immunolocalization of hepatic CYP1A1/1B1/ 1A2 proteins is not uniform after exposure to TCDD, The mechanism for the regio-specific induction of hepatic P450s by TCDD is unknown, but may involve the differential distribution of participants in the AhR-mediated pathway and/or regional P450 isozymes, as well as, non-uniform distribution/sequestration of TCDD, Therefore, this study examined the effects of TCDD in unfractionated, centrilobular and periportal hepatocytes isolated from female Sprague-Dawley rats acutely exposed (3 days) to a single oral dose of 0.01-10.0 mu g [(3)H]TCDD/kg. A dose-dependent increase in concentration of TCDD was accompanied by a dose-dependent increase in CYP1A1, CYP1A2, and CYP1B1 mRNA expression and associated enzymes in all liver-cell populations. Centrilobular hepatocytes showed a 2.7- to 4.5-fold higher concentration of TCDD as compared to the periportal hepatocytes at doses up to 0.3 mu g TCDD/kg, Centrilobular hepatocytes also exhibited an elevated MROD activity as compared to the periportal hepatocytes at doses up to 0.3 mu g TCDD/kg, Furthermore, centrilobular hepatocytes showed an elevated concentration of induced CYP1A2 and CYP1B1 mRNA as compared to periportal hepatocytes within the 0.01- and 0.3-mu g TCDD/kg-treatment groups. This is the first study to demonstrate that a dose-dependent difference in distribution of TCDD exists between centrilobular and periportal cells that might be related to regional differences in P450 induction. C1 Univ N Carolina, Chapel Hill, NC USA. NIEHS, Lab Computat Biol & Rick Anal, Res Triangle Pk, NC 27709 USA. Natl Publ Hlth Inst, Alcohol Res Ctr, Helsinki, Finland. RP Santostefano, MJ (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, Expt Toxicol Div, Pharmacokinet Branch, Mail Drop 74, Res Triangle Pk, NC 27711 USA. EM santostefano.michael@epamail.epa.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU NIEHS NIH HHS [1 F32 ES05701-01A1] NR 71 TC 20 Z9 22 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 1999 VL 52 IS 1 BP 9 EP 19 DI 10.1093/toxsci/52.1.9 PG 11 WC Toxicology SC Toxicology GA 255VH UT WOS:000083690500002 PM 10568693 ER PT J AU Chapin, RE Delaney, J Wang, YF Lanning, L Davis, B Collins, B Mintz, N Wolfe, G AF Chapin, RE Delaney, J Wang, YF Lanning, L Davis, B Collins, B Mintz, N Wolfe, G TI The effects of 4-nonylphenol in rats: A multigeneration reproduction study SO TOXICOLOGICAL SCIENCES LA English DT Article DE alkyphenols; gestational exposure; multigeneration; nonylphenol ethoxylate; reproduction study ID SERUM HORMONE CONCENTRATIONS; CD BR RATS; BREAST-CANCER; RAINBOW-TROUT; SPERM COUNTS; DOSE LEVELS; CHEMICALS; 17-BETA-ESTRADIOL; NONYLPHENOL; ETHOXYLATES AB The alkylphenol breakdown products of alkylphenol ethoxylates have been shown in in vitro studies to be weakly estrogenic, but few in vivo data address this issue in mammals. Because estrogens have been found to be most potent during developmental/perinatal exposures, this study maximized developmental exposure to nonylphenol (NP) by treating 3.5 generations of Sprague-Dawley rats to NP in diet at 200, 650, and 2000 ppm to determine the range and severity of any toxicity. Dose rate was higher for younger rats; calculated dose ranges were 9-35, 30-100, and 100-350 mg/kg/d for the low (200NP), middle (650NP), and high (2000NP) dose groups, respectively. There were adult (F-0, F-1, F-2)and postnatal day (and) 21 (F-1, F-2, F-3) necropsies; the oldest F-3 rats were killed on pnd 55-58. Body weight gain was reduced by 8-10% in the 650NP and 2000NP groups. Vaginal opening was accelerated by approximate to 2 days (650NP) and approximate to 6 days (2000NP) in F-1, F-2, and F-3 generations. Uterine weights at pnd 21 were increased in 650NP (14%) and 2000NP (50%) F-1 females, but not in other generations. Testis descent, anogenital distance, and preputial separation were not consistently changed. No consistent changes were seen in pup number, weight or viability, litter indices, or other functional reproductive measures. Relative ovary weight in F-2 adults was decreased at 650NP and 2000NP by 12%; relative ovary was unchanged in other generations. Follicle counts were unchanged in F-2 adults. Sperm indices, including CASA measures, were unchanged in F-0 and F-1 males. In F-2 rats, epididymal sperm density was reduced by 8% and 13% at 650NP and 2000NP, respectively. Testicular spermatid count was reduced by 13% in 2000NP F-2 males; testis and epididymis weights were unchanged, Erosion of gastric and duodenal mucosa was monitored grossly and microscopically, and never found. Kidney weights were increased in 650NP and 2000NP males, and renal medullary tubular dilatation and cyst formation were noted in all generations of males, and often at the lowest dose tested. These data show that NP had limited effects on the reproductive system in the presence of measurable nephro toxicity. The F-2-sperm effects are either statistical/biological "noise," or imply heretofore unknown pharmacokinetics or tosicodynamics. These sperm data should be interpreted cautiously until the findings are repeated. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Pathol Associates Int, Frederick, MD 21701 USA. ROW Sci, Gaithersburg, MD 20878 USA. Analyt Sci Inc, Durham, NC 27713 USA. RP Chapin, RE (reprint author), NIEHS, POB 12233,MD B3-05, Res Triangle Pk, NC 27709 USA. OI Chapin, Robert/0000-0002-5997-1261 FU NIEHS NIH HHS [N01-ES-55386] NR 41 TC 117 Z9 121 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 1999 VL 52 IS 1 BP 80 EP 91 DI 10.1093/toxsci/52.1.80 PG 12 WC Toxicology SC Toxicology GA 255VH UT WOS:000083690500010 PM 10568701 ER PT J AU Brown, P Cervenakova, L McShane, LM Barber, P Rubenstein, R Drohan, WN AF Brown, P Cervenakova, L McShane, LM Barber, P Rubenstein, R Drohan, WN TI Further studies of blood infectivity in an experimental model of transmissible spongiform encephalopathy, with an explanation of why blood components do not transmit Creutzfeldt-Jakob disease in humans SO TRANSFUSION LA English DT Article ID PLASMA DERIVATIVES; POOL SIZE; PRION AB BACKGROUND: Solid evidence from experimentally infected animals and fragmentary evidence from naturally infected humans indicate that blood may contain low levels of the infectious agent of Creutzfeldt-Jakob disease (CJD), yet blood components have never been identified as a cause of CJD in humans. STUDY DESIGN AND METHODS: Blood components and plasma fractions were prepared from the pooled blood of mice that had earlier been infected with a mouse-adapted strain of human transmissible spongiform encephalopathy (TSE). Infectivity bioassays were conducted in healthy mice, and the brains of all assay animals dying during the course of the experiments were examined for the presence of proteinase-resistant protein. RESULTS: Infectivity in the blood during the preclinical phase of disease occurred in the buffy coat at infectious unit (IU) levels between 6 and 12 per mt and was either absent or present in only trace amounts in plasma and plasma fractions. Infectivity rose sharply at the onset of clinical signs to levels of approximately 100 IU per mt of buffy coat, 20 IU per mt of plasma, 2 IU per mt of cryoprecipitate, and less than 1 IU per mt of fractions IV and V. Plasma infectivity was not eliminated by either white cell-reduction filtration or high-speed centrifugation. Approximately seven times more plasma and five times more buffy coat were needed to transmit disease by the intravenous route than by the intracerebral route. CONCLUSION: Epidemiologic evidence of the absence in humans of disease transmission from plasma components can probably be explained by I)the absence of significant plasma infectivity until the onset of symptomatic disease, and comparatively low levels of infectivity during the symptomatic stage of disease; 2) the reduction of infectivity during plasma processing; and 3) the need for at least five to seven times more infectious agent to transmit disease by the intravenous than intracerebral route. These and other factors probably also account for the absence of transmission after the administration of whole blood or blood components. C1 NINDS, Lab CNS Studies, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Jerome H Holland Lab, Rockville, MD USA. Allergan Pharmaceut Inc, Otisville, NY USA. Ins Bas Res Dev Disabil, Staten Isl, NY USA. RP Brown, P (reprint author), NINDS, Lab CNS Studies, NIH, Bldg 36,Room 4A 05,36 Convent Dr,MSC 4122, Bethesda, MD 20892 USA. NR 15 TC 227 Z9 232 U1 0 U2 4 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV-DEC PY 1999 VL 39 IS 11-12 BP 1169 EP 1178 DI 10.1046/j.1537-2995.1999.39111169.x PG 10 WC Hematology SC Hematology GA 263KR UT WOS:000084124300003 PM 10604242 ER PT J AU Melaragno, MG Fridell, YWC Berk, BC AF Melaragno, MG Fridell, YWC Berk, BC TI The Gas6/Axl system - A novel regulator of vascular cell function SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Article ID RECEPTOR TYROSINE KINASE; ARREST-SPECIFIC GENE-6; GROWTH-ARREST; SMOOTH-MUSCLE; SURVIVAL ACTIVITIES; PROTEIN-S; AXL; EXPRESSION; LIGAND; FIBROBLASTS AB Signal transduction downstream of tyrosine kinase has become an increasingly important area of study in cardiovascular biology. In this review, we consider the experimental evidence pointing to significant roles for the Axl receptor tyrosine kinase and its ligand, Gas6, in the vasculature. An introduction to the Gas6/Axl system and a discussion of its discovery is followed by a summary of the data regarding expression of Gas6/Axl in injured arteries. We conclude by discussing mechanisms by which Gas6/Axl signaling may impact on the response of blood vessels to injury, thereby contributing to the development of atherosclerosis and/or restenosis. C1 Univ Rochester, Cardiovasc Res Ctr, Rochester, NY 14642 USA. NCI, Div Clin Sci, NIH, Gaithersburg, MD USA. RP Berk, BC (reprint author), Univ Rochester, Cardiovasc Res Ctr, 601 Elmwood Ave,Box 679, Rochester, NY 14642 USA. OI Berk, Bradford/0000-0002-2767-4115 NR 29 TC 53 Z9 54 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD NOV PY 1999 VL 9 IS 8 BP 250 EP 253 DI 10.1016/S1050-1738(00)00027-X PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 384AH UT WOS:000165916500006 PM 11094334 ER PT J AU Elenkov, IJ Chrousos, GP AF Elenkov, IJ Chrousos, GP TI Stress hormones, Th1/Th2 patterns, pro/anti-inflammatory cytokines and susceptibility to disease SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; TUMOR-NECROSIS-FACTOR; MAST-CELL DEGRANULATION; IL-12 PRODUCTION; T-CELLS; HUMAN INTERLEUKIN-12; CD4(+) LYMPHOCYTES; HUMAN MONOCYTES; ACTH-SECRETION; NERVOUS-SYSTEM AB In general, stress has been regarded as immunosuppressive. Recent evidence, however, indicates that acute, subacute or chronic stress might suppress cellular immunity but boost humoral immunity. This is mediated by a differential effect of stress hormones, the glucocorticoids and catecholamines, on T helper 1 (Th1)/Th2 cells and type 1/type 2 cytokine production. Furthermore, acute stress might induce pro-inflammatory activities in certain tissues through neural activation of the peripheral corticotropin-releasing hormone-mast cell-histamine axis. Through the above mechanisms, stress might influence the onset and/or course of infectious, autoimmune/inflammatory, allergic and neoplastic diseases. C1 NICHHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Elenkov, IJ (reprint author), NICHHD, Pediat Endocrinol Sect, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 64 TC 421 Z9 448 U1 2 U2 24 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 NOV PY 1999 VL 10 IS 9 BP 359 EP 368 DI 10.1016/S1043-2760(99)00188-5 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 248BC UT WOS:000083254600003 ER PT J AU Gelboin, HV Krausz, KW Gonzalez, FJ Yang, TJ AF Gelboin, HV Krausz, KW Gonzalez, FJ Yang, TJ TI Inhibitory monoclonal antibodies to human cytochrome P450 enzymes: a new avenue for drug discovery SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID HUMAN LIVER-MICROSOMES; O-DEETHYLATION; METABOLISM; 1A2; CYP3A4; HYDROXYLATION; SPECIFICITY; IMIPRAMINE; EXPRESSION; BUFURALOL C1 NCI, NIH, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Gelboin, HV (reprint author), NCI, NIH, Mol Carcinogenesis Lab, Bldg 37,Room 3E24,37 Convent Dr, Bethesda, MD 20892 USA. NR 51 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD NOV PY 1999 VL 20 IS 11 BP 432 EP 438 DI 10.1016/S0165-6147(99)01382-6 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 252CD UT WOS:000083482400001 PM 10542439 ER PT J AU Redegeld, FA Caldwell, CC Sitkovsky, MV AF Redegeld, FA Caldwell, CC Sitkovsky, MV TI Ecto-protein kinases: ectodomain phosphorylation as a novel target for pharmacological manipulation? SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID FIBROBLAST GROWTH-FACTOR; LONG-TERM POTENTIATION; CELL-SURFACE PROTEIN; NUCLEOTIDE-BINDING-PROTEINS; ECTOPROTEIN KINASE; EXTRACELLULAR ATP; ENDOTHELIAL-CELLS; EFFECTOR FUNCTIONS; MEDIATED PHOSPHORYLATION; ADENOSINE-TRIPHOSPHATE AB An increasing number of studies document the presence of protein kinases facing outwards at the cell surface of a diverse array of cells. These ecto-protein kinases phosphorylate cell-surface proteins and soluble extracellular substrates, and thus could affect many physiological processes involving cell-cell contacts, cellular differentiation and proliferation, ion fluxes and cellular activation. To date, only limited attention has been paid to exploring ecto-protein kinases as possible pharmacological targets. Here, the identification and physiological role of ecto-protein kinases in different biological systems is described; it is suggested that ecto-protein kinases are attractive and novel candidates for pharmacological manipulation under various (patho)physiological conditions. C1 Univ Utrecht, Inst Pharmaceut Sci, Dept Pharmacol & Pathophysiol, NL-3508 TB Utrecht, Netherlands. NIAID, Biochem & Immunopharmacol Sect, Immunol Lab, NIH, Bethesda, MD 20814 USA. RP Redegeld, FA (reprint author), Univ Utrecht, Inst Pharmaceut Sci, Dept Pharmacol & Pathophysiol, POB 80082, NL-3508 TB Utrecht, Netherlands. RI Redegeld, Frank/O-6534-2016; OI Redegeld, Frank/0000-0001-8830-7960; Caldwell, Charles/0000-0003-1692-4550 NR 98 TC 74 Z9 76 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD NOV PY 1999 VL 20 IS 11 BP 453 EP 459 DI 10.1016/S0165-6147(99)01399-1 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 252CD UT WOS:000083482400007 PM 10542445 ER PT J AU Nagai, Y Helwegen, J Fleg, JL Kemper, MK Earley, CJ Rywik, TM Wijn, P Metter, EJ AF Nagai, Y Helwegen, J Fleg, JL Kemper, MK Earley, CJ Rywik, TM Wijn, P Metter, EJ TI Decay Index: A new carotid Doppler waveform measure associated with the Windkessel function of elastic arteries SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE carotid arteries; Doppler; Windkessel function; peripheral resistance ID CORONARY HEART-DISEASE; AORTIC COMPLIANCE; PRESSURE; FLOW; STIFFNESS; DECREASE; AGE AB The Windkessel function of elastic arteries determines the postpeak contour of the internal carotid artery (ICA) Doppler waveform. To introduce an indicator for the function, the postpeak contour was reproduced by an exponential function, and the exponential coefficient was termed "Decay Index" (DI), DI obtained from 108 stenosis-free ICAs (55.2 +/- 15.8 y) was compared with surrogate measures for the Windkessel function (aortic pulse wave velocity, pulse pressure) and BCA peripheral resistance (resistive index, pulsatility index, systolic-to-diastolic ratio). DI was moderately correlated with the Windkessel and the resistance measures (r ranged 0.44-0.57), To clarify these intercorrelations, principal component analysis revealed two components. The first was loaded by the resistance measures (component load greater than or equal to 0.93) although the second was loaded by the Windkessel measures and DI (greater than or equal to 0.70), supporting an association between DI and the Windkessel function, Thus, DI is likely to represent an indicator for the Windkessel function. (C) 1999 World Federation for Ultrasound in Medicine & Biology. C1 NIA, NIH, Clin Invest Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Osaka Univ, Sch Med, Dept Internal Med & Therapeut, Osaka, Japan. Eindhoven Univ Technol, Dept Phys Grp Phys Informat, NL-5600 MB Eindhoven, Netherlands. Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. NIA, NIH, Cardiovasc Res Lab, Baltimore, MD 21224 USA. St Josephs Hosp, Veldhoven, Netherlands. RP Metter, EJ (reprint author), NIA, NIH, Clin Invest Lab, Gerontol Res Ctr, Box 06,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 20 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD NOV PY 1999 VL 25 IS 9 BP 1371 EP 1376 DI 10.1016/S0301-5629(99)00100-3 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 255UL UT WOS:000083688500006 PM 10626624 ER PT J AU Pannek, J Lakshmanan, K Pound, CR Lemkin, PF Epstein, JI Partin, AW AF Pannek, J Lakshmanan, K Pound, CR Lemkin, PF Epstein, JI Partin, AW TI Nuclear shape and nuclear matrix protein composition in prostate and seminal vesicles SO UROLOGY LA English DT Article ID ROUNDNESS FACTOR MEASUREMENT; CELL STRUCTURE; CANCER; MORPHOMETRY; CARCINOMA; PROGNOSIS; DIFFERENTIATION; IDENTIFICATION; ORGANIZATION; PATTERNS AB Objectives. The nucleus controls cell function and behavior. The nuclear matrix determines internal nuclear changes. Two-dimensional gel electrophoresis is the reference standard for the analysis of nuclear matrix protein (NMP) composition. Differences in NMP composition should therefore be reflected by changes in nuclear shape. We investigated the differences in NMP composition and nuclear morphometry of the prostate and seminal vesicles. Both tissues are androgen-dependent sex accessory organs with completely different biologic behavior. Methods. High-resolution two-dimensional gel electrophoresis and silver staining were used to evaluate NMP composition from histologically normal prostate and seminal vesicle epithelial cells. Nuclear morphometry, performed using a computer-assisted image analysis system, described the distribution, variability, and extremes of nuclear shape. Results, NMP composition analysis demonstrated that both tissues have a similar NMP composition, and tissue-specific NMPs that were consistently present in all specimens of each tissue could not be demonstrated. Nuclear morphometry showed a significantly greater heterogeneity in nuclear shape in the seminal vesicles than in the prostate. Conclusions. The striking similarity of the NMP composition demonstrates the close biologic relationship between prostate and seminal vesicle tissue. The similar NMP composition does not correlate with the marked alterations in nuclear shape and structure between these tissues. Therefore, nuclear morphometry may depict differences in the functional state of a similar set of NMPs, shown by two-dimensional gel electrophoresis, which may be responsible for the different biologic behavior of these tissues. UROLOGY 54: 934-939, 1999. (C) 1999, Elsevier Science Inc. C1 Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NCI, Image Proc Sect, Frederick, MD 21701 USA. RP Partin, AW (reprint author), Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, 600 N Wolfe St, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA58236] NR 32 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD NOV PY 1999 VL 54 IS 5 BP 934 EP 939 DI 10.1016/S0090-4295(99)00275-7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 253BE UT WOS:000083536100039 PM 10565764 ER PT J AU Terman, M Terman, JS Ross, DC AF Terman, M Terman, JS Ross, DC TI Bright light and high-density negative air ionization reduces symptoms of seasonal affective disorder SO WESTERN JOURNAL OF MEDICINE LA English DT Article C1 New York State Psychiat Inst, New York, NY 10032 USA. NIH, Bethesda, MD USA. RP Terman, M (reprint author), New York State Psychiat Inst, 1051 Riverside Dr,Unit 50, New York, NY 10032 USA. OI Partonen, Timo/0000-0003-1951-2455 NR 4 TC 0 Z9 0 U1 2 U2 4 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD NOV-DEC PY 1999 VL 171 IS 5-6 BP 315 EP 316 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 267HJ UT WOS:000084352100015 ER PT J AU Bastian, LA McBride, CM Halabi, S Fish, LJ Skinner, CS Kaplan, EB Bosworth, HB Rimer, BK Siegler, IC AF Bastian, LA McBride, CM Halabi, S Fish, LJ Skinner, CS Kaplan, EB Bosworth, HB Rimer, BK Siegler, IC TI Attitudes and knowledge associated with being undecided about hormone replacement therapy: Results from a community sample SO WOMENS HEALTH ISSUES LA English DT Article ID POSTMENOPAUSAL WOMEN; HEART-DISEASE; RISK; METAANALYSIS; PREVENTION; MENOPAUSE; CANCER AB HRT has important potential public health benefits because it can delay the age of onset and reduce the risk of many chronic diseases. However, the inherent complexity of HRT risk and benefit analyses necessary for a woman to make an informed decision about whether to use HRT presents a significant challenge. To date, decision-aid interventions have primarily been evaluated with clinic-based samples of women who may or may not represent the needs of women in the community. This paper reports data from the baseline assessment of participants in a randomized controlled trial designed to evaluate the efficacy of a tailored decision-aid intervention on HRT decision making. Of the community sample of 581 women ages 45-54 who were interviewed by telephone, 318 were determined to be menopausal and were included in this report. Fully one-third (n = 104) of these menopausal women were undecided about using HRT; 55% (n = 176) had decided to use HRT and 12% (n = 38) had decided against using HRT. Women who were undecided about HRT use were significantly different from the other two groups in their income, stage of menopause, prior use of HRT, hysterectomy rates, attitudes about menopause, and knowledge about HRT. This paper describes directions and strengths of these differences. Findings suggest that future decision-aid interventions with potential for dissemination outside of clinical settings would benefit this undecided group. C1 Durham Vet Affairs Med Ctr, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27705 USA. Durham Vet Affairs Med Ctr, Dept Internal Med, Durham, NC USA. Durham Vet Affairs Med Ctr, Dept Community & Family Med, Durham, NC USA. Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. NCI, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Bastian, LA (reprint author), Durham Vet Affairs Med Ctr, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, 508 Fulton St 152, Durham, NC 27705 USA. NR 22 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD NOV-DEC PY 1999 VL 9 IS 6 BP 330 EP 337 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 334PW UT WOS:000088195700007 ER PT J AU Korn, EL Midthune, D Chen, TT Rubinstein, LV Christian, MC Simon, RM AF Korn, EL Midthune, D Chen, TT Rubinstein, LV Christian, MC Simon, RM TI Another look at two phase I clinical trial designs - Commentary SO STATISTICS IN MEDICINE LA English DT Editorial Material ID CONTINUAL REASSESSMENT METHOD; CANCER C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. NCI, Biometr Branch, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch, EPN-739, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 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 OCT 30 PY 1999 VL 18 IS 20 BP 2691 EP 2692 DI 10.1002/(SICI)1097-0258(19991030)18:20<2691::AID-SIM194>3.0.CO;2-0 PG 2 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 246WH UT WOS:000083187500002 ER PT J AU Troendle, JF AF Troendle, JF TI Approximating the power of Wilcoxon's rank-sum test against shift alternatives SO STATISTICS IN MEDICINE LA English DT Article ID 2-SAMPLE AB Three methods of approximating the power of Wilcoxon's rank-sum test against shift alternatives are studied. They are obtained by using a Gaussian assumption, Edgeworth expansion, or bootstrap. It is assumed that a historical data set is available to use in estimating the shape of the distribution. The methods are compared through simulation across several different distributional types, The results indicate that the bootstrap generally gives the most reliable approximation, however the Edgeworth expansion has the practical advantage that a lower bound on the power can be roughly approximated, The methods are illustrated on muscle strength data from patients with osteogenesis imperfecta, Published in 1999 by John Wiley & Sons, Ltd. This is US Government work and is in the public domain in the United States. C1 NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Troendle, JF (reprint author), NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH, Bld 6100 Rm 7B13, Bethesda, MD 20892 USA. NR 6 TC 7 Z9 7 U1 0 U2 0 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 OCT 30 PY 1999 VL 18 IS 20 BP 2763 EP 2773 PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 246WH UT WOS:000083187500008 PM 10521865 ER PT J AU Angeloni, D Lindor, NM Pack, S Latif, F Wei, MH Lerman, MI AF Angeloni, D Lindor, NM Pack, S Latif, F Wei, MH Lerman, MI TI CALL gene is haploinsufficient in a 3p-syndrome patient SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CALL; 3p-syndrome; IQ ID KARYOTYPE-PHENOTYPE CORRELATION; CELL-ADHESION MOLECULE; SHORT ARM; CHROMOSOME-3; DELETION; IDENTIFICATION; CLONING AB The 3p- syndrome results from deletion of a terminal, segment of the short arm of one chromosome 3 (3p25-->pter), and is characterized by multiple congenital anomalies and mental retardation. Due to its variable expression, it is assumed this disorder is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype, In an effort to discover genes contributing to mental deflects in 3p- syndrome, we determined whether the CALL gene, mapped to 3p26.1 and coding far a neural recognition molecule, is deleted in a boy with this disorder. We found that the break in this patient is distal to the VHL gene, removing D3S18 and the CALL loci, The deletion of one copy of the CALL gene might be responsible for mental defects in patients with 3p- syndrome. Published 1999 Wiley-Liss, Inc.(dagger) C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Mayo Clin, Dept Med Genet, Rochester, MN USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Angeloni, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Bldg 560,Room 12-68, Frederick, MD 21702 USA. RI Pack, Svetlana/C-2020-2014 FU NCI NIH HHS [N01-CO-56000] NR 17 TC 70 Z9 73 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 29 PY 1999 VL 86 IS 5 BP 482 EP 485 DI 10.1002/(SICI)1096-8628(19991029)86:5<482::AID-AJMG15>3.0.CO;2-L PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 243WC UT WOS:000083019600015 PM 10508992 ER PT J AU Huang, BY Wang, S Qin, DY Boutjdir, M El-Sherif, N AF Huang, BY Wang, S Qin, DY Boutjdir, M El-Sherif, N TI Diminished basal phosphorylation level of phospholamban in the postinfarction remodeled rat ventricle - Role of beta-adrenergic pathway, G(i) protein, phosphodiesterase, and phosphatases SO CIRCULATION RESEARCH LA English DT Article DE phospholamban; phosphatase; postmyocardial infarction; sarcoplasmic reticulum ID SARCOPLASMIC-RETICULUM CA2+-ATPASE; STAGE HEART-FAILURE; EXPERIMENTAL MYOCARDIAL-INFARCTION; FAILING HUMAN MYOCARDIUM; MESSENGER-RNA; GENE-EXPRESSION; CONTRACTILE DYSFUNCTION; CARDIAC-MUSCLE; TROPONIN-I; CA-2+-ATPASE AB Three weeks after myocardial infarction (MI) in the rat, remodeled hypertrophy of noninfarcted myocardium is at its maximum and the heart is in a compensated stage with no evidence of heart failure. Our hemodynamic measurements at this stage showed a slight but insignificant decrease of +dP/dt but a significantly higher left ventricular end-diastolic pressure. To investigate the basis of the diastolic dysfunction, we explored possible defects in the beta-adrenergic receptor-G(s/i) protein-adenylyl cyclase-cAMP-protein kinase A-phosphatase pathway, as well as molecular or functional alterations of sarcoplasmic reticulum Ca2+-ATPase and phospholamban (PLB). We found no significant difference in both mRNA and protein levels of sarcoplasmic reticulum Ca2+-ATPase and PLB in post-MI left ventricle compared with control. However, the basal levels of both the protein kinase A-phosphorylated site (Ser16) of PLB (p16-PLB) and the calcium/calmodulin-dependent protein kinase-phosphorylated site (Thr17) of PLB (p17-PLB) were decreased by 76% and 51% in post-MI myocytes (P < 0.05), respectively. No change was found in the P-adrenoceptor density, G(s alpha) protein level, or adenylyl cyclase activity. Inhibition of phosphodiesterase and G(i) protein by Ro-20-1724 and pertussis toxin respectively, did not correct the decreased p16-PLB or p17-PLB levels. Stimulation of beta-adrenoceptor or adenylyl cyclase increased both p16-PLB and p17-PLB in post-MI myocytes to the same levels as in sham myocytes, suggesting that decreased p16-PLB and p17-PLB in post-MI myocytes is not due to a decrease in the generation of p16-PLB or p17-PLB. We found that type I phosphatase activity was increased by 32% (P < 0.05) with no change in phosphatase 2A activity. Okadaic acid, a protein phosphatase inhibitor, significantly increased p16-PLB and p17-PLB levels in post-MI myocytes and partially corrected the prolonged relaxation of the [Ca2+](i) transient. In summary, prolonged relaxation of post-MI remodeled myocardium could be explained, in part, by altered basal levels of p16-PLB and p17-PLB caused by increased protein phosphatase 1 activity. C1 SUNY Hlth Sci Ctr, Div Cardiol, Dept Med, Brooklyn, NY 11203 USA. Vet Affairs Med Ctr, Brooklyn, NY USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP El-Sherif, N (reprint author), SUNY Hlth Sci Ctr, Div Cardiol, Dept Med, Box 1199,450 Clarkson Ave, Brooklyn, NY 11203 USA. NR 56 TC 74 Z9 75 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 OCT 29 PY 1999 VL 85 IS 9 BP 848 EP 855 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 260BU UT WOS:000083929100010 PM 10532953 ER PT J AU Al-Hasani, H Yver, DR Cushman, SW AF Al-Hasani, H Yver, DR Cushman, SW TI Overexpression of the glucose transporter GLUT4 in adipose cells interferes with insulin-stimulated translocation SO FEBS LETTERS LA English DT Article DE GLUT4; insulin; adipose cell; overexpression; translocation; exocytosis ID TRANSGENIC MICE; SUBCELLULAR TRAFFICKING; SNAP RECEPTORS; RAT; LOCALIZATION; MEMBRANE; VESICLES; SURFACE; PROTEIN; MUSCLE AB In adipose cells, insulin induces the translocation of GLUT4 by stimulating their exocytosis from a basal intracellular compartment to the plasma membrane. Increasing overexpression of a hemagglutinin (HA) epitope-tagged GLUT4 in rat adipose cells results in a roughly proportional increase in cell surface HA-GLUT4 levels in the basal state, accompanied by a marked reduction of the fold HA-GLUT4 translocation in response to insulin. Using biochemical methods and cotransfection experiments with differently epitope-tagged GLUT4, wt show that overexpression of GLUT4 does not affect the intracellular sequestration of GLUT4 in the absence of insulin, but rather reduces the relative insulin-stimulated GLUT4 translocation to the plasma membrane, In contrast, overexpression of GLUT1 does not interfere with the targeting of GLUT4 and vice versa, These results suggest that the mechanism involved in the intracellular sequestration of GLUT4 has a high capacity whereas the mechanism for GLUT4 translocation is readily saturated by overexpression of GLUT4, implicating an active translocation machinery in the exocytosis of GLUT4. (C) 1999 Federation of European Biochemical Societies. C1 NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Al-Hasani, H (reprint author), Univ Cologne, Inst Biochem, Otto Fischer Str 12-14, D-50674 Cologne, Germany. NR 24 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 29 PY 1999 VL 460 IS 2 BP 338 EP 342 DI 10.1016/S0014-5793(99)01369-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 252MG UT WOS:000083504800028 PM 10544260 ER PT J AU Qu, BH Karas, M Koval, A LeRoith, D AF Qu, BH Karas, M Koval, A LeRoith, D TI Insulin receptor substrate-4 enhances insulin-like growth factor-I-induced cell proliferation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RAT ADIPOSE-CELLS; SIGNAL-TRANSDUCTION; PHOSPHOTYROSINE PROTEIN; TYROSINE KINASE; IRS-1; DOMAIN; TRANSFORMATION; TRANSLOCATION; ACTIVATION; ADIPOCYTES AB The insulin receptor substrates (IRSs)-1-4 play important roles in signal transduction emanating from the insulin and insulin-like growth factor (IGF)-I receptors. IRS-4 is the most recently characterized member, which has been found primarily in human cells and tissues. It interacts with SH2-containing proteins such ars phosphatidylinositol 3'-kinase (PI3K), Grb2, Crk-II, and CrkL. In this study, we transfected IRS-4 in mouse NIH-3T3 cells that overexpress IGF-I receptors. Clones expressing IRS-4 showed enhanced cellular proliferation when cells were cultured in 1% fetal bovine serum without added IGF-I. Addition of IGF-I enhanced cellular proliferation in cells overexpressing the IGF-I receptor alone but had an even greater proliferative effect in cells overexpressing both the IGF-I receptors and IRS-4. When etoposide and methylmethane sulfonate (MMS), both DNA damaging agents, were added to the cells, they uniformly induced cell cycle arrest. Fluorescence-activated cell sorter analysis demonstrated that the arrest of the cell cycle occurred at the G(1) checkpoint, and furthermore no significant degree of apoptosis was demonstrated with the use of either agent. In cells, overexpressing IGF-I receptors alone, IG;F-I addition enhanced cellular proliferation, even in the presence of etoposide and MMS. In cells overexpressing IGF-I receptors and IRS-4, the effect of IGF-I in overcoming the cell cycle arrest was even more pronounced. These results suggest that IRS-4 is implicated in the IGF-I receptor mitogenic signaling pathway. C1 NIDDK, Clin Endocrinol Branch, NIH, Sect Mol & Cellular Physiol, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Sect Mol & Cellular Physiol, Rm 8D12,Bldg 10, Bethesda, MD 20892 USA. NR 29 TC 40 Z9 43 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 29 PY 1999 VL 274 IS 44 BP 31179 EP 31184 DI 10.1074/jbc.274.44.31179 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250FY UT WOS:000083379400014 PM 10531310 ER PT J AU Ro, HS Miles, EW AF Ro, HS Miles, EW TI Catalytic mechanism of the tryptophan synthase alpha(2)beta(2) complex - Effects of pH, isotopic substitution, and allosteric ligands SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; INDUCED CONFORMATIONAL-CHANGES; O-ACETYLSERINE SULFHYDRYLASE; CARBON CARBON LYASES; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; BETA-SUBUNIT; L-SERINE; PYRIDOXAL-PHOSPHATE; INTERSUBUNIT COMMUNICATION AB The mechanism of the tryptophan synthase alpha(2)beta(2) complex from Salmonella typhimurium is explored by determining the effects of pH, of temperature, and of isotopic substitution on the pyridoxal phosphate-dependent reaction of L-serine with indole to form L-tryptophan, The pH dependence of the kinetic parameters indicates that three ionizing groups are involved in substrate binding and catalysis with pK(a)1 = 6.5, pK(a)2 = 7.3, and pK(a)3 = 8.2-9. A significant primary isotope effect (similar to 3.5) on V and V/K is observed at low pH (pH 7), but not at high pH (pH 9), indicating that the base that accepts the alpha-proton (beta Lys-87) is protonated at low pH, slowing the abstraction of the alpha-proton and making this step at least partially rate- limiting. pK(a)2 is assigned to beta Lys-87 on the basis of the kinetic isotope effect results and of the observation that the competitive inhibitors glycine and oxindolyl-L-alanine display single pK(i) values of 7.3. The residue with this pK(a) (beta Lys-87) must be unprotonated for binding glycine or oxindolyl-L-alanine and, by inference, L-serine. Investigations of the temperature dependence of the pK(a) values support the assignment of pK(a)2 to beta Lys-87 and suggest that the ionizing residue with pK(a)1 could be a carboxylate, possibly beta Asp-305, and that the residue associated with a conformational change at pK(a)3 may be beta Lys-167. The occurrence of a closed to open conformational conversion at high pH is supported by investigations of the effects of pH on reaction specificity and on the equilibrium distribution of enzyme-substrate intermediates. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Miles, EW (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rm 225,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. EM EdithM@intra.niddk.nih.gov NR 51 TC 11 Z9 11 U1 2 U2 7 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 OCT 29 PY 1999 VL 274 IS 44 BP 31189 EP 31194 DI 10.1074/jbc.274.44.31189 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250FY UT WOS:000083379400016 PM 10531312 ER PT J AU Tapia, JA Ferris, HA Jensen, RT Garcia, LJ AF Tapia, JA Ferris, HA Jensen, RT Garcia, LJ TI Cholecystokinin activates PYK2/CAK beta by a phospholipase C-dependent mechanism and its association with the mitogen-activated protein kinase signaling pathway in pancreatic acinar cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; EPIDERMAL GROWTH-FACTOR; STIMULATES TYROSINE PHOSPHORYLATION; VASCULAR SMOOTH-MUSCLE; LIVER EPITHELIAL-CELLS; N-TERMINAL KINASE; SWISS 3T3 CELLS; ANGIOTENSIN-II; COUPLED RECEPTORS; MAP-KINASE AB PYK2/CAK beta is a recently described cytoplasmic tyrosine kinase related to p125 focal adhesion kinase (p125(FAK)) that can be activated by a number of stimuli including growth factors, lipids, and some G protein-coupled receptors. Studies suggest PYK2/CAK beta may be important for coupling various G protein-coupled receptors to the mitogen-activated protein kinase (MAPK) cascade. The hormone neurotransmitter cholecystokinin (CCK) is known to activate both phospholipase C-dependent cascades and MAPK signaling pathways; however, the relationship between these remain unclear. In rat pancreatic acini, CCK-8 (10 nM) rapidly stimulated tyrosine phosphorylation and! activation of PYK2/CAK beta by both activation of high affinity and low affinity CCKA receptor states. Blockage of CCK-stimulated increases in protein kinase C activity or CCK-stimulated increases in [Ca2+](i), inhibited by 40-50% PYK2/CAK beta but not p125FAK tyrosine phosphorylation. Simultaneous blockage of both phospholipase C cascades inhibited PYK2/CAK beta tyrosine phosphorylation completely and p125(FAK) tyrosine phosphorylation by 50%. CCK-8 stimulated a rapid increase in PYK2/CAK beta kinase activity assessed by both an in vitro kinase assay and autophosphorylation. Total PYK2/CAK beta under basal conditions was largely localized (77 +/- 7%) in the membrane fraction, whereas total p125(FAK) was largely localized (86 +/- 3%) in the cytosolic fraction. With CCK stimulation, both p125(FAK) and PYK2/CAK beta translocated to the plasma membrane. Moreover CCK stimulation causes a rapid formation of both PYK2/CAK beta-Grb2 and PYK2/CAK beta-Crk complexes. These results demonstrate that PYK2/CAK beta and p125(FAK) are regulated differently by CCKA receptor stimulation and that PYK2/CAK beta is probably an important mediator of downstream signals by CCK-8, especially in its ability to activate the MAPK signaling pathway, which possibly mediates CCK growth effects in normal and neoplastic tissues. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Extremadura, Dept Fisiol, Caceres 10071, Spain. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, 10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. RI Garcia-Marin, Luis /L-4680-2014; Tapia, Jose/C-5181-2008 OI Garcia-Marin, Luis /0000-0002-1795-7381; Tapia, Jose/0000-0002-3614-6867 NR 95 TC 50 Z9 51 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 29 PY 1999 VL 274 IS 44 BP 31261 EP 31271 DI 10.1074/jbc.274.44.31261 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250FY UT WOS:000083379400027 PM 10531323 ER PT J AU Choi, CY Lee, YM Kim, YH Park, T Jeon, BH Schulz, RA Kim, Y AF Choi, CY Lee, YM Kim, YH Park, T Jeon, BH Schulz, RA Kim, Y TI The homeodomain transcription factor NK-4 acts as either a transcriptional activator or repressor and interacts with the p300 coactivator and the Groucho corepressor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING SPECIFICITY; GERM-CELL MIGRATION; GENE-EXPRESSION; HOMEOBOX GENES; COOPERATIVE INTERACTIONS; PROTEIN-INTERACTION; GONADAL MESODERM; DROSOPHILA CBP; HEART; TINMAN AB NK-4 (tinman) encodes an NK-2 class homeodomain transcription factor that is required for development of the Drosophila dorsal mesoderm, including heart. Genetic evidence suggests its important role in mesoderm subdivision, yet the properties of NK-4 as a transcriptional regulator and the mechanism of gene transcription by NK-4 are not completely understood. Here, we describe its properties as a transcription factor and its interaction with the p300 coactivator and the Groucho corepressor. We demonstrate that NK-4 can activate or repress target genes in cultured cells, depending on functional domains that are conserved between Drosophila melanogaster and Drosophila virilis NK-4 genes. Using GAL4-NK-4 fusion constructs, we have mapped a transcriptional activation domain (amino acids 1-110) and repression domains (amino acids 111-188 and time homeodomain) and found an inhibitory function for the homeodomain in transactivation by NK-4. Furthermore, we demonstrate that NK-4-dependent transactivation is augmented by the p300 coactivator and show that NK-4 physically interacts with p300 via the activation domain. In addition, cotransfection experiments indicate that the repressor activity of NK-4 is strongly enhanced by the Groucho corepressor. Using immunoprecipitation and in vitro pull-down assays, we show that NK-4 directly interacts with the Groucho corepressor, for which the homeodomain is required. Together, our results indicate that NK-4 can act as either a transcriptional activator or repressor and provide the first evidence of NK-4 interactions with the p300 coactivator and the Groucho corepressor. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. Konkuk Univ, Dept Mol Biol, Chungju, South Korea. Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. RP Kim, Y (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10 Rm 8N228,10 Ctr Dr MSC1762, Bethesda, MD 20892 USA. EM yongsok@helix.nih.gov NR 71 TC 51 Z9 51 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 29 PY 1999 VL 274 IS 44 BP 31543 EP 31552 DI 10.1074/jbc.274.44.31543 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250FY UT WOS:000083379400061 PM 10531357 ER PT J AU Alberdi, E Aymerich, MS Becerra, SP AF Alberdi, E Aymerich, MS Becerra, SP TI Binding of pigment epithelium-derived factor (PEDF) to retinoblastoma cells and cerebellar granule neurons - Evidence for a PEDF receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENZYME COMPLEX RECEPTOR; AMYLOID-BETA PEPTIDE; NEUROTROPHIC ACTIVITY; NONINHIBITORY SERPIN; NEURITE OUTGROWTH; HEPATOMA-CELLS; NERVOUS-SYSTEM; BOVINE EYES; PROTEIN; GENE AB Pigment epithelium-derived factor (PEDF);has neuronal differentiation and survival;activity on retinoblastoma and cerebellar granule (CG) cells. Here, we investigated the presence of PEDF receptors on retinoblastoma Y-79 and CG cells. PEDF radiolabeled with I-125 remained biologically active and was used for radioligand binding analysis. The binding was saturable and specific to a single class of receptors on both cells and with similar affinities (K-d = 1.7-3.6 nM, B-max = 10.5-2.7 x 10(5) sites/Y-79 cell; and K-d = 3.2 nM, B-max = 1.1 x 10(3) sites/CG cell). A polyclonal antiserum to PEDF, previously shown to block the PEDF neurotrophic activity, prevented the I-125-PEDF binding. We designed two peptides from a region previously shown to confer the neurotrophic property to human PEDF, synthetic peptides 34-mer (positions 44-77) and 44-mer (positions 78-121). Only peptide 44-mer competed for the binding to Y-79 cell receptors (EC50 = 5 nM) and exhibited neuronal differentiating activity. PEDF affinity column chromatography of membrane proteins from both cell types revealed a PEDF-binding protein of similar to 80 kDa. These results are the first demonstration of at PEDF-binding protein with characteristics of a PEDF receptor and suggest that the region comprising amino acid positions 78-121 of PEDF might be involved in ligand-receptor interactions. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bldg 6,Rm 308,6 Ctr Dr,MSC 2740, Bethesda, MD 20892 USA. OI Alberdi, Elena/0000-0002-8000-142X NR 44 TC 102 Z9 108 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 OCT 29 PY 1999 VL 274 IS 44 BP 31605 EP 31612 DI 10.1074/jbc.274.44.31605 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250FY UT WOS:000083379400071 PM 10531367 ER PT J AU Bidwell, LM McManus, ME Gaedigk, A Kakuta, Y Negishi, M Pedersen, L Martin, JL AF Bidwell, LM McManus, ME Gaedigk, A Kakuta, Y Negishi, M Pedersen, L Martin, JL TI Crystal structure of human catecholamine sulfotransferase SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE dopamine; SULT1A3; sulfotransferase; protein structure; catecholamine ID MOLECULAR-CLONING; FLAVONOL 3-SULFOTRANSFERASE; PHENOL SULFOTRANSFERASE; MUTATIONAL ANALYSIS; PROTEIN MODELS; ACTIVE-SITE; SULFATE; EXPRESSION; PURIFICATION; DISORDERS AB Sulfonation, like phosphorylation, can modify the activity of a variety of biological molecules. The sulfotransferase enzymes sulfonate neurotransmitters, drugs, steroid hormones, dietary carcinogens and proteins. SULT1A3 specifically sulfonates catecholamines such as dopamine, adrenaline and noradrenaline. The crystal structure of SULT1A3 with a sulfate bound at the active site, has been determined at 2.4 Angstrom resolution. Although the core alpha/beta fold is like that of estrogen and heparan sulfotransferases, major differences occur in and around the active site. Most notably, several regions Surrounding the active site, including a section of 40 residues, are disordered in SULT1A3. Regions that are topologically equivalent to the disordered parts of SULT1A3 are involved in substrate and cofactor binding in estrogen and heparan sulfotransferase. Flexibility in these regions suggests that ligand binding elicits a disorder-order transition in and around the active site of sulfotransferases and might contribute to the broad substrate specificity of these enzymes. (C) 1999 Academic Press. C1 Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. Univ Queensland, Dept Physiol & Pharmacol, Brisbane, Qld 4072, Australia. Childrens Mercy Hosp, Dept Clin Pharmacol & Toxicol, Kansas City, MO 64108 USA. NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Martin, JL (reprint author), Univ Queensland, Ctr Drug Design & Dev, Brisbane, Qld 4072, Australia. OI Martin, Jennifer L./0000-0002-9225-8863 NR 51 TC 80 Z9 85 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 29 PY 1999 VL 293 IS 3 BP 521 EP 530 DI 10.1006/jmbi.1999.3153 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250XF UT WOS:000083415000007 PM 10543947 ER PT J AU Padberg, F Feneberg, W Schmidt, S Schwarz, MJ Korschenhausen, D Greenberg, BD Nolde, T Muller, N Trapmann, H Konig, N Moller, HJ Hampel, H AF Padberg, F Feneberg, W Schmidt, S Schwarz, MJ Korschenhausen, D Greenberg, BD Nolde, T Muller, N Trapmann, H Konig, N Moller, HJ Hampel, H TI CSF and serum levels of soluble interleukin-6 receptors (sIL-6R and sgp130), but not of interleukin-6 are altered in multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci DE multiple sclerosis; CSF; serum; cytokines; interleukin-6; interleukin-6 receptor; gp130 ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MYELIN OLIGODENDROCYTE GLYCOPROTEIN; MESSENGER-RNA EXPRESSION; IL-6-DEFICIENT MICE; CEREBROSPINAL-FLUID; IL-6 RECEPTOR; T-CELL; GP130; CYTOKINES AB Interleukin-6 (IL-6) has recently been implicated in multiple sclerosis (MS), since IL-6 deficient mice were resistant to a demyelinating form of experimental autoimmune encephalomyelitis and IL-6 expression was upregulated in MS. The cytokine IL-6 and its action mediating soluble receptors (sIL-6R and sgp130) were measured in cerebrospinal fluid (CSF) and serum of 61 MS patients and 39 controls. In the presence of unchanged IL-6 concentrations, sn-6R and sgp130 serum levels were significantly increased in MS and correlated with disease severity. Furthermore, sgp130 CSF levels were decreased in MS, suggesting a possibly altered IL-6 regulation in the CSF. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Munich, Dept Psychiat, D-80336 Munich, Germany. Marianne Strauss Hosp, Multiple Sclerosis Ctr, D-82335 Kempfenhausen, Germany. Univ Bonn, Dept Neurol, D-53105 Bonn, Germany. NIMH, NIH, Bethesda, MD 20892 USA. Dr Schreiber Hosp, D-81679 Munich, Germany. RP Padberg, F (reprint author), Univ Munich, Dept Psychiat, Nussbaumstr 7, D-80336 Munich, Germany. NR 33 TC 50 Z9 51 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 OCT 29 PY 1999 VL 99 IS 2 BP 218 EP 223 DI 10.1016/S0165-5728(99)00120-4 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 239HP UT WOS:000082762900009 PM 10505978 ER PT J AU Waalkes, MP Anver, MR Diwan, BA AF Waalkes, MP Anver, MR Diwan, BA TI Chronic toxic and carcinogenic effects of oral cadmium in the noble (NBL/Cr) rat: Induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID LEYDIG-CELL TUMORS; WISTAR CRL-(WI)BR RATS; DOSE-RESPONSE ANALYSIS; LEAD ACETATE; RENAL CARCINOGENESIS; INJECTION SITE; CANCER; PROMOTION; ACID; MECHANISM AB Based on the occurrence of pulmonary cancers in exposed populations, cadmium is classified as a human carcinogen. More controversial target sites for cadmium in humans include the prostate and kidney, where some studies have shown a link between cadmium and cancer. in Wistar rats cadmium induces tumors in the ventral prostate. The relevance of such lesions to humans is debated since the rat ventral lobe, unlike the dorsolateral lobe, has no embryological homolog in the human prostate. Cadmium has not been linked with renal tumors in rodents but is a potent nephrotoxin. In this work we studied the effects of oral cadmium in the Noble (NBL/Cr) rat with particular attention to proliferative lesions of the prostate and kidneys. Cadmium (as CdCl2) was given ad libitum throughout the study in the drinking water at doses of 0, 25, 50, 100, and 200 ppm Cd to groups (initial n = 30) of male rats, which were observed for up to 102 wk. At the lower doses of cadmium (less than or equal to 50 ppm) a clear dose-related increase in total proliferative lesions of the prostate (ventral and dorsolateral lesions combined) occurred (0 ppm = 21% incidence, 25 ppm = 46%, 50 ppm = 50%; bend p < .03). These lesions were described as intraepithelial hyperplasia with occasional areas of atypical epithelial cells without stromal invasion. The lesions occurred primarily in the dorsolateral prostate with cadmium exposure and most frequently showed three or more foci within each specimen. At higher doses, prostatic proliferative lesions declined to control levels. The loss of prostatic response at the higher doses was likely due to diminished testicular function secondary to cadmium treatment. This was reflected in lesions indicative of testicular hypofunction at the highest cadmium dose, namely, interstitial cell hyperplasia, and a strong correlation between cadmium dose and total proliferative lesions of the testes (hyperplasias and tumors combined). Renal tumors (mainly mesenchymal and pelvic transitional cell), although few in number, showed a positive correlation with cadmium dose, as did pelvic transitional epithelial hyperplasia. Renal lesions were not associated with any cadmium-induced changes in age-related chronic nephropathy. The incidence of pheochromocytomas of the adrenal was increased by cadmium but only at the 50 ppm dose. inflammatory lesions of the liver and spleen were common at higher doses and showed strong trends based on dose. These results indicate that oral cadmium can induce proliferative lesions in the prostate and kidney of the Noble rat. The finding of proliferative lesions of dorsolateral prostate in rats has presumed relevance to human prostate cancers. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. NCI, Pathol Histol Lab, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 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 46 TC 65 Z9 66 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0098-4108 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD OCT 29 PY 1999 VL 58 IS 4 BP 199 EP 214 DI 10.1080/009841099157296 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 251YW UT WOS:000083474800002 PM 10591488 ER PT J AU Krause, RM AF Krause, RM TI Paul Ehrlich and O.T. Avery: pathfinders in the search for immunity SO VACCINE LA English DT Article; Proceedings Paper CT 4th European Conference on Vaccinology: the Societal Value of Vaccination CY MAR 17-19, 1999 CL BRIGHTON, ENGLAND SP European Vaccine Manufacturers ID PREVENTION; DISEASES AB This paper is concerned with the use of passive immunity for the prevention and treatment of infections from a historic perspective, particularly in regard to the research of Paul Ehrlich on diphtheria and that of O.T. Avery on pneumonia. It is timely to reexamine this matter, particularly in regard to virus infections, in view of the difficulties in developing antiviral drugs. In addition, specific antibodies can serve as an alternative therapy for antibiotic resistant microbes. It is worth recalling in the history of vaccine development that success in passive immunity has been the key element in devising a successful strategy to develop a vaccine to produce humoral immunity. Published by Elsevier Science Ltd. C1 Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. RP Krause, RM (reprint author), Fogarty Int Ctr, NIH, 9000 Rockville Pike,Bldg 16,Room 202, Bethesda, MD 20892 USA. NR 11 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 29 PY 1999 VL 17 SU 3 BP S64 EP S67 DI 10.1016/S0264-410X(99)00296-0 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 260RA UT WOS:000083962600015 PM 10559538 ER PT J AU Chun, TW Davey, RT Engel, D Lane, HC Fauci, AS AF Chun, TW Davey, RT Engel, D Lane, HC Fauci, AS TI AIDS - Re-emergence of HIV after stopping therapy SO NATURE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; ANTIRETROVIRAL THERAPY; INDINAVIR C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 200 Z9 203 U1 1 U2 10 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 28 PY 1999 VL 401 IS 6756 BP 874 EP 875 DI 10.1038/44755 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 251UL UT WOS:000083464700044 PM 10553903 ER PT J AU Koch, CA Doppman, JL Watson, JC Patronas, NJ Nieman, LK AF Koch, CA Doppman, JL Watson, JC Patronas, NJ Nieman, LK TI Spinal epidural lipomatosis in a patient with the ectopic corticotropin syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Koch, CA (reprint author), NIH, Bethesda, MD 20892 USA. RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 5 TC 18 Z9 18 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 OCT 28 PY 1999 VL 341 IS 18 BP 1399 EP 1400 DI 10.1056/NEJM199910283411814 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 249XE UT WOS:000083357800021 PM 10577094 ER PT J AU Shack, S Gorospe, M Fawcett, TW Hudgins, WR Holbrook, NJ AF Shack, S Gorospe, M Fawcett, TW Hudgins, WR Holbrook, NJ TI Activation of the cholesterol pathway and Ras maturation in response to stress SO ONCOGENE LA English DT Article DE cholesterol; 3-hydroxy-3-methylglutaryl-CoA reductase; ras; stress ID MAP KINASE KINASE; PROTEIN-KINASE; P21RAS ISOPRENYLATION; CELLS; TRANSFORMATION; PRENYLATION; EXPRESSION; INHIBITOR; REDUCTASE; PLANTS AB All cells depend on sterols and isoprenoids derived from mevalonate (MVA) for growth, differentiation, and maintenance of homeostatic functions. In plants, environmental insults like heat and sunlight trigger the synthesis of isoprene, also derived from MVA, and this phenomenon has been associated with enhanced tolerance to heat. Here, we show that in human prostate adenocarcinoma PC-3M cells heat shock leads to activation of the MVA pathway. This is characterized by a dose- and time-dependent elevation in 3-hydroxy3methylglutaryl-coenzyme A reductase (HMGR) activity; enhanced sterol and isoprenoid synthesis, and increased protein prenylation, Furthermore, prenylation and subsequent membrane localization of Ras, a central player in cell signaling, was rapidly induced following heat stress. These effects were dose-dependent, augmented with repeated insults, and were prevented by culturing cells in the presence of lovastatin, a competitive inhibitor of HMGR, Enhanced Ras maturation by heat stress was also associated with a heightened activation of extracellular signal-regulated kinase (ERK), a key mediator of both mitogenic and stress signaling pathways, in response to subsequent growth factor stimulation. Thus, activation of the MVA pathway may constitute an important adaptive host response to stress, and have significant implications to carcinogenesis. C1 NIA, Gerontol Res Ctr, Biol Chem Lab, Cell Stress & Aging Sect,NIH, Baltimore, MD 21224 USA. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Holbrook, NJ (reprint author), NIA, Gerontol Res Ctr, Biol Chem Lab, Cell Stress & Aging Sect,NIH, 5600 Nathan Shock Dr,Box 12, Baltimore, MD 21224 USA. NR 43 TC 26 Z9 26 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 28 PY 1999 VL 18 IS 44 BP 6021 EP 6028 DI 10.1038/sj.onc.1203002 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 249XU UT WOS:000083359100008 PM 10557091 ER PT J AU Smith, LM Wise, SC Hendricks, DT Sabichi, AL Bos, T Reddy, P Brown, PH Birrer, MJ AF Smith, LM Wise, SC Hendricks, DT Sabichi, AL Bos, T Reddy, P Brown, PH Birrer, MJ TI cJun overexpression in MCF-7 breast cancer cells produces a tumorigenic, invasive and hormone resistant phenotype SO ONCOGENE LA English DT Article DE cJun; AP-1; breast cancer; tumorigenicity; invasion; hormone resistance ID RAT EMBRYO CELLS; C-JUN; AP-1 ACTIVITY; DNA-BINDING; GLUCOCORTICOID RECEPTOR; MALIGNANT PROGRESSION; INDEPENDENT GROWTH; MESSENGER-RNA; EXPRESSION; PROTEIN AB We have previously demonstrated decreased Jun/AP-1 activity in the breast cancer cell line MCF-7 when compared to normal or immortalized mammary epithelial cells. In this paper, we overexpress Jun in MCF-7 cells (MCF7Jun) and demonstrate that it results in diverse biologic and biochemical changes, which mimic those seen clinically in breast cancer. Overexpression of Jun causes significant alterations in the composition of AP-1, decreased junB and increased fr a-l expression and results in an increased biologic aggressiveness. MCF7Jun cells exhibit increased cellular motility, increased expression of a matrix degrading enzyme MMP-9, increased in vitro chemoinvasion and tumor formation in nude mice in the absence of exogenous estrogens. Furthermore, MCF7Jun cells are unresponsive to the growth stimulating effects of estrogen and growth inhibitory effects of tamoxifen. Analysis of the estrogen receptor (ER) expression and activity showed that the MCF7Jun cells have no detectable ER. MCF-7 cells overexpressing mutant forms of cJun were responsive to the growth stimulatory effects of estrogen indicating that full-length cJun is required to acquire the estrogen-independent phenotype in breast cancer cells. C1 NCI, Med Branch, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA. Eastern Virginia Med Sch, Dept Microbiol & Immunol, Norfolk, VA USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Birrer, MJ (reprint author), 9610 Med Ctr Dr,Room 300, Rockville, MD 20850 USA. NR 44 TC 151 Z9 158 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 28 PY 1999 VL 18 IS 44 BP 6063 EP 6070 DI 10.1038/sj.onc.1202989 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 249XU UT WOS:000083359100012 PM 10557095 ER PT J AU Dai, LX Miura, RM AF Dai, LX Miura, RM TI A lattice cellular automata model for ion diffusion in the brain-cell microenvironment and determination of tortuosity and volume fraction SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE brain-cell microenvironment; lattice cellular automata; lattice Boltzmann equation; ion diffusion; tortuosity; volume fraction; porous medium ID GAS AUTOMATA; POROUS-MEDIA; SYSTEMS; SPACE; CEREBELLUM; PARAMETERS; EQUATION; DYNAMICS; TISSUE; SLICES AB In the brain-cell microenvironment, the movement of ions is by diffusion when there is not any electrical activity in either the cells or the externally applied electric field. In this complex medium, the primary constraints on long-range diffusion are due to the geometrical properties of the medium, especially tortuosity and volume fraction, which are lumped parameters that incorporate local geometrical properties such as connectivity and pore size. In this paper, we study the effects of these geometrical properties in mimicking the experimental situation in the brain. We build a lattice cellular automata model for ion diffusion within the brain-cell microenvironment and perform numerical simulations using the corresponding lattice Boltzmann equation. In this model, particle injection mimics extracellular ion injection from a microelectrode in experiments. As an application of the model, we combine the results from the simulations with porous media theory to compute tortuosities and volume fractions for various regular and irregular porous media. Porous media theory previously had been combined with diffusion experiments in brain tissue to determine tortuosity and volume fraction. As in the case of the diffusion experiments, porous media theory gives a good approximation to the numerical simulations. We conclude that the lattice Boltzmann equation can accurately describe ion diffusion in the extracellular space of brain tissue. C1 Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. Univ British Columbia, Inst Appl Math, Vancouver, BC V6T 1Z2, Canada. NIDDK, Math Res Branch, NIH, Bethesda, MD 20814 USA. Univ British Columbia, Dept Pharmacol & Therapeut, Vancouver, BC V6T 1Z3, Canada. RP Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. EM dai@math.ubc.ca; miura@math.ubc.ca NR 46 TC 8 Z9 9 U1 0 U2 0 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 EI 1095-712X J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD OCT 28 PY 1999 VL 59 IS 6 BP 2247 EP 2273 DI 10.1137/S0036139997323942 PG 27 WC Mathematics, Applied SC Mathematics GA 254JH UT WOS:000083607800014 ER PT J AU El-Ghundi, M Fletcher, PJ Drago, J Sibley, DR O'Dowd, BF George, SR AF El-Ghundi, M Fletcher, PJ Drago, J Sibley, DR O'Dowd, BF George, SR TI Spatial learning deficit in dopamine D-1 receptor knockout mice SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Morris water maze; spatial learning; dopamine D-1 receptor-deficient mouse; spontaneous alternation; locomotor activity; passive avoidance behavior ID LONG-TERM POTENTIATION; HIPPOCAMPAL ACETYLCHOLINE-RELEASE; WORKING-MEMORY PERFORMANCE; PREFRONTAL CORTEX; D1 RECEPTORS; MUTANT MICE; COGNITIVE PERFORMANCE; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; AGED MONKEYS AB Dopamine D-1 receptors are expressed in the hippocampus and prefrontal cortex, suggesting a role in cognition. Dopamine D-1 receptor-deficient mice (D-1 - / -) were used to investigate the role of this receptor in spatial learning and memory. Using the Morris water maze, mice were trained to locate a hidden platform. Subsequently, the platform was removed from the maze and mice were scored for the percentage of time spent in the target quadrant and the number of crossings through the target position. D-1 - /- mice had significantly longer escape latencies compared to wild-type (D-1 + / +) and heterozygous (D-1 + / -) littermates and showed absence of spatial bias during the probe trials. In a visually cued task, D-1 - / - mice performed better than on the hidden platform trials, but maintained slightly higher escape latencies than D-1 + / + and D-1 + / - mice. Naive D-1 - / - mice exposed only to the cued task eventually acquired identical escape latencies as the D-1 + / + and D-1 + / - mice. Sensorimotor reflexes, locomotor activity, spontaneous alternation and contextual learning were not different among the groups. These results indicate that D-1 - / - mice have a deficit in spatial learning without visual or motor impairment, suggesting that dopamine D-1 receptors are involved in at least one form of the cognitive processes. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA. Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. RP George, SR (reprint author), Univ Toronto, Dept Med & Pharmacol, Room 4358,Med Sci Bldg,1 Kings Coll Circle, Toronto, ON M5S 1A8, Canada. NR 81 TC 117 Z9 118 U1 2 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 27 PY 1999 VL 383 IS 2 BP 95 EP 106 DI 10.1016/S0014-2999(99)00573-7 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 259DZ UT WOS:000083880400001 PM 10585522 ER PT J AU Yanovski, JA Yanovski, SZ AF Yanovski, JA Yanovski, SZ TI Recent advances in basic obesity research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-MASS INDEX; LEPTIN RECEPTOR; FRAMESHIFT MUTATION; REARED APART; EARLY-ONSET; GENE; WEIGHT; MICE; PROTEIN; INTERVENTION C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 37 TC 62 Z9 64 U1 0 U2 4 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 OCT 27 PY 1999 VL 282 IS 16 BP 1504 EP 1506 DI 10.1001/jama.282.16.1504 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 248MB UT WOS:000083277800001 PM 10546681 ER PT J AU Alexander, JW Light, JA Donaldson, LA Delmonico, FL Diethelm, AG Wilkinson, A Rosenthal, JT Thistlethwaite, JR Hunsicker, LG Matas, AJ First, MR Reinsmoen, NL Rose, SM AF Alexander, JW Light, JA Donaldson, LA Delmonico, FL Diethelm, AG Wilkinson, A Rosenthal, JT Thistlethwaite, JR Hunsicker, LG Matas, AJ First, MR Reinsmoen, NL Rose, SM CA Cooperative Clin Trials Transplant TI Evaluation of pre- and posttransplant donor-specific transfusion/cyclosporine A in non-HLA identical living donor kidney transplant recipients SO TRANSPLANTATION LA English DT Article ID ANTIGEN-SPECIFIC HYPOREACTIVITY; BLOOD-TRANSFUSION; ALLOGENEIC MICROCHIMERISM; RENAL-TRANSPLANTATION; ALLOGRAFT SURVIVAL; GRAFT-SURVIVAL; CYCLOSPORINE; LUNG; DST; INDUCTION AB Background. The beneficial effects of donor specific transfusion (DST) have become controversial in the cyclosporine era, This study was performed to evaluate the potential benefits of a new protocol for administering DSTs in the perioperative period. Methods. Non-HLA identical living donor kidney transplant recipients were randomized prospectively to control or to receive a DST 24 hr before transplant and 7-10 days posttransplant, All patients received similar immunosuppression according to protocol. Results. The protocol had 212 evaluable patients (115 transfused and 97 control). There were no differences in 1- and a-year graft and patient survival, causes of graft failure, incidence and types of infection, repeat hospitalization, or the ability to withdraw steroids. Immunological hyporesponsiveness (by mixed lymphocyte culture) occurred more frequently in transfused patients (18%) than controls (3%) (P=0.04), Blood stored for greater than or equal to 3 days was associated with fewer early rejections than blood stored less than or equal to 2 days. Overall, class II antigen mismatches were associated with more rejection episodes than class I antigen mismatches. However, transfused patients, but not control patients, with more class I antigen mismatches were more likely to have rejections. Conclusions. Administration of DSTs by the method described had no practical influence on patient or graft survival for up to 2 years. However, donor-specific hyporesponsiveness was more common in transfused patients (18 vs. 3%). Longer follow-up will be needed to determine whether DST will be associated with long-term benefit. C1 Univ Cincinnati, Med Ctr, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. Washington Hosp Ctr, Dept Transplantat, Washington, DC 20010 USA. EMMES Corp, Potomac, MD 20854 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Alabama, Sch Med, Birmingham, AL 35294 USA. Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA 90095 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Iowa, Div Nephrol, Iowa City, IA 52242 USA. Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. NIAID, Genet & Transplantat Branch, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. RP Alexander, JW (reprint author), Univ Cincinnati, Med Ctr, Coll Med, Dept Surg, 231 Bethesda Ave, Cincinnati, OH 45267 USA. NR 26 TC 15 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 1999 VL 68 IS 8 BP 1117 EP 1124 DI 10.1097/00007890-199910270-00010 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 252HT UT WOS:000083496600010 PM 10551639 ER PT J AU Chu, RA Takei, J Barchi, JJ Bai, YW AF Chu, RA Takei, J Barchi, JJ Bai, YW TI Relationship between the native-state hydrogen exchange and the folding pathways of barnase SO BIOCHEMISTRY LA English DT Article ID DENATURANT CONCENTRATION; TRANSITION-STATE; RIBONUCLEASE-A; CYTOCHROME-C; EQUILIBRIUM; INTERMEDIATE; NMR; STABILITY; EXTRAPOLATION; DEPENDENCE AB The previous native-state hydrogen exchange experiment with barnase failed to detect any partially unfolded intermediate state which was contrary to the experimental results from kinetic deuterium hydrogen exchange pulse labeling and protein engineering studies. This has been taken to suggest that the native-state hydrogen exchange method cannot be used alone as an analytical tool to study the folding pathways of proteins. Here, we revisited the pulse labeling experiment with barnase and detected no stable folding intermediate. This finding allows a reconciliation of the native-state HX data and the folding pathway of barnase. Along with alternative theoretical interpretations for a curved chevron plot of protein folding, these data suggest that further investigation of the nature of the intermediate of barnase is needed. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bai, YW (reprint author), NCI, Biochem Lab, NIH, Bldg 37,Room 4A-01, Bethesda, MD 20892 USA. RI Barchi Jr., Joseph/N-3784-2014 NR 42 TC 20 Z9 20 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 26 PY 1999 VL 38 IS 43 BP 14119 EP 14124 DI 10.1021/bi991799y PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250YL UT WOS:000083417800001 PM 10571984 ER PT J AU Bai, RL Durso, NA Sackett, DL Hamel, E AF Bai, RL Durso, NA Sackett, DL Hamel, E TI Interactions of the sponge-derived antimitotic tripeptide hemiasterlin with tubulin: Comparison with dolastatin 10 and cryptophycin 1 SO BIOCHEMISTRY LA English DT Article ID ANTINEOPLASTIC AGENTS; CYTOTOXIC PEPTIDES; VINCA DOMAIN; BINDING; NUCLEOTIDE; AGGREGATION; VINBLASTINE; SITES; BRAIN AB The sponge-derived antimitotic tripeptide hemiasterlin was previously shown to inhibit tubulin polymerization. We have now demonstrated that hemiasterlin resembles most other antimitotic peptides in noncompetitively inhibiting the binding of vinblastine to tubulin (apparent K-i value, 7.0 mu M), competitively inhibiting the binding of dolastatin 10 to tubulin (apparent K-i value, 2.0 mu M), stabilizing the colchicine binding activity of tubulin, inhibiting nucleotide exchange on beta-tubulin, and inducing the formation of tubulin oligomers that are stable to gel filtration in the absence of free drug, even at low drug concentrations. The tubulin oligomerization reaction induced by hemiasterlin was compared to the reactions induced by dolastatin 10 and cryptophycin 1. Like dolastatin 10, hemiasterlin induced formation of a tubulin aggregate that had the morphological appearance primarily of ring-like structures with a diameter of about 40 nm, while the morphology of the cryptophycin 1 aggregate consisted primarily of smaller rings (diameter about 30 nm). However, the hemiasterlin aggregate differed from the dolastatin 10 aggregate in that its formation was not associated with turbidity development, and the morphology of the hemiasterlin aggregate (as opposed to the dolastatin 10 aggregate) did not change greatly when microtubule-associated proteins were present (tight coils and pinwheels are observed with dolastatin 10 but not with hemiasterlin or cryptophycin 1). Opacification of tubulin-dolastatin 10 mixtures was inhibited by hemiasterlin at 22 degrees C and stimulated at 0 degrees C, while cryptophycin 1 was inhibitory at both reaction temperatures. C1 NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment & Diag,Frederick Canc Res & De, Frederick, MD 21702 USA. RP Hamel, E (reprint author), NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, POB B,Bldg 469,Room 237, Frederick, MD 21702 USA. NR 31 TC 73 Z9 78 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 26 PY 1999 VL 38 IS 43 BP 14302 EP 14310 DI 10.1021/bi991323e PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250YL UT WOS:000083417800022 PM 10572005 ER PT J AU Lee, CH Murphy, MR Lee, JS Chung, JH AF Lee, CH Murphy, MR Lee, JS Chung, JH TI Targeting a SWI/SNF-related chromatin remodeling complex to the beta-globin promoter in erythroid cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOCUS-CONTROL REGION; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; GLUCOCORTICOID RECEPTOR; NUCLEOSOME DISRUPTION; TRANSGENIC MICE; 5' HS-2; BINDING; YEAST; DELETION AB Chromatin remodeling complexes such as the SWI/SNF complex make DNA accessible to transcription factors by disrupting nucleosomes. However, it is not known how such complexes are targeted to the promoter. For example, a SWI/SNF1-like chromatin remodeling complex erythroid Kruppel-like factor (EKLF) coactivator-remodeling complex 1 (E-RC1) disrupts the nucleosomes over the human beta-globin promoter in an EKLF-dependent manner. However, it is not known whether E-RC1 is targeted specifically to the beta-globin promoter or whether E-RC1 is randomly targeted, but its activity is evident only at the beta-globin promoter. Because E-RC1 cannot remodel chromatin over the beta-globin promoter without EKLF in vitro, it has been proposed that SWI/SNF1-like complexes such as E-RC1 are targeted specifically to the promoter by selectively interacting with promoter-associated transcription factors such as EKLF. In this report, we test this hypothesis in the cellular context by using the ProteIN POsition Identification with Nuclease Tail (PIN*POINT) assay. We find that the Brahma-related gene (BRG) 1 and BRG1-associated factor (BAF) 170 subunits of E-RC1 are both recruited near the transcription initiation site of the beta-globin promoter. On transiently transfected templates, both the locus control region and the EKLF-binding site are important for their recruitment to the beta-globin promoter in mouse erythroleukemia cells. When the beta-globin promoter was linked to the cytomegalovirus enhancer, the E-RC1 complex was not recruited, suggesting that recruitment of the E-RC1 complex is not a general property of enhancers. C1 NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Chung, JH (reprint author), NHLBI, Mol Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 41 TC 80 Z9 81 U1 1 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 OCT 26 PY 1999 VL 96 IS 22 BP 12311 EP 12315 DI 10.1073/pnas.96.22.12311 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000023 PM 10535918 ER PT J AU Kim, YH Choi, CY Kim, Y AF Kim, YH Choi, CY Kim, Y TI Covalent modification of the homeodomain-interacting protein kinase 2 (HIPK2) by the ubiquitin-like protein SUMO-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GTPASE-ACTIVATING PROTEIN; NUCLEAR-PORE COMPLEX; CONJUGATING ENZYME; DOMAIN-10 ND10; PML; RANGAP1; IDENTIFICATION; TRANSCRIPTION; REPLICATION; SEQUENCE AB Posttranslational modifications such as ubiquitination and phosphorylation play an important role in the regulation of cellular protein function, Homeodomain-interacting protein kinase 2 (HIPK2) is a member of the recently identified family of nuclear protein kinases that act as corepressors far homeodomain transcription factors. Here, we show that HIPK2 is regulated by a ubiquitin-like protein, SUMO-1. We demonstrate that HIPK2 localizes to nuclear speckles (dots) by means of a speckle-retention signal. This speckle-retention signal contains a domain that interacts with a mouse ubiquitin-like protein conjugating (E2) enzyme, mUBC9, In cultured cells, HIPK2 is covalently modified by SUMO-1, and the SUMO-1 modification of HIPK2 correlates with its localization to nuclear speckles (dots). Thus, our results provide firm evidence that the nuclear protein kinase HIPK2 can be covalently modified by SUMO-1, which directs its localization to nuclear speckles (dots). C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, Y (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Room 8N228,10 Ctr Dr,MSC1762, Bethesda, MD 20892 USA. NR 39 TC 135 Z9 139 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 OCT 26 PY 1999 VL 96 IS 22 BP 12350 EP 12355 DI 10.1073/pnas.96.22.12350 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000030 PM 10535925 ER PT J AU Iwai, K Yamanaka, K Kamura, T Minato, N Conaway, RC Canaway, JW Klausner, RD Pause, A AF Iwai, K Yamanaka, K Kamura, T Minato, N Conaway, RC Canaway, JW Klausner, RD Pause, A TI Identification of the von Hippel-Lindau tumor-suppressor protein as part of an active E3 ubiquitin ligase complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; FACTOR MESSENGER-RNA; RENAL-CARCINOMA; GENE-PRODUCT; BINDING; SYSTEM; FAMILY; PROTEOLYSIS; PATHWAY AB Mutations of von Hippel-Lindau disease (VHL) tumor-suppressor gene product (pVHL) are found in patients with dominant inherited VHL syndrome and in the vast majority of sporadic clear cell renal carcinomas. The function of the pVHL protein has not been clarified. pVHL has been shown to form a complex with elongin B and elongin C (VBC) and with cullin (CUL)-2. In light of the structural analogy of VBC-CUL-2 to SKP1-CUL-1-F-box ubiquitin ligases, the ubiquitin ligase activity of VBC-CUL-2 was examined in this study. We show that VBC-CUL-2 exhibits ubiquitin ligase activity, and we identified UbcH5a, b, and c, but not CDC34, as the ubiquitin-conjugating enzymes of the VBC-CUL-2 ubiquitin ligase. The protein Rbx1/ROC1 enhances ligase activity of VBC-CUL-2 as it does in the SKP1-CUL-1-F-box protein ligase complex. We also found that pVHL associates with two proteins, p100 and p220, which migrate at a similar molecular weight as two major bands in the ubiquitination assay. Furthermore, naturally occurring pVHL missense mutations, including mutants capable of forming a complex with elongin B-elongin C-CUL-2, fail to associate with p100 and pun and cannot exhibit the E3 ligase activity. These results suggest that pVHL might he the substrate recognition subunit of the VBC-CUL-2 E3 ligase. This is also, to our knowledge, the first example of a human tumor-suppressor protein being directly involved in the ubiquitin conjugation system which leads to the targeted degradation of substrate proteins. C1 Kyoto Univ, Grad Sch Biostudies, Dept Mol & Syst Biol, Sakyo Ku, Kyoto 6068501, Japan. Oklahoma Med Res Fdn, Howard Hughes Med Inst, Program Mol Cell Biol, Oklahoma City, OK 73104 USA. NCI, Off Director, Bethesda, MD 20892 USA. Max Planck Inst Biochem, Mol Oncol Grp, D-82152 Martinsried, Germany. RP Iwai, K (reprint author), Kyoto Univ, Grad Sch Biostudies, Dept Mol & Syst Biol, Sakyo Ku, Yoshida Konoe Cho, Kyoto 6068501, Japan. RI Yamanaka, Koji/H-5806-2011; OI Yamanaka, Koji/0000-0003-4655-0035; Conaway, Joan/0000-0002-2786-0663 NR 45 TC 347 Z9 351 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 OCT 26 PY 1999 VL 96 IS 22 BP 12436 EP 12441 DI 10.1073/pnas.96.22.12436 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000045 PM 10535940 ER PT J AU Heyer, J Escalante-Alcalde, D Lia, M Boettinger, E Edelmann, W Stewart, CL Kucherlapati, R AF Heyer, J Escalante-Alcalde, D Lia, M Boettinger, E Edelmann, W Stewart, CL Kucherlapati, R TI Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; TGF-BETA SUPERFAMILY; MAD-RELATED PROTEIN; GROWTH-FACTOR-BETA; MOUSE EMBRYOS; PRIMITIVE ENDODERM; NODAL EXPRESSION; SONIC-HEDGEHOG; SMAD PROTEINS; DNA-BINDING AB SMAD2 is a member of the transforming growth factor beta and activin-signaling pathway, To examine the role of Smad2 in postgastrulation development, we independently generated mice with a null mutation in this gene. Smad2-deficient embryos die around day 7.5 of gestation because of failure of gastrulation and failure to establish an anterior-posterior (A-P) axis. Expression of the homeobox gene Hex (the earliest known marker of the A-P polarity and the prospective head organizer) was found to be missing in Smad2-deficient embryos. Homozygous mutant embryos and embryonic stem cells formed mesoderm derivatives revealing that mesoderm induction is SMAD2 independent. In the presence of wild-type extraembryonic tissues, Smad2-deficient embryos developed beyond 7.5 and up to 10.5 days postcoitum, demonstrating a requirement for SMAD2 in extraembryonic tissues for the generation of an A-P axis and gastrulation, The rescued postgastrulation embryos showed malformation of head structures, abnormal embryo turning, and cyclopia. Our results show that Smad2 expression is required at several stages during embryogenesis. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. NCI, Frederick Canc Res & Dev Ctr, Basic Res Program, Adv BioSci Lab,Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Kucherlapati, R (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [CA67944, CA13330, P30 CA013330]; NIDDK NIH HHS [R01 DK056077] NR 47 TC 119 Z9 124 U1 1 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 OCT 26 PY 1999 VL 96 IS 22 BP 12595 EP 12600 DI 10.1073/pnas.96.22.12595 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000072 PM 10535967 ER PT J AU Remaley, AT Rust, S Rosier, M Knapper, C Naudin, L Broccardo, C Peterson, KM Koch, C Arnould, I Prades, C Duverger, N Funke, H Assman, G Dinger, M Dean, M Chimini, G Santamarina-Fojo, S Fredrickson, DS Denefle, P Brewer, HB AF Remaley, AT Rust, S Rosier, M Knapper, C Naudin, L Broccardo, C Peterson, KM Koch, C Arnould, I Prades, C Duverger, N Funke, H Assman, G Dinger, M Dean, M Chimini, G Santamarina-Fojo, S Fredrickson, DS Denefle, P Brewer, HB TI Human ATP-binding cassette transporter 1 (ABC1): Genomic organization and identification of the genetic defect in the original Tangier disease kindred SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE high density lipoproteins; cholesterol; atherosclerosis ID APOLIPOPROTEIN-A-I; CELLULAR CHOLESTEROL; DENSITY-LIPOPROTEINS; PROTEIN; EFFLUX; HDL; PHOSPHOLIPIDS; SUPERFAMILY; FIBROBLASTS; ENGULFMENT AB Tangier disease is characterized by low serum high density lipoproteins and a biochemical defect in the cellular efflux of lipids to high density lipoproteins. ABC1. a member of the ATP-binding cassette family. recently has been identified as the defective gene in Tangier disease. We report here the organization of the human ABC1 gene and the identification of a mutation in the ABC1 gene from the original Tangier disease kindred. The organization of the human ABC1 gene is similar to that of the mouse ABC1 gene and other related ABC genes. The ABC1 gene contains 49 exons that range in size from 33 to 249 bp and is over 70 kb in length. Sequence analysis of the ABC1 gene revealed that the proband for Tangier disease was homozygous for a deletion of nucleotides 3283 and 3284 (TC) in exon 22. The deletion results in a frameshift mutation and a premature stop codon starting at nucleotide 3375. The product is predicted to encode a nonfunctional protein of 1.084 aa, which is approximately half the size of the full-length ABC1 protein. The loss of a Mn/1 restriction site, which results from the deletion, was used to establish the genotype of the rest of the kindred. In summary, we report on the genomic organization of the human ABC1 gene and identify a frameshift mutation in the ABC1 gene of the index Ease of Tangier disease. These results will be useful in the future characterization of the structure and function of the ABC1 gene and the analysis of additional ABC1 mutations in patients with Tangier disease. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Rhone Poulenc Rorer, Core Genomics & Cardiovasc Dept, F-91006 Every, France. Univ Munster, Inst Arterioskleroseforsch, D-48149 Munster, Germany. Ctr Immunol Marseille Luminy, F-13288 Marseille, France. NCI, NIH, Frederick, MD 21702 USA. RP Brewer, HB (reprint author), NHLBI, Mol Dis Branch, NIH, 10-7N115,10 Ctr Dr, Bethesda, MD 20892 USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 49 TC 199 Z9 204 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 OCT 26 PY 1999 VL 96 IS 22 BP 12685 EP 12690 DI 10.1073/pnas.96.22.12685 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000088 PM 10535983 ER PT J AU Buffet, PA Gamain, B Scheidig, C Baruch, D Smith, JD Hernandez-Rivas, R Pouvelle, B Oishi, S Fujii, N Fusai, T Parzy, D Miller, LH Gysin, J Scherf, A AF Buffet, PA Gamain, B Scheidig, C Baruch, D Smith, JD Hernandez-Rivas, R Pouvelle, B Oishi, S Fujii, N Fusai, T Parzy, D Miller, LH Gysin, J Scherf, A TI Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: A receptor for human placental infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ERYTHROCYTE-MEMBRANE PROTEIN-1; ANTIGENIC VARIATION; VAR GENES; ADHERENCE; MOLECULE-1; MALARIA; SURFACE; PFEMP1; IDENTIFICATION; EXPRESSION AB Malaria during the first pregnancy causes a high rate of fetal and neonatal death. The decreasing susceptibility during subsequent pregnancies correlates with acquisition of antibodies that block binding of infected red cells to chondroitin sulfate A (CSA), a receptor for parasites in the placenta. Here we identify a domain within a particular Plasmodium falciparum erythrocyte membrane protein 1 that binds CSA, We cloned a var gene expressed in CSA-binding parasitized red blood cells (PRBCs). The gene had eight receptor-like domains, each of which was expressed on the surface of Chinese hamster ovary cells and was tested for CSA binding. CSA linked to biotin used as a probe demonstrated that two Duffy-binding-like (DBL) domains (DBL3 and DBU) bound CSA. DBL7, but not DBU, also bound chondroitin sulfate C (CSC) linked to biotin. a negatively charged sugar that does not support PRBC adhesion. Furthermore, CSA, but not CSC, blocked the interaction with DBL3 both CSA and CSC blocked binding to DBL7. Thus, only the DBL3 domain displays the same binding specificity as PRBCs. Because protective antibodies present after pregnancy block binding to CSA of parasites from different path of the world, DBL-3, although variant, may induce cross-reactive immunity that will protect pregnant women and their fetuses. C1 Inst Pasteur, CNRS, URA 1960, Unite Biol Interact Hote Parasite, F-75724 Paris, France. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. IPN, CINVESTAV, Dept Biomed Mol, Mexico City 07000, DF, Mexico. Univ Aix Marseille 2, Unite Parasitol Expt, F-13385 Marseille, France. Kyoto Univ, Grad Sch Pharmaceut Sci, Div Phys & Organ Chem, Kyoto 606, Japan. IMTSSA, Unite Parasitol, F-13998 Marseille, France. RP Scherf, A (reprint author), Inst Pasteur, CNRS, URA 1960, Unite Biol Interact Hote Parasite, 25 Rue Dr Roux, F-75724 Paris, France. RI Scherf, Artur/A-9674-2014; Oishi, Shinya/C-1350-2011 OI Oishi, Shinya/0000-0002-2833-2539 NR 24 TC 196 Z9 197 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 OCT 26 PY 1999 VL 96 IS 22 BP 12743 EP 12748 DI 10.1073/pnas.96.22.12743 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000098 PM 10535993 ER PT J AU Ogawa, S Chan, J Chester, AE Gustafsson, JA Korach, KS Pfaff, DW AF Ogawa, S Chan, J Chester, AE Gustafsson, JA Korach, KS Pfaff, DW TI Survival of reproductive behaviors in estrogen receptor beta gene-deficient (beta ERKO) male and female mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE testosterone; progesterone; lordosis; sexual behavior; aggression ID MESSENGER-RNA; ALPHA; DISRUPTION; TESTOSTERONE; ROLES AB Previously, it was shown that the lack of a functional estrogen receptor (ER) alpha gene (ER alpha) greatly affects reproduction-related behaviors in both female and male mice. However, widespread expression of a novel second ER gene, ER beta, demanded that we examine the possible participation of ER beta in regulation of these behaviors. In dramatic contrast to our results with ER alpha knockout (alpha ERKO) males, beta ERKO males performed at least as well as wildtype controls in sexual behavior tests. Moreover, not only did beta ERKO males exhibit normal male-typical aggressive behavior, including offensive attacks, but they also showed higher levels of aggression than wild-type mice under certain conditions of social experience. These data revealed a significant interaction between genotype and social experience with respect to aggressive behavior. Finally, females racking a functional beta isoform of the ER gene showed normal lordosis and courtship behaviors, extending in some cases beyond the day of behavioral estrus. These results highlight the importance of ER alpha for the normal expression of natural reproductive behaviors in both sexes and also provide a background for future studies evaluating ER beta gene contributions to other, nonreproductive behaviors. C1 Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden. RP Ogawa, S (reprint author), Rockefeller Univ, Neurobiol & Behav Lab, 1230 York Ave,Box 275, New York, NY 10021 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NICHD NIH HHS [HD-05751, R01 HD005751, R37 HD005751] NR 26 TC 256 Z9 261 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 1999 VL 96 IS 22 BP 12887 EP 12892 DI 10.1073/pnas.96.22.12887 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000123 PM 10536018 ER PT J AU Lee, SH Mouradian, MM AF Lee, SH Mouradian, MM TI Up-regulation of D-1A dopamine receptor gene transcription by estrogen SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE up-regulation; D-1A; dopamine receptor gene transcription; estrogen ID RESPONSIVE ELEMENT; RAT; PROMOTER; ACTIVATION; BINDING; MEMORY; DOMAIN; REGION AB Estrogen exerts complex physiologic effects on brain functions which could partly be mediated through modulation of the dopaminergic system. Transcription control of the human D-1A dopamine receptor gene by estrogenic stimulation was studied in the D-1A expressing neuroblastoma cell line SK-N-MC. Transient co-transfection of D-1A gene promoter-CAT constructs along with expression vectors for steroid hormone receptors indicated that estrogen, but not progesterone or glucocorticoid, receptors up-regulate transcription of this gene by about 1.7-fold. Serial 5' deletion mutants of the D-1A gene upstream region localized the estrogen responsive segment between nucleotides -1472 and -1342 relative to the initiator methionine, This region contains a half palindrome (TGACC) for the consensus estrogen responsive element (ERE). Additional co-transfection experiments revealed that estrogen receptors specifically activate the upstream D-1A promoter but not the downstream promoter located in the intron of this gene. Consistent with transient co-transfection experiments, 17 beta-estradiol treatment of SK-N-MC cells transfected with an estrogen receptor expression vector resulted in an approximately 20% increase in steady-state levels of long D-1A transcripts derived from the upstream promoter but not of short transcripts originating from the intron promoter. These observations demonstrate a molecular basis for estrogen induced up-regulation of D-1A gene transcription and provide a mechanism for modulation of central dopaminergic functions by this hormone. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Genet Pharmacol Unit, Expt Therapeut Branch, NIH, Bldg 10,Room 5C116,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 33 TC 48 Z9 49 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT 25 PY 1999 VL 156 IS 1-2 BP 151 EP 157 DI 10.1016/S0303-7207(99)00133-1 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 250VU UT WOS:000083410600017 PM 10612433 ER PT J AU Antzutkin, ON AF Antzutkin, ON TI Sideband manipulation in magic-angle-spinning nuclear magnetic resonance SO PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY LA English DT Review DE solid state nuclear magnetic resonance (SS NMR); propagators; cross-polarization/magic-angle-spinning (CP/MAS); chemical shift anisotropy (CSA) analysis; total suppression of spinning sidebands (TOSS); phase adjusted spinning sidebands (PASS); 2D-phase adjusted spinning sidebands (2D-PASS); isotropic rotation sequences (IRS) ID SOLID-STATE NMR; CHEMICAL-SHIFT ANISOTROPY; HIGH-RESOLUTION NMR; INTEGER QUADRUPOLAR NUCLEI; TENSOR PRINCIPAL VALUES; MULTIPLE-PULSE NMR; ROTATING SOLIDS; MAS-NMR; BAND SEPARATION; CORRELATION SPECTROSCOPY C1 Univ Lulea, Div Inorgan Chem, S-97187 Lulea, Sweden. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Antzutkin, ON (reprint author), Univ Lulea, Div Inorgan Chem, S-97187 Lulea, Sweden. EM antzut@speck.niddk.nib.gov NR 105 TC 87 Z9 87 U1 2 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6565 J9 PROG NUCL MAG RES SP JI Prog. Nucl. Magn. Reson. Spectrosc. PD OCT 25 PY 1999 VL 35 IS 3 BP 203 EP 266 DI 10.1016/S0079-6565(99)00010-2 PG 64 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Chemistry; Physics; Spectroscopy GA 257YJ UT WOS:000083810100001 ER PT J AU Hill, SA Shuh, M Derse, D AF Hill, SA Shuh, M Derse, D TI Comparisons of defective HTLV-I proviruses predict the mode of origin and coding potential of internally deleted genomes SO VIROLOGY LA English DT Article ID T-CELL LEUKEMIA; VIRUS TYPE-I; COMPLETE NUCLEOTIDE-SEQUENCE; VACUOLAR H+-ATPASE; PX MESSENGER-RNA; MOLECULAR CLONE; PROTEIN; EXPRESSION; RETROVIRUS; LYMPHOMA AB Cell lines infected with a variety of HTLV-I isolates were examined for the presence of defective proviruses that contain deletions spanning the gag, pol, and env genes. Internally deleted proviruses were identified by Southern blotting and by PCR amplification with 5' and 3' primers complementary to gag and tax sequences, respectively. PCR products representing eight defective proviruses from seven different cell lines were subsequently cloned and sequenced. The objectives of this study were twofold: first, we sought to determine whether nucleotide sequences surrounding sites of deletion shared common features that might reveal the mechanisms by which the defective genomes originated. Second, we asked whether deleted proviruses encode Gag fusion proteins with related C-terminal residues derived from open reading frames in the pX region. While most of the defective proviruses had incurred a single, targe deletion, two of them displayed a more complex pattern of multiple rearrangements. Alignments of bases flanking the 5' and 3' deletion endpoints within each provirus showed tracts of sequence identity consistent with a mechanism involving aberrant intramolecular strand-transfer events during replication. We suggest that the amount or activity of HTLV-I polymerase in virions may contribute both to the poor infectivity of the virus and to the high deletion frequency. Two of the eight proviruses that were examined encoded a gag gene joined to an extended open reading frame; the other six had very short open reading frames (one to six amino acids) derived from pX or env regions joined to gag that showed no apparent amino acid sequence similarity. (C) 1999 Academic Press. C1 NCI, Basic Res Lab, FCRDC, Frederick, MD 21702 USA. RP Derse, D (reprint author), NCI, Basic Res Lab, FCRDC, Frederick, MD 21702 USA. NR 50 TC 9 Z9 11 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 OCT 25 PY 1999 VL 263 IS 2 BP 273 EP 281 DI 10.1006/viro.1999.9922 PG 9 WC Virology SC Virology GA 251AG UT WOS:000083422000002 PM 10544101 ER PT J AU Frisch, M Biggar, RJ AF Frisch, M Biggar, RJ TI Aetiological parallel between tonsillar and anogenital squamous-cell carcinomas SO LANCET LA English DT Article ID CANCER AB Patients with human papillomavirus (HPV)-associated anogenital cancers had a 4.3-fold increased risk of tonsillar squamous-cell carcinoma. These cancer types also have histopathological and molecular biological similarities. Thus HPV may be aetiologically important in tonsillar carcinogenesis. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Statens Serum Inst, Danish Epidemiol Sci Ctr, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. RP Frisch, M (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 8009, Rockville, MD 20852 USA. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 5 TC 72 Z9 75 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 23 PY 1999 VL 354 IS 9188 BP 1442 EP 1443 DI 10.1016/S0140-6736(99)92824-6 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 248LY UT WOS:000083277400017 PM 10543674 ER PT J AU Litvan, I AF Litvan, I TI Atypical parkinsonism in the French West Indies SO LANCET LA English DT Letter ID PROGRESSIVE SUPRANUCLEAR PALSY; RICHARDSON-OLSZEWSKI-SYNDROME; DIAGNOSIS; CRITERIA C1 Henry M Jackson Fdn, Neuropharmacol Unit, Def & Vet Cognit Head Injury Program, Bethesda, MD 20817 USA. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20817 USA. RP Litvan, I (reprint author), Henry M Jackson Fdn, Neuropharmacol Unit, Def & Vet Cognit Head Injury Program, Bethesda, MD 20817 USA. OI Litvan, Irene/0000-0002-3485-3445 NR 4 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 23 PY 1999 VL 354 IS 9188 BP 1472 EP 1473 DI 10.1016/S0140-6736(05)77611-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 248LY UT WOS:000083277400050 PM 10543694 ER PT J AU Pinto, LA Berzofsky, JA Fowke, KR Little, RF Merced-Galindez, F Humphrey, R Ahlers, J Dunlop, N Cohen, RB Steinberg, SM Nara, P Shearer, GM Yarchoan, R AF Pinto, LA Berzofsky, JA Fowke, KR Little, RF Merced-Galindez, F Humphrey, R Ahlers, J Dunlop, N Cohen, RB Steinberg, SM Nara, P Shearer, GM Yarchoan, R TI HIV-specific immunity following immunization with HIV synthetic envelope peptides in asymptomatic HIV-infected patients SO AIDS LA English DT Article DE peptide vaccine; HIV-1 envelope; T helper responses; cytotoxic T lymphocytes; HIV-1 patients ID IMMUNODEFICIENCY-VIRUS ENVELOPE; CYTOTOXIC T-LYMPHOCYTES; NEUTRALIZING-ANTIBODY; CELL RESPONSES; SEROPOSITIVE INDIVIDUALS; IMMUNODOMINANT EPITOPE; VACCINE CONSTRUCTS; V3 LOOP; IN-VIVO; HELPER AB Objective: A phase I trial was conducted to evaluate the safety and immunogenicity of an HIV synthetic peptide vaccine in HIV-seropositive individuals. The immunogens used in this study were PCLUS 3-18MN and PCLUS 6.1-18MN envelope peptides. Methods: Eight HIV-infected patients received six subcutaneous injections of 160 mu g PCLUS 3-18MN in Montanide ISA 51 and were followed longitudinally for a year after the first immunization. Peripheral blood mononuclear cells (PBMC) were tested for peptide-specific T helper and cytotoxic T cell (CTL) responses, HIV-1(MN) neutralizing antibodies and antibodies against HIV PCLUS 3 and P18 MN peptides. Results: PCLUS 3-18MN-specific T helper responses were significantly increased at 36 weeks (P < 0.05, after adjustment for multiple comparisons) following initial immunization with PCLUS 3-18MN. A P18MN-specific CTL response, not present prior to vaccination, was observed after immunization in one patient. Serum HIV-1(MN)-neutralizing antibody titers increased in each of the three patients who had low titers prior to immunization. Plasma HIV RNA levels and CD4 cell counts did not change appreciably during the study period. Conclusions: This trial demonstrates that both peptides can be safely administered to HIV-infected individuals and that PCLUS 3-18MN induces increases in HIV peptide-specific immune responses. (C) 1999 Lippincott Williams & Wilkins. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Tumor Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pinto, LA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. OI Fowke, Keith/0000-0001-8227-6649 NR 54 TC 38 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 22 PY 1999 VL 13 IS 15 BP 2003 EP 2012 DI 10.1097/00002030-199910220-00002 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 249KA UT WOS:000083331200002 PM 10546852 ER PT J AU Gray, RH Wawer, MJ Sewankambo, NK Serwadda, D Li, CJ Moulton, LH Lutalo, T Wabwire-Mangen, F Meehan, MP Ahmed, S Paxton, LA Kiwanuka, N Nalugoda, F Korenromp, EL Quinn, TC AF Gray, RH Wawer, MJ Sewankambo, NK Serwadda, D Li, CJ Moulton, LH Lutalo, T Wabwire-Mangen, F Meehan, MP Ahmed, S Paxton, LA Kiwanuka, N Nalugoda, F Korenromp, EL Quinn, TC CA Rakai Project Team TI Relative risks and population attributable fraction of incident HIV associated with symptoms of sexually transmitted diseases and treatable symptomatic sexually transmitted diseases in Rakai District, Uganda SO AIDS LA English DT Article DE HIV incidence; STD; relative risk; population attributable fraction ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED TRIAL; GENITAL ULCER DISEASE; HIV-1-INFECTED MEN; RURAL TANZANIA; TRANSMISSION; PREVENTION; INFECTION AB Objectives: To assess the linkage of sexually transmitted disease (STD) symptoms and treatable STD to HIV incidence. Design: Analysis of a randomized trial of STD control for HIV prevention, Rakai, Uganda. Methods: Consenting adults 15-59 years of age were seen at 10-monthly home visits, interviewed regarding STD symptoms, and asked to provide samples for HIV and STD diagnoses. HIV incidence was determined in 8089 HIV-negative subjects over 10 457 person years. Adjusted rate ratios (RR) and 95% confidence intervals (CI) of HIV acquisition associated with genital ulcer disease (CUD) and discharge/dysuria were used to estimate the population attributable fraction (PAF) of HIV acquisition. HIV transmission risks associated with STD symptoms in HIV-positive partners of 167 HIV discordant couples and the numbers of sexual partners reported by HIV-positive subjects were used to estimate the PAF of HIV transmission attributable to STD. Results: HIV prevalence was 16%. The risk of HIV acquisition was increased with CUD (RR 3.14; CT 1.98-4.98) and in males with discharge/dysuria (RR 2.44; CI 1.17-5.12), but not in females with discharge/dysuria. The PAF of HIV acquisition was 9.5% (CI 2.8-15.8%) with any of the three STD symptoms. The PAF for CUD was 8.8% (CI 3.7-13.8), but only 8.2% of reported GUD was caused by treatable syphilis or chancroid. The PAF for discharge/dysuria in males was 6.7% (Ct 1.1-13.8), but only 25% of symptomatic males had concurrent gonorrhea or chlamydial infection. No significant differences were seen in PAF between study treatment arms. The PAF of HIV transmission associated with STD symptoms in HIV-positive persons was indirectly estimated to be 10.4%. Conclusion: In this mature, generalized HIV epidemic setting, most HIV seroconversion occurs without recognized STD symptoms or curable STD detected by screening. Therefore, syndromic management or other strategies of STD treatment are unlikely to substantially reduce HIV incidence in this population. However, STD is associated with significant HIV risk at the individual level, and STD management is needed to protect individuals. (C) 1999 Lippincott Williams & Williams. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Int Hlth & Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. Columbia Univ, Ctr Populat & Family Hlth, Sch Publ Hlth, New York, NY 10027 USA. Makerere Univ, Dept Med, Kampala, Uganda. Makerere Univ, Clin Epidemiol Unit, Kampala, Uganda. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Uganda Virus Res Inst, Rakai Project, Entebbe, Uganda. Erasmus Univ, Dept Publ Hlth, Rotterdam, Netherlands. NIAID, Bethesda, MD 20892 USA. RP Gray, RH (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Populat & Family Hlth Sci, 615 N Wolfe St, Baltimore, MD 21205 USA. OI Sewankambo, Nelson/0000-0001-9362-053X; Moulton, Lawrence/0000-0001-7041-7387 FU NIAID NIH HHS [R01 AI34826, R01 AI34826S]; NICHD NIH HHS [5P30HD06826] NR 27 TC 85 Z9 85 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 22 PY 1999 VL 13 IS 15 BP 2113 EP 2123 DI 10.1097/00002030-199910220-00015 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 249KA UT WOS:000083331200015 PM 10546865 ER PT J AU Sajan, MP Standaert, ML Bandyopadhyay, G Quon, RJ Burke, TR Farese, RV AF Sajan, MP Standaert, ML Bandyopadhyay, G Quon, RJ Burke, TR Farese, RV TI Protein kinase C-zeta and phosphoinositide-dependent protein kinase-1 are required for insulin-induced activation of ERK in rat adipocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-SYNTHASE KINASE-3; GLUCOSE-TRANSPORT; PHOSPHATIDYLINOSITOL 3-KINASE; 3T3-L1 ADIPOCYTES; SIGNALING PATHWAY; GROWTH-FACTOR; MAP KINASE; WORTMANNIN; STIMULATION; INVOLVEMENT AB The mechanisms used by insulin to activate the multifunctional intracellular effecters, extracellular signal-regulated kinases 1 and 2 (ERK1/2), are only partly understood and appear to vary in different cell types. Presently, in rat adipocytes, we found that insulin-induced activation of ERK was blocked (a) by chemical inhibitors of both phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC)-zeta, and, moreover, (b) by transient expression of both dominant-negative Delta p85 PI3K subunit and kinase-inactive PKC-zeta. Further, insulin effects on ERK were inhibited by kinase-inactive 3-phosphoinositide-dependent protein kinase-1 (PDK-1), and by mutation of Thr-410 in the activation loop of PKC-zeta, which is the target of PDK-1 and is essential for PI3K/PDK-1-dependent activation of PKC-C In addition to requirements for PI3K, PDK-1, and PKC-zeta, we found that a tyrosine kinase (presumably the insulin receptor), the SH2 domain of GRB2, SOS, RAS, RAF, and MEK1 were required for insulin effects on ERK in the rat adipocyte. Our findings therefore suggested that PDK-1 and PKC-zeta serve as a downstream effecters of PI3K, and act in conjunction with GRB2, SOS, RAS, and RAF, to activate MEK and ERK during insulin action in rat adipocytes. C1 Univ S Florida, James A Haley Vet Hosp, Coll Med, Res Serv VAR 151, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Farese, RV (reprint author), Univ S Florida, James A Haley Vet Hosp, Coll Med, Res Serv VAR 151, 13000 Bruce B Downs Blvd, Tampa, FL 33612 USA. RI Burke, Terrence/N-2601-2014; Farese, Robert/B-3605-2015 FU NIDDK NIH HHS [R01 DK065969] NR 32 TC 94 Z9 95 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 OCT 22 PY 1999 VL 274 IS 43 BP 30495 EP 30500 DI 10.1074/jbc.274.43.30495 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248LT UT WOS:000083276700026 PM 10521430 ER PT J AU Kim, SY Grant, P Lee, JH Pant, HC Steinert, PM AF Kim, SY Grant, P Lee, JH Pant, HC Steinert, PM TI Differential expression of multiple transglutaminases in human brain - Increased expression and cross-linking by transglutaminases 1 and 2 in Alzheimer's disease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; CORNIFIED CELL-ENVELOPE; TISSUE TRANSGLUTAMINASE; PROTRANSGLUTAMINASE-E; CDNA CLONES; RAT-BRAIN; PROTEINS; ENZYME; CALPAIN; FORMS AB The transglutaminase (TGase) family of enzymes, of which seven different members are known in the human genome, participate in many biological processes involving cross-linking proteins into large macromolecular assemblies. The TGase 2 enzyme is known to be present in neuronal tissues and may play a role in neuronal degenerative diseases such as Alzheimer's disease (AD) by aberrantly cross-linking proteins. In this paper, we demonstrate by reverse transcriptase-polymase chain reaction and immunological methods with specific antibodies that in fact three members, the TGase 1, TGase 2, and TGase 3 enzymes, and are differentially expressed in various regions of normal human brain tissues. Interestingly, the TGase 1 and 3 enzymes and their proteolytically processed forms are involved in terminal differentiation programs of epithelial cell development and barrier function. In addition, we found that the levels of expression and activity of the TGase 1 and 2 enzymes were both increased in the cortex and cerebellum of AD patients. Furthermore, whereas normal brain tissues contain approximate to 1 residue of cross-link/10,000 residues, AD patient cortex and cerebellum tissues contain 30-50 residues of cross-link/10,000 residues. Together, these findings suggest that multiple TGase enzymes are involved in normal neuronal structure and function, but their elevated expression and cross-linking activity may also contribute to neuronal degenerative disease. C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Chungnam Natl Univ, Sch Med, Dept Dermatol, Taejon, South Korea. RP Steinert, PM (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 6,Rm 425, Bethesda, MD 20892 USA. NR 52 TC 167 Z9 170 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 22 PY 1999 VL 274 IS 43 BP 30715 EP 30721 DI 10.1074/jbc.274.43.30715 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248LT UT WOS:000083276700056 PM 10521460 ER PT J AU Igishi, T Fukuhara, S Patel, V Katz, BZ Yamada, KR Gutkind, JS AF Igishi, T Fukuhara, S Patel, V Katz, BZ Yamada, KR Gutkind, JS TI Divergent signaling pathways link focal adhesion kinase to mitogen-activated protein kinase cascades - Evidence for a role of paxillin in c-Jun NH2-terminal kinase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MEDIATED TYROSINE PHOSPHORYLATION; BETA-GAMMA-SUBUNITS; COUPLED RECEPTORS; PHOSPHATIDYLINOSITOL 3-KINASE; MAP KINASE; V-CRK; TRANSDUCTION PATHWAY; SUBSTRATE P130(CAS); CELL-SURVIVAL; SRC AB Stimulation of a number of cell surface receptors, including integrins and Cf protein-coupled receptors, results in the activation of a non-receptor tyrosine kinase known as focal adhesion kinase (FAK), In turn, this kinase is believed to play a critical role in signaling to intracellular kinase cascades controlling gene expression such as extracellular signal-regulated kinases (ERKs), by a yet poorly defined mechanism, Furthermore, whether this tyrosine kinase also mediates the activation of other mitogen-activated protein kinase family members, such as c-Jun NH2-terminal kinases (JNKs), is still unclear. We show here that the activation of FAK by anchoring to the cell membrane is itself sufficient to stimulate potently both ERK and JNK. These effects were found to be phosphatidylinositol 5-kinase-independent, as FAK effectively stimulated Akt, and wortmannin suppressed Akt but not ERK or JNK: activation. As previously reported by others, activation of ERK correlated with the ability of FAK to induce tyrosine phosphorylation of Shc. Surprisingly, however, stimulation of JNK was not dependent on the kinase activity of FAK or on the ability to induce tyrosine phosphorylation of FAK substrates. Instead, we provide evidence that FAK may stimulate JNK through a novel pathway involving the recruitment of paxillin to the plasma membrane and the subsequent activation of a biochemical route dependent on small GTP-binding proteins of the Rho family. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Rm 212, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; OI Yamada, Kenneth/0000-0003-1512-6805 NR 61 TC 70 Z9 70 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 OCT 22 PY 1999 VL 274 IS 43 BP 30738 EP 30746 DI 10.1074/jbc.274.43.30738 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248LT UT WOS:000083276700059 PM 10521463 ER PT J AU Spanaki, MV Siegel, H Kopylev, L Fazilat, S Dean, A Liow, K Ben-Menachem, E Gaillard, WD Theodore, WH AF Spanaki, MV Siegel, H Kopylev, L Fazilat, S Dean, A Liow, K Ben-Menachem, E Gaillard, WD Theodore, WH TI The effect of vigabatrin (gamma-vinyl GABA) on cerebral blood flow and metabolism SO NEUROLOGY LA English DT Article DE epilepsy; PET; vigabatrin; GABA; cerebral metabolism; cerebral blood flow ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-METABOLISM; EPILEPTIC PATIENTS; ANTIEPILEPTIC DRUGS; ACTION-POTENTIALS; SODIUM VALPROATE; BRAIN; ACID; ANTICONVULSANT; PERFORMANCE AB Objective: To investigate the effect of vigabatrin(VGB; gamma-vinyl gamma-aminobutyric acid [GABA]), a selective irreversible GABA-transaminase inhibitor, on cerebral metabolic rate for glucose (CMRGlc) and cerebral blood flow (CBF) measured with F-18-fluorodeoxyglucose (EDG) PET and O-15 water PET. Background: Antiepileptic drugs (AEDs) reduce CMRGlc to varying degrees. Phenobarbital causes a mean decrease of 30 to 40%. Phenytoin, carbamazepine (CBZ), and valproate (VPA) cause milder reductions in CMRGlc. The combination of VPA with CBZ results in a greater decrease than either drug alone. The effect of novel AEDs on both CBF and CMRGlc has not been studied extensively. Methods: Fourteen patients with refractory complex partial seizures on CBZ monotherapy for 4 weeks were included in the study. All patients had baseline F-18-FDG and O-15 water PET studies followed by double-blind randomization to placebo (PLC) or VGB while on continuous CBZ treatment. PET scans were repeated after an interval of 2 months on target dose of VGB (50 mg/kg) or PLC. Quantitative PET data analysis was performed using a region of interest template. Significance was tested with the Wilcoxon rank sum test. Results: No statistically significant difference in age, duration of epilepsy, or CZ levels was observed in the two patient groups. VGB reduced global CMRGlc by 8.1 +/- 6.5% and global CBF by 13.1 +/- 10.4%. The change in CMRGlc was different in patients taking VGB compared with those on PLC (p < 0.04). VGB patients showed regional decreases in both CMRGlc and CBF, particularly in temporal lobes. CSF total GABA increased in the VGB patient group (1.48 +/- 1.06 versus 4.03 +/- 4.19 nm/mL). The increase differed from the PLC group (p < 0.03). We found a strong relation between decreased total CSF GABA and increased CMRGlc in the VGB patient group (R-2 = 0.82, p < 0.01). Conclusions: Vigabatrin (VGB) causes mild reductions in both cerebral blood flow (CBP) and cerebral metabolic rate for glucose (CMRGlc) in contrast to other drugs such as barbiturates, which are direct agonists at the gamma-aminobutyric acid-benzodiazepine receptor complex. Conventional AEDs depress CBF and CMRGlc to a greater degree than does VGB. The relatively mild reduction could be due to pre- as well as postsynaptic effects or a use-dependent mechanism. C1 NINDS, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biometry & Field Studies Branch, NIH, Bethesda, MD 20892 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Dept Clin Neurosci, Gothenburg, Sweden. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Theodore, WH (reprint author), NINDS, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,10 Ctr Dr,MSC 1408, Bethesda, MD 20892 USA. NR 40 TC 33 Z9 34 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 22 PY 1999 VL 53 IS 7 BP 1518 EP 1522 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 246TJ UT WOS:000083180400025 PM 10534261 ER PT J AU Wang, HY Jiang, XM Gozes, I Fridkin, M Brenneman, DE Ganea, D AF Wang, HY Jiang, XM Gozes, I Fridkin, M Brenneman, DE Ganea, D TI Vasoactive intestinal peptide inhibits cytokine production in T lymphocytes through cAMP-dependent and cAMP-independent mechanisms SO REGULATORY PEPTIDES LA English DT Article DE PACAP; VIP-agonists; -antagonists; IL-2; IL-10; transduction pathways ID ACTIVATED PROTEIN-KINASE; N-TERMINAL KINASE; INTRACELLULAR CALCIUM; MURINE LYMPHOCYTES; DOWN-REGULATION; MESSENGER-RNA; VIP RECEPTORS; CYCLIC-AMP; CELLS; EXPRESSION AB Previous reports indicate that VIP and the structurally related peptide PACAP inhibit IL-2 and IL-10 production in antigen-stimulated T lymphocytes. Intracellular cAMP elevation appears to be the primary transduction pathway involved. However, in the lower concentration range, an additional, cAMP-independent transduction pathway appears to mediate the VIP inhibition of cytokine production. Here, we address this question by using VIP agonists and antagonists which act through cAMP-dependent and -independent pathways. The antagonists based on the neurotensin-VIP hybrid molecule did not affect the inhibitory effect of VIP/PACAP on IL-2 and IL-10 production, confirming that astrocytes and T lymphocytes express different receptors, A lipophilic antagonist with increased membrane permeability, partially reversed the inhibitory effect of VIP/PACAP, forskolin, prostaglandin E2, and 8-bromo-cAMP without significantly affecting cAMP levels, suggesting that it acts downstream of cAMP. Two VIP agonists inhibit IL-2 and IL-10 production. One of the agonists increases cAMP, whereas the second one does not induce cAMP/cGMP. Our results indicate that VIP inhibits cytokine production in stimulated CD4+ T cells through two separate mechanisms, which involve both cAMP-dependent and cAMP-independent transduction pathways. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Rutgers State Univ, Dept Biol Sci, Newark, NJ 07102 USA. Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Organ Chem, IL-76100 Rehovot, Israel. NICHHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD 20895 USA. RP Ganea, D (reprint author), Rutgers State Univ, Dept Biol Sci, 101 Warren St, Newark, NJ 07102 USA. FU NIAID NIH HHS [AI41786-01R21, AI41786-02]; NIMH NIH HHS [MH49079-01A3] NR 42 TC 26 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD OCT 22 PY 1999 VL 84 IS 1-3 BP 55 EP 67 DI 10.1016/S0167-0115(99)00068-3 PG 13 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 245HE UT WOS:000083100100008 PM 10535409 ER PT J AU Tella, SR Schindler, CW Goldberg, SR AF Tella, SR Schindler, CW Goldberg, SR TI Cardiovascular responses to cocaine self-administration: acute and chronic tolerance SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; self-administration; cardiovascular effect; reinforcing effect; acute tolerance; chronic tolerance ID NEURONAL MONOAMINE UPTAKE; CENTRAL-NERVOUS-SYSTEM; CONSCIOUS RATS; NEURAL MECHANISMS; SQUIRREL-MONKEYS; HEART-RATE; STIMULATION; DRUGS; DOGS; HUMANS AB The nature and the mechanism of tolerance to the cardiovascular responses to cocaine self-administration were studied in rats implanted with telemetric devices. The first infusion of cocaine (1 mg/kg/infusion) on day I of testing produced rapid and brief increases in mean arterial blood pressure and in heart rate. Subsequent infusions in the same session produced minimal effects. With chronic testing, there were gradual reductions in cardiovascular responses to the first infusion in the daily session and enhancements in the daily cocaine intake, with significant changes occurring by the fourth week of the testing. Following saline extinction testing (for 5 days), reinstatement of cocaine during week 6 led to a partial and short lasting (less than or equal to 3 sessions) recovery from the chronic tolerance to the rapid cardiovascular responses to cocaine. There were significant enhancements in cardiovascular responses to post-session norepinephrine during week 2 and marked reductions during week 6 as compared to corresponding control responses. There were marked reductions in the cardiovascular responses to post-session tyramine tested during week 3. These data indicate that self-administered cocaine produces rapid and brief cardiovascular responses which undergo both within-session acute tolerance and a between-session, reversible chronic tolerance. Adrenergic adaptive mechanisms mediate the chronic tolerance. The development of chronic cardiovascular tolerance to cocaine temporally parallels that of the apparent tolerance to its reinforcing effects. Doses of cocaine that maintain self-administration behavior inhibit the norepinephrine transporter at peripheral sympathetic nerve terminals. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC 20007 USA. NIDA, Preclin Pharmacol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Tella, SR (reprint author), Georgetown Univ, Sch Med, Dept Pharmacol, Med Dent Bldg,C405,3900 Reservoir Rd NW, Washington, DC 20007 USA. FU NIDA NIH HHS [DA08830] NR 47 TC 22 Z9 22 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 21 PY 1999 VL 383 IS 1 BP 57 EP 68 DI 10.1016/S0014-2999(99)00582-8 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 251RQ UT WOS:000083459000009 PM 10556682 ER PT J AU Husbands, SM Izenwasser, S Kopajtic, T Bowen, WD Vilner, BJ Katz, JL Newman, AH AF Husbands, SM Izenwasser, S Kopajtic, T Bowen, WD Vilner, BJ Katz, JL Newman, AH TI Structure-activity relationships at the monoamine transporters and sigma receptors for a novel series of 9-[3-(cis-3,5-dimethyl-1-piperazinyl)-propyl]carbazole (rimcazole) analogues SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DOPAMINE REUPTAKE INHIBITORS; ANTIPSYCHOTIC AGENT; SIGMA-RECEPTOR; 1-<2-ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES GBR-12935; CAUDATE-PUTAMEN; LIGAND-BINDING; HIGH-AFFINITY; BW U-234; COCAINE; POTENT AB 9-[3-(cis-3,5-Dimethyl-1-piperazinyl)propyl]carbazole (rimcazole) has been characterized as a a receptor antagonist that binds to the dopamine transporter with moderate affinity (K-i = 224 nM). Although the binding affinities at the dopamine transporter of rimcazole and cocaine are comparable, rimcazole only depressed locomotor activity in mice and antagonized the stimulant effects produced by cocaine. The neurochemical mechanisms underlying the attenuation of cocaine's effects are not understood, although interaction at a low affinity site/state of the dopamine transporter has been suggested. To explore further this class of compounds, a series of rimcazole analogues was designed and synthesized. Displacement of [H-3]WIN 35,428 binding at the dopamine transporter in rat caudate-putamen revealed that aromatic substitutions on rimcazole were not well tolerated, generally, with significant reductions in affinity for the 3,6-dibromo (5; K-i = 3890 nM), 1,3,6-tribromo (6; K-i = 30300 nM), 3-amino (8; K-i = 2400 nM), and 3,6-dinitro (9; K-i = 174000 nM) analogues. The N-phenylpropyl group was the only terminal piperazine nitrogen substituent that retained moderate affinity at the dopamine transporter (11; K-i = 263 nM). Analogues in which the carbazole ring was replaced with a freely rotating diphenylamine moiety were also prepared. Although the diphenylamino analogue in which the terminal piperazine nitrogen was unsubstituted, as in rimcazole, demonstrated relatively low binding affinity at the dopamine transporter (24; K-i = 813 nM), the N-phenylpropyl analogue was found to have the highest affinity for the dopamine transporter within the series (25; K-i = 61.0 nM). All of the analogues that had affinity for the dopamine transporter inhibited [H-3]-dopamine uptake in synaptosomes, and potencies for these two effects showed a positive correlation (r(2) = 0.7731, p = 0.0018). Several of the analogues displaced [H-3]paroxetine from serotonin transporters with moderate to high affinity, with the N-phenylpropyl derivative (11) having the highest affinity (K-i = 44.5 nM). In contrast, none of the analogues recognized the norepinephrine transporter with an affinity of <1.3 mu M . Binding affinities for sigma(1) and sigma(2) receptors were also determined, and several of the compounds were more potent than rimcazole with affinities ranging from 97 nM to >6 mu M at ol sites and 145 to 1990 nM sigma(2) sites. The compound with the highest affinity (25) at ol sites was also the compound with highest affinity at the dopamine transporter. These novel rimcazole analogues may provide important tools with which to characterize the relationship between the low affinity site or state of the dopamine transporter, sigma receptors, and their potential roles in modulating cocaine's psychostimulant actions. C1 NIDA, Intramural Res Program, Med Chem Sect, Baltimore, MD 21224 USA. NIDA, Intramural Res Program, Psychobiol Sect, Baltimore, MD 21224 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Newman, AH (reprint author), NIDA, Intramural Res Program, Med Chem Sect, POB 5180, Baltimore, MD 21224 USA. RI Husbands, Stephen/D-5926-2011; Izenwasser, Sari/G-9193-2012; OI Husbands, Stephen/0000-0002-9928-6322 NR 30 TC 35 Z9 38 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 21 PY 1999 VL 42 IS 21 BP 4446 EP 4455 DI 10.1021/jm9902943 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 247ZR UT WOS:000083251300018 PM 10543888 ER PT J AU Vazquez-Torres, A Jones-Carson, J Baumler, AJ Falkow, S Valdivia, R Brown, W Le, M Berggren, R Parks, WT Fang, FC AF Vazquez-Torres, A Jones-Carson, J Baumler, AJ Falkow, S Valdivia, R Brown, W Le, M Berggren, R Parks, WT Fang, FC TI Extraintestinal dissemination of Salmonella by CD18-expressing phagocytes SO NATURE LA English DT Article ID PEYERS-PATCHES; M-CELLS; TYPHIMURIUM; IDENTIFICATION; MUTANTS; IMMUNIZATION; CONSTRUCTION; EXPRESSION; MUTATIONS; INFECTION AB Specialized epithelia known as M cells overlying the lymphoid follicles of Peyer's patches are important in the mucosal immune system, but also provide a portal of entry for pathogens such as Salmonella typhimurium, Mycobacterium bovis, Shigella flexneri, Yersinia enterocolitica and reoviruses(1-4). Penetration of intestinal M cells and epithelial cells by Salmonella typhimurium requires the invasion genes of Salmonella Pathogenicity Island 1 (SPI1)(3,5-9) SPI1-deficient S, typhimurium strains gain access to the spleen following oral administration and cause lethal infection in mice(5) without invading M cells(3,9) or localizing in Payer's patches(10), which indicates that Salmonella uses an alternative strategy to disseminate from the gastrointestinal tract, Here we report that Salmonella is transported from the gastrointestinal tract to the bloodstream by CD18-expressing phagocytes, and that CD18-deficient mice are resistant to dissemination of Salmonella to the liver and spleen after oral administration. This CD18-dependent pathway of extraintestinal dissemination may be important for the development of systemic immunity to gastrointestinal pathogens, because oral challenge with SPI1-deficient S. typhimurium elicits a specific systemic Ige humoral immune response, despite an inability to stimulate production of specific mucosal IgA. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Natl Jewish Ctr Immunol & Resp Med, Dept Immunol, Denver, CO 80262 USA. Texas A&M Univ, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Vet Affairs Med Ctr, Dept Med, Denver, CO 80262 USA. NCI, Cel Regulat & Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Fang, FC (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RI Baumler, Andreas/H-2301-2011; OI Baumler, Andreas/0000-0001-9152-7809; Fang, Ferric/0000-0002-3243-110X; Parks, W. Tony/0000-0001-7341-3277 NR 29 TC 361 Z9 369 U1 1 U2 20 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 21 PY 1999 VL 401 IS 6755 BP 804 EP 808 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250BG UT WOS:000083368700056 PM 10548107 ER PT J AU Kim, YS Burns, AL Goldsmith, PK Heppner, C Park, SY Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ AF Kim, YS Burns, AL Goldsmith, PK Heppner, C Park, SY Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ TI Stable overexpression of MEN1 suppresses tumorigenicity of RAS SO ONCOGENE LA English DT Article DE menin; MEN1; RAS; neoplasia; NIH3T3; oncogene; tumor suppressor ID ENDOCRINE NEOPLASIA TYPE-1; HUMAN CANCER-CELLS; MUTATION ANALYSIS; GENE; PROTEIN; GROWTH; TRANSFORMATION; ACTIVATION; ONCOGENE; PATHWAY AB Although there is indirect genetic evidence that MEN1, the gene for multiple endocrine neoplasia type 1, is a tumor suppressor gene, little is known about the MEN1-encoded protein, menin. Menin was stably overexpressed in a well-characterized murine tumor cell line, (valine-12)-RAS-transformed NTH3T3 cells. Menin overexpression reverted the morphology of the RAS-transformed NIH3T3 cells towards the more flattened and more spread, fibroblastic shape of wild type NIH3T3 cells. The proliferation rate of the RAS-transformed cells in 0.5% calf serum was also slower with menin overexpression. Menin overexpression reduced the RAS-induced clonogenicity in soft agar. Menin also reduced tumor growth after injection of cells in nude mice. In conclusion, stable overexpression of MEN1 suppressed partially the RAS-mediated tumor phenotype in vitro and in vivo. Overexpressed menin protein had biological effects, directly supporting MEN1 gene function as a tumor suppressor. C1 NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), Bldg 10,Room 9C-101,10 Ctr Dr,MSC 1802, Bethesda, MD 20892 USA. NR 34 TC 81 Z9 83 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 21 PY 1999 VL 18 IS 43 BP 5936 EP 5942 DI 10.1038/sj.onc.1203005 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 248JE UT WOS:000083270700010 PM 10557080 ER PT J AU Jovanovic, SV Steenken, S Boone, CW Simic, MG AF Jovanovic, SV Steenken, S Boone, CW Simic, MG TI H-atom transfer is a preferred antioxidant mechanism of curcumin SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ONE-ELECTRON REDUCTION; RADICAL SCAVENGING ACTIVITY; LASER FLASH-PHOTOLYSIS; PULSE-RADIOLYSIS; PHENOXYL RADICALS; REDOX POTENTIALS AB Antioxidant mechanisms of curcumin, bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, have been studied by laser flash photolysis and pulse radiolysis. The keto-enol-enolate equilibrium of the heptadienone moiety of curcumin determines its physicochemical and antioxidant properties. In neutral and acidic aqueous solutions (from pH 3 to 7), the keto form dominates, and curcumin acts as an extraordinarily potent H-atom donor. The reaction rate constant with the methyl radical (3.5 +/- 0.3) x 10(9) M-1 s(-1) is close to diffusion control in 40% aqueous DMSO at pH 5. The tert-butoxyl radical reacts with curcumin in acetonitrile solutions at a diffusion controlled rate, k = (7.5 +/- 0.8) x 10(9) M-1 s(-1). The apparent site of reaction is the central CH2 group in the heptadienone link, which has two labile hydrogens. This is supported by comparing the reaction patterns of curcumin and dehydrozingerone (DHZ) ("half-curcumin", 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one). DHZ does not react With the methyl radical, indicating that the presence of the labile hydrogens is crucial for the H-atom donating ability of curcumin. The tert-butoxyl radical reacts with DHZ at almost an order of magnitude lower rate (1.1 +/- 0.1) x 10(9) M-1 s(-1), clearly abstracting an H-atom from the phenolic OH group. The reaction mechanism of curcumin changes dramatically above pH 8, where the enolate form of the heptadienone link predominates. As a consequence, the reaction of the methyl radical diminishes completely in alkaline media, and the phenolic part of the molecule takes over as (electron donor) reaction site. The electron donating ability of curcumin is assessed from the measurements of one-electron-transfer equilibria of DHZ radicals. Reduction potential of the DHZ phenoxyl radical, E(pH = 6.5) = 0.83 +/- 0.06 V, and E(pH = 13.0) = 0.47 +/- 0.06 V vs NHE, which may be expected for an ortho-methoxy-substituted phenoxyl radical, indicate only moderate electron-donating ability. The importance of H-atom donation vs electron donation in free radical scavenging and antioxidant mechanisms of curcumin is discussed. C1 Helix Int, Nepean, ON K2E 7R9, Canada. Max Planck Inst Strahlenchem, D-4330 Mulheim, Germany. Techlog Inc, Gaithersburg, MD USA. NCI, Bethesda, MD 20892 USA. RP Jovanovic, SV (reprint author), Helix Int, 381 Viewmount Dr, Nepean, ON K2E 7R9, Canada. NR 35 TC 215 Z9 222 U1 1 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 20 PY 1999 VL 121 IS 41 BP 9677 EP 9681 DI 10.1021/ja991446m PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 248MV UT WOS:000083280100024 ER PT J AU Potosky, AL Harlan, LC Stanford, JL Gilliland, FD Hamilton, AS Albertsen, PC Eley, JW Liff, JM Deapen, D Stephenson, RA Legler, J Ferrans, CE Talcott, JA Litwin, MS AF Potosky, AL Harlan, LC Stanford, JL Gilliland, FD Hamilton, AS Albertsen, PC Eley, JW Liff, JM Deapen, D Stephenson, RA Legler, J Ferrans, CE Talcott, JA Litwin, MS TI Prostate cancer practice patterns and quality of life: The prostate cancer outcomes study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LONG-TERM SURVIVAL; RADICAL PROSTATECTOMY; OF-LIFE; PATIENT; POPULATION; SURVEILLANCE; EPIDEMIOLOGY; DECISION; THERAPY; MEN C1 NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Mexico Tumor Registry, Albuquerque, NM USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. Emory Univ, Rollins Sch Publ Hlth, Georgia Ctr Canc Stat, Atlanta, GA 30322 USA. Univ Utah, Dept Med, Div Urol, Salt Lake City, UT 84112 USA. Univ Illinois, Coll Nursing, Chicago, IL USA. Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. RP Potosky, AL (reprint author), NIH, EPN, Rm 313,6130 Execut Blvd MSC 7344, Bethesda, MD 20892 USA. NR 43 TC 158 Z9 159 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 20 PY 1999 VL 91 IS 20 BP 1719 EP 1724 DI 10.1093/jnci/91.20.1719 PG 6 WC Oncology SC Oncology GA 247XP UT WOS:000083246500009 PM 10528021 ER PT J AU Carter, HB Landis, PK Metter, EJ Fleisher, LA Pearson, JD AF Carter, HB Landis, PK Metter, EJ Fleisher, LA Pearson, JD TI Prostate-specific antigen testing of older men SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CANCER AB Background: Elevated serum prostate-specific antigen (PSA) levels are predictive of a future diagnosis of prostate cancer. To test the hypothesis that older men with low PSA levels may require less intensive PSA testing because of a reduced prostate cancer detection rate, we evaluated the association between age, baseline PSA level, and prostate cancer detection. Methods: We conducted a prospective cohort study among participants in a study of aging who had serial PSA measurements taken from age 60 or 65 years until they either were diagnosed with prostate cancer (cancer case subjects) or reached the age of 75 years (subjects without prostate cancer). The time of cancer detection among cancer case subjects was defined as the measurement date on which a PSA level above 4.0 ng/mL was detected (i.e., PSA conversion), Cancer case subjects and subjects without prostate cancer were analyzed according to baseline PSA level and age. Results: All cancer case subjects in the 60-year-old cohort had baseline PSA levels above 0.5 ng/mL, and 14 of 15 cancer cases that would have been detected by a PSA conversion among the 65-year-old cohort were associated with baseline PSA levels of 1.1 ng/mL or more. If PSA testing were discontinued in men aged 65 years with PSA levels of 0.5 ng/mL or less, 100% (95% confidence interval [CI] = 78%-100%) of the cancers would still be detected by age 75 years; if PSA testing were discontinued in men aged 65 years who had PSA levels of 1.0 ng/mL or less, 94% (95% CI = 70%-100%) of the cancers would still be detected by age 75 years. Conclusions: These data suggest that a decrease in the intensity of screening among older men with low PSA values may not lead to an increase in undetected prostate cancer. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, James Buchanan Brady Urol Inst,Dept Urol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, James Buchanan Brady Urol Inst,Dept Anesthesiol, Baltimore, MD 21287 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Merck Res Labs, Dept Epidemiol, Blue Bell, PA USA. RP Carter, HB (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Hosp, James Buchanan Brady Urol Inst,Dept Urol, 600 N Wolfe St, Baltimore, MD 21287 USA. FU NCI NIH HHS [P50 CA058236, CA58236] NR 12 TC 18 Z9 18 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 OCT 20 PY 1999 VL 91 IS 20 BP 1733 EP 1737 DI 10.1093/jnci/91.20.1733 PG 5 WC Oncology SC Oncology GA 247XP UT WOS:000083246500011 PM 10528023 ER PT J AU Woodson, K Tangrea, JA Barrett, MJ Virtamo, J Taylor, PR Albanes, D AF Woodson, K Tangrea, JA Barrett, MJ Virtamo, J Taylor, PR Albanes, D TI Serum alpha-tocopherol and subsequent risk of lung cancer among male smokers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VITAMIN-E; BETA-CAROTENE; CIGARETTE-SMOKE; FREE-RADICALS; FOLLOW-UP; PLASMA; ANTIOXIDANTS; INHIBITION; ACID; MEN AB Background: Higher blood levels of alpha-tocopherol, the predominant form of vitamin E, have been associated in some studies with a reduced risk of lung cancer, but other studies have yielded conflicting results. To clarify this association, we examined the relationship between prospectively collected serum alpha-tocopherol and lung cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. Methods: The ATBC Study was a randomized, clinical trial of 29133 white male smokers from Finland who mere 50-69 years old and who had received alpha-tocopherol (50 mg), beta-carotene (20 mg), both, or neither daily for 5-8 years. Data regarding medical histories, smoking, and dietary factors were obtained at study entry, as was a serum specimen for baseline alpha-tocopherol determination, alpha-Tocopherol measurements were available for 29102 of the men, among whom 1144 incident cases of lung cancer were diagnosed during a median observation period of 7.7 years. The association between alpha-tocopherol and lung cancer was evaluated with the use of multivariate proportional hazards regression. Results: A 19% reduction in lung cancer incidence was observed in the highest versus lowest quintile of serum alpha-tocopherol (relative risk = 0.81; 95% confidence interval = 0.67-0.97), There was a stronger inverse association among younger men (<60 years), among men with less cumulative tobacco exposure (<40 years of smoking), and possibly among men receiving a-tocopherol supplementation, Conclusions: In the ATBC Study cohort, higher serum alpha-tocopherol status is associated with lower lung cancer risk; this relationship appears stronger among younger persons and among those with less cumulative smoke exposure, These findings suggest that high levels of alpha-tocopherol, if present during the early critical stages of tumorigenesis, may inhibit lung cancer development. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Natl Publ Hlth Inst, Helsinki, Finland. RP Woodson, K (reprint author), NIH, 6006 Execut Blvd MSC 7058, Bethesda, MD 20892 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01CN45165] NR 34 TC 65 Z9 66 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 OCT 20 PY 1999 VL 91 IS 20 BP 1738 EP 1743 DI 10.1093/jnci/91.20.1738 PG 6 WC Oncology SC Oncology GA 247XP UT WOS:000083246500012 PM 10528024 ER PT J AU Gnant, MFX Noll, LA Irvine, KR Puhlmann, M Terrill, RE Alexander, HR Bartlett, DL AF Gnant, MFX Noll, LA Irvine, KR Puhlmann, M Terrill, RE Alexander, HR Bartlett, DL TI Tumor-specific gene delivery using recombinant vaccinia virus in a rabbit model of liver metastases SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INTENSITY FOCUSED ULTRASOUND; HEPATIC-ARTERY; PORTAL-VEIN; VECTORS; THERAPY; CANCER; VACCINATION; EXPRESSION; INTRAARTERIAL; IMPLANTATION AB Background: Several approaches to gene therapy for cancer have yielded promising results in rodent models. The translation of these results to the clinical realm has been delayed by the lack of tumor models in large animals We investigated the pattern of transgene (i.e., foreign or introduced gene) expression and virus vector elimination after systemic gene delivery using a thymidine kinase-negative vaccinia virus in a rabbit model of disseminated liver metastases. Methods: VX-2 rabbit carcinoma cells were maintained by serial transplantation in the thigh muscles of New Zealand White rabbits, and disseminated liver metastases were established by direct injection of tumor cells into the portal vein of the animals. Different doses of a recombinant thymidine kinase-negative vaccinia virus vector encoding the firefly luciferase reporter gene (i.e., transgene) were injected into tumor-bearing rabbits, Transgene activity in tumors and other organs was measured at multiple time points thereafter, The pattern of development of antibodies against the vaccinia virus vector was also examined. Two-tailed Student's paired t test was used for comparisons of transgene activity, Results: Transgene expression was increased in tumors by at least 16-fold in comparison with expression in other tissues by day 4 after vector injection (all P<.001) and was maintained for approximately 1 meek, providing evidence of tumor-specific gene delivery in this model. Rapid elimination of the circulating vector by the host immune system was observed. Anti-vector antibodies were detectable in serum as early as day 6 and were maintained for more than 3 months. Conclusions: Tumor-specific gene delivery is possible after systemic injection of a thymidine kinase-negative vaccinia virus vector in a model of rabbit liver metastases, Al-though the period of transgene expression appears limited because of a rapid immune response, the therapeutic window might be sufficient for an enzyme/prodrug gene therapy approach in clinical application. C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. Univ Vienna, Dept Surg, Vienna, Austria. NCI, Lab Anim Med Sect, Anim Sci Branch, Div Basic Sci, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NIH, Bldg 10,Rm 2B07, Bethesda, MD 20892 USA. OI Gnant, Michael/0000-0003-1002-2118 NR 39 TC 47 Z9 49 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 OCT 20 PY 1999 VL 91 IS 20 BP 1744 EP 1750 DI 10.1093/jnci/91.20.1744 PG 7 WC Oncology SC Oncology GA 247XP UT WOS:000083246500013 PM 10528025 ER PT J AU Bubendorf, L Kolmer, M Kononen, J Koivisto, P Mousses, S Chen, YD Mahlamaki, E Schraml, P Moch, H Willi, N Elkahloun, AG Pretlow, TG Gasser, TC Mihatsch, MJ Sauter, G Kallioniemi, OP AF Bubendorf, L Kolmer, M Kononen, J Koivisto, P Mousses, S Chen, YD Mahlamaki, E Schraml, P Moch, H Willi, N Elkahloun, AG Pretlow, TG Gasser, TC Mihatsch, MJ Sauter, G Kallioniemi, OP TI Hormone therapy failure in human prostate cancer: Analysis by complementary DNA and issue microarrays SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FACTOR-BINDING-PROTEINS; HEAT-SHOCK-PROTEIN; GROWTH-FACTOR-I; PROGRAMMED CELL-DEATH; BREAST-CANCER; GENE-EXPRESSION; DRUG-RESISTANCE; STROMAL CELLS; IGF-SYSTEM; APOPTOSIS AB Background: The molecular mechanisms underlying the progression of prostate cancer during hormonal therapy have remained poorly understood. In this study, we developed a new strategy for the identification of differentially expressed genes in hormone-refractory human prostate cancer by use of a combination of complementary DNA (cDNA) and tissue microarray technologies, Methods: Differences in gene expression between hormone-refractory CWR22R prostate cancer xenografts (human prostate cancer transplanted into nude mice) and a xenograft of the parental, hormone-sensitive CWR22 strain were analyzed by use of cDNA microarray technology. To validate the data from cDNA microarrays on clinical prostate cancer specimens, a tissue microarray of specimens from 26 prostates with benign prostatic hyperplasia, 208 primary prostate cancers, and 30 hormone-refractory local recurrences was constructed and used fur immunohistochemical detection of protein expression. Results: Among 5184 genes surveyed with cDNA microarray technology, expression of 37 (0.7%) was increased more than twofold in the hormone-refractory CWR22R xenografts compared with the CWR22 xenograft; expression of 135 (2.6%) genes was reduced by more than 50%. The genes encoding insulin-like growth factor-binding protein 2 (IGFBP2) and 27-kd heat-shock protein (HSP27) were among the most consistently overexpressed genes in the CWR22R tumors. Immunohistochemical analysis of tissue microarrays demonstrated high expression of IGFBP2 protein in 100% of the hormone-refractory clinical tumors, in 36% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001). Overexpression of HSP27 protein was demonstrated in 31% of the hormone-refractory tumors, in 5% of the primary tumors, and in 0% of the benign prostatic specimens (two-sided P =.0001), Conclusions: The combination of cDNA and tissue microarray technologies enables rapid identification of genes associated with progression of prostate cancer to the hormone-refractory slate and may facilitate analysis of the role of the encoded gene products in the pathogenesis of human prostate cancer. C1 Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD USA. Tampere Univ Hosp, Canc Genet Lab, Tampere, Finland. Univ Basel, Inst Pathol, Basel, Switzerland. Univ Basel, Urol Clin, Basel, Switzerland. Res Genet Inc, Huntsville, AL USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. RP Kallioniemi, OP (reprint author), NIH, 49 Convent Dr,MSC 4470,Rm 4A24, Bethesda, MD 20892 USA. RI Kallioniemi, Olli/H-5111-2011; Bubendorfl, Lukas/H-5880-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NCI NIH HHS [CA57179] NR 46 TC 263 Z9 287 U1 2 U2 6 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 OCT 20 PY 1999 VL 91 IS 20 BP 1758 EP 1764 DI 10.1093/jnci/91.20.1758 PG 7 WC Oncology SC Oncology GA 247XP UT WOS:000083246500015 PM 10528027 ER PT J AU Shu, XO Linet, MS Steinbuch, M Wen, WQ Buckley, JD Neglia, JP Potter, JD Reaman, GH Robison, LL AF Shu, XO Linet, MS Steinbuch, M Wen, WQ Buckley, JD Neglia, JP Potter, JD Reaman, GH Robison, LL TI Breast-feeding and risk of childhood acute leukemia SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN-MILK; CANCER; EPIDEMIOLOGY; INFECTIONS; EXPOSURE; CHILDREN; LYMPHOMA; INFANTS; LIFE AB Background: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. Methods: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. Results: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91), A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93), The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for MO, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. Conclusion: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breastfeeding on leukemogenesis in children. C1 Univ Minnesota, Div Pediat Epidemiol & Clin Res, Minneapolis, MN USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. Childrens Natl Med Ctr, Dept Pediat Hematol Oncol, Washington, DC 20010 USA. RP Shu, XO (reprint author), Univ S Carolina, Sch Med, Dept Pediat, 15 Med Pk,Suite 301, Columbia, SC 29203 USA. OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [CA13539, CA48051, CA49450] NR 42 TC 101 Z9 103 U1 2 U2 6 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 OCT 20 PY 1999 VL 91 IS 20 BP 1765 EP 1772 DI 10.1093/jnci/91.20.1765 PG 8 WC Oncology SC Oncology GA 247XP UT WOS:000083246500016 PM 10528028 ER PT J AU Engels, EA Eastman, H Ablashi, DV Wilks, RJ Braham, J Manns, A AF Engels, EA Eastman, H Ablashi, DV Wilks, RJ Braham, J Manns, A TI Risk of transfusion-associated transmission of human herpesvirus 8 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8 INFECTION; SEXUAL TRANSMISSION; BLOOD; ANTIBODIES; DONORS; AIDS C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Adv Biotechnol Inc, Columbia, MD USA. Univ W Indies, Trop Metab Res Unit, Kingston 7, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. RP Engels, EA (reprint author), NIH, 6120 Execut Blvd,MSC 7248, Bethesda, MD 20822 USA. NR 26 TC 44 Z9 46 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 OCT 20 PY 1999 VL 91 IS 20 BP 1773 EP 1775 DI 10.1093/jnci/91.20.1773 PG 3 WC Oncology SC Oncology GA 247XP UT WOS:000083246500017 PM 10528029 ER PT J AU Stratakis, CA Sarlis, N Kirschner, LS Carney, JA Doppman, JL Nieman, LK Chrousos, GP Papanicolaou, DA AF Stratakis, CA Sarlis, N Kirschner, LS Carney, JA Doppman, JL Nieman, LK Chrousos, GP Papanicolaou, DA TI Paradoxical response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE dexamethasone; adrenocortical disorder, primary, pigmented; adrenocortical disorder, macronodular; Carney complex; Cushing syndrome ID GASTRIC-INHIBITORY POLYPEPTIDE; FAMILIAL CUSHINGS-SYNDROME; CARNEY COMPLEX; ADRENAL-CELLS; FREE CORTISOL; RARE CAUSE; DYSPLASIA; MYXOMAS; SUBTYPE; CT AB Background: Primary pigmented nodular adrenocortical disease causes the Cushing syndrome in children and young adults and is most frequently associated with the Carney complex. Objective: To evaluate diagnostic tests for primary pigmented nodular adrenocortical disease. Design: Retrospective cohort study. Setting: Tertiary care center. Patients: 21 patients with primary pigmented nodular adrenocortical disease. The control groups consisted of 9 patients with macronodular adrenocortical disease and 15 patients with primary unilateral adrenocortical disease (single adenomas). Measurements: Clinical characteristics, radiologic imaging, and a 6-day Liddle test with determination of urinary free cortisol and 17-hydroxycorticosteroid excretion. Results: Adrenal imaging and other tests were of limited value for the diagnosis of primary pigmented nodular adrenocortical disease. The Liddle test, however, distinguished patients with this disorder from those with other primary adrenocortical lesions. An increase of 50% or more in urinary free cortisol levels on day 6 of the Liddle test identified 9 of 13 patients (69.2% [95% Cl, 46.6% to 91.8%]) with primary pigmented nodular adrenocortical disease, excluded all patients with macronodular adrenocortical disease, and was present in only 3 of the 15 patients with single adrenocortical adenomas (20% [Cl, 0% to 40.2%]). An increase in urinary free cortisol excretion of 100% or more on day 6 of the Liddle test identified only patients with primary pigmented nodular adrenocortical disease. Conclusions: Patients with primary pigmented nodular adrenocortical disease responded to dexamethasone with a paradoxical increase in glucocorticoid excretion during the Liddle test. This feature distinguishes such patients from those who have the Cushing syndrome caused by other primary adrenal disorders and may lead to timely detection of the Carney complex (a potentially fatal disorder) in asymptomatic patients. C1 NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 41 TC 109 Z9 117 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 OCT 19 PY 1999 VL 131 IS 8 BP 585 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 246ZR UT WOS:000083196600005 PM 10523219 ER PT J AU Hrycyna, CA Ramachandra, M Germann, UA Cheng, PW Pastan, I Gottesman, MM AF Hrycyna, CA Ramachandra, M Germann, UA Cheng, PW Pastan, I Gottesman, MM TI Both ATP sites of human P-glycoprotein are essential but not symmetric SO BIOCHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE PROTEIN; CATALYTIC TRANSITION-STATE; NUCLEOTIDE-BINDING SITES; MONOCLONAL-ANTIBODIES; FUNCTIONAL EXPRESSION; BACTERIAL TRANSPORT; CYSTIC-FIBROSIS; TUMOR-CELLS; HYDROLYSIS; MDR1 AB Human P-glycoprotein (P-gp) is a cell surface drug efflux pump that contains two nucleotide binding domains (NBDs), Mutations were made in each of the Walker B consensus motifs of the NBDs at positions D555N and D1200N, thought to be involved in Mg2+ binding. Although the mutant and wild-type P-gps were expressed equivalently at the cell surface and bound the drug analogue [I-125]iodoarylazidoprazosin ([I-125]IAAP) comparably, neither of the mutant proteins was able to transport fluorescent substrates nor had detectable basal nor drug-stimulated ATPase activities. The wild-type and D1200N P-gps were labeled comparably with [alpha-P-32]-8-azido-ATP at a subsaturating concentration of 2.5 mu M, whereas labeling of the D555N mutant was severely impaired. Mild trypsin digestion, to cleave the protein into two halves, demonstrated that the N-half of the wild-type and D1200N proteins was labeled preferentially with [alpha-P-32]-8-azido-ATP. [alpha-P-32]-8-Azido-ATP labeling at 4 degrees C was inhibited in a concentration-dependent manner by ATP with half-maximal inhibition at approximately 10-20 mu M for the P-gp-D1200N mutant and wild-type P-gp. A chimeric protein containing two N-half NBDs was found to be functional for transport and was also asymmetric with respect to [alpha-P-32]-8-azido-ATP labeling, suggesting that the context of the ATP site rather than its exact sequence is an important determinant for ATP binding. By use of [alpha-P-32]-8-azido-ATP and vanadate trapping, it was determined that the C-half of wild-type P-gp was labeled preferentially under hydrolysis conditions; however, the N-half was still capable of being labeled with [alpha-P-32]-8-azido-ATP. Neither mutant was labeled under vanadate trapping conditions, indicating loss of ATP hydrolysis activity in the mutants. In confirmation of the lack of ATP hydrolysis, no inhibition of [I-125]IAAP labeling was observed in the mutants in the presence of vanadate. Taken together, these data suggest that the two NBDs are asymmetric and intimately linked and that a conformational change in the protein may occur upon ATP hydrolysis. Furthermore, these data are consistent with a model in which binding of ATP to one site affects ATP hydrolysis at the second site. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 55 TC 121 Z9 121 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 19 PY 1999 VL 38 IS 42 BP 13887 EP 13899 DI 10.1021/bi991115m PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248RD UT WOS:000083288400014 PM 10529234 ER PT J AU Bebenek, K Boyer, JC Kunkel, TA AF Bebenek, K Boyer, JC Kunkel, TA TI The base substitution fidelity of HIV-1 reverse transcriptase on DNA and RNA templates probed with 8-oxo-deoxyguanosine triphosphate SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE base analog; transversions; oxidative stress; fidelity; base substitutions ID STATE KINETIC-ANALYSIS; POLYMERASE-BETA; CRYSTAL-STRUCTURE; 8-OXODEOXYGUANOSINE TRIPHOSPHATE; ANGSTROM RESOLUTION; STEADY-STATE; REPLICATION; MECHANISM; COMPLEX AB We have used 8-O-dGTP, a mutagenic nucleotide generated by oxidative metabolism, to probe the misincorporation potential of HIV-1 reverse transcriptase (RT) during DNA synthesis templated by the same nucleotide sequence as either RNA or DNA. With either template, 8-O-dGMP was misincorporated opposite template A, yielding characteristic A --> C transversions. The error rate with DNA was similar to that with RNA, suggesting that base misincorporation by the RT during first-strand and second-strand replication may contribute equally to the HIV-1 base substitution mutation rate. The rate of 8-O-dGMP misincorporation differed by more than 10-fold among the 20 adenines in the M13mp2 template where A --> C transversions can be detected. The transversion distribution was similar with the two templates, indicating that the effects of flanking nucleotides on misincorporation rates were similar. This is consistent with structural and biochemical data suggesting that HIV-1 RT binds RNA.DNA and DNA.DNA template-primers in the same orientation. The similarities in error rates and distribution further indicate that, despite differences in the structures of free RNA DNA and DNA DNA duplexes (e.g., minor groove dimensions), the polymerase active site that assembles upon substrate binding establishes a similar degree of nucleotide selectivity with both types of template-primers. Comparison of the RT error distribution to that observed with two Pol I family DNA polymerases and a Pol alpha family polymerase revealed common hot and cold spots for misincorporation. This suggests that the local nucleotide sequence influences the nucleotide selectivity of four polymerases in a similar manner, despite their differences in structure, biochemical properties, and functions. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. NR 32 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 19 PY 1999 VL 429 IS 2 BP 149 EP 158 DI 10.1016/S0027-5107(99)00119-0 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 246JC UT WOS:000083159800001 PM 10526200 ER PT J AU Sussman, HE Olivero, OA Meng, QX Pietras, SM Poirier, MC O'Neill, JP Finette, BA Bauer, MJ Walker, VE AF Sussman, HE Olivero, OA Meng, QX Pietras, SM Poirier, MC O'Neill, JP Finette, BA Bauer, MJ Walker, VE TI Genotoxicity of 3 '-azido-3 '-deoxythymidine in the human lymphoblastoid cell line, TK6: relationships between DNA incorporation, mutant frequency, and spectrum of deletion mutations in HPRT SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE AZT; TK6 cells; HPRT; mutagenicity; mutational spectrum ID 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE AZT; LOCUS; GENE; ZIDOVUDINE; APOPTOSIS; P53; METABOLISM; MICE AB Perinatal treatment with 3'-azido-3'-deoxythymidine (AZT) has been found to reduce the rate of maternal-infant transmission of HIV; however, AZT is genotoxic in mammalian cells in vitro and induces tumors in the offspring of mice treated in utero. The purpose of the present study was to investigate the relationships between incorporation of AZT into DNA, and the frequency and spectrum of mutations at the HPRT locus of the human lymphoblastoid cell line, TK6, following in vitro exposures to AZT. Cells were cultured in medium containing 0 or 300 mu M AZT for 1, 3, or 6 day(s) (n = 5/group). The effects of exposure duration on incorporation of AZT into DNA and HPRT mutant frequency were determined using an AZT radioimmunoassay and a cell cloning assay, respectively. AZT accumulated in DNA in a supralinear manner, approaching a plateau at 6 days of treatment (101.9 +/- 14.7 molecules AZT/10(6) nucleotides). After 3 days of AZT exposure, HPRT mutant frequency was significantly increased (1.8-fold, p = 0.016) compared to background (mutant frequency = 3.78 X 10(-6)). Multiplex PCR amplification of genomic DNA was used to determine the frequency of exon deletions in HPRT mutant clones from untreated cells versus AZT-treated cells. Molecular analyses of AZT-induced mutations revealed a significant difference in the frequency of total gene deletions (44/120 vs. 18/114 in controls, p = 0.004 by the Mann-Whitney U-statistic). In fact, the Chi-square test of homogeneity demonstrate that the differences between the control and AZT-treatment groups is attributed mainly to this increase in total gene deletion mutations (p = 0.00001). These data indicate that the primary mechanism of AZT mutagenicity in human TK6 cells is through the production of large deletions which occur as a result of AZT incorporation into DNA and subsequent chain termination. The data imply that perinatal chemoprophylaxis with AZT may put children of HIV-infected women at potential risk for genetic damage. (C) 1999 Elsevier Science B.V. All rights reserved. C1 New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12203 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Vermont, Genet Lab, Burlington, VT 05401 USA. Univ Vermont, Dept Pediat, Burlington, VT 05405 USA. RP Walker, VE (reprint author), New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. FU NCI NIH HHS [1R01CA77737-01]; NHLBI NIH HHS [1R29HO35309-0191]; NICHD NIH HHS [R01HD33648-01A1] NR 24 TC 52 Z9 52 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 19 PY 1999 VL 429 IS 2 BP 249 EP 259 DI 10.1016/S0027-5107(99)00111-6 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 246JC UT WOS:000083159800010 PM 10526209 ER PT J AU Mendelson, WB Basile, AS AF Mendelson, WB Basile, AS TI The hypnotic actions of oleamide are blocked by a camabinoid receptor antagonist SO NEUROREPORT LA English DT Article DE cannabinoid receptor; fatty acid amides; hypnotics; oleamide; sleep ID CANNABINOID RECEPTOR; SLEEP INDUCTION; BRAIN LIPIDS; ANANDAMIDE; NEURONS; MEMORY AB THE unsaturated fatty acid amide oleamide (OA), which accumulates in the CSF of rats during sleep deprivation, induces electroencephalographically measured sleep when administered intracerebroventricularly. The mechanism of sleep induction by OA is unclear but may derive from enhancements of GABA or 5-HT receptor function, or alternatively from changes in the catabolism or uptake of the related fatty acid amide anandamide, an endogenous cannabinoid-l (CBI) receptor ligand. The present study tests the fatter hypothesis by administering OA alone and in combination with the CBI receptor antagonist SR141716. As previously reported, 2.8 mu g OA administered intracerebroventricularly significantly shorten ed electroencephalographic sleep latency. SR141716 in a dose of 3 mu g had no effects on sleep by itself, but when co-administered with OA prevented its sleep-inducing effects. These data suggest that at least one aspect of the hypnotic action of OA involves interactions with the CB1 receptor system, possibly by blocking the metabolism of the endogenous CBI receptor agonist anandamide. (C) 1999 Lippincott Williams & Wilkins. C1 Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. NIDDK, Neurosci Grp, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Mendelson, WB (reprint author), Univ Chicago, Dept Psychiat, 5841 Maryland Ave,MC3077, Chicago, IL 60637 USA. FU NHLBI NIH HHS [K07 HL03640] NR 14 TC 44 Z9 46 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 OCT 19 PY 1999 VL 10 IS 15 BP 3237 EP 3239 DI 10.1097/00001756-199910190-00021 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 247YY UT WOS:000083249600022 PM 10574567 ER PT J AU Klar, AJS AF Klar, AJS TI Genetic models for handedness, brain lateralization, schizophrenia, and manic-depression SO SCHIZOPHRENIA RESEARCH LA English DT Article DE brain lateralization; genetic models; handedness; manic-depression; schizophrenia ID FISSION YEAST; SUSCEPTIBILITY GENE; EPIGENETIC STATES; BIPOLAR DISORDER; DNA STRANDS; ILLNESS; FAMILY; CHROMOSOME-18; INHERITANCE; ASYMMETRY AB There has been a long-standing debate to explain the complex correlation of development of human hand preference with brain lateralization, and occasionally, the correlation of both lateralizations with psychiatric disorders. A major unanswered question in this debate is whether nature (i.e., genetics) or nurture (environment/culture) controls the development of these attributes of human behavior. Simple genetic models have failed to satisfactorily explain the mode of inheritance of psychotic disorders as well as of the handedness trait. This paper advances several hypothetical and testable genetic models to explain the complex inheritance of these traits. In one model, brain lateralization is proposed to result from nonrandom segregation of the 'Watson' and 'Crick' strands of a particular chromosome, causing hemisphere lateralization, and that a gene, designated RGHT(for right), is further proposed to be responsible for the distribution of DNA chains to specific hemispheres. Accordingly, dominant, familially inherited schizophrenia and bipolar disorders are postulated to result from chromosomal rearrangements disrupting strand segregation, while sporadic cases are proposed to occur at increased frequencies in individuals with the recessive handedness genotype. Finally, discordance in monozygotic twins is suggested to occur due to developmental differences in brain lateralization in twins of the recessive genotype. Psychotic disorders are suggested to be due to developmental anomalies of cerebral asymmetry. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Gene Regulat & Chromosome Biol Lab, POB B,Bldg 539, Frederick, MD 21702 USA. NR 59 TC 62 Z9 66 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT 19 PY 1999 VL 39 IS 3 BP 207 EP 218 DI 10.1016/S0920-9964(99)00075-4 PG 12 WC Psychiatry SC Psychiatry GA 239HB UT WOS:000082761800006 PM 10507513 ER PT J AU Lee, J Park, SU Kim, JY Kim, JK Lee, J Oh, U Marquez, VE Beheshti, M Wang, QJ Modarres, S Blumberg, PM AF Lee, J Park, SU Kim, JY Kim, JK Lee, J Oh, U Marquez, VE Beheshti, M Wang, QJ Modarres, S Blumberg, PM TI 3-acyloxy-2-phenalkylpropyl amides and esters of homovanillic acid as novel vanilloid receptor agonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID ROOT GANGLION NEURONS; CAPSAICIN RECEPTOR; RESINIFERATOXIN ANALOGS; RESINIFERONOL; LIGANDS; STIMULATION; ANTAGONIST; DISCOVERY; BINDING; CHANNEL AB A series of 3-acyloxy-2-phenalkylpropyl amides and esters of homovanillic acid were designed and synthesized as vanilloid receptor agonists containing the three principal pharmacophores of resiniferatoxin. Amide analogues 23, 5 and II were found to be potent agonists in vanilloid receptor assay both for ligand binding and for activation. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Labs Med Chem, Kwanak Ku, Seoul 151742, South Korea. Seoul Natl Univ, Coll Pharm, CRI, Sensory Res Grp,Kwanak Ku, Seoul 151742, South Korea. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Labs Med Chem, Kwanak Ku, Seoul 151742, South Korea. RI Wang, Qiming/B-6064-2012; OI Lee, Jiyoun/0000-0003-3819-5889 NR 24 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 18 PY 1999 VL 9 IS 20 BP 2909 EP 2914 DI 10.1016/S0960-894X(99)00513-2 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 247WM UT WOS:000083244000002 PM 10571146 ER PT J AU Katz, E Ma, J Kyle, D Ziffer, H AF Katz, E Ma, J Kyle, D Ziffer, H TI Structure and antimalarial activity of adducts of 11-azaartemisinin with conjugated terminal acetylenes SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID N-SUBSTITUTED 11-AZAARTEMISININS; ARTEMISININ; DERIVATIVES; QINGHAOSU AB Several N-substituted 11-azaartemisinins were prepared from 11-azaartemisinin in high yield by the DMAP catalyzed addition of terminal acetylenes conjugated with electron-withdrawing groups. Their antimalarial activities against two drug-resistant strains of Plasmodium falciparum were determined. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. NCI, Bioorgan Chem Lab, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Parasitol, Washington, DC 20307 USA. RP Katz, E (reprint author), NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. NR 10 TC 13 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 18 PY 1999 VL 9 IS 20 BP 2969 EP 2972 DI 10.1016/S0960-894X(99)00506-5 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 247WM UT WOS:000083244000013 PM 10571157 ER PT J AU Thomas, JB Herault, XM Rothman, RB Burgess, JP Mascarella, SW Xu, H Horel, RB Dersch, CM Carroll, FI AF Thomas, JB Herault, XM Rothman, RB Burgess, JP Mascarella, SW Xu, H Horel, RB Dersch, CM Carroll, FI TI (+/-)-4-[(N-allyl-cis-3-methyl-4-piperidinyl)phenylamino]-N,N-diethylben zamide displays selective binding for the delta opiod receptor SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID AGONISTS; POTENT AB Racemic 4-[(N-allyl-cis-3-methyl-4-piperidinyl)phenylamino]-N,N-diethylbenzamide (3a) was synthesized and found to have good affinity and selectivity for the 6 receptor. These compounds can be viewed as an analog of BW373U86 and SNC-80 where an internal piperazine nitrogen has been transposed with a benzylic carbon. Functionally, 3a behaves as an agonist at the 6 receptor with no measurable stimulation of either the mu or kappa receptor subtypes and was found to be devoid of any measurable amount of antagonist activity for any opioid receptor. A comparison of 3a to SNC-80 and DPDPE in the [S-35]GTP gamma S functional assay suggests that 3a may be more like the peptide DPDPE. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Addict Res Sect, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. RP Thomas, JB (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIDA NIH HHS [DA09045] NR 10 TC 9 Z9 9 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 18 PY 1999 VL 9 IS 20 BP 3053 EP 3056 DI 10.1016/S0960-894X(99)00525-9 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 247WM UT WOS:000083244000030 PM 10571174 ER PT J AU Xu, XM Carlson, BA Kim, LK Lee, BJ Hatfield, DL Diamond, AM AF Xu, XM Carlson, BA Kim, LK Lee, BJ Hatfield, DL Diamond, AM TI Analysis of selenocysteine (Sec) tRNA([Ser]Sec) genes in Chinese hamsters SO GENE LA English DT Article DE cloning; pseudogenes; selenium; transcription ID TRANSFER-RNA; PLANT-MITOCHONDRIA; OVARY CELLS; ANTICODON; DNA AB Several recent observations have indicated that the primary structure of the Chinese hamster selenocysteine tRNA([Ser]Sec) is different than those of other mammalian species. These reports prompted us to investigate the gene sequence for this tRNA in Chinese hamsters. Southern blotting of Chinese hamster ovary (CHO) genomic DNA derived from cultured cells with a tRNA([Ser]Sec) probe indicated several hybridizing bands, and each of the corresponding genetic loci was isolated fi-om a recombinant CHO library by molecular cloning. Sequence analysis of these regions indicated three likely pseudogenes and a single functional gene whose sequence differed from those of other mammals. Of these, only one pseudogene and the putative functional gene are actively transcribed following their microinjection into Xenopus oocytes. The possibility that the functional CHO tRNA([Ser]Sec) evolved from an edited transcript is discussed. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Illinois, Dept Human & Nutr & Dietet, Chicago, IL 60612 USA. NIH, Sect Mol Biol Selenium, Basic Res Labs, Div Basic Sci,Natl Canc Inst, Bethesda, MD 20892 USA. Seoul Natl Univ, Inst Mol Biol & Genet, Genet Mol Lab, Seoul 151742, South Korea. RP Diamond, AM (reprint author), Univ Illinois, Dept Human & Nutr & Dietet, Chicago, IL 60612 USA. FU NCI NIH HHS [R01 CA81153] NR 18 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 18 PY 1999 VL 239 IS 1 BP 49 EP 53 DI 10.1016/S0378-1119(99)00382-0 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 248TN UT WOS:000083291600005 PM 10571033 ER PT J AU Brebion, G Amador, X Smith, MJ Malaspina, D Sharif, Z Gorman, JM AF Brebion, G Amador, X Smith, MJ Malaspina, D Sharif, Z Gorman, JM TI Opposite links of positive and negative symptomatology with memory errors in schizophrenia SO PSYCHIATRY RESEARCH LA English DT Article DE source monitoring; false alarms; hallucinations; delusions ID AUDITORY HALLUCINATIONS; SYMPTOMS; IMPAIRMENT; DISCRIMINATION AB We wished to confirm and extend a previous correlational study of our group, suggesting that positive symptoms in schizophrenia were linked to an increase in certain types of memory errors, and negative symptoms to a decrease in other types of errors. A post-hoc analysis was conducted in 33 schizophrenic patients and 40 normal control subjects on memory errors collected in a free recall task and two types of recognition tasks. The memory errors were intrusions and list errors in free recall, and decision bias towards false alarms in recognition, all assumed to reflect a source-monitoring failure. In a first analysis, the patient sample was split along the median for positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS). In a second analysis, it was split along the median for negative symptoms as rated by the Scale for the Assessment of Negative Symptoms (SANS). Patients with high ratings of positive symptoms made more memory errors (intrusions, list errors, false alarms) than those with low ratings, supporting the hypothesis of a link between positive symptomatology and source-monitoring failure. On the other hand, patients with high ratings of negative symptoms made fewer of these errors than the other patients. Fewer errors were specifically associated with more affective flattening, alogia and anhedonia, whereas avolition was entirely unrelated to them. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Inst Psychiat, Dept Psychol Med, London SE5 8AZ, England. New York State Psychiat Inst, Schizophrenia Res Unit, New York, NY 10032 USA. Inst Psychiat, Dept Psychol Med, London SE5 8AZ, England. NIMH, Clin Studies Lab, Bethesda, MD 20892 USA. Creedmoor Psychiat Ctr, Schizophrenia Res Unit, New York, NY USA. RP Brebion, G (reprint author), Inst Psychiat, Dept Psychol Med, 103 Denmark Hill, London SE5 8AZ, England. FU NIMH NIH HHS [5P20MH50727] NR 27 TC 38 Z9 38 U1 5 U2 7 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 OCT 18 PY 1999 VL 88 IS 1 BP 15 EP 24 DI 10.1016/S0165-1781(99)00076-1 PG 10 WC Psychiatry SC Psychiatry GA 255JH UT WOS:000083665400002 PM 10641583 ER PT J AU Merrill, RM Feuer, EJ Warren, JL Schussler, N Stephenson, RA AF Merrill, RM Feuer, EJ Warren, JL Schussler, N Stephenson, RA TI Role of transurethral resection of the prostate in population-based prostate cancer incidence rates SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Medicare; prostatectomy; prostate-specific antigen; prostatic neoplasms; SEER Program ID RISING INCIDENCE; CARCINOMA; TRENDS; REGISTRY; RISE; MEN; HMO AB The extensive pool of asymptomatic prostate disease in the population, which increases substantially with age, suggests that the frequent use of transurethral resection of the prostate (TURP) in recent decades has had a large effect on prostate cancer incidence. The authors identified the effect of TURF-detected prostate cancer on the observed incidence rates between 1973 and 1993 for men aged 65 years and older. They linked population-based cancer registry data from the Surveillance, Epidemiology, and End Results Program to Medicare records between 1986 and 1993 to determine whether a TURF occurred sufficiently close to the time of a prostate cancer diagnosis for them to assume that it led to the diagnosis. TURF-detected cases prior to 1986 were calculated using an indirect method that involved multiplying the TURF procedure rate in the general population (from the National Hospital Discharge Survey) by estimates of the proportion of TURPs resulting in a prostate cancer diagnosis (from Medicare data and the literature). TURF explained much of the observed increase in overall prostate cancer Incidence between 1973 and 1986 and possibly all of it in men aged 70 years and older. However, its influence on the trend and overall magnitude of the rates diminished between 1987 and 1993. The changing role of TURF in detecting prostate cancer is attributed to changes in medical technology and screening practices. The declining influence of TURF on prostate cancer incidence is likely to have continued beyond the study period due to the recent introduction and increasing use of medications for treating obstructive uropathy. C1 Brigham Young Univ, Dept Hlth Sci, Provo, UT 84602 USA. Univ Utah, Sch Med, Dept Family & Prevent Med, Div Epidemiol, Salt Lake City, UT 84112 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Appl Res Branch, Bethesda, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. Univ Utah, Sch Med, Div Urol, Salt Lake City, UT USA. RP Merrill, RM (reprint author), Brigham Young Univ, Dept Hlth Sci, Provo, UT 84602 USA. NR 47 TC 40 Z9 41 U1 0 U2 1 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 OCT 15 PY 1999 VL 150 IS 8 BP 848 EP 860 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 244YY UT WOS:000083079400009 PM 10522656 ER PT J AU Calis, KA Cullinane, AM Horne, MK AF Calis, KA Cullinane, AM Horne, MK TI Bioactivity of cryopreserved alteplase solutions SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; CENTRAL VENOUS CATHETERS C1 NIH, Drug Informat Serv, Dept Pharm, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, CPD, WGMCC, Bethesda, MD 20892 USA. NIH, Hematol Serv, CPD, WGMCC, Bethesda, MD 20892 USA. RP Calis, KA (reprint author), NIH, Drug Informat Serv, Dept Pharm, Warren G Magnuson Clin Ctr, Bldg 10,Room 1S-259,10 Ctr Dr,MSC 1196, Bethesda, MD 20892 USA. NR 6 TC 18 Z9 18 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 OCT 15 PY 1999 VL 56 IS 20 BP 2056 EP 2057 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248FZ UT WOS:000083265600016 PM 10541033 ER PT J AU Qian, XH Zhou, W Khaledi, MG Tomer, KB AF Qian, XH Zhou, W Khaledi, MG Tomer, KB TI Direct analysis of the products of sequential cleavages of peptides and proteins affinity-bound to immobilized metal ion beads by matrix-assisted laser desorption/ionization mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE MALD/TOF/MS; immobilized metal ionaffinity chromatography; protein synthesis error ID ESCHERICHIA-COLI; MONOCLONAL-ANTIBODY; CARBOXYPEPTIDASE-Y; CHROMATOGRAPHY; PURIFICATION; EXPRESSION; ADSORBENT; DOMAINS; EPITOPE; MS AB Consecutive enzymatic reactions on analytes affinity-bound to immobilized metal ion beads with subsequent direct analysis of the products by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry have been used for detecting protein synthesis errors occuring at the N-terminus. The usefulness of this method was demonstrated by analyzing two commercially available recombinant HIV proteins with affinity tags at the N-terminus, and histatin-5, a peptide with multiple histidine residues. The high specificity, sensitivity, and speed of analysis make this method especially useful in obtaining N-terminal sequencing information of histidine-tagged recombinant proteins. (C) 1999 Academic Press. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Chem, Raleigh, NC 27695 USA. RP Tomer, KB (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 26 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT 15 PY 1999 VL 274 IS 2 BP 174 EP 180 DI 10.1006/abio.1999.4268 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 246FF UT WOS:000083153200003 PM 10527513 ER PT J AU Langenbach, R Loftin, C Lee, C Tiano, H AF Langenbach, R Loftin, C Lee, C Tiano, H TI Cyclooxygenase knockout mice - Models for elucidating isoform-specific functions SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE cyclooxygenases; knockout; Ptgs; NSAIDs; cancer; reproduction; gastric ulceration; inflammation ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTAGLANDIN-G/H SYNTHASE; INDUCED COLON CARCINOGENESIS; ENDOPEROXIDE-H SYNTHASE-1; ACTIVATED RECEPTOR-ALPHA; NITRIC-OXIDE SYNTHASE; MESSENGER-RNA; DUCTUS-ARTERIOSUS; EPITHELIAL-CELLS; GENE-EXPRESSION AB The development of cyclooxygenase (COX) deficient mice has allowed investigation into the individual physiological roles of the COX-I and COX-2 isoforms. In the following article, the phenotypes of the two Ptgs (genes coding for COX-1 and COX-2) knockouts are summarized, and recent studies to investigate the effects of COX deficiency on cancer susceptibility, inflammatory response, gastric ulceration, and female reproductive processes are discussed. Also, the development and potential uses of mice deficient in both COX isoforms and mice containing only a single copy of one isoform are discussed. Additionally, when the data permit, the effects of genetic ablation of COX activity are compared with those of pharmacological inhibition of COX activity by nonsteroidal anti-inflammatory drugs. The data suggest that prostaglandins derived via the individual COX isoforms have separate as well as common functions. However, for the maintenance of normal physiology, it appears that deficiency of COX-2 has mure profound effects than deficiency of COX-1. (C) 1999 Elsevier Science Inc. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Langenbach, R (reprint author), NIEHS, 101 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 108 TC 151 Z9 155 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 15 PY 1999 VL 58 IS 8 BP 1237 EP 1246 DI 10.1016/S0006-2952(99)00158-6 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 233BB UT WOS:000082404700002 PM 10487525 ER PT J AU Shore, D Hyman, SE AF Shore, D Hyman, SE TI NIMH symptom challenge and medication discontinuation Workshop SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Shore, D (reprint author), NIMH, 6001 Execut Blvd,Room 8235,MSC 9669, Bethesda, MD 20892 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 1999 VL 46 IS 8 BP 1009 EP 1010 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 246FB UT WOS:000083152800002 PM 10536734 ER PT J AU Shore, D Hyman, SE AF Shore, D Hyman, SE TI An NIMH commentary on the NBAC report SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Shore, D (reprint author), NIMH, 6001 Execut Blvd,Room 8235,MSC 9669, Bethesda, MD 20892 USA. NR 0 TC 15 Z9 16 U1 0 U2 0 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 OCT 15 PY 1999 VL 46 IS 8 BP 1013 EP 1016 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 246FB UT WOS:000083152800004 PM 10536736 ER PT J AU Rosenstein, DL AF Rosenstein, DL TI IRB review of psychiatric medication discontinuation and symptom-provoking studies SO BIOLOGICAL PSYCHIATRY LA English DT Review DE challenge studies; medication discontinuation; bioethics; IRB; vulnerable subjects; safeguards AB Federal regulations governing human subjects research call for additional protections for the "mentally disabled." However, there is currently no consensus definition of mental disability or guidelines for how these research subjects should be protected. This ambiguity complicates the work of institutional review boards (IRBs) charged with the review and approval of protocols involving psychiatric medication discontinuation and symptom provocation. It is particularly important for these studies to be reviewed within the larger context of the research program in which they are conducted. The author proposes a process for IRB review of these studies, which includes the implementation of additional safeguards for subjects determined by the IRB to be vulnerable. Recommendations also are made for training psychiatric clinical investigators in issues related to research bioethics. C1 NIMH, Off Clin Director, Bethesda, MD 20892 USA. RP Rosenstein, DL (reprint author), NIMH, Off Clin Director, Bldg 10,Room 3N242,10 Ctr Dr MSC 1277, Bethesda, MD 20892 USA. NR 8 TC 6 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 1999 VL 46 IS 8 BP 1039 EP 1043 DI 10.1016/S0006-3223(99)00168-7 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 246FB UT WOS:000083152800008 PM 10536740 ER PT J AU Vitiello, B Jensen, PS Hoagwood, K AF Vitiello, B Jensen, PS Hoagwood, K TI Integrating science and ethics in child and adolescent psychiatry research SO BIOLOGICAL PSYCHIATRY LA English DT Review DE child; psychiatry; research; ethics ID DISORDERS; HYPERACTIVITY; DEPRESSION; THERAPIES AB Research to elucidate the biological bases of psychopathology in children and adolescents is needed to understand pathogenesis and to develop effective and safe treatment and preventive interventions. Because of the effect of development, data collected in adults are not always applicable to youth, and direct participation of children in research is necessary. Many medications are currently used in the community to treat children and adolescents with neuropsychiatric disorders without adequate data about their safety and efficacy. Conducting research in children requires attention to specific ethical and regulatory factors. In deciding whether miners can participate in a study with potential direct benefit to the research subjects, the most important variable to consider is the balance between risks and potential benefit, in the context of the seleriry of the child's condition and the available alternatives. Research with no potential benefit to the participants is guided by the concepts of minimal risk (which may apply more 20 normal children) and minor increase over minimal risk (perhaps more relevant to children affected by psychopathology). Recently conducted studies relevant to this issue are reviewed. Of paramount importance is the ratio of risk/scientific value of the proposed experiment. In fact, no research is justifiable, no matter how low the risk may be, unless the potential yield of the study is important and may help advance our understanding of normal functioning and mental illness. C1 NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Child & Adolescent Treatment & Prevent Intervent, Room 7149,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. OI Jensen, Peter/0000-0003-2387-0650 NR 21 TC 15 Z9 15 U1 0 U2 2 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 OCT 15 PY 1999 VL 46 IS 8 BP 1044 EP 1049 DI 10.1016/S0006-3223(99)00162-6 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 246FB UT WOS:000083152800009 PM 10536741 ER PT J AU Wyatt, RJ Henter, ID Bartko, JJ AF Wyatt, RJ Henter, ID Bartko, JJ TI The long-term effects of placebo in patients with chronic schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; placebo; antipsychotic medications ID MEDICATION-FREE RESEARCH; FOLLOW-UP; 1ST-EPISODE SCHIZOPHRENIA; TREATMENT RESPONSE; TIME-COURSE; PSYCHOSIS; DRUG; NEUROLEPTICS AB Background: It has been hypothesized that placebo periods may increase long-term morbidity for patients with schizophrenia. in this study, the long-ter-m effect of a placebo period was evaluated in a group of relatively treatment-refractory patients with chronic schizophrenia. Methods: This retrospective study examined behavioral raring scores for 127 patients with chronic schizophrenia who were placed in a double-blind placebo study on the inpatient units of the National Institute of Mental Health Neuropsychiatric Research Hospital. Patients were rated daily with rite Psychiatric Symptom Assessment Scale (PSAS), an extended and anchored version of the Brief Psychiatric Rating Scale (BPRS). At the end of the placebo phase, most patients were placed on haloperidol, Pre-placebo baseline PSAS ratings were compared with, first, discharge ratings ann second, post-placebo ratings. To determine expected variability in the course of illness, patients in the placebo group were compared with patients hospitalized during the same time period but who did not enter the placebo study. Results: By discharge, ratings for placebo patients had returned to baseline. Post-placebo ratings were quite variable. Although many of the placebo patients had returned to baseline by day 3 of the post-placebo phase, others had not returned to baseline by post-placebo cia!, 42. PSAS Total Scores for patients who left the study early were no different at baseline, placebo, or through post-placebo day 35 compared with patients who completed the study. Conclusions: The results indicate that given a sufficiently lengthy recovery period, patients with chronic schizophrenia who go through a placebo phase return to baseline, but that the speed with which theory attain that recovery is highly variable. C1 NIMH, NIH, Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Wyatt, RJ (reprint author), NIMH, NIH, Neuropsychiat Branch, 15 North Dr,MSC 2668,Suite 20, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 MH999999] NR 48 TC 21 Z9 21 U1 0 U2 0 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 OCT 15 PY 1999 VL 46 IS 8 BP 1092 EP 1105 DI 10.1016/S0006-3223(99)00227-9 PG 14 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 246FB UT WOS:000083152800013 PM 10536745 ER PT J AU Jones, KD Aoki, Y Chang, Y Moore, PS Yarchoan, R Tosato, G AF Jones, KD Aoki, Y Chang, Y Moore, PS Yarchoan, R Tosato, G TI Involvement of interleukin-10 (IL-10) and viral IL-6 in the spontaneous growth of Kaposi's sarcoma herpesvirus-associated infected primary effusion lymphoma cells SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; HUMAN B-CELLS; DNA-SEQUENCES; MEMBRANE-PROTEIN; LYMPHOCYTES-B; AIDS; TRANSFORMATION; EXPRESSION; CYTOKINE AB Primary effusion lymphoma (PEL) is a distinct type of lymphoma associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection. To determine the factors responsible for the unrestrained proliferation of PEL, we have studied the growth factor requirements of the PEL-derived BCBL-1 and BC-1 cell lines. Both cell lines were found to be autocrine growth factor dependent and to release human interleukin-6 (IL-6), viral IL-6 (vIL-6), and human IL-10 in the culture supernatant. To establish whether these cytokines contribute to autocrine growth, neutralizing antibodies against human IL-6, vIL-6, human IL-10, and soluble IL-10 receptor were used. These experiments showed that human IL-10 and, to a lesser degree, vIL-6 serve as autocrine growth factors for BCBL-1 and BC-1 cells. Thus, human IL-10 and vIL-6 are growth factors released and used by PEL cells for autonomous proliferation and may be critical to the development and progression of PEL. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. Columbia Univ, Sch Publ Hlth, Dept Pathol, New York, NY USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Room 2D16,Bldg 29A,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Chang, Yuan/F-4146-2011; Moore, Patrick/F-3960-2011 OI Moore, Patrick/0000-0002-8132-858X NR 45 TC 168 Z9 171 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 OCT 15 PY 1999 VL 94 IS 8 BP 2871 EP 2879 PG 9 WC Hematology SC Hematology GA 244PM UT WOS:000083060000037 PM 10515891 ER PT J AU Greene, MH AF Greene, MH TI The genetics of hereditary melanoma and nevi - 1998 update SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society 2nd National Conference on Cancer Genetics CY JUN 26-28, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Canc Soc DE hereditary melanoma; dysplastic nevi; CDKN2A; CDK4; melanoma/astrocytoma syndrome ID CUTANEOUS MALIGNANT-MELANOMA; ATYPICAL-MOLE SYNDROME; SPORADIC DYSPLASTIC NEVUS; SUSCEPTIBILITY LOCUS MLM; MULTICENTER CASE-CONTROL; TUMOR-SUPPRESSOR GENE; PROSPECTIVE FOLLOW-UP; FAMILIAL MELANOMA; RISK-FACTORS; MELANOCYTIC NEVI AB Although the first English-language report of melanoma in 1820 contained a description of a melanoma-prone family, it was 1983 before formal genetic analysis suggested an autosomal dominant mode of inheritance for both melanoma and the then newly described melanoma precursor, dysplastic nevi (DN). Subsequent genetic studies have assumed this model to be correct, although when viewed in aggregate, the data are inconsistent. The first proposed melanoma gene (CMM1) was mapped to chromosome 1p36. This gene assignment has,lot been confirmed. A second melanoma gene, designated CMM2, has been mapped to chromosome 9p21. This gene assignment has been confirmed, and the cell cycle regulator CDKN2A has been proposed as the candidate gene, Germline mutations in this gene have been identified in about 20% of melanoma-prone families that have been studied to date, Pancreatic cancer occurs excessively in melanoma families with germline mutations in CDKN2A. Germline mutations in the cyclin-dependent kinase gene CDK4 (chromosome 12q14) have been described in three melanoma families. This finding represents a third melanoma gene but one that accounts for only a tiny fraction of all hereditary melanoma. Recently, a familial melanoma-astrocytoma syndrome has been reported. Large germline deletions of 9p21 occur in these families, with the p19 gene implicated in its pathogenesis. At present, clinical predictive genetic testing for mutations in the CDKN2A gene is available commercially, but its use has been limited by uncertainty as to how test results would affect the management of melanoma-prone family members. Currently, management recommendations include monthly skin self-examination, clinical skin examination once or twice yearly, a low threshold for simple excision of changing pigmented lesions, moderation of sun exposure, and appropriate use of sunscreens. A heritable determinant for total nevus number has been suggested by twin studies. Other data suggest the presence of a major gene responsible for "total nevus density" in melanoma-prone families. Approximately 55% of the mole phenotype in multiplex melanoma families was explained by this proposed gene, An autosomal dominant mode of inheritance has been proposed for DN, and data exist to suggest that DN may be a pleiotropic manifestation of the 1p36 familial melanoma gene. However, there clearly are melanoma-prone families that do not express the dysplastic nevus trait, and some of the families linked to CDKN2A also present with dysplastic nevi. Several studies have shown a surprisingly high prevalence of DN on the skin of family members of probands with DN. In light of the extensive evidence documenting that persons with DN (both sporadic and familial) have an increased prospective risk of melanoma, these family studies suggest that relatives of persons with DN should be examined for both DN and melanoma. Genetic determinants play a major role in the pathogenesis of normal nevi, DN, and melanoma. Identifying the molecular basis of these genetic events promises to enhance melanoma risk-reduction strategies and, ultimately, reduce melanoma-associated mortality. (C) 1999 American Cancer Society. C1 Mayo Clin, Div Hematol Oncol, Scottsdale, AZ USA. RP Greene, MH (reprint author), NCI, 6120 Execut Blvd,EPS 7022, Rockville, MD 20852 USA. NR 123 TC 9 Z9 9 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1999 VL 86 IS 8 SU S BP 1644 EP 1657 DI 10.1002/(SICI)1097-0142(19991015)86:8+<1644::AID-CNCR3>3.0.CO;2-S PG 14 WC Oncology SC Oncology GA 246XH UT WOS:000083189800003 ER PT J AU Hawk, E Lubet, R Limburg, P AF Hawk, E Lubet, R Limburg, P TI Chemoprevention in hereditary colorectal cancer syndromes SO CANCER LA English DT Article; Proceedings Paper CT American-Cancer-Society 2nd National Conference on Cancer Genetics CY JUN 26-28, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Canc Soc DE chemoprevention; colorectal cancer; familial adenomatous polyposis; genetic; hereditary nonpolyposis colorectal cancer; nonsteroidal antiinflammatory drugs ID FAMILIAL ADENOMATOUS POLYPOSIS; APC(DELTA-716) KNOCKOUT MICE; SPONTANEOUS INTESTINAL ADENOMAS; EPITHELIAL-CELL PROLIFERATION; MIN MOUSE MODEL; SULINDAC THERAPY; RECTAL POLYPS; COLON CARCINOGENESIS; PROSTAGLANDIN LEVELS; GARDNERS-SYNDROME AB Understanding of the neoplastic events involved in heritable colorectal cancer syndromes is increasing at the molecular and clinical levels. This knowledge is foundational to cancer chemoprevention, which attempts to inhibit or reverse the tumorigenic process through pharmacologic interventions applied before cancer occurrence. We reviewed all relevant published reports identified from Medline databases (1966-1998) regarding cancer chemoprevention in familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, and heritable colorectal cancer cohorts, including rodent models of these diseases. Additional references were obtained from citations listed in the reviewed reports. A large amount of experience exists with cancer chemopreventive agents in both genetically-based rodent models and patient populations with familial adenomatous polyposis. These studies have provided important data on the natural history of neoplasia in this syndrome and have identified several classes of compounds with chemopreventive activity. Cyclooxygenase inhibitors, for example, yield substantial cancer prevention in animals and adenoma regression in humans, although reductions or delays in cancer incidence have not been proven to date. The data from chemoprevention studies in hereditary nonpolyposis colorectal cancer or other familial nonpolyposis colorectal cancer syndromes are less mature. Persons in heritable colorectal cancer cohorts are at substantial risk for early-onset malignancy in multiple target organs and therefore represent ideal subjects for cancer chemoprevention trials. The goals of chemoprevention are to reduce cancer risk and improve quality of life. Eventual success in family cancer cohorts may be measured through declines in the frequency of invasive surveillance procedures, surgical resections, neoplasia incidence, and cancer-related deaths. Disease-modifying agents that have shown promise in preliminary efficacy trials with intermediate endpoints require further testing to establish definitive clinical effectiveness. The lessons learned in these high-risk cohorts map have application to the prevention of colorectal cancers arising in the sporadic setting as well. (C) 1999 American Cancer Society. C1 NCI, Div Canc Prevent, Gastrointestinal & Other Canc Res Grp, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Off Prevent Oncol, Bethesda, MD 20892 USA. RP Hawk, E (reprint author), NCI, EPN, DCP CPRP, Chemoprevent Branch, Suite 201,6130 Execut Blvd,MSC-7322, Bethesda, MD 20892 USA. NR 111 TC 4 Z9 4 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 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 1999 VL 86 IS 8 SU S BP 1731 EP 1743 DI 10.1002/(SICI)1097-0142(19991015)86:8+<1731::AID-CNCR12>3.0.CO;2-U PG 13 WC Oncology SC Oncology GA 246XH UT WOS:000083189800012 ER PT J AU Hodge, JW Schlom, A AF Hodge, JW Schlom, A TI Comparative studies of a retrovirus versus a poxvirus vector in whole tumor-cell vaccines SO CANCER RESEARCH LA English DT Article ID GENE-TRANSFER; COSTIMULATORY MOLECULES; ANTITUMOR RESPONSES; MURINE; IMMUNITY; VIRUS; B7-1; CONSTRUCTION; CANCER; EXPRESSION AB A number of experimental and clinical studies have used retroviral vectors to express transgenes in whole tumor-cell vaccines. Recently, poxvirus vectors such as vaccinia or avipox have been used toward this goal. The studies reported here compare for the first time the use of a retroviral vector versus a poxvirus vector (vaccinia) in whale tumor-cell vaccines, The transgene used was the T-cell costimulatory molecule B7-1, and the tumor was the weakly or noninmunogenic MC38 murine colon adenocarcinoma. Recombinant retrovirus (R-B7) and the recombinant vaccinia (V-B7) induced equivalent expression of B7 on the surface of the carcinoma cell. Using live whole-tumor cell as as vaccine, cells transduced via recombinant retrovirus (MC38/R-B7) and recombinant vaccinia (MC38/V-B7) equally induced protection against challenge by native MC38 cells 14 days later. Upon rechallenge with native MC38 cells 40 days later, however, the MC38/R-B7 vaccine was shown to be less effective than the MC38/V-B7 vaccine. Similar results were obtained when the tumor cells were irradiated prior to administration. When comparative studies were conducted in which X-irradiated tumor-cell vaccines were given to mice bearing experimental lung metastases, the MC38/V-B7 vaccine was shown to be significantly (P = 0.0351) more effective than the MC38/R-B7 vaccine. Additional studies were carried out in mice that had received vaccinia virus previously. Again, the X-irradiated MC38/V-B7 vaccine was statistically (P = 0.024) more effective than the MC38/R-B7 vaccine in the elimination of metastases. When the naive and vaccinia-immune mice for each vaccination group were combined for meta-analysis (n = 16), the MC38/V-B7 was significantly more effective than the MC38/ R-B7 in the treatment of pulmonary metastases (P = 0.0014) in this model. These studies thus demonstrate for the first time that a whole tumor-cell vaccine (either live or X-irradiated) containing a vaccinia transgene is at least as efficient, and sometimes more efficient, in inducing antitumor effects compared with the same vaccine using a retrovirus to express the transgene. The implications for the clinical applications of such approaches are discussed. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, A (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Room 8B07, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 34 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1999 VL 59 IS 20 BP 5106 EP 5111 PG 6 WC Oncology SC Oncology GA 248GU UT WOS:000083267400012 PM 10537283 ER PT J AU Gho, YS Kleinnan, HK Sosne, G AF Gho, YS Kleinnan, HK Sosne, G TI Angiogenic activity of human soluble intercellular adhesion molecule-1 SO CANCER RESEARCH LA English DT Article ID MELANOMA CELL-LINES; ENDOTHELIAL-CELLS; ICAM-1; GROWTH; EXPRESSION; MATRIGEL; RELEASE; FORMS; MICE AB Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in a number of pathological conditions associated with angiogenesis, including tumor growth. Because the increased levels of sICAM-1 suggested that it may be angiogenic, we tested the ability of sICAM-1 to promote angiogenesis, Human recombinant sICAM-1 stimulates chemokinetic endothelial cell migration, endothelial cell tube formation on Matrigel,and sprouting of aortic rings, sICAM-1 also mediates angiogenesis in the chick chorioallantoic membrane assay. Additionally, we found a M-r 49,000 molecule that binds to sICAM-1 that may be the surface Ligand on endothelial cells, The evidence that sICAM-1 has angiogenic activity suggests a possible role linking inflammation and neovascularization, Furthermore, sICAM-1 may enhance tumor growth by promoting angiogenesis and escape from immunosurveillance. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Kleinnan, HK (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 433,30 Convent Dr, Bethesda, MD 20892 USA. NR 23 TC 92 Z9 94 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1999 VL 59 IS 20 BP 5128 EP 5132 PG 5 WC Oncology SC Oncology GA 248GU UT WOS:000083267400016 PM 10537287 ER PT J AU Stillwell, WG Turesky, RJ Sinha, R Tannenbaum, SR AF Stillwell, WG Turesky, RJ Sinha, R Tannenbaum, SR TI N-oxidative metabolism of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in humans: Excretion of the N-2-glucuronide conjugate of 2-hydroxyamino-MeIQx in urine SO CANCER RESEARCH LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; BORNE CARCINOGEN 2-AMINO-3,8-DIMETHYLIMIDAZO<4,5-F>QUINOXALINE; RAT-LIVER MICROSOMES; CYTOCHROME P4501A2; COOKED FOODS; FRIED MEAT; ACTIVATION; CANCER; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; ACETYLTRANSFERASE AB 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a major heterocyclic aromatic amine (HAA) formed in cooked meats, is metabolically transformed to mutagenic/carcinogenic Intermediates, Cytochrome P4501A2 (CYP1A2)-mediated N-hydroxylation followed by phase II O-esterification by N-acetyltransferase (NAT2) are generally regarded as activation processes in which MeIQx and other HAAs are converted to genotoxic species, In this study, we determined the relationship between the activities of these two enzymes and the urinary excretion level of the N-2-glucuronide conjugate of 2-hydroxyamino-MeIQx-N-2-(beta-1-glucosiduronyl)-2-hydroxyamino-3,8- dimethylimidazo[4,5-f]quinoxaline (N-OH-MeIQx-N-2-glucuronide)-among healthy subjects fed a uniform diet containing high-temperature cooked meat, The individuals (n = 66) in the study ate meat containing known amounts of MeIQx, and urine was collected from 0 to 12 h after the meal. After addition of the deuterium-labeled internal standard to urine, N-OH-MeIQx-N-2-glucuronide was isolated using solid-phase extraction and immunoaffinity separation, The isolated conjugate was converted to the deaminated product 2-hydroxy-3,8 dimethylimidazo[4,5-f]quinoxaline (2-OH-MeIQx) by heating with acetic acid, 2-OH-MeIQx and its deuterated analogue were derivatized to form the corresponding 3,5-bis(trifluoromethyl)benzyl ether derivatives and analyzed by capillary gas chromatography-negative ion chemical ionization mass spectrometry using selected ion monitoring procedures, The subjects in the study excreted an average of 9.4 +/- 3.0% (+/-SD) of an ingested dose of MeIQx as N-OH-MeIQx-N-2-glucuronide in urine; the range varied from 22 to 17.1%. A significant correlation was found between the level of N-OH-MeIQx-N-2-glucuronide in urine and the amount of MeIQx ingested (r(s) = 0.44; P = 0.0002), The excretion level of N-OH-MeIQx-N-2-glucuronide in urine was not associated with the enzyme activities of NAT2 or CYP1A2. This is expected with the latter enzyme because the metabolism of MeIQx is first order and very rapid at the amounts ingested, The amount of N-OH-MeIQx-N-2-glucuronide in urine was not correlated with the age or sex of the individuals, Our results indicate that biotransformation of MeIQx via CYP1A2 oxidation to form the N-hydroxylamine followed by N-2-glucuronidation Is a general pathway of MeIQx metabolism in humans; the variability in the excreted levels of N-OH-MeIQx-N-2-glucuronide is probably due to interindividual differences in UDP-glucuronosyltransferase activity and/or excretion pathways. C1 MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne, Switzerland. NCI, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Stillwell, WG (reprint author), MIT, Div Bioengn & Environm Hlth, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NIEHS NIH HHS [ES05622] NR 42 TC 33 Z9 34 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1999 VL 59 IS 20 BP 5154 EP 5159 PG 6 WC Oncology SC Oncology GA 248GU UT WOS:000083267400020 PM 10537291 ER PT J AU Wildner, O Blaese, RM Candotti, F AF Wildner, O Blaese, RM Candotti, F TI Enzyme prodrug gene therapy: Synergistic use of the herpes simplex virus-cellular thymidine kinase/ganciclovir system and thymidylate synthase inhibitors for the treatment of colon cancer SO CANCER RESEARCH LA English DT Article ID DOUBLE SUICIDE GENE; IN-VIVO; CYTOSINE DEAMINASE; KINASE GENE; NUCLEOSIDE ANALOGS; BRAIN-TUMORS; CELLS; GANCICLOVIR; ACYCLOVIR; MECHANISM AB The goal of this study was to improve the therapeutic index of the herpes simplex virus-thymidine kinase/ganciclovir (HSV-tk/GCV) system by the addition of thymidylate synthase (TS) inhibitors. For this, we assessed the potential of GCV to synergistically interact with 5-fluorouracil (5-FU), ZD1694 (Tomudex), and (E)-5-(2-bromovinyl)-2'-deoxyuridine in HSV-tk-expressing murine MC38 STK and human HT-29 STK colon carcinoma cell Lines. Synergistic cell killing was observed in a clonogenic assay over most of the cytotoxic dose range by the median-effect principle of Chou and Talalay (T.C, Chou and P, Talalay, Adv, Enzyme Regul,, 22: 27-55, 1984), In a s.c, HT-29 STK xenograft tumor model, we demonstrated that the combination of GCV and 5-FU resulted in statistically significant enhanced animal survival over single-agent treatment. Furthermore, we showed that the combination of GCV and ZD1694 in association with the HSV-tk/GCV system was at least as effective as GCV/5-FU in vitro and in vivo. The mechanism for the observed synergy is most likely attributable to the increased GCV phosphorylation in the presence of the tested TS inhibitors. Our data suggest that the HSV-tk/GCV metabolic suicide gene transfer system could serve as an adjuvant of the presently used TS inhibitors, thus potentially improving the efficacy of present cancer gene therapy approaches. C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Wildner, O (reprint author), Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. NR 49 TC 34 Z9 36 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1999 VL 59 IS 20 BP 5233 EP 5238 PG 6 WC Oncology SC Oncology GA 248GU UT WOS:000083267400031 PM 10537302 ER PT J AU Birrer, MJ Hendricks, D Farley, J Sundborg, MJ Bonome, T Walts, MJ Geradts, J AF Birrer, MJ Hendricks, D Farley, J Sundborg, MJ Bonome, T Walts, MJ Geradts, J TI Abnormal Fhit expression in malignant and premalignant lesions of the cervix SO CANCER RESEARCH LA English DT Article ID CANCER CELL-LINES; PROTEIN EXPRESSION; TUMOR-CELLS; LUNG-CANCER; GENE; CARCINOMA; CHROMOSOME-3P; 3P14.2; HEAD; 3P AB Genetic analysis of cervical cancer has demonstrated frequent allelic loss in the 3p chromosomal region. The newly described gene FHIT is located at chromosome region 3p14.2, and its expression has been demonstrated previously by reverse transcription-PCR to be abnormal in a majority of cervical cancer cell lines, In this study, 98 different lesions of the cervix were examined for Fhit expression by immunohistochemical staining Whereas normal cervical epithelium demonstrated diffuse, moderate to intense cytoplasmic staining, many pathological lesions of the cervix displayed reduced or absent Fhit expression. Sixty-one percent of squamous carcinomas and 40% of adenocarcinomas of the cervix had abnormal Fhit expression, Sixty-five preneoplastic lesions of the cervix were examined, Eleven of 33 high-grade squamous intraepithelial lesions and 1 of 12 low-grade squamous intraepithelial lesions had abnormal Fhit expression, In summary, Fhit expression is frequently abnormal in both glandular and squamous cervical cancers, with a higher frequency of Fhit alterations observed in squamous lesions, In addition, abnormal Fhit expression can he detected in some preneoplastic lesions of the ectocervix, Alterations in Fhit expression may be an important marker of early progression in the development of cancers of the cervix. C1 NCI, Med Branch, Div Clin Sci, NIH, Rockville, MD 20850 USA. RP Birrer, MJ (reprint author), Key W Res Ctr, Bldg C,Suite 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. NR 26 TC 51 Z9 65 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 1999 VL 59 IS 20 BP 5270 EP 5274 PG 5 WC Oncology SC Oncology GA 248GU UT WOS:000083267400037 PM 10537308 ER PT J AU Zhang, JA Kovac, P AF Zhang, JA Kovac, P TI Studies on vaccines against cholera. Synthesis of neoglycoconjugates from the hexasaccharide determinant of Vibrio cholerae O : 1, serotype Ogawa, by single-point attachment or by attachment of the hapten in the form of clusters SO CARBOHYDRATE RESEARCH LA English DT Article DE glycoconjugate; oligosaccharide; glycocluster; subcarrier; synthetic vaccine ID BRUCELLA-A ANTIGEN; O-POLYSACCHARIDE; C-13-NMR SPECTRA; COUPLING REAGENT; BLOCK SYNTHESIS; PROTEINS; GLYCOSIDES; LINKING; ACID; PENTASACCHARIDE AB The terminal hexasaccharide of the O-antigen of Vibrio cholerae O:1, serotype Ogawa, has been synthesized in the form of a glycoside whose aglycon (linker) allows conjugation to carrier proteins by reductive amination. The conjugate obtained from direct, single-point attachment of the linker-equipped hapten to chicken serum albumin (CSA) contained seven hapten residues/CSA. A neoglycoconjugate containing the carbohydrate antigen in the form of clusters was obtained using, as a hapten subcarrier, an oligopeptide containing 16 amino groups. It was treated with a limited amount of hapten, to give a hapten-carrying subcarrier (HCS). Subsequent conjugation of HCS to CSA, using squaric acid diethyl ester as a conjugation reagent, gave a cross-linked, glycocluster conjugate containing 51% (w/w) of the carbohydrate. Published by Elsevier Science Ltd. C1 NIDDK, NIH, Med Chem Lab, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, NIH, Med Chem Lab, 8 Ctr Dr, Bethesda, MD 20892 USA. NR 38 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD OCT 15 PY 1999 VL 321 IS 3-4 BP 157 EP 167 DI 10.1016/S0008-6215(99)00185-8 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 263BM UT WOS:000084102800002 PM 10614066 ER PT J AU Cremona, O Di Paolo, G Wenk, MR Luthi, A Kim, WT Takei, K Daniell, L Nemoto, Y Shears, SB Flavell, RA McCormick, DA De Camilli, P AF Cremona, O Di Paolo, G Wenk, MR Luthi, A Kim, WT Takei, K Daniell, L Nemoto, Y Shears, SB Flavell, RA McCormick, DA De Camilli, P TI Essential role of phosphoinositide metabolism in synaptic vesicle recycling SO CELL LA English DT Article ID NERVE-TERMINALS; INOSITOL PHOSPHOLIPIDS; NONUNIFORM PROBABILITY; MEDIATED ENDOCYTOSIS; TRANSFER PROTEIN; YEAST GOLGI; BINDING; MEMBRANE; DYNAMIN; SYNAPTOJANIN AB Growing evidence suggests that phosphoinositides play an important role in membrane traffic. A polyphosphoinositide phosphatase, synaptojanin 1, was identified as a major presynaptic protein associated with endocytic coated intermediates. We report here that synaptojanin 1-deficient mice exhibit neurological defects and die shortly after birth. In neurons of mutant animals, PI(4,5)beta(2) levels are increased, and clathrin-coated vesicles accumulate in the cytomatrix-rich area that surrounds the synaptic vesicle cluster in nerve endings. In cell-free assays, reduced phosphoinositide phosphatase activity correlated with increased association of clathrin coats with liposomes. Intracellular recording in hippocampal slices revealed enhanced synaptic depression during prolonged high-frequency stimulation followed by delayed recovery. These results provide genetic evidence far a crucial role of phosphoinositide metabolism in synaptic vesicle recycling. C1 Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Neurobiol Sect, New Haven, CT 06510 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. Univ Piemonte Orientale A Avogadro, Dipartimento Sci Med, I-28100 Novara, Italy. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP De Camilli, P (reprint author), Yale Univ, Sch Med, Howard Hughes Med Inst, 333 Cedar St, New Haven, CT 06510 USA. RI Kobelt, Liza/F-5926-2011; Wenk, Markus/D-1441-2014; McCormick, David/J-2649-2015 OI McCormick, David/0000-0002-9803-8335 FU NINDS NIH HHS [NS26143, NS36251, NS46128]; Telethon [D.061, D.111] NR 59 TC 486 Z9 501 U1 3 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 15 PY 1999 VL 99 IS 2 BP 179 EP 188 DI 10.1016/S0092-8674(00)81649-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 246JB UT WOS:000083159700008 PM 10535736 ER PT J AU Folsch, H Ohno, H Bonifacino, JS Mellman, I AF Folsch, H Ohno, H Bonifacino, JS Mellman, I TI A novel clathrin adaptor complex mediates basolateral targeting in polarized epithelial cells SO CELL LA English DT Article ID POLYMERIC IMMUNOGLOBULIN RECEPTOR; DARBY CANINE KIDNEY; MDCK CELLS; SORTING SIGNALS; CYTOPLASMIC DOMAIN; MEMBRANE-PROTEINS; PLASMA-MEMBRANE; STRUCTURAL REQUIREMENTS; GOLGI-COMPLEX; FC-RECEPTORS AB Although polarized epithelial cells are well known to maintain distinct apical and basolateral plasma membrane domains, the mechanisms responsible for targeting membrane proteins to the apical or basolateral surfaces have remained elusive. We have identified a novel form of the AP-1 clathrin adaptor complex that contains as one of its subunits mu 1B, an epithelial cell-specific homolog of the ubiquitously expressed mu 1A. LLC-PK1 kidney epithelial cells do not express mu 1B and missort many basolateral proteins to the apical surface. Stable expression of mu 1B selectively restored basolateral targeting, improved the overall organization of LLC-PK1 monolayers, and had no effect on apical targeting. We conclude that basolateral sorting is mediated by an epithelial cell-specific version of the AP-1 complex containing mu 1B. C1 Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Ludwig Inst Canc Res, New Haven, CT 06520 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Canc Res Inst, Div Mol Membrane Biol, Kanazawa, Ishikawa 9200934, Japan. RP Mellman, I (reprint author), Yale Univ, Sch Med, Dept Cell Biol, 333 Cedar St, New Haven, CT 06520 USA. RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Folsch, Heike/0000-0003-0897-0311; Bonifacino, Juan S./0000-0002-5673-6370 FU NIGMS NIH HHS [GM-29765] NR 46 TC 382 Z9 384 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 15 PY 1999 VL 99 IS 2 BP 189 EP 198 DI 10.1016/S0092-8674(00)81650-5 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 246JB UT WOS:000083159700009 PM 10535737 ER PT J AU Poulin, N Boiko, I MacAulay, C Boone, C Nishioka, K Hittelman, W Mitchell, MF AF Poulin, N Boiko, I MacAulay, C Boone, C Nishioka, K Hittelman, W Mitchell, MF TI Nuclear morphometry as an intermediate endpoint biomarker in chemoprevention of cervical carcinoma using alpha-difluoromethylornithine SO CYTOMETRY LA English DT Article ID ORNITHINE DECARBOXYLASE OVEREXPRESSION; TRANS-RETINOIC ACID; PHASE-I TRIAL; INTRAEPITHELIAL NEOPLASIA; HUMAN PAPILLOMAVIRUS; GENITAL-TRACT; REPRODUCIBILITY; DYSPLASIA; CELLS; MOUSE AB The use of nuclear morphometry as an intermediate endpoint biomarker is described in a Phase I, dose-seeking trial of chemoprevention of cervical cancer, using the agent alpha-difluoromethylornithine (DFMO). Thirty patients with grade III cervical intraepithelial neoplasia (CIN III) were enrolled, and these received daily doses of DFMO at 0.06-1.0 mg/m(2) for a period of 1 month. Fifteen patients were observed to have a complete or partial regressive response to the agent, as assessed by histopathology. No significant differences in cell feature measurements were found between responders and nonresponders in specimens obtained before treatment, indicating that it may be difficult to predict response on the basis of these measurements. In specimens collected after treatment, large differences in morphometric features were observed between responders and nonresponders, indicating a differential effect of DFMO. Significantly modulated features were considered in terms of their correlations with CIN grade, which was determined from an independent set of measurements from archival tissue. Differences between features were consistent with a deletion of cells with high grade nuclei in the responders, and with the persistence of a more heterogeneous population of high grade cells in the nonresponders. Based on an independent set of measurements from archival material, a morphometric index of progression was derived, yielding a quantitative measure of the degree of nuclear atypia in these lesions. When applied to this trial, the morphometric index was seen to be specifically and consistently decreased in responsive lesions, and unchanged in nonresponders. The study indicates that morphometric features fulfill the requirements for an intermediate endpoint biomarker of cervical, cancer chemoprevention. (C) 1999 Wiley-Liss, Inc. C1 British Columbia Canc Agcy, British Columbia Res Ctr, Vancouver, BC V5Z 1L3, Canada. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. Natl Canc Inst, Div Canc Prevent, Chemoprevent Branch, Houston, TX USA. RP Poulin, N (reprint author), British Columbia Canc Agcy, British Columbia Res Ctr, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. FU NCI NIH HHS [N01CN25433B, N01CN25433A] NR 32 TC 14 Z9 15 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 0196-4763 J9 CYTOMETRY JI Cytometry PD OCT 15 PY 1999 VL 38 IS 5 BP 214 EP 223 DI 10.1002/(SICI)1097-0320(19991015)38:5<214::AID-CYTO3>3.0.CO;2-6 PG 10 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249UU UT WOS:000083352300003 PM 10516607 ER PT J AU Self, T Sobe, T Copeland, NG Jenkins, NA Avraham, KB Steel, KP AF Self, T Sobe, T Copeland, NG Jenkins, NA Avraham, KB Steel, KP TI Role of myosin VI in the differentiation of cochlear hair cells SO DEVELOPMENTAL BIOLOGY LA English DT Article DE myosin VI; genetic deafness; Snell's waltzer; mouse mutant; cochlear hair cells; microvilli; unconventional myosin ID SCANNING-ELECTRON-MICROSCOPY; BRUSH-BORDER CYTOSKELETON; UNCONVENTIONAL MYOSIN; INNER-EAR; STRUCTURAL INTEGRITY; GUINEA-PIG; DEAFNESS; GENE; MEMBRANE; TRANSPORT AB The mouse mutant Snell's waltzer (sv) has an intragenic deletion of the Myo6 gene, which encodes the unconventional myosin molecule myosin VI (K. B. Avraham et al., 1995, Net. Genet. 11, 369-375). Snell's waltzer mutants exhibit behavioural abnormalities suggestive of an inner ear defect, including lack of responsiveness to sound, hyperactivity, head tossing, and circling. We have investigated the effects of a lack of myosin VI on the development of the sensory hair cells of the cochlea in these mutants. In normal mice, the hair cells sprout microvilli on their upper surface, and some of these grow to form a crescent or V-shaped array of modified microvilli, the stereocilia. In the mutants, early stages of stereocilia development appear to proceed normally because at birth many stereocilia bundles have a normal appearance, but in places there are signs of disorganisation of the bundles. Over the next few days, the stereocilia become progressively more disorganised and fuse together. Practically all hair cells show fused stereocilia by 3 days after birth, and there is extensive stereocilia fusion by 7 days. By 20 days, giant stereocilia are observed on top of the hair cells. At 1 and 3 days after birth, hair cells of mutants and controls take up the membrane dye FM1-43, suggesting that endocytosis occurs in mutant hair cells. One possible model for the fusion is that myosin VI may be involved in anchoring the apical hair cell membrane to the underlying actin-rich cuticular plate, and in the absence of normal myosin VI this apical membrane will tend to pull up between stereocilia, leading to fusion. (C) 1999 Academic Press. C1 MRC, Inst Hearing Res, Nottingham NG7 2RD, England. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Steel, KP (reprint author), MRC, Inst Hearing Res, Univ Pk, Nottingham NG7 2RD, England. EM karen@ihr.mrc.ac.uk NR 47 TC 158 Z9 159 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 OCT 15 PY 1999 VL 214 IS 2 BP 331 EP 341 DI 10.1006/dbio.1999.9424 PG 11 WC Developmental Biology SC Developmental Biology GA 250KN UT WOS:000083387700007 PM 10525338 ER PT J AU Li, Q Imhof, A Collingwood, TN Urnov, FD Wolffe, AP AF Li, Q Imhof, A Collingwood, TN Urnov, FD Wolffe, AP TI p300 stimulates transcription instigated by ligand-bound thyroid hormone receptor at a step subsequent to chromatin disruption SO EMBO JOURNAL LA English DT Review DE chromatin disruption; E1A; non-histone acetylation; nuclear receptors; p300 ID RNA-POLYMERASE-II; HISTONE ACETYLTRANSFERASE ACTIVITY; PROMOTER IN-VIVO; ACIDIC ACTIVATION DOMAINS; NUCLEOSOME CORE PARTICLE; YEAST SWI/SNF COMPLEX; LINKING NUMBER CHANGE; TATA-BINDING PROTEIN; BETA-GLOBIN GENE; NUCLEAR RECEPTOR AB We investigate the role of the transcriptional coactivator p300 in gene activation by thyroid hormone receptor (TR) on addition of ligand. The ligand-bound TR targets chromatin disruption independently of gene activation, Exogenous p300 facilitates transcription from a disrupted chromatin template, but does not itself disrupt chromatin in the presence or absence of ligand-bound receptor, Nevertheless, the acetyltransferase activity of p300 is required to facilitate transcription from a disrupted chromatin template, Expression of E1A prevents aspects of chromatin remodeling and transcriptional activation dependent on TR and p300. E1A selectively inhibits the acetylation of non-histone substrates, EIA does not prevent the assembly of a DNase I-hypersensitive site induced by TR, but does inhibit topological alterations and the loss of canonical nucleosome arrays dependent on the addition of ligand. Mutants of EIA incompetent far interaction with p300 partially inhibit chromatin disruption but still allow nuclear receptors to activate transcription. We conclude that p300 has no essential role in chromatin disruption, but makes use of acetyltransferase activity to stimulate transcription at a subsequent step. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. OI Li, Qiao/0000-0002-5941-1985 NR 183 TC 66 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 15 PY 1999 VL 18 IS 20 BP 5634 EP 5652 DI 10.1093/emboj/18.20.5634 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 249KG UT WOS:000083331800018 PM 10523307 ER PT J AU Ponting, CP Pallen, MJ AF Ponting, CP Pallen, MJ TI beta-Propeller repeats and a PDZ domain in the tricorn protease: predicted self-compartmentalisation and C-terminal polypeptide-binding strategies of substrate selection SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE proteasome; tail-specific protease; PDZ domain; self-compartmentalisation; intracellular proteolysis; giant protease ID CRYSTAL-STRUCTURE; SEQUENCE ALIGNMENT; 20S PROTEASOME; RESOLUTION; PROTEINS; DEGRADATION; ACIDOPHILUM; COMPLEX; SYSTEM; PLANTS AB Prokaryotic proteases demonstrate a variety of substrate-selection strategies that prevent uncontrolled protein degradation. Proteasomes and ClpXP-like proteases form oligomeric structures that exclude large substrates from central solvated chambers containing their active sites. Monomeric prolyl oligopeptidases have been shown to contain beta-propeller structures that similarly reduce access to their catalytic residues. By contrast, Tsp-like enzymes contain PDZ domains that are thought to specifically target C-terminal polypeptides. We have investigated the sequence of Thermoplasma acidophilum? I tricorn protease using recently-developed database search methods. The tricorn protease is known to associate into a 20 hexamer capsid enclosing an extremely large cavity that is 37 nm in diameter. II is unknown, however, how this enzyme selects its small oligopeptide substrates. Our results demonstrate the presence in tricorn protease of a PDZ domain and two predicted six-bladed beta-propeller domains. We suggest that the PDZ domain is involved in targeting non-polar C-terminal peptides, similar to those generated by the T. acidophilum proteasome, whereas the beta-propeller domains serve to exclude large substrates from the tricorn protease active site in a similar manner to that previously indicated for prolyl oligopeptidase. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. St Bartholomews & Royal London Sch Med & Dent, Dept Med Microbiol, Mol Pathogenesis Res Grp, London EC1A 7BE, England. RP Ponting, CP (reprint author), Univ Oxford, Dept Human Anat & Genet, MRC, Funct Genet Unit, S Pk Rd, Oxford OX1 3QX, England. EM ponting@molbiol.ox.ac.uk RI Pallen, Mark/E-7619-2011; OI Pallen, Mark/0000-0003-1807-3657 NR 33 TC 15 Z9 16 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD OCT 15 PY 1999 VL 179 IS 2 BP 447 EP 451 DI 10.1016/S0378-1097(99)00418-8 PG 5 WC Microbiology SC Microbiology GA 245QH UT WOS:000083119300035 PM 10518749 ER PT J AU Deb-Rinker, P Klempan, TA O'Reilly, RL Torrey, EF Singh, SM AF Deb-Rinker, P Klempan, TA O'Reilly, RL Torrey, EF Singh, SM TI Molecular characterization of a MSRV-like sequence identified by RDA from monozygotic twin pairs discordant for schizophrenia SO GENOMICS LA English DT Article ID ENDOGENOUS RETROVIRUSES; CYTOSINE METHYLATION; MULTIPLE-SCLEROSIS; BIPOLAR DISORDER; ELEMENTS; DISEASE; CLONING; GENOMES; VIRUSES; GENE AB Retroviral-related amplicons were used in modified RDA to identify four sequences from affected members of three pairs of monozygotic twins discordant for schizophrenia. One sequence (schizophrenia associated retrovirus, SZRV-1, GenBank Accession No. AF135487) is characterized here. It is similar to two known sequences of retroviral origin: multiple sclerosis-associated retrovirus, MSRV (GenBank Accession No. AF009668), and ERV-9 (GenBank Accession No. S77575). It is present in multiple copies in the human genome and has been localized to six different chromosomal sites. A zooblot shows that this multicopy sequence is predominant in the primate lineage and present in rhesus monkeys and humans. SZRV-1 is expressed as a 9-kb RNA band in the placenta. This could offer support to the hypothesis that retroviral sequences transposing during fetal growth may alter neurodevelopmental genes and cause diseases, although its direct involvement in the causation of schizophrenia remains to be established. (C) 1999 Academic Press. C1 Univ Western Ontario, Dept Zool, Mol Genet Unit, London, ON N6A 5B7, Canada. Univ Western Ontario, Div Med Genet, London, ON N6A 5B7, Canada. Univ Western Ontario, Dept Psychiat, London, ON N6A 5B7, Canada. NIMH, Stanley Fdn Res Programs, Neurosci Ctr St Elizabeths, Washington, DC 20032 USA. London Hlth Sci Ctr, Child Hlth Res Inst, Mol Med Genet Program, London, ON N6A 2V5, Canada. RP Singh, SM (reprint author), Univ Western Ontario, Dept Zool, Mol Genet Unit, London, ON N6A 5B7, Canada. NR 40 TC 44 Z9 44 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 OCT 15 PY 1999 VL 61 IS 2 BP 133 EP 144 DI 10.1006/geno.1999.5946 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 248JB UT WOS:000083270400003 PM 10534399 ER PT J AU Romanienko, PJ Camerini-Otero, RD AF Romanienko, PJ Camerini-Otero, RD TI Cloning, characterization, and localization of mouse and human SPO11 SO GENOMICS LA English DT Article ID DOUBLE-STRAND BREAKS; HOMOLOGOUS CHROMOSOME SYNAPSIS; SYNAPTONEMAL COMPLEX-FORMATION; MEIOTIC GENE CONVERSION; SACCHAROMYCES-CEREVISIAE; DNA-REPAIR; DROSOPHILA-MELANOGASTER; ESCHERICHIA-COLI; INITIATION SITE; RECOMBINATION AB Spo11 is a meiosis-specific protein in yeast that has been found covalently bound to DNA double-strand breaks (DSBs) during the early stages of meiosis. These DSBs initiate homologous recombination, which is required for proper segregation of chromosomes and the generation of genetic diversity during meiosis. Here we report the cloning, characterization, tissue expression, and chromosomal localization of both mouse and human homologues of Spo11. The putative mouse and human proteins are 82% identical and share approximately 25% identity with other family members. Northern blot analysis revealed testis-specific expression for both genes, but RT-PCR results showed ubiquitous expression of at least a portion of Spo11 in mouse. Human SPO11 was also detected in several somatic tissues. Mouse Spo11 was localized to chromosome 2H4, and human SPO11 was localized to chromosome 20q13.2-q13.3, a region amplified in some breast and ovarian tumors. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 10,Room 9D20, Bethesda, MD 20892 USA. NR 41 TC 102 Z9 109 U1 0 U2 7 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 OCT 15 PY 1999 VL 61 IS 2 BP 156 EP 169 DI 10.1006/geno.1999.5955 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 248JB UT WOS:000083270400005 PM 10534401 ER PT J AU Keeney, S Baudat, F Angeles, M Zhou, ZH Copeland, NG Jenkins, NA Manova, K Jasin, M AF Keeney, S Baudat, F Angeles, M Zhou, ZH Copeland, NG Jenkins, NA Manova, K Jasin, M TI A mouse homolog of the Saccharomyces cerevisiae meiotic recombination DNA transesterase Spo11p SO GENOMICS LA English DT Article ID DOUBLE-STRAND BREAKS; SYNAPTONEMAL COMPLEX-FORMATION; CHROMOSOME SYNAPSIS; INITIATION SITE; YEAST MEIOSIS; DMC1; MECHANISM; PROPHASE; GENE; TOPOISOMERASES AB The Saccharomyces cerevisiae Spell protein is thought to catalyze formation of the DNA double-strand breaks that initiate meiotic recombination. We have cloned cDNA and genomic DNA for a mouse gene encoding a protein with significant sequence similarity to conserved domains found in proteins of the Spo11p family. This putative mouse Spell gene maps to the distal region of chromosome 2 (homologous to human chromosome 20q13.2-q13.3) and comprises at least 12 exons, spanning approximately 15-18 kb. Strong expression of the Spell message is seen in juvenile and adult testis by RNA in situ hybridization, RT-PCR, and Northern blot, with much weaker expression in thymus and brain. In situ hybridization detects expression in oocytes of embryonic ovary, but not of adult ovary. RT-PCR and in situ hybridization analyses of a time course of juvenile testis development indicate that Spell expression begins in early meiotic Prophase I, prior to the pachytene stage, with increasing accumulation of mRNA through the pachytene stage. Taken together, these results strongly suggest that this gene encodes the functional homolog of yeast Spo11p, which in turn suggests that the mechanism of meiotic recombination initiation is conserved between yeast and mammals. (C) 1999 Academic Press. C1 Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Keeney, S (reprint author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, 1275 York Ave, New York, NY 10021 USA. OI Keeney, Scott/0000-0002-1283-6417 FU NHGRI NIH HHS [HG01740]; NIGMS NIH HHS [GM58673-01] NR 50 TC 79 Z9 81 U1 1 U2 6 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 OCT 15 PY 1999 VL 61 IS 2 BP 170 EP 182 DI 10.1006/geno.1999.5956 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 248JB UT WOS:000083270400006 PM 10534402 ER PT J AU Wang, XT Gorospe, M Holbrook, NJ AF Wang, XT Gorospe, M Holbrook, NJ TI gadd45 is not required for activation of c-Jun N-terminal kinase or p38 during acute stress SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; RESPONSES; PATHWAYS; CASCADES AB Cells respond to environmental stress with activation of c-Jun N-terminal kinase (JNK) and p38. Recent studies have implicated Gadd45 and two related proteins, MyD118/Gadd45 beta and CR6/Gadd45 gamma, as initiators of JNK/p38 signaling via their interaction with an upstream kinase MTK1. It was proposed that stress-induced expression of the Gadd45-related proteins leads to MTK1 activation and subsequent JNK/p38 activation. Using embryo fibroblasts from gadd45-null mice, we have addressed the requirement for Gadd45 in mediating JNK/p38 activation during acute stress. Comparison of JNH/p38 activities in response to methyl methanesulfonate, hydrogen peroxide, WC irradiation, sorbitol, and anisomycin treatment of gadd45(+/+) and gadd45(-/-) fibroblasts revealed no deficiency in JNK/p38 activation in gadd45(-/-) fibroblasts. In addition, in wild type cells, JNK and p38 activation significantly preceded gadd45 induction with all stresses. Examination of myd118/ gadd45 beta and cr6/gadd45 gamma expression in gadd45(+/+) and gadd45(-/-) fibroblasts revealed similar induction patterns in the two cell types, which, like gadd45 expression, was delayed relative to JNK/p38 activation. We conclude that gadd45 expression is not required for activation of JNK/p38 by environmental stresses, nor are stress-induced increases in myd118/gadd45 beta and cr6/ gadd45 gamma expression necessary for kinase activation in response to such insults. C1 NIA, Cell Stress & Aging Sect, Biol Chem Lab, NIH, Baltimore, MD 21224 USA. RP Holbrook, NJ (reprint author), NIA, Cell Stress & Aging Sect, Biol Chem Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 22 TC 45 Z9 46 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1999 VL 274 IS 42 BP 29599 EP 29602 DI 10.1074/jbc.274.42.29599 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246QQ UT WOS:000083176400005 PM 10514426 ER PT J AU Witteveen, CFB Giovanelli, J Kaufman, S AF Witteveen, CFB Giovanelli, J Kaufman, S TI Reactivity of tetrahydrobiopterin bound to nitric-oxide synthase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHENYLALANINE-HYDROXYLASE; L-ARGININE; REDUCTIVE ACTIVATION; FLAVIN SEMIQUINONE; HYDROGEN-PEROXIDE; NO SYNTHASE; HEME IRON; BRAIN; GENERATION; SUPEROXIDE AB Levels of tetrahydrobiopterin (BH4) bound to nitric-oxide synthase (NOS) were examined during multiple turnovers of the enzyme in the presence of an NADPH-regenerating system. Our findings show that NOS-bound BH4 does not remain in a static state but undergoes redox reactions. Under these experimental conditions, the redox state of BH4 was determined by the balance between calcium/calmodulin (Ca2+/CaM)dependent oxidation of BH4 mediated by the uncoupled formation of superoxide/hydrogen peroxide on the one hand and by reductive regeneration of BH4 on the other hand. BH4 oxidation was appreciably increased in the presence of arginine. Levels of NOS-bound BH4 were also examined under single turnover conditions in the absence of an NADPH-regenerating system and in the presence of added superoxide dismutase and catalase to suppress the accumulation of superoxide and hydrogen peroxide. BH4 oxidation was again dependent on Ca2+/CaM. The insensitivity to superoxide dismutase and catalase suggested that the single turnover oxidation of BH4 did not proceed through superoxide/peroxide, although the involvement of these oxidants could not be definitively excluded. The amount of BH4 oxidized was highest in the presence of arginine, and this oxidation significantly exceeded that in the presence of N-G-hydroxy-L-arginine, The findings that single turnover oxidation of BH4 is stimulated by arginine in the presence of Ca2+/CaM and that BH4 is regenerated are consistent with a role for the pterin as an electron donor in product formation; this role remains to be defined. C1 NIMH, Neurochem Lab, Bethesda, MD 20892 USA. RP Giovanelli, J (reprint author), NIMH, Neurochem Lab, Bldg 36,Rm 3D30,36 Convent Dr,MSC 4096, Bethesda, MD 20892 USA. NR 68 TC 27 Z9 28 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1999 VL 274 IS 42 BP 29755 EP 29762 DI 10.1074/jbc.274.42.29755 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246QQ UT WOS:000083176400030 PM 10514451 ER PT J AU Danilkovitch, A Miller, M Leonard, EJ AF Danilkovitch, A Miller, M Leonard, EJ TI Interaction of macrophage-stimulating protein with its receptor - Residues critical for beta chain binding and evidence for independent alpha chain binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE; MET PROTOONCOGENE; GENE-PRODUCT; EXPRESSION; DOMAIN; FAMILY; MSP; IDENTIFICATION; SPECIFICITY AB Macrophage-stimulating protein (MSP) and hepatocyte growth factor/scatter factor (HGF/SF) are plasminogen-related growth and motility factors that interact with cell-surface protein tyrosine kinase receptors. Each one is a heterodimeric protein comprising a disulfide-linked alpha chain and a serine protease-like beta chain. Despite structural similarities between MSP and HGF, the primary receptor binding site is located on the alpha chain of HGF/SF but on the beta chain of MSP. To obtain insight into the structural basis for MSP beta chain binding, beta chain structure was modeled from coordinates of an existing model of the HGF beta chain. The model revealed that the region corresponding to the S1 specificity pocket in trypsin is filled by the Asn(682)/Glu(648) interacting pair, leaving a shallow cavity far possible beta chain interaction with the receptor. Mutants in this region were created, and their binding characteristics were determined. A double mutation of Asn(682)/Glu(648) caused diminished binding of the P chain to the MSP receptor, and a single mutation of neighboring Arg(683) completely abolished binding. Thus, this region of the molecule is critical for binding. We also found that at equimolar concentrations of free alpha and beta chains, LY chain binding to receptor was detectable, at levels considerably lower than beta chain binding. The EC(50) values determined by quantitative enzyme-linked immunosorbent assay are 0.25 and 16.9 nM for beta and alpha chain, respectively. The data suggest that MSP has two independent binding sites with high and low affinities located in beta and alpha chain, respectively, and that the two sites together mediate receptor dimerization and subsequent activation. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. RP Danilkovitch, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Bldg 560,Rm 12-46, Frederick, MD 21702 USA. EM danilkovitch@mail.ncifcrf.gov RI Miller, Maria/I-1636-2013 OI Miller, Maria/0000-0003-0252-5348 NR 36 TC 25 Z9 26 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 1999 VL 274 IS 42 BP 29937 EP 29943 DI 10.1074/jbc.274.42.29937 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246QQ UT WOS:000083176400055 PM 10514476 ER PT J AU Petrotchenko, EV Doerflein, ME Kakuta, Y Pedersen, LC Negishi, M AF Petrotchenko, EV Doerflein, ME Kakuta, Y Pedersen, LC Negishi, M TI Substrate gating confers steroid specificity to estrogen sulfotransferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SULFATASE ACTIVITY; MOLECULAR-BIOLOGY; CRYSTAL-STRUCTURE; SULFURYL TRANSFER; MECHANISM AB Estrogen sulfotransferase (EST) exhibits a high substrate specificity and catalytic efficiency toward estro; gens such as estradiol (E2) but insignificant ability to sulfate hydroxysteroids such as dehydroepiandrosterone (DHEA). To provide the structural basis for this estrogen specificity, we mutated amino acid residues that constitute the substrate-binding site of EST. Among these mutants, only Tyr-81 decreased E2 and increased DHEA sulfotransferase activities. Substitution for Tyr-81 by smaller hydrophobic residues increased K-m(E2) for E2 activity, whereas the K-cat(E2) remained relatively constant. The Y81L mutant exhibited the same DHEA activity as wild-type hydroxysteroid sulfotransferase, for which K-m(DHEA) remained relatively constant, and k(cat(DHEA)) was markedly increased. The side chain of Tyr-81 is directed at the A-ring of the E2 molecule in the substrate-binding pocket of EST, constituting a steric gate with Phe-142 sandwiching E2 from the opposite side. The present mutagenesis study indicates that the 3b-hydroxyl group of the DHEA molecule is excluded from the catalytic site of EST through steric hindrance of Tyr-81 with the C-19 methyl group of DHEA. Thus, this stricture-like gating caused by steric hindrance appears to be a structural principle for conferring estrogen specificity to EST. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 24 TC 40 Z9 41 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 OCT 15 PY 1999 VL 274 IS 42 BP 30019 EP 30022 DI 10.1074/jbc.274.42.30019 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246QQ UT WOS:000083176400065 PM 10514486 ER PT J AU Aman, MJ Migone, TS Sasaki, A Ascherman, DP Zhu, MH Soldaini, E Imada, K Miyajima, A Yoshimura, A Leonard, WJ AF Aman, MJ Migone, TS Sasaki, A Ascherman, DP Zhu, MH Soldaini, E Imada, K Miyajima, A Yoshimura, A Leonard, WJ TI CIS associates with the interleukin-2 receptor beta chain and inhibits interleukin-2-dependent signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED STAT INHIBITOR; IL-2 RECEPTOR; ALPHA-CHAIN; CYTOPLASMIC DOMAINS; MULTIPLE CYTOKINES; JAK-STAT5 PATHWAY; SH2 DOMAIN; GENE; PROTEIN; ACTIVATION AB CIS is a cytokine-induced SH2-containing protein that was originally cloned as an interleukin (IL)-3-inducible gene. CIS is known to associate with the IL-3 receptor beta chain and erythropoietin receptor and to inhibit signaling mediated by IL-3 and erythropoietin. We now demonstrate that CLS also interacts with the IL-2 receptor beta chain (IL-2R beta), This interaction requires the A region of IL-2R beta (residues 313-382), which also mediates the association of IL-2R beta with Lck and Jak3. Correspondingly, CIS inhibits functions associated with both of these kinases: Lck-mediated phosphorylation of IL-2R beta and IL-2-mediated activation of Stat5. Thus, we demonstrate that CIS can negatively control at least two independent IL-2 signaling pathways. Although a functional SH2 binding domain of CIS was not required for its interaction with IL-2R beta in vitro, its phosphotyrosine binding capability was essential for the inhibitory action of CIS. On this basis, we have generated a mutant form of CIS protein with an altered SH2 domain that acts as a dominant negative and should prove useful in further understanding CIS action. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan. Kurume Univ, Inst Life Sci, Kurume, Fukuoka 8390861, Japan. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. RI Yoshimura, Akihiko/K-5515-2013 NR 42 TC 65 Z9 66 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 OCT 15 PY 1999 VL 274 IS 42 BP 30266 EP 30272 DI 10.1074/jbc.274.42.30266 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 246QQ UT WOS:000083176400099 PM 10514520 ER PT J AU Huestis, MA Oyler, JM Cone, EJ Wstadik, AT Schoendorfer, D Joseph, RE AF Huestis, MA Oyler, JM Cone, EJ Wstadik, AT Schoendorfer, D Joseph, RE TI Sweat testing for cocaine, codeine and metabolites by gas chromatography - mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B LA English DT Review DE reviews; sweat; cocaine; codeine ID URINARY-EXCRETION; DRUG-USE; HAIR; SALIVA; PHARMACOKINETICS; PERSPIRATION; DISPOSITION; HUMANS; PATCH; BENZOYLECGONINE AB Sweat testing for drugs of abuse provides a convenient and considerably less invasive method for monitoring drug exposure than blood or urine. Numerous devices have been developed for collection of sweat specimens. The most common device in current use is the PharmChek(TM) Sweat Patch, which usually is worn by an individual for five to ten days. This device has been utilized in several field trials comparing sweat test results to conventional urinalysis and the results have been favorable. Two new Fast Patch devices have been developed and tested that allow rapid collection of sweat specimens. The Hand-held Fast Patch was applied to the palm of the hand and the Torso Fast Patch was applied to the abdomen or the sides of the trunk (flanks) of volunteer subjects participating in a research study. Both patches employed heat-induced sweat stimulation and a larger cellulose pad for increased drug collection. Sweat specimens were collected for 30 min at various times following administration of cocaine or codeine in controlled dosing studies. After patch removal, the cellulose pad was extracted with sodium acetate buffer, followed by solid-phase extraction. Extracts were derivatized and analyzed by gas chromatography mass spectrometry (GC-MS) simultaneously for cocaine, codeine and metabolites. Cocaine and codeine were the primary analytes detected in sweat. Peak cocaine and codeine concentrations ranged from 33 to 3579 ng/patch and 11 to 1123 ng/patch, respectively, across all doses for the Hand-held Patch compared to 22-1463 ng/patch and 12-360 ng/patch, respectively, for the Torso Fast Patch. Peak concentrations generally occurred 4.5-24 h after dosing. Both drugs could be detected for at least 48 h after dosing. Considerably smaller concentrations of metabolites of cocaine and codeine were also present in some patches. Generally, concentrations of cocaine and codeine were higher in sweat specimens collected with the Hand-held Fast Patch than for the Torso Fast Patch. Drug concentrations were also considerably higher than those reported for the PharmChek(TM) Sweat Patch. The predominance of cocaine and codeine in sweat over metabolites is consistent with earlier studies of cocaine and codeine secretion in sweat. Multiple mechanisms appear to be operative in determining the amount of drug and metabolite secreted in sweat including passive diffusion from blood into sweat glands and outward transdermal migration of the drug. Additional important factors are the physico-chemical properties of the drug analyte, specific characteristics of the sweat collection device, site of sweat collection and, in this study, the application of heat to increase the amount of drug secreted. Published by Elsevier Science B.V. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Sudormed Inc, Santa Ana, CA USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 550 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 52 TC 58 Z9 59 U1 3 U2 19 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 OCT 15 PY 1999 VL 733 IS 1-2 BP 247 EP 264 DI 10.1016/S0378-4347(99)00246-7 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 251XG UT WOS:000083471200014 PM 10572984 ER PT J AU Staples, JE Gasiewicz, TA Fiore, NC Lubahn, DB Korach, KS Silverstone, AE AF Staples, JE Gasiewicz, TA Fiore, NC Lubahn, DB Korach, KS Silverstone, AE TI Estrogen receptor alpha is necessary in thymic development and estradiol-induced thymic alterations SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEX-HORMONES; ER-BETA; TISSUE DISTRIBUTION; GONADAL-STEROIDS; IMMUNE-SYSTEM; T-CELLS; GENE; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; DISRUPTION; MOUSE AB Estrogens affect the development, maturation, and function of multiple organ systems, including the immune system, One of the main targets of estrogens in the immune system is the thymus, which undergoes atrophy and phenotypic alterations when exposed to elevated levels of estrogen, To determine how estrogens influence the thymus and affect T cell development, estrogen receptor alpha (ER alpha) knockout (ERKO) mice were examined. ERKO mice have significantly smaller thymi than their wild-type (WT) littermates. Construction of ER radiation bone marrow chimeras indicated that the smaller thymi were due to a lack of ERa in radiation-resistant tissues rather than hemopoietic elements. ERKO mice were also susceptible to estradiol-induced thymic atrophy, but the extent of their atrophy was less than what was seen in WT mice, The estradiol-treated ERKO mice failed, however, to manifest alterations in their thymic CD4/CD8 phenotypes compared with WT mice. Therefore, ER alpha is essential in nonhemopoietic cells to obtain a full-sized thymus, and ERalpha also mediates some of the response of the thymus to elevated estrogen levels. Finally, these results suggest that in addition to ER alpha, another receptor pathway is involved in estradiol-induced thymic atrophy. C1 SUNY Hlth Sci Ctr, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. Univ Rochester, Sch Med, Environm Hlth Sci Ctr, Dept Environm Med, Rochester, NY 14642 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. RP Silverstone, AE (reprint author), SUNY Hlth Sci Ctr, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NIEHS NIH HHS [ES01247, ES07216, ES04862] NR 41 TC 116 Z9 120 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 1999 VL 163 IS 8 BP 4168 EP 4174 PG 7 WC Immunology SC Immunology GA 243AK UT WOS:000082974800013 PM 10510352 ER PT J AU Ludviksson, BR Ehrhardt, RO Strober, W AF Ludviksson, BR Ehrhardt, RO Strober, W TI Role of IL-12 in intrathymic negative selection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; DOUBLE-POSITIVE THYMOCYTES; RECEPTOR TRANSGENIC MICE; CD4(+)CD8(+) THYMOCYTES; INDUCED APOPTOSIS; INTERFERON-GAMMA; CLONAL DELETION; TYROSINE PHOSPHORYLATION; CD4+CD8+ THYMOCYTES; IMMATURE THYMOCYTES AB Cytokines are central regulatory elements in peripheral lymphocyte differentiation, but their role in T cell ontogeny is poorly defined. In the present study, we evaluated the role of IL-12 in thymocyte selection more directly by determining its role in two models of in vive negative selection. In initial studies we demonstrated that abundant intrathymic IL-12 synthesis occurs during OVA peptide-induced negative selection of thymocytes in neonatal OVA-TCR transgenic mice, and such synthesis is associated with increased IL-12R beta 2-chain expression as well as STAT4 intracellular signaling. In further studies, we showed that this form of negative selection was occurring at the alpha beta TCR(low)CD4(low)CD8(low) stage and was prevented by the coadministration of anti-IL-12, In addition, the IL-12-dependent thymocyte depletion was occurring through an intrathymic apoptosis mechanism, also prevented by administration of anti-IL-12. Finally, ne showed that IL-12 p40(-/-) mice displayed aberrant negative selection of double positive CD4(+) CD8(+) thymocytes when injected with anti-CD3 mAb. These studies suggest that intact intrathymic IL-12 production is necessary for the negative selection of thymocytes occurring in relation to a high "self" Ag load, possible through its ability to induce the thymocyte maturation and cytokine production necessary for such selection. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Ludviksson, BR (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, 10 Ctr Dr,Bldg 10,R11N238, Bethesda, MD 20892 USA. OI Ludviksson, Bjorn/0000-0002-6445-148X NR 71 TC 20 Z9 21 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 OCT 15 PY 1999 VL 163 IS 8 BP 4349 EP 4359 PG 11 WC Immunology SC Immunology GA 243AK UT WOS:000082974800036 PM 10510375 ER PT J AU Kenney, RT Sacks, DL Sypek, JP Vilela, L Gam, AA Evans-Davis, K AF Kenney, RT Sacks, DL Sypek, JP Vilela, L Gam, AA Evans-Davis, K TI Protective immunity using recombinant human IL-12 and alum as adjuvants in a primate model of cutaneous leishmaniasis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AMERICAN TEGUMENTARY LEISHMANIASIS; MAJOR PLUS BCG; PROPHYLACTIC IMMUNIZATION; SUBCUTANEOUS IMMUNIZATION; NONHUMAN-PRIMATES; VERVET MONKEYS; MURINE MODEL; VACCINE; INFECTION; INTERLEUKIN-12 AB Protection from cutaneous leishmaniasis, a chronic ulcerating skin lesion affecting millions, has been achieved historically using live virulent preparations of the parasite. Killed or recombinant Ags that could be safer as vaccines generally require an adjuvant for induction of a strong Th1 response in murine models. Murine rIL-12 as an adjuvant with soluble Leishmania Ag has been shown to protect susceptible mice. We used 48 rhesus macaques to assess the safety, immunogenicity, and efficacy of a vaccine combining heat-killed Leishmania amazonensis with human rIL-12 (rhIL-12) and alum (aluminum hydroxide gel) as adjuvants. The single s.c. vaccination was found to be safe and immunogenic, although a small transient s.c. nodule developed at the site. Groups receiving rhIL-12 had an augmented in vitro Ag-specific IFN-gamma response after vaccination, as well as increased production of IgG. No increase in IL-4 or IL-10 was found in cell culture supernatants from either control or experimental groups. Delayed hypersensitivity reactions were not predictive of protection. Intradermal forehead challenge infection with 10(7) metacyclic L. amazonensis promastigotes at 4 wk demonstrated protective immunity in all 12 monkeys receiving 2 mu g rhIL-12 with alum and Ag. Partial efficacy was seen with lower doses of rhIL-12 and in groups lacking either adjuvant. Thus, a single dose vaccine with killed Ag using rhIL-12 and alum as adjuvants was safe and fully effective in this primate model of cutaneous leishmaniasis. This study extends the murine data to primates, and provides a basis for further human trials. C1 US FDA, Ctr Biol Evaluat & Res, Lab Parasit Biol & Biochem, Bethesda, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Vet Med, Bethesda, MD 20852 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Genet Inst, Andover, MA 01810 USA. Biotechnol Unit, Biobras, Montes Claros, Brazil. RP Kenney, RT (reprint author), 1401 Rockville Pike,HFM-416, Rockville, MD 20852 USA. NR 50 TC 97 Z9 101 U1 1 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 OCT 15 PY 1999 VL 163 IS 8 BP 4481 EP 4488 PG 8 WC Immunology SC Immunology GA 243AK UT WOS:000082974800051 PM 10510390 ER PT J AU Panchenko, VA Glasser, CR Partin, KM Mayer, ML AF Panchenko, VA Glasser, CR Partin, KM Mayer, ML TI Amino acid substitutions in the pore of rat glutamate receptors at sites influencing block by polyamines SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID RECTIFIER K+ CHANNELS; INWARD RECTIFICATION; XENOPUS OOCYTES; STRUCTURAL DETERMINANTS; INTRACELLULAR SPERMINE; ENDOGENOUS POLYAMINES; POTASSIUM CHANNELS; RECOMBINANT AMPA; ION SELECTIVITY; SUBUNIT AB 1. The effect on polyamine block of mutations at the Q/R site and the conserved negative charge +4 site in AMPA and kainate receptors was studied using the rat glutamate receptor GluR6 expressed in Xenopus oocytes and human embryonic kidney (HEK) cells. 2. Introduction of negative charge at the Q/R site increased the equilibrium dissociation constant at 0 mV (K-d(0)) for spermine from 1.3 to 4.0 mu m (Q590E); the smaller side chains Q590D and Q590N had K-d(0) values of 47 and 20 mu m. Reductions in spermine affinity were also obtained for the small hydrophobic residues Q590V and Q590A, with K-d(0) values of 3.6 and 8.8 mu m. Positively charged side chains produced outward rectifying responses similar to those recorded for GluR6(Q) with polyamine-free conditions, suggesting a complete absence of voltage-dependent block by spermine. 3. Substitution of tryptophan at the Q/R site produced high-affinity block with a K-d(0) of 190 pm. In Xenopus oocytes no outward current was observed at potentials up to +200 mV. A much smaller increase in affinity was observed fur Q590F and Q590Y, which had K-d(0) values of 0.28 and 0.83 mu m, respectively. 4. The Q590H mutant gave weakly birectifying responses strikingly different from those for other mutants. When ionization of the His group was increased by raising the external hydrogen ion concentration, responses became outward rectifying. The ratios of the conductance at 100 mV over that at -100 mV for Q590H were 0.52 at pH 8.3 and 2.5 at pH 5.3. 5. Neutralization of charge or aromatic residues at the +4 site produced a large reduction of spermine affinity, with K-d(0) values for E594N, E594Q and E594W of 109, 1020 and 2150 mu m, respectively. In the absence of polyamines, E594K and E594R produced strongly inward rectifying responses while E594Q, E594A and E594W were birectifying. 6. A model for permeant block allowed quantitative comparisons between mutants. Despite large changes in well depth and barrier heights, there was little change in the voltage dependence of block for both Q/R and +4 site mutants. We propose a model with a distributed binding site for polyamines in which the +4 site is located near the: entrance to the channel. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Room 5A78,49 Convent Dr, Bethesda, MD 20892 USA. RI Mayer, Mark/H-5500-2013; Partin, Kathryn/A-8706-2015 OI Partin, Kathryn/0000-0003-3801-3299 NR 50 TC 37 Z9 37 U1 0 U2 1 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 OCT 15 PY 1999 VL 520 IS 2 BP 337 EP 357 DI 10.1111/j.1469-7793.1999.t01-1-00337.x PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 252RX UT WOS:000083517000003 PM 10523404 ER PT J AU Gladen, BC Schecter, AJ Papke, O Shkyryak-Nyzhnyk, ZA Hryhorczuk, DO Little, RE AF Gladen, BC Schecter, AJ Papke, O Shkyryak-Nyzhnyk, ZA Hryhorczuk, DO Little, RE TI Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID PCBS; BLOOD AB Substantial environmental pollution has been alleged in Ukraine, but little information is available to allow an assessment of the possible impact on humans. To help remedy this lack of information, it was of interest to investigate whether certain polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or coplanar polychlorinated biphenyls (PCBs) were elevated in people from Ukraine. Samples of breast milk were obtained from 200 women from the cities of Kyiv and Dniprodzerzhinsk; Kyiv is the capital and Dniprodzerzhinsk is a highly industrialized city. The samples were combined into four pools by city and age, and analyzed for 7 PCDDs, 10 PCDFs, and 2 coplanar PCBs (126 and 169). The total of the measured PCDDs, expressed as toxic equivalents, ranged from 5.1 to 7.6 pg/g lipid; for PCDFs from 3.6 to 5.2, and for PCBs from 11 to 18 pg/g lipid. Results from the two cities were similar; older women had slightly higher concentrations than did younger women. Levels of these compounds seen in Ukraine were similar to or lower than those seen in other recent studies from European and Asian countries. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. SUNY Binghamton, Binghamton, NY USA. ERGO Forschungsgesells MBH, Hamburg, Germany. Inst Pediat Obstet & Gynecol, Kyiv, Ukraine. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. RP Gladen, BC (reprint author), NIEHS, Biostat Branch, Mail Drop A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. NR 24 TC 26 Z9 27 U1 2 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0098-4108 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD OCT 15 PY 1999 VL 58 IS 3 BP 119 EP 127 DI 10.1080/009841099157331 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 242HN UT WOS:000082934600001 PM 10522644 ER PT J AU Cort, JR Koonin, EV Bash, PA Kennedy, MA AF Cort, JR Koonin, EV Bash, PA Kennedy, MA TI A phylogenetic approach to target selection for structural genomics: solution structure of YciH SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-BINDING DOMAIN; RESONANCE ASSIGNMENTS; COUPLING-CONSTANTS; PROTEIN STRUCTURES; ESCHERICHIA-COLI; SEX-LETHAL; NMR; SEQUENCE; C-13; H-1 AB Structural genomics presents an enormous challenge with up to 100 000 protein targets in the human genome alone. At current rates of structure determination, judicious selection of targets is neccessary. Here, a phylogenetic approach to target selection is described which makes use of the National Center for Biotechnology Information database of Clusters of Orthologous Groups (COGS). The strategy is designed so that each new protein structure is likely to provide novel sequence-fold information. To demonstrate this approach, the NMR solution structure of YciH (COG0023), a putative translation initiation factor from Escherichia coli, has been determined and its fold classified. YciH is an ortholog of eIF-1/SUI1, an integral component of the translation initiation complex in eukaryotes, The structure consists of two antiparallel alpha-helices packed against the same side of a five-stranded beta-sheet. The first 31 residues of the 11.5 kDa protein are unstructured in solution. Comparative analysis indicates that the folded portion of YciH resembles a number of structures with the alpha-beta plait topology, though its sequence is not homologous to any of them. Thus, the phylogenetic approach to target selection described here was used successfully to identify a new homologous superfamily within this topology. C1 Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Northwestern Univ, Dept Mol Pharmacol & Biol Chem, Chicago, IL 60611 USA. RP Kennedy, MA (reprint author), Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA. NR 50 TC 38 Z9 40 U1 0 U2 0 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 OCT 15 PY 1999 VL 27 IS 20 BP 4018 EP 4027 DI 10.1093/nar/27.20.4018 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 247BU UT WOS:000083201400009 PM 10497266 ER PT J AU Hacia, JG Novotny, EA Mayer, RA Woski, SA Ashlock, MA Collins, FS AF Hacia, JG Novotny, EA Mayer, RA Woski, SA Ashlock, MA Collins, FS TI Design of modified oligodeoxyribonucleotide probes to detect telomere repeat sequences in FISH assays SO NUCLEIC ACIDS RESEARCH LA English DT Article ID IN-SITU HYBRIDIZATION; HUMAN-CHROMOSOMES; INCOMPLETE EXCHANGES; PROPYNE ANALOGS; DNA-SEQUENCES; PNA PROBE; OLIGODEOXYNUCLEOTIDES; OLIGONUCLEOTIDES; AMPLIFICATION; LOCALIZATION AB A series of dye-labeled oligonucleotide probes containing base and sugar modifications were tested for the ability to detect telomeric repeat sequences in FISH assays. These modified oligonucleotides, all 18 nt in length, were complementary to either the cytidine-rich (C(3)TA(2))(n) or guanosine-rich (T(2)AG(3))(n) telomere target sequences, Oligonucleotides were modified to either increase target affinity by enhancing duplex stability [2'-OMe ribose sugars and 5-(1-propynyl)pyrimidine residues] or inhibit the formation of inter- or intramolecular structures (7-deazaguanosine and 6-thioguanosine residues), which might interfere with binding to the target. Several dye-labeled oligonucleotide probes were found that could effectively stain the telomeric repeat sequences of either cytidine- or guanosine-rich strands in a specific manner. Such probes could be used as an alternative to peptide nucleic acids for investigating the dynamics of telomere length and maintenance. In principle, these relatively inexpensive and readily synthesized modified oligonucleotides could be used for other FISH-related assays. C1 NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. RP Collins, FS (reprint author), NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NR 46 TC 10 Z9 11 U1 0 U2 6 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 OCT 15 PY 1999 VL 27 IS 20 BP 4034 EP 4039 DI 10.1093/nar/27.20.4034 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 247BU UT WOS:000083201400011 PM 10497268 ER PT J AU Boguski, MS AF Boguski, MS TI Biosequence exegesis SO SCIENCE LA English DT Editorial Material ID SEQUENCE AB Annotation of Large-scale gene sequence data will benefit from comprehensive and consistent application of well-documented, standard analysis methods and from progressive and vigilant efforts to ensure quality and utility and to keep the annotation up to date. However, it is imperative to Learn how to apply information derived from functional genomics and proteomics technologies to conceptualize and explain the behaviors of biological systems. Quantitative and dynamical models of systems behaviors will supersede the Limited and static forms of single-gene annotation that are now the norm. Molecular biological epistemology will increasingly encompass both teleological and causal explanations. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Boguski, MS (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 14 TC 44 Z9 47 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 15 PY 1999 VL 286 IS 5439 BP 453 EP 455 DI 10.1126/science.286.5439.453 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245RD UT WOS:000083121200045 PM 10521334 ER PT J AU Strausberg, RL Feingold, EA Klausner, RD Collins, FS AF Strausberg, RL Feingold, EA Klausner, RD Collins, FS TI The mammalian gene collection SO SCIENCE LA English DT Editorial Material ID HUMAN-GENOME-PROJECT; EXPRESSION; SEQUENCE; CDNA AB The Mammalian Cone Collection (MGC) project is a new effort by the NIH to generate full-length complementary DNA (cDNA) resources. This project will provide publicly accessible resources to the full research community. The MGC project entails the production of libraries, sequencing, and database and repository development, as well as the support of Library construction, sequencing, and analytic technologies dedicated to the goal of obtaining a full set of human and other mammalian full-length (open reading frame) sequences and clones of expressed genes. C1 NCI, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 16 TC 196 Z9 204 U1 2 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 15 PY 1999 VL 286 IS 5439 BP 455 EP 457 DI 10.1126/science.286.5439.455 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245RD UT WOS:000083121200046 PM 10521335 ER PT J AU O'Brien, SJ Menotti-Raymond, M Murphy, WJ Nash, WG Wienberg, J Stanyon, R Copeland, NG Jenkins, NA Womack, JE Graves, JAM AF O'Brien, SJ Menotti-Raymond, M Murphy, WJ Nash, WG Wienberg, J Stanyon, R Copeland, NG Jenkins, NA Womack, JE Graves, JAM TI The promise of comparative genomics in mammals SO SCIENCE LA English DT Review ID GENETIC-LINKAGE MAP; QUANTITATIVE-TRAIT LOCI; SPONTANEOUSLY HYPERTENSIVE RAT; CHEMOKINE RECEPTOR CXCR4; IN-SITU HYBRIDIZATION; ZOO-FISH; CHROMOSOMAL EVOLUTION; BLOOD-PRESSURE; Y-CHROMOSOME; CARNIVORE KARYOTYPE AB Dense genetic maps of human, mouse, and rat genomes that are based on coding genes and on microsatellite and single-nucleotide polymorphism markers have been complemented by precise gene homolog alignment with moderate-resolution maps of Livestock, companion animals, and additional mammal species. Comparative genetic assessment expands the utility of these maps in gene discovery, in functional genomics, and in tracking the evolutionary forces that sculpted the genome organization of modern mammalian species. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Mammalian Genet Lab, Adv Biosci Labs, Frederick, MD 21702 USA. Texas A&M Univ, Coll Vet Med, Dept Vet Pathol, College Stn, TX 77843 USA. La Trobe Univ, Dept Genet & Evolut, Melbourne, Vic 3083, Australia. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. RI Graves, Jennifer/A-1387-2008; OI Stanyon, Roscoe/0000-0002-7229-1092 NR 203 TC 341 Z9 348 U1 1 U2 30 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 15 PY 1999 VL 286 IS 5439 BP 458 EP + DI 10.1126/science.286.5439.458 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245RD UT WOS:000083121200047 PM 10521336 ER PT J AU Wolffe, AP Matzke, MA AF Wolffe, AP Matzke, MA TI Epigenetics: Regulation through repression SO SCIENCE LA English DT Review ID X-CHROMOSOME INACTIVATION; TRANSCRIPTION FACTOR ACCESS; BINDING-PROTEIN MECP2; DE-NOVO METHYLATION; DNA METHYLATION; HISTONE ACETYLATION; TRANSPOSABLE ELEMENT; CYTOSINE METHYLATION; CHROMATIN STRUCTURE; II TRANSCRIPTION AB Epigenetics is the study of heritable changes in gene expression that occur without a change in DNA sequence. Epigenetic phenomena have major economic and medical relevance, and several, such as imprinting and paramutation, violate Mendelian principles. Recent discoveries Link the recognition of nucleic acid sequence homology to the targeting of DNA methylation, chromosome remodeling, and RNA turnover. Although epigenetic mechanisms help to protect cells from parasitic elements, this defense can complicate the genetic manipulation of plants and animals. Essential for normal development, epigenetic controls become misdirected in cancer cells and other human disease syndromes. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Austrian Acad Sci, Inst Mol Biol, A-5020 Salzburg, Austria. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. EM awlme@helix.nih.gov; amatzke@server1.imolbio.oeaw.ac.at NR 166 TC 685 Z9 771 U1 20 U2 228 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 15 PY 1999 VL 286 IS 5439 BP 481 EP 486 DI 10.1126/science.286.5439.481 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245RD UT WOS:000083121200049 PM 10521337 ER PT J AU Yang, D Chertov, O Bykovskaia, N Chen, Q Buffo, MJ Shogan, J Anderson, M Schroder, JM Wang, JM Howard, OMZ Oppenheim, JJ AF Yang, D Chertov, O Bykovskaia, N Chen, Q Buffo, MJ Shogan, J Anderson, M Schroder, JM Wang, JM Howard, OMZ Oppenheim, JJ TI beta-defensins: Linking innate and adaptive immunity through dendritic and T cell CCR6 SO SCIENCE LA English DT Article ID CHEMOKINE RECEPTOR; CYSTIC-FIBROSIS; PROTEIN; PEPTIDE; HIV-1; IDENTIFICATION; INTERACTS; MIGRATION; RANTES; PLASMA AB Defensins contribute to host defense by disrupting the cytoplasmic membrane of microorganisms. This report shows that human beta-defensins are also chemotactic for immature dendritic cells and memory T cells. Human beta-defensin was selectively chemotactic for cells stably transfected to express human CCR6, a chemokine receptor preferentially expressed by immature dendritic cells and memory T cells. The beta-defensin-induced chemotaxis was sensitive to pertussis toxin and inhibited by antibodies to CCR6. The binding of iodinated LARC, the chemokine Ligand for CCR6, to CCR6-transfected cells was competitively displaced by beta-defensin. Thus, beta-defensins may promote adaptive immune responses by recruiting dendritic and T cells to the site of microbial invasion through interaction with CCR6. C1 NCI, Mol Immunoregulat Lab, Div Basic Sci, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Allegheny Univ Hlth Sci, Pittsburgh, PA 15212 USA. Magainin Res Inst, Plymouth Meeting, PA 19642 USA. Univ Kiel, Dept Dermatol, D-24105 Kiel, Germany. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Div Basic Sci, SAIC Frederick,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RI Schroeder, Jens/B-3994-2009; Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-56000] NR 26 TC 1164 Z9 1274 U1 8 U2 40 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 15 PY 1999 VL 286 IS 5439 BP 525 EP 528 DI 10.1126/science.286.5439.525 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245RD UT WOS:000083121200059 PM 10521347 ER PT J AU Pouliot, JJ Yao, KC Robertson, CA Nash, HA AF Pouliot, JJ Yao, KC Robertson, CA Nash, HA TI Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes SO SCIENCE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; CELL-DEATH; DRUGS; DISRUPTION; DELETION; PROTEIN; ENZYME AB Covalent intermediates between topoisomerase I and DNA can become dead-end complexes that read to cell death. Here, the isolation of the gene for an enzyme that can hydrolyze the bond between this protein and DNA is described. Enzyme-defective mutants of yeast are hypersensitive to treatments that increase the amount of covalent complexes, indicative of enzyme involvement in repair. The gene is conserved in eukaryotes and identifies a family of enzymes that has not been previously recognized. The presence of this gene in humans may have implications for the effectiveness of topoisomerase I poisons, such as the camptothecins, in chemotherapy. C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP NIMH, Mol Biol Lab, Bldg 36,Room 1B08, Bethesda, MD 20892 USA. EM nash@codon.nih.gov NR 20 TC 234 Z9 239 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD OCT 15 PY 1999 VL 286 IS 5439 BP 552 EP 555 DI 10.1126/science.286.5439.552 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 245RD UT WOS:000083121200066 PM 10521354 ER PT J AU Fay, MP AF Fay, MP TI Comparing several score tests for interval censored data (vol 18, pg 273, 1999) SO STATISTICS IN MEDICINE LA English DT Correction C1 NCI, Bethesda, MD 20892 USA. RP Fay, MP (reprint author), NCI, Execut Plaza N,Suite 313,6130 Execut Blvd MSC 734, Bethesda, MD 20892 USA. RI Fay, Michael/A-2974-2008 NR 1 TC 0 Z9 0 U1 0 U2 0 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 OCT 15 PY 1999 VL 18 IS 19 BP 2681 EP 2681 PG 1 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 242WT UT WOS:000082965200012 ER PT J AU Horiuchi, M Caughey, B AF Horiuchi, M Caughey, B TI Prion protein interconversions and the transmissible spongiform encephalopathies SO STRUCTURE WITH FOLDING & DESIGN LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; STRAUSSLER-SCHEINKER DISEASE; SCRAPIE-ASSOCIATED FORM; CELL-FREE CONVERSION; SYNTHETIC PEPTIDES; CULTURED-CELLS; DOMAIN PRP(121-231); NEUROBLASTOMA-CELLS; STRAIN VARIATION; RESISTANT FORMS C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caughey, B (reprint author), NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 95 TC 72 Z9 73 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0969-2126 J9 STRUCT FOLD DES JI Struct. Fold. Des. PD OCT 15 PY 1999 VL 7 IS 10 BP R231 EP R240 DI 10.1016/S0969-2126(00)80049-0 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 248HC UT WOS:000083268200002 PM 10545332 ER PT J AU Constan, AA Sprankle, CS Peters, JM Kedderis, GL Everitt, JI Wong, BA Gonzalez, FL Butterworth, BE AF Constan, AA Sprankle, CS Peters, JM Kedderis, GL Everitt, JI Wong, BA Gonzalez, FL Butterworth, BE TI Metabolism of chloroform by cytochrome P450 2E1 is required for induction of toxicity in the liver, kidney, and nose of male mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID FEMALE B6C3F(1) MICE; MALE F344 RATS; CELL-PROLIFERATION; DRINKING-WATER; RISK ASSESSMENT; HEPATOTOXICITY; EXPOSURE; 1-AMINOBENZOTRIAZOLE; NEPHROTOXICITY; CARCINOGENS AB Chloroform is a nongenotoxic-cytotoxic liver and kidney carcinogen and nasal toxicant in some strains and sexes of rodents. Substantial evidence indicates that tumor induction is secondary to events associated with cytolethality and regenerative cell proliferation. Therefore, pathways leading to toxicity, such as metabolic activation, become critical information in mechanism-based risk assessments. The purpose of this study was to determine the degree to which chloroform-induced cytotoxicity is dependent on the cytochromes P450 in general and P450 2E1 in particular. Male B6C3F(1), Sv/129 wild-type (Cyp2e1+/+), and Sv/129 CYP2E1 knockout (Cyp2e1-/- or Cyp2e1-null) mice were exposed 6 h/day for 4 consecutive days to 90 ppm chloroform by inhalation. Parallel control and treated groups, excluding Cyp2e1-null mice, also received an i.p. injection (150 mg/kg) of the irreversible cytochrome P450 inhibitor 1-aminobenzotriazole (ABT) twice on the day before exposures began and 1 h before every exposure. Cells in S-phase were labeled by infusion of BrdU via an implanted osmotic pump for 3.5 days prior to necropsy, and the labeling index was quantified immunohistochemically. B6C3F(1) and Sv/129 wild-type mice exposed to chloroform alone had extensive hepatic and renal necrosis with significant regenerative cell proliferation. These animals had minimal toxicity in the nasal turbinates with focal periosteal cell proliferation. Administration of ABT completely protected against the hepatic, renal, and nasal toxic effects of chloroform. Induced pathological changes and regenerative cell proliferation were absent in these target sites in Cyp2e1-/- mice exposed to 90 ppm chloroform. These findings indicate that metabolism is obligatory for the development of chloroform-induced hepatic, renal, and nasal toxicity and that cytochrome P450 2E1 appears to be the only enzyme responsible for this cytotoxic-related metabolic conversion under these exposure conditions. (C) 1999 Academic Press. C1 Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Butterworth, BE (reprint author), Chem Ind Inst Toxicol, 6 Davis Dr,POB 12137, Res Triangle Pk, NC 27709 USA. RI Peters, Jeffrey/D-8847-2011 NR 41 TC 75 Z9 77 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD OCT 15 PY 1999 VL 160 IS 2 BP 120 EP 126 DI 10.1006/taap.1999.8756 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 250TX UT WOS:000083405200002 PM 10527910 ER PT J AU Mhatre, AN Steinbach, S Hribar, K Hoque, ATMS Lalwani, AK AF Mhatre, AN Steinbach, S Hribar, K Hoque, ATMS Lalwani, AK TI Identification of aquaporin 5 (AQP5) within the cochlea: cDNA cloning and in situ localization SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID WATER-CHANNEL; INNER-EAR; MUTATIONS; EXPRESSION; FAMILY; MOUSE; GENE AB Dysfunction of fluid and electrolyte homeostasis is considered to cause variety of inner ear disorders. One group of candidate proteins that may play a critical role in the inner ear fluid homeostasis is the aquaporins, a family of proteins whose members have well defined roles in fluid transport in variety of organs. This study reports the identification of AQP5, a member of the aquaporin family, within the rat inner ear and its in situ localization. AQP5 was initially identified within rat cochlear RNA via RT-PCR and sequence analysis of the amplified fragments, Immunoblot of cochlear homogenate yielded a predominant AQP5-immunoreactive band of M-r 35 kDa. The anti-AQPB immunoreactivity, indicating expression of the AQP5 polypeptide, was localized within the cochlea in situ to the cell types that form the lateral wall of the cochlear duct-the external sulcus (ES) cells and the cells of the spiral prominence. Expression of AQP5 was observed in the apical turn but not the basal turn of the cochlea; nor was it observed in the vestibular neuroepithelia or its supporting cells. The restricted expression of AQP5 to the apical turns of the cochlea suggests its potential role in low frequency hearing. (C) 1999 Academic Press. C1 Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Lab Mol Otol, Epstein Labs, San Francisco, CA 94143 USA. Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Lalwani, AK (reprint author), Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, Lab Mol Otol, Epstein Labs, 583 Parnassus Ave,U490A, San Francisco, CA 94143 USA. NR 25 TC 42 Z9 44 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 OCT 14 PY 1999 VL 264 IS 1 BP 157 EP 162 DI 10.1006/bbrc.1999.1323 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 246FJ UT WOS:000083153500028 PM 10527857 ER PT J AU Requena, JR Stadtman, ER AF Requena, JR Stadtman, ER TI Conversion of lysine to N-epsilon-(carboxymethyl)lysine increases susceptibility of proteins to metal-catalyzed oxidation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GLYCATION END-PRODUCT; GLUTAMINE-SYNTHETASE; LIPID-PEROXIDATION; DISEASE; DAMAGE; IDENTIFICATION; CONSEQUENCES; MECHANISM; SITE AB Metal-catalyzed oxidation (MCO) of proteins leads to the conversion of some amino acid residues to carbonyl derivatives, and may result in loss of protein function. It is well documented that reactions with oxidation products of sugars, lipids, and amino acids can lead to the conversion of some lysine residues of proteins to N-epsilon-(carboxymethyl)lysine (CML) derivatives, and that this increases their metal binding capacity. Because post-translational modifications that enhance their metal binding capacity should also increase their susceptibility to MCO, we have investigated the effect of lysine carboxymethylation on the oxidation of bovine serum albumin (BSA) by the Fe3+/ascorbate system. Introduction of similar to 10 or more mol CML/mol BSA led to increased formation of carbonyls and of the specific oxidation products glutamic and adipic semialdehydes. These results support the view that the generation of CML derivatives on proteins may contribute to the oxidative damage that is associated with aging and a number of age-related diseases. (C) 1999 Academic Press. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Requena, JR (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3,Room 118,3 Ctr Dr,MSC-0320, Bethesda, MD 20892 USA. NR 29 TC 31 Z9 32 U1 1 U2 8 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 OCT 14 PY 1999 VL 264 IS 1 BP 207 EP 211 DI 10.1006/bbrc.1999.1502 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 246FJ UT WOS:000083153500037 PM 10527866 ER PT J AU Koonin, EV Aravind, L Hofmann, K Tschopp, J Dixit, VM AF Koonin, EV Aravind, L Hofmann, K Tschopp, J Dixit, VM TI Apoptosis - Searching for FLASH domains SO NATURE LA English DT Article ID SEQUENCES; DATABASE C1 NIH, Natl Lib Med, NCBI, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. MEMOREC Stoffel GmbH, Bioinformat Grp, D-50829 Cologne, Germany. Univ Lausanne, Inst Biochem, Lausanne Branch, CH-1066 Epalinges, Switzerland. Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. RP Koonin, EV (reprint author), NIH, Natl Lib Med, NCBI, Bethesda, MD 20894 USA. RI Hofmann, Kay/D-6714-2011; dixit, vishva/A-4496-2012 OI Hofmann, Kay/0000-0002-2289-9083; dixit, vishva/0000-0001-6983-0326 NR 12 TC 20 Z9 21 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 14 PY 1999 VL 401 IS 6754 BP 662 EP 662 DI 10.1038/44317 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 247EJ UT WOS:000083207400045 PM 10537104 ER PT J AU Bach, PB Cramer, LD Warren, JL Begg, CB AF Bach, PB Cramer, LD Warren, JL Begg, CB TI Racial differences in the treatment of early-stage lung cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SOCIAL-FACTORS; THERAPY; VALIDATION; MORTALITY; MORBIDITY; SURVIVAL AB Background If discovered at an early stage, non-small-cell lung cancer is potentially curable by surgical resection. However, two disparities have been noted between black patients and white patients with this disease. Blacks are less likely to receive surgical treatment than whites, and they are likely to die sooner than whites. We undertook a population-based study to estimate the disparity in the rates of surgical treatment and to evaluate the extent to which this disparity is associated with differences in overall survival. Methods We studied all black patients and white patients 65 years of age or older who were given a diagnosis of resectable non-small-cell lung cancer (stage I or II) between 1985 and 1993 and who resided in 1 of the 10 study areas of the Surveillance, Epidemiology, and End Results (SEER) program (10,984 patients). Data on the diagnosis, stage of disease, treatment, and demographic characteristics of the patients were obtained from the SEER data base. Information on coexisting illnesses, type of Medicare coverage, and survival was obtained from linked Medicare inpatient-discharge records. Results The rate of surgery was 12.7 percentage points lower for black patients than for white patients (64.0 percent vs. 76.7 percent, P<0.001), and the five-year survival rate was also lower for blacks (26.4 percent vs. 34.1 percent, P<0.001). However, among the patients undergoing surgery, survival was similar for the two racial groups, as it was among those who did not undergo surgery. Furthermore, analyses in which adjustments were made for factors that are predictive of either candidacy for surgery or survival did not alter the influence of race on these outcomes. Conclusions Our analyses suggest that the lower survival rate among black patients with early-stage, non-small-cell lung cancer, as compared with white patients, is largely explained by the lower rate of surgical treatment among blacks. Efforts to increase the rate of surgical treatment for black patients appear to be a promising way of improving survival in this group. (N Engl J Med 1999;341:1198-205.) (C)1999, Massachusetts Medical Society. C1 Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Pulm Serv, New York, NY 10021 USA. NCI, Appl Res Branch, Bethesda, MD USA. RP Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, 1275 York Ave,Box 221, New York, NY 10021 USA. NR 30 TC 605 Z9 608 U1 4 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 14 PY 1999 VL 341 IS 16 BP 1198 EP 1205 DI 10.1056/NEJM199910143411606 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 245BY UT WOS:000083087400006 PM 10519898 ER PT J AU Jansen, AP Colburn, NH Verma, AK AF Jansen, AP Colburn, NH Verma, AK TI Tumor promoter-induced ornithine decarboxylase gene expression occurs independently of AP-1 activation SO ONCOGENE LA English DT Article DE c-Jun; phorbol ester; TPA; ODC; cell transformation ID PROTEIN KINASE-C; ALPHA-DIFLUOROMETHYLORNITHINE; MOUSE SKIN; IRREVERSIBLE INHIBITOR; INDUCED TRANSFORMATION; PHORBOL ESTERS; JB6 CELLS; RECEPTOR; MYC; 12-O-TETRADECANOYLPHORBOL-13-ACETATE AB Activator protein 1 (AP-1) transactivation and ornithine decarboxylase (ODC) activity have been established as essential downstream effecters of mouse skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA), Previous studies have shown that inhibition of either AP-1 transactivation or ODC activity suppressed tumor promoter-induced transformation. By utilizing the JB6 mouse epidermal cell system, the present study determined whether TPA-induced ODC gene expression and activity is independent of AP-1 transactivation. In three independent JB6 (P+) clones, stably expressing dominant negative c-jun, TPA-induced ODC gene expression and activity were similar compared to JB6 P+ cells expressing vector-control alone, while AP-1-dependent transcription was inhibited, Transformation-insensitive JB6 (P-) cells, which lack TPA-inducible c-jun expression, also exhibited similar induction of ODC activity by TPA. alpha-Difluoromethylornithine, an irreversible inhibitor of ODC, attenuated, at an equivalent IC50, both TPA-induced ODC activity and anchorage-independent growth of JB6 P+ cells, despite no inhibition of AP-1 transactivation. Taken together, the results presented indicate that TPA-induced ODC gene expression and activity are independent of AP-1 transactivation. Because inhibition of either AP-1 or ODC precludes TPA-induced transformation, and because ODC is independent of AP-1, we propose that there are at least two pathways to transformation. Each pathway is required but not sufficient for transformation. C1 Univ Wisconsin, Sch Med, Ctr Comprehens Canc, Dept Human Oncol, Madison, WI 53792 USA. NCI, Lab Biochem Physiol, Frederick, MD 21702 USA. RP Verma, AK (reprint author), Univ Wisconsin, Sch Med, Ctr Comprehens Canc, Dept Human Oncol, K4-532,CSC,600 Highland Ave, Madison, WI 53792 USA. FU NCI NIH HHS [R01 CA42585] NR 41 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 14 PY 1999 VL 18 IS 42 BP 5806 EP 5813 DI 10.1038/sj.onc.1202965 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 245FG UT WOS:000083095100009 PM 10523861 ER PT J AU Wyatt, LS Whitehead, SS Venanzi, KA Murphy, BR Moss, B AF Wyatt, LS Whitehead, SS Venanzi, KA Murphy, BR Moss, B TI Priming and boosting immunity to respiratory syncytial virus by recombinant replication-defective vaccinia virus MVA SO VACCINE LA English DT Article DE respiratory syncytial virus; vaccinia virus; MVA strain ID TEMPERATURE-SENSITIVE MUTANT; F-GLYCOPROTEIN; HOST-RANGE; RHESUS-MONKEYS; PROTECTS MICE; RSV CHALLENGE; COTTON RATS; ANKARA; IMMUNIZATION; IMMUNOGENICITY AB Intranasal and intramuscular immunizations of mice with the highly attenuated MVA strain of vaccinia virus expressing the respiratory syncytial virus (RSV) F or G glycoprotein induced higher RSV antibody titers than those achieved by infection with RSV and greatly restricted the replication of RS challenge virus in both the upper and lower respiratory tracts. In addition, a recombinant MVA expressing both RSV F and G was stable and was as immunogenic as a combination of two single recombinant viruses. The levels of antibodies to RSV F and G, induced by previous intranasal infection with attenuated RSV, were boosted by intramuscular immunization with recombinant MVA. These data support further development of recombinant MVA as a RSV vaccine. (C) 1999 Published by Elsevier Science Ltd. All rights reserved. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr MSC 0445, Bethesda, MD 20892 USA. NR 33 TC 66 Z9 66 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 14 PY 1999 VL 18 IS 5-6 BP 392 EP 397 DI 10.1016/S0264-410X(99)00257-1 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 250PR UT WOS:000083397200003 PM 10519927 ER PT J AU Skiadopoulos, MH Tao, T Surman, SR Collins, PL Murphy, BR AF Skiadopoulos, MH Tao, T Surman, SR Collins, PL Murphy, BR TI Generation of a parainfluenza virus type 1 vaccine candidate by replacing the HN and F glycoproteins of the live-attenuated PIV3 cp45 vaccine virus with their PIV1 counterparts SO VACCINE LA English DT Article DE PIV1; candidate vaccine; phenotypes ID RESPIRATORY SYNCYTIAL VIRUS; GENE-EXPRESSION; RECOVERY; RNA; MUTANT; CDNA AB Parainfluenza virus type 1 (PIV1) is a major cause of croup in infants and young children, and a vaccine is needed to prevent the serious disease caused by this virus. In the present study, a live attenuated PIV1 vaccine candidate was generated by modification of the extensively-studied PIV3 cold-passaged (cp) cp45 vaccine candidate using the techniques of reverse genetics. The HN and F glycoproteins of the PIV3 cp45 candidate vaccine virus were replaced with those of PIV1. This created a live attenuated PIV1 Vaccine candidate, termed rPIV3-1 cp45, which contained the attenuated background of the PIV3 cp45 vaccine virus together with the HN and F protective antigens of PIV1. Three of the 15 mutations of cp45 lie within the HN and F genes, and those in the F gene are attenuating. Thus, some attenuation might be lost by the HN and F glycoprotein replacement. To address this issue we also constructed a derivative of PIV3 cp45, designated rPIV3 cp45 (FwtHNwt), that possessed wild type PIV3 HN and F glycoproteins but retained the 12 other cp45 mutations. rPIV3 cp45 (FwtHNwt) replicated in the respiratory tract of hamsters to a level three- to four-fold higher than rPIV3 cp45, indicating that loss of the two attenuating mutations in the cp45 F gene effected a slight reduction in the overall attenuation of cp45 for hamsters. However, the chimeric rPIV3-1 cp45 virus was about 5-fold more restricted in replication in hamsters than rPIV3 cp45 and about 15- to 20-fold more restricted than rPIV3 cp45 (FwtHNwt). This suggests that two components contribute to the attenuation of the new chimeric rPIV3-1 cp45 PIV1 vaccine candidate: one being the 12 cp45 mutations, which provide most of the observed attenuation, and the other resulting from the introduction of the heterologous PIV1 HN and F proteins into PIV3 (i.e., a chimerization effect), rPIV3-1 cp45 was observed to be immunogenic and protective against challenge with wild type PIV1 in hamsters. This virus shows sufficient promise that it should be evaluated further as a candidate live attenuated vaccine strain for preventing severe lower respiratory tract PIV1 disease in infants and young children. Published by Elsevier Science Ltd. C1 NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Skiadopoulos, MH (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bldg 7,Rm 106,7 Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. NR 20 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 14 PY 1999 VL 18 IS 5-6 BP 503 EP 510 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 250PR UT WOS:000083397200016 PM 10519940 ER PT J AU Keitel, WA Kester, KE Atmar, RL White, AC Bond, NH Holland, CA Krzych, U Palmer, DR Egan, A Diggs, C Ballou, WR Hall, BF Kaslow, D AF Keitel, WA Kester, KE Atmar, RL White, AC Bond, NH Holland, CA Krzych, U Palmer, DR Egan, A Diggs, C Ballou, WR Hall, BF Kaslow, D TI Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein I (msp-1(19)) and T helper epitopes of tetanus toxoid SO VACCINE LA English DT Article DE malaria vaccines; Plasmodium falciparum; merozoite surface protein ID MALARIA VACCINE; CELL EPITOPES; ANTIBODIES; ANTIGEN; IMMUNOGENICITY; LIPOSOMES; RESPONSES; IMMUNITY AB The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase 1 trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-1(19)) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toroid T-helper epitopes P30 and P2. The first 2 doses of MSP-1(19) were well tolerated. Hypersensitivity reactions occurred in 3 subjects after the third dose of MSP-1(19), including bilateral injection site reactions in 2 tone with generalized skin rash), and probable histamine-associated hypotension in 1. Serum antibody responses to MSP-1(19) occurred in 5/16, 9/16 and 0/8 subjects given 20 mu g of MSP-119, 200 mu g of MSP-1(19), and control vaccines (hepatitis B or Td), respectively. Both MSP-1(19) vaccines were immunogenic in humans, but changes in formulation will be necessary to improve safety and immunogenicity profiles. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Immunol, Washington, DC 20307 USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. US Agcy Int Dev, Malaria Vaccine Dev Program, Washington, DC 20523 USA. NIAID, Div Microbial & Infect Dis, Bethesda, MD 20892 USA. RP Keitel, WA (reprint author), Baylor Coll Med, Dept Microbiol & Immunol, 1 Baylor Plaza, Houston, TX 77030 USA. RI Kester, Kent/A-2114-2011; Holland, Carolyn/B-7880-2011 OI Kester, Kent/0000-0002-5056-0802; FU NIAID NIH HHS [N01-AI-25135] NR 25 TC 65 Z9 65 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 14 PY 1999 VL 18 IS 5-6 BP 531 EP 539 DI 10.1016/S0264-410X(99)00221-2 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 250PR UT WOS:000083397200020 PM 10519944 ER PT J AU Leshner, AI AF Leshner, AI TI Science-based views of drug addiction and its treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SELF-MEDICATION HYPOTHESIS; ABUSE TREATMENT; FOLLOW-UP; DEPENDENCE; DISORDERS; HEALTH C1 NIDA, NIH, Bethesda, MD USA. RP Leshner, AI (reprint author), 6001 Execut Blvd,Room 5274,MSC9581, Bethesda, MD 20892 USA. NR 26 TC 87 Z9 87 U1 1 U2 10 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 OCT 13 PY 1999 VL 282 IS 14 BP 1314 EP 1316 DI 10.1001/jama.282.14.1314 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 243MB UT WOS:000083000800001 PM 10527162 ER PT J AU Lubkowski, J Dauter, Z Yang, F Alexandratos, J Merkel, G Skalka, AM Wlodawer, A AF Lubkowski, J Dauter, Z Yang, F Alexandratos, J Merkel, G Skalka, AM Wlodawer, A TI Atomic resolution structures of the core domain of avian sarcoma virus integrase and its D64N mutant SO BIOCHEMISTRY LA English DT Article ID FELINE IMMUNODEFICIENCY VIRUS; HIV-1 INTEGRASE; CATALYTIC DOMAIN; ACTIVE-SITE; CRYSTAL-STRUCTURES; DIVALENT-CATIONS; PROTEIN; REFINEMENT; SIMILARITY; BINDING AB Six crystal structures of the core domain of integrase (IN) from avian sarcoma virus (ASV) and its active-site derivative containing an Asp64 --> Asn substitution have been solved at atomic resolution ranging 1.02-1.42 Angstrom. The high-quality data provide new structural information about the active site of the enzyme and clarify previous inconsistencies in the description of this fragment. The very high resolution of the data and excellent quality of the refined models explain the dynamic properties of IN and the multiple conformations of its disordered residues. They also allow an accurate description of the solvent structure and help to locate other molecules bound to the enzyme. A detailed analysis of the flexible active-site region, in particular the loop formed by residues 144-154, suggests conformational changes which may be associated with substrate binding and enzymatic activity. The pH-dependent conformational changes of the active-site loop correlates with the pH vs activity profile observed for ASV IN. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. Fox Chase Canc Ctr, Inst Canc Res, Philadelphia, PA 19111 USA. RP Wlodawer, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Macromol Struct Lab, Frederick, MD 21702 USA. FU NCI NIH HHS [CA-06927, CA-47486] NR 39 TC 34 Z9 36 U1 0 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 OCT 12 PY 1999 VL 38 IS 41 BP 13512 EP 13522 DI 10.1021/bi991362q PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250MC UT WOS:000083391300008 PM 10521258 ER PT J AU Kowlessur, D Kaufman, S AF Kowlessur, D Kaufman, S TI Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE tryptophan hydroxylase; tetrahydrobiopterin; melatonin; hyperphenylalaninemia; carbinolamine dehydratase ID AMINO-ACID HYDROXYLASES; DEPENDENT PROTEIN-KINASE; PHENYLALANINE-HYDROXYLASE; RAT-LIVER; 4A-CARBINOLAMINE DEHYDRATASE; TYROSINE 3-MONOOXYGENASE; HUMAN BRAIN; RABBIT; CDNA; PHOSPHORYLATION AB The first step in the biosynthesis of melatonin in the pineal gland is the hydroxylation of tryptophan to 5-hydroxytryptophan. A cDNA of human tryptophan hydroxylase (TPH) was cloned from a library of human pineal gland and expressed in Escherichia coli. This cDNA sequence is identical to the cDNA sequence published from the human carcinoid tissue [1]. This human pineal hydroxylase gene encodes a protein of 444 amino acids and a molecular mass of 51 kDa estimated for the purified enzyme. Tryptophan hydroxylase from human brainstem exhibits high sequence homology (93% identity) with the human pineal hydroxylase. The recombinant tryptophan hydroxylase exists in solution as tetramers. The expressed human pineal tryptophan hydroxylase has a specific activity of 600 nmol/min/mg when measured in the presence of tetrahydrobiopterin and L-tryptophan. The enzyme catalyzes the hydroxylation of tryptophan and phenylalanine at comparable rates. Phosphorylation of the hydroxylase by protein kinase A or calmodulin-dependent kinase II results in the incorporation of 1 mol of phosphate/mol of subunit, but this degree of phosphorylation leads to only a modest (30%) increase in BH4-dependent activity when assayed in the presence of 14-3-3. Rapid scanning ultraviolet spectroscopy has revealed the formation of the transient intermediate compound, 4 alpha-hydroxytetrahydrobiopterin, during the hydroxylation of either tryptophan or phenylalanine catalyzed by the recombinant pineal TPH. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIMH, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Kaufman, S (reprint author), NIMH, Neurochem Lab, NIH, Bldg 36,Room 3D-30,36,Convent Dr MSC 4096, Bethesda, MD 20892 USA. NR 57 TC 14 Z9 14 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD OCT 12 PY 1999 VL 1434 IS 2 BP 317 EP 330 DI 10.1016/S0167-4838(99)00184-3 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 247HH UT WOS:000083215000009 PM 10525150 ER PT J AU Dalakas, MC AF Dalakas, MC TI Why drugs fail in postpolio syndrome - Lessons from another clinical trial SO NEUROLOGY LA English DT Editorial Material ID MUSCULAR-ATROPHY; POLIOMYELITIS C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 8 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1166 EP 1167 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200002 PM 10522866 ER PT J AU Swoboda, KJ Hyland, K Goldstein, DS Kuban, KCK Arnold, LA Holmes, CS Levy, HL AF Swoboda, KJ Hyland, K Goldstein, DS Kuban, KCK Arnold, LA Holmes, CS Levy, HL TI Clinical and therapeutic observations in aromatic L-amino acid decarboxylase deficiency SO NEUROLOGY LA English DT Article DE aromatic L-amino acid decarboxylase deficiency; neurotransmitter deficiency; oculogyric crises; dystonia ID CEREBROSPINAL-FLUID; SEROTONIN RECEPTORS; DOPAMINE-RECEPTORS; LOCALIZATION; PHARMACOLOGY; METABOLISM; DIAGNOSIS; FEATURES; NEURONS; GENE AB Objectives: To elucidate the phenotype in aromatic L-amino acid decarboxylase (AADC) deficiency, a rare autosomal recessive disorder of neurotransmitter synthesis, and report preliminary treatment observations with directed therapy of the associated neurotransmitter deficiencies. Background: AADC is a required enzyme in dopamine, norepinephrine, epinephrine, and serotonin biosynthesis. Five patients have been previously reported. Responses to treatment interventions in these patients have been mixed. Methods: Clinical and biochemical evaluation and therapeutic trials were performed in two children over a 26-month period. Results: Characteristic features included axial hypotonia, hypokinesia, and athetosis, with superimposed episodes of ocular convergence spasm, oculogyric crises, dystonia, and limb rigidity. Catecholamine deficiency was manifest by ptosis, nasal congestion, paroxysmal diaphoresis, temperature instability, and blood pressure lability. Abnormal sleep, feeding difficulties, and esophageal reflux were typical. Significant therapeutic benefit was observed in one child with a combination of pergolide, trihexyphenidyl, and tranylcypromine. Preliminary trials using serotonin receptor agonists or reuptake inhibitors resulted in adverse effects. Conclusions: The movement disorder in AADC deficiency, particularly the characteristic eye movement abnormalities, should facilitate the identification of patients with this rare but possibly underrecognized disorder. Directed therapy of the underlying dopamine and norepinephrine deficiency may be beneficial in some cases. C1 Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Baylor Univ, Med Ctr, Inst Metab Dis, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75235 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Floating Hosp Children, Dept Neurol, Boston, MA USA. RP Swoboda, KJ (reprint author), Univ Utah, Sch Med, Dept Neurol, Room 3R210,50 N Med Dr, Salt Lake City, UT 84132 USA. NR 29 TC 49 Z9 50 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1205 EP 1211 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200011 PM 10522874 ER PT J AU Lopez, OL Litvan, I Catt, KE Stowe, R Klunk, W Kaufer, DI Becker, JT DeKosky, ST AF Lopez, OL Litvan, I Catt, KE Stowe, R Klunk, W Kaufer, DI Becker, JT DeKosky, ST TI Accuracy of four clinical diagnostic criteria for the diagnosis of neurodegenerative dementias SO NEUROLOGY LA English DT Article DE neurodegenerative dementias; diagnostic criteria; AD; frontotemporal loss dementia; progressive supranuclear palsy; dementia with Lewy bodies ID PROGRESSIVE SUPRANUCLEAR PALSY; LEWY BODY DISEASE; RICHARDSON-OLSZEWSKI-SYNDROME; PROBABLE ALZHEIMERS-DISEASE; ADRDA WORK GROUP; PARKINSONS-DISEASE; SENILE DEMENTIA; FRONTOTEMPORAL DEMENTIA; INTERRATER RELIABILITY; INTERNATIONAL WORKSHOP AB Objective: To evaluate the inter-rater reliability and validity of clinical diagnostic criteria for neurodegenerative dementias. Background: Inter-rater accuracy of the diagnosis of AD has been explored, but there are few accuracy studies for progressive supranuclear palsy (PSP) and frontotemporal lobe dementia (FTD), Furthermore, there have been no simultaneous accuracy studies in a mixed sample of patients with cortical and subcortical neurodegenerative processes. Methods: Four experienced clinicians reviewed first-visit-clinical data abstracted from the records of 40 pathologically diagnosed demented subjects. They were asked to apply the NINCDS-ADRDA criteria for AD, the NINDS-SPSP clinical criteria for PSP, the Lund and Manchester criteria for FTD, and the Consensus Guidelines for the Clinical Diagnosis of Dementia with Lewy Bodies (DLB). Results: The generalized kappa for AD was 0.73, for PSP 0.82, for FTD 0.75, and for DLB 0.37. The kappa pool test showed a statistically significant difference between DLB and the other disease processes, and no differences were observed among AD, FTD, and PSP. The mean sensitivity for AD was 95%, for PSP 75%, for FTD 97%, and for DLB 34%. The mean specificity for AD was 79%, for PSP 98.5% for FTD 97%, and for DLB 94%. Conclusions: We found improved inter-rater reliability for the diagnosis of AD among clinicians compared with earlier studies. Similarly, there was a near-perfect and substantial inter-rater agreement fur the diagnosis of PSP and FTD. The sensitivity for the diagnosis of AD was high, although clinicians overdiagnosed this condition. However, there was a reasonable accuracy for the diagnosis of PSP and FTD. Heterogeneity of the clinical presentation of DLB significantly affected inter-rater agreement-and accuracy. The use of multiple diagnostic criteria for cortical and subcortical dementia increases the level of clinical diagnostic accuracy. C1 Alzheimers Dis Res Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. NINDS, Med Neurol Branch, Bethesda, MD 20892 USA. Highland Dr VAMC, Neurobehav Unit, Pittsburgh, PA USA. RP Lopez, OL (reprint author), Neuropsychol Res Program, 3600 Forbes Ave,Suite 502, Pittsburgh, PA 15213 USA. OI Klunk, William/0000-0001-5512-0251; Litvan, Irene/0000-0002-3485-3445 FU NIA NIH HHS [AG 03705, AG 05133]; NIMH NIH HHS [K02-MH01077] NR 49 TC 157 Z9 159 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1292 EP 1299 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200024 PM 10522887 ER PT J AU Maraganore, DM Anderson, DW Bower, JH McDonnell, SK Rocca, WA AF Maraganore, DM Anderson, DW Bower, JH McDonnell, SK Rocca, WA TI Autopsy patterns for Parkinson's disease and related disorders in Olmsted County, Minnesota SO NEUROLOGY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Academy-of-Neurology CY APR 25-MAY 02, 1998 CL MINNEAPOLIS, MINNESOTA SP Amer Acad Neurol DE autopsy patterns; PD ID CLINICAL-DIAGNOSIS; ACCURACY AB Using a records-linkage system, we determined the frequency and distribution of brain autopsies in residents of Olmsted County, Minnesota, in whom parkinsonism developed during 1976 through 1990. Of the 364 incident cases identified, 235 patients were deceased at the time of record abstraction. The overall autopsy rate was low (23%). Diagnostic certainty (for PD), diagnostic type (PD versus other parkinsonism), sex, age at death, and location at death were important selection factors for autopsy. C1 Mayo Clin & Mayo Fdn, Dept Neurol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Maraganore, DM (reprint author), Mayo Clin & Mayo Fdn, Dept Neurol, 200 1st St Sw, Rochester, MN 55905 USA. FU NIAMS NIH HHS [AR30582]; NINDS NIH HHS [NS33978] NR 8 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 1999 VL 53 IS 6 BP 1342 EP 1344 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 243UT UT WOS:000083016200034 PM 10522897 ER PT J AU Caloca, MJ Garcia-Bermejo, ML Blumberg, PM Lewin, NE Kremmer, E Mischak, H Wang, SM Nacro, K Bienfait, B Marquez, VE Kazanietz, MG AF Caloca, MJ Garcia-Bermejo, ML Blumberg, PM Lewin, NE Kremmer, E Mischak, H Wang, SM Nacro, K Bienfait, B Marquez, VE Kazanietz, MG TI beta 2-chimaerin is a novel target for diacylglycerol: Binding properties and changes in subcellular localization mediated by ligand binding to its C1 domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-C; CONFORMATIONALLY CONSTRAINED ANALOGS; GTPASE-ACTIVATING PROTEIN; PHORBOL ESTER BINDING; CYSTEINE-RICH DOMAIN; PK-C; GAMMA-LACTONES; DIFFERENTIAL REGULATION; N-CHIMAERIN; DELTA AB The members of the chimaerin family of Rac-GTPase-activating proteins possess a single C1 domain with high homology to those present in protein kinase C (PKC) isozymes. This domain in PKCs is involved in phorbol ester and diacylglycerol (DAG) binding. We previously have demonstrated that one of the chimaerin isoforms, beta 2-chimaerin, binds phorbol esters with high affinity. In this study we analyzed the properties of beta 2-chimaerin as a DAG receptor by using a series of conformationally constrained cyclic DAG analogues (DAG lactones) as probes. We identified analogs that bind to beta 2-chimaerin with more than 100-fold higher affinity than 1-oleoyl-2-acetylglycerol. The potencies of these analogs approach those of the potent phorbol ester tumor promoters. The different DAG lactones show some selectivity for this novel receptor compared with PKC alpha, Cellular studies revealed that these DAG analogs induce translocation of beta 2-chimaerin from cytosolic (soluble) to particulate fractions. Using green fluorescent protein-fusion proteins for beta 2-chimaerin we determined that this novel receptor translocates to the perinuclear region after treatment with DAG lactones, Binding and translocation were prevented by mutation of the conserved Cys-246 in the C1 domain. The structural homology between the C1 domain of beta 2-chimaerin and the C1b domain of PKC delta also was confirmed by modeling analysis, Our results demonstrate that beta 2-chimaerin is a high affinity receptor for DAG through binding to its C1 domain and supports the emerging concept that multiple pathways transduce signaling through DAG and the phorbol esters. C1 Univ Penn, Sch Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Bethesda, MD 20892 USA. GSF Forschungszentrum Umwelt & Gesundheit, Inst Immunol, D-81377 Munich, Germany. Med Hsch Hannover, Dept Nephrol, D-30625 Hannover, Germany. Georgetown Univ, Med Ctr, Georgetown Inst Cognit & Computat Sci, Washington, DC 20007 USA. RP Kazanietz, MG (reprint author), Univ Penn, Sch Med, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. RI Mischak, Harald/E-8685-2011; Caloca, Maria-Jose/K-9357-2014; Garcia-Bermejo, Maria Laura/E-1542-2015; OI Caloca, Maria-Jose/0000-0002-1003-2685 FU NCI NIH HHS [R01 CA074197] NR 40 TC 86 Z9 86 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 12 PY 1999 VL 96 IS 21 BP 11854 EP 11859 DI 10.1073/pnas.96.21.11854 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246MD UT WOS:000083166800033 PM 10518540 ER PT J AU Aprelikova, ON Fang, BS Meissner, EG Cotter, S Campbell, M Kuthiala, A Bessho, M Jensen, RA Liu, ET AF Aprelikova, ON Fang, BS Meissner, EG Cotter, S Campbell, M Kuthiala, A Bessho, M Jensen, RA Liu, ET TI BRCA1-associated growth arrest is RB-dependent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTIONAL ACTIVATION; CELL-CYCLE; BRCA1; BREAST; EXPRESSION; CANCER; P53; TRANSFORMATION; PROLIFERATION; INHIBITION AB BRCA1 is a susceptibility gene for breast and ovarian cancer with growth-inhibitory activity for which the mechanism of action remains unclear, When introduced into cells, BRCA1 inhibits growth of some but not all cell lines. In an attempt to uncover the mechanism of growth suppression by BRCA1, we examined a panel of cell lines for their ability to reduce colony outgrowth in response to BRCA1 overexpression. Of all variables tested, only those cells with wild-type pRb were sensitive to BRCA1-induced growth suppression. In cells with an intact rb gene, inactivation of pRb by HPV E7 abrogates the growth arrest imposed by BRCA1. In accordance with these observations, we found that BRCA1 could not suppress BrdUrd uptake in primary fibroblasts from rb-/- mice and exhibited an intermediate ability to inhibit DNA synthesis in rb+/- as compared with rb+/+ cells, We further found that the BRCA1 protein complexes with the hypophosphorylated form of pRb, This binding is localized to amino acids 304-394 of BRCA1 protein and requires the ABC domain of pRb. In-frame deletion of BRCA1 fragment involved in interaction with pRb completely abolished the growth-suppressive property of BRCA1. Although it has been reported that BRCA1 interacts with p53, we find the p53 status did not affect the ability of BRCA1 to suppress colony formation, Our data suggest that the growth suppressor function of BRCA1 depends, at least in part, on Rb. C1 NCI, Div Clin Sci, Sect Mol Signalling & Oncogenesis, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN 37232 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Liu, ET (reprint author), NCI, Div Clin Sci, Sect Mol Signalling & Oncogenesis, 31-3A11,31 Ctr Dr,MSC-2440, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008; Jensen, Roy/B-9739-2011 OI Jensen, Roy/0000-0003-4430-2281 FU NCI NIH HHS [P50 CA058223, P50 CA58223-04] NR 22 TC 104 Z9 106 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 OCT 12 PY 1999 VL 96 IS 21 BP 11866 EP 11871 DI 10.1073/pnas.96.21.11866 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246MD UT WOS:000083166800035 PM 10518542 ER PT J AU Gerlach, VL Aravind, L Gotway, G Schultz, RA Koonin, EV Friedberg, EC AF Gerlach, VL Aravind, L Gotway, G Schultz, RA Koonin, EV Friedberg, EC TI Human and mouse homologs of Escherichia coli DinB (DNA polymerase IV), members of the UmuC/DinB superfamily SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SOS-INDUCED MUTAGENESIS; SACCHAROMYCES-CEREVISIAE; RECA PROTEIN; GENE; IDENTIFICATION; SEQUENCE; UMUC; COMPLEX AB understand the mechanisms underlying mutagenesis in eukaryotes better, we have cloned mouse and human homologs of the Escherichia coli dinB gene. E, coli dinB encodes DNA polymerase IV and greatly increases spontaneous mutations when overexpressed, The mouse and human DinB1 amino acid sequences share significant identity with E. coli DinB, including distinct motifs implicated in catalysis, suggesting conservation of the polymerase function. These proteins are members of a large superfamily of DNA damage-bypass replication proteins, including the E. coli proteins UmuC and DinB and the Saccharomyces cerevisiae proteins Rev1 and Rad30, In a phylogenetic Free, the mouse and human DinB1 proteins specifically group with E. coli DinB, suggesting a mitochondrial origin for these genes. The human DINB1 gene is localized to chromosome 5q13 and is widely expressed. C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Genome Sci & Technol Ctr, Dallas, TX 75235 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. RP Friedberg, EC (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. FU NCI NIH HHS [F32 CA075733, CA69029, CA75733] NR 35 TC 174 Z9 179 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 12 PY 1999 VL 96 IS 21 BP 11922 EP 11927 DI 10.1073/pnas.96.21.11922 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246MD UT WOS:000083166800045 PM 10518552 ER PT J AU Ohya, K Kajigaya, S Kitanaka, A Yoshida, K Miyazato, A Yamashita, Y Yamanaka, T Ikeda, U Shimada, K Ozawa, K Mano, H AF Ohya, K Kajigaya, S Kitanaka, A Yoshida, K Miyazato, A Yamashita, Y Yamanaka, T Ikeda, U Shimada, K Ozawa, K Mano, H TI Molecular cloning of a docking protein, BRDG1, that acts downstream of the Tec tyrosine kinase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; COLONY-STIMULATING FACTOR; HOMOLOGY DOMAIN; CELL LINE; PH DOMAIN; ACTIVATION; RECEPTOR; FAMILY; SRC; EXPRESSION AB Tee, Btk, Itk, Bmx, and Txk constitute the Tec family of protein tyrosine kinases (PTKs), a family with the distinct feature of containing a pleckstrin homology (PH) domain. Tec acts in signaling pathways triggered by the B cell antigen receptor (BCR), cytokine receptors, integrins, and receptor-type PTKs. Although upstream regulators of Tec family kinases are relatively well characterized, little is known of the downstream effecters of these enzymes. The yeast two-hybrid system has identified several proteins that interact with the kinase domain of Tee, one of which is now revealed to he a previously unknown docking protein termed BRDG1 (BCR downstream signaling 1). BRDG1 contains a proline-rich motif, a PH domain, and multiple tyrosine residues that are potential target sites for Src homology 2 domains. In 293 cells expressing recombinant BRDG1 and Various PTKs, Tec and Pyk2, but not Btk, Bmx, Lyn, Syk, or c-Abl, induced marked phosphorylation of BRDG1 on tyrosine residues. BRDG1 was also phosphorylated by Tec directly in vitro. Efficient phosphorylation of BRDG1 by Tec required the PH and SH2 domains as well as the kinase domain of the latter. Furthermore, BRDG1 was shown to participate in a positive feedback loop by increasing the activity of Tec. BRDG1 transcripts are abundant in the human B cell line Ramos, and the endogenous protein underwent tyrosine phosphorylation in response to BCR stimulation. BRDG1 thus appears to function as a docking protein acting downstream of Tec in BCR signaling. C1 Jichi Med Sch, Dept Mol Biol, Minami Kawachi, Tochigi 3290498, Japan. Jichi Med Sch, Dept Cardiol, Minami Kawachi, Tochigi 3290498, Japan. Jichi Med Sch, Dept Hematol, Minami Kawachi, Tochigi 3290498, Japan. Omiya Med Ctr, Omiya, Saitama 3308503, Japan. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Kagawa Med Univ, Dept Internal Med 1, Kagawa 7610793, Japan. RP Mano, H (reprint author), Jichi Med Sch, Dept Mol Biol, 3311-1 Yakushiji, Minami Kawachi, Tochigi 3290498, Japan. NR 44 TC 30 Z9 34 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 12 PY 1999 VL 96 IS 21 BP 11976 EP 11981 DI 10.1073/pnas.96.21.11976 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 246MD UT WOS:000083166800054 PM 10518561 ER PT J AU Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Wilson, PWF Levy, D AF Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Wilson, PWF Levy, D TI Cross-classification of JNC VI blood pressure stages and risk groups in the framingham heart study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HYPERTENSION; PREVALENCE; HEALTH; POPULATION; DISEASE; METAANALYSIS; THERAPIES; OUTCOMES AB Background: The recently published Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) includes a classification of blood pressure stages and a new risk stratification component. Patients with high-normal blood pressure or hypertension are strati fled into risk group A (no associated cardiovascular disease risk factors, no target organ damage or cardiovascular disease); group B (1 greater than or equal to associated cardiovascular disease risk factor excluding diabetes, no target organ damage or cardiovascular disease); or group C (diabetes or target organ damage or cardiovascular disease). Objective: To examine the prevalence of risk groups and blood pressure stages in a community-based sample. Methods: We evaluated 4962 subjects from the Framingham Heart Study and Framingham Offspring Study examined between 1990 and 1995. We cross-classified men and women separately according to their JNC VI blood pressure stages and risk groups. Results: In the whole sample, 43.7% had optimal or normal blood pressure and 13.4% had high-normal blood pressure; 12.9% had stage 1 hypertension and 30.0% had stage 2 or greater hypertension or were receiving medication. As blood pressure stage increased, the proportion of subjects in group A decreased, whereas the proportion in group C increased. Among those with high-normal blood pressure or hypertension, only 2.4% (all women) were in risk group a, 59.3% were in group B, and 38.2% were in group C. In the high-normal or by pertensive group, 39.4% qualified for lifestyle modification as the initial intervention according to JNC VI recommendations, whereas 60.6% were eligible for initial drug therapy or were already receiving drug therapy. Nearly one third of high-normal subjects were in risk group C, in which early drug therapy may be needed. Among those in stage 1, only 4.0% were in group A, in which prolonged lifestyle modification is recommended. Conclusions: These results protide a foundation for estimating the number of individuals with hypertension who fall into different risk groups that require different treatment approaches. With nearly 50 million individuals with hypertension in the United States, there are important implications for clinicians and policymakers if JNC VI recommendations are widely adopted in clinical practice. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiol Div,Dept Med, Boston, MA USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-38038] NR 27 TC 32 Z9 36 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 11 PY 1999 VL 159 IS 18 BP 2206 EP 2212 DI 10.1001/archinte.159.18.2206 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 247EY UT WOS:000083208700012 PM 10527298 ER PT J AU Newton, TF Kalechstein, A Beckson, M Bartzokis, G Bridge, TP Ling, W AF Newton, TF Kalechstein, A Beckson, M Bartzokis, G Bridge, TP Ling, W TI Effects of selegiline pretreatment on response to experimental cocaine administration SO PSYCHIATRY RESEARCH LA English DT Article DE cocaine dependence; deprenyl; monoamine oxidase B inhibitor; euphoria; subjective mood ratings; cardiovascular system ID QUANTITATIVE ENZYME AUTORADIOGRAPHY; MAO-B; HUMANS; DESIPRAMINE; ABUSE AB Several medications have been reported to alter the subjective effects of experimentally administered cocaine. We studied the effects of selegiline, a monoamine oxidase B inhibitor, on the subjective effects of experimentally administered cocaine in chronically cocaine-dependent subjects. Eight subjects completed a protocol that involved repeated administrations of cocaine before and after treatment with selegiline, given in extended release form, 10 mg per day, Four days of treatment with selegiline was associated with decreased self-reported 'high' and 'stimulated' feelings after cocaine administration, measured as the area under the curve. Changes in other subjective effects were less pronounced. Selegiline pretreatment had minimal effects on the cardiovascular responses to cocaine administration. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. VA Medicat Dev Res Unit, Los Angeles, CA 90073 USA. N Little Rock VA Med Ctr, Psychiat Serv 116A NLR, N Little Rock, AR 72114 USA. NIDA, Medicat Dev Div, Rockville, MD 20857 USA. RP Newton, TF (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Room C8-846 NPI,760 Westwood Blvd, Los Angeles, CA 90024 USA. RI Bartzokis, George/K-2409-2013; OI newton, thomas/0000-0002-3198-5901 NR 21 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD OCT 11 PY 1999 VL 87 IS 2-3 BP 101 EP 106 DI 10.1016/S0165-1781(99)00058-X PG 6 WC Psychiatry SC Psychiatry GA 247ZB UT WOS:000083249900001 ER PT J AU Fang, H Pincus, S AF Fang, H Pincus, S TI Spontaneous activation of human immunodeficiency virus type 1 in an immunotoxin-resistant variant T cell line SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID NF-KAPPA-B; LONG TERMINAL REPEAT; TRANS-ACTIVATION; GENE-EXPRESSION; CD4 EXPRESSION; LATENCY; HIV; INFECTIVITY; INDUCTION; SEQUENCE AB We have previously used immunotoxins to select for HIV-1 variant cells that transcribe HIV at extremely low levels and fail to produce HIV proteins. Further observation of one of these variants (E9) demonstrated spontaneous in vitro activation of HIV production, The mechanism of activation is different from that of U1 and ACH-2, two other cell lines that can be activated to express HIV in vitro. C1 Montana State Univ, Dept Microbiol, Bozeman, MT 59717 USA. NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, Hamilton, MT 59840 USA. RP Pincus, S (reprint author), Montana State Univ, Dept Microbiol, POB 173520, Bozeman, MT 59717 USA. FU NCI NIH HHS [CA74690] NR 20 TC 0 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT 10 PY 1999 VL 15 IS 15 BP 1345 EP 1349 DI 10.1089/088922299310052 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 242LE UT WOS:000082941900004 PM 10515150 ER PT J AU Poulsen, DJ Favara, C Snyder, EY Portis, J Chesebro, B AF Poulsen, DJ Favara, C Snyder, EY Portis, J Chesebro, B TI Increased neurovirulence of polytropic mouse retroviruses delivered by inoculation of brain with infected neural stem cells SO VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; NERVOUS-SYSTEM DISEASE; LONG TERMINAL REPEAT; AIDS PATIENTS; MICROGLIAL CELLS; ENVELOPE GENE; SEQUENCES; TYPE-1; ENCEPHALOPATHY; DEGENERATION AB Following intraperitoneal (IP) inoculation of neonatal mice, the polytropic recombinant murine leukemia virus (MuLV), Fr98, induces a severe brain disease characterized by ataxia, seizures and death. In contrast, no apparent clinical neurological disease is seen after IP infection with Fr54, a polytropic MULV differing from Fr98 in its envelope gene sequences. In the brain both Fr98 and Fr54 infect primarily capillary endothelial cells and microglia. However, the level of microglial infection by Fr98 is twofold higher than by Fr54, which might account for the difference in neurovirulence. In the present study, in order to test directly whether an increase in the number of microglia infected by Fr54 would be sufficient to induce clinical disease, we attempted to increase the level of Fr54 in the brain by changing the route of infection. After intraventricular inoculation with Fr54-infected neural stem cells (clone C17.2), a well-established vehicle for delivery of viruses and genes to the brain, mice became ataxic and died 4 weeks postinfection. In these mice induction of brain disease was correlated with a higher level of viral antigen in the cerebrum and an increase in the number of infected microglial cells in all brain regions examined compared with mice inoculated IP. In contrast, mice inoculated with neural stem cells infected with an ecotropic nonneurovirulent murine leukemia virus, FB29, developed no clinical disease in spite of evidence for widespread infection of microglia in brain. Since the main differences between Fr54 and FB29 are in the SU (gp70) region of the envelope gene, this region is most likely to account for the differences in induction of CNS disease seen in the current experiments. (C) 1999 Academic Press. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Poulsen, DJ (reprint author), Thomas Jefferson Univ, CNS Gene Therapy Ctr, 1025 Walnut,Suite 511, Philadelphia, PA 19107 USA. NR 31 TC 14 Z9 14 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 OCT 10 PY 1999 VL 263 IS 1 BP 23 EP 29 DI 10.1006/viro.1999.9917 PG 7 WC Virology SC Virology GA 246JZ UT WOS:000083161800003 PM 10544079 ER PT J AU Tu, H Gao, L Shi, ST Taylor, DR Yang, T Mircheff, AK Wen, YM Gorbalenya, AE Hwang, SB Lai, MMC AF Tu, H Gao, L Shi, ST Taylor, DR Yang, T Mircheff, AK Wen, YM Gorbalenya, AE Hwang, SB Lai, MMC TI Hepatitis C virus RNA polymerase and NS5A complex with a SNARE-like protein SO VIROLOGY LA English DT Article ID INTEGRAL MEMBRANE-PROTEIN; NONSTRUCTURAL PROTEINS; REPLICATION COMPLEXES; ENDOPLASMIC-RETICULUM; 5A PROTEIN; IDENTIFICATION; LOCALIZATION; FUSION; CELLS; NS3 AB Hepatitis C virus (HCV) NS5A is a phosphoprotein that possesses a cryptic trans-activation activity. To investigate its potential role in viral replication, we searched for the cellular proteins interacting with NS5A protein by yeast two-hybrid screening of a human hepatocyte cDNA library. We identified a newly discovered soluble N-erhylmaleimide-sensitive factor attachment protein receptor-like protein termed human vesicle-associated membrane protein-associated protein of 33 kDa (hVAP-33). In vitro binding assay and in vivo coimmunoprecipitation studies confirmed the interaction between hVAP-33 and NS5A. interestingly hVAP-33 was also shown to interact with NS5B, the Viral RNA-dependent RNA polymerase. NS5A and NS5B bind to different domains of hVAP-53: NS5A binds to the C-terminus, whereas NS5B binds to the N-terminus of hVAP-33. Immunofluorescent staining showed a significant colocalization of hVAP-33 with both NS5A and NS5B proteins. hVAP-33 contains a coiled-coil domain followed by a membrane-spanning domain at its C-terminus. Cell fractionation analysis revealed that hVAP-33 is predominantly associated with the ER, the Golgi complex, and the prelysosomal membrane, consistent with its potential role in intracellular membrane trafficking. These interactions provide a mechanism for membrane association of the HCV RNA replication complex and further suggest that NS5A is a part of the viral RNA replication complex. (C) 1999 Academic Press. C1 Univ So Calif, Sch Med, Dept Mol Microbiol & Immunol, Howard Hughes Med Inst, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Physiol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Biophys, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. Shanghai Med Univ, Inst Mol Virol, Shanghai 200032, Peoples R China. NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. Hallym Univ, Inst Environm & Life Sci, Chunchon 200702, South Korea. RP Lai, MMC (reprint author), Univ So Calif, Sch Med, Dept Mol Microbiol & Immunol, Howard Hughes Med Inst, 2011 Zonal Ave,HMR-401, Los Angeles, CA 90033 USA. RI Lai, Michael Ming-Chao/I-7001-2012; Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [AI40038] NR 56 TC 181 Z9 189 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 1999 VL 263 IS 1 BP 30 EP 41 DI 10.1006/viro.1999.9893 PG 12 WC Virology SC Virology GA 246JZ UT WOS:000083161800004 PM 10544080 ER PT J AU Cai, T Yu, P Tagle, DA Xia, JH AF Cai, T Yu, P Tagle, DA Xia, JH TI Duplication of 7p21.2 -> pter due to maternal 7p;21q translocation: implications for critical segment assignment in the 7p duplication syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE 7p duplication; syndrome; craniofacial development; mental retardation ID SAETHRE-CHOTZEN-SYNDROME; DIRECT TANDEM DUPLICATION; PARTIAL TRISOMY; SHORT ARM; PERICENTRIC-INVERSION; HOMEOBOX GENE; UNBALANCED TRANSLOCATION; BALANCED TRANSLOCATIONS; MOLECULAR-CLONING; DOWN-SYNDROME AB We describe a 1-year-old boy with mental and physical retardation, a large anterior fontanel, brachycephaly with flat occiput, short and stubby fingers, generalized hypotonia, ocular hypertelorism, low-nasal bridge, long philtrum, high-narrow palate, apparently low-set ears, and a small mandible. Cytogenetic analysis utilizing high resolution chromosome banding technique showed an unbalanced karyotype consisting of 46,XY,add(21)(q22.3) that originated from maternal balanced translocation between chromosomes 7 and 21. Fluorescence in situ hybridization (FISH) using microdissected library probe pool from chromosome 7 confirmed the additional material on 21q was derived from chromosome 7. Our results indicated that the patient had an unbalanced translocation, 46,XY,der(21)t(7;21)(p21.2;q22.3)mat, which resulted in duplication for distal 7p. Our patient is similar to reported cases with a 7p15-->pter or larger duplication of 7p, suggesting that the critical segment causing the characteristic phenotype of 7p duplication syndrome, including large anterior fontanel, exists at 7p21.2 or 7p21.2-->pter. Am. J. Med. Genet. 86:305-311, 1999. (C) 1999 Wiley-Liss, Inc. C1 Hunan Med Univ, Natl Lab Med Genet, Zhengzhou, Peoples R China. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. RP Cai, T (reprint author), NIDCR, Expt Med Sect, NIH, 30 Convent Dr MSC4322,Bldg 30-Rm 122, Bethesda, MD 20892 USA. NR 64 TC 22 Z9 22 U1 2 U2 3 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 OCT 8 PY 1999 VL 86 IS 4 BP 305 EP 311 DI 10.1002/(SICI)1096-8628(19991008)86:4<305::AID-AJMG1>3.0.CO;2-B PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 241RP UT WOS:000082896600001 PM 10494083 ER PT J AU Fanos, JH Gatti, RA AF Fanos, JH Gatti, RA TI A mark on the arm: Myths of carrier status in sibs of individuals with ataxia-telangiectasia SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ataxia-telangiectasia; sibs; carrier status; family dynamics; genetic counseling; genetic testing ID CYSTIC-FIBROSIS; HUNTINGTON DISEASE; BREAST-CANCER; ATM MUTATIONS; FAMILIES; GENE; HETEROZYGOTES; POPULATION; KNOWLEDGE; ATTITUDES AB The ATM gene, mutated in ataxia-telangiectasia (A-T), was identified by positional cloning. The discovery of the ATM gene now allows the identification of A-T heterozygotes [Telatar et al., 1998], who may be at increased risk of cancer. The purpose of this study was to (a) identify sib's interest in carrier testing, (b) explore perception of carrier status, and (c) assess levels of understanding of genetics of A-T. This is the sib component of a study of 103 parents and sibs (68 parents and 35 sibs) of individuals with A-T. Thirty-five sibs from 24 families, including 26 adults and 9 adolescents, drawn from the University of California, Los Angeles, the A-T Clinical Center at the Johns Hopkins University School of Medicine, and the A-T Children's Project, were interviewed. Eighty-five percent of adult sibs stated correctly that if a child has A-T, both parents are heterozygotes; 76% knew the A-T gene had been identified. Ninety-two percent would request carrier testing for themselves if available. Seventy-nine percent would want their child tested for carrier status prior to the age of 18. Seventy-three percent believed that being a carrier is associated with increased health risks. Sibs have numerous misconceptions surrounding carrier status and genetics of A-T. Provision of factual information about genetic transmission is necessary, but unfortunately insufficient, to counter deeply held views of self and others. Genetic counseling, which explores the way in which this information is filtered and interpreted, could be an effective tool in dispelling family myths. We conclude that A-T sibs need comprehensive support in relation to carrier testing. Am. J. Med. Genet. 86:338-346, 1999, (C) 1999 Wiley-Liss, Inc. C1 Calif Pacific Med Ctr, Res Inst, Dept Pediat, San Francisco, CA 94115 USA. Calif Pacific Med Ctr, Res Inst, Dept Med, San Francisco, CA 94115 USA. Calif Pacific Med Ctr, Res Inst, Dept Psychiat, San Francisco, CA 94115 USA. NIH, Natl Human Genome Res Inst, Med Genet Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. RP Fanos, JH (reprint author), Calif Pacific Med Ctr, Res Inst, Dept Pediat, 2340 Clay St, San Francisco, CA 94115 USA. NR 44 TC 21 Z9 21 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD OCT 8 PY 1999 VL 86 IS 4 BP 338 EP 346 DI 10.1002/(SICI)1096-8628(19991008)86:4<338::AID-AJMG8>3.0.CO;2-F PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 241RP UT WOS:000082896600008 PM 10494090 ER PT J AU Blagosklonny, MV Fojo, T AF Blagosklonny, MV Fojo, T TI Molecular effects of paclitaxel: Myths and reality (a critical review) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN OVARIAN-CANCER; TAXOL-INDUCED APOPTOSIS; ACTIVATED PROTEIN-KINASES; CYCLE-DEPENDENT PHOSPHORYLATION; PROGRAMMED CELL-DEATH; TYROSINE PHOSPHORYLATION; MICROTUBULE DYNAMICS; MITOTIC BLOCK; P53 FUNCTION; BCL-2 PHOSPHORYLATION AB Recent studies on paclitaxel (Taxol), a microtubule-stabilizing agent and effective anti-cancer drug, have identified numerous cellular and molecular effects, such as induction of cytokines and tumor-suppressor genes, indirect cytotoxicity due to secretion of tumor necrosis factor, vast activation of signal-transduction pathways and selective activity against cells lacking functional p53, Some of these results, including the immediate activation of signaling pathways and gene expression, have been observed only with paclitaxel concentrations 1,000-fold higher than those required for mitotic arrest and apoptosis. The effects of loss of p53 on paclitaxel cytotoxicity depend on cell type (normal murine fibroblasts vs. human cancer cells) and duration of exposure to paclitaxel; p53 status marginally affects paclitaxel sensitivity in human cancer. Although the biochemistry of mitosis and meiosis has been studied independently of research on the mechanism of action of anti-cancer drugs, it eventually provided insight into the effects of paclitaxel. For example, serine protein phosphorylation, which occurs during mitotic arrest or meiosis, explains paclitaxel-induced hyperphosphorylation of Bcl-2 and Bcl-xL, Although some observations are disputed, such mitotic arrest correlates with paclitaxel cytotoxicity, while there is currently no evidence that any paclitaxel effect at clinically relevant concentrations is independent of its tubulin-binding properties. Thus, paclitaxel exerts two types of effect: mitotic arrest with coincidental serine protein phosphorylation and cytotoxicity at clinically relevant concentrations as well as immediate activation of tyrosine kinase pathways and activation of gene expression at much higher concentrations. (C) 1999 Wiley-Liss, Inc. 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 96 TC 285 Z9 294 U1 7 U2 34 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 OCT 8 PY 1999 VL 83 IS 2 BP 151 EP 156 DI 10.1002/(SICI)1097-0215(19991008)83:2<151::AID-IJC1>3.0.CO;2-5 PG 6 WC Oncology SC Oncology GA 237FZ UT WOS:000082646000001 PM 10471519 ER PT J AU Jeang, KT Xiao, H Rich, EK AF Jeang, KT Xiao, H Rich, EK TI Multifaceted activities of the HIV-1 transactivator of transcription, Tat SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-II; LONG TERMINAL REPEAT; CREB-BINDING-PROTEIN; 2ND CODING EXON; FACTOR P-TEFB; TYPE-1 TAT; ACTIVATED TRANSCRIPTION; MUTATIONAL ANALYSIS; FUNCTIONAL DOMAINS C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 91 TC 292 Z9 306 U1 4 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 8 PY 1999 VL 274 IS 41 BP 28837 EP 28840 DI 10.1074/jbc.274.41.28837 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800001 PM 10506122 ER PT J AU Miki, K Eddy, EM AF Miki, K Eddy, EM TI Single amino acids determine specificity of binding of protein kinase A regulatory subunits by protein kinase A anchoring proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID II-BETA; MOLECULAR CHARACTERIZATION; RI-ALPHA; LOCALIZATION; ASSOCIATION; DOMAIN; CELLS; CDNA; IDENTIFICATION; CYTOSKELETON AB Cyclic AMP-dependent protein kinase is tethered to protein kinase A anchoring proteins (AKAPs) through regulatory subunits (R) by RI alpha-specific, RII alpha-specific, or RI alpha/RII alpha dual-specific binding. Ala- and Vat-scanning mutagenesis determined that hydrophobic amino acids at three homologous positions are required for binding of RI alpha to FSC1/AKAP82 domain B and RII alpha to AKAP Ht31. A mutation at the middle position reversed the binding specificity of both AKAPs, and mutations at this same position of the dual-specific domain A of FSC1/AKAP82 converted it into either an RI alpha or RII alpha binding domain. This suggests that hydrophobic amino acids at three conserved positions within the primary sequence and an amphipathic helix of AKAPs are required for cyclic AMP-dependent protein kinase binding, with the size of the aliphatic side chain at the middle position determining RI alpha or RII alpha binding specificity. C1 NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, MD C4-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 32 TC 57 Z9 57 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 OCT 8 PY 1999 VL 274 IS 41 BP 29057 EP 29062 DI 10.1074/jbc.274.41.29057 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800036 PM 10506157 ER PT J AU Matsuura, H Sakaue, M Subbaramaiah, K Kamitani, H Eling, TE Dannenberg, AJ Tanabe, T Inoue, H Arata, J Jetten, AM AF Matsuura, H Sakaue, M Subbaramaiah, K Kamitani, H Eling, TE Dannenberg, AJ Tanabe, T Inoue, H Arata, J Jetten, AM TI Regulation of cyclooxygenase-2 by interferon gamma and transforming growth factor alpha in normal human epidermal keratinocytes and squamous carcinoma cells - Role of mitogen-activated protein kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROSTAGLANDIN-ENDOPEROXIDE SYNTHASE-2; NECROSIS-FACTOR-ALPHA; CULTURED HUMAN KERATINOCYTES; VASCULAR ENDOTHELIAL-CELLS; FACTOR RECEPTOR ACTIVATION; MAMMARY EPITHELIAL-CELLS; COLON-CANCER CELLS; NF-KAPPA-B; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION AB Treatment of normal human epidermal keratinocytes (NHEK) with interferon-gamma (IFN-gamma) causes a 9-fold increase in the level of cyclooxggenase-2 (COX-2) mRNA expression. Nuclear run-off assays indicate that this induction is at least partly due to increased transcription. Activation of the epidermal growth factor receptor (EGFR) signaling pathway due to the enhanced transforming growth factor alpha (TGF alpha) expression plays an important role in the induction of COX-2 by IFN-gamma. This is supported by the ability of TGF alpha to rapidly induce COX-2 and the inhibition of the IFN-gamma-mediated COX-2 mRNA induction by an EGFR antibody and EGFR-selective kinase inhibitors. Deletion and mutation analysis indicates the importance of the proximal cAMP-response element/ATF site in the transcriptional control of this gene by TGF alpha. The increase in COX-2 mRNA by TGF alpha requires activation of both the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) pathways. Inhibition of p38 MAPK decreases the stability of COX-2 mRNA, while inhibition of MAPK/ERK kinase (MEK) does not. These results suggest that the p38 MAPK signaling pathway controls COX-2 at the level of mRNA stability, while the ERK signaling pathway regulates COX-2 at the level of transcription. In contrast to NHEK IFN-gamma and TGF alpha are not very effective in inducing TGF alpha or COX-2 expression in several squamous carcinoma cell lines, indicating alterations in both IFN-gamma and TGF alpha response pathways. C1 NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Eicosanoid Biochem Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. New York Presbyterian Hosp, Strang Canc Prevent Ctr, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Div Digest Dis, New York, NY 10021 USA. Natl Cardiovasc Ctr, Res Inst, Dept Pharmacol, Suita, Osaka 5658565, Japan. Okayama Univ, Sch Med, Dept Dermatol, Okayama 700, Japan. RP Jetten, AM (reprint author), NIEHS, Cell Biol Sect, Pulm Pathobiol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 83 TC 162 Z9 165 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 8 PY 1999 VL 274 IS 41 BP 29138 EP 29148 DI 10.1074/jbc.274.41.29138 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800048 PM 10506169 ER PT J AU Shan, XC Wange, RL AF Shan, XC Wange, RL TI Itk/Emt/Tsk activation in response to CD3 cross-linking in Jurkat T cells requires ZAP-70 and Lat and is independent of membrane recruitment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-TYROSINE KINASE; PLECKSTRIN HOMOLOGY DOMAINS; TEC FAMILY; PHOSPHATIDYLINOSITOL 3-KINASE; ANTIGEN RECEPTOR; ITK; PHOSPHORYLATION; INTERLEUKIN-2; TCR; ASSOCIATION AB The Tec family tyrosine kinase, Itk has been implicated in T cell antigen receptor (TCR) signaling, yet little is known about Itk regulation. Here, we investigate the role of the tyrosine kinase ZAP-70 in regulating Itk. Whereas Itk was activated in Jurkat T cells in response to CD3 cross-linking, Itk activation was defective in the ZAP-70-deficient P116 Jurkat T cell line. Itk responsiveness to TCR engagement was restored in Pile cells stably transfected with ZAP-70 cDNA, ZAP-70 itself could not directly phosphorylate the Itk kinase domain, indicating an indirect regulation of Itk activity. No role was found for ZAP-70 in regulating Itk recruitment to the plasma membrane, an event that has been suggested to be rate-limiting for the activation of Tec family kinases. Indeed, Itk was found to be constitutively targeted to the membrane fraction in both Jurkat and P116 cells. Lat, a prominent in vivo substrate of ZAP-70 that mediates assembly of multimolecular signaling complexes at the plasma membrane of T cells was also found to be required for TCR-stimulated Itk activation. Itk could not be activated by CD3 cross-linking in a Lat-negative cell line, unless Lat expression was restored. Lat and Itk were observed to co-associate in response to CD3 crosslinking in Jurkat T cells, but not in pile T cells. The Lat-Itk association correlated with Lat tyrosine phosphorylation, which was deficient in the P116 T cells. These data suggest that ZAP-70 and Lat play important, probably sequential, roles in regulating the activation of Itk following TCR engagement. C1 NIA, Biol Chem Lab, Gerontol Res Ctr, IRP,NIH, Baltimore, MD 21224 USA. RP Wange, RL (reprint author), NIA, Biol Chem Lab, Gerontol Res Ctr, IRP,NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 56 TC 76 Z9 80 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 OCT 8 PY 1999 VL 274 IS 41 BP 29323 EP 29330 DI 10.1074/jbc.274.41.29323 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800071 PM 10506192 ER PT J AU Chew, LJ Huang, F Boutin, JM Gallo, V AF Chew, LJ Huang, F Boutin, JM Gallo, V TI Identification of nuclear orphan receptors as regulators of expression of a neurotransmitter receptor gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR COUP; RETINOIC ACID RECEPTORS; CENTRAL-NERVOUS-SYSTEM; COREPRESSOR N-COR; THYROID-HORMONE; RESPONSE ELEMENTS; FACTOR-I; NGFI-B; AMPA/KAINATE RECEPTORS; MULTIPLE MECHANISMS AB Nuclear orphan receptors are known to be important mediators of neurogenesis, but the target genes of these transcription factors in the vertebrate nervous system remain largely undefined, We have previously shown that a 500-base pair fragment in the first intron of the GRIK5 gene, which encodes the kainate-preferring glutamate receptor subunit KA2, down-regulates gene expression. In our present studies, mutation of an Ii-base pair element within this fragment resulted in a loss of nuclear protein binding and reverses negative regulation by the intron. Using yeast one-hybrid screening, we have identified intron-binding proteins from rat brain as COUP-TFI, EAR2, and NURR1. Gel shift studies with postnatal day 2 rat brain extract indicate the presence of COUP-TFs, EAR2, and NURR1 in the DNA-protein complex. Competition assays with GRIK5-binding site mutations show that the recombinant clones exhibit differential binding characteristics and suggest that the DNA-protein complex from postnatal day 2 rat brain may consist primarily of EAR2. The DNA binding activity was also observed to be enriched in rat neural tissue and developmentally regulated. Co-transfection assays showed that recombinant nuclear orphan receptors function as transcriptional repressors in both CV1 cells and rat CG4 oligodendrocyte cells. Direct interaction of the orphan receptors with and relief of repression by TFIIB indicate likely role(s) in active and/or transrepression. Our findings are thus consistent with the notion that multiple nuclear orphan receptors can regulate the transcription of a widely expressed neurotransmitter receptor gene by binding a common element in an intron and directly modulating the activity of the transcription machinery. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Univ Montreal, Ctr Hosp, Dept Med, Montreal, PQ H2W 1T8, Canada. Univ Montreal, Ctr Hosp, Div Endocrinol, Montreal, PQ H2W 1T8, Canada. RP Gallo, V (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, 49 Convent Dr,Bldg 49,Rm 5A78, Bethesda, MD 20892 USA. NR 74 TC 15 Z9 19 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 8 PY 1999 VL 274 IS 41 BP 29366 EP 29375 DI 10.1074/jbc.274.41.29366 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800076 PM 10506197 ER PT J AU O'Reilly, MS Wiederschain, D Stetler-Stevenson, WG Folkman, J Moses, MA AF O'Reilly, MS Wiederschain, D Stetler-Stevenson, WG Folkman, J Moses, MA TI Regulation of angiostatin production by matrix metalloproteinase-2 in a model of concomitant resistance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SELECTIN ADHESION MOLECULE; LEWIS-LUNG-CARCINOMA; GROWTH-FACTOR; ANGIOGENESIS INHIBITOR; ENDOTHELIAL-CELLS; IDENTIFICATION; COLLAGENASE; IV; PLASMINOGEN; ECTODOMAIN AB We have previously reported the identification of the endogenous angiogenesis inhibitor angiostatin, a specific inhibitor of endothelial cell proliferation in vitro and angiogenesis in vivo. In our original studies, we demonstrated that a Lewis lung carcinoma (LLC-LM) primary tumor could suppress the growth of its metastases by generating angiostatin. Angiostatin, a 38-kDa internal fragment of plasminogen, was purified from the serum and urine of mice bearing LLC-LM, and its discovery provides the first proven mechanism for concomitant resistance (O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R. A, Moses, BZ A, Lane, W. S., Cao, Y., Sage, E. II., and Folkman, J. (1999 Cell 79, 315-328). Subsequently, we have shown that systemic administration of angiostatin can regress a wide variety of malignant tumors in vivo. However, at the time of our initial discovery of angiostatin, the source of the protein was unclear. We hypothesized that the tumor or stromal cells might produce an enzyme that could cleave plasminogen sequestered by the primary tumor into angiostatin. Alternatively, we speculated that the tumor cells might express angiostatin. By Northern analysis, however, we have found no evidence that the tumor cells express angiostatin or other fragments of plasminogen (data not shown). me now report that gelatinase A (matrix metalloproteinase-2), produced directly by the LLC-LM cells, is responsible for the production of angiostatin, which suppresses the growth of metastases in our original model. C1 Childrens Hosp, Dept Surg, Surg Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Moses, MA (reprint author), Childrens Hosp, Dept Surg, Surg Res Lab, Boston, MA 02115 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 29 TC 196 Z9 200 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 OCT 8 PY 1999 VL 274 IS 41 BP 29568 EP 29571 DI 10.1074/jbc.274.41.29568 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 243VH UT WOS:000083017800103 PM 10506224 ER PT J AU Yang, FQ Zhang, TY Tian, GL Cao, HF Liu, QH Ito, Y AF Yang, FQ Zhang, TY Tian, GL Cao, HF Liu, QH Ito, Y TI Preparative isolation and purification of hydroxyanthraquinones from Rheum officinale Baill by high-speed counter-current chromatography using pH-modulated stepwise elution SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Rheum officinale; plant materials; hydroxyanthraquinones; anthraquinones; quinones ID SEPARATION; FLAVONOIDS AB Analytical and preparative high-speed counter-current chromatography was successfully used for the isolation and purification of hydroxyanthraquinones from Rheum officinale Baill (Dahuang) using pH-modulated stepwise elution. Four major components including chrysophanol, emodin, physcion and aloe-emodin were isolated each at over 98% purity. Published by Elsevier Science B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Beijing Inst New Technol Applicat, Beijing 100035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10,Rm 7N322, Bethesda, MD 20892 USA. NR 4 TC 74 Z9 82 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD OCT 8 PY 1999 VL 858 IS 1 BP 103 EP 107 DI 10.1016/S0021-9673(99)00827-4 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 245CE UT WOS:000083088000009 PM 10544895 ER PT J AU McCarter, GC Reichling, DB Levine, JD AF McCarter, GC Reichling, DB Levine, JD TI Mechanical transduction by rat dorsal root ganglion neurons in vitro SO NEUROSCIENCE LETTERS LA English DT Article DE mechanical transduction; mechanosensitive current; dorsal root ganglion; sensory neuron; patch-clamp; rat ID ION CHANNELS; IN-VITRO; STIMULATION AB Although it is generally presumed that mechanical sensitivity of somatosensory nerve fibers results from the activation of mechanosensitive ion channels, a mechanically-gated whole-cell current has never been demonstrated in dorsal root ganglion (DRG) neurons, We performed patch clamp experiments on rat DRG neurons in culture, and report the first mechanically-activated current in somatosensory neurons (I-mech) This whole-cell current is observed in most dorsal root ganglion neurons but not in non-sensory sympathetic ganglion neurons. The current-voltage relation of I-mech indicates that it is a non-selective cation current. Sensitivity of I-mech to block by gadolinium suggests that it may be mediated by a member of a family of mechanosensitive non-selective cation channels observed in many cell types. Sensitivity to benzamil supports this idea, and further suggests that the current might be mediated by a member of the degenerin/epithelial sodium channel (DEG/ENaC) family. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif San Francisco, NIH Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, C-522-Box 0440,521 Parnassus Ave, San Francisco, CA 94143 USA. FU NINDS NIH HHS [NS21467] NR 16 TC 136 Z9 142 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 8 PY 1999 VL 273 IS 3 BP 179 EP 182 DI 10.1016/S0304-3940(99)00665-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 241PQ UT WOS:000082892100010 PM 10515188 ER PT J AU Cassman, M Norvell, JC AF Cassman, M Norvell, JC TI Support for structural genomics and synchrotrons SO SCIENCE LA English DT Letter C1 NIGMS, NIH, Bethesda, MD 20892 USA. RP Cassman, M (reprint author), NIGMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 8 PY 1999 VL 286 IS 5438 BP 239 EP 240 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 243YE UT WOS:000083024400021 PM 10577190 ER PT J AU Copley, RR Ponting, CP Bork, P AF Copley, RR Ponting, CP Bork, P TI Phospholipases A2 and Wnts are unlikely to share a common ancestor SO CURRENT BIOLOGY LA English DT Letter C1 European Mol Biol Lab, D-69117 Heidelberg, Germany. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Copley, RR (reprint author), European Mol Biol Lab, Meyerhofstr 1, D-69117 Heidelberg, Germany. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 0 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 7 PY 1999 VL 9 IS 19 BP R718 EP R718 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 244VQ UT WOS:000083071800006 PM 10712041 ER PT J AU Guschin, D Wolffe, AP AF Guschin, D Wolffe, AP TI Transcriptional control: SWItched-on mobility SO CURRENT BIOLOGY LA English DT Article ID HISTONES AB Recent studies have shown that two nucleosome-remodeling complexes, NURF and CHRAC, open chromatin for transcription and replication by using their common catalytic subunit, the nucleosomal ATPase ISWI, to increase the mobility of nucleosomes relative to DNA sequence. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Guschin, D (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 12 TC 13 Z9 13 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 7 PY 1999 VL 9 IS 19 BP R742 EP R746 DI 10.1016/S0960-9822(99)80473-4 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 244VQ UT WOS:000083071800014 PM 10530996 ER PT J AU Xie, XQ Han, XW Chen, JZ Eissenstat, M Makriyannis, A AF Xie, XQ Han, XW Chen, JZ Eissenstat, M Makriyannis, A TI High-resolution NMR and computer modeling studies of the cannabimimetic aminoalkylindole prototype WIN-55212-2 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CANNABINOID RECEPTOR; SPECTROSCOPY; AGONISTS; PRAVADOLINE; INDOLES AB Aminoalkylindoles (AAIs), although structurally dissimilar from the classical cannabinoids (CCs), are known to be capable of binding to cannabinoid receptors and of evoking cannabimimetic responses. However, their mode of binding remains unknown, In this communication, we have carried out further studies on the AAI prototype (R)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl] (1-naphthalenyl)methanone (WIN-55212-2, 1) by the combined use of high-resolution 2D NMR and computer modeling. Our results suggest that the minimum energy conformations of the molecule 1 have distinct pharmacophoric features: (i) The naphthyl ring is oriented off the plane of the benzoxazine ring by approximately 59 degrees with the carbonyl C=O group pointing toward the C2-CH3 group. (ii) At the C10-position the axial morpholinomethyl conformation is preferred over the equatorial in order to relieve a steric interaction with the C2-methyl group. The preferred conformer as defined by the three key pharmacophores, naphthyl, morpholino, and 3-keto groups, shows that the morpholinyl ring of the molecule 1 deviates from the plane of the benzoxazine ring by about 32 degrees and orients in the left molecular quadrant. This model supports the hypothesis that a certain deviation of the morpholino group from the plane of the indole ring in compound 1 is essential for cannabimimetic activity. We postulate that such an alignment by the respective pharmacophores allows them to interact optimally with the receptor. The results should help us to better understand the pharmacophoric requirements of the AAIs and serve as a basis for future SAR studies and drug design. C1 Univ Connecticut, IMS, Sch Pharm, Dept Pharmaceut Sci, Storrs, CT 06269 USA. Univ Connecticut, Dept Cell & Mol Biol, Storrs, CT 06269 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Struct Biochem Program, Frederick, MD 21702 USA. RP Xie, XQ (reprint author), Univ Connecticut, IMS, Sch Pharm, Dept Pharmaceut Sci, U-136, Storrs, CT 06269 USA. FU NIDA NIH HHS [DA11510] NR 27 TC 16 Z9 17 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 7 PY 1999 VL 42 IS 20 BP 4021 EP 4027 DI 10.1021/jm980592k PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 244EV UT WOS:000083039600002 PM 10514272 ER PT J AU Zhang, SX Bastow, KF Tachibana, Y Kuo, SC Hamel, E Mauger, A Narayanan, VL Lee, KH AF Zhang, SX Bastow, KF Tachibana, Y Kuo, SC Hamel, E Mauger, A Narayanan, VL Lee, KH TI Antitumor agents. 196. Substituted 2-thienyl-1,8-naphthyridin-4-ones: Their synthesis, cytotoxicity, and inhibition of tubulin polymerization SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIMITOTIC NATURAL-PRODUCTS; BIOLOGICAL EVALUATION; ANALOGS; 2-PHENYL-4-QUINOLONES; IDENTIFICATION; COLCHICINE AB As part of our continuing search for potential anticancer drug candidates in the 2-aryl-1,8-naphthyridin-4-one series, we have synthesized a series of substituted 8-thienyl-1,8-naphthyridin-4-ones. Most compounds showed significant cytotoxic effects (log GI(50) < -4.0; log molar drug concentration required to cause 50% growth inhibition) against a variety of human tumor cell lines in the National Cancer Institute's in vitro screen, including cells derived from solid tumors such as non-small-cell lung, colon, central nervous system, melanoma, ovarian, prostate, and breast cancers. The most active compounds (31-33, 40) demonstrated strong cytotoxic effects with ED(50) values in the micromolar or submicromolar range in most of the tumor cell lines. The most cytotoxic compounds inhibited tubulin polymerization at concentrations substoichiometric to the tubulin concentration. The most potent inhibitors of polymerization (40, 42, 43) had effects comparable to those of the potent antimitotic natural products podophyllotoxin and combretastatin A-4 and to that of NSC 664171, a particularly potent, structurally related analogue. Only compound 40 was a potent inhibitor of the binding of radiolabeled colchicine to tubulin, and it was both the most cytotoxic agent and the most effective inhibitor of polymerization among the newly synthesized compounds. C1 Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. China Med Coll, Grad Inst Pharmaceut Chem, Taichung 400, Taiwan. NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Canc Res Ctr, Frederick, MD 21702 USA. NCI, Drug Synth & Chem Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. RP Lee, KH (reprint author), Univ N Carolina, Sch Pharm, Div Med Chem & Nat Prod, Nat Prod Lab, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [CA-17625] NR 31 TC 74 Z9 74 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 7 PY 1999 VL 42 IS 20 BP 4081 EP 4087 DI 10.1021/jm990208z PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 244EV UT WOS:000083039600008 PM 10514278 ER PT J AU Lee, J Kang, JH Lee, SY Han, KC Torres, CM Bhattacharyya, DK Blumberg, PM Marquez, VE AF Lee, J Kang, JH Lee, SY Han, KC Torres, CM Bhattacharyya, DK Blumberg, PM Marquez, VE TI Protein kinase C ligands based on tetrahydrofuran templates containing a new set of phorbol ester pharmacophores SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONFORMATIONALLY CONSTRAINED ANALOGS; GAMMA-BUTYROLACTONE SKELETON; RIGID DIACYLGLYCEROL ANALOGS; 5-DISUBSTITUTED TETRAHYDRO-2-FURANONE TEMPLATE; PK-C; TUMOR PROMOTERS; BINDING-AFFINITY; STRUCTURAL BASIS; SN-2 CARBONYLS; DELTA-LACTONES AB A series of substituted tetrahydrofurans with an embedded glycerol backbone carrying additional tetrahydrofuranylideneacetate or tetrahydrofuranylacetate motifs were grouped into four distinct templates (I-IV) according to stereochemistry. The compounds were designed to mimic three essential pharmacophores (C-3-C=O, C-20-OH and C-13-C=O) of the phorbol esters according to a new, revised model. The tetrahydrofuran ring was constructed from glycidyl 4-methoxyphenyl ether, and the structures of the isomeric templates were assigned by NMR spectroscopy, including NOE. The binding affinity for protein kinase C (PKC) was assessed in terms of the ability of the ligands to displace bound [H-3-20]phorbol 12,13-dibutyrate (PDBU) from a recombinant alpha isozyme of PKC. Geometric Z- and E-isomers (1 and 3, respectively) containing a tetrahydrofuranylideneacetate motif were the most potent ligands with identical K-i values of 0.35 mu M. Molecular modeling studies of the four templates showed that the rms values when fitted to a prototypical phorbol 12,13-diacetate ester correlated inversely with affinities in the following order: I approximate to II > III > TV. These compounds represent the first generation of rigid glycerol templates seeking to mimic the binding of the C-13-C=O of the phorbol esters. The binding affinities of the most potent compounds are in the same range of the diacylglycerols (DAGs) despite the lack of a phorbol ester C-9-OH pharmacophore surrogate. This finding confirms that mimicking the binding of the C-13-C=O pharmacophore of phorbol is a useful strategy. However, since the C-9-OH and C-13-C=O in the phorbol esters appear to form an intramolecular hydrogen bond that functions as a combined pharmacophore, it is possible the lack of this combined motif in the target templates restricts the compounds from reaching higher binding affinities. C1 Seoul Natl Univ, Coll Pharm, Med Chem Lab, Kwanak Ku, Seoul 151742, South Korea. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Med Chem Lab, Kwanak Ku, Seoul 151742, South Korea. NR 44 TC 11 Z9 11 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 7 PY 1999 VL 42 IS 20 BP 4129 EP 4139 DI 10.1021/jm980713g PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 244EV UT WOS:000083039600013 PM 10514283 ER PT J AU Kashiyama, E Hutchinson, I Chua, MS Stinson, SF Phillips, LR Kaur, G Sausville, EA Bradshaw, TD Westwell, AD Stevens, MFG AF Kashiyama, E Hutchinson, I Chua, MS Stinson, SF Phillips, LR Kaur, G Sausville, EA Bradshaw, TD Westwell, AD Stevens, MFG TI Antitumor benzothiazoles. 8. Synthesis, metabolic formation, and biological properties of the C- and N-oxidation products of antitumor 2-(4-aminophenyl)benzothiazoles SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CELL-LINE; PROTEIN AB 2-(4-Aminophenyl)benzothiazoles 1 and their N-acetylated forms have been converted to C- and N-hydroxylated derivatives to investigate the role of metabolic oxidation in the mode of action of this series of compounds. 2-(4-Amino-3-methylphenyl)benzothiazole (1a, DF 203, NSC 674495) is a novel and potent antitumor agent with selective growth inhibitory properties against human cancer cell lines. Very low IC50 values (<0.1 mu M) were encountered in the most sensitive breast cancer cell lines, MCF-7 and T-47D, whereas renal cell line TK-10 was weakly inhibited by la. Cell lines from the same tissue origin, MDA-MB-435 (breast), CAKI-1 (renal), and A498 (renal), were insensitive to 1a. Accumulation and metabolism of la were observed in sensitive cell lines only, with the highest rate of metabolism occurring in the most sensitive MCF-7 and T-47D cells. Thus, differential uptake and metabolism of 1a by cancer cell lines may underlie its selective profile of anticancer activity. A major metabolite in these sensitive cell lines has been identified as 2-(4-amino-3-methylphenyl)-6-hydroxybenzothiazole (6c). Hydroxylation of 1a was not detected in the homogenate of previously untreated MCF-7, T-47D, and TK-10 cells but was readily observed in homogenates of sensitive cells that were pretreated with 1a. Accumulation and covalent binding of [C-14]1a derived radioactivity was observed in the sensitive MCF-7 cell line but not in the insensitive MDA-MB-435 cell line. The mechanism of growth inhibition by 1a, which is unknown, may be dependent on the differential metabolism of the drug to an activated form by sensitive cell Lines only and its covalent binding to an intracellular protein. However, the 6-hydroxy derivative 6c is not the 'active' metabolite since, like all other C- and N-hydroxylated benzothiazoles examined in this study, it is devoid of antitumor properties in vitro. C1 Univ Nottingham, Sch Pharmaceut Sci, Canc Res Labs, Nottingham NG7 2RD, England. NCI, Pharmacol & Expt Therapeut Sect, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Div Canc Treatment & Diag, Frederick, MD 21701 USA. RP Stevens, MFG (reprint author), Univ Nottingham, Sch Pharmaceut Sci, Canc Res Labs, Nottingham NG7 2RD, England. RI Westwell, Andrew/M-8126-2014 OI Westwell, Andrew/0000-0002-5166-9236 NR 16 TC 208 Z9 216 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 7 PY 1999 VL 42 IS 20 BP 4172 EP 4184 DI 10.1021/jm990104o PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 244EV UT WOS:000083039600017 PM 10514287 ER PT J AU Xie, RY Li, AH Ji, XD Melman, N Olah, ME Stiles, GL Jacobson, KA AF Xie, RY Li, AH Ji, XD Melman, N Olah, ME Stiles, GL Jacobson, KA TI Selective A(3) adenosine receptor antagonists: Water-soluble 3,5-diacyl-1,2,4-trialkylpyridinium salts and their oxidative generation from dihydropyridine precursors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; RAT-BRAIN; BIOLOGICAL-MEMBRANES; IMPROVED DELIVERY; MAST-CELLS; DERIVATIVES; STIMULATION; LIGANDS; SYSTEM AB A(3) adenosine receptor antagonists are sought for their potential antiinflammatory, antiasthmatic, and antiischemic properties. We have found that 3,5-diacyl-1,2,4-trialkyl-6-phenylpyridinium derivatives constitute a novel class of selective A(3) adenosine receptor antagonists. The structure-activity relationships of this class of antagonists, incorporating the 3-thioester, have been explored. The most potent analogue in this group was 2,4-diethyl-1-methyl-3-(ethylsulfanylcarbonyl)-5-ethyloxycarbon-6-phenylpyridinium iodide (11), which had an equilibrium inhibition constant (K-i) value of 219 nM at human A(3) receptors (binding of [I-125]-AB-MECA (N-6-(4-amino-3-iodobenzyl)-5'-N-methylcarbamoyladenosine)) expressed in Chinese hamster ovary (CHO) cells and > 10 mu M at rat brain A(1) and A(2A) receptors and at recombinant human A(2B) receptors. Compound 11 could be generated through oxidation of the corresponding 3,5-diacyl-1,2,4-trialkyl-6-phenyl-1,4-dihydropyridine, 24, with iodine or in the presence of rat brain homogenates. A 6-cyclopentyl analogue was shown to increase affinity at human A(3) receptors upon oxidation from the 1-methyl-1,4-dihydropyridine analogue, 25, to the corresponding pyridinium derivative, 23 (K-i 695 nM), suggesting a prodrug scheme. Homologation of the M-methylpyridinium derivatives to N-ethyl and N-propyl at the 1-position caused a progressive reduction in the affinity at A(3) receptors. Modifications of the alkyl groups at the 2-, 3-, 4-, and 5-positions failed to improve potency in binding at A(3) receptors. The pyridinium antagonists are not as potent as other recently reported, selective A(3) receptor antagonists; however, they display uniquely high water solubility (43 mM for 11). Compound 11 antagonized the inhibition of adenylate cyclase elicited by IB-MECA in CHO cells expressing the human A(3) adenosine receptor, with a K-B value of 399 nM, and did not act as an agonist, demonstrating that the pyridinium salts are pure antagonists. C1 NIDDK, Mol Recognit Sec, LBC, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pharmacol, Durham, NC 27710 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sec, LBC, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 31 TC 11 Z9 11 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 7 PY 1999 VL 42 IS 20 BP 4232 EP 4238 DI 10.1021/jm990234x PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 244EV UT WOS:000083039600023 PM 10514293 ER PT J AU Walsh, TJ Arndt, C Dismukes, W AF Walsh, TJ Arndt, C Dismukes, W TI Liposomal amphotericin B for fever and neutropenia - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Alabama, Birmingham, AL 35294 USA. RP Walsh, TJ (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 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 OCT 7 PY 1999 VL 341 IS 15 BP 1154 EP 1155 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 245BW UT WOS:000083087200018 ER PT J AU Kuzmin, I Geil, L Ge, HY Bengtsson, U Duh, FM Stanbridge, EJ Lerman, MI AF Kuzmin, I Geil, L Ge, HY Bengtsson, U Duh, FM Stanbridge, EJ Lerman, MI TI Analysis of aberrant methylation of the VHL gene by transgenes, monochromosome transfer, and cell fusion SO ONCOGENE LA English DT Article DE VHL; methylation; tumor suppressor genes ID TUMOR-SUPPRESSOR GENE; PRADER-WILLI SYNDROMES; DNA METHYLATION; RENAL-CARCINOMA; CPG ISLAND; IMPRINTING DEFECTS; ANGELMAN-SYNDROME; MUTATIONS; IDENTIFICATION; CHROMOSOME AB Several tumor suppressor genes were shown to be inactivated by a process involving aberrant de novo methylation of their GC-rich promoters which is usually associated with transcriptional repression, The mechanisms underlying this process are poorly understood. In particular this abnormal methylation may be caused and/or maintained by either deficiency of some tl ails-acting factor(s) or by various malfunctions acting in cis, Here we studied the nature of aberrant methylation of the ron Hippel-Lindau (VHL) disease tumor suppressor gene in a human clear cell renal carcinoma cell line, UOK 121, that contains a silent hypermethylated endogenous VHL allele, First, we transfected unmethylated VHL transgenes, driven by the VHL promoter, into UOK 121 cells. Next, to exclude possible position effects that may influence methylation of the introduced VHL genes, we transferred a single chromosome 3, carrying an apparently normal hypomethylated VHL allele into the UOK 121 cells. Finally, ne created somatic cell hybrids between UOK 121 and UMRC 6 cells containing a mutant VHL-expressing hypomethylated allele, In these three experiments both the methylation of the VHL promoter and the transcriptional status of the introduced and endogenous VHL alleles remained unchanged. Our results demonstrate that the putative tr ans-acting factors present in the UOK 121 and UMRC 6 cells are unable to induce changes in methylation pattern of the VHL alleles in all cell lines and hybrids studied. Taken together, the results indicate that ris-specific local features are pivotal in maintaining and perpetuating aberrant methylation of the VHL CpG island. Contribution of some putative tr ans-acting factors cannot be excluded during a period when the aberrant VHL methylation pattern was first generated. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Kuzmin, I (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. FU NCI NIH HHS [CA19401, N01-CO-56000] NR 26 TC 18 Z9 21 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 7 PY 1999 VL 18 IS 41 BP 5672 EP 5679 DI 10.1038/sj.onc.1202959 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 243UW UT WOS:000083016500008 PM 10523847 ER PT J AU Takimoto, M Mao, PZ Wei, G Yamazaki, H Miura, T Johnson, AC Kuzumaki, N AF Takimoto, M Mao, PZ Wei, G Yamazaki, H Miura, T Johnson, AC Kuzumaki, N TI Molecular analysis of the GCF gene identifies revisions to the cDNA and amino acid sequences SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE GCF; revision; cDNA and amino acid sequences; transcription ID PROMOTER REGION; REPRESSES TRANSCRIPTION; BINDING FACTOR; CELL-LINES; RECEPTOR; CLONING; ORGANIZATION; EXPRESSION; SUBUNIT AB GC factor (GCF) was reported as a transcriptional regulator that binds to a specific GC-rich sequence in the epidermal growth factor receptor (EGFR) gene promoter and represses its expression. In this paper, we present the data on three revisions of the cDNA sequence that lead to significant changes of the amino acid sequences of the published GCF. Firstly, 5'-rapid amplification of cDNA end (5'-RACE) analysis revealed that the 308 nucleotides of 5'-end of the previously published GCF cDNA does not exist at the 5'-end of the RACE product. Simultaneously, the correct 5'-end cDNA sequence of 31 nucleotides was identified. Secondly, the 'T' at the position 787 of the published GCF cDNA was not observed. Finally, a new sequence of 114 nucleotides was identified between the positions 851 and 852 of the published cDNA sequence. The revisions result in a GCF cDNA of 2661 nucleotides that encodes a protein of 781 amino acids, replacing the highly basic region of the amino-terminus of the published GCF with a new sequence of 147 amino acids. In this era of massive gene cloning and sequencing, this study is a warning to the biological research of recent years. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Hokkaido Univ, Sch Med, Inst Canc, Div Gene Regulat,Kita Ku, Sapporo, Hokkaido 0608638, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Takimoto, M (reprint author), Hokkaido Univ, Sch Med, Inst Canc, Div Gene Regulat,Kita Ku, N15,W7, Sapporo, Hokkaido 0608638, Japan. RI Takimoto, Masato/D-9653-2012 NR 21 TC 10 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD OCT 6 PY 1999 VL 1447 IS 1 BP 125 EP 131 DI 10.1016/S0167-4781(99)00127-X PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 242AE UT WOS:000082915400016 PM 10500253 ER PT J AU Hayden, FG Treanor, JJ Fritz, RS Lobo, M Betts, RF Miller, M Kinnersley, N Mills, RG Ward, P Straus, SE AF Hayden, FG Treanor, JJ Fritz, RS Lobo, M Betts, RF Miller, M Kinnersley, N Mills, RG Ward, P Straus, SE TI Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza - Randomized controlled trials for prevention and treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GG167 4-GUANIDINO-2,4-DIDEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID; A VIRUS-INFECTION; SIALIC-ACID; EFFICACY; REPLICATION; AMANTADINE; SAFETY; MICE; HYDROCHLORIDE; PROPHYLAXIS AB Context Influenza virus neuraminidase is thought to be essential for virus replication in humans; however, to date, available neuraminidase inhibitors are limited to zanamivir, which is topically administered. Objective To determine the safety, tolerability, and antiviral activity of oral neuraminidase inhibitor oseltamivir (GS4104/Ro64-0796) for prevention and the early treatment of influenza in experimentally infected humans. Design Two randomized, double-blind, placebo-controlled trials conducted between June and July 1997. Setting Individual hotel rooms; 2 large US university medical schools. Participants A total of 117 healthy adult volunteers (aged 18-40 years; median age, 21 years) who were susceptible (hemagglutination-inhibition antibody titer less than or equal to 1:8). Interventions All subjects were inoculated intranasally with influenza A/Texas/36/91 (H1N1) virus. For the prophylaxis study, oral oseltamivir (100 mg once daily [n = 12], 100 mg twice daily [n = 12], or matching placebo [n = 13], starting 26 hours before virus inoculation) was administered. For the treatment study, the same drug was given (20 mg, 100 mg, or 200 mg twice daily, 200 mg once daily, or matching placebo [n = 16], in each group starting 28 hours after inoculation). All regimens were continued for 5 days. Main Outcome Measures Comparing placebo groups with pooled treatment groups, for prophylaxis, outcomes included frequency of infection and viral shedding; for treatment, viral shedding in titers. Results In the prophylaxis study, 8 (67%) of 12 placebo and 8 (38%) of 21 oseltamivir recipients became infected (P = .16; efficacy, 61%); 6 (50%) placebo compared with 0 oseltamivir recipients shed virus (P<.001; efficacy, 100%), and 33% of placebo but no oseltamivir recipient had infection-related respiratory illness (P<.01). Among infected subjects in the treatment study (n = 69), the viral titer area under the curve of the combined oseltamivir groups (n = 56) was lower (median [interquartile range {IQR}], 80 [23-151] vs 273 [79-306] log(10) tissue culture-infective doses(50) per milliliter x hour; P = .02) than the placebo group (n = 13), and the median (IQR) duration of viral shedding with therapy was reduced from 107 (83-131) to 58 (35-59) hours (P = .003). Oseltamivir treatment also reduced symptom scores (median [IQR] score-hours, 225 [97-349] vs 400 [189-645]; P = .05), and nasal proinflammatory cytokine levels. Transient mild to moderate nausea after dosing was observed in 15 (17%) of 88 oseltamivir and 2 (7%) of 29 placebo recipients (95% confidence interval for difference, -11% to 68%), which was largely prevented by ingestion with food. Conclusions In these trials, prophylaxis and early treatment with oral oseltamivir were both associated with significant antiviral and clinical effects in experimental human influenza. C1 Univ Virginia, Hlth Sci Ctr, Sch Med, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Rochester, Sch Med, Rochester, NY USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Gilead Sci Inc, Foster City, CA 94404 USA. Roche Discovery Welwyn Hoffman LaRoche & Co, Welwyn Garden City, Herts, England. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. RP Hayden, FG (reprint author), Univ Virginia, Hlth Sci Ctr, Sch Med, Dept Internal Med, Box 473, Charlottesville, VA 22908 USA. FU NCI NIH HHS [N01-CO-56000] NR 39 TC 355 Z9 374 U1 3 U2 21 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 OCT 6 PY 1999 VL 282 IS 13 BP 1240 EP 1246 DI 10.1001/jama.282.13.1240 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 241UM UT WOS:000082901100031 PM 10517426 ER PT J AU Clore, GM Garrett, DS AF Clore, GM Garrett, DS TI R-factor, free R, and complete cross-validation for dipolar coupling refinement of NMR structures SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; MACROMOLECULAR STRUCTURES; ORIENTED MACROMOLECULES; PROTEIN; MAGNITUDE; DISTANCES; QUALITY; PHASE AB NMR structure determination of macromolecules involves a minimization problem in which atomic models, subject to restraints relating to idealized covalent geometry and nonbonded contacts, are fitted to experimental observables. The latter comprise restraints between atoms separated by less than or equal to 6 Angstrom, such as NOE-derived interproton distances, torsion angles, coupling constants, and chemical shifts, as well as restraints that provide direct information on long-range order such as dipolar couplings. An expression for the dipolar coupling R-factor is derived which provides a quantitative and readily interpretable measure of the agreement between observed and calculated dipolar couplings. The dipolar R-factor expresses the ratio of the observed rms difference between observed and calculated values with that expected for a totally random distribution of vectors. The latter can be calculated exactly from the magnitude of the alignment tensor. The dipolar R-factor scales between 0 and 1, where a value of 0 indicates perfect agreement between observed and calculated dipolar couplings, and a completely random structure yields a value of 1. The dipolar coupling R-factor is readily amenable to complete cross-validation, with multiple pairs of working and test data sets, thereby permitting one to assess the quality of the fit to the experimental dipolar couplings and to avoid overfitting the experimental data. The application of the dipolar R-factor with complete cross-validation is demonstrated using experimental data for the protein cyanovirin-N. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 27 TC 200 Z9 203 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 6 PY 1999 VL 121 IS 39 BP 9008 EP 9012 DI 10.1021/ja991789k PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 243QX UT WOS:000083009700006 ER PT J AU Bernstein, L Deapen, D Cerhan, JR Schwartz, SM Liff, J McGann-Maloney, E Perlman, JA Ford, L AF Bernstein, L Deapen, D Cerhan, JR Schwartz, SM Liff, J McGann-Maloney, E Perlman, JA Ford, L TI Tamoxifen therapy for breast cancer and endometrial cancer risk SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HORMONE-BINDING GLOBULIN; SURGICAL-ADJUVANT-BREAST; NORMAL PREMENOPAUSAL; PREVENTION; WOMEN; TRIAL; ADENOCARCINOMA; ESTRADIOL AB Background: Tamoxifen is effective in treating breast cancer, reduces breast cancer incidence among high-risk women, and is associated with increased endometrial cancer risk, This study was designed to examine the possible modifying effects of endometrial cancer risk factors on the tamoxifen-endometrial cancer association. Methods: We conducted a case-control study of endometrial cancer (324 case patients and 671 individually matched control subjects) nested within a population-based cohort of patients with breast cancer diagnosed from 1978 through 1992 within four regions of the United States. We obtained information on breast cancer treatment and endometrial cancer risk factors through interviews and reviews of medical records. All P values reported are two-sided. Results: Endometrial cancer risk was associated with tamoxifen therapy for breast cancer (odds ratio = 1.52; 95% confidence interval [CI] = 1.07-2.17). Risk increased with duration of tamoxifen use (P for trend =.0002), Women with more than 5 years of exposure to tamoxifen had 4.06-fold greater odds of developing endometrial cancer than nonusers (95% CI = 1.74-9.47). Prior use of estrogen replacement therapy (ERT) increased risk associated with tamoxifen use (P for homogeneity of trends <.0001), Risk associated with tamoxifen use was stronger among heavier women than among thinner women, although trends did not differ statistically (P =.10). Tamoxifen dose-response effects were more pronounced among women with both previous ERT exposure and higher body mass index than among women in other risk groups, Conclusions: ERT use and obesity, both established endometrial cancer risk factors and markers of estrogen exposure, substantially modify the association between tamoxifen use and endometrial cancer risk among patients with breast cancer. Women with positive ERT histories and those who are obese, when prescribed tamoxifen, may warrant closer surveillance for endometrial cancer than women without such histories. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA. US Publ Hlth Serv, Washington, DC USA. Epimedix, Washington, DC USA. NCI, Div Canc Prevent, Bethesda, MD USA. RP Bernstein, L (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,MS 44, Los Angeles, CA 90033 USA. NR 35 TC 190 Z9 191 U1 0 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 OCT 6 PY 1999 VL 91 IS 19 BP 1654 EP 1662 DI 10.1093/jnci/91.19.1654 PG 9 WC Oncology SC Oncology GA 242GP UT WOS:000082932400013 PM 10511593 ER PT J AU Mitsiades, N Poulaki, V Leone, A Tsokos, M AF Mitsiades, N Poulaki, V Leone, A Tsokos, M TI Fas-mediated apoptosis in Ewing's sarcoma cell lines by metalloproteinase inhibitors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OVARIAN-CARCINOMA XENOGRAFTS; SOLUBLE FORM; MATRIX METALLOPROTEINASES; DOWN-REGULATION; IN-VIVO; PANCREATIC-CANCER; LIGAND EXPRESSION; MOLECULAR-CLONING; INTERFERON-GAMMA; IMMUNE PRIVILEGE AB Background: Fas ligand (FasL) is a transmembrane protein that induces apoptosis (programmed cell death) in susceptible cells by interacting with its receptor, Fas. Transmembrane Fast is cleaved by a metalloproteinase enzyme into a soluble form that is released into the extracellular medium. Tumors of the Ewing's sarcoma family express functional transmembrane Fast and release soluble Fast. This cleavage is inhibited by a matrix metalloproteinase inhibitor (MMPI). We therefore hypothesized that MMPIs can lead to apoptosis of tumor cells by inducing accumulation of transmembrane FasL. Methods: Ewing's sarcoma and neuroblastoma cell lines were treated with two synthetic MMPIs (BB-3103 and A-151011) and examined for apoptosis and expression of FasL and Fas, Results: Although MMPIs increase levels of FasL and Fas proteins on the surface of all tumor cells studied, they induced apoptosis in Fas-sensitive but not in Fas-resistant cell lines; the induction of apoptosis was inhibited by a Fas-neutralizing antibody. The increase in protein expression was not associated with enhanced transcription. Treatment with an MMPI sensitized the Ewing's sarcoma cells to Fas-activating antibody and to doxorubicin-induced apoptosis. Conclusions: MMPIs cause accumulation of transmembrane FasL by inhibiting its cleavage, accumulation of Fas (probably secondarily to FasL cleavage inhibition), and decreased levels of soluble FasL. These effects lead to apoptosis in Fas-sensitive cell lines. The observed cooperative action of MMPIs and doxorubicin suggests a possible role of MMPIs in combination treatments with standard apoptosis-inducing chemotherapeutic agents. C1 NCI, Pathol Lab, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Mitsiades, N (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, 149 13th St,7th Floor, Charlestown, MA 02129 USA. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 57 TC 42 Z9 42 U1 2 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 OCT 6 PY 1999 VL 91 IS 19 BP 1678 EP 1684 DI 10.1093/jnci/91.19.1678 PG 7 WC Oncology SC Oncology GA 242GP UT WOS:000082932400016 PM 10511596 ER PT J AU Shen, T Vortmeyer, AO Zhuang, ZP Tavassoli, FA AF Shen, T Vortmeyer, AO Zhuang, ZP Tavassoli, FA TI High frequency of allelic loss of BRCA2 gene in pregnancy-associated breast carcinoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID HETEROZYGOSITY; CANCER; WOMEN C1 Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Shen, T (reprint author), Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, 14th St & Alaska Ave NW, Washington, DC 20306 USA. NR 7 TC 18 Z9 19 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 OCT 6 PY 1999 VL 91 IS 19 BP 1686 EP 1687 DI 10.1093/jnci/91.19.1686 PG 2 WC Oncology SC Oncology GA 242GP UT WOS:000082932400019 PM 10511599 ER PT J AU Huff, J Waalkes, M Nyska, A Chan, P AF Huff, J Waalkes, M Nyska, A Chan, P TI Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NIEHS, Div Intramural Res, Res Triangle Pk, NC 27709 USA. NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. RP Huff, J (reprint author), NIEHS, Div Intramural Res, POB 12233, Res Triangle Pk, NC 27709 USA. NR 7 TC 12 Z9 12 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 6 PY 1999 VL 91 IS 19 BP 1690 EP 1691 DI 10.1093/jnci/91.19.1690 PG 2 WC Oncology SC Oncology GA 242GP UT WOS:000082932400023 PM 10511603 ER PT J AU Dosemeci, A Reese, TS Petersen, JD Choi, C Beushausen, S AF Dosemeci, A Reese, TS Petersen, JD Choi, C Beushausen, S TI Localization of the linker domain of Ca2+/calmodulin-dependent protein kinase II SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE CaMKII; CaM kinase II; calmodulin-dependent; protein kinase; molecular shadowing ID MULTIFUNCTIONAL CAM KINASE; CALMODULIN-BINDING; CA-2+ CALMODULIN; AUTOPHOSPHORYLATION; ALPHA; EXPRESSION AB Electron micrographs of rotary shadowed replicas of alpha-Ca2+/calmodulin-dependent protein kinase II reveal a flower-shaped multimeric molecule with a central particle surrounded by 8-10 smaller peripheral particles. Peripheral particles are attached to the central particle by thin arms or "linkers." Movement of peripheral particles to contact each other for autophosphorylation is likely to involve these linkers. It has generally been accepted that the segment 317-328 of the alpha-subunit constitutes the linker domain. In the present study we test this assumption by generating a mutant lacking the proposed sequence. The mutant has biochemical and morphological properties similar to those of the wild type, and a thin linker is occasionally observed in replicas from either type. The results indicate that the deleted sequence does not correspond to the linker domain. This conclusion, combined with observations from two recent studies which identify the C-terminal domain involved in oligomerization, narrows down the location of the linker domain within the sequence 330-354. (C) 1999 Academic Press. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Dosemeci, A (reprint author), NINDS, Neurobiol Lab, NIH, Bldg 36,2A21, Bethesda, MD 20892 USA. OI Petersen, Jennifer/0000-0003-1107-8535 NR 14 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 5 PY 1999 VL 263 IS 3 BP 657 EP 662 DI 10.1006/bbrc.1999.1433 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 243VL UT WOS:000083018100011 PM 10512734 ER PT J AU Milstien, S Katusic, Z AF Milstien, S Katusic, Z TI Oxidation of tetrahydrobiopterin by peroxynitrite: Implications for vascular endothelial function SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE SYNTHASE; PHENYLALANINE HYDROXYLASE; SUPEROXIDE GENERATION; CHEMISTRY AB Subsaturating levels of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase (NOS), can lead to endothelial dysfunction as a result of decreased production of nitric oxide. Furthermore, insufficient BH4 can also result in NOS-uncoupled production of reactive oxygen intermediates, such as superoxide anion and hydrogen peroxide. Nitric oxide and superoxide react rapidly to form peroxynitrite, which may be the reactive species responsible for many of the toxic effects of nitric oxide, Here we show that BH4 is a primary target for peroxynitrite-catalyzed oxidation because at pH 7.4, physiologically relevant concentrations of HH, are oxidized rapidly by low concentrations of peroxynitrite. Peroxynitrite oxidizes BH4 to quinonoid 5,6-dihydrobiopterin and a large proportion of the quinonoid isomer readily loses its side chain to form 7,8-dihydropterin which is not a cofactor for nitric oxide synthase, Thus, abnormally low levels of BH4 can promote a cycle of its own destruction mediated by nitric oxide synthase-dependent formation of peroxynitrite, This mechanism might contribute to vascular endothelial dysfunction induced by oxidative stress, (C) 1999 Academic Press. C1 NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Anesthesiol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Pharmacol, Rochester, MN 55905 USA. RP Milstien, S (reprint author), NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [HL-53542] NR 24 TC 308 Z9 318 U1 1 U2 6 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 OCT 5 PY 1999 VL 263 IS 3 BP 681 EP 684 DI 10.1006/bbrc.1999.1422 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 243VL UT WOS:000083018100016 PM 10512739 ER PT J AU Wada, A Mori, N Oishi, K Hojo, H Nakahara, Y Hamanaka, Y Nagashima, M Sekine, I Ogushi, K Niidome, T Nagatake, T Moss, J Hirayama, T AF Wada, A Mori, N Oishi, K Hojo, H Nakahara, Y Hamanaka, Y Nagashima, M Sekine, I Ogushi, K Niidome, T Nagatake, T Moss, J Hirayama, T TI Induction of human beta-defensin-2 mRNA expression by Helicobacter pylori in human gastric cell line MKN45 cells on cag Pathogenicity Island SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ANTIMICROBIAL PEPTIDE GENE; EPITHELIAL-CELLS; VACUOLATING CYTOTOXIN; VIRULENCE FACTORS; BETA-DEFENSIN; PANETH CELLS; UREASE; SYSTEM; HBD-1; LUNG AB Helicobacter pylori is an etiological agent of gastritis, peptic ulcer, and gastric cancer. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide which belongs to one of the most important host defense systems against bacterial infection in several epithelial tissues. We studied the effect of H. pylori on the expression of hBD-2 mRNA in MKN45 gastric mucosal cells. H. pylori, but not culture filtrate, increased the hBD-2 mRNA level in MKN45 cells; the inductive effect of H. pylori was not detected with Intestine 407 cells. Among H. pylori strains, strain OHPC0002, which lacks a cag Pathogenicity Island (PAI), did not induce hBD-2 mRNA in MKN45 cells. These results suggested that H; pylori cag PAI is critical for the induction of hBD-2 mRNA in MKN45 cells. Exposure of MKN45 cells to Salmonella typhimurium, S. enteritidis, S. typhi, and S. dublin, but not Escherichia coli ML35, also resulted in induction of hBD-2 mRNA. (C) 1999 Academic Press. C1 Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. Nagasaki Univ, Inst Trop Med, Dept Internal Med, Nagasaki 8528523, Japan. Tokai Univ, Dept Ind Chem, Hiratsuka, Kanagawa 2591292, Japan. Nagasaki Univ, Sch Med, Dept Mol Pathol, Atom Bomb Dis Inst, Nagasaki 8528523, Japan. Nagasaki Univ, Sch Med, Fac Engn, Dept Appl Chem, Nagasaki 8528523, Japan. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 8528523, Japan. RI Niidome, Takuro/F-1508-2010 OI Niidome, Takuro/0000-0002-8070-8708 NR 27 TC 55 Z9 59 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 5 PY 1999 VL 263 IS 3 BP 770 EP 774 DI 10.1006/bbrc.1999.1452 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 243VL UT WOS:000083018100032 PM 10512755 ER PT J AU Imhof, A Wolffe, AP AF Imhof, A Wolffe, AP TI Purification and properties of the Xenopus Hat1 acetyltransferase: Association with the 14-3-3 proteins in the oocyte nucleus SO BIOCHEMISTRY LA English DT Article ID LINKING HISTONE ACETYLATION; NEWLY REPLICATED CHROMATIN; NEWLY SYNTHESIZED HISTONES; CRUCIFORM BINDING-PROTEIN; ASSEMBLY FACTOR-I; DNA-REPLICATION; TRANSCRIPTION COMPLEX; SIGNALING PROTEINS; EGG EXTRACTS; NEGATIVE REGULATOR AB We have purified the Xenopus histone acetyltransferase Hat1 holoenzyme from oocytes. The holoenzyme contains the catalytic subunit Hat1, the retinoblastoma associated protein RbAp48, and members of the phosphoserine binding family of 14-3-3 proteins. We have determined that the Hat1 holoenzyme specifically acetylates free histone H4 but not nucleosomal histones. RbAp48 is a phosphoprotein that contains a consensus recognition motif for the 14-3-3 proteins. The 14-3-3 proteins provide a regulatory function for the activity of many phosphoproteins. We find that the hugely abundant Hat1 holoenzyme is present in 10 000-fold excess over somatic cell levels. The holoenzyme is localized in the oocyte nucleus where acetylated histones are stored. The oocyte form of the Xenopus Hat1 holoenzyme may represent a specialized storage form of histone acetyltransferase. Following oocyte maturation and subsequent embryogenesis, the Hat1 enzyme is redistributed to the cytoplasm, where new histones are synthesized. 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 92 TC 47 Z9 48 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 5 PY 1999 VL 38 IS 40 BP 13085 EP 13093 DI 10.1021/bi9912490 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244CF UT WOS:000083033700014 PM 10529179 ER PT J AU Jin, AJ Edidin, M Nossal, R Gershfeld, NL AF Jin, AJ Edidin, M Nossal, R Gershfeld, NL TI A singular state of membrane lipids at cell growth temperatures SO BIOCHEMISTRY LA English DT Article ID PHOSPHOLIPID SURFACE BILAYERS; AIR-WATER-INTERFACE; DIFFUSION; PROTEINS AB Cells adjust their membrane lipid composition when they adapt to grow at different temperatures. The consequences of this adjustment for membrane properties and functions are not well understood. Our report shows that the temperature dependence of the diffusion of a probe molecule in multilayers formed from total lipid extracts of E. coli has an anomalous maximum at a temperature corresponding to the growth temperature of each bacterial preparation (25, 29, and 32 degrees C). This increase in the lateral diffusion coefficient, D, is characteristic of membrane lipids in a critical state, for which large fluctuations of molecular area in the plane of the bilayer are expected. Therefore, changes in lipid composition may be due to a requirement that cells maintain their membranes in a state where molecular interactions and reaction rates are readily modulated by small, local perturbations of membrane organization. C1 NIAMSD, Phys Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Gershfeld, NL (reprint author), NIAMSD, Phys Biol Lab, NIH, Bldg 6,Room 139, Bethesda, MD 20892 USA. EM ngo@cu.nih.gov OI Jin, Albert/0000-0003-3826-1081 FU NIAID NIH HHS [AI14584] NR 24 TC 21 Z9 21 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 5 PY 1999 VL 38 IS 40 BP 13275 EP 13278 DI 10.1021/bi9912084 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 244CF UT WOS:000083033700036 PM 10529201 ER PT J AU Zhou, YF Shou, M Guetta, E Guzman, R Unger, EF Yu, ZX Zhang, J Finkel, T Epstein, SE AF Zhou, YF Shou, M Guetta, E Guzman, R Unger, EF Yu, ZX Zhang, J Finkel, T Epstein, SE TI Cytomegalovirus infection of rats increases the neointimal response to vascular injury without consistent evidence of direct infection of the vascular wall SO CIRCULATION LA English DT Article DE viruses; balloon; restenosis; atherosclerosis; cytokines ID SMOOTH-MUSCLE CELLS; IMMEDIATE-EARLY GENES; MESSENGER-RNA EXPRESSION; ENDOTHELIAL-CELLS; AORTIC ALLOGRAFTS; VIRAL-INFECTION; POTENTIAL ROLE; GROWTH-FACTOR; PROLIFERATION; VIRUS AB Background-Previous studies suggest that infection may play a role in restenosis and atherogenesis; cytomegalovirus (CMV) is one of the implicated pathogens. To determine a potential causal role of CMV in these disease processes, we assessed whether CMV infection increases the neointimal response to injury of the rat carotid artery. Methods and Results-Carotid injury was performed on 60 rats; immediately thereafter, 30 rats were infected with rat CMV, and the other 30 were mock-infected. Six weeks later, rats were euthanized, and the salivary glands, spleen, and carotid arteries were harvested. CMV infection was associated with significant exacerbation of the neointimal response to injury (neointimal to medial ratio 0.81 +/- 0.59 versus 0.31 +/- 0.38 in CMV-infected versus control rats; P<0.0001). This occurred despite absence of infectious virus from vascular tissues and detection of CMV DNA by polymerase chain reaction in the injured artery only at day 3 after infection. Persistent distant infection, associated with systemic cytokine response, was evidenced by isolation of infectious virus from homogenates of both salivary glands and spleen and by higher serum levels of interleukin (IL)-2 and IL-4 (but not interferon-gamma and tumor necrosis factor-alpha) in infected versus noninfected rats. Conclusions-CMV infection of immunocompetent adult rats increases the neointimal response to vascular injury, suggesting that CMV may play a causal role in atherosclerosis/restenosis. Importantly, this CMV-induced response occurs even without the presence of virus in the vascular wall, suggesting that inflammatory and immune responses to infection of nonvascular tissues may contribute to the vascular response to injury. C1 Washington Hosp Ctr, Cardiovasc Res Fdn, Washington, DC 20010 USA. NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Ctr Clin, Bethesda, MD 20892 USA. RP Zhou, YF (reprint author), Washington Hosp Ctr, Cardiovasc Res Fdn, Suite 4B-1,110 Irving St, Washington, DC 20010 USA. NR 39 TC 60 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 5 PY 1999 VL 100 IS 14 BP 1569 EP 1575 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 244ZG UT WOS:000083080200013 PM 10510062 ER PT J AU Imafuku, I Masaki, T Waragai, M Takeuchi, S Kawabata, M Hirai, SI Ohno, S Nee, LE Lippa, CF Kanazawa, I Imagawa, M Okazawa, H AF Imafuku, I Masaki, T Waragai, M Takeuchi, S Kawabata, M Hirai, SI Ohno, S Nee, LE Lippa, CF Kanazawa, I Imagawa, M Okazawa, H TI Presenilin 1 suppresses the function of c-jun homodimers via interaction with QM/Jif-1 SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Alzheimer's disease; presenilin-1; c-jun; cell death; QM/Jif-1 ID EMBRYONAL CARCINOMA-CELLS; ALZHEIMERS-DISEASE; TRANSCRIPTION FACTOR; BINDING PROTEIN; INDUCED APOPTOSIS; TUMOR-SUPPRESSOR; EXPRESSION; BRAIN; DEATH; MICE AB Presenilin 1 (PS1) is the causative gene for an autosomal dominant familial Alzheimer's disease (AD)mapped to chromosome 14. Here we show that QM/Jun-interacting factor (Jif)-1, a negative regulator of c-Jun, is a candidate to mediate the function of PSI in the cell. We screened for proteins that bind to PS1 from a human embryonic brain cDNA library using the two-hybrid method and isolated one clone encoding the QM/Jif-1 gene. The binding of QM/Jif-1 to full-length PS1 was confirmed in vitro by pull-down assay, and in vivo by immunoprecipitation assays with human samples, including AD brains. Immunoelectronmicroscopic analysis showed that QM/Jif-1 and PS1 are colocalized at the endoplasmic reticulum, and the nuclear matrix in human brain neurons. Chloramphenicol acetyltransferase assays in F9 cells showed that PS1 suppresses transactivation by c-Jun/c-Jun but not by c-Jun/c-Fos heterodimers, consistent with the reported function of QM/Jif-1. By monitoring fluorescent recombinant protein and by gel mobility shift assays, PS1 was shown to accelerate the translocation of QM from the cytoplasm to the nucleus and to thereby suppress the binding of c-Jun homodimer to 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive element (TRE). PSI suppressed c-jun-associated apoptosis by retinoic acid in F9 embryonic carcinoma cells, whereas this suppression of apoptosis is attenuated by mutation in PS1. Collectively, the novel function of PS1 via QM/Jif-1 influences c-jun-mediated transcription and apoptosis. C1 Univ Tokyo, Grad Sch Med, Dept Neurol, Tokyo 1138655, Japan. Natl Def Med Coll, Dept Internal Med 3, Tokorozawa, Saitama 3598513, Japan. Japanese Fdn Canc Res, Inst Canc, Dept Biochem, Tokyo 1700012, Japan. Yokohama City Univ, Sch Med, Dept Biol Mol, Yokohama, Kanagawa 236, Japan. NINDS, Family Studies Unit, NIH, Bethesda, MD 20892 USA. Med Coll Penn & Hahnemann Univ, Dept Neurol, Philadelphia, PA 19129 USA. Osaka Univ, Grad Sch Pharmaceut Sci, Lab Environm Bioichem, Osaka 5650871, Japan. RP Okazawa, H (reprint author), Univ Tokyo, Fac Med, Dept Neurol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 113, Japan. RI Ohno, Shigeo/B-1768-2010 OI Ohno, Shigeo/0000-0002-1294-5269 NR 56 TC 57 Z9 57 U1 0 U2 0 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 OCT 4 PY 1999 VL 147 IS 1 BP 121 EP 133 DI 10.1083/jcb.147.1.121 PG 13 WC Cell Biology SC Cell Biology GA 242QW UT WOS:000082953900012 PM 10508860 ER PT J AU Perlmutter, SJ Leitman, SF Garvey, MA Hamburger, S Feldman, E Leonard, HL Swedo, SE AF Perlmutter, SJ Leitman, SF Garvey, MA Hamburger, S Feldman, E Leonard, HL Swedo, SE TI Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood SO LANCET LA English DT Article ID AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS; TOURETTE-SYNDROME; RHEUMATIC-FEVER; CHILDREN; ANTIBODIES; ADOLESCENTS; RELIABILITY; VALIDITY; CHOREA; SCALE AB Background In children, exacerbations of ties and obsessive symptoms may occur after infection with group A P-haemolytic streptococci. If post-streptococcal autoimmunity is the cause of the exacerbations, then children might respond to immunomodulatory treatments such as plasma exchange or intravenous immunoglobulin (IVIG), We studied whether plasma exchange or IVIG would be better than placebo (sham IVIG) in reducing severity of neuropsychiatric symptoms. Methods Children with severe, infection-triggered exacerbations of obsessive-compulsive disorder (OCD) or tic disorders, including Tourette syndrome, were randomly assigned treatment with plasma exchange (five single-volume exchanges over 2 weeks), IVIG (1 g/kg daily on 2 consecutive days), or placebo (saline solution given in the same manner as IVIG), Symptom severity was rated at baseline, and at 1 month and 12 months after treatment by use of standard assessment scales for OCD, ties, anxiety, depression, and global function. Findings 30 children entered the study and 29 completed the trial. Ten received plasma exchange, nine IVIG, and ten placebo. At 1 month, the IVIG and plasma-exchange groups showed striking improvements in obsessive-compulsive symptoms (mean improvement on children's Yale-Brown obsessive compulsive scale score of 12 [45%] and 13 [58%], respectively), anxiety (2.1 [31%] and 3.0 [47%] improvement on National Institute of Mental Health anxiety scale), and overall functioning(2.9 [33%] and 2.8 [35%] improvement on National Institute of Mental Health global scale). Tic symptoms were also significantly improved by plasma exchange (mean change on Tourette syndrome unified rating scale of 49%). Treatment gains were maintained at 1 year, with 14 (82%) of 17 children "much' or "very much" improved over baseline (seven of eight for plasma exchange, seven of nine for IVIG), Interpretation Plasma exchange and IVIG were both effective in lessening of symptom severity for children with infection-triggered OCD and tic disorders. Further studies are needed to determine the active mechanism of these interventions, and to determine which children with OCD and tic disorders will benefit from immunomodulatory therapies. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD USA. NIMH, Child Psychiat Branch, Bethesda, MD USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), 10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA. NR 29 TC 286 Z9 297 U1 5 U2 8 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 2 PY 1999 VL 354 IS 9185 BP 1153 EP 1158 DI 10.1016/S0140-6736(98)12297-3 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 242QX UT WOS:000082954100010 PM 10513708 ER PT J AU Dignam, J Fisher, B AF Dignam, J Fisher, B TI Tamoxifen for intraductal cancer - Reply SO LANCET LA English DT Letter C1 Four Allegheny Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Four Allegheny Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 2 PY 1999 VL 354 IS 9185 BP 1211 EP 1212 DI 10.1016/S0140-6736(05)75422-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 242QX UT WOS:000082954100062 ER PT J AU Pinn, VW AF Pinn, VW TI Women's health research: Progress and future directions SO ACADEMIC MEDICINE LA English DT Editorial Material C1 NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 1999 VL 74 IS 10 BP 1104 EP 1105 DI 10.1097/00001888-199910000-00013 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 248QU UT WOS:000083287500021 PM 10536632 ER PT J AU Nodine, CF Kundel, HL Mello-Thoms, C Weinstein, SP Orel, SG Sullivan, DC Conant, EF AF Nodine, CF Kundel, HL Mello-Thoms, C Weinstein, SP Orel, SG Sullivan, DC Conant, EF TI How experience and training influence mammography expertise SO ACADEMIC RADIOLOGY LA English DT Article DE breast radiography; education; radiology and radiologists ID PERFORMANCE; SEARCH; VARIABILITY; PERCEPTION; CHESS; TIME AB Rationale and Objectives. The authors evaluated the influence of perceptual and cognitive skills in mammography detection and interpretation by testing three groups representing different levels of mammography expertise in terms of experience, training, and talent with a mammography screening-diagnostic task. Materials and Methods. One hundred fifty mammograms, composed of unilateral cranial-caudal and mediolateral oblique views, were displayed in pairs on a digital workstation to 19 radiology residents, three experienced mammographers, and nine mammography technologists. One-third of the mammograms showed malignant lesions; two-thirds were malignancy-free. Observers interacted with the display to indicate whether each image contained no malignant lesions or suspicious lesions indicating malignancy. Decision time was measured as the lesions were localized, classified, and rated for decision confidence. Results. Compared with performance of experts, alternative free response operating characteristic performance for residents was significantly lower and equivalent to that of technologists. Analysis of overall performance showed that, as level of expertise decreased, false-positive results exerted a greater effect on overall decision accuracy over the time course of image perception. This defines the decision speed-accuracy relationship that characterizes mammography expertise. Conclusion. Differences in resident performance resulted primarily from lack of perceptual-learning experience during mammography training, which limited object recognition skills and made it difficult to determine differences between malignant lesions, benign lesions, and normal image perturbations. A proposed solution is systematic mentor-guided training that links image perception to feedback about the reasons underlying decision making. C1 Univ Penn, Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. NCI, Rockville, MD USA. RP Nodine, CF (reprint author), Univ Penn, Sch Med, Dept Radiol, 308 Stemmler Hall,36th & Hamilton Walk, Philadelphia, PA 19104 USA. OI Weinstein, Susan/0000-0001-6159-1500 NR 21 TC 94 Z9 95 U1 0 U2 7 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 1999 VL 6 IS 10 BP 575 EP 585 DI 10.1016/S1076-6332(99)80252-9 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296PW UT WOS:000086033700004 PM 10516859 ER PT J AU Gracely, RH AF Gracely, RH TI Pain measurement SO ACTA ANAESTHESIOLOGICA SCANDINAVICA LA English DT Article; Proceedings Paper CT 2nd International Copenhagen Pain Symposium - Aspects of Chronic Pain CY 1999 CL COPENHAGEN, DENMARK SP DuraScan, Jansen-Cilag, Lundbeck Pharma, Meda, Knoll, Norpharma, Nycomed Denmark, Pharmacia & Upjohn, Searle Scandinavia, Acta Anaesthesiol Scandinavica, Danish Can Soc DE nociceptors; A beta fibers; central sensitization; supraspinal pain processing ID POSITRON-EMISSION-TOMOGRAPHY; QUANTITATIVE SENSORY EXAMINATION; CEREBRAL EVOKED-POTENTIALS; ELECTRICAL SOURCE ANALYSIS; HUMAN CINGULATE CORTEX; NOXIOUS HEAT STIMULI; SECONDARY HYPERALGESIA; CO2-LASER STIMULATION; EPIDURAL-ANESTHESIA; NERVE-STIMULATION AB Increasing evidence from laboratory methods in humans and animals indicates that pain arises from, and is modulated by, a number of mechanisms. In addition, these mechanisms are not static but change as pain persists. Recent human studies have demonstrated new aspects of pain processing at all levels of the central nervous system. Studies of the influence of analgesic agents on a large number of experimental pain measures have shown a preferential effect of opioids for attenuating the central integration of prolonged stimuli while local anesthetics may be more effective for brief stimulation. Studies of NK1 antagonists in man have shown results similar to those found with animals. There is little effect on brief stimulation of A delta and C-fiber nociceptors, including conditions Mat can evoke central summation. However, these antagonists, which block Me effects of substance P, are effective in more persistent states such as postsurgical pain. Persistent pain can also alter the function of the large diameter A beta touch afferents, ranging from increased tactile sensitivity in inflammatory conditions to frank allodynia following nerve injury or focal nociceptor stimulation. Recent advances in evaluation of supraspinal pain processing in humans have demonstrated pain-related activation using both methods that assess synchronized neural activity and methods that infer this activity in the whole brain by local changes in regional cerebral blood flow. These methods have begun to identify brain regions associated with the multiple dimensions and processing of painful stimulation and the modulation of these processes by pharmacological agents and non-pharmacological interventions. C1 NIH, Bethesda, MD 20892 USA. RP Gracely, RH (reprint author), NIH, Bldg 10,Room 1N-103, Bethesda, MD 20892 USA. NR 91 TC 40 Z9 43 U1 1 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-5172 J9 ACTA ANAESTH SCAND JI Acta Anaesthesiol. Scand. PD OCT PY 1999 VL 43 IS 9 BP 897 EP 908 DI 10.1034/j.1399-6576.1999.430907.x PG 12 WC Anesthesiology SC Anesthesiology GA 243XR UT WOS:000083023200006 PM 10522737 ER PT J AU Dauter, Z AF Dauter, Z TI Data-collection strategies SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID RAY DATA-COLLECTION AB The optimal strategy for collecting X-ray diffraction data from macromolecular crystals is discussed. Two kinds of factors influencing the completeness of data are considered. The first are geometric, arising from the symmetry of the reciprocal lattice and from the experimental setup; they affect quantitatively the completeness of the measured set of reflections. The second concern the quality, or information content, of the recorded intensities of these measured reflections. C1 NCI, Frederick & Brookhaven Natl Lab, Upton, NY 11973 USA. RP Dauter, Z (reprint author), NCI, Frederick & Brookhaven Natl Lab, Bldg 725A-X9, Upton, NY 11973 USA. NR 9 TC 81 Z9 85 U1 4 U2 10 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD OCT PY 1999 VL 55 BP 1703 EP 1717 DI 10.1107/S0907444999008367 PN 10 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 247QZ UT WOS:000083232600011 PM 10531520 ER PT J AU Evans, D Ganguli, M Harris, T Kawas, C Larson, EB AF Evans, D Ganguli, M Harris, T Kawas, C Larson, EB TI Women and Alzheimer disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Editorial Material C1 Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. RP Evans, D (reprint author), 8912 Copenhaver Dr, Potomac, MD 20854 USA. RI Ganguli, Mary/A-3638-2013; MORAN, CATHERINE/C-9539-2015 NR 0 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 1999 VL 13 IS 4 BP 187 EP 189 DI 10.1097/00002093-199910000-00002 PG 3 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 268NV UT WOS:000084423200002 PM 10609666 ER PT J AU van den Bree, MBM Eaves, LJ Dwyer, JT AF van den Bree, MBM Eaves, LJ Dwyer, JT TI Genetic and environmental influences on eating patterns of twins aged >= 50 y SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE twins; semiquantitative food-frequency questionnaire; eating patterns; genetic influences; environmental influences; sex; eating behavior ID FOOD PREFERENCES; DIETARY-INTAKE; FAMILY RESEMBLANCE; CLUSTER-ANALYSIS; ENERGY-INTAKE; HEALTH; VALIDATION; SIMILARITY; CHILDRENS; VARIABLES AB Background: Clinicians and researchers could benefit from a greater understanding of the role of genetic and environmental factors in human eating behavior. Objective: Our aim was to estimate the relative influence of genetic and environmental factors on habitual eating patterns in middle-aged and elderly men and women. Design: Male and female twins (n = 4640) aged greater than or equal to 50 y completed a mailed version of the National Cancer Institute food-frequency questionnaire. Factor analysis was performed to identify eating patterns among respondents. Estimates of genetic, common environmental (shared by family members), and specific environmental (unique to an individual) influences were obtained for food use, serving size, and consumption frequency by comparing monozygotic and dizygotic twin-pair groups with structural equation analysis. Results: Two independent eating patterns were identified: the first consisted of items high in fat, salt, and sugar, and the second reflected healthful eating habits. Although the influence of environmental factors was larger, between 15% and 38% of the total variation in pattern 1 and between 33% and 40% in pattern 2 were explained by genetic influences. Models accounting for sex differences in genetic and environmental estimates fit the data significantly better for food use and serving size of foods in eating pattern 1 and for food use in eating pattern 2. Conclusion: Although 60-85% of the variability in eating patterns was associated with environmental factors, genetic influences were also apparent and there was some evidence of sex specificity. These findings may be important in crafting dietary interventions and predicting adherence to these interventions. C1 Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. Tufts Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Nutr, Jean Mayer Human Nutr Res Ctr Aging, Boston, MA USA. New England Med Ctr, Frances Stern Nutr Ctr, Boston, MA 02111 USA. RP van den Bree, MBM (reprint author), NIDA, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. RI turton, miranda/F-4682-2011 FU NIAAA NIH HHS [AA-06781] NR 53 TC 54 Z9 59 U1 2 U2 5 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1999 VL 70 IS 4 BP 456 EP 465 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 239PR UT WOS:000082779100007 PM 10500013 ER PT J AU Ponnamperuma, RM Kirchhof, SM Trifiletti, L De Luca, LM AF Ponnamperuma, RM Kirchhof, SM Trifiletti, L De Luca, LM TI Ovariectomy increases squamous metaplasia of the uterine horns and survival of SENCAR mice fed a vitamin A-deficient diet SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE retinoic acid; estrogen; female reproductive epithelium; ovariectomy; survival; vitamin A deficiency; differentiation; mice ID RETINOIC ACID; EXPRESSION; CARCINOGENESIS; EPITHELIUM; ESTROGEN; RECEPTOR AB Background: Retinoic acid is necessary for the growth and differentiation of organisms and exerts its molecular actions by binding to specific nuclear receptors that belong to the thyroid-steroid hormone receptor superfamily. Steroids and retinoids control the differentiation of the female reproductive epithelia: estrogen maintains the squamous differentiation of vaginal and ectocervical epithelia, whereas retinoic acid maintains the simple columnar endocervical and uterine epithelia. These lining epithelia transform into a squamous metaplastic phenotype in vitamin A-deficient animals. Furthermore, mortality due to vitamin A deficiency is usually attributed to infection resulting in part from dysfunction of the protective epithelia. Objective: Our objective was to test the hypothesis that estrogen depletion might change the squamous metaplastic response to vitamin A deficiency and affect animal survival. Design: We used female SENCAR mice maintained on a purified vitamin A-deficient diet containing either 0 or 3 mu g retinoic acid/g diet. Mice were either ovariectomized or intact. Squamous cells arising in the normally simple columnar epithelium of the endocervix and uterine cavity were monitored by keratin 5 expression with immunohistochemistry. Results: Ovariectomy did not change the time to onset of vitamin A deficiency. It increased the number of squamous metaplastic cells and prolonged survival in mice consuming a vitamin A-deficient diet by as much as 40%. Conclusions: Factors other than epithelial differentiation per se control survival outcome of vitamin A-deficient mice. The results also show a significant increase in longevity of vitamin A-deficient mice when ovariectomized. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Differentiat Control Sect, NIH, Bethesda, MD 20892 USA. ROW Sci Inc, Gaithersburg, MD 20877 USA. RP De Luca, LM (reprint author), NIH Bldg 37,Room 3A-17,37 Convent Dr, Bethesda, MD 20892 USA. NR 11 TC 21 Z9 21 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1999 VL 70 IS 4 BP 502 EP 508 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 239PR UT WOS:000082779100013 PM 10500019 ER PT J AU Kim, SK AF Kim, SK TI National Institutes of Health workshop: Role of nutrient regulation of signal transduction in metabolic diseases - Foreword SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article C1 NIH, Nutr Study Sect, Nutr & Metab Sci Initial Rev Grp, Ctr Sci Rev, Bethesda, MD 20892 USA. RP Kim, SK (reprint author), NIH, Nutr Study Sect, Nutr & Metab Sci Initial Rev Grp, Ctr Sci Rev, Rockledge 2,Room 6178,MSC 7892,6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 1999 VL 70 IS 4 BP 544 EP 544 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 239PR UT WOS:000082779100018 PM 10500024 ER PT J AU Lei, JY Guo, XD Duray, PH AF Lei, JY Guo, XD Duray, PH TI Recent observations in comparison of human and reservoir host histopathology SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 1999 VL 112 IS 4 MA 64 BP 553 EP 554 PG 2 WC Pathology SC Pathology GA 239DV UT WOS:000082754300074 ER PT J AU Wilcox, AJ AF Wilcox, AJ TI The health of our children SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material RP Wilcox, AJ (reprint author), NIH, Natl inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 12 TC 3 Z9 3 U1 0 U2 0 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 OCT 1 PY 1999 VL 150 IS 7 BP 665 EP 666 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 241EV UT WOS:000082870500001 PM 10512419 ER PT J AU Naficy, AB Abu-Elyazeed, R Holmes, JL Rao, MR Savarino, SJ Kim, Y Wierzba, TF Peruski, L Lee, YJ Gentsch, JR Glass, RI Clemens, JD AF Naficy, AB Abu-Elyazeed, R Holmes, JL Rao, MR Savarino, SJ Kim, Y Wierzba, TF Peruski, L Lee, YJ Gentsch, JR Glass, RI Clemens, JD TI Epidemiology of rotavirus diarrhea in Egyptian children and implications for disease control SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast feeding; child; cohort studies; diarrhea; immunization; rotavirus ID LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE CHAIN-REACTION; DEVELOPING-COUNTRIES; YOUNG-CHILDREN; EFFICACY; VACCINE; INFANTS; ENTEROPATHOGENS; IDENTIFICATION; IMMUNOGENICITY AB Reliable epidemiologic data are essential for formulating effective policy to control rotavirus disease through immunization. The objective of this study was to describe the epidemiology of rotavirus diarrhea in a population-based cohort of children under 3 years of age residing in Abu Homos, Egypt, in 1995-1996. Rotavirus diarrhea incidence rates (episodes per person-year) were 0.13 for infants aged <6 months, 0.61 for those aged 6-11 months, 0.17 for those aged 12-23 months, and 0.15 for those aged 24-35 months. Fifty-six percent of children with rotavirus diarrhea had clinical dehydration; 90% of rotavirus diarrheal episodes occurred between July and November. In infants under I year of age, receipt of breast milk was associated with a lower incidence of rotavirus diarrhea. No other sociodemographic or environmental factor was found to be significantly associated with rotavirus diarrhea. Of 46 rotavirus isolates with strains identified, 41 (89%) were G serotypes 1 and 2. Rotavirus diarrhea was a major cause of morbidity in this cohort. Promotion of breastfeeding may exert a protective effect in young infants in this setting, but improvements in water and sanitation are unlikely to be effective preventive measures. The use of effective immunization against rotavirus in early infancy should be considered a public health priority. C1 NICHHD, Epidemiol Branch, Rockville, MD 20852 USA. US Naval Med Res Unit 3, Cairo, Egypt. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA USA. NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. RP Naficy, AB (reprint author), NICHHD, Epidemiol Branch, 6100 Execut Blvd,Room7B03, Rockville, MD 20852 USA. FU NICHD NIH HHS [Y1-HD-0026-01] NR 29 TC 61 Z9 65 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 OCT 1 PY 1999 VL 150 IS 7 BP 770 EP 777 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 241EV UT WOS:000082870500013 PM 10512431 ER PT J AU Otterson, GA Modi, S Nguyen, K Coxon, AB Kaye, FJ AF Otterson, GA Modi, S Nguyen, K Coxon, AB Kaye, FJ TI Temperature-sensitive RB mutations linked to incomplete penetrance of familial retinoblastoma in 12 families SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GERM-LINE MUTATIONS; HEREDITARY RETINOBLASTOMA; SPONTANEOUS REGRESSION; MILD EXPRESSION; GENE; PROTEIN; CANCER; PHENOTYPE; RETINOMA; PRODUCT AB The tumor-suppressor activity of the retinoblastoma protein (RB) is encoded within a protein-binding ("pocket") domain that is targeted for mutations in all cases of familial retinoblastoma and in many common adult cancers. Although familial retinoblastoma is a paradigm for a highly penetrant, recessive model of tumorigenesis, the molecular basis for the phenotype of incomplete penetrance of familial retinoblastoma is undefined. We studied the RE pocket-binding properties of three independent, mutant RE alleles that are present in the germline of 12 kindreds with the phenotype of incomplete penetrance of familial retinoblastoma. Each arises from alterations of single codons within the RE pocket domain (designated "Delta 480," "661W," or "712R"). Under the same conditions, we studied the properties of wild-type (WT) RE, an RE point mutant isolated from a lung carcinoma sample (706F) and an adjacent, in vitro-generated point mutant (707W). The Delta 480, 661W, and 712R mutants lack pocket protein-binding activity in vitro but retain the WT ability to undergo cyclin-mediated phosphorylation in vivo. Each of the low-penetrant RE mutants exhibits marked enhancement of pocket protein binding when the cells are grown at reduced temperature. In contrast, in this temperature range, no change in binding activity is seen with WT RE, the 706F mutant, or the 707W mutant. We have demonstrated that many families with incomplete penetrance of familial retinoblastoma carry unstable, mutant RE alleles with temperature-sensitive pocket protein-binding activity. The variable frequency for tumor development in these families may result from reversible fluctuations in a threshold level of RE pocket-binding activity. C1 NCI, Div Clin Sci, Med Branch, Dept Genet, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Bethesda, MD USA. RP Kaye, FJ (reprint author), Naval Hosp, Bldg 8-Room 5101, Bethesda, MD 20889 USA. RI kaye, frederic/E-2437-2011 NR 33 TC 24 Z9 25 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 BP 1040 EP 1046 DI 10.1086/302581 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 241XW UT WOS:000082910000012 PM 10486322 ER PT J AU Su, B Jin, L Hu, F Xiao, JH Luo, JC Lu, DR Zhang, WL Chu, JY Du, RF Geng, ZC Qiu, XF Xue, JL Tan, JZ O'Brien, SJ Chakraborty, R AF Su, B Jin, L Hu, F Xiao, JH Luo, JC Lu, DR Zhang, WL Chu, JY Du, RF Geng, ZC Qiu, XF Xue, JL Tan, JZ O'Brien, SJ Chakraborty, R TI Distribution of two HIV-1-resistant polymorphisms (SDF1-3 ' A and CCR2-641) in east Asian and world populations and its implication in AIDS epidemiology SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID HIV-1 INFECTION; GENETIC RESTRICTION; CHEMOKINE RECEPTORS; DISEASE PROGRESSION; RESISTANCE; CCR5; ALLELE; PATHOGENESIS; INDIVIDUALS; DELETION AB Chemokine receptor CCR2 and stromal-derived factor (SDF-1) are involved in HIV infection and AIDS symptom onset. Recent cohort studies showed that point mutations in these two genes, CCR2-64I and SDF1-3'A, can delay AIDS onset greater than or equal to 16 years after seroconversions. The protective effect of CCR2-64I is dominant, whereas that of SDF1-3'A is recessive. SDF1-3'A homozygotes also showed possible protection against HIV-1 infection. In this study, we surveyed the frequency distributions of the two alleles at both loci in world populations, with emphasis on those in east Asia. The CCR2-64I frequencies do not vary significantly in the different continents, having a range of 0.1-0.2 in most populations. A decreasing dine of the CCR2-64I frequency from north to south was observed in east Asia. In contrast, the distribution of SDF1-3'A in world populations varies substantially, and the highest frequency was observed in Oceanian populations. Moreover, an increasing dine of the SDF1-3'A frequency from north to south was observed in east Asia. The relative hazard values were computed to evaluate the risk of AIDS onset on the basis of two-locus genotypes in the east Asian and world populations. C1 Univ Texas, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77225 USA. Fudan Univ, Inst Genet, Shanghai, Peoples R China. Jingan Cent Hosp, Shanghai, Peoples R China. Suzhou Med Sch, Suzhou, Jiangsu, Peoples R China. Chinese Acad Med Sci, Inst Med Biol, Kunming, Yunnan, Peoples R China. Chinese Acad Sci, Inst Genet, Beijing, Peoples R China. NCI, Lab Genome Divers, Frederick, MD 21701 USA. RP Jin, L (reprint author), Univ Texas, Sch Publ Hlth, Ctr Human Genet, 6901 Bertner Ave,POB 20334, Houston, TX 77225 USA. RI MOE Key Lab at Fudan University, Contemp Anthropology/A-1772-2010; Jin, Li/C-1468-2009 OI Jin, Li/0000-0002-4546-2415 FU NIGMS NIH HHS [R01 GM041399, R01GM41399, R01GM55759] NR 18 TC 39 Z9 46 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 BP 1047 EP 1053 DI 10.1086/302568 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 241XW UT WOS:000082910000013 PM 10486323 ER PT J AU Aksentijevich, I Galon, J McDermott, MF Ortman, R O'Shea, JJ Kastner, DL AF Aksentijevich, I Galon, J McDermott, MF Ortman, R O'Shea, JJ Kastner, DL TI TNF receptor associated periodic fever syndromes (TRAPS): novel TNFR1 mutations and early experience with etanercept therapy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD USA. Royal London Hosp, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1570 BP A281 EP A281 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801573 ER PT J AU Alexander, C Auburger, G AF Alexander, C Auburger, G TI Construction of a sequence-ready 1.5 Mb PAC contig covering the whole OPA1 candidate region on chromosome 3q28-q29. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Hosp, Dept Neurol, Neurogenet Lab, Duesseldorf, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1571 BP A281 EP A281 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801571 ER PT J AU Altarescu, G Goldfarb, L Park, KY Kaneski, C Litvak, S Schiffmann, R AF Altarescu, G Goldfarb, L Park, KY Kaneski, C Litvak, S Schiffmann, R TI Detection of 16 new mutations in Fabry disease. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1274 BP A230 EP A230 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801274 ER PT J AU Anderson, DW Griffith, AJ Rudy, S San Agustin, T Friedman, TB Morell, RJ AF Anderson, DW Griffith, AJ Rudy, S San Agustin, T Friedman, TB Morell, RJ TI A new locus for autosomal dominant hearing loss DFNA28 mapped to chomosome 8q22. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCD, NIH, Mol Genet Lab, Rockville, MD USA. US Dept Educ, NIDRR, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1336 BP A241 EP A241 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801339 ER PT J AU Anikster, Y Touchman, JW Orvisky, E Krasnewich, D Green, ED Gahl, WA AF Anikster, Y Touchman, JW Orvisky, E Krasnewich, D Green, ED Gahl, WA TI A novel carbohydrate-kinase gene on chromosome 17p13, contiguous with CTNS, is homozygously deleted in approximately half the patients with Nephropathic Cystinosis (NC). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, HDB, Bethesda, MD USA. NHGRI, Intramural Sequencing Ctr, NIH, Bethesda, MD USA. NIMH, NSB, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 240 BP A46 EP A46 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800243 ER PT J AU Aylsworth, AS Kelly, TE Blanton, SH Spector, E Fordham, LA Stevenson, RE Sollenberger, J Francomano, CA Bellus, GA AF Aylsworth, AS Kelly, TE Blanton, SH Spector, E Fordham, LA Stevenson, RE Sollenberger, J Francomano, CA Bellus, GA TI Genetic heterogeneity and therapy potential in hypochondroplasia (HCH): Preliminary observations and proposal for an international collaborative study. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Natl Human Genome Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 756 BP A141 EP A141 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800757 ER PT J AU Bale, SJ Rogers, GR Bailey, R Austin, F Marini, JC Cabral, WA Compton, JG Paton, W AF Bale, SJ Rogers, GR Bailey, R Austin, F Marini, JC Cabral, WA Compton, JG Paton, W TI Homozygosity mapping identifies the chromosomal location of a rare congenital contracture gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Alaska Nat Med Ctr, Anchorage, AK USA. NICHD, NIH, Bethesda, MD USA. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1580 BP A282 EP A282 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801581 ER PT J AU Barber, TD Friedman, TB AF Barber, TD Friedman, TB TI CASTing for genes regulated by PAX3 during embryonic development and cancer epigenesis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCD, NIH, Rockville, MD USA. MSU, Genet Program, E Lansing, MI USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 993 BP A181 EP A181 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800994 ER PT J AU Basu, S Ashley-Koch, A Wolpert, CM Menold, MM Matsumoto, N Powell, CM Qumsiyeh, MB Cuccaro, ML Ledbetter, DH Green, ED Vance, JM Pericak-Vance, MA Gilbert, JR AF Basu, S Ashley-Koch, A Wolpert, CM Menold, MM Matsumoto, N Powell, CM Qumsiyeh, MB Cuccaro, ML Ledbetter, DH Green, ED Vance, JM Pericak-Vance, MA Gilbert, JR TI Autistic Disorder and chromosome 7: Analysis of an inversion breakpoint in a multiplex family. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. Univ S Carolina, WS Hall Psychiat Inst, Columbia, SC 29208 USA. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1471 BP A264 EP A264 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801473 ER PT J AU Battaile, KP Maslen, CL Porter, FD Steiner, RD AF Battaile, KP Maslen, CL Porter, FD Steiner, RD TI A simple PCR based assay allows detection of a common mutation, IVS8-1GC, in DHCR7 in Smith-Lemli-Opitz Syndrome patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. NICHHD, Heritable Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1280 BP A231 EP A231 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801280 ER PT J AU Batzer, M Nasidze, I Sherry, S Risch, G Robichaux, M Stoneking, M AF Batzer, M Nasidze, I Sherry, S Risch, G Robichaux, M Stoneking, M TI Alu insertion polymorphisms and human genomic diversity. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Louisiana State Univ, Med Ctr, Dept Pathol, New Orleans, LA 70112 USA. Max Planck Inst Evolutionary Anthropol, Leipzig, Germany. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 211 BP A41 EP A41 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800212 ER PT J AU Beiraghi, S Miller-Chrisholm, A Kimberling, WJ Sun, C Wang, Y Russell, L Khoshnevisan, M Storm, AL Long, RE Witt, PD Mazaheri, M Diehl, SR AF Beiraghi, S Miller-Chrisholm, A Kimberling, WJ Sun, C Wang, Y Russell, L Khoshnevisan, M Storm, AL Long, RE Witt, PD Mazaheri, M Diehl, SR TI Confirmation of linkage of Van der Woude syndrome to chromosome 1q32: Evidence of association with STR alleles suggests possible unique origin of the disease mutation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Nebraska, Med Ctr, Omaha, NE USA. Natl Inst Dent & Craniofacial Res, Carniofacial Epidemiol & Genet Branch, NIH, Bethesda, MD USA. Boys Town Natl Res Hosp, Ctr Hereditary Commun Disorders, Omaha, NE USA. Univ Arizona, Arizona Hlth Sci Ctr, Dept Pediat, Tucson, AZ USA. St Louis Childrens Hosp, St Louis, MO 63178 USA. Lancaster Cleft Palate Clin, Lancaster, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1350 BP A243 EP A243 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801352 ER PT J AU Bellus, GA Speiser, PW Webster, MK Donoghue, DJ Francomano, CA AF Bellus, GA Speiser, PW Webster, MK Donoghue, DJ Francomano, CA TI Fibroblast growth factor receptor 3 (FGFR3) Lys650Asn mutation causes hypochondroplasia. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. NYU, N Shore Univ Hosp, Sch Med, Dept Pediat, Manhasset, NY USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1585 BP A283 EP A283 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801584 ER PT J AU Ben-Yosef, T Francomano, CA AF Ben-Yosef, T Francomano, CA TI Characterization of the human Talin gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 995 BP A182 EP A182 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800998 ER PT J AU Bergen, AW Wilhelm, L Vallejo, R Kim, S McKeane, D Robin, R Goldman, D Long, JC AF Bergen, AW Wilhelm, L Vallejo, R Kim, S McKeane, D Robin, R Goldman, D Long, JC TI Association between alcohol dependence and 5-locus haplotypes on chromosome 11p15.5 in an American Indian population. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 69 BP A14 EP A14 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800070 ER PT J AU Biesecker, BB Ishibe, N Hadley, DW Giambarresi, TR Kase, RG Lerman, C Struewing, JP AF Biesecker, BB Ishibe, N Hadley, DW Giambarresi, TR Kase, RG Lerman, C Struewing, JP TI Psychosocial factors predicting genetic testing decisions in members of hereditary breast and ovarian cancer families. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIH, NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NIH, NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC USA. NIH, NCI, Lab Populat Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 628 BP A119 EP A119 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800631 ER PT J AU Biesecker, LG Graham, JM Grebe, T Neri, G Pagon, R Bonneman, C Partington, M Killoran, C AF Biesecker, LG Graham, JM Grebe, T Neri, G Pagon, R Bonneman, C Partington, M Killoran, C TI Mutational spectrum of Pallister-Hall syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Cattolica Sacro Cuore, I-00168 Rome, Italy. Univ Arizona, Phoenix, AZ USA. NHGRI, LGDR, Genet Dis Res Branch, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1591 BP A284 EP A284 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801590 ER PT J AU Blancato, JK Lin, T Veytsman, G Crouch, RJ Cerritelli, SM Gropman, A Smith, ACM AF Blancato, JK Lin, T Veytsman, G Crouch, RJ Cerritelli, SM Gropman, A Smith, ACM TI RNASEH1 gene in 17p11.2 deleted in Smith-Magenis syndrome (SMS). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. NICHD, Genet Mol Lab, NIH, Bethesda, MD USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 770 BP A143 EP A143 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800770 ER PT J AU Boyadjiev, SA Zwaan, J Justice, CM McKusick, VA Jabak, M Wilson, AF Jabs, EW AF Boyadjiev, SA Zwaan, J Justice, CM McKusick, VA Jabak, M Wilson, AF Jabs, EW TI Cranio-lenticulo-sutural dysplasia: Clinical and molecular studies of a new syndrome. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Johns Hopkins Univ, Inst Med Genet, Baltimore, MD USA. Univ Texas, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78284 USA. King Khalid Eye Specialist Hosp, Riyadh 11462, Saudi Arabia. NHGRI, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 263 BP A50 EP A50 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800264 ER PT J AU Brown, TC Kozma, C Meck, J AF Brown, TC Kozma, C Meck, J TI Mild clinical features of 18q deletion and trisomy 19q seen in a child with a never 18;19 translocation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, Genet Studies Sect, LSB, NIH, Bethesda, MD USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept OB GYN, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 775 BP A144 EP A144 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800778 ER PT J AU Bubendorf, L Kononen, J Barlund, M Kallioniemi, A Grigorian, A Sauter, G Dougherty, ER Kallioniemi, OP AF Bubendorf, L Kononen, J Barlund, M Kallioniemi, A Grigorian, A Sauter, G Dougherty, ER Kallioniemi, OP TI Tissue microarray FISH and digital imaging: Towards automated analysis of thousands of tumors with thousands of probes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. Texas A&M Univ, College Stn, TX 77843 USA. Univ Basel, CH-4003 Basel, Switzerland. RI Kallioniemi, Olli/H-4738-2012; Kallioniemi, Olli/H-5111-2011 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 316 BP A61 EP A61 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800316 ER PT J AU Bucher, C Torhorst, J Bubendorf, L Schraml, P Kononen, J Moch, H Mihatsch, M Kallioniemi, O Sauter, G AF Bucher, C Torhorst, J Bubendorf, L Schraml, P Kononen, J Moch, H Mihatsch, M Kallioniemi, O Sauter, G TI Tissue microarrays ("tissue chips") for high-throughput cancer genetics: Linking molecular changes to clinical endpoints. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Basel, Inst Pathol, Basel, Switzerland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. RI bucher, christoph/A-2520-2008; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 0 TC 8 Z9 8 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 43 BP A10 EP A10 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800046 ER PT J AU Cabral, WA Marini, JC AF Cabral, WA Marini, JC TI Cell-specific processing of mutant type I collagen in three probands with Osteogenesis imperfecta. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1606 BP A287 EP A287 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801609 ER PT J AU Caldwell, GM Day, CD Cooper, PR Eddy, RL Hejtmancik, F Evans, GA Smith, RJH Morton, CC Higgins, MJ Shows, TB AF Caldwell, GM Day, CD Cooper, PR Eddy, RL Hejtmancik, F Evans, GA Smith, RJH Morton, CC Higgins, MJ Shows, TB TI Transcript map of the Usher syndrome 1C gene locus on chromosome 11p14-15.1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Roswell Pk Canc Inst, Canc Genet, Buffalo, NY 14263 USA. Univ Iowa, Dept Otolaryngol, Iowa City, IA 52242 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, McDermott Ctr Genome Res, Dallas, TX USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1230 BP A223 EP A223 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801231 ER PT J AU Callahan, M Samimi, R Tayebi, N Sidransky, E AF Callahan, M Samimi, R Tayebi, N Sidransky, E TI Evolution of the glucocerebrosidase pseudogene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIMH, DHHS, PHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1002 BP A183 EP A183 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801002 ER PT J AU Carlin, ME Redman, JR Aguilar, MC McLean, SD Glenn, GA AF Carlin, ME Redman, JR Aguilar, MC McLean, SD Glenn, GA CA TEXGENE Ethics Educ Subcommittees TI Drama helps tell our tales. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 TEXGENE Eth & Euc Subcomm, San Antonio, TX USA. Genet & Dev Ctr SW, Ft Worth, TX USA. NIH, Washington, DC USA. CHRISTUS Santa Rosa Hlth Care, San Antonio, TX USA. USA Corp, San Antonio, TX USA. Univ Texas, Hlth Care Ctr, TEXGENE Eth & Educ Subcomm, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1052 BP A191 EP A191 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801053 ER PT J AU Carpenter, CL London, SJ AF Carpenter, CL London, SJ TI Lung cancer risk associated with family histories of smoking and lung cancer. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 USC, Norris Compr Cncr, Los Angeles, CA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 638 BP A120 EP A120 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800639 ER PT J AU Carpten, J Robbins, C Sood, R Bonner, T Makalowska, I Stephan, D Smith, J Scott, N Faruque, M Pinkett, H Graham, C Connors, T Morgenbesser, S Su, K Klingler, K Landes, G Gregory, S Williams, H Isaacs, W Trent, J AF Carpten, J Robbins, C Sood, R Bonner, T Makalowska, I Stephan, D Smith, J Scott, N Faruque, M Pinkett, H Graham, C Connors, T Morgenbesser, S Su, K Klingler, K Landes, G Gregory, S Williams, H Isaacs, W Trent, J TI A physical and transcription map of 1q24.3-q31.1 for the identification of hereditary disease genes including HPC1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Genzyme Genet Corp, Framingham, MA USA. Johns Hopkins Hosp, Brady Urol Clin, Baltimore, MD 21287 USA. NIMH, NIH, Bethesda, MD 20892 USA. Sanger Genome Sequencing Ctr, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1232 BP A223 EP A223 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801232 ER PT J AU Cervenakova, L Buetefisch, C Lee, HS Taller, I Stone, G Gibbs, CJ Brown, P Hallett, M Gambetti, P Goldfarb, LG AF Cervenakova, L Buetefisch, C Lee, HS Taller, I Stone, G Gibbs, CJ Brown, P Hallett, M Gambetti, P Goldfarb, LG TI Novel prion protein sequence variant associated with familiar encephalopathy. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1613 BP A288 EP A288 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801613 ER PT J AU Chae, JJ Centola, M Aksentijevich, I Dutra, A Tran, M Nagaraju, K Kingma, DW Liu, PP Kastner, DL AF Chae, JJ Centola, M Aksentijevich, I Dutra, A Tran, M Nagaraju, K Kingma, DW Liu, PP Kastner, DL TI Cloning and characterization of the mouse and rat homologs of MEFV, the gene for familial Mediterranean fever. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMSD, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Bethesda, MD USA. NCI, 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 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1004 BP A183 EP A183 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801003 ER PT J AU Chernoff, EJ Nunes, M White, B McClellan, J Coll, E Maggio, K Levin, S AF Chernoff, EJ Nunes, M White, B McClellan, J Coll, E Maggio, K Levin, S TI Fragile X premutation status in a male with mental retardation. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NICHD, Heritable Disorders Branch, NIH, Bethesda, MD USA. USAF, Ctr Med Genet, Med Grp 81, Keesler AFB, MS USA. Nichols Inst, Quest Diagnost, San Juan Capistrano, CA USA. Walter Reed Army Med Ctr, Dept Dermatol, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 781 BP A145 EP A145 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800784 ER PT J AU Clark, VJ Peterson, RJ Dean, M AF Clark, VJ Peterson, RJ Dean, M TI Haplotype analysis of chemokine receptor polymorphisms. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Genom Divers, FCRDC, Frederick, MD 21701 USA. Penn State Univ, Intercoll Grad Program Genet, University Pk, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1094 BP A199 EP A199 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801096 ER PT J AU Clifford, RJ Edmonson, MN Scherpbier, T Hu, Y Nguyen, C Voltz, AK Buetow, KH AF Clifford, RJ Edmonson, MN Scherpbier, T Hu, Y Nguyen, C Voltz, AK Buetow, KH TI All over the map: An integrated physical and genetic map of single nucleotide polymorphisms. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, LPG, DCEG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 512 BP A98 EP A98 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800512 ER PT J AU Cocchia, M Huber, R Pantano, S Ko, M Schlessinger, D AF Cocchia, M Huber, R Pantano, S Ko, M Schlessinger, D TI PLAC1, an X-linked unique marker gene for placenta. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1010 BP A184 EP A184 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801009 ER PT J AU Compton, JG DiGiovanna, JJ Johnston, K Fleckman, P Bale, SJ AF Compton, JG DiGiovanna, JJ Johnston, K Fleckman, P Bale, SJ TI The absent granular layer histology in Ichthyosis vulgaris is linked to the dermal differentiation complex on chromosome 1. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Brown Univ, Dept Dermatol, Providence, RI 02912 USA. 1st Med Grp, Serv Dermatol, Langley AFB, VA USA. Univ Washington, Dept Med Dermatol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 513 BP A98 EP A98 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800515 ER PT J AU Cooney, KA Chen, H Ray, ME Brierley, K Perrone, E Bock, CH Gillanders, E Lange, EM AF Cooney, KA Chen, H Ray, ME Brierley, K Perrone, E Bock, CH Gillanders, E Lange, EM TI Linkage analysis of 153 prostate cancer families over a 30 cM region containing the putative susceptibility locus HPCX. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Radiat Oncol & Biostat, Ann Arbor, MI 48109 USA. Natl Human Genome Res Inst, Canc Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 652 BP A123 EP A123 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800655 ER PT J AU Crisponi, L Uda, M Rocchi, M Ma, P Chen, E MacMillan, S Schlessinger, D Boccone, L Cao, A Pilla, G AF Crisponi, L Uda, M Rocchi, M Ma, P Chen, E MacMillan, S Schlessinger, D Boccone, L Cao, A Pilla, G TI Fine mapping of an X-breakpoint from a balanced (X;3) translocation in a female patient with nonspecific mental retardation (MRX), and identification of a new MRX candidate gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 CNR, IRTAM, Cagliari, Italy. Univ Bari, Bari, Italy. Perkin Elmer Corp, Foster City, CA USA. Washington Univ, St Louis, MO USA. NIA, HIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 478 BP A91 EP A91 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800479 ER PT J AU Cupples, LA Ordovas, JM Wilson, PWF Schaefer, EJ AF Cupples, LA Ordovas, JM Wilson, PWF Schaefer, EJ TI The TaqI(B) polymorphism in the CETP gene is associated with variation in high density lipoprotein. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Boston Univ, Sch Publ Hlth, Dept Epid Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, NIH, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1630 BP A291 EP A291 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801633 ER PT J AU Deitz, AC Hein, DW Hayes, RB Rothman, N Chow, W Zheng, W Rebbeck, TR AF Deitz, AC Hein, DW Hayes, RB Rothman, N Chow, W Zheng, W Rebbeck, TR TI Effect of biomarker misclassification: Comparison of two N-acetyltransferase 2 (NAT2) genotyping methods. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ S Carolina, Sch Publ Hlth, Columbia, SC 29208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1099 BP A200 EP A200 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801099 ER PT J AU Diehl, SR Khoshnevisan, MH Wyszynski, DF Wu, T Miller-Chisholm, A AF Diehl, SR Khoshnevisan, MH Wyszynski, DF Wu, T Miller-Chisholm, A TI Maternal multivitamin use, genetic variation in folate metabolism and risk of oral clefts. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCR, Craniofacial Epidemiol & Genet Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1499 BP A269 EP A269 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801502 ER PT J AU Dracheva, S Remmers, E Gulko, P Kawahito, Y Longman, R Wang, J Shepard, J Ge, L Joe, B Cannon, G Griffiths, M Wilder, R AF Dracheva, S Remmers, E Gulko, P Kawahito, Y Longman, R Wang, J Shepard, J Ge, L Joe, B Cannon, G Griffiths, M Wilder, R TI An integrated genetic linkage map with 1140 markers constructed from five F2 crosses of autoimmune disease-prone and -resistant inbred rat strains. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIAMS, ARB, NIH, Bethesda, MD USA. Univ Utah, Vet Affairs Med Ctr, Res Serv, Salt Lake City, UT USA. Univ Utah, Dept Med Rheumatol, Salt Lake City, UT USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Kyoto Prefectural Univ Med, Kyoto 602, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 516 BP A99 EP A99 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800517 ER PT J AU Durmowicz, MC Schlessinger, D AF Durmowicz, MC Schlessinger, D TI Characterization of an enhancer region of the X-linked anhidrotic ectodermal dysplasia (EDA) gene. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIA, Genet Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1018 BP A186 EP A186 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801019 ER PT J AU Durrani, SAK Tifft, CJ AF Durrani, SAK Tifft, CJ TI Acrocallosal syndrome with MRI findings of perisylvian syndrome: expansion of the phenotype. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 797 BP A147 EP A147 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800798 ER PT J AU Ebbers, SM Hirsh-Yechezkel, G Chetrit, A Modan, B Struewing, JP AF Ebbers, SM Hirsh-Yechezkel, G Chetrit, A Modan, B Struewing, JP TI Reproducibility of a fluorescent-based test for three BRCA1/BRCA2 mutations in blood and paraffin tissue samples. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Chaim Sheba Med Ctr, Dept Clin Epidemiol, IL-52621 Tel Hashomer, Israel. RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 661 BP A124 EP A124 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800660 ER PT J AU Erdos, MR Braun, A Mohike, K Silander, K Ghosh, S Collins, FS AF Erdos, MR Braun, A Mohike, K Silander, K Ghosh, S Collins, FS CA FUSION Study Grp TI MALDI-TOF mass spectrometry for high throughput SNP detection: Application to type 2 diabetes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NHGRI, NIH, Bethesda, MD USA. Sequenom Inc, San Diego, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1381 BP A248 EP A248 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801380 ER PT J AU Everman, DB Polinkovsky, A Francomano, CA Graham, JM Goodman, FR Neri, G Morrison, S Robin, NH Warman, ML AF Everman, DB Polinkovsky, A Francomano, CA Graham, JM Goodman, FR Neri, G Morrison, S Robin, NH Warman, ML TI Additional CDMP1 mutations suggest that brachydactyly type C is locus homogeneous and incompletely penetrant. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Case Western Reserve Univ Hosp, Cleveland, OH 44106 USA. NIH, NHGRI, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Inst Child Hlth, London, England. Univ Cattolica Sacro Cuore, I-00168 Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1647 BP A294 EP A294 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801648 ER PT J AU Fan, JQ Nakao, S Kaneski, CR Brady, RO Desnick, RJ Suzuki, Y Ishii, S AF Fan, JQ Nakao, S Kaneski, CR Brady, RO Desnick, RJ Suzuki, Y Ishii, S TI Intracellular enhancement of alpha-galactosidase A activity in 31 Fabry lymphoblasts and fibroblasts by 1-deoxy-galactonojirimycin. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Mt Sinai Sch Med, Dept Human Genet, New York, NY USA. Kagoshima Univ, Fac Med, Kagoshima 890, Japan. NIH, DMNB, Bethesda, MD 20892 USA. Tokyo Metropolitan Inst Med Sci, Tokyo 113, Japan. Usuki BioRes Ctr, Oita, Japan. NR 0 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1733 BP A308 EP A308 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801734 ER PT J AU Fanos, JH Puck, JM AF Fanos, JH Puck, JM TI Long-term on siblings of growing up with a brother with X-linked severe combined immunodeficiency. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Calif Pacific Med Ctr, Inst Res, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 56 BP A12 EP A12 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800058 ER PT J AU Fisher, P Das, K Das, MK Reddy, PA Reddy, PH Mastana, SS AF Fisher, P Das, K Das, MK Reddy, PA Reddy, PH Mastana, SS TI MtDNA variation in Central Indian populations. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Loughborough, Dept Human Sci, Loughborough, Leics, England. ISI, Anthropometry & Human Genet Unit, Calcutta, W Bengal, India. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1114 BP A202 EP A202 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801115 ER PT J AU Forlino, A Marini, JC AF Forlino, A Marini, JC TI Phenotypic variability in a murine model for the dominant negative disorder Osteogenesis Imperfecta. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 HDB, SCTD, Bethesda, MD USA. NICHD, NIH, Bethesda, MD USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 242 BP A46 EP A46 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800244 ER PT J AU Fridell, RA Boger, EA San Agustin, T Brownstein, MJ Friedman, TB Morelli, RJ AF Fridell, RA Boger, EA San Agustin, T Brownstein, MJ Friedman, TB Morelli, RJ TI DFNA27, a new locus for autosomal dominant hearing impairment on chromosome 4. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 NIDCD, Genet Mol Lab, NIH, Rockville, MD USA. DOED, NIDRR, Washington, DC USA. NIMH, Genet Lab, NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1388 BP A249 EP A249 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801389 ER PT J AU Friderici, KH Morell, RJ Wei, S Elfenbein, JL Levine, S Friedman, TB Fisher, RA AF Friderici, KH Morell, RJ Wei, S Elfenbein, JL Levine, S Friedman, TB Fisher, RA TI A new locus for late-onset, progressive, hereditary hearing loss (DFNA20) maps to 17q25. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Pediat & Human Dev, E Lansing, MI 48824 USA. Michigan State Univ, Dept Audiol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Speech Sci, E Lansing, MI 48824 USA. NIDCD, Genet Mol Lab, NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 1656 BP A295 EP A295 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879801658 ER PT J AU Friedman, JM Woods, R Joe, H Evans, DGR Wallace, A Mautner, VF Kluwe, L Parry, DM Rouleau, GA Baser, ME AF Friedman, JM Woods, R Joe, H Evans, DGR Wallace, A Mautner, VF Kluwe, L Parry, DM Rouleau, GA Baser, ME TI Germ-line NF2 mutation type, location, and phenotype in neurofibromatosis 2. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Stat, Vancouver, BC V5Z 1M9, Canada. St Marys Hosp, Manchester M13 0JH, Lancs, England. Univ Hamburg, Hamburg, Germany. Klinikum Nord Ochsenzoll, Hamburg, Germany. NCI, Bethesda, MD 20892 USA. McGill Univ, Montreal, PQ, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 1999 VL 65 IS 4 SU S MA 673 BP A126 EP A126 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 241JQ UT WOS:000082879800672 ER EF